WorldWideScience

Sample records for heavy-chain isotype patterns

  1. Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity

    DEFF Research Database (Denmark)

    Barington, T; Juul, Lars; Gyhrs, A

    1994-01-01

    The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or D...... of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed....

  2. Evidence for Ig Light Chain Isotype Exclusion in Shark B Lymphocytes Suggests Ordered Mechanisms.

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Haines, Ashley; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2017-09-01

    Unlike most vertebrates, the shark IgL gene organization precludes secondary rearrangements that delete self-reactive VJ rearranged genes. Nurse sharks express four L chain isotypes, κ, λ, σ, and σ-2, encoded by 35 functional minigenes or clusters. The sequence of gene activation/expression and receptor editing of these isotypes have not been studied. We therefore investigated the extent of isotypic exclusion in separated B cell subpopulations. Surface Ig (sIg)κ-expressing cells, isolated with mAb LK14 that recognizes Cκ, carry predominantly nonproductive rearrangements of other L chain isotypes. Conversely, after depletion with LK14, sIgM + cells contained largely nonproductive κ and enrichment for in-frame VJ of the others. Because some isotypic inclusion was observed at the mRNA level, expression in the BCR was examined. Functional λ mRNA was obtained, as expected, from the LK14-depleted population, but was also in sIgκ + splenocytes. Whereas λ somatic mutants from the depleted sample displayed evidence of positive selection, the λ genes in sIgκ + cells accumulated bystander mutations indicating a failure to express their products at the cell surface in association with the BCR H chain. In conclusion, a shark B cell expresses one L chain isotype at the surface and other isotypes as nonproductive VJ, sterile transcripts, or in-frame VJ whose products may not associate with the H chain. Based on the mRNA content found in the B cell subpopulations, an order of L chain gene activation is suggested as: σ-2 followed by κ, then σ and λ. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. A monoclonal antibody distinguishes between two IgM heavy chain isotypes in Atlantic salmon and brown trout: protein characterization, 3D modeling and epitope mapping.

    Science.gov (United States)

    Kamil, Atif; Falk, Knut; Sharma, Animesh; Raae, Arnt; Berven, Frode; Koppang, Erling Olaf; Hordvik, Ivar

    2011-09-01

    Atlantic salmon (Salmo salar) and brown trout (Salmo trutta) possess two distinct subpopulations of IgM which can be separated by anion exchange chromatography. Accordingly, there are two isotypic μ genes in these species, related to ancestral tetraploidy. In the present work it was verified by mass spectrometry that IgM of peak 1 (subpopulation 1) have heavy chains previously designated as μB type whereas IgM of peak 2 (subpopulation 2) have heavy chains of μA type. Two adjacent cysteine residues are present near the C-terminal part of μB, in contrast to one cysteine residue in μA. Salmon IgM of both peak 1 and peak 2 contain light chains of the two most common isotypes: IgL1 and IgL3. In contrast to salmon and brown trout, IgM of rainbow trout (Oncorhynchus mykiss) is eluted in a single peak when subjected to anion exchange chromatography. Surprisingly, a monoclonal antibody MAb4C10 against rainbow trout IgM, reacted with μA in salmon, whereas in brown trout it reacted with μB. It is plausible to assume that DNA has been exchanged between the paralogous A and B loci during evolution while maintaining the two sub-variants, with and without the extra cysteine. MAb4C10 was conjugated to magnetic beads and used to separate cells, demonstrating that μ transcripts residing from captured cells were primarily of A type in salmon and B type in brown trout. An analysis of amino acid substitutions in μA and μB of salmon and brown trout indicated that the third constant domain is essential for MAb4C10 binding. This was supported by 3D modeling and was finally verified by studies of MAb4C10 reactivity with a series of recombinant μ3 constructs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Application of monoclonal antibodies in functional and comparative investigations of heavy-chain immunoglobulins in new world camelids.

    Science.gov (United States)

    Daley, L P; Gagliardo, L F; Duffy, M S; Smith, M C; Appleton, J A

    2005-03-01

    Of the three immunoglobulin G (IgG) isotypes described to occur in camelids, IgG2 and IgG3 are distinct in that they do not incorporate light chains. These heavy-chain antibodies (HCAbs) constitute approximately 50% of the IgG in llama serum and as much as 75% of the IgG in camel serum. We have produced isotype-specific mouse monoclonal antibodies (MAbs) in order to investigate the roles of HCAbs in camelid immunity. Seventeen stable hybridomas were cloned, and three MAbs that were specific for epitopes on the gamma chains of llama IgG1, IgG2, or IgG3 were characterized in detail. Affinity chromatography revealed that each MAb bound its isotype in solution in llama serum. The antibodies bound to the corresponding alpaca IgGs, to guanaco IgG1 and IgG2, and to camel IgG1. Interestingly, anti-IgG2 MAbs bound three heavy-chain species in llama serum, confirming the presence of three IgG2 subisotypes. Two IgG2 subisotypes were detected in alpaca and guanaco sera. The MAbs detected llama serum IgGs when they were bound to antigen in enzyme-linked immunosorbent assays and were used to discern among isotypes induced during infection with a parasitic nematode. Diseased animals, infected with Parelaphostrongylus tenuis, did not produce antigen-specific HCAbs; rather, they produced the conventional isotype, IgG1, exclusively. Our data document the utility of these MAbs in functional and physiologic investigations of the immune systems of New World camelids.

  5. Antibody Heavy Chain Variable Domains of Different Germline Gene Origins Diversify through Different Paths

    Directory of Open Access Journals (Sweden)

    Ufuk Kirik

    2017-11-01

    Full Text Available B cells produce antibodies, key effector molecules in health and disease. They mature their properties, including their affinity for antigen, through hypermutation events; processes that involve, e.g., base substitution, codon insertion and deletion, often in association with an isotype switch. Investigations of antibody evolution define modes whereby particular antibody responses are able to form, and such studies provide insight important for instance for development of efficient vaccines. Antibody evolution is also used in vitro for the design of antibodies with improved properties. To better understand the basic concepts of antibody evolution, we analyzed the mutational paths, both in terms of amino acid substitution and insertions and deletions, taken by antibodies of the IgG isotype. The analysis focused on the evolution of the heavy chain variable domain of sets of antibodies, each with an origin in 1 of 11 different germline genes representing six human heavy chain germline gene subgroups. Investigated genes were isolated from cells of human bone marrow, a major site of antibody production, and characterized by next-generation sequencing and an in-house bioinformatics pipeline. Apart from substitutions within the complementarity determining regions, multiple framework residues including those in protein cores were targets of extensive diversification. Diversity, both in terms of substitutions, and insertions and deletions, in antibodies is focused to different positions in the sequence in a germline gene-unique manner. Altogether, our findings create a framework for understanding patterns of evolution of antibodies from defined germline genes.

  6. Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

    Science.gov (United States)

    Ghiotto, Fabio; Marcatili, Paolo; Tenca, Claudya; Calevo, Maria Grazia; Yan, Xiao-Jie; Albesiano, Emilia; Bagnara, Davide; Colombo, Monica; Cutrona, Giovanna; Chu, Charles C; Morabito, Fortunato; Bruno, Silvia; Ferrarini, Manlio; Tramontano, Anna; Fais, Franco; Chiorazzi, Nicholas

    2011-01-01

    B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV–diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation. PMID:21785810

  7. Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

    KAUST Repository

    Ghiotto, Fabio; Marcatili, Paolo

    2011-01-01

    B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV-diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥ 2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation.

  8. The evolution of multiple isotypic IgM heavy chain genes in the shark.

    Science.gov (United States)

    Lee, Victor; Huang, Jing Li; Lui, Ming Fai; Malecek, Karolina; Ohta, Yuko; Mooers, Arne; Hsu, Ellen

    2008-06-01

    The IgM H chain gene organization of cartilaginous fishes consists of 15-200 miniloci, each with a few gene segments (V(H)-D1-D2-J(H)) and one C gene. This is a gene arrangement ancestral to the complex IgH locus that exists in all other vertebrate classes. To understand the molecular evolution of this system, we studied the nurse shark, which has relatively fewer loci, and characterized the IgH isotypes for organization, functionality, and the somatic diversification mechanisms that act upon them. Gene numbers differ slightly between individuals ( approximately 15), but five active IgM subclasses are always present. Each gene undergoes rearrangement that is strictly confined within the minilocus; in B cells there is no interaction between adjacent loci located > or =120 kb apart. Without combinatorial events, the shark IgM H chain repertoire is based on junctional diversity and, subsequently, somatic hypermutation. We suggest that the significant contribution by junctional diversification reflects the selected novelty introduced by RAG in the early vertebrate ancestor, whereas combinatorial diversity coevolved with the complex translocon organization. Moreover, unlike other cartilaginous fishes, there are no germline-joined VDJ at any nurse shark mu locus, and we suggest that such genes, when functional, are species-specific and may have specialized roles. With an entire complement of IgM genes available for the first time, phylogenetic analyses were performed to examine how the multiple Ig loci evolved. We found that all domains changed at comparable rates, but V(H) appears to be under strong positive selection for increased amino acid sequence diversity, and surprisingly, so does Cmicro2.

  9. Heavy Chain Diseases

    Science.gov (United States)

    ... of heavy chain produced: Alpha Gamma Mu Alpha Heavy Chain Disease Alpha heavy chain disease (IgA heavy ... the disease or lead to a remission. Gamma Heavy Chain Disease Gamma heavy chain disease (IgG heavy ...

  10. Distribution of kappa and lambda light chain isotypes among human blood immunoglobulin-secreting cells after vaccination with pneumococcal polysaccharides

    DEFF Research Database (Denmark)

    Heilmann, C; Barington, T

    1989-01-01

    The light chain isotype of immunoglobulin-secreting blood cells was investigated by means of monolayer plaque-forming cell assays allowing direct immunofluorescence staining for cytoplasmic kappa and lambda light chains in centre cells. The study revealed that cultured, polyclonally activated...

  11. Hotspots for Vitamin-Steroid-Thyroid Hormone Response Elements Within Switch Regions of Immunoglobulin Heavy Chain Loci Predict a Direct Influence of Vitamins and Hormones on B Cell Class Switch Recombination.

    Science.gov (United States)

    Hurwitz, Julia L; Penkert, Rhiannon R; Xu, Beisi; Fan, Yiping; Partridge, Janet F; Maul, Robert W; Gearhart, Patricia J

    2016-03-01

    Vitamin A deficiencies are common throughout the world and have a significant negative influence on immune protection against viral infections. Mouse models demonstrate that the production of IgA, a first line of defense against viruses at mucosal sites, is inhibited in the context of vitamin A deficiency. In vitro, the addition of vitamin A to activated B cells can enhance IgA expression, but downregulate IgE. Previous reports have demonstrated that vitamin A modifies cytokine patterns, and in so doing may influence antibody isotype expression by an indirect mechanism. However, we have now discovered hundreds of potential response elements among Sμ, Sɛ, and Sα switch sites within immunoglobulin heavy chain loci. These hotspots appear in both mouse and human loci and include targets for vitamin receptors and related proteins (e.g., estrogen receptors) in the nuclear receptor superfamily. Full response elements with direct repeats are relatively infrequent or absent in Sγ regions although half-sites are present. Based on these results, we pose a hypothesis that nuclear receptors have a direct effect on the immunoglobulin heavy chain class switch recombination event. We propose that vitamin A may alter S site accessibility to activation-induced deaminase and nonhomologous end-joining machinery, thereby influencing the isotype switch, antibody production, and protection against viral infections at mucosal sites.

  12. The properties of the single chicken MHC classical class II alpha chain (B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules

    DEFF Research Database (Denmark)

    Salomonsen, Jan; Marston, Denise; Avila, David

    2003-01-01

    for the cloning and sequencing of the cDNA. We found only one class II alpha chain transcript, which bears the major features of a classical class II alpha sequence, including the critical peptide-binding residues. The chicken sequence is more similar to human DR than to the DQ, DP, DO or DM isotypes, most...... the mammalian DR and E isotypes in three properties: the presence of the critical peptide-binding residues, the low level of polymorphism and sequence diversity, and the recombinational separation from the class II beta chain genes. These results indicate that the sequence features of this lineage are both......In mammals, there are MHC class II molecules with distinctive sequence features, such as the classical isotypes DR, DQ and DP. These particular isotypes have not been reported in non-mammalian vertebrates. We have isolated the class II (B-L) alpha chain from outbred chickens as the basis...

  13. Biased immunoglobulin light chain gene usage in the shark1

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-01-01

    This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

  14. Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide.

    Science.gov (United States)

    Sanford, J E; Lupan, D M; Schlageter, A M; Kozel, T R

    1990-01-01

    The in vivo properties of an immunoglobulin isotype-switch family of monoclonal antibodies specific for the polysaccharide capsule of Cryptococcus neoformans were examined in a murine model of cryptococcosis. Subclass-switch variants were isolated by sequential sublining of an immunoglobulin G subclass 1 (IgG1)-secreting cell line. Antibodies of the IgG1, IgG2a, and IgG2b isotypes with identical reactivities with cryptococcal polysaccharide were prepared. The antibodies had the distinct biological properties associated with the heavy chains of each respective isotype. The antibodies were used prophylactically or therapeutically in an attempt to alter the course of cryptococcal infection in mice. Survival of mice and a tissue census of the numbers of viable cryptococci in the lung, spleen, and brain were used as indicators of efficacy. Passive immunization with the IgG2a and IgG2b antibodies effected a reduction in the numbers of cryptococci in lung and spleen. Passive immunization with the IgG1 antibody was markedly less effective. Passive immunization had little or no effect on the numbers of cryptococci in brain tissue, regardless of the immunoglobulin isotype. Despite apparent efficacy with regard to reduction in the numbers of yeast cells in the lung and spleen, the results showed no improvement in survival from murine cryptococcosis. Our results indicate that passive immunization produces a modest effect on the course of murine cryptococcosis in tissues other than brain. However, under the experimental conditions used, such treatment does not have a measurable impact on the ultimate outcome of the infection. PMID:2341184

  15. Three IgH isotypes, IgM, IgA and IgY are expressed in Gentoo penguin and zebra finch

    Science.gov (United States)

    Han, Haitang; Zhao, Yaofeng; Pan, Qingjie; Ren, Liming

    2017-01-01

    Previous studies on a limited number of birds suggested that the IgD-encoding gene was absent in birds. However, one of our recent studies showed that the gene was definitely expressed in the ostrich and emu. Interestingly, we also identified subclass diversification of IgM and IgY in these two birds. To better understand immunoglobulin genes in birds, in this study, we analyzed the immunoglobulin heavy chain genes in the zebra finch (Taeniopygia guttata) and Gentoo penguin (Pygoscelis papua), belonging respectively to the order Passeriformes, the most successful bird order in terms of species diversity and numbers, and Sphenisciformes, a relatively primitive avian order. Similar to the results obtained in chickens and ducks, only three genes encoding immunoglobulin heavy chain isotypes, IgM, IgA and IgY, were identified in both species. Besides, we detected a transcript encoding a short membrane-bound IgA lacking the last two CH exons in the Gentoo penguin. We did not find any evidence supporting the presence of IgD gene or subclass diversification of IgM/IgY in penguin or zebra finch. The obtained data in our study provide more insights into the immunoglobulin heavy chain genes in birds and may help to better understand the evolution of immunoglobulin genes in tetrapods. PMID:28403146

  16. Three IgH isotypes, IgM, IgA and IgY are expressed in Gentoo penguin and zebra finch.

    Science.gov (United States)

    Han, Binyue; Li, Yan; Han, Haitang; Zhao, Yaofeng; Pan, Qingjie; Ren, Liming

    2017-01-01

    Previous studies on a limited number of birds suggested that the IgD-encoding gene was absent in birds. However, one of our recent studies showed that the gene was definitely expressed in the ostrich and emu. Interestingly, we also identified subclass diversification of IgM and IgY in these two birds. To better understand immunoglobulin genes in birds, in this study, we analyzed the immunoglobulin heavy chain genes in the zebra finch (Taeniopygia guttata) and Gentoo penguin (Pygoscelis papua), belonging respectively to the order Passeriformes, the most successful bird order in terms of species diversity and numbers, and Sphenisciformes, a relatively primitive avian order. Similar to the results obtained in chickens and ducks, only three genes encoding immunoglobulin heavy chain isotypes, IgM, IgA and IgY, were identified in both species. Besides, we detected a transcript encoding a short membrane-bound IgA lacking the last two CH exons in the Gentoo penguin. We did not find any evidence supporting the presence of IgD gene or subclass diversification of IgM/IgY in penguin or zebra finch. The obtained data in our study provide more insights into the immunoglobulin heavy chain genes in birds and may help to better understand the evolution of immunoglobulin genes in tetrapods.

  17. Mouse myeloma cells that make short immunoglobulin heavy chains: pleiotropic effects on glycosylation and chain assembly

    OpenAIRE

    1984-01-01

    Two variants in immunoglobulin heavy chain production, derived from the MPC 11 mouse myeloma cell line, make short heavy (H) chains with identical precise deletions of the CH3 domain. The CH3 domain is expressed in the H chain mRNA from both variants. Although in vitro translation of this mRNA produces one H chain species, deleted heavy chains are secreted as heavy-light (HL) and H2L2 moieties in contrast to MPC 11, which secretes only H2L2 . The heavy chains of HL apparently contain more car...

  18. Shark Ig light chain junctions are as diverse as in heavy chains.

    Science.gov (United States)

    Fleurant, Marshall; Changchien, Lily; Chen, Chin-Tung; Flajnik, Martin F; Hsu, Ellen

    2004-11-01

    We have characterized a small family of four genes encoding one of the three nurse shark Ig L chain isotypes, called NS5. All NS5 cDNA sequences are encoded by three loci, of which two are organized as conventional clusters, each consisting of a V and J gene segment that can recombine and one C region exon; the third contains a germline-joined VJ in-frame and the fourth locus is a pseudogene. This is the second nurse shark L chain type where both germline-joined and split V-J organizations have been found. Since there are only two rearranging Ig loci, it was possible for the first time to examine junctional diversity in defined fish Ig genes, comparing productive vs nonproductive rearrangements. N region addition was found to be considerably more extensive in length and in frequency than any other vertebrate L chain so far reported and rivals that in H chain. We put forth the speculation that the unprecedented efficiency of N region addition (87-93% of NS5 sequences) may be a result not only of simultaneous H and L chain rearrangement in the shark but also of processing events that afford greater accessibility of the V or J gene coding ends to terminal deoxynucleotidyltransferase.

  19. Somatic hypermutation and junctional diversification at Ig heavy chain loci in the nurse shark.

    Science.gov (United States)

    Malecek, Karolina; Brandman, Julie; Brodsky, Jennie E; Ohta, Yuko; Flajnik, Martin F; Hsu, Ellen

    2005-12-15

    We estimate there are approximately 15 IgM H chain loci in the nurse shark genome and have characterized one locus. It consists of one V, two D, and one J germline gene segments, and the constant (C) region can be distinguished from all of the others by a unique combination of restriction endonuclease sites in Cmu2. On the basis of these Cmu2 markers, 22 cDNA clones were selected from an epigonal organ cDNA library from the same individual; their C region sequences proved to be the same up to the polyadenylation site. With the identification of the corresponding germline gene segments, CDR3 from shark H chain rearrangements could be analyzed precisely, for the first time. Considerable diversity was generated by trimming and N addition at the three junctions and by varied recombination patterns of the two D gene segments. The cDNA sequences originated from independent rearrangements events, and most carried both single and contiguous substitutions. The 53 point mutations occurred with a bias for transition changes (53%), whereas the 78 tandem substitutions, mostly 2-4 bp long, do not (36%). The nature of the substitution patterns is the same as for mutants from six loci of two nurse shark L chain isotypes, showing that somatic hypermutation events are very similar at both H and L chain genes in this early vertebrate. The cis-regulatory elements targeting somatic hypermutation must have already existed in the ancestral Ig gene, before H and L chain divergence.

  20. Three IgH isotypes, IgM, IgA and IgY are expressed in Gentoo penguin and zebra finch.

    Directory of Open Access Journals (Sweden)

    Binyue Han

    Full Text Available Previous studies on a limited number of birds suggested that the IgD-encoding gene was absent in birds. However, one of our recent studies showed that the gene was definitely expressed in the ostrich and emu. Interestingly, we also identified subclass diversification of IgM and IgY in these two birds. To better understand immunoglobulin genes in birds, in this study, we analyzed the immunoglobulin heavy chain genes in the zebra finch (Taeniopygia guttata and Gentoo penguin (Pygoscelis papua, belonging respectively to the order Passeriformes, the most successful bird order in terms of species diversity and numbers, and Sphenisciformes, a relatively primitive avian order. Similar to the results obtained in chickens and ducks, only three genes encoding immunoglobulin heavy chain isotypes, IgM, IgA and IgY, were identified in both species. Besides, we detected a transcript encoding a short membrane-bound IgA lacking the last two CH exons in the Gentoo penguin. We did not find any evidence supporting the presence of IgD gene or subclass diversification of IgM/IgY in penguin or zebra finch. The obtained data in our study provide more insights into the immunoglobulin heavy chain genes in birds and may help to better understand the evolution of immunoglobulin genes in tetrapods.

  1. Biased Immunoglobulin Light Chain Gene Usage in the Shark.

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-10-15

    This study of a large family of κ L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, μ and ω, and four L chain isotypes, κ, λ, σ, and σ-2). The shark κ clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an ~500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ~39 κ clusters are prerearranged in the germline (germline joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, nonproductive, and sterile transcripts of the κ clusters compared with the other three L chain isotypes. κ cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and nonproductive rearrangements. These results show that the individual activation of the spatially distant κ clusters is nonrandom. Although both split and germline-joined κ genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. Copyright © 2015 by The American Association of Immunologists, Inc.

  2. Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exchange induced by a universal gene replacement vector.

    Science.gov (United States)

    Kardinal, C; Selmayr, M; Mocikat, R

    1996-11-01

    Gene targeting at the immunoglobulin loci of B cells is an efficient tool for studying immunoglobulin expression or generating chimeric antibodies. We have shown that vector integration induced by human immunoglobulin G1 (IgG1) insertion vectors results in subsequent vector excision mediated by the duplicated target sequence, whereas replacement events which could be induced by the same constructs remain stable. We could demonstrate that the distribution of the vector homology strongly influences the genetic stability obtained. To this end we developed a novel type of a heavy chain replacement vector making use of the heavy chain class switch recombination sequence. Despite the presence of a two-sided homology this construct is universally applicable irrespective of the constant gene region utilized by the B cell. In comparison to an integration vector the frequency of stable incorporation was strongly increased, but we still observed vector excision, although at a markedly reduced rate. The latter events even occurred with circular constructs. Linearization of the construct at various sites and the comparison with an integration vector that carries the identical homology sequence, but differs in the distribution of homology, revealed the following features of homologous recombination of immunoglobulin genes: (i) the integration frequency is only determined by the length of the homology flank where the cross-over takes place; (ii) a 5' flank that does not meet the minimum requirement of homology length cannot be complemented by a sufficient 3' flank; (iii) free vector ends play a role for integration as well as for replacement targeting; (iv) truncating recombination events are suppressed in the presence of two flanks. Furthermore, we show that the switch region that was used as 3' flank is non-functional in an inverted orientation.

  3. Multiple nuclear dots and rim-like/membranous IgG isotypes in primary biliary cirrhosis.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Ferri, Silvia; Pappas, Georgios; Volta, Umberto; Menichella, Rita; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi

    2009-03-01

    Anti nuclear (ANA) immunomorphological patterns such as multiple nuclear dots (MND) and rim-like/membranous (RL/M) are considered highly specific but little sensitive for primary biliary cirrhosis (PBC) diagnosis. To evaluate frequency and clinical significance of MND and RL/M in PBC patients when investigated at the level of immunoglobulin G isotypes. MND and RL/M pattern have been tested in 141 PBC sera and 230 pathological controls using HEp-2 cells as substrate and anti- total IgG and individual IgG subclasses (IgG1, IgG2, IgG3, IgG4) as specific antisera. One hundred and fourteen of 141 (80%) PBC patients had RL/M or MND pattern when IgG subclasses were used as revealing reagents (vs. 34% when anti total IgG were used, p < 0.0001). The prevalent isotype was IgG1 for RL/M, and IgG2 for MND pattern. None of controls was positive. No clinical differences in terms of severity and outcome of disease have been observed in PBC patients positive for MND and RL/M when investigated with IgG isotypes. The research for RL/M and MND pattern at level of IgG isotype determines a wide gain in terms of sensitivity without a loss of specificity. In Italian PBC patients MND and RL/M pattern did not seem to characterize any subgroup of patients with a poorer prognosis.

  4. Comparative analysis of novel autoantibody isotypes against citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)(542-556) peptide in serum from Taiwanese females with rheumatoid arthritis, primary Sjögren's syndrome and secondary Sjögren's syndrome in rheumatoid arthritis.

    Science.gov (United States)

    Liao, Chen-Chung; Chou, Pei-Lun; Cheng, Chao-Wen; Chang, Yu-Sheng; Chi, Wei-Ming; Tsai, Kai-Leun; Chen, Wei-Jung; Kung, Ting-Shuan; Tai, Chih-Chun; Lee, Kuan-Wei; Chen, You-Chia; Lin, Ching-Yu

    2016-06-01

    The purpose of this study was to discover and validate inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) as novel biomarkers, and evaluate autoantibody isotypes against an unmodified and citrullinated ITIH3(542-556) peptide among Taiwanese female patients with rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), secondary Sjögren's syndrome in rheumatoid arthritis (RA-sSS), and healthy controls (HCs). We used concanavalin A (Con A) affinity chromatography, 1-D SDS-PAGE, and label-free nano-LC-MS/MS to screen biomarker candidates (serum-derived Con A-captured proteins) and then identify PTMs of validated biomarkers (serum proteins) using pooled serum from 7 RA-sSS female patients and 7 age-matched HCs (the discovery set). Furthermore, the protein level and autoantibody isotype analyses were further validated against individual serum from 18 HCs, 18 RA, 18 pSS, and 18 RA-sSS patients (the validation set). Con A-bound ITIH3 was identified and validated as the only differentially expressed protein, which was elevated. Additionally, 2 novel PTMs in ITIH3 were identified and included citrullination at arginine-(546) and arginine-(556), and hexosamine at tryptophan-(558). Further, concentrations of anti-citrullinatd-ITIH3(542-556) peptide autoantibodies significantly increased in patients with RA, pSS, and RA-sSS compared to HCs. Especially, autoantibody IgM against the citrullinated-ITIH3(542-556) peptide showed better diagnostic performance in discriminating both RA versus pSS and pSS versus RA-sSS. By using comparative proteomic analysis of serum samples, the current study discovered and validates differentially expressed Con A-bound ITIH3 as a potential biomarker for secondary Sjögren's syndrome (SS) in rheumatoid arthritis (RA) patients and healthy controls (HCs). Besides, hexosamine and citrullination on ITIH3 were further identified. Through analyzing autoantibody isotypes against the citrullinated ITIH3 peptide, patients with RA, primary SS, and RA

  5. Excessive amounts of mu heavy chain block B-cell development.

    Science.gov (United States)

    Zhu, Lingqiao; Chang, Cheong-Hee; Dunnick, Wesley

    2011-09-01

    Antigen-independent B-cell development occurs in several stages that depend on the expression of Ig heavy and light chain. We identified a line of mice that lacked mature B cells in the spleen. This mouse line carried approximately 11 copies of a transgene of the murine heavy chain constant region locus, and B-lineage cells expressed excessive amounts of the intracellular μ heavy chain. B-cell development failed in the bone marrow at the pro/pre B-cell transition, and examination of other lines with various copy numbers of the same transgene suggested that deficiencies in B-cell development increased with increased transgene copy number. Expression of a transgenic (Tg) light chain along with the Tg μ heavy chain led to minimal rescue of B-cell development in the bone marrow and B cells in the spleen. There are several potential mechanisms for the death of pro/pre B cells as a consequence of excess heavy chain expression.

  6. Heavy chain only antibodies

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

  7. Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome.

    Science.gov (United States)

    Wang, Chen; Su, Wei; Cai, Qian-Qian; Cai, Hao; Ji, Wei; Di, Qian; Duan, Ming-Hui; Cao, Xin-Xin; Zhou, Dao-Bin; Li, Jian

    2016-07-01

    POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain (HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis (P = 0.021; hazard ratio [HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival (P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna

    2011-03-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  9. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-01-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  10. Ikaros controls isotype selection during immunoglobulin class switch recombination.

    Science.gov (United States)

    Sellars, MacLean; Reina-San-Martin, Bernardo; Kastner, Philippe; Chan, Susan

    2009-05-11

    Class switch recombination (CSR) allows the humoral immune response to exploit different effector pathways through specific secondary antibody isotypes. However, the molecular mechanisms and factors that control immunoglobulin (Ig) isotype choice for CSR are unclear. We report that deficiency for the Ikaros transcription factor results in increased and ectopic CSR to IgG(2b) and IgG(2a), and reduced CSR to all other isotypes, regardless of stimulation. Ikaros suppresses active chromatin marks, transcription, and activation-induced cytidine deaminase (AID) accessibility at the gamma2b and gamma2a genes to inhibit class switching to these isotypes. Further, Ikaros directly regulates isotype gene transcription as it directly binds the Igh 3' enhancer and interacts with isotype gene promoters. Finally, Ikaros-mediated repression of gamma2b and gamma2a transcription promotes switching to other isotype genes by allowing them to compete for AID-mediated recombination at the single-cell level. Thus, our results reveal transcriptional competition between constant region genes in individual cells to be a critical and general mechanism for isotype specification during CSR. We show that Ikaros is a master regulator of this competition.

  11. Heavy subgraph pairs for traceability of block-chains

    Directory of Open Access Journals (Sweden)

    Li Binlong

    2014-05-01

    Full Text Available A graph is called traceable if it contains a Hamilton path, i.e., a path containing all its vertices. Let G be a graph on n vertices. We say that an induced subgraph of G is o−1-heavy if it contains two nonadjacent vertices which satisfy an Ore-type degree condition for traceability, i.e., with degree sum at least n−1 in G. A block-chain is a graph whose block graph is a path, i.e., it is either a P1, P2, or a 2-connected graph, or a graph with at least one cut vertex and exactly two end-blocks. Obviously, every traceable graph is a block-chain, but the reverse does not hold. In this paper we characterize all the pairs of connected o−1-heavy graphs that guarantee traceability of block-chains. Our main result is a common extension of earlier work on degree sum conditions, forbidden subgraph conditions and heavy subgraph conditions for traceability

  12. Diversity Analysis of the Immunoglobulin M Heavy Chain Gene in ...

    African Journals Online (AJOL)

    A full-length cDNA encoding the immunoglobulin (IgM) heavy chain gene of Nile tilapia was successfully cloned using the 5' and 3' RACE techniques. The complete cDNA of the Nile tilapia IgM heavy chain gene is 1,921 bp in length and has an open reading frame (ORF) of 1,740 bp, which corresponds to 580 amino acid ...

  13. Characterization of the interaction between the heavy and light chains of bovine factor Va.

    Science.gov (United States)

    Walker, F J

    1992-10-05

    Bovine factor Va has been previously been shown to consist of heavy (M(r) = 94,000) and light chains (M(r) = 81,000), that interact in a manner dependent upon the presence of either calcium or manganese ions. In an attempt to understand the mechanism of subunit interaction we have studied the effects of temperature and ions on factor Va stability. The rates of formation of factor Va from isolated chains and dissociation were temperature-dependent with an energy of activation of 6.2 and 1.3 kcal mol-1, respectively. The yield of factor Va from isolated chains was inversely related to the amount of time the chains were incubated at 4 degrees C. Incubation of individual chains revealed that the heavy chain is cold-labile, an effect that is reversible. Manganese ion was observed to prevent the conversion to the inactive form. High salt tends to stabilize the two-chain structure of factor Va, but is inhibitory to its formation from isolated chains. High concentrations of either manganese or calcium ions also inhibited reconstitution of activity. The light chain, in particular, was sensitive to the presence of manganese or calcium ion. Heavy chain that had been cleaved by activated protein C had a weakened interaction with the light chain, and the resulting complex had no procoagulant activity. Cooling of the heavy chain to 4 degrees C enhanced its intrinsic fluorescence. Manganese ion prevented some of this enhancement. The heavy chain fluorescence returned to the room temperature value with a half-life of approximately 10 min. In the presence of manganese ion relaxation was accelerated. The intrinsic fluorescence of activated protein C-cleaved heavy chain was not increased when the temperature was decreased. These data suggest that the heavy chain can exist in two forms. Elevated temperature converts it to a form that can bind ions and have a productive interaction with the light chain. However, conditions that prevent the heavy chain from combining with the light

  14. The generation and selection of single-domain, v region libraries from nurse sharks.

    Science.gov (United States)

    Flajnik, Martin F; Dooley, Helen

    2009-01-01

    The cartilaginous fish (sharks, skates, and rays) are the oldest phylogenetic group in which a human-type adaptive immune system and immunoglobulins (Igs) have been found. In addition to their conventional (heavy-light chain heterodimeric) isotypes, IgM and IgW, sharks produce the novel isotype, IgNAR, a heavy chain homodimer that does not associate with light chains. Instead, its variable (V) regions act as independent, soluble units in order to bind antigen. In this chapter, we detail our immunization protocol in order to raise a humoral IgNAR response in the nurse shark (Ginglymostoma cirratum) and the subsequent cloning of the single-domain V regions from this isotype in order to select antigen-specific binders by phage display.

  15. Determination of allergen specificity by heavy chains in grass pollen allergen-specific IgE antibodies.

    Science.gov (United States)

    Gadermaier, Elisabeth; Flicker, Sabine; Lupinek, Christian; Steinberger, Peter; Valenta, Rudolf

    2013-04-01

    Affinity and clonality of allergen-specific IgE antibodies are important determinants for the magnitude of IgE-mediated allergic inflammation. We sought to analyze the contribution of heavy and light chains of human allergen-specific IgE antibodies for allergen specificity and to test whether promiscuous pairing of heavy and light chains with different allergen specificity allows binding and might affect affinity. Ten IgE Fabs specific for 3 non-cross-reactive major timothy grass pollen allergens (Phl p 1, Phl p 2, and Phl p 5) obtained by means of combinatorial cloning from patients with grass pollen allergy were used to construct stable recombinant single chain variable fragments (ScFvs) representing the original Fabs and shuffled ScFvs in which heavy chains were recombined with light chains from IgE Fabs with specificity for other allergens by using the pCANTAB 5 E expression system. Possible ancestor genes for the heavy chain and light chain variable region-encoding genes were determined by using sequence comparison with the ImMunoGeneTics database, and their chromosomal locations were determined. Recombinant ScFvs were tested for allergen specificity and epitope recognition by means of direct and sandwich ELISA, and affinity by using surface plasmon resonance experiments. The shuffling experiments demonstrate that promiscuous pairing of heavy and light chains is possible and maintains allergen specificity, which is mainly determined by the heavy chains. ScFvs consisting of different heavy and light chains exhibited different affinities and even epitope specificity for the corresponding allergen. Our results indicate that allergen specificity of allergen-specific IgE is mainly determined by the heavy chains. Different heavy and light chain pairings in allergen-specific IgE antibodies affect affinity and epitope specificity and thus might influence clinical reactivity to allergens. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by

  16. Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide.

    Science.gov (United States)

    Schlageter, A M; Kozel, T R

    1990-06-01

    A family of immunoglobulin isotype-switch variants was isolated by sib selection from a murine hybridoma which produced an immunoglobulin G subclass 1 (IgG1) antibody specific for the capsular polysaccharide of Cryptococcus neoformans. Antibodies of the IgG1, IgG2a, and IgG2b isotypes had similar serotype specificity patterns in double immunodiffusion assays which used polysaccharides of the four cryptococcal serotypes as antigens. A quantitative difference in the ability of the isotypes to form a precipitate with the polysaccharide was observed in a double immunodiffusion assay and confirmed in a quantitative precipitin assay. The relative precipitating activity of the antibodies was IgG2a greater than IgG1 much greater than IgG2b. Analysis by enzyme-linked immunosorbent assay of the reactivity of the three isotypes with cryptococcal polysaccharide showed identical titers and slopes, suggesting that the variable region of the class-switch antibodies was unaltered. This system allowed us to examine the effect of the Fc portion of the antibody on opsonization of encapsulated cryptococci. Yeast cells were precoated with antibodies of each isotype and incubated with murine macrophages or cultured human monocytes. Antibodies of all three isotypes exhibited a dose-dependent opsonization for phagocytosis by both human and murine phagocytes. The relative opsonic activity of the antibodies was IgG2a greater than IgG1 greater than IgG2b.

  17. Tubulointerstitial nephritis accompanying gamma-heavy chain deposition and gamma-heavy chain restricted plasma cells in the kidney.

    Science.gov (United States)

    Nayer, Ali; Green, Dollie F; Gonzalez-Suarez, Maria L; Sujoy, Victoria; Ikpatt, Offiong F; Thomas, David B

    2014-09-01

    Monoclonal immunoglobulin heavy chain (HC) diseases are rare proliferative disorders of B lymphocytes or plasma cells characterized by the presence of monoclonal α-, µ-, or γ-HC without associated light chains in the blood, urine, or both. We report a 59-year-old woman with a history of Hodgkin disease who developed hypercalcemia, proteinuria, and impaired kidney function. Protein electrophoresis and immunofixation displayed γ-HC without associated light chains in the serum and urine. Pathologic examination demonstrated severe tubulointerstitial nephritis associated with diffuse and strong linear staining of the glomerular and tubular basement membranes as well as Bowman capsules for γ-HC, but not for κ- or λ-light chains. Immunohistochemical examination of the kidney and bone marrow demonstrated numerous CD138+ plasma cells immunoreactive for γ-HC, but not for κ- or λ-light chains. This is the first report of tubulointerstitial nephritis associated with γ-HC deposition and γ-HC restricted plasma cells in the kidney. This report heightens awareness about tubulointerstitial nephritis as a possible manifestation of γ-HC deposition in the kidney.

  18. Stability of llama heavy chain antibody fragments under extreme conditions

    NARCIS (Netherlands)

    Dolk, E.

    2004-01-01

    Camelids have next to their normal antibodies, a unique subset of antibodies lacking light chains. The resulting single binding domain, VHH, of these heavy chain antibodies consequently have unique properties. A high stability is one of these properties, which was investigated in this thesis. The

  19. Ku70 is required for late B cell development and immunoglobulin heavy chain class switching.

    Science.gov (United States)

    Manis, J P; Gu, Y; Lansford, R; Sonoda, E; Ferrini, R; Davidson, L; Rajewsky, K; Alt, F W

    1998-06-15

    Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70(-/-) (K70T) mice, like recombination activating gene (RAG)-1- or RAG-2-deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et al. 1997. Immunity. 7:653-665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. J. Exp. Med. 186:921-929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig lambda light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325-332). K70T/HL mice had significant numbers of peripheral surface IgM+ B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have

  20. Acquired cutis laxa associated with light and heavy chain deposition disease

    Directory of Open Access Journals (Sweden)

    Reena A Majithia

    2018-01-01

    Full Text Available Acquired cutis laxa (ACL is a rare connective tissue disorder characterized by pendulous and coarsely wrinkled skin. There have been few cases of its association to monoclonal immunoglobulin deposition disease (MIDD, which constitutes the light chain (LCDD, heavy chain (HCDD, and light and heavy chain (LHCDD deposition disease. MIDD predominantly involves the kidney. Skin is the next common organ to be affected by HCDD, which presents as ACL. We report the case of a 40-year-old male who presented with ACL associated with LHCDD. The clinical features of ACL in the present case appeared prior to the development of clinical features related to LHCDD.

  1. Diversity analysis of the immunoglobulin M heavy chain gene in Nile ...

    African Journals Online (AJOL)

    nu tom

    2015-07-22

    Jul 22, 2015 ... related industries and supply chains, such as hatcheries, feed manufacturers ... system has a high risk of disease outbreaks. The bulk of ...... immunoglobulin heavy-chain locus in zebrafish: identification and expression of a ...

  2. Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease.

    Science.gov (United States)

    Priyamvada, P S; Morkhandikar, S; Srinivas, B H; Parameswaran, S

    2015-01-01

    Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda) AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

  3.  Variable fragments of heavy chain antibodies (VHHs: a new magic bullet molecule of medicine?

    Directory of Open Access Journals (Sweden)

    Dorota Smolarek

    2012-06-01

    Full Text Available  Serum of animals belonging to the Camelidae family (camels and llamas contains fully active antibodies that are naturally devoid of light chains. Variable domains derived from heavy chain antibodies (hcAb called VHHs or nanobodies™ can bind antigens as effectively as full-length antibodies and are easy to clone and express. Because of their potential, VHHs are being intensively studied as potential therapeutic, diagnostic and imaging tools. The paper reviews the molecular background of heavy chain antibodies and describes methods of obtaining recombinant fragments of heavy chain antibodies as well as their therapeutic, diagnostic and other applications.

  4. Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease

    Directory of Open Access Journals (Sweden)

    P S Priyamvada

    2015-01-01

    Full Text Available Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig light chains. In heavy chain amyloidosis (AH, deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL, the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

  5. Tubulin-isotype analysis of two grass species-resistant to dinitroaniline herbicides.

    Science.gov (United States)

    Waldin, T R; Ellis, J R; Hussey, P J

    1992-09-01

    Trifluralin-resistant biotypes of Eleusine indica (L.) Gaertn. (goosegrass) and Setaria viridis (L.) Beauv. (green foxtail) exhibit cross-resistance to other dinitroaniline herbicides. Since microtubules are considered the primary target site for dinitroaniline herbicides we investigated whether the differential sensitivity of resistant and susceptible biotypes of these species results from modified tubulin polypeptides. One-dimensional and two-dimensional polyacrylamide gel electrophoresis combined with immunoblotting using well-characterised anti-tubulin monoclonal antibodies were used to display the family of tubulin isotypes in each species. Seedlings of E. indica exhibited four β-tubulin isotypes and one α-tubulin isotype, whereas those of S. viridis exhibited two β-tubulin and two α-tubulin isotypes. Comparison of the susceptible and resistant biotypes within each species revealed no differences in electrophoretic properties of the multiple tubulin isotypes. These results provide no evidence that resistance to dinitroaniline herbicides is associated with a modified tubulin polypeptide in these biotypes of E. indica or S. viridis.

  6. Purification and characterization of parvalbumin isotypes from grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Li, Zheng; You, Juan; Luo, Yongkang; Wu, Jianping

    2014-07-02

    The prevalence of fish allergy is rapidly increasing because of a growing fish consumption driven mainly by a positive image of the fish and health relationship. The purpose of this study was to characterize parvalbumin isotypes from grass carp (Ctenopharyngodon idella), one of the most frequently consumed freshwater fish in China. Three parvalbumin isotypes were purified using consecutive gel filtration and reverse-phase chromatography and denoted as PVI, PVII, and PVIII. The molecular weights of the isotypes were determined to be 11.968, 11.430, and 11.512 kDa, respectively. PVI showed 74% matched amino acids sequence with PV isotype 4a from Danio rerio, while PVII and PVIII showed 46% matched amino acids sequence with PV isotypes from Hypophthalmichthys molitrix. PVII is the dominant allergen, but it was liable to gastrointestinal enzymes as PVIII; however, PVI was resistant to pepsin digestion. A further study is to characterize the epitopes of PVII, the dominant allergen.

  7. Isotype by Otto Neurath

    Directory of Open Access Journals (Sweden)

    Malysheva O. A.

    2016-04-01

    Full Text Available the article deals with the theoretical basis of the infographic and its practical impact on the person’s attention by the example of the book of Otto Neurath's about the international pictorial language. This shows the relevance of design methods of Isotype system and its influence on modern infographic.

  8. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics

    Directory of Open Access Journals (Sweden)

    Peter Bannas

    2017-11-01

    Full Text Available Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL. The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL. VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv. scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa and nanobody-based human heavy chain antibodies (75 kDa can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb. Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo. Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo. Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody

  9. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics.

    Science.gov (United States)

    Bannas, Peter; Hambach, Julia; Koch-Nolte, Friedrich

    2017-01-01

    Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv). scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa) and nanobody-based human heavy chain antibodies (75 kDa) can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb). Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo . Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo . Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody-based human heavy

  10. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna

    2011-06-28

    The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen.

  11. The motion planning problem and exponential stabilization of a heavy chain. Part II

    OpenAIRE

    Piotr Grabowski

    2008-01-01

    This is the second part of paper [P. Grabowski, The motion planning problem and exponential stabilization of a heavy chain. Part I, to appear in International Journal of Control], where a model of a heavy chain system with a punctual load (tip mass) in the form of a system of partial differential equations was interpreted as an abstract semigroup system and then analysed on a Hilbert state space. In particular, in [P. Grabowski, The motion planning problem and exponential stabilization of a h...

  12. Clathrin Heavy Chain Is Important for Viability, Oviposition, Embryogenesis and, Possibly, Systemic RNAi Response in the Predatory Mite Metaseiulus occidentalis

    Science.gov (United States)

    Wu, Ke; Hoy, Marjorie A.

    2014-01-01

    Clathrin heavy chain has been shown to be important for viability, embryogenesis, and RNA interference (RNAi) in arthropods such as Drosophila melanogaster. However, the functional roles of clathrin heavy chain in chelicerate arthropods, such as the predatory mite Metaseiulus occidentalis, remain unknown. We previously showed that dsRNA ingestion, followed by feeding on spider mites, induced systemic and robust RNAi in M. occidentalis females. In the current study, we performed a loss-of-function analysis of the clathrin heavy chain gene in M. occidentalis using RNAi. We showed that ingestion of clathrin heavy chain dsRNA by M. occidentalis females resulted in gene knockdown and reduced longevity. In addition, clathrin heavy chain dsRNA treatment almost completely abolished oviposition by M. occidentalis females and the few eggs produced did not hatch. Finally, we demonstrated that clathrin heavy chain gene knockdown in M. occidentalis females significantly reduced a subsequent RNAi response induced by ingestion of cathepsin L dsRNA. The last finding suggests that clathrin heavy chain may be involved in systemic RNAi responses mediated by orally delivered dsRNAs in M. occidentalis. PMID:25329675

  13. Dynein Heavy Chain, Encoded by Two Genes in Agaricomycetes, Is Required for Nuclear Migration in Schizophyllum commune.

    Directory of Open Access Journals (Sweden)

    Melanie Brunsch

    Full Text Available The white-rot fungus Schizophyllum commune (Agaricomycetes was used to study the cell biology of microtubular trafficking during mating interactions, when the two partners exchange nuclei, which are transported along microtubule tracks. For this transport activity, the motor protein dynein is required. In S. commune, the dynein heavy chain is encoded in two parts by two separate genes, dhc1 and dhc2. The N-terminal protein Dhc1 supplies the dimerization domain, while Dhc2 encodes the motor machinery and the microtubule binding domain. This split motor protein is unique to Basidiomycota, where three different sequence patterns suggest independent split events during evolution. To investigate the function of the dynein heavy chain, the gene dhc1 and the motor domain in dhc2 were deleted. Both resulting mutants were viable, but revealed phenotypes in hyphal growth morphology and mating behavior as well as in sexual development. Viability of strain Δdhc2 is due to the higher expression of kinesin-2 and kinesin-14, which was proven via RNA sequencing.

  14. Detection of clonal immunoglobulin heavy chain gene rearrangements by the polymerase chain reaction and capillary gel electrophoresis.

    Science.gov (United States)

    Fan, Hongxin; Robetorye, Ryan S

    2013-01-01

    Although well-established diagnostic criteria exist for mature B-cell neoplasms, a definitive diagnosis of a B-cell lymphoproliferative disorder cannot always be obtained using more conventional techniques such as flow cytometric immunophenotyping, conventional cytogenetics, fluorescence in situ hybridization, or immunohistochemistry. However, because B-cell malignancies contain identically rearranged immunoglobulin heavy chain genes, the polymerase chain reaction (PCR) can be a fast, convenient, and dependable option to identify clonal B-cell processes. This chapter describes the use of PCR and capillary electrophoresis to identify clonal immunoglobulin heavy chain (IGH) variable and joining region (VH-JH) gene rearrangements (IGH VH-JH PCR) using a commercially available method employing multiple multiplex PCR tubes that was originally developed as the result of a large European BIOMED-2 collaborative study (Invivoscribe Technologies). The core protocol involves the use of three separate master mix tubes that target the conserved framework (FR1, FR2, and FR3) and joining (J) regions of the IGH gene. Analysis of these three framework regions can detect approximately 88% of clonal IGH gene rearrangements.

  15. Complement component C1r mediated cleavage of the heavy chain of the major histocompatibility class I antigens

    DEFF Research Database (Denmark)

    Eriksson, H; Nissen, Mogens Holst

    1992-01-01

    Apart from cleaving C1s, we demonstrate for the first time that: 1) at concentrations found in serum, the activated forms of the complement components C1r in addition to C1s can cleave the heavy chain of MHC class I antigens, 2) the cleavage by C1r and C1s is seemingly dependent upon a native con......-chain of MHC class I was shown to take place between the alpha 2- and alpha 3- domains as estimated by the Con A-Sepharose precipitation pattern on SDS-PAGE. The alpha 1/alpha 2 fragment was still shown to interact with beta 2-microglobulin as shown by immunoprecipitation....

