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Sample records for subsection e1 relevancy

  1. Studies in Coprinus III — Coprinus section Veliformes. Subdivision and revision of subsection Nivei emend

    NARCIS (Netherlands)

    Uljé, C.B.; Noordeloos, M.E.

    1993-01-01

    Coprinus section Veliformes is defined and delimited to comprise four subsections: subsection Micacei, subsection Domestici, subsection Nivei, and subsection Narcotici, subsection nov. A key to the subsections is given. Subsection Nivei is emended, including also most taxa of subsection Flocculosi

  2. Ecological units of the Northern Region: Subsections

    Science.gov (United States)

    John A. Nesser; Gary L. Ford; C. Lee Maynard; Debbie Dumroese

    1997-01-01

    Ecological units are described at the subsection level of the Forest Service National Hierarchical Framework of Ecological Units. A total of 91 subsections are delineated on the 1996 map "Ecological Units of the Northern Region: Subsections," based on physical and biological criteria. This document consists of descriptions of the climate, geomorphology,...

  3. A new species in Coprinus subsection Setulosi

    NARCIS (Netherlands)

    Uljé, C.B.; Verbeken, A.

    2002-01-01

    Coprinus canistri spec. nov. is proposed. It belongs to the subsection Setulosi because of the presence of pileo- and caulocystidia. A comparison is given with C. subimpatiens and C. congregatus, on account of similar microscopical characters.

  4. Taxonomic revision of Elaphoglossum subsection Muscosa (Dryopteridaceae)

    NARCIS (Netherlands)

    Vasco, A.

    2011-01-01

    The present paper provides a monograph of Elaphoglossum subsect. Muscosa, a monophyletic group supported by molecular phylogenetic analyses. The monograph includes keys, full synonymy, descriptions, representative specimens examined, an index to collectors’ names and numbers, illustrations, spore

  5. Additional studies in Coprinus subsection Glabri

    NARCIS (Netherlands)

    Uljé, C.B.; Bender, H.

    1997-01-01

    First Coprinus lilatinctus, belonging to subsect. Glabri, is described as new. Secondly, nomenclatural reasons are given for Coprinus nudiceps P.D. Orton to be replaced by the older name C. schroeteri P. Karst. Type studies of both taxa are given and their synonymy is discussed. To facilitate

  6. Type studies in Coprinus subsection Lanatuli

    NARCIS (Netherlands)

    Uljé, C.B.; Noordeloos, M.E.

    2001-01-01

    As a prelude to a monograph of the genus Coprinus, types were studied of a number of species said to belong to Coprinus subsection Lanatuli (Coprinus alnivorus. C. alutaceivelatus, C. ammophilae, C. arachnoideus, C. asterophoroides, C. brunneistragulatus, C. bubalinus, C. citrinovelatus, C.

  7. 22 CFR 505.13 - General exemptions (Subsection (j)).

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true General exemptions (Subsection (j)). 505.13... exemptions (Subsection (j)). (a) General exemptions are available for systems of records which are maintained by the Central Intelligence Agency (Subsection (j)(1)), or maintained by an agency which performs as...

  8. 22 CFR 505.14 - Specific exemptions (Subsection (k)).

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Specific exemptions (Subsection (k)). 505.14... exemptions (Subsection (k)). The specific exemptions focus more on the nature of the records in the system of...) Subsection (k)(1). Records which are specifically authorized under criteria established under an Executive...

  9. The taxonomy of the European species of Hebeloma section Denudata subsections Hiemalia, Echinospora subsect. nov. and Clepsydroida subsect. nov. and five new species

    DEFF Research Database (Denmark)

    Eberhardt, Ursula; Beker, Henry J.; Vesterholt, Jan Hansen

    2016-01-01

    ., H. populinum, and H. rostratum sp. nov. We provide descriptions of all three of these species in order to clarify the taxonomy of this section. We provide a key to H. sect. Denudata and the discussed subsections. For the majority of the taxa there is good overall consistency between morphological...... and phylogenetic delimitation and, where the information exists, thanks to Aanen and Kuyper's work, biological delimitation....

  10. Taxonomy, systematics, and biogeography of Ficus subsection Urostigma (Moraceae)

    NARCIS (Netherlands)

    Chantarasuwan, Bhanumas

    2014-01-01

    Five research methods were used in Taxonomy, Systematics, and Biogeography of Ficus subsection Urostigma(Moraceae); Morphological characters, leaf anatomy, pollen morphology, molecular phylogeny, and historical biogeography. Seven topics are the result: 1) A revision was made based on morphology in

  11. Studies in Coprinus—II. Subsection Setulosi of section Pseudocoprinus

    NARCIS (Netherlands)

    Ujlé, C.B.; Bas, C.

    1991-01-01

    A key is given to the Netherlands’ species of subsect. Setulosi J. Lange of Coprinus sect. Pseudocoprinus (Kühn.) P.D. Orton & Watling. Some additional species are also included. All species dealt with are concisely described and fully discussed. A few probably new species are described ad interim.

  12. Missile total and subsection weight and size estimation equations

    OpenAIRE

    Nowell, John B., Jr.

    1992-01-01

    Approved for public release; distribution is unlimited This study utilizes regression analysis to develop equations which relate missile overall and subsection weights and geometries, including wings and fins, to variables which are considered to be the input for a new design in the conceptual or preliminary design phase, These variables include packaging requirements such as maximum length, diameter and weight, as well as performance characteristics such as mission an range. Data for th...

  13. Studies in Coprinus IV — Coprinus section coprinus. Subdivision and revision of subsection Alachuani

    NARCIS (Netherlands)

    Uljé, C.B.; Noordeloos, M.E.

    1997-01-01

    Coprinus section Coprinus is defined and delimited to comprise four subsections: Atramentarii, Coprinus, Lanatuli and Alachuani. A key to the subsections is given as well as a key to the species of subsection Alachuani known from the Netherlands or to be expected in the Netherlands on account of

  14. Studies in Coprinus IV — Coprinus section coprinus. Subdivision and revision of subsection Alachuani

    OpenAIRE

    Uljé, C.B.; Noordeloos, M.E.

    1997-01-01

    Coprinus section Coprinus is defined and delimited to comprise four subsections: Atramentarii, Coprinus, Lanatuli and Alachuani. A key to the subsections is given as well as a key to the species of subsection Alachuani known from the Netherlands or to be expected in the Netherlands on account of records from neighbouring countries. Three new species, Coprinus epichloeus, Coprinus fluvialis and Coprinus sclerotiorum are described as well as a new variety of C. urticicola: var. salicicola. In a...

  15. Studies in Coprinus V — Coprinus section Coprinus. Revision of subsection Lanatuli Sing

    NARCIS (Netherlands)

    Uljé, C.B.; Noordeloos, M.E.

    1999-01-01

    A key is given to the species of subsection Lanatuli known from the Netherlands or to be expected in the Netherlands on account of records from neighbouring countries. For a key to the subsections in Coprinus section Coprinus see Uljé & Noordel., Persoonia 16 (1997) 267. Coprinus bicornis and C.

  16. The E1 proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bergvall, Monika [Molecular Virology Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 Pine avenue West, Montreal, QC, Canada H2W 1R7 (Canada); Department of Microbiology and Immunology, McGill University, Montreal, QC (Canada); Melendy, Thomas [Departments of Microbiology and Immunology, Biochemistry and the Witebsky Center for Microbial Pathogenesis, University of Buffalo, 210 Biomedical Research Building, School of Medicine and Biomedical Sciences, Buffalo, NY 14214 (United States); Archambault, Jacques, E-mail: jacques.archambault@ircm.qc.ca [Molecular Virology Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 Pine avenue West, Montreal, QC, Canada H2W 1R7 (Canada); Department of Microbiology and Immunology, McGill University, Montreal, QC (Canada); Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC (Canada)

    2013-10-15

    E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. - Highlights: • The papillomavirus E1 helicase orchestrates replication of the viral DNA genome. • E1 assembles into a double-hexamer at the viral origin with the help of E2. • E1 interacts with cellular DNA replication factors. • E1 unwinds DNA using a spiral escalator mechanism. • Nuclear accumulation of E1 is regulated by post-translational modifications.

  17. Studies in Coprinus V — Coprinus section Coprinus. Revision of subsection Lanatuli Sing

    OpenAIRE

    Uljé, C.B.; Noordeloos, M.E.

    1999-01-01

    A key is given to the species of subsection Lanatuli known from the Netherlands or to be expected in the Netherlands on account of records from neighbouring countries. For a key to the subsections in Coprinus section Coprinus see Uljé & Noordel., Persoonia 16 (1997) 267. Coprinus bicornis and C. spelaiophilus are described as new species. In addition the following species are fully described: C. ammophilae, C. calosporus, C. cinereus, C. erythrocephalus, C. geesterani, C. jonesii, C. krieglst...

  18. Needle Terpenes as Chemotaxonomic Markers in Pinus: Subsections Pinus and Pinaster.

    Science.gov (United States)

    Mitić, Zorica S; Jovanović, Snežana Č; Zlatković, Bojan K; Nikolić, Biljana M; Stojanović, Gordana S; Marin, Petar D

    2017-05-01

    Chemical compositions of needle essential oils of 27 taxa from the section Pinus, including 20 and 7 taxa of the subsections Pinus and Pinaster, respectively, were compared in order to determine chemotaxonomic significance of terpenes at infrageneric level. According to analysis of variance, six out of 31 studied terpene characters were characterized by a high level of significance, indicating statistically significant difference between the examined subsections. Agglomerative hierarchical cluster analysis has shown separation of eight groups, where representatives of subsect. Pinaster were distributed within the first seven groups on the dendrogram together with P. nigra subsp. laricio and P. merkusii from the subsect. Pinus. On the other hand, the eighth group included the majority of the members of subsect. Pinus. Our findings, based on terpene characters, complement those obtained from morphological, biochemical, and molecular parameters studied over the past two decades. In addition, results presented in this article confirmed that terpenes are good markers at infrageneric level. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  19. Serum proteins in endogamous Brahmin sub-sects of Andhra Pradesh.

    Science.gov (United States)

    Char, K S; Rao, P R

    1983-01-01

    Haptoglobin phenotypes and rare variants of transferrin and albumin are reported in six endogamous Brahmin sub-sects, viz., Niyogi, Madwa, Dravida, Vadahalai, Tengalai and Vaidiki from Andhra Pradesh. Samples were collected from Vaidiki subsect from three different locations to study the genetic variation, if any, resulting from geographic isolation. The Hp1 gene frequency ranged from 0.1124 to 0.2064. A fast heterozygote transferrin variant and three albumin slow variants showing different electrophoretic mobility are reported for the first time in the Brahmin populations of South India.

  20. Chang'E-1

    Indian Academy of Sciences (India)

    China plans to implement its first lunar exploration mission Chang'E-1 by 2007. The mission objectives are. • to obtain a three-dimensional stereo image of the lunar surface,. • to determine distribution of some useful elements and to estimate their abundance,. • to survey the thickness of lunar soil and to evaluate resource of.

  1. Team-Based Learning in a Subsection of a Veterinary Course as Compared to Standard Lectures

    Science.gov (United States)

    Malone, Erin; Spieth, Amie

    2012-01-01

    Team-Based Learning (TBL) maximizes class time for student practice in complex problems using peer learning in an instructor-guided format. Generally entire courses are structured using the comprehensive guidelines of TBL. We used TBL in a subsection of a veterinary course to determine if it remained effective in this format. One section of the…

  2. Studies in Coprinus—I. Subsections Auricomi and Glabri of Coprinus section Pseudocoprinus

    NARCIS (Netherlands)

    Uljé, C.B.; Bas, C.

    1988-01-01

    A key is given to the Netherlands’ species of subsect. Auricomi Sing. and Glabri J. Lange of Coprinus sect. Pseudocoprinus (Kühn.) Orton & Watling. All species concerned are concisely described and amply discussed. Coprinus plicatilis var. microsporus Kühn. is raised to species level as C. kuehneri

  3. Colonization and diversification of the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) on the Canary Islands.

    Science.gov (United States)

    Sun, Ye; Li, Yanshu; Vargas-Mendoza, Carlos Fabián; Wang, Faguo; Xing, Fuwu

    2016-09-29

    Diversification between islands and ecological radiation within islands are postulated to have occurred in the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) on the Canary Islands. In this study, the biogeographical pattern of 11 species of subsect. Macaronesicae and the genetic differentiation among five species were investigated to distinguish the potential mode and mechanism of diversification and speciation. The biogeographical patterns and genetic structure were examined using statistical dispersal-vicariance analysis, Bayesian phylogenetic analysis, reduced median-joining haplotype network analysis, and discriminant analysis of principal components. The gene flow between related species was evaluated with an isolation-with-migration model. The ancestral range of the species of subsect. Macaronesicae was inferred to be Tenerife and the Cape Verde Islands, and Tenerife-La Gomera acted as sources of diversity to other islands of the Canary Islands. Inter-island colonization of E. lamarckii among the western islands and a colonization of E. regis-jubae from Gran Canaria to northern Africa were revealed. Both diversification between islands and radiation within islands have been revealed in the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) of the Canary Islands. It was clear that this group began the speciation process in Tenerife-La Gomera, and this process occurred with gene flow between some related species.

  4. Regulatory Safety Issues in the Structural Design Criteria of ASME Section III Subsection NH and for Very High Temperatures for VHTR & GEN IV

    Energy Technology Data Exchange (ETDEWEB)

    William J. O’Donnell; Donald S. Griffin

    2007-05-07

    The objective of this task is to identify issues relevant to ASME Section III, Subsection NH [1], and related Code Cases that must be resolved for licensing purposes for VHTGRs (Very High Temperature Gas Reactor concepts such as those of PBMR, Areva, and GA); and to identify the material models, design criteria, and analysis methods that need to be added to the ASME Code to cover the unresolved safety issues. Subsection NH was originally developed to provide structural design criteria and limits for elevated-temperature design of Liquid Metal Fast Breeder Reactor (LMFBR) systems and some gas-cooled systems. The U.S. Nuclear Regulatory Commission (NRC) and its Advisory Committee for Reactor Safeguards (ACRS) reviewed the design limits and procedures in the process of reviewing the Clinch River Breeder Reactor (CRBR) for a construction permit in the late 1970s and early 1980s, and identified issues that needed resolution. In the years since then, the NRC and various contractors have evaluated the applicability of the ASME Code and Code Cases to high-temperature reactor designs such as the VHTGRs, and identified issues that need to be resolved to provide a regulatory basis for licensing. This Report describes: (1) NRC and ACRS safety concerns raised during the licensing process of CRBR , (2) how some of these issues are addressed by the current Subsection NH of the ASME Code; and (3) the material models, design criteria, and analysis methods that need to be added to the ASME Code and Code Cases to cover unresolved regulatory issues for very high temperature service.

  5. A simple device for subsectioning aqueous sediments from the box or spade corer

    Digital Repository Service at National Institute of Oceanography (India)

    Valsangkar, A.B.

    ] by using an additional key. The ring(s) thus help to obtain fine scale sediment sub-section(s) [18] above the sub-core [16] (Figure 2). The rings of plastic or flexible material can also be used externally to achieve the purpose. Accessories 1) Acrylic... on the top of the sub-core. The sediment thus exposed on the top is sectioned, packed in the plastic bag and numbered. Similarly, other three 0.5 cm sections are removed and packed. By this way first top 2 cm sediment is sub-divided in to four parts of 0...

  6. Cellular fatty acid composition of cyanobacteria assigned to subsection II, order Pleurocapsales.

    Science.gov (United States)

    Caudales, R; Wells, J M; Butterfield, J E

    2000-05-01

    The cellular fatty acid composition of five of the six genera of unicellular cyanobacteria in subsection II, Pleurocapsales (Dermocarpa, Xenococcus, Dermocarpella, Myxosarcina and the Pleurocapsa assemblage) contained high proportions of saturated straight-chain fatty acids (26-41% of the total) and unsaturated straight chains (40-67%). Isomers of 16:1 were the main monounsaturated acid component (11-59%). Polyunsaturated acids were present at trace levels (0-1% or less) in Xenococcus and Myxosarcina, at concentrations of less than 7% in Dermocarpa, Dermocarpella, Pleurocapsa and CCMP 1489, and at high concentrations (35% or more) in Chroococcidiopsis. Chroococcidiopsis was also different in terms of the percentage of 16:1 isomers (10-12%) compared to other genera (30-59%), and in terms of total 16-carbon and 18-carbon fatty acids. In general, the composition and heterogeneity of fatty acids in the order Pleurocapsales was similar to that reported for the unicellular cyanobacteria of subsection I, order Chroococcales.

  7. A Review & Assessment of Current Operating Conditions Allowable Stresses in ASME Section III Subsection NH

    Energy Technology Data Exchange (ETDEWEB)

    R. W. Swindeman

    2009-12-14

    The current operating condition allowable stresses provided in ASME Section III, Subsection NH were reviewed for consistency with the criteria used to establish the stress allowables and with the allowable stresses provided in ASME Section II, Part D. It was found that the S{sub o} values in ASME III-NH were consistent with the S values in ASME IID for the five materials of interest. However, it was found that 0.80 S{sub r} was less than S{sub o} for some temperatures for four of the materials. Only values for alloy 800H appeared to be consistent with the criteria on which S{sub o} values are established. With the intent of undertaking a more detailed evaluation of issues related to the allowable stresses in ASME III-NH, the availabilities of databases for the five materials were reviewed and augmented databases were assembled.

  8. A New Classification of Ficus Subsection Urostigma (Moraceae Based on Four Nuclear DNA Markers (ITS, ETS, G3pdh, and ncpGS, Morphology and Leaf Anatomy.

    Directory of Open Access Journals (Sweden)

    Bhanumas Chantarasuwan

    Full Text Available Ficus subsection Urostigma as currently circumscribed contains 27 species, distributed in Africa, Asia, Australia and the Pacific, and is of key importance to understand the origin and evolution of Ficus and the fig-wasp mutualism. The species of subsection Urostigma are very variable in morphological characters and exhibit a wide range of often partly overlapping distributions, which makes identification often difficult. The systematic classification within and between this subsection and others is problematic, e.g., it is still unclear where to classify F. amplissima and F. rumphii. To clarify the circumscription of subsection Urostigma, a phylogenetic reconstruction based on four nuclear DNA markers (ITS, ETS, G3pdh, and ncpGS combined with morphology and leaf anatomy is conducted. The phylogenetic tree based on the combined datasets shows that F. madagascariensis, a Madagascan species, is sister to the remainder of subsect. Urostigma. Ficus amplissima and F. rumphii, formerly constituting sect. Leucogyne, appear to be imbedded in subsect. Conosycea. The result of the phylogenetic analysis necessitates nomenclatural adjustments. A new classification of Ficus subsection Urostigma is presented along with the morphological and leaf anatomical apomorphies typical for the clades. Two new species are described ─ one in subsect. Urostigma, the other in Conosycea. One variety is raised to species level.

  9. Taxonomic revision of the tropical African group of Carex subsect. Elatae (sect. Spirostachyae, Cyperaceae

    Directory of Open Access Journals (Sweden)

    Escudero, Marcial

    2011-12-01

    Full Text Available The tropical African monophyletic group of Carex subsect. Elatae (sect. Spirostachyae is distributed in continental tropical Africa, Madagascar, the Mascarene archipelago, and Bioko Island (32 km off the coast of West Africa, in the Gulf of Guinea. The first monographic treatment of this Carex group, as well as of the tribe Cariceae, was published by Kükenthal (as sect. Elatae Kük.. Recently, the first molecular (nrDNA, cpDNA phylogeny of Carex sect. Elatae has been published, which also included the species of sect. Spirostachyae. In the resulting consensus trees, most species of sect. Elatae were embedded within core Spirostachyae and so this section was joined with sect. Spirostachyae as subsect. Elatae. Within subsect. Elatae, several groups were described, one of which was termed the “tropical African group”. Here we present a taxonomic revision of this group, based on more than 280 vouchers from 29 herbaria as well as in field trips in Tropical Africa. In the revision, we recognise 12 species (16 taxa within the tropical African group, and so have somewhat modified our previous view, in which 10 species, 12 taxa were listed. One new species from Tanzania is included in this treatment, C. uluguruensis Luceño & M. Escudero. Several combinations are made, C. cyrtosaccus is treated as a synonym of C. vallis-rosetto and, finally, the binomial C. greenwayi has been recognised.Las especies de la subsección Elatae (sección Spirostachyae del género Carex que se distribuyen por África tropical continental, Madagascar, el archipiélago de las Mascareñas y la isla de Bioko (a 32 km del litoral de África occidental, en el golfo de Guinea forman un grupo monofilético. El primer tratamiento taxonómico de este grupo de cárices, así como de la tribu Cariceae en su conjunto, fue elaborado por Kükenthal (sección Elatae Kük.; recientemente, se ha publicado el primer estudio de filogenia molecular (nrDNA, cpDNA de los táxones de este grupo

  10. Notes on Elaphoglossum (Lomariopsidaceae section Polytrichia subsection Hybrida in Mexico and Central America

    Directory of Open Access Journals (Sweden)

    Alexander Fco. Rojas-Alvarado

    2003-03-01

    Full Text Available In Elaphoglossum sect. Polytrichia subsect. Hybrida six new species are described: E. angustiob-longum A. Rojas, E. baquianorum A. Rojas, E. cotoi A. Rojas, E. jinoteganum A. Rojas, E. neeanum A. Rojas and E. silencioanum A. Rojas. New combination is made for Elaphoglossum mexicanum (E. Fourn. A. Rojas. Two species are reported: E. barbatum (H. Karst. Hieron. and E. scolopendrifolium (Raddi J. Sm. Two species are redefined: E. erinaceum (Fée T. Moore and E. tambillense (Hook. T. Moore. E. pallidum (Baker ex Jenman C. Chr. Is eliminated for Mexico and Central America. Of the new species only E. neeanum is present outside of the region. A key is given to those species in Mexico and Central America.Seis especies nuevas son descritas: Elaphoglossum angustioblongum A. Rojas, E. baquianorum A. Rojas, E. cotoi A. Rojas, E. jinoteganum A. Rojas, E. neeanum A. Rojas y E. silencioanum A. Rojas. La especie Elaphoglossum mexicanum (E. Fourn. A. Rojas es combinada; las especies E. barbatum (H. Karst. Hieron. y E. scolopendrifolium (Raddi J. Sm. son registradas; además, E. erinaceum (Fée T. Moore y E. tambillense (Hook. T. Moore son redefinidas, y E. pallidum (Baker ex Jenman C. Chr. no se distribuye en México y Centroamérica. De las especies nuevas sólo E. neeanum se encuentra fuera de la región. Se proporciona una clave para reconocer las especies de México y Centro América.

  11. Update and Improve Subsection NH –– Alternative Simplified Creep-Fatigue Design Methods

    Energy Technology Data Exchange (ETDEWEB)

    Tai Asayama

    2009-10-26

    This report described the results of investigation on Task 10 of DOE/ASME Materials NGNP/Generation IV Project based on a contract between ASME Standards Technology, LLC (ASME ST-LLC) and Japan Atomic Energy Agency (JAEA). Task 10 is to Update and Improve Subsection NH -- Alternative Simplified Creep-Fatigue Design Methods. Five newly proposed promising creep-fatigue evaluation methods were investigated. Those are (1) modified ductility exhaustion method, (2) strain range separation method, (3) approach for pressure vessel application, (4) hybrid method of time fraction and ductility exhaustion, and (5) simplified model test approach. The outlines of those methods are presented first, and predictability of experimental results of these methods is demonstrated using the creep-fatigue data collected in previous Tasks 3 and 5. All the methods (except the simplified model test approach which is not ready for application) predicted experimental results fairly accurately. On the other hand, predicted creep-fatigue life in long-term regions showed considerable differences among the methodologies. These differences come from the concepts each method is based on. All the new methods investigated in this report have advantages over the currently employed time fraction rule and offer technical insights that should be thought much of in the improvement of creep-fatigue evaluation procedures. The main points of the modified ductility exhaustion method, the strain range separation method, the approach for pressure vessel application and the hybrid method can be reflected in the improvement of the current time fraction rule. The simplified mode test approach would offer a whole new advantage including robustness and simplicity which are definitely attractive but this approach is yet to be validated for implementation at this point. Therefore, this report recommends the following two steps as a course of improvement of NH based on newly proposed creep-fatigue evaluation

  12. Taxonomical and nomenclatural notes on Centaurea: A proposal of classification, a description of new sections and subsections, and a species list of the redefined section Centaurea

    Directory of Open Access Journals (Sweden)

    Hilpold, A.

    2014-12-01

    Full Text Available In this paper, we summarize the results of our long-date research on the genus Centaurea. The first part of the paper deals with the overall classification of the genus, which we propose to divide into three subgenera: subgenus Centaurea, subgenus Cyanus and subgenus Lopholoma. The second part of this publication gives a recopilation of the species of the redefined section Centaurea, a group that includes former sections Acrolophus (sect. Centaurea s. str., Phalolepis and Willkommia, together with taxonomical, geographical, ecological and karyological considerations. Finally, new descriptions or nomenclatural combinations are proposed to correlate nomenclature to the new classification: a new combination (sect. Acrocentron subsect. Chamaecyanus is proposed in subgenus Lopholoma; three new sections (sects. Akamantis, Cnicus, and Hyerapolitanae are described in subgenus Centaurea; two subsections (subsects. Phalolepis and Willkommia in sect. Centaurea; and three subsections (subsects. Exarata, Jacea, and Subtilis in sect. Phrygia.En este trabajo presentamos los resultados de nuestras investigaciones de larga fecha en el género Centaurea. La primera parte del trabajo trata de la clasificación del género, que proponemos dividir en tres subgéneros: subgénero Centaurea, subgénero Cyanus y subgénero Lopholoma. La segunda parte es una recopilación de las especies de la redefinida sección Centaurea, que incluye las antiguas secciones Acrolophus (sect. Centaurea s. str., Phalolepis y Willkommia, junto con consideraciones geográficas, ecológicas y cariológicas. Por último, proponemos nuevas secciones, subsecciones y combinaciones para correlacionar nomenclatura y clasificación: proponemos una nueva (sect. Acrocentron subsect. Chamaecyanus en el subgénero Lopholoma; se describen tres secciones nuevas (sects. Akamantis, Cnicus y Hyerapolitanae en el subgénero Centaurea; dos subsecciones (subsects. Phalolepis and Willkommia en la secci

  13. POLLEN AND SEED SURFACE MORFOLOGY IN SOME REPRESENTATIVES OF THE GENUS RHODODENDRON SUBSECT. RHODORASTRUM (ERICACEAE IN THE RUSSIAN FAR EAST

    Directory of Open Access Journals (Sweden)

    I. M. Koksheeva

    2015-05-01

    Full Text Available Comparative study of pollen and seed morphology of three species of Rhododendron L. subsect. Rhodorastrum (Maxim. Cullen (Rh. dauricum L., Rh. mucronolatum Turcz., Rh. sichotense Pojark. is performed. Results of discriminant analysis of the total of morphometric characters of pollen and seeds have proved the distinctness of all three species from each other. Differences of polen are observed in the type of sculpture (granulate, rugulate, microrugulate and in the diameter of tetrads. The coefficient of elongation of the exotesta cells is established as a valuable morphometric character

  14. Energy neutral: the human foot and ankle subsections combine to produce near zero net mechanical work during walking.

    Science.gov (United States)

    Takahashi, Kota Z; Worster, Kate; Bruening, Dustin A

    2017-11-13

    The human foot and ankle system is equipped with structures that can produce mechanical work through elastic (e.g., Achilles tendon, plantar fascia) or viscoelastic (e.g., heel pad) mechanisms, or by active muscle contractions. Yet, quantifying the work distribution among various subsections of the foot and ankle can be difficult, in large part due to a lack of objective methods for partitioning the forces acting underneath the stance foot. In this study, we deconstructed the mechanical work production during barefoot walking in a segment-by-segment manner (hallux, forefoot, hindfoot, and shank). This was accomplished by isolating the forces acting within each foot segment through controlling the placement of the participants' foot as it contacted a ground-mounted force platform. Combined with an analysis that incorporated non-rigid mechanics, we quantified the total work production distal to each of the four isolated segments. We found that various subsections within the foot and ankle showed disparate work distribution, particularly within structures distal to the hindfoot. When accounting for all sources of positive and negative work distal to the shank (i.e., ankle joint and all foot structures), these structures resembled an energy-neutral system that produced net mechanical work close to zero (-0.012 ± 0.054 J/kg).

  15. CYP2E1 hydroxylation of aniline involves negative cooperativity.

    Science.gov (United States)

    Hartman, Jessica H; Knott, Katie; Miller, Grover P

    2014-02-01

    CYP2E1 plays a role in the metabolic activation and elimination of aniline, yet there are conflicting reports on its mechanism of action, and hence relevance, in aniline metabolism. Based on our work with similar compounds, we hypothesized that aniline binds two CYP2E1 sites during metabolism resulting in cooperative reaction kinetics and tested this hypothesis through rigorous in vitro studies. The kinetic profile for recombinant CYP2E1 demonstrated significant negative cooperativity based on a fit of data to the Hill equation (n=0.56). Mechanistically, the data were best explained through a two-binding site cooperative model in which aniline binds with high affinity (K(s)=30 μM) followed by a second weaker binding event (K(ss)=1100 uM) resulting in a threefold increase in the oxidation rate. Binding sites for aniline were confirmed by inhibition studies with 4-methylpyrazole. Inhibitor phenotyping experiments with human liver microsomes validated the central role for CYP2E1 in aniline hydroxylation and indicated minor roles for CYP2A6 and CYP2C9. Importantly, inhibition of minor metabolic pathways resulted in a kinetic profile for microsomal CYP2E1 that replicated the preferred mechanism and parameters observed with the recombinant enzyme. Scaled modeling of in vitro CYP2E1 metabolism of aniline to in vivo clearance, especially at low aniline levels, led to significant deviations from the traditional model based on non-cooperative, Michaelis-Menten kinetics. These findings provide a critical mechanistic perspective on the potential importance of CYP2E1 in the metabolic activation and elimination of aniline as well as the first experimental evidence of a negatively cooperative metabolic reaction catalyzed by CYP2E1. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis.

    Science.gov (United States)

    Lee, Chun-Teh; Teles, Ricardo; Kantarci, Alpdogan; Chen, Tsute; McCafferty, Jon; Starr, Jacqueline R; Brito, Luciana Carla Neves; Paster, Bruce J; Van Dyke, Thomas E

    2016-10-01

    Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the periodontal biofilm. Promoters of active resolution of inflammation, including resolvin E1 (RvE1), effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes. Two clinically relevant experiments were performed in rats: prevention and treatment of ligature-induced periodontitis with RvE1 topical treatment. The gingival transcriptome was evaluated by RNA sequencing of mRNA. The composition of the subgingival microbiota was characterized by 16S rDNA sequencing. Periodontitis was assessed by bone morphometric measurements and histomorphometry of block sections. H&E and tartrate-resistant acid phosphatase staining were used to characterize and quantify inflammatory changes. RvE1 treatment prevented bone loss in ligature-induced periodontitis. Osteoclast density and inflammatory cell infiltration in the RvE1 groups were lower than those in the placebo group. RvE1 treatment reduced expression of inflammation-related genes, returning the expression profile to one more similar to health. Treatment of established periodontitis with RvE1 reversed bone loss, reversed inflammatory gene expression, and reduced osteoclast density. Assessment of the rat subgingival microbiota after RvE1 treatment revealed marked changes in both prevention and treatment experiments. The data suggest that modulation of local inflammation has a major role in shaping the composition of the subgingival microbiota. Copyright © 2016 by The American Association of Immunologists, Inc.

  17. Report on the FY17 Development of Computer Program for ASME Section III, Division 5, Subsection HB, Subpart B Rules

    Energy Technology Data Exchange (ETDEWEB)

    Swindeman, M. J. [Argonne National Lab. (ANL), Argonne, IL (United States); Jetter, R. I. [Argonne National Lab. (ANL), Argonne, IL (United States); Sham, T. -L. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-01-01

    One of the objectives of the high temperature design methodology activities is to develop and validate both improvements and the basic features of ASME Boiler and Pressure Vessel Code, Section III, Rules for Construction of Nuclear Facility Components, Division 5, High Temperature Reactors, Subsection HB, Subpart B (HBB). The overall scope of this task is to develop a computer program to aid assessment procedures of components under specified loading conditions in accordance with the elevated temperature design requirements for Division 5 Class A components. There are many features and alternative paths of varying complexity in HBB. The initial focus of this computer program is a basic path through the various options for a single reference material, 316H stainless steel. However, the computer program is being structured for eventual incorporation all of the features and permitted materials of HBB. This report will first provide a description of the overall computer program, particular challenges in developing numerical procedures for the assessment, and an overall approach to computer program development. This is followed by a more comprehensive appendix, which is the draft computer program manual for the program development. The strain limits rules have been implemented in the computer program. The evaluation of creep-fatigue damage will be implemented in future work scope.

  18. Verification of Allowable Stresses In ASME Section III Subsection NH For Grade 91 Steel & Alloy 800H

    Energy Technology Data Exchange (ETDEWEB)

    R. W. Swindeman; M. J. Swindeman; B. W. Roberts; B. E. Thurgood; D. L. Marriott

    2007-11-30

    The database for the creep-rupture of 9Cr-1Mo-V (Grade 91) steel was collected and reviewed to determine if it met the needs for recommending time-dependent strength values, S{sub t}, for coverage in ASME Section III Subsection NH (ASME III-NH) to 650 C (1200 F) and 600,000 hours. The accumulated database included over 300 tests for 1% total strain, nearly 400 tests for tertiary creep, and nearly 1700 tests to rupture. Procedures for analyzing creep and rupture data for ASME III-NH were reviewed and compared to the procedures used to develop the current allowable stress values for Gr 91 for ASME II-D. The criteria in ASME III-NH for estimating S{sub t} included the average strength for 1% total strain for times to 600,000 hours, 80% of the minimum strength for tertiary creep for times to 600,000 hours, and 67% of the minimum rupture strength values for times to 600,000 hours. Time-temperature-stress parametric formulations were selected to correlate the data and make predictions of the long-time strength. It was found that the stress corresponding to 1% total strain and the initiation of tertiary creep were not the controlling criteria over the temperature-time range of concern. It was found that small adjustments to the current values in III-NH could be introduced but that the existing values were conservative and could be retained. The existing database was found to be adequate to extend the coverage to 600,000 hours for temperatures below 650 C (1200 F).

  19. Ecological Subsections of Minnesota

    Data.gov (United States)

    Minnesota Department of Natural Resources — This coverage provides information for the third level of the Ecological Classification System. The boundaries of the polygons of this coverage were derived from...

  20. Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication

    Directory of Open Access Journals (Sweden)

    Natascha Krömmelbein

    2016-02-01

    Full Text Available The human cytomegalovirus (HCMV replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production.

  1. Many trained at E1 Salvador center.

    Science.gov (United States)

    1970-02-01

    The Family Planning Association of E1 Salvador is conducting regular week-long courses in family planning for doctors, nurses, social workers and other interested people in El Salvador and the surrounding countries of Guatemala, Honduras, Nicaragua, Costa Rica and Panama. Twelve regional courses on population dynamics, the physiology of reproduction and family planning were held in the academic year 1968-69 at the Faculty of Medicine at the University of El Salvador. Because the demand for places far exceeds the capacity of the Association's training unit, careful selection of candidates is made through consultation with the national family planning associations. Most of those trained are doctors who are being specially equipped to carry out family planning work either as part of government maternal and child health centres or in Association clinics. Many places are also found for nurses and some social workers also attend in order to build up teams for effective clinic management. A few journalists and teachers have been among the trainees as well as groups of religious leaders including Roman Catholics. Lecturers are mainly university personnel drawn from a wide range of disciplines in order to relate family planning not only to health and medicine but also to socio-economic aspects and community welfare. The El Salvador Association, an IPPF member, gets financial support from the Population Council for the training programme but hopes eventually that responsibility for continuing the courses will be taken over by the Government, probably through the Ministry of Education. Another pace-setting activity of the Association has been its close contacts with industry, particulary through the efforts of its President, Mr. Lucio Burgos, General Manager of the El Salvador Power Company, who has gained the interest and support of business and union leaders. Not only do these groups help the work of the Association through fund-raising and public relations activities, but

  2. Main: 1E1E [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1E トウモロコシ Corn Zea mays L. Beta-Glucosidase, Chloroplast Precursor Name=Glu1; Zea...TDDAYASQEVNGPDGKPIGPPMGNPWIYMYPEGLKDLLMIMKNKYGNPPIYITENGIGDVDTKETPLPMEAALNDYKRLDYIQRHIATLKESIDLGSNVQGYFAWSLLDNFEWFAGFTERYGIVYVDRNNNCTRYMKESAKWLKEFNTAKKPSKKILTPA corn_1E1E.jpg ...

  3. Olive cultivar origin is a major cause of polymorphism for Ole e 1 pollen allergen

    Directory of Open Access Journals (Sweden)

    Alché Juan

    2008-01-01

    Full Text Available Abstract Background Pollens from different olive (Olea europaea L. cultivars have been shown to differ significantly in their content in Ole e 1 and in their overall allergenicity. This allergen is, in addition, characterized by a high degree of polymorphism in its sequence. The purpose of this study is to evaluate the putative presence of divergences in Ole e 1 sequences from different olive cultivars. Results RNA from pollen individually collected from 10 olive cultivars was used to amplify Ole e 1 sequences by RT-PCR, and the sequences were analyzed by using different bioinformatics tools. Numerous nucleotide substitutions were detected throughout the sequences, many of which resulted in amino acid substitutions in the deduced protein sequences. In most cases variability within a single variety was much lower than among varieties. Key amino acid changes in comparison with "canonical" sequences previously described in the literature included: a the substitution of C19-relevant to the disulphide bond structure of the protein-, b the presence of an additional N-glycosylation motif, and c point substitutions affecting regions of Ole e 1 already described like relevant for the immunogenicity/allergenicity of the protein. Conclusion Varietal origin of olive pollen is a major factor determining the diversity of Ole e 1 variants. We consider this information of capital importance for the optimal design of efficient and safe allergen formulations, and useful for the genetic engineering of modified forms of the allergen among other applications.

  4. 29 CFR 2584.8477(e)-1 - General.

    Science.gov (United States)

    2010-07-01

    ... Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR FIDUCIARY RESPONSIBILITY UNDER THE FEDERAL EMPLOYEES' RETIREMENT SYSTEM ACT OF 1986 RULES AND REGULATIONS FOR THE ALLOCATION OF FIDUCIARY RESPONSIBILITY § 2584.8477(e)-1 General. 5 U.S.C. 8477(e)(1)(E...

  5. 26 CFR 1.642(e)-1 - Depreciation and depletion.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Depreciation and depletion. 1.642(e)-1 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(e)-1 Depreciation and depletion. An estate or trust is allowed the deductions for depreciation and depletion, but only to the extent the...

  6. Pollen from different olive tree cultivars contains varying amounts of the major allergen Ole e 1.

    Science.gov (United States)

    Castro, Antonio Jesús; de Dios Alché, Juan; Cuevas, Julián; Romero, Pedro José; Alché, Víctor; Rodríguez-García, María Isabel

    2003-07-01

    Commercial olive pollen from uncertain cultivar origin is the common material used for clinical and biological studies. We aimed to assess the putative heterogeneity of olive cultivars with regard to the presence of the major pollen allergen Ole e 1 and to determine whether these differences have clinical relevance. The Ole e 1 content of several cultivars was determined by immunoblotting and ultrastructural immunocytochemistry and compared to that of a commercially available olive pollen extract designed for diagnosis. Reverse transcription-polymerase chain reaction analysis of Ole e 1 transcripts was also performed. Crude protein extracts were used to carry out skin prick tests (SPTs) on 30 allergic patients in order to evaluate the clinical importance of such differences. Ole e 1 was present in all cultivars, although significant quantitative differences were detected. Ole e 1 transcripts positively correlated with the amount of the allergen. Significant variations in the average reactivity of allergic patients to SPTs were observed depending on the cultivar considered. The presence of the Ole e 1 allergen in all the cultivars suggests that this allergen may play an essential biological role. The expression of the allergen is controlled at the transcriptional level. The significant differences in the Ole e 1 content are likely responsible for the different average reactivity exhibited by patients to the cultivars studied, although the role of other allergens cannot be excluded. Our results suggest that the use of the commercial pollen mixtures currently available may lead to mistakes in allergy diagnosis and to limited success in immunotherapy. Therefore, further standardization is strongly recommended. Copyright 2003 S. Karger AG, Basel

  7. E1A expression dysregulates IL-8 production and suppresses IL-6 production by lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Snoek Mieke

    2005-09-01

    Full Text Available Abstract Background The adenoviral protein E1A has been proposed to play a role in the pathophysiology of COPD, in particular by increasing IL-8 gene transcription of lung epithelial cells in response to cigarette smoke-constituents such as LPS. As IL-8 production is also under tight post-transcriptional control, we planned to study whether E1A affected IL-8 production post-transcriptionally. The production of IL-6 by E1A-positive cells had not been addressed and was studied in parallel. Based on our previous work into the regulation of IL-8 and IL-6 production in airway epithelial cells, we used the lung epithelial-like cell line NCI-H292 to generate stable transfectants expressing either E1A and/or E1B, which is known to frequently co-integrate with E1A. We analyzed IL-8 and IL-6 production and the underlying regulatory processes in response to LPS and TNF-α. Methods Stable transfectants were generated and characterized with immunohistochemistry, western blot and flow cytometry. IL-8 and IL-6 protein production was measured by ELISA. Levels of IL-8 and IL-6 mRNA were measured using specific radiolabeled probes. EMSA was used to assess transcriptional activation of relevant transcription factors. Post-transcriptional regulation of mRNA half-life was measured by Actinomycin D chase experiments. Results Most of the sixteen E1A-expressing transfectants showed suppression of IL-6 production, indicative of biologically active E1A. Significant but no uniform effects on IL-8 production, nor on transcriptional and post-transcriptional regulation of IL-8 production, were observed in the panel of E1A-expressing transfectants. E1B expression exerted similar effects as E1A on IL-8 production. Conclusion Our results indicate that integration of adenoviral DNA and expression of E1A and E1B can either increase or decrease IL-8 production. Furthermore, we conclude that expression of E1A suppresses IL-6 production. These findings question the unique role of E1

  8. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  9. Why relevance theory is relevant for lexicography

    DEFF Research Database (Denmark)

    Bothma, Theo; Tarp, Sven

    2014-01-01

    This article starts by providing a brief summary of relevance theory in information science in relation to the function theory of lexicography, explaining the different types of relevance, viz. objective system relevance and the subjective types of relevance, i.e. topical, cognitive, situational...... that is very important for lexicography as well as for information science, viz. functional relevance. Since all lexicographic work is ultimately aimed at satisfying users’ information needs, the article then discusses why the lexicographer should take note of all these types of relevance when planning a new...... dictionary project, identifying new tasks and responsibilities of the modern lexicographer. The article furthermore discusses how relevance theory impacts on teaching dictionary culture and reference skills. By integrating insights from lexicography and information science, the article contributes to new...

  10. Euphorbia L. subsect. Esula (Boiss. in DC. Pax in the Iberian Peninsula. Leaf surface, chromosome numbers and taxonomic treatment

    Directory of Open Access Journals (Sweden)

    Molero, Julià

    1992-12-01

    Full Text Available We present a taxonomic study of the representatives or Euphorbia subsect. Esula in the Iberian Peninsula. Prior to this, a first section is included on the study of the leaf surface and a second section on chromosome numbers.
    The section on leaf surface is based on a study of the leaves or 45 populations of Iberian and European taxa of the subsections using a light microscope and SEM. The characters analyzed are cell shape, morphology of the cells and stomata (primary and secondary sculpture and epicuticular waxes (tertiary sculpture. Some microcharacters of the leaf surface proved particularly usefu1for taxonomical purposes. Thus the basic type of stoma and the distribution model of the stomata on the two sides of the leaf are characters which make it possible to separate taxa as closely related as E. esula L. subsp. esula and E. esula L. subsp orientalis (Boiss. in DC. Molero & Rovira. The morphological type of the epicuticular waxes also enables us to differentiate between E.graminifolia Vill. and E. esula aggr. And to distinguish subsp. bolosii Molero & Rovira from the remaining subespecies in E. nevadensis Boiss. & Reuter.
    Cytogenetic investigation reveals the presence of only the diploid cytotype (2n=10 in E. cyparissias L. and E. esula L. subsp. esula in the Iberian Peninsula. We describe for the first time in E. nevadensis s.1. a polyploidy complex with a base of x= 10 in which the diploid level (2n=20 is present in all subspecies; the tetraploid level (2n=40 is present in E. nevadensis subsp. nevadensis and the hexaploid level (2n=60 is found in E. nevadensis subsp. bolosii. Chromosome number is not a parameter that can be used for taxonomic purposes. In E. nevadensis, cytogenetic differentiation has followed its own course, with no apparent relationship to the process of morphological

  11. Genetic, morphological, geographical and ecological approaches reveal phylogenetic relationships in complex groups, an example of recently diverged pinyon pine species (Subsection Cembroides).

    Science.gov (United States)

    Flores-Rentería, Lluvia; Wegier, Ana; Ortega Del Vecchyo, Diego; Ortíz-Medrano, Alejandra; Piñero, Daniel; Whipple, Amy V; Molina-Freaner, Francisco; Domínguez, César A

    2013-12-01

    Elucidating phylogenetic relationships and species boundaries within complex taxonomic groups is challenging for intrinsic and extrinsic (i.e., technical) reasons. Mexican pinyon pines are a complex group whose phylogenetic relationships and species boundaries have been widely studied but poorly resolved, partly due to intrinsic ecological and evolutionary features such as low morphological and genetic differentiation caused by recent divergence, hybridization and introgression. Extrinsic factors such as limited sampling and difficulty in selecting informative molecular markers have also impeded progress. Some of the Mexican pinyon pines are of conservation concern but others may remain unprotected because the species boundaries have not been established. In this study we combined approaches to resolve the phylogenetic relationships in this complex group and to establish species boundaries in four recently diverged taxa: P. discolor, P. johannis, P. culminicola and P. cembroides. We performed phylogenetic analyses using the chloroplast markers matK and psbA-trnH as well as complete and partial chloroplast genomes of species of Subsection Cembroides. Additionally, we performed a phylogeographic analysis combining genetic data (18 chloroplast markers), morphological data and geographical data to define species boundaries in four recently diverged taxa. Ecological divergence was supported by differences in climate among localities for distinct genetic lineages. Whereas the phylogenetic analysis inferred with matK and psbA-trnH was unable to resolve the relationships in this complex group, we obtained a resolved phylogeny with the use of the chloroplast genomes. The resolved phylogeny was concordant with a haplotype network obtained using chloroplast markers. In species with potential for recent divergence, hybridization or introgression, nonhierarchical network-based approaches are probably more appropriate to protect against misclassification due to incomplete

  12. Deep learning relevance

    DEFF Research Database (Denmark)

    Lioma, Christina; Larsen, Birger; Petersen, Casper

    2016-01-01

    train a Recurrent Neural Network (RNN) on existing relevant information to that query. We then use the RNN to "deep learn" a single, synthetic, and we assume, relevant document for that query. We design a crowdsourcing experiment to assess how relevant the "deep learned" document is, compared...... to existing relevant documents. Users are shown a query and four wordclouds (of three existing relevant documents and our deep learned synthetic document). The synthetic document is ranked on average most relevant of all....

  13. Project FOOTPRINT: Substation modeling and simulations for E1 pulses

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Scott D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Larson, D. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kirkendall, B. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-11-06

    This report includes a presentation with an: Introduction to CW coupling; Introduction to single-pulse coupling; Description of E1 waveforms; Structures in a substation yard --articulated (as part of the substation's defined electrical functionality)--unarticulated (not as part of the substation's defined electrical functionality); Coupling --electrical coupling (capacitive coupling) --magnetic coupling (inductive coupling); Connectivity to long-line transmission lines; Control infrastructure; Summary; and References.

  14. Discovery and Classification of DES15E1iuh

    Science.gov (United States)

    Smith, M.; Sullivan, M.; Childress, M.; D'Andrea, C.; Lewis, G. F.; Mould, J.; Lidman, C.; Tucker, B. E.; Sharp, R.; Yuan, F.; Martini, P.; Brown, P. J.; Krisciunas, K.; Suntzeff, N.; Nichol, R.; Papadopoulos, A.; Maartens, R.; Gupta, R.; Kovacs, E.; Kuhlmann, S.; Spinka, H.; Ahn, E.; Finley, D. A.; Frieman, J.; Marriner, J.; Wester, W.; Aldering, G.; Kim, A. G.; Thomas, R. C.; Barbary, K.; Bloom, J. S.; Goldstein, D.; Nugent, P.; Perlmutter, S.; Foley, R. J.; Casas, R.; Castander, F. J.; Desai, S.; Paech, K.; Smith, R. C.; Schubnell, M.; Kessler, R.; Lasker, J.; Scolnic, D.; Brout, D. J.; Gladney, L.; Sako, M.; Wolf, R. C.

    2015-10-01

    We report optical spectroscopy of DES15E1iuh discovered by the Dark Energy Survey. We obtained spectra using the X-SHOOTER instrument (wavelength range 380-950nm) on the Very Large Telescope (VLT) of the European Southern Observatory (ESO) and the AAOmega Spectrograph (Saunders et al. 2004, SPIE, 5492, 389; wavelength range 370-885nm) and the 2dF fibre positioner at the Anglo-Australian Telescope (AAT).

  15. Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers

    Science.gov (United States)

    2016-10-01

    resistance to platinum, management of CCNE1-amplified ovarian cancers is challenging. In this research, we evaluate three novel strategies against...AWARD NUMBER: W81XWH-15-1-0564 TITLE: Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers PRINCIPAL INVESTIGATOR: Panagiotis A...Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including

  16. The chang’E-1 topographic atlas of the Moon

    CERN Document Server

    Li, Chunlai; Mu, Lingli; Ren, Xin; Zuo, Wei

    2016-01-01

    This atlas is based on the lunar global Digital Elevation Models (DEM) of Chang'E-1 (CE-1), and presents CCD stereo image data with digital photogrammetry. The spatial resolution of the DEM in this atlas is 500m, with horizontal accuracy of 192m and vertical accuracy of 120m. Color-shaded relief maps with contour lines are used to show the lunar topographical characteristics. The topographical data gathered by CE-1 can provide fundamental information for the study of lunar topographical, morphological and geological structures, as well as for lunar evolution research.

  17. Dissecting the roles of E1A and E1B in adenoviral replication and RCAd-enhanced RDAd transduction efficacy on tumor cells.

    Science.gov (United States)

    Wei, Fang; Wang, Huiping; Chen, Xiafang; Li, Chuanyuan; Huang, Qian

    2014-10-01

    Oncolytic viruses have recently received widespread attention for their potential in innovative cancer therapy. Many telomerase promoter-regulated oncolytic adenoviral vectors retain E1A and E1B. However, the functions of E1A and E1B proteins in the oncolytic role of replication-competent adenovirus (RCAd) and RCAd enhanced transduction of replication defective adenoviruses (RDAd) have not been addressed well. In this study, we constructed viruses expressing E1A alone, E1A plus E1B-19 kDa, and E1A plus E1B-19 kDa/55 kDa. We then tested their roles in oncolysis and replication of RCAd as well as their roles in RCAd enhanced transfection rate and transgene expression of RDAd in various cancer cells in vitro and in xenografted human NCI-H460 tumors in nude mice. We demonstrated that RCAds expressing E1A alone and plus E1B-19 kDa exhibited an obvious ability in replication and oncolytic effects as well as enhanced RDAd replication and transgene expression, with the former showed more effective oncolysis, while the latter exhibited superior viral replication and transgene promotion activity. However, RCAd expressing both E1A and E1B-19 kDa/55 kDa was clearly worst in all these abilities. The effects of E1A and E1B observed through using RCAd were further validated by using plasmids expressing E1A alone, E1A plus E1B-19 kDa, and E1A plus E1B-19 kDa/55 kDa proteins. Our study provided evidence that E1A was essential for inducing replication and oncolytic effects of RCAd as well as RCAd enhanced RDAd transduction, and expression of E1B-19 kDa other than E1B-55 kDa could promote these effects. E1B-55 kDa is not necessary for the oncolytic effects of adenoviruses and somehow inhibits RCAd-mediated RDAd replication and transgene expression.

  18. Hepatitis C virus (HCV) E1 and E2 protein regions that specifically bind to HepG2 cells.

    Science.gov (United States)

    Garcia, Javier Eduardo; Puentes, Alvaro; Súarez, Jorge; López, Ramses; Vera, Ricardo; Rodríguez, Luis Eduardo; Ocampo, Marisol; Curtidor, Hernando; Guzman, Fanny; Urquiza, Mauricio; Patarroyo, Manuel Elkin

    2002-02-01

    Identify hepatitis C virus (HCV) sequences in E1 and E2 protein binding to HepG2. Synthetic 20-mer long, ten-residue overlapped peptides, from E1 and E2 proteins, were tested in HepG2 or Raji cell-binding assays. Affinity constants, binding site number per cell and Hill coefficients were determined by saturation assay for high activity binding peptides (HABPs). Receptors for HepG2 cell were determined by cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Twelve HABPs were found in HCV genotype 1a, allowing six hepatocyte-binding sequences (HBSs) to be defined: two peptide-binding regions in E1 HABPs 4913 (YQVRNSTGLYHVTNDCPNSS) and 4918 (MTPTVATRDGKLPATQLRRHY). Four hepatocyte-binding regions were defined in E2: region-I, peptide 4931 (ETHVTGGSAGHTVSGFVSLLY); region-II, 4937-4939 (HHKFNSSGCPERLASCRPLTDFDQGWGPISYANGSGPDQR); region-III, 4943-4945 (PVYCFTPSPVVVGTTDRSGAPTYSWGENDTDVFVLNNTR) and region-IV, 4949-4952 (CGAPPCVIGGAGNNTLHCPTDCFRKHPDATYSRCGSGPWITPRCLVDYPY). The underlined sequences are most relevant in the binding process. HABPs 4913 and 4938 also bind to CD81 positive Raji cells. Region-II 4938 HABPs bind to 50 and 60kDa HepG2 cell membrane surface proteins. Six HVRs to the HepG2 were identified. Some HABPs have been previously found to be antigenic and immunogenic. HABPs, 4918 (from E1), 4938, 4949, 4950, 4951 and 4952 (from E2) have not been previously recognised. These HABPs could be relevant to HCV invasion of hepatocytes.

  19. Low Cost Network Emulator with Ethernet and E1 Interfaces

    Directory of Open Access Journals (Sweden)

    Zbynek Kocur

    2010-01-01

    Full Text Available Contemporary Next Generation Networks (NGN are mainly built on the Internet Protocol (IP and Ethernet. Major challenge for emerging types of wired and wireless IP-based networks is to provide an adequate Quality of Service (QoS for different services. The quality of evaluation requires a detailed knowledge of the performance requirements for particular services and applications. The paper is primarily oriented to the end-to-end testing for the Ethernet-based terminal equipment. The low cost Ethernet network emulator was developed on the Department of Telecommunication Technology of the Faculty of Electrical Engineering of the Czech Technical University in Prague. The extension for emulation network with the E1 interfaces and TDM over IP transmission can be used with external converters.

  20. Online drug databases: a new method to assess and compare inclusion of clinically relevant information.

    Science.gov (United States)

    Silva, Cristina; Fresco, Paula; Monteiro, Joaquim; Rama, Ana Cristina Ribeiro

    2013-08-01

    Evidence-Based Practice requires health care decisions to be based on the best available evidence. The model "Information Mastery" proposes that clinicians should use sources of information that have previously evaluated relevance and validity, provided at the point of care. Drug databases (DB) allow easy and fast access to information and have the benefit of more frequent content updates. Relevant information, in the context of drug therapy, is that which supports safe and effective use of medicines. Accordingly, the European Guideline on the Summary of Product Characteristics (EG-SmPC) was used as a standard to evaluate the inclusion of relevant information contents in DB. To develop and test a method to evaluate relevancy of DB contents, by assessing the inclusion of information items deemed relevant for effective and safe drug use. Hierarchical organisation and selection of the principles defined in the EGSmPC; definition of criteria to assess inclusion of selected information items; creation of a categorisation and quantification system that allows score calculation; calculation of relative differences (RD) of scores for comparison with an "ideal" database, defined as the one that achieves the best quantification possible for each of the information items; pilot test on a sample of 9 drug databases, using 10 drugs frequently associated in literature with morbidity-mortality and also being widely consumed in Portugal. Main outcome measure Calculate individual and global scores for clinically relevant information items of drug monographs in databases, using the categorisation and quantification system created. A--Method development: selection of sections, subsections, relevant information items and corresponding requisites; system to categorise and quantify their inclusion; score and RD calculation procedure. B--Pilot test: calculated scores for the 9 databases; globally, all databases evaluated significantly differed from the "ideal" database; some DB performed

  1. E1 and M1 strength functions at low energy

    Science.gov (United States)

    Schwengner, Ronald; Massarczyk, Ralph; Bemmerer, Daniel; Beyer, Roland; Junghans, Arnd R.; Kögler, Toni; Rusev, Gencho; Tonchev, Anton P.; Tornow, Werner; Wagner, Andreas

    2017-09-01

    We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  2. Relevance Matrices in LVQ

    NARCIS (Netherlands)

    Schneider, Petra; Biehl, Michael; Hammer, Barbara; Verleysen, Michel

    2007-01-01

    We propose a new matrix learning scheme to extend Generalized Relevance Learning Vector Quantization (GRLVQ). By introducing a full matrix of relevance factors in the distance measure, correlations between different features and their importance for the classification scheme can be taken into

  3. Roles of cytochrome P4502E1 gene polymorphisms and the risks of alcoholic liver disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Tao Zeng

    Full Text Available BACKGROUND: Previous studies investigating the association between cytochrome P4502E1 (CYP2E1 polymorphisms and the risk of alcoholic liver diseases (ALD have yielded conflicting results. Thus, a meta-analysis was performed to clarify the association between CYP2E1 polymorphisms and the risks of ALD. METHODS: A comprehensive literature search was conducted to identify the relevant studies. The fixed or random effect model was selected based on the heterogeneity test among studies. Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS: A total of 27 and 9 studies were finally included for the association between the CYP2E1 Pst I/Rsa I or Dra I polymorphisms and the risks of ALD, respectively. Overall, the combined results showed that homozygous genotype c2c2 was significantly associated with increase risk of ALD in worldwide populations (c2c2 vs. c1c1: OR = 3.12, 95%CI 1.91-5.11 when ALD patients were compared with alcoholics without ALD. Significant associations between CYP2E1 Pst I/Rsa I polymorphism and ALD risk were also observed in Asians (c2c2 vs. c1c1: OR = 4.11, 95%CI 2.32-7.29 and in Caucasians (c2c2/c1c2 vs. c1c1: OR = 1.58, 95%CI 1.04-2.42 when ALD patients were compared with alcoholics without ALD. However, subgroup analysis stratified by ALD types showed that CYP2E1 Pst I/Rsa I polymorphism was not significantly associated with the risks of alcoholic cirrhosis (ALC. No significant association was observed between CYP2E1 Dra I polymorphism and ALD risks. CONCLUSION: This meta-analysis suggested that CYP2E1 Pst I/Rsa I polymorphism might be not significantly associated with advanced form of ALD (ALC, but might be significantly associated with other form of ALD such as steatosis, hepatisis, fibrosis. Furthermore, CYP2E1 Dra I polymorphism might be not significantly associated with the ALD risks. Since potential confounders could not be ruled out completely, further studies were needed to confirm

  4. Culturally Relevant Cyberbullying Prevention

    OpenAIRE

    Phillips, Gregory John

    2017-01-01

    In this action research study, I, along with a student intervention committee of 14 members, developed a cyberbullying intervention for a large urban high school on the west coast. This high school contained a predominantly African American student population. I aimed to discover culturally relevant cyberbullying prevention strategies for African American students. The intervention committee selected video safety messages featuring African American actors as the most culturally relevant cyber...

  5. Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

    DEFF Research Database (Denmark)

    Savelyeva, I.; Dobbelstein, M.

    2011-01-01

    Wild-type adenovirus type 5 eliminates p53 through the E1B-55 kDa and E4-34 kDa gene products. Deletion or mutation of E1B-55 kDa has long been thought to confer p53-selective replication of oncolytic viruses. We show here that infection with E1B-defective adenovirus mutants induces massive...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

  6. Structural and Dynamic Characterization of the Molecular Hub Early Region 1A (E1A) from Human Adenovirus.

    Science.gov (United States)

    Hošek, Tomáš; Calçada, Eduardo O; Nogueira, Marcela Oliveira; Salvi, Michele; Pagani, Talita Duarte; Felli, Isabella C; Pierattelli, Roberta

    2016-09-05

    The small-DNA human adenovirus encodes one of the most versatile molecular hubs, the E1A protein. This protein is essential for productive viral infection in human cells and a vast amount of biologically relevant data are available on its interactions with host proteins. Up to now, however, no high-resolution structural and dynamic information on E1A is available despite its important biological role. Among the different spliced variants of E1A, two are expressed at high level in the early stage of infection. These are 243 and 289 residues isoforms. Herein, we present their NMR characterization, showing that they are both highly disordered, but also demonstrate a certain heterogeneous behavior in terms of structural and dynamic properties. Furthermore, we present the characterization of the isolated domain of the longer variant, known as CR3. This study opens the way to understanding at the molecular level how E1A functions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Attenuation of prostaglandin E1‑induced osteoprotegerin synthesis in osteoblasts by normoxic HIF inducers.

    Science.gov (United States)

    Kuroyanagi, Gen; Tokuda, Haruhiko; Yamamoto, Naohiro; Kainuma, Shingo; Fujita, Kazuhiko; Ohguchi, Reou; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Otsuka, Takanobu

    2017-04-01

    Mimosine, which is a natural plant amino acid present in the Leucaena genus, is able to induce hypoxia‑inducible factors (HIFs). Previous evidence has indicated that HIF regulates angiogenesis‑osteogenesis coupling in bone metabolism, and it has previously been reported that mimosine inhibits prostaglandin (PG)F2α‑induced osteoprotegerin (OPG) synthesis without affecting interleukin‑6 (IL‑6) production in osteoblast‑like MC3T3‑E1 cells. In addition, PGE1 has been demonstrated to induce OPG synthesis via activation of p38 mitogen‑activated protein (MAP) kinase and stress‑activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) in these cells, and PGE1 stimulates IL‑6 production via the activation of protein kinase A. In the present study, the effects of mimosine on the PGE1‑stimulated synthesis of OPG and IL‑6 were investigated in osteoblast‑like MC3T3‑E1 cells. The concentrations of OPG and IL‑6 were measured using relevant ELISA kits. OPG mRNA was measured by semi‑quantitative reverse transcription polymerase chain reaction. The phosphorylation of p38 MAP kinase and SAPK/JNK was analyzed by western blotting. Mimosine significantly reduced PGE1‑induced release of OPG and OPG mRNA expression levels without affecting the release of IL‑6. In addition, deferoxamine, which is also a normoxic HIF inducer, significantly inhibited PGE1‑induced OPG release and OPG mRNA expression levels; however, it had little effect on IL‑6 release. Furthermore, mimosine and deferoxamine failed to affect PGE1‑stimulated phosphorylation of p38 MAP kinase or SAPK/JNK. These results strongly suggest that normoxic HIF inducers attenuate PGE1‑stimulated OPG synthesis without affecting IL‑6 production in osteoblasts.

  8. Korrek, volledig, relevant

    DEFF Research Database (Denmark)

    Bergenholtz, Henning; Gouws, Rufus

    2007-01-01

    as detrimental to the status of a dictionary as a container of linguistic knowledge. This paper shows that, from a lexicographic perspective, such a distinction is not relevant. What is important is that definitions should contain information that is relevant to and needed by the target users of that specific......In explanatory dictionaries, both general language dictionaries and dictionaries dealing with languages for special purposes, the lexicographic definition is an important item to present the meaning of a given lemma. Due to a strong linguistic bias, resulting from an approach prevalent in the early...