  16. Direct photoaffinity labeling by nucleotides of the apparent catalytic site on the heavy chains of smooth muscle and Acanthamoeba myosins

    International Nuclear Information System (INIS)

    Maruta, H.; Korn, E.D.

    1981-01-01

    The heavy chains of Acanthamoeba myosins, IA, IB and II, turkey gizzard myosin, and rabbit skeletal muscle myosin subfragment-1 were specifically labeled by radioactive ATP, ADP, and UTP, each of which is a substrate or product of myosin ATPase activity, when irradiated with uv light at 0 0 C. With UTP, as much as 0.45 mol/mol of Acanthamoeba myosin IA heavy chain and 1 mol/mol of turkey gizzard myosin heavy chain was incorporated. Evidence that the ligands were associated with the catalytic site included the observations that reaction occurred only with nucleotides that are substrates or products of the ATPase activity; that the reaction was blocked by pyrophosphate which is an inhibitor of the ATPase activity; that ATP was bound as ADP; and that label was probably restricted to a single peptide following limited subtilisin proteolysis of labeled Acanthamoeba myosin IA heavy chain and extensive cleavage with CNBr and trypsin of labeled turkey gizzard myosin heavy chain

  17. Porcine circovirus type 2 ORF4 protein binds heavy chain ferritin

    Indian Academy of Sciences (India)

    Porcine circovirus type 2 ORF4 protein binds heavy chain ferritin. Qizhuang Lv Kangkang Guo Tao Wang ... Keywords. Cellular protein; FHC; ORF4 protein; porcine circovirus type 2 (PCV2); yeast two-hybrid ... Journal of Biosciences | News ...

  18. Increased incidence of transient homogeneous immunoglobulins in irradiated and reconstituted C57BL/KaLwRij mice treated with 2'-deoxyguanosine

    International Nuclear Information System (INIS)

    Akker, Th.W. van den; Gillen, A.P.; Bril, H.; Brenner, R.; Radl, J.

    1983-01-01

    Prolonged administration of micromolar amounts of 2'-deoxyguanosine (dGuo) to lethally irradiated and reconstituted mice led to an increased incidence of transient homogeneous immunoglobulins (H-Ig) in their sera. Analysis of the heavy and light chain isotype distribution among the H-Ig revealed more of the IgG2b and IgG3 isotypes and less of the IgM isotype and the lambda light chain containing H-Ig in the dGuo-treated group as compared to the control group. The increased incidence of H-Ig was preceded by a decreased suppressor T cell generation and activation in the dGuo treated group. These data indicate that deficient suppressor T cell plays an important role in the development of transient H-Ig. (author)

  19. Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

    Directory of Open Access Journals (Sweden)

    Robert D. Bremel

    2014-10-01

    Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

  20. Myosin heavy chain expression in rabbit masseter muscle during postnatal development

    NARCIS (Netherlands)

    Bredman, J. J.; Weijs, W. A.; Korfage, H. A.; Brugman, P.; Moorman, A. F.

    1992-01-01

    The expression of isoforms of myosin heavy chain (MHC) during postnatal development was studied in the masseter muscle of the rabbit. Evidence is presented that in addition to adult fast and slow myosin, the rabbit masseter contains neonatal and 'cardiac' alpha-MHC. During postnatal growth myosin

  1. Heritability of antibody isotype and subclass responses to Plasmodium falciparum antigens.

    Directory of Open Access Journals (Sweden)

    Nancy O Duah

    2009-10-01

    Full Text Available It is important to understand the extent to which genetic factors regulate acquired immunity to common infections. A classical twin study design is useful to estimate the heritable component of variation in measurable immune parameters.This study assessed the relative heritability of different plasma antibody isotypes and subclasses (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE naturally acquired to P. falciparum blood stage antigens AMA1, MSP1-19, MSP2 (two allelic types and MSP3 (two allelic types. Separate analyses were performed on plasma from 213 pairs of Gambian adult twins, 199 child twin pairs sampled in a dry season when there was little malaria transmission, and another set of 107 child twin pairs sampled at the end of the annual wet season when malaria was common. There were significantly positive heritability (h(2 estimates for 48% (20/42 of the specific antibody assays (for the seven isotypes and subclasses to the six antigens tested among the adults, 48% (20/42 among the children in the dry season and 31% (13/42 among the children in the wet season. In children, there were significant heritability estimates for IgG4 reactivity against each of the antigens, and this subclass had higher heritability than the other subclasses and isotypes. In adults, 75% (15/20 of the significantly heritable antigen-specific isotype responses were attributable to non-HLA class II genetic variation, whereas none showed a significant HLA contribution.Genome-wide approaches are now warranted to map the major genetic determinants of variable antibody isotype and subclass responses to malaria, alongside evaluation of their impact on infection and disease. Although plasma levels of IgG4 to malaria antigens are generally low, the exceptionally high heritability of levels of this subclass in children deserves particular investigation.

  2. Serial cerebrospinal fluid neurofilament heavy chain levels in severe Guillain-Barre syndrome

    NARCIS (Netherlands)

    Dujmovic, I.; Lunn, M.P.; Reilly, M.M.; Petzold, A.

    2013-01-01

    Introduction: Proximal axonotmesis results in the release of neurofilament (Nf) proteins into the cerebrospinal fluid (CSF) in patients with Guillain-Barré syndrome (GBS). High CSF levels of the phosphorylated form of Nf-heavy chain (NfH

  3. Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood

    NARCIS (Netherlands)

    Blanco, E. (Elena); M. Perez-Andres; Arriba-Méndez, S. (Sonia); Contreras-Sanfeliciano, T. (Teresa); I. Criado (Ignacio); Pelak, O. (Ondrej); Serra-Caetano, A. (Ana); A. Romero (Alfonso); N. Puig (Noemí); Remesal, A. (Ana); Torres Canizales, J. (Juan); E. Lopez-Granados (Eduardo); T. Kalina (Tomas); Sousa, A.E. (Ana E.); M.C. van Zelm (Menno); M. van der Burg (Mirjam); J.J.M. van Dongen (Jacques); Orfao, A. (Alberto)

    2018-01-01

    textabstractBackground: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity, and neoplasia. Immunoglobulin heavy chain (IgH) isotype serum levels can partly explain such age-related differences, but

  4. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  5. Expression of porcine myosin heavy chain 1 gene in Berkshire loins ...

    African Journals Online (AJOL)

    Expression of porcine myosin heavy chain 1 gene in Berkshire loins with a high pH24 value. Jin Hun Kang, Woo Young Bang, Eun Jung Kwon, Yong Hwa Lee, Da Hye Park, Eun Seok Cho, Min Ji Kim, Jong-Soon Choi, Hwa Chun Park, Beom Young Park, Chul Wook Kim ...

  6. Porous silicon biosensor for detection of variable domain of heavy-chain of HCAb antibody

    Science.gov (United States)

    Zhang, Hong-yan; Lü, Xiao-yi; Jia, Zhen-hong; Li, Jiang-wei; Zhang, Fu-chun

    2012-03-01

    In this paper, we produce porous silicon (PSi) by electrochemical etching, and it is the first time to evaluate the performance of label-free porous silicon biosensor for detection of variable domain of heavy chain of heavy-chain antibody (VHH). The binding of hen egg white lysozyme (HEWL) and VHH causes a red shift in the reflection spectrum of the biosensor. The red shift is proportional to the VHH concentration in the range from 14 g·ml-1 to 30 g·ml-1 with a detection limit of 0.648 ng·ml-1. The research is useful for the development of label-free biosensor applied in the rapid and sensitive determination of small molecules.

  7. Antibody isotype responses to egg antigens in human chronic Schistosomiasis mansoni before and after treatment

    Directory of Open Access Journals (Sweden)

    Gomes Yara M

    2002-01-01

    Full Text Available In the present communication we analyzed the levels of IgG1, IgG2, IgG3, IgG4 and IgE isotypes to soluble egg antigen of Schistosoma mansoni by ELISA in individuals from an endemic area for schistosomiasis in Northeast Brazil. The analysis was performed before and after treatment to evaluate the age-dependent pattern, and to identify differences in the reactivities to antigens. Our results suggest that schistosomiasis treatment would not interfere with this sort of immune response.

  8. Postnatal development of cerebellar zones revealed by neurofilament heavy chain protein expression

    Directory of Open Access Journals (Sweden)

    Joshua J White

    2013-05-01

    Full Text Available The cerebellum is organized into parasagittal zones that control sensory-motor behavior. Although the architecture of adult zones is well understood, very little is known about how zones emerge during development. Understanding the process of zone formation is an essential step towards unraveling how circuits are constructed to support specific behaviors. Therefore, we focused this study on postnatal development to determine the spatial and temporal changes that establish zonal patterns during circuit formation. We used a combination of wholemount and tissue section immunohistochemistry in mice to show that the cytoskeletal protein neurofilament heavy chain (NFH is a robust marker for postnatal cerebellar zonal patterning. The patterned expression of NFH is initiated shortly after birth, and compared to the domains of several known zonal markers such as zebrin II, HSP25, neurogranin, and phospholipase Cβ4 (PLCβ4, NFH does not exhibit transient expression patterns that are typically remodeled between stages, and the adult zones do not emerge after a period of uniform expression in all lobules. Instead, we found that throughout postnatal development NFH gradually reveals distinct zones in each cerebellar lobule. The boundaries of individual NFH zones sharpen over time, as zones are refined during the second and third weeks after birth. Double labeling with neurogranin and PLCβ4 further revealed that although the postnatal expression of NFH is spatially and temporally unique, its pattern of zones respects a fundamental and well-known molecular topography in the cerebellum. The dynamics of NFH expression support the hypothesis that adult circuits are derived from an embryonic map that is refined into zones during the first three-weeks of life.

  9. Autoantibodies in SLE: Specificities, Isotypes and Receptors

    Directory of Open Access Journals (Sweden)

    Barbara Dema

    2016-01-01

    Full Text Available Systemic Lupus Erythematosus (SLE is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

  10. Use of bortezomib in heavy-chain deposition disease: a report of 3 cases.

    Science.gov (United States)

    Patel, Kinjal; Dillon, John J; Leung, Nelson; Bomback, Andrew S; Appel, Gerald B; D'Agati, Vivette; Canetta, Pietro A

    2014-07-01

    Heavy-chain deposition disease (HCDD) is a rare complication of plasma cell dyscrasia in which monoclonal heavy chains deposit in glomerular and tubular basement membranes of the kidney. Clinical and pathologic features of HCDD have been well described in case reports and series, but evidence supporting specific therapies is sparse. Historically, the disease has had a poor prognosis, intensifying the need to clarify optimal treatments. We describe 3 cases of HCDD with biopsy-proven glomerular involvement, severe nephrotic syndrome, and decline in kidney function that were treated successfully with bortezomib, a proteasome inhibitor. None of these patients had multiple myeloma. In all cases, bortezomib-based therapy resulted in sustained resolution of nephrotic syndrome and improvement in kidney function. All 3 patients developed peripheral neuropathy; otherwise, treatment was well tolerated. To our knowledge, this is the first description of the clinical effectiveness of bortezomib against HCDD. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  11. Rationalization of paclitaxel insensitivity of yeast β-tubulin and human βIII-tubulin isotype using principal component analysis

    Directory of Open Access Journals (Sweden)

    Das Lalita

    2012-08-01

    Full Text Available Abstract Background The chemotherapeutic agent paclitaxel arrests cell division by binding to the hetero-dimeric protein tubulin. Subtle differences in tubulin sequences, across eukaryotes and among β-tubulin isotypes, can have profound impact on paclitaxel-tubulin binding. To capture the experimentally observed paclitaxel-resistance of human βIII tubulin isotype and yeast β-tubulin, within a common theoretical framework, we have performed structural principal component analyses of β-tubulin sequences across eukaryotes. Results The paclitaxel-resistance of human βIII tubulin isotype and yeast β-tubulin uniquely mapped on to the lowest two principal components, defining the paclitaxel-binding site residues of β-tubulin. The molecular mechanisms behind paclitaxel-resistance, mediated through key residues, were identified from structural consequences of characteristic mutations that confer paclitaxel-resistance. Specifically, Ala277 in βIII isotype was shown to be crucial for paclitaxel-resistance. Conclusions The present analysis captures the origin of two apparently unrelated events, paclitaxel-insensitivity of yeast tubulin and human βIII tubulin isotype, through two common collective sequence vectors.

  12. Improved production and function of llama heavy chain antibody fragments by molecular evolution

    NARCIS (Netherlands)

    Linden, van der R.H.; Geus, de B.; Frenken, G.J.; Peters, H.; Verrips, C.T.

    2000-01-01

    The aim of this study was to improve production level of llama heavy chain antibody fragments (V (HH)) in Saccharomyces cerevisiae while retaining functional characteristics. For this purpose, the DNA shuffling technique was used on llama V (HH) fragments specific for the azo-dye reactive red-6. In

  13. Gm typing by immunoglobulin heavy-chain gene RFLP analysis.

    OpenAIRE

    Jazwinska, E C; Dunckley, H; Propert, D N; Gatenby, P A; Serjeantson, S W

    1988-01-01

    This study was undertaken to investigate a means of assigning Gm allotypes to Caucasians by RFLP analysis. A single immunoglobulin heavy-chain gamma-4 cDNA probe (HU gamma 4) was hybridized with genomic DNA digested separately with two restriction enzymes, TaqI and PvuII. Results showed excellent correlation (P less than .001) between serologically defined Gm allotypes G1m(1), G1m(2), G2m(23), and G1m;G3m (3;5,10) and RFLPs identified with the (HU gamma 4) probe. We conclude that it is now po...

  14. Early Bronchus-Associated Lymphoid Tissue Lymphoma Diagnosed with Immunoglobulin Heavy Chain Molecular Testing

    Directory of Open Access Journals (Sweden)

    Pen Li

    2016-01-01

    Full Text Available When extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT, a low grade B-cell lymphoma, arises in the lung it is referred to as bronchus-associated lymphoid tissue (BALT lymphoma. We describe a patient with a history of Sjögren’s syndrome and rheumatoid arthritis with dyspnea and imaging consistent with lymphoid interstitial pneumonia (LIP. However, while histology and immunohistochemistry lacked definitive features of a lymphoma, immunoglobulin heavy chain (IgH polymerase chain reaction testing demonstrated B-cell monoclonality, consistent with an early BALT lymphoma.

  15. Expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori

    NARCIS (Netherlands)

    Joosten, V.; Gouka, R.J.; Hondel, C.A.M.J.J. van den; Verrips, C.T.; Lokman, B.C.

    2005-01-01

    We report the expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori. Fragments encoding VHHs were cloned in a suitable Aspergillus expression vector and transformants secreting VHH fragments were analysed for integrated gene copy-numbers, mRNA

  16. Behind Isotype Charts: The Design of Number-Fact Pictures

    DEFF Research Database (Denmark)

    Pedersen, Pia

    2017-01-01

    For more than 40 years, Marie Neurath designed ISOTYPE charts using pictograms as graphical units to make a variety of information more accessible for the layman. She was a transformer linking science and design by using the benefits of both worlds to meet the public’s interests. Significant insi...

  17. IgG isotypic antibodies to crude Plasmodium falciparum blood-stage ...

    African Journals Online (AJOL)

    Methods: Levels of IgG (IgG1-IgG4) and IgM to crude P. falciparum blood stage antigen ... dosage influenced P. falciparum-specific isotypic antibody responses to blood stage .... exposed Swedish donors. ..... with adverse pregnancy outcomes.

  18. Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

    Science.gov (United States)

    Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2018-01-01

    Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

  19. Construction and characterization of the alpha form of a cardiac myosin heavy chain cDNA clone and its developmental expression in the Syrian hamster.

    OpenAIRE

    Liew, C C; Jandreski, M A

    1986-01-01

    A cDNA clone, pVHC1, was isolated from a Syrian hamster heart cDNA library and was compared to the rat alpha (pCMHC21) and beta (pCMHC5) ventricular myosin heavy chain cDNA clones. The DNA sequence and amino acid sequence deducted from the DNA show more homology with pCMHC21 than pCMHC5. This indicates that pVHC1 is an alpha ventricular myosin heavy chain cDNA clone. However, even though pVHC1 shows a high degree of nucleotide and amino acid conservation with the rat myosin heavy chain sequen...

  20. Iron Deposition and Ferritin Heavy Chain (Fth Localization in Rodent Teeth

    Directory of Open Access Journals (Sweden)

    Wen Xin

    2013-01-01

    Full Text Available Abstract Background An iron rich layer on the labial surface is characteristic of the enamel of rodent incisors. In order to address a role for iron content in continuously growing incisors during odontogenesis, we studied iron deposition patterns in enamel and dentine using Perls’ blue staining and ferritin heavy chain (Fth immunolocalization. Fth expression is regulated by iron level; therefore its localization can be used as a sensitive indicator for iron deposition. Results Sagittal sections of 4-week old rat incisors showed a gradual increase in iron level in the enamel organ from secretory to maturation stages. In addition, iron was detected in ameloblasts of erupting third molars of 4-week old rats, suggesting iron plays a role in both incisor and molar development. In odontoblasts, the presence of iron was demonstrated, and this is consistent with iron’s role in collagen synthesis. Using postnatal 3-, 6-, 9-day old mice, the spatial and temporal expression of Fth in tooth development again indicated the presence of iron in mature ameloblasts and odontoblasts. Conclusions While these data do not explain what functional role iron has in tooth formation, it does highlight a significant molecular activity associated with the formation of the rodent dentition.

  1. Menstrual Patterns and Treatment of Heavy Menstrual Bleeding in Adolescents with Bleeding Disorders.

    Science.gov (United States)

    Dowlut-McElroy, Tazim; Williams, Karen B; Carpenter, Shannon L; Strickland, Julie L

    2015-12-01

    To characterize menstrual bleeding patterns and treatment of heavy menstrual bleeding in adolescents with bleeding disorders. We conducted a retrospective review of female patients aged nine to 21 years with known bleeding disorders who attended a pediatric gynecology, hematology, and comprehensive hematology/gynecology clinic at a children's hospital in a metropolitan area. Prevalence of heavy menstrual bleeding at menarche, prolonged menses, and irregular menses among girls with bleeding disorders and patterns of initial and subsequent treatment for heavy menstrual bleeding in girls with bleeding disorders. Of 115 participants aged nine to 21 years with known bleeding disorders, 102 were included in the final analysis. Of the 69 postmenarcheal girls, almost half (32/69, 46.4%) noted heavy menstrual bleeding at menarche. Girls with von Willebrand disease were more likely to have menses lasting longer than seven days. Only 28% of girls had discussed a treatment plan for heavy menstrual bleeding before menarche. Hormonal therapy was most commonly used as initial treatment of heavy menstrual bleeding. Half (53%) of the girls failed initial treatment. Combination (hormonal and non-hormonal therapy) was more frequently used for subsequent treatment. Adolescents with bleeding disorders are at risk of heavy bleeding at and after menarche. Consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  2. Detection of heavy-metal ions using liquid crystal droplet patterns modulated by interaction between negatively charged carboxylate and heavy-metal cations.

    Science.gov (United States)

    Han, Gyeo-Re; Jang, Chang-Hyun

    2014-10-01

    Herein, we demonstrated a simple, sensitive, and rapid label-free detection method for heavy-metal (HM) ions using liquid crystal (LC) droplet patterns on a solid surface. Stearic-acid-doped LC droplet patterns were spontaneously generated on an n-octyltrichlorosilane (OTS)-treated glass substrate by evaporating a solution of the nematic LC, 4-cyano-4'-pentylbiphenyl (5CB), dissolved in heptane. The optical appearance of the droplet patterns was a dark crossed texture when in contact with air, which represents the homeotropic orientation of the LC. This was caused by the steric interaction between the LC molecules and the alkyl chains of the OTS-treated surface. The dark crossed appearance of the acid-doped LC patterns was maintained after the addition of phosphate buffered saline (PBS) solution (pH 8.1 at 25°C). The deprotonated stearic-acid molecules self-assembled through the LC/aqueous interface, thereby supporting the homeotropic anchoring of 5CB. However, the optical image of the acid-doped LC droplet patterns incubated with PBS containing HM ions appeared bright, indicating a planar orientation of 5CB at the aqueous/LC droplet interface. This dark to bright transition of the LC patterns was caused by HM ions attached to the deprotonated carboxylate moiety, followed by the sequential interruption of the self-assembly of the stearic acid at the LC/aqueous interface. The results showed that the acid-doped LC pattern system not only enabled the highly sensitive detection of HM ions at a sub-nanomolar concentration but it also facilitated rapid detection (<10 min) with simple procedures. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Purification of correctly oxidized MHC class I heavy-chain molecules under denaturing conditions: a novel strategy exploiting disulfide assisted protein folding

    DEFF Research Database (Denmark)

    Ferré, Henrik; Ruffet, Emmanuel; Blicher, Thomas

    2003-01-01

    The aim of this study has been to develop a strategy for purifying correctly oxidized denatured major histocompability complex class I (MHC-I) heavy-chain molecules, which on dilution, fold efficiently and become functional. Expression of heavy-chain molecules in bacteria results in the formation...... of insoluble cellular inclusion bodies, which must be solubilized under denaturing conditions. Their subsequent purification and refolding is complicated by the fact that (1). correct folding can only take place in combined presence of beta(2)-microglobulin and a binding peptide; and (2). optimal in vitro...... conditions for disulfide bond formation ( approximately pH 8) and peptide binding ( approximately pH 6.6) are far from complementary. Here we present a two-step strategy, which relies on uncoupling the events of disulfide bond formation and peptide binding. In the first phase, heavy-chain molecules...

  4. Purification of correctly oxidized MHC class I heavy-chain molecules under denaturing conditions: A novel strategy exploiting disulfide assisted protein folding

    DEFF Research Database (Denmark)

    Ferré, Henrik; Ruffet, E.; Blicher, T.

    2003-01-01

    The aim of this study has been to develop a strategy for purifying correctly oxidized denatured major histocompability complex class I (MHC-I) heavy-chain molecules, which on dilution, fold efficiently and become functional. Expression of heavy-chain molecules in bacteria results in the formation...... of insoluble cellular inclusion bodies, which must be solubilized under denaturing conditions. Their subsequent purification and refolding is complicated by the fact that (1) correct folding can only take place in combined presence of beta(2)-microglobulin and a binding peptide; and (2) optimal in vitro...... conditions for disulfide bond formation (similar topH 8) and peptide binding (similar topH 6.6) are far from complementary. Here we present a two-step strategy, which relies on uncoupling the events of disulfide bond formation and peptide binding. In the first phase, heavy-chain molecules with correct...

  5. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Tramontano, Anna

    2011-01-01

    of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface

  6. Characterization of a specific monoclonal antibody against immunoglobulin light kappa/L1 chain in olive flounder (Paralichthys olivaceus)

    DEFF Research Database (Denmark)

    Kim, Young Kyu; Lee, Jung Seok; Jung, Jae Wook

    2017-01-01

    Immunoglobulins (Ig) are heterodimeric proteins that play critical roles in the adaptive immune system of vertebrates. Because of their plasticity, teleostean Igs are more diverse, and thus do not conform to mammalian classifications. Because of this, mammalian-based Ig cell markers cannot be used...... successfully to study immune responses in fish. There is therefore a need to produce Ig-specific cell markers for fish. Here, we attempted to identify the specific isotype detected by an Ig light chain-specific monoclonal antibody (anti-olive flounder IgL-mAb: M7C3-4) that we had previously produced [11......]. Three newly identified sequences of the Ig light chain from olive flounder were classified according to their isotypes. Subsequent analyses revealed that M7C3-4 was able to specifically detect lymphocytes expressing one of the κ chains (Igκ-a) in olive flounder. Interestingly, Igκ-a+ B cells were more...

  7. Interaction of soil heavy metal pollution with industrialisation and the landscape pattern in Taiyuan city, China.

    Science.gov (United States)

    Liu, Yong; Su, Chao; Zhang, Hong; Li, Xiaoting; Pei, Jingfei

    2014-01-01

    Many studies indicated that industrialization and urbanization caused serious soil heavy metal pollution from industrialized age. However, fewer previous studies have conducted a combined analysis of the landscape pattern, urbanization, industrialization, and heavy metal pollution. This paper was aimed at exploring the relationships of heavy metals in the soil (Pb, Cu, Ni, As, Cd, Cr, Hg, and Zn) with landscape pattern, industrialisation, urbanisation in Taiyuan city using multivariate analysis. The multivariate analysis included correlation analysis, analysis of variance (ANOVA), independent-sample T test, and principal component analysis (PCA). Geographic information system (GIS) was also applied to determine the spatial distribution of the heavy metals. The spatial distribution maps showed that the heavy metal pollution of the soil was more serious in the centre of the study area. The results of the multivariate analysis indicated that the correlations among heavy metals were significant, and industrialisation could significantly affect the concentrations of some heavy metals. Landscape diversity showed a significant negative correlation with the heavy metal concentrations. The PCA showed that a two-factor model for heavy metal pollution, industrialisation, and the landscape pattern could effectively demonstrate the relationships between these variables. The model explained 86.71% of the total variance of the data. Moreover, the first factor was mainly loaded with the comprehensive pollution index (P), and the second factor was primarily loaded with landscape diversity and dominance (H and D). An ordination of 80 samples could show the pollution pattern of all the samples. The results revealed that local industrialisation caused heavy metal pollution of the soil, but such pollution could respond negatively to the landscape pattern. The results of the study could provide a basis for agricultural, suburban, and urban planning.

  8. The spectrum of neutrophilic dermatoses associated with monoclonal gammopathy: Association with IgA isotype and inflammatory profile.

    Science.gov (United States)

    Szalat, Raphael; Monsel, Gentiane; Le Goff, Wilfried; Battistella, Maxime; Bengouffa, Djaouida; Schlageter, Marie-Helene; Bouaziz, Jean-David; Arnulf, Bertrand; Vignon, Marguerite; Lesnik, Philippe; Saussine, Anne; Malphettes, Marion; Lazareth, Anne; Vignon-Pennamen, Marie-Dominique; Bagot, Martine; Brouet, Jean-Claude; Fermand, Jean-Paul; Rybojad, Michel; Asli, Bouchra

    2015-11-01

    Neutrophilic dermatoses refer to a group of cutaneous inflammatory disorders characterized by neutrophilic infiltration of the skin. Neutrophilic dermatoses have been reported in association with various conditions including autoimmune diseases, inflammatory bowel diseases, and neoplasia. In the later condition, myeloproliferative disorders and monoclonal gammopathy (monoclonal immunoglobulin [MIg]) are the most frequent. Only few data are available in case of neutrophilic dermatoses associated with MIg regarding the pathophysiology and the clinical outcome. We sought to gain further insight into clinical and biological aspects of neutrophilic dermatoses associated with MIg. We report a retrospective series of 26 patients with neutrophilic dermatoses associated with MIg focusing on clinical and biological aspects, with a study of a large panel of cytokines, chemokines, and adhesion molecules. This study reveals an association between MIg IgA isotype and neutrophilic dermatoses, and a specific inflammatory pattern including elevated interleukin 6, vascular endothelial growth factor, monocyte chemotactic protein-1, epidermal growth factor, and intercellular adhesion molecule-1. This is a retrospective study from a single institution with a limited number of participants. Our data highlight a strong association between IgA isotype and neutrophilic dermatoses, and the existence of a specific inflammatory profile involving several molecules. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  9. Myosin heavy chain composition of tiger (Panthera tigris) and cheetah (Acinonyx jubatus) hindlimb muscles.

    Science.gov (United States)

    Hyatt, Jon-Philippe K; Roy, Roland R; Rugg, Stuart; Talmadge, Robert J

    2010-01-01

    Felids have a wide range of locomotor activity patterns and maximal running speeds, including the very fast cheetah (Acinonyx jubatas), the roaming tiger (Panthera tigris), and the relatively sedentary domestic cat (Felis catus). As previous studies have suggested a relationship between the amount and type of activity and the myosin heavy chain (MHC) isoform composition of a muscle, we assessed the MHC isoform composition of selected hindlimb muscles from these three felid species with differing activity regimens. Using gel electrophoresis, western blotting, histochemistry, and immunohistochemistry with MHC isoform-specific antibodies, we compared the MHC composition in the tibialis anterior, medial gastrocnemius (MG), plantaris (Plt), and soleus muscles of the tiger, cheetah, and domestic cat. The soleus muscle was absent in the cheetah. At least one slow (type I) and three fast (types IIa, IIx, and IIb) MHC isoforms were present in the muscles of each felid. The tiger had a high combined percentage of the characteristically slower isoforms (MHCs I and IIa) in the MG (62%) and the Plt (86%), whereas these percentages were relatively low in the MG (44%) and Plt (55%) of the cheetah. In general, the MHC isoform characteristics of the hindlimb muscles matched the daily activity patterns of these felids: the tiger has daily demands for covering long distances, whereas the cheetah has requirements for speed and power. (c) 2009 Wiley-Liss, Inc.

  10. Career Patterns of Supply Chain Executives

    DEFF Research Database (Denmark)

    Flöthmann, Christoph; Hoberg, Kai

    2017-01-01

    career patterns for SCEs. They differ in terms of the individuals' previous professional experience, educational background, and the time they needed to arrive in an executive position. By characterizing the backgrounds and career paths of SCEs, we show that supply chain management (SCM) is truly a cross......This exploratory study analyzes the careers of 307 supply chain executives (SCEs). Motivated by career theory, our findings create new knowledge about the educational backgrounds and career paths that lead to SCE positions. Based on an optimal matching analysis, we are able to distinguish among six......-functional profession. Our findings suggest that previous staff responsibility appears to be a more important hiring criterion than extensive SCM experience. While 56% of the executives had prior staff responsibility, only 12% of the cumulated careers were actually spent inside the SCM function....

  11. [Changes in titin and myosin heavy chain isoform composition in skeletal muscles of Mongolian gerbil (Meriones unguiculatus) after 12-day spaceflight].

    Science.gov (United States)

    Okuneva, A D; Vikhliantsev, I M; Shpagina, M D; Rogachevskiĭ, V V; Khutsian, S S; Poddubnaia, Z A; Grigor'ev, A I

    2012-01-01

    Changes of titin and myosin heavy chain isoform composition in skeletal muscles (m. soleus, m. gastrocnemius, m. tibialis anterior, m. psoas major) in Mongolian Gerbil (Meriones unguiculatus ) were investigated after 12-day spaceflight on board of Russian space vehicle "Foton-M3". In m. psoas and m. soleus in the gerbils from "Flight" group the expected increase in the content of fast myosin heavy chain isoforms (IIxd and IIa, respectively) were observed. No significant differences were found in the content of IIxd and IIa isoforms of myosin heavy chain in m. tibialis anterior in the gerbils from control group as compared to that in "Flight" group. An unexpected increase in the content of slow myosin heavy chain I isoform and a decrease in the content of fast IIx/d isoform in m. gastrocnemius of the gerbils from "Flight" group were observed. In skeletal muscles of the gerbils from "Flight" group the relative content of titin N2A-isoform was reduced (by 1,2-1,7 times), although the content of its NT-isoform, which was revealed in striated muscles of mammals in our experiments earlier, remained the same. When the content of titin N2A-isoform was decreased, no predictable abnormalities in sarcomeric structure and contractile ability of skeletal muscles in the gerbils from "Flight" group were found. An assumption on the leading role of titin NT-isoform in maintenance of structural and functional properties of striated muscles of mammals was made.

  12. Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies

    Directory of Open Access Journals (Sweden)

    Katherine E. Harris

    2018-04-01

    Full Text Available We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1. This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.

  13. Immunoglobulin heavy chain exclusion in the shark.

    Directory of Open Access Journals (Sweden)

    Karolina Malecek

    2008-06-01

    Full Text Available The adaptive immune system depends on specific antigen receptors, immunoglobulins (Ig in B lymphocytes and T cell receptors (TCR in T lymphocytes. Adaptive responses to immune challenge are based on the expression of a single species of antigen receptor per cell; and in B cells, this is mediated in part by allelic exclusion at the Ig heavy (H chain locus. How allelic exclusion is regulated is unclear; we considered that sharks, the oldest vertebrates possessing the Ig/TCR-based immune system, would yield insights not previously approachable and reveal the primordial basis of the regulation of allelic exclusion. Sharks have an IgH locus organization consisting of 15-200 independently rearranging miniloci (VH-D1-D2-JH-Cmu, a gene organization that is considered ancestral to the tetrapod and bony fish IgH locus. We found that rearrangement takes place only within a minilocus, and the recombining gene segments are assembled simultaneously and randomly. Only one or few H chain genes were fully rearranged in each shark B cell, whereas the other loci retained their germline configuration. In contrast, most IgH were partially rearranged in every thymocyte (developing T cell examined, but no IgH transcripts were detected. The distinction between B and T cells in their IgH configurations and transcription reveals a heretofore unsuspected chromatin state permissive for rearrangement in precursor lymphocytes, and suggests that controlled limitation of B cell lineage-specific factors mediate regulated rearrangement and allelic exclusion. This regulation may be shared by higher vertebrates in which additional mechanistic and regulatory elements have evolved with their structurally complex IgH locus.

  14. Isotype Visualizations. A Chance for Participation & Civic Education

    Directory of Open Access Journals (Sweden)

    Eva Mayr

    2014-12-01

    Full Text Available In the 1920s, Otto Neurath proposed a method for pictorial statistics called “Isotype”. The Isotype pictorial statistics were intended to educate the broad public and enable them to participate in society. This method is reviewed with respect to its relevance and potential for information visualization nowadays. Though some aspects are outdated, the basic approach has still potential for information visualization and civic education. Possible new media applications are presented and their impact for civic education and participation is discussed.

  15. Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide.

    OpenAIRE

    Sanford, J E; Lupan, D M; Schlageter, A M; Kozel, T R

    1990-01-01

    The in vivo properties of an immunoglobulin isotype-switch family of monoclonal antibodies specific for the polysaccharide capsule of Cryptococcus neoformans were examined in a murine model of cryptococcosis. Subclass-switch variants were isolated by sequential sublining of an immunoglobulin G subclass 1 (IgG1)-secreting cell line. Antibodies of the IgG1, IgG2a, and IgG2b isotypes with identical reactivities with cryptococcal polysaccharide were prepared. The antibodies had the distinct biolo...

  16. Homologous recombination in hybridoma cells: heavy chain chimeric antibody produced by gene targeting.

    OpenAIRE

    Fell, H P; Yarnold, S; Hellström, I; Hellström, K E; Folger, K R

    1989-01-01

    We demonstrate that murine myeloma cells can efficiently mediate homologous recombination. The murine myeloma cell line J558L was shown to appropriately recombine two transfected DNA molecules in approximately 30% of cells that received and integrated intact copies of both molecules. This activity was then exploited to direct major reconstructions of an endogenous locus within a hybridoma cell line. Production of antigen-specific chimeric heavy chain was achieved by targeting the human IgG1 h...

  17. Soil Heavy Metal Concentration Patterns at Two Speed Zones along ...

    African Journals Online (AJOL)

    Soil Heavy Metal Concentration Patterns at Two Speed Zones along the Gaborone- Tlokweng Border Post Highway, Southeast Botswana. ... Since 1988 Botswana has been experiencing an unprecedented increase in vehicular traffic which is suspected to be having contamination effects on soils along heavily used roads ...

  18. Angular distributions of elastic and quasi elastic heavy-ion collisions. Pattern analysis

    International Nuclear Information System (INIS)

    Da Silveira, R.

    1980-06-01

    The emergence, as well as the evolution, of the most typical patterns observed in the angular distributions of elastic scattering and surface transfer between heavy-nuclei, is discussed. Starting from the semi-classical approximation, Thom's classification theorem is evoked to further illuminate the connection between these patterns and the collision parameters

  19. Isotypes and antigenic profiles of pemphigus foliaceus and pemphigus vulgaris autoantibodies.

    Science.gov (United States)

    Hacker, Mary K; Janson, Marleen; Fairley, Janet A; Lin, Mong-Shang

    2002-10-01

    In this study we systematically characterized isotype profiles and antigenic and tissue specificity of antidesmoglein autoantibodies from patients with pemphigus foliaceus (PF) and pemphigus vulgaris (PV) using enzyme-linked immunoabsorbent assays (ELISA), indirect immunofluorescence (IIF) staining, and immunoblotting (IB). In PF, we found that IgG1 antidesmoglein-1 (Dsg1) reacts with a linear epitope(s) on the ectodomain of Dsg1, while its IgG4 counterpart recognizes a conformational epitope(s). These two subclasses of anti-Dsg1 are both capable of recognizing tissues from monkey esophagus and adult human skin, but IgG1 is not able to react with mouse skin, which may explain why this isotype of anti-Dsg1 failed to induce PF-like lesions in the passive transfer animal model. In mucosal PV patients, we found that both IgG1 and IgG4 only recognized monkey esophagus tissue by IIF, except in one patient, indicating that these antibodies react with a unique conformational epitope(s) that is present in mucosal but not skin tissue. In generalized PV, IgG1 anti-Dsg3 autoantibodies appeared to recognize a linear epitope(s) on the Dsg3 ectodomain. In contrast, IgG4 anti-Dsg3 antibodies recognized both linear and conformational epitopes on the Dsg3 molecule. Interestingly, the IgG1 anti-Dsg3 antibodies failed to react with human and mouse skin tissues, suggesting that this subclass of autoantibodies may not play an essential role in the development of PV suprabasilar lesions. In summary, we conclude that this study further elucidates the pathological mechanisms of PF and PV autoantibodies by revealing their distinct isotype and antigenic profiles. This information may help us to better understand the autoimmune mechanisms underlying the development of pemphigus.

  20. Dendritic cells support production of IgA and other non-IgM isotypes in clonal microculture.

    Science.gov (United States)

    Schrader, C E; George, A; Kerlin, R L; Cebra, J J

    1990-01-01

    Microcultures of helper T (Th) cells and a few appropriately primed murine B cells can be used to detect cognate T-B interactions which lead to clonal production of IgM, IgG1, and IgE. However, IgG2, IgG3, and IgA are very rarely expressed. We have found that the addition of dendritic cells to such cultures creates an extremely supportive environment for clones expressing IgA with other isotypes, as well as clones expressing only detectable IgA. Typically, 400 dendritic cells were added to 3000 conalbumin-specific Th cells (D10.G4.1) and 30 hapten-specific Peyer's patch (PP) B cells with antigen in 15 microliters. The response was antigen dependent and clonal. Almost half of the clones expressed only non-IgM isotypes, 43% expressed some IgA, and 14% expressed some IgG3; isotype diversity increased over time. Dendritic cells from PP and spleen were found to be equally supportive, and allowed the number of T cells required in microculture to be decreased from 3000 to 400. However, T cell proliferation was not required for the supportive effect of dendritic cells. Surface IgD-bearing cells were also found to switch to IgA production in microculture as judged by their generating clones expressing IgM along with IgA and other isotypes. Again, IgA was usually expressed only in the presence of dendritic cells. The mechanism may involve dendritic cell-induced T cell activation and/or dendritic cell factors, and is under investigation.

  1. EFFECT OF COST INCREMENT DISTRIBUTION PATTERNS ON THE PERFORMANCE OF JIT SUPPLY CHAIN

    Directory of Open Access Journals (Sweden)

    Ayu Bidiawati J.R

    2008-01-01

    Full Text Available Cost is an important consideration in supply chain (SC optimisation. This is due to emphasis placed on cost reduction in order to optimise profit. Some researchers use cost as one of their performance measures and others propose ways of accurately calculating cost. As product moves across SC, the product cost also increases. This paper studied the effect of cost increment distribution patterns on the performance of a JIT Supply Chain. In particular, it is necessary to know if inventory allocation across SC needs to be modified to accommodate different cost increment distribution patterns. It was found that funnel is still the best card distribution pattern for JIT-SC regardless the cost increment distribution patterns used.

  2. Adult fast myosin pattern and Ca2+-induced slow myosin pattern in primary skeletal muscle culture

    Science.gov (United States)

    Kubis, Hans-Peter; Haller, Ernst-August; Wetzel, Petra; Gros, Gerolf

    1997-01-01

    A primary muscle cell culture derived from newborn rabbit muscle and growing on microcarriers in suspension was established. When cultured for several weeks, the myotubes in this model develop the completely adult pattern of fast myosin light and heavy chains. When Ca2+ ionophore is added to the culture medium on day 11, raising intracellular [Ca2+] about 10-fold, the myotubes develop to exhibit properties of an adult slow muscle by day 30, expressing slow myosin light as well as heavy chains, elevated citrate synthase, and reduced lactate dehydrogenase. The remarkable plasticity of these myotubes becomes apparent, when 8 days after withdrawal of the ionophore a marked slow-to-fast transition, as judged from the expression of isomyosins and metabolic enzymes, occurs. PMID:9108130

  3. Generation of human Fab antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

    Science.gov (United States)

    Andris-Widhopf, Jennifer; Steinberger, Peter; Fuller, Roberta; Rader, Christoph; Barbas, Carlos F

    2011-09-01

    The development of therapeutic antibodies for use in the treatment of human diseases has long been a goal for many researchers in the antibody field. One way to obtain these antibodies is through phage-display libraries constructed from human lymphocytes. This protocol describes the construction of human Fab (fragment antigen binding) antibody libraries. In this method, the individual rearranged heavy- and light-chain variable regions are amplified separately and are linked through a series of overlap polymerase chain reaction (PCR) steps to give the final Fab products that are used for cloning.

  4. Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth

    International Nuclear Information System (INIS)

    Quackenbush, E.; Clabby, M.; Gottesdiener, K.M.; Barbosa, J.; Jones, N.H.; Strominger, J.L.; Speck, S.; Leiden, J.M.

    1987-01-01

    Complementary DNA (cDNA) clones encoding the heavy chain of the heterodimeric human membrane glycoprotein 4F2 have been isolated by immunoscreening of a λgt11 expression library. The identity of these clones has been confirmed by hybridization to RNA and DNA prepared from mouse L-cell transfectants, which were produced by whole cell gene transfer and selected for cell-surface expression of the human 4F2 heavy chain. DNA sequence analysis suggest that the 4F2 heavy-chain cDNAs encode an approximately 526-amino acid type II membrane glycoprotein, which is composed of a large C-terminal extracellular domain, a single potential transmembrane region, and a 50-81 amino acid N-terminal intracytoplasmic domain. Southern blotting experiments have shown that the 4F2 heavy-chain cDNAs are derived from a single-copy gene that has been highly conserved during mammalian evolution

  5. Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA.

    Science.gov (United States)

    Xu, Yuanyuan; Yamada, Toshiyuki; Satoh, Takahiko; Okuda, Yasuaki

    2006-01-01

    Serum amyloid A (SAA), a plasma precursor of reactive amyloid deposits, is a multigene product. SAA1 and SAA2, with primary structures that are 93% identical (98 of 104 amino acids), behave as acute phase proteins, as demonstrated by their increasing levels in plasma. Heretofore, it has been understood that SAA1 predominates and functions as an isotype in plasma. However, accurate measurements differentiating the two isotypes have not been reported. In this study, using monoclonal antibodies specific for SAA1, we developed an enzyme-linked immunosorbent assay (ELISA) for SAA1. The levels and ratios of SAA1 in total SAA (TSAA) were investigated in healthy subjects and patients with rheumatoid arthritis (RA). The SAA1/TSAA ratio was 74 +/- 12% and 77 +/- 12% in healthy subjects and RA patients, respectively. In RA patients, the ratios were not influenced by SAA1 genotype, which has been proposed to affect plasma SAA values. The kinetics of SAA1 in inflamed patients undergoing hemodialysis was found to be parallel with total SAA and C-reactive protein. Finally, this study confirmed that SAA1 is a major isotype of acute phase SAA and may determine total SAA values. This specific assay could be used in the evaluation of SAA behavior in several clinical conditions.

  6. The porcine antibody repertoire: Variations on the textbook theme

    Directory of Open Access Journals (Sweden)

    John eButler

    2012-06-01

    Full Text Available The genes encoding the heavy and light chains of swine antibodies are organized in the same manner as in other eutherian mammals. There are ~ 30 VH genes, two functional DH genes and one functional JH gene. There are 14-60 V genes and 5 J segments, >22V genes and at least four JC cassettes. The heavy chain constant regions encode the same repertoire of isotypes common to other eutherian mammals. The piglet models offers advantage over rodent models since the fetal repertoire develops without maternal influences and the precocial nature of their multiple offspring allows the experimenter to control the influences of environmental and maternal factors on repertoire development postnatally. B cell lymphogenesis in swine begins in the fetal yolk sac at 20 days of gestation (DG, moves to the fetal liver at 30 DG and eventually to the bone marrow which dominates until birth (114 DG and to at least 5 weeks postpartum. There is no evidence that the ileal Peyers patches are a site of B cell lymphogenesis or are required for B cell maintenance. Unlike rodents and humans, light chain rearrangement begins first in the lambda locus; kappa rearrangements are not seen until late gestation.Dissimilar to lab rodents and more in the direction of the rabbit, swine utilize a small number of VH genes to form >90% of their pre-immune repertoire. Diversification in response to environmental antigen does not alter this pattern and is achieved by somatic hypermutation (SHM of the same small number of VH genes. The situation for light chains is less-well studied, but certain V and J and V and J are dominant in transcripts. The transcribed and secreted pre-immune antibodies of the fetus include mainly IgM, IgA and IgG3; this last isotype may provide a type of first responder mucosal immunity. Development of functional adaptive immunity is dependent on bacterial PAMPs or PAMPs provided by viral infections, indicating the importance of innate

  7. Generation of human scFv antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

    Science.gov (United States)

    Andris-Widhopf, Jennifer; Steinberger, Peter; Fuller, Roberta; Rader, Christoph; Barbas, Carlos F

    2011-09-01

    The development of therapeutic antibodies for use in the treatment of human diseases has long been a goal for many researchers in the antibody field. One way to obtain these antibodies is through phage-display libraries constructed from human lymphocytes. This protocol describes the construction of human scFv (single chain antibody fragment) libraries using a short linker (GGSSRSS) or a long linker (GGSSRSSSSGGGGSGGGG). In this method, the individual rearranged heavy- and light-chain variable regions are amplified separately and are linked through a series of overlap polymerase chain reaction (PCR) steps to give the final scFv products that are used for cloning.

  8. Characterization of the immunoglobulin repertoire of the spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    Smith, Lauren E; Crouch, Kathryn; Cao, Wei; Müller, Mischa R; Wu, Leeying; Steven, John; Lee, Michael; Liang, Musen; Flajnik, Martin F; Shih, Heather H; Barelle, Caroline J; Paulsen, Janet; Gill, Davinder S; Dooley, Helen

    2012-04-01

    The cartilaginous fish (chimeras, sharks, skates and rays) are the oldest group relative to mammals in which an adaptive immune system founded upon immunoglobulins has been found. In this manuscript we characterize the immunoglobulins of the spiny dogfish (Squalus acanthias) at both the molecular and expressed protein levels. Despite the presence of hundreds of IgM clusters in this species the serum levels of this isotype are comparatively low. However, analysis of cDNA sequences and serum protein suggests microheterogeneity in the IgM heavy chains and supports the proposal that different clusters are preferentially used in the two forms (monomer or pentamer) of this isotype. We also found that the IgNAR isotype in this species exists in a previously unknown multimeric format in serum. Finally, we identified a new form of the IgW isotype (the shark IgD orthologue), in which the leader is spliced directly to the first constant domain, resulting in a molecule lacking an antigen-binding domain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia.

    Science.gov (United States)

    Nor, Azimah; Zabedah, Md Yunus; Norsiah, Md Desa; Ngu, Lock Hock; Suhaila, Abd Rahman

    2010-06-01

    Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.

  10. Comparative genomic analysis of the arthropod muscle myosin heavy chain genes allows ancestral gene reconstruction and reveals a new type of 'partially' processed pseudogene

    Directory of Open Access Journals (Sweden)

    Kollmar Martin

    2008-02-01

    Full Text Available Abstract Background Alternative splicing of mutually exclusive exons is an important mechanism for increasing protein diversity in eukaryotes. The insect Mhc (myosin heavy chain gene produces all different muscle myosins as a result of alternative splicing in contrast to most other organisms of the Metazoa lineage, that have a family of muscle genes with each gene coding for a protein specialized for a functional niche. Results The muscle myosin heavy chain genes of 22 species of the Arthropoda ranging from the waterflea to wasp and Drosophila have been annotated. The analysis of the gene structures allowed the reconstruction of an ancient muscle myosin heavy chain gene and showed that during evolution of the arthropods introns have mainly been lost in these genes although intron gain might have happened in a few cases. Surprisingly, the genome of Aedes aegypti contains another and that of Culex pipiens quinquefasciatus two further muscle myosin heavy chain genes, called Mhc3 and Mhc4, that contain only one variant of the corresponding alternative exons of the Mhc1 gene. Mhc3 transcription in Aedes aegypti is documented by EST data. Mhc3 and Mhc4 inserted in the Aedes and Culex genomes either by gene duplication followed by the loss of all but one variant of the alternative exons, or by incorporation of a transcript of which all other variants have been spliced out retaining the exon-intron structure. The second and more likely possibility represents a new type of a 'partially' processed pseudogene. Conclusion Based on the comparative genomic analysis of the alternatively spliced arthropod muscle myosin heavy chain genes we propose that the splicing process operates sequentially on the transcript. The process consists of the splicing of the mutually exclusive exons until one exon out of the cluster remains while retaining surrounding intronic sequence. In a second step splicing of introns takes place. A related mechanism could be responsible for

  11. Increased myosin heavy chain-beta with atrial expression of ventricular light chain-2 in canine cardiomyopathy.

    Science.gov (United States)

    Fuller, Geraldine A; Bicer, Sabahattin; Hamlin, Robert L; Yamaguchi, Mamoru; Reiser, Peter J

    2007-10-01

    Dilated cardiomyopathy is a naturally occurring disease in humans and dogs. Human studies have shown increased levels of myosin heavy chain (MHC)-beta in failing ventricles and the left atria (LA) and of ventricular light chain (VLC)-2 in the right atria in dilated cardiomyopathy. This study evaluates the levels of MHC-beta in all heart chambers in prolonged canine right ventricular pacing. In addition, we determined whether levels of VLC2 were altered in these hearts. Failing hearts demonstrated significantly increased levels of MHC-beta in the right atria, right atrial appendage, LA, left atrial appendage (LAA), and right ventricle compared with controls. Significant levels of VLC2 were detected in the right atria of paced hearts. Differences in MHC-beta expression were observed between the LA and the LAA of paced and control dogs. MHC-beta expression was significantly greater in the LA of paced and control dogs compared with their respective LAA. The cardiac myosin isoform shifts in this study were similar to those observed in end-stage human heart failure and more severe than those reported in less prolonged pacing models, supporting the use of this model for further study of end-stage human heart failure. The observation of consistent differences between sampling sites, especially LA versus LAA, indicates the need for rigorous sampling consistency in future studies.

  12. T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis

    NARCIS (Netherlands)

    Yazdanbakhsh, M.; Paxton, W. A.; Kruize, Y. C.; Sartono, E.; Kurniawan, A.; van het Wout, A.; Selkirk, M. E.; Partono, F.; Maizels, R. M.

    1993-01-01

    To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43

  13. Socioeconomic status, eating patterns, and heavy metals exposure in women of childbearing age in Cali, Colombia

    Directory of Open Access Journals (Sweden)

    Roger Figueroa

    2017-09-01

    Conclusions: The findings showed that the studied population had access to heavy metal-contaminated food, which combined with the women’s cultural eating patterns, socioeconomic status, and metabolic characteristics led to a greater vulnerability to the effects of heavy metals exposure.

  14. Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state

    Science.gov (United States)

    Adams, G. R.; McCue, S. A.; Zeng, M.; Baldwin, K. M.

    1999-01-01

    During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.

  15. Bioaccumulative and conchological assessment of heavy metal transfer in a soil-plant-snail food chain

    Directory of Open Access Journals (Sweden)

    Nica Dragos V

    2012-06-01

    Full Text Available Abstract Background Copper (Cu, zinc (Zn, cadmium (Cd, and lead (Pb can pose serious threats to environmental health because they tend to bioaccumulate in terrestrial ecosystems. We investigated under field conditions the transfer of these heavy metals in a soil-plant-snail food chain in Banat area, Romania. The main goal of this paper was to assess the Roman snail (Helix pomatia usefulness in environmental monitoring as bioindicator of heavy metal accumulation. Eight sampling sites, selected by different history of heavy metal (HM exposure, were chosen to be sampled for soil, nettle leaves, and newly matured snails. This study also aimed to identify the putative effects of HM accumulation in the environment on phenotypic variability in selected shell features, which included shell height (SH, relative shell height (RSH, and whorl number (WN. Results Significantly higher amounts of HMs were accumulated in snail hepatopancreas and not in foot. Cu, Zn, and Cd have biomagnified in the snail body, particularly in the hepatopancreas. In contrast, Pb decreased when going up into the food chain. Zn, Cd, and Pb correlated highly with each other at all levels of the investigated food chain. Zn and Pb exhibited an effective soil–plant transfer, whereas in the snail body only foot Cu concentration was correlated with that in soil. There were significant differences among sampling sites for WN, SH, and RSH when compared with reference snails. WN was strongly correlated with Cd and Pb concentrations in nettle leaves but not with Cu and Zn. SH was independent of HM concentrations in soil, snail hepatopancreas, and foot. However, SH correlated negatively with nettle leaves concentrations for each HM except Cu. In contrast, RSH correlated significantly only with Pb concentration in hepatopancreas. Conclusions The snail hepatopancreas accumulates high amounts of HMs, and therefore, this organ can function as a reliable biomarker for tracking HM bioavailability

  16. Nuclear rotational population patterns in heavy-ion scattering and transfer reactions

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, J O; Stoyer, M A [Lawrence Berkeley Lab., CA (USA); Canto, L F; Donangelo, R [Universidade Federal do Rio de Janeiro, RJ (Brazil); Ring, P [Technische Univ. Muenchen, Garching (Germany, F.R.). Fakultaet fuer Physik

    1991-05-01

    A model of {sup 239}Pu with decoupled neutron is used for theoretical calculations of rotational population patterns in heavy ion inelastic scattering and one-neutron transfer reactions. The system treated in {sup 90}Zr on {sup 239}Pu at the near-barrier energy of 500 MeV and backscattering angles of 180deg and 140deg. The influence of the complex nuclear optical potential is seen to be very strong, and the Nilsson wave function of the odd neutron produces a distinctive pattern in the transfer reaction. (orig.).

  17. Reduction in beta-myosin heavy chains in stunned myocardium as assessed by nondenaturing gel electrophoresis.

    Science.gov (United States)

    Garcia, S C; Pomblum, V J; Gams, E; Rupp, H; Schipke, J D

    2007-09-01

    Myosin plays a key role in the structure and function of cardiac muscle. Three myosin isoenzymes (V(1), V(2), and V(3)) with different ATPase activities have been identified in mammalian ventricles based on their heavy chain constituents. The relative amount of myosin isoenzymes changes under physiological and pathological conditions. Until now, myosin isoenzymes have frequently been determined using either tube gel (nondenaturing) polyacrylamide gel electrophoresis (PAGE), or gradient or uniform sodium dodecyl sulfate (denaturing) PAGE. Both methods have disadvantages, e.g., a long running time. We developed, therefore, a uniform, nondenaturing PAGE with slab minigel format for analyzing the myosin isoenzymes in normoxic and stunned rabbit hearts. In normoxic hearts of adult rabbits, V(3) predominated over V(1) (46 vs 41%). In turn, in the stunned hearts, V(1) predominated over V(3) (70 vs 30%), and the heterodimeric V(2) was not anymore detectable. This alteration appears to result from a selective loss of myosin heavy chain (MHC)-beta. In parallel, the biochemical markers troponin I and creatine kinase were increased in the stunned hearts. We suggest that alterations of myosin isoenzymes in stunned myocardium can be monitored with native PAGE. The present analysis of myosin isoenzyme appears thus as a new tool for evaluating defects in MHC dimer formation in postischemic hearts.

  18. Characteristics and drug utilization patterns for heavy users of prescription drugs among the elderly

    DEFF Research Database (Denmark)

    Øymoen, Anita; Pottegård, Anton; Almarsdóttir, Anna Birna

    2015-01-01

    drug users accounted for 75.4% of their use in 2012, and five of these were cardiovascular drugs. The development over time for the ten most used drug classes followed the same pattern among heavy drug users and in the general population. CONCLUSION: There is a skewed utilization of prescription drugs...... frequently used drugs among heavy drug users and development in use over time. METHOD: This is a descriptive study. Heavy drug users were defined as the accumulated top 1 percentile who accounted for the largest share of prescription drug use measured in number of dispensed defined daily doses (DDDs...

  19. Plasma vitamin D-binding protein (GC) factors, immunoglobulin G heavy chain (GM) allotypes and immunoglobulin kappa light chain (KM1) allotype in patients with sarcoidosis and in healthy control subjects

    DEFF Research Database (Denmark)

    Milman, Nils; Thymann, Mariann; Graudal, Niels

    2002-01-01

    BACKGROUND AND AIM: Sarcoidosis is an immune disease with abnormalities in the production of vitamin D and immunoglobulins. The aim was to examine whether the distribution of plasma vitamin D-binding protein = group-specific component (GC) allotypes, immunoglobulin G heavy chain (GM) allotypes an...

  20. Phosphoneurofilament heavy chain and N-glycomics from the cerebrospinal fluid in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Gonçalves, Margarida; Tillack, Linda; de Carvalho, Mamede; Pinto, Susana; Conradt, Harald S; Costa, Júlia

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease of the motor neuron for which no clinically validated biomarkers have been identified. We have quantified by ELISA the biomarker phosphoneurofilament heavy chain (pNFH) in the cerebrospinal fluid (CSF) of ALS patients (n=29) and age-matched control patients with other diseases (n=19) by ELISA. Furthermore, we compared protein N-glycosylation of the CSF in ALS patients and controls, by applying a glycomics approach based on liquid chromatography and mass spectrometry. pNFH levels were significantly higher in ALS patients in comparison with controls (P<0.0001) in particular in fast progressors. The N-glycans found in the CSF were predominantly complex diantennary with sialic acid in α2,3- and α2,6-linkage, and bisecting N-acetylglucosamine-containing structures as well as peripherally fucosylated structures were found. As compared with controls the ALS group had a significant increase of a peak composed of the monosialylated diantennary glycans A2G2S(6)1 and FA2G2S(3)1 (P=0.0348). Our results underscore the value of pNFH as a biomarker in ALS. In addition, we identified a variation of the N-glycosylation pattern in ALS, suggesting that this change should be explored in future studies as potential biomarker. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Antibody dynamics in BRSV-infected Danish dairy herds as determined by isotype-specific immunoglobulins

    DEFF Research Database (Denmark)

    Uttenthal, Åse; Larsen, Lars Erik; Philipsen, J.S.

    2000-01-01

    Using specific ELISAs, antibody levels of four different isotypes to bovine respiratory syncytial virus (BRSV) were determined in calves, following experimental BRSV infection. Most calves experienced an increase in the specific IgM and IgG1 titres about 6-10 days after infection with BRSV. The Ig......M titre was transient showing positive titres for only 5-10 days, while specific IgG1 was present for a longer time. IgA was detected concomitantly with IgM but at a lower level. Production of IgG2 anti-BRSV antibodies was detected from 3 weeks after infection. In two closed herds, repeated blood......, another herd with acute BRSV was followed by weekly blood samples in six calves; in both herds IgM and IgG1 was detected shortly after the appearance of clinical signs. Serum samples from 50 Danish dairy herds (453 samples) were tested for immunoglobulins of the isotypes IgG1, IgG2 and IgM. The presence...

  2. Soliton patterns and breakup thresholds in hydrogen-bonded chains

    International Nuclear Information System (INIS)

    Tchakoutio Nguetcho, A.S.; Kofane, T.C.

    2006-12-01

    We study the dynamics of protons in hydrogen-bonded quasi one-dimensional networks in terms of a diatomic lattice model of protons and heavy ions, with a phi-four on-site substrate potential. We show that the model with linear and nonlinear coupling between lattice sites of the quartic type for the protons admits a richer dynamics that cannot be found with linear coupling. Depending on the two types of physical boundary conditions namely, the drop and condensate types of boundary conditions, and on conditions that require the presence of linear and nonlinear dispersion terms, soliton patterns that are represented by soliton with compact support, peak, drop, bell, cusp, shock, kink, bubble and loop solitons, are derived within a continuum approximation. The phase trajectories, as well as an analytical analysis, provide information on an disintegration of soliton patterns upon reaching some critical values of the lattice parameters. The total energies of soliton patterns are exactly calculated in the displacive limit. We also show that when the phonon anharmonism is taken into account, the width and the energy of soliton patterns are in qualitative agreement with experimental data. (author)

  3. Identification of 3-phase flow patterns of heavy oil from pressure drop and flow rate data

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco, F.; Bannwart, A.C.; Mendes, J.R.P. [Campinas State Univ., Sao Paulo (Brazil); Serapiao, A.B.S. [Sao Paulo State Univ., Sao Paulo (Brazil)

    2008-07-01

    Pipe flow of oil-gas-water mixtures poses a complex thermo-fluid dynamical problem. This paper examined the relationship between phase flow rates, flow pattern identification, and pressure drop in 3-phase water-assisted heavy oil in the presence of a gaseous phase. An artificial intelligence program called a support vector machine (SVM) was used to determine relevant parameters for flow pattern classification. Data from a 3-phase flow of heavy oil with gas and water in a vertical pipe was used in the study. The data were used to train the machine, which then predicted the flow pattern of the remaining data. Tests with different parameters and training data were then performed. The study showed that the proposed SVM flow pattern identification process accurately predicted flow patterns. It was concluded that the SVM took a relatively short amount of time to train. Future research is needed to apply the tool to larger flow datasets. 5 refs., 1 tab., 2 figs.

  4. [Socioeconomic status, eating patterns, and heavy metals exposure in women of childbearing age in Cali, Colombia].

    Science.gov (United States)

    Figueroa, Roger; Caicedo, Diana; Echeverry, Ghisliane; Peña, Miguel; Méndez, Fabián

    2017-09-01

    Global increase in food and water pollution is associated with health risk, which depends on the concentration, the dose, and the exposure time. This has raised concerns about the possible long-term effects of chronic exposure to low concentrations of heavy metals, such as lead, cadmium and mercury. To explore the relationship among socioeconomic status, eating patterns, and exposure to heavy metals among a population of women in Cali, Colombia. A total of 233 non-pregnant women of childbearing age living in the Aguablanca district of Cali, Colombia, were enrolled in the study. We gathered sociodemographic data, as well as information on housing conditions, exposure to heavy metals, frequency of food intake, and anthropometric measurements. Samples of lettuce, cabbage and fish (tilapia and butterfish) were collected to determine lead, cadmium, and mercury concentrations. Descriptive and multiple correspondence analyses were performed to establish eating patterns. Fish was served in each of the three main meals of the day, with a bigger serving at lunch time. Cadmium was found in three samples of butterfish at levels below the acceptable. Of those who ate fish more than once a week, 11.1% bought the product at a cadmium-positive store. The multiple correspondence analysis showed a positive relationship between being black and consuming butterfish and tilapia more than once per week. The findings showed that the studied population had access to heavy metal-contaminated food, which combined with the women's cultural eating patterns, socioeconomic status, and metabolic characteristics led to a greater vulnerability to the effects of heavy metals exposure.

  5. Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions

    Directory of Open Access Journals (Sweden)

    Catherine L Townsend

    2016-09-01

    Full Text Available Antibody variable regions are composed of a heavy and a light chain and in humans there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain CDR-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 - light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains, and probed the Protein Data Bank (PDB to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda and heavy chain gene rearrangements are correlated within donors, but can differ between donors. This indicates that TdT may work with differing efficiencies between different people, but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  6. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

    Science.gov (United States)

    Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  7. Home Health Chains and Practice Patterns: Evidence of 2008 Medicare Reimbursement Revision.

    Science.gov (United States)

    Huang, Sean Shenghsiu; Kim, Hyunjee

    2017-10-01

    Home health agencies (HHAs) are known to exploit the Medicare reimbursement schedule by targeting a specific number of therapy visits. These targeting behaviors cause unnecessary medical spending. The Centers for Medicare & Medicaid Services estimates that during fiscal year 2015, Medicare made more than $10 billion in improper payments to HHAs. Better understanding of heterogeneous gaming behaviors among HHAs can inform policy makers to more effectively oversee the home health care industry. This article aims to study how home health chains adjust and adopt new targeting behaviors as compared to independent agencies under the new reimbursement schedule. The analytic data are constructed from: (1) 5% randomly sampled Medicare home health claim data, and (2) HHA chain information extracted from the Medicare Cost Report. The study period spans from 2007 to 2010, and the sample includes 7800 unique HHAs and 380,118 treatment episodes. A multivariate regression model is used to determine whether chain and independent agencies change their practice patterns and adopt different targeting strategies after the revision of the reimbursement schedule in 2008. This study finds that independent agencies are more likely to target 6 and 14 visits, while chain agencies are more likely to target 20 visits. Such a change of practice patterns is more significant among for-profit HHAs. The authors expect these findings to inform policy makers that organizational structures, especially the combination of for-profit status and chain affiliation, should be taken into the consideration when detecting medical fraud and designing the reimbursement schedule.

  8. Comparison of new ELISA method with established SDS-PAGE method for determination of muscle myosin heavy chain isoforms

    Czech Academy of Sciences Publication Activity Database

    Říčný, Jan; Soukup, Tomáš

    2011-01-01

    Roč. 60, č. 6 (2011), s. 899-904 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA304/08/0256 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscle fiber types * myosin heavy chains * SDS - PAGE * immunoreactions * thyroid hormones * ELISA Subject RIV: EA - Cell Biology Impact factor: 1.555, year: 2011

  9. Modification of Antibody Function by Mutagenesis.

    Science.gov (United States)

    Dasch, James R; Dasch, Amy L

    2017-09-01

    The ability to "fine-tune" recombinant antibodies by mutagenesis separates recombinant antibodies from hybridoma-derived antibodies because the latter are locked with respect to their properties. Recombinant antibodies can be modified to suit the application: Changes in isotype, format (e.g., scFv, Fab, bispecific antibodies), and specificity can be made once the heavy- and light-chain sequences are available. After immunoglobulin heavy and light chains for a particular antibody have been cloned, the binding site-namely, the complementarity determining regions (CDR)-can be manipulated by mutagenesis to obtain antibody variants with improved properties. The method described here is relatively simple, uses commercially available reagents, and is effective. Using the pComb3H vector, a commercial mutagenesis kit, PfuTurbo polymerase (Agilent), and two mutagenic primers, a library of phage with mutagenized heavy and light CDR3 can be obtained. © 2017 Cold Spring Harbor Laboratory Press.

  10. Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and Semiquantitation

    Science.gov (United States)

    2016-01-01

    Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing “fit-for-purpose” bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma. PMID:27034966

  11. Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and Semiquantitation.

    Science.gov (United States)

    Chen, Lin-Zhi; Roos, David; Philip, Elsy

    2016-01-01

    Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing "fit-for-purpose" bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma.

  12. Myosin heavy chain composition of single fibres from m. biceps brachii of male body builders

    DEFF Research Database (Denmark)

    Klitgaard, H; Zhou, M.-Y.; Richter, Erik

    1990-01-01

    The myosin heavy chain (MHC) composition of single fibres from m. biceps brachii of young sedentary men (28 +/- 0.4 years, mean +/- SE, n = 4) and male body builders (25 +/- 2.0 years, n = 4) was analysed with a sensitive one-dimensional electrophoretic technique. Compared with sedentary men...... expression of MHC isoforms within histochemical type II fibres of human skeletal muscle with body building. Furthermore, in human skeletal muscle differences in expression of MHC isoforms may not always be reflected in the traditional histochemical classification of types I, IIa, IIb and IIc fibres....

  13. Immunoglobulin diversification in B cell malignancies: internal splicing of heavy chain variable region as a by-product of somatic hypermutation

    NARCIS (Netherlands)

    Bende, R. J.; Aarts, W. M.; Pals, S. T.; van Noesel, C. J. M.

    2002-01-01

    In this study we describe alternative splicing of somatically mutated immunoglobulin (Ig) variable heavy chain (V-H) genes in three distinct primary B cell non-Hodgkin's lymphomas (B-NHL). In two V4-34 expressing lymphomas, ie a post-germinal center type B cell chronic lymphocytic leukemia (B-CLL)

  14. Myosin heavy chain profile of equine gluteus medius muscle following prolonged draught-exercise training and detraining.

    Science.gov (United States)

    Serrano, A L; Rivero, J L

    2000-04-01

    Fourteen 4-year old Andalusian mares were used to examine the plasticity of myosin heavy chain (MHC) composition in horse skeletal muscle with heavy draught-exercise training and detraining. Seven horses underwent a training programme based on carriage exercises for 8 months. Afterwards, they were kept in paddocks for 3 months. The remaining seven animals were used as control horses. Three gluteus medius muscle biopsies were removed at depths of 20, 40 and 60 mm from each horse before (month 0), during the training (months 3 and 8) and after detraining (month 11). Myosin heavy chain composition was analysed by electrophoresis and immunohistochemically with anti-MHC monoclonal antibodies. Fibre areas, oxidative capacity and capillaries were studied histochemically. After 8 months of training, MHC-IIX and IIX fibres decreased whereas MHC-I and type I and I + IIA fibres increased. Neither MHC-IIA nor the percentage of IIA fibres changed when the data were considered as a whole, but the proportion of MHC-IIA increased in the superficial region of the muscle after 8 months of training. Mean areas of type II fibres were not affected by training and detraining, but the cross-sectional of type I fibres increased after 3 month of training and not further increases were recorded afterward. The percentage of high-oxidative capacity fibres and the number of capillaries per mm2 increased with training. Most of these muscular adaptations reverted after detraining. These results indicate that long term draught-exercise training induces a reversible transition of MHC composition in equine muscle in the order IIX --> IIA --> I. The physiological implication of these changes is an impact on the velocity of shortening and fatigue resistance of muscle fibres.

  15. Flow cytometric analysis of immunoglobulin heavy chain expression in B-cell lymphoma and reactive lymphoid hyperplasia

    Science.gov (United States)

    Grier, David D; Al-Quran, Samer Z; Cardona, Diana M; Li, Ying; Braylan, Raul C

    2012-01-01

    The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of clonal immunoglobulin (Ig) light chain expression. In some BCLs, the determination of clonality based on Ig light chain restriction may be difficult. The aim of our study was to assess the utility of flow cytometric analysis of surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes. HC expression on B-cells varied among different types of hyperplasias. In follicular hyperplasia, IgM and IgD expression was high in mantle cells while germinal center cells showed poor HC expression. In other hyperplasias, B cell compartments were blurred but generally showed high IgD and IgM expression. Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD expression was significantly lower in BCLs than in hyperplasias, a finding that can be useful in differentiating lymphoma from reactive processes. PMID:22400070

  16. A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity.

    Directory of Open Access Journals (Sweden)

    Géraldine De Muylder

    2013-10-01

    Full Text Available In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.

  17. Variants of synoptic-scale patterns inducing heavy rains in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Kašpar, Marek; Müller, Miloslav

    2010-01-01

    Roč. 35, 9-12 (2010), s. 477-483 ISSN 1474-7065 R&D Projects: GA AV ČR KJB300420701; GA AV ČR KJB300420802 Institutional research plan: CEZ:AV0Z30420517 Keywords : Widespread heavy rain * synoptic-scale pattern * moisture flux * classification Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 0.917, year: 2010

  18. The C-terminal amino acid of the MHC-I heavy chain is critical for binding to Derlin-1 in human cytomegalovirus US11-induced MHC-I degradation.

    Science.gov (United States)

    Cho, Sunglim; Kim, Bo Young; Ahn, Kwangseog; Jun, Youngsoo

    2013-01-01

    Derlin-1 plays a critical role in endoplasmic reticulum-associated protein degradation (ERAD) of a particular subset of proteins. Although it is generally accepted that Derlin-1 mediates the export of ERAD substrates from the ER to the cytosol, little is known about how Derlin-1 interacts with these substrates. Human cytomegalovirus (HCMV) US11 exploits Derlin-1-dependent ERAD to degrade major histocompatibility complex class I (MHC-I) molecules and evade immune surveillance. US11 requires the cytosolic tail of the MHC-I heavy chain to divert MHC-I molecules into the ERAD pathway for degradation; however, the underlying mechanisms remain unknown. Here, we show that the cytosolic tail of the MHC-I heavy chain, although not required for interaction with US11, is required for tight binding to Derlin-1 and thus for US11-induced dislocation of the MHC-I heavy chain to the cytosol for proteasomal degradation. Surprisingly, deletion of a single C-terminal amino acid from the cytosolic tail disrupted the interaction between MHC-I molecules and Derlin-1, rendering mutant MHC-I molecules resistant to US11-induced degradation. Consistently, deleting the C-terminal cytosolic region of Derlin-1 prevented it from binding to MHC-I molecules. Taken together, these results suggest that the cytosolic region of Derlin-1 is involved in ERAD substrate binding and that this interaction is critical for the Derlin-1-mediated dislocation of the MHC-I heavy chain to the cytosol during US11-induced MHC-I degradation.

  19. Detection of clonal B cells in microdissected reactive lymphoproliferations: possible diagnostic pitfalls in PCR analysis of immunoglobulin heavy chain gene rearrangement

    DEFF Research Database (Denmark)

    Zhou, X.G.; Sandvej, K.; Gregersen, Niels

    1999-01-01

    Aims-To evaluate the specificity of standard and fluorescence based (GENESCAN) polymerase chain reaction (PCR) immunoglobulin heavy chain (IgH) gene rearrangement analysis in complete and microdissected paraffin wax embedded sections from lymphoid proliferations. Methods-PCR IgH gene rearrangement...... because of preferential priming or detection of local B cell clones. Data from clonal analysis of small, microdissected or lymphocyte poor samples must be evaluated critically. It is recommended that analyses should be run in parallel on at least two tissue specimens. Only reproducible bands present...

  20. Cloning of cDNAs coding for the heavy chain region and connecting region of human factor V, a blood coagulation factor with four types of internal repeats

    International Nuclear Information System (INIS)

    Kane, W.H.; Ichinose, A.; Hagen, F.S.; Davie, E.W.

    1987-01-01

    Human factor V is a high molecular weight plasma glycoprotein that participates as a cofactor in the conversion of prothrombin to thrombin by factor X/sub a/. Prior to its participation in the coagulation cascade, factor V is converted to factor V/sub a/ by thrombin generating a heavy chain and a light chain, and these two chains are held together by calcium ions. A connecting region originally located between the heavy and light chains is liberated during the activation reaction. In a previous study, a cDNA of 2970 nucleotides that codes for the carboxyl-terminal 938 amino acids of factor V was isolated and characterized from a Hep G2 cDNA library. This cDNA has been used to obtain additional clones from Hep G2 and human liver cDNA libraries. Furthermore, a Hep G2 cDNA library prepared with an oligonucleotide from the 5' end of these cDNAs was screened to obtain overlapping cDNA clones that code for the amino-terminal region of the molecule. The composite sequence of these clones spans 6911 nucleotides and is consistent with the size of the factor V message present in Hep G2 cells (approximately 7 kilobases). The cDNA codes for a leader sequence of 28 amino acids and a mature protein of 2196 amino acids. The amino acid sequence predicted from the cDNA was in complete agreement with 139 amino acid residues that were identified by Edman degradation of cyanogen bromide peptides isolated from the heavy chain region and connecting region of plasma factor V. The domain structure of human factor V is similar to that previously reported for human coagulation factor VIII. Two types of tandem repeats (17 and 9 amino acids) have also been identified in the connecting region of factor V. The present data indicate that the amino acid sequence in the heavy and light chain regions of factor V is ∼ 40% identical with the corresponding regions of factor VIII

  1. Serum Anti-Vibrio cholerae Immunoglobulin Isotype in BALB/c Mice Immunized With ompW-Loaded Chitosan

    Directory of Open Access Journals (Sweden)

    Mahdi Fasihi-Ramandi

    2016-05-01

    Full Text Available Background: Chitosan, a liner polysaccharide, is a biocompatible and safe material for the delivery of therapeutic proteins and antigens, particularly via mucosal systems. Objectives: In this study, the production of antibodies in response to outermembrane protein W (ompW-loaded chitosan in BALB/c mice was evaluated. Materials and Methods: Mice were subjected to intraperitoneal injection of ompW or nasal administration of ompW-loaded chitosan on days 1, 14, and 28, and the antibodies were measured on day 42 with ELISA. Results: The titration of antibodies indicated that the nasal administration of ompW-loaded chitosan was better able to stimulate the immune response compared to intraperitoneal injections. However, the titration of total and IgG isotypes showed a significant difference between intraperitoneal and nasal immunization (P < 0.01. A significant difference was also seen in serum IgA isotypes at over 1/80 titrations, but not at lower dilutions (P < 0.01. Despite the serum antibodies, the results of lavage fluid analysis revealed that the IgG and IgA isotypes in the mice subjected to nasal immunization with ompW-loaded chitosan were significantly higher than in the other group (P < 0.01. Conclusions: Based on the preliminary results presented in this research, it is suggested that ompW-loaded chitosan could be a suitable choice for nasal application to immunize the host against Vibrio cholerae. However, more work is required to determine the efficiency of the antibodies in neutralizing the bacterial toxin or bacterial movement.

  2. A Comprehensive Analysis of the Phylogeny, Genomic Organization and Expression of Immunoglobulin Light Chain Genes in Alligator sinensis, an Endangered Reptile Species.

    Directory of Open Access Journals (Sweden)

    Xifeng Wang

    Full Text Available Crocodilians are evolutionarily distinct reptiles that are distantly related to lizards and are thought to be the closest relatives of birds. Compared with birds and mammals, few studies have investigated the Ig light chain of crocodilians. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC library and available genome data, we characterized the genomic organization of the Alligator sinensis IgL gene loci. The Alligator sinensis has two IgL isotypes, λ and κ, the same as Anolis carolinensis. The Igλ locus contains 6 Cλ genes, each preceded by a Jλ gene, and 86 potentially functional Vλ genes upstream of (Jλ-Cλn. The Igκ locus contains a single Cκ gene, 6 Jκs and 62 functional Vκs. All VL genes are classified into a total of 31 families: 19 Vλ families and 12 Vκ families. Based on an analysis of the chromosomal location of the light chain genes among mammals, birds, lizards and frogs, the data further confirm that there are two IgL isotypes in the Alligator sinensis: Igλ and Igκ. By analyzing the cloned Igλ/κ cDNA, we identified a biased usage pattern of V families in the expressed Vλ and Vκ. An analysis of the junctions of the recombined VJ revealed the presence of N and P nucleotides in both expressed λ and κ sequences. Phylogenetic analysis of the V genes revealed V families shared by mammals, birds, reptiles and Xenopus, suggesting that these conserved V families are orthologous and have been retained during the evolution of IgL. Our data suggest that the Alligator sinensis IgL gene repertoire is highly diverse and complex and provide insight into immunoglobulin gene evolution in vertebrates.

  3. A Comprehensive Analysis of the Phylogeny, Genomic Organization and Expression of Immunoglobulin Light Chain Genes in Alligator sinensis, an Endangered Reptile Species

    Science.gov (United States)

    Lu, Yan; Zhang, Chenglin; Wu, Xiaobing; Han, Haitang; Zhao, Yaofeng; Ren, Liming

    2016-01-01

    Crocodilians are evolutionarily distinct reptiles that are distantly related to lizards and are thought to be the closest relatives of birds. Compared with birds and mammals, few studies have investigated the Ig light chain of crocodilians. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC) library and available genome data, we characterized the genomic organization of the Alligator sinensis IgL gene loci. The Alligator sinensis has two IgL isotypes, λ and κ, the same as Anolis carolinensis. The Igλ locus contains 6 Cλ genes, each preceded by a Jλ gene, and 86 potentially functional Vλ genes upstream of (Jλ-Cλ)n. The Igκ locus contains a single Cκ gene, 6 Jκs and 62 functional Vκs. All VL genes are classified into a total of 31 families: 19 Vλ families and 12 Vκ families. Based on an analysis of the chromosomal location of the light chain genes among mammals, birds, lizards and frogs, the data further confirm that there are two IgL isotypes in the Alligator sinensis: Igλ and Igκ. By analyzing the cloned Igλ/κ cDNA, we identified a biased usage pattern of V families in the expressed Vλ and Vκ. An analysis of the junctions of the recombined VJ revealed the presence of N and P nucleotides in both expressed λ and κ sequences. Phylogenetic analysis of the V genes revealed V families shared by mammals, birds, reptiles and Xenopus, suggesting that these conserved V families are orthologous and have been retained during the evolution of IgL. Our data suggest that the Alligator sinensis IgL gene repertoire is highly diverse and complex and provide insight into immunoglobulin gene evolution in vertebrates. PMID:26901135

  4. Agile supply chain capabilities: emerging patterns as a determinant of competitive objectives

    Science.gov (United States)

    Yusuf, Yahaya Y.; Adeleye, E. O.; Sivayoganathan, K.

    2001-10-01

    Turbulent change caused by factors such as changing customer and technological requirements threatens manufacturers through lower product life cycles, profits and bleak survival prospects. Therefore, several companies are stressing flexibility and agility in order to respond, real time, to the unique needs of customers and markets. However, the resource competencies required are often difficult to mobilise and retain by single companies. It is therefore imperative for companies to co-operate and leverage complementary competencies. To this end, legally separate and spatially distributed companies are becoming integrated through Internet-based technologies. The paper reviews emerging patterns in supply chain integration. It also explores the relationship between the emerging patterns and attainment of competitive objectives. The results reported in the paper are based on data from a survey by questionnaire. The survey involved 600 companies in the UK, as part of a larger study of agile manufacturing. The study was driven by a conceptual model, which relates supply chain practices to competitive objectives. The analysis involves the use of factor analysis to reduce research variables to a few principal components. Subsequently, multiple regression was conducted to study the relationship amongst the reduced variables. The results validate the proposed conceptual model and lend credence to current thinking that supply chain integration is a vital tool for competitive advantage.

  5. Identification of high-mannose and multiantennary complex-type N-linked glycans containing alpha-galactose epitopes from Nurse shark IgM heavy chain.

    Science.gov (United States)

    Harvey, David J; Crispin, Max; Moffatt, Beryl E; Smith, Sylvia L; Sim, Robert B; Rudd, Pauline M; Dwek, Raymond A

    2009-11-01

    MALDI-TOF mass spectrometry, negative ion nano-electrospray MS/MS and exoglycosidase digestion were used to identify 36 N-linked glycans from 19S IgM heavy chain derived from the nurse shark (Ginglymostoma cirratum). The major glycan was the high-mannose compound, Man(6)GlcNAc(2) accompanied by small amounts of Man(5)GlcNAc(2), Man(7)GlcNAc(2) and Man(8)GlcNAc(2). Bi- and tri-antennary (isomer with a branched 3-antenna) complex-type glycans were also abundant, most contained a bisecting GlcNAc residue (beta1-->4-linked to the central mannose) and with varying numbers of alpha-galactose residues capping the antennae. Small amounts of monosialylated glycans were also found. This appears to be the first comprehensive study of glycosylation in this species of animal. The glycosylation pattern has implications for the mechanism of activation of the complement system by nurse shark IgM.

  6. Expression of smooth muscle and non-muscle myosin heavy chain isoforms in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Rovner, A.S.; Murphy, R.A.; Owens, G.K.

    1986-01-01

    Immunocytochemical studies of cultured smooth muscle cells (SMCs) have disagreed on the nature of myosin expression. This investigation was undertaken to test for the presence of heterogeneous myosin heavy chain (MHC) isoforms in cell culture as a possible explanation for these results. Previously, Rovner et al. detected two MHCs in intact smooth muscles which differed in molecular weight by ca. 4000 daltons (SM1 and SM2) using a 3-4% acrylamide gradient SDS gel system. When sub-confluent primary cultures of rat aorta SMCs were assayed by this system, SM1 and SM2 were seen, along with large amounts of a third, unique MHC, NM, which closely resembled the MHC from human platelet in size and antigenicity. Data from 35 S-methionine autoradiograms showed that the log growth phase SMC cultures were producing almost exclusively NM, but the growth arrest, post-confluent cultures synthesized increased relative amounts of the SM MHC forms and contained comparable amounts of SM1, SM2, and NM. The same patterns of MHC synthesis were seen in sub-passaged SMCs. The expression of the SM-specific forms of myosin in quiescent, post-confluent cultures parallels that of smooth muscle actin suggesting that density induced growth arrest promotes cytodifferentiation in cultured vascular SMCs

  7. Comparing domain interactions within antibody Fabs with kappa and lambda light chains.

    Science.gov (United States)

    Toughiri, Raheleh; Wu, Xiufeng; Ruiz, Diana; Huang, Flora; Crissman, John W; Dickey, Mark; Froning, Karen; Conner, Elaine M; Cujec, Thomas P; Demarest, Stephen J

    2016-10-01

    IgG antibodies are multi-domain proteins with complex inter-domain interactions. Human IgG heavy chains (HCs) associate with light chains (LCs) of the κ or λ isotype to form mature antibodies capable of binding antigen. The HC/LC interaction involves 4 domains: VH and CH1 from the HC and VL and CL from the LC. Human Fabs with κ LCs have been well characterized for their unfolding behaviors and demonstrate a significant level of cooperativity and stabilization when all 4 domains are intact. Very little is known regarding the thermodynamic properties of human Fabs with λ LCs. Here, we dissect the domain contributions to Fab stability for both κ and λ LC-containing Fabs. We find the cooperativity of unfolding between the constant domains, CH1/Cλ, and variable domains, VH/Vλ, within λ LC-containing Fabs is significantly weaker than that of κ LC-containing Fabs. The data suggests there may not be an evolutionary necessity for strong variable/constant domain cooperativity within λ LC-containing Fabs. After investigating the biophysical properties of Fabs with mismatched variable and constant domain subunits (e.g., VH/Vκ paired with CH1/Cλ or T cell receptor Cα/Cβ), the major role of the constant domains for both κ- and λ-containing Fabs may be to reduce the hydrophobic exposure at the VH/VL interface. Even though Fabs with these non-native pairings were thermodynamically less stable, they secreted well from mammalian cells as well behaved monodisperse proteins, which was in contrast to what was observed with the VH/Vκ and VH/Vλ scFvs that secreted as a mixture of monomer and aggregates.

  8. Characterization of human cardiac myosin heavy chain genes

    International Nuclear Information System (INIS)

    Yamauchi-Takihara, K.; Sole, M.J.; Liew, J.; Ing, D.; Liew, C.C.

    1989-01-01

    The authors have isolated and analyzed the structure of the genes coding for the α and β forms of the human cardiac myosin heavy chain (MYHC). Detailed analysis of four overlapping MYHC genomic clones shows that the α-MYHC and β-MYHC genes constitute a total length of 51 kilobases and are tandemly linked. The β-MYHC-encoding gene, predominantly expressed in the normal human ventricle and also in slow-twitch skeletal muscle, is located 4.5 kilobases upstream of the α-MYHC-encoding gene, which is predominantly expressed in normal human atrium. The authors have determined the nucleotide sequences of the β form of the MYHC gene, which is 100% homologous to the cardiac MYHC cDNA clone (pHMC3). It is unlikely that the divergence of a few nucleotide sequences from the cardiac β-MYHC cDNA clone (pHMC3) reported in a MYHC cDNA clone (PSMHCZ) from skeletal muscle is due to a splicing mechanism. This finding suggests that the same β form of the cardiac MYHC gene is expressed in both ventricular and slow-twitch skeletal muscle. The promoter regions of both α- and β-MYHC genes, as well as the first four coding regions in the respective genes, have also been sequenced. The sequences in the 5'-flanking region of the α- and β-MYHC-encoding genes diverge extensively from one another, suggesting that expression of the α- and β-MYHC genes is independently regulated

  9. [Use of new immunoglobulin isotype-specific ELISA-systems to detect Salmonella infections in pigs].

    Science.gov (United States)

    Ehlers, Joachim; Alt, Michael; Trepnau, Daniela; Lehmann, Jörg

    2006-01-01

    In Germany, the program for controlling salmonella infections in pigs is based on tests detecting salmonella-lipopolysaccharide (LPS) induced antibodies in meat-juice or blood. These conventional tests which are based on the technology of enzyme-linked immunosorbent assay (ELISA) detect exclusively or mainly immunoglobulin(lg)G antibodies. Meanwhile, novel ELISA systems (WCE-ELISA, 3-Isotype-Screening-ELISA) have been developed, which additionally detect the antibody classes IgM and IgA.This fact enables the registration of fresh salmonella infections (starting with day 5 p.i.) and thus, the distinction between early and older infections. The results show that animals with early salmonella infections appear significantly more often in herds with a high than with a low prevalence. With the newly developed tests this group of animals can be detected much more efficiently and precisely than with the tests used so far. Due to their clearly improved sensitivity the application of the WCE-ELISA and the 3-Isotype-Screening-ELISA in terms of the QS-Salmonella-Monitoring program can therefore significantly improve the selection of farms with potential salmonella excretors. Additionally, the WCE-ELISA can be applied very suitable for the examination of individual animals.

  10. Selection and characterization of naturally occurring single-domain (IgNAR) antibody fragments from immunized sharks by phage display.

    Science.gov (United States)

    Dooley, Helen; Flajnik, Martin F; Porter, Andrew J

    2003-09-01

    The novel immunoglobulin isotype novel antigen receptor (IgNAR) is found in cartilaginous fish and is composed of a heavy-chain homodimer that does not associate with light chains. The variable regions of IgNAR function as independent domains similar to those found in the heavy-chain immunoglobulins of Camelids. Here, we describe the successful cloning and generation of a phage-displayed, single-domain library based upon the variable domain of IgNAR. Selection of such a library generated from nurse sharks (Ginglymostoma cirratum) immunized with the model antigen hen egg-white lysozyme (HEL) enabled the successful isolation of intact antigen-specific binders matured in vivo. The selected variable domains were shown to be functionally expressed in Escherichia coli, extremely stable, and bind to antigen specifically with an affinity in the nanomolar range. This approach can therefore be considered as an alternative route for the isolation of minimal antigen-binding fragments with favorable characteristics.

  11. Shark IgW C region diversification through RNA processing and isotype switching.

    Science.gov (United States)

    Zhang, Cecilia; Du Pasquier, Louis; Hsu, Ellen

    2013-09-15

    Sharks and skates represent the earliest vertebrates with an adaptive immune system based on lymphocyte Ag receptors generated by V(D)J recombination. Shark B cells express two classical Igs, IgM and IgW, encoded by an early, alternative gene organization consisting of numerous autonomous miniloci, where the individual gene cluster carries a few rearranging gene segments and one C region, μ or ω. We have characterized eight distinct Ig miniloci encoding the nurse shark ω H chain. Each cluster consists of VH, D, and JH segments and six to eight C domain exons. Two interspersed secretory exons, in addition to the 3'-most C exon with tailpiece, provide the gene cluster with the ability to generate at least six secreted isoforms that differ as to polypeptide length and C domain combination. All clusters appear to be functional, as judged by the capability for rearrangement and absence of defects in the deduced amino acid sequence. We previously showed that IgW VDJ can perform isotype switching to μ C regions; in this study, we found that switching also occurs between ω clusters. Thus, C region diversification for any IgW VDJ can take place at the DNA level by switching to other ω or μ C regions, as well as by RNA processing to generate different C isoforms. The wide array of pathogens recognized by Abs requires different disposal pathways, and our findings demonstrate complex and unique pathways for C effector function diversity that evolved independently in cartilaginous fishes.

  12. Tracing heavy metals in 'swine manure - maggot - chicken' production chain.

    Science.gov (United States)

    Wang, Wanqiang; Zhang, Wenjuan; Wang, Xiaoping; Lei, Chaoliang; Tang, Rui; Zhang, Feng; Yang, Qizhi; Zhu, Fen

    2017-08-21

    With the development of large-scale livestock farming, manure pollution has drawn much attention. Conversion by insects is a rapid and cost-effective new method for manure management. Swine manure conversion with maggots (Musca domestica larvae) has developed, and the harvested maggots are often used as animal feed. However, the flow of heavy metals from manure to downstream processes cannot be ignored, and therefore, heavy metal content was measured in untreated raw manure, maggot-treated manure, harvested maggots and maggot-eating chickens (chest muscle and liver) to evaluate potential heavy metal risks. The levels of zinc, copper, chromium, selenium, cadmium and lead had significant differences between untreated raw manure and maggot-treated manure. The concentrations of all detected heavy metals, except for cadmium and selenium, in maggots met the limits established by the feed or feed additive standards of many countries. The bioaccumulation factor (BAF) of heavy metals decreased with the increase of the maggot instar, indicating that heavy metals were discharged from the bodies of maggots with the growth of maggots. Also, the contents of overall heavy metals in chickens fed harvested maggots met the standards for food. In conclusion, regarding heavy metals, it is eco-safe to use maggots in manure management.

  13. Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

    Energy Technology Data Exchange (ETDEWEB)

    Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina; Daum, Gabor; Kuckwa, Jessica; Kastl, Lena; Buttgereit, Detlev [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany); Renkawitz-Pohl, Renate, E-mail: renkawit@biologie.uni-marburg.de [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany)

    2013-02-15

    Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sites (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity.

  14. Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

    International Nuclear Information System (INIS)

    Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina; Daum, Gabor; Kuckwa, Jessica; Kastl, Lena; Buttgereit, Detlev; Renkawitz-Pohl, Renate

    2013-01-01

    Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sites (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity

  15. The first dose of a Haemophilus influenzae type b conjugate vaccine reactivates memory B cells: evidence for extensive clonal selection, intraclonal affinity maturation, and multiple isotype switches to IgA2

    DEFF Research Database (Denmark)

    Hougs, L; Juul, L; Ditzel, H J

    1999-01-01

    selected, and expanded population of cells existing before vaccination, i.e., memory B cells. The dominating heavy and light chains of the response were combined in a Fab that bound HibCP. It was shown that the shared heavy and light chain mutations increased the affinity for HibCP considerably, indicating...

  16. Inhalation deposition and retention patterns of a U-Pu chain aggregate aerosol

    International Nuclear Information System (INIS)

    Briant, J.K.; Sanders, C.L.

    1987-01-01

    Chain aggregate aerosol particles are normally formed during many high-temperature combustion and vaporization processes. The shape of chain aggregate aerosol particles could have an effect on the pattern of inhalation deposition and retention of the particles in the respiratory tract. A chain aggregate aerosol of nuclear reactor fuel could be present as an inhalation hazard if it were released to the atmosphere after a meltdown, core-disruptive accident. Rats were exposed to a chain aggregate U-Pu aerosol made by laser vaporization of mixed-oxide, breeder reactor fuel (20% plutonium dioxide and 80% uranium dioxide), then sacrificed to measure the clearance and retention of the fuel aerosol particles. Deposition of the 0.7-micron (activity median aerodynamic equivalent diameter) aerosol particles resulted in an average initial lung burden of 4140 Bq alpha activity. The chain aggregate particle shape was not a major factor in the total deposition; however, it may have influenced the regional distribution of the activity deposited. Retention of the particles in the upper airways of the tracheobronchial tree was on the order of 1% of the concurrent lung burden, which is consistent with recent data of other investigations. This study indicates that insoluble chain aggregate particles are retained in the tracheobronchial airways to a degree similar to simple spherically shaped particles of equivalent volume diameter

  17. Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Daniela Sieghart

    2018-04-01

    Full Text Available Anti-citrullinated protein antibodies (ACPA and rheumatoid factor (RF are the most commonly used diagnostic markers of rheumatoid arthritis (RA. These antibodies are predominantly of the immunoglobulin (Ig M (RF or IgG (ACPA isotype. Other subtypes of both antibodies—particularly IgA isotypes and other autoantibodies—such as RA33 antibodies—have been repeatedly reported but their diagnostic value has still not been fully elucidated. Here, we investigated the prevalence of IgA, IgG, and IgM subtypes of RF, ACPA, and RA33 antibodies in patients with RA. To determine the diagnostic specificity and sensitivity sera from 290 RA patients (165 early and 125 established disease, 261 disease controls and 100 healthy subjects were tested for the presence of IgA, IgG, and IgM isotypes of RF, ACPA, and RA33 by EliA™ platform (Phadia AB, Uppsala, Sweden. The most specific antibodies were IgG-ACPA, IgA-ACPA, and IgG-RF showing specificities >98%, closely followed by IgG- and IgA-RA33 while IgM subtypes were somewhat less specific, ranging from 95.8% (RA33 to 90% (RF. On the other hand, IgM-RF was the most sensitive subtype (65% followed by IgG-ACPA (59.5% and IgA-RF (50.7%. Other subtypes were less sensitive ranging from 35 (IgA-ACPA to 6% (IgA-RA33. RA33 antibodies as well as IgA-RF and IgA-ACPA were found to increase the diagnostic sensitivity of serological testing since they were detected also in seronegative patients reducing their number from 109 to 85. Moreover, analyzing IgM-RF by EliA™ proved more sensitive than measuring RF by nephelometry and further reduced the number of seronegative patients to 76 individuals. Importantly, among antibody positive individuals, RA patients were found having significantly more antibodies (≥3 than disease controls which generally showed one or two antibody species. Thus, increasing the number of autoantibodies in serological routine testing provides valuable additional information allowing to better

  18. Designing Optimal LNG Station Network for U.S. Heavy-Duty Freight Trucks using Temporally and Spatially Explicit Supply Chain Optimization

    Science.gov (United States)

    Lee, Allen

    The recent natural gas boom has opened much discussion about the potential of natural gas and specifically Liquefied Natural Gas (LNG) in the United States transportation sector. The switch from diesel to natural gas vehicles would reduce foreign dependence on oil, spur domestic economic growth, and potentially reduce greenhouse gas emissions. LNG provides the most potential for the medium to heavy-duty vehicle market partially due to unstable oil prices and stagnant natural gas prices. As long as the abundance of unconventional gas in the United States remains cheap, fuel switching to natural gas could provide significant cost savings for long haul freight industry. Amid a growing LNG station network and ever increasing demand for freight movement, LNG heavy-duty truck sales are less than anticipated and the industry as a whole is less economic than expected. In spite of much existing and mature natural gas infrastructure, the supply chain for LNG is different and requires explicit and careful planning. This thesis proposes research to explore the claim that the largest obstacle to widespread LNG market penetration is sub-optimal infrastructure planning. No other study we are aware of has explicitly explored the LNG transportation fuel supply chain for heavy-duty freight trucks. This thesis presents a novel methodology that links a network infrastructure optimization model (represents supply side) with a vehicle stock and economic payback model (represents demand side). The model characterizes both a temporal and spatial optimization model of future LNG transportation fuel supply chains in the United States. The principal research goal is to assess the economic feasibility of the current LNG transportation fuel industry and to determine an optimal pathway to achieve ubiquitous commercialization of LNG vehicles in the heavy-duty transport sector. The results indicate that LNG is not economic as a heavy-duty truck fuel until 2030 under current market conditions

  19. 3D Architecture, dynamics as well as functional implications of genome organization of the Prader-Willi/Angelmann syndrome region & the Immunoglobin Heavy-Chain locus

    NARCIS (Netherlands)

    T.A. Knoch (Tobias)

    2008-01-01

    textabstractThe general 3D architecture of the immunoglobin heavy-chain (Igh) locus was determined by a novel interdisciplinary combination of high-resolution FISH and high-resolution epifluorescence spectral distance microscopy with analytical analysis, computer simulations, as well as

  20. Production of bifunctional proteins by Aspergillus awamori: Llama variable heavy chain antibody fragment (VHH) R9 coupled to Arthromyces ramosus peroxidase (ARP)

    NARCIS (Netherlands)

    Joosten, V.; Roelofs, M.S.; Dries, N. van den; Goosen, T.; Verrips, C.T.; Hondel, C.A.M.J.J. van den; Lokman, B.C.