  9. Sulforaphane Induces Nrf2 and Protects Against CYP2E1-dependent Binge Alcohol –induced Liver Steatosis

    Science.gov (United States)

    Zhou, Richard; Lin, Jianjun; Wu, Defeng

    2013-01-01

    Background The mechanism(s) by which alcohol causes cell injury are still not clear but a major mechanism appears to be the role of lipid peroxidation and oxidative stress in alcohol toxicity. CYP2E1-generated ROS contributes to the ethanol-induced oxidant stress and inhibition of CYP2E1 activity decreases ethanol-induced fatty liver. The transcription factor Nrf2 regulates the expression of many cytoprotective enzymes which results in cellular protection against a variety of toxins. Method The current study was designed to evaluate the ability of sulforaphane, an activator of Nrf2, to blunt CYP2E1-dependent, ethanol-induced steatosis in vivo and in vitro. Results The sulforaphane treatment activated Nrf2, increased levels of the Nrf2 target heme oxygenase -1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-Nitrotyrosine protein adducts and an increase in GSH levels after the acute ethanol treatment. It decreased ethanol-elevated liver levels of triglycerides and cholesterol and Oil Red O staining. Similar results were found in vitro as addition of sulforaphane to HepG2 E47 cells, which express CYP2E1, elevated Nrf2 levels and decreased the accumulation of lipid in cells cultured with ethanol. Sulforaphane treatment had no effect on levels of or activity of CYP2E1. Conclusions Sulforaphane proved to be an effective in vivo inhibitor of acute ethanol–induced fatty liver in mice. General significance The possible amelioration of liver injury which occurs under these conditions by chemical activators of Nrf2 is of clinical relevance and worthy of further study. PMID:24060752

  10. Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis.

    Science.gov (United States)

    Zhou, Richard; Lin, Jianjun; Wu, Defeng

    2014-01-01

    The mechanism(s) by which alcohol causes cell injury are still not clear but a major mechanism appears to be the role of lipid peroxidation and oxidative stress in alcohol toxicity. CYP2E1-generated ROS contributes to the ethanol-induced oxidant stress and inhibition of CYP2E1 activity decreases ethanol-induced fatty liver. The transcription factor Nrf2 regulates the expression of many cytoprotective enzymes which results in cellular protection against a variety of toxins. The current study was designed to evaluate the ability of sulforaphane, an activator of Nrf2, to blunt CYP2E1-dependent, ethanol-induced steatosis in vivo and in vitro. The sulforaphane treatment activated Nrf2, increased levels of the Nrf2 target heme oxygenase-1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-nitrotyrosine protein adducts and an increase in GSH levels after the acute ethanol treatment. It decreased ethanol-elevated liver levels of triglycerides and cholesterol and Oil Red O staining. Similar results were found in vitro as addition of sulforaphane to HepG2 E47 cells, which express CYP2E1, elevated Nrf2 levels and decreased the accumulation of lipid in cells cultured with ethanol. Sulforaphane treatment had no effect on levels of or activity of CYP2E1. Sulforaphane proved to be an effective in vivo inhibitor of acute ethanol-induced fatty liver in mice. The possible amelioration of liver injury which occurs under these conditions by chemical activators of Nrf2 is of clinical relevance and worthy of further study. © 2013.

  11. Data of evolutionary structure change: 1E1EA-2RGMB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1EA-2RGMB 1E1E 2RGM A B MLSPSEIPQRDWFPSDFTFGAATSAYQIEGAWNEDGKGESNWDHFCHNHPERILDG...SNSDIGANSYHMYKTDVRLLKEMGMDAYRFSISWPRILPKGTKEGGINPDGIKYYRNLINLLLENGIEPYVTIFHWDVPQALEEKYGGFLDKSHKSIVED...KEFNTA ---WLGGLSRAAFPKRFVFGTVTSAYQVEGMAASGGRGPSIWDAFAHT-PGNVAGNQNGDVATDQYHRYKEDVNLMKSLN...TPTSYSADWQVTYVFAK-NGKPIGPQANSNWLYIVPWGMYGCVNYIKQKYGNPTVVITENGMDQPAN----LSRDQYLRDTTRVHFYRSYLTQLKKAIDE... 2RGM B 2RGMB

  12. Data of evolutionary structure change: 1E1EB-2RGMB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1EB-2RGMB 1E1E 2RGM B B QNGVQMLSPSEIPQRDWFPSDFTFGAATSAYQIEGAWNEDGKGESNWDHFCHNHPE...RILDGSNSDIGANSYHMYKTDVRLLKEMGMDAYRFSISWPRILPKGTKEGGINPDGIKYYRNLINLLLENGIEPYVTIFHWDVPQALEEKYGGFLDKSHK...A --------WLGGLSRAAFPKRFVFGTVTSAYQVEGMAASGGRGPSIWDAFAHT-PGNVAGNQNGDVATDQYHRYKEDVNLMKSLN...TPTSYSADWQVTYVFAK-NGKPIGPQANSNWLYIVPWGMYGCVNYIKQKYGNPTVVITENGMDQPAN----LSRDQYLRDTTRVHFYRSYLTQLKKAIDE... 2RGM B 2RGMB

  13. The Relevance of Literature.

    Science.gov (United States)

    Dunham, L. L.

    1971-01-01

    The "legacy" of the humanities is discussed in terms of relevance, involvement, and other philosophical considerations. Reasons for studying foreign literature in language classes are developed in the article. Comment is also made on attitudes and ideas culled from the writings of Clifton Fadiman, Jean Paul Sartre, and James Baldwin. (RL)

  14. Is Information Still Relevant?

    Science.gov (United States)

    Ma, Lia

    2013-01-01

    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  15. Heat denaturation of Brazil nut allergen Ber e 1 in relation to food processing

    NARCIS (Netherlands)

    Boxtel, E.L. van; Koppelman, S.J.; Broek, L.A.M. van den; Gruppen, H.

    2008-01-01

    Ber e 1, a major allergen from Brazil nuts, is very stable to in vitro peptic digestion. As heat-induced denaturation may affect protein digestibility, the denaturation behaviour of Ber e 1 was investigated. The denaturation temperature of Ber e 1 varies from approximately 80-110 °C, depending on

  16. 17 CFR 270.30e-1 - Reports to stockholders of management companies.

    Science.gov (United States)

    2010-04-01

    ... shared address unless the company receives contrary instructions; (B) Include a toll-free telephone... management companies. 270.30e-1 Section 270.30e-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.30e-1 Reports to...

  17. 26 CFR 1.669(e)-1A - Pro rata portion of taxes deemed distributed.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Pro rata portion of taxes deemed distributed. 1.669(e)-1A Section 1.669(e)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Taxable Years Beginning Before January 1, 1969 § 1.669(e)-1A Pro rata portion of taxes deemed distributed...

  18. Heat denaturation of Brazil nut allergen Ber e 1 in relation to food processing

    NARCIS (Netherlands)

    Boxtel, van E.L.; Koppelman, S.J.; Broek, van den L.A.M.; Gruppen, H.

    2008-01-01

    Ber e 1, a major allergen from Brazil nuts, is very stable to in vitro peptic digestion. As heat-induced denaturation may affect protein digestibility, the denaturation behaviour of Ber e 1 was investigated. The denaturation temperature of Ber e 1 varies from approximately 80¿110 °C, depending on

  19. Absence of NR2E1 mutations in patients with aniridia

    DEFF Research Database (Denmark)

    Corso-Díaz, Ximena; Borrie, Adrienne E; Bonaguro, Russell

    2012-01-01

    Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other...

  20. As espécies de Croton L. sect. Cyclostigma Griseb. e Croton L. sect. Luntia (Raf. G. L. Webster subsect. Matourenses G. L. Webster (Euphorbiaceae s.s. ocorrentes na Amazônia brasileira Species of Croton L. sect. Cyclostigma Griseb. and Croton L. sect. Luntia (Raf. G. L. Webster subsect. Matourenses G. L. Webster (Euphorbiaceae s.s. occuring within Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Cavalcante Guimarães

    2010-09-01

    Full Text Available Como parte de uma revisão taxonômica das espécies de Croton L. na Amazônia brasileira, estudou-se as seguintes espécies de Croton sect. Cyclostigma Griseb. e Croton sect. Luntia (Raf. G. L. Webster subsect. Matourenses G. L. Webster: Croton urucurana Baill., C. draconoides Müll. Arg., C. trombetensis R. Secco, P. E. Berry & N.A. Rosa, C. sampatik Müll. Arg., C. palanostigma Kl., C. pullei Lanj. e C. matourensis Aubl. O estudo foi baseado em trabalho de campo realizado nos Estados do Pará e Maranhão, e em material depositado nos herbários IAN, INPA, MG e RB, incluindo tipos. Algumas dessas espécies, como C. urucurana, C. draconoides, C. palanostigma e C. sampatik , são frequentemente encontradas nos herbários com identificações equivocadas. São discutidas a posição taxonômica das espécies nas seções e suas afinidades, e uma chave dicotômica e ilustrações foram elaboradas para um melhor entendimento dos táxons.As part of a taxonomic revision of Brazilian Amazonia species of Croton L., the following species of Croton sect. Cyclostigma Griseb. and Croton sect. Luntia (Raf. G. L. Webster subsect. Matourenses G. L. Webster were studied: Croton urucurana Baill., C. draconoides Müll. Arg., C. trombetensis R. Secco, P. E. Berry & N.A. Rosa, C. sampatik Müll. Arg., C. palanostigma Kl., C. pullei Lanj. and C. matourensis Aubl. This study was based on field work in the States of Pará and Maranhão, and material deposited in herbaria IAN, INPA, MG e RB, including the types. Some of the species, such as C. urucurana, C. draconoides, C. palanostigma, and C. sampatik , are frequently found with misidentification in herbaria. The taxonomic position of the species within sections and their affinities are discussed, and a dychotomic key and illustrations were elaborated for a better understanding of the taxa.

  1. Clinical Relevance of Adipokines

    Directory of Open Access Journals (Sweden)

    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  2. Pioglitazone, quercetin and hydroxy citric acid effect on cytochrome P450 2E1 (CYP2E1) enzyme levels in experimentally induced non alcoholic steatohepatitis (NASH).

    Science.gov (United States)

    Surapaneni, K M; Priya, V V; Mallika, J

    2014-01-01

    Non-Alcoholic Steatohepatitis (NASH) is a severe form of Non Alcoholic Fatty Liver Disease (NAFLD) spectrum, which progresses to the end stage liver disease. A common denominator in the pathogenesis of insulin resistance and nonalcoholic steatohepatitis is increased oxidative stress. Hepatic induction of the pro-oxidant enzyme Cytochrome P450 2E1 (CYP2E1) occurs in both NAFLD and type-2 diabetes. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on liver CYP2E1 enzyme levels in experimentally induced NASH has been studied. The experimental protocol consists of 5 groups viz. Control (n = 6); NASH Induced (n=6); NASH + Pioglitazone (n=6); NASH + Quercetin (n=6); NASH + Hydroxy Citric Acid (n=6). CYP2E1 enzyme levels were detected in liver by immunoblot analysis in all the groups. CYP2E1 catalytic activity was increased in experimentally induced NASH group compared to control group as evidenced by the Immunoblot analysis. It revealed low CYP2E1 in the experimentally induced NASH, treated with pioglitazone, quercetin and hydroxy citric acid. Mild decrease in the levels of CYP2E1 level was observed in experimental NASH treated with pioglitazone compared to NASH group. Treatment with hydroxy citric acid also showed mild decrease in the levels of CYP2E1. On contrary to the action of pioglitazone and hydroxy citric acid, quercetin showed an approximate 2-fold decrease in the level of CYP2E1 in experimental NASH treated with quercetin compared to NASH group. Being a powerful antioxidant, quercetin offers absolute protection to liver against NASH by reducing the levels of CYP2E1 and, thereby, reducing CYP2E1 mediated oxidative stress, which is believed to be the one of the key factor in the pathogenesis of NASH. On the other hand, pioglitazone and hydroxy citric acid exerted limited effect on the levels of CYP2E1. This study showed the therapeutic value of quercetin, pioglitazone and hydroxy citric acid in treating NASH.

  3. AAV-2 Rep78 and HPV-16 E1 interact in vitro, modulating their ATPase activity.

    Science.gov (United States)

    Bandyopadhyay, Sarmistha; Raney, Kevin D; Liu, Yong; Hermonat, Paul L

    2008-01-15

    Adeno-associated virus (AAV) is a nonpathogenic single-stranded human parvovirus which usually requires the presence of a "helper" virus for strong DNA replication. In addition to adeno- and herpes viruses, human papillomavirus (HPV) can serve as an AAV helper. We recently published that HPV type 16 (HPV-16) E1 protein contributes significantly as an individual helper gene for AAV-2 DNA replication and transcription. As Rep78 and E1 are the corresponding DNA helicase/replication proteins of AAV and HPV, respectively, and Rep78 and E1 have a degree of homology, we assayed whether these two proteins interact physically. The full length proteins were purified from bacteria as GST-E1 and MBP-Rep78 and used in five assays to observe Rep78-E1 interactions. All five assays (pull-down, coimmunoprecipitation, enzyme-linked immunosorbent assay (ELISA), chemical cross-linking, and ATPase activity) provided evidence consistent with Rep78-E1 interaction. Most intriguing, an overall decrease in ATPase activity was observed when both proteins were present together. These data strongly suggest that E1 and Rep78 interact and that this interaction modulates at least some of their individual biochemical functions. This study adds to our understanding of AAV-HPV interaction biology, E1's modulation of Rep78 biochemistry, Rep78's modulation of E1 biochemistry and provides initial clues which may lead to the underlying mechanism of HPV E1 helper function for AAV DNA replication.

  4. Improved Plant-based Production of E1 endoglucanase Using Potato: Expression Optimization and Tissue Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Ziyu [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hooker, Brian S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Anderson, Daniel B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Thomas, Steven R. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2000-06-01

    Optimization of Acidothermus cellulolyticus endoglucanase (E1) gene expression in transgenic potato (Solanum tuberosum L.) was examined in this study, where the E1 coding sequence was transcribed under control of a leaf specific promoter (tomato RbcS-3C) or the Mac promoter (a hybrid promoter of mannopine synthase promoter and cauliflower mosaic virus 35S promoter enhancer region). Average E1 activity in leaf extracts of potato transformants, in which E1 protein was targeted by a chloroplast signal peptide and an apoplast signal peptide were much higher than those by an E1 native signal peptide and a vacuole signal peptide. E1 protein accumulated up to 2.6% of total leaf soluble protein, where E1 gene was under control of the RbcS-3C promoter, alfalfa mosaic virus 5-untranslated leader, and RbcS-2A signal peptide. E1 protein production, based on average E1 activity and E1 protein accumulation in leaf extracts, is higher in potato than those measured previously in transgenic tobacco bearing the same transgene constructs. Comparisons of E1 activity, protein accumulation, and relative mRNA levels showed that E1 expression under control of tomato RbcS-3C promoter was specifically localized in leaf tissues, while E1 gene was expressed in both leaf and tuber tissues under control of Mac promoter. This suggests dual-crop applications in which potato vines serve as enzyme production `bioreactors' while tubers are preserved for culinary applications.

  5. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

    Directory of Open Access Journals (Sweden)

    W. A. García-Suástegui

    2017-01-01

    Full Text Available Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.

  6. Largazole and its derivatives selectively inhibit ubiquitin activating enzyme (e1.

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    Dana Ungermannova

    Full Text Available Protein ubiquitination plays an important role in the regulation of almost every aspect of eukaryotic cellular function; therefore, its destabilization is often observed in most human diseases and cancers. Consequently, developing inhibitors of the ubiquitination system for the treatment of cancer has been a recent area of interest. Currently, only a few classes of compounds have been discovered to inhibit the ubiquitin-activating enzyme (E1 and only one class is relatively selective in E1 inhibition in cells. We now report that Largazole and its ester and ketone analogs selectively inhibit ubiquitin conjugation to p27(Kip1 and TRF1 in vitro. The inhibitory activity of these small molecules on ubiquitin conjugation has been traced to their inhibition of the ubiquitin E1 enzyme. To further dissect the mechanism of E1 inhibition, we analyzed the effects of these inhibitors on each of the two steps of E1 activation. We show that Largazole and its derivatives specifically inhibit the adenylation step of the E1 reaction while having no effect on thioester bond formation between ubiquitin and E1. E1 inhibition appears to be specific to human E1 as Largazole ketone fails to inhibit the activation of Uba1p, a homolog of E1 in Schizosaccharomyces pombe. Moreover, Largazole analogs do not significantly inhibit SUMO E1. Thus, Largazole and select analogs are a novel class of ubiquitin E1 inhibitors and valuable tools for studying ubiquitination in vitro. This class of compounds could be further developed and potentially be a useful tool in cells.

  7. 26 CFR 1.1059(e)-1 - Non-pro rata redemptions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Non-pro rata redemptions. 1.1059(e)-1 Section 1... (CONTINUED) INCOME TAXES Special Rules § 1.1059(e)-1 Non-pro rata redemptions. (a) In general. Section 1059(d... 1059(e)(1). For example, if a redemption of stock is not pro rata as to all shareholders, any amount...

  8. Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R. [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Yousef, Ahmed F. [Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi (United Arab Emirates); Zhang, Zhiying [College of Animal Science and Technologies, Northwest A and F University, Yangling, Shaanxi 712100 (China); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada)

    2014-04-15

    The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell. - Highlights: • HAdV E1A uses multiple mechanisms for nuclear import. • We identified an additional non-canonical NLS in the N-terminal/CR1 portion of E1A. • The new NLS does not contact importin-alpha directly. • All NLSs are functionally conserved in the E1A proteins of all 6 HAdV species.

  9. HPV E1 up-regulates replication-related biochemistries of AAV Rep78.

    Science.gov (United States)

    Bandyopadhyay, Sarmistha; Cao, Maohua; Liu, Yong; Hermonat, Paul L

    2010-06-20

    Human papillomavirus type 16 (HPV) E1 protein provides helper function for the adeno-associated virus type 2 (AAV) life cycle. E1 is the replication protein of HPV, analogous to AAV Rep78, but without the endonuclease/covalent attachment activity of Rep78. Previously we have shown that E1 and Rep78 interact in vitro. Here we investigated E1's effects on Rep78 interaction with AAV's inverted terminal repeat (ITR) DNA in vitro, using purified Rep78 and E1 proteins from bacteria. E1 enhanced Rep78-ITR binding, ATPase activity, Rep78-ITR-covalent linkage and Rep78-ITR-endonuclease activity (central to AAV replication). These enhancements occurred in a dose-dependent manner whenever assayed. However, overall Rep78-plus-E1 helicase activity was lower than Rep78's helicase activity. These data suggest that E1's broad-based helper function for the AAV life cycle (AAV DNA, mRNA, and protein levels are up-regulated by E1) is likely through its ability to enhance Rep78's critical replication-required biochemistries on ITR DNA. Published by Elsevier Inc.

  10. In vivo induction of hepatic P4502E1 by ethanol: role of increased enzyme synthesis.

    Science.gov (United States)

    Tsutsumi, M; Lasker, J M; Takahashi, T; Lieber, C S

    1993-07-01

    P4502E1 (2E1), an ethanol-inducible P450 enzyme, plays an important role in the bioactivation of certain hepatotoxins and chemical carcinogens. Different mechanisms of 2E1 induction by ethanol and other agents (e.g., acetone) have been proposed, ranging from enhanced de novo enzyme synthesis caused by an increase in 2E1 mRNA and/or the efficiency with which it is translated to decreased enzyme degradation stemming from substrate stabilization. To evaluate these mechanisms, we first examined the time course of hepatic 2E1 protein induction in rats pair-fed liquid diets containing 36% of total calories as either ethanol or dextrin-maltose (controls) for 28 days. Western blot analysis with anti-2E1 immunoglobulins revealed that 2E1 reached a new steady-state level (eightfold greater than that found with controls) after ethanol feeding for 10 days and remained elevated for the duration of treatment. Microsomal p-nitrophenol hydroxylation, a 2E1-catalyzed reaction, exhibited a similar induction time course, with the maximal increase in enzyme activity also observed on Day 10 of ethanol administration. We then determined steady-state 2E1 protein turnover in ethanol-fed and control animals that were given [35S]methionine plus[3H]aminolevulinate to radiolabel 2E1 apoprotein and the prosthetic heme group, respectively. Monophasic exponential decay curves showed that hepatic 2E1 protein and heme half-lives (27-28 h and 17 h, respectively) did not differ between the treatment groups. However, rates of 2E1 synthesis, assessed by measuring initial rates of incorporation of [35S]methionine and [3H]aminolevulinate into 2E1 apoprotein and heme, were increased in animals fed ethanol. Our results indicate that the in vivo induction of hepatic 2E1 protein by ethanol involves increased enzyme synthesis rather than decreased enzyme degradation. This enhancement of de novo 2E1 synthesis most likely entails the ethanol-mediated increase of steady-state levels of 2E1 mRNA and/or the

  11. Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 (UBE2E1 as a prognostic factor in acute myeloid leukemia

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    Hongmei Luo

    2016-11-01

    Full Text Available Abstract Background Previous research suggested that single gene expression might be correlated with acute myeloid leukemia (AML survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions. Methods We performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL AML patients by quantitative RT-PCR and survival analysis. Results Microarray-based analysis suggested that expression of eight genes was each associated with 1-year and 3-year AML OS in both GSE12417 and GSE8970 datasets (p < 0.05. Next, we validated our findings in an independent cohort of AML samples collected in our hospital. We found that ubiquitin-conjugating enzyme E2E1 (UBE2E1 expression was adversely correlated with AML survival (p = 0.04. Multivariable analysis showed that UBE2E1 high patients had a significant shorter OS and shorter progression-free survival after adjusting other known prognostic factors (p = 0.03. At last, we found that UBE2E1 expression was negatively correlated with patients’ response to induction chemotherapy (p < 0.05. Conclusions In summary, we demonstrated that UBE2E1 expression was a novel prognostic factor in adult, non-APL AML patients.

  12. Agile Systems Engineering-Kanban Scheduling Subsection

    Science.gov (United States)

    2017-03-10

    sufficiently to incorporate mechanisms to support the student’s experiment 7. Updated software is available through www.sercuarc.org 8. One journal ...indicators descripted by wi_dictionary. children [“1”, “2”, “3”] List of Children Work Items Event src_oc_id “1” Source OC id dst_oc_id “2

  13. A systematic evaluation of microRNAs in regulating human hepatic CYP2E1

    Science.gov (United States)

    Wang, Yong; Yu, Dianke; Tolleson, William H.; Yu, Li-Rong; Green, Bridgett; Zeng, Linjuan; Chen, Yinting; Chen, Si; Ren, Zhen; Guo, Lei; Tong, Weida; Guan, Huaijin; Ning, Baitang

    2017-01-01

    Cytochrome P450 2E1 (CYP2E1) is an important drug metabolizing enzyme for processing numerous xenobiotics in the liver, including acetaminophen and ethanol. Previous studies have shown that microRNAs (miRNAs) can suppress CYP2E1 expression by binding to the 3′-untranslated region (3′-UTR) of its transcript. However, a systematic analysis of CYP2E1 regulation by miRNAs has not been described. Here, we applied in silico, in vivo, and in vitro approaches to investigate miRNAs involved in the regulation of CYP2E1. Initially, potential miRNA binding sites in the CYP2E1 mRNA transcript were identified and screened using in silico methods. Next, inverse correlations were found in human liver samples between the expression of CYP2E1 mRNA and the levels of two miRNA species, hsa-miR-214-3p and hsa-miR-942-5p. In a HepG2-derived CYP2E1 over-expression cell model, hsa-miR-214-3p exhibited strong suppression of CYP2E1 expression by targeting the coding region of its mRNA transcript, but hsa-miR-942-5p did not inhibit CYP2E1 levels. Electrophoretic mobility shift assays confirmed that hsa-miR-214-3p recruited other cellular protein factors to form stable complexes with specific sequences present in the CYP2E1 mRNA open reading frame. Transfection of HepaRG cells with hsa-miR-214-3p mimics inhibited expression of the endogenous CYP2E1 gene. Further, hsa-miR-214-3p mimics partially blocked ethanol-dependent increases in CYP2E1 mRNA and protein levels in HepG2 cells and they reduced the release of alanine aminotransferase from CYP2E1-overexpressing HepG2 cells exposed to acetaminophen. These results substantiate the suppressing effect of hsa-miR-214-3p on CYP2E1 expression. PMID:28438567

  14. [E1A gene transfection of human undifferentiated thyroid cancer cell line HTC/3 by nanoparticles].

    Science.gov (United States)

    He, Xiang-Liang; He, Dong-Hua; Liao, Xiao-Xing; Zhan, Hong; Ma, Zhong-Fu; Wang, Xi-Fu; Li, Qing; Li, Xin; Li, Yu-Jie

    2007-12-01

    To prepare nanoparticles containing E1A gene and observe the efficiency and feasibility of transfecting E1A gene into human undifferentiated thyroid cancer cell line HTC/3. To examine the sensitivity of transgene cells to X-ray and X-ray-induced apoptosis in those cells. Nanoparticle-DNA complex was prepared with PLGA coating adenoviral early expression gene E1A, and the package efficiency, release progress in vitro, and size of the complex were determined. The nanoparticle-DNA was transfected into the HTC/3 cells. Lipofectamine was used to transfect E1A gene as a control. RT-PCR was used to examine E1A gene mRNA expression in the transfected cells. The survival ratio of HTC/3-E1A and control cells, and the growth inhibition ratio induced by different doses of X-ray in HTC/3-E1A cells were examined by MTT assay. The apoptosis in HTC/3-E1A cells induced by 2 Gy X-ray iradiation was examined by flow cytometry and DNA electrophoresis. The package efficiency, release progress in vitro, and size of the nanoparticle-DNA complex were 0.78%, 18 days, and 150-280 nm, respectively when transfected the plasmid at the same level, the nanoparticle group got more positive transgene cell clones than that in lipofectamine group, with a statistically significant difference (P HTC/3-E1A cells grew slowly, and their doubling time was prolongated (1.44 times in comparison with that in parental cells). According to IC50, the sensitivity of HTC/3-E1A cells to X-ray was improved 2.9 and 2.8 times, respectively, in comparison with that in HTC/3-Vect and HTC/3 cells. The ratio of subG0/G1 phase of HTC/3-E1A cells was significantly higher than that in HTC/3-Vect and HTC/3 cells (P HTC/3-E1A cells was significantly lower than that in HTC/3-Vect and HTC/3 cells (P HTC/3-E1A cells was observed by electrophoresis, but not found in HTC/3-Vect and HTC/3 cells. A nanoparticle-DNA complex has been successfully prepared, and it may carry a foreign gene into cells. The sensitivity of HTC/3-E1A cells

  15. Intracanal delivery of Resolvin E1 controls inflammation in necrotic immature rat teeth.

    Science.gov (United States)

    Scarparo, Roberta Kochenborger; Dondoni, Lenara; Böttcher, Daiana Elisabeth; Grecca, Fabiana Soares; Figueiredo, Jose Antonio P; Kantarci, Alpdogan; Van Dyke, Thomas E; Batista, Eraldo Luiz

    2014-05-01

    Pulp necrosis in immature teeth and the resulting periodontal apical inflammation negatively affect root formation. Resolvin E1 (RvE1) is a lipid-derived endogenous pro-resolution molecule that controls inflammation. The aim of this investigation was to evaluate the impact of RvE1 applied as an intracanal medication on root formation in nonvital immature teeth. To arrest root development, pulpectomy was performed in the lower first molars of 4-week-old Wistar rats. After 3 weeks, irrigation with 2.5% sodium hypochlorite and 0.9% sterile saline was performed, and either a triple antibiotic paste (TAP) or RvE1 in saline was applied into the root canals. In the control group, access openings drilled into molars were left exposed to the oral environment. Root development and periapical repair were evaluated radiographically and histologically at 3 and 6 weeks after treatment. RvE1 reduced periapical lesion size compared with the control at 3 weeks, which was similar to TAP. Inflammatory response in the RvE1-treated group was markedly reduced compared with both TAP and control specimens. At 6 weeks, root development was observed in both groups, but RvE1 treatment produced less cellularity with more regular calcified tissue deposition. RvE1 and TAP had a positive impact on reducing inflammation and promoting root formation. RvE1 was more effective in reducing inflammation at earlier stages. RvE1 has potential to be used as root canal dressing to control inflammation in endodontically compromised teeth before complete root formation. Stability of RvE1 within the root canal and its delivery are issues to be addressed before its clinical use. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Valerian: No Evidence for Clinically Relevant Interactions

    Directory of Open Access Journals (Sweden)

    Olaf Kelber

    2014-01-01

    Full Text Available In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

  17. Data of evolutionary structure change: 1E1CA-3BICA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E1CA-3BICA 1E1C 3BIC A A STLPRFDSVDLGNAPVPADAARRFEELAAKAGTGE----...yChain> 3BIC A 3BICA...ryChain> 3BIC A 3BICA LIEKMFQPKNS...D> 2 3BIC A 3BICAA 3BICA DNIKQ--QGLSV

  18. 40 CFR Figure E-1 to Subpart E of... - Designation Testing Checklist

    Science.gov (United States)

    2010-07-01

    ... Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Fig. E-1 Figure E-1 to Subpart E of Part 53... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Designation Testing Checklist E Figure...) AIR PROGRAMS (CONTINUED) AMBIENT AIR MONITORING REFERENCE AND EQUIVALENT METHODS Procedures for...

  19. Data of evolutionary structure change: 1AHPA-1E1YA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AHPA-1E1YA 1AHP 1E1Y A A -------------SQPIFNDKQFQEALSRQWQ-RYGLNSAAEMTPRQWWLAVSEAL...1AHP A 1AHPA KLAVV---HDKQV...1AHP A 1AHPA QATHAHPFDLTK...1AHP A 1AHPA RRHHLAGRELHEL...1AHP A 1AHPA SIGKQGGDPYLV

  20. Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells

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    Xiaoli Shi

    2016-01-01

    Full Text Available Nuclear receptor subfamily 2 group E member 1 (Nr2e1 has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

  1. Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen

    NARCIS (Netherlands)

    A. van Rongen (Anne); P.A.J. Välitalo (Pyry A. J.); M.Y. Peeters (Mariska); D. Boerma (Djamila); F.W. Huisman (Fokko W.); B. van Ramshorst (Bert); E.H.P.A. van Dongen (Eric); J.N. van den Anker (John); C.A.J. Knibbe (Catherijne)

    2016-01-01

    textabstractIntroduction: Acetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially

  2. Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen.

    NARCIS (Netherlands)

    Rongen, van A.; Välitalo, P.A.J.; Peeters, M.Y.; Boerma, D.; Huisman, F.W.; Ramshorst, van B.; Dongen, van E.P.; Anker, van den J.N.; Knibbe, C.A.J.

    2016-01-01

    INTRODUCTION Acetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially worsening the safety

  3. 26 CFR 31.3402(e)-1 - Included and excluded wages.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Included and excluded wages. 31.3402(e)-1... SOURCE Collection of Income Tax at Source § 31.3402(e)-1 Included and excluded wages. (a) If a portion of... not more than 31 consecutive days constitutes wages, and the remainder does not constitute wages, all...

  4. 77 FR 42677 - Special Conditions: General Electric CT7-2E1 Turboshaft Engine

    Science.gov (United States)

    2012-07-20

    ... Federal Aviation Administration 14 CFR Part 33 Special Conditions: General Electric CT7-2E1 Turboshaft Engine AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed special conditions. SUMMARY: This action proposes special conditions for the General Electric CT7-2E1 engine model. This...

  5. 29 CFR 2589.1 - Civil penalties under section 8477(e)(1)(B) of FERSA.

    Science.gov (United States)

    2010-07-01

    ... transaction penalty proceedings under FERSA section 8477(e)(1)(B). ... transaction with respect to the Thrift Savings Fund. The initial penalty under section 8477(e)(1)(B) is five percent of the “amount involved” in each such transaction for each year or part thereof during which the...

  6. Distinct Features of Cap Binding by eIF4E1b Proteins

    Science.gov (United States)

    Kubacka, Dorota; Miguel, Ricardo Núñez; Minshall, Nicola; Darzynkiewicz, Edward; Standart, Nancy; Zuberek, Joanna

    2015-01-01

    eIF4E1b, closely related to the canonical translation initiation factor 4E (eIF4E1a), cap-binding protein is highly expressed in mouse, Xenopus and zebrafish oocytes. We have previously characterized eIF4E1b as a component of the CPEB mRNP translation repressor complex along with the eIF4E-binding protein 4E-Transporter, the Xp54/DDX6 RNA helicase and additional RNA-binding proteins. eIF4E1b exhibited only very weak interactions with m7GTP-Sepharose and, rather than binding eIF4G, interacted with 4E-T. Here we undertook a detailed examination of both Xenopus and human eIF4E1b interactions with cap analogues using fluorescence titration and homology modeling. The predicted structure of eIF4E1b maintains the α + β fold characteristic of eIF4E proteins and its cap-binding pocket is similarly arranged by critical amino acids: Trp56, Trp102, Glu103, Trp166, Arg112, Arg157 and Lys162 and residues of the C-terminal loop. However, we demonstrate that eIF4E1b is 3-fold less well able to bind the cap than eIF4E1a, both proteins being highly stimulated by methylation at N7 of guanine. Moreover, eIF4E1b proteins are distinguishable from eIF4E1a by a set of conserved amino acid substitutions, several of which are located near to cap-binding residues. Indeed, eIF4E1b possesses several distinct features, namely, enhancement of cap binding by a benzyl group at N7 position of guanine, a reduced response to increasing length of the phosphate chain and increased binding to a cap separated by a linker from Sepharose, suggesting differences in the arrangement of the protein's core. In agreement, mutagenesis of the amino acids differentiating eIF4E1b from eIF4E1a reduces cap binding by eIF4E1a 2-fold, demonstrating their role in modulating cap binding. PMID:25463438

  7. New Protein Vector ApE1 for Targeted Delivery of Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    N. V. Pozdniakova

    2012-01-01

    Full Text Available A new chimeric gene ApE1 encoding the receptor-binding domain of the human alpha-fetoprotein fused to a sequence of 22 glutamic acid residues was constructed. A new bacterial producer strain E. coli SHExT7 ApE1 was selected for ApE1 production in a soluble state. A simplified method was developed to purify ApE1 from bacterial biomass. It was shown that the new vector protein selectively interacts with AFP receptors on the tumor cell surface and can be efficiently accumulated in tumor cells. In addition, ApE1 was shown to be stable in storage and during its chemical modification. An increased number of carboxyl groups in the molecule allows the production of cytotoxic compound conjugates with higher drug-loading capacity and enhanced tumor targeting potential.

  8. Effect of the pro-resolution lipid mediator Resolvin E1 (RvE1) on pulp tissues exposed to the oral environment.

    Science.gov (United States)

    Dondoni, L; Scarparo, R K; Kantarci, A; Van Dyke, T E; Figueiredo, J A P; Batista, E L

    2014-09-01

    To evaluate the effects of topical Resolvin E1 (RvE1) application on infected dental pulps. Forty-two male Wistar rats (n = 6 per three groups/and two time periods) were used. To induce inflammation, pulps in mandibular right first molars were accessed and then left exposed to the oral environment for 24 h. After this period, topical medication with a corticosteroid/antibiotic blend, or RvE1, or its vehicle (Ethanol 0.1%) was directly applied onto the pulp tissue and teeth were restored with silver amalgam. The effects of the protocols were evaluated histologically and compared with control pulps not exposed to the oral environment. The inflammatory changes after 24 and 72 h were assessed through a scoring method and analysed using the Kruskal-Wallis test followed by Dunn's. Differences were considered significant if P corticosteroid/antibiotic treatment were not effective in arresting severe inflammatory alterations of exposed pulps at 24 and 72 h (P 0.05, CI = 95%). A protective role for RvE1 in pulp inflammation was observed even in the presence of contamination, suggesting that it may be a candidate for a novel therapeutic strategy for conservative dental pulp treatment. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  9. GSTT1 and CYP2E1 polymorphisms and trihalomethanes in drinking water: effect on childhood leukemia.

    Science.gov (United States)

    Infante-Rivard, Claire; Amre, Devendra; Sinnett, Daniel

    2002-01-01

    The purpose of the study was to determine whether the risk of childhood acute lymphoblastic leukemia (ALL) associated with drinking water disinfection by-products was modified in the presence of variants in genes involved in the metabolism of trihalomethanes (THMs). We included a subset of cases from a population-based case-control study in a case-only study to estimate the interaction odds ratios (IORs) between prenatal and postnatal exposure to THMs and polymorphisms in the GSTT1 and CYP2E1 genes. We compared cases with and without a given variant regarding their exposure to THMs using unconditional logistic regression. The IOR for a postnatal average of total THM above the 95th percentile with GSTT1 null genotype was 9.1 [95% confidence interval (95% CI), 1.4-57.8]. With CYP2E1 (variant G-1259C, known as the allele CYP2E1*5), the effect of exposure during pregnancy for an average exposure to total THM at or above the 75th percentile was 9.7 (95% CI, 1.1-86.0). These results contrast strongly with those from our case-control analysis, in which we considered the exposure to THMs only in relation with ALL, and observed no increase in risk or very moderate ones. The present preliminary study shows suggestive but imprecise results. We found no similar results in the literature, underscoring the need for other studies as well as the potential usefulness of combining exposure and relevant genetic information in such studies. PMID:12055050

  10. Chang’E-1 precision orbit determination and lunar gravity field solution

    Science.gov (United States)

    Jianguo, Yan; Jinsong, Ping; Fei, Li; Jianfeng, Cao; Qian, Huang; Lihe, Fung

    2010-07-01

    In this paper we present results assessing the role of Very Long Baseline Interferometry (VLBI) tracking data through precision orbit determination (POD) during the check-out phase for Chang'E-1, and the lunar gravity field solution CEGM-01 based on the orbital tracking data acquired during the nominal phase of the mission. The POD of Chang'E-1 is performed using S-band two-way Range and Range Rate (R&RR) data, together with VLBI delay and delay rate observations. The role of the VLBI data in the POD of Chang'E-1 is analyzed, and the resulting orbital accuracies are estimated for different solution strategies. The final orbital accuracies proved that the VLBI tracking data can improve the Chang'E-1 POD significantly. Consequently, CEGM-01 based on six-month tracking data during Chang'E-1 nominal mission phase is presented, and the accuracy of the model is assessed by means of the gravity field power spectrum, admittance and coherence between gravity and topography, lunar surface gravity anomaly and POD for both Chang'E-1 and Lunar Prospector (LP). Our analysis indicates that CEGM-01 has significant improvements over a prior model (i.e. GLGM-2), and shows the potential of Chang'E-1 tracking data in high resolution lunar gravity field model solution by combining with SELENE and LP tracking data.

  11. Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease.

    Science.gov (United States)

    Aykanat, Alper; Yavuz, Taner; Özalkaya, Elif; Topçuoğlu, Sevilay; Ovalı, Fahri; Karatekin, Güner

    2016-01-01

    Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31%). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed.

  12. Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1.

    Science.gov (United States)

    Abrahams, Brett S; Kwok, Melvin C H; Trinh, Eric; Budaghzadeh, Saeed; Hossain, Sazzad M; Simpson, Elizabeth M

    2005-07-06

    "Fierce" mice, homozygous for the deletion of nuclear receptor 2E1 (NR2E1), show abnormal brain-eye development and pathological aggression. To evaluate functional equivalency between mouse and human NR2E1, we generated mice transgenic for a genomic clone spanning the human NR2E1 locus and bred these animals to fierce mice deleted for the corresponding mouse gene. In fierce mutants carrying human NR2E1, structural brain defects were eliminated and eye abnormalities ameliorated. Excitingly, behavior in these "rescue" mice was indistinguishable from controls. Because no artificial promoter was used to drive transgene expression, promoter and regulatory elements within the human NR2E1 clone are functional in mouse. Normal behavior in rescue animals suggests that mechanisms underlying the behavioral abnormalities in fierce mice may also be conserved in humans. Our data support the hypothesis that variation at NR2E1 may contribute to human behavioral disorders. Use of this rescue paradigm with other genes will permit the direct evaluation of human genes hypothesized to play a causal role in psychiatric disease but for which evidence is lacking or equivocal.

  13. Role of CYP2E1 genotypes in susceptibility to colorectal cancer in the Kashmiri population

    Directory of Open Access Journals (Sweden)

    Sameer A

    2011-10-01

    Full Text Available Abstract Cytochrome P450 2E1 (CYP2E1 is a key enzyme involved in the metabolic activation of procarcinogens such as N-nitrosoamines and low-molecular-weight organic compounds. The main aim of this study was to determine whether CYP450 2E1 polymorphisms are associated with the risk of colorectal cancer (CRC. We investigated the genotype distribution of the CYP2E1 gene RsaI and a 96-base pair (bp insertion in 86 CRC cases in comparison with 160 healthy subjects. We found the frequency of the CYP2E1 RsaI genotype to be 53.5 per cent (46/86 for c1/c1, 17.4 per cent (15/86 for c1/c2 and 29.1 per cent (25/86 for c2/c2, and the CYP2E1 98-bp insertion frequencies to be 63.9 per cent (55/86 for non-insertion (i/i, 22.1 per cent (19/86 for heterozygous insertion (i/I and 36.0 per cent (12/86 for homozygous insertion (I/I among CRC cases. We also found the CYP2E1 RsaI c2/c2 and CYP2E1 98-bp heterozygous i/I genotypes to be significantly associated with an increased risk of CRC (p = 0.01. We suggest that CYP2E1 polymorphisms are involved in the susceptibility to developing CRC in the ethnic Kashmiri population.

  14. Enterasys Networks delivers 10-Gigabit ethernet for the enterprise with new matrix E1 switching family

    CERN Multimedia

    2001-01-01

    Enterasys Networks Inc., today announced its new Matrix E1 family of 10-Gigabit and Gigabit Ethernet switches. The Matrix E1 Optical Access Switch (OAS) enables organizations to deliver applications at 10-Gb speeds across a single fibre optic pair. Jacques Altaber, deputy leader of IT at CERN said "High-bandwith solutions are essential to leveraging more computing power, so 10-Gb Ethernet is the next logical step for us...The Matrix E1 allows us to provide the networking support that our scientists need and gives us a certain future for bandwidth and computing expansion".

  15. Absence of NR2E1 mutations in patients with aniridia

    Science.gov (United States)

    Corso-Díaz, Ximena; Borrie, Adrienne E.; Bonaguro, Russell; Schuetz, Johanna M.; Rosenberg, Thomas; Jensen, Hanne; Brooks, Brian P.; MacDonald, Ian M.; Pasutto, Francesca; Walter, Michael A.; Grønskov, Karen; Brooks-Wilson, Angela

    2012-01-01

    Purpose Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congenital ocular malformations (anterior segment dysgenesis, congenital optic nerve malformation, and microphthalmia). Methods The NR2E1 coding region, 5′ and 3′ untranslated regions (UTRs), exon flanking regions including consensus splice sites, and six evolutionarily conserved non-coding candidate regulatory regions were analyzed by sequencing 58 probands with aniridia of whom 42 were negative for PAX6 mutations. Nineteen probands with anterior segment dysgenesis, one proband with optic nerve malformation, and two probands with microphthalmia were also sequenced. The control population comprised 376 healthy individuals. All sequences were analyzed against the GenBank sequence AL078596.8 for NR2E1. In addition, the coding region and flanking intronic sequences of FOXE3, FOXC1, PITX2, CYP1B1, PAX6, and B3GALTL were sequenced in one patient and his relatives. Results Sequencing analysis showed 17 NR2E1 variants including two novel rare non-coding variants (g.-1507G>A, g.14258C>T), and one novel rare coding variant (p.Arg274Gly). The latter was present in a male diagnosed with Peters’ anomaly who subsequently was found to have a known causative mutation for Peters’ plus syndrome in B3GALTL (c.660+1G>A). In addition, the NR2E1 novel rare variant Arg274Gly was present in the unaffected mother of the patient but absent in 746 control chromosomes. Conclusions We eliminated a major role for NR2E1 regulatory and coding mutations in aniridia and found a novel rare coding variant in NR2E1. In addition, we found no coding region variation in the control population for NR2E1, which further supports its previously reported high level of conservation and low genetic diversity

  16. DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization.

    Science.gov (United States)

    Brecik, Miroslav; Centárová, Ivana; Mukherjee, Raju; Kolly, Gaëlle S; Huszár, Stanislav; Bobovská, Adela; Kilacsková, Emöke; Mokošová, Veronika; Svetlíková, Zuzana; Šarkan, Michal; Neres, João; Korduláková, Jana; Cole, Stewart T; Mikušová, Katarína

    2015-07-17

    The flavo-enzyme DprE1 catalyzes a key epimerization step in the decaprenyl-phosphoryl d-arabinose (DPA) pathway, which is essential for mycobacterial cell wall biogenesis and targeted by several new tuberculosis drug candidates. Here, using differential radiolabeling with DPA precursors and high-resolution fluorescence microscopy, we disclose the unexpected extracytoplasmic localization of DprE1 and periplasmic synthesis of DPA. Collectively, this explains the vulnerability of DprE1 and the remarkable potency of the best inhibitors.

  17. Acetato(N-[(E-1-(6-methyl-2-pyridylmethylidene]-2-{2-[(E-1-(6-methyl-2-pyridylmethylideneamino]phenethyl}anilinenickel(II perchlorate

    Directory of Open Access Journals (Sweden)

    Hong-In Lee

    2010-10-01

    Full Text Available In the title complex, [Ni(CH3COO(C28H26N4]ClO4, the NiII atom is coordinated by two imine N atoms and two pyridine N atoms of the N-[(E-1-(6-methyl-2-pyridylmethylidene]-2-(2-[(E-1-(6-methyl-2-pyridylmethylideneamino]phenethylaniline donor ligand and two O atoms of the acetate ion in a distorted octahedral coordination. The average Ni—N and Ni—O bond lengths are 2.131 (13 and 2.098 (11 Å, respectively. An intramolecular N—H...O interaction occurs. Relatively weak intermolecular C—H...O interactions between the ligands and the ClO4− ions result in a chain extending along the b axis.

  18. E1, M1, E2 transition energies and probabilities of W$^{54+}$ ions

    CERN Document Server

    Ding, Xiao-bin; Liu, Jia-xin; Koike, Fumihiro; Murakami, Izumi; Kato, Daiji; Sakaue, Hiroyuki A; Nakamura, Nobuyuki; Dong, Chen-zhong

    2016-01-01

    A comprehensive theoretical study of the E1, M1, E2 transitions of Ca-like tungsten ions is presented. Using multi-configuration Dirac-Fock (MCDF) method with a restricted active space treatment, the wavelengths and probabilities of the M1 and E2 transitions between the multiplets of the ground state configuration ([Ne]3s$^{2}$3p$^{6}$3d$^{2}$) and of the E1 transitions between [Ne]3s$^{2}$3p$^{5}$3d$^{3}$ and [Ne]3s$^{2}$3p$^{6}$3d$^{2}$ have been calculated. The results are in reasonable agreement with available experimental data. The present E1 and M1 calculations are compared with previous theoretical values. For E2 transitions, the importance of electron correlation from 3s and 3p orbitals is pointed out. Several strong E1 transitions are predicted, which have potential advantage for plasma diagnostics.

  19. The C-terminal region of E1A: a molecular tool for cellular cartography.

    Science.gov (United States)

    Yousef, Ahmed F; Fonseca, Gregory J; Cohen, Michael J; Mymryk, Joe S

    2012-04-01

    The adenovirus E1A proteins function via protein-protein interactions. By making many connections with the cellular protein network, individual modules of this virally encoded hub reprogram numerous aspects of cell function and behavior. Although many of these interactions have been thoroughly studied, those mediated by the C-terminal region of E1A are less well understood. This review focuses on how this region of E1A affects cell cycle progression, apoptosis, senescence, transformation, and conversion of cells to an epithelial state through interactions with CTBP1/2, DYRK1A/B, FOXK1/2, and importin-α. Furthermore, novel potential pathways that the C-terminus of E1A influences through these connections with the cellular interaction network are discussed.

  20. Ber e 1 protein: the versatile major allergen from Brazil nut seeds.

    Science.gov (United States)

    Alcocer, Marcos; Rundqvist, Louise; Larsson, Göran

    2012-04-01

    Due mainly to its extremely high content of sulphur amino acids, Ber e 1 protein, the major allergen from Brazil nut, has attracted much scientific and press attention. Ber e 1 was the main target protein in early biotechnology transgenic work, in early processing studies of plant storage proteins, in plant vacuolar targeting studies and as the main protein in early nutritional supplementation experiments. Ber e 1 was also one of the first food allergens to be unintentionally transferred from one plant to another and was involved in the first reported case of systemic allergic reaction caused by a food allergen transferred in semen. In this review, many of the Ber e 1 unique biotechnological and structural functions are discussed with a particular emphasis on its use as model protein for studies of intrinsic allergenicity of food proteins.

  1. Tumor Suppression and Sensitization to Taxol Induced Apoptosis of E1A In Breast Cancer Cells

    National Research Council Canada - National Science Library

    Liao, Yong

    2004-01-01

    The purpose of this project is to study the molecular mechanisms underlying E1A's proapoptotic effect and anti-tumor activity and to dissect the functional domains of El A that are critical for its antitumor activity...

  2. Characterization of DprE1-Mediated Benzothiazinone Resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Foo, Caroline Shi-Yan; Lechartier, Benoit; Kolly, Gaëlle S; Boy-Röttger, Stefanie; Neres, João; Rybniker, Jan; Lupien, Andréanne; Sala, Claudia; Piton, Jérémie; Cole, Stewart T

    2016-11-01

    Benzothiazinones (BTZs) are a class of compounds found to be extremely potent against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains. The potency of BTZs is explained by their specificity for their target decaprenylphosphoryl-d-ribose oxidase (DprE1), in particular by covalent binding of the activated form of the compound to the critical cysteine 387 residue of the enzyme. To probe the role of C387, we used promiscuous site-directed mutagenesis to introduce other codons at this position into dprE1 of M. tuberculosis The resultant viable BTZ-resistant mutants were characterized in vitro, ex vivo, and biochemically to gain insight into the effects of these mutations on DprE1 function and on M. tuberculosis Five different mutations (C387G, C387A, C387S, C387N, and C387T) conferred various levels of resistance to BTZ and exhibited different phenotypes. The C387G and C387N mutations resulted in a lower growth rate of the mycobacterium on solid medium, which could be attributed to the significant decrease in the catalytic efficiency of the DprE1 enzyme. All five mutations rendered the mycobacterium less cytotoxic to macrophages. Finally, differences in the potencies of covalent and noncovalent DprE1 inhibitors in the presence of C387 mutations were revealed by enzymatic assays. As expected from the mechanism of action, the covalent inhibitor PBTZ169 only partially inhibited the mutant DprE1 enzymes compared to the near-complete inhibition with a noncovalent DprE1 inhibitor, Ty38c. This study emphasizes the importance of the C387 residue for DprE1 activity and for the killing action of covalent inhibitors such as BTZs and other recently identified nitroaromatic inhibitors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate

    KAUST Repository

    Ghorpade, Seema Arun

    2017-11-30

    Transition metal free, water based, greener protocol for allylic alkylation, allylic amination, O-allylation of (E)-1,3-diphenylallyl acetate is described. The developed methodology is applicable for a wide range of nucleophiles furnishing excellent yields of corresponding products up to 87% under mild reaction conditions. A Distinct effect of water and base is explored for allylic nucleophilic substitution reactions of (E)-1,3-diphenylallyl acetate.

  4. Evolution of the ubiquitin-activating enzyme Uba1 (E1)

    Science.gov (United States)

    Allan, Douglas C.; Phillips, J. C.

    2017-10-01

    Ubiquitin tags diseased proteins and initiates an enzyme conjugation cascade, which has three stages. The first-stage enzyme Uba1 (E1) has evolved only modestly from slime mold to humans, and is > 14 times larger than Ub. Here we use critical point thermodynamic scaling theory to connect Uba1 (E1) evolution from yeast and slime mold to fruit flies and humans to subtle changes in its amino acid sequences.

  5. The esg locus of Myxococcus xanthus encodes the E1 alpha and E1 beta subunits of a branched-chain keto acid dehydrogenase.

    Science.gov (United States)

    Toal, D R; Clifton, S W; Roe, B A; Downard, J

    1995-04-01

    The esg locus of Myxococcus xanthus appears to control the production of a signal that must be transmitted between cells for the completion of multicellular development. DNA sequence analysis suggested that the esg locus encodes the E1 decarboxylase (composed of E1 alpha and E1 beta subunits) of a branched-chain keto acid dehydrogenase (BCKAD) that is involved in branched-chain amino acid (BCAA) metabolism. The properties of an esg::Tn5 insertion mutant supported this conclusion. These properties include: (i) the growth yield of the mutant was reduced with increasing concentrations of the BCAAs in the medium while the growth yield of wild-type cells increased, (ii) mutant extracts were deficient in BCKAD activity, and (iii) growth of the mutant in media with short branched-chain fatty acids related to the expected products of the BCKAD helped to correct the mutant defects in growth, pigmentation and development. The esg BCKAD appears to be involved in the synthesis of long branched-chain fatty acids since the mutant contained reduced levels of this class of compounds. Our results are consistent with a model in which the esg-encoded enzyme is involved in the synthesis of branched-chain fatty acids during vegetative growth, and these compounds are used later in cell-cell signalling during development.

  6. The Frequency of Cytochrome P450 2E1 Polymorphisms in Black South Africans

    Directory of Open Access Journals (Sweden)

    Paul K. Chelule

    2006-01-01

    Full Text Available Polymorphisms in the promoter region of the Cytochrome P4502E1 (CYP2E1 gene reportedly modify the metabolic activity of CYP2E1 enzyme, and have been associated with increased susceptibility to squamous cell carcinoma (SCC of the oesophagus in high prevalence areas such as China. To assess the frequency of these polymorphisms in Black South Africans, a population with a high incidence of oesophageal SCC, this study examined genomic DNA from 331 subjects for restriction fragment length polymorphisms in the CYP2E1 (RsaI and PstI digestion. The frequency of the CYP2E1 c1/c1 and c1/c3 genotypes was 95% and 5% respectively. The frequency of the CYP2E1 allele distribution was found to be markedly different between Chinese and South African populations; hence it is important to place racial differences into consideration when proposing allelic variants as genetic markers for cancer.

  7. Catalytic activity and quantitation of cytochrome P-450 2E1 in prenatal human brain.

    Science.gov (United States)

    Brzezinski, M R; Boutelet-Bochan, H; Person, R E; Fantel, A G; Juchau, M R

    1999-06-01

    Cytochrome P-450 2E1 (CYP2E1) is a readily inducible hemoprotein that catalyzes the oxidation of endogenous compounds and many low molecular weight xenobiotics. As the major component of the microsomal ethanol oxidizing system, it contributes significantly to ethanol metabolism and the formation of the highly reactive metabolite acetaldehyde. The leaky property of this enzyme results in the generation of reactive oxygen species that can induce oxidative stress and cytotoxic conditions deleterious to development. To further investigate the proposed role of CYP2E1 in the etiology of alcohol teratogenesis, the current study focused on the quantification of CYP2E1 in prenatal human brain, a tissue that is highly vulnerable to the damaging effects of ethanol throughout gestation. In microsomal samples prepared from pools of brain tissues, immunoreactive protein was detected by Western blot analysis using enhanced chemiluminescence, whereas functional protein was estimated with an enzymatic assay using p-nitrophenol and an electrochemical detection system. CYP2E1 transcript was consistently detected in RNA samples prepared from individual brain tissues using the ribonuclease protection assay. Quantitative data were collected by scanning densitometry and phosphorimaging technology. There was a dramatic increase in human brain CYP2E1 content around gestational day 50 and a fairly constant level was maintained throughout the early fetal period, until at least day 113. The relatively low levels of the P-450 isoform present in conceptal brain may be sufficient to generate reactive intermediates that elicit neuroembryotoxicity following maternal alcohol consumption.

  8. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yongke Lu

    2015-10-01

    Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

  9. Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo.

    Science.gov (United States)

    Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M; Melendy, Thomas; Archambault, Jacques

    2016-01-06

    The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural

  10. Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

    Science.gov (United States)

    Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.

    2016-01-01

    ABSTRACT The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCE While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed

  11. Ethanol-mediated transplacental induction of CYP2E1 in fetal rat liver.

    Science.gov (United States)

    Carpenter, S P; Savage, D D; Schultz, E D; Raucy, J L

    1997-08-01

    We examined the potential for the widely consumed xenobiotic ethanol to transplacentally induce fetal rat CYP2E1. Throughout gestation, rat dams were fed a liquid diet containing 5% ethanol or two separate control diets. At 2 days before term, the dams were killed, and maternal and embryonic tissues were collected. Immunoblot analysis of microsomes from fetal liver, placenta and maternal brain revealed a band that comigrated with adult liver CYP2E1. The identity of the immunoreactive protein in placenta, brain and fetal liver was substantiated as CYP2E1 through restriction enzyme digestion of a reverse transcription-polymerase chain reaction product. Quantification of immunoblots containing microsomes from maternal and fetal liver of ethanol-treated dams displayed a 1.4- and 2.4-fold increase in CYP2E1, respectively, compared with microsomes from pair-fed controls. Chlorzoxazone and low substrate concentrations of N-nitrosodimethylamine were used as metabolic probes for CYP2E1. The rate of chlorzoxazone metabolism by maternal hepatic microsomes from dams fed the 5% ethanol diet was 2.6-fold greater than that of controls. Conversely, a negligible increase was observed in the rate of metabolism by hepatic microsomes from ethanol-exposed fetuses compared with pair-fed animals. When N-nitrosodimethylamine demethylation was examined, these same fetal samples exhibited greater rates of activity (1.5-fold) compared with microsomes from control animals. However, this increase was not as great as expected considering the 2.4-fold increase in CYP2E1 protein. Collectively, fetuses exposed to a 5% ethanol diet throughout gestation exhibited transplacental induction of an hepatic CYP2E1 that may possess different catalytic properties from the analogous adult enzyme.

  12. E1-mediated recruitment of a UAF1-USP deubiquitinase complex facilitates human papillomavirus DNA replication.

    Science.gov (United States)

    Lehoux, Michaël; Gagnon, David; Archambault, Jacques

    2014-08-01

    The human papillomavirus (HPV) E1 helicase promotes viral DNA replication through its DNA unwinding activity and association with host factors. The E1 proteins from anogenital HPV types interact with the cellular WD repeat-containing factor UAF1 (formerly known as p80). Specific amino acid substitutions in E1 that impair this interaction inhibit maintenance of the viral episome in immortalized keratinocytes and reduce viral DNA replication by up to 70% in transient assays. In this study, we determined by affinity purification of UAF1 that it interacts with three deubiquitinating enzymes in C33A cervical carcinoma cells: USP1, a nuclear protein, and the two cytoplasmic enzymes USP12 and USP46. Coimmunoprecipitation experiments indicated that E1 assembles into a ternary complex with UAF1 and any one of these three USPs. Moreover, expression of E1 leads to a redistribution of USP12 and USP46 from the cytoplasm to the nucleus. Chromatin immunoprecipitation studies further revealed that E1 recruits these threes USPs to the viral origin in association with UAF1. The function of USP1, USP12, and USP46 in viral DNA replication was investigated by overproduction of catalytically inactive versions of these enzymes in transient assays. All three dominant negative USPs reduced HPV31 DNA replication by up to 60%, an effect that was specific, as it was not observed in assays performed with a truncated E1 lacking the UAF1-binding domain or with bovine papillomavirus 1 E1, which does not bind UAF1. These results highlight the importance of the USP1, USP12, and USP46 deubiquitinating enzymes in anogenital HPV DNA replication. Human papillomaviruses are small DNA tumor viruses that induce benign and malignant lesions of the skin and mucosa. HPV types that infect the anogenital tract are the etiological agents of cervical cancer, the majority of anal cancers, and a growing proportion of head-and-neck cancers. Replication of the HPV genome requires the viral protein E1, a DNA helicase

  13. Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice

    Energy Technology Data Exchange (ETDEWEB)

    Hoffler, Undi [Department of Pharmacology, Meharry Medical College, Nashville, TN (United States); Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709 (United States); Dixon, Darlene [Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709 (United States); Peddada, Shyamal [Biostatics Branch, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709 (United States); Ghanayem, Burhan I. [Department of Pharmacology, Meharry Medical College, Nashville, TN (United States) and Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709 (United States)]. E-mail: ghanayem@niehs.nih.gov

    2005-05-02

    Urethane is a multi-site animal carcinogen and was classified as 'reasonably anticipated to be a human carcinogen.' Urethane is a fermentation by-product and found at appreciable levels in alcoholic beverages and foods such as bread and cheese. Recent work in this laboratory demonstrated for the first time that CYP2E1 is the principal enzyme responsible for urethane metabolism. The current studies were undertaken to assess the relationships between CYP2E1-mediated metabolism and urethane-induced genotoxicity and cell proliferation as determined by induction of micronucleated erythrocytes (MN) and expression of Ki-67, respectively, using CYP2E1-null and wild-type mice. Urethane was administered at 0 (vehicle), 1, 10, or 100 mg/kg/day (p.o.), 5 days/week for 6 weeks. A significant dose-dependent increase in MN was observed in wild-type mice; however, a slight increase was measured in the MN-polychromatic erythrocytes in CYP2E1-null mice treated with 100 mg/kg. A significant increase in the expression of Ki-67 was detected in the livers and the lungs (terminal bronchioles, alveoli, and bronchi) of wild-type mice administered 100 mg urethane/kg in comparison to controls. In contrast, CYP2E1-null mice administered this dose exhibited negligible alterations in Ki-67 expression in the livers and lungs compared to controls. Interestingly, while Ki-67 expression in the forestomach decreased in wild-type mice, it increased in CYP2E1-null mice. Subsequent comparative metabolism studies demonstrated that total urethane-derived radioactivity in the plasma, liver, and lung was significantly higher in CYP2E1-null versus wild-type mice and un-metabolized urethane constituted greater than 83% of the radioactivity in CYP2E1-null mice. Un-metabolized urethane was not detectable in the plasma, liver, and lung of wild-type mice. In conclusion, these data demonstrated that CYP2E1-mediated metabolism of urethane, presumably via epoxide formation, is necessary for the induction

  14. User perspectives on relevance criteria

    DEFF Research Database (Denmark)

    Maglaughlin, Kelly L.; Sonnenwald, Diane H.

    2002-01-01

    implications for relevance feedback in information retrieval systems, suggesting that systems accept and utilize multiple positive and negative relevance criteria from users. Systems designers may want to focus on supporting content criteria followed by full text criteria as these may provide the greatest cost...

  15. Expression and Characterization of Acidothermus celluloyticus E1 Endoglucanase in Transgenic Duckweed Lemna minor 8627

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Y.; Cheng, J. J.; Himmel, M. E.; Skory, C. D.; Adney, W. S.; Thomas, S. R.; Tisserat, B.; Nishimura, Y.; Yamamoto, Y. T.

    2007-01-01

    Endoglucanase E1 from Acidothermus cellulolyticus was expressed cytosolically under control of the cauliflower mosaic virus 35S promoter in transgenic duckweed, Lemna minor 8627 without any obvious observable phenotypic effects on morphology or rate of growth. The recombinant enzyme co-migrated with the purified catalytic domain fraction of the native E1 protein on western blot analysis, revealing that the cellulose-binding domain was cleaved near or in the linker region. The duckweed-expressed enzyme was biologically active and the expression level was up to 0.24% of total soluble protein. The endoglucanase activity with carboxymethylcellulose averaged 0.2 units mg protein{sup -1} extracted from fresh duckweed. The optimal temperature and pH for E1 enzyme activity were about 80 C and pH 5, respectively. While extraction with HEPES (N-[2-hydroxyethyl]piperazine-N{prime}-[2-ethanesulfonic acid]) buffer (pH 8) resulted in the highest recovery of total soluble proteins and E1 enzyme, extraction with citrate buffer (pH 4.8) at 65 C enriched relative amounts of E1 enzyme in the extract. This study demonstrates that duckweed may offer new options for the expression of cellulolytic enzymes in transgenic plants.

  16. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Roberta L. [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Wilkinson, John C., E-mail: john.wilkinson@ndsu.edu [Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Ornelles, David A., E-mail: ornelles@wakehealth.edu [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States)

    2014-05-15

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR.

  17. 2-Carboxyquinoxalines kill mycobacterium tuberculosis through noncovalent inhibition of DprE1.

    Science.gov (United States)

    Neres, João; Hartkoorn, Ruben C; Chiarelli, Laurent R; Gadupudi, Ramakrishna; Pasca, Maria Rosalia; Mori, Giorgia; Venturelli, Alberto; Savina, Svetlana; Makarov, Vadim; Kolly, Gaelle S; Molteni, Elisabetta; Binda, Claudia; Dhar, Neeraj; Ferrari, Stefania; Brodin, Priscille; Delorme, Vincent; Landry, Valérie; de Jesus Lopes Ribeiro, Ana Luisa; Farina, Davide; Saxena, Puneet; Pojer, Florence; Carta, Antonio; Luciani, Rosaria; Porta, Alessio; Zanoni, Giuseppe; De Rossi, Edda; Costi, Maria Paola; Riccardi, Giovanna; Cole, Stewart T

    2015-03-20

    Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification of lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC of 3.1 μM, Ty38c is bactericidal and active against intracellular bacteria. To investigate its mechanism of action, we isolated mutants resistant to Ty38c and sequenced their genomes. Mutations were found in rv3405c, coding for the transcriptional repressor of the divergently expressed rv3406 gene. Biochemical studies clearly showed that Rv3406 decarboxylates Ty38c into its inactive keto metabolite. The actual target was then identified by isolating Ty38c-resistant mutants of an M. tuberculosis strain lacking rv3406. Here, mutations were found in dprE1, encoding the decaprenylphosphoryl-d-ribose oxidase DprE1, essential for biogenesis of the mycobacterial cell wall. Genetics, biochemical validation, and X-ray crystallography revealed Ty38c to be a noncovalent, noncompetitive DprE1 inhibitor. Structure-activity relationship studies generated a family of DprE1 inhibitors with a range of IC50's and bactericidal activity. Co-crystal structures of DprE1 in complex with eight different quinoxaline analogs provided a high-resolution interaction map of the active site of this extremely vulnerable target in M. tuberculosis.

  18. CYP2E1 Potentiates Ethanol-induction of Hypoxia and HIF-1α in vivo

    Science.gov (United States)

    Wang, Xiaodong; Wu, Defeng; Yang, Lili; Gan, Lixia; Cederbaum, Arthur I

    2013-01-01

    Ethanol induces hypoxia and elevates HIF-1α in the liver. CYP2E1 plays a role in the mechanisms by which ethanol generates oxidative stress, fatty liver and liver injury. The current study evaluated whether CYP2E1 contributes to ethanol-induced hypoxia and activation of HIF-1α in vivo and whether HIF-1α protects against or promotes CYP2E1-dependent toxicity in vitro. Wild type (WT), CYP2E1-knockin (KI) and CYP2E1 knockout (KO) mice were fed ethanol chronically; pair fed controls received isocaloric dextrose. Ethanol produced liver injury in the KI mice to a much greater extent than in the WT and KO mice. Protein levels of HIF-1α and downstream targets of HIF-1α activation were elevated in the ethanol-fed KI mice compared to the WT and KO mice. Levels of HIF prolylhydroxlase 2 which promotes HIF-1α degradation were decreased in the ethanol-fed KI mice in association with the increases in HIF-1α. Hypoxia occurred in the ethanol-fed CYP2E1 KI mice as shown by an increased area of staining using the hypoxia-specific marker pimonidazole. Hypoxia was lower in the ethanol-fed WT mice and lowest in the ethanol fed KO mice and all the dextrose-fed mice. In situ double staining showed that pimonidazole and CYP2E1 were co-localized to the same area of injury in the hepatic centrilobule. Increased protein levels of HIF-1α were also found after acute ethanol treatment of KI mice. Treatment of HepG2 E47 cells which express CYP2E1 with ethanol plus arachidonic (AA) acid or ethanol plus buthionine sulfoximine (BSO) which depletes GSH caused loss of cell viability to greater extent than in HepG2 C34 cells which do not express CYP2E1. These treatments elevated protein levels of HIF-1α to a greater extent in E47 cells than C34 cells. 2-Methoxyestradiol, an inhibitor of HIF-1α, blunted the toxic effects of ethanol plus AA and ethanol plus BSO in the E47 cells in association with inhibition of HIF-1α. The HIF-1α inhibitor also blocked the elevated oxidative stress produced

  19. Quercetin prevents type 1 diabetic liver damage through inhibition of CYP2E1.

    Science.gov (United States)

    Maksymchuk, Oksana; Shysh, Angela; Rosohatska, Inna; Chashchyn, Mykola

    2017-12-01

    Increased CYP2E1 protein and activity levels can be the main cause of stress-mediated liver damage in diabetes. In this work we investigated the quercetin properties to prevent diabetic oxidative liver injury through inhibition of CYP2E1. Animals were randomly divided into three groups (n=5 for each group): non-diabetic control, STZ-diabetic rats and STZ-diabetic rats administered with quercetin (50mg/kg bw, per day, during 30days). Markers of oxidative stress and liver injury, hepatocyte ultrastructure and levels of CYP2E1 protein and activity were examined using biochemical, electron microscopy and molecular biological methods. It was shown that symptoms of diabetes (hyperglycemia, bodyweight loss, damaged hepatocyte ultrastructure), signs of oxidative stress in liver (2-fold intensification of peroxide process and 2-fold depletion of antioxidants) and serum markers of liver damage (3.5-, 1.5- and 5-fold increase in levels of ALT, AST and GGT, respectively) were present in STZ-diabetic rats. We found 3- and 2.5-fold increase in levels of protein and activity of CYP2E1 in the liver of STZ-diabetic rats. We demonstrated that the administration of quercetin leads to significant decrease in CYP2E1 activity (5- and 2-times compared to STZ-diabetic and control group, respectively). That was accompanied by normalization of pro-oxidant-antioxidant balance, improving the ultrastructure of hepatocytes and rates of serum markers of liver injury. CYP2E1 can play a crucial role in stress-induced pathological processes in the liver in diabetes, and the inhibition of the enzyme by quercetin during the development of diabetes mainly prevents the oxidative damage in liver. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Resolvin E1 Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation Induced Atherogenesis

    Science.gov (United States)

    Hasturk, Hatice; Abdallah, Rima; Kantarci, Alpdogan; Nguyen, Daniel; Giordano, Nicholas; Hamilton, James; Van Dyke, Thomas E.

    2015-01-01

    Objective Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared to diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation. Approach and Results Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by P. gingivalis in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4μg/site or 0.4 μg/site) topically applied 3-times/ week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology and ex vivo MRI. Serum levels of C-reactive protein (CRP) were evaluated as a measure of systemic inflammation.RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis (pperiodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared to no-treatment (pperiodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events. PMID:25792445

  1. Thionin-D4E1 chimeric protein protects plants against bacterial infections

    Energy Technology Data Exchange (ETDEWEB)

    Stover, Eddie W; Gupta, Goutam; Hao, Guixia

    2017-08-08

    The generation of a chimeric protein containing a first domain encoding either a pro-thionon or thionin, a second domain encoding D4E1 or pro-D4E1, and a third domain encoding a peptide linker located between the first domain and second domain is described. Either the first domain or the second domain is located at the amino terminal of the chimeric protein and the other domain (second domain or first domain, respectively) is located at the carboxyl terminal. The chimeric protein has antibacterial activity. Genetically altered plants and their progeny expressing a polynucleotide encoding the chimeric protein resist diseases caused by bacteria.

  2. E1a promotes c-Myc-dependent replicative stress: Implications in glioblastoma radiosensitization

    OpenAIRE

    Valero, María Llanos; Cimas, Francisco Jose; Arias, Laura; Melgar-Rojas, Pedro; García, Elena; Callejas-Valera, Juan Luis; García-Cano, Jesús; Serrano-Oviedo, Leticia; Ángel de la Cruz-Morcillo, Miguel; Sánchez-Pérez, Isabel; Sánchez-Prieto, Ricardo

    2013-01-01

    The E1a gene from adenovirus is known to be a potent inducer of chemo/radiosensitivity in a wide range of tumors. However, the molecular bases of its radiosensitizer properties are still poorly understood. In an attempt to study this effect, U87MG cells, derived from a radio-resistant tumor as glioblastoma, where infected with lentivirus carrying E1a gene developing an acute sensitivity to ionizing radiation. The induction of radiosensitivity correlated with a marked G2/M phase accumulation a...

  3. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: fjgonz@helix.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  4. A bilateral antidiuresis to renal artery infusion of prostaglandin E1 in dogs treated with phenylbutazone

    Science.gov (United States)

    Hall, W. J.; Hensey, O. J.; O'Neill, P.; Sheehan, J. D.

    1978-01-01

    1. In acute experiments, high levels of endogenous prostaglandins, provoked by operative stress, could obscure or alter the actions of infused prostaglandins on the kidney. For this reason we decided to compare the effects of infusing prostaglandin E1 into the renal artery of the dog before and after the administration of phenylbutazone, a prostaglandin synthetase inhibitor. 2. Infusion of prostaglandin E1 into the left renal artery of the pre-phenylbutazone treated dog undergoing a mannitol diuresis increased renal plasma flow, glomerular filtration rate and the excretion of salt and water. The findings are in general agreement with those reported by others. 3. Following phenylbutazone administration the vascular and saluretic actions of prostaglandin E1 were unchanged but a reduced diuretic effect was observed. The response to a low dose of prostaglandin E1 (0·05 μg/min) was reduced from 1·46 ± 0·15 to 0·96 ± 0·16 ml./min (P phenylbutazone treatment than before. The reduction in the diuretic response was of the same order as the decrease in the free water clearance response, while the increase in osmolar clearance was unchanged. 5. In water-loaded dogs treated with phenylbutazone, infusion of prostaglandin E1 into the left renal artery had a biphasic effect on urine output from the left kidney. An initial diuretic response to a low dose of prostaglandin E1 disappeared with the infusion of higher doses, and antidiuresis developed in the immediate post-infusion period. 6. As prostaglandin was infused into the left kidney progressive antidiuresis was seen in the non-infused right kidney. 7. It is concluded that endogenous prostaglandins do not obscure or alter the vascular and saluretic actions of intrarenal prostaglandin E1. The findings question the proposed link between the vascular and saluretic actions of this compound. 8. It is suggested that the reduced diuretic effect of prostaglandin E1 in series no. 1, and the antidiuresis in the water-loaded dogs

  5. Fundamental duties to be observed in the procedure of decommissioning industrial installations subject to licensing according to Para. 5 sub-section 3 of the German Emission Control Act (BImSchG). Die Grundpflichten bei der Einstellung des Betriebes genehmigungsbeduerftiger Anlagen gemaess Para. 5 Abs. 3 BImSchG

    Energy Technology Data Exchange (ETDEWEB)

    Dierkes, C.

    1994-01-01

    The main reason for adding Para. 5, sub-section 3 to the BImSchG, containing the fundamental duties to be observed by owners of installations in the decommissioning procedure and after, was the knowledge that shutdown plant and site still may continue to be a source of hazards. The study in hand investigates to what extent this Para. 5 sub-section 3 BImSchG is a suitable instrument for managing the harzards and other problems occurring in connection with decommissioned installations. The applicability of the provisions is examined, also with a view to shutdowns restricted to parts of plant or in time, and the duties to be fulfilled by (former) plant owners are reviewed in detail. A major aspect is the question whether the legal provisions are an adequate instrument to provide for due disposal of long-standing pollution or long-lasting waste. The study also addresses the duty to guarantee proper treatment of recyclable wastes, and the responsibilities of former and current owners. (orig./HP)

  6. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  7. Relevance theory: pragmatics and cognition.

    Science.gov (United States)

    Wearing, Catherine J

    2015-01-01

    Relevance Theory is a cognitively oriented theory of pragmatics, i.e., a theory of language use. It builds on the seminal work of H.P. Grice(1) to develop a pragmatic theory which is at once philosophically sensitive and empirically plausible (in both psychological and evolutionary terms). This entry reviews the central commitments and chief contributions of Relevance Theory, including its Gricean commitment to the centrality of intention-reading and inference in communication; the cognitively grounded notion of relevance which provides the mechanism for explaining pragmatic interpretation as an intention-driven, inferential process; and several key applications of the theory (lexical pragmatics, metaphor and irony, procedural meaning). Relevance Theory is an important contribution to our understanding of the pragmatics of communication. © 2014 John Wiley & Sons, Ltd.

  8. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  9. Emerging Concepts in the Resolution of Periodontal Inflammation: A Role for Resolvin E1

    Directory of Open Access Journals (Sweden)

    Maria G. Balta

    2017-12-01

    Full Text Available Inflammatory response is a protective biological process intended to eliminate the harmful effect of the insulting influx. Resolution of inflammation constitutes an active sequence of overlapping events mediated by specialized proresolving mediators, such as lipoxins, resolvins, protectins, and maresins, which originate from the enzymatic conversion of polyunsaturated fatty acids (PUFAs. An unresolved acute inflammatory response results in chronic inflammation, which is a leading cause of several common pathological conditions. Periodontitis is a biofilm-induced chronic inflammatory disease, which results in loss of periodontal connective tissue and alveolar bone support around the teeth, leading to tooth exfoliation. An inadequate proresolving host response may constitute a mechanism explaining the pathogenesis of periodontal disease. An emerging body of clinical and experimental evidence has focused on the underlying molecular mechanisms of resolvins and particularly Resolvin E1 (RvE1 in periodontitis. Recently, RvE1 has been directly correlated with the resolution of inflammation in periodontal disease. Herein, we provide a comprehensive overview of the literature regarding the role and possible mechanisms of action of RvE1 on different cell populations recruited in periodontal inflammation as well as its potential therapeutic implications. Along with recent data on the benefits of PUFAs supplementation in periodontal clinical parameters, we touch upon suggested future directions for research.

  10. Data of evolutionary structure change: 1B06E-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B06E-1UNFX 1B06 1UNF E X VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGY...GGG EEEEEEE EEE EEE HHHH HHHHHHHHHH EEHHHHHHHHHHHHHH EVID> LEU CA 300 PRO CA 361 1UNF... X 1UNFX AVNPLVWGGYY....128504991531372 5.267780780792236 EVID>

  11. 26 CFR 301.6223(e)-1 - Effect of Internal Revenue Service's failure to provide notice.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Effect of Internal Revenue Service's failure to... General § 301.6223(e)-1 Effect of Internal Revenue Service's failure to provide notice. (a) Notice group...), the Internal Revenue Service's failure to provide notice to a pass-thru partner entitled to notice...

  12. Heat denaturation of Brazil nut allergen Ber e 1 in relation to food processing.

    Science.gov (United States)

    van Boxtel, Evelien L; Koppelman, Stef J; van den Broek, Lambertus A M; Gruppen, Harry

    2008-10-15

    Ber e 1, a major allergen from Brazil nuts, is very stable to in vitro peptic digestion. As heat-induced denaturation may affect protein digestibility, the denaturation behaviour of Ber e 1 was investigated. The denaturation temperature of Ber e 1 varies from approximately 80-110°C, depending on the pH. Upon heating above its denaturation temperature at pH 7.0, the protein partly forms insoluble aggregates and partly dissociates into its polypeptides, whereas heating at pH 5.0 does neither induce aggregation, nor dissociation of the protein. The denaturation temperature of approximately 110°C at pH values corresponding to the general pH values of foods (pH 5-7) is very high and is expected to be even higher in Brazil nuts themselves. As a result, it is unlikely that heat processing causes the denaturation of all Ber e 1 present in food products. Consequently, the allergen is assumed to be consumed (mainly) in its native form, having a high stability towards pepsin digestion. Copyright © 2008 Elsevier Ltd. All rights reserved.

  13. 26 CFR 301.6511(e)-1 - Special rules applicable to manufactured sugar.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Special rules applicable to manufactured sugar... Assessment and Collection § 301.6511(e)-1 Special rules applicable to manufactured sugar. (a) Use as... the person entitled thereto. Such right accrues as of the date the manufactured sugar, or article...

  14. Two-step method for curing Escherichia coli of ColE1-derived plasmids

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne

    2008-01-01

    To cure Escherichia coli for plasmids derived from the ColE1 replicon advantage is taken of the fact that maintenance of this replicon requires a wild-type allele of polA, encoding DNA polymerase I. Curing is achieved by cotransduction of a mutant polA allele with metE::Tn10, fadAB::Tn10 or other...

  15. E-1 Dynamic Fluid-Flow Model Update: EASY/ROCETS Enhancement and Model Development Support

    Science.gov (United States)

    Follett, Randolph F.; Taylor, Robert P.

    1998-01-01

    This report documents the research conducted to update computer models for dynamic fluid flow simulation of the E-1 test stand subsystems at te NASA John C. Stennis Space Center.Work also involved significant upgrades to the capabilities of EASY/ROCKETS library through the inclusion of the NIST-12 thermodynamic property database and development of new control system modules.

  16. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis.

    Science.gov (United States)

    Makarov, Vadim; Neres, João; Hartkoorn, Ruben C; Ryabova, Olga B; Kazakova, Elena; Šarkan, Michal; Huszár, Stanislav; Piton, Jérémie; Kolly, Gaëlle S; Vocat, Anthony; Conroy, Trent M; Mikušová, Katarína; Cole, Stewart T

    2015-08-01

    8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal bond with Cys387 in the active site of DprE1. To date, substitution of the 8-nitro group has led to extensive loss of antimycobacterial activity. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml against M. tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration (IC50) values of <8 μM and present favorable in vitro absorption-distribution-metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. US NDC Modernization Iteration E1 Prototyping Report: User Interface Framework

    Energy Technology Data Exchange (ETDEWEB)

    Lober, Randall R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-12-01

    During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the User Interface Framework (UIF) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

  18. US NDC Modernization Iteration E1 Prototyping Report: Processing Control Framework

    Energy Technology Data Exchange (ETDEWEB)

    Prescott, Ryan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hamlet, Benjamin R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-12-01

    During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team developed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the processing control framework in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

  19. US NDC Modernization Iteration E1 Prototyping Report: Common Object Interface

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Jennifer E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hess, Michael M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-12-01

    During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the Common Object Interface (COI) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

  20. PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Birk, Jesper Bratz; Sacchetti, Massimo

    2006-01-01

    exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion...... extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1a site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during....... Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1a phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1a phosphorylation, but exercise overrules this effect of FFA on PDH-E1a...

  1. 26 CFR 1.665(e)-1A - Preceding taxable year.

    Science.gov (United States)

    2010-04-01

    ....665(e)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... trust to which an accumulation distribution consisting of undistributed net income or undistributed... distribution consisting of undistributed net income or undistributed capital gain may not be allocated or...

  2. 26 CFR 1.1397E-1T - Qualified zone academy bonds (temporary).

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Empowerment Zone Employment Credit § 1.1397E-1T Qualified... materials for education to be provided at such academy, and training teachers and other school personnel in... or train teachers. Section 1397E(d)(5)(C) and (D) provides that the term qualified purpose with...

  3. Osteogenic gene expression of murine osteoblastic (MC3T3-E1) cells under cyclic tension

    Science.gov (United States)

    Kao, C. T.; Chen, C. C.; Cheong, U.-I.; Liu, S. L.; Huang, T. H.

    2014-08-01

    Low-level laser therapy (LLLT) can promote cell proliferation. The remodeling ability of the tension side of orthodontic teeth affects post-orthodontic stability. The purpose of the present study was to investigate the osteogenic effects of LLLT on osteoblast-like cells treated with a simulated tension system that provides a mechanical tension regimen. Murine osteoblastic (MC3T3-E1) cells were cultured in a Flexcell strain unit with programmed loads of 12% elongation at a frequency of 0.5 Hz for 24 and 48 h. The cultured cells were treated with a low-level diode laser using powers of 5 J and 10 J. The proliferation of MC3T3-E1 cells was determined using the Alamar Blue assay. The expression of osteogenic genes (type I collagen (Col-1), osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), bone morphologic protein (BMP-2), and bone morphologic protein (BMP-4)) in MC3T3-E1 cells was analyzed using reverse transcription polymerase chain reaction (RT-PCR). The data were analyzed using one-way analysis of variance. The proliferation rate of tension-cultured MC3T3-E1 cells under 5 J and 10 J LLLT increased compared with that of the control group (p < 0.05). Prominent mineralization of the MC3T3-E1 cells was visible using a von Kossa stain in the 5 J LLLT group. Osteogenic genes (Col-1, OC, OPG and BMP-2) were significantly expressed in the MC3T3-E1 cells treated with 5 J and 10 J LLLT (p < 0.05). LLLT in tension-cultured MC3T3-E1 cells showed synergistic osteogenic effects, including increases in cell proliferation and Col-1, OPN, OC, OPG and BMP-2 gene expression. LLLT might be beneficial for bone remodeling on the tension side of orthodontics.

  4. Gender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1

    Science.gov (United States)

    Matsushita, Noriko; Hassanein, Mohamed T.; Martinez-Clemente, Marcos; Lazaro, Raul; French, Samuel W.; Xie, Wen; Lai, Keane; Karin, Michael; Tsukamoto, Hidekazu

    2017-01-01

    Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1), which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKβ of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKβ is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients. PMID:28797077

  5. Gender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1.

    Directory of Open Access Journals (Sweden)

    Noriko Matsushita

    Full Text Available Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1, which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKβ of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKβ is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients.

  6. Adenovirus E1A proteins direct subcellular redistribution of Nek9, a NimA-related kinase.

    Science.gov (United States)

    Pelka, Peter; Scimè, Anthony; Mandalfino, Christina; Joch, Monica; Abdulla, Parween; Whyte, Peter

    2007-07-01

    A monoclonal antibody raised against adenovirus E1A-associated cellular proteins recognized Nek9, a NimA-related protein kinase. Subcellular fractionation and immunofluorescence indicated that Nek9 was primarily cytoplasmic with a small portion located in the nucleus whereas E1A was primarily nuclear. Although co-immunoprecipitation experiments indicated that nuclear Nek9 interacted, directly or indirectly, with E1A, the major effect of E1A was to diminish the amount of Nek9 in the nucleus suggesting that E1A alters the subcellular distribution of Nek9 and that the interaction is transient. A Nek9 deletion mutant lacking a central RCC1-like domain interacted stably with E1A and accumulated in the nucleus in the presence of E1A, possibly representing an intermediate stage of the normally transient Nek9/E1A interaction. The interaction of Nek9 with E1A was dependent on the N-terminal sequences of E1A. Attempts to stably overexpress either Nek9 or the kinase-inactive mutant in various cell lines were unsuccessful; however, the presence of E1A allowed stable overexpression of both proteins. These results suggest that E1A disrupts a nuclear function of Nek9.

  7. Ad E1A 243R oncoprotein promotes association of proto-oncogene product MYC with the NuA4/Tip60 complex via the E1A N-terminal repression domain.

    Science.gov (United States)

    Zhao, Ling-Jun; Loewenstein, Paul M; Green, Maurice

    2016-12-01

    The adenovirus E1A 243R oncoprotein targets TRRAP, a scaffold protein that assembles histone acetyltransferase (HAT) complexes, such as the NuA4/Tip60 complex which mediates transcriptional activity of the proto-oncogene MYC and helps determine the cancer cell phenotype. How E1A transforms cells through TRRAP remains obscure. We performed proteomic analysis with the N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) and showed that E1A 1-80 interacts with TRRAP, p400, and three other members of the NuA4 complex - DMAP1, RUVBL1 and RUVBL2 - not previously shown to associate with E1A 243R. E1A 1-80 interacts with these NuA4 components and MYC through the E1A TRRAP-targeting domain. E1A 243R association with the NuA4 complex was demonstrated by co-immunoprecipitation and analysis with DMAP1, Tip60, and MYC. Significantly, E1A 243R promotes association of MYC/MAX with the NuA4/Tip60 complex, implicating the importance of the MYC/NuA4 pathway in cellular transformation by both MYC and E1A. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Sonochemical synthesis of novel pyrano[3,4-e][1,3]oxazines: A green protocol.

    Science.gov (United States)

    Saleh, Tamer S; Al-Bogami, Abdullah S; Mekky, Ahmed E M; Alkhathlan, Hamad Z

    2017-05-01

    The atom-efficient and green protocol for formation of pyrano[3,4-e][1,3]oxazines utilizing dimethyl carbonate under ultrasound irradiation in a presence of KF/basic alumina was reported. We provide a novel series of pyrano[3,4-e][1,3]oxazine derivatives interesting for biological screening tests. In general, it was found that ultrasound irradiations enable the reactions to occur which could not be carried out under silent conditions. These remarkable effects appeared in sonicated reactions can be reasonably interpreted in terms of acoustic cavitation phenomenon. Structures of the products were established on analytical and spectral data. This protocol offers several advantages attain many principles of green chemistry including, save energy, atom economy, clean reactions, inexpensive green reagent and use catalysts rather than stoichiometric reagents. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Ultrasound associated uptake of chitosan nanoparticles in MC3T3-E1 cells

    Science.gov (United States)

    Wu, Junyi

    Chitosan is a natural linear polysaccharide that has been well known for its applications in drug delivery system due to its unique physicochemical and biological properties. However, challenges still remain for it to become a fully realized therapeutic agent. In this study, we investigated the uptake of chitosan nanoparticles (CNP) under the ultrasound stimulation, using a model cell culture system (MC3T3-E1 mouse pre-osteoblasts). The CNP were fabricated by an ionic gelation method and were lyophilized prior to characterization and delivery to cells. Particle size and zeta potential were measured using Dynamic Light Scattering (DLS); the efficiency of chitosan complexation was measured using the ninhydrin assay. Cytotoxicity was examined by neutral red assay within 48 hours after delivery. The effect of ultrasound (US) on the efficiency of nanoparticle delivery to the MC3T3-E1 cells was examined at 1MHz and at either 1 or 2 W/cm2. Fluorescein isothiocyanate (FITC)-conjugated-CNP were used to visualize the internalized particles within the cytosol. The uptake of FITC-CNP exhibits a dose and time dependent effect, a strong FITC fluorescence was detected at the concentration of 500microg/mL under fluorescence microscope. Ultrasound assisted uptake of FITC-CNP performed a significant positive effect at 2W/cm2 with 60s of ultrasound exposure time. CNP displayed a slightly decrease in cell viability from 25microg/mL to 100microg/mL, while higher concentration of CNP facilitates the proliferation of MC3T3-E1 cells. Less than 10% of reduction in cell viability was observed for US at 1W/cm2 and 2W/cm2 with 30s and 60s of exposure time, which suggest a mild effect of US to MC3T3-E1 cell line.

  10. E1-catalyzed ubiquitin C-terminal amidation for the facile synthesis of deubiquitinase substrates.

    Science.gov (United States)

    Wang, Xiaoyan Aria; Kurra, Yadagiri; Huang, Ying; Lee, Yan-Jiun; Liu, Wenshe R

    2014-01-03

    Will Ub my partner? The ubiquitin (Ub)-activating enzyme (E1) was used to catalyze an amidation reaction to functionalize the C terminus of Ub with unique functional groups, such as thiol, azide, alkyne, and alkene groups, with high efficiency and yield (>90 %). These groups were then applied for the facile synthesis of fluorophore-conjugated ubiquitin and specifically conjugated diubiquitin substrates for deubiquitinases. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. A very simple and convenient synthesis of tosylethylene and (E)-1,2-ditosylethylene

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, D.A.; Arques, A.; Najera, C.; Sansano, J.M. [Departamento Quimica Organica, Facultad de Ciencias, Universidad de Alicante (Spain)

    1995-12-31

    A two-steps procedure for the synthesis of p-totyl vinyl sulfone in 80% yield by reaction of sodium p-toluenesulfinate with 1-bromo-2-chloro ethane followed by in situ dehydrochlorination with triethylamine is described. Iodosulfonylation of p-totyl vinyl sulfone with tosyl iodine and further in situ dehydroiodination with trietylamine affords stereo selectively (E)-1,2-ditosylethylene in 70% overall yield. (Author) 11 refs.

  12. Negatively cooperative binding properties of human cytochrome P450 2E1 with monocyclic substrates.

    Science.gov (United States)

    Ping, Jie; Wang, Ya-Jun; Wang, Jing-Fang; Li, Xuan; Li, Yi-Xue; Hao, Pei

    2012-09-01

    Human CYP2E1 accounts for almost 2% of total CYP enzymes in the liver cells, and plays a crucial role in the metabolism of small molecular weight compounds. This enzyme is associated with the nearly 6% metabolisms of the currently clinical drugs. However, it is found that CYP2E1 has a non-hyperbolic kinetic profile that can not be explained by the common Michaelis-Menten mechanism. Further studies show that the non-hyperbolic kinetic behaviors are associated with multiple substrate binding, which is also known as the cooperative binding properties. However, the detailed mechanism for the cooperative binding is not clear by now. In this paper, we summarized the experimental and theoretical studies on the cooperative binding mechanism. Based on the structural analysis, a second substrate binding site is confirmed in human CYP2E1, which is located neither in the region near Leu103, Leu210 and Phe478, nor far from the active site. Additionally, two important residues Thr303 and Phe478 are also identified to be the key factors in the cooperative binding on the short-range and long-range effects, respectively. The former plays a crucial role in the positioning of substrates and in proton delivery to the active site; the latter is located between the substrate access channel and the active site, and exhibits directly effects on substrate access or on substrate positioning in the active site. All these points can provide useful information for the cooperative binding in human CYP2E1, revealing the detailed mechanism for the non-hyperbolic kinetic behaviors.

  13. Mouse Spermatocytes Express CYP2E1 and Respond to Acrylamide Exposure

    Science.gov (United States)

    Nixon, Belinda J.; Katen, Aimee L.; Stanger, Simone J.; Schjenken, John E.; Nixon, Brett; Roman, Shaun D.

    2014-01-01

    Metabolism of xenobiotics by cytochrome P450s (encoded by the CYP genes) often leads to bio-activation, producing reactive metabolites that interfere with cellular processes and cause DNA damage. In the testes, DNA damage induced by xenobiotics has been associated with impaired spermatogenesis and adverse effects on reproductive health. We previously reported that chronic exposure to the reproductive toxicant, acrylamide, produced high levels of DNA damage in spermatocytes of Swiss mice. CYP2E1 metabolises acrylamide to glycidamide, which, unlike acrylamide, readily forms adducts with DNA. Thus, to investigate the mechanisms of acrylamide toxicity in mouse male germ cells, we examined the expression of the CYP, CYP2E1, which metabolises acrylamide. Using Q-PCR and immunohistochemistry, we establish that CYP2E1 is expressed in germ cells, in particular in spermatocytes. Additionally, CYP2E1 gene expression was upregulated in these cells following in vitro acrylamide exposure (1 µM, 18 h). Spermatocytes were isolated and treated with 1 µM acrylamide or 0.5 µM glycidamide for 18 hours and the presence of DNA-adducts was investigated using the comet assay, modified to detect DNA-adducts. Both compounds produced significant levels of DNA damage in spermatocytes, with a greater response observed following glycidamide exposure. A modified comet assay indicated that direct adduction of DNA by glycidamide was a major source of DNA damage. Oxidative stress played a small role in eliciting this damage, as a relatively modest effect was found in a comet assay modified to detect oxidative adducts following glycidamide exposure, and glutathione levels remained unchanged following treatment with either compound. Our results indicate that the male germ line has the capacity to respond to xenobiotic exposure by inducing detoxifying enzymes, and the DNA damage elicited by acrylamide in male germ cells is likely due to the formation of glycidamide adducts. PMID:24788432

  14. Roles of DNA polymerase I in leading and lagging-strand replication defined by a high-resolution mutation footprint of ColE1 plasmid replication.

    Science.gov (United States)

    Allen, Jennifer M; Simcha, David M; Ericson, Nolan G; Alexander, David L; Marquette, Jacob T; Van Biber, Benjamin P; Troll, Chris J; Karchin, Rachel; Bielas, Jason H; Loeb, Lawrence A; Camps, Manel

    2011-09-01

    DNA polymerase I (pol I) processes RNA primers during lagging-strand synthesis and fills small gaps during DNA repair reactions. However, it is unclear how pol I and pol III work together during replication and repair or how extensive pol I processing of Okazaki fragments is in vivo. Here, we address these questions by analyzing pol I mutations generated through error-prone replication of ColE1 plasmids. The data were obtained by direct sequencing, allowing an accurate determination of the mutation spectrum and distribution. Pol I's mutational footprint suggests: (i) during leading-strand replication pol I is gradually replaced by pol III over at least 1.3 kb; (ii) pol I processing of Okazaki fragments is limited to ∼20 nt and (iii) the size of Okazaki fragments is short (∼250 nt). While based on ColE1 plasmid replication, our findings are likely relevant to other pol I replicative processes such as chromosomal replication and DNA repair, which differ from ColE1 replication mostly at the recruitment steps. This mutation footprinting approach should help establish the role of other prokaryotic or eukaryotic polymerases in vivo, and provides a tool to investigate how sequence topology, DNA damage, or interactions with protein partners may affect the function of individual DNA polymerases.

  15. Effects of 6-Hydroxyflavone on Osteoblast Differentiation in MC3T3-E1 Cells

    Directory of Open Access Journals (Sweden)

    Chien-Hung Lai

    2014-01-01

    Full Text Available Osteoblast differentiation plays an essential role in bone integrity. Isoflavones and some flavonoids are reported to have osteogenic activity and potentially possess the ability to treat osteoporosis. However, limited information concerning the osteogenic characteristics of hydroxyflavones is available. This study investigates the effects of various hydroxyflavones on osteoblast differentiation in MC3T3-E1 cells. The results showed that 6-hydroxyflavone (6-OH-F and 7-hydroxyflavone (7-OH-F stimulated ALP activity. However, baicalein and luteolin inhibited ALP activity and flavone showed no effect. Up to 50 μM of each compound was used for cytotoxic effects study; flavone, 6-OH-F, and 7-OH-F had no cytotoxicity on MC3T3-E1 cells. Moreover, 6-OH-F activated AKT and serine/threonine kinases (also known as protein kinase B or PKB, extracellular signal-regulated kinases (ERK 1/2, and the c-Jun N-terminal kinase (JNK signaling pathways. On the other hand, 7-OH-F promoted osteoblast differentiation mainly by activating ERK 1/ 2 signaling pathways. Finally, after 5 weeks of 6-OH-F induction, MC3T3-E1 cells showed a significant increase in the calcein staining intensity relative to merely visible mineralization observed in cells cultured in the osteogenic medium only. These results suggested that 6-OH-F could activate AKT, ERK 1/2, and JNK signaling pathways to effectively promote osteoblastic differentiation.

  16. Comparison of chlorzoxazone one-sample methods to estimate CYP2E1 activity in humans

    DEFF Research Database (Denmark)

    Kramer, Iza; Dalhoff, Kim; Clemmesen, Jens O

    2003-01-01

    OBJECTIVE: Comparison of a one-sample with a multi-sample method (the metabolic fractional clearance) to estimate CYP2E1 activity in humans. METHODS: Healthy, male Caucasians ( n=19) were included. The multi-sample fractional clearance (Cl(fe)) of chlorzoxazone was compared with one-time-point cl......OBJECTIVE: Comparison of a one-sample with a multi-sample method (the metabolic fractional clearance) to estimate CYP2E1 activity in humans. METHODS: Healthy, male Caucasians ( n=19) were included. The multi-sample fractional clearance (Cl(fe)) of chlorzoxazone was compared with one......-time-point clearance estimation (Cl(est)) at 3, 4, 5 and 6 h. Furthermore, the metabolite/drug ratios (MRs) estimated from one-time-point samples at 1, 2, 3, 4, 5 and 6 h were compared with Cl(fe). RESULTS: The concordance between Cl(est) and Cl(fe) was highest at 6 h. The minimal mean prediction error (MPE) of Cl......-dose-sample estimates, Cl(est) at 3 h or 6 h, and MR at 3 h, can serve as reliable markers of CYP2E1 activity. The one-sample clearance method is an accurate, renal function-independent measure of the intrinsic activity; it is simple to use and easily applicable to humans....

  17. Ovarian Hormone Estrone Glucuronide (E1G) quantification-impedimetric electrochemical spectroscopy approach

    KAUST Repository

    Zia, Asif I.

    2013-12-01

    A study was conducted on detection and concentration measurement of estrone glucuronide (E1G), an important metabolite of the ovarian hormone estradiol, by using Electrochemical Impedance Spectroscopy (EIS) technique. A miniature planar Inter-digital (ID) capacitive sensor fabricated on single crystal silicon substrate with sputtered gold electrodes coupled with EIS was used to measure conductivity, permeability and dielectric properties of the said hormone metabolite. A thin film of Silicon Nitride (50 um) was coated on the sensor as passivation layer to avoid Faradic currents through the sensor. Impedance spectrums were obtained with various concentrations of E1G in buffer solution by exposing the samples to electrical perturbations at certain frequency range. Relationship of sample conductance with E1G concentration was studied on basis Randle\\'s equivalent circuit model and results were analyzed to deduce Constant Phase Equivalent (CPE) Circuit model in order to evaluate the double layer capacitance produced at the solution-electrode interface due to kinetic processes taking place in the electrochemical cell. The sensitivity of the sensor was evaluated against concentration. The result analysis confirmed that fabricated ID sensor together with EIS can provide a rapid and successful low cost sensing system which can help a lay user to determine peak time for feminine reproductive fertility at home without submitting samples for an expensive and time consuming laboratory test. © 2013 IEEE.

  18. Bacteriocin synthesis in uropathogenic and commensal Escherichia coli: colicin E1 is a potential virulence factor

    Directory of Open Access Journals (Sweden)

    Vališová Zuzana

    2010-11-01

    Full Text Available Abstract Background Bacteriocin production is an important characteristic of E. coli strains of human origin. To date, 26 colicin and 9 microcin types have been analyzed on a molecular level allowing molecular detection of the corresponding genes. The production incidence of 29 bacteriocin types and E. coli phylogroups were tested in a set of 361 E. coli strains isolated from human urinary tract infections (UTI and in 411 control strains isolated from feces of patients without bacterial gut infection. Results Production of 17 and 20 individual bacteriocin types was found in the UTI and control strains, respectively. Microcin H47 encoding determinants were found more often among UTI strains compared to controls (37.9% and 27.0% respectively, p = 0.02 and strains producing microcin H47 belonged predominantly to phylogroup B2 when compared to other bacteriocin producers (67.4% and 36.7%, respectively; p vice versa suggesting that pColE1 was independently associated with pColIa in UTI strains. Conclusion E. coli strains isolated from human urinary tract infections showed increased incidence of microcin H47 and colicin E1 production, respectively. Moreover, colicin E1 itself appears to be a potentially important virulence factor of certain uropathogenic E. coli strains.

  19. Effects of nicotine on cytochrome P450 2A6 and 2E1 activities

    Science.gov (United States)

    Hukkanen, Janne; Jacob, Peyton; Peng, Margaret; Dempsey, Delia; Benowitz, Neal L

    2010-01-01

    AIMS Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone, which are probe reactions for cytochrome P450 2A6 (CYP2A6) and CYP2E1 activities, respectively. We aimed to determine the role of nicotine in these metabolic effects of cigarette smoking. METHODS The study had a single-blind, randomized, crossover two-arm design. Twelve healthy smokers were given two transdermal patches with 42-mg nicotine a day or placebo patches, each for 10 days. The subjects abstained from smoking during the study arms. Oral chlorzoxazone was given on day 7 and deuterium-labelled nicotine-d2 and cotinine-d4 infusion on day 8. RESULTS There was no significant influence of transdermal nicotine administration on pharmacokinetic parameters of nicotine-d2 or on the formation of cotinine-d2. Nicotine decreased the volume of distribution (62.6 vs. 67.7 l, 95% confidence interval of the difference −9.7, −0.6, P= 0.047) of infused cotinine-d4. There were no significant differences in disposition kinetics of chlorzoxazone between the treatments. CONCLUSIONS CYP2A6 and CYP2E1 activities are not affected by nicotine. The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities remain unknown. PMID:20233178

  20. In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians.

    Science.gov (United States)

    Kim, R B; Yamazaki, H; Chiba, K; O'Shea, D; Mimura, M; Guengerich, F P; Ishizaki, T; Shimada, T; Wilkinson, G R

    1996-10-01

    Chlorzoxazone's disposition after oral administration was determined in 20 young healthy Caucasian men and a similar group of Japanese men. The drug's plasma concentrations were significantly higher and its rate of elimination slower in Japanese compared to Caucasian men. Accordingly, chlorzoxazone's oral clearance was smaller (40%) in Japanese men and a similar difference (30%) was still apparent after normalizing for body weight (3.74 +/- 1.23 versus 5.05 +/- 1.41 ml.min-1.kg-1, P relationships were found between measures of CYP2E1 activity, both in vivo and in vitro, and genomic polymorphisms in the CYP2E1 gene identified by Rsal/Pstl and Dral restriction fragment length polymorphisms. Collectively, these data show an interracial difference in CYP2E1 activity. Because this enzyme is importantly involved in the activation of environmental procarcinogens, such a difference may account, in part, for the lower rate of some cancers, e.g., lung cancer, in Japanese compared to Caucasians men.

  1. Ubiquitination independent of E1 and E2 enzymes by bacterial effectors

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Jiazhang; Sheedlo, Michael J.; Yu, Kaiwen; Tan, Yunhao; Nakayasu, Ernesto S.; Das, Chittaranjan; Liu, Xiaoyun; Luo, Zhao-Qing

    2016-04-06

    Signaling by ubiquitination regulates virtually every cellular process in eukaryotes. Covalent attachment of ubiquitin to a substrate is catalyzed by the E1, E2 and E3 three-enzyme cascade 1, which links the C terminus of ubiquitin via an isopeptide bond mostly to the ε-amino group of a lysine of the substrate. Given the essential roles of ubiquitination in the regulation of the immune system, it is not surprising that the ubiquitination network is a common target for diverse infectious agents 2. For example, many bacterial pathogens exploit ubiquitin signaling using virulence factors that function as E3 ligases, deubiquitinases 3 or as enzymes that directly attack ubiquitin 4. The bacterial pathogen Legionella pneumophila utilizes approximately 300 effectors that modulate diverse host processes to create a niche permissive for its replication in phagocytes 5. Here we demonstrate that members of the SidE effector family (SidEs) of L. pneumophila ubiquitinate multiple Rab small GTPases associated with the endoplasmic reticulum (ER). Moreover, we show that these proteins are capable of catalyzing ubiquitination without the need for the E1 and E2 enzymes. The E1/E2-independent ubiquitination catalyzed by these enzymes requires NAD but not ATP and Mg2+. A putative mono ADP-ribosyltransferase (mART) motif critical for the ubiquitination activity is also essential for the role of SidEs in intracellular bacterial replication in a protozoan host. These results establish that ubiquitination can be catalyzed by a single enzyme.

  2. The importance of being relevant

    Directory of Open Access Journals (Sweden)

    Snehlata eJaswal

    2012-08-01

    Full Text Available This review aims at an understanding of the binding process by synthesizing the extant perspectives regarding binding. It begins with a consideration of the biological explanations of binding, viz., conjunctive coding, synchrony, and reentrant mechanisms. Thereafter binding is reviewed as a psychological process guided by top down signals. The stages and types of binding proposed by various researchers are discussed in this section. The next section introduces Working Memory as the executive directing the top-down signals. After that it is described how Working Memory works by selecting relevant sensory input, followed by a detailed consideration of the debate regarding objects vs. features with the conclusion that relevance is the key factor determining what is processed. The next section considers other factors affecting the selection of relevant input. Then, we shift focus to describe what happens to irrelevant input – whether it is discarded at the outset or is gradually inhibited, and whether inhibition is a perceptual or post-perceptual process. The concluding section describes the process of binding as currently understood on the basis of the literature included in the review. To summarize, it appears that initially the ‘object’ is conceptualized as an instantaneous bundle of all features. However, only relevant features of stimuli are gradually integrated to form a stable representation of the object. Concomitantly, irrelevant features are removed from the object representations. Empirical evidence suggests that the inhibition of irrelevant features occurs over time and is thus presumably a process within Working Memory.

  3. Regularization in Matrix Relevance Learning

    NARCIS (Netherlands)

    Schneider, Petra; Bunte, Kerstin; Stiekema, Han; Hammer, Barbara; Villmann, Thomas; Biehl, Michael

    A In this paper, we present a regularization technique to extend recently proposed matrix learning schemes in learning vector quantization (LVQ). These learning algorithms extend the concept of adaptive distance measures in LVQ to the use of relevance matrices. In general, metric learning can

  4. Making Plant Biology Curricula Relevant.

    Science.gov (United States)

    Hershey, David R.

    1992-01-01

    Reviews rationale, purposes, challenges, and relevance of hands-on, plant biology curricula that have been developed in response to the limited use of plants in biology education. Discusses methods to maintain both instructional rigor and student interest in the following topics: cut flowers, container-growing media, fertilizers, hydroponics,…

  5. BIBLE TRANSLATION AND RELEVANCE THEORY

    African Journals Online (AJOL)

    Wilss's text book (Wilss 1982) suggests that the situation in general translation theory is not very different. It was precisely this model of communication theory that was challenged by Sperber and Wilson's relevance theory (Sperber & Wilson 1986; see also Wilson & Sperber 1987). Set within this context this paper seeks to ...

  6. Lexicography and the Relevance Criterion

    African Journals Online (AJOL)

    This will be done within the framework of the function theory .... Gouws (2011) supports this vision and stresses that learning from each other .... specific type of need, e.g. to solve a communicative or cognitive problem, ..... According to Borlund (2000) "the judgement of situational relevance ..... Management 36(4): 533-550.

  7. The adenovirus E1A N-terminal repression domain represses transcription from a chromatin template in vitro.

    Science.gov (United States)

    Loewenstein, Paul M; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Green, Maurice

    2012-06-20

    The adenovirus repression domain of E1A 243R at the E1A N-terminus (E1A 1-80) transcriptionally represses genes involved in differentiation and cell cycle progression. E1A 1-80 represses transcription in vitro from naked DNA templates through its interaction with p300 and TFIID. E1A 1-80 can also interact with several chromatin remodeling factors and associates with chromatin in vivo. We show here that E1A 243R and E1A 1-80 can repress transcription from a reconstituted chromatin template in vitro. Temporal analysis reveals strong repression by E1A 1-80 when added at pre-activation, activation and early transcription stages. Interestingly, E1A 1-80 can greatly enhance transcription from chromatin templates, but not from naked DNA, when added at pre-initiation complex (PIC) formation and transcription-initiation stages. These data reveal a new dimension for E1A 1-80's interface with chromatin and may reflect its interaction with key players in PIC formation, p300 and TFIID, and/or possibly a role in chromatin remodeling. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Farnesoid X receptor regulates SULT1E1 expression through inhibition of PGC1α binding to HNF4α.

    Science.gov (United States)

    Wang, Shuai; Yuan, Xue; Lu, Danyi; Guo, Lianxia; Wu, Baojian

    2017-12-01

    Sulfotransferase 1E1 (SULT1E1, also known as estrogen sulfotransferase) plays an important role in metabolism and detoxification of many endogenous and exogenous compounds (e.g., estrogens and flavonoids). Here we aimed to assess the effects of farnesoid X receptor (FXR) activation on SULT1E1 expression, and to determine the mechanism thereof. Treatment with specific FXR agonists (i.e., GW4064 and CDCA) significantly decreased both mRNA and protein levels of SULT1E1 in HepG2 cells. This was accompanied by a decrease in the enzymatic activity. The inhibitory effect was potentiated by FXR overexpression but attenuated by FXR knockdown, confirming FXR-dependent regulation of SULT1E1. Surprisingly, direct regulation of SULT1E1 by FXR was unlikely because FXR did not bind to SULT1E1 promoter or enhancer as revealed by chromatin immunoprecipitation (ChIP). Interestingly, SULT1E1 regulation was abolished when HNF4α (hepatocyte nuclear factor 4α, a known activator of SULT1E1) was silenced, supporting a critical role for HNF4α in FXR regulation of SULT1E1. Furthermore, a combination of ChIP, luciferase reporter and co-immunoprecipitation assays showed that FXR inhibited HNF4α transactivation of SULT1E1 by suppressed binding of the co-activator PGC1α (peroxisome proliferator-activated receptor-γ coactivator 1α) to HNF4α. In conclusion, FXR transcriptionally regulates SULT1E1 through inhibition of PGC1α binding to HNF4α. Targeting the FXR-SULT1E1 axis may represent a promising approach for management of estrogen-related diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8 + T cells aid progression of environment-linked nonalcoholic steatohepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Seth, Ratanesh Kumar; Das, Suvarthi [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kumar, Ashutosh [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Chanda, Anindya [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kadiiska, Maria B. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Michelotti, Gregory [Division of Gastroenterology, Duke University, Durham, NC 27707 (United States); Manautou, Jose [Dept. of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-3092 (United States); Diehl, Anna Mae [Division of Gastroenterology, Duke University, Durham, NC 27707 (United States); Chatterjee, Saurabh, E-mail: schatt@mailbox.sc.edu [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States)

    2014-01-01

    Environmental toxins induce a novel CYP2E1/leptin signaling axis in liver. This in turn activates a poorly characterized innate immune response that contributes to nonalcoholic steatohepatitis (NASH) progression. To identify the relevant subsets of T-lymphocytes in CYP2E1-dependent, environment-linked NASH, we utilized a model of diet induced obese (DIO) mice that are chronically exposed to bromodichloromethane. Mice deficient in CYP2E1, leptin (ob/ob mice), or both T and B cells (Pfp/Rag2 double knockout (KO) mice) were used to delineate the role of each of these factors in metabolic oxidative stress-induced T cell activation. Results revealed that elevated levels of lipid peroxidation, tyrosyl radical formation, mitochondrial tyrosine nitration and hepatic leptin as a consequence of metabolic oxidative stress caused increased levels of hepatic CD57, a marker of peripheral blood lymphocytes including NKT cells. CD8 + CD57 + cytotoxic T cells but not CD4 + CD57 + cells were significantly decreased in mice lacking CYP2E1 and leptin. There was a significant increase in the levels of T cell cytokines IL-2, IL-1β, and IFN-γ in bromodichloromethane exposed DIO mice but not in mice that lacked CYP2E1, leptin or T and B cells. Apoptosis as evidenced by TUNEL assay and levels of cleaved caspase-3 was significantly lower in leptin and Pfp/Rag2 KO mice and highly correlated with protection from NASH. The results described above suggest that higher levels of oxidative stress-induced leptin mediated CD8 + CD57 + T cells play an important role in the development of NASH. It also provides a novel insight of immune dysregulation and may be a key biomarker in NASH. - Highlights: • Metabolic oxidative stress caused increased levels of hepatic CD57 expression. • CD8+ CD57+ cytotoxic T cells were decreased in mice lacking CYP2E1 and leptin. • There was a significant increase in T cell cytokines in toxin-treated mice. • Apoptosis was significantly lower in leptin and Pfp

  10. 75 FR 53262 - Privacy Act of 1974; System of Records

    Science.gov (United States)

    2010-08-31

    ..., and analytics across multiple existing databases. The system also allows users to save their queries... sources, and witnesses. (4) From subsection (e)(1) because it is not always possible to know in advance... impossible to determine in advance what information is accurate, relevant, timely and complete. With time...

  11. Effects of ethanol on CYP2E1 levels and related oxidative stress using a standard balanced diet.

    Science.gov (United States)

    Azzalis, Ligia A; Fonseca, Fernando L A; Simon, Karin A; Schindler, Fernanda; Giavarotti, Leandro; Monteiro, Hugo P; Videla, Luis A; Junqueira, Virgínia B C

    2012-07-01

    Expression of cytochrome P4502E1 (CYP2E1) is very much influenced by nutritional factors, especially carbohydrate consumption, and various results concerning the expression of CYP2E1 were obtained with a low-carbohydrate diet. This study describes the effects of ethanol treatment on CYP2E1 levels and its relationship with oxidative stress using a balanced standard diet to avoid low or high carbohydrate consumption. Rats were fed for 1, 2, 3, or 4 weeks a commercial diet plus an ethanol-sucrose solution. The results have shown that ethanol administration was associated with CYP2E1 induction and stabilization without related oxidative stress. Our findings suggest that experimental models with a low-carbohydrate/high-fat diet produce some undesirable CYP2E1 changes that are not present when a balanced standard diet is given.

  12. A Generative Theory of Relevance

    Science.gov (United States)

    2004-09-01

    latent representation space . 2We need the Fubini -Tonelli theorem because the parameter space h is uncountable and the information representation space i...models can be expressed in a simple common form that is a direct consequence of De-Finetti’s representation theorem . We draw several unexpected...who defines relevance in terms of entailment (as in theorem -proving). Suppose G represents a logical proposition corresponding to a user’s request

  13. ON SPACELIKE BIHARMONIC SLANT HELICES ACCORDING TO BISHOP FRAME IN THE LORENTZIAN GROUP OF RIGID MOTIONS E(1,1

    Directory of Open Access Journals (Sweden)

    Talat Körpınar

    2012-01-01

    Full Text Available In this paper, we study spacelike biharmonic slant helices according to Bishop frame in the Lorentzian group of rigid motions E(1,1. We characterize the spacelike biharmonic slant helices in terms of their curvatures in the Lorentzian group of rigid motions E(1,1. Finally, we obtain parametric equations of spacelike biharmonic slant helices according to Bishop frame in the Lorentzian group of rigid motions E(1,1.

  14. E1 density transitions from the low-energy deuteron photodisintegration

    Energy Technology Data Exchange (ETDEWEB)

    Lipparini, E.; Orlandini, G. (Trento Univ. (Italy). Dipartimento di Fisica)

    1982-01-18

    The dynamical dipole polarizability and transition density for the deuteron are studied in the Bethe-Peierls model for deuteron photodisintegration. In two limiting values of the frequency of the oscillating field, the transition density is shown to have simple forms corresponding to pure surface and a mixing of surface and volume deformations respectively. Predictions for the low-sub(q) behaviour of the E1 form factor are given. A unitary transformation for the evaluation of the static polarizability in heavier nuclei is suggested.

  15. Alternative forms of lethality in mitomycin C-induced bacteria carrying ColE1 plasmids

    OpenAIRE

    Suit, Joan L.; Fan, M.-L. Judy; Sabik, Joseph F.; Labarre, Robert; Luria, S. E.

    1983-01-01

    We have studied the physiological effects of mitomycin C induction on cells carrying ColE1 plasmids with differing configurations of three genes: the structural gene coding for colicin (cea), a gene responsible for mitomycin C lethality (kil) that we located as part of an operon with cea, and the immunity (imm) gene, which lies near cea but is not in the same operon. kil is close to or overlaps imm. When cea+ plasmids are present mitomycin C induction results in 100-fold or greater increases ...

  16. Occupational Survey Report. Ground Radio Communications, AFSC 2E1X3

    Science.gov (United States)

    2003-10-01

    analyzed the data, and wrote the final report. Mr. Tyrone Hill provided computer-programming support, and Ms. Dolores Navarro and Ms. Sherry Evans...AFSC 2E1X3 members selected military-related education and training opportunities and medical/ dental care for AD members as their second and third...TRAINING OPPORTUNITIES 52 2.52 55 2.49 50 2.34 MEDICAL/ DENTAL CARE FOR AD MEMBER 60 2.57 55 2.56 53 2.48 MEDICAL/ DENTAL CARE FOR FAMILY MEMBERS 48

  17. Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers.

    Science.gov (United States)

    Bedada, Satish Kumar; Boga, Praveen Kumar

    2017-12-01

    1. The purpose of the present study was to investigate the effect of piperine (PIP) on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy volunteers. 2. An open-label, two period, sequential study was conducted in 12 healthy volunteers. A single dose of PIP 20 mg was administered daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed by HPLC. 3. Treatment with PIP significantly enhanced maximum plasma concentration (Cmax) (3.14-4.96 μg/mL), area under the curve (AUC) (10.46-17.78 μg h/mL), half life (T1/2) (1.26-1.82 h) and significantly decreased elimination rate constant (Kel) (0.57-0.41 h (-) (1)), apparent oral clearance (CL/F) (24.76-13.65 L/h) of CHZ when compared to control. In addition, treatment with PIP significantly decreased Cmax (0.22-0.15 μg/mL), AUC (0.94-0.68 μg h/mL), T1/2 (2.54-1.68 h) and significantly increased Kel (0.32-0.43 h (-) (1)) of 6-hydroxychlorzoxazone (6-OHCHZ) as compared to control. Furthermore, treatment with PIP significantly decreased metabolite to parent (6-OHCHZ/CHZ) ratios of Cmax, AUC, T1/2 and significantly increased Kel ratio of 6-OHCHZ/CHZ, which indicate the decreased formation of CHZ to 6-OHCHZ. 4. The results suggest that altered pharmacokinetics of CHZ might be attributed to PIP mediated inhibition of CYP2E1 enzyme, which indicate significant pharmacokinetic interaction present between PIP and CHZ. The inhibition of CYP2E1 by PIP may represent a novel therapeutic benefit for minimizing ethanol induced CYP2E1 enzyme activity and results in reduced hepatotoxicity of ethanol.

  18. Ethanol Induction of CYP2A5: Role of CYP2E1-ROS-Nrf2 Pathway

    Science.gov (United States)

    Lu, Yongke; Zhang, Xu Hannah

    2012-01-01

    Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1-dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same degree in wild-type (WT) mice and CYP2A5 knockout (Cyp2a5 –/–) mice, suggesting that unlike the CYP2E1-dependent ethanol induction of CYP2A5, ethanol induction of CYP2E1 is not CYP2A5 dependent. Microsomal ethanol oxidation was about 25% lower in Cyp2a5 –/– mice compared with that in WT mice, suggesting that CYP2A5 can oxidize ethanol although to a lesser extent than CYP2E1 does. CYP2A5 was induced by short-term ethanol consumption in human CYP2E1 transgenic knockin (Cyp2e1 –/– KI) mice but not in CYP2E1 knockout (Cyp2e1 –/–) mice. The redox-sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) was also induced by acute ethanol in Cyp2e1 –/– KI mice but not in Cyp2e1 –/– mice. Ethanol induction of CYP2A5 in Nrf2 knockout (Nrf2 –/–) mice was lower compared with that in WT mice, whereas CYP2E1 induction by ethanol was comparable in WT and Nrf2 –/– mice. Antioxidants (N-acetyl-cysteine and vitamin C), which blocked oxidative stress induced by chronic ethanol in WT mice and acute ethanol in Cyp2e1 –/– KI mice, also blunted the induction of CYP2A5 and Nrf2 by ethanol but not the induction of CYP2E1 by ethanol. These results suggest that oxidative stress induced by ethanol via induction of CYP2E1 upregulates Nrf2 activity, which in turn regulates ethanol induction of CYP2A5. Results obtained from primary hepatocytes, mice gavaged with binge ethanol or fed chronic ethanol, show that Nrf2-regulated ethanol induction of CYP2A5 protects against ethanol-induced steatosis. PMID:22552773

  19. Characterization of papillomavirus E1 helicase mutants defective for interaction with the SUMO-conjugating enzyme Ubc9.

    Science.gov (United States)

    Fradet-Turcotte, Amélie; Brault, Karine; Titolo, Steve; Howley, Peter M; Archambault, Jacques

    2009-12-20

    The E1 helicase from BPV and HPV16 interacts with Ubc9 to facilitate viral genome replication. We report that HPV11 E1 also interacts with Ubc9 in vitro and in the yeast two-hybrid system. Residues in E1 involved in oligomerization (353-435) were sufficient for binding to Ubc9 in vitro, but the origin-binding and ATPase domains were additionally required in yeast. Nuclear accumulation of BPV E1 was shown previously to depend on its interaction with Ubc9 and sumoylation on lysine 514. In contrast, HPV11 and HPV16 E1 mutants defective for Ubc9 binding remained nuclear even when the SUMO pathway was inhibited. Furthermore, we found that K514 in BPV E1 and the analogous K559 in HPV11 E1 are not essential for nuclear accumulation of E1. These results suggest that the interaction of E1 with Ubc9 is not essential for its nuclear accumulation but, rather, depends on its oligomerization and binding to DNA and ATP.

  20. A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes.

    Science.gov (United States)

    Mulder, Monique P C; Witting, Katharina; Berlin, Ilana; Pruneda, Jonathan N; Wu, Kuen-Phon; Chang, Jer-Gung; Merkx, Remco; Bialas, Johanna; Groettrup, Marcus; Vertegaal, Alfred C O; Schulman, Brenda A; Komander, David; Neefjes, Jacques; El Oualid, Farid; Ovaa, Huib

    2016-07-01

    Post-translational modifications of proteins with ubiquitin (Ub) and ubiquitin-like modifiers (Ubls), orchestrated by a cascade of specialized E1, E2 and E3 enzymes, control a wide range of cellular processes. To monitor catalysis along these complex reaction pathways, we developed a cascading activity-based probe, UbDha. Similarly to the native Ub, upon ATP-dependent activation by the E1, UbDha can travel downstream to the E2 (and subsequently E3) enzymes through sequential trans-thioesterifications. Unlike the native Ub, at each step along the cascade, UbDha has the option to react irreversibly with active site cysteine residues of target enzymes, thus enabling their detection. We show that our cascading probe 'hops' and 'traps' catalytically active Ub-modifying enzymes (but not their substrates) by a mechanism diversifiable to Ubls. Our founder methodology, amenable to structural studies, proteome-wide profiling and monitoring of enzymatic activity in living cells, presents novel and versatile tools to interrogate Ub and Ubl cascades.

  1. Molecular epidemiology of Chikungunya virus: mutation in E1 gene region.

    Science.gov (United States)

    Singh, Rishi K; Tiwari, Sarika; Mishra, Virendra K; Tiwari, Ruchi; Dhole, Tapan N

    2012-11-01

    Chikungunya virus is a mosquito-transmitted RNA virus and emerging as a pathogen that has a major public health impact because of the high morbidity including high fever, headache, rash, nausea, vomiting, myalgia, arthralgia with or without neurological manifestation or fulminant hepatitis. One hundred fifty-one patient samples were analyzed during the years 2006-2008, and compared conventional tests and CCRT-PCR (cell culture RT PCR). The conventional tests included ELISA, inoculation into C6/36 cell line and CPE were examined by PCR after RNA extraction. A total of 20/151 (13.2%), 8/151 (5.29%) and 7/151 (4.6%) samples were found to be positive by ELISA, cell culture and PCR, respectively. While 7/20 (35%) of the samples were positive by CCRT_PCR when ELISA 20 positive samples were detected. A total of 5/7 positive strains were sequenced in the E1 gene region. Remarkable changes (M269V, D284E, P294L, S295F, A316V, V322A, and C328W) were observed in the membrane fusion glycoprotein E1. These unique molecular features of the isolates with the continuing epidemic demonstrated high evolutionary potential and thereby indicating higher virulence. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. [Genetic polymorphism of cytochrome P450 2E1 and the risk of nasopharyngeal carcinoma].

    Science.gov (United States)

    Ben Chaaben, Arij; Abaza, Hajer; Douik, Hayet; Chaouch, Leila; Ayari, Fayza; Ouni, Nesrine; Mamoghli, Tasnim; Ben Guezella, Dorra; Mejri, Rachida; Harzallah, Latifa; Guemira, Fethi

    2015-12-01

    Cytochrome P450 2E1 (CYP2E1) is a detoxifying enzyme that belongs to the phase I metabolism of xenobiotics. This enzyme is encoded by a highly polymorphic gene whose common polymorphism corresponds to the substitution of cytosine (C) and thymine (T) at position -1019 (rs2031920). This polymorphism has been identified in several cancers including nasopharyngeal cancer (NPC). The study involved 124 patients with nasopharyngeal carcinoma, compared with 166 healthy controls. The presence or absence of the polymorphism is determined by PCR-RFLP. The frequency comparison between the two groups is determined by the χ(2) test. The analysis of our results showed a significant difference between the two groups regarding the mutant genotype (C2/C2) (5% vs. 0.5%, P=0.04) and has a risk factor for NPC in Tunisia (OR=8.39; CI 95% [0.99-388.1]). Also, the C2 allele was significantly associated with the group of patients than the control group (6% vs. 2%, P=0.016) and increased three times the risk of NPC in Tunisia (OR=2.99, CI 95% [1.12-8.79]). Our results confirm the results reported in other populations and emphasize the importance of the involvement of this gene in the development of detoxification of the NPC, which seems more and more strongly associated with environmental factors. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  3. Crystal structure of hyperthermophilic esterase EstE1 and the relationship between its dimerization and thermostability properties

    Directory of Open Access Journals (Sweden)

    Koh Eunhee

    2007-07-01

    Full Text Available Abstract Background EstE1 is a hyperthermophilic esterase belonging to the hormone-sensitive lipase family and was originally isolated by functional screening of a metagenomic library constructed from a thermal environmental sample. Dimers and oligomers may have been evolutionally selected in thermophiles because intersubunit interactions can confer thermostability on the proteins. The molecular mechanisms of thermostabilization of this extremely thermostable esterase are not well understood due to the lack of structural information. Results Here we report for the first time the 2.1-Å resolution crystal structure of EstE1. The three-dimensional structure of EstE1 exhibits a classic α/β hydrolase fold with a central parallel-stranded beta sheet surrounded by alpha helices on both sides. The residues Ser154, Asp251, and His281 form the catalytic triad motif commonly found in other α/β hydrolases. EstE1 exists as a dimer that is formed by hydrophobic interactions and salt bridges. Circular dichroism spectroscopy and heat inactivation kinetic analysis of EstE1 mutants, which were generated by structure-based site-directed mutagenesis of amino acid residues participating in EstE1 dimerization, revealed that hydrophobic interactions through Val274 and Phe276 on the β8 strand of each monomer play a major role in the dimerization of EstE1. In contrast, the intermolecular salt bridges contribute less significantly to the dimerization and thermostability of EstE1. Conclusion Our results suggest that intermolecular hydrophobic interactions are essential for the hyperthermostability of EstE1. The molecular mechanism that allows EstE1 to endure high temperature will provide guideline for rational design of a thermostable esterase/lipase using the lipolytic enzymes showing structural similarity to EstE1.