    2005-01-01

    The Arthromyces ramosus peroxidase gene (arp) was genetically fused to either the 5′- or 3′-terminal ends of the gene encoding llama variable heavy chain antibody fragment VHH R9, resulting in the fusion expression cassettes ARP-R9 or R9-ARP. Aspergillus awamori transformants were obtained which

  1. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  2. Human IgE is efficiently produced in glycosylated and biologically active form in lepidopteran cells

    DEFF Research Database (Denmark)

    Bantleon, Frank; Wolf, Sara; Seismann, Henning

    2016-01-01

    the recombinant production of the highly complex IgE isotype in insect cells. Recombinant IgE (rIgE) was efficiently assembled and secreted into the supernatant in yields of >30 mg/L. Purification from serum free medium using different downstream processing methods provided large amounts of rIgE. This exhibited...... a highly specific interaction with its antigen, therapeutic anti-IgE and its high affinity receptor, the FcεRI. Lectins and glyco-proteomic analyses proved the presence of prototypic insect type N-glycans on the epsilon heavy chain. Mediator release assays demonstrated a biological activity of the r......IgE comparable to IgE derived from mammalian cells. In summary the expression in insect cells provides rIgE with variant glycosylation pattern, but retained characteristics and biological activity. Therefore our data contribute to the understanding of functional and structural aspects and potential use of the Ig...

  3. A mechanical comparison of linear and double-looped hung supplemental heavy chain resistance to the back squat: a case study.

    Science.gov (United States)

    Neelly, Kurt R; Terry, Joseph G; Morris, Martin J

    2010-01-01

    A relatively new and scarcely researched technique to increase strength is the use of supplemental heavy chain resistance (SHCR) in conjunction with plate weights to provide variable resistance to free weight exercises. The purpose of this case study was to determine the actual resistance being provided by a double-looped versus a linear hung SHCR to the back squat exercise. The linear technique simply hangs the chain directly from the bar, whereas the double-looped technique uses a smaller chain to adjust the height of the looped chain. In both techniques, as the squat descends, chain weight is unloaded onto the floor, and as the squat ascends, chain weight is progressively loaded back as resistance. One experienced and trained male weight lifter (age = 33 yr; height = 1.83 m; weight = 111.4 kg) served as the subject. Plate weight was set at 84.1 kg, approximately 50% of the subject's 1 repetition maximum. The SHCR was affixed to load cells, sampling at a frequency of 500 Hz, which were affixed to the Olympic bar. Data were collected as the subject completed the back squat under the following conditions: double-looped 1 chain (9.6 kg), double-looped 2 chains (19.2 kg), linear 1 chain, and linear 2 chains. The double-looped SHCR resulted in a 78-89% unloading of the chain weight at the bottom of the squat, whereas the linear hanging SHCR resulted in only a 36-42% unloading. The double-looped technique provided nearly 2 times the variable resistance at the top of the squat compared with the linear hanging technique, showing that attention must be given to the technique used to hang SHCR.

  4. Protective Effects of Clenbuterol against Dexamethasone-Induced Masseter Muscle Atrophy and Myosin Heavy Chain Transition.

    Directory of Open Access Journals (Sweden)

    Daisuke Umeki

    Full Text Available Glucocorticoid has a direct catabolic effect on skeletal muscle, leading to muscle atrophy, but no effective pharmacotherapy is available. We reported that clenbuterol (CB induced masseter muscle hypertrophy and slow-to-fast myosin heavy chain (MHC isoform transition through direct muscle β2-adrenergic receptor stimulation. Thus, we hypothesized that CB would antagonize glucocorticoid (dexamethasone; DEX-induced muscle atrophy and fast-to-slow MHC isoform transition.We examined the effect of CB on DEX-induced masseter muscle atrophy by measuring masseter muscle weight, fiber diameter, cross-sectional area, and myosin heavy chain (MHC composition. To elucidate the mechanisms involved, we used immunoblotting to study the effects of CB on muscle hypertrophic signaling (insulin growth factor 1 (IGF1 expression, Akt/mammalian target of rapamycin (mTOR pathway, and calcineurin pathway and atrophic signaling (Akt/Forkhead box-O (FOXO pathway and myostatin expression in masseter muscle of rats treated with DEX and/or CB.Masseter muscle weight in the DEX-treated group was significantly lower than that in the Control group, as expected, but co-treatment with CB suppressed the DEX-induced masseter muscle atrophy, concomitantly with inhibition of fast-to-slow MHC isoforms transition. Activation of the Akt/mTOR pathway in masseter muscle of the DEX-treated group was significantly inhibited compared to that of the Control group, and CB suppressed this inhibition. DEX also suppressed expression of IGF1 (positive regulator of muscle growth, and CB attenuated this inhibition. Myostatin protein expression was unchanged. CB had no effect on activation of the Akt/FOXO pathway. These results indicate that CB antagonizes DEX-induced muscle atrophy and fast-to-slow MHC isoform transition via modulation of Akt/mTOR activity and IGF1 expression. CB might be a useful pharmacological agent for treatment of glucocorticoid-induced muscle atrophy.

  5. Floral Developmental Pattern Changes on Neoregelia‘Flandria’(BROMELIACEAE Analysed by Markov Chain methodologyADRIANA

    Directory of Open Access Journals (Sweden)

    Adriana Pico

    2003-01-01

    Full Text Available Neoregelia 'Flandria'and N. 'Van Durme'are ornamental cultivars of Bromelia.Propagation by seeds is not viable and prunes constitutes the only way to propagateavoiding alterations. In this article the developmental floral pattern of 72 Bromeliastreated with ANA 190 ppm (T1, Ethrel: ANA + ETHREL,(T2 y ETHREL, (T3 anddivided into two age groups: E1 y E2 are shown. The treatments studied generated moreelongated plants and six new patterns. Using the Markov chain methodology theprobability to evolve to any pattern and the percentage of each were studied.

  6. Myosin heavy chain expression in cranial, pectoral fin, and tail muscle regions of zebrafish embryos.

    Science.gov (United States)

    Peng, Mou-Yun; Wen, Hui-Ju; Shih, Li-Jane; Kuo, Ching-Ming; Hwang, Sheng-Ping L

    2002-12-01

    To investigate whether different myosin heavy chain (MHC) isoforms may constitute myofibrils in the trunk and tail musculature and if their respective expression may be regulated by spadetail (spt) and no tail (brachyury), we identified and characterized mRNA expression patterns of an embryonic- and tail muscle-specific MHC gene (named myhz2) during zebrafish development in wild type, spt, and ntl mutant embryos. The identified myhz2 MHC gene encodes a polypeptide containing 1,935 amino acids. Deduced amino acid comparisons showed that myhz2 MHC shared 92.6% sequence identity with that of carp fast skeletal MHC. Temporal and spatial myhz2 MHC mRNA expression patterns were analyzed by quantitative RT-PCR and whole-mount in situ hybridization using primer pairs and probes designed from the 3'-untranslated region (UTR). Temporally myhz2 MHC mRNA appears in pharyngula embryos and peaks in protruding-mouth larvae. The expression level decreased in 7-day-old hatching larvae, and mRNA expression was not detectable in adult fish. Spatially in pharyngula embryos, mRNA was localized only in the tail somite region, while in long-pec embryos, transcripts were also expressed in the two cranial muscle elements of the adductor mandibulae and medial rectus, as well as in pectoral fin muscles and the tail muscle region. Myhz2 MHC mRNA was expressed in most cranial muscle elements, pectoral fin muscles, and the tail muscle region of 3-day-old hatching larvae. In contrast, no expression of myhz2 MHC mRNA could be observed in spt prim-15 mutant embryos. In spt long-pec mutant embryos, transcripts were expressed in two cranial muscle elements and the tail muscle region, but not in pectoral fin muscles, while only trace amounts of myhz2 MHC mRNA were expressed in the remaining tail muscle region of 38 hpf and long-pec ntl mutant embryos. Copyright 2002 Wiley-Liss, Inc.

  7. Modified human beta 2-microglobulin (desLys(58)) displays decreased affinity for the heavy chain of MHC class I and induces nitric oxide production and apoptosis

    DEFF Research Database (Denmark)

    Wang, M; Harhaji, L; Lamberth, K

    2009-01-01

    Beta2-microglobulin (beta2m) is the light chain of major histocompatibility complex class I (MHC-I) molecules, and is a prerequisite for the binding of peptides to the heavy chain and their presentation to CD8+ T cells. beta2m can be modified in vivo and in vitro by proteolytic cleavage...... by complement C1 and subsequent carboxypeptidase B-like activity--processes that lead to the generation of desLys(58) beta2m (dbeta2m). This work aims to study the effect of dbeta2m on peptide binding to MHC-I, the influence of dbeta2m on the binding of beta2m to the MHC-I heavy chain and the biological...... activity of dbeta2m. Both beta2m and dbeta2m are able to support the generation of MHC-I/peptide complexes at 18 degrees C, but complexes formed in the presence of dbeta2m destabilize at 37 degrees C. Moreover, a 250 times higher concentration of dbeta2m than of beta2m is needed to displace MHC...

  8. Sequences of the joining region genes for immunoglobulin heavy chains and their role in generation of antibody diversity.

    OpenAIRE

    Gough, N M; Bernard, O

    1981-01-01

    To assess the contribution to immunoglobulin heavy chain diversity made by recombination between variable region (VH) genes and joining region (JH) genes, we have determined the sequence of about 2000 nucleotides spanning the rearranged JH gene cluster associated with the VH gene expressed in plasmacytoma HPC76. The active VH76 gene has recombined with the second germ-line JH gene. The region we have studied contains two other JH genes, designated JH3 and JH4. No other JH gene was found withi...

  9. ZAP-70 expression in B-cell chronic lymphocytic leukemia: evaluation by external (isotypic) or internal (T/NK cells) controls and correlation with IgV(H) mutations.

    Science.gov (United States)

    Zucchetto, Antonella; Bomben, Riccardo; Bo, Michele Dal; Nanni, Paola; Bulian, Pietro; Rossi, Francesca Maria; Del Principe, Maria Ilaria; Santini, Simone; Del Poeta, Giovanni; Degan, Massimo; Gattei, Valter

    2006-07-15

    Expression of T cell specific zeta-associated protein 70 (ZAP-70) by B-cell chronic lymphocytic leukemia (B-CLL) cells, as investigated by flow cytometry, has both prognostic relevance and predictive power as surrogate for immunoglobulin heavy chain variable region (IgV(H)) mutations, although a standardization of the cytometric protocol is still lacking. Flow cytometric analyses for ZAP-70 were performed in peripheral blood samples from 145 B-CLL (124 with IgV(H) mutations) by a standard three-color protocol. Identification of ZAP-70(+) cell population was based on an external negative control, i.e., the isotypic control (ISO method) or an internal positive control, i.e., the population of residual normal T/NK cells (TNK method). A comparison between these two approaches was performed. While 86/145 cases were concordant as for ZAP-70 expression according to the two methods (ISO(+)TNK(+) or ISO(-)TNK(-)), 59/145 cases had discordant ZAP-70 expression, mainly (56/59) showing a ISO(+)TNK(-) profile. These latter cases express higher levels of ZAP-70 in their normal T cell component. Moreover, discordant ISO(+)TNK(-) cases had a IgV(H) gene mutation profile similar to that of concordantly positive cases and different from ZAP-70 concordantly negative B-CLL. Analysis of ZAP-70 expression by B-CLL cells by using the ISO method allows to overcome the variability in the expression of ZAP-70 by residual T cells and yields a better correlation with IgV(H) gene mutations. A receiver operating characteristic analysis suggests to employ a higher cut-off than the commonly used 20%. A parallel evaluation of the prognostic value of ZAP-70 expression, as determined according to the ISO and TNK methods, is still needed. (c) 2006 International Society for Analytical Cytology.

  10. Production of bifunctional proteins by Aspergillus awamori: Llama variable heavy chain antibody fragment (V-HH) R9 coupled to Arthromyces ramosus peroxidase (ARP)

    NARCIS (Netherlands)

    Joosten, V.; Roelofs, M.S.; Dries, van den N.; Goosen, T.; Verrips, C.T.; Hondel, van den C.A.M.J.J.; Lokman, B.C.

    2005-01-01

    The Arthromyces ramosus peroxidase gene (arp) was genetically fused to either the 5'- or 3'-terminal ends of the gene encoding llama variable heavy chain antibody fragment V-HH R9, resulting in the fusion expression cassettes ARP-R9 or R9-ARP. Aspergillus awamori transformants were obtained which

  11. Force decay evaluation of thermoplastic and thermoset elastomeric chains: A mechanical design comparison.

    Science.gov (United States)

    Masoud, Ahmed I; Tsay, T Peter; BeGole, Ellen; Bedran-Russo, Ana K

    2014-11-01

    To compare the following over a period of 8 weeks: (1) force decay between thermoplastic (TP) and thermoset (TS) elastomeric chains; (2) force decay between light (200-g) and heavy (350-g) initial forces; and (3) force decay between direct chains and chain loops (stretched from one pin around the second pin and back to the first pin). TP and TS chains were obtained from American Orthodontics™ (AOTP, AOTS) and ORMCO™ (OrTP, OrTS). Each of the four chain groups was subdivided into four subgroups with 10 specimens per subgroup: (1) direct chains light force, (2) direct chains heavy force, (3) chain loops light force, and (4) chain loops heavy force. The experiment was performed in artificial saliva (pH of 6.75) at 37°C. A significant difference was found between TP and TS chains, with an average mean difference of around 20% more force decay found in the TP chains (P < .001, α  =  .05). There was no significant difference between direct chains and chain loops except in OrTP, in which direct chains showed more force decay. There was also no significant difference in force decay identified when using light vs heavy forces. TS chains decayed less than TP chains, and chain loop retraction was beneficial only when using OrTP chains. Contrary to the interchangeable use of TP and TS chains in the published literature and in clinical practice, this study demonstrates that they perform differently under stress and that a clear distinction should be made between the two.

  12. Turing patterns and long-time behavior in a three-species food-chain model

    KAUST Repository

    Parshad, Rana D.

    2014-08-01

    We consider a spatially explicit three-species food chain model, describing generalist top predator-specialist middle predator-prey dynamics. We investigate the long-time dynamics of the model and show the existence of a finite dimensional global attractor in the product space, L2(Ω). We perform linear stability analysis and show that the model exhibits the phenomenon of Turing instability, as well as diffusion induced chaos. Various Turing patterns such as stripe patterns, mesh patterns, spot patterns, labyrinth patterns and weaving patterns are obtained, via numerical simulations in 1d as well as in 2d. The Turing and non-Turing space, in terms of model parameters, is also explored. Finally, we use methods from nonlinear time series analysis to reconstruct a low dimensional chaotic attractor of the model, and estimate its fractal dimension. This provides a lower bound, for the fractal dimension of the attractor, of the spatially explicit model. © 2014 Elsevier Inc.

  13. Biosynthesis and characterization of a non-repetitive polypeptide derived from silk fibroin heavy chain

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Gaoqiang; Wu, Mingyang; Yi, Honggen; Wang, Jiannan, E-mail: wangjn@suda.edu.cn

    2016-02-01

    Silk fibroin heavy chain is the major protein component of Bombyx mori silk fibroin and is composed of 12 repetitive and 11 non-repetitive regions, with the non-repetitive domain consisting of a hydrophilic polypeptide chain. In order to determine the biomedical function of the non-repetitive domain or potentially use it to modify hydrophobic biomaterials, high-purity isolation is necessary. Previously, we cloned and extended a gene motif (f(1)) encoding the non-repetitive domain. Here, this motif and its multimers are inserted into a glutathione S-transferase (GST)-tagged fusion-protein expression vector. Motif f(1) and multimers f(4) and f(8) were expressed in Escherichia coli BL21 cells following isopropyl β-D-1-thiogalactopyranoside induction, purified by GST-affinity chromatography, and single bands of purified fusion proteins GST-F(1), GST-F(4), and GST-F(8), were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Target polypeptides F(1), F(4), and F(8), were cleaved clearly from the GST-fusion tag following thrombin digestion. Mass spectrometry results indicate that the molecular weights associated with fusion proteins GST-F(1), GST-F(4), and GST-F(8) are 31.5, 43.8, and 59.0 kDa, respectively, and with the cleaved polypeptides F(1), F(4), and F(8) are 4.8, 16.8, and 32.8 kDa, respectively. The F(1), F(4), and F(8) polypeptide chains are negatively charged with isoelectric points (pI) of 3.3, 3.2, and 3.0, respectively. The molecular weight and pI values of the polypeptide chains are consistent with the predicted values and the amino acid compositions similar to predicted sequences. FTIR and CD results show the molecular conformation of F(1) was mainly random coil, and more stable α-helix structure formed in longer molecular chain. - Highlights: • A non-repetitive domain and its multimers of silk fibroin were expressed by E. coli. • The corresponding target polypeptides F(1), F(4) and F(8) were cleaved clearly. • Their

  14. Immunogenicity and Protective Efficacy of Brugia malayi Heavy Chain Myosin as Homologous DNA, Protein and Heterologous DNA/Protein Prime Boost Vaccine in Rodent Model.

    Directory of Open Access Journals (Sweden)

    Jyoti Gupta

    Full Text Available We earlier demonstrated the immunoprophylactic efficacy of recombinant heavy chain myosin (Bm-Myo of Brugia malayi (B. malayi in rodent models. In the current study, further attempts have been made to improve this efficacy by employing alternate approaches such as homologous DNA (pcD-Myo and heterologous DNA/protein prime boost (pcD-Myo+Bm-Myo in BALB/c mouse model. The gene bm-myo was cloned in a mammalian expression vector pcDNA 3.1(+ and protein expression was confirmed in mammalian Vero cell line. A significant degree of protection (79.2%±2.32 against L3 challenge in pcD-Myo+Bm-Myo immunized group was observed which was much higher than that exerted by Bm-Myo (66.6%±2.23 and pcD-Myo (41.6%±2.45. In the heterologous immunized group, the percentage of peritoneal leukocytes such as macrophages, neutrophils, B cells and T cells marginally increased and their population augmented further significantly following L3 challenge. pcD-Myo+Bm-Myo immunization elicited robust cellular and humoral immune responses as compared to pcD-Myo and Bm-Myo groups as evidenced by an increased accumulation of CD4+, CD8+ T cells and CD19+ B cells in the mouse spleen and activation of peritoneal macrophages. Though immunized animals produced antigen-specific IgG antibodies and isotypes, sera of mice receiving pcD-Myo+Bm-Myo or Bm-Myo developed much higher antibody levels than other groups and there was profound antibody-dependent cellular adhesion and cytotoxicity (ADCC to B. malayi infective larvae (L3. pcD-Myo+Bm-Myo as well as Bm-Myo mice generated a mixed T helper cell phenotype as evidenced by the production of both pro-inflammatory (IL-2, IFN-γ and anti-inflammatory (IL-4, IL-10 cytokines. Mice receiving pcD-Myo on contrary displayed a polarized pro-inflammatory immune response. The findings suggest that the priming of animals with DNA followed by protein booster generates heightened and mixed pro- and anti-inflammatory immune responses that are capable of

  15. Monoclonal antibodies and toxins--a perspective on function and isotype.

    Science.gov (United States)

    Chow, Siu-Kei; Casadevall, Arturo

    2012-06-01

    Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs) with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins--Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB)--and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions.

  16. Rapid switch-off of the human myosin heavy chain IIX gene after heavy load muscle contractions is sustained for at least four days.

    Science.gov (United States)

    Andersen, J L; Gruschy-Knudsen, T

    2018-02-01

    Long-term heavy load contractions decrease the relative amount of the myosin heavy chain (MHC) IIX isoform in human skeletal muscle, but the timing of the down-regulation in the short term is unknown. Untrained subjects performed two resistance bouts, in two consecutive days, with one leg, the other leg serving as a control (age 24±1, n=5). Muscle biopsies were obtained in both legs before, immediately after, and 24, 54, and 96 hours after exercise. Serial cryosection analysis combined immunohistochemistry and ATPase histochemistry with In Situ hybridization to identify the distribution of MHC isoforms and their corresponding transcripts, enabling identification of transitional fibers. Fibers positive solely for MHC IIX mRNA decreased in the exercised leg throughout the study period. At 96 hours post-exercise, no fibers solely expressed MHC IIX mRNA. In contrast, the number of fibers expressing MHC IIA mRNA increased throughout the study period. The percentage of fibers expressing mRNA for MHC I was unchanged in both legs at all time points. Pronounced depletion of glycogen in the MHC IIX fibers of the exercised leg verifies that the type IIX fibers were active during the heavy load contractions. Major mismatch between MHC at the mRNA and protein levels was only found in the fibers of the exercised leg. These data provide unequivocal in situ evidence of an immediate shutdown of the MHC IIX gene after resistance exercise. A further novel finding was that the silencing of the MHC IIX gene is sustained at least 4 days after removal of the stimulus. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. A single-chain fusion molecule consisting of peptide, major histocompatibility gene complex class I heavy chain and beta2-microglobulin can fold partially correctly, but binds peptide inefficiently

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Buus, S

    1999-01-01

    of a recombinant murine MHC-I molecule, which could be produced in large amounts in bacteria. The recombinant MHC-I protein was expressed as a single molecule (PepSc) consisting of the antigenic peptide linked to the MHC-I heavy chain and further linked to human beta2-microglobulin (hbeta2m). The PepSc molecule...... electrophoresis (SDS-PAGE). Serological analysis revealed the presence of some, but not all, MHC-I-specific epitopes. Biochemically, PepSc could bind peptide, however, rather ineffectively. We suggest that a partially correctly refolded MHC-I has been obtained....

  18. Differential expression of largemouth bass (Micropterus salmoides) estrogen receptor isotypes alpha, beta, and gamma by estradiol.

    Science.gov (United States)

    Sabo-Attwood, Tara; Kroll, Kevin J; Denslow, Nancy D

    2004-04-15

    The expression levels of three estrogen receptor (ER) isotypes alpha, beta, and gamma were quantified in female largemouth bass (Micropterus salmoides) (LMB) liver, ovary, brain, and pituitary tissues. ER alpha and beta expression predominated in the liver, while ERs beta and gamma predominated in the other tissues. Temporally in females, ER alpha was highly up-regulated, ER gamma was slightly up-regulated, and ER beta levels remained unchanged in the liver when plasma 17-beta estradiol (E2) and vitellogenin (Vtg) levels were elevated in the spring. In ovarian tissue from these same fish, all three ERs were maximally expressed in the fall, during early oocyte development and prior to peak plasma E2 levels. When males were injected with E2, ER alpha was highly inducible, ER gamma was moderately up-regulated, and ER beta levels were not affected. None of the ER isotypes were induced by E2 in gonadal tissues. These results combined suggest that the ERs themselves are not regulated in the same manner by E2, and furthermore, do not contribute equally to the transcriptional regulation of genes involved in fish reproduction such as Vtg.

  19. First molecular and biochemical analysis of in vivo affinity maturation in an ectothermic vertebrate.

    Science.gov (United States)

    Dooley, Helen; Stanfield, Robyn L; Brady, Rebecca A; Flajnik, Martin F

    2006-02-07

    The cartilaginous fish are the oldest phylogenetic group in which Igs have been found. Sharks produce a unique Ig isotype, IgNAR, a heavy-chain homodimer that does not associate with light chains. Instead, the variable (V) regions of IgNAR bind antigen as soluble single domains. Our group has shown that IgNAR plays an integral part in the humoral response of nurse sharks (Ginglymostoma cirratum) upon antigen challenge. Here, we generated phage-displayed libraries of IgNAR V regions from an immunized animal and found a family of clones derived from the same rearrangement event but differentially mutated during expansion. Because of the cluster organization of shark Ig genes and the paucicopy nature of IgNAR, we were able to construct the putative ancestor of this family. By studying mutations in the context of clone affinities, we found evidence that affinity maturation occurs for this isotype. Subsequently, we were able to identify mutations important in the affinity improvement of this family. Because the family clones were all obtained after immunization, they provide insight into the in vivo maturation mechanisms, in general, and for single-domain antibody fragments.

  20. Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

    Science.gov (United States)

    di Maso, N. A.; Caiozzo, V. J.; Baldwin, K. M.

    2000-01-01

    The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

  1. Anti-DNA antibodies: Sequencing, cloning, and expression

    Energy Technology Data Exchange (ETDEWEB)

    Barry, M.M.

    1992-01-01

    To gain some insight into the mechanism of systemic lupus erythematosus, and the interactions involved in proteins binding to DNA four anti-DNA antibodies have been investigated. Two of the antibodies, Hed 10 and Jel 242, have previously been prepared from female NZB/NZW mice which develop an autoimmune disease resembling human SLE. The remaining two antibodies, Jel 72 and Jel 318, have previously been produced via immunization of C57BL/6 mice. The isotypes of the four antibodies investigated in this thesis were determined by an enzyme-linked-immunosorbent assay. All four antibodies contained [kappa] light chains and [gamma]2a heavy chains except Jel 318 which contains a [gamma]2b heavy chain. The complete variable regions of the heavy and light chains of these four antibodies were sequenced from their respective mRNAs. The gene segments and variable gene families expressed in each antibody were identified. Analysis of the genes used in the autoimmune anti-DNA antibodies and those produced by immunization indicated no obvious differences to account for their different origins. Examination of the amino acid residues present in the complementary-determining regions of these four antibodies indicates a preference for aromatic amino acids. Jel 72 and Jel 242 contain three arginine residues in the third complementary-determining region. A single-chain Fv and the variable region of the heavy chain of Hed 10 were expressed in Escherichia coli. Expression resulted in the production of a 26,000 M[sub r] protein and a 15,000 M[sub r] protein. An immunoblot indicated that the 26,000 M[sub r] protein was the Fv for Hed 10, while the 15,000 M[sub r] protein was shown to bind poly (dT). The contribution of the heavy chain to DNA binding was assessed.

  2. Effect of ageing on the myosin heavy chain composition of the human sternocleidomastoid muscle.

    Science.gov (United States)

    Meznaric, M; Eržen, I; Karen, P; Cvetko, E

    2018-03-01

    The myosin heavy chain (MyHC) composition of ageing limb muscles is transformed into a slower phenotype and expresses fast-twitch fibre type atrophy, presumably due to age-related motor unit remodelling and a change in the patterns of physical activity. It is not known if ageing affects the sternocleidomastoid muscle (SCM) in a similar way. The goal of the study was to analyze the MyHC composition and the size of muscle fibres in the ageing SCM by immunohistochemical methods and quantitative analysis and stereology using our own software for morphometry. We hypothesize that with ageing the MyHC composition of SCM transforms similarly as in ageing limb muscles, but the size of the muscle fibres is less effected as in limb muscles. The study was performed on the autopsy samples of the SCM in 12 older males. The results were compared with those published in our previous study on 15 young adult males. An ageing SCM transforms into a slower MyHC profile: the percentage of slow-twitch fibres is enhanced (numerical proportion 44.6 vs. 31.5%, Pfibres is diminished (numerical proportion 14.1 vs. 26.8%, Pfast-twitch fibres expressing MyHC-2a and 2x is smaller (50.6 vs. 63.5%, Pfibres expressing the fastest myosin isoform MyHC-2x is smaller too (19.0 vs. 34.5%, Pfibres expressing the fastest MyHC-2x provide circumstantial evidence for: (i) more fast-twitch than slow-twitch motor units being lost; and (ii) reinnervation by the surviving motor units. There appears to be no significant influence on muscle fibre size, which is congruent with relatively unchanged SCM activity during life. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms

    Science.gov (United States)

    Bamman, M. M.; Clarke, M. S.; Talmadge, R. J.; Feeback, D. L.

    1999-01-01

    Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

  4. Monoclonal Antibodies and Toxins—A Perspective on Function and Isotype

    Directory of Open Access Journals (Sweden)

    Siu-Kei Chow

    2012-06-01

    Full Text Available Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins—Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB—and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions.

  5. Monoclonal Antibodies and Toxins—A Perspective on Function and Isotype

    Science.gov (United States)

    Chow, Siu-Kei; Casadevall, Arturo

    2012-01-01

    Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs) with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins—Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB)—and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions. PMID:22822456

  6. Computational mining for hypothetical patterns of amino acid side chains in protein data bank (PDB)

    Science.gov (United States)

    Ghani, Nur Syatila Ab; Firdaus-Raih, Mohd

    2018-04-01

    The three-dimensional structure of a protein can provide insights regarding its function. Functional relationship between proteins can be inferred from fold and sequence similarities. In certain cases, sequence or fold comparison fails to conclude homology between proteins with similar mechanism. Since the structure is more conserved than the sequence, a constellation of functional residues can be similarly arranged among proteins of similar mechanism. Local structural similarity searches are able to detect such constellation of amino acids among distinct proteins, which can be useful to annotate proteins of unknown function. Detection of such patterns of amino acids on a large scale can increase the repertoire of important 3D motifs since available known 3D motifs currently, could not compensate the ever-increasing numbers of uncharacterized proteins to be annotated. Here, a computational platform for an automated detection of 3D motifs is described. A fuzzy-pattern searching algorithm derived from IMagine an Amino Acid 3D Arrangement search EnGINE (IMAAAGINE) was implemented to develop an automated method for searching of hypothetical patterns of amino acid side chains in Protein Data Bank (PDB), without the need for prior knowledge on related sequence or structure of pattern of interest. We present an example of the searches, which is the detection of a hypothetical pattern derived from known structural motif of C2H2 structural pattern from zinc fingers. The conservation of particular patterns of amino acid side chains in unrelated proteins is highlighted. This approach can act as a complementary method for available structure- and sequence-based platforms and may contribute in improving functional association between proteins.

  7. Spatiotemporal Patterns in a Ratio-Dependent Food Chain Model with Reaction-Diffusion

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2014-01-01

    Full Text Available Predator-prey models describe biological phenomena of pursuit-evasion interaction. And this interaction exists widely in the world for the necessary energy supplement of species. In this paper, we have investigated a ratio-dependent spatially extended food chain model. Based on the bifurcation analysis (Hopf and Turing, we give the spatial pattern formation via numerical simulation, that is, the evolution process of the system near the coexistence equilibrium point (u2*,v2*,w2*, and find that the model dynamics exhibits complex pattern replication. For fixed parameters, on increasing the control parameter c1, the sequence “holes → holes-stripe mixtures → stripes → spots-stripe mixtures → spots” pattern is observed. And in the case of pure Hopf instability, the model exhibits chaotic wave pattern replication. Furthermore, we consider the pattern formation in the case of which the top predator is extinct, that is, the evolution process of the system near the equilibrium point (u1*,v1*,0, and find that the model dynamics exhibits stripes-spots pattern replication. Our results show that reaction-diffusion model is an appropriate tool for investigating fundamental mechanism of complex spatiotemporal dynamics. It will be useful for studying the dynamic complexity of ecosystems.

  8. Vegetation pattern and heavy metal accumulation at a mine tailing at Gyöngyösoroszi, hungary.

    Science.gov (United States)

    Tamás, János; Kovács, Alza

    2005-01-01

    Vegetation at an abandoned heavy metal bearing mine tailing may have multifunctional roles such as modification of water balance, erosion control and landscape rehabilitation. Research on the vegetation of mine tailings can provide useful information on tolerance, accumulation and translocation properties of species potentially applicable at moderately contaminated sites. Analyses of the relationship between heavy metal content (Pb, Zn and Cu) and vegetation in a mine tailing were carried out. These analyses included: (1) spatial analysis of relationship among heavy metal distribution, pH and vegetation patterns, and (2) analysis of heavy metal accumulation and translocation in some plant species. Presence of vegetation was found to be significantly dependent on pH value, which confirms that phytotoxicity is a function of element concentration in solution, which is primarily controlled by pH value in mine tailings. Among the most abundant plant species, dewberry (Rubus caesius), vipersbugloss (Echium vulgare), scarlet pimpernel (Anagallis arvensis) and narrowleaf plantain (Plantago lanceolata) accumulate significant amounts of Pb, Cu and Zn, while in the case of annual bluegrass (Poa annua) only Pb can be measured in elevated contents. Considering the translocation features, scarlet pimpernel, narrowleaf plantain, and dewberry accumulate heavy metals primarily in their roots, while heavy metal concentration in vipersbugloss and annual bluegrass is higher in the shoots.

  9. Role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells

    International Nuclear Information System (INIS)

    Miller, A.; Morse, H.C. III; Winkelstein, J.; Nathanson, N.

    1978-01-01

    The avirulent high egg passage (HEP) strain of rabies virus produces an inapparent infection limited to the central nervous system (CNS) in intracerebrally inoculated adult mice. Heavy chain isotype (anti-μ antiserum) immunosuppression potentiates the infection, with a mortality of about 60% and with elevated virus titers in the brain. Anti-μ-treated mice fail to raise antibody responses to rabies virus although their T cell function is normal when measured by the concanavalin A response of splenic lymphocytes. This indicates that the B cell response plays an important role in clearance of rabies virus from the neuroparenchyma. Treatment with cyclophosphamide or by adult thymectomy, x-irradiation, and bone marrow reconstitution potentiates HEP infection to a greater extent than does isotype supression. Since these suppressive techniques impair both T and B lymphocyte responses, the data suggest that cellular immune mechanisms may also contribute to host defenses against this central nervous system (CNS) virus infection

  10. SNPs within the beta myosin heavy chain (MYH7 and the pyruvate kinase muscle (PKM2 genes in horse

    Directory of Open Access Journals (Sweden)

    Vincenzo Russo

    2010-01-01

    Full Text Available Two highly expressed skeletal muscle genes (the MYH7 gene encoding the myosin heavy chain slow/β-cardiac isoform and the PKM2 gene encoding the pyruvate kinase muscle isoforms were investigated with the objective to identify DNA markers in horses. A panel of DNA samples from different horse breeds was analysed using a PCR-single strand conformation polymorphism (SSCP approach. Four and two alleles were identified for the MYH7 and PKM2 loci, respectively. Mendelian inheritance of alleles of the two investigated genes was confirmed analysing horse families. Sequencing of PCR products obtained from the MYH7 and PKM2 genes made it possible to characterise two SSCP alleles for each gene. The polymorphisms found in the MYH7 and PKM2 genes were further studied in 61 and 68 horses of three (Italian Heavy Draught Horse, Italian Saddler and Murgese and five (Franches-Montagnes, Haflinger, Italian Heavy Draught Horse, Murgese and Standardbred breeds, respectively. Allele frequencies of the two loci varied among the considered breeds. The SNPs discovery in MYH7 and PKM2 genes makes it possible to locate new molecular markers to ECA1. The identified markers could be used in association analysis with performance traits in horses.

  11. Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin

    DEFF Research Database (Denmark)

    Kriajevska, M; Bronstein, I B; Scott, D J

    2000-01-01

    a regulatory role in the myosin assembly. In the presence of calcium, Mts1 binds at the C-terminal end of the myosin heavy chain close to the site of phosphorylation by protein kinase CK2 (Ser1944). In the present study, we have shown that interaction of Mts1 with the human platelet myosin or C...

  12. Pattern of structural relationships of the effects of consumption values on product perceived value and purchase intention of chain stores customers

    Directory of Open Access Journals (Sweden)

    Chiman Maleki

    2016-11-01

    Full Text Available In recent years, chain stores have experienced quick growth and used marketing strategies of advertisement and branding to expand their business. The aim of this study is to examine the effects of consumption values on perceived value and purchase intention of customers of Refah Chain Store of Sanandaj City. The present study is survey-description in methodology, and an applied research based on structural equation modeling in objective. Measurement tool is a questionnaire based on Almokarami model (2013 and Kaunas’ (2013 distributed among a sample of 384 people including customers of Refah Chain Store of sanandaji City randomly chosen. Findings of this study indicate a significant relationship between variables of the research and a good fit for the established pattern. Thus, consumption values affect customers’ perceived value, consumption values affect customers’ purchase intention and perceived value affects customers’ purchase intention in Refah Chain Stores of Sanandaj City. Also based on findings of study of figures, significance of research conceptual pattern and good fit for the posed pattern are confirmed.

  13. Heavy oil, water and air three-phase flow patterns in horizontal pipes; Padroes de escoamento trifasico de oleo pesado, agua e ar em tubulacoes horizontais

    Energy Technology Data Exchange (ETDEWEB)

    Trevisan, Francisco Exaltacao; Bannwart, Antonio Carlos [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil)

    2004-07-01

    A significant extent of the Brazilian oil reserves consists of heavy oil, and its importance and economic value have been increasing in the last years. However, these oils, besides their elevated densities (API degree lower than 20), have viscosities higher than 100 mPa.s, which make it more difficult their transportation in pipelines. A solution for this problem is the injection of water in the pipe, which causes a reduction of the friction factor and, consequently, of the energy expend for a given oil flow rate. The two-phase flow of heavy oil and water has been the object of a number of recent studies, and concepts such as the core-flow technology can be useful for heavy oil transportation. But in production operations, gas is also present, initially dissolved in the oil phase then leaving the solution to form a free gas phase if the pressure drops below the bubble point pressure, the study of three-phase flow of heavy oil, water and gas is in order. The present paper presents the experimental work developed to evaluate the effect that this third phase causes on the heavy oil-water two-phase flow pattern. Initially two-phase flow of heavy and gas-water was studied to establish the flow rate ranges that cover the main patterns already known. The superficial velocities used varied from 0,04 to 0,5 m/s for water, 0,01 to 22 m/s for gas and 0,02 to 1,2 m/s for oil. After that, three-phase flow patterns were visually determined through a 2,84 cm i.d. plexiglas tube using a high-speed camera. Nine three-phase flow patterns were identified which are presented visually and described. These flow-patterns are also presented in flow maps where the effect of the gas phase can be observed. Water was the continuous phase for all flow patterns observed, ensuring a low pressure drop along the pipe. (author)

  14. Interaction of thyroid state and denervation on skeletal myosin heavy chain expression

    Science.gov (United States)

    Haddad, F.; Arnold, C.; Zeng, M.; Baldwin, K.

    1997-01-01

    The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

  15. Spatial patterns of heavy metals in soil under different geological structures and land uses for assessing metal enrichments.

    Science.gov (United States)

    Krami, Loghman Khoda; Amiri, Fazel; Sefiyanian, Alireza; Shariff, Abdul Rashid B Mohamed; Tabatabaie, Tayebeh; Pradhan, Biswajeet

    2013-12-01

    One hundred and thirty composite soil samples were collected from Hamedan county, Iran to characterize the spatial distribution and trace the sources of heavy metals including As, Cd, Co, Cr, Cu, Ni, Pb, V, Zn, and Fe. The multivariate gap statistical analysis was used; for interrelation of spatial patterns of pollution, the disjunctive kriging and geoenrichment factor (EF(G)) techniques were applied. Heavy metals and soil properties were grouped using agglomerative hierarchical clustering and gap statistic. Principal component analysis was used for identification of the source of metals in a set of data. Geostatistics was used for the geospatial data processing. Based on the comparison between the original data and background values of the ten metals, the disjunctive kriging and EF(G) techniques were used to quantify their geospatial patterns and assess the contamination levels of the heavy metals. The spatial distribution map combined with the statistical analysis showed that the main source of Cr, Co, Ni, Zn, Pb, and V in group A land use (agriculture, rocky, and urban) was geogenic; the origin of As, Cd, and Cu was industrial and agricultural activities (anthropogenic sources). In group B land use (rangeland and orchards), the origin of metals (Cr, Co, Ni, Zn, and V) was mainly controlled by natural factors and As, Cd, Cu, and Pb had been added by organic factors. In group C land use (water), the origin of most heavy metals is natural without anthropogenic sources. The Cd and As pollution was relatively more serious in different land use. The EF(G) technique used confirmed the anthropogenic influence of heavy metal pollution. All metals showed concentrations substantially higher than their background values, suggesting anthropogenic pollution.

  16. Non-stationary analysis of the frequency and intensity of heavy precipitation over Canada and their relations to large-scale climate patterns

    Science.gov (United States)

    Tan, Xuezhi; Gan, Thian Yew

    2017-05-01

    In recent years, because the frequency and severity of floods have increased across Canada, it is important to understand the characteristics of Canadian heavy precipitation. Long-term precipitation data of 463 gauging stations of Canada were analyzed using non-stationary generalized extreme value distribution (GEV), Poisson distribution and generalized Pareto (GP) distribution. Time-varying covariates that represent large-scale climate patterns such as El Niño Southern Oscillation (ENSO), North Atlantic Oscillation (NAO), Pacific decadal oscillation (PDO) and North Pacific Oscillation (NP) were incorporated to parameters of GEV, Poisson and GP distributions. Results show that GEV distributions tend to under-estimate annual maximum daily precipitation (AMP) of western and eastern coastal regions of Canada, compared to GP distributions. Poisson regressions show that temporal clusters of heavy precipitation events in Canada are related to large-scale climate patterns. By modeling AMP time series with non-stationary GEV and heavy precipitation with non-stationary GP distributions, it is evident that AMP and heavy precipitation of Canada show strong non-stationarities (abrupt and slowly varying changes) likely because of the influence of large-scale climate patterns. AMP in southwestern coastal regions, southern Canadian Prairies and the Great Lakes tend to be higher in El Niño than in La Niña years, while AMP of other regions of Canada tends to be lower in El Niño than in La Niña years. The influence of ENSO on heavy precipitation was spatially consistent but stronger than on AMP. The effect of PDO, NAO and NP on extreme precipitation is also statistically significant at some stations across Canada.

  17. Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch

    Directory of Open Access Journals (Sweden)

    Chen CH

    2012-02-01

    Full Text Available Chia-Hung Chen1,*, Yu-Ling Lin1,*, Yen-Ku Liu1, Pei-Juin He2, Ching-Min Lin1, Yi-Han Chiu2, Chang-Jer Wu3, Tian-Lu Cheng4, Shih-Jen Liu5,6,**, Kuang-Wen Liao1,2,**1Institute of Molecular Medicine and Bioengineering, 2Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 3Department of Food Science, National Taiwan Ocean University, Keelung, 4Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 5National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, 6Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, , *Chia-Hung Chen and Yu-Ling Lin contributed equally to this work**Kuang-Wen Liao and Shih-Jen Liu contributed equally to this workAbstract: The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC] adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund's adjuvant, LPPC preferentially activates Th1-immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed

  18. Binding of human beta 2-microglobulin to murine EL4 thymoma cells upregulates MHC class I heavy-chain epitopes, inhibits IL-2 secretion and induces resistance to killing by natural killer cells

    DEFF Research Database (Denmark)

    Claësson, M H; Nissen, Mogens Holst

    1994-01-01

    line (ABLS-8), X63 B-lymphoma cells and YAC cells did not bind h beta 2m. In two of the T lymphomas, EL4 and BW5147, binding of h beta 2m led to an increase in major histocompatibility complex class I (MHC-I) heavy-chain epitope expression as measured by anti-H-2K/D antibody binding and FACS analysis....... EL4 cells which had bound h beta 2m decreased their rate of constitutive IL-2 secretion and became resistant to activated natural killer (NK) cell killing. The present data suggest the binding of h beta 2m to mouse T cells leads to conformational changes of MHC-I heavy chains which influence both...

  19. Influenza virus neutralizing antibodies and IgG isotype profiles after immunization of mice with influenza A subunit vaccine using various adjuvants

    NARCIS (Netherlands)

    Benne, CA; Harmsen, M; vanderGraaff, W; Verheul, AFM; Snippe, H; Kraaijeveld, CA

    The influence of various adjuvants on the development of influenza virus neutralizing antibodies and distribution of anti-influenza virus IgG isotypes after immunization of mice with influenza A (H3N2) subunit vaccine was investigated. Serum titres of influenza virus neutralizing antibodies and

  20. Longitudinal relationships between college education and patterns of heavy drinking: A comparison between Caucasians and African Americans

    Science.gov (United States)

    Chen, Pan; Jacobson, Kristen C.

    2013-01-01

    Purpose The current study compared longitudinal relationships between college education and patterns of heavy drinking from early adolescence to adulthood for Caucasians and African Americans. Methods Data were collected from N=9,988 non-Hispanic Caucasian and African American participants from all four waves of the National Longitudinal Study of Adolescent Health. Growth curve modeling tested differences in rates of change and levels of heavy drinking from ages 13–31 among non-college youth, college withdrawers, 2-year-college graduates, and 4-year-college graduates, and compared these differences for Caucasians and African Americans. Results There were significant racial differences in relationships between college education with both changes in and levels of heavy drinking. Rates of change of heavy drinking differed significantly across the college education groups examined for Caucasians but not for African Americans. In addition, Caucasians who graduated from 4-year colleges showed the highest levels of heavy drinking after age 20, although differences between the four groups diminished by the early 30s. In contrast, for African Americans, graduates from 2- or 4-year colleges did not show higher levels of heavy drinking from ages 20–31 than the non-college group. Instead, African American participants who withdrew from college without an associate’s, bachelor’s, or professional degree consistently exhibited the highest levels of heavy drinking from ages 26–31. Conclusions The relationship between college education and increased levels of heavy drinking in young adulthood is significant for Caucasians but not African Americans. Conversely, African Americans are likely to be more adversely affected than Caucasians by college withdrawal. PMID:23707401

  1. Longitudinal relationships between college education and patterns of heavy drinking: a comparison between Caucasians and African-Americans.

    Science.gov (United States)

    Chen, Pan; Jacobson, Kristen C

    2013-09-01

    The current study compared longitudinal relationships between college education and patterns of heavy drinking from early adolescence to adulthood for Caucasians and African-Americans. We analyzed data from 9,988 non-Hispanic Caucasian and African-American participants from all four waves of the National Longitudinal Study of Adolescent Health. Growth curve modeling tested differences in rates of change and levels of heavy drinking from ages 13 to 31 years among non-college youth, college withdrawers, 2-year college graduates, and 4-year college graduates, and compared these differences for Caucasians and African-Americans. There were significant racial differences in relationships between college education with both changes in and levels of heavy drinking. Rates of change of heavy drinking differed significantly across the college education groups examined for Caucasians but not for African-Americans. In addition, Caucasians who graduated from 4-year colleges showed the highest levels of heavy drinking after age 20 years, although differences among the four groups diminished by the early 30s. In contrast, for African-Americans, graduates from 2- or 4-year colleges did not show higher levels of heavy drinking from ages 20 to 31 years than the non-college group. Instead, African-American participants who withdrew from college without an associate's, bachelor's, or professional degree consistently exhibited the highest levels of heavy drinking from ages 26 to 31 years. The relationship between college education and increased levels of heavy drinking in young adulthood is significant for Caucasians but not African-Americans. Conversely, African-Americans are likely to be more adversely affected than are Caucasians by college withdrawal. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  2. Smoking and heavy drinking patterns in rural, urban and rural-to-urban migrants: the PERU MIGRANT Study.