  4. SPAK and OSR1 Sensitive Cell Membrane Protein Abundance and Activity of KCNQ1/E1 K+ Channels

    Directory of Open Access Journals (Sweden)

    Bernat Elvira

    2015-11-01

    Full Text Available Background/Aims: KCNQ1/E1 channels are expressed in diverse tissues and serve a variety of functions including endolymph secretion in the inner ear, cardiac repolarization, epithelial transport and cell volume regulation. Kinases involved in regulation of epithelial transport and cell volume include SPAK (SPS1-related proline/alanine-rich kinase and OSR1 (oxidative stress-responsive kinase 1, which are under control of WNK (with-no-K[Lys] kinases. The present study explored whether KCNQ1/E1 channels are regulated by SPAK and/or OSR1. Methods: cRNA encoding KCNQ1/E1 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 and catalytically inactive D164AOSR1. Voltage gated K+ channel activity was quantified utilizing dual electrode voltage clamp and KCNQ1/E1 channel protein abundance in the cell membrane utilizing chemiluminescence of KCNQ1/E1 containing an extracellular Flag tag epitope (KCNQ1-Flag/E1. Results: KCNQ1/E1 activity and KCNQ1-Flag/E1 protein abundance were significantly enhanced by wild-type SPAK and T233ESPAK, but not by T233ASPAK and D212ASPAK. Similarly, KCNQ1/E1 activity and KCNQ1-Flag/E1 protein abundance were significantly increased by wild-type OSR1 and T185EOSR1, but not by T185AOSR1 and D164AOSR1. Conclusions: SPAK and OSR1 participate in the regulation of KCNQ1/E1 protein abundance and activity.

  5. SPAK and OSR1 Sensitive Cell Membrane Protein Abundance and Activity of KCNQ1/E1 K+ Channels.

    Science.gov (United States)

    Elvira, Bernat; Warsi, Jamshed; Fezai, Myriam; Munoz, Carlos; Lang, Florian

    2015-01-01

    KCNQ1/E1 channels are expressed in diverse tissues and serve a variety of functions including endolymph secretion in the inner ear, cardiac repolarization, epithelial transport and cell volume regulation. Kinases involved in regulation of epithelial transport and cell volume include SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether KCNQ1/E1 channels are regulated by SPAK and/or OSR1. cRNA encoding KCNQ1/E1 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 and catalytically inactive D164AOSR1. Voltage gated K+ channel activity was quantified utilizing dual electrode voltage clamp and KCNQ1/E1 channel protein abundance in the cell membrane utilizing chemiluminescence of KCNQ1/E1 containing an extracellular Flag tag epitope (KCNQ1-Flag/E1). KCNQ1/E1 activity and KCNQ1-Flag/E1 protein abundance were significantly enhanced by wild-type SPAK and T233ESPAK, but not by T233ASPAK and D212ASPAK. Similarly, KCNQ1/E1 activity and KCNQ1-Flag/E1 protein abundance were significantly increased by wild-type OSR1 and T185EOSR1, but not by T185AOSR1 and D164AOSR1. SPAK and OSR1 participate in the regulation of KCNQ1/E1 protein abundance and activity. © 2015 S. Karger AG, Basel.

  6. Situating relevance: exploring individual relevance assessments in context

    Directory of Open Access Journals (Sweden)

    Theresa Dirndorfer Anderson

    2001-01-01

    Full Text Available This paper discusses some of the challenges encountered whilst researching and writing a thesis that explores individual understandings of relevance and topic. It is based upon a discussion paper and presentation prepared as part of the Doctoral Workshop held during the ISIC 2000 Conference in Borås, Sweden. The focus of this paper is the doing of qualitative research. To provide a framework for this discussion, the key assumptions that have shaped the author's thesis are presented in the first section of this paper. The paper then focuses on some of the dilemmas of qualitative research encountered during the research and writing of this thesis, giving particular attention to the notion of context and the writing of qualitative research. Forthcoming results from the thesis are mentioned in the closing section. A Thesis Summary is also provided at the end of this paper.

  7. omm>e1nit}'¢acquiredPneumon1'a in Hospitahked Urban

    African Journals Online (AJOL)

    with the syndrome definition of pneumonia,11 with or without the clinical features of measles, or pertussis. Using .a pre-coded questionnaire, the relevant disease symptoms and physical signs were recorded, as were selected risk factors5 such as immunization status, 'feeding practices, household circumstances including ...

  8. 26 CFR 1.1033(e)-1 - Sale or exchange of livestock solely on account of drought.

    Science.gov (United States)

    2010-04-01

    ... of drought. 1.1033(e)-1 Section 1.1033(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Sale or exchange of livestock solely on account of drought. (a) The sale or exchange of livestock... if the sale or exchange of such livestock by the taxpayer is solely on account of drought. Section...

  9. Functional analysis of the C-terminal region of human adenovirus E1A reveals a misidentified nuclear localization signal

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Michael J.; King, Cason R.; Dikeakos, Jimmy D. [Department of Microbiology and Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada (Canada); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada (Canada); Department of Oncology, The University of Western Ontario, London Regional Cancer Centre, Ontario (Canada)

    2014-11-15

    The immortalizing function of the human adenovirus 5 E1A oncoprotein requires efficient localization to the nucleus. In 1987, a consensus monopartite nuclear localization sequence (NLS) was identified at the C-terminus of E1A. Since that time, various experiments have suggested that other regions of E1A influence nuclear import. In addition, a novel bipartite NLS was recently predicted at the C-terminal region of E1A in silico. In this study, we used immunofluorescence microscopy and co-immunoprecipitation analysis with importin-α to verify that full nuclear localization of E1A requires the well characterized NLS spanning residues 285–289, as well as a second basic patch situated between residues 258 and 263 ({sup 258}RVGGRRQAVECIEDLLNEPGQPLDLSCKRPRP{sup 289}). Thus, the originally described NLS located at the C-terminus of E1A is actually a bipartite signal, which had been misidentified in the existing literature as a monopartite signal, altering our understanding of one of the oldest documented NLSs. - Highlights: • Human adenovirus E1A is localized to the nucleus. • The C-terminus of E1A contains a bipartite nuclear localization signal (NLS). • This signal was previously misidentified to be a monopartite NLS. • Key basic amino acid residues within this sequence are highly conserved.

  10. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

    Directory of Open Access Journals (Sweden)

    Elodie Beaumont

    Full Text Available Various strategies involving the use of hepatitis C virus (HCV E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

  11. mUBC9, a novel adenovirus E1A-interacting protein that complements a yeast cell cycle defect

    NARCIS (Netherlands)

    Hateboer, G.; Hijmans, E. M.; Nooij, J. B. D.; Schlenker, S.; Jentsch, S.; Bernards, R.A.

    1996-01-01

    Adenovirus E1A encodes two nuclear phosphoproteins that can transform primary rodent fibroblasts in culture. Transformation by E1A is mediated at least in part through binding to several cellular proteins, including the three members of the retinoblastoma family of growth inhibitory proteins. We

  12. Crystal structure of (E-1-(4-chlorophenylethanone O-dehydroabietyloxime

    Directory of Open Access Journals (Sweden)

    Jian-Qiang Zheng

    2014-09-01

    Full Text Available The title compound, C28H34ClNO2 {systematic name: (E-1-(4-chlorophenylethanone O-[(1R,4aS,10aR-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carbonyl]oxime}, was synthesized from dehydroabietic acid. In the dehydroabietyl moiety, the central and terminal cyclohexane rings display chair and half-chair conformations, respectively, and a trans-ring junction. The C=N bond is in an E conformation and the C—O—N=C torsion angle is 148.1 (5°. No directional interactions except van der Waals contacts occur in the crystal structure.

  13. Health sector response to security threats during the civil war in E1 Salvador.

    Science.gov (United States)

    Brentlinger, P. E.

    1996-01-01

    During the recent civil war in E1 Salvador, as in other modern wars, human rights abuses adversely affected health workers, patients, and medical facilities. The abuses themselves have been described in reports of human rights advocacy organisations but health sector adaptations to a hostile wartime environment have not. Agencies engaged in health work during the civil war adapted parties such as training of community based lay health workers, use of simple technology, concealment of patients and medical supplies, denunciation of human rights abuses, and multilevel negotiations in order to continue providing services. The Salvadorean experience may serve as a helpful case study for medical personnel working in wars elsewhere. Images p1471-a p1472-a p1473-a PMID:8973238

  14. Current status of the verification and processing system GALILÉE-1 for evaluated data

    Science.gov (United States)

    Coste-Delclaux, Mireille; Jouanne, Cédric; Moreau, Frédéric; Mounier, Claude; Visonneau, Thierry; Dolci, Florence

    2017-09-01

    This paper describes the current status of GALILÉE-1 that is the new verification and processing system for evaluated data, developed at CEA. It consists of various components respectively dedicated to read/write the evaluated data whatever the format is, to diagnose inconsistencies in the evaluated data and to provide continuous-energy and multigroup data as well as probability tables for transport and depletion codes. All these components are written in C+ + language and share the same objects. Cross-comparisons with other processing systems (NJOY, CALENDF or PREPRO) are systematically carried out at each step in order to fully master possible discrepancies. Some results of such comparisons are provided.

  15. Joint Tracking of Chang'E-1 with VLBI and USB

    Science.gov (United States)

    Hu, Xiaogong

    Chinese lunar exploration mission Chang'E-I made use of a Chinese Unified S-Band (USB) system and a network of four Very Long Baseline Interferometry (VLBI) antennas to meet the orbit determination/predication requirements of spacecraft tracking and scientific data analysis, which for the first time handled telemetry and control for a spacecraft at a distance of about 380,000 km. Chang'E-1 provided a perfect chance to quantify the contributions of VLBI to orbit determination/predication, and to test and evaluate the performance of the USB-VLBI joint system. We investigate in this paper the quality of the data and analyze the precision of orbit determination with different data arcs and data combinations during the 2-week journey from Earth to Chang'E-1's lunar mission orbit, using GEODYN II orbit determination software. The residuals of VLBI delay is about 3 ns (RMS, root-mean-squares), the residuals of VLBI delay-rate is about 0.6 ps/s, the residuals of ranging is about 1 2 m and Doppler is about 1 cm/s. Three flight phases are invistigated, namely 3 phasing orbits near Earth, the translunar trajectory and the lunar catputed orbits. We found including of VLBI data substantially improved orbit precision for short data arcs, therefore VLBI played an important role in assessing spacecraft manuvore performance. Given the differential nature of VLBI observables and their errors mostly from BBC's nonlinear phase-frequency responses, it appears for longer data arcs the VLBI contribution is relatively minor. We conclude that for Chang'E-I, the inclusion of VLBI data improved substantially the performance of orbit determination and prediction, even though the VLBI data acquisition and correlation imposes a major burden on data processing.

  16. The Relevance of Hegel's Logic

    Directory of Open Access Journals (Sweden)

    John W Burbidge

    2007-12-01

    Full Text Available Hegel defines his Logic as the science that thinks about thinking.nbsp; But when we interpret that work as outlining what happens when we reason we are vulnerable to Fregersquo;s charge of psychologism.nbsp; I use Hegelrsquo;s tripartite distinction among understanding, dialectical and speculative reason as operations of pure thought to suggest how thinking can work with objective concepts.nbsp; In the last analysis, however, our ability to move from the subjective contingency of representations and ideas to the pure concepts we think develops from mechanical memory, which separates sign from sense so hat we can focus simply on the latter.nbsp; By becoming aware of the connections that underlie our thinking processes we may be able to both move beyond the abstractions of symbolic logic and clarify what informal logicians call relevance.

  17. The Improved Relevance Voxel Machine

    DEFF Research Database (Denmark)

    Ganz, Melanie; Sabuncu, Mert; Van Leemput, Koen

    Machine (RVM) [4] in 2001. While the concept of RVM was intriguing, problems with the approach were the run time which is approximately cubic in the number of basis functions as well as the greedy optimization. Hence, different approaches to overcome these shortcomings were developed, e.g. [5] or [6......The concept of sparse Bayesian learning has received much attention in the machine learning literature as a means of achieving parsimonious representations of features used in regression and classification. It is an important family of algorithms for sparse signal recovery and compressed sensing......] as well as Tipping himself in [7] (FastRVM). Recently, Sabuncu and Van Leemput [8, 9] extended the relevance vector machine by incorporating an additional spatial regularization term in the Gaussian prior on the regression weights or classification features (RVoxM). RVoxM encourages spatial clustering...

  18. Molecular basis of maple syrup urine disease: Novel mutations at the E1[alpha] locus that impair E1([alpha][sub 2][beta][sub 2]) assembly or decrease steady-state E1[alpha] mRNA levels of branched-chain [alpha]-keto acid dehydrogenase complex

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, J.L.; Fisher, C.R.; Chuang, D.T.; Cox, R.P. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States))

    1994-08-01

    The authors report the occurrence of three novel mutations in the E1[alpha] (BCKDHA) locus of the branched-chain [alpha]-keto acid dehydrogenase (BCKAD) complex that cause maple syrup urine disease (MSUD). An 8-bp deletion in exon 7 is present in one allele of a compound-heterozygous patient (GM-649). A single C nucleotide insertion in exon 2 occurs in one allele of an intermediate-MSUD patient (Lo). The second allele of patient Lo carries an A-to-G transition in exon 9 of the E1[alpha] gene. This missense mutation changes Tyr-368 to Cys (Y368C) in the E1[alpha] subunit. Both the 8-bp deletion and the single C insertion generate a downstream nonsense codon. Both mutations appear to be associated with a low abundance of the mutant E1[alpha] mRNA, as determined by allele-specific oligonucleotide probing. Transfection studies strongly suggest that the Y368C substitution in the E1[alpha] subunit impairs its proper assembly with the normal E1[beta]. Unassembled as well as misassembled E1[alpha] and E1[beta] subunits are degraded in the cell. 32 refs., 8 figs.

  19. The molecular mechanism regulating 24-hour rhythm of CYP2E1 expression in the mouse liver.

    Science.gov (United States)

    Matsunaga, Naoya; Ikeda, Misaki; Takiguchi, Takako; Koyanagi, Satoru; Ohdo, Shigehiro

    2008-07-01

    Cytochrome P450 2E1 (CYP2E1) is clinically and toxicologically important and exhibits 24-hour periodicity in its activity. In the present study, we investigated whether hepatic nuclear factor-1alpha (HNF-1alpha) and clock genes with a striking 24-hour rhythm in mouse liver contributed to the 24-hour regulation of CYP2E1 expression. The results demonstrated that the expression of CYP2E1 messenger RNA (mRNA) in the liver was affected by HNF-1alpha and the circadian organization of molecular clocks. The mRNA levels of CYP2E1 in the liver increased from the late light phase to the early dark phase. Luciferase reporter gene analysis revealed that HNF-1alpha activated CYP2E1 promoter activity, which was restricted by CRY1, a member of the circadian organization of molecular clocks. Repressor activity of CRY1 was observed on the HNF-1alpha binding site of the CYP2E1 promoter region with mutated E-box. Serum shock induced approximately 24-hour oscillation in CYP2E1 mRNA in HepG2. Transfection of HNF-1alpha and CRY1 small interfering RNA dampened the oscillation of CYP2E1 mRNA in HepG2. Chromatin immunoprecipitation assay in the CYP2E1 promoter indicated that HNF-1alpha binding to the CYP2E1 promoter increased from the late light phase to the early dark phase. Using the chromatin immunoprecipitation reimmunoprecipitation assay, time-dependent differences were demonstrated for CRY1 protein interaction with HNF-1alpha transcriptional complexes, including coactivator p300 on the HNF-1alpha binding site in the CYP2E1 promoter. Our results suggest that the transcription activator of HNF-1alpha acts periodically and the negative limbs of molecular clocks periodically inhibit CYP2E1 transcription, resulting in the 24-hour rhythm of its mRNA expression.

  20. HBx inhibits CYP2E1 gene expression via downregulating HNF4α in human hepatoma cells.

    Directory of Open Access Journals (Sweden)

    Hongming Liu

    Full Text Available CYP2E1, one of the cytochrome P450 mixed-function oxidases located predominantly in liver, plays a key role in metabolism of xenobiotics including ethanol and procarcinogens. Recently, down-expression of CYP2E1 was found in hepatocellular carcinoma (HCC with the majority to be chronic hepatitis B virus (HBV carriers. In this study, we tested a hypothesis that HBx may inhibit CYP2E1 gene expression via hepatocyte nuclear factor 4α (HNF4α. By enforced HBx gene expression in cultured HepG2 cells, we determined the effect of HBx on CYP2E1 mRNA and protein expression. With a bioinformatics analysis, we found a consensus HNF-4α binding sequence located on -318 to -294 bp upstream of human CYP2E1 promoter. Using reporter gene assay and site-directed mutagenesis, we have shown that mutation of this site dramatically decreased CYP2E1 promoter activity. By silencing endogenous HNF-4α, we have further validated knockdown of HNF-4α significantly decreased CYP2E1 expression. Ectopic overexpression of HBx in HepG2 cells inhibits HNF-4α expression, and HNF-4α levels were inversely correlated with viral proteins both in HBV-infected HepG2215 cells and as well as HBV positive HCC liver tissues. Moreover, the HBx-induced CYP2E1 reduction could be rescued by ectopic supplement of HNF4α protein expression. Furthermore, human hepatoma cells C34, which do not express CYP2E1, shows enhanced cell growth rate compared to E47, which constitutively expresses CYP2E1. In addition, the significantly altered liver proteins in CYP2E1 knockout mice were detected with proteomics analysis. Together, HBx inhibits human CYP2E1 gene expression via downregulating HNF4α which contributes to promotion of human hepatoma cell growth. The elucidation of a HBx-HNF4α-CYP2E1 pathway provides novel insight into the molecular mechanism underlining chronic HBV infection associated hepatocarcinogenesis.

  1. [The relevance of ethology for psychiatry].

    Science.gov (United States)

    Brüne, M

    1998-07-01

    Darwin's evolutionary theory was the starting point for ethology, associated with an impact on scientific psychiatry. Psychiatry and ethology have common scientific and methodological prerequisites: inductive and deductive methods and "gestalt theory" as a basis for observing and describing behaviour patterns with subsequent causal analysis. There have been early endeavours to anchor ethological thinking in psychiatry but this tendency did not prevail for the following reasons: on the one hand, the methodology of ethology was immature or not applicable to man, whereas on the other hand the dominating experiential phenomenological school of Karl Jaspers and Kurt Schneider stressed the privileged position of human thinking, perception, and feeling. These fundamental categories of human existence did not appear amenable to any causal ethological analysis. Psychiatry and evolutionary biology were linked in an atrocious manner during the Nazi regime, both being abused for propaganda purposes and genocide. More recently, there is a "reconciliation" of both disciplines. In psychiatric nosology, operational, behaviour-oriented diagnostic systems have been introduced; ethology has opened up for theories of learning; new subsections like human ethology and sociobiology have evolved. The seeming incompatibility of (behavioural) biological psychiatry and experiential phenomenological psychopathology may be overcome on the basis of Konrad Lorenz' evolutionary epistemology. The functional analysis of human feeling and behaviour in psychotic disorders on the basis of Jackson's theory of the evolution and dissolution of the nervous system may serve as an example. The significance of an "ethological psychiatry" for diagnostic and therapeutical processes of psychiatric disorders derive from prognostic possibilities and the analysis of non-verbal communication in therapist-patient-interactions, but have not yet been systematically investigated.

  2. E1^E4-mediated keratin phosphorylation and ubiquitylation: a mechanism for keratin depletion in HPV16-infected epithelium

    Science.gov (United States)

    McIntosh, Pauline B.; Laskey, Peter; Sullivan, Kate; Davy, Clare; Wang, Qian; Jackson, Deborah J.; Griffin, Heather M.; Doorbar, John

    2010-01-01

    The keratin IF network of epidermal keratinocytes provides a protective barrier against mechanical insult, it is also a major player in absorbing stress in these cells. The human papilloma virus (HPV) type 16 E1^E4 protein accumulates in the upper layers of HPV16-infected epithelium and is known to associate with and reorganise the keratin IF network in cells in culture. Here, we show that this function is conserved amongst a number of HPV alpha-group E1^E4 proteins and that the differentiation-dependent keratins are also targeted. Using time-lapse microscopy, HPV16 E1^E4 was found to effect a dramatic cessation of keratin IF network dynamics by associating with both soluble and insoluble keratin. Network disruption was accompanied by keratin hyperphosphorylation at several sites, including K8 S73, which is typically phosphorylated in response to stress stimuli. Keratin immunoprecipitated from E1^E4-expressing cells was also found to be ubiquitylated, indicating that it is targeted for proteasomal degradation. Interestingly, the accumulation of hyperphosphorylated, ubiquitylated E1^E4-keratin structures was found to result in an impairment of proteasomal function. These observations shed new light on the mechanism of keratin IF network reorganisation mediated by HPV16 E1^E4 and provide an insight into the depletion of keratin co-incident with E1^E4 accumulation observed in HPV-infected epithelium. PMID:20663917

  3. Water scarcity and economic damage in Europe: regionally relevant simulations from 2000 to 2050

    Science.gov (United States)

    Bernhard, Jeroen; de Roo, Ad; Bisselink, Bernard; Gelati, Emiliano; Karssenberg, Derek; de Jong, Steven

    2017-04-01

    Water availability is unequally distributed across Europe. Where certain regions experience a surplus of water, other areas have limited water availability which causes economic damage to the water using sectors such as households, industries or agriculture. Future changes in climatic and socio-economic conditions are expected to further increase the competition for available water that is already present in Europe. This means there is an increasing need for models that are able to simulate this multi-sectorial system of water availability and demand and incorporate the socio-economic component required for robust decisions and policy support. We present our modelling study which is focused at providing regionally relevant pan-European water scarcity and economic damage simulations. First we developed regionally relevant pan-European water demand simulations for the household and industry sector from 2000 up to 2050. For the household sector we developed a model to simulate water use based on water price, income and several other relevant variables at NUTS-3 level (over 1200 regions in Europe). Alternatively, we modelled industrial water use based on regionally downscaled water productivity values at the national level for ten sub-sections of the NACE (Nomenclature of Economic Activities) classification for economic activities. Subsequently we used scenario projections of our explanatory variables to make scenario simulations of water demand from 2000 up to 2050 at pan-European scale with unprecedented spatial and sub-sectorial detail. In order to analyze the European water use system we integrated these water demand scenarios into the hydrological rainfall-runoff model called LISFLOOD (Distributed Water Balance and Flood Simulation Model), which incorporates a vegetation module for the simulation of crop yield and irrigation water demand of the agriculture sector. We simulated river discharge and groundwater availability for abstractions of water using sectors

  4. Adenovirus E1A targets the DREF nuclear factor to regulate virus gene expression, DNA replication, and growth.

    Science.gov (United States)

    Radko, Sandi; Koleva, Maria; James, Kris M D; Jung, Richard; Mymryk, Joe S; Pelka, Peter

    2014-11-01

    The adenovirus E1A gene is the first gene expressed upon viral infection. E1A remodels the cellular environment to maximize permissivity for viral replication. E1A is also the major transactivator of viral early gene expression and a coregulator of a large number of cellular genes. E1A carries out its functions predominantly by binding to cellular regulatory proteins and altering their activities. The unstructured nature of E1A enables it to bind to a large variety of cellular proteins and form new molecular complexes with novel functions. The C terminus of E1A is the least-characterized region of the protein, with few known binding partners. Here we report the identification of cellular factor DREF (ZBED1) as a novel and direct binding partner of E1A. Our studies identify a dual role for DREF in the viral life cycle. DREF contributes to activation of gene expression from all viral promoters early in infection. Unexpectedly, it also functions as a growth restriction factor for adenovirus as knockdown of DREF enhances virus growth and increases viral genome copy number late in the infection. We also identify DREF as a component of viral replication centers. E1A affects the subcellular distribution of DREF within PML bodies and enhances DREF SUMOylation. Our findings identify DREF as a novel E1A C terminus binding partner and provide evidence supporting a role for DREF in viral replication. This work identifies the putative transcription factor DREF as a new target of the E1A oncoproteins of human adenovirus. DREF was found to primarily localize with PML nuclear bodies in uninfected cells and to relocalize into virus replication centers during infection. DREF was also found to be SUMOylated, and this was enhanced in the presence of E1A. Knockdown of DREF reduced the levels of viral transcripts detected at 20 h, but not at 40 h, postinfection, increased overall virus yield, and enhanced viral DNA replication. DREF was also found to localize to viral promoters during

  5. Targeting CCl4 -induced liver fibrosis by RNA interference-mediated inhibition of cyclin E1 in mice.

    Science.gov (United States)

    Bangen, Jörg-Martin; Hammerich, Linda; Sonntag, Roland; Baues, Maike; Haas, Ute; Lambertz, Daniela; Longerich, Thomas; Lammers, Twan; Tacke, Frank; Trautwein, Christian; Liedtke, Christian

    2017-10-01

    Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSCs). Cyclin E1 (CcnE1) is the regulatory subunit of the cyclin-dependent kinase 2 (Cdk2) and controls cell cycle re-entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation, and survival of HSCs and protects from liver fibrogenesis. The aim of the present study was to translate these findings into preclinical applications using an RNA interference (RNAi)-based approach. CcnE1-siRNA (small interfering RNA) efficiently inhibited CcnE1 gene expression in murine and human HSC cell lines and in primary HSCs, resulting in diminished proliferation and increased cell death. In C57BL/6 wild-type (WT) mice, delivery of stabilized siRNA using a liposome-based carrier targeted approximately 95% of HSCs, 70% of hepatocytes, and 40% of CD45+ cells after single injection. Acute CCl4 -mediated liver injury in WT mice induced endogenous CcnE1 expression and proliferation of surviving hepatocytes and nonparenchymal cells, including CD45+ leukocytes. Pretreatment with CcnE1-siRNA reverted CcnE1 induction to baseline levels of healthy mice, which was associated with reduced liver injury, diminished proliferation of hepatocytes and leukocytes, and attenuated overall inflammatory response. For induction of liver fibrosis, WT mice were challenged with CCl4 for 4-6 weeks. Co-treatment with CcnE1-siRNA once a week was sufficient to continuously block CcnE1 expression and cell-cycle activity of hepatocytes and nonparenchymal cells, resulting in significantly ameliorated liver fibrosis and inflammation. Importantly, CcnE1-siRNA also prevented progression of liver fibrosis if applied after onset of chronic liver injury. Therapeutic targeting of CcnE1 in vivo using RNAi is feasible and has high antifibrotic activity. (Hepatology 2017;66:1242-1257). © 2017 by the American Association for the Study of Liver Diseases.

  6. Vygotsky's Crisis: Argument, context, relevance.

    Science.gov (United States)

    Hyman, Ludmila

    2012-06-01

    Vygotsky's The Historical Significance of the Crisis in Psychology (1926-1927) is an important text in the history and philosophy of psychology that has only become available to scholars in 1982 in Russian, and in 1997 in English. The goal of this paper is to introduce Vygotsky's conception of psychology to a wider audience. I argue that Vygotsky's argument about the "crisis" in psychology and its resolution can be fully understood only in the context of his social and political thinking. Vygotsky shared the enthusiasm, widespread among Russian leftist intelligentsia in the 1920s, that Soviet society had launched an unprecedented social experiment: The socialist revolution opened the way for establishing social conditions that would let the individual flourish. For Vygotsky, this meant that "a new man" of the future would become "the first and only species in biology that would create itself." He envisioned psychology as a science that would serve this humanist teleology. I propose that The Crisis is relevant today insofar as it helps us define a fundamental problem: How can we systematically account for the development of knowledge in psychology? I evaluate how Vygotsky addresses this problem as a historian of the crisis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. E1 oscillator strengths and transition rates among levels of Cl I

    Science.gov (United States)

    Oliver, P.; Hibbert, A.

    2013-07-01

    We present oscillator strengths and transition rates of E1 transitions between the fine-structure levels belonging to the configurations 3s23p5, 3s3p6, and 3s23p4nl, where nl= 4s, 5s, 6s, 4p, 5p, 3d, 4d. The calculations have used extensive configuration interaction (CI) wavefunctions, with the associated Hamiltonian matrix adjusted to ensure that the eigenenergies agree with experimental energy level data ('fine tuning'). There are consequential small changes in the CI mixing coefficients from their ab initio values and these corrected coefficients are used in the calculation of the transition data. The method of optimization of the orbital radial functions (expressed in terms of Slater-type orbitals) is described and the radial function parameters are also presented. We show some comparisons between our work and those of earlier calculations and demonstrate how the inclusion of relativistic effects (which we achieve through the use of the Breit-Pauli approximation) can result in a substantial redistribution of the oscillator strength from the LS calculation. We also demonstrate that the fine-tuning process can make, particularly for intercombination lines, a substantial improvement in the agreement between theoretical and experimental oscillator strengths.

  8. MC3T3-E1 Cells on Titanium Surfaces with Nanometer Smoothness and Fibronectin Immobilization

    Directory of Open Access Journals (Sweden)

    Tohru Hayakawa

    2012-01-01

    Full Text Available The present study was aimed to evaluate the viability and total protein contents of osteoblast-like cells on the titanium surface with different surface mechanical treatment, namely, nanometer smoothing (Ra: approximately 2.0 nm and sandblasting (Ra: approximately 1.0 μm, and biochemical treatment, namely, with or without fibronectin immobilization. Fibronectin could be easily immobilized by tresyl chloride-activation technique. MC3T3-E1 cells were seeded on the different titanium surfaces. Cell viability was determined by MTT assay. At 1 day of cell culture, there were no significant differences in cell viability among four different titanium surfaces. At 11 days, sandblasted titanium surface with fibronectin immobilization showed the significantly highest cell viability than other titanium surface. No significant differences existed for total protein contents among four different titanium surfaces at 11 days of cell culture. Scanning electron microscopy observation revealed that smoothness of titanium surface produced more spread cell morphologies, but that fibronectin immobilization did not cause any changes of the morphologies of attached cells. Fibronectin immobilization provided greater amount of the number of attached cells and better arrangement of attached cells. In conclusion, the combination of sandblasting and fibronectin immobilization enhanced the cell viability and fibronectin immobilization providing better arrangements of attached cells.

  9. Impaired phagocytosis in localized aggressive periodontitis: rescue by Resolvin E1.

    Directory of Open Access Journals (Sweden)

    Gabrielle Fredman

    Full Text Available Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18 surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A(4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1-100 nM, rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression.

  10. Alteration of therapeutic efficacy of lipid microspheres incorporating prostaglandin E1 by mixing with aqueous solution.

    Science.gov (United States)

    Komori, Yukiko; Aiba, Tetsuya; Kushima, Miki; Kawasaki, Hiromu; Kurosaki, Yuji

    2007-04-01

    To clarify whether the therapeutic efficacy of lipid microspheres incorporating prostaglandin E(1) (lipo-PGE(1)) is altered when mixed and coinfused with clinical solutions, the original lipo-PGE(1) solution (20 microg/mL) was mixed with three clinical infusion solutions: 0.9% sodium chloride solution, Hartmann's solution, and fat emulsion for parenteral nutrition. These diluted lipo-PGE(1) (2 microg/mL) solutions were administered to rats, and their hemodynamic and antiplatelet effects were examined. Peripheral blood flow was increased by 76 +/- 4% from the control level when the lipo-PGE(1) solution diluted with the fat emulsion was administered, while it was increased by 43 +/- 6% and 36 +/- 7%, respectively, when the lipo-PGE(1) solutions diluted with 0.9% sodium chloride and Hartmann's solution were administered. As for the antiplatelet effects of the lipo-PGE(1) solutions, the progression of digit gangrene in thromboangiitis obliterans (TAO) rats was significantly suppressed by the administration of lipo-PGE(1) solution diluted with the fat emulsion, but it was not suppressed by lipo-PGE(1) solution diluted with 0.9% sodium chloride. These findings indicate that the therapeutic efficacy of lipo-PGE(1) is decreased when it is mixed with an aqueous solution such as 0.9% sodium chloride. (c) 2007 Wiley-Liss, Inc.

  11. EVALUATION OF RATIONAL FUNCTION MODEL FOR GEOMETRIC MODELING OF CHANG'E-1 CCD IMAGES

    Directory of Open Access Journals (Sweden)

    Y. Liu

    2012-08-01

    Full Text Available Rational Function Model (RFM is a generic geometric model that has been widely used in geometric processing of high-resolution earth-observation satellite images, due to its generality and excellent capability of fitting complex rigorous sensor models. In this paper, the feasibility and precision of RFM for geometric modeling of China's Chang'E-1 (CE-1 lunar orbiter images is presented. The RFM parameters of forward-, nadir- and backward-looking CE-1 images are generated though least squares solution using virtual control points derived from the rigorous sensor model. The precision of the RFM is evaluated by comparing with the rigorous sensor model in both image space and object space. Experimental results using nine images from three orbits show that RFM can precisely fit the rigorous sensor model of CE-1 CCD images with a RMS residual error of 1/100 pixel level in image space and less than 5 meters in object space. This indicates that it is feasible to use RFM to describe the imaging geometry of CE-1 CCD images and spacecraft position and orientation. RFM will enable planetary data centers to have an option to supply RFM parameters of orbital images while keeping the original orbit trajectory data confidential.

  12. Prostaglandin E1 inhibits endocytosis in the β-cell endocytosis.

    Science.gov (United States)

    Zhao, Ying; Fang, Qinghua; Straub, Susanne G; Lindau, Manfred; Sharp, Geoffrey W G

    2016-06-01

    Prostaglandins inhibit insulin secretion in a manner similar to that of norepinephrine (NE) and somatostatin. As NE inhibits endocytosis as well as exocytosis, we have now examined the modulation of endocytosis by prostaglandin E1 (PGE1). Endocytosis following exocytosis was recorded by whole-cell patch clamp capacitance measurements in INS-832/13 cells. Prolonged depolarizing pulses producing a high level of Ca(2+) influx were used to stimulate maximal exocytosis and to deplete the readily releasable pool (RRP) of granules. This high Ca(2+) influx eliminates the inhibitory effect of PGE1 on exocytosis and allows specific characterization of the inhibitory effect of PGE1 on the subsequent compensatory endocytosis. After stimulating exocytosis, endocytosis was apparent under control conditions but was inhibited by PGE1 in a Pertussis toxin-sensitive (PTX)-insensitive manner. Dialyzing a synthetic peptide mimicking the C-terminus of the α-subunit of the heterotrimeric G-protein Gz into the cells blocked the inhibition of endocytosis by PGE1, whereas a control-randomized peptide was without effect. These results demonstrate that PGE1 inhibits endocytosis and Gz mediates the inhibition. © 2016 Society for Endocrinology.

  13. ON THE QUESTIONS OF THE NUCLEAR LEVEL DENSITY AND THE E1 PHOTON STRENGTH FUNCTIONS

    Energy Technology Data Exchange (ETDEWEB)

    MUGHABGHAB,S.F.; DUNFORD,C.L.

    1999-11-15

    New results were derived from average level spacings of neutron resonances for the spin dispersion parameter of the nuclear level density, which demonstrated the influence of shell effects, as well as the interplay of nucleon pairing correlations for nuclei in the mass range from {sup 29}Si to {sup 241}Pu. The volume and surface components of the nuclear level density parameter, as well as the shell-damping factor, were determined as, a{sub v} = 0.076 {+-} 0.009 MeV{sup {minus}1} , a{sub s} = 0.180 {+-} 0.047 MeV{sup {minus}1}, and y{sub 0} = 0.047 {+-} 0.04 MeV{+-}, respectively. The effective nucleon mass at the Fermi surface is derived as m*/m = 1.09 {+-} 0.13. New evidence is presented for a dipole-quadrupole interaction term in the primary E1 transitions of average resonance capture data. This evidence is obtained by testing a proposed generalized Landau Fermi liquid model for spherical and deformed nuclei, which includes the effect of the dipole-quadrupole interaction. The Landau-Migdal interaction constant and the effective nucleon mass, are determined as F{sub 0}{prime} = 1.49 {+-} 0.08, and m*/m=1.04 {+-} 0.07, respectively.

  14. Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation.

    Science.gov (United States)

    Cheng, Ying; Liu, Miao; Hu, Huijing; Liu, Daozhou; Zhou, Siyuan

    2016-04-01

    Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.

  15. Modulation of Osteogenesis in MC3T3-E1 Cells by Different Frequency Electrical Stimulation.

    Directory of Open Access Journals (Sweden)

    Yu Wang

    Full Text Available Electrical stimulation (ES is therapeutic to many bone diseases, from promoting fracture regeneration to orthopedic intervention. The application of ES offers substantial therapeutic potential, while optimal ES parameters and the underlying mechanisms responsible for the positive clinical impact are poorly understood. In this study, we assembled an ES cell culture and monitoring device. Mc-3T3-E1 cells were subjected to different frequency to investigate the effect of osteogenesis. Cell proliferation, DNA synthesis, the mRNA levels of osteosis-related genes, the activity of alkaline phosphatase (ALP, and intracellular concentration of Ca2+ were thoroughly evaluated. We found that 100 Hz could up-regulate the mRNA levels of collagen I, collagen II and Runx2. On the contrary, ES could down-regulate the mRNA levels of osteopontin (OPN. ALP activity assay and Fast Blue RR salt stain showed that 100 Hz could accelerate cells differentiation. Compared to the control group, 100 Hz could promote cell proliferation. Furthermore, 1 Hz to 10 Hz could improve calcium deposition in the intracellular matrix. Overall, these results indicate that 100Hz ES exhibits superior potentialities in osteogenesis, which should be beneficial for the clinical applications of ES for the treatment of bone diseases.

  16. The molecular mechanism regulating 24-hour rhythm of CYP2E1 expression in the mouse liver

    National Research Council Canada - National Science Library

    Matsunaga, Naoya; Ikeda, Misaki; Takiguchi, Takako; Koyanagi, Satoru; Ohdo, Shigehiro

    2008-01-01

    .... In the present study, we investigated whether hepatic nuclear factor-1alpha (HNF-1alpha) and clock genes with a striking 24-hour rhythm in mouse liver contributed to the 24-hour regulation of CYP2E1 expression...

  17. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez-Garza, Octavio, E-mail: ojimenezgarza@ugto.mx [Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato (Mexico); Baccarelli, Andrea A.; Byun, Hyang-Min [Laboratory of Environmental Epigenetics, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115 (United States); Márquez-Gamiño, Sergio [Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato (Mexico); Barrón-Vivanco, Briscia Socorro [Environmental Toxicology and Pollution Laboratory, Nayarit Autonomous University, Av. Ciudad de la Cultura s/n, “Amado Nervo”, Tepic, Nayarit C.P. 63155 (Mexico); Albores, Arnulfo [Department of Toxicology, CINVESTAV, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, 07360 Mexico DF (Mexico)

    2015-08-01

    Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. Goal: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. Methods: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86 +/− 7 mg/m{sup 3}) and 24 administrative workers (reference group, mean levels 0.21 +/− 0.02 mg/m{sup 3}) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. Results: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r = − .36, p < 0.05), as well as for IL6 promoter methylation levels (r = .44, p < 0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p = 0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r = − .37, p < 0.05 and r = − .34, p < 0.05 respectively). Conclusion: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. - Highlights: • We investigated gene-specific methylation in persons chronically exposed to toluene. • In a previous study, a reduced CYP2E1 activity was observed in these participants. • CYP2E1

  18. CYP2E1PstI/RsaI polymorphism and interaction with tobacco, alcohol and GSTs in gastric cancer susceptibility: A meta-analysis of the literature.

    NARCIS (Netherlands)

    S. Boccia (Stefania); S. de Lauretis (Angelo); F. Gianfagna (Francesco); C.M. van Duijn (Cornelia); G. Ricciardi (Gualtiero)

    2007-01-01

    textabstractStudies investigating the association between cytochrome P450 2E1 (CYP2E1) 5'-flanking region (PstI/RsaI) polymorphism and gastric cancer risk report conflicting results. The rationale for this meta-analysis was to determine whether CYP2E1*2 (c2) variant allele of CYP2E1 increases

  19. The human papillomavirus DNA helicase E1 binds, stimulates, and confers processivity to cellular DNA polymerase epsilon

    Science.gov (United States)

    Chojnacki, Michaelle

    2018-01-01

    Abstract The papillomavirus (PV) helicase protein E1 recruits components of the cellular DNA replication machinery to the PV replication fork, such as Replication Protein A (RPA), DNA polymerase α-primase (pol α) and topoisomerase I (topo I). Here we show that E1 binds to DNA polymerase ϵ (pol ϵ) and dramatically stimulates the DNA synthesis activity of pol ϵ. This stimulation of pol ϵ by E1 is highly specific and occurs even in the absence of the known pol ϵ cofactors Replication Factor C (RFC), Proliferating Cell Nuclear Antigen (PCNA) and RPA. This stimulation is due to an increase in the processivity of pol ϵ and occurs independently of pol ϵ’s replication cofactors. This increase in processivity is dependent on the ability of the E1 helicase to hydrolyze ATP, suggesting it is dependent on E1’s helicase action. In addition, RPA, thought to be vital for processive DNA synthesis by both pol ϵ and pol δ, was found to be dispensable for processive synthesis by pol ϵ in the presence of E1. Overall, E1 appears to be conferring processivity to pol ϵ by directly tethering pol ϵ to the DNA parental strand and towing ϵ behind the E1 helicase as the replication fork progresses; and thereby apparently obviating the need for RPA for leading strand synthesis. Thus far only pol α and pol δ have been implicated in the DNA replication of mammalian viruses; this is the first reported example of a virus recruiting pol ϵ. Furthermore, this demonstrates a unique capacity of a viral helicase having evolved to stimulate a cellular replicative DNA polymerase. PMID:29155954

  20. E1A Interacts with Two Opposing Transcriptional Pathways To Induce Quiescent Cells into S Phase ▿

    Science.gov (United States)

    Sha, Jingfeng; Ghosh, Mrinal K.; Zhang, Keman; Harter, Marian L.

    2010-01-01

    Despite data suggesting that the adenovirus E1A protein of 243 amino acids creates an S-phase environment in quiescent cells by overcoming the nucleosomal repression of E2F-regulated genes, the precise mechanisms underlying E1A's ability in this process have not yet been defined at the biochemical level. In this study, we show by kinetic analysis that E1A, as opposed to an E1A mutant failing to bind p130, can temporally eliminate corepressor complexes consisting of p130-E2F4 and HDAC1/2-mSin3B from the promoters of E2F-regulated genes in quiescent cells. Once the complexes are removed, the di-methylation of H3K9 at these promoters becomes dramatically diminished, and this in turn allows for the acetylation of H3K9/14 and the recruitment of activating E2F family members, which is then followed by the transcriptional activity of the E2F-regulated genes. Remarkably, although an E1A mutant that can no longer bind to a histone acetyltransferase (PCAF) is as capable as wild-type E1A in eliminating corepressor complexes and methyl groups from the promoters of these genes, it cannot mediate the acetylation of H3K9/14 or induce their transcription. These findings suggest that corepressors as well as coactivators are acted upon by E1A to derepress E2F-regulated genes in quiescent cells. Thus, our results highlight for the first time a functional relationship between E1A and two transcriptional pathways of differing functions for transitioning cells out of quiescence and into S phase. PMID:20089639

  1. [Cloning and functional analysis of cysI gene involved in siderophores biosynthesis in Pseudomonas mosselii E1].

    Science.gov (United States)

    Huang, Wei-Hong; Ding, Yan-Qin; Yao, Liang-Tong; Du, Zhi-Bing; Du, Bing-Hai

    2007-10-01

    A siderophores-producing strain E1 was isolated from the rhizosphere of cotton. Its 16S rDNA is identical to that of Pseudomonas mosselii sp. nov. at 100% level. The suicide plasmid pRL1063a carrying Tn5-1063 was introduced into E1 by triparental mating and 1000 transposon insertion mutants were subsequently screened using CAS assay. One mutant deficiency in siderophores production was obtained, namely, E1-185. DNA sequences flanking Tn5-1063 of E1-185 was amplified by TAIL-PCR. According to the DNA sequencing results, it is found that Tn5-1063 was inserted into cysI gene. The cysI of E1 is identical to that of Pseudomonas entomophila. L48 at 96% level, and similarity of amino acid sequences of their CysI is 97% . The cysI gene is required for the synthesis of cysteine. However, The ability in siderophores production of E1-185 on the plate of CAS with cysteine was recovered. It is indicated that cysI play an important role during the synthesis of siderophores. It was supposed that cysI is involved in the synthesis of acyl-S-PCPs, which is the key protein in the synthesis pathway of siderophores.

  2. Rhes, a Physiologic Regulator of Sumoylation, Enhances Cross-sumoylation between the Basic Sumoylation Enzymes E1 and Ubc9*

    Science.gov (United States)

    Subramaniam, Srinivasa; Mealer, Robert G.; Sixt, Katherine M.; Barrow, Roxanne K.; Usiello, Alessandro; Snyder, Solomon H.

    2010-01-01

    We recently reported that the small G-protein Rhes has the properties of a SUMO-E3 ligase and mediates mutant huntingtin (mHtt) cytotoxicity. We now demonstrate that Rhes is a physiologic regulator of sumoylation, which is markedly reduced in the corpus striatum of Rhes-deleted mice. Sumoylation involves activation and transfer of small ubiquitin-like modifier (SUMO) from the thioester of E1 to the thioester of Ubc9 (E2) and final transfer to lysines on target proteins, which is enhanced by E3s. We show that E1 transfers SUMO from its thioester directly to lysine residues on Ubc9, forming isopeptide linkages. Conversely, sumoylation on E1 requires transfer of SUMO from the thioester of Ubc9. Thus, the process regarded as “autosumoylation” reflects intermolecular transfer between E1 and Ubc9, which we designate “cross-sumoylation.” Rhes binds directly to both E1 and Ubc9, enhancing cross-sumoylation as well as thioester transfer from E1 to Ubc9. PMID:20424159

  3. Rhes, a physiologic regulator of sumoylation, enhances cross-sumoylation between the basic sumoylation enzymes E1 and Ubc9.

    Science.gov (United States)

    Subramaniam, Srinivasa; Mealer, Robert G; Sixt, Katherine M; Barrow, Roxanne K; Usiello, Alessandro; Snyder, Solomon H

    2010-07-02

    We recently reported that the small G-protein Rhes has the properties of a SUMO-E3 ligase and mediates mutant huntingtin (mHtt) cytotoxicity. We now demonstrate that Rhes is a physiologic regulator of sumoylation, which is markedly reduced in the corpus striatum of Rhes-deleted mice. Sumoylation involves activation and transfer of small ubiquitin-like modifier (SUMO) from the thioester of E1 to the thioester of Ubc9 (E2) and final transfer to lysines on target proteins, which is enhanced by E3s. We show that E1 transfers SUMO from its thioester directly to lysine residues on Ubc9, forming isopeptide linkages. Conversely, sumoylation on E1 requires transfer of SUMO from the thioester of Ubc9. Thus, the process regarded as "autosumoylation" reflects intermolecular transfer between E1 and Ubc9, which we designate "cross-sumoylation." Rhes binds directly to both E1 and Ubc9, enhancing cross-sumoylation as well as thioester transfer from E1 to Ubc9.

  4. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit.

    Science.gov (United States)

    Jiménez-Garza, Octavio; Baccarelli, Andrea A; Byun, Hyang-Min; Márquez-Gamiño, Sergio; Barrón-Vivanco, Briscia Socorro; Albores, Arnulfo

    2015-08-01

    CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86+/-7mg/m(3)) and 24 administrative workers (reference group, mean levels 0.21+/-0.02mg/m(3)) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r=-.36, ptoluene-exposed smokers compared to nonsmokers (p=0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r=-.37, ptoluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Laboratory Animal Medicine: Teaching for Relevance

    Science.gov (United States)

    Harkness, J. E.

    1977-01-01

    A mechanism for augmenting the relevance of instruction in laboratory animal medicine is suggested: the identification of practice-relevant content. This identification helps foster a positive attitude toward the subject and facilitates the retention of information. (LBH)

  6. Does relevance matter in academic policy research?

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars.......A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars....

  7. Response of MC3T3-E1cells on microroughen bioactive glass coated zirconia

    Directory of Open Access Journals (Sweden)

    Sapna Laxmi Tuladhar

    2017-10-01

    Full Text Available Background & Objectives:The objective of this study was to determine the cellular response of micro-roughened bioactive glass coated zirconia substrate (ZBR and non roughen bioactive glass coated zirconia substrate (ZB, and compare them with uncoated zirconia substrate (Z.  Materials & Methods:Surface micro-roughening was obtained using an Al2O3 sandblasting method. Abrasive blasting of zirconia coated bioactive glass produced an irregular finish with surface roughness average Ra 0.85 µm as determined by profilometer and scan electron microscope. Surface roughness of the samples in ascending order was ZBR>ZB>Z. Murine derived preosteoblast (MC3T3-E1 cells were seeded on the samples, and the cell morphology, growth, differentiation, were observed. Cell morphology was evaluated by means of scanning electron microscope (SEM, while cell proliferation and differentiation using MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide test and alkaline phosphates activity respectively. Results:The cell growth on all the samples continual increase with culturing up to 5days, showing good cell viability. However, there was no significant difference (p>0.05 with respect to the Z, ZB, and ZBR at day 5 at MTT assay. In particular, the alkaline phosphatase (ALP activity of the cells was significantly higher on the ZB and ZBR than Z samples at both 7 and 14 days.   Conclusion:Our findings demonstrate that bioactive glass coated surface was found to have better surface conditions to regulate bone cell differentiation 

  8. Effect of acetaminophen on osteoblastic differentiation and migration of MC3T3-E1 cells.

    Science.gov (United States)

    Nakatsu, Yoshihiro; Nakagawa, Fumio; Higashi, Sen; Ohsumi, Tomoko; Shiiba, Shunji; Watanabe, Seiji; Takeuchi, Hiroshi

    2017-07-15

    N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear. Therefore, we investigated the effect of APAP on osteoblastic differentiation and cell migration, with a particular focus on TRP channels and CB1. Effects of APAP on osteoblastic differentiation and cell migration of MC3T3-E1, a mouse pre-osteoblast cell line, were assessed by the increase in alkaline phosphatase (ALP) activity, and both wound-healing and transwell-migration assays, respectively. APAP dose-dependently inhibited osteoblastic differentiation, which was well correlated with the effects on COX activity compared with other NSAIDs. In contrast, cell migration was promoted by APAP, and this effect was not correlated with COX inhibition. None of the agonists or antagonists of TRP channels and the CB receptor affected the APAP-induced cell migration, while the effect of APAP on cell migration was abolished by down-regulating TRPV4 gene expression. APAP inhibited osteoblastic differentiation via COX inactivation while it promoted cell migration independently of previously known targets such as COX, TRPV1, TRPA1 channels, and CB receptors, but through the mechanism involving TRPV4. APAP may have still unidentified molecular targets that modify cellular functions. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Lanreotide inhibits human jejunal secretion induced by prostaglandin E1 in healthy volunteers.

    Science.gov (United States)

    Sobhani, I; René, E; Ramdani, A; Bayod, F; Sabbagh, L C; Thomas, F; Mignon, M

    1996-02-01

    1. Somatostatin inhibits hormonal secretions in the gastrointestinal tract. Somatostatin analogues are used in the treatment of VIPome-related watery diarrhoea. In addition, more than 10% of patients with AIDS suffer from diarrhoea likely due to the increased intestinal secretion of water and ions. However, the direct effect of somatostatin on the flux of water and ions in the intestine has not been, so far, analyzed in vivo. The aim of the present study was to evaluate the effect of lanreotide, a somatostatin analogue, on the movements of water and ions in the jejunum in man. 2. Accordingly, 10 healthy volunteers (age 18-35 years, mean 27) and two patients with AIDS (26 and 33 years) suffering from water diarrhoea (> 800 ml day-1) underwent intestinal perfusion using a four lumen tube with proximal occluding balloon. The segment tested was 25 cm long. The jejunum was infused by an isotonic control saline solution containing polyethylene glycol (PEG) as nonabsorbable marker. Basal jejunal secretions were measured in all subjects. Prostaglandin E1 (PGE1) was administered intraluminally to stimulate jejunal secretion in healthy volunteers. The effect of intravenous lanreotide on the jejunal PGE1-induced secretions of water and electrolytes was analysed in healthy subjects and on the basal secretions in AIDS patients. Each period was analyzed on the basis of three (10 min) successive intestinal juice collections after 20-30 min equilibration time. The antisecretory effect of lanreotide was evaluated in each subject as the difference between fluxes compared to the control period. 3. In healthy volunteers, PGE1 induced secretion of H2O, Na+, K+ and Cl- in the jejunum and lanreotide reduced significantly PGE1-induced response. In both AIDS patients basal fluxes of water and ions were reduced by lanreotide in a dose-dependent manner. 4. Somatostatin can reduce stimulated-jejunal secretion of ions and water in normal subjects and may improve water diarrhoea in AIDS

  10. The human orphan nuclear receptor tailless (TLX, NR2E1 is druggable.

    Directory of Open Access Journals (Sweden)

    Cindy Benod

    Full Text Available Nuclear receptors (NRs are an important group of ligand-dependent transcriptional factors. Presently, no natural or synthetic ligand has been identified for a large group of orphan NRs. Small molecules to target these orphan NRs will provide unique resources for uncovering regulatory systems that impact human health and to modulate these pathways with drugs. The orphan NR tailless (TLX, NR2E1, a transcriptional repressor, is a major player in neurogenesis and Neural Stem Cell (NSC derived brain tumors. No chemical probes that modulate TLX activity are available, and it is not clear whether TLX is druggable. To assess TLX ligand binding capacity, we created homology models of the TLX ligand binding domain (LBD. Results suggest that TLX belongs to an emerging class of NRs that lack LBD helices α1 and α2 and that it has potential to form a large open ligand binding pocket (LBP. Using a medium throughput screening strategy, we investigated direct binding of 20,000 compounds to purified human TLX protein and verified interactions with a secondary (orthogonal assay. We then assessed effects of verified binders on TLX activity using luciferase assays. As a result, we report identification of three compounds (ccrp1, ccrp2 and ccrp3 that bind to recombinant TLX protein with affinities in the high nanomolar to low micromolar range and enhance TLX transcriptional repressive activity. We conclude that TLX is druggable and propose that our lead compounds could serve as scaffolds to derive more potent ligands. While our ligands potentiate TLX repressive activity, the question of whether it is possible to develop ligands to de-repress TLX activity remains open.

  11. The human orphan nuclear receptor tailless (TLX, NR2E1) is druggable.

    Science.gov (United States)

    Benod, Cindy; Villagomez, Rosa; Filgueira, Carly S; Hwang, Peter K; Leonard, Paul G; Poncet-Montange, Guillaume; Rajagopalan, Senapathy; Fletterick, Robert J; Gustafsson, Jan-Åke; Webb, Paul

    2014-01-01

    Nuclear receptors (NRs) are an important group of ligand-dependent transcriptional factors. Presently, no natural or synthetic ligand has been identified for a large group of orphan NRs. Small molecules to target these orphan NRs will provide unique resources for uncovering regulatory systems that impact human health and to modulate these pathways with drugs. The orphan NR tailless (TLX, NR2E1), a transcriptional repressor, is a major player in neurogenesis and Neural Stem Cell (NSC) derived brain tumors. No chemical probes that modulate TLX activity are available, and it is not clear whether TLX is druggable. To assess TLX ligand binding capacity, we created homology models of the TLX ligand binding domain (LBD). Results suggest that TLX belongs to an emerging class of NRs that lack LBD helices α1 and α2 and that it has potential to form a large open ligand binding pocket (LBP). Using a medium throughput screening strategy, we investigated direct binding of 20,000 compounds to purified human TLX protein and verified interactions with a secondary (orthogonal) assay. We then assessed effects of verified binders on TLX activity using luciferase assays. As a result, we report identification of three compounds (ccrp1, ccrp2 and ccrp3) that bind to recombinant TLX protein with affinities in the high nanomolar to low micromolar range and enhance TLX transcriptional repressive activity. We conclude that TLX is druggable and propose that our lead compounds could serve as scaffolds to derive more potent ligands. While our ligands potentiate TLX repressive activity, the question of whether it is possible to develop ligands to de-repress TLX activity remains open.

  12. The Need for Culturally Relevant Dance Education

    Science.gov (United States)

    McCarthy-Brown, Nyama

    2009-01-01

    There is a need for culturally relevant teaching in dance education. Many dance teachers have heard the buzz words "culturally relevant teaching methods." Yet these dance educators acknowledge that the "dance culture" is not always synonymous with "culturally relevant." This paper examines the issue of culturally…

  13. The Personal Relevance of the Social Studies.

    Science.gov (United States)

    VanSickle, Ronald L.

    1990-01-01

    Conceptualizes a personal-relevance framework derived from Ronald L. VanSickle's five areas of life integrated with four general motivating goals from Abraham Maslow's hierarchy of needs and Richard and Patricia Schmuck's social motivation theory. Illustrates ways to apply the personal relevance framework to make social studies more relevant to…

  14. Ethanol metabolism by alcohol dehydrogenase or cytochrome P4502E1 differentially impairs hepatic protein trafficking and growth hormone signaling.

    Science.gov (United States)

    Doody, Erin E; Groebner, Jennifer L; Walker, Jetta R; Frizol, Brittnee M; Tuma, Dean J; Fernandez, David J; Tuma, Pamela L

    2017-12-01

    The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P 450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress. We have previously shown that microtubules are hyperacetylated in ethanol-treated polarized, hepatic WIF-B cells and livers from ethanol-fed rats. We have also shown that enhanced protein acetylation correlates with impaired clathrin-mediated endocytosis, constitutive secretion, and nuclear translocation and that the defects are likely mediated by acetaldehyde. However, the roles of CYP2E1-generated metabolites and ROS in microtubule acetylation and these alcohol-induced impairments have not been examined. To determine if CYP2E1-mediated alcohol metabolism is required for enhanced acetylation and the trafficking defects, we coincubated cells with ethanol and diallyl sulfide (DAS; a CYP2E1 inhibitor) or N -acetyl cysteine (NAC; an antioxidant). Both agents failed to prevent microtubule hyperacetylation in ethanol-treated cells and also failed to prevent impaired secretion or clathrin-mediated endocytosis. Somewhat surprisingly, both DAS and NAC prevented impaired STAT5B nuclear translocation. Further examination of microtubule-independent steps of the pathway revealed that Jak2/STAT5B activation by growth hormone was prevented by DAS and NAC. These results were confirmed in ethanol-exposed HepG2 cells expressing only ADH or CYP2E1. Using quantitative RT-PCR, we further determined that ethanol exposure led to blunted growth hormone-mediated gene expression. In conclusion, we determined that alcohol-induced microtubule acetylation and associated defects in microtubule-dependent trafficking are mediated by ADH metabolism whereas impaired microtubule-independent Jak2/STAT5B activation is mediated by CYP2E1 activity. NEW & NOTEWORTHY Impaired growth hormone-mediated signaling is observed in ethanol

  15. Mechanism-based inactivation of cytochromes P450 2E1 and 2E1 T303A by tert-butyl acetylenes: characterization of reactive intermediate adducts to the heme and apoprotein.

    Science.gov (United States)

    Blobaum, Anna L; Kent, Ute M; Alworth, William L; Hollenberg, Paul F

    2002-12-01

    The kinetics for the inactivation of cytochrome P450 2E1 and the mutant P450 2E1 T303A by tert-butyl acetylene (tBA) and tert-butyl 1-methyl-2-propynyl ether (tBMP) were investigated. The two acetylenes inactivated the 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC) O-deethylation activity of purified rabbit P450s 2E1 and 2E1 T303A in a reconstituted system in a time-, concentration-, and NADPH-dependent manner. The K(I) values for the inactivation of P450s 2E1 and 2E1 T303A by tBA were 1.0 and 2.0 mM, the k(inact) values were 0.20 and 0.38 min(-)(1), and the t(1/2) values were 3.5 and 1.8 min, respectively. The K(I) values for the tBMP-inactivated P450s were 0.1 and 1.0 mM, the k(inact) values were 0.12 and 0.07 min(-)(1), and the t(1/)(2) values were 5.9 and 10.2 min, respectively. Losses in enzyme activity occurred with concurrent losses in the P450 CO spectrum and P450 heme, which were accompanied by the appearance of two different tBA- or tBMP-modified heme products in each inactivated sample. LC-MS analysis of the adducts showed masses of 661 or 705 Da, consistent with the mass of an iron-depleted heme plus the masses of a tBA or tBMP reactive intermediate and one oxygen atom, respectively. Only the tBA-inactivated P450 2E1 revealed a tBA-adducted apoprotein with an increase in mass of 99 Da, corresponding to the mass of tBA plus one oxygen atom. Surprisingly, the inactivation, CO spectral and heme loss, and heme adduct formation of the tBA-inactivated T303A mutant were completely reversible after dialysis. In addition, metabolism of para-nitrophenol was not compromised by the tBA-inactivated T303A mutant. Therefore, our studies on the inactivation of P450s 2E1 and 2E1 T303A by tBA and tBMP suggest the existence of three distinct mechanisms for inactivation, among which includes a novel, reversible heme alkylation that has not been previously described with P450 enzymes.

  16. Immunological characterization of a modified vaccinia virus Ankara vector expressing the human papillomavirus 16 E1 protein.

    Science.gov (United States)

    Remy-Ziller, Christelle; Germain, Claire; Spindler, Anita; Hoffmann, Chantal; Silvestre, Nathalie; Rooke, Ronald; Bonnefoy, Jean-Yves; Préville, Xavier

    2014-02-01

    Women showing normal cytology but diagnosed with a persistent high-risk human papillomavirus (HR-HPV) infection have a higher risk of developing high-grade cervical intraepithelial neoplasia and cervical cancer than noninfected women. As no therapeutic management other than surveillance is offered to these women, there is a major challenge to develop novel targeted therapies dedicated to the treatment of these patients. As such, E1 and E2 antigens, expressed early in the HPV life cycle, represent very interesting candidates. Both proteins are necessary for maintaining coordinated viral replication and gene synthesis during the differentiation process of the epithelium and are essential for the virus to complete its normal and propagative replication cycle. In the present study, we evaluated a new active targeted immunotherapeutic, a modified vaccinia virus Ankara (MVA) vector containing the E1 sequence of HPV16, aimed at inducing cellular immune responses with the potential to help and clear persistent HPV16-related infection. We carried out an extensive comparative time course analysis of the cellular immune responses induced by different schedules of immunization in C57BL/6 mice. We showed that multiple injections of MVA-E1 allowed sustained HPV16 E1-specific cellular immune responses in vaccinated mice and had no impact on the exhaustion phenotype of the generated HPV16 E1-specific CD8⁺ T cells, but they led to the differentiation of multifunctional effector T cells with high cytotoxic capacity. This study provides proof of concept that an MVA expressing HPV16 E1 can induce robust and long-lasting E1-specific responses and warrants further development of this candidate.

  17. Oncolytic E1B 55KDa-deleted adenovirus replication is independent of p53 levels in cancer cells.

    Science.gov (United States)

    Abbas, B M; El-Mogy, M A; Haj-Ahmad, Y

    2017-08-15

    Oncolytic adenoviruses represent a new approach for cancer therapy due to its tumor specificity. E1B 55kDa-deleted adenovirus type 5 (Ad5dlE1B 55kDa) is a promising therapeutic agent that can selectively replicate in and lyse p53 defective cancer cells. However, the overall efficacy has shown varying degrees of success with raised doubts about the correlation between p53 status and E1B-deleted adenovirus replication ability. In this study, we investigated the relationship between the efficiency of Ad5dlE1B 55kDa replication and p53 levels in cancer cells. Five transient p53 expression vectors were engineered to expresses different p53 levels in transfected cells. Then, the effect of the variable p53 levels and cellular backgrounds on the replication efficiency of oncolytic Ad5dlE1B 55kDa was evaluated in H1299 and HeLa cell lines. We found that the replication efficiency of these oncolytic viruses is dependent on the status, but not the expression levels, of p53. Ad5dlE1B 55kDa was shown to have selective replication activity in H1299 cells (p53-null) and decreased viral replication in HeLa cells (p53-positive), relative to the wild-type adenovirus in both cell lines. Our findings suggest that there is a relation between the E1B-deleted adenovirus replication and the presence as well as the activity of p53, independent of its quantity.