    Science.gov (United States)

    Taype-Rondan, Alvaro; Bernabe-Ortiz, Antonio; Alvarado, Germán F; Gilman, Robert H; Smeeth, Liam; Miranda, J Jaime

    2017-02-03

    Previous studies have found mixed results about cigarette and alcohol consumption patterns among rural-to-urban migrants. Moreover, there are limited longitudinal data about consumption patterns in this population. As such, this study aimed to compare the smoking and heavy drinking prevalence among rural, urban, and rural-to-urban migrants in Peru, as well as the smoking and heavy drinking incidence in a 5-year follow-up. We analyzed the PERU MIGRANT Study data from rural, urban, and rural-to-urban migrant populations in Peru. The baseline study was carried out in 2006-2007 and follow-up was performed five years later. For the baseline data analysis, the prevalence of lifetime smoking, current smokers, and heavy drinking was compared by population group using prevalence ratios (PR) and 95% confidence intervals (95% CI). For the longitudinal analysis, the incidence of smoking and heavy drinking was compared by population group with risk ratios (RR) and 95% CI. Poisson regression with robust variance was used to calculate both PRs and RRs. We analyzed data from 988 participants: 200 rural dwellers, 589 migrants, and 199 urban dwellers. Compared with migrants, lifetime smoking prevalence was higher in the urban group (PR = 2.29, 95% CI = 1.64-3.20), but lower in the rural group (PR = 0.55, 95% CI = 0.31-0.99). Compared with migrants, the urban group had a higher current smoking prevalence (PR = 2.29, 95% CI = 1.26-4.16), and a higher smoking incidence (RR = 2.75, 95% CI = 1.03-7.34). Current smoking prevalence and smoking incidence showed no significant difference between rural and migrant groups. The prevalence and incidence of heavy drinking was similar across the three population groups. Our results show a trend in lifetime smoking prevalence (urban > migrant > rural), while smoking incidence was similar between migrant and rural groups, but higher in the urban group. In addition, our results suggest that different

  3. Smoking and heavy drinking patterns in rural, urban and rural-to-urban migrants: the PERU MIGRANT Study

    Directory of Open Access Journals (Sweden)

    Alvaro Taype-Rondan

    2017-02-01

    Full Text Available Abstract Background Previous studies have found mixed results about cigarette and alcohol consumption patterns among rural-to-urban migrants. Moreover, there are limited longitudinal data about consumption patterns in this population. As such, this study aimed to compare the smoking and heavy drinking prevalence among rural, urban, and rural-to-urban migrants in Peru, as well as the smoking and heavy drinking incidence in a 5-year follow-up. Methods We analyzed the PERU MIGRANT Study data from rural, urban, and rural-to-urban migrant populations in Peru. The baseline study was carried out in 2006–2007 and follow-up was performed five years later. For the baseline data analysis, the prevalence of lifetime smoking, current smokers, and heavy drinking was compared by population group using prevalence ratios (PR and 95% confidence intervals (95% CI. For the longitudinal analysis, the incidence of smoking and heavy drinking was compared by population group with risk ratios (RR and 95% CI. Poisson regression with robust variance was used to calculate both PRs and RRs. Results We analyzed data from 988 participants: 200 rural dwellers, 589 migrants, and 199 urban dwellers. Compared with migrants, lifetime smoking prevalence was higher in the urban group (PR = 2.29, 95% CI = 1.64–3.20, but lower in the rural group (PR = 0.55, 95% CI = 0.31–0.99. Compared with migrants, the urban group had a higher current smoking prevalence (PR = 2.29, 95% CI = 1.26–4.16, and a higher smoking incidence (RR = 2.75, 95% CI = 1.03–7.34. Current smoking prevalence and smoking incidence showed no significant difference between rural and migrant groups. The prevalence and incidence of heavy drinking was similar across the three population groups. Conclusions Our results show a trend in lifetime smoking prevalence (urban > migrant > rural, while smoking incidence was similar between migrant and rural groups, but higher in the

  4. Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies.

    Science.gov (United States)

    Lee, Won Sok; Singh, Gurmukh

    2018-07-01

    Quantitative evaluation of serum free light chains is recommended for the work up of monoclonal gammopathies. Immunoglobulin light chains are generally produced in excess of heavy chains. In patients with monoclonal gammopathy, κ/λ ratio is abnormal less frequently with lambda chain lesions. This study was undertaken to ascertain if the levels of overproduction of the two light chain types and their detection rates are different in patients with neoplastic monoclonal gammopathies. Results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein electrophoresis (UPEP), urine protein immunofixation electrophoresis (UIFE), and serum free light chain assay (SFLCA) in patients with monoclonal gammopathies were examined retrospectively. The κ/λ ratios were appropriately abnormal more often in kappa chain lesions. Ratios of κ/λ were normal in about 25% of patients with lambda chain lesions in whom free homogenous lambda light chains were detectable in urine. An illustrative case suggests underproduction of free lambda light chains, in some instances. The lower prevalence of lambda dominant κ/λ ratio in lesions with lambda light chains is estimated to be due to relative under-detection of lambda dominant κ/λ ratio in about 25% of the patients and because lambda chains are not produced in as much excess of heavy chains as are kappa chains, in about 5% of the patients. The results question the medical necessity and clinical usefulness of the serum free light chain assay. UPEP/UIFE is under-utilized.

  5. Breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis

    International Nuclear Information System (INIS)

    Baer, R.; Heppell, A.; Taylor, A.M.R.; Rabbitts, P.H.; Boullier, B.; Rabbitts, T.H.

    1987-01-01

    T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32 - the same bands in which the T-cell receptor (TCR) α-chain and immunoglobulin heavy chain genes have been mapped, respectively. Patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. The authors describe DNA rearrangements of the TCR α-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR α-chain variable (V/sub α/) and joining (J/sub α/) gene segments. The other allele of the TCR α-chain gene features a DNA rearrangement, about 50 kilobases from the TCR α-chain constant (C/sub α/) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J/sub α/) segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C/sub μ/. These results imply that 14q32 sequences located at an undetermined distance downstream of immunoglobulin C/sub μ/ locus can contribute to the development of T-cell tumors

  6. Antibiotics and heavy metals resistance patterns of Enterococcus faecalis and faecium bacteria isolated from the human and the livestock sources

    Directory of Open Access Journals (Sweden)

    Yaser Sharifi

    2015-12-01

    Full Text Available Background: Enterococci have emerged as a major cause of nosocomial infections and within this group, Enterococcus faecalis and Enterococcus faecium cause the majority of human and livestock enterococcal infections. In this article, we tried to determine antibiotics and metals resistance patterns of E. faecalis and E. faecium strains. Methods: One hundred sixty different strains of E. faecalis and E. faecium were collected from livestock sewage and the human fecal waste during 15 months. Then bacterial antibiotics sensitivity tests were carried out using the Agar disc diffusion method. Results: Generally, 100% of E. faecalis strains separated from human and livestock sources (i.e. sheep showed penicillin (P/ kanamycin (K/ nitrofurantoin (N/ loracarbef (L/ Ciprofloxacin (Cc/ ampicillin (AN/ nalidixic acid (NA/ sulfamethoxazole (S antibiotics resistance patterns. In addition, 55% of isolated E. faecium showed P/S/AN/NA antibiotics resistance patterns. Each strain showed a resistance to at least two aminoglycoside antibiotics. However, E. faecalis strains from human and the livestock sources showed 94% and 100% of resistance to nitrofurantoin, respectively. The effects of different metal concentrations was evaluated in both strains. The agar dilution method was applied in this stage. Hg at 0.05 mmol/L of minimum inhibitory concentration (MIC showed toxicity to both the human and livestock Enterococcus strains. Cadmium at 1 mmol/L and 0.5 mmol/L concentrations had the most toxicity to E. faecalis and E. faecium strains, respectively. Obviously, toxicity to bacteria is less than other metals. As a result, Zn/Ni/Cu/Co resistance pattern is suggested for both strains. Finally, antibiotics and heavy metals resistance patterns were monitored simultaneously. Conclusion: Almost all E. faecalis strains isolated from humans and livestock showed antibiotics and heavy metals resistance patterns of P/K/L/Cc/S/AN/NA/Zn/Cu/Co simultaneously. Moreover, 55% of E

  7. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies.

    Science.gov (United States)

    Tschumper, R C; Dispenzieri, A; Abraham, R S; Henderson, K J; Jelinek, D F

    2013-04-19

    Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.

  8. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies

    International Nuclear Information System (INIS)

    Tschumper, R C; Dispenzieri, A; Abraham, R S; Henderson, K J; Jelinek, D F

    2013-01-01

    Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis

  9. Selected mineral and heavy metal concentrations in blood and ...

    African Journals Online (AJOL)

    Unknown

    Pb in the dead vultures were generally above values characteristic of heavy metal poisoning. ... of the food chain), may accumulate and concentrate heavy metals in their ..... µg/g wet weight) (Honda et al., 1990), which validates the order of ...

  10. Measured and simulated heavy-ion beam loss patterns at the CERN Large Hadron Collider

    Science.gov (United States)

    Hermes, P. D.; Bruce, R.; Jowett, J. M.; Redaelli, S.; Salvachua Ferrando, B.; Valentino, G.; Wollmann, D.

    2016-05-01

    The Large Hadron Collider (LHC) at CERN pushes forward to new regimes in terms of beam energy and intensity. In view of the combination of very energetic and intense beams together with sensitive machine components, in particular the superconducting magnets, the LHC is equipped with a collimation system to provide protection and intercept uncontrolled beam losses. Beam losses could cause a superconducting magnet to quench, or in the worst case, damage the hardware. The collimation system, which is optimized to provide a good protection with proton beams, has shown a cleaning efficiency with heavy-ion beams which is worse by up to two orders of magnitude. The reason for this reduced cleaning efficiency is the fragmentation of heavy-ion beams into isotopes with a different mass to charge ratios because of the interaction with the collimator material. In order to ensure sufficient collimation performance in future ion runs, a detailed theoretical understanding of ion collimation is needed. The simulation of heavy-ion collimation must include processes in which 82 + 208Pb ions fragment into dozens of new isotopes. The ions and their fragments must be tracked inside the magnetic lattice of the LHC to determine their loss positions. This paper gives an overview of physical processes important for the description of heavy-ion loss patterns. Loss maps simulated by means of the two tools ICOSIM [1,2] and the newly developed STIER (SixTrack with Ion-Equivalent Rigidities) are compared with experimental data measured during LHC operation. The comparison shows that the tool STIER is in better agreement.

  11. Massively parallel amplicon sequencing reveals isotype-specific variability of antimicrobial peptide transcripts in Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Umberto Rosani

    Full Text Available BACKGROUND: Effective innate responses against potential pathogens are essential in the living world and possibly contributed to the evolutionary success of invertebrates. Taken together, antimicrobial peptide (AMP precursors of defensin, mytilin, myticin and mytimycin can represent about 40% of the hemocyte transcriptome in mussels injected with viral-like and bacterial preparations, and unique profiles of myticin C variants are expressed in single mussels. Based on amplicon pyrosequencing, we have ascertained and compared the natural and Vibrio-induced diversity of AMP transcripts in mussel hemocytes from three European regions. METHODOLOGY/PRINCIPAL FINDINGS: Hemolymph was collected from mussels farmed in the coastal regions of Palavas (France, Vigo (Spain and Venice (Italy. To represent the AMP families known in M. galloprovincialis, nine transcript sequences have been selected, amplified from hemocyte RNA and subjected to pyrosequencing. Hemolymph from farmed (offshore and wild (lagoon Venice mussels, both injected with 10(7 Vibrio cells, were similarly processed. Amplicon pyrosequencing emphasized the AMP transcript diversity, with Single Nucleotide Changes (SNC minimal for mytilin B/C and maximal for arthropod-like defensin and myticin C. Ratio of non-synonymous vs. synonymous changes also greatly differed between AMP isotypes. Overall, each amplicon revealed similar levels of nucleotidic variation across geographical regions, with two main sequence patterns confirmed for mytimycin and no substantial changes after immunostimulation. CONCLUSIONS/SIGNIFICANCE: Barcoding and bidirectional pyrosequencing allowed us to map and compare the transcript diversity of known mussel AMPs. Though most of the genuine cds variation was common to the analyzed samples we could estimate from 9 to 106 peptide variants in hemolymph pools representing 100 mussels, depending on the AMP isoform and sampling site. In this study, no prevailing SNC patterns related

  12. Proteolysis of the heavy chain of major histocompatibility complex class I antigens by complement component C1s

    DEFF Research Database (Denmark)

    Eriksson, H; Nissen, Mogens Holst

    1990-01-01

    weights of the fragments are in agreement with the cleavage located in the area between the disulphide loops of the alpha 2-and alpha 3-domains of the heavy chain. In addition human C1s complement is able to cleave H-2 antigens from mouse in a similar fashion but not rat MHC class I antigen or mouse MHC...... class II antigen (I-Ad). Mouse MHC class I antigen-specific determinants could also be detected in supernatant from mouse spleen cells incubated with C1r and C1s. These results indicate the presence in the body fluids of a non-membrane-bound soluble form of the alpha 1-and alpha 2-domains which...

  13. Assessing potential dietary toxicity of heavy metals in selected vegetables and food crops.

    Science.gov (United States)

    Islam, Ejaz ul; Yang, Xiao-e; He, Zhen-li; Mahmood, Qaisar

    2007-01-01

    Heavy metals, such as cadmium, copper, lead, chromium and mercury, are important environmental pollutants, particularly in areas with high anthropogenic pressure. Their presence in the atmosphere, soil and water, even in traces can cause serious problems to all organisms, and heavy metal bioaccumulation in the food chain especially can be highly dangerous to human health. Heavy metals enter the human body mainly through two routes namely: inhalation and ingestion, ingestion being the main route of exposure to these elements in human population. Heavy metals intake by human populations through food chain has been reported in many countries. Soil threshold for heavy metal toxicity is an important factor affecting soil environmental capacity of heavy metal and determines heavy metal cumulative loading limits. For soil-plant system, heavy metal toxicity threshold is the highest permissible content in the soil (total or bioavailable concentration) that does not pose any phytotoxic effects or heavy metals in the edible parts of the crops does not exceed food hygiene standards. Factors affecting the thresholds of dietary toxicity of heavy metal in soil-crop system include: soil type which includes soil pH, organic matter content, clay mineral and other soil chemical and biochemical properties; and crop species or cultivars regulated by genetic basis for heavy metal transport and accumulation in plants. In addition, the interactions of soil-plant root-microbes play important roles in regulating heavy metal movement from soil to the edible parts of crops. Agronomic practices such as fertilizer and water managements as well as crop rotation system can affect bioavailability and crop accumulation of heavy metals, thus influencing the thresholds for assessing dietary toxicity of heavy metals in the food chain. This paper reviews the phytotoxic effects and bioaccumulation of heavy metals in vegetables and food crops and assesses soil heavy metal thresholds for potential dietary

  14. σ-Bond Electron Delocalization in Oligosilanes as Function of Substitution Pattern, Chain Length, and Spatial Orientation

    Directory of Open Access Journals (Sweden)

    Johann Hlina

    2016-08-01

    Full Text Available Polysilanes are known to exhibit the interesting property of σ-bond electron delocalization. By employing optical spectroscopy (UV-vis, it is possible to judge the degree of delocalization and also differentiate parts of the molecules which are conjugated or not. The current study compares oligosilanes of similar chain length but different substitution pattern. The size of the substituents determines the spatial orientation of the main chain and also controls the conformational flexibility. The chemical nature of the substituents affects the orbital energies of the molecules and thus the positions of the absorption bands.

  15. Integrability in heavy quark effective theory

    Science.gov (United States)

    Braun, Vladimir M.; Ji, Yao; Manashov, Alexander N.

    2018-06-01

    It was found that renormalization group equations in the heavy-quark effective theory (HQET) for the operators involving one effective heavy quark and light degrees of freedom are completely integrable in some cases and are related to spin chain models with the Hamiltonian commuting with the nondiagonal entry C( u) of the monodromy matrix. In this work we provide a more complete mathematical treatment of such spin chains in the QISM framework. We also discuss the relation of integrable models that appear in the HQET context with the large-spin limit of integrable models in QCD with light quarks. We find that the conserved charges and the "ground state" wave functions in HQET models can be obtained from the light-quark counterparts in a certain scaling limit.

  16. Comparison of myosin heavy chain mRNAs, protein isoforms and fiber type proportions in the rat slow and fast muscles

    Czech Academy of Sciences Publication Activity Database

    Žurmanová, J.; Soukup, Tomáš

    2013-01-01

    Roč. 62, č. 4 (2013), s. 445-453 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA304/08/0256; GA ČR(CZ) GA305/09/1228; GA MŠk(CZ) 7AMB12SK158; GA MŠk(CZ) LH12058 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : rat * soleus * extensor digitorum longus * myosin heavy chain isoforms * muscle gene expression * quantitative Real Time RT-PCR * SDS - PAGE * fiber type analysis Subject RIV: EA - Cell Biology Impact factor: 1.487, year: 2013

  17. Spatial pattern of heavy metals accumulation risk in urban soils of Beijing and its influencing factors

    International Nuclear Information System (INIS)

    Liu, Rui; Wang, Meie; Chen, Weiping; Peng, Chi

    2016-01-01

    Accumulations of heavy metals in urban soils are highly spatial heterogeneity and affected by multiple factors including soil properties, land use and pattern, population and climatic conditions. We studied accumulation risks of Cd, Cu, Pb and Zn in unban soils of Beijing and their influencing based on the regression tree analysis and a GIS-based overlay model. Result shows that Zinc causes the most extensive soil pollution and Cu result in the most acute soil pollution. The soil's organic carbon content and CEC and population growth are the most significant factors affecting heavy metal accumulation. Other influence factors in land use pattern, urban landscape, and wind speed also contributed, but less pronounced. The soils in areas with higher degree of urbanization and surrounded by intense vehicular traffics have higher accumulation risk of Cd, Cu, Pb, and Zn. - Highlights: • Zn accumulations were the most extensive and Cu accumulations were the most acute. • Accumulations of Cd, Cu, Pb and Zn in urban soils were caused by different sets of influence factors. • Soil's organic carbon content and CEC and population growth were the most significant factors. • Accumulation risks were highly related with urbanization level and human activities. - A combined approach of employing geographical information systems and regression tree analyses identify the potential risks of accumulation Cd, Cu, Pb, and Zn in urban soils according to soil properties, urban land use patterns, urban landscape, demographics, and microclimatic conditions.

  18. α-decay chains and cluster-decays of superheavy 269-27110 nuclei

    International Nuclear Information System (INIS)

    Sushil Kumar; Rajesh Kumar; Balasubramaniam, M.; Gupta, Raj K.

    2001-01-01

    Due to the availability of radioactive nuclear beams (RNB) and the advancement in accelerator technology, it is now possible to synthesize very heavy elements (Z> 100), called superheavy elements. It is a well established fact that these superheavy elements, due to their shorter lifetime, decay via successive alpha emissions and at a later stage undergo spontaneous fission. Several such decay chains are now observed. An attempt is made to fit all such known decay chains and the results of the three observed α-decay chains of Z=110 ( 269-271 10) nuclei are presented. The model used is the preformed cluster model (PCM). Also, an attempt is made for the first time to find the possibility of any branching to heavy-cluster emissions in these chains

  19. Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT

    International Nuclear Information System (INIS)

    Gnagnarella, Patrizia; Maisonneuve, Patrick; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia

    2013-01-01

    The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95 % CI = 0.31–0.80; P-trend = 0.02). Participants classified in the high “vitamins and fiber” pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95 % CI = 0.36–0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the “vitamin and fiber” nutrient pattern were associated with reduced lung cancer incidence.

  20. Heavy subgraph pairs for traceability of block-chains

    NARCIS (Netherlands)

    Li, Binlong; Li, Binlong; Broersma, Haitze J.; Zhang, Shenggui

    2014-01-01

    A graph is called traceable if it contains a Hamilton path, i.e., a path containing all its vertices. Let G be a graph on n vertices. We say that an induced subgraph of G is o-1-heavy if it contains two nonadjacent vertices which satisfy an Ore-type degree condition for traceability, i.e., with

  1. Detection of Bovine IgG Isotypes in a PPA-ELISA for Johne's Disease Diagnosis in Infected Herds.

    Science.gov (United States)

    Fernández, Bárbara; Gilardoni, Liliana Rosa; Jolly, Ana; Colavecchia, Silvia Beatriz; Paolicchi, Fernando Alberto; Mundo, Silvia Leonor

    2012-01-01

    Johne's Disease or Paratuberculosis is a chronic granulomatous enteritis disease affecting ruminants. Detection of subclinically infected animals is difficult, hampering the control of this disease. The aim of this work was to evaluate the performance of detection of IgG isotypes in a PPA-ELISA to improve the recognition of cattle naturally infected with Map in different stages. A total of 108 animals from Tuberculosis-free herds were grouped as follows: exposed (n = 30), subclinically infected (n = 26), clinically infected (n = 14), and healthy controls (n = 38). Receiver-operating characteristic (ROC) curves of isotypes/PPA-ELISAs were constructed and areas under the curves were compared to evaluate the performance of each test. Our study demonstrated that the conventional PPA-ELISA (detecting IgG) is the best to identify clinically infected animals with high sensitivity (92.9%) and specificity (100%). Meanwhile, IgG2/PPA-ELISA improved the number of subclinically infected cattle detected as compared with conventional IgG/PPA-ELISA (53.8 versus 23.1%). In addition, it had the maximum sensitivity (65.0%, taking into account all Map-infected cattle). In conclusion, the combination of IgG and IgG2/PPA-ELISAs may improve the identification of Map-infected cattle in different stages of disease. The usefulness of IgG2 detection in serological tests for Johne's Disease diagnosis should be further evaluated.

  2. Primary structure of bovine calpactin I heavy chain (p36), a major cellular substrate for retroviral protein-tyrosine kinases: homology with the human phospholipase A2 inhibitor lipocortin

    DEFF Research Database (Denmark)

    Kristensen, Torsten; Sarin, C J; Hunter, T

    1986-01-01

    An amplified Okayama-Berg plasmid cDNA library was constructed from total poly(A)+ RNA isolated from the Madin-Darby bovine kidney cell line MDBK. This library was screened with a partial murine calpactin I heavy chain (p36) cDNA clone, the identification of which was based on bovine p36 tryptic ...

  3. The Compact and Biologically Relevant Structure of Inter-α-inhibitor Is Maintained by the Chondroitin Sulfate Chain and Divalent Cations.

    Science.gov (United States)

    Scavenius, Carsten; Nikolajsen, Camilla Lund; Stenvang, Marcel; Thøgersen, Ida B; Wyrożemski, Łukasz; Wisniewski, Hans-Georg; Otzen, Daniel E; Sanggaard, Kristian W; Enghild, Jan J

    2016-02-26

    Inter-α-inhibitor is a proteoglycan of unique structure. The protein consists of three subunits, heavy chain 1, heavy chain 2, and bikunin covalently joined by a chondroitin sulfate chain originating at Ser-10 of bikunin. Inter-α-inhibitor interacts with an inflammation-associated protein, tumor necrosis factor-inducible gene 6 protein, in the extracellular matrix. This interaction leads to transfer of the heavy chains from the chondroitin sulfate of inter-α-inhibitor to hyaluronan and consequently to matrix stabilization. Divalent cations and heavy chain 2 are essential co-factors in this transfer reaction. In the present study, we have investigated how divalent cations in concert with the chondroitin sulfate chain influence the structure and stability of inter-α-inhibitor. The results showed that Mg(2+) or Mn(2+), but not Ca(2+), induced a conformational change in inter-α-inhibitor as evidenced by a decrease in the Stokes radius and a bikunin chondroitin sulfate-dependent increase of the thermodynamic stability. This structure was shown to be essential for the ability of inter-α-inhibitor to participate in extracellular matrix stabilization. In addition, the data revealed that bikunin was positioned adjacent to both heavy chains and that the two heavy chains also were in close proximity. The chondroitin sulfate chain interacted with all protein components and inter-α-inhibitor dissociated when it was degraded. Conventional purification protocols result in the removal of the Mg(2+) found in plasma and because divalent cations influence the conformation and affect function it is important to consider this when characterizing the biological activity of inter-α-inhibitor. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG.

    Science.gov (United States)

    Rumfelt, L L; Avila, D; Diaz, M; Bartl, S; McKinney, E C; Flajnik, M F

    2001-02-13

    In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM(1gj), from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells ("germline-joined"). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H(1gj) in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H(1gj) chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM(1gj). Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system.

  5. Heavy Metal Pollution of Lakes along the Mid-Lower Reaches of the Yangtze River in China: Intensity, Sources and Spatial Patterns

    Science.gov (United States)

    Zeng, Haiao; Wu, Jinglu

    2013-01-01

    Lakes in the middle and lower reaches of the Yangtze River form a shallow lake group unique in the World that is becoming increasingly polluted by heavy metals. Previous studies have largely focused on individual lakes, with limited exploration of the regional pattern of heavy metal pollution of the lake group in this area. This paper explores the sources, intensity and spatial patterns of heavy metal pollution of lake sediments. A total of 45 sample lakes were selected and the concentrations of key metal elements in the sediments of each lake were measured. The cluster analysis (CA), principal component analysis (PCA) and Geo-accumulation index (Ig) analysis permitted analysis of the source and pollution intensity of the target lakes. Results suggested a notable spatial variation amongst the sample lakes. Lakes in the upper part of the lower reach of the Yangtze River surrounded by typical urban landscapes were strongly or extremely polluted, with high concentrations of Pb, Zn, Cu and Cd in their sediments. This was attributed to large amount of untreated industrial discharges and municipal sewage produced within the lake catchments. In contrast, the heavy-metal pollution of lakes in the Taihu Delta area was notably lower due to industrial restructuring and implementation of effective environmental protection measures. Lakes along the middle reach of Yangtze River surrounded by agricultural areas were unpolluted to moderately polluted by heavy metals overall. Our results suggested that lakes in the central part of China require immediate attention and efforts should be made to implement management plans to prevent further degradation of water quality in these lakes. PMID:23442559

  6. Role of a Novel Human Leukocyte Antigen-DQA1*01:02;DRB1*15:01 Mixed Isotype Heterodimer in the Pathogenesis of “Humanized” Multiple Sclerosis-like Disease*

    Science.gov (United States)

    Kaushansky, Nathali; Eisenstein, Miriam; Boura-Halfon, Sigalit; Hansen, Bjarke Endel; Nielsen, Claus Henrik; Milo, Ron; Zeilig, Gabriel; Lassmann, Hans; Altmann, Daniel M.; Ben-Nun, Avraham

    2015-01-01

    Gene-wide association and candidate gene studies indicate that the greatest effect on multiple sclerosis (MS) risk is driven by the HLA-DRB1*15:01 allele within the HLA-DR15 haplotype (HLA-DRB1*15:01-DQA1*01:02-DQB1*0602-DRB5*01:01). Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies, whether the functionally relevant effect derives from DRB1*15:01 only, from its neighboring DQA1*01:02-DQB1*06:02 or DRB5*01:01 genes of HLA-DR15 haplotype, or from their combinations or epistatic interactions. Here, we analyzed the impact of the different HLA-DR15 haplotype alleles on disease susceptibility in a new “humanized” model of MS induced in HLA-transgenic (Tg) mice by human oligodendrocyte-specific protein (OSP)/claudin-11 (hOSP), one of the bona fide potential primary target antigens in MS. We show that the hOSP-associated MS-like disease is dominated by the DRB1*15:01 allele not only as the DRA1*01:01;DRB1*15:01 isotypic heterodimer but also, unexpectedly, as a functional DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. The contribution of HLA-DQA1/DRB1 mixed isotype heterodimer to OSP pathogenesis was revealed in (DRB1*1501xDQB1*0602)F1 double-Tg mice immunized with hOSP(142–161) peptide, where the encephalitogenic potential of prevalent DRB1*1501/hOSP(142–161)-reactive Th1/Th17 cells is hindered due to a single amino acid difference in the OSP(142–161) region between humans and mice; this impedes binding of DRB1*1501 to the mouse OSP(142–161) epitope in the mouse CNS while exposing functional binding of mouse OSP(142–161) to DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. This study, which shows for the first time a functional HLA-DQA1/DRB1 mixed isotype heterodimer and its potential association with disease susceptibility, provides a rationale for a potential effect on MS risk from DQA1*01:02 through functional DQA1*01:02;DRB1*15:01 antigen presentation. Furthermore, it highlights a potential contribution to MS

  7. Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2009-01-01

    BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from Darawe...

  8. RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization.

    Science.gov (United States)

    Lordier, Larissa; Bluteau, Dominique; Jalil, Abdelali; Legrand, Céline; Pan, Jiajia; Rameau, Philippe; Jouni, Dima; Bluteau, Olivier; Mercher, Thomas; Leon, Catherine; Gachet, Christian; Debili, Najet; Vainchenker, William; Raslova, Hana; Chang, Yunhua

    2012-03-06

    Megakaryocytes are unique mammalian cells that undergo polyploidization (endomitosis) during differentiation, leading to an increase in cell size and protein production that precedes platelet production. Recent evidence demonstrates that endomitosis is a consequence of a late failure in cytokinesis associated with a contractile ring defect. Here we show that the non-muscle myosin IIB heavy chain (MYH10) is expressed in immature megakaryocytes and specifically localizes in the contractile ring. MYH10 downmodulation by short hairpin RNA increases polyploidization by inhibiting the return of 4N cells to 2N, but other regulators, such as of the G1/S transition, might regulate further polyploidization of the 4N cells. Conversely, re-expression of MYH10 in the megakaryocytes prevents polyploidization and the transition of 2N to 4N cells. During polyploidization, MYH10 expression is repressed by the major megakaryocyte transcription factor RUNX1. Thus, RUNX1-mediated silencing of MYH10 is required for the switch from mitosis to endomitosis, linking polyploidization with megakaryocyte differentiation.

  9. Quantification of alpha-tubulin isotypes by sandwich ELISA with signal amplification through biotinyl-tyramide or immuno-PCR

    Czech Academy of Sciences Publication Activity Database

    Dráberová, Eduarda; Stegurová, Lucie; Sulimenko, Vadym; Hájková, Zuzana; Dráber, Petr; Dráber, Pavel

    2013-01-01

    Roč. 395, 1-2 (2013), s. 63-70 ISSN 0022-1759 R&D Projects: GA AV ČR KAN200520701; GA ČR GAP302/12/1673; GA ČR GPP302/11/P709; GA ČR GAP302/10/1759; GA ČR GA301/09/1826; GA MŠk(CZ) LD13015; GA MŠk LD12073 Institutional support: RVO:68378050 Keywords : alpha-tubulin isotypes * biotinyl-tyramide * ELISA * immuno-PCR * mast cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.005, year: 2013

  10. Heavy metals anthropogenic pollutants in Austria

    International Nuclear Information System (INIS)

    Anderl, M.; Gager, M.; Gugele, B.; Huttunen, K.; Kurzweil, A.; Poupa, S.; Ritter, M.; Wappel, D.; Wieser, M.

    2004-01-01

    Several heavy metals from anthropogenic sources are emitted in the atmosphere damaging the air quality and the human health, besides they accumulate on the soil and lately are transmitted into the human food chain. Therefore at international level there is a concern to reduce them. Austrian heavy metals emissions (cadmium, mercury and lead) during 1990-2002 are given including an analysis of causes and sources. Lead is the main pollutant and the main sector responsible is the industry. 5 figs. (nevyjel)

  11. Interplay Between Side Chain Pattern, Polymer Aggregation, and Charge Carrier Dynamics in PBDTTPD:PCBM Bulk-Heterojunction Solar Cells

    KAUST Repository

    Dyer-Smith, Clare

    2015-05-01

    Poly(benzo[1,2-b:4,5-b′]dithiophene–alt–thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymer donors with linear side-chains yield bulk-heterojunction (BHJ) solar cell power conversion efficiencies (PCEs) of about 4% with phenyl-C71-butyric acid methyl ester (PC71BM) as the acceptor, while a PBDTTPD polymer with a combination of branched and linear substituents yields a doubling of the PCE to 8%. Using transient optical spectroscopy it is shown that while the exciton dissociation and ultrafast charge generation steps are not strongly affected by the side chain modifications, the polymer with branched side chains exhibits a decreased rate of nongeminate recombination and a lower fraction of sub-nanosecond geminate recombination. In turn the yield of long-lived charge carriers increases, resulting in a 33% increase in short circuit current (J sc). In parallel, the two polymers show distinct grazing incidence X-ray scattering spectra indicative of the presence of stacks with different orientation patterns in optimized thin-film BHJ devices. Independent of the packing pattern the spectroscopic data also reveals the existence of polymer aggregates in the pristine polymer films as well as in both blends which trap excitons and hinder their dissociation.

  12. Topological analysis of long-chain branching patterns in polyolefins.

    Science.gov (United States)

    Bonchev, D; Markel, E; Dekmezian, A

    2001-01-01

    Patterns in molecular topology and complexity for long-chain branching are quantitatively described. The Wiener number, the topological complexity index, and a new index of 3-starness are used to quantify polymer structure. General formulas for these indices were derived for the cases of 3-arm star, H-shaped, and B-arm comb polymers. The factors affecting complexity in monodisperse polymer systems are ranked as follows: number of arms > arm length > arm central position approximately equal to arm clustering > total molecular weight approximately equal to backbone molecular weight. Topological indices change rapidly and then plateau as the molecular weight of branches on a polyolefin backbone increases from 0 to 5 kD. Complexity calculations relate 2-arm or 3-arm comb structures to the corresponding 3-arm stars of equivalent complexity but much higher molecular weight. In a subsequent paper, we report the application of topological analysis for developing structure/property relationships for monodisperse polymers. While the focus of the present work is on the description of monodisperse, well-defined architectures, the methods may be extended to the description of polydisperse systems.

  13. Immunoglobulin heavy and light chains and T-cell receptor beta and gamma chains PCR assessment on cytological samples. A study comparing FTA cards and cryopreserved lymph node fine-needle cytology.

    Science.gov (United States)

    Peluso, A L; Cozzolino, I; Bottiglieri, A; Lucchese, L; Di Crescenzo, R M; Langella, M; Selleri, C; Zeppa, P

    2017-06-01

    To evaluate and compare the DNA yield and quality extracted from lymph node fine needle cytology (FNC) samples stored on FTA cards to those cryopreserved, and to assess the immunoglobulin heavy and light chains (IGHK) and T-Cell receptor beta and gamma chains (TCRBG) PCR tests. DNA extractions were performed on FNC of 80 non-Hodgkin lymphomas (NHL), four myelomas and 56 benign reactive hyperplasias (BRH) cryopreserved and stored on FTA cards. The JAK2 gene was amplified to assess the DNA integrity and the IGHK/TCRBG clonality status was tested. IGHK monoclonality was found in 99% of B-cell NHL and 100% of myeloma. TCRBG monoclonality was found in 100% of T-cell NHL. TCRBG polyclonality was detected in 97% of B-cell NHL, 100% of myeloma and 96% of BRH. IGHK/TCRBG PCR data were confirmed by histological and/or follow-up controls. No differences were found in the DNA quality between cryopreservation and FTA cards storage methods. IGHK/TCRBG PCR of the lymphoproliferative process on FTA cards is comparable to those cryopreserved. FTA cards can be used to store lymph node FNC for further molecular investigations. © 2016 John Wiley & Sons Ltd.

  14. Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

    International Nuclear Information System (INIS)

    Sindi, Ramya A.; Harris, Wayne; Arnott, Gordon; Flaskos, John; Lloyd Mills, Chris; Hargreaves, Alan J.

    2016-01-01

    Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

  15. Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

    Energy Technology Data Exchange (ETDEWEB)

    Sindi, Ramya A., E-mail: ramya.sindi2010@my.ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); School of Applied Medical Sciences, Umm Al-Qura University, Makkah (Saudi Arabia); Harris, Wayne [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Arnott, Gordon [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Flaskos, John [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Lloyd Mills, Chris [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Hargreaves, Alan J., E-mail: alan.hargreaves@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

    2016-10-01

    Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

  16. Chagas' disease: IgG isotypes against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens of Trypanosoma cruzi in chronic Chagasic patients.

    Science.gov (United States)

    Verçosa, A F A; Lorena, V M B; Carvalho, C L; Melo, M F A D; Cavalcanti, M G A; Silva, E D; Ferreira, A G P; Pereira, V R A; Souza, W V; Gomes, Y M

    2007-01-01

    The wide range of clinical Chagas' disease manifestations, of which heart involvement is the most significant, because of its characteristics, frequency and consequences, and lack of treatment and cure, justify research in this area. Specific immunoglobulin G (IgG) antibody subclasses have been associated with human Chagas' disease. Thus, in this study, the profile of IgG subclasses against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive T. cruzi-specific antigens was correlated with cardiac (CARD, n=33), cardiodigestive (CD, n=7), and indeterminate (IND, n=20) forms of Chagas' disease by indirect enzyme-linked immunosorbent assay (ELISA). IgG subclasses were detected in almost all Chagas patients studied. Nevertheless, only specific IgG2 isotype FRA was found with a significant statistical difference in CARD patients when compared to IND patients. This result suggests the potential use of this isotype for prognostic purposes, for monitoring the progression of chronic Chagas' disease, and for predicting the risk of CARD damage. This is important information, as it could help physicians to evaluate and manage the treatment of their patients. However, a follow-up study is necessary to confirm our result. (c) 2007 Wiley-Liss, Inc.

  17. Botulinum neurotoxin type A radiolabeled at either the light or the heavy chain

    International Nuclear Information System (INIS)

    Dekleva, M.L.; DasGupta, B.R.; Sathyamoorthy, V.

    1989-01-01

    Botulinum neurotoxin (NT) has two distinct structural regions called L and H chains (approximately 50 and approximately 100 kDa, respectively). Although the H chain is responsible for binding of the NT to neuronal cells, it is not known which of the subunits is internalized and therefore responsible for causing the blockage of acetylcholine release in susceptible neuronal cells. In this report we describe for the first time the preparation of type A NT which is selectively radiolabeled at either the L or the H chain subunit. Such NT preparations will be useful as tools for determining the distribution of L and H chains in poisoned neuronal cells and the role that each subunit plays in inducing toxicity. The L and H chains of the NT (approximately 150 kDa) were separated, purified, and then individually radiolabeled by reductive methylation of the lysine residues using [3H]- or [14C]formaldehyde. The labeled L and H chains were reconjugated with the complementary unlabeled L and H chains. Formation of -S-S- and noncovalent bonds between the L and H chains regenerated the approximately 150 kDa NT. Autoradiographs of sodium dodecyl sulfate polyacrylamide gels confirmed that each reconstituted NT preparation was labeled at only one subunit chain. NT selectively labeled at either the L or the H chain had specific radioactivities of ca. 25-30 and 45-55 microCi/mumol, respectively, and toxicity (mouse LD50/mg protein) values of 2.2 +/- 1.1 X 10(7) and 3.0 +/- 1.0 X 10(7), respectively. A linear increase in the specific radioactivity of L and H chain subunits was observed with increasing concentrations of 3H- or 14C-labeled formaldehyde in the reaction mixture and with increasing concentrations of L or H chain in the reaction mixture

  18. Radioimmunoassay of myosin heavy beta chains in human serum for the evaluation of the size of myocardial infarction: correlation with myocardial Tl-201 SPECT and cardiac angioscintigraphy

    International Nuclear Information System (INIS)

    Facello, A.; Gries, P.; Demangeat, C.; Brunot, B.; Roul, G.; Demangeat, J.L.; Moulichon, M.; Bareiss, P.; Sacrez, A.; Constantinesco, A.

    1990-01-01

    To determine the relationship between serum levels of myosin heavy beta chains assessed by an IRMA technique and other radionuclide and enzymatic parameters in the evaluation of the size of myocardial infarction, we studied 22 patients with acute myocardial infarction. Blood samples taken daily between 1st to 13th day of evolution allow the determination of peak and integral of myosine release that showed a good correlation (p [fr

  19. Creating a multi-national development platform: Thorium energy and rare earth value chain

    International Nuclear Information System (INIS)

    Kennedy, J.; Kutsch, J.

    2014-01-01

    Rare earths and thorium are linked at the mineralogical level. Changes in thorium regulations and liabilities resulted in the development of excessive market concentrations in the rare earth value chain. High value monazite rare earth resources, a by-product of heavy mineral sands mining, constituted a significant portion of global rare earth supply (and nearly 100% of heavy rare earths) until legislative changes, interpretation and enforcement regarding “source materials” in the early 1980s eliminated these materials from the supply chain.

  20. Levels of myosin heavy chain mRNA transcripts and protein isoforms in the fast extensor digitorum longus muscle of 7-month-old rats with chronic thyroid status alterations

    Czech Academy of Sciences Publication Activity Database

    Vadászová, Adriana; Hudecová, S.; Križanová, O.; Soukup, Tomáš

    2006-01-01

    Roč. 55, č. 6 (2006), s. 707-710 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA304/05/0327 Grant - others:VEGA(SK) 2/4106; NATO(XE) 979876; SAV(SK) APVT-51-027404; MYORES(XE) 511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : myosin heavy chain isoforms * thyroid hormones * muscle differentiation Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  1. Topological b-hadron decay reconstruction and application for heavy-flavour jet tagging in ATLAS

    CERN Document Server

    Gilles, Geoffrey; The ATLAS collaboration

    2017-01-01

    The identification of jets originating from the hadronisation of heavy-flavour quarks represents a key ingredient in the physics program of the ATLAS experiment. Exploiting the topological structure of weak b- and c-hadron decays, the multi-vertex finder algorithm - JetFitter - tries to reconstruct the full b-hadron decay chain inside b-jets and provides a complementary approach to conventional secondary vertex finder algorithms. Based on the hypothesis that the primary and displaced b- and c-hadron decay vertices lie on a common line approximating the b-hadron flight direction, an extension of the Kalman Filter formalism for vertex reconstruction implemented in JetFitter allows to solve this pattern recognition problem. Detailed information on the reconstructed decay cascades is then used to identify and discriminate heavy-flavour jets. This poster presents the principle of this algorithm and its performance in the context of a recent optimization campaign performed in view of the 2017 LHC data-taking by the...

  2. Generation and Characterization of Polyclonal Antibody Against Part of Immunoglobulin Constant Heavy υ Chain of Goose

    Science.gov (United States)

    Zhao, Panpan; Guo, Yongli; Ma, Bo; Wang, Junwei

    2014-01-01

    Immunoglobulin Y (abbreviated as IgY) is a type of immunoglobulin that is the major antibody in bird, reptile, and lungfish blood. IgY consists of two light (λ) and two heavy (υ) chains. In the present study, polyclonal antibody against IgYFc was generated and evaluated. rIgYCυ3/Cυ4 was expressed in Escherichia coli, purified and utilized to raise polyclonal antibody in rabbit. High affinity antisera were obtained, which successfully detected the antigen at a dilution of 1:204,800 for ELISA assay. The antibody can specifically recognize both rIgYCυ3/Cυ4 and native IgY by Western bolt analysis. Furthermore, the serum of Grus japonensis or immunoglobulin of chicken, duck, turkey, and silkie samples and dynamic changes of serum GoIgY after immunogenicity with GPV-VP3-virus-like particles (GPV-VP3-VLPs) can be detected with the anti-GoIgYFc polyclonal antibody. These results suggested that the antibody is valuable for the investigation of biochemical properties and biological functions of GoIgY. PMID:25171010

  3. A Mouse Neurodegenerative Dynein Heavy Chain Mutation Alters Dynein Motility and Localization in Neurospora crassa

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2013-01-01

    Cytoplasmic dynein is responsible for the transport and delivery of cargoes in organisms ranging from humans to fungi. Dysfunction of dynein motor machinery due to mutations in dynein or its activating complex dynactin can result in one of several neurological diseases in mammals. The mouse Legs at odd angles (Loa) mutation in the tail domain of the dynein heavy chain has been shown to lead to progressive neurodegeneration in mice. The mechanism by which the Loa mutation affects dynein function is just beginning to be understood. In this work, we generated the dynein tail mutation observed in Loa mice into the Neurospora crassa genome and utilized cell biological and complementing biochemical approaches to characterize how that tail mutation affected dynein function. We determined that the Loa mutation exhibits several subtle defects upon dynein function in N. crassa that were not seen in mice, including alterations in dynein localization, impaired velocity of vesicle transport, and in the biochemical properties of purified motors. Our work provides new information on the role of the tail domain on dynein function and points out areas of future research that will be of interest to pursue in mammalian systems. PMID:22991199

  4. Study of heavy quark production with the Mark II at PEP

    International Nuclear Information System (INIS)

    Abrams, G.; Amidei, D.; Baden, A.

    1983-10-01

    The methods adopted by the Mark II collaboration to study heavy quark production at PEP are described. Two complementary techniques are used: D* tagging using the decay chain D* + . D 0 π + , D 0 → K - π + , and inclusive lepton tagging using the characteristic p/sub T/ distributions to distinguish contributions from b and c quarks. These techniques are used to derive information about heavy quark fragmentation and about the weak coupling of heavy quarks

  5. B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy.

    Science.gov (United States)

    Beausang, John F; Fan, H Christina; Sit, Rene; Hutchins, Maria U; Jirage, Kshama; Curtis, Rachael; Hutchins, Edward; Quake, Stephen R; Yabu, Julie M

    2017-01-13

    Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels. Responders to desensitization had a decrease of 5% points or greater in cumulated calculated panel reactive antibody (cPRA) levels, and non-responders had no decrease in cPRA. Dominant B cell clones were not observed in highly sensitized candidates, suggesting that the B cells responsible for sensitization are either not present in peripheral blood or present at comparable levels to other circulating B cells. Candidates that responded to desensitization therapy had pre-treatment repertoires composed of a larger fraction of class-switched (IgG and IgA) isotypes compared to non-responding candidates. After B cell depleting therapy, the proportion of switched isotypes increased and the mutation frequencies of the remaining non-switched isotypes (IgM and IgD) increased in both responders and non-responders, perhaps representing a shift in the repertoire towards memory B cells or plasmablasts. Conversely, after transplantation, non-switched isotypes with fewer mutations increased, suggesting a shift in the repertoire towards naïve B cells. Relative abundance of different B cell isotypes is strongly perturbed by desensitization therapy and transplantation, potentially reflecting changes in the relative

  6. A biosensor for cadmium based on bioconvective patterns

    Science.gov (United States)

    Noever, David A.; Matsos, Helen C.

    1990-01-01

    An 'in vitro' method for monitoring cadmium, one of the most lethal bivalent heavy metals, can detect biologically active levels. The effects of cadmium tend to concentrate in protozoa far above natural levels and therein begin transferring through freshwater food chains to animals and humans. In a small sample volume (approximately 5 ml) the method uses the toxic response to the protozoa, Tetrahymena pyriformis, to cadmium. The assay relies on macroscopic bioconvective patterns to measure the toxic response, giving a sensitivity better than 1 micro-g/1 and a toxicity threshold to 7 micro-g/1 for Cd(2+). Cadmium hinders pattern formation in a dose-dependent manner. Arrested organism growth arises from slowed division and mutation to non-dividing classes. Unlike previous efforts, this method can be performed in a shallow flow device and does not require electronic or chemical analyses to monitor toxicity.

  7. An IPC-based Prolog design pattern for integrating backward chaining inference into applications or embedded systems

    Directory of Open Access Journals (Sweden)

    Li Guoqi

    2014-12-01

    Full Text Available Prolog is one of the most important candidates to build expert systems and AI-related programs and has potential applications in embedded systems. However, Prolog is not suitable to develop many kinds of components, such as data acquisition and task scheduling, which are also crucial. To make the best use of the advantages and bypass the disadvantages, it is attractive to integrate Prolog with programs developed by other languages. In this paper, an IPC-based method is used to integrate backward chaining inference implemented by Prolog into applications or embedded systems. A Prolog design pattern is derived from the method for reuse, whose principle and definition are provided in detail. Additionally, the design pattern is applied to a target system, which is free software, to verify its feasibility. The detailed implementation of the application is given to clarify the design pattern. The design pattern can be further applied to wide range applications and embedded systems and the method described in this paper can also be adopted for other logic programming languages.

  8. Applications of stochastic models and geostatistical analyses to study sources and spatial patterns of soil heavy metals in a metalliferous industrial district of China.