  18. Differential polarization of immune responses by plant 2S seed albumins, Ber e 1, and SFA8.

    Science.gov (United States)

    Kean, Dorothy E; Goodridge, Helen S; McGuinness, Stephen; Harnett, Margaret M; Alcocer, Marcos J C; Harnett, William

    2006-08-01

    The plant 2S seed albumins Ber e 1 and SFA8, although structurally very similar, vary with respect to their allergenic properties. Whereas the former represents a major allergen, the latter appears to promote only weak allergenic responses. The aim of this investigation was to determine whether the allergenic properties of Ber e 1 and SFA8 reflected differential polarization of dendritic cell (DC) and Th cell responses. We thus investigated the effect of recombinant forms of both allergens on DC and Th cell responses as indicated by cell surface phenotype and cytokine production. Exposure of murine DCs to SFA8, but not Ber e 1, resulted in production of the cytokines IL-12 p40 and TNF-alpha by a mechanism independent of recognition by TLRs. Furthermore, depending on the mouse strain used, increased expression of MHC class II and costimulatory molecules such as CD40, CD80, and CD86 was associated with exposure to SFA8, but not Ber e 1. In coculture experiments using the DO11.10 transgenic T cell that recognizes OVA peptide, DCs exposed to both allergens induced T cells to produce IFN-gamma, but only Ber e 1 could induce significant production of IL-4 and IL-5. Likewise, analysis of transcription factors shows increased T-bet with respect to both allergens, but also GATA-3 with respect to Ber e 1. Overall, our data are consistent with the idea that the ability of Ber e 1, but not SFA8, to act as a potent allergen may reflect differences in their ability to induce IL-12 production.

  19. Solution structure, copper binding and backbone dynamics of recombinant Ber e 1-the major allergen from Brazil nut.

    Science.gov (United States)

    Rundqvist, Louise; Tengel, Tobias; Zdunek, Janusz; Björn, Erik; Schleucher, Jürgen; Alcocer, Marcos J C; Larsson, Göran

    2012-01-01

    The 2S albumin Ber e 1 is the major allergen in Brazil nuts. Previous findings indicated that the protein alone does not cause an allergenic response in mice, but the addition of components from a Brazil nut lipid fraction were required. Structural details of Ber e 1 may contribute to the understanding of the allergenic properties of the protein and its potential interaction partners. The solution structure of recombinant Ber e 1 was solved using NMR spectroscopy and measurements of the protein back bone dynamics at a residue-specific level were extracted using (15)N-spin relaxation. A hydrophobic cavity was identified in the structure of Ber e 1. Using the paramagnetic relaxation enhancement property of Cu(2+) in conjunction with NMR, it was shown that Ber e 1 is able to specifically interact with the divalent copper ion and the binding site was modeled into the structure. The IgE binding region as well as the copper binding site show increased dynamics on both fast ps-ns timescale as well as slower µs-ms timescale. The overall fold of Ber e 1 is similar to other 2S albumins, but the hydrophobic cavity resembles that of a homologous non-specific lipid transfer protein. Ber e 1 is the first 2S albumin shown to interact with Cu(2+) ions. This Cu(2+) binding has minimal effect on the electrostatic potential on the surface of the protein, but the charge distribution within the hydrophobic cavity is significantly altered. As the hydrophobic cavity is likely to be involved in a putative lipid interaction the Cu(2+) can in turn affect the interaction that is essential to provoke an allergenic response.

  20. Solution Structure, Copper Binding and Backbone Dynamics of Recombinant Ber e 1–The Major Allergen from Brazil Nut

    Science.gov (United States)

    Rundqvist, Louise; Tengel, Tobias; Zdunek, Janusz; Björn, Erik; Schleucher, Jürgen; Alcocer, Marcos J. C.; Larsson, Göran

    2012-01-01

    Background The 2S albumin Ber e 1 is the major allergen in Brazil nuts. Previous findings indicated that the protein alone does not cause an allergenic response in mice, but the addition of components from a Brazil nut lipid fraction were required. Structural details of Ber e 1 may contribute to the understanding of the allergenic properties of the protein and its potential interaction partners. Methodology/Principal Findings The solution structure of recombinant Ber e 1 was solved using NMR spectroscopy and measurements of the protein back bone dynamics at a residue-specific level were extracted using 15N-spin relaxation. A hydrophobic cavity was identified in the structure of Ber e 1. Using the paramagnetic relaxation enhancement property of Cu2+ in conjunction with NMR, it was shown that Ber e 1 is able to specifically interact with the divalent copper ion and the binding site was modeled into the structure. The IgE binding region as well as the copper binding site show increased dynamics on both fast ps-ns timescale as well as slower µs-ms timescale. Conclusions/Significance The overall fold of Ber e 1 is similar to other 2S albumins, but the hydrophobic cavity resembles that of a homologous non-specific lipid transfer protein. Ber e 1 is the first 2S albumin shown to interact with Cu2+ ions. This Cu2+ binding has minimal effect on the electrostatic potential on the surface of the protein, but the charge distribution within the hydrophobic cavity is significantly altered. As the hydrophobic cavity is likely to be involved in a putative lipid interaction the Cu2+ can in turn affect the interaction that is essential to provoke an allergenic response. PMID:23056307

  1. Structural Dissection of a Gating Mechanism Preventing Misactivation of Ubiquitin by NEDD8’s E1

    Energy Technology Data Exchange (ETDEWEB)

    Souphron,J.; Waddell, M.; Paydar, A.; Tokgöz-Gromley, Z.; Roussel, M.; Schulman, B.

    2008-01-01

    Post-translational covalent modification by ubiquitin and ubiquitin-like proteins (UBLs) is a major eukaryotic mechanism for regulating protein function. In general, each UBL has its own E1 that serves as the entry point for a cascade. The E1 first binds the UBL and catalyzes adenylation of the UBL's C-terminus, prior to promoting UBL transfer to a downstream E2. Ubiquitin's Arg 72, which corresponds to Ala72 in the UBL NEDD8, is a key E1 selectivity determinant: swapping ubiquitin and NEDD8 residue 72 identity was shown previously to swap their E1 specificity. Correspondingly, Arg190 in the UBA3 subunit of NEDD8's heterodimeric E1 (the APPBP1-UBA3 complex), which corresponds to a Gln in ubiquitin's E1 UBA1, is a key UBL selectivity determinant. Here, we dissect this specificity with biochemical and X-ray crystallographic analysis of APPBP1-UBA3-NEDD8 complexes in which NEDD8's residue 72 and UBA3's residue 190 are substituted with different combinations of Ala, Arg, or Gln. APPBP1-UBA3's preference for NEDD8's Ala72 appears to be indirect, due to proper positioning of UBA3's Arg190. By contrast, our data are consistent with direct positive interactions between ubiquitin's Arg72 and an E1's Gln. However, APPBP1-UBA3's failure to interact with a UBL having Arg72 is not due to a lack of this favorable interaction, but rather arises from UBA3's Arg190 acting as a negative gate. Thus, parallel residues from different UBL pathways can utilize distinct mechanisms to dictate interaction selectivity, and specificity can be amplified by barriers that prevent binding to components of different conjugation cascades.

  2. Polyphosphates inhibit extracellular matrix mineralization in MC3T3-E1 osteoblast cultures.

    Science.gov (United States)

    Hoac, Betty; Kiffer-Moreira, Tina; Millán, José Luis; McKee, Marc D

    2013-04-01

    Studies on various compounds of inorganic phosphate, as well as on organic phosphate added by post-translational phosphorylation of proteins, all demonstrate a central role for phosphate in biomineralization processes. Inorganic polyphosphates are chains of orthophosphates linked by phosphoanhydride bonds that can be up to hundreds of orthophosphates in length. The role of polyphosphates in mammalian systems, where they are ubiquitous in cells, tissues and bodily fluids, and are at particularly high levels in osteoblasts, is not well understood. In cell-free systems, polyphosphates inhibit hydroxyapatite nucleation, crystal formation and growth, and solubility. In animal studies, polyphosphate injections inhibit induced ectopic calcification. While recent work has proposed an integrated view of polyphosphate function in bone, little experimental data for bone are available. Here we demonstrate in osteoblast cultures producing an abundant collagenous matrix that normally show robust mineralization, that two polyphosphates (PolyP5 and PolyP65, polyphosphates of 5 and 65 phosphate residues in length) are potent mineralization inhibitors. Twelve-day MC3T3-E1 osteoblast cultures with added ascorbic acid (for collagen matrix assembly) and β-glycerophosphate (a source of phosphate for mineralization) were treated with either PolyP5 or PolyP65. Von Kossa staining and calcium quantification revealed that mineralization was inhibited in a dose-dependent manner by both polyphosphates, with complete mineralization inhibition at 10μM. Cell proliferation and collagen assembly were unaffected by polyphosphate treatment, indicating that polyphosphate inhibition of mineralization results not from cell and matrix effects but from direct inhibition of mineralization. This was confirmed by showing that PolyP5 and PolyP65 bound to synthetic hydroxyapatite in a concentration-dependent manner. Tissue-nonspecific alkaline phosphatase (TNAP, ALPL) efficiently hydrolyzed the two PolyPs as

  3. Mapping Lunar global chemical composition from Chang'E-1 IIM data

    Science.gov (United States)

    Yan, Bokun; Xiong, Sheng Qing; Wu, Yunzhao; Wang, Zhenchao; Dong, Lina; Gan, Fuping; Yang, Suming; Wang, Runsheng

    2012-07-01

    The global distribution of the chemical composition of the lunar surface is an important factor helping us to understand the formation and evolution of the Moon. In this paper, formulas were established for deriving FeO, TiO2, Al2O3 and MnO abundances from Chang'E-1 (CE-1) Interference Imaging Spectrometer (IIM) data on the basis of the method "color ratio of UV/VIS and NIR/VIS versus VIS reflectance diagram" which was put forward by Lucey and Blewett. Global high-resolution maps (200 m/pixel) of FeO, TiO2, Al2O3 and MnO were produced, and then compared qualitatively with results from Clementine UVVIS, Lunar Prospector (LP) Gamma-Ray Spectrometer (GRS) and Neutron Prospector (NS) data. The abundance ranges of the above four elements are 0-21.0 wt%, 0-9.5 wt%, 5.4-32.1 wt%, and 0.015-0.28 wt% respectively. The abundance range of FeO is consistent with the results from LP-GRS data reported by Gillis et al. (2004), and the abundance range of TiO2 is consistent with the results from LP-NS data reported by Elphic et al. (2002). Relative abundance distributions of FeO and TiO2 from Clementine and IIM data are slightly different from those from LP-GRS and LP-NS data. In map from the LP-GRS data, FeO abundances are the highest at Oceanus Procellarum and Mare Imbrium. However, in the map from CE-1 IIM data they are the highest at Oceanus Procellarum and Mare Tranquillitatis. Although the spatial resolution of these maps is high, caution must be taken when the maps in this paper are used at the crater scale because they suffer from errors owing to topographically induced shading. In future work, a high-accuracy DEM from Lunar Reconnaissance Orbiter Mission Laser Altimeter (LOLA) data coupled with a photometric model can probably be used to resolve this problem.

  4. Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Mervi E. Hyvönen

    2015-01-01

    Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

  5. The adenovirus oncoprotein E1a stimulates binding of transcription factor ETF to transcriptionally activate the p53 gene.

    Science.gov (United States)

    Hale, T K; Braithwaite, A W

    1999-08-20

    Expression of the tumor suppressor protein p53 plays an important role in regulating the cellular response to DNA damage. During adenovirus infection, levels of p53 protein also increase. It has been shown that this increase is due not only to increased stability of the p53 protein but to the transcriptional activation of the p53 gene during infection. We demonstrate here that the E1a proteins of adenovirus are responsible for activating the mouse p53 gene and that both major E1a proteins, 243R and 289R, are required for complete activation. E1a brings about the binding of two cellular transcription factors to the mouse p53 promoter. One of these, ETF, binds to three upstream sites in the p53 promoter and one downstream site, whereas E2F binds to one upstream site in the presence of E1a. Our studies indicate that E2F binding is not essential for activation of the p53 promoter but that ETF is. Our data indicate the ETF site located downstream of the start site of transcription is the key site in conferring E1a responsiveness on the p53 promoter.

  6. Acetato?(N-[(E)-1-(6-methyl-2-pyrid?yl)methyl?idene]-2-{2-[(E)-1-(6-methyl-2-pyrid?yl)methyl?idene?amino]?pheneth?yl}aniline)nickel(II) perchlorate

    OpenAIRE

    Sarkar, Shuranjan; Lee, Hajin; Lee, Hong-In

    2010-01-01

    In the title complex, [Ni(CH3COO)(C28H26N4)]ClO4, the NiII atom is coordinated by two imine N atoms and two pyridine N atoms of the N-[(E)-1-(6-methyl-2-pyridyl)methylidene]-2-(2-[(E)-1-(6-methyl-2-pyridyl)methylideneamino]phenethyl)aniline donor ligand and two O atoms of the acetate ion in a distorted octahedral coordination. The average Ni—N and Ni—O bond lengths are 2.131 (13) and 2.098 (11) Å, respectively. An intramolecular N&...

  7. Cytochrome P450 2E1 potentiates ethanol induction of hypoxia and HIF-1α in vivo.

    Science.gov (United States)

    Wang, Xiaodong; Wu, Defeng; Yang, Lili; Gan, Lixia; Cederbaum, Arthur I

    2013-10-01

    Ethanol induces hypoxia and elevates HIF-1α in the liver. CYP2E1 plays a role in the mechanisms by which ethanol generates oxidative stress, fatty liver, and liver injury. This study evaluated whether CYP2E1 contributes to ethanol-induced hypoxia and activation of HIF-1α in vivo and whether HIF-1α protects against or promotes CYP2E1-dependent toxicity in vitro. Wild-type (WT), CYP2E1-knock-in (KI), and CYP2E1 knockout (KO) mice were fed ethanol chronically; pair-fed controls received isocaloric dextrose. Ethanol produced liver injury in the KI mice to a much greater extent than in the WT and KO mice. Protein levels of HIF-1α and downstream targets of HIF-1α activation were elevated in the ethanol-fed KI mice compared to the WT and KO mice. Levels of HIF prolyl hydroxylase 2, which promotes HIF-1α degradation, were decreased in the ethanol-fed KI mice in association with the increases in HIF-1α. Hypoxia occurred in the ethanol-fed CYP2E1 KI mice as shown by an increased area of staining using the hypoxia-specific marker pimonidazole. Hypoxia was lower in the ethanol-fed WT mice and lowest in the ethanol-fed KO mice and all the dextrose-fed mice. In situ double staining showed that pimonidazole and CYP2E1 were colocalized to the same area of injury in the hepatic centrilobule. Increased protein levels of HIF-1α were also found after acute ethanol treatment of KI mice. Treatment of HepG2 E47 cells, which express CYP2E1, with ethanol plus arachidonic acid (AA) or ethanol plus buthionine sulfoximine (BSO), which depletes glutathione, caused loss of cell viability to a greater extent than in HepG2 C34 cells, which do not express CYP2E1. These treatments elevated protein levels of HIF-1α to a greater extent in E47 cells than in C34 cells. 2-Methoxyestradiol, an inhibitor of HIF-1α, blunted the toxic effects of ethanol plus AA and ethanol plus BSO in the E47 cells in association with inhibition of HIF-1α. The HIF-1α inhibitor also blocked the elevated oxidative

  8. Genotype and allelic frequencies of CYP2E1*5B polymorphism in the southwest population of Iran

    Directory of Open Access Journals (Sweden)

    Fatemeh Zanganeh

    2014-10-01

    Full Text Available Background: Cytochrome P450 2E1 (CYP2E1 is a main enzyme which plays a major role in activating and detoxifying many xenobiotics, carcinogens and drugs. Available studies suggest that CYP2E1 single nucleotide polymorphisms (SNPs are involved in the risk of developing certain cancers after exposure to carcinogens. The purpose of the present study was to assess genotype and allele frequencies of polymorphic CYP2E1*5B in the Iranian population. Material and Methods: This study was performed on 200 healthy individuals (female: 100, male: 100 in medical laboratories of Ahvaz during 2011. The CYP2E1 *5B (rs3813867 G-1293C assessment was carried out using PCR-RFLP method. The data were analyzed with ĸ2 and hardy-Weinberg Equation statistically methods. Results: The frequency of *1A/*1A (c1/c1, *1A/*5B (c1/c2 and *5B/*5B (c2/c2 genotypes was computed 97, 3 and 0 percent, respectively. The frequency of *1A (c1 and *5B (c2 alleles was computed 98.5 and 1.5 percent, respectively. No statistically significant difference was between two genders (p>0.05. Conclusion: The genotype distribution and allele frequencies of CYP2E1*5B polymorphism were similar to Turkish and some of the European populations. However, there are significant interethnic differences when the Iranian population is compared with the Eastern Asian, American and some of the European populations. The allelic distribution of this polymorphism did not vary with gender.

  9. Occupational Toluene Exposure Induces Cytochrome P450 2E1 mRNA Expression in Peripheral Lymphocytes

    Science.gov (United States)

    Mendoza-Cantú, Ania; Castorena-Torres, Fabiola; de León, Mario Bermúdez; Cisneros, Bulmaro; López-Carrillo, Lizbeth; Rojas-García, Aurora E.; Aguilar-Salinas, Alberto; Manno, Maurizio; Albores, Arnulfo

    2006-01-01

    Print workers are exposed to organic solvents, of which the systemic toxicant toluene is a main component. Toluene induces expression of cytochrome P450 2E1 (CYP2E1), an enzyme involved in its own metabolism and that of other protoxicants, including some procarcinogens. Therefore, we investigated the association between toluene exposure and the CYP2E1 response, as assessed by mRNA content in peripheral lymphocytes or the 6-hydroxychlorzoxazone (6OH-CHZ)/chlorzoxazone (CHZ) quotient (known as CHZ metabolic ratio) in plasma, and the role of genotype (5′-flanking region RsaI/PstI polymorphic sites) in 97 male print workers. The geometric mean (GM) of toluene concentration in the air was 52.80 ppm (10–760 ppm); 54% of the study participants were exposed to toluene concentrations that exceeded the maximum permissible exposure level (MPEL). The GM of urinary hippuric acid at the end of a work shift (0.041 g/g creatinine) was elevated relative to that before the shift (0.027 g/g creatinine; p < 0.05). The GM of the CHZ metabolic ratio was 0.33 (0–9.3), with 40% of the subjects having ratios below the GM. However, the average CYP2E1 mRNA level in peripheral lymphocytes was 1.07 (0.30–3.08), and CYP2E1 mRNA levels within subjects correlated with the toluene exposure ratio (environmental toluene concentration:urinary hippuric acid concentration) (p = 0.014). Genotype did not alter the association between the toluene exposure ratio and mRNA content. In summary, with further validation, CYP2E1 mRNA content in peripheral lymphocytes could be a sensitive and noninvasive biomarker for the continuous monitoring of toluene effects in exposed persons. PMID:16581535

  10. Influence of plant lipids on immune responses in mice to the major Brazil nut allergen Ber e 1.

    Science.gov (United States)

    Dearman, R J; Alcocer, M J C; Kimber, I

    2007-04-01

    Lipids, particularly bacterial lipopolysaccharide, can impact on immune responses to proteins, with low doses enhancing type 2 responses. We have examined the influence of natural plant lipid extracts on antibody responses provoked in mice by recombinant Ber e 1, the major allergen in Brazil nuts. BALB/c strain mice were immunized (by intraperitoneal injection) with natural or recombinant Ber e l produced in Pichia pastoris and admixed with various lipid fractions isolated from Brazil nuts. Serum samples were analysed for specific IgE antibody by homologous passive cutaneous anaphylaxis assay and for IgG by enzyme-linked immunosorbant assay. Exposure to recombinant (lipid-free) Ber e 1 alone failed to induce detectable IgG or IgE antibody. Co-administration of the total lipid fraction (with reduced triglyceride levels), sterol-rich, or polar lipid fractions, resulted in marked adjuvant effects on IgG and IgE. However, the beta-sitosterol and glycolipid-rich fractions were associated with only low-level IgG antibody, and had little impact on IgE antibody production. Natural Ber e 1 containing endogenous lipids also provoked IgG and IgE antibody responses. Identical IgE and IgG antibody responses were detected regardless of whether natural or recombinant Ber e 1 was used as substrates for analyses. Endogenous Brazil nut lipids are required for the induction of optimal antibody responses to Ber e 1 in the BALB/c strain mouse. Appropriate antibody binding sites are present on both natural and recombinant forms of Ber e 1, suggesting that the impact of lipid is at the induction phase, rather than antibody recognition, and is possibly required for efficient antigen presentation.

  11. The sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat cardiomyocytes.

    Science.gov (United States)

    Nesher, Nir; Zlotkin, Eliahu; Hochner, Binyamin

    2014-07-01

    AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia diaphana, contains 44 amino acids and has a molecular mass of 4907 Da. It was previously found to resemble other sea anemone type 1 and 2 Na+ channel toxins, enhancing contractions of rat cardiomyocytes and slowing their twitch relaxation; however, it did not induce spontaneous twitches. AdE-1 increased the duration of the cardiomyocyte action potential and decreased its amplitude and its time-to-peak in a concentration-dependent manner, without affecting its threshold and cell resting potential. Nor did it generate the early and delayed after-depolarizations characteristic of sea anemone Na+ channel toxins. To further understand its mechanism of action we investigated the effect of AdE-1 on the major ion currents of rat cardiomyocytes. In the present study we show that AdE-1 markedly slowed inactivation of the Na+ current, enhancing and prolonging the current influx with no effect on current activation, possibly through direct interaction with the site 3 receptor of the Na+ channel. No significant effect of AdE-1 on the Ca2+ current was observed, but, unexpectedly, AdE-1 significantly increased the amplitude of the transient component of the K+ current, shifting the current threshold to more negative membrane potentials. This effect on the K+ current has not been found in any other sea anemone toxin and may explain the exclusive reduction in action potential amplitude and the absence of the action potential disorders found with other toxins, such as early and delayed after-depolarizations.

  12. Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex.

    Science.gov (United States)

    Patel, Mulchand S; Korotchkina, Lioubov G; Sidhu, Sukhdeep

    2009-11-01

    The human (h) pyruvate dehydrogenase complex (hPDC) consists of multiple copies of several components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), dihydrolipoamide dehydrogenase (E3), E3-binding protein (BP), and specific kinases and phosphatases. Mammalian PDC has a well organized structure with an icosahedral symmetry of the central E2/BP core to which the other component proteins bind non-covalently. Both hE2 and hBP consist of three well defined domains, namely the lipoyl domain, the subunit-binding domain and the inner domain, connected with flexible linkers. hE1 (alpha(2)beta(2)) binds to the subunit-binding domain of hE2; whereas hE3 binds to the E3-binding domain of hBP. Among several residues of the C-terminal surface of the hE1beta E1betaD289 was found to interact with hE2K276. The C-terminal residue I329 of the hE1beta did not participate in binding to hE2. This latter finding shows specificity in the interaction between E1beta and E2 in hPDC. The selective binding between hE3 and the E3-binding domain of hBP was investigated using specific mutants. E3R460G and E3340K showed significant reductions in affinity for hBP as determined by surface plasmon resonance. Both residues are involved in the structural organization of the binding site on hE3. Substitution of I157, N137 and R155 of hBP resulted in variable increases in the K(D) for binding with wild-type hE3, suggesting that the binding results from several weak electrostatic bonds and hydrophobic interactions among residues of hBP with residues at the interface of dimeric hE3. These results provide insight in the mono-specificity of binding of E1 to E2 and E3 to BP in hPDC and showed the differences in the binding of peripheral components (E1 and E3) in human and bacterial PDCs.

  13. CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

    Directory of Open Access Journals (Sweden)

    Rossini A.

    2006-01-01

    Full Text Available Cytochrome P450 (CYP is a superfamily of enzymes involved in the metabolism of endogenous compounds and xenobiotics. CYP2A6 catalyzes the oxidation of nicotine and the activation of carcinogens such as aflatoxin B1 and nitrosamines. CYP2E1 metabolizes ethanol and other low-molecular weight compounds and can also activate nitrosamines. The CYP2A6 and CYP2E1 genes are polymorphic, altering their catalytic activities and susceptibility to cancer and other diseases. A number of polymorphisms described are ethnic-dependent. In the present study, we determined the genotype and allele frequencies of the main CYP2A6 and CYP2E1 polymorphisms in a group of 289 volunteers recruited at the Central Laboratory of Hospital Universitário Pedro Ernesto. They had been residing in the city of Rio de Janeiro for at least 6 months and were divided into two groups according to skin color (white and non-white. The alleles were determined by allele specific PCR (CYP2A6 or by PCR-RFLP (CYP2E1. The frequencies of the CYP2A6*1B and CYP2A6*2 alleles were 0.29 and 0.02 for white individuals and 0.24 and 0.01 for non-white individuals, respectively. The CYP2A6*5 allele was not found in the population studied. Regarding the CYP2E1*5B allele, we found a frequency of 0.07 in white individuals, which was statistically different (P < 0.05 from that present in non-white individuals (0.03. CYP2E1*6 allele frequency was the same (0.08 in both groups. The frequencies of CYP2A6*1B, CYP2A6*2 and CYP2E1*6 alleles in Brazilians are similar to those found in Caucasians and African-Americans, but the frequency of the CYP2E1*5B allele is higher in Brazilians.

  14. E1^E4-mediated keratin phosphorylation and ubiquitylation: a mechanism for keratin depletion in HPV16-infected epithelium

    OpenAIRE

    McIntosh, Pauline B.; Laskey, Peter; Sullivan, Kate; Davy, Clare; Wang, Qian; Jackson, Deborah J.; Griffin, Heather M.; Doorbar, John

    2010-01-01

    The keratin IF network of epidermal keratinocytes provides a protective barrier against mechanical insult, it is also a major player in absorbing stress in these cells. The human papilloma virus (HPV) type 16 E1^E4 protein accumulates in the upper layers of HPV16-infected epithelium and is known to associate with and reorganise the keratin IF network in cells in culture. Here, we show that this function is conserved amongst a number of HPV alpha-group E1^E4 proteins and that the differentiati...

  15. CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

    Directory of Open Access Journals (Sweden)

    A. Rossini

    2006-02-01

    Full Text Available Cytochrome P450 (CYP is a superfamily of enzymes involved in the metabolism of endogenous compounds and xenobiotics. CYP2A6 catalyzes the oxidation of nicotine and the activation of carcinogens such as aflatoxin B1 and nitrosamines. CYP2E1 metabolizes ethanol and other low-molecular weight compounds and can also activate nitrosamines. The CYP2A6 and CYP2E1 genes are polymorphic, altering their catalytic activities and susceptibility to cancer and other diseases. A number of polymorphisms described are ethnic-dependent. In the present study, we determined the genotype and allele frequencies of the main CYP2A6 and CYP2E1 polymorphisms in a group of 289 volunteers recruited at the Central Laboratory of Hospital Universitário Pedro Ernesto. They had been residing in the city of Rio de Janeiro for at least 6 months and were divided into two groups according to skin color (white and non-white. The alleles were determined by allele specific PCR (CYP2A6 or by PCR-RFLP (CYP2E1. The frequencies of the CYP2A6*1B and CYP2A6*2 alleles were 0.29 and 0.02 for white individuals and 0.24 and 0.01 for non-white individuals, respectively. The CYP2A6*5 allele was not found in the population studied. Regarding the CYP2E1*5B allele, we found a frequency of 0.07 in white individuals, which was statistically different (P < 0.05 from that present in non-white individuals (0.03. CYP2E1*6 allele frequency was the same (0.08 in both groups. The frequencies of CYP2A6*1B, CYP2A6*2 and CYP2E1*6 alleles in Brazilians are similar to those found in Caucasians and African-Americans, but the frequency of the CYP2E1*5B allele is higher in Brazilians.

  16. Linking task analysis to information relevance.

    Science.gov (United States)

    Durso, Francis T; Sethumadhavan, Arathi; Crutchfield, Jerry

    2008-10-01

    The main objective of this study is to present a methodology for computing information relevance. Relevance is a pervasive term used in several domains, such as pragmatics, information science, and psychology. Quantifying the relevance of information can be helpful in effective display design. Displays should be designed so that the more relevant information is more easily accessed. This procedure focuses on computing the relevance of a piece of information by taking into account three aspects of tasks that use the information: the number of different tasks that make use of the information, the frequency of occurrence of those tasks, and the criticality of those tasks. The methodology can be used to compute the aggregate relevance of a piece of information for a particular component of a system or for the entire system. This methodology was illustrated using the domain of air traffic control (ATC). In support of the validity of the methodology, we were able to confirm the value of weather information and traffic information in ATC towers. The method can be used to derive information relevance, a characteristic of information that has implications for display design for any domain. Designers can use information about aggregate relevance to design information displays that feature the most relevant information.

  17. Relevance: An Interdisciplinary and Information Science Perspective

    Directory of Open Access Journals (Sweden)

    Howard Greisdorf

    2000-01-01

    Full Text Available Although relevance has represented a key concept in the field of information science for evaluating information retrieval effectiveness, the broader context established by interdisciplinary frameworks could provide greater depth and breadth to on-going research in the field. This work provides an overview of the nature of relevance in the field of information science with a cursory view of how cross-disciplinary approaches to relevance could represent avenues for further investigation into the evaluative characteristics of relevance as a means for enhanced understanding of human information behavior.

  18. Intra-arterial infusion of prostaglandin E1 in normal subjects and patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Nielsen, P E; Nielsen, S L; Holstein, P

    1976-01-01

    Acute vasodilatation was produced by infusion of prostaglandin E1 (PGE1) in the femoral artery in 6 patients with occlusive arterial disease of the legs and in 3 normal subjects. The effect on blood flow and on blood pressure was measured at different segments of the leg with the strain gauge...

  19. ILS Element E1 Maintenance Planning: Distribution Program and User’s Manual. Version 1.0

    Science.gov (United States)

    1991-04-01

    For a single digit , enter a blank space or zero to the left of the digit . The program accepts only actual dates. If an incorrect date is entered...Documentation for Comoleteness and Firmaness E1.2-1 What stage of develooment- are you in?: "o Concept Exploration "o Development and Validation "o Full Scale

  20. Mobilization properties of small ColE1-like plasmids carrying kanamycin resistance gene isolated from Salmonella enterica serotypes

    Science.gov (United States)

    Background: Previously we isolated and characterized various groups of small kanamycin resistance (KanR) ColE1-like plasmids from different serotypes of Salmonella enterica isolates. These plasmids all carried the aph(3)-I gene encoding the aminoglycoside phosphotransferase responsible for the kanam...

  1. The making of S{u00E1mi ethnography : contested authorities and negotiated representations / Kristin Kuutma

    Index Scriptorium Estoniae

    Kuutma, Kristin, 1959-

    2008-01-01

    Vaadeldakse saami autori Johan Turi raamatut Muitalus s{u00E1miid birra (1910) ja selle tõlget taani keelede Emilie Demant Hatti poolt ning uuritakse, millist autoritaarsust ja kultuurilist poeetikat see peegeldab ja millist sotsiaalset ja kultuurilist kriitikat ta edasi arendab

  2. Solution structure, copper binding and backbone dynamics of recombinant Ber e 1-the major allergen from Brazil nut

    National Research Council Canada - National Science Library

    Rundqvist, Louise; Tengel, Tobias; Zdunek, Janusz; Björn, Erik; Schleucher, Jürgen; Alcocer, Marcos J C; Larsson, Göran

    2012-01-01

    The 2S albumin Ber e 1 is the major allergen in Brazil nuts. Previous findings indicated that the protein alone does not cause an allergenic response in mice, but the addition of components from a Brazil nut lipid fraction were required...

  3. Prostaglandin E1 treatment in ductus dependent congenital cardiac malformation. A review of the treatment of 34 neonates

    DEFF Research Database (Denmark)

    Høst, A; Halken, S; Kamper, J

    1988-01-01

    Thirty-four sick neonates with major duct dependent cardiac defects were given short term (1 h-408 h) intravenous infusions of prostaglandin E1 (alprostadil) in doses varying between 0.1 micrograms/kg/min (starting dose) and 0.01 micrograms/kg/min. The aim of the study was to establish an effecti...

  4. 26 CFR 301.6503(e)-1 - Suspension of running of period of limitation; certain powers of appointment.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Suspension of running of period of limitation... Limitations Limitations on Assessment and Collection § 301.6503(e)-1 Suspension of running of period of... complied with, the running of the period of limitation for assessment or collection of any estate tax...

  5. Combined administration of resolvin E1 and lipoxin A4 resolves inflammation in a murine model of Alzheimer's disease.

    Science.gov (United States)

    Kantarci, Alpdogan; Aytan, Nurgul; Palaska, Iro; Stephens, Danielle; Crabtree, Leah; Benincasa, Claudia; Jenkins, Bruce G; Carreras, Isabel; Dedeoglu, Alpaslan

    2017-11-07

    Dysfunction in the resolution of inflammation may play a key role in Alzheimer's disease (AD). In this study, we found that the levels of specialized pro-resolving lipid mediators (SPMs) in the hippocampus of 5xFAD mice are significantly lower than in non-transgenic littermates. We, therefore, tested the hypothesis that treatment with resolvin E1 (RvE1) and lipoxin A4 (LXA4) alone or in combination will reverse the neuroinflammatory process and decrease Aβ pathology. 5xFAD mice were treated intraperitoneally starting at 1month of age with RvE1 or LXA4 alone or in combination at a dose of 1.5 μg/kg, 3 times a week until 3months of age. We found that treatment with RvE1 or LXA4 alone or in combination increased the concentration of RvE1, LXA4, and RvD2 in the hippocampus as measured by ELISA. Combination treatment of RvE1 and LXA4 had a more potent effect on the activation of microglia and astrocytes than either treatment alone, measured by immunohistochemistry with Iba1 and GFAP antibodies, respectively. The concentrations of Aβ40 and Aβ42 were measured by ELISA and the percentage of Aβ plaques were analyzed by immunohistochemistry. All treatments single and in combination, decreased the measures of Aβ pathology and restored the homeostasis reversing the inflammatory process for inflammatory cytokines and chemokines (GM-CSF, IFN-γ, IL-1β, IL-6, IL-10, TNF-α, MCP-1, MIP-1α, MIP-1β, and RANTES) as measured by multiplex immunoassay. Overall, the study showed that the levels of SPMs in the hippocampus of 5xFAD mice were significantly lower than in wild-type mice; that treatment with RvE1 and LXA4 restored the level of these compounds, reversed the inflammatory process, and decreased the neuroinflammation associated with Aβ pathology in 5xFAD mice. Copyright © 2017. Published by Elsevier Inc.

  6. Ethanol-induced oxidative stress via the CYP2E1 pathway disrupts adiponectin secretion from adipocytes.

    Science.gov (United States)

    Tang, Hui; Sebastian, Becky M; Axhemi, Armend; Chen, Xiaocong; Hillian, Antoinette D; Jacobsen, Donald W; Nagy, Laura E

    2012-02-01

    Adipose tissue is an important target for ethanol action. One important effect of ethanol is to reduce the secretion of adiponectin from adipocytes; this decrease is associated with lowered circulating adiponectin in rodent models of chronic ethanol feeding. Adiponectin is an insulin-sensitizing, anti-inflammatory adipokine; decreased adiponectin activity may contribute to tissue injury in response to chronic ethanol. Here, we investigated the role of cytochrome P450 2E1 (CYP2E1) and oxidative stress in the mechanism for impaired adiponectin secretion from adipocytes in response to ethanol. Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. 3T3-L1 adipocyte cultures, expressing CYP2E1 or not, were exposed to ethanol or 4-hydroxynonenal (4-HNE). Chronic ethanol feeding to rats suppressed the secretion of adiponectin from isolated epididymal adipocytes. Ethanol feeding induced the expression of CYP2E1 in adipocytes and increased markers of oxidative stress, including 4-HNE and protein carbonyls. Because adiponectin is posttranslationally processed in the endoplasmic reticulum and Golgi, we investigated the impact of ethanol on the redox status of high-density microsomes. Chronic ethanol decreased the ratio of reduced glutathione to oxidized glutathione (4.6:1, pair-fed; 2.9:1, ethanol-fed) in high-density microsomes isolated from rat epididymal adipose tissue. We next utilized the 3T3-L1 adipocyte-like cell model to interrogate the mechanisms for impaired adiponectin secretion. Culture of 3T3-L1 adipocytes overexpressing exogenous CYP2E1, but not those overexpressing antisense CYP2E1, with ethanol increased oxidative stress and impaired adiponectin secretion from intracellular pools. Consistent with a role of oxidative stress in impaired adiponectin secretion, challenge of 3T3-L1 adipocytes with 4-HNE also reduced adiponectin mRNA expression and secretion, without affecting intracellular adiponectin

  7. Ghrelin inhibits the apoptosis of MC3T3-E1 cells through ERK and AKT signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Qiu-Hua; Liu, Yuan; Wu, Shan-Shan; Cui, Rong-Rong; Yuan, Ling-Qing, E-mail: allenylq@hotmail.com; Liao, Er-Yuan, E-mail: eyliao@21cn.com

    2013-11-01

    Ghrelin is a 28-amino-acid peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR) and strongly stimulates the release of growth hormone from the hypothalamus–pituitary axis. Previous studies have identified the important physiological effects of ghrelin on bone metabolism, such as regulating proliferation and differentiation of osteoblasts, independent of GH/IGF-1 axis. However, research on effects and mechanisms of ghrelin on osteoblast apoptosis is still rare. In this study, we identified expression of GHSR in MC3T3-E1 cells and determined the effects of ghrelin on the apoptosis of osteoblastic MC3T3-E1 cells and the mechanism involved. Our data demonstrated that ghrelin inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as determined by terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate nick end-labeling (TUNEL) and ELISA assays. Moreover, ghrelin upregulated Bcl-2 expression and downregulated Bax expression in a dose-dependent manner. Our study also showed decreased activated caspase-3 activity under the treatment of ghrelin. Further study suggested that ghrelin stimulated the phosphorylation of ERK and AKT. Pretreatment of cells with the ERK inhibitor PD98059, PI3K inhibitor LY294002, and GHSR-siRNA blocked the ghrelin-induced activation of ERK and AKT, respectively; however, ghrelin did not stimulate the phosphorylation of p38 or JNK. PD90859, LY294002 and GHSR-siRNA attenuated the anti-apoptosis effect of ghrelin in MC3T3-E1 cells. In conclusion, ghrelin inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, which may be mediated by activating the GHSR/ERK and GHSR/PI3K/AKT signaling pathways. - Highlights: • We explored the effects of ghrelin on serum deprivation-induced MC3T3-E1 cells apoptosis. • Both ELISA and TUNEL were used to detect the apoptosis. • The receptor of ghrelin, GHSR, was expressed in MC3T3-E1

  8. Relevance and problem choice in design science

    NARCIS (Netherlands)

    Wieringa, Roelf J.

    2010-01-01

    The supposed opposition of rigor versus relevance is based on the mistaken idea that rigor consists of linear technology transfer combined with positivistic science, and ignores the context-dependence of relevance as well as the incorporation of conditions of practice necessary for applicability of

  9. Does relevance matter in academic policy research

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    A reflection on whether relevance matters in tourism policy research, and if so, to whom/what should it matter......A reflection on whether relevance matters in tourism policy research, and if so, to whom/what should it matter...

  10. Translation as secondary communication. The relevance theory ...

    African Journals Online (AJOL)

    Ernst-August Gutt started one of the greatest translation debates of the past ten years when he suggested that relevance theory holds the key to providing a unified account of translation. The bulk of the debate has been between practitioners of functional equivalence and advocates of a relevance theoretic approach to ...

  11. A cognitive approach to relevance of science

    NARCIS (Netherlands)

    Rip, Arie

    1997-01-01

    The Starnberg finalization thesis offered a cognitive diagnosis of the relevance of science. With the present changes in science and its links with society, this remains important, but needs to be broadened. Relevance occurred and continues to occur locally, and can be taken up in local¿cosmopolitan

  12. Crystal Structure of UBA2ufd-Ubc9: Insights into E1-E2 Interactions in Sumo Pathways

    Science.gov (United States)

    Hunt, Harold W.; Seyedin, Steven N.; Miller, David W.; Miller, Darcie J.; Huang, Danny T.; Schulman, Brenda A.

    2010-01-01

    Canonical ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, DNA replication, and mitosis. Sumo conjugation is initiated by the heterodimeric Aos1-Uba2 E1 enzyme (in humans called Sae1-Uba2), which activates Sumo's C-terminus, binds the dedicated E2 enzyme Ubc9, and promotes Sumo C-terminal transfer between the Uba2 and Ubc9 catalytic cysteines. To gain insights into details of E1-E2 interactions in the Sumo pathway, we determined crystal structures of the C-terminal ubiquitin fold domain (ufd) from yeast Uba2 (Uba2ufd), alone and in complex with Ubc9. The overall structures of both yeast Uba2ufd and Ubc9 superimpose well on their individual human counterparts, suggesting conservation of fundamental features of Sumo conjugation. Docking the Uba2ufd-Ubc9 and prior full-length human Uba2 structures allows generation of models for steps in Sumo transfer from Uba2 to Ubc9, and supports the notion that Uba2 undergoes remarkable conformational changes during the reaction. Comparisons to previous structures from the NEDD8 cascade demonstrate that UBL cascades generally utilize some parallel E1-E2 interaction surfaces. In addition, the structure of the Uba2ufd-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps. The results suggest mechanisms establishing specificity and order in Sumo conjugation cascades. PMID:21209884

  13. Crystal Structure of UBA2[superscript ufd]-Ubc9: Insights into E1-E2 Interactions in Sumo Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Taherbhoy, Asad M.; Hunt, Harold W.; Seyedin, Steven N.; Miller, David W.; Miller, Darcie J.; Huang, Danny T.; Schulman, Brenda A. (SJCH)

    2012-04-30

    Canonical ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, DNA replication, and mitosis. Sumo conjugation is initiated by the heterodimeric Aos1-Uba2 E1 enzyme (in humans called Sae1-Uba2), which activates Sumo's C-terminus, binds the dedicated E2 enzyme Ubc9, and promotes Sumo C-terminal transfer between the Uba2 and Ubc9 catalytic cysteines. To gain insights into details of E1-E2 interactions in the Sumo pathway, we determined crystal structures of the C-terminal ubiquitin fold domain (ufd) from yeast Uba2 (Uba2{sup ufd}), alone and in complex with Ubc9. The overall structures of both yeast Uba2{sup ufd} and Ubc9 superimpose well on their individual human counterparts, suggesting conservation of fundamental features of Sumo conjugation. Docking the Uba2{sup ufd}-Ubc9 and prior full-length human Uba2 structures allows generation of models for steps in Sumo transfer from Uba2 to Ubc9, and supports the notion that Uba2 undergoes remarkable conformational changes during the reaction. Comparisons to previous structures from the NEDD8 cascade demonstrate that UBL cascades generally utilize some parallel E1-E2 interaction surfaces. In addition, the structure of the Uba2{sup ufd}-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps. The results suggest mechanisms establishing specificity and order in Sumo conjugation cascades.

  14. Crystal structure of UBA2(ufd)-Ubc9: insights into E1-E2 interactions in Sumo pathways.

    Science.gov (United States)

    Wang, Jing; Taherbhoy, Asad M; Hunt, Harold W; Seyedin, Steven N; Miller, David W; Miller, Darcie J; Huang, Danny T; Schulman, Brenda A

    2010-12-30

    Canonical ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, DNA replication, and mitosis. Sumo conjugation is initiated by the heterodimeric Aos1-Uba2 E1 enzyme (in humans called Sae1-Uba2), which activates Sumo's C-terminus, binds the dedicated E2 enzyme Ubc9, and promotes Sumo C-terminal transfer between the Uba2 and Ubc9 catalytic cysteines. To gain insights into details of E1-E2 interactions in the Sumo pathway, we determined crystal structures of the C-terminal ubiquitin fold domain (ufd) from yeast Uba2 (Uba2(ufd)), alone and in complex with Ubc9. The overall structures of both yeast Uba2(ufd) and Ubc9 superimpose well on their individual human counterparts, suggesting conservation of fundamental features of Sumo conjugation. Docking the Uba2(ufd)-Ubc9 and prior full-length human Uba2 structures allows generation of models for steps in Sumo transfer from Uba2 to Ubc9, and supports the notion that Uba2 undergoes remarkable conformational changes during the reaction. Comparisons to previous structures from the NEDD8 cascade demonstrate that UBL cascades generally utilize some parallel E1-E2 interaction surfaces. In addition, the structure of the Uba2(ufd)-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps. The results suggest mechanisms establishing specificity and order in Sumo conjugation cascades.

  15. Crystal structure of UBA2(ufd-Ubc9: insights into E1-E2 interactions in Sumo pathways.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2010-12-01

    Full Text Available Canonical ubiquitin-like proteins (UBLs such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, DNA replication, and mitosis. Sumo conjugation is initiated by the heterodimeric Aos1-Uba2 E1 enzyme (in humans called Sae1-Uba2, which activates Sumo's C-terminus, binds the dedicated E2 enzyme Ubc9, and promotes Sumo C-terminal transfer between the Uba2 and Ubc9 catalytic cysteines. To gain insights into details of E1-E2 interactions in the Sumo pathway, we determined crystal structures of the C-terminal ubiquitin fold domain (ufd from yeast Uba2 (Uba2(ufd, alone and in complex with Ubc9. The overall structures of both yeast Uba2(ufd and Ubc9 superimpose well on their individual human counterparts, suggesting conservation of fundamental features of Sumo conjugation. Docking the Uba2(ufd-Ubc9 and prior full-length human Uba2 structures allows generation of models for steps in Sumo transfer from Uba2 to Ubc9, and supports the notion that Uba2 undergoes remarkable conformational changes during the reaction. Comparisons to previous structures from the NEDD8 cascade demonstrate that UBL cascades generally utilize some parallel E1-E2 interaction surfaces. In addition, the structure of the Uba2(ufd-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps. The results suggest mechanisms establishing specificity and order in Sumo conjugation cascades.

  16. Gene order for rubella virus structural proteins is NH/sub 2/-C-E2-E1-COOH

    Energy Technology Data Exchange (ETDEWEB)

    Oker-Blom, C.

    1984-08-01

    The order of translation in vivo of the genes coding for rubella virus structural proteins was studied in infected B-Vero cells. The proteins were sequentially pulse-chase labeled with (/sup 35/S)methionine after synchronization of translation initiation with hypertonic salt treatment. A sequential labeling procedure (window-labeling) to specifically label defined segments of the structural proteins was also used. The labeled proteins were identified by sodium dodecyl sulfate-gel electrophoresis after immunoprecipitation with specific antisera directed against the two virion glycoproteins (E1 and E2a/E2b) and the nucleocapsid (C) protein. The order of translation was found to be NH/sub 2/-C-E2-E1-COOH. We have previously shown that the structural proteins are synthesized in vitro from a cytoplasmic 24S subgenomic mRNA as a 110,000-dalton (p110) precursor. Here, it is shown that p110 is precipitated with anti-C, anti-E2, and anti-E1 sera, indicating that p110 is the precursor of all three structural proteins. Two major in vitro translation products (M/sub r/s, 66,000 and 62,000) that could represent preterminated polypeptide chains or proteolytic cleavage products were precipitated with anti-C and anti-Es sera, but not with anti-E1 serum, indicating, in conformity with the in vivo results, that the genes for the C and E2 proteins are adjacent to each other. Using these specific antisera, we have also confirmed the identity of the unglycosylated forms of E1 (M/sub r/, 53,000) and E2 (M/sub r/ 30,000) immunoprecipitated from tunicamycin-treated infected cells. 18 references, 6 figures.

  17. A negative cooperativity mechanism of human CYP2E1 inferred from molecular dynamics simulations and free energy calculations.

    Science.gov (United States)

    Li, Jue; Wei, Dong-Qing; Wang, Jing-Fang; Li, Yi-Xue

    2011-12-27

    Human cytochrome P450 2E1 (CYP2E1) participates in the metabolism of over 2% of all the oral drugs. A hallmark peculiar feature of this enzyme is that it exhibits a pronounced negative cooperativity in substrate binding. However the mechanism by which the negative cooperativity occurs is unclear. Here, we performed molecular dynamics simulations and free energy calculations on human CYP2E1 to examine the structural differences between the substrate-free and the enzymes with one and two aniline molecules bound. Our results indicate that although the effector substrate does not bind in the active site cavity, it still can directly interact with the active site residues of human CYP2E1. The interaction of the effector substrate with the active site leads to a reorientation of active site residues, which thereby weakens the interactions of the active substrate with this site. We also identify a conserved residue T303 that plays a crucial role in the negative cooperative binding on the short-range effects. This residue is a key factor in the positioning of substrates and in proton delivery to the active site. Additionally, a long-range effect of the effector substrate is identified in which F478 is proposed to play a key role. As located in the interface between the active and effector sites, this residue structurally links the active and effector sites and is found to play a significant role in affecting substrate access and ligand positioning within the active site. In the negative cooperative binding, this residue can decrease the interactions of the active substrate with the active site by π-π stacking which then lowers the hydroxylation activity for the active substrate. These findings are in agreement with previous experimental observations and thus provide detailed atomistic insight into the poorly understood mechanism of the negative cooperativity in human CYP2E1.

  18. The effect of lycopene on the total cytochrome P450, CYP1A2 and CYP2E1

    Directory of Open Access Journals (Sweden)

    Melva Louisa

    2009-12-01

    Full Text Available Aim: Some carotenoids such as canthaxantin, astaxanthin and beta apo-8’-carotenal were reported to have modulatoryeffect on the cytochrome P450. The present study was conducted to investigate the effects of lycopene, a nonprovitamin A carotenoid, on microsomal cytochrome P450, CYP1A2 and CYP2E1.Methods: Total cytochrome P450 levels, CYP1A2 and CYP2E1-catalyzed reactions (acetanilide 4-hydroxylation and p-nitrophenol hydroxylation were studied in the liver microsomes of male Sprague Dawley rats. Microsomes were prepared using differential centrifugation combined with calcium aggregation method. Lycopene was orally administered in the dosages of 0, 25, 50 or 100 mg/kgBW/day for 14 days in a repeated fashion. Data were analyzed using ANOVA test.Results: Total cytochrome P450 level and acetanilide 4-hydroxylase activity were unaffected by any of the treatments. The CYP2E1 probe enzyme (p-nitrophenol hydroxylase was significantly reduced by repeated administration of 100mg/ kgBW/day lycopene (7.88 + 2.04 vs 12.26 + 2.77 n mol/min/mg prot.Conclusion: The present results suggest that lycopene does not affect the total cytochrome P450 or CYP1A2 activity but it inhibits the activity of CYP2E1 (p-nitrophenol hydroxylase in the rat. (Med J Indones 2009; 18: 233-8Keywords: lycopene, cytochrome P450, CYP1A2, CYP2E1

  19. Bovine collagen peptides compounds promote the proliferation and differentiation of MC3T3-E1 pre-osteoblasts.

    Directory of Open Access Journals (Sweden)

    JunLi Liu

    Full Text Available OBJECTIVE: Collagen peptides (CP compounds, as bone health supplements, are known to play a role in the treatment of osteoporosis. However, the molecular mechanisms of this process remain unclear. This study aimed to investigate the effects of bovine CP compounds on the proliferation and differentiation of MC3T3-E1 cells. METHODS: Mouse pre-osteoblast cell line MC3T3-E1 subclone 4 cells were treated with bovine CP compounds. Cell proliferation was analyzed by MTT assays and the cell cycle was evaluated by flow cytometry scanning. Furthermore, MC3T3-E1 cell differentiation was analyzed at the RNA level by real-time PCR and at the protein level by western blot analysis for runt-related transcription factor 2 (Runx2, a colorimetric p-nitrophenyl phosphate assay for alkaline phosphatase (ALP, and ELISA for osteocalcin (OC. Finally, alizarin red staining for mineralization was measured using Image Software Pro Plus 6.0. RESULTS: Cell proliferation was very efficient after treatment with different concentrations of bovine CP compounds, and the best concentration was 3 mg/mL. Bovine CP compounds significantly increased the percentage of MC3T3-E1 cells in G2/S phase. Runx2 expression, ALP activity, and OC production were significantly increased after treatment with bovine CP compounds for 7 or 14 days. Quantitative analyses with alizarin red staining showed significantly increased mineralization of MC3T3-E1 cells after treatment with bovine CP compounds for 14 or 21 days. CONCLUSIONS: Bovine CP compounds increased osteoblast proliferation, and played positive roles in osteoblast differentiation and mineralized bone matrix formation. Taking all the experiments together, our study indicates a molecular mechanism for the potential treatment of osteoarthritis and osteoporosis.

  20. Atmospheric volatilization and distribution of (Z)- and (E)-1,3-dichloropropene in field beds with and without plastic covers.

    Science.gov (United States)

    Thomas, John E; Allen, L Hartwell; McCormack, Leslie A; Vu, Joseph C; Dickson, Donald W; Ou, Li-Tse

    2004-01-01

    The fumigant 1,3-dichloropropene (1,3-D) is considered to be a potential replacement for methyl bromide when methyl bromide is phased out in 2005. This study on surface emissions and subsurface diffusion of 1,3-D in a Florida sandy soil was conducted in field beds with or without plastic covers. After injection of the commercial fumigant Telone II by conventional chisels to field beds at 30cm depth which were covered with polyethylene film (PE), virtually impermeable film, or no cover (bare), (Z)- and (E)-1,3-D rapidly diffused upward. Twenty hours after injection, majority of (Z)- and (E)-1,3-D had moved upward from 30 cm depth to the layer of 5-20 cm depth. Downward movement of the two isomers in the beds with or without a plastic cover was not significant. (Z)-1,3-D diffused more rapidly than (E)-1,3-D. Virtually impermeable films (VIF) had a good capacity to retain (Z)- and (E)-1,3-D in soil pore air space. Vapor concentrations of the two isomers in the shallow subsurface of the field bed covered with VIF were greater than that in the two beds covered with polyethylene film (PE) or no cover (bare). In addition, VIF cover provided more uniform distribution of (Z)- and (E)-1,3-D in shallow subsurface than PE cover or no cover. Virtually impermeable film also had a better capability to retard surface emissions of the two isomers from soil in field beds than PE cover or no cover.

  1. Xanthates As Useful Probes for Testing the Active Sites of Cytochromes P450 4A11 and 2E1

    Directory of Open Access Journals (Sweden)

    Tsveta Stoyanova

    2017-09-01

    Full Text Available Xanthates (alkyl or aryl derivatives of dithiocarbonic acid have been shown to be selective mechanism-based inactivators of cytochromes P450 2B1/2B6 and 2E1 due to covalent binding of a reactive intermediate to apoprotein after double hydrogen abstraction at α-carbon atom, suggesting interaction of the xanthate dithiocarbonic head with the enzyme heme. The structures of xanthates with a long alkyl chain are similar to the fatty acids. Saturated fatty acids (FA such as lauric acid (LA, are metabolized by different cytochrome P450 isoforms to ω- and (ω-1-hydroxy products, in humans done by CYP4A11 and CYP2E1, respectively. In the present study we aimed at elucidating the possible interactions of xanthates with two cytochrome P450 isoforms CYP4A11 and CYP2E1 involved in the metabolism of the FA. Our experiments showed that LA-ω-hydroxylation by CYP4A11 is inhibited in a competitive manner by xanthates with long alkyl chain (C12-xanthate being the most potent inhibitor. On the other hand LA-(ω-1-hydroxylation reaction by purified CYP2E1 is inactivated by a mechanism-based type. The suggested differences in the interactions of C12-xanthate with the two cytochrome P450 isoforms were investigated by molecular modeling using docking approach. The results suggested that in CYP2E1 active site C12-xanthate coordinates to the heme with its most vulnerable dithiocarbonic head leading to a mechanism-based inactivation. In CYP4A11 xanthate alkyl chain is exposed to the heme, thus, a potenial ω-hydroxylated xanthate product could be formed, which could inhibit in a competitive manner the hydroxylation of LA. The observed differences of xanthates interactions with the active sites of the two similar cytochrome P450 isoforms (CYP4A11 and CYP2E1 involved in the metabolism of FA, which lead to different changes in the enzyme activity, suggest that xanthates can be used as probing tools for analyzing enzyme active sites when exploring useful and selective

  2. The foundation of the concept of relevance

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2010-01-01

    reexamined the concept of relevance in information science, but have neglected the subject knowledge view, hence basic theoretical assumptions seem not to have been properly addressed. It is as urgent now as it was in 1975 seriously to consider “the subject knowledge view” of relevance (which may also...... be termed “the epistemological view”). The concept of relevance, like other basic concepts, is influenced by overall approaches to information science, such as the cognitive view and the domain-analytic view. There is today a trend toward a social paradigm for information science. This paper offers...

  3. A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process

    Directory of Open Access Journals (Sweden)

    El Sawaf Gamal

    2009-07-01

    region of E1, reducing the fusion process in vitro, strongly reduced the amount of cross-recurrence further supporting interaction between this region and FP. Conclusion Our results support a fusion model for HCV in which the FP and the C-terminal region of E1 are juxtaposed and interact in the post-fusion structure. These findings have general implications for viruses, as any visualization of the post-fusion FP-TM complex has been precluded by the impossibility to obtain crystallised viral fusion proteins containing the trans-membrane region. This limitation gives to sequence based modelling efforts a crucial role in the sketching of a molecular interpretation of the fusion process. Moreover, our data also have a more general relevance for cell biology as the mechanism of intracellular fusion showed remarkable similarities with viral fusion

  4. Pressure-induced magnetic collapse and metallization of TlF e1.6S e2

    Science.gov (United States)

    Naumov, P. G.; Filsinger, K.; Shylin, S. I.; Barkalov, O. I.; Ksenofontov, V.; Qi, Y.; Palasyuk, T.; Schnelle, W.; Medvedev, S. A.; Greenblatt, M.; Felser, C.

    2017-08-01

    The crystal structure, magnetic ordering, and electrical resistivity of TlF e1.6S e2 were studied at high pressures. Below ˜7 GPa , TlF e1.6S e2 is an antiferromagnetically ordered semiconductor with a ThC r2S i2 -type structure. The insulator-to-metal transformation observed at a pressure of ˜7 GPa is accompanied by a loss of magnetic ordering and an isostructural phase transition. In the pressure range ˜7.5 -11 GPa a remarkable downturn in resistivity, which resembles a superconducting transition, is observed below 15 K. We discuss this feature as the possible onset of superconductivity originating from a phase separation in a small fraction of the sample in the vicinity of the magnetic transition.

  5. Synthesis, Physical Characterization, Antibacterial and Antifungal activities of a novel bis(3-((E-1-(2-hydroxyphenylethylideneaminophenylmethanone

    Directory of Open Access Journals (Sweden)

    S. Rezaei

    2006-06-01

    Full Text Available Bis (3-((E-1-(2-hydroxyphenyl ethylideneamino phenyl methanone has been synthesized in this paper and its structure was confirmed by 1H-NMR, 13C-NMR, IR and Mass spectra. Its AM1 and B3LYP/6-31G* calculations to characterize the physical properties of this molecule has been also presented. Finally, the antifungal and antibacterial activities of this derivative have been evaluated.

  6. [3H]-thymidine labelling of DNA triggers apoptosis potentiated by E1A-adenoviral protein.

    Science.gov (United States)

    Orlov, S N; Pchejetski, D V; Sarkissian, S D; Adarichev, V; Taurin, S; Pshezhetsky, A V; Tremblay, J; Maximov, G V; deBlois, D; Bennett, M R; Hamet, P

    2003-03-01

    [(3)H]-thymidine is commonly used to analyze the accumulation of [(3)H]-labeled chromatin fragments in cells undergoing apoptosis. This study shows that [(3)H]-thymidine incorporation within DNA is sufficient per se to inhibit growth and to induce apoptosis in canine kidney epithelial cells and porcine aorta endothelial cells. Despite high-level [(3)H]-thymidine-DNA labeling, rat vascular smooth muscle cells (VSMC) showed only modest inhibition of growth and induction of apoptosis compared to other cell types. Similarly to serum deprivation, apoptosis triggered by [(3)H]-thymidine labeling was sharply potentiated by VSMC transfection with a functional analogue of c-myc, E1A-adenoviral protein (VSMC-E1A), and was suppressed by stimulation of cAMP signaling with forskolin as well as by and Na/K pump inhibition with ouabain. Both apoptosis induction and growth suppression seen in [(3)H]-thymidine-treated VSMC-E1A were reduced by the pan-caspase inhibitor z-VAD.fmk. Thus, our results show that the differential efficiency of the apoptotic machinery determines cell type-specific attenuation of growth in cells with [(3)H]-thymidine-labeled DNA. They also demonstrate that [(3)H]-thymidine-treated and serum-deprived VSMC employ common intermediates of the apoptotic machinery, including steps that are potentiated by E1A-adenoviral protein and inhibited by activation of cAMP signaling as well as by inversion of the intracellular [Na(+)](i)/[K(+)](i) ratio.

  7. Lokal østrogen-fobehandling reducerer aborttiden ven prostaglandin E1 analog-induceret abort i 2. trimester

    DEFF Research Database (Denmark)

    Petersen, Lone Kjeld; Uldbjerg, N; Allen, J G

    1991-01-01

    Twenty-eight patients (median gestational age 17 weeks) referred for induction of second trimester abortion, were randomized to intracervical preliminary treatment by either 50 mg 17 beta-oestradiol or placebo. Abortion was then induced by 1 mg prostaglandin E1 vagitories. The preliminary treatment...... caused a significant rise in cervical score and a significant reduction in induction-abortion time especially by reducing the number of patients with prolonged induction-abortion time. Udgivelsesdato: 1991-May-20...

  8. Functional expression of 5-HT{sub 2A} receptor in osteoblastic MC3T3-E1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirai, Takao; Kaneshige, Kota; Kurosaki, Teruko [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan); Nishio, Hiroaki, E-mail: nishio@fupharm.fukuyama-u.ac.jp [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan)

    2010-05-28

    In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT{sub 2} receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT{sub 2A} and 5-HT{sub 2C} receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT{sub 2A} receptor specific antagonist. Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT{sub 2A} receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells.

  9. Management of newborns with duct-dependent congenital heart disease with prostaglandin E1 – Slovenian guidelines

    OpenAIRE

    Mojca Grošelj Grenc; Maja Pavčnik Arnol; Gorazd Kalan; Tomaž Podnar; Ivan Vidmar

    2012-01-01

    Background: Early recognition of duct-dependent congenital heart disease in newborns with duct-dependent pulmonary or systemic blood flow or transposition of the great arteries is critical for early introduction of prostaglandin E1 (PGE1), which allows stabilization of the newborn till cardiac catheterization or surgical intervention. Indications for PGE1, management of newborns with duct-dependent congenital heart disease and interventions in case of side effects of PGE1 are reviewed. Con...

  10. CYP2E1 Rsa I/Pst I polymorphism contributes to oral cancer susceptibility: a meta-analysis.

    Science.gov (United States)

    Niu, Yuming; Hu, Yuanyuan; Wu, Mingyue; Jiang, Fei; Shen, Ming; Tang, Chunbo; Chen, Ning

    2012-01-01

    Previous data on association between CYP2E1 Rsa I/Pst I polymorphism and oral cancer risk were controversial. To investigate the association between CYP2E1 Rsa I/Pst I polymorphism and oral cancer risk. We performed a meta-analysis to assess the relationship between oral cancer and genotype with English language until June 2010. Twelve published case-control studies of 1259 patients with oral cancer and 2262 controls were acquired. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association in codominant and dominant models. Overall, the pooled ORs indicated a significant association between CYP2E1 Rsa I/Pst I polymorphism and oral cancer risk (for c1/c2 vs. c1/c1: OR=1.30, 95% CI=1.04-1.62, Pheterogeneity=0.57; for (c1/c2+c2/c2) vs. c1/c1: OR=1.32, 95% CI=1.07-1.64, Pheterogeneity=0.57, respectively). In subgroup analysis by race, the same significant risks were found among Asian (for c1/c2 vs. c1/c1: OR=1.41, 95% CI=1.05-1.91, Pheterogeneity=0.92; for (c1/c2+c2/c2) vs. c1/c1: OR=1.43, 95% CI=1.08-1.88, Pheterogeneity=0.97, respectively). In conclusion, this meta-analysis demonstrates that CYP2E1 Rsa I/Pst I c2 allele may be a biomarker for oral cancer, especially among Asian populations.

  11. Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering.

    Science.gov (United States)

    Raza, M Hashim; Mattera, Rafael; Morell, Robert; Sainz, Eduardo; Rahn, Rachel; Gutierrez, Joanne; Paris, Emily; Root, Jessica; Solomon, Beth; Brewer, Carmen; Basra, M Asim Raza; Khan, Shaheen; Riazuddin, Sheikh; Braun, Allen; Bonifacino, Juan S; Drayna, Dennis

    2015-11-05

    Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of-function mutations in this gene. AP4E1 encodes the ε subunit of the heterotetrameric (ε-β4-μ4-σ4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the μ4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6-phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Ranking Music Data by Relevance and Importance

    DEFF Research Database (Denmark)

    Ruxanda, Maria Magdalena; Nanopoulos, Alexandros; Jensen, Christian Søndergaard

    2008-01-01

    Due to the rapidly increasing availability of audio files on the Web, it is relevant to augment search engines with advanced audio search functionality. In this context, the ranking of the retrieved music is an important issue. This paper proposes a music ranking method capable of flexibly fusing...... the relevance and importance of music. The proposed method may support users with diverse needs when searching for music....

  13. DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication

    Directory of Open Access Journals (Sweden)

    Molly L. Bristol

    2016-06-01

    Full Text Available Human papillomaviruses (HPVs are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1, does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

  14. 2-aminopurine enhances the oncolytic activity of an E1b-deleted adenovirus in hepatocellular carcinoma cells.

    Science.gov (United States)

    Sharon, David; Schümann, Michael; MacLeod, Sheena; McPherson, Robyn; Chaurasiya, Shyambabu; Shaw, Andrew; Hitt, Mary M

    2013-01-01

    Adenoviruses with deletions of viral genes have been extensively studied as potential cancer therapeutics. Although a high degree of cancer selectivity has been demonstrated with these conditionally replicating adenoviruses, low levels of virus replication can be detected in normal cells. Furthermore, these mutations were also found to reduce the activity of the replicating viruses in certain cancer cells. Recent studies have shown that co-administration of chemotherapeutic drugs may increase the activity of these viruses without affecting their specificity. We constructed an adenovirus with deletions of both the E1b and the VA-RNA genes and found that replication of this virus was selective for human hepatocellular carcinoma (HCC) cell lines when compared to normal cell lines. Furthermore, we show that 2-aminopurine (2'AP) treatment selectively enhanced virus replication and virus-mediated death of HCC cells. 2'AP did not compensate for the loss of VA-RNA activities, but rather the loss of an E1b-55K activity, such as the DNA damage response, suggesting that co-administration of 2'AP derivatives that block host DNA damage response, may increase the oncolytic activity of AdΔE1bΔVA without reducing its selectivity for HCC cells.

  15. 2-aminopurine enhances the oncolytic activity of an E1b-deleted adenovirus in hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    David Sharon

    Full Text Available Adenoviruses with deletions of viral genes have been extensively studied as potential cancer therapeutics. Although a high degree of cancer selectivity has been demonstrated with these conditionally replicating adenoviruses, low levels of virus replication can be detected in normal cells. Furthermore, these mutations were also found to reduce the activity of the replicating viruses in certain cancer cells. Recent studies have shown that co-administration of chemotherapeutic drugs may increase the activity of these viruses without affecting their specificity. We constructed an adenovirus with deletions of both the E1b and the VA-RNA genes and found that replication of this virus was selective for human hepatocellular carcinoma (HCC cell lines when compared to normal cell lines. Furthermore, we show that 2-aminopurine (2'AP treatment selectively enhanced virus replication and virus-mediated death of HCC cells. 2'AP did not compensate for the loss of VA-RNA activities, but rather the loss of an E1b-55K activity, such as the DNA damage response, suggesting that co-administration of 2'AP derivatives that block host DNA damage response, may increase the oncolytic activity of AdΔE1bΔVA without reducing its selectivity for HCC cells.

  16. The Effect of Smoking on Necrosis Rate in Digital Replantation and Revascularization with Prostaglandin E1 Therapy: A Retrospective Study.

    Science.gov (United States)

    Nishijima, Akio; Yamamoto, Naoto; Yanagibayashi, Satoshi; Yoshida, Ryuichi; Takikawa, Megumi; Kouno, Rie; Gosho, Masahiko

    2016-10-01

    Most microsurgeons believe that smoking and severity of injury adversely affect the outcome of digital replantation surgery. As countermeasures, several pharmacologic agents have been used for the perioperative period. The purpose of this retrospective study was to examine whether the rate of necrosis is appreciably different across smokers versus nonsmokers with prostaglandin E1 therapy. The authors' study subjects included 144 patients (184 digits) who underwent replantation or revascularization between August of 2013 and August of 2015.The primary outcome was the incidence of total necrosis after replantation surgery, and the secondary outcomes were the rate of overall necrosis, proportion of total necrosis to overall necrosis, and total success. Intravenous administration of prostaglandin E1 was performed at the rate of 120 μg/day for 7 days after surgery in all patients. These outcomes of each injury type were compared between smoking and nonsmoking groups. Among the 184 injured digits, the incidence of total necrosis in smokers (23 percent) was higher than that in nonsmokers (17 percent), although no significant difference was shown (p = 0.36). The adjusted odds ratio was 1.17 (95 percent CI, 0.51 to 2.69). Similarly, there was no significant difference in the secondary outcomes between the two groups. The authors' retrospective study found no significant difference in the formation or extent of necrosis after replantation or revascularization between smoking and nonsmoking groups when all patients were treated with prostaglandin E1. Risk, II.

  17. STABILITAS EPIGALOKATEKIN GALAT DALAM KRIM EKSTRAK TEH HIJAU DENGAN VARIASI KONSENTRASI ANTIOKSIDAN VITAMIN C 1% DAN VITAMIN E 1%

    Directory of Open Access Journals (Sweden)

    Nining Sugihartini

    2016-11-01

    Full Text Available Epigallocatechingallate (EGCG in green tea extract has activity as an anti-inflammatory agent. On the other hand the stability of EGCG is poor because of the oxidation. The aim of this study was to determine the influence of Vitamine C and Vitamine E in formulation of green tea extract cream to the stabiliy of EGCG. The green tea extract was obtained from the extraction process by infundation followed by fractination with ethyl acetate as the solvent. The three formulas were compiled in similar composition with the concentration of vitamine C 1% (FI, Vitamine E 1% (FII and there was no Vitamine C and Vitamine E (FIII as a control. The EGCG level was determinated by TLC-densitometry methode. The stability parameter was determinated by calculated of the Q10 of each formula. The result of this study showed that the parameter of t90 of EGCG with Vitamine C 1%, Vitamine E 1% and control addition were 0.0108 hours, 0.0087 hours, 0.0084 hours, respectively. Stability of EGCG in green tea leaf extract cream with addition of the vitamin C 1% was higher than it stability with the addition of vitamin E 1%. The concentration of Vitamin C 1% was the optimum concentration as antioxidant in formulation of green tea extract cream.

  18. DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication.

    Science.gov (United States)

    Bristol, Molly L; Wang, Xu; Smith, Nathan W; Son, Minkyeong P; Evans, Michael R; Morgan, Iain M

    2016-06-22

    Human papillomaviruses (HPVs) are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR) pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs) could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1), does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

  19. Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells

    Energy Technology Data Exchange (ETDEWEB)

    Kimira, Yoshifumi, E-mail: kimira@josai.ac.jp [Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295 (Japan); Ogura, Kana; Taniuchi, Yuri [Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295 (Japan); Kataoka, Aya; Inoue, Naoki; Sugihara, Fumihito [Nitta Gelatin Inc., Peptide Division, 2-22 Futamata, Yao, Osaka 581-0024 (Japan); Nakatani, Sachie; Shimizu, Jun; Wada, Masahiro; Mano, Hiroshi [Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295 (Japan)

    2014-10-24

    Highlights: • Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization. • Pro-Hyp significantly increased alkaline phosphatase activity. • Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. - Abstract: Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. The objective of this study was to investigate the effects of Pro-Hyp on the proliferation and differentiation of MC3T3-E1 osteoblastic cells. Addition of Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization but alkaline phosphatase activity was significantly increased. Furthermore, cells treated with Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. These results indicate that Pro-Hyp promotes osteoblast differentiation. This study demonstrates for the first time that Pro-Hyp has a positive effect on osteoblast differentiation with upregulation of Runx2, Osterix, and Collα1 gene expression.

  20. PPARγ inhibits inflammation and RANKL expression in epoxy resin-based sealer-induced osteoblast precursor cells E1 cells.

    Science.gov (United States)

    Kim, Tae-Gun; Lee, Young-Hee; Bhattari, Govinda; Lee, Nan-Hee; Lee, Kwang-Won; Yi, Ho-Keun; Yu, Mi-Kyung

    2013-01-01

    The AH26 of epoxy resin-based sealer is used widely owing to its excellent physical characteristics but it induces oxidative stress and cytotoxicity at the periapical tissues. AH26 exhibited cytotoxicity towards MC-3T3-E1 cells, which resulted in mitochondria-mediated apoptosis. Peroxisome proliferator-activated receptor (PPARγ) has an anti-inflammatory effect in several tissue and cells, but its action of AH26-related inflammation is not completely understood. The aim of this study is to investigate the anti-inflammatory and anti-osteoclastic mechanisms of PPARγ in AH26-induced MC-3T3 E1 cells. AH26 was prepared according to the manufacturer's instructions. The 1-day extraction sample, which was diluted by 30%, was tested in this experiment. Recombinant deficiency adenoviral PPARγ (Ad/PPARγ) was used to examine PPARγ over-expression in MC-3T3 E1 cells. AH26-induced reactive oxygen species (ROS) formation was analysed using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) with fluorescence-activated cell sorting (FACS), and the expression of receptor activator of nuclear factor-κB ligand (RANKL) and inflammatory molecules was determined by immunoblotting. The anti-inflammatory and anti-osteoclastic mechanisms of the PPARγ-involved signal pathway was examined by immunoblotting. The AH26 elutes induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), RANKL expression and ROS formation. In addition, the AH26 elutes suppressed the expression of PPARγ. However, the recovery of PPARγ expression with Ad/PPARγ resulted in the inhibition of iNOS, COX-2, RANKL and ROS formation despite the AH26 treatment in MC-3T3 E1 cells. The mechanism of PPARγ was confirmed by the blocking of nuclear factor kappa B (NF-κB) translocation to the nucleus after the suppression of ERK1/2, SAPK/JNK and AP-1 in AH26-induced MC-3T3 E1 cells. From this result, PPARγ acts to inhibit bone destruction in AH26-induced bone cells. Therefore, the anti-inflammatory and

  1. Rethinking "relevance": South African psychology in context.

    Science.gov (United States)

    Long, Wahbie

    2013-02-01

    This article examines the phenomenon known as the "relevance debate" in South African psychology. It begins with a historical overview of the contours of the discipline in that country before describing the controversy's international dimensions, namely, the revolutionary politics of 1960s higher education and the subsequent emergence of cognate versions of the debate in American, European, and "Third World" psychology. The article then details how South Africa's "relevance" project enjoyed a special affinity with an assortment of ethnic-cultural, national, and continental myths and metaphors, all of which served the interests of the political formations of the day. It discusses how, in present-day South Africa, the intelligentsia has become an important catalyst for the so-called African Renaissance, which seeks to provide "relevant" solutions for the regeneration of African society. However, the global hegemony of what began in the 1970s as a "second academic revolution," aided by the lifting of the academic boycott of South Africa, has blunted the once critical edge of "relevance" discourse. A new mode of knowledge production now holds sway, the outcome of a dramatic reformulation of the capitalist manifesto in which the values of the "May 68" generation have been hijacked by a managerialist rationality. In light of the capitalization of the knowledge-production enterprise, it is concluded that the idiom of "relevance" has outlived its usefulness.

  2. Annealing mechanisms of self-interstitial related defect E1=E{sub c}-0.39 eV in irradiated silicon

    Energy Technology Data Exchange (ETDEWEB)

    Abdullin, Kh.A., E-mail: kh.a.abdullin@mail.ru [National Nanotechnology Open Laboratory, al-Farabi Kazakh National University, 71 al-Farabi Str., 050060 Almaty (Kazakhstan); Mukashev, B.N. [National Nanotechnology Open Laboratory, al-Farabi Kazakh National University, 71 al-Farabi Str., 050060 Almaty (Kazakhstan)

    2012-07-01

    DLTS and thermally stimulated capacitance (TSCap) studies of {alpha}-particle irradiated p-Si were undertaken to obtain additional information about the self-interstitial related defect E1=E{sub c}-0.39 eV. The E1 defect can be retained frozen up to room temperature without any minority carrier injection, but under injection conditions at 77-300 K the E1 becomes mobile. As a result of annealing of the E1 defect, the carbon interstitial concentration grows. The E1 defect production rate under reverse bias as well as thermal annealing behavior depends strongly on the temperature and impurity concentration. Numerical estimates of the E1 migration via a Bourgoin-Corbett mechanism are in good agreement with the experimental data obtained.

  3. Is relevance theory applicable to proverbs’ translation?

    Directory of Open Access Journals (Sweden)

    Pegulescu Anca-Mariana

    2016-01-01

    Full Text Available Translation, viewed as a multi-faceted task, can arise different types of difficulties. Proverbs have been considered special patterns, displaying sometimes hidden meanings or suggesting morals issuing from a particular example. These paremic units - the proverbs - conveyed feelings, states of mind, behaviours or ‘metaphorical descriptions of certain situations’(Krikmann. Starting from Savory’s list of pair-wise contradictory translation principles, I intend to prove that the link between different ‘forms’ and their ‘contents’ lies in the principle of relevance when referring to proverbs. Even if relevance theory is not a theory of linguistic structure - and many translation problems imply structural mismatches - relevance theory offers insights about contextual information. Proverbs are seen as texts in themselves. My analysis will target the ethnofields of ‘to buy’ and ‘to sell’ in English proverbs and their Romanian corresponding versions.

  4. Identifying Critical States through the Relevance Index

    Directory of Open Access Journals (Sweden)

    Andrea Roli

    2017-02-01

    Full Text Available The identification of critical states is a major task in complex systems, and the availability of measures to detect such conditions is of utmost importance. In general, criticality refers to the existence of two qualitatively different behaviors that the same system can exhibit, depending on the values of some parameters. In this paper, we show that the relevance index may be effectively used to identify critical states in complex systems. The relevance index was originally developed to identify relevant sets of variables in dynamical systems, but in this paper, we show that it is also able to capture features of criticality. The index is applied to two prominent examples showing slightly different meanings of criticality, namely the Ising model and random Boolean networks. Results show that this index is maximized at critical states and is robust with respect to system size and sampling effort. It can therefore be used to detect criticality.

  5. (E-1-Phenylethanone semicarbazone

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2009-08-01

    Full Text Available In the title compound, C9H11N3O, the benzene ring is disordered over two positions with refined occupancies of 0.922 (5 and 0.078 (5. The program PLATON [Spek (2009. Acta Cryst. D65, 148–155] recommends the solution in the space group C2/m with a = 7.3050 (3, b = 6.6745 (2, c = 18.3853 (6 Å and β = 96.986 (2°. However, the large number of non-extinct reflections needed to be ignored if C2/m is chosen suggested that the space group is incorrect, even though the R values are lower than that for P21/c. The semicarbazone group is essentially planar, with a maximum deviation of 0.046 (1 Å for one of the N atoms. The mean plane of the semicarbazone group forms dihedral angles of 33.61 (8 and 39.1 (9° with the benzene ring of the major and minor components, respectively. In the crystal structure, molecules are linked by intermolecular N—H...O hydrogen bonds into extended chains along the c axis. The crystal structure is further stabilized by weak intermolucular C—H...π interactions.

  6. High glucose impaired estrogen receptor alpha signaling via β-catenin in osteoblastic MC3T3-E1.

    Science.gov (United States)

    Wang, Rui; Gao, Dong; Zhou, Yin; Chen, Lu; Luo, Bin; Yu, Yanrong; Li, Hao; Hu, Jiawei; Huang, Qiren; He, Ming; Peng, Weijie; Luo, Dan

    2017-11-01

    Diabetic Mellitus is a risk factor for osteoporosis. It has been suggested that altered estrogen or estrogen receptor α/β (ERα/β) signaling may be involved in diabetic osteoporosis. The present study is to investigate the effects of high glucose on ERα/β signaling in osteoblastic MC3T3-E1 and how the altered signaling of ERα/β affect osteoblastic bone formation. ERα/β signaling was demonstrated as ERα/β protein expression (Western Blotting) and ER transcription activity (Luciferase Reporter assays). Proliferation (WSK-1 assaying), differentiation (ALP staining) and mineralization (Alizalard Red staining) of MC3T3-E1 were examined to evaluate bone formation function. It has been found that high glucose increased ERα/β expression dose-dependently and time-dependently, but high glucose (33mM) decreased ERα transcription activity. 17β-estradiol increased the ERα/β expression dose-dependently in normal medium, but decreased the ERα/β expression dose-dependently in medium with high glucose (33mM). High glucose decreased bone formation and also decreased the osteogenic effects of 17β-estradiol (10 -8 M). High glucose decreased β-catenin expression dose-dependently and time-dependently. LiCl, an inhibitor of β-catenin degradation, decreased ERα expression but increased ERα transcription activity. When compared with high glucose treatment, LiCl (5mM) increased ALP activity and calcified nodes. Besides, high glucose also decreased the protein expression PI-3K, pAKT/AKT, GSK-3β. In conclusion, the present study suggested that high glucose may impair ERα transcription activity by inhibiting β-catenin signaling in osteoblastic MC3T3-E1, leading decreased bone formation ligand-dependently or ligand-independently. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The simulation of lunar gravity field recovery from D-VLBI of Chang’E-1 and SELENE lunar orbiters

    Science.gov (United States)

    Yan, Jianguo; Ping, Jingsong; Matsumoto, K.; Li, Fei

    2008-07-01

    The lunar gravity field is a foundation to study the lunar interior structure, and to recover the evolution history of the Moon. It is still an open and key topic for lunar science. For above mentioned reasons, it becomes one of the important scientific objectives of recent lunar missions, such as KAGUYA (SELENE) the Japanese lunar mission and Chang’E-1, the Chinese lunar mission. The Chang’E-1 and the SELENE were successfully launched in 2007. It is estimated that these two missions can fly around the Moon longer than 6 months simultaneously. In these two missions, the Chinese new VLBI (Very Long Baseline Interferometry) network will be applied for precise orbit determination (POD) by using a differential VLBI (D-VLBI) method during the mission period. The same-beam D-VLBI technique will contribute to recover the lunar gravity field together with other conventional observables, i.e. R&RR (Range and Range Rate) and multi-way Doppler. Taking VLBI tracking conditions into consideration and using the GEODYNII/SOVLE software of GSFC/NASA/USA [Rowlands, D.D., Marshall, J.A., Mccarthy, J., et al. GEODYN II System Description, vols. 1 5. Contractor Report, Hughes STX Corp. Greenbelt, MD, 1997; Ullman, R.E. SOLVE program: mathematical formulation and guide to user input, Hughes/STX Contractor Report, Contract NAS5-31760. NASA Goddard Space Flight Center, Greenbelt, Maryland, 1994], we simulated the lunar gravity field recovering ability with and without D-VLBI between the Chang’E-1 and SELENE main satellite. The cases of overlapped flying and tracking period of 30 days, 60 days and 90 days have been analyzed, respectively. The results show that D-VLBI tracking between two lunar satellites can improve the gravity field recovery remarkably. The results and methods introduced in this paper will benefit the actual missions.

  8. Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy

    Science.gov (United States)

    Huang, Shuai; Zou, Xiao; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Liang, Ye-You; Deng, Chun-Yu; Kuang, Su-Juan; Zhang, Meng-Zhen; Liao, Yu-Lin; Zheng, Xi-Long; Yu, Xi-Yong; Shan, Zhi-Xin

    2015-01-01

    Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR-16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post-transcriptionally by miR-16. In addition, the signal transducer and activator of transcription-3 and c-Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR-16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR-16 might be a target to manage cardiac hypertrophy. PMID:25583328

  9. Sulfation of fulvestrant by human liver cytosols and recombinant SULT1A1 and SULT1E1

    Directory of Open Access Journals (Sweden)

    Edavana VK

    2011-11-01

    Full Text Available Vineetha Koroth Edavana1, Xinfeng Yu1, Ishwori B Dhakal1, Suzanne Williams1, Baitang Ning2, Ian T Cook3, David Caldwell1, Charles N Falany3, Susan Kadlubar11Division of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA; 3Department of Pharmacology, University of Alabama, Birmingham, AL, USAAbstract: Fulvestrant (Faslodex™ is a pure antiestrogen that is approved to treat hormone receptor-positive metastatic breast cancer in postmenopausal women. Previous studies have demonstrated that fulvestrant metabolism in humans involves cytochromes P450 and UDP-glucuronosyltransferases (UGTs. To date, fulvestrant sulfation has not been characterized. This study examined fulvestrant sulfation with nine recombinant sulfotransferases and found that only SULT1A1 and SULT1E1 displayed catalytic activity toward this substrate, with Km of 4.2 ± 0.99 and 0.2 ± 0.16 µM, respectively. In vitro assays of 104 human liver cytosols revealed marked individual variability that was highly correlated with β-naphthol sulfation (SULT1A1 diagnostic substrate; r = 0.98, P < 0.0001, but not with 17ß-estradiol sulfation (SULT1E1 diagnostic substrate; r = 0.16, P = 0.10. Fulvestrant sulfation was correlated with both SULT1A1*1/2 genotype (P value = 0.023 and copy number (P < 0.0001. These studies suggest that factors influencing SULT1A1/1E1 tissue expression and/or enzymatic activity could influence the efficacy of fulvestrant therapy.Keywords: fulvestrant, sulfotransferase, genotype, copy number

  10. Role of cleavage at the core-E1 junction of hepatitis C virus polyprotein in viral morphogenesis

    Science.gov (United States)

    Pène, Véronique; Lemasson, Matthieu; Harper, Francis; Pierron, Gérard; Rosenberg, Arielle R.

    2017-01-01

    In hepatitis C virus (HCV) polyprotein sequence, core protein terminates with E1 envelope signal peptide. Cleavage by signal peptidase (SP) separates E1 from the complete form of core protein, anchored in the endoplasmic reticulum (ER) membrane by the signal peptide. Subsequent cleavage of the signal peptide by signal-peptide peptidase (SPP) releases the mature form of core protein, which preferentially relocates to lipid droplets. Both of these cleavages are required for the HCV infectious cycle, supporting the idea that HCV assembly begins at the surface of lipid droplets, yet SPP-catalyzed cleavage is dispensable for initiation of budding in the ER. Here we have addressed at what step(s) of the HCV infectious cycle SP-catalyzed cleavage at the core-E1 junction is required. Taking advantage of the sole system that has allowed visualization of HCV budding events in the ER lumen of mammalian cells, we showed that, unexpectedly, mutations abolishing this cleavage did not prevent but instead tended to promote the initiation of viral budding. Moreover, even though no viral particles were released from Huh-7 cells transfected with a full-length HCV genome bearing these mutations, intracellular viral particles containing core protein protected by a membrane envelope were formed. These were visualized by electron microscopy as capsid-containing particles with a diameter of about 70 nm and 40 nm before and after delipidation, respectively, comparable to intracellular wild-type particle precursors except that they were non-infectious. Thus, our results show that SP-catalyzed cleavage is dispensable for HCV budding per se, but is required for the viral particles to acquire their infectivity and secretion. These data support the idea that HCV assembly occurs in concert with budding at the ER membrane. Furthermore, capsid-containing particles did not accumulate in the absence of SP-catalyzed cleavage, suggesting the quality of newly formed viral particles is controlled before

  11. 26 CFR 54.4980E-1 - Requirement of return and time for filing of the excise tax under section 4980E.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Requirement of return and time for filing of the excise tax under section 4980E. 54.4980E-1 Section 54.4980E-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980E-1 Requirement of return and time...

  12. 26 CFR 1.404(e)-1A - Contributions on behalf of a self-employed individual to or under a qualified pension, annuity...

    Science.gov (United States)

    2010-04-01

    ... individual to or under a qualified pension, annuity, or profit-sharing plan. 1.404(e)-1A Section 1.404(e)-1A...) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.404(e)-1A Contributions on behalf of a self-employed individual to or under a qualified pension, annuity, or profit-sharing plan. (a) In...

  13. Identity theory and personality theory: mutual relevance.

    Science.gov (United States)

    Stryker, Sheldon

    2007-12-01

    Some personality psychologists have found a structural symbolic interactionist frame and identity theory relevant to their work. This frame and theory, developed in sociology, are first reviewed. Emphasized in the review are a multiple identity conception of self, identities as internalized expectations derived from roles embedded in organized networks of social interaction, and a view of social structures as facilitators in bringing people into networks or constraints in keeping them out, subsequently, attention turns to a discussion of the mutual relevance of structural symbolic interactionism/identity theory and personality theory, looking to extensions of the current literature on these topics.

  14. Multimedia search engine with relevance feedback

    Science.gov (United States)

    Ciocca, Gianluigi; Schettini, Raimondo

    2001-12-01

    We present here a web-based protytpe for the interactive search of items in quality electronic catalogues. The system based on a multimedia information retrieval architecture, allows the user to query a multimedia database according to several retrieval strategies, and progressively refine the system's response by indicating the relevance, or non-relevance of the items retrieved. Once a subset of images meeting the user's information needs have been identified, these images can be displayed in a virtual exhibition that can be visited interactively by the user exploiting VRML technology.

  15. [Neurolaw: its relevance for forensic psychiatry].

    Science.gov (United States)

    Meynen, G

    2014-01-01

    Neurolaw is a new interdisciplinary area of research which investigates, from different perspectives, the significance of the neurosciences for law. To clarify the relevance of neurolaw for forensic psychiatry. The importance of neurolaw developments for forensic psychiatry was analysed on the basis of recent literature. Some of the developments in the field of neurolaw research concern issues that are currently evaluated by forensic psychiatrists, such as risk of recidivism and legal insanity. Developments in neurolaw are relevant for forensic psychiatry in a number of ways. An important problem, not yet resolved, is to what extent psychiatry will be prepared to help in shaping these developments.

  16. Efficient synthesis of novel azo compounds based on pyrimido[4,5-e][1,3,4]thiadiazine

    Directory of Open Access Journals (Sweden)

    Mohsen Nikpour

    2012-12-01

    Full Text Available Some new 5-bromo-2,4-dichloro-6-alkylpyrimidines were prepared by sequential treatment of 6-alkyl-pyrimidin-2,4(1H,3H-diones with bromine and phosphoryl chloride. Condensation of the dithizone with 5-bromo-2,4-dichloro-6-alkylpyrimidines in alkaline acetonitrile achieved 5-alkyl-7-chloro-3-phenylazo-1-phenyl-1H-pyrimido[4,5-e][1,3,4] thiadiazines. 7-chlorine atom of these compounds was replaced by secondary amines in boiling ethanol to afford their 7-amino derivatives. DOI: http://dx.doi.org/10.4314/bcse.v26i1.12

  17. High-yield production of a chimeric glycoprotein based on permuted E1 and E2 HCV envelope ectodomains

    OpenAIRE

    Tello, Daniel; Rodríguez-Rodríguez, Mar; Yélamos, Belén; Gómez-Gutiérrez, Julián; Peterson, Darrell L.; Gavilanes, Francisco

    2015-01-01

    In this report it is described for the first time the expression and purification of large quantities of a oluble and correctly folded chimeric recombinant protein, E2661E1340, containing the permuted Hepatitis C virus (HCV) glycoprotein ectodomains E1 (amino acids 192-340) and E2 (amino acids 384-661). Using the baculovirus/insect cell expression system, 8mg of secreted protein were purified from 1L of culture media, a yield 4 times higher than the described for its counterpart E1341E2661. T...

  18. Hepatotoxicity and P-4502E1-dependent metabolic oxidation of N,N-dimethylformamide in rats and mice.

    Science.gov (United States)

    Chieli, E; Saviozzi, M; Menicagli, S; Branca, T; Gervasi, P G

    1995-01-01

    A comparative biochemical and histological study on the hepatotoxicity of a single dose of N,N-dimethylformamide (DMF) and N-methylformamide (NMF) in control and acetone-treated SD male rats and CD-1 male mice was performed. In control and acetone-pretreated rats, neither DMF nor NMF caused hepatic damage or elevation of plasma transaminases. In contrast, in acetonized but not in control mice, DMF administration yielded some evidence of liver necrosis and elevation of ALAT (alanine-amino transferase) activity. After a DMF dose of 1000 mg/kg, ALAT activity was found 1215 +/- 832 mU/ml and 47 +/- 18 mU/ml in acetonized and control mice, respectively. NMF treatment was hepatotoxic in control mice and lethal in acetonized mice. In control mice, an NMF dose of 600 mg/kg increased ALAT activity from a basal value of 35 +/- 5 to 2210 +/- 1898 mU/ml. When the oxidative metabolism of DMF was investigated, microsomes from both rats and mice preinduced by acetone increased the demethylation rate of DMF 7 to 10-fold compared to that (about 0.25 nmol/min per mg protein) of the corresponding control microsomes. The enzymatic affinities for DMF oxidation, however, were different: in mice the Km (0.05 mM) was one order of magnitude lower than that (0.56 mM) found in rats. The experiments performed with purified rat and mouse P-450 2E1 in a reconstituted system confirmed that the P-450 2E1 isoforms are very active catalysts towards DMF oxidation (the turnover was about 10 nmol/min per nmol P-450 for both enzymes) but with a strikingly different affinity. Whereas the Km for mouse P-450 2E1 was 0.08 +/- 0.03 mM, that for rat P-450 2E1 was 1.1 +/- 0.2 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Intra-arterial infusion of prostaglandin E1 in normal subjects and patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Nielsen, P E; Nielsen, S L; Holstein, P

    1976-01-01

    Acute vasodilatation was produced by infusion of prostaglandin E1 (PGE1) in the femoral artery in 6 patients with occlusive arterial disease of the legs and in 3 normal subjects. The effect on blood flow and on blood pressure was measured at different segments of the leg with the strain gauge...... technique, isotope clearance technique, and photoelectric technique. Skin temperature was measured at different levels by using thermocouples. The blood pressure on the legs decreased at all segments during vasodilatation as well in patients as in controls. The blood flow increased in all segments in normal...

  20. Surface behavior of peptides from E1 GBV-C protein: Interaction with anionic model membranes and importance in HIV-1 FP inhibition.

    Science.gov (United States)

    Galatola, R; Cruz, A; Gómara, M J; Prat, J; Alsina, M A; Haro, I; Pujol, M

    2015-02-01

    The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural analogs (E1P8-12), (E1P8-13), and (E1P8-21) with anionic lipid membranes (POPG vesicles and POPG, DPPG or DPPC/DPPG (2:1) monolayers) and their association with HIV-1 fusion peptide (HIV-1 FP) inhibition at the membrane level were studied using biophysical methods. All peptides showed surface activity but leakage experiments in vesicles as well as insertion kinetics in monolayers and lipid/peptide miscibility indicated a low level of interaction: neither E1P8 nor its analogs induced the release of vesicular content and the exclusion pressure values (πe) were clearly lower than the biological membrane pressure (24-30 mN m(-1)) and the HIV-1 FP (35 mN m(-1)). Miscibility was elucidated in terms of the additivity rule and excess free energy of mixing (GE). E1P8, E1P8-12 and E1P8-21 (but not E1P8-13) induced expansion of the POPG monolayer. The mixing process is not thermodynamically favored as the positive GE values indicate. To determine how E1 peptides interfere in the action of HIV-1 FP at the membrane level, mixed monolayers of HIV-1 FP/E1 peptides (2:1) and POPG were obtained. E1P8 and its derivative E1P8-21 showed the greatest HIV-1 FP inhibition. The LC-LE phase lipid behavior was morphologically examined via fluorescence microscopy (FM) and atomic force microscopy (AFM). Images revealed that the E1 peptides modify HIV-1 FP-lipid interaction. This fact may be attributed to a peptide/peptide interaction as indicated by AFM results. Finally, hemolysis assay demonstrated that E1 peptides inhibit HIV-1 FP activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. The role of reactive oxygen species (ROS and cytochrome P-450 2E1 in the generation of carcinogenic etheno-DNA adducts

    Directory of Open Access Journals (Sweden)

    Kirsten Linhart

    2014-01-01

    Full Text Available Exocyclic etheno-DNA adducts are mutagenic and carcinogenic and are formed by the reaction of lipidperoxidation (LPO products such as 4-hydoxynonenal or malondialdehyde with DNA bases. LPO products are generated either via inflammation driven oxidative stress or via the induction of cytochrome P-450 2E1 (CYP2E1. In the liver CYP2E1 is induced by various compounds including free fatty acids, acetone and ethanol. Increased levels of CYP2E1 and thus, oxidative stress are observed in the liver of patients with non-alcoholic steatohepatitis (NASH as well as in the chronic alcoholic. In addition, chronic ethanol ingestion also increases CYP2E1 in the mucosa of the oesophagus and colon. In all these tissues CYP2E1 correlates significantly with the levels of carcinogenic etheno-DNA adducts. In contrast, in patients with non-alcoholic steatohepatitis (NASH hepatic etheno-DNA adducts do not correlate with CYP2E1 indicating that in NASH etheno-DNA adducts formation is predominately driven by inflammation rather than by CYP2E1 induction. Since etheno-DNA adducts are strong mutagens producing various types of base pair substitution mutations as well as other types of genetic damage, it is strongly believed that they are involved in ethanol mediated carcinogenesis primarily driven by the induction of CYP2E1.

  2. Characterization of Autoantibodies against the E1 Subunit of Branched-Chain 2-Oxoacid Dehydrogenase in Patients with Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Tsutomu Mori

    2012-01-01

    Full Text Available Primary biliary cirrhosis (PBC is characterized by antimitochondrial antibodies (AMAs that react with the lipoyl-containing E2 subunits of 2-oxoacid dehydrogenase complexes such as BCOADC and PDC. The lipoyl domains of E2 contain the major epitopes essential for immunopathology. However, the non-lipoyl-containing E1 subunits are also frequently targeted. Since anti-E1 antibodies always appear in combination with anti-E2 antibodies, the mechanisms underlying the autoimmunity against E1 may be linked to, but distinct from, those against E2. Here, we demonstrate that intermolecular and intramolecular determinant spreading underlies the autoimmunity against E1. We performed characterizations and epitope mapping for anti-BCOADC-E1 antibodies from both the intermolecular and intramolecular points of view. The antibody reactivities form a cluster against the BCOADC complex that is distinct from that against the PDC complex, and the anti-BCOADC-E1 antibodies arise as part of the cluster against the BCOADC complex. Multiple epitopes are present on the surface of the BCOADC-E1 molecule, and the major epitope overlaps with the active center. Sera with anti-BCOADC-E1 antibodies strongly inhibited the enzyme activity. These findings suggest that the E1 subunit as part of the native BCOADC complex is an immunogen, and that determinant spreading is involved in the pathogenesis of AMA production.

  3. Is Enterprise Education Relevant to Social Enterprise?

    Science.gov (United States)

    Bridge, Simon

    2015-01-01

    Purpose: Both enterprise education and social enterprise have become fashionable but what, if any, should be the connections between them? The purpose of this paper is to explore those connections and to reflect on what relevance the two concepts might have for each other. Design/methodology/approach: Both enterprise education and social…

  4. Ecologically relevant stress resistance: from microarrays and ...

    Indian Academy of Sciences (India)

    2004-10-15

    Oct 15, 2004 ... Home; Journals; Journal of Biosciences; Volume 29; Issue 4. Ecologically relevant stress resistance: from microarrays and quantitative trait loci to candidate genes – A research plan and preliminary results using Drosophila as a model organism and climatic and genetic stress as model stresses.

  5. Ecologically relevant stress resistance: from microarrays and ...

    Indian Academy of Sciences (India)

    Unknown

    2004-10-15

    Oct 15, 2004 ... quantitative trait loci to candidate genes – A research plan and preliminary results using ... [Loeschcke V, Sørensen J G and Kristensen T N 2004 Ecologically relevant stress resistance: from microarrays and quantitative trait loci to candidate genes ..... heritability of fitness and non-fitness traits (fertility, heat.

  6. [Airway anatomy : Relevant structures in emergency medicine].

    Science.gov (United States)

    Schulze, M; Wree, A

    2017-09-01

    The subject of this article is the anatomy of the respiratory tract with an emphasis on the larynx. A differentiation is made between the upper and lower airways according to topographical and functional aspects, the limits of which are marked by the lower section of the larynx. The focus is on the anatomy of the structures involved, which are relevant for emergency medicine.

  7. Where's the Race in Culturally Relevant Pedagogy?

    Science.gov (United States)

    Milner, H. Richard, IV

    2017-01-01

    Background/Context: When Ladson-Billings described the pedagogical practices of successful teachers of African American children and consequently conceptualized culturally relevant pedagogy as an analytic resource to describe and make sense of pedagogical practices of teachers, her discussion was situated in a frame that examined instructional…

  8. Endorsing cultural relevance whilst scaffolding academic literacies ...

    African Journals Online (AJOL)

    The learners of the case study brought individual cultural identities toa higher educational environment that often did not acknowledge diverse culturalroots. Thus, a culturally relevant topic was included in the English learning situationto motivate the learners in the negotiation of meaning via scientific language patternsthat ...

  9. The Relevant Physical Trace in Criminal Investigation

    Directory of Open Access Journals (Sweden)

    Durdica Hazard

    2016-01-01

    Full Text Available A criminal investigation requires the forensic scientist to search and to interpret vestiges of a criminal act that happened in the past. The forensic scientist is one of the many stakeholders who take part in the information quest within the criminal justice system. She reads the investigation scene in search of physical traces that should enable her to tell the story of the offense/crime that allegedly occurred. The challenge for any investigator is to detect and recognize relevant physical traces in order to provide clues for investigation and intelligence purposes, and that will constitute sound and relevant evidence for the court. This article shows how important it is to consider the relevancy of physical traces from the beginning of the investigation and what might influence the evaluation process. The exchange and management of information between the investigation stakeholders are important. Relevancy is a dimension that needs to be understood from the standpoints of law enforcement personnel and forensic scientists with the aim of strengthening investigation and ultimately the overall judicial process.

  10. The Current Relevance and Applications of Erythrocyte ...

    African Journals Online (AJOL)

    The erythrocyte sedimentation rate (ESR) is a simple and inexpensive laboratory test. It is commonly used to assess the acute phase response. A review of relevant literature was done to evaluate the role of the ESR and its importance in different clinical conditions both inflammatory and non-inflammatory. Despite the critical ...

  11. Seeking Relevance: American Political Science and America

    Science.gov (United States)

    Maranto, Robert; Woessner, Matthew C.

    2012-01-01

    In this article, the authors talk about the relevance of American political science and America. Political science has enormous strengths in its highly talented practitioners and sophisticated methods. However, its disconnection from its host society, while not so severe as for fields like English and sociology, nonetheless poses an existential…

  12. The Relevance of Causal Social Construction

    Directory of Open Access Journals (Sweden)

    Marques Teresa

    2017-02-01

    Full Text Available Social constructionist claims are surprising and interesting when they entail that presumably natural kinds are in fact socially constructed. The claims are interesting because of their theoretical and political importance. Authors like Díaz-León argue that constitutive social construction is more relevant for achieving social justice than causal social construction. This paper challenges this claim. Assuming there are socially salient groups that are discriminated against, the paper presents a dilemma: if there were no constitutively constructed social kinds, the causes of the discrimination of existing social groups would have to be addressed, and understanding causal social construction would be relevant to achieve social justice. On the other hand, not all possible constitutively socially constructed kinds are actual social kinds. If an existing social group is constitutively constructed as a social kind K, the fact that it actually exists as a K has social causes. Again, causal social construction is relevant. The paper argues that (i for any actual social kind X, if X is constitutively socially constructed as K, then it is also causally socially constructed; and (ii causal social construction is at least as relevant as constitutive social construction for concerns of social justice. For illustration, I draw upon two phenomena that are presumed to contribute towards the discrimination of women: (i the poor performance effects of stereotype threat, and (ii the silencing effects of gendered language use.

  13. Women with epilepsy: clinically relevant issues

    OpenAIRE

    Bangar, Santosh; Shastri, Abhishek; El-Sayeh, Hany; Cavanna, Andrea E.

    2016-01-01

    Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (includi...

  14. Student Part Time Jobs: Relevant or Nonrelevant

    Science.gov (United States)

    Hay, John E.; And Others

    1970-01-01

    Some study conclusions agree: (1) students with jobs relevant to their majors achieve better than students in nonrelevant jobs: (2) students working more than 15 hours per week generally earn lower GPA's than those working fewer hours; and (3) students working a moderate number of hours achieve as well as or better than nonworking students.…

  15. Inferring feature relevances from metric learning

    DEFF Research Database (Denmark)

    Schulz, Alexander; Mokbel, Bassam; Biehl, Michael

    2015-01-01

    Powerful metric learning algorithms have been proposed in the last years which do not only greatly enhance the accuracy of distance-based classifiers and nearest neighbor database retrieval, but which also enable the interpretability of these operations by assigning explicit relevance weights to ...

  16. Culturally Relevant Pedagogy: Clashes and Confrontations

    Science.gov (United States)

    Scherff, Lisa, Ed.; Spector, Karen, Ed.

    2010-01-01

    The authors in this edited volume reflect on their experiences with culturally relevant pedagogy--as students, as teachers, as researchers--and how these experiences were often at odds with their backgrounds and/or expectations. Each of the authors speaks to the complexity and difficulty in attempting to address students' cultures, create learning…

  17. Relevance of microelectronic education to industrial needs

    Science.gov (United States)

    Prince, J. L.; Lathrop, J. W.

    1977-01-01

    The relevance of microelectronic education to industrial needs was evaluated, and four categories were surveyed: (1) facts and rules; (2) skills; (3) personality; and (4) deductive-inductive reasoning. Examples of specific items in each category are given to illustrate their meaning and it was indicated as to which items in each category are strongly impacted by microelectronics courses and laboratories.

  18. Bible Translation And Relevance Theory | Deist | Stellenbosch ...

    African Journals Online (AJOL)

    Stellenbosch Papers in Linguistics Plus. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 22 (1992) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Bible Translation And Relevance Theory. F Deist. Abstract. No abstract ...

  19. Experimental design optimization for screening relevant free ...

    African Journals Online (AJOL)

    Experimental design methodology was used to optimize the HPLC separation of various relevant phenolic acids from an artificial mixture. The effect of four characteristic factors of the HPLC procedure on the Chromatographic Response Function was investigated by a Central Composite Face-Centred Design and Multi ...

  20. Interpersonal communication: It's relevance to nursing practice ...

    African Journals Online (AJOL)

    This paper is aimed at highlighting how essential interpersonal communication is necessary for establishing rapport, understanding the needs of the patients and planning effective intervention for meeting holistic health care. To be continually relevant, Nurses have to improve on their communication skills to meet the ...

  1. Relevance of integrating Information Communication Technology (ICT)

    African Journals Online (AJOL)

    The paper examined the tool of Information Communication Technology (ICT), its relevance and the need to integrate it into teacher formation programmes in Nigerian universities. The paper defined ICT in pedagogical context and so established its implicatians in education management for teacher education.

  2. Pragmatic inferences and self-relevant judgments

    DEFF Research Database (Denmark)

    Puente-Diaz, Rogelio; Cavazos Arroyo, Judith; Brem, Alexander

    2016-01-01

    with a representative sample of the adult population of Mexico showed that participants evaluated themselves more posi- tively on a bipolar than a unipolar scale. Age did not moderate this relationship. Results from studies 2 and 3 also showed a significant influence of type of scale on self-relevant judgments...

  3. 33 CFR 51.8 - Relevant considerations.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Relevant considerations. 51.8 Section 51.8 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PERSONNEL COAST... which is brought to the board's attention. (b) The applicant's capability to serve. In determining the...

  4. The Relevance of Cosmopolitanism for Moral Education

    Science.gov (United States)

    Merry, Michael S.; de Ruyter, Doret J.

    2011-01-01

    In this article we defend a moral conception of cosmopolitanism and its relevance for moral education. Our moral conception of cosmopolitanism presumes that persons possess an inherent dignity in the Kantian sense and therefore they should be recognised as ends-in-themselves. We argue that cosmopolitan ideals can inspire moral educators to awaken…

  5. The relevance of cosmopolitanism for moral education

    NARCIS (Netherlands)

    Merry, M.S.; de Ruyter, D.J.

    2011-01-01

    In this article we defend a moral conception of cosmopolitanism and its relevance for moral education. Our moral conception of cosmopolitanism presumes that persons possess an inherent dignity in the Kantian sense and therefore they should be recognised as ends-in-themselves. We argue that

  6. Relevance theory explains the selection task.

    Science.gov (United States)

    Sperber, D; Cara, F; Girotto, V

    1995-10-01

    We propose a general and predictive explanation of the Wason Selection Task (where subjects are asked to select evidence for testing a conditional "rule"). Our explanation is based on a reanalysis of the task, and on Relevance Theory. We argue that subjects' selections in all true versions of the Selection Task result from the following procedure. Subjects infer from the rule directly testable consequences. They infer them in their order of accessibility, and stop when the resulting interpretation of the rule meets their expectations of relevance. Subjects then select the cards that may test the consequences they have inferred from the rule. Order of accessibility of consequences and expectations of relevance vary with rule and context, and so, therefore, does subjects' performance. By devising appropriate rule-context pairs, we predict that correct performance can be elicited in any conceptual domain. We corroborate this prediction with four experiments. We argue that past results properly reanalyzed confirm our account. We discuss the relevance of the Selection Task to the study of reasoning.

  7. Possessives and relevance | Taylor | Stellenbosch Papers in ...

    African Journals Online (AJOL)

    Stellenbosch Papers in Linguistics. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 26 (1993) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Possessives and relevance. J R Taylor. Abstract. No abstract.

  8. Gel Microstructure Regulates Proliferation and Differentiation of MC3T3-E1 Cells Encapsulated in Alginate Beads

    Science.gov (United States)

    Lee, Baek-Hee; Li, Bing; Guelcher, Scott A.

    2012-01-01

    For cell transplantation into damaged tissues, viable cells must be delivered to the defect site in a suitable carrier. However, the hypoxic and nutrient-limited environment in the carrier can induce massive cell death. The aims of this study were to increase the viability and regulate the behavior of osteoprogenitor cells encapsulated in alginate hydrogels through control of the gel microstructure. Cell survivability in alginate beads was improved through the use of α-MEM as the solvent for alginic acid sodium salt and CaCl2 solutions, which supplied additional nutrients for the cells compared to water or buffer. The mesh size and shear modulus of the hydrogel were hypothesized to regulate proliferation and differentiation of osteoprogenitor cells. MC3T3-E1 cells demonstrated enhanced osteoblast differentiation when encapsulated in high-density alginate with smaller mesh size and more rigid mechanical properties, as confirmed by increased alkaline phosphatase activity and osteocalcin secretion. However, MC3T3-E1 cells encapsulated in low-density alginate beads with a larger mesh size and more compliant mechanical properties exhibited increased proliferation. These results demonstrate that the microstructure of alginate hydrogels can regulate the behavior of osteoprogenitor cells, thus suggesting that the tuning the properties of the gel may be a useful approach for enhancing new bone formation. PMID:22306825

  9. Chronic myeloid leukemia with an e1a3 BCR-ABL fusion protein: transformation to lymphoid blast crisis.

    Science.gov (United States)

    Martinez-Serra, Jordi; Del Campo, Raquel; Gutierrez, Antonio; Antich, Jose Luis; Ginard, Magdalena; Durán, Maria A; Bento, Leyre; Ros, Teresa; Amat, Juan C; Vidal, Carmen; Iglesias, Julio F; Orlinska, Izabela; Besalduch, Joan

    2014-01-01

    Chronic myelogenous leukemia (CML) results from the neoplastic transformation of a hematopoietic stem cell. CML is cytogenetically characterized by the presence of the Philadelphia chromosome (Ph'). Most patients with CML express e13a2 or e14a2 mRNAs that result from a rearrangement of the major breakpoint cluster regions (M-BCR) generating the 210-kDa (p210BCR-ABL) fusion proteins b2a2 or b3a2 respectively. The e1a3 CML-related atypical translocation has been reported with an indolent clinical course, low leukocyte count, long chronic phase even without treatment and good response to therapy. We report the case of a patient initially diagnosed as CML in chronic phase whose cells expressed the e1a3 variant. The patient readily responded to imatinib 400 mg with the achievement of a rapid complete cytogenetic response and the normalization of the blood count values, but after 5 months transformed into lymphoid blast crisis.

  10. Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine

    Energy Technology Data Exchange (ETDEWEB)

    DeVore, Natasha M.; Meneely, Kathleen M.; Bart, Aaron G.; Stephens, Eva S.; Battaile, Kevin P.; Scott, Emily E. (Kansas); (HWMRI)

    2013-11-20

    Human xenobiotic-metabolizing cytochrome P450 (CYP) enzymes can each bind and monooxygenate a diverse set of substrates, including drugs, often producing a variety of metabolites. Additionally, a single ligand can interact with multiple CYP enzymes, but often the protein structural similarities and differences that mediate such overlapping selectivity are not well understood. Even though the CYP superfamily has a highly canonical global protein fold, there are large variations in the active site size, topology, and conformational flexibility. We have determined how a related set of three human CYP enzymes bind and interact with a common inhibitor, the muscarinic receptor agonist drug pilocarpine. Pilocarpine binds and inhibits the hepatic CYP2A6 and respiratory CYP2A13 enzymes much more efficiently than the hepatic CYP2E1 enzyme. To elucidate key residues involved in pilocarpine binding, crystal structures of CYP2A6 (2.4 {angstrom}), CYP2A13 (3.0 {angstrom}), CYP2E1 (2.35 {angstrom}), and the CYP2A6 mutant enzyme, CYP2A6 I208S/I300F/G301A/S369G (2.1 {angstrom}) have been determined with pilocarpine in the active site. In all four structures, pilocarpine coordinates to the heme iron, but comparisons reveal how individual residues lining the active sites of these three distinct human enzymes interact differently with the inhibitor pilocarpine.

  11. Linarin isolated from Buddleja officinalis prevents hydrogen peroxide-induced dysfunction in osteoblastic MC3T3-E1 cells.

    Science.gov (United States)

    Kim, Young Ho; Lee, Young Soon; Choi, Eun Mi

    2011-01-01

    The flowers and leaves buds of Buddleja officinalis MAXIM (Buddlejaceae) are used to treat eye troubles, hernia, gonorrhea and liver troubles in Asia. To elucidate the protective effects of linarin isolated from B. officinalis on the response of osteoblast to oxidative stress, osteoblastic MC3T3-E1 cells were pre-incubated with linarin for 1h before treatment with 0.3mM H(2)O(2) for 48h, and markers of osteoblast function and oxidative damage were examined. Linarin significantly (P<0.05) increased cell survival, alkaline phosphatase (ALP) activity, collagen content, calcium deposition, and osteocalcin secretion and decreased the production of receptor activator of nuclear factor-kB ligand (RANKL), protein carbonyl (PCO), and malondialdehyde (MDA) of osteoblastic MC3T3-E1 cells in the presence of hydrogen peroxide. These results demonstrate that linarin can protect osteoblasts against hydrogen peroxide-induced osteoblastic dysfunction and may exert anti-resorptive actions, at least in part, via the reduction of RANKL and oxidative damage. 2011 Elsevier Inc. All rights reserved.

  12. Synthesis of polypyrrole nanowires with positive effect on MC3T3-E1 cell functions through electrical stimulation.

    Science.gov (United States)

    He, Yuan; Wang, Shihui; Mu, Jing; Dai, Lingfeng; Zhang, Zhong; Sun, Yanan; Shi, Wei; Ge, Dongtao

    2017-02-01

    Conducting polymer polypyrrole (PPy) possesses good biocompatibility and conductivity and has been used as functional coatings in bone tissue regeneration. In this study, a cholic acid doped PPy nanowires (PPy NWs) coating was electrochemically polymerized on the surface of titanium (Ti). The porous intertwined PPy NWs coating exhibited excellent electrical conductivity and electrochemical activity, better hydrophilicity and higher surface energy. In vitro cell experiments demonstrated that the PPy NWs coating together with a 10μA substrate-mediate electrical stimulation (ES) was capable to positive regulate the functions of MC3T3-E1 such as cell adhesion, proliferation and differentiation. Further long-term functions of cell tests including alkaline phosphatase (ALP) activity, bone-carboxyglutamic acid-containing protein (BGP) and calcium deposition were all thoroughly increased. These confirmed that the combination of PPy NWs and ES could accelerate MC3T3-E1 cells mature and osteogenesis. Hence, the PPy NWs coating was an electro bioactive coating and may have potential applications in the treatment of bone damage repairing and regeneration with ES. Copyright © 2016. Published by Elsevier B.V.

  13. Reactive oxygen species regulatory mechanisms associated with rapid response of MC3T3-E1 cells for vibration stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ling; Gan, Xueqi; Zhu, Zhuoli; Yang, Yang; He, Yuting; Yu, Haiyang, E-mail: yhyang6812@scu.edu.cn

    2016-02-12

    Although many previous studies have shown that refractory period-dependent memory effect of vibration stress is anabolic for skeletal homeostasis, little is known about the rapid response of osteoblasts simply derived from vibration itself. In view of the potential role of reactive oxygen species (ROS) in mediating differentiated activity of osteoblasts, whether and how ROS regulates the rapid effect of vibration deserve to be demonstrated. Our findings indicated that MC3T3-E1 cells underwent decreased gene expression of Runx2, Col-I and ALP and impaired ALP activity accompanied by increased mitochondrial fission immediately after vibration loading. Moreover, we also revealed the involvement of ERK-Drp1 signal transduction in ROS regulatory mechanisms responsible for the rapid effect of vibration stress. - Highlights: • ROS contributed to the rapid response of MC3T3-E1 cells for vibration stress. • Imbalance of mitochondrial dynamics were linked to the LMHFV-derived rapid response. • The role of ERK-Drp1 signal pathway in the LMHFV-derived osteoblast rapid response.

  14. Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

    Science.gov (United States)

    Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

    2015-01-01

    The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB.

  15. Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G., E-mail: chinnag@slu.edu

    2013-09-01

    Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.

  16. Mutations in the human papillomavirus type 16 E2 protein identify multiple regions of the protein involved in binding to E1.

    Science.gov (United States)

    Piccini, A; Storey, A; Massimi, P; Banks, L

    1995-11-01

    Human papillomavirus type 16 (HPV-16) DNA replicates episomally and requires two virally expressed proteins, E1 and E2. The E1 protein has both helicase and ATPase activities and is absolutely required for viral DNA replication. The E2 protein is a potent transcriptional activator and greatly increases viral DNA replication by colocalizing E1 to the origin of replication. Recently, we characterized a region of the E2 protein essential for the binding to E1. In this study we have analysed in further detail the nature of the association between E1 and E2. Using an extensive set of E2 mutant proteins we have identified two widely separate regions of the E2 protein which are essential for binding to E1. Interestingly, two E2 mutants which fail to bind E1 also fail to activate gene expression, indicating the existence of multifunctional domains on the E2 protein. In addition, cotransfection of E1 with E2 significantly increases E2 transcriptional activity on an heterologous promoter.

  17. Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation.

    Science.gov (United States)

    Yousef, A F; Fonseca, G J; Pelka, P; Ablack, J N G; Walsh, C; Dick, F A; Bazett-Jones, D P; Shaw, G S; Mymryk, J S

    2010-08-19

    Hub proteins have central roles in regulating cellular processes. By targeting a single cellular hub, a viral oncogene may gain control over an entire module in the cellular interaction network that is potentially comprised of hundreds of proteins. The adenovirus E1A oncoprotein is a viral hub that interacts with many cellular hub proteins by short linear motifs/molecular recognition features (MoRFs). These interactions transform the architecture of the cellular protein interaction network and virtually reprogram the cell. To identify additional MoRFs within E1A, we screened portions of E1A for their ability to activate yeast pseudohyphal growth or differentiation. This identified a novel functional region within E1A conserved region 2 comprised of the sequence EVIDLT. This MoRF is necessary and sufficient to bind the N-terminal region of the SUMO conjugase UBC9, which also interacts with SUMO noncovalently and is involved in polySUMOylation. Our results suggest that E1A interferes with polySUMOylation, but not with monoSUMOylation. These data provide the first insight into the consequences of the interaction of E1A with UBC9, which was initially described in 1996. We further demonstrate that polySUMOylation regulates pseudohyphal growth and promyelocytic leukemia body reorganization by E1A. In conclusion, the interaction of the E1A oncogene with UBC9 mimics the normal binding between SUMO and UBC9 and represents a novel mechanism to modulate polySUMOylation.

  18. Retina restored and brain abnormalities ameliorated by single-copy knock-in of human NR2E1 in null mice.

    Science.gov (United States)

    Schmouth, J-F; Banks, K G; Mathelier, A; Gregory-Evans, C Y; Castellarin, M; Holt, R A; Gregory-Evans, K; Wasserman, W W; Simpson, E M

    2012-04-01

    Nr2e1 encodes a stem cell fate determinant of the mouse forebrain and retina. Abnormal regulation of this gene results in retinal, brain, and behavioral abnormalities in mice. However, little is known about the functionality of human NR2E1. We investigated this functionality using a novel knock-in humanized-mouse strain carrying a single-copy bacterial artificial chromosome (BAC). We also documented, for the first time, the expression pattern of the human BAC, using an NR2E1-lacZ reporter strain. Unexpectedly, cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1. These results correlated with an absence of NR2E1-lacZ reporter expression in the dorsal pallium of embryos and proliferative cells of adult brains. Surprisingly, retinal histology and electroretinograms demonstrated complete correction of the retina-null phenotype. These results correlated with appropriate expression of the NR2E1-lacZ reporter in developing and adult retina. We conclude that the human BAC contained all the elements allowing correction of the mouse-null phenotype in the retina, while missing key regulatory regions important for proper spatiotemporal brain expression. This is the first time a separation of regulatory mechanisms governing NR2E1 has been demonstrated. Furthermore, candidate genomic regions controlling expression in proliferating cells during neurogenesis were identified.

  19. Different activities of the adenovirus types 5 and 12 E1A regions in transformation with the EJ Ha-ras oncogene

    NARCIS (Netherlands)

    Jochemsen, A.G.; Bernards, R.A.; Kranen, H.J. van; Houweling, A.; Bos, J.L.; Eb, A.J. van der

    1986-01-01

    We have compared the capacities of the E1A regions of nononcogenic adenovirus type 5 (Ad5) and highly oncogenic Ad12 to cooperate with the EJ bladder carcinoma Ha-ras-1 oncogene in the transformation of primary baby rat kidney cells. Both E1A regions, when cotransfected with the Ha-ras oncogene,

  20. Hyperactivity, startle reactivity and cell-proliferation deficits are resistant to chronic lithium treatment in adult Nr2e1(frc/frc) mice.

    Science.gov (United States)

    Wong, B K Y; Hossain, S M; Trinh, E; Ottmann, G A; Budaghzadeh, S; Zheng, Q Y; Simpson, E M

    2010-10-01

    The NR2E1 region on Chromosome 6q21-22 has been repeatedly linked to bipolar disorder (BP) and NR2E1 has been associated with BP, and more specifically bipolar I disorder (BPI). In addition, patient sequencing has shown an enrichment of rare candidate-regulatory variants. Interestingly, mice carrying either spontaneous (Nr2e1(frc) ) or targeted (Tlx(-) ) deletions of Nr2e1 (here collectively known as Nr2e1-null) show similar neurological and behavioral anomalies, including hypoplasia of the cerebrum, reduced neural stem cell proliferation, extreme aggression and deficits in fear conditioning; these are the traits that have been observed in some patients with BP. Thus, NR2E1 is a positional and functional candidate for a role in BP. However, no Nr2e1-null mice have been fully evaluated for behaviors used to model BP in rodents or pharmacological responses to drugs effective in treating BP symptoms. In this study we examine Nr2e1(frc/frc) mice, homozygous for the spontaneous deletion, for abnormalities in activity, learning and information processing, and cell proliferation; these are the phenotypes that are either affected in patients with BP or commonly assessed in rodent models of BP. The effect of lithium, a drug used to treat BP, was also evaluated for its ability to attenuate Nr2e1(frc/frc) behavioral and neural stem cell-proliferation phenotypes. We show for the first time that Nr2e1-null mice exhibit extreme hyperactivity in the open field as early as postnatal day 18 and in the home cage, deficits in open-field habituation and passive avoidance, and surprisingly, an absence of acoustic startle. We observed a reduction in neural stem/progenitor cell proliferation in Nr2e1(frc/frc) mice, similar to that seen in other Nr2e1-null strains. These behavioral and cell-proliferation phenotypes were resistant to chronic-adult-lithium treatment. Thus, Nr2e1(frc/frc) mice exhibit behavioral traits used to model BP in rodents, but our results do not support Nr2e1(frc

  1. Hyperactivity, startle reactivity and cell-proliferation deficits are resistant to chronic lithium treatment in adult Nr2e1frc/frc mice

    Science.gov (United States)

    Wong, Bibiana K.Y.; Hossain, Sazzad M.; Trinh, Eric; Ottmann, Glen A.; Budaghzadeh, Saeed; Zheng, Qing Y.; Simpson, Elizabeth M.

    2012-01-01

    The NR2E1 region on Chromosome 6q21-22 has been repeatedly linked to bipolar disorder (BP) and NR2E1 has been associated with BP, and more specifically bipolar I disorder (BPI). In addition, patient sequencing has revealed an enrichment of rare candidate-regulatory variants. Interestingly, mice carrying either spontaneous (Nr2e1frc) or targeted (Tlx−) deletions of Nr2e1 (here collectively known as Nr2e1-null) show similar neurological and behavioral anomalies, including: hypoplasia of the cerebrum, reduced neural stem cell proliferation, extreme aggression, and deficits in fear conditioning; traits that have been observed in some patients with BP. Thus, NR2E1 is a positional and functional candidate for a role in BP. However, no Nr2e1-null mice have been fully evaluated for behaviors used to model BP in rodents or pharmacological responses to drugs effective in treating BP symptoms. In this study we examine Nr2e1frc/frc mice, homozygous for the spontaneous deletion, for abnormalities in activity, learning and information processing, and cell proliferation; phenotypes that are either affected in patients with BP or commonly assessed in rodent models of BP. The effect of lithium, a drug used to treat BP, was also evaluated for its ability to attenuate Nr2e1frc/frc behavioral and neural stem cell proliferation phenotypes. We show for the first time that Nr2e1-null mice exhibit extreme hyperactivity in the open field as early as postnatal day 18 and in the home cage, deficits in open-field habituation and passive avoidance, and, surprisingly, an absence of acoustic startle. We observed a reduction in neural stem/progenitor cell proliferation in Nr2e1frc/frc mice, similar to that seen in other Nr2e1-null strains. These behavioral and cell-proliferation phenotypes were resistant to chronic-adult-lithium treatment. Thus, Nr2e1frc/frc mice exhibit behavioral traits used to model BP in rodents, but our results do not support Nr2e1frc/frc mice as pharmacological models for

  2. Scale Effects in Moral Relevance Assessment.

    Science.gov (United States)

    Nagel, Jonas; Rybak, Andrej

    2017-03-01

    Research on moral judgment often employs bipolar rating scales to assess whether the difference between two contrasted options is judged to be morally relevant. We give an account of how different numbers of response options provided on such scales (odd vs. even) change the meaning of the test question by communicating different implicit presuppositions. We demonstrate experimentally that these changes can qualitatively affect the moral relevance judgments that subjects express in response to a given judgment problem. Several alternative explanations in terms of trivial measurement distortion are tested and refuted, and we present suggestive evidence as to what kind of factors might be prone to scale effects. The findings underscore that expressed moral judgments are constructed ad hoc and do not necessarily reflect the content of underlying stable moral commitments. We discuss implications for theories and methodology in moral psychology and in judgment and decision-making research more generally.