    Science.gov (United States)

    Zhong, Buqing; Liang, Tao; Wang, Lingqing; Li, Kexin

    2014-08-15

    An extensive soil survey was conducted to study pollution sources and delineate contamination of heavy metals in one of the metalliferous industrial bases, in the karst areas of southwest China. A total of 597 topsoil samples were collected and the concentrations of five heavy metals, namely Cd, As (metalloid), Pb, Hg and Cr were analyzed. Stochastic models including a conditional inference tree (CIT) and a finite mixture distribution model (FMDM) were applied to identify the sources and partition the contribution from natural and anthropogenic sources for heavy metal in topsoils of the study area. Regression trees for Cd, As, Pb and Hg were proved to depend mostly on indicators of anthropogenic activities such as industrial type and distance from urban area, while the regression tree for Cr was found to be mainly influenced by the geogenic characteristics. The FMDM analysis showed that the geometric means of modeled background values for Cd, As, Pb, Hg and Cr were close to their background values previously reported in the study area, while the contamination of Cd and Hg were widespread in the study area, imposing potentially detrimental effects on organisms through the food chain. Finally, the probabilities of single and multiple heavy metals exceeding the threshold values derived from the FMDM were estimated using indicator kriging (IK) and multivariate indicator kriging (MVIK). The high probabilities exceeding the thresholds of heavy metals were associated with metalliferous production and atmospheric deposition of heavy metals transported from the urban and industrial areas. Geostatistics coupled with stochastic models provide an effective way to delineate multiple heavy metal pollution to facilitate improved environmental management. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. COAXIAL DISK SHUNT FOR MEASURING IN THE HEAVY-CURRENT CHAIN OF HIGH-VOLTAGE GENERATOR OF STORM DISCHARGES OF IMPULSES OF CURRENT OF ARTIFICIAL LIGHTNING WITH THE INTEGRAL OF ACTION TO 15•106 J/OHM

    Directory of Open Access Journals (Sweden)

    M. I. Baranov

    2017-10-01

    Full Text Available Purpose. Description of construction and basic technical descriptions developed and created in Research & Design Institute «Molniya» National Technical University «Kharkiv Polytechnic Institute» high-voltage heavy-current coaxial disk shunt of type of SC-300M2, allowing reliably to measure the peak-temporal parameters (PTP of impulses of current of artificial lightning in wide peak and temporal ranges with the integral of their action to 15·106 J/Ohm. Methodology. Electrophysics bases of high-voltage impulsive technique, scientific and technical bases of development and creation of high-voltage heavy-current impulsive electrical equipment, including the powerful generators of current of lightning (GCL, and also measuring methods in bit chains powerful high-voltage GCL AVP large impulsive currents of micro- and millisecond temporal ranges. Results. Offered and described new construction of measuring high-voltage heavy-current shunt, containing a measuring round disk from stainless steel easily soiled a 12Х18Н10Т thickness 2 mm and external diameter 80 mm. Experimental a way impulsive active resistance of RS≈0,08 mOhm of the indicated measuring disk and on his basis a calculation coefficient transformation is found of SS of coaxial disk shunt of type of SC-300M2, numeral equal in the concerted mode of operations of his coaxial cable line (CCL SS≈2/RS≈25·103 A/V. It is rotined that it is expedient to use this value SS for measuring in the heavy-current bit chain of GCL ATP impulsive A- and repeated impulsive D- component of current of artificial lightning, and also ATP of aperiodic impulse of current of artificial lightning of temporal form 10 μc/350 μc. It is set that taking into account application in the end CCL of shunt of a co-ordinate divizor of voltage with two output coaxial sockets 1:1 (for SSA≈25·103 A/V and 1:2 (SSC≈12,5·103 A/V at measuring of ATP intermediate B-, protracted C- and shortened protracted C

  10. Sub-isotypic differences in the immunoglobulin G response to Lawsonia intracellularis in vaccinated, seropositive, and equine proliferative enteropathy-affected horses.

    Science.gov (United States)

    Page, Allen E; Stills, Harold F; Horohov, David W

    2014-12-15

    In the horse, Lawsonia intracellularis infection results in equine proliferative enteropathy (EPE). While upwards of 100% of weanlings on an endemic farm may seroconvert, only a small percentage (approximately 5%) will develop clinical disease. Cell-mediated immune mechanisms likely play a role in resistance to L. intracellularis and the absence of a L. intracellularis-specific IFN-γ response has been associated with the development of EPE. The goal of this study was to determine whether protection from clinical EPE is associated with the induction of a systemic IgG sub-isotypic response consistent with a Th1-type cytokine response. To describe their L. intracellularis/EPE status, horses enrolled in this study were placed into one of three categories: seropositive-only, vaccinated, and presumptive clinical EPE. An existing ELISA method was modified to detect L. intracellularis-specific IgG(a), IgG(b), and IgG(t) antibodies using the mouse anti-equine hybridomas CVS-48, CVS-39, and CVS-40, respectively. Additionally, the existing ELISA method was used to quantify total IgG antibodies specific for L. intracellularis for comparison between the groups. Total L. intracellularis-specific IgG was found to be significantly higher (pequine IgG sub-isotypes may provide additional information once these become commercially available. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Flexibility of the myosin heavy chain: direct evidence that the region containing SH/sub 1/ and SH/sub 2/ can move 10 /Angstrom/ under the influence of nucleotide binding

    Energy Technology Data Exchange (ETDEWEB)

    Huston, E.E.; Grammer, J.C.; Yount, R.G.

    1988-12-13

    Previous experiments demonstrated that two thiols of skeletal myosin subfragment 1 (SF/sub 1/) could be oxidized to a disulfide bond by treatment with a 2-fold excess of 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) in the presence of MgADP. The resulting characteristic changes in the ATPase activities of SF/sub 1/ and the fact that MgADP was stably trapped at the active site, suggested that the two thiols cross-linked were SH/sub 1/ (Cys-707) and SH/sub 2/ (Cys-697) from the myosin heavy chain. To verify this suggestion, SF/sub 1/, after DTNB treatment as above, was treated with an excess of N-ethylmaleimide to block all accessible thiols. The single protein disulfide produced by DTNB oxidation was reduced with dithioerythritol and the modified SF/sub 1/ internally cross-linked with equimolar (/sup 14/C)p-phenylenedimaleimide (pPDM) in the presence of MgADP. After extensive trypsinization, the major /sup 14/C-labeled peptide was isolated, characterized, and shown to be Cys-Asn-Gly-Val-Leu-Gly-Ile-Arg-Ile-Cys-Arg, in which the two cysteines were cross-linked by pPDM. This peptide is known to contain SH/sub 2/ and SH/sub 1/ in this order and to come from residues 697-708 in the rabbit skeletal myosin heavy chain. Parallel experiments with (/sup 14/C)pPDM and unmodified SF/sub 1/ similar to those above gave an identical SH/sub 1/, SH/sub 2/ tryptic peptide, verifying earlier labeling results. These combined results demonstrate that SH/sub 1/ and SH/sub 2/ cross-linked by pPDM (12-13 /Angstrom/, S to S) or by oxidation with DTNB (2 /Angstrom/, S to S) can move a minimum of 10 /Angstrom/ under the influence of nucleotide binding. Because these residues are separated by only nine amino acids in the primary sequence, this small section of the heavy chain must possess extraordinary flexibility.

  12. Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease

    DEFF Research Database (Denmark)

    Pecci, A.; Panza, E.; Pujol-Moix, N.

    2008-01-01

    MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness...... to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis. We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis...... and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC...

  13. Camelid-derived heavy-chain nanobody against Clostridium botulinum neurotoxin E in Pichia pastoris.

    Science.gov (United States)

    Baghban, Roghayyeh; Gargari, Seyed Latif Mousavi; Rajabibazl, Masoumeh; Nazarian, Shahram; Bakherad, Hamid

    2016-01-01

    Botulinum neurotoxins (BoNTs) result in severe and often fatal disease, botulism. Common remedial measures such as equine antitoxin and human botulism immunoglobulin in turn are problematic and time-consuming. Therefore, diagnosis and therapy of BoNTs are vital. The variable domain of heavy-chain antibodies (VHH) has unique features, such as the ability to identify and bind specifically to target epitopes and ease of production in bacteria and yeast. The Pichia pastoris is suitable for expression of recombinant antibody fragments. Disulfide bond formation and correct folds of protein with a high yield are some of the advantages of this eukaryotic host. In this study, we have expressed and purified the camelid VHH against BoNT/E in P. pastoris. The final yield of P. pastoris-expressed antibody was estimated to be 16 mg/l, which is higher than that expressed by Escherichia coli. The nanobody expressed in P. pastoris neutralized 4LD50 of the BoNT/E upon i.p. injection in 25% of mice. The nanobody expressed in E. coli extended the mice's survival to 1.5-fold compared to the control. This experiment indicated that the quality of expressed protein in the yeast is superior to that of the bacterial expression. Favorable protein folding by P. pastoris seems to play a role in its better toxin-binding property. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  14. Levels of myosin heavy chain mRNA transcripts and content of protein isoforms in the slow soleus muscle of 7 month-old rats with altered thyroid status

    Czech Academy of Sciences Publication Activity Database

    Vadászová, Adriana; Hudecová, S.; Križanová, O.; Soukup, Tomáš

    2006-01-01

    Roč. 55, č. 2 (2006), s. 221-225 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GD305/03/H148; GA ČR(CZ) GA304/05/0327 Grant - others:VEGA(SK) 2/6078; SAV(SK) APVT-51-027404; NATO(XE) 979876; MYORES(XE) 511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : myosin heavy chain * thyroid hormones status * mRNA transcripts Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  15. The influence of post-growth annealing on the optical properties of InAs quantum dot chains grown on pre-patterned GaAs(100)

    International Nuclear Information System (INIS)

    Hakkarainen, T V; Polojärvi, V; Schramm, A; Tommila, J; Guina, M

    2012-01-01

    We report on the effect of post-growth thermal annealing of [011]-, [01 1-bar ]-, and [010]-oriented quantum dot chains grown by molecular beam epitaxy on GaAs(100) substrates patterned by UV-nanoimprint lithography. We show that the quantum dot chains experience a blueshift of the photoluminescence energy, spectral narrowing, and a reduction of the intersubband energy separation during annealing. The photoluminescence blueshift is more rapid for the quantum dot chains than for self-assembled quantum dots that were used as a reference. Furthermore, we studied polarization resolved photoluminescence and observed that annealing reduces the intrinsic optical anisotropy of the quantum dot chains and the self-assembled quantum dots. (paper)

  16. Efficient heterologous expression and secretion in Aspergillus oryzae of a llama variable heavy-chain antibody fragment V(HH) against EGFR.

    Science.gov (United States)

    Okazaki, Fumiyoshi; Aoki, Jun-ichi; Tabuchi, Soichiro; Tanaka, Tsutomu; Ogino, Chiaki; Kondo, Akihiko

    2012-10-01

    We have constructed a filamentous fungus Aspergillus oryzae that secretes a llama variable heavy-chain antibody fragment (V(HH)) that binds specifically to epidermal growth factor receptor (EGFR) in a culture medium. A major improvement in yield was achieved by fusing the V(HH) with a Taka-amylase A signal sequence (sTAA) and a segment of 28 amino acids from the N-terminal region of Rhizopus oryzae lipase (N28). The yields of secreted, immunologically active anti-EGFR V(HH) reached 73.8 mg/1 in a Sakaguchi flask. The V(HH) fragments were released from the sTAA or N28 proteins by an indigenous A. oryzae protease during cultivation. The purified recombinant V(HH) fragment was specifically recognized and could bind to the EGFR with a high affinity.

  17. Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Rai, Taranjit Singh; Ahmad, Shamim; Bahl, Ajay

    2009-01-01

    The aim of the current study was to determine the frequency of mutations in the beta-myosin heavy chain gene (MYH7) in a cohort of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and their families, and to investigate correlations between genotype and phenotype. About 130...... consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene. The control group for genetic studies consisted of 100 healthy subjects. We report 14...... mutations in 6 probands (5 probands in HCM and 1 proband in DCM) and their family members. Out of these 6 mutations, 3 are new and are being reported for the first time. One known mutation (p.Gly716Arg) was found to be "de novo" which resulted in severe asymmetric septal hypertrophy (31 mm) and resulted...

  18. Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements

    International Nuclear Information System (INIS)

    Schroeder, H.W. Jr.; Walter, M.A.; Hofker, M.H.; Ebens, A.; Van Dijk, K.W.; Liao, L.C.; Cox, D.W.; Milner, E.C.B.; Perlmutter, R.M.

    1988-01-01

    Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (V H ), diversity (D H ), and joining (J H ) region gene segments appears preferentially in the human fetal repertoire. The authors report here that one of these early-expressed V H elements (termed V H 6) is the most 3' V H gene segment, positioned 77 kilobases on the 5' side of the J H locus and immediately adjacent to a set of previously described D H sequences. In addition to providing a physical map linking human V H , D H , and J H elements, these results support the view that the programmed development of the antibody V H repertoire is determined in part by the chromosomal position of these gene segments

  19. High production of llama variable heavy-chain antibody fragment (VHH) fused to various reader proteins by Aspergillus oryzae.

    Science.gov (United States)

    Hisada, Hiromoto; Tsutsumi, Hiroko; Ishida, Hiroki; Hata, Yoji

    2013-01-01

    Llama variable heavy-chain antibody fragment (VHH) fused to four different reader proteins was produced and secreted in culture medium by Aspergillus oryzae. These fusion proteins consisted of N-terminal reader proteins, VHH, and a C-terminal his-tag sequence which facilitated purification using one-step his-tag affinity chromatography. SDS-PAGE analysis of the deglycosylated purified fusion proteins confirmed that the molecular weight of each corresponded to the expected sum of VHH and the respective reader proteins. The apparent high molecular weight reader protein glucoamylase (GlaB) was found to be suitable for efficient VHH production. The GlaB-VHH-His protein bound its antigen, human chorionic gonadotropin, and was detectable by a new ELISA-based method using a coupled assay with glucoamylase, glucose oxidase, peroxidase, maltose, and 3,3',5,5'-tetramethylbenzidine as substrates. Addition of potassium phosphate to the culture medium induced secretion of 0.61 mg GlaB-VHH-His protein/ml culture medium in 5 days.

  20. Applications of stochastic models and geostatistical analyses to study sources and spatial patterns of soil heavy metals in a metalliferous industrial district of China

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Buqing; Liang, Tao, E-mail: liangt@igsnrr.ac.cn; Wang, Lingqing; Li, Kexin

    2014-08-15

    An extensive soil survey was conducted to study pollution sources and delineate contamination of heavy metals in one of the metalliferous industrial bases, in the karst areas of southwest China. A total of 597 topsoil samples were collected and the concentrations of five heavy metals, namely Cd, As (metalloid), Pb, Hg and Cr were analyzed. Stochastic models including a conditional inference tree (CIT) and a finite mixture distribution model (FMDM) were applied to identify the sources and partition the contribution from natural and anthropogenic sources for heavy metal in topsoils of the study area. Regression trees for Cd, As, Pb and Hg were proved to depend mostly on indicators of anthropogenic activities such as industrial type and distance from urban area, while the regression tree for Cr was found to be mainly influenced by the geogenic characteristics. The FMDM analysis showed that the geometric means of modeled background values for Cd, As, Pb, Hg and Cr were close to their background values previously reported in the study area, while the contamination of Cd and Hg were widespread in the study area, imposing potentially detrimental effects on organisms through the food chain. Finally, the probabilities of single and multiple heavy metals exceeding the threshold values derived from the FMDM were estimated using indicator kriging (IK) and multivariate indicator kriging (MVIK). The high probabilities exceeding the thresholds of heavy metals were associated with metalliferous production and atmospheric deposition of heavy metals transported from the urban and industrial areas. Geostatistics coupled with stochastic models provide an effective way to delineate multiple heavy metal pollution to facilitate improved environmental management. - Highlights: • Conditional inference tree can identify variables controlling metal distribution. • Finite mixture distribution model can partition natural and anthropogenic sources. • Geostatistics with stochastic models

  1. Applications of stochastic models and geostatistical analyses to study sources and spatial patterns of soil heavy metals in a metalliferous industrial district of China

    International Nuclear Information System (INIS)

    Zhong, Buqing; Liang, Tao; Wang, Lingqing; Li, Kexin

    2014-01-01

    An extensive soil survey was conducted to study pollution sources and delineate contamination of heavy metals in one of the metalliferous industrial bases, in the karst areas of southwest China. A total of 597 topsoil samples were collected and the concentrations of five heavy metals, namely Cd, As (metalloid), Pb, Hg and Cr were analyzed. Stochastic models including a conditional inference tree (CIT) and a finite mixture distribution model (FMDM) were applied to identify the sources and partition the contribution from natural and anthropogenic sources for heavy metal in topsoils of the study area. Regression trees for Cd, As, Pb and Hg were proved to depend mostly on indicators of anthropogenic activities such as industrial type and distance from urban area, while the regression tree for Cr was found to be mainly influenced by the geogenic characteristics. The FMDM analysis showed that the geometric means of modeled background values for Cd, As, Pb, Hg and Cr were close to their background values previously reported in the study area, while the contamination of Cd and Hg were widespread in the study area, imposing potentially detrimental effects on organisms through the food chain. Finally, the probabilities of single and multiple heavy metals exceeding the threshold values derived from the FMDM were estimated using indicator kriging (IK) and multivariate indicator kriging (MVIK). The high probabilities exceeding the thresholds of heavy metals were associated with metalliferous production and atmospheric deposition of heavy metals transported from the urban and industrial areas. Geostatistics coupled with stochastic models provide an effective way to delineate multiple heavy metal pollution to facilitate improved environmental management. - Highlights: • Conditional inference tree can identify variables controlling metal distribution. • Finite mixture distribution model can partition natural and anthropogenic sources. • Geostatistics with stochastic models

  2. Differential muscular myosin heavy chain expression of the pectoral and pelvic girdles during early growth in the king penguin (Aptenodytes patagonicus) chick.

    Science.gov (United States)

    Erbrech, Aude; Robin, Jean-Patrice; Guérin, Nathalie; Groscolas, René; Gilbert, Caroline; Martrette, Jean-Marc

    2011-06-01

    Continuous growth, associated with a steady parental food supply, is a general pattern in offspring development. So that young chicks can acquire their locomotor independence, this period is usually marked by a fast maturation of muscles, during which different myosin heavy chain (MyHC) isoforms are expressed. However, parental food provisioning may fluctuate seasonally, and offspring therefore face a challenge to ensure the necessary maturation of their tissues when energy is limited. To address this trade-off we investigated muscle maturation in both the pectoral and pelvic girdles of king penguin chicks. This species has an exceptionally long rearing period (1 year), which is prolonged when parental food provisioning is drastically reduced during the sub-Antarctic winter. Approximately 1 month post hatching, chicks acquire a functional pedestrian locomotion, which uses pelvic muscles, whereas swimming, which uses the pectoral muscles, only occurs 1 year later. We therefore tested the hypothesis that the MyHC content of the leg muscles reaches a mature state before those of the pectoral muscles. We found that leg muscle MyHC composition changed with the progressive acquisition of pedestrian locomotion, whereas pectoral muscle fibres reached their mature MyHC profile as early as hatching. Contrary to our predictions, the acquisition of the adult profile in pectoral muscles could be related to an early maturation of the contractile muscular proteins, presumably associated with early thermoregulatory capacities of chicks, necessary for survival in their cold environment. This differential maturation appears to reconcile both the locomotor and environmental constraints of king penguin chicks during growth.

  3. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

    Science.gov (United States)

    Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

    2016-08-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  4. A theory of traffic congestion at heavy bottlenecks

    Energy Technology Data Exchange (ETDEWEB)

    Kerner, Boris S [Daimler AG, GR/ETI, HPC: G021, 71059 Sindelfingen (Germany)

    2008-05-30

    Spatiotemporal features and physics of vehicular traffic congestion occurring due to heavy highway bottlenecks caused for example by bad weather conditions or accidents are found based on simulations in the framework of three-phase traffic theory. A model of a heavy bottleneck is presented. Under a continuous non-limited increase in bottleneck strength, i.e., when the average flow rate within a congested pattern allowed by the heavy bottleneck decreases continuously up to zero, the evolution of the traffic phases in congested traffic, synchronized flow and wide moving jams, is studied. It is found that at a small enough flow rate within the congested pattern, the pattern exhibits a non-regular structure: a pinch region of synchronized flow within the pattern disappears and appears randomly over time; wide moving jams upstream of the pinch region exhibit a complex non-regular dynamics in which the jams appear and disappear randomly. At greater bottleneck strengths, wide moving jams merge onto a mega-wide moving jam (mega-jam) within which low-speed patterns with a complex non-regular spatiotemporal dynamics occur. We show that when the bottleneck strength is great enough, only the mega-jam survives and synchronized flow remains only within its downstream front separating free flow and congested traffic. Theoretical results presented can explain why no sequence of wide moving jams can often be distinguished in non-homogeneous traffic congestion measured at very heavy bottlenecks caused by bad weather conditions or accidents.

  5. A theory of traffic congestion at heavy bottlenecks

    International Nuclear Information System (INIS)

    Kerner, Boris S

    2008-01-01

    Spatiotemporal features and physics of vehicular traffic congestion occurring due to heavy highway bottlenecks caused for example by bad weather conditions or accidents are found based on simulations in the framework of three-phase traffic theory. A model of a heavy bottleneck is presented. Under a continuous non-limited increase in bottleneck strength, i.e., when the average flow rate within a congested pattern allowed by the heavy bottleneck decreases continuously up to zero, the evolution of the traffic phases in congested traffic, synchronized flow and wide moving jams, is studied. It is found that at a small enough flow rate within the congested pattern, the pattern exhibits a non-regular structure: a pinch region of synchronized flow within the pattern disappears and appears randomly over time; wide moving jams upstream of the pinch region exhibit a complex non-regular dynamics in which the jams appear and disappear randomly. At greater bottleneck strengths, wide moving jams merge onto a mega-wide moving jam (mega-jam) within which low-speed patterns with a complex non-regular spatiotemporal dynamics occur. We show that when the bottleneck strength is great enough, only the mega-jam survives and synchronized flow remains only within its downstream front separating free flow and congested traffic. Theoretical results presented can explain why no sequence of wide moving jams can often be distinguished in non-homogeneous traffic congestion measured at very heavy bottlenecks caused by bad weather conditions or accidents

  6. Clathrin heavy chain 1 is required for spindle assembly and chromosome congression in mouse oocytes.

    Science.gov (United States)

    Zhao, Jie; Wang, Lu; Zhou, Hong-Xia; Liu, Li; Lu, Angeleem; Li, Guang-Peng; Schatten, Heide; Liang, Cheng-Guang

    2013-10-01

    Clathrin heavy chain 1 (CLTC) has been considered a “moonlighting protein” which acts in membrane trafficking during interphase and in stabilizing spindle fibers during mitosis. However, its roles in meiosis, especially in mammalian oocyte maturation, remain unclear. This study investigated CLTC expression and function in spindle formation and chromosome congression during mouse oocyte meiotic maturation. Our results showed that the expression level of CLTC increased after germinal vesicle breakdown (GVBD) and peaked in the M phase. Immunostaining results showed CLTC distribution throughout the cytoplasm in a cell cycle-dependent manner. Appearance and disappearance of CLTC along with β-tubulin (TUBB) could be observed during spindle dynamic changes. To explore the relationship between CLTC and microtubule dynamics, oocytes at metaphase were treated with taxol or nocodazole. CLTC colocalized with TUBB at the enlarged spindle and with cytoplasmic asters after taxol treatment; it disassembled and distributed into the cytoplasm along with TUBB after nocodazole treatment. Disruption of CLTC function using stealth siRNA caused a decreased first polar body extrusion rate and extensive spindle formation and chromosome congression defects. Taken together, these results show that CLTC plays an important role in spindle assembly and chromosome congression through a microtubule correlation mechanism during mouse oocyte maturation.

  7. Dlc1 interaction with non-muscle myosin heavy chain II-A (Myh9 and Rac1 activation

    Directory of Open Access Journals (Sweden)

    Mohammad G. Sabbir

    2016-04-01

    Full Text Available The Deleted in liver cancer 1 (Dlc1 gene codes for a Rho GTPase-activating protein that also acts as a tumour suppressor gene. Several studies have consistently found that overexpression leads to excessive cell elongation, cytoskeleton changes and subsequent cell death. However, none of these studies have been able to satisfactorily explain the Dlc1-induced cell morphological phenotypes and the function of the different Dlc1 isoforms. Therefore, we have studied the interacting proteins associated with the three major Dlc1 transcriptional isoforms using a mass spectrometric approach in Dlc1 overexpressing cells. We have found and validated novel interacting partners in constitutive Dlc1-expressing cells. Our study has shown that Dlc1 interacts with non-muscle myosin heavy chain II-A (Myh9, plectin and spectrin proteins in different multiprotein complexes. Overexpression of Dlc1 led to increased phosphorylation of Myh9 protein and activation of Rac1 GTPase. These data support a role for Dlc1 in induced cell elongation morphology and provide some molecular targets for further analysis of this phenotype.

  8. Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

    Science.gov (United States)

    Baldwin, K. M.; Haddad, F.

    2001-01-01

    The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T(3), 3,5,3'-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T(3)/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T(3) or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T(3) and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of

  9. Reflection of serum immunoglobulin isotypes in the egg yolk of laying hens immunized with enterotoxigenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Nagendra Nath Barman

    2014-09-01

    Full Text Available Aim: The aim was to study the seroconversion and development of egg yolk immunoglobulins in adult laying White Leghorn hens immunized against an isolate of enterotoxigenic Escherichia coli (ETEC bearing K91 and K88ac antigens, obtained from diarrheic piglet. Materials and Methods: Adult laying White Leghorn hens were immunized with inactivated enterotoxic E. coli strain isolated originally from a case of piglet diarrhea following recommended schedule. The development of whole antibodies and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA. Piglets suffering from diarrhea with fecal samples positive for ETEC were fed with egg yolk and compared with diarrheic control group. Results: The serum and egg yolk ELISA antibody titer against E. coli strain used in the present study was as high as 2666.66±307.92 and 933.33±203.67 respectively on 50 day-post-vaccination (DPV. The immunoglobulin Y (IgY was the predominant isotype in serum and egg yolk, which reached the peak titer of 2200±519.61 in serum on 40 DPV and 800±244.94 in egg yolk on 50 DPV. IgM titer in serum and egg yolk was found to be meager, and no IgA could be detected. Diarrheic piglets fed with the egg yolk suspension from immunized hens showed a promising result in controlling diarrhea. Conclusion: Egg yolk antibodies are considered a suitable immunotherapeutic alternative to conventional antibiotic therapy. High titer of egg yolk antibodies raised in the immunized hen against an isolate of ETEC holds the potential to be used for passive protection of diarrheic piglets during their most susceptible period of infection.

  10. Effects of alkyl chain length and substituent pattern of fullerene bis-adducts on film structures and photovoltaic properties of bulk heterojunction solar cells.

    Science.gov (United States)

    Tao, Ran; Umeyama, Tomokazu; Kurotobi, Kei; Imahori, Hiroshi

    2014-10-08

    A series of alkoxycarbonyl-substituted dihydronaphthyl-based [60]fullerene bis-adduct derivatives (denoted as C2BA, C4BA, and C6BA with the alkyl chain of ethyl, n-butyl, and n-hexyl, respectively) have been synthesized to investigate the effects of alkyl chain length and substituent pattern of fullerene bis-adducts on the film structures and photovoltaic properties of bulk heterojunction polymer solar cells. The shorter alkyl chain length caused lower solubility of the fullerene bis-adducts (C6BA > C4BA > C2BA), thereby resulting in the increased separation difficulty of respective bis-adduct isomers. The device performance based on poly(3-hexylthiophene) (P3HT) and the fullerene bis-adduct regioisomer mixtures was enhanced by shortening the alkyl chain length. When using the regioisomerically separated fullerene bis-adducts, the devices based on trans-2 and a mixture of trans-4 and e of C4BA exhibited the highest power conversion efficiencies of ca. 2.4%, which are considerably higher than those of the C6BA counterparts (ca. 1.4%) and the C4BA regioisomer mixture (1.10%). The film morphologies as well as electron mobilities of the P3HT:bis-adduct blend films were found to affect the photovoltaic properties considerably. These results reveal that the alkyl chain length and substituent pattern of fullerene bis-adducts significantly influence the photovoltaic properties as well as the film structures of bulk heterojunction solar cells.

  11. Dependence of crystallite formation and preferential backbone orientations on the side chain pattern in PBDTTPD polymers

    KAUST Repository

    El Labban, Abdulrahman

    2014-11-26

    (Figure Presented) Alkyl substituents appended to the π-conjugated main chain account for the solution-processability and film-forming properties of most π-conjugated polymers for organic electronic device applications, including field-effect transistors (FETs) and bulk-heterojunction (BHJ) solar cells. Beyond film-forming properties, recent work has emphasized the determining role that side-chain substituents play on polymer self-assembly and thin-film nanostructural order, and, in turn, on device performance. However, the factors that determine polymer crystallite orientation in thin-films, implying preferential backbone orientation relative to the device substrate, are a matter of some debate, and these structural changes remain difficult to anticipate. In this report, we show how systematic changes in the side-chain pattern of poly(benzo[1,2-b:4,5-b′]dithiophene-alt-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers can (i) influence the propensity of the polymer to order in the π-stacking direction, and (ii) direct the preferential orientation of the polymer crystallites in thin films (e.g., "face-on" vs "edge-on"). Oriented crystallites, specifically crystallites that are well-ordered in the π-stacking direction, are believed to be a key contributor to improved thin-film device performance in both FETs and BHJ solar cells.

  12. Discrepant Patterns of Heavy Drinking, Marijuana Use, and Smoking and Intimate Partner Violence: Results from the California Community Health Study of Couples

    Science.gov (United States)

    Cunradi, Carol B.; Todd, Michael; Mair, Christina

    2015-01-01

    This study analyzed whether discrepant (husband or wife use only) or concordant (both partners use) patterns of heavy drinking, marijuana use, and smoking are associated with increased risk for male-to-female partner violence and female-to-male partner violence among adult couples. Based on a geographic sample of married or cohabiting couples…

  13. Biotin-avidin sandwich elisa with specific human isotypes IgG1 and IgG4 for Culicidae mosquito blood meal identification from an epizootic yellow fever area in Brazil

    Directory of Open Access Journals (Sweden)

    AM Marassá

    2009-01-01

    Full Text Available With a view toward investigating the feeding behavior of Culicidae mosquitoes from an area of epizootic yellow fever transmission in the municipalities of Garruchos and Santo Antônio das Missões, Rio Grande do Sul State, Brazil, specimens were collected by aspiration from September 2005 to April 2007. The engorged females were submitted to blood meal identification by enzyme-linked immunosorbent assay (ELISA. A total of 142 blood-engorged samples were examined for human or monkey blood through species-specific IgG. Additional tests for specificity utilizing isotypes IgG1 and IgG4 of human monoclonal antibodies showed that only anti-human IgG1 was effective in recognizing blood meals of human origin. The results indicated a significant difference (p = 0.027 in detection patterns in samples of Haemagogus leucocelaenus recorded from human blood meals at Santo Antônio das Missões, which suggests some degree of exposure, since it was an area where epizootic outbreaks have been reported.

  14. Synthesis of compact patterns for NMR relaxation decay in intelligent "electronic tongue" for analyzing heavy oil composition

    Science.gov (United States)

    Lapshenkov, E. M.; Volkov, V. Y.; Kulagin, V. P.

    2018-05-01

    The article is devoted to the problem of pattern creation of the NMR sensor signal for subsequent recognition by the artificial neural network in the intelligent device "the electronic tongue". The specific problem of removing redundant data from the spin-spin relaxation signal pattern that is used as a source of information in analyzing the composition of oil and petroleum products is considered. The method is proposed that makes it possible to remove redundant data of the relaxation decay pattern but without introducing additional distortion. This method is based on combining some relaxation decay curve intervals that increment below the noise level such that the increment of the combined intervals is above the noise level. In this case, the relaxation decay curve samples that are located inside the combined intervals are removed from the pattern. This method was tested on the heavy-oil NMR signal patterns that were created by using the Carr-Purcell-Meibum-Gill (CPMG) sequence for recording the relaxation process. Parameters of CPMG sequence are: 100 μs - time interval between 180° pulses, 0.4s - duration of measurement. As a result, it was revealed that the proposed method allowed one to reduce the number of samples 15 times (from 4000 to 270), and the maximum detected root mean square error (RMS error) equals 0.00239 (equivalent to signal-to-noise ratio 418).

  15. Remediation of heavy metal contaminated ecosystem: an overview on technology advancement

    International Nuclear Information System (INIS)

    Singh, A.; Prasad, S. M.

    2015-01-01

    The issue of heavy metal pollution is very much concerned because of their toxicity for plant, animal and human beings and their lack of biodegradability. Excess concentrations of heavy metals have adverse effect on plant metabolic activities hence affect the food production, quantitatively and qualitatively. Heavy metal when reaches human tissues through various absorption pathways such as direct ingestion, dermal contact, diet through the soil-food chain, inhalation, and oral intake may seriously affect their health. Therefore, several management practices are being applied to minimize metal toxicity by attenuating the availability of metal to the plants. Some of the traditional methods are either extremely costly or they are simply applied to isolate contaminated site. The biology based technology like use of hyper metal accumulator plants occurring naturally or created by transgenic technology, in recent years draws great attention to remediate heavy metal contamination. Recently, applications of nanoparticle for metal remediation are also attracting great research interest due to their exceptional adsorption and mechanical properties and unique electrical property, highly chemical stability, and large specific surface area. Thus the present review deals with different management approaches to reduce level of metal contamination in soil and finally to the food chain

  16. Pollution Status of Pakistan: A Retrospective Review on Heavy Metal Contamination of Water, Soil, and Vegetables

    Directory of Open Access Journals (Sweden)

    Amir Waseem

    2014-01-01

    Full Text Available Trace heavy metals, such as arsenic, cadmium, lead, chromium, nickel, and mercury, are important environmental pollutants, particularly in areas with high anthropogenic pressure. In addition to these metals, copper, manganese, iron, and zinc are also important trace micronutrients. The presence of trace heavy metals in the atmosphere, soil, and water can cause serious problems to all organisms, and the ubiquitous bioavailability of these heavy metal can result in bioaccumulation in the food chain which especially can be highly dangerous to human health. This study reviews the heavy metal contamination in several areas of Pakistan over the past few years, particularly to assess the heavy metal contamination in water (ground water, surface water, and waste water, soil, sediments, particulate matter, and vegetables. The listed contaminations affect the drinking water quality, ecological environment, and food chain. Moreover, the toxicity induced by contaminated water, soil, and vegetables poses serious threat to human health.

  17. Heavy metals in the landscape components of the Kalmykia

    Directory of Open Access Journals (Sweden)

    L. Ch. Sangadzhieva

    2010-01-01

    Full Text Available The concentrations of heavy metals (Cr, Co, Ni, Cu, Zn, Cd, Pb in the soil of nord-west part of Precaspian low-land and their subsequent distribution over the trophic chain: plant fodder - sheep are investiqаtеd. It was revealed that the highest biogenic accumulation is characteristic of Zn and Cu at all the levels of trophic chain. An increase in the transition coefficients for the most toxic elements Pb, Cd is observed, which is an evidence of their accumulation in the higher levels of trophic chain.

  18. Human antibody responses to Schistosoma mansoni: does antigen directed, isotype restriction result in the production of blocking antibodies?

    Directory of Open Access Journals (Sweden)

    David W. Dunne

    1987-01-01

    Full Text Available After treatment young Kenyan schoolchildren are highly susceptible to reinfection with Schistosoma mansoni. Older children and adults are resistant to reinfection. There is no evidence that this age related resistance is due to a slow development of protective immunological mechanisms, rather, it appears that young children are susceptible because of the presence of blocking antibodies which decline with age, thus allowing the expression of protective responses. Correlations between antibody responses to different stages of the parasite life-cycle suggest that, in young children, antigen directed, isotype restriction of the response against cross-reactive polysaccharide egg antigens results in an ineffectual, or even blocking antibody response to the schistosomulum.

  19. Functional Role of PPARs in Ruminants: Potential Targets for Fine-Tuning Metabolism during Growth and Lactation

    Science.gov (United States)

    Chen, Shuowen; Khan, Muhammad J.; Loor, Juan J.

    2013-01-01

    Characterization and biological roles of the peroxisome proliferator-activated receptor (PPAR) isotypes are well known in monogastrics, but not in ruminants. However, a wealth of information has accumulated in little more than a decade on ruminant PPARs including isotype tissue distribution, response to synthetic and natural agonists, gene targets, and factors affecting their expression. Functional characterization demonstrated that, as in monogastrics, the PPAR isotypes control expression of genes involved in lipid metabolism, anti-inflammatory response, development, and growth. Contrary to mouse, however, the PPARγ gene network appears to controls milk fat synthesis in lactating ruminants. As in monogastrics, PPAR isotypes in ruminants are activated by long-chain fatty acids, therefore, making them ideal candidates for fine-tuning metabolism in this species via nutrients. In this regard, using information accumulated in ruminants and monogastrics, we propose a model of PPAR isotype-driven biological functions encompassing key tissues during the peripartal period in dairy cattle. PMID:23737762

  20. Poisoning of domestic animals with heavy metals

    Directory of Open Access Journals (Sweden)

    Velev Romel

    2009-01-01

    Full Text Available The term heavy metal refers to a metal that has a relatively high density and is toxic for animal and human organism at low concentrations. Heavy metals are natural components of the Earth's crust. They cannot be degraded or destroyed. To a small extent they enter animal organism via food, drinking water and air. Some heavy metals (e.g cooper, iron, chromium, zinc are essential in very low concentrations for the survival of all forms of life. These are described as essential trace elements. However, when they are present in greater quantities, like the heavy metals lead, cadmium and mercury which are already toxic in very low concentrations, they can cause metabolic anomalies or poisoning. Heavy metal poisoning of domestic animals could result, for instance, from drinking-water contamination, high ambient air concentrations near emission sources, or intake via the food chain. Heavy metals are dangerous because they tend to bioaccumulate in a biological organism over time. Manifestation of toxicity of individual heavy metals varies considerably, depending on dose and time of exposure, species, gender and environmental and nutritional factors. Large differences exist between the effects of a single exposure to a high concentration, and chronic exposures to lower doses. The aim of this work is to present the source of poisoning and toxicity of some heavy metals (lead, mercury, cadmium, thallium, arsenic, as well as new data about effects of those heavy metals on the health of domestic animals. .

  1. Impacts from Land Use Pattern on Spatial Distribution of Cultivated Soil Heavy Metal Pollution in Typical Rural-Urban Fringe of Northeast China.

    Science.gov (United States)

    Li, Wenbo; Wang, Dongyan; Wang, Qing; Liu, Shuhan; Zhu, Yuanli; Wu, Wenjun

    2017-03-22

    Under rapid urban sprawl in Northeast China, land conversions are not only encroaching on the quantity of cultivated lands, but also posing a great threat to black soil conservation and food security. This study's aim is to explore the spatial relationship between comprehensive cultivated soil heavy metal pollution and peri-urban land use patterns in the black soil region. We applied spatial lag regression to analyze the relationship between PLI (pollution load index) and influencing factors of land use by taking suburban cultivated land of Changchun Kuancheng District as an empirical case. The results indicate the following: (1) Similar spatial distribution characteristics are detected between Pb, Cu, and Zn, between Cr and Ni, and between Hg and Cd. The Yitong River catchment in the central region, and the residential community of Lanjia County in the west, are the main hotspots for eight heavy metals and PLI. Beihu Wetland Park, with a larger-area distribution of ecological land in the southeast, has low level for both heavy metal concentrations and PLI values. Spatial distribution characteristics of cultivated heavy metals are related to types of surrounding land use and industry; (2) Spatial lag regression has a better fit for PLI than the ordinary least squares regression. The regression results indicate the inverse relationship between heavy metal pollution degree and distance from long-standing residential land and surface water. Following rapid urban land expansion and a longer accumulation period, residential land sprawl is going to threaten cultivated land with heavy metal pollution in the suburban black soil region, and cultivated land irrigated with urban river water in the suburbs will have a higher tendency for heavy metal pollution.

  2. Impacts from Land Use Pattern on Spatial Distribution of Cultivated Soil Heavy Metal Pollution in Typical Rural-Urban Fringe of Northeast China

    Science.gov (United States)

    Li, Wenbo; Wang, Dongyan; Wang, Qing; Liu, Shuhan; Zhu, Yuanli; Wu, Wenjun

    2017-01-01

    Under rapid urban sprawl in Northeast China, land conversions are not only encroaching on the quantity of cultivated lands, but also posing a great threat to black soil conservation and food security. This study’s aim is to explore the spatial relationship between comprehensive cultivated soil heavy metal pollution and peri-urban land use patterns in the black soil region. We applied spatial lag regression to analyze the relationship between PLI (pollution load index) and influencing factors of land use by taking suburban cultivated land of Changchun Kuancheng District as an empirical case. The results indicate the following: (1) Similar spatial distribution characteristics are detected between Pb, Cu, and Zn, between Cr and Ni, and between Hg and Cd. The Yitong River catchment in the central region, and the residential community of Lanjia County in the west, are the main hotspots for eight heavy metals and PLI. Beihu Wetland Park, with a larger-area distribution of ecological land in the southeast, has low level for both heavy metal concentrations and PLI values. Spatial distribution characteristics of cultivated heavy metals are related to types of surrounding land use and industry; (2) Spatial lag regression has a better fit for PLI than the ordinary least squares regression. The regression results indicate the inverse relationship between heavy metal pollution degree and distance from long-standing residential land and surface water. Following rapid urban land expansion and a longer accumulation period, residential land sprawl is going to threaten cultivated land with heavy metal pollution in the suburban black soil region, and cultivated land irrigated with urban river water in the suburbs will have a higher tendency for heavy metal pollution. PMID:28327541

  3. Combination of neurofilament heavy chain and complement c3 as CSF biomarkers for ALS

    Science.gov (United States)

    Ganesalingam, Jeban; An, Jiyan; Shaw, Christopher E; Shaw, Gerry; Lacomis, David; Bowser, Robert

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease with an average survival of 3 years from symptom onset. Rapid and conclusive early diagnosis is essential if interventions with disease-modifying therapies are to be successful. Cytoskeletal modification and inflammation are known to occur during the pathogenesis of ALS. We measured levels of cytoskeletal proteins and inflammatory markers in the cerebrospinal fluid (CSF) of ALS, disease controls and healthy subjects. We determined threshold values for each protein that provided the optimal sensitivity and specificity for ALS within a training set, as determined by receiver operating characteristic (ROC) analysis. Interestingly, the optimal assay was a ratio of the levels for phosphorylated neurofilament heavy chain and complement C3 (pNFH/C3). We next applied this assay to a separate test set of CSF samples to verify our results. Overall, the predictive pNFH/C3 ratio identified ALS with 87.3% sensitivity and 94.6% specificity in a total of 71 ALS subjects, 52 disease control subjects and 40 healthy subjects. In addition, the level of CSF pNFH correlated with survival of ALS patients. We also detected increased pNFH in the plasma of ALS patients and observed a correlation between CSF and plasma pNFH levels within the same subjects. These findings support large-scale prospective biomarker studies to determine the clinical utility of diagnostic and prognostic signatures in ALS. PMID:21418221

  4. Heavy metal pollution of agricultural soils

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, S.C.

    1975-01-01

    Inputs of heavy metals to soils have increased recently and there is much concern that they may be toxic at various stages along the food chain and ultimately to man. Cobalt, copper, iron, manganese, molybdenum, zinc, chromium, nickel, cadmium and lead move from geochemical sources to plants and then to animals and man; they then are returned in various forms to soil to complete the cycle. The ways in which heavy metals may be added to soils are reviewed. They include: aerial inputs by air pollution, fertilizers, pesticides, farm slurries and sewage sludge. Possibly the source of contamination which is to have the most impact on soils used for the production of crops is sewage sludge. The fate of heavy metal added to soils is discussed in relation to form, mobility, uptake by plants, effect of soil conditions on availability to plants, and toxicity to animals. 56 references.

  5. Chains versus Independents: Newspaper and Market Characteristics.

    Science.gov (United States)

    Hale, F. Dennis

    A study examined the marketing differences between large chain newspapers and small chain and independent newspapers by analyzing differences in characteristics of the newspapers, patterns of circulation, economic and social conditions of the market, and competition from other print media. The 200 newspapers studied--113 large chain and 87 small…

  6. Equity in multiproduct supply chain network

    Directory of Open Access Journals (Sweden)

    Mina SAEE BOSTANABAD

    2013-01-01

    Full Text Available In this paper, multiproduct supply chain network is investigated with equity consideration,namely, obtaining the optimal flow pattern, in such a way that no user in the network can increasehis(her benefit with change in product’s sending path. However, each kind of products, has anindividual cost function and, at the same time, contributes to its own and other product’s cost functionin an individual way. An algorithm is developed to find optimal flow pattern for such multiproductsupply chain network.

  7. Decay of heavy and superheavy nuclei

    Indian Academy of Sciences (India)

    April 2014 physics pp. 705–715. Decay of heavy and superheavy nuclei ... study on the feasibility of observing α decay chains from the isotopes of the ... studies on 284−286115 and 288−292117 will be a guide to future experiments. .... ratio of the α decay from the ground state of the parent nucleus to the level i of the.

  8. MFI ratio estimation of ZAP-70 in B-CLL by flow cytometry can be improved by considering the isotype-matched antibody signal.

    Science.gov (United States)

    Marquez, M-E; Deglesne, P-A; Suarez, G; Romano, E

    2011-04-01

    The IgV(H) mutational status of B-cell chronic lymphocytic leukemia (B-CLL) is of prognostic value. Expression of ZAP-70 in B-CLL is a surrogate marker for IgV(H) unmutated (UM). As determination of IgV(H) mutational status involves a methodology currently unavailable for most clinical laboratories, it is important to have available a reliable technique for ZAP-70 estimation in B-CLL. Flow cytometry (FC) is a convenient technique for this purpose. However, there is still no adequate way for data analysis, which would prevent the assignment of false positive or negative expression. We have modified the currently most accepted technique, which uses the ratio of the mean fluorescent index (MFI) of B-CLL to T cells. The MFI for parallel antibody isotype staining is subtracted from the ZAP-70 MFI of both B-CLL and T cells. We validated this technique comparing the results obtained for ZAP-70 expression by FC with those obtained with quantitative PCR for the same patients. We applied the technique in a series of 53 patients. With this modification, a better correlation between ZAP-70 expression and IgV(H) UM was obtained. Thus, the MFI ratio B-CLL/T cell corrected by isotype is a reliable analysis technique to estimate ZAP-70 expression in B-CLL. © 2010 Blackwell Publishing Ltd.

  9. Determination of some heavy metals concentration in the tissues of ...

    African Journals Online (AJOL)

    Jen

    Department of Pure and Industrial Chemistry, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria ... contamination (e.g. lead pipes), high ambient air concentrations near emission ... Thus heavy metals acquired through the food chain as a.

  10. Improving the accuracy of the structure prediction of the third hypervariable loop of the heavy chains of antibodies.

    KAUST Repository

    Messih, Mario Abdel; Lepore, Rosalba; Marcatili, Paolo; Tramontano, Anna

    2014-01-01

    MOTIVATION: Antibodies are able to recognize a wide range of antigens through their complementary determining regions formed by six hypervariable loops. Predicting the 3D structure of these loops is essential for the analysis and reengineering of novel antibodies with enhanced affinity and specificity. The canonical structure model allows high accuracy prediction for five of the loops. The third loop of the heavy chain, H3, is the hardest to predict because of its diversity in structure, length and sequence composition. RESULTS: We describe a method, based on the Random Forest automatic learning technique, to select structural templates for H3 loops among a dataset of candidates. These can be used to predict the structure of the loop with a higher accuracy than that achieved by any of the presently available methods. The method also has the advantage of being extremely fast and returning a reliable estimate of the model quality. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at http://www.biocomputing.it/H3Loopred/ .

  11. Improving the accuracy of the structure prediction of the third hypervariable loop of the heavy chains of antibodies.

    KAUST Repository

    Messih, Mario Abdel

    2014-06-13

    MOTIVATION: Antibodies are able to recognize a wide range of antigens through their complementary determining regions formed by six hypervariable loops. Predicting the 3D structure of these loops is essential for the analysis and reengineering of novel antibodies with enhanced affinity and specificity. The canonical structure model allows high accuracy prediction for five of the loops. The third loop of the heavy chain, H3, is the hardest to predict because of its diversity in structure, length and sequence composition. RESULTS: We describe a method, based on the Random Forest automatic learning technique, to select structural templates for H3 loops among a dataset of candidates. These can be used to predict the structure of the loop with a higher accuracy than that achieved by any of the presently available methods. The method also has the advantage of being extremely fast and returning a reliable estimate of the model quality. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at http://www.biocomputing.it/H3Loopred/ .

  12. Heavy metals and metalloids as a cause for protein misfolding and aggregation.

    Science.gov (United States)

    Tamás, Markus J; Sharma, Sandeep K; Ibstedt, Sebastian; Jacobson, Therese; Christen, Philipp

    2014-02-25

    While the toxicity of metals and metalloids, like arsenic, cadmium, mercury, lead and chromium, is undisputed, the underlying molecular mechanisms are not entirely clear. General consensus holds that proteins are the prime targets; heavy metals interfere with the physiological activity of specific, particularly susceptible proteins, either by forming a complex with functional side chain groups or by displacing essential metal ions in metalloproteins. Recent studies have revealed an additional mode of metal action targeted at proteins in a non-native state; certain heavy metals and metalloids have been found to inhibit the in vitro refolding of chemically denatured proteins, to interfere with protein folding in vivo and to cause aggregation of nascent proteins in living cells. Apparently, unfolded proteins with motile backbone and side chains are considerably more prone to engage in stable, pluridentate metal complexes than native proteins with their well-defined 3D structure. By interfering with the folding process, heavy metal ions and metalloids profoundly affect protein homeostasis and cell viability. This review describes how heavy metals impede protein folding and promote protein aggregation, how cells regulate quality control systems to protect themselves from metal toxicity and how metals might contribute to protein misfolding disorders.