  3. Tomographic diagnosis and relevant aspects of otosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Gaiotti, Juliana Oggioni; Gomes, Natalia Delage; Costa, Ana Maria Doffemond; Villela, Caroline Laurita Batista Couto; Moreira, Wanderval; Diniz, Renata Lopes Furletti Caldeira, E-mail: jugaiotti@gmail.com [Hospital Mater Dei-Mater Imagem, Belo Horizonte, MG (Brazil)

    2013-09-15

    A literature review and pictorial essay were developed to discuss the importance of knowing the main findings and locations of otosclerosis at multidetector computed tomography (MDCT). The authors performed a retrospective review of cases of otosclerosis diagnosed in their institution by means of high resolution multidetector computed tomography. Otosclerosis corresponds to otic capsule dysplasia characterized by metabolic derangement of its endochondral layer. Such condition constitutes a relevant cause of sensorineural hearing loss, affecting about 7% to 10% of the general population. The diagnosis is usually clinical, but imaging methods play a significant role in the anatomical detailing, differential diagnosis, surgical planning and evaluation of postoperative complications. Among such methods, the relevance of MDCT is highlighted. Radiologists should be familiar with the MDCT findings of otosclerosis, as well as with the temporal bone anatomy to assist in the appropriate clinical management of this disease. (author)

  4. Industrial Mobilization: The Relevant History. Revised

    Science.gov (United States)

    1983-01-01

    Industry , in order to establish requirements for construction of new facilities 7. To minimize requirements for new construction in wartime by proper...Mobilization: What Management Is Doing. New York, N.Y.: Controllership Foundation, Inc., 1951. " Industry on Guard," Modern Industry . Reprint by the... Industrial Mobilization: The Relevant History ’ DTIC Roderick L. Vawter DELECT DEC 7 1983 Ap~~~Pr,.d•public release;• ---.--- BU’UON- ’T TE q A ’te

  5. Editorial: Relevance Theory and Intercultural Communication Problems

    OpenAIRE

    Piskorska, Agnieszka

    2017-01-01

    This editorial to the special issue of RiL dedicated to relevance theory and problems of intercultural communication addresses the general requirements that a theory of communication must meet to be applicable to the analysis of intercultural communication. Then it discusses criticism levelled against Grice’s theory of conversational implicature and Brown and Levinson’s theory of politeness on the grounds that these theories were not universal enough to be applied to all data. Finally, it off...

  6. Graphene Oxide Hybridized nHAC/PLGA Scaffolds Facilitate the Proliferation of MC3T3-E1 Cells

    Science.gov (United States)

    Liang, Chunyong; Luo, Yongchao; Yang, Guodong; Xia, Dan; Liu, Lei; Zhang, Xiaomin; Wang, Hongshui

    2018-01-01

    Biodegradable porous biomaterial scaffolds play a critical role in bone regeneration. In this study, the porous nano-hydroxyapatite/collagen/poly(lactic-co-glycolic acid)/graphene oxide (nHAC/PLGA/GO) composite scaffolds containing different amount of GO were fabricated by freeze-drying method. The results show that the synthesized scaffolds possess a three-dimensional porous structure. GO slightly improves the hydrophilicity of the scaffolds and reinforces their mechanical strength. Young's modulus of the 1.5 wt% GO incorporated scaffold is greatly increased compared to the control sample. The in vitro experiments show that the nHAC/PLGA/GO (1.5 wt%) scaffolds significantly cell adhesion and proliferation of osteoblast cells (MC3T3-E1). This present study indicates that the nHAC/PLGA/GO scaffolds have excellent cytocompatibility and bone regeneration ability, thus it has high potential to be used as scaffolds in the field of bone tissue engineering.

  7. Intra-arterial infusion of prostaglandin E1 in normal subjects and patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Nielsen, P E; Nielsen, S L; Holstein, P

    1976-01-01

    Acute vasodilatation was produced by infusion of prostaglandin E1 (PGE1) in the femoral artery in 6 patients with occlusive arterial disease of the legs and in 3 normal subjects. The effect on blood flow and on blood pressure was measured at different segments of the leg with the strain gauge...... technique, isotope clearance technique, and photoelectric technique. Skin temperature was measured at different levels by using thermocouples. The blood pressure on the legs decreased at all segments during vasodilatation as well in patients as in controls. The blood flow increased in all segments in normal...... controls. In patients the blood flow increased proximally in the legs. Distally, however, no increase could be demonstrated. As a good effect of PGE1, on ischaemic rest pains has been reported, mechanisms other than vasodilatation should probably be considered....

  8. KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification

    DEFF Research Database (Denmark)

    Bürck, Carolin; Mund, Andreas; Berscheminski, Julia

    2016-01-01

    characterized, but represent a decisive moment in establishing a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin associated transcription factor regulates the dynamic organization of host chromatin structure via its ability to influence epigenetic marks...... and chromatin compaction. In response to DNA damage, KAP1 is phosphorylated and functionally inactive, resulting in chromatin relaxation. We discovered that KAP1 posttranslational modification is dramatically altered during HAdV infection to limit the antiviral capacity of this host restriction factor, which...... epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism. IMPORTANCE: Here we describe a novel cellular restriction factor for Human Adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation...

  9. Transient electronic anisotropy in overdoped NaF e1 -xC oxAs superconductors

    Science.gov (United States)

    Liu, Shenghua; Zhang, Chunfeng; Deng, Qiang; Wen, Hai-hu; Li, Jian-xin; Chia, Elbert E. M.; Wang, Xiaoyong; Xiao, Min

    2018-01-01

    By combining polarized pump-probe spectroscopic and Laue x-ray diffraction measurements, we have observed nonequivalent transient optical responses with the probe beam polarized along the x and y axes in overdoped NaF e1 -xC oxAs superconductors. Such transient anisotropic behavior has been uncovered in the tetragonal phase with the doping level and temperature range far from the borders of static nematic phases. The measured transient anisotropy can be well explained as a result of nematic fluctuation driven by an orbital order with energy splitting of the dx z- and dy z-dominant bands. In addition, the doping level dependence and the pressure effect of the crossover temperature show significant differences between the transient nematic fluctuation and static nematic phase, implying spin and orbital orders may play different roles in static and transient nematic behaviors.

  10. The value relevance of environmental emissions

    Directory of Open Access Journals (Sweden)

    Melinda Lydia Nelwan

    2016-07-01

    Full Text Available This study examines whether environmental performance has value relevance by investigating the relations between environmental emissions and stock prices for the U.S. public companies. The previous studies argued that the conjectured relations between accounting performance measures and environmental performance do not have a strong theoretical basis, and the modeling of relations between market per-formance measures and environmental performance do not adequately consider the relevance of accounting performance to market value. Therefore, this study examines whether publicly reported environmental emissions provide incremental information to accounting earnings in pricing companies stocks. It is done among the complete set of industries covered by Toxics Release Inventory (TRI reporting for the period 2007 to 2010. Using Ohlson model but modified to include different types of emis-sions, it is found that ground emissions (underground injection and land emissions are value relevant but other emission types (air and water and transferred-out emis-sions appear to not provide incremental information in the valuation model. The result in this study raise concerns that different types of emissions are assessed differently by the market, confirming that studies should not aggregate such measures.

  11. Selection of relevant dietary indicators for health.

    Science.gov (United States)

    Steingrímsdóttir, L; Ovesen, L; Moreiras, O; Jacob, S

    2002-05-01

    To define a set of dietary components that are relevant determinants for health in Europe. The selected components are intended to serve as nutrition indicators for health in the European Health Monitoring Programme and, as such, must be limited in number, relevant to health in Europe and practical for all involved countries with respect to data gathering and comparability of data. Major nutrition factors were determined by reviewing relevant epidemiological and clinical literature in nutrition and health as well as referring to reports from international expert groups, including the report from the project Nutrition and Diet for Healthy Lifestyles in Europe. The selection of factors was also based on the relative ease and cost involved for participating countries to obtain comparable and valid data. The selected factors include foods or food groups as well as individual nutrients. Biomarkers are suggested for selected nutrients that pose the greatest difficulty in obtaining valid and comparable data from dietary studies. The following list of diet indicators for health monitoring in Europe was agreed upon by the EFCOSUM group in 2001, in order of priority: vegetables, fruit, bread, fish, saturated fatty acids as percentage of energy (%E), total fat as %E, and ethanol in grams per day. Biomarkers were suggested for the following nutrients: folate, vitamin D, iron, iodine and sodium. Energy has to be assessed in order to calculate %E from total fat and saturated fatty acids.

  12. Monochloramine Cometabolism by Nitrifying Biofilm Relevant ...

    Science.gov (United States)

    Recently, biological monochloramine removal (i.e., cometabolism) by a pure culture ammonia–oxidizing bacteria, Nitrosomonas europaea, and a nitrifying mixed–culture have been shown to increase monochloramine demand. Although important, these previous suspended culture batch kinetic experiments were not representative of drinking water distribution systems where bacteria grow predominantly as biofilm attached to pipe walls or sediments and physiological differences may exist between suspension and biofilm growth. Therefore, the current research was an important next step in extending the previous results to investigate monochloramine cometabolism by biofilm grown in annular reactors under drinking water relevant conditions. Estimated monochloramine cometabolism kinetics were similar to those of ammonia metabolism, and monochloramine cometabolism was a significant loss mechanism (25–40% of the observed monochloramine loss). These results demonstrated that monochloramine cometabolism occurred in drinking water relevant nitrifying biofilm; thus, cometabolism may be a significant contribution to monochloramine loss during nitrification episodes in distribution systems. Investigate whether or not nitrifying biofilm can biologically transform monochloramine under drinking water relevant conditions.

  13. Poly-γ-glutamic acid productivity of Bacillus subtilis BsE1 has positive function in motility and biocontrol against Fusarium graminearum.

    Science.gov (United States)

    Wang, Luyao; Wang, Ning; Mi, Dandan; Luo, Yuming; Guo, Jianhua

    2017-07-01

    In this study, we investigate the relationship between γ-PGA productivity and biocontrol capacity of Bacillus subtilis BsE1; one bacterial isolate displayed 62.14% biocontrol efficacy against Fusarium root rot. The γ-PGA yield assay, motility assay, wheat root colonization assay, and biological control assay were analysed in different γ-PGA yield mutants of BsE1. The pgsB (PGA-synthase-CapB gene) deleted mutant of BsE1 reduced γ-PGA yield and exhibited apparent decline of in vitro motile ability. Deletion of pgsB impaired colonizing capacity of BsE1 on wheat root in 30 days, also lowered biocontrol efficacies from 62.08% (wild type BsE1) to 14.22% in greenhouse experiment against Fusarium root rot. The knockout of pgdS and ggt (genes relate to two γ-PGA degrading enzymes) on BsE1, leads to a considerable improvement in polymer yield and biocontrol efficacy, which attains higher level compared with wild type BsE1. Compared with ΔpgsB mutant, defense genes related to reactive oxygen species (ROS) and phytoalexin expressed changes by notable levels on wheat roots treated with BsE1, demonstrating the functional role γ-PGA plays in biocontrol against Fusarium root rot. γ-PGA is not only important to the motile and plant root colonization ability of BsE1, but also essential to the biological control performed by BsE1 against Fusarium root rot. Our goal in this study is to reveals a new perspective of BCAs screening on bacterial isolates, without good performance during pre-assays of antagonism ability.

  14. Lunar iron and optical maturity mapping: Results from partial least squares modeling of Chang'E-1 IIM data

    Science.gov (United States)

    Sun, Lingzhi; Ling, Zongcheng; Zhang, Jiang; Li, Bo; Chen, Jian; Wu, Zhongchen; Liu, Jianzhong

    2016-12-01

    Iron and optical maturity (OMAT) are two key geological marks of the Moon that closely related to its geochemical evolution and interactions between surface and space environment. We apply Partial Least Squares (PLS) regression to Chang'E-1 Imaging Interferometer (IIM) (32 bands between 480 and 960 nm) in mapping lunar global FeO and OMAT, and the FeO and OMAT values are derived based on reasonable spectral parameters (absorbance, band ratios, TiO2 and maturity sensitive parameters, etc.). After been calibrated by the FeO map from Lunar Prospector Gamma-Ray Spectrometer (LP-GRS), the global FeO map derived from PLS modeling shows a quantitatively more reasonable result consistent with previous remote sensing results (LP) as well as lunar feldspathic meteorite studies and Chang'E-3 landing site. Based on the new FeO map by Chang'E-1, we discover a compositional inhomogeneity across lunar highland regions, which has not been suggested by previous datasets (e.g., Clementine UVVIS). Furthermore, we suggest that at least part of the FeO enrichments in highlands would be caused by mixing of highland and mare materials. The IIM derived OMAT map does not suggest a dichotomy of the lunar highlands and mare regions, implying the compositional differences between those two terrains have been suppressed. We further check the maturity effect for the young mare basalts (medium and high FeO and TiO2 show a linear decrease with ages; (2) units with ultrahigh-FeO (>20 wt%) and ultrahigh-TiO2 (>10 wt%) tend to have greater OMAT values and vary little with ages; (3) this may be due to the distinct optical maturity effects of ultramafic minerals (i.e., ultrahigh Fe and Ti) and/or the spectral blue shifts of abundant ilmenite.

  15. Effect of Launaea procumbens extract on oxidative marker, p53, and CYP 2E1: a randomized control study

    Directory of Open Access Journals (Sweden)

    Rahmat Ali Khan

    2016-03-01

    Full Text Available Background: Ethyl acetate extracts of Launaea procumbens is used for the treatment of liver dysfunction as an herbal medicine in Pakistan. In this study, the protective effects of ethyl acetate extracts were evaluated against CCl4-induced liver injuries in rat. Methods: To examine the protective effects against oxidative stress of carbon tetrachloride in rats, 30 male rats were equally divided into 5 groups (6 rats. Among five groups, one was treated with CCl4 (3 ml/kg i.p. in olive oil b.w. twice a week for 4 weeks. Others were orally fed with extracts (100, 200 mg/kg b.w., with CCl4 twice a week for 4 weeks. Results: Administration of CCl4 altered the serum marker enzymes, lipid profile, CYP 2E1, p53 expression, antioxidant enzymes, nuclear organizer regions (AgNORs, and DNA. Supplement of L. procumbens ameliorated the effects of CCl4, improved CYP 2E1, p53, and increased the activities of antioxidant enzymes while activity of liver marker enzymes (ALP, ALT, AST, g-GT and contents of lipid per oxidation contents (TBARS, AgNORs, and DNA fragmentation were decreased. Similarly body weight was increased while liver and relative liver weight was decreased with co-administration of various extracts, suggesting that L. procumbens effectively protect liver against the CCl4-induced oxidative damage in rats. Conclusion: The hepatoprotective and free radical scavenging effects might be due to the presence of bioactive constituents in the extract.

  16. ACCURATE REGISTRATION OF THE CHANG’E-1 IIM DATA BASED ON LRO LROC-WAC MOSICA DATA

    Directory of Open Access Journals (Sweden)

    Z. Yang

    2017-07-01

    Full Text Available In the detection of the moon, the visible and near-infrared reflectance data of the lunar material are important information sources for lunar chemical substances and mineral inversion. The Interferometer Imaging Spectrometer (IIM aboard the Chang'E-1 lunar orbiter is the first multispectral imaging spectrometer for Chinese lunar missions. In this paper, we use the mosaic image of global moon acquired by the Wide-angle Camera (WAC of the Lunar Reconnaissance Orbiter Camera (LROC to realize the accurate registration of Chang'E-1 IIM hyperspectral images. Due to the lack of GCPs, the emphasis of this work is to find a huge number of homologous points. The method proposed in this paper is to obtain several homologous points by manually matching, and then we utilize those points to calculate the initial homography matrix of LROC-WAC image and IIM image. This matrix is used to predict the area on IIM image where homologous points may be located, and the locations of the homologous points are determined by the orientation correlation in frequency domain. Finally we save the parts of homologous points which satisfied the conversion relationship of initial homography matrix to calculate homography matrix again. We use this iterative way to obtain a more accurate location of the homologous points. In this process, we take into account that the geometric deformations of different regions on IIM image are quite different. Therefore, we added image threshold segmentation based on the initial homography matrix in the experiment, and completed the above work of finding the homologous points on the segmented images. The final realization of registration accuracy of IIM images are in 1–2 pixels (RMSE. This provides a reliable data assurance for the subsequent study of using IIM images to inverse the lunar elements.

  17. Accurate Registration of the CHANG'E-1 Iim Data Based on Lro Lroc-Wac Mosica Data

    Science.gov (United States)

    Yang, Z.; Kang, Z.

    2017-07-01

    In the detection of the moon, the visible and near-infrared reflectance data of the lunar material are important information sources for lunar chemical substances and mineral inversion. The Interferometer Imaging Spectrometer (IIM) aboard the Chang'E-1 lunar orbiter is the first multispectral imaging spectrometer for Chinese lunar missions. In this paper, we use the mosaic image of global moon acquired by the Wide-angle Camera (WAC) of the Lunar Reconnaissance Orbiter Camera (LROC) to realize the accurate registration of Chang'E-1 IIM hyperspectral images. Due to the lack of GCPs, the emphasis of this work is to find a huge number of homologous points. The method proposed in this paper is to obtain several homologous points by manually matching, and then we utilize those points to calculate the initial homography matrix of LROC-WAC image and IIM image. This matrix is used to predict the area on IIM image where homologous points may be located, and the locations of the homologous points are determined by the orientation correlation in frequency domain. Finally we save the parts of homologous points which satisfied the conversion relationship of initial homography matrix to calculate homography matrix again. We use this iterative way to obtain a more accurate location of the homologous points. In this process, we take into account that the geometric deformations of different regions on IIM image are quite different. Therefore, we added image threshold segmentation based on the initial homography matrix in the experiment, and completed the above work of finding the homologous points on the segmented images. The final realization of registration accuracy of IIM images are in 1-2 pixels (RMSE). This provides a reliable data assurance for the subsequent study of using IIM images to inverse the lunar elements.

  18. ISG15 is critical in the control of Chikungunya virus infection independent of UbE1L mediated conjugation.

    Directory of Open Access Journals (Sweden)

    Scott W Werneke

    2011-10-01

    Full Text Available Chikungunya virus (CHIKV is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L⁻/⁻ mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT and ISG15⁻/⁻ mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15⁻/⁻ mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection.

  19. ISG15 is critical in the control of Chikungunya virus infection independent of UbE1L mediated conjugation.

    Science.gov (United States)

    Werneke, Scott W; Schilte, Clementine; Rohatgi, Anjali; Monte, Kristen J; Michault, Alain; Arenzana-Seisdedos, Fernando; Vanlandingham, Dana L; Higgs, Stephen; Fontanet, Arnaud; Albert, Matthew L; Lenschow, Deborah J

    2011-10-01

    Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L⁻/⁻ mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15⁻/⁻ mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15⁻/⁻ mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection.

  20. Sanguis Draconis resin stimulates osteoblast alkaline phosphatase activity and mineralization in MC3T3-E1 cells.

    Science.gov (United States)

    Wang, Weizhuo; Olson, Douglas; Cheng, Bin; Guo, Xiong; Wang, Kunzheng

    2012-06-26

    Sanguis Draconis (SD), "Dragon's Blood", is a resin that is obtained from Daemonorops draco (Palmae). Used in traditional medicine, it has shown activity in the prevention of osteoporosis as well as promoting the healing of bone fractures. In this study, the effects of Sanguis Dranonis ethanol extract on β-glycerolphosphate and ascorbic acid induced differentiation using mouse calvaria origin MC3T3-E1 osteoblastic cells was examined. We looked at osteoblast differentiation, proliferation, and mineralization by measuring alkaline phosphatase (ALP) and specific bone marker activities. Osteoblast-like MC3T3-E1 cells were cultured in various concentrations of SD ethanol extract (0.005-1mg/mL) during the osteoblast differentiation period (1, 5, 15, and 25 days). As measured by 3-[4,5-dimethylthiazol-2-y]-2,5-diphenyltetrazolium bromide assay, SD extracts increased cell proliferation as compared to control. The most pronounced effect was observed at the concentration range between 0.01 and 0.1 mg/mL (P<0.01). This SD stimulatory effect for cell proliferation was observed during the whole osteogenic period. Cellular (synthesized) ALP activity was increased during 15 days of culture, and was confirmed by the staining of ALP activity on cell matrix layers for matrix calcification. SD stimulatory effect for cell mineralization we observed in 14 and 21 days. Elevated mRNA or protein levels of bone morphogenetic protein-2(BMP 2), the differentiation marker osteocalcin, osteopontin, collgen I, and a master osteogenic transcription factor, Runx2, were observed in SD-treated cells. These results suggest that SD may increase osteogenic effect by stimulating cell ALP activity and affect the BMP signaling pathway cascades in osteoblastic cells, then promotes osteoblast differentiation, mineralization, and bone formation. Copyright © 2012. Published by Elsevier Ireland Ltd.

  1. The impact of positive, negative and topical relevance feedback

    NARCIS (Netherlands)

    Kaptein, Rianne; Kamps, Jaap; Hiemstra, Djoerd

    2008-01-01

    This document contains a description of experiments for the 2008 Relevance Feedback track. We experiment with different amounts of feedback, including negative relevance feedback. Feedback is implemented using massive weighted query expansion. Parsimonious query expansion using only relevant

  2. The impact of positive, negative and topical relevance feedback

    NARCIS (Netherlands)

    Kaptein, R.; Kamps, J.; Hiemstra, D.; Voorhees, E.M.; Buckland, L.P.

    2009-01-01

    This document contains a description of experiments for the 2008 Relevance Feedback track. We experiment with different amounts of feedback, including negative relevance feedback. Feedback is implemented using massive weighted query expansion. Parsimonious query expansion using only relevant

  3. Heterologous Acidothermus cellulolyticus 1,4-β-Endoglucanase E1 Produced Within the Corn Biomass Converts Corn Stover Into Glucose

    Science.gov (United States)

    Ransom, Callista; Balan, Venkatesh; Biswas, Gadab; Dale, Bruce; Crockett, Elaine; Sticklen, Mariam

    Commercial conversion of lignocellulosic biomass to fermentable sugars requires inexpensive bulk production of biologically active cellulase enzymes, which might be achieved through direct production of these enzymes within the biomass crops. Transgenic corn plants containing the catalytic domain of Acidothermus cellulolyticus E1 endo-1,4-β glucanase and the bar bialaphos resistance coding sequences were generated after Biolistic® (BioRad Hercules, CA) bombardment of immature embryo-derived cells. E1 sequences were regulated under the control of the cauliflower mosaic virus 35S promoter and tobacco mosaic virus translational enhancer, and E1 protein was targeted to the apoplast using the signal peptide of tobacco pathogenesis-related protein to achieve accumulation of this enzyme. The integration, expression, and segregation of E1 and bar transgenes were demonstrated, respectively, through Southern and Western blotting, and progeny analyses. Accumulation of up to 1.13% of transgenic plant total soluble proteins was detected as biologically active E1 by enzymatic activity assay. The corn-produced, heterologous E1 could successfully convert ammonia fiber explosion-pretreated corn stover polysaccharides into glucose as a fermentable sugar for ethanol production, confirming that the E1 enzyme is produced in its active from.

  4. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes

    DEFF Research Database (Denmark)

    Fattaey, A R; Harlow, E; Helin, K

    1993-01-01

    for binding to a number of cellular proteins, including pRB and p107. Through the use of a number of glutathione S-transferase fusion proteins representing different regions of E1A, as well as in vivo expression of E1A proteins containing deletions of either conserved region 1 (CR1) or CR2, we find that CR2...... of E1A can form stable complexes with E2F. E1A proteins containing both CR1 and CR2 also associate with E2F, although the presence of these proteins results in the release of free E2F from its complexes. In vitro reconstitution experiments indicate that E1A-E2F interactions are not direct and that pRB...... can serve to facilitate these interactions. Complexes containing E1A, p107, cyclin A, and E2F were identified in vivo, which indicates that E1A may associate with E2F through either p107 or pRB. Peptide competition experiments demonstrate that the pRB-binding domain of the human E2F-1 protein can...

  5. Correlation between spermatogenesis disorders and rat testes CYP2E1 mRNA contents under experimental alcoholism or type I diabetes.

    Science.gov (United States)

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M

    2014-09-01

    The aim of the study was to investigate the correlation between spermatogenesis disorders and CYP2E1 mRNA contents in testes of rats with experimental alcoholism or type I diabetes. Two pathological states characterized by CYP2E1 induction were simulated on Wistar male rats: experimental alcoholism and type I diabetes. As controls for each state, equal number of animals (of the same age and weight) were used. Morphological evaluation of rat testes was carried out. The spermatogenic epithelium state was estimated by four points system. CYP2E1 mRNA expression was rated by method of reverse transcriptase polymerase chain reaction. Pearson correlation coefficients were used for describing relationships between variables. The presence of alcoholism and diabetes-mediated quantitative and qualitative changes in male rat spermatogenic epithelium in comparison with norm has been demonstrated. The increased levels of testes CYP2E1 have been fixed simultaneously. CYP2E1 mRNA content negatively strongly correlated with spermatogenic index value (r=-0.99; Palcoholism. The strong correlation between CYP2E1 mRNA content and number of spermatogonia (r=0.99; P<0.001) and "windows" occurrence (r=0.96; P<0.001) has been fixed in diabetic rats testes. Present investigation has demonstrated that the testicular failure following chronic ethanol consumption and diabetes type I in male rats accompanied CYP2E1 mRNA over-expression in testes. The correlation between the levels of CYP2E1 mRNA in testes and spermatogenesis disorders allow supposing the involvement of CYP2E1 into the non-specific pathogenetic mechanisms of male infertility under above-mentioned pathologies. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Relevance of Allergy in Adult Asthma

    Science.gov (United States)

    Mathur, Sameer K.; Viswanathan, Ravi K.

    2014-01-01

    Recent studies on asthma have demonstrated multiple phenotypes of asthma, based on the clinical characteristics of the disease. With the current interest in personalized medicine, the question arises whether the presence of allergic sensitization has any relevance for these phenotypes and the management of asthma. This review will examine the current knowledge of asthma phenotypes and the impact of atopy on asthma diagnosis and severity in adults. In addition, this review will address whether therapies targeted at the atopic axis help improve asthma outcomes, including lung function indices and exacerbations. PMID:24643812

  7. Identifying Relevant Studies in Software Engineering

    DEFF Research Database (Denmark)

    Zhang, He; Ali Babar, Muhammad; Tell, Paolo

    2011-01-01

    Context: Systematic literature review (SLR) has become an important research methodology in software engineering since the introduction of evidence-based software engineering (EBSE) in 2004. One critical step in applying this methodology is to design and execute appropriate and effective search....... Objective: The main objective of the research reported in this paper is to improve the search step of undertaking SLRs in software engineering (SE) by devising and evaluating systematic and practical approaches to identifying relevant studies in SE. Method: We have systematically selected and analytically...

  8. [Clinical relevance of cardiopulmonary reflexes in anesthesiology].

    Science.gov (United States)

    Guerri-Guttenberg, R A; Siaba-Serrate, F; Cacheiro, F J

    2013-10-01

    The baroreflex, chemoreflex, pulmonary reflexes, Bezold-Jarisch and Bainbridge reflexes and their interaction with local mechanisms, are a demonstration of the richness of cardiovascular responses that occur in human beings. As well as these, the anesthesiologist must contend with other variables that interact by attenuating or accentuating cardiopulmonary reflexes such as, anesthetic drugs, surgical manipulation, and patient positioning. In the present article we review these reflexes and their clinical relevance in anesthesiology. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  9. Has Financial Statement Information become Less Relevant?

    DEFF Research Database (Denmark)

    Thinggaard, Frank; Damkier, Jesper

    as the total market-adjusted return that could be earned from investment strategies based on foreknowledge of financial statement information. It answers the question: Are investments based on financial statement information able to capture progressively less information in security returns over time......? The sample is based on non-financial companies listed on the Copenhagen Stock Exchange in the period 1984-2002. Our analyses show that all the applied accounting measures are value-relevant as investment strategies based on the information earn positive market-adjusted returns in our sample period...

  10. Estrone-1-sulphate (E1S) has impact on the kinetics parameters of transporter mediated taurine and glutamate influx in Caco-2 cells

    DEFF Research Database (Denmark)

    Steffansen, Bente; El-Sayed, F

    Previously, we have suggested estrone-1-sulfate (E1S) to be intercalated into the phospholipid membrane 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC). The overall hypothesis of the present study was that E1S intercalation in the cell membrane of Caco-2 cells may changes the functionality...... of membrane transporters. The aim was therefore to investigate if addition of E1S to the growth medium of Caco-2 cells before but not during the influx study, change the kinetic parameters of transporter-mediated influx of taurine and glutamate by respective TAUT and EAAT transporters. The results show that 4...

  11. Disabled People as Culturally Relevant Teachers

    Directory of Open Access Journals (Sweden)

    Gail Pritchard

    2010-04-01

    Full Text Available This paper contends that disabled teachers are in such short supply as to be invisible even amongst minority teachers from already vastly marginalised populations. This is not simply because discriminatory practices are embedded within employment policies of educational systems, but deeply held socio-cultural attitudes also prevent disabled people accessing and attaining basic and later, higher levels of academic achievement. The central argument here is a simple one; disabled people as teachers offer a unique knowledge standpoint, challenge the animosity of dominant cultural beliefs around disability as analogous with passivity or non-achieving, and provide a source of resistance, solace and resolution for students they teach. Disabled people as educators enact exemplary pedagogic justice and socially inclusive practice. The aim of this paper is to explore the benefits to students and places of higher education alike of embracing both the person and the role of the teacher with disability as culturally relevant educators. Keywords: minority teachers, marginality, disability, cultural relevance, higher education

  12. Relevancy Ranking of Satellite Dataset Search Results

    Science.gov (United States)

    Lynnes, Christopher; Quinn, Patrick; Norton, James

    2017-01-01

    As the Variety of Earth science datasets increases, science researchers find it more challenging to discover and select the datasets that best fit their needs. The most common way of search providers to address this problem is to rank the datasets returned for a query by their likely relevance to the user. Large web page search engines typically use text matching supplemented with reverse link counts, semantic annotations and user intent modeling. However, this produces uneven results when applied to dataset metadata records simply externalized as a web page. Fortunately, data and search provides have decades of experience in serving data user communities, allowing them to form heuristics that leverage the structure in the metadata together with knowledge about the user community. Some of these heuristics include specific ways of matching the user input to the essential measurements in the dataset and determining overlaps of time range and spatial areas. Heuristics based on the novelty of the datasets can prioritize later, better versions of data over similar predecessors. And knowledge of how different user types and communities use data can be brought to bear in cases where characteristics of the user (discipline, expertise) or their intent (applications, research) can be divined. The Earth Observing System Data and Information System has begun implementing some of these heuristics in the relevancy algorithm of its Common Metadata Repository search engine.

  13. Equilibration Time Scales of Physically Relevant Observables

    Directory of Open Access Journals (Sweden)

    Luis Pedro García-Pintos

    2017-08-01

    Full Text Available We address the problem of understanding, from first principles, the conditions under which a quantum system equilibrates rapidly with respect to a concrete observable. On the one hand, previously known general upper bounds on the time scales of equilibration were unrealistically long, with times scaling linearly with the dimension of the Hilbert space. These bounds proved to be tight since particular constructions of observables scaling in this way were found. On the other hand, the computed equilibration time scales for certain classes of typical measurements, or under the evolution of typical Hamiltonians, are unrealistically short. However, most physically relevant situations fall outside these two classes. In this paper, we provide a new upper bound on the equilibration time scales which, under some physically reasonable conditions, give much more realistic results than previously known. In particular, we apply this result to the paradigmatic case of a system interacting with a thermal bath, where we obtain an upper bound for the equilibration time scale independent of the size of the bath. In this way, we find general conditions that single out observables with realistic equilibration times within a physically relevant setup.

  14. Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions

    Science.gov (United States)

    Pavalko, F. M.; Chen, N. X.; Turner, C. H.; Burr, D. B.; Atkinson, S.; Hsieh, Y. F.; Qiu, J.; Duncan, R. L.

    1998-01-01

    Mechanical stimulation of bone induces new bone formation in vivo and increases the metabolic activity and gene expression of osteoblasts in culture. We investigated the role of the actin cytoskeleton and actin-membrane interactions in the transmission of mechanical signals leading to altered gene expression in cultured MC3T3-E1 osteoblasts. Application of fluid shear to osteoblasts caused reorganization of actin filaments into contractile stress fibers and involved recruitment of beta1-integrins and alpha-actinin to focal adhesions. Fluid shear also increased expression of two proteins linked to mechanotransduction in vivo, cyclooxygenase-2 (COX-2) and the early response gene product c-fos. Inhibition of actin stress fiber development by treatment of cells with cytochalasin D, by expression of a dominant negative form of the small GTPase Rho, or by microinjection into cells of a proteolytic fragment of alpha-actinin that inhibits alpha-actinin-mediated anchoring of actin filaments to integrins at the plasma membrane each blocked fluid-shear-induced gene expression in osteoblasts. We conclude that fluid shear-induced mechanical signaling in osteoblasts leads to increased expression of COX-2 and c-Fos through a mechanism that involves reorganization of the actin cytoskeleton. Thus Rho-mediated stress fiber formation and the alpha-actinin-dependent anchorage of stress fibers to integrins in focal adhesions may promote fluid shear-induced metabolic changes in bone cells.

  15. Regulation of the L-arabinose operon in strains of Escherichia coli containing ColE1-ara hybrid plasmids.

    Science.gov (United States)

    Wallace, L J; Wilcox, G

    1979-06-20

    Hybrid plasmids were constructed from fragments of F'ara episomes formed by the restriction endonuclease EcoRI and a linear form of the plasmid ColE1 created by cleavage with EcoRI. Hybrid plasmids were constructed containing the entire ara region or the ara region with various parts deleted. E. coli K12 host strains were constructed which contained different deletions of the ara region. The hybrid plasmids were transferred to those strains whose ara deletion complemented that of the plasmid. The initial differential rates of synthesis of L-arabinose isomerase, the product of the araA gene, were determined for the Ara+, plasmid containing strains. These studies demonstrated that strains containing delta(araOIBA)718 produce elevated levels of araC protein, suggesting the araC promoter has been altered by this deletion. Evidence is also presented which suggests that araC protein activates the ara-BAD operon to higher levels when it is present in cis rather than trans. Amplification of the products of the cloned genes is observed when compared to haploid levels in some cases.

  16. Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Koichi, E-mail: shimada-ki@dent.nihon-u.ac.jp [Department of Periodontology, Nihon University School of Dentistry, Tokyo (Japan); Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo (Japan); Ikeda, Kyoko [Department of Periodontology, Nihon University School of Dentistry, Tokyo (Japan); Ito, Koichi [Department of Periodontology, Nihon University School of Dentistry, Tokyo (Japan); Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo (Japan)

    2009-12-18

    Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and maturation. In mammals, the BMP-induced receptor-regulated Smads form complexes with Smad4. These complexes translocate and accumulate in the nucleus, where they regulate the transcription of various target genes. However, the function of Smad4 remains unclear. We performed a yeast two-hybrid screen using Smad4 as bait and a cDNA library derived from bone marrow, to indentify the proteins interacting with Smad4. cDNA clones for Tumor necrosis factor (TNF) receptor-associated factor 2 (Traf2) were identified, and the interaction between the endogenous proteins was confirmed in the mouse osteoblast cell line MC3T3-E1. To investigate the function of Traf2, we silenced it with siRNA. The level of BMP-2 protein in the medium, the expression levels of the Bmp2 gene and BMP-induced transcription factor genes, including Runx2, Dlx5, Msx2, and Sp7, and the phosphorylated-Smad1 protein level were increased in cells transfected with Traf2 siRNA. The nuclear accumulation of Smad1 increased with TNF-{alpha} stimulation for 30 min at Traf2 silencing. These results suggest that the TNF-{alpha}-stimulated nuclear accumulation of Smad1 may be dependent on Traf2. Thus, the interaction between Traf2 and Smad4 may play a role in the cross-talk between TNF-{alpha} and BMP signaling pathways.

  17. Genes Responsive to Low-Intensity Pulsed Ultrasound in MC3T3-E1 Preosteoblast Cells

    Directory of Open Access Journals (Sweden)

    Yoshiaki Tabuchi

    2013-11-01

    Full Text Available Although low-intensity pulsed ultrasound (LIPUS has been shown to enhance bone fracture healing, the underlying mechanism of LIPUS remains to be fully elucidated. Here, to better understand the molecular mechanism underlying cellular responses to LIPUS, we investigated gene expression profiles in mouse MC3T3-E1 preosteoblast cells exposed to LIPUS using high-density oligonucleotide microarrays and computational gene expression analysis tools. Although treatment of the cells with a single 20-min LIPUS (1.5 MHz, 30 mW/cm2 did not affect the cell growth or alkaline phosphatase activity, the treatment significantly increased the mRNA level of Bglap. Microarray analysis demonstrated that 38 genes were upregulated and 37 genes were downregulated by 1.5-fold or more in the cells at 24-h post-treatment. Ingenuity pathway analysis demonstrated that the gene network U (up contained many upregulated genes that were mainly associated with bone morphology in the category of biological functions of skeletal and muscular system development and function. Moreover, the biological function of the gene network D (down, which contained downregulated genes, was associated with gene expression, the cell cycle and connective tissue development and function. These results should help to further clarify the molecular basis of the mechanisms of the LIPUS response in osteoblast cells.

  18. High-yield production of a chimeric glycoprotein based on permuted E1 and E2 HCV envelope ectodomains.

    Science.gov (United States)

    Tello, Daniel; Rodríguez-Rodríguez, Mar; Yélamos, Belén; Gómez-Gutiérrez, Julián; Peterson, Darrell L; Gavilanes, Francisco

    2015-03-01

    In this report it is described for the first time the expression and purification of large quantities of a soluble and correctly folded chimeric recombinant protein, E2661E1340, containing the permuted Hepatitis C virus (HCV) glycoprotein ectodomains E1 (amino acids 192-340) and E2 (amino acids 384-661). Using the baculovirus/insect cell expression system, 8mg of secreted protein were purified from 1L of culture media, a yield 4 times higher than the described for its counterpart E1341E2661. This permuted chimeric protein is glycosylated and possesses a high tendency to self-associate. The fluorescence emission spectrum indicates that Trp residues occupy a relatively low hydrophobic environment. The secondary structure was determined by deconvolution of the far-UV circular dichroism spectrum yielding 13% α-helix structure, 49% extended structure and 38% non-ordered structure. E2661E1340 binds to antibodies present in human sera from HCV-positive patients, a binding that is blocked at different levels by a rabbit anti-E2661 antibody. All these structural and antigenic features of E2661E1340 are very similar to those described for E1340E2661, Thus, this high-yield isolated chimeric protein may be a valuable tool to study the first steps of the HCV infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. MC3T3-E1 cell response to stainless steel 316L with different surface treatments.

    Science.gov (United States)

    Zhang, Hongyu; Han, Jianmin; Sun, Yulong; Huang, Yongling; Zhou, Ming

    2015-11-01

    In the present study, stainless steel 316L samples with polishing, aluminum oxide blasting, and hydroxyapatite (HA) coating were prepared and characterized through a scanning electron microscope (SEM), optical interferometer (surface roughness, Sq), contact angle, surface composition and phase composition analyses. Osteoblast-like MC3T3-E1 cell adhesion on the samples was investigated by cell morphology using a SEM (4h, 1d, 3d, 7d), and cell proliferation was assessed by MTT method at 1d, 3d, and 7d. In addition, adsorption of bovine serum albumin on the samples was evaluated at 1h. The polished sample was smooth (Sq: 1.8nm), and the blasted and HA coated samples were much rougher (Sq: 3.2μm and 7.8μm). Within 1d of incubation, the HA coated samples showed the best cell morphology (e.g., flattened shape and complete spread), but there was no significant difference after 3d and 7d of incubation for all the samples. The absorbance value for the HA coated samples was the highest after 1d and 3d of incubation, indicating better cell viability. However, it reduced to the lowest value at 7d. Protein adsorption on the HA coated samples was the highest at 1h. The results indicate that rough stainless steel surface improves cell adhesion and morphology, and HA coating contributes to superior cell adhesion, but inhibits cell proliferation. Copyright © 2015. Published by Elsevier B.V.

  20. Effect of hierarchical pore structure on ALP expression of MC3T3-E1 cells on bioglass films.

    Science.gov (United States)

    Yu, Cuixia; Zhuang, Junjun; Dong, Lingqing; Cheng, Kui; Weng, Wenjian

    2017-08-01

    Hierarchical porous bioglass films on the tantalum were designed to enhance osteointegration of metallic implants. The films were prepared by a sol-gel method using P123 as the mesopore template and polystyrene microsphere as the nanopore template. The films with 5.4nm mesopores and 100nm nanopores (MBG-100) elicited an obviously elongated morphology of the cultured MC3T3-E1 cells, as a result, a higher alkaline phosphatase level was expressed. It is suggested that the nanopores play an important role in regulating cellular behavior by initial protein adsorption through nanopore curvatures. The mesopores were proven very effective for loading rhBMP-2, and the rhBMP-2 loaded on MBG-100 films showed a better function of enhancing osteogenic differentiation, which is attributed to that the nanopore structure could expedite rhBMP-2 release and provide a microenvironment for intensifying the interaction of rhBMP-2 with the cells. Hence, the cell osteogenic differentiation can be enhanced by hierarchical porous bioglass films through both the porous structure and rhBMP-2 induction. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Triaxiality and isospin-forbidden E1 decays in the N=Z nucleus sup 64 Ge

    Energy Technology Data Exchange (ETDEWEB)

    Ennis, P.J.; Lister, C.J. (A.W. Wright Nuclear Structure Lab., Yale Univ., New Haven, CT (United States)); Gelletly, W.; Price, H.G. (SERC Daresbury Lab., Warrington (United Kingdom)); Varly, B.J. (Schuster Lab., Univ. Manchester (United Kingdom)); Butler, P.A.; Hoare, T. (Oliver Lodge Lab., Univ. Liverpool (United Kingdom)); Cwiok, S. (Inst. of Physics, Warsaw Inst. of Tech. (Poland)); Nazarewicz, W. (Joint Inst. of Heavy-Ion Research, Holifield Heavy-Ion Research Facility, Oak Ridge, TN (United States))

    1991-12-16

    The neutron-deficient isotope {sup 64}{sub 32}Ge{sub 32} was produced in the reaction {sup 12}C({sup 54}Fe, 2n{gamma}){sup 64}Ge at a beam energy of 165 MeV. The production cross section for {sup 64}Ge was measured to be 640{+-}70 {mu}b, which represents only {proportional to}0.1% of the total fusion cross section. The Daresbury recoil separator was operated in conjunction with a large {gamma}-array to study recoil-{gamma}{gamma} correlations and measure recoil-{gamma} angular distributions. A level scheme for {sup 64}Ge was constructed containing 19 levels. The nucleus appears to have a structure consistent with a {gamma}-soft shape. Shape changes induced by aligned g{sub 9/2} nucleons are discussed. An overview of octupole correlations in the A{approx equal}60-80 mass region is given. Evidence for forbidden E1 transitions was found which is indicative of considerable isospin mixing. (orig.).

  2. Refinement of lunar TiO2 analysis with multispectral features of Chang'E-1 IIM data

    Science.gov (United States)

    Wang, Xianmin; Zhu, Peimin

    2013-01-01

    We develop a method based on the samples from Apollo and Luna landing sites to determine lunar TiO2 content with Chang'E-1 interference imaging spectrometer (IIM) imagery. By analyzing the nonlinear relationship between the optical and compositional parameters of lunar soil samples, the method employs two Support Vector Machines (SVMs) to estimate the titanium abundance of the lunar surface. Developed with the soil compositions of the Apollo and Luna sample-return stations, the RMS (root mean square) error of our method is 0.24 wt% TiO2, and the correlation coefficient of the TiO2 values and our predicted ones is 99.72 %. Compared with the other 3 models, the method proposed in this paper exhibits a good performance for determining the chemical composition of the lunar surface. TiO2 maps of Sinus Iridum, part of the Marius Hills plateau, and part of Mare Smythii are produced using our method, which could be useful for future lunar missions.

  3. (E-1-(2-Aminophenyl-3-(benzo[d][1,3]dioxol-5-ylprop-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Rodrigo Abonia

    2016-12-01

    Full Text Available The title chalcone (E-1-(2-aminophenyl-3-(benzo[d][1,3]dioxol-5-ylprop-2-en-1-one was obtained in 76% yield from a NaOH catalyzed Claisen–Schmidt condensation reaction between o-aminoacetophenone and piperonal. This product will be used as a key precursor for the development of an alternative route for the total synthesis of the alkaloid Graveoline. Single crystals of the title compound suitable for X-ray diffraction were grown via slow evaporation in ethanol at room temperature. A complete crystallographic study was performed in depth to unequivocally confirm its structure. The crystal structure of the title o-aminochalcone, C16H13NO3, shows two molecules per asymmetric unit (Z = 4 and adopts an E configuration about the C=C double bond. In the title compound, the mean plane of the non-H atoms of the central chalcone fragment C—C(O—C—C—C is as follow: [root-mean-square (r.m.s. deviation = 0.0210 Å for A–B and 0.0493 for C–D molecules]. In the crystal, molecules are linked by N–H...O and C–H...O, hydrogen bonds forming S(6, R22(6 and edge-fused R44(24rings along with C(18 chains running parallel to (110.

  4. Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow.

    Science.gov (United States)

    Li, Jia-Hui; Yang, Peng; Li, Ai-Li; Wang, Yong; Ke, Yuan-Nan; Li, Xian-Lun

    2011-08-01

    To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). Twenty-two male Chinese mini-swines were randomized into three groups: six in a sham-operation group, and eight each in the control and lipo-PGE1 groups. The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was completely occluded for 2 h, and then reperfused for 3 h. Lipo-PGE1 (1 μg/kg) was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group. Hemodynamic data and proinflammatory cytokines were examined before AMI, 2 h after occlusion, and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining were performed to evaluate the myocardial no-reflow area (NRA). Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI (Pinfarction reperfusion (Pporcine model of myocardial infarction reperfusion no-reflow, decreasing NRA and attenuating the inflammatory response.

  5. Susceptibility of Aedes albopictus and Aedes aegypti to three imported Chikungunya virus strains, including the E1/226V variant in Taiwan

    National Research Council Canada - National Science Library

    Chen, Tien-Huang; Jian, Shu-Wan; Wang, Chih-Yuan; Lin, Cheo; Wang, Pei-Feng; Su, Chien-Ling; Teng, Hwa-Jen; Shu, Pei-Yun; Wu, Ho-Sheng

    2015-01-01

    An E1/226V variant Chikungunya virus (CHIKV) efficiently transmitted by Aedes albopictus to humans poses a significant threat to public health for those areas with the presence of Aedes albopictus, including Taiwan...

  6. Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Yanxin [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); Guo, Huanhuan [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); Changchun Brother Biotech Co., Ltd., Changchun, 130000 (China); Hu, Ningning; He, Dongyun [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China); Zhang, Shi [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); School of Clinical Medicine, Jilin University, Changchun 130001 (China); Chu, Yunjie [Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021 (China); Huang, Yubin [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Li, Xiao, E-mail: lixiao06@mails.jlu.edu.cn [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China); Sun, LiLi, E-mail: linjiaxiaoya@163.com [Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun 130012 (China); Jin, Ningyi, E-mail: ningyij@126.com [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China)

    2014-10-15

    Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose > 5 × 10{sup 10} VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25 × 10{sup 10} VP/kg) and beagles (2.5 × 10{sup 9} VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35 × 10{sup 10} VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67 × 10{sup 8} VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. - Highlights: • We use the rodents and non-rodents animal models to evaluation Ad-hTERT-E1a-Apoptin. • Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. • Demonstrate the safety and feasibility dose of injected Ad-hTERT-E

  7. Initial association of NR2E1 with bipolar disorder and identification of candidate mutations in bipolar disorder, schizophrenia, and aggression through resequencing.

    Science.gov (United States)

    Kumar, Ravinesh A; McGhee, Kevin A; Leach, Stephen; Bonaguro, Russell; Maclean, Alan; Aguirre-Hernandez, Rosalia; Abrahams, Brett S; Coccaro, Emil F; Hodgins, Sheilagh; Turecki, Gustavo; Condon, Anne; Muir, Walter J; Brooks-Wilson, Angela R; Blackwood, Douglas H; Simpson, Elizabeth M

    2008-09-05

    Nuclear receptor 2E1 gene (NR2E1) resides within a 6q21-22 locus for bipolar disorder and schizophrenia. Mice deleted for Nr2e1 show altered neurogenesis, cortical and limbic abnormalities, aggression, hyperexcitability, and cognitive impairment. NR2E1 is therefore a positional and functional candidate for involvement in mental illness. We performed association analyses in 394 patients with bipolar disorder, 396 with schizophrenia, and 479 controls using six common markers and haplotypes. We also performed a comprehensive mutation screen of NR2E1, resequencing its entire coding region, complete 5' and 3' untranslated regions, consensus splice-sites, and evolutionarily conserved regions in 126 humans with bipolar disorder, schizophrenia, or aggressive disorders. NR2E1 was associated with bipolar disorder I and II [odds ratio (OR = 0.77, P = 0.013), bipolar disorder I (OR = 0.77, P = 0.015), bipolar disorder in females (OR = 0.72, P = 0.009), and with age at onset < or = 25 years (OR = 0.67, P = 0.006)], all of which remained significant after correcting for multiple comparisons. We identified eight novel candidate mutations that were absent in 325 controls; four of these were predicted to alter known neural transcription factor binding sites. Analyses of NR2E1 mRNA in human brain revealed forebrain-specific transcription. The data presented support the hypothesis that genetic variation at NR2E1 may be associated with susceptibility to brain-behavior disorders. 2008 Wiley-Liss, Inc.

  8. Susceptibility of Aedes albopictus and Aedes aegypti to three imported Chikungunya virus strains, including the E1/226V variant in Taiwan

    OpenAIRE

    Chen, Tien-Huang; Jian, Shu-Wan; Wang, Chih-Yuan; Lin, Cheo; Wang, Pei-Feng; Su, Chien-Ling; Teng, Hwa-Jen; Shu, Pei-Yun; Wu, Ho-Sheng

    2015-01-01

    An E1/226V variant Chikungunya virus (CHIKV) efficiently transmitted by Aedes albopictus to humans poses a significant threat to public health for those areas with the presence of Aedes albopictus, including Taiwan. Methods: We infected three imported CHIKV isolates including the E1/226V variant with Ae. albopictus and Aedes aegypti in the laboratory to understand the disease risk. Viral RNA was measured by real time reverse transcription polymerase chain reaction. Results: The viral su...

  9. Human liver estrone (E1), Estradiol (E2) and dehydroepiandrosterone (DHEA) sulfotransferases (STs): Comparison with thermostable (TS) and thermolabile (TL) phenol sulfotransferase (PST) activities

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, J.S.; Watson, R.W.G.; Weinshilboum, R.M. (Mayo Clinic/Mayo Foundation, Rochester, MN (United States))

    1991-03-11

    Sulfation plays an important role in the metabolism of E1, E2 and DHEA in humans. The relationship between the enzymes that catalyze the sulfation of E1, E2 and DHEA and TS and TL PST is unclear. The authors compared thermal stability, sensitivity to inhibition by 2,6-dichloro-4-nitrophenol (DCNP) and individual variation in the regulation of these steroid ST activities with those of TS PST and TL PST in the human liver. E2 ST and TS PST had very similar thermal stabilities. The thermal inactivation profile of E1 ST suggested that this activity might be related to both DHEA ST and TS PST. DCNP inhibition studies also showed similar profiles for E2 ST and TS PST, with a small resistant component for E2 ST. A multiphasic profile for DCNP inhibition of E1 ST activity was found. Finally, studies performed with human liver sample showed significant correlations between E2 ST and TS PST, E1 ST and DHEA ST, E2 St and E1 ST, and, to a lesser degree, between E1 ST and TS PST and E2 ST and DHEA ST. TL PST was not correlated significantly with any of the other activities. These results suggest that the sulfation of E2 in human liver is catalyzed predominantly by TS PST, although DHEA ST may also play a role. Their results also suggest that the sulfation of E1 is catalyzed by DHEA ST and by TS PST, although other ST(s) could also be involved.

  10. Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study.

    Science.gov (United States)

    He, Haifeng; Xia, Hongying; Xia, Qin; Ren, Yanliang; He, Hongwu

    2017-10-15

    By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel 'open-chain' classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1-23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC 50 =0.15-23.55μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC 50 values of 0.60, 0.15, 0.39 and 0.34μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Structures of Human Cyctochrome P450 2E1: Insights Into the Binding of Inhibitors And Both Small Molecular Weight And Fatty Acid Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Porubsky, P.R.; Meneely, K.M.; Scott, E.E.

    2009-05-21

    Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates >70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 {angstrom} for an indazole complex and 2.6 {angstrom} for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr{sup 303} within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe{sup 478} aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved {sup 216}QXXNN{sup 220} residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed {omega}-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids.

  12. ISG15 Arg151 and the ISG15-Conjugating Enzyme UbE1L Are Important for Innate Immune Control of Sindbis Virus▿

    Science.gov (United States)

    Giannakopoulos, Nadia V.; Arutyunova, Elena; Lai, Caroline; Lenschow, Deborah J.; Haas, Arthur L.; Virgin, Herbert Whiting

    2009-01-01

    Interferon (IFN)-stimulated gene 15 (ISG15) is a ubiquitin-like molecule that conjugates to target proteins via a C-terminal LRLRGG motif and has antiviral function in vivo. We used structural modeling to predict human ISG15 (hISG15) residues important for interacting with its E1 enzyme, UbE1L. Kinetic analysis revealed that mutation of arginine 153 to alanine (R153A) ablated hISG15-hUbE1L binding and transthiolation of UbcH8. Mutation of other predicted UbE1L-interacting residues had minimal effects on the transfer of ISG15 from UbE1L to UbcH8. The capacity of hISG15 R153A to form protein conjugates in 293T cells was markedly diminished. Mutation of the homologous residue in mouse ISG15 (mISG15), arginine 151, to alanine (R151A) also attenuated protein ISGylation following transfection into 293T cells. We assessed the role of ISG15-UbE1L interactions in control of virus infection by constructing double subgenomic Sindbis viruses that expressed the mISG15 R151A mutant. While expression of mISG15 protected alpha/beta-IFN-receptor-deficient (IFN-αβR−/−) mice from lethality following Sindbis virus infection, expression of mISG15 R151A conferred no survival benefit. The R151A mutation also attenuated ISG15's ability to decrease Sindbis virus replication in IFN-αβR−/− mice or prolong survival of ISG15−/− mice. The importance of UbE1L was confirmed by demonstrating that mice lacking this ISG15 E1 enzyme were highly susceptible to Sindbis virus infection. Together, these data support a role for protein conjugation in the antiviral effects of ISG15. PMID:19073728

  13. Alcohol dehydrogenase and cytochrome P450 2E1 can be induced by long-term exposure to ethanol in cultured liver HEP-G2 cells.

    Science.gov (United States)

    Balusikova, Kamila; Kovar, Jan

    2013-09-01

    It has been shown in previous studies that liver HEP-G2 cells (human hepatocellular carcinoma) lose their ability to express active alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1). Although both are ethanol-inducible enzymes, short-term exposure to ethanol does not cause any changes in expression or activity in cultured HEP-G2 cells. Therefore, we tested the effect of long-term exposure to ethanol on the expression and activity of both ADH and CYP2E1 in these cells. The expression of ADH and CYP2E1 was assessed at the mRNA and/or protein level using real-time PCR and Western blot analysis. Specific colorimetric assays were used for the measurement of ADH and CYP2E1 enzymatic activities. Caco-2 cells (active CYP2E1 and inactive ADH) were used as control cells. Significantly increased protein expression of ADH (about 2.5-fold) as well as CYP2E1 (about 1.6-fold) was found in HEP-G2 cells after long-term (12 mo) exposure to ethanol. The activity of ADH and CYP2E1 was also significantly increased from 12 ± 3 and 6 ± 1 nmol/h/mg of total protein to 191 ± 9 and 57 ± 9 nmol/h/mg of total protein, respectively. We suggest that the loss of activity of ethanol-metabolizing enzymes in cultured HEP-G2 cells is reversible and can be induced by prolonged exposure to ethanol. We are therefore able to reactivate HEP-G2 cells metabolic functions concerning ethanol oxidation just by modification of in vitro culture conditions without necessity of transfection with its side effect - enzyme overexpression.

  14. A systems biology analysis of the changes in gene expression via silencing of HPV-18 E1 expression in HeLa cells.

    Science.gov (United States)

    Castillo, Andres; Wang, Lu; Koriyama, Chihaya; Eizuru, Yoshito; Jordan, King; Akiba, Suminori

    2014-10-01

    Previous studies have reported the detection of a truncated E1 mRNA generated from HPV-18 in HeLa cells. Although it is unclear whether a truncated E1 protein could function as a replicative helicase for viral replication, it would still retain binding sites for potential interactions with different host cell proteins. Furthermore, in this study, we found evidence in support of expression of full-length HPV-18 E1 mRNA in HeLa cells. To determine whether interactions between E1 and cellular proteins play an important role in cellular processes other than viral replication, genome-wide expression profiles of HPV-18 positive HeLa cells were compared before and after the siRNA knockdown of E1 expression. Differential expression and gene set enrichment analysis uncovered four functionally related sets of genes implicated in host defence mechanisms against viral infection. These included the toll-like receptor, interferon and apoptosis pathways, along with the antiviral interferon-stimulated gene set. In addition, we found that the transcriptional coactivator E1A-binding protein p300 (EP300) was downregulated, which is interesting given that EP300 is thought to be required for the transcription of HPV-18 genes in HeLa cells. The observed changes in gene expression produced via the silencing of HPV-18 E1 expression in HeLa cells indicate that in addition to its well-known role in viral replication, the E1 protein may also play an important role in mitigating the host's ability to defend against viral infection.

  15. Journals publishing research relevant to stroke rehabilitation.

    Science.gov (United States)

    Bohannon, R W; Puharic, T; Roberts, D

    1992-01-01

    The purpose of this brief article is to provide a list of core journals relevant to stroke rehabilitation and to indicate the adequacy of five bibliographic indexing services in covering them. Citation analysis yielded a list of 30 core journals. No indexing service's data base included all of the 28 journals used in evaluating comprehensiveness. All services except the Cumulative Index of Nursing and Allied Health, however, included over 71% of the journals. To be completely comprehensive in journal coverage, any pair of indexes had to include AMED/ CATS. The all too common reliance on Index Medicus/Medline will result in a relatively thorough but clearly incomplete search. Copyright © 1992 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Review of relevant studies of isolated systems

    DEFF Research Database (Denmark)

    Hansen, L.H.; Lundsager, P.

    2001-01-01

    The report presents the results of a review of studies relating to integration of wind energy in isolated power supply systems, based on a systematic literature survey. The purpose of the study is to develop a methodology consisting of a set of guidelinesfor wind energy projects in isolated energy......, most notably the IEC/PAS 62111 specification. The amount of wind energy literature related to the subject is excessively large, and a complete review inwhich every relevant abstract is identified and examined is not feasible within the framework of this (or probably any other) study. The review results...... have been organised according to the following keywords: methods & guides, economics, concept ofapplication, system solutions, case studies, financial programmes, dedicated software tools. None of the found references presents methods or tools that contradict the philosophy of Risø's methodology...

  17. Carryover negligibility and relevance in bioequivalence studies.

    Science.gov (United States)

    Ocaña, Jordi; Sanchez O, Maria P; Carrasco, Josep L

    2015-01-01

    The carryover effect is a recurring issue in the pharmaceutical field. It may strongly influence the final outcome of an average bioequivalence study. Testing a null hypothesis of zero carryover is useless: not rejecting it does not guarantee the non-existence of carryover, and rejecting it is not informative of the true degree of carryover and its influence on the validity of the final outcome of the bioequivalence study. We propose a more consistent approach: even if some carryover is present, is it enough to seriously distort the study conclusions or is it negligible? This is the central aim of this paper, which focuses on average bioequivalence studies based on 2 × 2 crossover designs and on the main problem associated with carryover: type I error inflation. We propose an equivalence testing approach to these questions and suggest reasonable negligibility or relevance limits for carryover. Finally, we illustrate this approach on some real datasets. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Is Witsenhausen's counterexample a relevant toy?

    CERN Document Server

    Grover, Pulkit

    2010-01-01

    This paper answers a question raised by Doyle on the relevance of the Witsenhausen counterexample as a toy decentralized control problem. The question has two sides, the first of which focuses on the lack of an external channel in the counterexample. Using existing results, we argue that the core difficulty in the counterexample is retained even in the presence of such a channel. The second side questions the LQG formulation of the counterexample. We consider alternative formulations and show that the understanding developed for the LQG case guides the investigation for these other cases as well. Specifically, we consider 1) a variation on the original counterexample with general, but bounded, noise distributions, and 2) an adversarial extension with bounded disturbance and quadratic costs. For each of these formulations, we show that quantization-based nonlinear strategies outperform linear strategies by an arbitrarily large factor. Further, these nonlinear strategies also perform within a constant factor of...

  19. Relevance of instantons in Burgers turbulence

    Science.gov (United States)

    Grafke, T.; Grauer, R.; Schäfer, T.; Vanden-Eijnden, E.

    2015-02-01

    Instanton calculations are performed in the context of stationary Burgers turbulence to estimate the tails of the probability density function (PDF) of velocity gradients. These results are then compared to those obtained from massive direct numerical simulations (DNS) of the randomly forced Burgers equation. The instanton predictions are shown to agree with the DNS in a wide range of regimes, including those that are far from the limiting cases previously considered in the literature. These results settle the controversy of the relevance of the instanton approach for the prediction of the velocity gradient PDF tail exponents. They also demonstrate the usefulness of the instanton formalism in Burgers turbulence, and suggest that this approach may be applicable in other contexts, such as 2D and 3D turbulence in compressible and incompressible flows.

  20. Catalyst Deactivation: Control Relevance of Model Assumptions

    Directory of Open Access Journals (Sweden)

    Bernt Lie

    2000-10-01

    Full Text Available Two principles for describing catalyst deactivation are discussed, one based on the deactivation mechanism, the other based on the activity and catalyst age distribution. When the model is based upon activity decay, it is common to use a mean activity developed from the steady-state residence time distribution. We compare control-relevant properties of such an approach with those of a model based upon the deactivation mechanism. Using a continuous stirred tank reactor as an example, we show that the mechanistic approach and the population balance approach lead to identical models. However, common additional assumptions used for activity-based models lead to model properties that may deviate considerably from the correct one.

  1. To be or not to be relevant

    DEFF Research Database (Denmark)

    Kann-Rasmussen, Nanna

    What is the purpose and legitimacy of arts and culture in society today? Do arts and culture have a role to play relation to social and political purposes? Alternatively, do the arts represent an absolute otherness in relation to the rest of society? Artists and scholars have discussed...... the assumption that the encounter between citizens and culture or the arts would ‘build’ and empower the individual, and thus contribute to the strengthening of democratic society. Cultural policy thus largely followed this line through arms-length support for arts and artists (the producers) as well...... for a cultural institution to be societally relevant. According to Kann-Rasmussen (2016), the term ‘societal relevance’ signifies two meanings. The term covers cultural institutions’ contribution to cultural policy’s original purpose of ensuring public enlightenment and education, and it relates to cultural...

  2. Tetracycline actions relevant to rosacea treatment.

    Science.gov (United States)

    Korting, H C; Schöllmann, C

    2009-01-01

    Until today, the pathogenesis of rosacea is not known in detail. Yet in recent years evidence has been accumulating that rosacea with its common symptoms such as inflammatory lesions, erythema, telangiectasia, phymatous changes, and ocular symptoms is of inflammatory nature. Tetracycline derivatives like doxycycline successfully used in the treatment of skin diseases like acne and rosacea seem to inhibit different inflammatory pathways involved in the pathogenesis by various modes of action. Although data for skin diseases are relatively scanty, the following modes of action of tetracyclines seem to be most relevant for an effective treatment of acne and rosacea: inhibition of matrix metalloproteinases, downmodulation of cytokines, inhibition of cell movement and proliferation, inhibition of granuloma formation, inhibition of reactive oxygen species, nitric oxide, and angiogenesis, whereas inhibition of phospholipase A2 seems to be of lower importance. The role of the saprophytic mite Demodex folliculorum remains to be clarified. Additional studies are necessary to further elucidate how tetracyclines work in rosacea treatment.

  3. Relevant Animal Models in Dermatophyte Research.

    Science.gov (United States)

    Cambier, Ludivine; Heinen, Marie-Pierre; Mignon, Bernard

    2017-02-01

    Dermatophytoses are common superficial fungal infections affecting both humans and animals. They are provoked by filamentous fungi called dermatophytes specialized in the degradation of keratinized structures, which allows them to induce skin, hair and nail infections. Despite their high incidence, little investigation has been performed for the understanding of these infections compared to fungal opportunistic infections and most of the studies were based on in vitro experiments. The development of animal models for dermatophyte research is required to evaluate new treatments against dermatophytoses or to increase knowledge about fungal pathogenicity factors or host immune response mechanisms. The guinea pig has been the most often used animal model to evaluate efficacy of antifungal compounds against dermatophytes, while mouse models were preferred to study the immune response generated during the disease. Here, we review the relevant animal models that were developed for dermatophyte research and we discuss the advantages and disadvantages of the selected species, especially guinea pig and mouse.