  13. Antibody isotype analysis of malaria-nematode co-infection: problems and solutions associated with cross-reactivity

    Directory of Open Access Journals (Sweden)

    Graham Andrea L

    2010-02-01

    Full Text Available Abstract Background Antibody isotype responses can be useful as indicators of immune bias during infection. In studies of parasite co-infection however, interpretation of immune bias is complicated by the occurrence of cross-reactive antibodies. To confidently attribute shifts in immune bias to the presence of a co-infecting parasite, we suggest practical approaches to account for antibody cross-reactivity. The potential for cross-reactive antibodies to influence disease outcome is also discussed. Results Utilising two murine models of malaria-helminth co-infection we analysed antibody responses of mice singly- or co-infected with Plasmodium chabaudi chabaudi and Nippostrongylus brasiliensis or Litomosoides sigmodontis. We observed cross-reactive antibody responses that recognised antigens from both pathogens irrespective of whether crude parasite antigen preparations or purified recombinant proteins were used in ELISA. These responses were not apparent in control mice. The relative strength of cross-reactive versus antigen-specific responses was determined by calculating antibody titre. In addition, we analysed antibody binding to periodate-treated antigens, to distinguish responses targeted to protein versus carbohydrate moieties. Periodate treatment affected both antigen-specific and cross-reactive responses. For example, malaria-induced cross-reactive IgG1 responses were found to target the carbohydrate component of the helminth antigen, as they were not detected following periodate treatment. Interestingly, periodate treatment of recombinant malaria antigen Merozoite Surface Protein-119 (MSP-119 resulted in increased detection of antigen-specific IgG2a responses in malaria-infected mice. This suggests that glycosylation may have been masking protein epitopes and that periodate-treated MSP-119 may more closely reflect the natural non-glycosylated antigen seen during infection. Conclusions In order to utilize antibody isotypes as a measure of

  14. Physicochemical characteristics and heavy metal levels in soil ...

    African Journals Online (AJOL)

    Distribution pattern of heavy metals in petrol stations, abattoirs, mechanic workshops and hospital incinerator sites were Mn > Zn > Pb > Cd, while for dumpsites Zn > Mn > Pb > Cd. Pollution index indicated that soil qualities varied between slightly contaminated to severely polluted status. This showed that the heavy metal ...

  15. Determination of Heavy Metal Genotoxicity and their Accumulation ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Johannesburg, P.O. Box 17011, Doornfontein 2028, Johannesburg, Republic of South Africa. ... effects that could result from exposure of fish to heavy metals in the Asa River, Ilorin, Nigeria. ... through food chains and this creates public health ...... cultivated in sewage-fed fish farms. Food Chem. Toxicol. 45. (2),. 210-215.

  16. High-throughput sequencing of natively paired antibody chains provides evidence for original antigenic sin shaping the antibody response to influenza vaccination.

    Science.gov (United States)

    Tan, Yann-Chong; Blum, Lisa K; Kongpachith, Sarah; Ju, Chia-Hsin; Cai, Xiaoyong; Lindstrom, Tamsin M; Sokolove, Jeremy; Robinson, William H

    2014-03-01

    We developed a DNA barcoding method to enable high-throughput sequencing of the cognate heavy- and light-chain pairs of the antibodies expressed by individual B cells. We used this approach to elucidate the plasmablast antibody response to influenza vaccination. We show that >75% of the rationally selected plasmablast antibodies bind and neutralize influenza, and that antibodies from clonal families, defined by sharing both heavy-chain VJ and light-chain VJ sequence usage, do so most effectively. Vaccine-induced heavy-chain VJ regions contained on average >20 nucleotide mutations as compared to their predicted germline gene sequences, and some vaccine-induced antibodies exhibited higher binding affinities for hemagglutinins derived from prior years' seasonal influenza as compared to their affinities for the immunization strains. Our results show that influenza vaccination induces the recall of memory B cells that express antibodies that previously underwent affinity maturation against prior years' seasonal influenza, suggesting that 'original antigenic sin' shapes the antibody response to influenza vaccination. Published by Elsevier Inc.

  17. Manifestation of the structure of heavy nuclei in their alpha decays

    Energy Technology Data Exchange (ETDEWEB)

    Adamian, G. G., E-mail: adamian@theor.jinr.ru; Antonenko, N. V.; Bezbakh, A. N.; Malov, L. A. [Joint Institute for Nuclear Research (Russian Federation)

    2016-11-15

    Low-lying one- and two-quasiparticle states of heavy nuclei are predicted. Alpha-decay chains, including those that proceed through isomeric states, are examined on the basis of the predicted properties of superheavy nuclei.

  18. Deletional rearrangement in the human T-cell receptor α-chain locus

    International Nuclear Information System (INIS)

    de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

    1987-01-01

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed α and β. In the course of characterizing human T-cell tumors with an immature (CD4 - , CD8 - ) surface phenotype, the authors detected a 2-kilobase α-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early α) located between the α-chain variable- and joining-region genes had been spliced to the α constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the α gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature α gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the γδ heterodimeric receptor and is deleted from mature (αβ-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (γδ-expressing) T cells and mature (αβ-expressing) T cells

  19. Endocytosis-independent function of clathrin heavy chain in the control of basal NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Man Lyang Kim

    Full Text Available BACKGROUND: Nuclear factor-κB (NF-κB is a transcription factor that regulates the transcription of genes involved in a variety of biological processes, including innate and adaptive immunity, stress responses and cell proliferation. Constitutive or excessive NF-κB activity has been associated with inflammatory disorders and higher risk of cancer. In contrast to the mechanisms controlling inducible activation, the regulation of basal NF-κB activation is not well understood. Here we test whether clathrin heavy chain (CHC contributes to the regulation of basal NF-κB activity in epithelial cells. METHODOLOGY: Using RNA interference to reduce endogenous CHC expression, we found that CHC is required to prevent constitutive activation of NF-κB and gene expression. Immunofluorescence staining showed constitutive nuclear localization of the NF-κB subunit p65 in absence of stimulation after CHC knockdown. Elevated basal p65 nuclear localization is caused by constitutive phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα through an IκB kinase α (IKKα-dependent mechanism. The role of CHC in NF-κB signaling is functionally relevant as constitutive expression of the proinflammatory chemokine interleukin-8 (IL-8, whose expression is regulated by NF-κB, was found after CHC knockdown. Disruption of clathrin-mediated endocytosis by chemical inhibition or depletion of the μ2-subunit of the endocytosis adaptor protein AP-2, and knockdown of clathrin light chain a (CHLa, failed to induce constitutive NF-κB activation and IL-8 expression, showing that CHC acts on NF-κB independently of endocytosis and CLCa. CONCLUSIONS: We conclude that CHC functions as a built-in molecular brake that ensures a tight control of basal NF-κB activation and gene expression in unstimulated cells. Furthermore, our data suggest a potential link between a defect in CHC expression and chronic inflammation disorder and cancer.

  20. Removal of round off errors in the matrix exponential method for solving the heavy nuclide chain

    International Nuclear Information System (INIS)

    Lee, Hyun Chul; Noh, Jae Man; Joo, Hyung Kook

    2005-01-01

    Many nodal codes for core simulation adopt the micro-depletion procedure for the depletion analysis. Unlike the macro-depletion procedure, the microdepletion procedure uses micro-cross sections and number densities of important nuclides to generate the macro cross section of a spatial calculational node. Therefore, it needs to solve the chain equations of the nuclides of interest to obtain their number densities. There are several methods such as the matrix exponential method (MEM) and the chain linearization method (CLM) for solving the nuclide chain equations. The former solves chain equations exactly even when the cycles that come from the alpha decay exist in the chain while the latter solves the chain approximately when the cycles exist in the chain. The former has another advantage over the latter. Many nodal codes for depletion analysis, such as MASTER, solve only the hard coded nuclide chains with the CLM. Therefore, if we want to extend the chain by adding some more nuclides to the chain, we have to modify the source code. In contrast, we can extend the chain just by modifying the input in the MEM because it is easy to implement the MEM solver for solving an arbitrary nuclide chain. In spite of these advantages of the MEM, many nodal codes adopt the chain linearization because the former has a large round off error when the flux level is very high or short lived or strong absorber nuclides exist in the chain. In this paper, we propose a new technique to remove the round off errors in the MEM and we compared the performance of the two methods

  1. Bioremediation of Toxic Heavy Metals: A Patent Review.

    Science.gov (United States)

    Verma, Neelam; Sharma, Rajni

    2017-01-01

    The global industrialization is fulfilling the demands of modern population at the cost of environmental exposure to various contaminants including heavy metals. These heavy metals affect water and soil quality. Moreover, these enter into the food chain and exhibit their lethal effects on the human health even when present at slightly higher concentration than required for normal metabolism. To the worst of their part, the heavy metals may become carcinogenic. Henceforth, the efficient removal of heavy metals is the demand of sustainable development. Remedy: Bioremediation is the 'green' imperative technique for the heavy metal removal without creating secondary metabolites in the ecosystem. The metabolic potential of several bacterial, algal, fungal as well as plant species has the efficiency to exterminate the heavy metals from the contaminated sites. Different strategies like bioaccumulation, biosorption, biotransformation, rhizofilteration, bioextraction and volatilization are employed for removal of heavy metals by the biological species. Bioremediation approach is presenting a splendid alternate for conventional expensive and inefficient methods for the heavy metal removal. The patents granted on the bioremediation of toxic heavy metals are summarized in the present manuscript which supported the applicability of bioremediation technique at commercial scale. However, the implementation of the present information and advanced research are mandatory to further explore the concealed potential of biological species to resume the originality of the environment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Structure predictions of two Bauhinia variegata lectins reveal patterns of C-terminal properties in single chain legume lectins.

    Science.gov (United States)

    Moreira, Gustavo M S G; Conceição, Fabricio R; McBride, Alan J A; Pinto, Luciano da S

    2013-01-01

    Bauhinia variegata lectins (BVL-I and BVL-II) are single chain lectins isolated from the plant Bauhinia variegata. Single chain lectins undergo post-translational processing on its N-terminal and C-terminal regions, which determines their physiological targeting, carbohydrate binding activity and pattern of quaternary association. These two lectins are isoforms, BVL-I being highly glycosylated, and thus far, it has not been possible to determine their structures. The present study used prediction and validation algorithms to elucidate the likely structures of BVL-I and -II. The program Bhageerath-H was chosen from among three different structure prediction programs due to its better overall reliability. In order to predict the C-terminal region cleavage sites, other lectins known to have this modification were analysed and three rules were created: (1) the first amino acid of the excised peptide is small or hydrophobic; (2) the cleavage occurs after an acid, polar, or hydrophobic residue, but not after a basic one; and (3) the cleavage spot is located 5-8 residues after a conserved Leu amino acid. These rules predicted that BVL-I and -II would have fifteen C-terminal residues cleaved, and this was confirmed experimentally by Edman degradation sequencing of BVL-I. Furthermore, the C-terminal analyses predicted that only BVL-II underwent α-helical folding in this region, similar to that seen in SBA and DBL. Conversely, BVL-I and -II contained four conserved regions of a GS-I association, providing evidence of a previously undescribed X4+unusual oligomerisation between the truncated BVL-I and the intact BVL-II. This is the first report on the structural analysis of lectins from Bauhinia spp. and therefore is important for the characterisation C-terminal cleavage and patterns of quaternary association of single chain lectins.

  3. Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

    1987-01-01

    The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

  4. Significant Features of Warm Season Water Vapor Flux Related to Heavy Rainfall and Draught in Japan

    Science.gov (United States)

    Nishiyama, Koji; Iseri, Yoshihiko; Jinno, Kenji

    2009-11-01

    In this study, our objective is to reveal complicated relationships between spatial water vapor inflow patterns and heavy rainfall activities in Kyushu located in the western part of Japan, using the outcomes of pattern recognition of water vapor inflow, based on the Self-Organizing Map. Consequently, it could be confirmed that water vapor inflow patterns control the distribution and the frequency of heavy rainfall depending on the direction of their fluxes and the intensity of Precipitable water. Historically serious flood disasters in South Kyushu in 1993 were characterized by high frequency of the water vapor inflow patterns linking to heavy rainfall. On the other hand, severe draught in 1994 was characterized by inactive frontal activity that do not related to heavy rainfall.

  5. Large-scale chromatin remodeling at the immunoglobulin heavy chain locus: a paradigm for multigene regulation.

    Science.gov (United States)

    Bolland, Daniel J; Wood, Andrew L; Corcoran, Anne E

    2009-01-01

    V(D)J recombination in lymphocytes is the cutting and pasting together of antigen receptor genes in cis to generate the enormous variety of coding sequences required to produce diverse antigen receptor proteins. It is the key role of the adaptive immune response, which must potentially combat millions of different foreign antigens. Most antigen receptor loci have evolved to be extremely large and contain multiple individual V, D and J genes. The immunoglobulin heavy chain (Igh) and immunoglobulin kappa light chain (Igk) loci are the largest multigene loci in the mammalian genome and V(D)J recombination is one of the most complicated genetic processes in the nucleus. The challenge for the appropriate lymphocyte is one of macro-management-to make all of the antigen receptor genes in a particular locus available for recombination at the appropriate developmental time-point. Conversely, these large loci must be kept closed in lymphocytes in which they do not normally recombine, to guard against genomic instability generated by the DNA double strand breaks inherent to the V(D)J recombination process. To manage all of these demanding criteria, V(D)J recombination is regulated at numerous levels. It is restricted to lymphocytes since the Rag genes which control the DNA double-strand break step of recombination are only expressed in these cells. Within the lymphocyte lineage, immunoglobulin recombination is restricted to B-lymphocytes and TCR recombination to T-lymphocytes by regulation of locus accessibility, which occurs at multiple levels. Accessibility of recombination signal sequences (RSSs) flanking individual V, D and J genes at the nucleosomal level is the key micro-management mechanism, which is discussed in greater detail in other chapters. This chapter will explore how the antigen receptor loci are regulated as a whole, focussing on the Igh locus as a paradigm for the mechanisms involved. Numerous recent studies have begun to unravel the complex and

  6. Surface mu heavy chain signals down-regulation of the V(D)J-recombinase machinery in the absence of surrogate light chain components.

    Science.gov (United States)

    Galler, Gunther R; Mundt, Cornelia; Parker, Mathew; Pelanda, Roberta; Mårtensson, Inga-Lill; Winkler, Thomas H

    2004-06-07

    Early B cell development is characterized by stepwise, ordered rearrangement of the immunoglobulin (Ig) heavy (HC) and light (LC) chain genes. Only one of the two alleles of these genes is used to produce a receptor, a phenomenon referred to as allelic exclusion. It has been suggested that pre-B cell receptor (pre-BCR) signals are responsible for down-regulation of the VDJH-recombinase machinery (Rag1, Rag2, and terminal deoxynucleotidyl transferase [TdT]), thereby preventing further rearrangement on the second HC allele. Using a mouse model, we show that expression of an inducible muHC transgene in Rag2-/- pro-B cells induces down-regulation of the following: (a) TdT protein, (b) a transgenic green fluorescent protein reporter reflecting endogenous Rag2 expression, and (c) Rag1 primary transcripts. Similar effects were also observed in the absence of surrogate LC (SLC) components, but not in the absence of the signaling subunit Ig-alpha. Furthermore, in wild-type mice and in mice lacking either lambda5, VpreB1/2, or the entire SLC, the TdT protein is down-regulated in muHC+LC- pre-B cells. Surprisingly, muHC without LC is expressed on the surface of pro-/pre-B cells from lambda5-/-, VpreB1-/-VpreB2-/-, and SLC-/- mice. Thus, SLC or LC is not required for muHC cell surface expression and signaling in these cells. Therefore, these findings offer an explanation for the occurrence of HC allelic exclusion in mice lacking SLC components.

  7. Proceedings of the heavy oil Latin America congress 2011

    International Nuclear Information System (INIS)

    2011-01-01

    This conference brought experts together to explore the challenges faced and opportunities available in the dynamic emerging market for heavy oil which Latin America offers. The conference was attended by over 700 delegates from around the world representing official and private agencies, Latin American governments, national oil companies and service companies in heavy oil producing countries. These participants were given the opportunity to learn about the entire value chain of Latin America's heavy oil industry, with emphasis on balancing challenging environmental and social issues with operational best practices, and they also the opportunity to share their knowledge and expertise with their peers. 17 of the 29 papers presented during this conference have been catalogued separately for inclusion in this database.

  8. Resistance change effect in SrTiO3/Si (001) isotype heterojunction

    Science.gov (United States)

    Huang, Xiushi; Gao, Zhaomeng; Li, Pei; Wang, Longfei; Liu, Xiansheng; Zhang, Weifeng; Guo, Haizhong

    2018-02-01

    Resistance switching has been observed in double and multi-layer structures of ferroelectric films. The higher switching ratio opens up a vast path for emerging ferroelectric semiconductor devices. An n-n+ isotype heterojunction has been fabricated by depositing an oxide SrTiO3 layer on a conventional n-type Si (001) substrate (SrTiO3/Si) by pulsed laser disposition. Rectification and resistive switching behaviors in the n-n+ SrTiO3/Si heterojunction were observed by a conductive atomic force microscopy, and the n-n+ SrTiO3/Si heterojunction exhibits excellent endurance and retention characteristics. The possible mechanism was proposed based on the band structure of the n-n+ SrTiO3/Si heterojunction, and the observed electrical behaviors could be attributed to the modulation effect of the electric field reversal on the width of accumulation and the depletion region, as well as the height of potential of the n-n+ junction formed at the STO/Si interface. Moreover, oxygen vacancies are also indicated to play a crucial role in causing insulator to semiconductor transition. These results open the way to potential application in future microelectronic devices based on perovskite oxide layers on conventional semiconductors.

  9. Cost burden and treatment patterns associated with management of heavy menstrual bleeding.

    Science.gov (United States)

    Jensen, Jeffrey T; Lefebvre, Patrick; Laliberté, François; Sarda, Sujata P; Law, Amy; Pocoski, Jennifer; Duh, Mei Sheng

    2012-05-01

    This study evaluated the healthcare resource use, work productivity loss, costs, and treatment patterns associated with newly diagnosed idiopathic heavy menstrual bleeding (HMB) using a large employer database. Medical and pharmacy claims (1998-2009) from 55 self-insured U.S. companies were analyzed. Women aged 18-52 years with ≥2 HMB claims (ICD-9 626.2, 627.0) and continuously enrolled for ≥6 months before the first claim were matched 1:1 with controls. Exclusion criteria were cancer, pregnancy, and infertility; HMB-related uterine conditions; endometrial ablation; hysterectomy; anticoagulant medications; and other known HMB causes. All-cause healthcare resource use and costs were compared between the HMB and control cohorts using statistical methods accounting for matched study design. Treatment patterns were examined for HMB subjects. HMB and control cohorts (n=29,842 in both) were matched and balanced in baseline characteristics and costs. During follow-up, HMB subjects had significantly higher all-cause resource use than did control subjects: hospitalization incidence rate ratio (IRR)=2.70 (95% confidence interval [CI] 2.62-2.79); emergency room visits IRR=1.35 (95% CI 1.31-1.38); outpatient visits IRR=1.29 (95% CI 1.29-1.30). Average annualized all-cause costs were also higher for HMB subjects than controls (mean difference $2,607, pCosts associated with HMB claims represented 50% ($1,313) of the all-cause cost difference. Of HMB subjects, 63.2% underwent surgical treatment as initial therapy. In this large matched-cohort study, an idiopathic diagnosis of HMB was associated with high rates of surgical intervention and increased healthcare resource use and costs.

  10. Bioaccumulation of heavy metals by Dyera costulata cultivated in ...

    African Journals Online (AJOL)

    High concentrations of heavy metals are harmful to plants, animals and humans and their potential accumulation in human tissues and bio-magnification through the food chain cause serious health hazards. An experiment was conducted in the glasshouse to evaluate the potential of Dyera costulata as a bioaccumulator to ...

  11. Mutation induction by heavy ions

    Science.gov (United States)

    Kiefer, J.; Stoll, U.; Schneider, E.

    1994-10-01

    Mutation induction by heavy ions is compared in yeast and mammalian cells. Since mutants can only be recovered in survivors the influence of inactivation cross sections has to be taken into account. It is shown that both the size of the sensitive cellular site as well as track structure play an important role. Another parameter which influences the probability of mutation induction is repair: Contrary to naive assumptions primary radiation damage does not directly lead to mutations but requires modification to reconstitute the genetic machinery so that mutants can survive. The molecular structure of mutations was analyzed after exposure to deuterons by amplification with the aid of polymerase chain reaction. The results-although preliminary-demonstrate that even with densely ionizing particles a large fraction does not carry big deletions which suggests that point mutations may also be induced by heavy ions.

  12. Differences in mitochondrial gene expression profiles, enzyme activities and myosin heavy chain types in yak versus bovine skeletal muscles.

    Science.gov (United States)

    Lin, Y Q; Xu, Y O; Yue, Y; Jin, S Y; Qu, Y; Dong, F; Li, Y P; Zheng, Y C

    2012-08-29

    Hypoxia can affect energy metabolism. We examined gene expression and enzyme activity related to mitochondrial energy metabolism, as well as myosin heavy chain (MyHC) types in yaks (Bos grunniens) living at high altitudes. Real-time quantitative PCR assays indicated that the yak has significantly lower levels of carnitine palmitoyltransferase (CPT) mRNA in the biceps femoris and lower levels of uncoupling protein 3 (UCP3) mRNA in both biceps femoris and longissimus dorsi than in Yellow cattle. No significant differences between yak and Yellow cattle were observed in the activities of mitochondrial β-hydroxyacyl-CoA dehydrogenase, isocitrate dehydrogenase and cytochrome oxidase in the same muscles. Semi-quantitative RT-PCR analysis showed that the MyHC 1 mRNA levels in yak biceps femoris was lower than in Yellow cattle. We conclude that the yak has significantly lower mRNA levels of CPT, UCP3, and MyHC 1 in biceps femoris than in Yellow cattle, suggesting that the yak biceps femoris has lower fatty acid oxidation capacity and greater glycolytic metabolic potential.

  13. Drinking Level, Drinking Pattern, and Twenty-Year Total Mortality Among Late-Life Drinkers.

    Science.gov (United States)

    Holahan, Charles J; Schutte, Kathleen K; Brennan, Penny L; Holahan, Carole K; Moos, Rudolf H

    2015-07-01

    Research on moderate drinking has focused on the average level of drinking. Recently, however, investigators have begun to consider the role of the pattern of drinking, particularly heavy episodic drinking, in mortality. The present study examined the combined roles of average drinking level (moderate vs. high) and drinking pattern (regular vs. heavy episodic) in 20-year total mortality among late-life drinkers. The sample comprised 1,121 adults ages 55-65 years. Alcohol consumption was assessed at baseline, and total mortality was indexed across 20 years. We used multiple logistic regression analyses controlling for a broad set of sociodemographic, behavioral, and health status covariates. Among individuals whose high level of drinking placed them at risk, a heavy episodic drinking pattern did not increase mortality odds compared with a regular drinking pattern. Conversely, among individuals who engage in a moderate level of drinking, prior findings showed that a heavy episodic drinking pattern did increase mortality risk compared with a regular drinking pattern. Correspondingly, a high compared with a moderate drinking level increased mortality risk among individuals maintaining a regular drinking pattern, but not among individuals engaging in a heavy episodic drinking pattern, whose pattern of consumption had already placed them at risk. Findings highlight that low-risk drinking requires that older adults drink low to moderate average levels of alcohol and avoid heavy episodic drinking. Heavy episodic drinking is frequent among late-middle-aged and older adults and needs to be addressed along with average consumption in understanding the health risks of late-life drinkers.

  14. Cell surface engineering of microorganisms towards adsorption of heavy metals.

    Science.gov (United States)

    Li, Peng-Song; Tao, Hu-Chun

    2015-06-01

    Heavy metal contamination has become a worldwide environmental concern due to its toxicity, non-degradability and food-chain bioaccumulation. Conventional physical and chemical treatment methods for heavy metal removal have disadvantages such as cost-intensiveness, incomplete removal, secondary pollution and the lack of metal specificity. Microbial biomass-based biosorption is one of the approaches gaining increasing attention because it is effective, cheap, and environmental friendly and can work well at low concentrations. To enhance the adsorption properties of microbial cells to heavy metal ions, the cell surface display of various metal-binding proteins/peptides have been performed using a cell surface engineering approach. The surface engineering of Gram-negative bacteria, Gram-positive bacteria and yeast towards the adsorption of heavy metals are reviewed in this article. The problems and future perspectives of this technology are discussed.

  15. JIT supply chain; an investigation through general system theory

    Directory of Open Access Journals (Sweden)

    O P Mishra

    2013-03-01

    Full Text Available This paper explains theoretical approach of the four theories of General system Theory (GST developed by Yourdon (1989 [Yourdon, E. (1989. Modern Structured Analysis. Yourdon Press, Prentice-Hall International, Englewood Cliffs, New Jersey. Senge] while applying it in information technology and subsequently used by caddy (2007 [Caddy I.N., & Helou, M.M. (2007. Supply chains and their management: Application of general systems theory. Journal of Retailing and Consumer Services, 14, 319–327.] in field of supply chain and management. JIT philosophy in core activities of supply chain i.e. procurement, production processes, and logistics are discussed through general system theory. The growing structure of the supply chain poses the implication restrictions and requires a heavy support system, many times a compromise is done while implementing JIT. The study would be useful to understand the general trends generated naturally regarding the adoption of the JIT philosophy in the supply chain.

  16. Dynein light chain family in Tetrahymena thermophila.

    Science.gov (United States)

    Wilkes, David E; Rajagopalan, Vidyalakshmi; Chan, Clarence W C; Kniazeva, Ekaterina; Wiedeman, Alice E; Asai, David J

    2007-02-01

    Dyneins are large protein complexes that produce directed movement on microtubules. In situ, dyneins comprise combinations of heavy, intermediate, light-intermediate, and light chains. The light chains regulate the locations and activities of dyneins but their functions are not completely understood. We have searched the recently sequenced Tetrahymena thermophila macronuclear genome to describe the entire family of dynein light chains expressed in this organism. We identified fourteen genes encoding putative dynein light chains and seven genes encoding light chain-like proteins. RNA-directed PCR revealed that all 21 genes were expressed. Quantitative real time reverse transcription PCR showed that many of these genes were upregulated after deciliation, indicating that these proteins are present in cilia. Using the nomenclature developed in Chlamydomonas, Tetrahymena expresses two isoforms each of LC2, LC4, LC7, and Tctex1, three isoforms of p28, and six LC8/LC8-like isoforms. Tetrahymena also expresses two LC3-like genes. No Tetrahymena orthologue was found for Chlamydomonas LC5 or LC6. This study provides a complete description of the different genes and isoforms of the dynein light chains that are expressed in Tetrahymena, a model organism in which the targeted manipulation of genes is straightforward. (c) 2006 Wiley-Liss, Inc.

  17. Ecotoxic heavy metals transformation by bacteria and fungi in aquatic ecosystem.

    Science.gov (United States)

    Chaturvedi, Amiy Dutt; Pal, Dharm; Penta, Santhosh; Kumar, Awanish

    2015-10-01

    Water is the most important and vital molecule of our planet and covers 75% of earth surface. But it is getting polluted due to high industrial growth. The heavy metals produced by industrial activities are recurrently added to it and considered as dangerous pollutants. Increasing concentration of toxic heavy metals (Pb(2+), Cd(2+), Hg(2+), Ni(2+)) in water is a severe threat for human. Heavy metal contaminated water is highly carcinogenic and poisonous at even relatively low concentrations. When they discharged in water bodies, they dissolve in the water and are distributed in the food chain. Bacteria and fungi are efficient microbes that frequently transform heavy metals and remove toxicity. The application of bacteria and fungi may offer cost benefit in water treatment plants for heavy metal transformation and directly related to public health and environmental safety issues. The heavy metals transformation rate in water is also dependent on the enzymatic capability of microorganisms. By transforming toxic heavy metals microbes sustain aquatic and terrestrial life. Therefore the application of microbiological biomass for heavy metal transformation and removal from aquatic ecosystem is highly significant and striking. This paper reviews the microbial transformation of heavy metal, microbe metal interaction and different approaches for microbial heavy metal remediation from water bodies.

  18. Bone lesions in Chinese POEMS syndrome patients: imaging characteristics and clinical implications.

    Science.gov (United States)

    Wang, Fengdan; Huang, Xufei; Zhang, Yan; Li, Jian; Zhou, Daobin; Jin, Zhengyu

    2016-01-01

    Objective. Bone lesion is crucial for diagnosing and management of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin change (POEMS) syndrome, a rare plasma cell disorder. This study is to compare the effectiveness of X-ray skeletal survey (SS) and computed tomography (CT) for detecting bone lesions in Chinese POEMS syndrome patients, and to investigate the relationship between bone lesion features and serum markers. Methods. SS and chest/abdomen/pelvic CT images of 38 Chinese patients (26 males, 12 females, aged 21-70 years) with POEMS syndrome recruited at our medical center between January 2013 and January 2015 were retrospectively analyzed. Bone lesions identified by CT were further categorized according to the size (10 mm) and appearance (osteosclerotic, lytic, mixed). The percentage of plasma cells in bone marrow smears, type of immunoglobulin, platelet (Plt), and levels of serum bone metabolic markers and inflammatory factors including alkaline phosphatase (ALP), calcium, phosphate, parathyroid hormone (PTH), beta-isomerized C-telopeptide (β-CTx), vascular endothelial growth factor (VEGF), and interleukin (IL)-6 levels were also recorded. Results. Of the 38 POEMS syndrome patients, the immunoglobulin heavy chain isotypes were IgA in 25 patients (65.8%; 25/38) and IgG in 13 patients (34.2%; 13/38), and the light chain isotypes were λ in 35 patients (92.1%; 35/38) and κ in 3 patients (7.9%; 3/38). There were 23 patients with thrombocytosis. More patients with bone lesions were detected by CT than by SS (97.4% vs. 86.8%). The most commonly affected location was the pelvis (89.5%), followed by the spine, clavicle/scapula/sternum/ribs, skull, and long bones. Of the 38 POEMS syndrome patients, 35 (94.6%) had osteosclerotic and 32 (86.5%) had mixed lesions. Osteosclerotic lesions were typically scattered, variable in size, and plaque-like, whereas mixed lesions were pouch-shaped or soup bubble-like with a clear sclerotic margin and were

  19. Characterisation of myosin heavy chain gene variants in the fast and slow muscle fibres of gammarid amphipods.

    Science.gov (United States)

    Whiteley, N M; Magnay, J L; McCleary, S J; Nia, S Khazraee; El Haj, A J; Rock, J

    2010-10-01

    Recent molecular work has revealed a large diversity of myosin heavy chain (MyHC) gene variants in the abdominal musculature of gammarid amphipods. An unusual truncated MyHC transcript from the loop 1 region (Variant A(3)) was consistently observed in multiple species and populations. The current study aimed to determine whether this MyHC variant is specific to a particular muscle fibre type, as a change in net charge to the loop 1 region of Variant A(3) could be functionally significant. The localisation of different fibre types within the abdominal musculature of several gammarid species revealed that the deep flexor and extensor muscles are fast-twitch muscle fibres. The dorsal superficial muscles were identified as slow fibres and the muscles extrinsic to the pleopods were identified as intermediate fibres. Amplification of loop 1 region mRNA from isolated superficial extensor and deep flexor muscles, and subsequent liquid chromatography and sequence analysis revealed that Variant A(3) was the primary MyHC variant in slow muscles, and the conserved A(1) sequence was the primary variant in fast muscles. The specific role of Variant A(3) in the slow muscles remains to be investigated. 2010 Elsevier Inc. All rights reserved.

  20. Bioaccumulation of heavy metals in water, sediment and fish ...

    African Journals Online (AJOL)

    Dr. Hnay

    2012-09-25

    Sep 25, 2012 ... these pollutants is the chemical substances that stay longer and become toxic in water columns. Within them, heavy metals have positive effects on the vital activities of several organisms and impairment in food chain by affecting biological activities of the living organisms in ecosystem (Gundogu and Erden ...

  1. Analysis of Some Heavy Metals in Grass ( Paspalum Orbiculare ...

    African Journals Online (AJOL)

    The increased deposition of trace metals from vehicle exhausts on plants has raised concerns about the risks of the quality of food consumed by humans since the heavy metals emitted through the exhaust by vehicles can enter food chain through deposition on grass grazed by animals. Grass (Paspalum Orbiculare) and ...

  2. Methylation patterns in sentinel genes in peripheral blood cells of heavy smokers: Influence of cruciferous vegetables in an intervention study.

    Science.gov (United States)

    Scoccianti, Chiara; Ricceri, Fulvio; Ferrari, Pietro; Cuenin, Cyrille; Sacerdote, Carlotta; Polidoro, Silvia; Jenab, Mazda; Hainaut, Pierre; Vineis, Paolo; Herceg, Zdenko

    2011-09-01

    Changes in DNA methylation patterns are a hallmark of tobacco-induced carcinogenesis. We have conducted a randomized 4-week intervention trial to investigate the effects of three dietary regimens to modify DNA methylation patterns in peripheral white blood cells of heavy smokers. A group of 88 smokers were randomly assigned to and distributed among three diets, including (1) normal isocaloric diet (balanced in fruits and vegetables), according to international guidelines; (2) a diet enriched in flavonoids and isothiocyanates (particularly cruciferous vegetables); (3) a regimen consisting of diet 1 supplemented with flavonoids (green tea and soy products). Methylation patterns were analyzed by pyrosequencing in LINE1 (Long Interspersed DNA Elements), RASSF1A, ARF and CDKN2a (tumor suppressor genes), MLH1 (mismatch DNA repair) and MTHFR (folate metabolism). Three distinct patterns of methylation were observed. In LINE1, methylation showed a small but reproducible increase with all three regimens. MTHFR was constitutively methylated with no significant modulation by diets. The four other loci showed low basal levels of methylation with no substantial change after intervention. These data suggest that the isocaloric diet may stabilize global epigenetic (LINE1 DNA methylation) patterns in peripheral white blood cells but does not provide evidence for methylation changes in specific genes associated with this short-term dietary intervention.

  3. Supply chain management models, applications, and research directions

    CERN Document Server

    Pardalos, Panos; Romeijn, H

    2005-01-01

    This work brings together some of the most up to date research in the application of operations research and mathematical modeling te- niques to problems arising in supply chain management and e-Commerce. While research in the broad area of supply chain management enc- passes a wide range of topics and methodologies, we believe this book provides a good snapshot of current quantitative modeling approaches, issues, and trends within the field. Each chapter is a self-contained study of a timely and relevant research problem in supply chain mana- ment. The individual works place a heavy emphasis on the application of modeling techniques to real world management problems. In many instances, the actual results from applying these techniques in practice are highlighted. In addition, each chapter provides important mana- rial insights that apply to general supply chain management practice. The book is divided into three parts. The first part contains ch- ters that address the new and rapidly growing role of the inte...

  4. Network analysis of pig movements: Loyalty patterns and contact chains of different holding types in Denmark.

    Science.gov (United States)

    Schulz, Jana; Boklund, Anette; Halasa, Tariq H B; Toft, Nils; Lentz, Hartmut H K

    2017-01-01

    Understanding animal movements is an important factor for the development of meaningful surveillance and control programs, but also for the development of disease spread models. We analysed the Danish pig movement network using static and temporal network analysis tools to provide deeper insight in the connection between holdings dealing with pigs, such as breeding and multiplier herds, production herds, slaughterhouses or traders. Pig movements, which occurred between 1st January 2006 and 31st December 2015 in Denmark, were summarized to investigate temporal trends such as the number of active holdings, the number of registered movements and the number of pigs moved. To identify holdings and holding types with potentially higher risk for introduction or spread of diseases via pig movements, we determined loyalty patterns, annual network components and contact chains for the 24 registered holding types. The total number of active holdings as well as the number of pig movements decreased during the study period while the holding sizes increased. Around 60-90% of connections between two pig holdings were present in two consecutive years and around one third of the connections persisted within the considered time period. Weaner herds showed the highest level of in-loyalty, whereas we observed an intermediate level of in-loyalty for all breeding sites and for production herds. Boar stations, production herds and trade herds showed a high level of out-loyalty. Production herds constituted the highest proportion of holdings in the largest strongly connected component. All production sites showed low levels of in-going contact chains and we observed a high level of out-going contact chain for breeding and multiplier herds. Except for livestock auctions, all transit sites also showed low levels of out-going contact chains. Our results reflect the pyramidal structure of the underlying network. Based on the considered disease, the time frame for the calculation of network

  5. Network analysis of pig movements: Loyalty patterns and contact chains of different holding types in Denmark.

    Directory of Open Access Journals (Sweden)

    Jana Schulz

    Full Text Available Understanding animal movements is an important factor for the development of meaningful surveillance and control programs, but also for the development of disease spread models. We analysed the Danish pig movement network using static and temporal network analysis tools to provide deeper insight in the connection between holdings dealing with pigs, such as breeding and multiplier herds, production herds, slaughterhouses or traders. Pig movements, which occurred between 1st January 2006 and 31st December 2015 in Denmark, were summarized to investigate temporal trends such as the number of active holdings, the number of registered movements and the number of pigs moved. To identify holdings and holding types with potentially higher risk for introduction or spread of diseases via pig movements, we determined loyalty patterns, annual network components and contact chains for the 24 registered holding types. The total number of active holdings as well as the number of pig movements decreased during the study period while the holding sizes increased. Around 60-90% of connections between two pig holdings were present in two consecutive years and around one third of the connections persisted within the considered time period. Weaner herds showed the highest level of in-loyalty, whereas we observed an intermediate level of in-loyalty for all breeding sites and for production herds. Boar stations, production herds and trade herds showed a high level of out-loyalty. Production herds constituted the highest proportion of holdings in the largest strongly connected component. All production sites showed low levels of in-going contact chains and we observed a high level of out-going contact chain for breeding and multiplier herds. Except for livestock auctions, all transit sites also showed low levels of out-going contact chains. Our results reflect the pyramidal structure of the underlying network. Based on the considered disease, the time frame for the

  6. Heavy oil in Saskatchewan: Building on strengths

    International Nuclear Information System (INIS)

    1994-02-01

    Saskatchewan has reserves of 17.6 billion bbl of heavy oil located in the west-central part of the province. The first oil well was drilled in 1945 and production of heavy oil has increased gradually, reaching 79,000 bbl/d in 1992. In recent years, the production pattern has not matched trends in investment; since 1982/83, the relative proportion of heavy oil drilling has declined significantly. A study is presented which analyzes trends in heavy oil investment, production, economics, and markets, with a focus on determining the causes for lack of investment in the heavy oil sector and evaluating the opportunities and constraints for long-term sustainability of this industry. Industry background is provided, with presentation of the key resource characteristics, reserve potential, and production and investment trends. Markets both in Canada and the USA are analyzed in detail, possible future trends are suggested. The effect of development of refinery capacity on heavy oil developments is examined. The logistics of shipping heavy oil to markets are detailed. The economics of Saskatchewan heavy oil production are established, taking into account all relevant cost components including taxes, royalties, and netbacks to producers. Issues of relevance affecting the heavy oil industry are discussed, including the need for environmental safeguards. 25 figs., 24 tabs

  7. Real Time RT-PCR with a Newly Designed Set of Promers Confirmed the Presence of 2b and 2x/d Myosim Heavy Chain mRNAs in the Rat Slow Soleus Muscle

    Czech Academy of Sciences Publication Activity Database

    Žurmanová, Jitka; Půta, F.; Stopková, R.; Soukup, Tomáš

    2008-01-01

    Roč. 57, č. 6 (2008), s. 973-978 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA305/06/1115; GA ČR(CZ) GA304/08/0256 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat slow soleus muscle * myosin heavy chain isoforms * real time RT-PCR Subject RIV: ED - Physiology Impact factor: 1.653, year: 2008

  8. Microbes in Heavy Metal Remediation: A Review on Current Trends and Patents.

    Science.gov (United States)

    Mishra, Geetesh Kumar

    2017-01-01

    Heavy metal pollution in the environmental samples like soil, water and runoff water is a worldwide problem. Such contamination of environmental matrices by the heavy metals accumulates due to various activities involving human driven sources and industries, although agriculture and sewage disposal are the largest source for the heavy metal contamination. Disposal of heavy metals or waste products containing heavy metals in the environment postures a trivial threat to public safety and health. Heavy metals are persistence and they can also cause biomagnifications and accumulate in food chain. Microbial bioremediation of heavy metal is emerging as an effective technique. Microbial bioremediation is a highly efficient environmental friendly procedure which also reduces the cost of cleanup process associated with heavy metal contamination. New methods for removal of heavy metals from the environmental samples are under development and most recent advancements have been made in exploring the knowledge of metal-microbes interactions and its use for heavy metal remediation. This review paper will focus on the microbial bioremediation process and highlight some of the newly developed patented methods for microbial bioremediation of the heavy metals from the environmental samples using microbial populations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Data on heavy metals and selected anions in the Persian popular herbal distillates

    OpenAIRE

    Keshtkar, Mozhgan; Dobaradaran, Sina; Soleimani, Farshid; Karbasdehi, Vahid Noroozi; Mohammadi, Mohammad Javad; Mirahmadi, Roghayeh; Ghasemi, Fatemeh Faraji

    2016-01-01

    In this data article, we determined the concentration levels of heavy metals including Pb, Co, Cd, Mn, Mg, Fe and Cu as well as selected anions including NO3− , NO2−, PO4−3 and SO4−2 in the most used and popular herbal distillates in Iran. It is well known that heavy metals may pose a serious health hazard due to their bioaccumulation throughout the trophic chain (“Heavy metals (Cd, Cu, Ni and Pb) content in two fish species of Persian Gulf in Bushehr Port, Iran” (Dobaradaran et al., 2013) [1...

  10. [Distribution patterns and pollution assessments of heavy metals in the Spartina alterniflora salt-marsh wetland of Rudong, Jiangsu province].

    Science.gov (United States)

    Zhang, Long-Hui; Du, Yong-Fen; Wang, Dan-Dan; Gao, Shu; Gao, Wen-Hua

    2014-06-01

    To understand the ecological impact of Spartina alterniflora on the coastal wetland environment, field survey was carried out in July, 2010, over the intertidal areas of Rudong coast, Jiangsu province; sediment samples were collected from a series of stations with different conditions of vegetation cover and S. alterniflora growth. The contents of eight heavy metals, together with sediment composition and total organic carbon were analyzed to reveal the distribution patterns of the heavy metals. Environmental quality status was evaluated using both the index of geoaccumulation (I(geo)) and the index of the Håkanson ecological risk. The analytical results showed that the average contents of Pb, Cd, As, Hg, Cr, Cu, Ni and Zn were below the standard for the Category I sediment quality, among which Cd, Hg, Ni and Zn exceeded the sediment background value of the region. On the whole, the contents of eight heavy metals in vegetation areas were higher than those associated with the adjacent bare flat areas. These data sets indicate a non-polluted condition in term of I(geo) estimation; however, a critical state of low to moderate degrees of pollution and a low level of risk were deduced according to the index of the Håkanson potential ecological risk. Both indices suggested that the pollution level of Hg and Cd were the highest among the eight metals measured. Along the transection from seaward to landward, the contents of As, Cu and Hg, their indices of I(geo) and Håkanson ecological risk all showed an increasing tread, in accordance with the condition of vegetation cover. Along the coastline with S. alterniflora being distributed in patchiness, all metal contents and their ecological risk level values for the marshes were higher than those for the unvegetated sediments nearby; moreover, except for Hg, other seven metals exhibited relatively low values than those in the shore-normal section with a better S. alterniflora growth. These findings indicate that S

  11. Landscaping the structures of GAVI country vaccine supply chains and testing the effects of radical redesign.

    Science.gov (United States)

    Lee, Bruce Y; Connor, Diana L; Wateska, Angela R; Norman, Bryan A; Rajgopal, Jayant; Cakouros, Brigid E; Chen, Sheng-I; Claypool, Erin G; Haidari, Leila A; Karir, Veena; Leonard, Jim; Mueller, Leslie E; Paul, Proma; Schmitz, Michelle M; Welling, Joel S; Weng, Yu-Ting; Brown, Shawn T

    2015-08-26

    Many of the world's vaccine supply chains do not adequately provide vaccines, prompting several questions: how are vaccine supply chains currently structured, are these structures closely tailored to individual countries, and should these supply chains be radically redesigned? We segmented the 57 GAVI-eligible countries' vaccine supply chains based on their structure/morphology, analyzed whether these segments correlated with differences in country characteristics, and then utilized HERMES to develop a detailed simulation model of three sample countries' supply chains and explore the cost and impact of various alternative structures. The majority of supply chains (34 of 57) consist of four levels, despite serving a wide diversity of geographical areas and population sizes. These four-level supply chains loosely fall into three clusters [(1) 18 countries relatively more bottom-heavy, i.e., many more storage locations lower in the supply chain, (2) seven with relatively more storage locations in both top and lower levels, and (3) nine comparatively more top-heavy] which do not correlate closely with any of the country characteristics considered. For all three cluster types, our HERMES modeling found that simplified systems (a central location shipping directly to immunization locations with a limited number of Hubs in between) resulted in lower operating costs. A standard four-tier design template may have been followed for most countries and raises the possibility that simpler and more tailored designs may be warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Heavy Traffic Feasible Hybrid Intracycle and Cyclic Sleep for Power Saving in 10G-EPON

    Directory of Open Access Journals (Sweden)

    Xintian Hu

    2014-01-01

    Full Text Available Energy consumption in optical access networks costs carriers substantial operational expense (OPEX every year and is one of contributing factors for the global warming. To reduce energy consumption in the 10-gigabit Ethernet passive optical network (10G-EPON, a hybrid intracycle and cyclic sleep mechanism is proposed in this paper. Under heavy traffic load, optical network units (ONUs can utilize short idle slots within each scheduling cycle to enter intracycle sleep without postponing data transmission. In this way, energy conservation is achieved even under heavy traffic load with quality of service (QoS guarantee. Under light traffic load, ONUs perform long cyclic sleep for several scheduling cycles. The adoption of cyclic sleep instead of intracycle sleep under light traffic load can reduce unnecessary frequent transitions between sleep and full active work caused by using intracycle sleep. Further, the Markov chain of the proposed mechanism is established. The performances of the proposed mechanism and existing approaches are analyzed quantitatively based on the chain. For the proposed mechanism, power saving ability with QoS guarantee even under heavy traffic and better power saving performance than existing approaches are verified by the quantitative analysis. Moreover, simulations validate the above conclusions based on the chain.

  13. HEAVY METAL AND ANTIBIOTIC RESISTANCE BACTERIA IN MARINE SEDIMENT OF PAHANG COASTAL WATER

    Directory of Open Access Journals (Sweden)

    Zaima Azira

    2018-01-01

    Full Text Available The presence of heavy metal and antibiotic resistance bacteria in the marine sediment may indicate heavy metal pollution and antibiotic abuse present in the environment. In this study, a total of 89 bacteria isolated from sediment collected in Teluk Chempedak and Pantai Batu Hitam of Pahang coastal water underwent heavy metal resistance test against Chromium, Cadmium, Nickel, Copper and Cobalt. Previously, these isolates were found to exhibit antibiotic resistance capabilities to at least 5 antibiotics tested. Heavy metal resistance pattern for isolates from Teluk Chempedak was in the form of Cr > Ni >Co >Cd = Cu while for isolates from Pantai Batu Hitam showed a pattern of Cr = Ni >Co >Cu >Cd. Further investigation on the identity of selected isolates that exhibited both antibiotic and heavy metals resistance capabilities using 16S rRNA gene sequences revealed isolates with closest similarities to Staphylococcus saprophyticus and Brevundimonas vesicularis..

  14. Altered phenotypic expression of immunoglobulin heavy-chain variable-region (VH) genes in Alicia rabbits probably reflects a small deletion in the VH genes closest to the joining region.

    Science.gov (United States)

    Allegrucci, M; Newman, B A; Young-Cooper, G O; Alexander, C B; Meier, D; Kelus, A S; Mage, R G

    1990-07-01

    Rabbits of the Alicia strain have a mutation (ali) that segregates with the immunoglobulin heavy-chain (lgh) locus and has a cis effect upon the expression of heavy-chain variable-region (VH) genes encoding the a2 allotype. In heterozygous a1/ali or a3/ali rabbits, serum immunoglobulins are almost entirely the products of the normal a1 or a3 allele and only traces of a2 immunoglobulin are detectable. Adult homozygous ali/ali rabbits likewise have normal immunoglobulin levels resulting from increased production of a-negative immunoglobulins and some residual ability to produce the a2 allotype. By contrast, the majority of the immunoglobulins of wild-type a2 rabbits are a2-positive and only a small percentage are a-negative. Genomic DNAs from homozygous mutant and wild-type animals were indistinguishable by Southern analyses using a variety of restriction enzyme digests and lgh probes. However, when digests with infrequently cutting enzymes were analyzed by transverse alternating-field electrophoresis, the ali DNA fragments were 10-15 kilobases smaller than the wild type. These fragments hybridized to probes both for VH and for a region of DNA a few kilobases downstream of the VH genes nearest the joining region. We suggest that this relatively small deletion affects a segment containing 3' VH genes with important regulatory functions, the loss of which leads to the ali phenotype. These results, and the fact that the 3' VH genes rearrange early in B-cell development, indicate that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression.

  15. Pollution load index for heavy metals in Mian-Ab plain soil, Khuzestan, Iran

    OpenAIRE

    Jorfi, Sahand; Maleki, Rohangiz; Jaafarzadeh, Neemat; Ahmadi, Mehdi

    2017-01-01

    Soil pollution by heavy metals is a major concern in agricultural area. Potential impact of heavy metals in agricultural soil on human health by accumulating in food chain demonstrated elsewhere.In this regard Mian-Ab plain as a major agricultural site of Khuzestan province considered for Arsenic, cadmium and lead concentration as the main potential toxic pollutants in soil. 50 topsoil samples were collected and analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Also Contamina...