  4. Towards increased policy relevance in energy modeling

    Energy Technology Data Exchange (ETDEWEB)

    Worrell, Ernst; Ramesohl, Stephan; Boyd, Gale

    2003-07-29

    Historically, most energy models were reasonably equipped to assess the impact of a subsidy or change in taxation, but are often insufficient to assess the impact of more innovative policy instruments. We evaluate the models used to assess future energy use, focusing on industrial energy use. We explore approaches to engineering-economic analysis that could help improve the realism and policy relevance of engineering-economic modeling frameworks. We also explore solutions to strengthen the policy usefulness of engineering-economic analysis that can be built from a framework of multi-disciplinary cooperation. We focus on the so-called ''engineering-economic'' (or ''bottom-up'') models, as they include the amount of detail that is commonly needed to model policy scenarios. We identify research priorities for the modeling framework, technology representation in models, policy evaluation and modeling of decision-making behavior.

  5. Placebo response: relevance to the rheumatic diseases.

    Science.gov (United States)

    Pollo, Antonella; Benedetti, Fabrizio

    2008-05-01

    Recent interest in the neurobiology of the placebo effect has brought about a new awareness of its potential exploitation for patient benefit, framing it as a positive context effect with the power to influence therapy outcome. Among the different placebo effects described in clinical conditions and experimental settings, placebo analgesia is of particular relevance to the rheumatologist. Placebo analgesia is the field that has most contributed to our understanding of the multiple mechanisms underlying this phenomenon. The possible clinical applications of placebo studies range from the design of clinical trials incorporating specific recommendations and minimizing the use of placebo arms to the optimization of the context surrounding the patient so that the placebo component in any treatment is maximized.

  6. Immunization of rabbits with cottontail rabbit papillomavirus E1 and E2 genes: protective immunity induced by gene gun-mediated intracutaneous delivery but not by intramuscular injection.

    Science.gov (United States)

    Han, R; Reed, C A; Cladel, N M; Christensen, N D

    2000-07-01

    We previously demonstrated that gene gun-based intracutaneous vaccination of rabbits with a combination of, but not with individual papillomavirus E1, E2, E6 and E7 genes provided complete protection against cottontail rabbit papillomavirus (CRPV) infection. In the present study, we tested whether vaccination of inbred and outbred rabbits with a combination of CRPV E1 and E2 genes could provide complete protection against virus infection. In the first experiment, gene gun-based intracutaneous vaccination with E1 and E2 genes prevented papilloma formation in the majority of inbred rabbits and promoted systemic papilloma regression in one non-protected rabbit. In contrast, needle-mediated intramuscular injection of E1 and E2 genes did not prevent papilloma formation nor promoted systemic papilloma regression, indicating an absence of strong protective immunity. In the second experiment, six outbred rabbits were immunized by gene gun-based intracutaneous administration of the E1 and E2 genes. Prevention of papilloma formation or systemic papilloma regression was observed in three vaccinated rabbits. Papillomas persisted on the remaining three rabbits, but were significantly smaller than that on control rabbits. These results suggested that gene gun-based intracutaneous vaccination with the combination of papillomavirus E1 and E2 genes induced strong protective antivirus immunity but may be insufficient for complete protection in an outbred population.

  7. Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women

    Directory of Open Access Journals (Sweden)

    NELSON M VARELA

    2008-01-01

    Full Text Available CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it with clinical and histological features in 48 female obese NASH patients. Subjects were divided into three groups: (i normal; (ii steatosis; and (iii steatohepatitis. CYP2E1 protein level was assayed in microsomes from liver biopsies, and in vivo chlorzoxazone hydroxylation was determined by HPLC. Genomic DNA was isolated for genotype analysis through PCR. The results showed that liver CYP2E1 content was significantly higher in the steatohepatitis (45%; p=0.024 and steatosis (22%; p=0.032 group compared with normal group. Chlorzoxazone hydroxylase activity showed significant enhancement in the steatohepatitis group (15%, p=0.027 compared with the normal group. c2 rare allele of RsallPstl polymorphisms but no C allele of Dral polymorphism was positively associated with CHZ hydroxylation, which in turn is correlated with liver CYP2E1 content (r=0.59; p=0.026. In conclusion, c2 allele is positively associated with liver injury in NASH. This allele may determine a higher transcriptional activity of the gene, with consequent enhancement in pro-oxidant activity of CYP2E1 thus affording liver toxicity

  8. The Search For The Cp-violating Emission Of An E1 Photon From The Kaon Long Decays To Positive Pion Negative Pion Gamma

    CERN Document Server

    Shields, J M

    2005-01-01

    A search for the CP-violating electric dipole (E1) direct emission contribution to the KL → π+π −γ decay is performed using data from the 1997 KTeV/E832 experiment. Because the KL → π +π−γ decay mode is massively dominated by the CP-violating inner bremsstrahlung (IB) and the CP-conserving magnetic dipole (M1) direct emission processes, previous analyses have neglected the E1 contribution. Therefore, this measurement is the first attempt to directly quantify the size of the E1 decay process. This E1 transition is one of the very few CP-violating processes that is accessible to experiment and, in principle, will produce new insights into the structure of the neutral kaon. The result of this analysis is that the E1 contribution is below the threshold of sensitivity, and therefore an upper bound of |g E1| < 0.14 (90% CL) is reported. In the process of obtaining this upper limit, high resolution measurements of fit parame...

  9. Relevance Vector Machine for Survival Analysis.

    Science.gov (United States)

    Kiaee, Farkhondeh; Sheikhzadeh, Hamid; Mahabadi, Samaneh Eftekhari

    2016-03-01

    An accelerated failure time (AFT) model has been widely used for the analysis of censored survival or failure time data. However, the AFT imposes the restrictive log-linear relation between the survival time and the explanatory variables. In this paper, we introduce a relevance vector machine survival (RVMS) model based on Weibull AFT model that enables the use of kernel framework to automatically learn the possible nonlinear effects of the input explanatory variables on target survival times. We take advantage of the Bayesian inference technique in order to estimate the model parameters. We also introduce two approaches to accelerate the RVMS training. In the first approach, an efficient smooth prior is employed that improves the degree of sparsity. In the second approach, a fast marginal likelihood maximization procedure is used for obtaining a sparse solution of survival analysis task by sequential addition and deletion of candidate basis functions. These two approaches, denoted by smooth RVMS and fast RVMS, typically use fewer basis functions than RVMS and improve the RVMS training time; however, they cause a slight degradation in the RVMS performance. We compare the RVMS and the two accelerated approaches with the previous sparse kernel survival analysis method on a synthetic data set as well as six real-world data sets. The proposed kernel survival analysis models have been discovered to be more accurate in prediction, although they benefit from extra sparsity. The main advantages of our proposed models are: 1) extra sparsity that leads to a better generalization and avoids overfitting; 2) automatic relevance sample determination based on data that provide more accuracy, in particular for highly censored survival data; and 3) flexibility to utilize arbitrary number and types of kernel functions (e.g., non-Mercer kernels and multikernel learning).

  10. Climate Relevant Processes On The Barents Shelf

    Science.gov (United States)

    Hatten, K.; Schrum, C.; Harms, I.

    The Artic Shelf, and especially the Barents Shelf , are key regions in the North At- lantic climate system. Climatic relevant processes on the shelf are on the one hand the water mass transformation and on the other hand the strong air/sea exchange. Air/sea interaction and resulting sea ice development cause water mass transformation and de- velopment of cold and salty deep water on the shelf region. The outflow of this dense water mass into the Arctic Ocean is responsible for the stabilization of the permanent halocline in the Arctic Ocean and therefore for the isolation of the cold and fresh arctic surface water from the saltier and warmer Atlantic deep water in the Arctic Ocean, and thus for preservation of the Arctic Ocean sea ice. The second climatic relevant process, the direct air/sea exchange, i.e. the annual mean heat release to the atmosphere, plays a key role as energy source for the atmosphere. Both processes are subject to strong inter-annual variability and influenced by mesoscale structures in the ice field, and thus can be assumed to be less good described by the large scale atmospheric and oceanic models. This was the background of the development of a regional eddy resolving model of the Barents Sea. Results of a multi-year model simulation will be presented and related to flux estimates from global atmospheric re-analysis, to highlight the in- fluence of mesoscale variability in the sea ice coverage on the air sea exchange and on the water mass transformation.

  11. The clinical relevance of Tarlov cysts.

    Science.gov (United States)

    Langdown, Andrew John; Grundy, Julian R B; Birch, Nicholas C

    2005-02-01

    The sacral perineural cyst was first described by Tarlov in 1938 as an incidental finding at autopsy. There are very few data in the literature regarding the role of Tarlov cysts in causing symptoms, however. Most studies report low numbers, and consequently, the recommendations for treatment are vague. Our aim, therefore, is to present further detail regarding the clinical relevance of Tarlov cysts and to identify whether or not they are a cause of lumbosacral spinal canal stenosis symptoms. Over a 5-year period, 3535 patients underwent magnetic resonance imaging (MRI) scan for lumbosacral symptoms. Fifty-four patients were identified as having Tarlov cysts, and their clinical picture was correlated with the findings on MRI. The majority of Tarlov cysts (n = 38) cannot be held responsible for patients' symptoms and are clinically unimportant. However, we encountered several patients in whom Tarlov cysts (n = 9) occurred at the same level as another pathology. In these cases, the cyst itself did not require any specific therapy; treatment was directed at the other pathology, and uneventful symptom resolution occurred. A smaller subgroup of cysts (n = 7) are the main cause of patients' symptoms and may require specific treatment to facilitate local decompression. The majority of Tarlov cysts are incidental findings on MRI. Where confusion exists as to the clinical relevance of a Tarlov cyst, treatment of the primary pathology (ie, non-Tarlov lesion) is usually sufficient. Tarlov cysts may, however, be responsible for a patient's symptoms; possible mechanisms by which this may occur and treatment strategies are discussed.

  12. Fear conditioning to subliminal fear relevant and non fear relevant stimuli.

    Directory of Open Access Journals (Sweden)

    Ottmar V Lipp

    Full Text Available A growing body of evidence suggests that conscious visual awareness is not a prerequisite for human fear learning. For instance, humans can learn to be fearful of subliminal fear relevant images--images depicting stimuli thought to have been fear relevant in our evolutionary context, such as snakes, spiders, and angry human faces. Such stimuli could have a privileged status in relation to manipulations used to suppress usually salient images from awareness, possibly due to the existence of a designated sub-cortical 'fear module'. Here we assess this proposition, and find it wanting. We use binocular masking to suppress awareness of images of snakes and wallabies (particularly cute, non-threatening marsupials. We find that subliminal presentations of both classes of image can induce differential fear conditioning. These data show that learning, as indexed by fear conditioning, is neither contingent on conscious visual awareness nor on subliminal conditional stimuli being fear relevant.

  13. Fbw7α and Fbw7γ collaborate to shuttle cyclin E1 into the nucleolus for multiubiquitylation.

    Science.gov (United States)

    Bhaskaran, Nimesh; van Drogen, Frank; Ng, Hwee-Fang; Kumar, Raman; Ekholm-Reed, Susanna; Peter, Matthias; Sangfelt, Olle; Reed, Steven I

    2013-01-01

    Cyclin E1, an activator of cyclin-dependent kinase 2 (Cdk2) that promotes replicative functions, is normally expressed periodically within the mammalian cell cycle, peaking at the G(1)-S-phase transition. This periodicity is achieved by E2F-dependent transcription in late G(1) and early S phases and by ubiquitin-mediated proteolysis. The ubiquitin ligase that targets phosphorylated cyclin E is SCF(Fbw7) (also known as SCF(Cdc4)), a member of the cullin ring ligase (CRL) family. Fbw7, a substrate adaptor subunit, is expressed as three splice-variant isoforms with different subcellular distributions: Fbw7α is nucleoplasmic but excluded from the nucleolus, Fbw7β is cytoplasmic, and Fbw7γ is nucleolar. Degradation of cyclin E in vivo requires SCF complexes containing Fbw7α and Fbw7γ, respectively. In vitro reconstitution showed that the role of SCF(Fbw7α) in cyclin E degradation, rather than ubiquitylation, is to serve as a cofactor of the prolyl cis-trans isomerase Pin1 in the isomerization of a noncanonical proline-proline bond in the cyclin E phosphodegron. This isomerization is required for subsequent binding and ubiquitylation by SCF(Fbw7γ). Here we show that Pin1-mediated isomerization of the cyclin E phosphodegron and subsequent binding to Fbw7γ drive nucleolar localization of cyclin E, where it is ubiquitylated by SCF(Fbw7γ) prior to its degradation by the proteasome. It is possible that this constitutes a mechanism for rapid inactivation of phosphorylated cyclin E by nucleolar sequestration prior to its multiubiquitylation and degradation.

  14. Biophysical investigations of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide.

    Science.gov (United States)

    Sánchez-Martín, Maria Jesús; Urbán, Patricia; Pujol, Montserrat; Haro, Isabel; Alsina, M Asunción; Busquets, M Antònia

    2011-10-24

    Five peptide sequences corresponding to the E1 protein of GBV-C [NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18), and AQLVGELGSLYGPLSVSA (P22)] were synthesized because they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP)-vesicle interaction. In this work the interaction of these peptides with the HIV-1 FP, as well as with membrane models, was analyzed to corroborate their inhibition ability and to understand if the interaction with the fusion peptide takes place in solution or at the membrane level. Several studies were carried out on aggregation and membrane fusion, surface Plasmon resonance, and conformational analysis by circular dichroism. Moreover, in vitro toxicity assays, including cytotoxicity studies in 3T3 fibroblasts and hemolysis assays in human red blood cells, were performed to evaluate if these peptides could be potentially used in anti-HIV-1 therapy. Results show that P10 is not capable of inhibiting membrane fusion caused by HIV-1 and it aggregates liposomes and fuses membranes, thus we decided to discard it for futures studies. P18 and P22 do not inhibit membrane fusion, but they inhibit the ability of HIV-1 FP to form pores in bilayers, thus we have not discarded them yet. P7 and P8 were selected as the best candidates for future studies because they are capable of inhibiting membrane fusion and the interaction of HIV-1 FP with bilayers. Therefore, these peptides could be potentially used in future anti-HIV-1 research. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. RIGOROUS PHOTOGRAMMETRIC PROCESSING OF CHANG'E-1 AND CHANG'E-2 STEREO IMAGERY FOR LUNAR TOPOGRAPHIC MAPPING

    Directory of Open Access Journals (Sweden)

    K. Di

    2012-07-01

    Full Text Available Chang'E-1(CE-1 and Chang'E-2(CE-2 are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D coordinate of a ground point in lunar body-fixed (LBF coordinate system can be calculated by space intersection from the image coordinates of con-jugate points in stereo images, and the image coordinates can be calculated from 3D coordinates by back-projection. Due to uncer-tainties of the orbit and the camera, the back-projected image points are different from the measured points. In order to reduce these inconsistencies and improve precision, we proposed two methods to refine the rigorous sensor model: 1 refining EOPs by correcting the attitude angle bias, 2 refining the interior orientation model by calibration of the relative position of the two linear CCD arrays. Experimental results show that the mean back-projection residuals of CE-1 images are reduced to better than 1/100 pixel by method 1 and the mean back-projection residuals of CE-2 images are reduced from over 20 pixels to 0.02 pixel by method 2. Consequently, high precision DEM (Digital Elevation Model and DOM (Digital Ortho Map are automatically generated.

  16. Effect of prostaglandins E1, E2, and F2 alpha on osteoclast formation in mouse bone marrow cultures

    Energy Technology Data Exchange (ETDEWEB)

    Collins, D.A.; Chambers, T.J. (St. George' s Hospital Medical School, London (United Kingdom))

    1991-02-01

    Prostaglandins (PG) act as direct inhibitors of mature osteoclasts, but although resorption-inhibition is also observed initially PG increase bone resorption in organ culture. This suggests that PG influence bone resorption in organ culture through actions on cell types other than mature osteoclasts. We have therefore tested the effects of PG E1, E2, and F2 alpha on the differentiation of osteoclastic phenotype in mouse bone marrow cultures using bone resorption and calcitonin receptors (CTR) as markers of osteoclastic differentiation. We found that PGE2 (10{sup {minus} 6}-10{sup {minus} 9} M) and PGE1 (10{sup {minus} 6} - 10{sup {minus} 7} M) induced a significant increase in CTR-positive cell numbers, to levels five to eight times those seen in controls and similar to the number induced by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Bone resorption was increased (10{sup {minus} 7} M PGE2 and 10{sup {minus} 6} M PGE1) in association with the increased CTR-positive cell numbers, suggesting that the PG also induced resorptive function. 1,25-(OH)2D3 increased both the number of CTR-positive cells and the extent of resorption per cell; the additional presence of PG did not affect the number of CTR-positive cells but did reduce bone resorption compared with 1,25-(OH)2D3 alone. PGF2 alpha had no significant effect on CTR-positive cell induction or bone resorption. The results suggest that PGE1 and E2 induce osteoclastic differentiation in mouse bone marrow cultures and inhibit the function of the osteoclasts thus formed.

  17. Red yeast rice stimulates osteoblast proliferation and increases alkaline phosphatase activity in MC3T3-E1 cells.

    Science.gov (United States)

    Cho, Young-Eun; Alcantara, Ethel; Kumaran, Santhy; Son, Kun-Ho; Sohn, Ho-Yong; Lee, Jong-Hwa; Choi, Chung-Sig; Ha, Tae-Youl; Kwun, In-Sook

    2010-07-01

    Red yeast (Monascus purpureus) is used as a traditional hypocholesterolemic dietary food component in Asia due to its bioactive component, lovastatin. Recently, new evidence suggesting that the statins in red yeast enhance bone formation has been reported, but more research is still needed in order to support these claims of osteogenic effects. Therefore, in this study, we hypothesized that red yeast rice (in which red yeast is fermented) can improve osteogenic function through osteoblast cell proliferation and differentiation. We studied the effect of methanol extract of red yeast rice powder (RYRP) on osteoblast proliferation and differentiation by measuring mitochondrial enzyme activity and bone marker alkaline phosphatase (ALP) activity, respectively. Osteoblast-like MC3T3-E1 cells were cultured in various concentrations of RYRP methanol extract (0.001-1 mg/mL) during the osteoblast differentiation period (1, 5, 10, and 15 days). As measured by 3-[4,5-dimethylthiazol-2-y]-2,5-diphenyltetrazolium bromide assay, RYRP extracts stimulated cell proliferation during a 24-hour period, compared to cooked white rice powder extract. The most pronounced effect was observed at the concentration range between 0.075 and 0.1 mg/mL. This RYRP stimulatory effect for cell proliferation was observed during the whole osteogenic period. Cellular (synthesized) ALP activity was increased at a RYRP extract concentration of 0.075 mg/mL during 15 days of culture, but the medium (secreted) ALP activity did not show any significant change. This cellular ALP activity stimulation by RYRP extract was confirmed by the staining of ALP activity on cell matrix layers for matrix calcification. The results imply that RYRP extract may increase osteogenic effect by stimulating cell proliferation and ALP activity in osteoblastic cells. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Occurrence of sulfonated steroids and ovarian expression of steroid sulfatase and SULT1E1 in cyclic cows.

    Science.gov (United States)

    Blaschka, Carina; Schuler, Gerhard; Sánchez-Guijo, Alberto; Zimmer, Bettina; Feller, Sabine; Kotarski, Franziska; Wudy, Stefan A; Wrenzycki, Christine

    2017-12-17

    Historically sulfonated steroids were primarily considered as inactive metabolites destined for elimination. However, more recently they have been increasingly recognized as precursors for the production of bioactive steroids in target tissues and as functional molecules without preceding hydrolysis. In order to comprehensively characterize their occurrence in cyclic cows and their formation and hydrolysis in bovine ovarian steroidogenesis, ovaries from cyclic cows were screened for the expression of oestrogen sulfotransferase (SULTE1) and steroid sulfatase (STS) by Western blot and immunohistochemistry. Moreover, a broad spectrum of 13 sulfonated steroids was measured applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) in blood samples collected from three cycling heifers during defined stages of the ovarian cycle and in fluid obtained from ovarian follicles of different size. SULT1E1 was undetectable in ovarian tissues. For STS only a weak immunostaining was found predominantly in granulosa cells of larger follicles. However, no specific band occurred in Western blot. In blood, concentrations of all sulfonated steroids investigated were below the limit of quantification (LOQ). In follicular fluid, only cholesterol sulfate was measured in considerable concentrations (328.3 ± 63.8 ng/ml). However, the role of cholesterol sulfate in bovine follicular steroidogenesis remains unclear as concentrations were obviously unrelated to follicular size. The remaining sulfonated steroids investigated were undetectable or only slightly exceeded LOQ in a minor proportion of samples. The results are clearly contrary to a role of sulfonated steroids as important precursors, intermediates or products of bovine ovarian steroidogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Functional PstI/RsaI polymorphism in CYP2E1 is associated with the development, progression and poor outcome of gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jin Feng

    Full Text Available BACKGROUND: Cytochrome P450 2E1 (CYP2E1, an ethanol-inducible enzyme, has been shown to metabolically activate various carcinogens, which is critical for the development and progression of cancers. It has demonstrated that CYP2E1 polymorphisms alter the transcriptional activity of the gene. However, studies on the association between CYP2E1 polymorphisms (PstI/RsaI or DraI and gastric cancer have reported conflicting results. Thus, the aim of the present study was to investigate whether CYP2E1 polymorphisms is associated with the development and progression of gastric cancer and its prognosis in Chinese patients. METHODS: A case-control study was conducted in which CYP2E1 PstI/RsaI and DraI polymorphisms were analyzed in 510 Chinese patients with gastric cancer and 510 age- and sex- matched healthy controls by PCR-RFLP. Odds ratios were estimated by multivariate logistic regression, and the lifetime was calculated by Kaplan-Meier survival curves. In addition, a meta-analysis was also conducted to verify the findings. RESULTS: For CYP2E1 PstI/RsaI polymorphism, C2C2 homozygotes (OR = 2.15; CI: 1.18-3.94 and C2 carriers (OR = 1.48; CI: 1.13-1.96 were associated with an increased risk of gastric cancer when compared with C1C1 homozygotes. Both C1C2 and C2C2 genotypes were associated with advanced stage, but not the grade of gastric cancer. Moreover, C2C2 genotype was identified as an independent marker of poor overall survival for gastric cancer. However, there was not any significant association between CYP2E1 DraI polymorphism and the risk of gastric cancer. In the meta-analysis, pooled data from 13 studies confirmed that the CYP2E1 PstI/RsaI polymorphism was associated with a significantly increased risk of gastric cancer. CONCLUSION: CYP2E1 PstI/RsaI polymorphism is associated with increased risk of development, progression and poor prognosis of gastric cancer in Chinese patients. Pooled data from 13 studies, mainly in Asian countries, are in

  20. The Relevance of Aggression and the Aggression of Relevance: The Rise of the Accreditation Marketing Machine

    Science.gov (United States)

    Lowrie, Anthony

    2008-01-01

    Purpose: The purpose of this paper is to illustrate how language functions to construct relevance at moments of articulation and how language functions as an aggressive marketing practice to promote a self-regulated (production-oriented) system of accreditation. Design/methodology/approach: Drawing on the political theory of Laclau and Lacanian…

  1. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  2. Ligand Exchange Kinetics of Environmentally Relevant Metals

    Energy Technology Data Exchange (ETDEWEB)

    Panasci, Adele Frances [Univ. of California, Davis, CA (United States)

    2014-07-15

    The interactions of ground water with minerals and contaminants are of broad interest for geochemists but are not well understood. Experiments on the molecular scale can determine reaction parameters (i.e. rates of ligand exchange, activation entropy, activation entropy, and activation volume) that can be used in computations to gain insight into reactions that occur in natural groundwaters. Experiments to determine the rate of isotopic ligand exchange for three environmentally relevant metals, rhodium (Rh), iron (Fe), and neptunium (Np), are described. Many environmental transformations of metals (e.g. reduction) in soil occur at trivalent centers, Fe(III) in particular. Contaminant ions absorb to mineral surfaces via ligand exchange, and the reversal of this reaction can be dangerous, releasing contaminants into the environment. Ferric iron is difficult to study spectroscopically because most of its complexes are paramagnetic and are generally reactive toward ligand exchange; therefore, Rh(III), which is diamagnetic and less reactive, was used to study substitution reactions that are analogous to those that occur on mineral oxide surfaces. Studies on both Np(V) and Np(VI) are important in their own right, as 237Np is a radioactive transuranic element with a half-life of 2 million years.

  3. Accreditation - Its relevance for laboratories measuring radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Palsson, S.E. [Icelandic Radiation Protection Inst. (Iceland)

    2001-11-01

    Accreditation is an internationally recognised way for laboratories to demonstrate their competence. Obtaining and maintaining accreditation is, however, a costly and time-consuming procedure. The benefits of accreditation also depend on the role of the laboratory. Accreditation may be of limited relevance for a research laboratory, but essential for a laboratory associated with a national authority and e.g. issuing certificates. This report describes work done within the NKSBOK-1.1 sub-project on introducing accreditation to Nordic laboratories measuring radionuclides. Initially the focus was on the new standard ISO/IEC 17025, which was just in a draft form at the time, but which provides now a new framework for accreditation of laboratories. Later the focus was widened to include a general introduction to accreditation and providing through seminars a forum for exchanging views on the experience laboratories have had in this field. Copies of overheads from the last such seminar are included in the appendix to this report. (au)

  4. Quantifying the Behavioural Relevance of Hippocampal Neurogenesis

    Science.gov (United States)

    Lazic, Stanley E.; Fuss, Johannes; Gass, Peter

    2014-01-01

    Few studies that examine the neurogenesis–behaviour relationship formally establish covariation between neurogenesis and behaviour or rule out competing explanations. The behavioural relevance of neurogenesis might therefore be overestimated if other mechanisms account for some, or even all, of the experimental effects. A systematic review of the literature was conducted and the data reanalysed using causal mediation analysis, which can estimate the behavioural contribution of new hippocampal neurons separately from other mechanisms that might be operating. Results from eleven eligible individual studies were then combined in a meta-analysis to increase precision (representing data from 215 animals) and showed that neurogenesis made a negligible contribution to behaviour (standarised effect  = 0.15; 95% CI  = −0.04 to 0.34; p = 0.128); other mechanisms accounted for the majority of experimental effects (standardised effect  = 1.06; 95% CI  = 0.74 to 1.38; p = 1.7×10−11). PMID:25426717

  5. Extracellular vesicles: fundamentals and clinical relevance

    Directory of Open Access Journals (Sweden)

    Wael Nassar

    2015-01-01

    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  6. Relevance of vestibulospinal tests after unilateral neurolabyrinthitis

    Directory of Open Access Journals (Sweden)

    Babić Borivoj B.

    2003-01-01

    Full Text Available In this paper we wanted to assess clinical relevance of two vestibulospinal tests: standing test (derived from Romberg test and past pointing test. In retrospective and prospective study 42 patients have been tested with standing test and 50 patients with past pointing test. All patients suffered from unilateral neurolabyrinthitis that had started from one day to two years prior to examination. All patients had unilateral areflexion, or hyporeflexion on caloric test using 10°C water. Control group consisted of 32 healthy individuals for both tests. Results show that both tests correctly indicate side of the lesion but only during first week of illness. Moreover, even during that first week sensitivity of both tests was below 50 %, which means that more then half results from patients fall within normal findings. We conclude that vestibulospinal tests do not deserve prominent place in assessing patients with vestibular syndrom. Conclusions must be made according to findings obtained from much more precise vestibuloocular tests.

  7. Clinical embryology teaching: is it relevant anymore?

    Science.gov (United States)

    Scott, Karen M; Charles, Antony Robert; Holland, Andrew J A

    2013-10-01

    Embryology finds itself jostling for precious space in the crowded medical curriculum, yet remains important for helping students understand birth defects. It has been suggested that teaching embryology through clinical scenarios can increase its relevance and interest. The aim of this research was to determine the attitudes of final-year medical students to learning embryology and whether clinical scenarios aid understanding. Final-year medical students undertaking their paediatric rotation in 2009 and 2010 were invited to attend an optional lecture on clinical embryology and participate in the research. In the lecture, three clinical scenarios were presented, in which the lecturer traced the normal development of a foetus and the abnormal development that resulted in a birth defect. Outcomes were assessed quantitatively using a paper-based survey. The vast majority of students who valued embryology teaching in their medical programme thought it would assist them with clinical management, and believed learning through case scenarios helped their understanding. Students were divided in their beliefs about when embryology should be taught in the medical programme and whether it would increase their workload. Embryology teaching appears to be a valuable part of the medical curriculum. Embryology teaching was valued when taught in the clinical environment in later years of the medical programme. Students, clinicians and medical educators should be proactive in finding clinical learning opportunities for embryology teaching. © 2013 Royal Australasian College of Surgeons.

  8. Relevance of postprandial lipemia in metabolic syndrome.

    Science.gov (United States)

    Garcia-Rios, Antonio; Delgado-Lista, Javier; Perez-Martinez, Pablo; Delgado-Casado, Nieves; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

    2013-11-01

    Metabolic Syndrome (MetS) is a complex disorder defined by the aggregation of interconnected cardiometabolic risk factors which increase the risk of diabetes mellitus type 2 and cardiovascular disease (CVD). MetS is currently a matter of concern and it will continue to be in the future, since there is likely to be a dramatic increase in its prevalence, and subjects with MetS will have an increased risk of mortality, mainly through CVD. Moreover, the implications on the global health burden and the worldwide epidemic of this complex disorder will impact greatly on socioeconomic cost. MetS is therefore a matter of serious concern and we need to understand its etiology in order to improve strategies of treatment and prevention. In this regard, postprandial lipemia has increased in importance over the last few years as it has been demonstrated to influence the development of atherosclerosis. In addition, in modern times, fasting is not the typical physiological state of humans; in fact, they spend most of the time in the postprandial state. However, although it is obvious that postprandial lipemia is present in conditions of obesity, little is known about the relevance of postprandial lipemia in MetS. In the current review, we will explore some aspects of postprandial lipemia which could be of interest for understanding the pathogenesis of this complex disorder and which may help us advance towards more personalized nutrition.

  9. Symptoms Relevant to Surveillance for Ovarian Cancer

    Science.gov (United States)

    Ore, Robert M.; Baldwin, Lauren; Woolum, Dylan; Elliott, Erika; Wijers, Christiaan; Chen, Chieh-Yu; Miller, Rachel W.; DeSimone, Christopher P.; Ueland, Frederick R.; Kryscio, Richard J.; van Nagell, John R.; Pavlik, Edward J.

    2017-01-01

    To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3%) decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p Women reporting at least one symptom expressed more confidence (41,984/52,379 = 80.2%) than women reporting no symptoms (11,882/18,355 = 64.7%), p Confidence was unrelated to history of hormone replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89). The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported. PMID:28335512

  10. Media and mental illness: Relevance to India

    Directory of Open Access Journals (Sweden)

    S K Padhy

    2014-01-01

    Full Text Available Media has a complex interrelationship with mental illnesses. This narrative review takes a look at the various ways in which media and mental illnesses interact. Relevant scientific literature and electronic databases were searched, including Pubmed and GoogleScholar, to identify studies, viewpoints and recommendations using keywords related to media and mental illnesses. This review discusses both the positive and the negative portrayals of mental illnesses through the media. The portrayal of mental health professionals and psychiatric treatment is also discussed. The theories explaining the relationship of how media influences the attitudes and behavior are discussed. Media has also been suggested to be a risk factor for the genesis or exacerbation of mental illnesses like eating disorders and substance use disorders. The potential use of media to understand the psychopathology and plight of those with psychiatric disorders is referred to. The manner in which media can be used as a tool for change to reduce the stigma surrounding mental illnesses is explored.

  11. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    A. V. Oberemko

    2014-12-01

    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  12. Mathematical Properties Relevant to Geomagnetic Field Modeling

    DEFF Research Database (Denmark)

    Sabaka, Terence J.; Hulot, Gauthier; Olsen, Nils

    2010-01-01

    Geomagnetic field modeling consists in converting large numbers of magnetic observations into a linear combination of elementary mathematical functions that best describes those observations.The set of numerical coefficients defining this linear combination is then what one refers to as a geomagn......Geomagnetic field modeling consists in converting large numbers of magnetic observations into a linear combination of elementary mathematical functions that best describes those observations.The set of numerical coefficients defining this linear combination is then what one refers...... be directly measured. In this chapter, the mathematical foundation of global (as opposed to regional) geomagnetic field modeling is reviewed, and the spatial modeling of the field in spherical coordinates is focussed. Time can be dealt with as an independent variable and is not explicitly considered.......The relevant elementary mathematical functions are introduced, their properties are reviewed, and how they can be used to describe the magnetic field in a source-free (such as the Earth’s neutral atmosphere) or source-dense (such as the ionosphere) environment is explained. Completeness and uniqueness...

  13. Symptoms Relevant to Surveillance for Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Robert M. Ore

    2017-03-01

    Full Text Available To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS. Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073% for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3% decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p < 0.0001. Women reporting at least one symptom expressed more confidence (41,984/52,379 = 80.2% than women reporting no symptoms (11,882/18,355 = 64.7%, p < 0.0001. Confidence was unrelated to history of hormone replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89. The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported.

  14. Effects of a recombinant gene expression on ColE1-like plasmid segregation in Escherichia coli.

    Science.gov (United States)

    Popov, Mladen; Petrov, Stefan; Nacheva, Genoveva; Ivanov, Ivan; Reichl, Udo

    2011-03-01

    Segregation of expression plasmids leads to loss of recombinant DNA from transformed bacterial cells due to the irregular distribution of plasmids between the daughter cells during cell division. Under non-selective conditions this segregational instability results in a heterogeneous population of cells, where the non-productive plasmid-free cells overgrow the plasmid-bearing cells thus decreasing the yield of recombinant protein. Amongst the factors affecting segregational plasmid instability are: the plasmid design, plasmid copy-number, host cell genotype, fermentation conditions etc. This study aims to investigate the influence of transcription and translation on the segregation of recombinant plasmids designed for constitutive gene expression in Escherichia coli LE392 at glucose-limited continuous cultivation. To this end a series of pBR322-based plasmids carrying a synthetic human interferon-gamma (hIFNγ) gene placed under the control of different regulatory elements (promoter and ribosome-binding sites) were used as a model. Bacterial growth and product formation kinetics of transformed E. coli LE392 cells cultivated continuously were described by a structured kinetic model proposed by Lee et al. (1985). The obtained results demonstrated that both transcription and translation efficiency strongly affected plasmid segregation. The segregation of plasmid having a deleted promoter did not exceed 5% after 190 h of cultivation. The observed high plasmid stability was not related with an increase in the plasmid copy-number. A reverse correlation between the yield of recombinant protein (as modulated by using different ribosome binding sites) and segregational plasmid stability (determined by the above model) was also observed. Switching-off transcription of the hIFNγ gene has a stabilising effect on ColE1-like plasmids against segregation, which is not associated with an increase in the plasmid copy-number. The increased constitutive gene expression has a

  15. Effects of a recombinant gene expression on ColE1-like plasmid segregation in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ivanov Ivan

    2011-03-01

    Full Text Available Abstract Background Segregation of expression plasmids leads to loss of recombinant DNA from transformed bacterial cells due to the irregular distribution of plasmids between the daughter cells during cell division. Under non-selective conditions this segregational instability results in a heterogeneous population of cells, where the non-productive plasmid-free cells overgrow the plasmid-bearing cells thus decreasing the yield of recombinant protein. Amongst the factors affecting segregational plasmid instability are: the plasmid design, plasmid copy-number, host cell genotype, fermentation conditions etc. This study aims to investigate the influence of transcription and translation on the segregation of recombinant plasmids designed for constitutive gene expression in Escherichia coli LE392 at glucose-limited continuous cultivation. To this end a series of pBR322-based plasmids carrying a synthetic human interferon-gamma (hIFNγ gene placed under the control of different regulatory elements (promoter and ribosome-binding sites were used as a model. Results Bacterial growth and product formation kinetics of transformed E. coli LE392 cells cultivated continuously were described by a structured kinetic model proposed by Lee et al. (1985. The obtained results demonstrated that both transcription and translation efficiency strongly affected plasmid segregation. The segregation of plasmid having a deleted promoter did not exceed 5% after 190 h of cultivation. The observed high plasmid stability was not related with an increase in the plasmid copy-number. A reverse correlation between the yield of recombinant protein (as modulated by using different ribosome binding sites and segregational plasmid stability (determined by the above model was also observed. Conclusions Switching-off transcription of the hIFNγ gene has a stabilising effect on ColE1-like plasmids against segregation, which is not associated with an increase in the plasmid copy

  16. Accelerated evolution of 3'avian FOXE1 genes, and thyroid and feather specific expression of chicken FoxE1

    Directory of Open Access Journals (Sweden)

    Antin Parker B

    2011-10-01

    Full Text Available Abstract Background The forkhead transcription factor gene E1 (FOXE1 plays an important role in regulation of thyroid development, palate formation and hair morphogenesis in mammals. However, avian FOXE1 genes have not been characterized and as such, codon evolution of FOXE1 orthologs in a broader evolutionary context of mammals and birds is not known. Results In this study we identified the avian FOXE1 gene in chicken, turkey and zebra finch, all of which consist of a single exon. Chicken and zebra finch FOXE1 are uniquely located on the sex-determining Z chromosome. In situ hybridization shows that chicken FOXE1 is specifically expressed in the developing thyroid. Its expression is initiated at the placode stage and is maintained during the stages of vesicle formation and follicle primordia. Based on this expression pattern, we propose that avian FOXE1 may be involved in regulating the evagination and morphogenesis of thyroid. Chicken FOXE1 is also expressed in growing feathers. Sequence analysis identified two microdeletions in the avian FOXE1 genes, corresponding to the loss of a transferable repression domain and an engrailed homology motif 1 (Eh1 C-terminal to the forkhead domain. The avian FOXE1 proteins exhibit a significant sequence divergence of the C-terminus compared to those of amphibian and mammalian FOXE1. The codon evolution analysis (dN/dS of FOXE1 shows a significantly increased dN/dS ratio in the avian lineages, consistent with either a relaxed purifying selection or positive selection on a few residues in avian FOXE1 evolution. Further site specific analysis indicates that while relaxed purifying selection is likely to be a predominant cause of accelerated evolution at the 3'-region of avian FOXE1, a few residues might have evolved under positive selection. Conclusions We have identified three avian FOXE1 genes based on synteny and sequence similarity as well as characterized the expression pattern of the chicken FOXE1 gene

  17. Fusion of the BCL9 HD2 domain to E1A increases the cytopathic effect of an oncolytic adenovirus that targets colon cancer cells

    Directory of Open Access Journals (Sweden)

    Pittet Anne-Laure

    2006-10-01

    Full Text Available Abstract Background The Wnt signaling pathway is activated by mutations in the APC and β-catenin genes in many types of human cancer. β-catenin is stabilized by these mutations and activates transcription in part by acting as a bridge between Tcf/LEF proteins and the HD2 domain of the BCL9 coactivator. We have previously described oncolytic adenoviruses with binding sites for Tcf/LEF transcription factors inserted into the early viral promoters. These viruses replicate selectively in cells with activation of the Wnt pathway. To increase the activity of these viruses we have fused the viral transactivator E1A to the BCL9 HD2 domain. Methods Luciferase assays, co-immunoprecipitation and Western blotting, immunofluorescent cell staining and cytopathic effect assays were used to characterize the E1A-HD2 fusion protein and virus in vitro. Growth curves of subcutaneous SW620 colon cancer xenografts were used to characterize the virus in vivo. Results The E1A-HD2 fusion protein binds to β-catenin in vivo and activates a Tcf-regulated luciferase reporter better than wild-type E1A in cells with activated Wnt signaling. Expression of the E1A-HD2 protein promotes nuclear import of β-catenin, mediated by the strong nuclear localization signal in E1A. Tcf-regulated viruses expressing the fusion protein show increased expression of viral proteins and a five-fold increase in cytopathic effect (CPE in colorectal cancer cell lines. There was no change in viral protein expression or CPE in HeLa cells, indicating that E1A-HD2 viruses retain selectivity for cells with activation of the Wnt signaling pathway. Despite increasing the cytopathic effect of the virus in vitro, fusion of the HD2 domain to E1A did not increase the burst size of the virus in vitro or the anti-tumor effect of the virus in an SW620 xenograft model in vivo. Conclusion Despite an increase in the nuclear pool of β-catenin, the effects on viral activity in colon cancer cells were small

  18. A prospective randomized study to optimize the dosage of trimix ingredients and compare its efficacy and safety with prostaglandin E1.

    Science.gov (United States)

    Seyam, R; Mohamed, K; Akhras, A Al; Rashwan, H

    2005-01-01

    Intracavernous injection of Trimix (Tx) is indicated for patients unsuitable for prostaglandin E1 (PgE1) injection due to lack of response, pain or cost. We believe that the ideal ratio of ingredient doses in Tx is yet to be found. We postulated that increasing the doses of individual drug components in an orderly manner would convey important data on penile hemodynamic response. Such information is needed to choose an effective and less costly alternative to PgE1 with least side effects. We set out to evaluate the impact of varying the ingredient dosage on response and short-term safety of Tx compared with PgE1. We prospectively randomized 180 consecutive patients with erectile dysfunction into nine equal groups and each group received a different dose of Tx, namely phentolamine (1 mg) plus one dose of PgE1 (2.5, 5 or 10 microg) and one dose of papaverine (5, 10 or 20 mg). Each patient was injected with 20 microg PgE1 and one dose of Tx in two clinic visits 1 week apart. Following injection, duplex ultrasound of cavernous arteries and axial rigidometry were carried out. Patients ranked the quality of erection, estimated overall satisfaction and reported time to detumescence and side effects. Patients' mean age was 50.5+/-11.7 y with underlying organic condition in 91.1%. There were no significant differences between PgE1 and Tx with regard to peak cavernous artery flow, time to erection, patients' satisfaction, average axial rigidity and pain. PgE1 produced higher end diastolic velocity, shorter duration of erection and less priapism. Patients did not show a preference for either drug or any particular dosage. We conclude that even at the smallest dose of ingredients of Tx, there are no significant differences in hemodynamic effects, rigidity, pain and self-satisfaction between the two drugs. However, Tx produces a longer duration of erection and more priapism than PgE1.

  19. Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models*

    Science.gov (United States)

    Bansal, Seema; Anandatheerthavarada, Hindupur K.; Prabu, Govindaswamy K.; Milne, Ginger L.; Martin, Martha V.; Guengerich, F. Peter; Avadhani, Narayan G.

    2013-01-01

    Human polymorphisms in the 5′-upstream regulatory regions and also protein coding regions of cytochrome P450 2E1 (CYP2E1) are known to be associated with several diseases, including cancer and alcohol liver toxicity. In this study, we report novel mutations in the N-terminal protein targeting regions of CYP2E1 that markedly affect subcellular localization of the protein. Variant W23R/W30R protein (termed W23/30R) is preferentially targeted to mitochondria but very poorly to the endoplasmic reticulum, whereas the L32N protein is preferentially targeted to the endoplasmic reticulum and poorly to mitochondria. These results explain the physiological significance of bimodal CYP targeting to the endoplasmic reticulum and mitochondria previously described. COS-7 cells and HepG2 cells stably expressing W23/30R mutations showed markedly increased alcohol toxicity in terms of increased production of reactive oxygen species, respiratory dysfunction, and loss of cytochrome c oxidase subunits and activity. Stable cells expressing the L32N variant, on the other hand, were relatively less responsive to alcohol-induced toxicity and mitochondrial dysfunction. These results further support our previous data, based on mutational studies involving altered targeting, indicating that mitochondria-targeted CYP2E1 plays an important role in alcohol liver toxicity. The results also provide an interesting new link to genetic variations affecting subcellular distribution of CYP2E1 with alcohol-induced toxicity. PMID:23471973

  20. PprM is necessary for up-regulation of katE1, encoding the major catalase of Deinococcus radiodurans, under unstressed culture conditions.

    Science.gov (United States)

    Jeong, Sun-Wook; Seo, Ho Seong; Kim, Min-Kyu; Choi, Jong-Il; Lim, Heon-Man; Lim, Sangyong

    2016-06-01

    Deinococcus radiodurans is a poly-extremophilic organism, capable of tolerating a wide variety of different stresses, such as gamma/ultraviolet radiation, desiccation, and oxidative stress. PprM, a cold shock protein homolog, is involved in the radiation resistance of D. radiodurans, but its role in the oxidative stress response has not been investigated. In this study, we investigated the effect of pprM mutation on catalase gene expression. pprM disruption decreased the mRNA and protein levels of KatE1, which is the major catalase in D. radiodurans, under normal culture conditions. A pprM mutant strain (pprM MT) exhibited decreased catalase activity, and its resistance to hydrogen peroxide (H2O2) decreased accordingly compared with that of the wild-type strain. We confirmed that RecG helicase negatively regulates katE1 under normal culture conditions. Among katE1 transcriptional regulators, the positive regulator drRRA was not altered in pprM (-), while the negative regulators perR, dtxR, and recG were activated more than 2.5-fold in pprM MT. These findings suggest that PprM is necessary for KatE1 production under normal culture conditions by down-regulation of katE1 negative regulators.

  1. E2F activates late-G1 events but cannot replace E1A in inducing S phase in terminally differentiated skeletal muscle cells

    DEFF Research Database (Denmark)

    Pajalunga, D; Tognozzi, D; Tiainen, M

    1999-01-01

    that overexpression of E2F-1, E2F-2 and E2F-4, or a chimeric E2F-4 tethered to a nuclear localization signal cannot reactivate postmitotic skeletal muscle cells (myotubes). This is not due to lack of transcriptional activity, as demonstrated on both a reporter construct and a number of endogenous target genes......We have previously shown that the adenovirus E1A oncogene can reactivate the cell cycle in terminally differentiated cells. Current models imply that much or all of this E1A activity is mediated by the release of the E2F transcription factors from pocket-protein control. In contrast, we show here...... in the presence of E1A, as dominant-negative DP-1 mutants inhibit E1A-mediated cell cycle reentry. Our data show that, to reactivate myotubes, E1A must exert other functions, in addition to releasing E2F. They also establish mouse myotubes as an experimental system uniquely suited to study the most direct E2F...

  2. 3,4-Dihidro-1,1-diokso-2H-benzo[e] [1,2]tiazīnu sintēze

    OpenAIRE

    Paass, Einārs

    2011-01-01

    3,4-Dihidro-1,1-diokso-2H-benzo[e][1,2]tiazīnu sintēze. Paass E., zinātniskie vadītāji M. Sc. Bluķe Z., Dr.chem. Kauss V. Bakalaura darbs, 36 lappuses, 29 attēli, 5 tabulas, 25 literatūras avoti. Latviešu valodā. 1,1-DIOKSO-2H-BENZO[e][1,2]TIAZĪNS, 1,1-DIOKSO-3,4-DIHIDRO-2H-BENZO[e][1,2]TIAZĪN-3-KARBONSKĀBES METILESTERIS, REDUCĒŠANA, HIDROGENĒŠANA, SAHARĪNS Darbā apkopotas 1,1-diokso-2H-benzo[e][1,2]tiazīnu un 3,4-dihidro-1,1-diokso-2H-benzo[e][1,2]tiazīnu sintēzes metodes. Pēc literat...

  3. The UGA-CiE1 cell line from Chrysodeixis includens exhibits characteristics of granulocytes and is permissive to infection by two viruses.

    Science.gov (United States)

    Johnson, Jena A; Bitra, Kavita; Zhang, Shu; Wang, Lihua; Lynn, Dwight E; Strand, Michael R

    2010-05-01

    The soybean looper, Chrysodeixis (Pseudoplusia) includens (Lepidoptera: Noctuidae) is an economically important insect pest and a highly permissive host for the parasitoid Microplitis demolitor and its associated polydnavirus M. demolitor bracovirus (MdBV). Here we established a cell line from C. includens embryos designated UGA-CiE1 cells. CiE1 cells morphologically resemble granulocytes, which are a subpopulation of C. includens hemocytes. Antibody and RT-PCR analyses indicated that CiE1 cells express several molecular and functional markers that identify granulocytes. We further determined that CiE1 cells are permissive to infection by MdBV, exhibiting alterations very similar to MdBV-infected granulocytes, and Autographa californica multiple nucleopolyhedrosis virus (AcMNPV). Combined with the ability to transfect CiE1 cells with high efficiency and knock down expression of viral genes by RNA interference, we conclude this cell line has several attributes of value for studying immune interactions with polydnaviruses and potentially other pathogens. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Relevance of ellipse eccentricity for camera calibration

    Science.gov (United States)

    Mordwinzew, W.; Tietz, B.; Boochs, F.; Paulus, D.

    2015-05-01

    of ellipse eccentricity on image blocks cannot be modeled in a straight forward fashion. Instead, simulations can help make the impact visible, and to distinguish critical or less critical situations. In particular, this might be of importance for calibrations, as undetected influence on the results will affect further projects where the same camera will be used. This paper therefore aims to point out the influence of ellipse eccentricities on camera calibrations, by using two typical calibration bodies: planar and cube shaped calibration. In the first step, their relevance and influence on the image measurements, object- and camera geometry is shown with numeric examples. Differences and similarities between both calibration bodies are identified and discussed. In the second step, practical relevance of a correction is proven in a real calibration. Finally, a conclusion is drawn followed by recommendations to handle ellipse eccentricity in the practice.

  5. Relevant optical properties for direct restorative materials.

    Science.gov (United States)

    Pecho, Oscar E; Ghinea, Razvan; do Amaral, Erika A Navarro; Cardona, Juan C; Della Bona, Alvaro; Pérez, María M

    2016-05-01

    To evaluate relevant optical properties of esthetic direct restorative materials focusing on whitened and translucent shades. Enamel (E), body (B), dentin (D), translucent (T) and whitened (Wh) shades for E (WhE) and B (WhB) from a restorative system (Filtek Supreme XTE, 3M ESPE) were evaluated. Samples (1 mm thick) were prepared. Spectral reflectance (R%) and color coordinates (L*, a*, b*, C* and h°) were measured against black and white backgrounds, using a spectroradiometer, in a viewing booth, with CIE D65 illuminant and d/0° geometry. Scattering (S) and absorption (K) coefficients and transmittance (T%) were calculated using Kubelka-Munk's equations. Translucency (TP) and opalescence (OP) parameters and whiteness index (W*) were obtained from differences of CIELAB color coordinates. R%, S, K and T% curves from all shades were compared using VAF (Variance Accounting For) coefficient with Cauchy-Schwarz inequality. Color coordinates and optical parameters were statistically analyzed using one-way ANOVA, Tukey's test with Bonferroni correction (α=0.0007). Spectral behavior of R% and S were different for T shades. In addition, T shades showed the lowest R%, S and K values, as well as the highest T%, TP an OP values. In most cases, WhB shades showed different color and optical properties (including TP and W*) than their corresponding B shades. WhE shades showed similar mean W* values and higher mean T% and TP values than E shades. When using whitened or translucent composites, the final color is influenced not only by the intraoral background but also by the color and optical properties of multilayers used in the esthetic restoration. Copyright © 2016 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  6. Pure neuritic leprosy: Current status and relevance.

    Science.gov (United States)

    Rao, P Narasimha; Suneetha, Sujai

    2016-01-01

    Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.

  7. Periodontal innate immune mechanisms relevant to obesity.

    Science.gov (United States)

    Amar, S; Leeman, S

    2013-10-01

    Obesity affects over 35% of the adult population of the USA, and obesity-related illnesses have emerged as the leading cause of preventable death worldwide, according to the World Health Organization. Obesity's secondary morbidities include increased risk of cardiovascular disease, type II diabetes, and cancer, in addition to increased occurrence and severity of infections. Sedentary lifestyle and weight gain caused by consumption of a high-fat diet contribute to the development of obesity, with individuals having a body mass index (BMI) score > 30 being considered obese. Genetic models of obesity (ob/ob mice, db/db mice, and fa/fa rats) have been insufficient to study human obesity because of the overall lack of genetic causes for obesity in human populations. To date, the diet-induced obese (DIO) mouse model best serves research studies relevant to human health. Periodontal disease presents with a wide range of clinical variability and severity. Research in the past decade has shed substantial light on both the initiating infectious agents and host immunological responses in periodontal disease. Up to 46% of the general population harbors the microorganism(s) associated with periodontal disease, although many are able to limit the progression of periodontal disease or even clear the organism(s) if infected. In the last decade, several epidemiological studies have found an association between obesity and increased incidence of periodontal disease. This review focuses on exploring the immunological consequences of obesity that exacerbate effects of infection by pathogens, with focus on infection by the periodontal bacterium Porphyromonas gingivalis as a running example. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

  8. Pure neuritic leprosy: Current status and relevance

    Directory of Open Access Journals (Sweden)

    P Narasimha Rao

    2016-01-01

    Full Text Available Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.

  9. In Vivo Photoacoustic and Fluorescence Cystography Using Clinically Relevant Dual Modal Indocyanine Green

    Directory of Open Access Journals (Sweden)

    Sungjo Park

    2014-10-01

    Full Text Available Conventional X-ray-based cystography uses radio-opaque materials, but this method uses harmful ionizing radiation and is not sensitive. In this study, we demonstrate nonionizing and noninvasive photoacoustic (PA and fluorescence (FL cystography using clinically relevant indocyanine green (ICG in vivo. After transurethral injection of ICG into rats through a catheter, their bladders were photoacoustically and fluorescently visualized. A deeply positioned bladder below the skin surface (i.e., ~1.5–5 mm was clearly visible in the PA and FL image using a laser pulse energy of less than 2 mJ/cm2 (1/15 of the safety limit. Then, the in vivo imaging results were validated through in situ studies. Our results suggest that dual modal cystography can provide a nonionizing and noninvasive imaging tool for bladder mapping.

  10. Autonomia e relevância dos regimes The autonomy and relevance of regimes

    Directory of Open Access Journals (Sweden)

    Gustavo Seignemartin de Carvalho

    2005-12-01

    Full Text Available Teorias institucionalistas na disciplina de relações internacionais usualmente definem regimes como um conjunto de normas e regras formais ou informais que permitem a convergência de expectativas ou a padronização do comportamento de seus participantes em uma determinada área de interesses com o objetivo de resolver problemas de coordenação que tenderiam a resultados não pareto-eficientes. Como estas definições baseadas meramente na "eficiência" dos regimes não parecem suficientes para explicar sua efetividade, o presente artigo propõe uma definição diferente para regimes: a de arranjos políticos que permitem a redistribuição dos ganhos da cooperação pelos participantes em uma determinada área de interesses em um contexto de interdependência. Regimes possuiriam efetividade pela sua autonomia e relevância, ou seja, por possuírem existência objetiva autônoma da de seus participantes e por influenciarem seu comportamento e expectativas de maneiras que não podem ser reduzidas à ação individual de nenhum deles. O artigo inicia-se com uma breve discussão sobre as dificuldades terminológicas associadas ao estudo de regimes e a definição dos conceitos de autonomia e relevância. Em seguida, classifica os diversos autores participantes do debate em duas perspectivas distintas, uma que nega (não-autonomistas e outra que atribui (autonomistas aos regimes autonomia e relevância, e faz uma breve análise dos autores e tradições mais significativos para o debate, aprofundando-se nos autonomistas e nos argumentos que reforçam a hipótese aqui apresentada. Ao final, o artigo propõe uma decomposição analítica dos regimes nos quatro elementos principais que lhes propiciam autonomia e relevância: normatividade, atores, especificidade da área de interesses e interdependência complexa com o contexto.Regimes are defined by institutionalist theories in the discipline of International Relations as formal or informal sets

  11. Computational Prediction of the Heterodimeric and Higher-Order Structure of gpE1/gpE2 Envelope Glycoproteins Encoded by Hepatitis C Virus.

    Science.gov (United States)

    Freedman, Holly; Logan, Michael R; Hockman, Darren; Koehler Leman, Julia; Law, John Lok Man; Houghton, Michael

    2017-04-15

    Despite the recent success of newly developed direct-acting antivirals against hepatitis C, the disease continues to be a global health threat due to the lack of diagnosis of most carriers and the high cost of treatment. The heterodimer formed by glycoproteins E1 and E2 within the hepatitis C virus (HCV) lipid envelope is a potential vaccine candidate and antiviral target. While the structure of E1/E2 has not yet been resolved, partial crystal structures of the E1 and E2 ectodomains have been determined. The unresolved parts of the structure are within the realm of what can be modeled with current computational modeling tools. Furthermore, a variety of additional experimental data is available to support computational predictions of E1/E2 structure, such as data from antibody binding studies, cryo-electron microscopy (cryo-EM), mutational analyses, peptide binding analysis, linker-scanning mutagenesis, and nuclear magnetic resonance (NMR) studies. In accordance with these rich experimental data, we have built an in silico model of the full-length E1/E2 heterodimer. Our model supports that E1/E2 assembles into a trimer, which was previously suggested from a study by Falson and coworkers (P. Falson, B. Bartosch, K. Alsaleh, B. A. Tews, A. Loquet, Y. Ciczora, L. Riva, C. Montigny, C. Montpellier, G. Duverlie, E. I. Pecheur, M. le Maire, F. L. Cosset, J. Dubuisson, and F. Penin, J. Virol. 89:10333-10346, 2015, https://doi.org/10.1128/JVI.00991-15). Size exclusion chromatography and Western blotting data obtained by using purified recombinant E1/E2 support our hypothesis. Our model suggests that during virus assembly, the trimer of E1/E2 may be further assembled into a pentamer, with 12 pentamers comprising a single HCV virion. We anticipate that this new model will provide a useful framework for HCV envelope structure and the development of antiviral strategies. IMPORTANCE One hundred fifty million people have been estimated to be infected with hepatitis C virus, and

  12. Experiments with positive, negative and topical relevance feedback

    NARCIS (Netherlands)

    Kaptein, R.; Kamps, J.; Li, R.; Hiemstra, D.

    2008-01-01

    This document contains a description of experiments for the 2008 Relevance Feedback track. We experiment with different amounts of feedback, including negative relevance feedback. Feedback is implemented using massive weighted query expansion. Parsimonious query expansion using Dirichlet smoothing

  13. Additive effects of mitochondrion-targeted cytochrome CYP2E1 and alcohol toxicity on cytochrome c oxidase function and stability of respirosome complexes.

    Science.gov (United States)

    Bansal, Seema; Srinivasan, Satish; Anandasadagopan, Sureshkumar; Chowdhury, Anindya Roy; Selvaraj, Venkatesh; Kalyanaraman, Balaraman; Joseph, Joy; Avadhani, Narayan G

    2012-05-04

    Alcohol treatment induces oxidative stress by a combination of increased production of partially reduced oxygen species and decreased cellular antioxidant pool, including GSH. Recently, we showed that mitochondrion-targeted CYP2E1 augments alcohol-mediated toxicity, causing an increase in reactive oxygen species production and oxidative stress. Here, we show that cytochrome c oxidase (CcO), the terminal oxidase of the mitochondrial respiratory chain, is a critical target of CYP2E1-mediated alcohol toxicity. COS-7 and Hep G2 cell lines expressing predominantly mitochondrion-targeted (Mt(++)) CYP2E1 and livers from alcohol-treated rats showed loss of CcO activity and increased protein carbonylation, which was accompanied by a decline in the steady state levels of subunits I, IVI1, and Vb of the CcO complex. This was also accompanied by reduced mitochondrial DNA content and reduced mitochondrial mRNA. These changes were more prominent in Mt(++) cells in comparison with wild type (WT) CYP2E1-expressing or ER(+) (mostly microsome-targeted) cells. In addition, mitochondrion-specific antioxidants, ubiquinol conjugated to triphenyl phosphonium, triphenylphosphonium conjugated carboxyl proxyl, and the CYP2E1 inhibitor diallyl sulfide prevented the loss of CcO activity and the CcO subunits, most likely through reduced oxidative damage to the enzyme complex. Our results suggest that damage to CcO and dissociation of respirosome complexes are critical factors in alcohol-induced toxicity, which is augmented by mitochondrion-targeted CYP2E1. We propose that CcO is one of the direct and immediate targets of alcohol-induced toxicity causing respiratory dysfunction.

  14. Establishment and validation of new complementing cells for production of E1-deleted adenovirus vectors in serum-free suspension culture.

    Science.gov (United States)

    Gilbert, Rénald; Guilbault, Claire; Gagnon, David; Bernier, Alice; Bourget, Lucie; Elahi, Seyyed Mehdy; Kamen, Amine; Massie, Bernard

    2014-11-01

    E1-deleted adenovirus vectors (AdV) are important gene transfer vehicles for gene therapy and vaccination. Amplification of AdV must take place in cells that express the adenovirus E1A and E1B genes. Sequence homology between AdV and the E1 genes integrated within the complementing cells should be minimal to reduce the odds of generating replication-competent adenovirus (RCA). The present study describes the establishment of AdV complementing cells constructed by stable transfection of the minimal E1A and E1B genes into human lung carcinoma (A549). Because some transgene products can be cytotoxic, the cells were engineered to stably express the repressor of the cumate-switch (CymR) to silence transgene transcription during vector growth. For regulatory compliance and to facilitate the scale-up, the resulting complementing cells (SF-BMAdR) were adapted to serum-free suspension culture. The best clone of SF-BMAdR produced AdV carrying an innocuous transgene to the same level as 293 cells, but titers were better for AdV carrying transgene for a cytotoxic product. Elevated titers were maintained for at least two months in suspension culture in the absence of selective agent and the cells did not produce RCA. Because of their advantageous properties, SF-BMAdR cells should become an important tool for developing large-scale production processes of AdV for research and clinical applications. Copyright © 2014. Published by Elsevier B.V.

  15. Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications.

    Science.gov (United States)

    Kumar, Santosh; Sinha, Namita; Gerth, Kelli A; Rahman, Mohammad A; Yallapu, Murali M; Midde, Narasimha M

    2017-09-23

    Cytochrome P450 (CYP) enzymes metabolize the majority of xenobiotics and are mainly found in hepatic and some extra-hepatic cells. However, their presence and functional role in exosomes, small extracellular vesicles that are secreted from various cells into extracellular fluids including plasma, is unknown. In this study, we analyzed the expression and biological activity of CYP enzymes in human plasma exosomes. First, we optimized isolation of plasma exosomes and characterized them for their physical properties and quality. The results showed that the purity of exosomes (exosomal CYP mRNAs, proteins, and enzyme activity. The results showed that the relative level of CYP enzymes in exosomes is higher than in plasma, suggesting their specific packaging in exosomes. Of the seven CYP enzymes tested, the mRNA of CYP1B1, CYP2A6, CYP2E1, and CYP3A4 were detectable in exosomes. Interestingly, the relative level of CYP2E1 mRNA was >500-fold higher than the other CYPs. The results from the Western blot showed detectable levels of CYP1A1, CYP1B1, CYP2A6, CYP2E1, and CYP3A4. Our results also demonstrated that exosomal CYP2E1 and CYP3A4 show appreciable activity relative to their respective positive controls (CYP-induced baculosomes). Our results also showed that CYP2E1 is expressed relatively higher in plasma exosomes than hepatic and monocytic cells and exosomes derived from these cells. In conclusion, this is the first evidence of the specific packaging and circulation of CYP enzymes, especially CYP2E1, in human plasma exosomes. The findings have biological and clinical significance in terms of their implications in cellular communications and potential use of plasma exosomal CYPs as biomarkers. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in mice and antibody production after oral vaccination.

    Science.gov (United States)

    Clarke, Jihong Liu; Paruch, Lisa; Dobrica, Mihaela-Olivia; Caras, Iuliana; Tucureanu, Catalin; Onu, Adrian; Ciulean, Sonya; Stavaru, Crina; Eerde, Andre; Wang, Yanliang; Steen, Hege; Haugslien, Sissel; Petrareanu, Catalina; Lazar, Catalin; Popescu, Costin-Ioan; Bock, Ralph; Dubuisson, Jean; Branza-Nichita, Norica

    2017-12-01

    The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500 000 die yearly from HCV-related liver pathologies. To date, there is no licensed vaccine available to prevent HCV infection and production of a HCV vaccine remains a major challenge. Here, we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium-mediated transient expression technology. The wild-type dimer (E1E2) and a variant without an N-glycosylation site in the E2 polypeptide (E1E2∆N6) were expressed, and appropriate N-glycosylation pattern and functionality of the E1E2 dimers were demonstrated. The humoral immune response induced by the HCV proteins was investigated in mice following oral administration of lettuce antigens with or without previous intramuscular prime with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding only resulted in development of weak serum levels of anti-HCV IgM for both antigens; however, the E1