  16. Levels and distribution patterns of short chain chlorinated paraffins in sewage sludge of wastewater treatment plants in China

    International Nuclear Information System (INIS)

    Zeng Lixi; Wang Thanh; Ruan Ting; Liu Qian; Wang Yawei; Jiang Guibin

    2012-01-01

    Short chain chlorinated paraffins (SCCPs) are listed as persistent organic pollutant candidates in the Stockholm Convention and are receiving more and more attentions worldwide. In general, concentrations of contaminants in sewage sludge can give an important indication on their pollution levels at a local/regional basis. In this study, SCCPs were investigated in sewage sludge samples collected from 52 wastewater treatment plants in China. Concentrations of total SCCPs (ΣSCCPs) in sludge were in the range of 0.80–52.7 μg/g dry weight (dw), with a mean value of 10.7 μg/g dw. Most of SCCPs in the sludge samples showed a similar congener distribution patterns, and C 11 and Cl 7,8 were identified as the dominant carbon and chlorine congener groups. Significant linear relationships were found among different SCCP congener groups (r 2 ≥ 0.9). High concentrations of SCCPs in sewage sludge imply that SCCPs are widely present in China. - Highlights: ► Levels and distribution patterns of SCCPs were studied in sewage sludge in China. ► Concentrations of total SCCPs in sludge ranged from 0.8 to 52.7 μg/g dry weight. ► C 11 and Cl 7,8 were identified as the dominant congener groups within SCCPs. ► Significant linear relationships were found among SCCP congener groups (r 2 ≥ 0.9). ► SCCPs are present in household products and can be exposing to human. - High levels of short chain chlorinated paraffins in sewage sludge of wastewater treatment plants in China have been found.

  17. Contribution of dietary patterns to blood heavy metal concentrations in Korean adults: findings from the Fifth Korea National Health and Nutrition Examination Survey 2010.

    Science.gov (United States)

    Chung, Hye-Kyung; Park, Ju Yeon; Cho, Yoonsu; Shin, Min-Jeong

    2013-12-01

    The aim of the present study was to evaluate the associations between dietary patterns and blood levels of lead and mercury in Korean adults. A total of 858 Korean adults (≥20 years) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) V-1 2010 were included in this study. Data of biochemical measurements including blood lead and mercury levels, nutrients intakes and anthropometric measurements were acquired. 'Balanced diet', 'Grain and kimchi', and 'Alcohol and noodle' dietary patterns were derived from a factor analysis, and the subjects were divided into tertiles by each dietary pattern score. A logistic multiple regression analysis showed that the balanced diet pattern was negatively associated with blood levels of lead before and after adjustment. On the other hand, the alcohol and noodle pattern was positively associated with blood lead and mercury levels. These results indicate that the alcohol and noodle dietary pattern characterized by high alcohol consumption and lack of various foods, and the balanced dietary pattern, including vegetable, fish, meat and milk intake, was associated with the blood concentrations of heavy metals in Korean adults. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Social-Ecological Patterns of Soil Heavy Metals Based on a Self-Organizing Map (SOM: A Case Study in Beijing, China

    Directory of Open Access Journals (Sweden)

    Binwu Wang

    2014-03-01

    Full Text Available The regional management of trace elements in soils requires understanding the interaction between the natural system and human socio-economic activities. In this study, a social-ecological patterns of heavy metals (SEPHM approach was proposed to identify the heavy metal concentration patterns and processes in different ecoregions of Beijing (China based on a self-organizing map (SOM. Potential ecological risk index (RI values of Cr, Ni, Zn, Hg, Cu, As, Cd and Pb were calculated for 1,018 surface soil samples. These data were averaged in accordance with 253 communities and/or towns, and compared with demographic, agriculture structure, geomorphology, climate, land use/cover, and soil-forming parent material to discover the SEPHM. Multivariate statistical techniques were further applied to interpret the control factors of each SEPHM. SOM application clustered the 253 towns into nine groups on the map size of 12 × 7 plane (quantization error 1.809; topographic error, 0.0079. The distribution characteristics and Spearman rank correlation coefficients of RIs were strongly associated with the population density, vegetation index, industrial and mining land percent and road density. The RIs were relatively high in which towns in a highly urbanized area with large human population density exist, while low RIs occurred in mountainous and high vegetation cover areas. The resulting dataset identifies the SEPHM of Beijing and links the apparent results of RIs to driving factors, thus serving as an excellent data source to inform policy makers for legislative and land management actions.

  19. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats. The 2nd report

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Xiao Dong Wang; Nagaoka, Shunji; Nojima, Kumie

    2004-01-01

    We examined the effects of acute exposure of heavy ion on the properties of motoneurons and their innervating muscle fibers. A 40 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in five 8-week-old male rats. Five male rats served as controls. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were analyzed. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no changes in the number of motoneurons between the control and heavy-ion-exposed rats. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in motoneurons of the heavy-ion-exposed rats. There were no changes in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the muscles between the control and heavy-ion-exposed rats. It is concluded that a 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there were no influences on the properties of muscle fibers which they innervate. (author)

  20. Crystal structures of a copper(II and the isotypic nickel(II and palladium(II complexes of the ligand (E-1-[(2,4,6-tribromophenyldiazenyl]naphthalen-2-ol

    Directory of Open Access Journals (Sweden)

    Souheyla Chetioui

    2016-08-01

    Full Text Available In the copper(II complex, bis{(E-1-[(2,4,6-tribromophenyldiazenyl]naphthalen-2-olato}copper(II, [Cu(C16H8Br3N2O2], (I, the metal cation is coordinated by two N atoms and two O atoms from two bidentate (E-1-[(2,4,6-tribromophenyldiazenyl]naphthalen-2-olate ligands, forming a slightly distorted square-planar environment. In one of the ligands, the tribromobenzene ring is inclined to the naphthalene ring system by 37.4 (5°, creating a weak intramolecular Cu...Br interaction [3.134 (2 Å], while in the other ligand, the tribromobenzene ring is inclined to the naphthalene ring system by 72.1 (6°. In the isotypic nickel(II and palladium(II complexes, namely bis{(E-1-[(2,4,6-tribromophenyldiazenyl]naphthalen-2-olato}nickel(II, [Ni(C16H8Br3N2O2], (II, and bis{(E-1-[(2,4,6-tribromophenyldiazenyl]naphthalen-2-olato}palladium(II, [Pd(C16H8Br3N2O2], (III, respectively, the metal atoms are located on centres of inversion, hence the metal coordination spheres have perfect square-planar geometries. The tribromobenzene rings are inclined to the naphthalene ring systems by 80.79 (18° in (II and by 80.8 (3° in (III. In the crystal of (I, molecules are linked by C—H...Br hydrogen bonds, forming chains along [010]. The chains are linked by C—H...π interactions, forming sheets parallel to (011. In the crystals of (II and (III, molecules are linked by C—H...π interactions, forming slabs parallel to (10-1. For the copper(II complex (I, a region of disordered electron density was corrected for using the SQUEEZE routine in PLATON [Spek (2015. Acta Cryst. C71, 9–18]. The formula mass and unit-cell characteristics of the disordered solvent molecules were not taken into account during refinement.

  1. Computational Experiment Approach to Controlled Evolution of Procurement Pattern in Cluster Supply Chain

    Directory of Open Access Journals (Sweden)

    Xiao Xue

    2015-01-01

    Full Text Available Companies have been aware of the benefits of developing Cluster Supply Chains (CSCs, and they are spending a great deal of time and money attempting to develop the new business pattern. Yet, the traditional techniques for identifying CSCs have strong theoretical antecedents, but seem to have little traction in the field. We believe this is because the standard techniques fail to capture evolution over time, nor provide useful intervention measures to reach goals. To address these problems, we introduce an agent-based modeling approach to evaluate CSCs. Taking collaborative procurement as research object, our approach is composed of three parts: model construction, model instantiation, and computational experiment. We use the approach to explore the service charging policy problem in collaborative procurement. Three kinds of service charging polices are compared in the same experiment environment. Finally, “Fixed Cost” is identified as the optimal policy under the stable market environment. The case study can help us to understand the workflow of applying the approach, and provide valuable decision support applications to industry.

  2. Myosin heavy-chain isoforms in the flight and leg muscles of hummingbirds and zebra finches.

    Science.gov (United States)

    Velten, Brandy P; Welch, Kenneth C

    2014-06-01

    Myosin heavy chain (MHC) isoform complement is intimately related to a muscle's contractile properties, yet relatively little is known about avian MHC isoforms or how they may vary with fiber type and/or the contractile properties of a muscle. The rapid shortening of muscles necessary to power flight at the high wingbeat frequencies of ruby-throated hummingbirds and zebra finches (25-60 Hz), along with the varied morphology and use of the hummingbird hindlimb, provides a unique opportunity to understand how contractile and morphological properties of avian muscle may be reflected in MHC expression. Isoforms of the hummingbird and zebra finch flight and hindlimb muscles were electrophoretically separated and compared with those of other avian species representing different contractile properties and fiber types. The flight muscles of the study species operate at drastically different contraction rates and are composed of different histochemically defined fiber types, yet each exhibited the same, single MHC isoform corresponding to the chicken adult fast isoform. Thus, despite quantitative differences in the contractile demands of flight muscles across species, this isoform appears necessary for meeting the performance demands of avian powered flight. Variation in flight muscle contractile performance across species may be due to differences in the structural composition of this conserved isoform and/or variation within other mechanically linked proteins. The leg muscles were more varied in their MHC isoform composition across both muscles and species. The disparity in hindlimb MHC expression between hummingbirds and the other species highlights previously observed differences in fiber type composition and thrust production during take-off. Copyright © 2014 the American Physiological Society.

  3. Many Routes to an Antibody Heavy-Chain CDR3: Necessary, Yet Insufficient, for Specific Binding

    Science.gov (United States)

    D’Angelo, Sara; Ferrara, Fortunato; Naranjo, Leslie; Erasmus, M. Frank; Hraber, Peter; Bradbury, Andrew R. M.

    2018-01-01

    Because of its great potential for diversity, the immunoglobulin heavy-chain complementarity-determining region 3 (HCDR3) is taken as an antibody molecule’s most important component in conferring binding activity and specificity. For this reason, HCDR3s have been used as unique identifiers to investigate adaptive immune responses in vivo and to characterize in vitro selection outputs where display systems were employed. Here, we show that many different HCDR3s can be identified within a target-specific antibody population after in vitro selection. For each identified HCDR3, a number of different antibodies bearing differences elsewhere can be found. In such selected populations, all antibodies with the same HCDR3 recognize the target, albeit at different affinities. In contrast, within unselected populations, the majority of antibodies with the same HCDR3 sequence do not bind the target. In one HCDR3 examined in depth, all target-specific antibodies were derived from the same VDJ rearrangement, while non-binding antibodies with the same HCDR3 were derived from many different V and D gene rearrangements. Careful examination of previously published in vivo datasets reveals that HCDR3s shared between, and within, different individuals can also originate from rearrangements of different V and D genes, with up to 26 different rearrangements yielding the same identical HCDR3 sequence. On the basis of these observations, we conclude that the same HCDR3 can be generated by many different rearrangements, but that specific target binding is an outcome of unique rearrangements and VL pairing: the HCDR3 is necessary, albeit insufficient, for specific antibody binding. PMID:29568296

  4. Quantifying Short-Chain Chlorinated Paraffin Congener Groups.

    Science.gov (United States)

    Yuan, Bo; Bogdal, Christian; Berger, Urs; MacLeod, Matthew; Gebbink, Wouter A; Alsberg, Tomas; de Wit, Cynthia A

    2017-09-19

    Accurate quantification of short-chain chlorinated paraffins (SCCPs) poses an exceptional challenge to analytical chemists. SCCPs are complex mixtures of chlorinated alkanes with variable chain length and chlorination level; congeners with a fixed chain length (n) and number of chlorines (m) are referred to as a "congener group" C n Cl m . Recently, we resolved individual C n Cl m by mathematically deconvolving soft ionization high-resolution mass spectra of SCCP mixtures. Here we extend the method to quantifying C n Cl m by introducing C n Cl m specific response factors (RFs) that are calculated from 17 SCCP chain-length standards with a single carbon chain length and variable chlorination level. The signal pattern of each standard is measured on APCI-QTOF-MS. RFs of each C n Cl m are obtained by pairwise optimization of the normal distribution's fit to the signal patterns of the 17 chain-length standards. The method was verified by quantifying SCCP technical mixtures and spiked environmental samples with accuracies of 82-123% and 76-109%, respectively. The absolute differences between calculated and manufacturer-reported chlorination degrees were -0.9 to 1.0%Cl for SCCP mixtures of 49-71%Cl. The quantification method has been replicated with ECNI magnetic sector MS and ECNI-Q-Orbitrap-MS. C n Cl m concentrations determined with the three instruments were highly correlated (R 2 > 0.90) with each other.

  5. Surficial and vertical distribution of heavy metals in different estuary wetlands in the Pearl river, South China

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Honggang; Cui, Baoshan [State Key Joint Laboratory of Environmental Simulation and Pollution Control, School of Environment, Beijing Normal University, Beijing (China); Zhang, Kejiang [Xinjiang Research Center of Water and Wastewater Treatment, Xinjiang Deland Co., LTD., Urumqi (China)

    2012-10-15

    A total of 87 soil profiles sampled from five types of wetlands in the Pearl River estuary were analyzed to investigate the surficial and vertical distributions of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn). The results show that wetlands directly connected with rivers (e.g., riparian wetlands, estuarine wetlands, and mangrove wetlands) has much higher metal concentrations than those indirectly connected with rivers (e.g., pond wetlands and reclaimed wetlands). The river water is the major pollution source for all investigated heavy metals. The vertical distribution of heavy metals can be classified into three patterns: (i) linear distribution pattern. The concentration of heavy metals gradually decreases with an increase in soil depth (for riparian and estuarine wetlands); (ii) irregular and stable pattern (for pond and reclaimed wetlands); and (iii) middle enrichment pattern (for mangrove wetlands). In addition to river-borne inputs, a variety of vegetation composition, hydraulic conditions, and human activities also contribute to the variation in distribution of heavy metals in different wetlands. Soil properties (e.g., particle size, pH, salinity, and SOM) also affect the distribution of trace metals in each soil layer. The major pollution source of heavy metals is industrial wastewater. Other sources include agriculture and domestic premises, and atmospheric deposition. This study provides a sound basis for the risk assessment of heavy metals in the studied wetlands and for wetland conservation in general. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Heavy metal bioaccumulation in the organisms at hydrothermal fields of the Mid-Atlantic Ridge and East-Pacific Rise

    International Nuclear Information System (INIS)

    Demina, L.L.; Galkin, S.V.

    2008-01-01

    The influence of geochemical environment as well as biological parameters on the heavy metal bioaccumulation in the hydrothermal fauna at certain fields of the Mid-Atlantic ridge (MAR) and East Pacific Rise (EPR) are studied. The highest concentration of Fe, Zn, Cu, Mn, Ni, Cr, Co, Pb, Cd, Ag, Se, Sb, As, and Hg were detected in the tubes of the most thermophilic organism Alvinella caudata inhabited sulfide chimneys at 9 0 50 ' N EPR, i.e. at place where the influence of hydrothermal fluids was the maximal. Elevated heavy metals levels were typical for organs associated with the endo symbiotic bacteria activity, such as gills of specialized mussels Bathymodiolus, clams Archivestica gigas (Calyptogena magnifica), trophosome of vestimentifera Riftia, maxillipeds of shrimps Rimicaris exoculata. Inter-site (Broken Spur vs. Rainbow) comparison of the partitioning of metals within soft tissues has revealed that metal concentrations in the fauna habitats is an important albeit not the single factor that controls the metal content in the interior organs of the taxa. The external parts of mussels, such as shells, demonstrate patterns of bioaccumulation reflecting the metal concentrations in the micro-habitats. In spite of the minimal metal content was found in the mussel shells, they serve as a great reservoirs for heavy metal deposition and storage at the hydrothermal regions. For some elements a trend of heavy metal transferring through the food chains was revealed. There were no clear dependence between age of mussels and metal content (except Hg) in the soft tissues

  7. Tip stabilizer for a chain saw. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Morabit, V.D.

    1993-09-10

    Prior to receiving the grant, Utilitip was faced with an idea that truly worked, however only a very limited line of component parts would fit various types of chain saws on the market. It also suffered from a severe problem when engaged in the ground of soil penetrating the saw chain area, thus eliminating one of the major benefits of keeping the chain sharp. Consequently, the grant funding was directed towards extending the tooling capabilities to produce parts for a much wider variety of chain saws that are on the market, and further by developing an effective flexible soil shield to prevent abrasive soil entry into the saw chain. Utilitip was able to complete a full set of design for a wide variety of large and small chain saws. This incorporated a design and fabrication of a small Utilitip, as well as a small anti-kickback device. In addition, tooling was also further developed for the large Utilitip and the large anti-kickback device. Accordingly, multiple tools are available for all combinations, as well as back-up provisions. Utilitip, Inc. invented a special, flexible attachment to be glued and/or molded to the tip guard. The soil shield prevents abrasive soil from coming into the chain area. In addition, it allows a flexible arrangement to allow the chain saw to be released from brush without binding. Otherwise, a larger, rigid soil shield would hold or restrict the saw in heavy brush. The rubber shield will flex out of the say and reduce, if not eliminate, this harmful binding.

  8. Food patterns of Australian children ages 9 to 13 y in relation to ω-3 long chain polyunsaturated intake.

    Science.gov (United States)

    Rahmawaty, Setyaningrum; Lyons-Wall, Philippa; Batterham, Marijka; Charlton, Karen; Meyer, Barbara J

    2014-02-01

    The aim of this study was to examine food patterns of Australian children ages 9 to 13 y in relation to ω-3 long-chain polyunsaturated fatty acid (ω-3 LCPUFA) intake. Secondary analysis was conducted on nationally representative food data of 1110 Australian children ages 9 to 13 y (525 boys and 585 girls) that was obtained using two 24-h recalls. Principle component factor analysis was used to identify food patterns. Discriminant function analysis was used to identify the relationship between the food patterns and total ω-3 LCPUFA intake. Four major food patterns emerged for each sex. For boys these were labeled: "snack foods," "soft drinks," "vegetables," and "pork and meat chops, steak, and mince." For girls they were labeled: "vegetables," "take-away," "tea, coffee, iced coffee drinks" and "canned meals and soup." Fish consumption bought from take-away outlets was more frequently consumed in the "soft drink" (r = 0.577) and take-away (r = 0.485) food pattern in boys and girls, respectively. In contrast, fish prepared at home was more often consumed in "vegetables" in both boys (r = 0.018) and girls (r = 0.106), as well as in the "pork and meat chops, steak and mince" food pattern in boys (r = 0.060). There was a trend that in boys, the "vegetables" group discriminated children who consumed ω-3 LCPUFA levels similar to adequate intakes (AI) (P = 0.067), whereas in girls, the take-away food pattern discriminated for being a fish consumer (P = 0.060). Dietary patterns associated with a high consumption of vegetables and "take-aways" food that include meat and fish are likely to positively influence dietary ω-3 LCPUFA intake in Australian children. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH genes in multiple human solid tumors: A systematic expression analysis

    Directory of Open Access Journals (Sweden)

    Werbowetski-Ogilvie Tamra

    2008-01-01

    Full Text Available Abstract Background The inter-alpha-trypsin inhibitors (ITI are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by AMBP – and five homologous heavy chains (encoded by ITIH1, ITIH2, ITIH3, ITIH4, and ITIH5, contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis. Methods We systematically investigated differential gene expression of the ITIH gene family, as well as AMBP and the interacting partner TNFAIP6 in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas using cDNA dot blot analysis (Cancer Profiling Array, CPA, semiquantitative RT-PCR and immunohistochemistry. Results We found that ITIH genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, ITIH genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose ITIH2 expression in human breast cancer. Loss of ITIH2 expression in 70% of cases (n = 50, CPA could be confirmed by real-time PCR in an additional set of breast cancers (n = 36. Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p Conclusion Altogether, this is the first systematic analysis on the differential expression of ITIH genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.

  10. Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains

    International Nuclear Information System (INIS)

    Leger, J.; Chevalier, J.; Larue, C.; Gautier, P.; Planchenault, J.; Aumaitre, E.; Messner, P.; Puech, P.; Saccavini, J.C.; Pau, B.

    1991-01-01

    The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis

  11. Human health risk from soil heavy metal contamination under different land uses near Dabaoshan Mine, Southern China

    International Nuclear Information System (INIS)

    Zhao, Huarong; Xia, Beicheng; Fan, Chen; Zhao, Peng; Shen, Shili

    2012-01-01

    Soil heavy metal contamination is a major environmental concern, and the ecological risk associated with heavy metals is increasing. In this paper, we investigated heavy metal contamination near Dabaoshan Mine by: using sequential indicator simulation to delineate the spatial patterns of soil data; fitting multiple linear regression models for heavy metal uptake by crops; interpreting land uses from remote sensing images and integrating the spatial patterns, uptake models and land uses into a dose–response model for human health risks from heavy metals. The areas with elevated soil heavy metal concentrations are mainly located at the Dabaoshan Mine site and in the watershed basins of the Hengshi, Tielong and Chuandu rivers. The average concentrations of Cu, Zn, Cd and Pb in soil in the study area are all above the natural soil background levels, but Cd is the major contributor to human health risk in the area. Areas of low soil pH are also found throughout the watershed basins of the Hengshi, Tielong and Chuandu rivers. Of the different land use types in the study area, agricultural and residential land uses have the highest human health risk because ingestion is the dominant exposure pathway for heavy metals. The spatial patterns of the heavy metal concentrations and soil pH indicate that the areas with the highest human health risk regions do not directly coincide with the areas of highest heavy metal concentrations, but do coincide with the areas of lower soil pH. The contamination with high concentrations of heavy metals provides the risk source, but the combination of high heavy metal concentrations, low pH and agricultural or residential land use is required for human health risks to be present. The spatial pattern of the hazard quotients indicates that Cd is the most important pollutant contributing to the human health risk. - Highlights: ►The distribution of Cu, Zn, Cd, Pb and pH in soil were analyzed near Dabaoshan Mine. ►Heavy metal uptake models in

  12. The triple-A supply chain.

    Science.gov (United States)

    Lee, Hau L

    2004-10-01

    Building a strong supply chain is essential for business success. But when it comes to improving their supply chains, few companies take the right approach. Many businesses work to make their chains faster or more cost-effective, assuming that those steps are the keys to competitive advantage. To the contrary: Supply chains that focus on speed and costs tend to deteriorate over time. The author has spent 15 years studying more than 60 companies to gain insight into this and other supply chain dilemmas. His conclusion: Only companies that build supply chains that are agile, adaptable, and aligned get ahead of their rivals. All three components are essential; without any one of them, supply chains break down. Great companies create supply chains that respond to abrupt changes in markets. Agility is critical because in most industries, both demand and supply fluctuate rapidly and widely. Supply chains typically cope by playing speed against costs, but agile ones respond both quickly and cost-efficiently. Great companies also adapt their supply networks when markets or strategies change. The best supply chains allow managers to identify structural shifts early by recording the latest data, filtering out noise, and tracking key patterns. Finally, great companies align the interests of the partners in their supply chains with their own. That's important because every firm is concerned solely with its own interests. If its goals are out of alignment with those of other partners in the supply chain, performance will suffer. When companies hear about the triple-A supply chain, they assume that building one will require increased technology and investment. But most firms already have the infrastructure in place to create one. A fresh attitude alone can go a long way toward making it happen.

  13. Activity modulation of microbial enzymes by llama (Lama glama) heavy-chain polyclonal antibodies during in vivo immune responses.

    Science.gov (United States)

    Ferrari, A; Weill, F S; Paz, M L; Cela, E M; González Maglio, D H; Leoni, J

    2012-03-01

    Since they were first described in 1993, it was found that recombinant variable fragments (rVHHs) of heavy-chain antibodies (HCAbs) from Camelidae have unusual biophysical properties, as well as a special ability to interact with epitopes that are cryptic for conventional Abs. It has been assumed that in vivo raised polyclonal HCAbs (pHCAbs) should behave in a similar manner than rVHHs; however, this assumption has not been tested sufficiently. Furthermore, our own preliminary work on a single serum sample from a llama immunized with a β-lactamase, has suggested that pHCAbs have no special ability to down-modulate catalytic activity. In this work, we further explored the interaction of pHCAbs from four llamas raised against two microbial enzymes and analyzed it within a short and a long immunization plan. The relative contribution of pHCAbs to serum titer was found to be low compared with that of the most abundant conventional subisotype (IgG(1)), during the whole immunization schedule. Furthermore, pHCAbs not only failed to inhibit the enzymes, but also activated one of them. Altogether, these results suggest that raising high titer inhibitory HCAbs is not a straightforward strategy - neither as a biotechnological strategy nor in the biological context of an immune response against infection - as raising inhibitory rVHHs.

  14. MR molecular imaging of tumours using ferritin heavy chain reporter gene expression mediated by the hTERT promoter

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yan [Third Military Medical University, Department of Radiology, XinQiao Hospital, ChongQing (China); The First Affiliated Hospital of ChengDu Medical College, Department of Radiology, ChengDu (China); Gong, Ming-fu; Yang, Hua; Zhang, Song; Wang, Guang-xian; Su, Tong-sheng; Wen, Li; Zhang, Dong [Third Military Medical University, Department of Radiology, XinQiao Hospital, ChongQing (China)

    2016-11-15

    Using the human telomerase reverse transcriptase (hTERT) promoter and the modified ferritin heavy chain (Fth) reporter gene, reporter gene expression for MRI was examined in telomerase positive and negative tumour cells and xenografts. Activity of the reporter gene expression vector Lenti-hTERT-Fth1-3FLAG-Puro was compared to constitutive CMV-driven expression and to the untransfected parental control in five tumour cell lines: A549, SKOV3, 293T, U2OS and HPDLF. In vitro, transfected cells were evaluated for FLAG-tagged protein expression, iron accumulation and transverse relaxation. In vivo, tumours transduced by lentiviral vector injection were imaged using T2*WI. Changes in tumour signal intensity were validated by histology. Only telomerase positive tumour cells expressed FLAG-tagged Fth and displayed an increase in R2* above the parental control, with a corresponding change in T2*WI. In addition, only telomerase positive tumours, transduced by injection of the reporter gene expression construct, exhibited a change in signal intensity on T2*WI. Tumour histology verified the expression of FLAG-tagged Fth and iron accumulation in telomerase positive tissue. Reporter gene expression for MRI, using the Fth reporter and the hTERT promoter, may be a useful strategy for the non-invasive diagnosis of many types of cancer. (orig.)

  15. Impact of heavy metal toxicity and constructed wetland system as a tool in remediation.

    Science.gov (United States)

    Usharani, B; Vasudevan, N

    2016-01-01

    The objective of this review is to throw light upon the global concern of heavy metal-contaminated sites and their remediation through an ecofriendly approach. Accumulated heavy metals in soil and water bodies gain entry through the food chain and pose serious threat to all forms of life. This has engendered interest in phytoremediation techniques where hyperaccumulators are used. Constructed wetland has a pivotal role and is a cost-effective technique in the remediation of heavy metals. Metal availability and mobility are influenced by the addition of chelating agents, which enhance the availability of metal uptake. This review helps in identifying the critical knowledge gaps and areas to enhance research in the future to develop strategies such as genetically engineered hyperaccumulators to attain an environment devoid of heavy metal contamination.

  16. Atmospheric heavy metal deposition in Europe estimated by moss analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ruehling, Aa. [Swedish Environmental Research Inst., Lund (Sweden). Dept. of Ecology

    1995-12-31

    Atmospheric heavy metal deposition in Europe including 21 countries was monitored in 1990-1992 by the moss technique. This technique is based on the fact that the concentrations of heavy metals in moss are closely correlated to atmospheric deposition. This was the first attempt to map heavy metal deposition in this large area. The objectives of the project were to characterise qualitatively and quantitatively the regional atmospheric deposition pattern of heavy metals in background areas in Europe, to indicate the location of important heavy metal pollution sources and to allow retrospective comparisons with similar studies. The present survey is a follow-up of a joint Danish and Swedish project in 1980 and an extended survey in 1985 within the framework of the Nordic Council of Ministers. In Sweden, heavy-metal deposition was first mapped on a nation-wide scale in 1968-1971 and 1975. (author)

  17. Atmospheric heavy metal deposition in Europe estimated by moss analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ruehling, Aa [Swedish Environmental Research Inst., Lund (Sweden). Dept. of Ecology

    1996-12-31

    Atmospheric heavy metal deposition in Europe including 21 countries was monitored in 1990-1992 by the moss technique. This technique is based on the fact that the concentrations of heavy metals in moss are closely correlated to atmospheric deposition. This was the first attempt to map heavy metal deposition in this large area. The objectives of the project were to characterise qualitatively and quantitatively the regional atmospheric deposition pattern of heavy metals in background areas in Europe, to indicate the location of important heavy metal pollution sources and to allow retrospective comparisons with similar studies. The present survey is a follow-up of a joint Danish and Swedish project in 1980 and an extended survey in 1985 within the framework of the Nordic Council of Ministers. In Sweden, heavy-metal deposition was first mapped on a nation-wide scale in 1968-1971 and 1975. (author)

  18. Predictors of chain acquisition among independent dialysis facilities.

    Science.gov (United States)

    Pozniak, Alyssa S; Hirth, Richard A; Banaszak-Holl, Jane; Wheeler, John R C

    2010-04-01

    To determine the predictors of chain acquisition among independent dialysis providers. Retrospective facility-level data combined from CMS Cost Reports, Medical Evidence Forms, Annual Facility Surveys, and claims for 1996-2003. Independent dialysis facilities' probability of acquisition by a dialysis chain (overall and by chain size) was estimated using a discrete time hazard rate model, controlling for financial and clinical performance, practice patterns, market factors, and other facility characteristics. The sample includes all U.S. freestanding dialysis facilities that report not being chain affiliated for at least 1 year between 1997 and 2003. Above-average costs and better quality outcomes are significant determinants of dialysis chain acquisition. Facilities in larger markets were more likely to be acquired by a chain. Furthermore, small dialysis chains have different acquisition strategies than large chains. Dialysis chains appear to employ a mix of turn-around and cream-skimming strategies. Poor financial health is a predictor of chain acquisition as in other health care sectors, but the increased likelihood of chain acquisition among higher quality facilities is unique to the dialysis industry. Significant differences among predictors of acquisition by small and large chains reinforce the importance of using a richer classification for chain status.

  19. Synthesis, structure and optical properties of two isotypic crystals, Na3MO4Cl (M=W, Mo)

    International Nuclear Information System (INIS)

    Han, Shujuan; Bai, Chunyan; Zhang, Bingbing; Yang, Zhihua; Pan, Shilie

    2016-01-01

    Two isotypic compounds, Na 3 MO 4 Cl (M = W, Mo) have been obtained from the high temperature solution, and their structures were determined by single-crystal X-ray diffraction. Both of them crystallize in the space group P4/nmm of tetragonal system with the unit cells: a=7.5181(15), c=5.360(2) for Na 3 WO 4 Cl and a=7.4942(12), c=5.3409(18) for Na 3 MoO 4 Cl. The structure exhibits a 3D network built up by the ClNa 6 groups, and the MO 4 groups reside in the tunnels of the 3D network. The structural similarities and differences between Na 3 MO 4 Cl (M=W, Mo) and Sr 3 MO 4 F (M=Al, Ga) have been discussed. Meanwhile, detailed structure comparison analyses between Na 3 MO 4 Cl (M=W, Mo) and Na 3 MO 4 F (M=W, Mo) indicate that the different connection modes of ClNa 6 and FNa 6 make Na 3 MO 4 Cl and Na 3 MO 4 F crystallize in different structures. The IR spectra were used to verify the validity of the structure. The diffuse reflectance spectra show that the UV absorption edges are about 249 nm (4.99 eV) and 265 nm (4.69 eV) for Na 3 WO 4 Cl and Na 3 MoO 4 Cl, respectively. In addition, the first-principles theoretical studies are also carried out to aid the understanding of electronic structures and linear optical properties. - Graphical abstract: Two isotypic compounds, Na 3 MO 4 Cl (M=W, Mo) have been obtained from the high temperature solution. Both of them crystallize in the space group P4/nmm of tetragonal system. The structure exhibits a 3D network built up by the ClNa 6 groups, and the MO 4 groups reside in the tunnels of the 3D network. - Highlights: • Structure and properties of Na 3 MO 4 Cl (M=W, Mo) are reported for the first time. • They show a 3D network built by ClNa 6 , and WO 4 lies in the tunnels of the network. • IR spectra were used to verify the validity of the structure. • Band structures and density of states have been calculated.

  20. Chimeric Anti-Human Podoplanin Antibody NZ-12 of Lambda Light Chain Exerts Higher Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity Compared with NZ-8 of Kappa Light Chain.

    Science.gov (United States)

    Kaneko, Mika K; Abe, Shinji; Ogasawara, Satoshi; Fujii, Yuki; Yamada, Shinji; Murata, Takeshi; Uchida, Hiroaki; Tahara, Hideaki; Nishioka, Yasuhiko; Kato, Yukinari

    2017-02-01

    Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG 2a , lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis. Human-rat chimeric antibody, NZ-8, was previously developed using variable regions of NZ-1 and human constant regions of heavy chain (IgG 1 ) and light chain (kappa chain). Although NZ-8 showed high antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cells, the binding affinity of NZ-8 was lower than that of NZ-1. Herein, we produced a novel human-rat chimeric antibody, NZ-12, the constant regions of which consist of IgG 1 heavy chain and lambda light chain. Using flow cytometry, we demonstrated that the binding affinity of NZ-12 was much higher than that of NZ-8. Furthermore, ADCC and CDC activities of NZ-12 were significantly increased against glioblastoma cell lines (LN319 and D397) and lung cancer cell line (PC-10). These results suggested that NZ-12 could become a promising therapeutic antibody against podoplanin-expressing brain tumors and lung cancers.

  1. The Role of BPM in the IT Value-Chain

    DEFF Research Database (Denmark)

    Møller, Charles

    2012-01-01

    Systems. This is studied through an analysis of the emerging architectures in four recent cases of BPM adoption in large enterprises. The cases are analyzed using an IT value chain framework. The cross case analysis suggest that a stable pattern emerges and the new role of BPM in managing the IT value...... chain is discussed. This paper suggests that research and the management of the IT value chain is an important emerging topic....

  2. Heavy-heavy and heavy-light quarks interactions generated by QCD vacuum

    Directory of Open Access Journals (Sweden)

    Musakhanov Mirzayusuf

    2017-01-01

    Full Text Available The QCD vacuum is populated by instantons that correspond to the tunneling processes in the vacuum. This mechanism creates the strong vacuum gluon fields. As result, the QCD vacuum instantons induce very strong interactions between light quarks, initially almost massless. Such a strong interactions bring a large dynamical mass M of the light quarks and bound them to produce almost massless pions in accordance with the spontaneous breaking of the chiral symmetry (SBCS. On the other hand, the QCD vacuum instantons also interact with heavy quarks and responsible for the generation of the heavy-heavy and heavy-light quarks interactions, with a traces of the SBCS. If we take the average instanton size ρ¯=0.33$\\bar \\rho = 0.33$ fm, and the average inter-instanton distance R¯=1$\\bar R = 1$ fm we obtain the dynamical light quark mass to be M = 365 MeV and the instanton media contribution to the heavy quark mass ΔM=70 MeV. These factors define the coupling between heavy-light and heavy-heavy quarks induced by the QCD vacuum instantons. We consider first the instanton effects on the heavy-heavy quarks potential, including its spin-dependent part. We also discuss those effects on the masses of the charmonia and their hyperfine mass splittings. At the second part we discuss the interaction between a heavy and light quarks generated by instantons and it’s effects.

  3. Signal peptide-dependent inhibition of MHC class I heavy chain translation by rhesus cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Colin J Powers

    2008-10-01

    Full Text Available The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit MHC-I assembly with viral peptides, thus preventing cytotoxic T cell recognition. Since HCMV lacking US2-11 is no longer able to block assembly and transport of MHC-I, we examined whether this is also observed for RhCMV lacking the corresponding region. Unexpectedly, recombinant RhCMV lacking US2-11 was still able to inhibit MHC-I expression in infected fibroblasts, suggesting the presence of an additional MHC-I evasion mechanism. Progressive deletion analysis of RhCMV-specific genomic regions revealed that MHC-I expression is fully restored upon additional deletion of rh178. The protein encoded by this RhCMV-specific open reading frame is anchored in the endoplasmic reticulum membrane. In the presence of rh178, RhCMV prevented MHC-I heavy chain (HC expression, but did not inhibit mRNA transcription or association of HC mRNA with translating ribosomes. Proteasome inhibitors stabilized a HC degradation intermediate in the absence of rh178, but not in its presence, suggesting that rh178 prevents completion of HC translation. This interference was signal sequence-dependent since replacing the signal peptide with that of CD4 or murine HC rendered human HCs resistant to rh178. We have identified an inhibitor of antigen presentation encoded by rhesus cytomegalovirus unique in both its lack of homology to any other known protein and in its mechanism of action. By preventing signal sequence-dependent HC translocation, rh178 acts prior to US2, US3 and US11 which attack MHC-I proteins after protein synthesis is completed. Rh178 is the first viral protein known to interfere at this step of the MHC-I pathway, thus taking advantage of the conserved nature of HC leader peptides, and represents a new mechanism of translational interference.

  4. Response of rhizosphere microbial community structure and diversity to heavy metal co-pollution in arable soil.

    Science.gov (United States)

    Deng, Linjing; Zeng, Guangming; Fan, Changzheng; Lu, Lunhui; Chen, Xunfeng; Chen, Ming; Wu, Haipeng; He, Xiaoxiao; He, Yan

    2015-10-01

    Due to the emerging environmental issues related to heavy metals, concern about the soil quality of farming lands near manufacturing district is increasing. Investigating the function of soil microorganisms exposed to long-term heavy metal contamination is meaningful and important for agricultural soil utilization. This article studied the potential influence of several heavy metals on microbial biomass, activity, abundance, and community composition in arable soil near industrial estate in Zhuzhou, Hunan province, China. The results showed that soil organic contents (SOC) were significantly positive correlated with heavy metals, whereas dehydrogenase activity (DHA) was greatly depressed by the heavy metal stress. Negative correlation was found between heavy metals and basal soil respiration (BSR), and no correlation was found between heavy metals and microbial biomass content (MBC). The quantitative PCR (QPCR) and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis could suggest that heavy metal pollution has significantly decreased abundance of bacteria and fungi and also changed their community structure. The results could contribute to evaluate heavy metal pollution level in soil. By combining different environmental parameters, it would promote the better understanding of heavy metal effect on the size, structure, and activity of microbial community in arable soil.

  5. Main-chain-directed strategy for the assignment of 1H NMR spectra of proteins

    International Nuclear Information System (INIS)

    Englander, S.W.; Wand, A.J.

    1987-01-01

    A strategy for assigning the resonances in two-dimensional (2D) NMR spectra of proteins is described. The method emphasizes the analysis of through-space relationships between protons by use of the two-dimensional nuclear Overhauser effect (NOE) experiment. NOE patterns used in the algorithm were derived from a statistical analysis of the combinations of short proton-proton distances observed in the high-resolution crystal structures of 21 proteins. One starts with a search for authentic main-chain NH-C/sub α/H-C/sub β/H J-coupled units, which can be found with high reliability. The many main-chain units of a protein are then placed in their proper juxtaposition by recognition of predefined NOE connectivity patterns. To discover these connectivities, the 2D NOE spectrum is examined, in a prescribed order, for the distinct NOE patterns characteristic of helices, sheets, turns, and extended chain. Finally, the recognition of a few amino acid side-chain types places the discovered secondary structure elements within the polypeptide sequences. Unlike the sequential assignment approach, the main-chain-directed strategy does not rely on the difficult task of recognizing many side-chain spin systems in J-correlated spectra, the assignment process is not in general sequential with the polypeptide chain, and the prescribed connectivity patterns are cyclic rather than linear. The latter characteristic avoids ambiguous branch points in the analysis and imposed an internally confirmatory property on each forward step

  6. National pattern for heavy metal contamination of topsoil in remote farmland impacted by haze pollution in China

    Science.gov (United States)

    Luo, Zhuanxi; Gao, Meirong; Luo, Xiaosan; Yan, Changzhou

    2016-03-01

    The influence of haze pollution on heavy metal transport into farmland topsoil has received little attention. This study reports on heavy metal concentrations in topsoil from remote farmland in China as well as the spatial similarity and correlation to such heavy metals in atmospheric particulate matter (APM). Heavy metal concentrations in topsoil from remote farmland significantly increased over time. Moreover, stations in the mid-eastern region of China accounted for greater than 55% of total stations that exhibited higher concentrations in 2010 than 2005. This spatial trend was consistent with changes observed in APM where mass concentrations of heavy metals were also found to be higher in the mid-eastern region of China. Heavy metals in APM have already likely caused contamination in remote farmland topsoil, particularly in the mid-eastern region of China. This is primarily due to long-range transport and deposition of APM owing that no pesticides or fertilizers have been used in the remote farmland stations selected and no industries were situated nearby. Regarding the large-scale, severe haze pollution occurring in China today, it is urgent to ascertain the accumulation of heavy metals in farmland topsoil resulting from APM as well as its subsequent potential mechanisms and ecological risks.

  7. Spatial patterns of heavy metal accumulation in sediments and macrophytes of Bellandur wetland, Bangalore.

    Science.gov (United States)

    Ramachandra, T V; Sudarshan, P B; Mahesh, M K; Vinay, S

    2018-01-15

    Heavy metals are one among the toxic chemicals and accumulation in sediments and plants has been posing serious health impacts. Wetlands aid as kidneys of the landscape and help in remediation through uptake of nutrients, heavy metals and other contaminants. The analyses of macrophytes and sediment samples help in evaluating pollution status in aquatic environment. In this study concentration of six heavy metals (Cadmium (Cd), Chromium (Cr), Copper (Cu), Nickel (Ni), Lead (Pb) and Zinc (Zn)) were assessed in sediment and dominant macrophyte samples collected from Bellandur Lake, largest Lake of Bangalore, India. Sediment samples reveal of heavy metals in the inlet regions and shore samples. The accumulation of metals in sediments were in the order of Zn > Cu > Cr > Pb > Ni > Cd. All metals exceeded the critical limits of metals in the sediment. Concentration of different metals in the macrophyte samples ranked as: Cr > Cu > Zn > Pb > Ni > Cd. Chromium and Copper were found to be more than critical range. Typha angustata had the higher accumulation of all metals except chromium. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Downstream lightening and upward heavying, sorting of sediments of uniform grain size but differing in density

    Science.gov (United States)

    Viparelli, E.; Solari, L.; Hill, K. M.

    2014-12-01

    Downstream fining, i.e. the tendency for a gradual decrease in grain size in the downstream direction, has been observed and studied in alluvial rivers and in laboratory flumes. Laboratory experiments and field observations show that the vertical sorting pattern over a small Gilbert delta front is characterized by an upward fining profile, with preferential deposition of coarse particles in the lowermost part of the deposit. The present work is an attempt to answer the following questions. Are there analogous sorting patterns in mixtures of sediment particles having the same grain size but differing density? To investigate this, we performed experiments at the Hydrosystems Laboratory at the University of Illinois at Urbana-Champaign. During the experiments a Gilbert delta formed and migrated downstream allowing for the study of transport and sorting processes on the surface and within the deposit. The experimental results show 1) preferential deposition of heavy particles in the upstream part of the deposit associated with a pattern of "downstream lightening"; and 2) a vertical sorting pattern over the delta front characterized by a pattern of "upward heavying" with preferential deposition of light particles in the lowermost part of the deposit. The observed downstream lightening is analogous of the downstream fining with preferential deposition of heavy (coarse) particles in the upstream part of the deposit. The observed upward heavying was unexpected because, considering the particle mass alone, the heavy (coarse) particles should have been preferentially deposited in the lowermost part of the deposit. Further, the application of classical fractional bedload transport relations suggests that in the case of mixtures of particles of uniform size and different densities equal mobility is not approached. We hypothesize that granular physics mechanisms traditionally associated with sheared granular flows may be responsible for the observed upward heavying and for the

  9. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

    Science.gov (United States)

    French, Martyn A; Abudulai, Laila N; Fernandez, Sonia

    2013-08-09

    The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  10. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

    Directory of Open Access Journals (Sweden)

    Sonia Fernandez

    2013-08-01

    Full Text Available The development of vaccines to treat and prevent human immunodeficiency virus (HIV infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK cell responses and plasmacytoid dendritic cell (pDC responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  11. Immunoglobulin heavy-chain fluorescence in situ hybridization-chromogenic in situ hybridization DNA probe split signal in the clonality assessment of lymphoproliferative processes on cytological samples.

    Science.gov (United States)

    Zeppa, Pio; Sosa Fernandez, Laura Virginia; Cozzolino, Immacolata; Ronga, Valentina; Genesio, Rita; Salatiello, Maria; Picardi, Marco; Malapelle, Umberto; Troncone, Giancarlo; Vigliar, Elena

    2012-12-25

    The human immunoglobulin heavy-chain (IGH) locus at chromosome 14q32 is frequently involved in different translocations of non-Hodgkin lymphoma (NHL), and the detection of any breakage involving the IGH locus should identify a B-cell NHL. The split-signal IGH fluorescence in situ hybridization-chromogenic in situ hybridization (FISH-CISH) DNA probe is a mixture of 2 fluorochrome-labeled DNAs: a green one that binds the telomeric segment and a red one that binds the centromeric segment, both on the IGH breakpoint. In the current study, the authors tested the capability of the IGH FISH-CISH DNA probe to detect IGH translocations and diagnose B-cell lymphoproliferative processes on cytological samples. Fifty cytological specimens from cases of lymphoproliferative processes were tested using the split-signal IGH FISH-CISH DNA probe and the results were compared with light-chain assessment by flow cytometry (FC), IGH status was tested by polymerase chain reaction (PCR), and clinicohistological data. The signal score produced comparable results on FISH and CISH analysis and detected 29 positive, 15 negative, and 6 inadequate cases; there were 29 true-positive cases (66%), 9 true-negative cases (20%), 6 false-negative cases (14%), and no false-positive cases (0%). Comparing the sensitivity of the IGH FISH-CISH DNA split probe with FC and PCR, the highest sensitivity was obtained by FC, followed by FISH-CISH and PCR. The split-signal IGH FISH-CISH DNA probe is effective in detecting any translocation involving the IGH locus. This probe can be used on different samples from different B-cell lymphoproliferative processes, although it is not useful for classifying specific entities. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society. Copyright © 2012 American Cancer Society.

  12. Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity

    Directory of Open Access Journals (Sweden)

    Masanori Matsui

    2014-01-01

    Full Text Available We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL recognition in vitro compared to wild-type HLA-A*02:01. This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L that is located in the peptide-binding groove. To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers. We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP-derived peptide, β2 microglobulin and the H74L heavy chain. HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated. It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP. These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.

  13. distribution pattern of some he funtua textile li ttern of some heavy ...

    African Journals Online (AJOL)

    user pc

    2017-12-02

    Dec 2, 2017 ... ic Absorption Spectrometry, Funtua textile, Heavy metals, Particulate any materials .... was potentially highly bioavailable for plant uptake (Uba et al., 2008 ..... Y.A Dalltu approved the design and supervised the experiment.

  14. Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis

    International Nuclear Information System (INIS)

    Hamm, Alexander; Knuechel, Ruth; Dahl, Edgar; Veeck, Juergen; Bektas, Nuran; Wild, Peter J; Hartmann, Arndt; Heindrichs, Uwe; Kristiansen, Glen; Werbowetski-Ogilvie, Tamra; Del Maestro, Rolando

    2008-01-01

    The inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by AMBP – and five homologous heavy chains (encoded by ITIH1, ITIH2, ITIH3, ITIH4, and ITIH5), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis. We systematically investigated differential gene expression of the ITIH gene family, as well as AMBP and the interacting partner TNFAIP6 in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry. We found that ITIH genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, ITIH genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose ITIH2 expression in human breast cancer. Loss of ITIH2 expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule. Altogether, this is the first systematic analysis on the differential expression of ITIH genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies

  15. Decoupling the IT Value-chain

    DEFF Research Database (Denmark)

    Møller, Charles

    using an IT-based value chain framework. The cross case analysis suggest that a stable pattern emerges and the new role of ES in managing business processes is discussed. The paper suggests that two important architectural structures emerge and it is proposed that the management of these structures...

  16. Heavy quark effective theory and heavy baryon transitions

    International Nuclear Information System (INIS)

    Hussain, F.

    1992-01-01

    The heavy quark effective theory (HQET) is applied to study the weak decay of heavy mesons and heavy baryons and to predict the form factors for heavy to heavy and heavy to light transitions. 28 refs, 10 figs, 2 tabs

  17. Proteomic demonstration of the recurrent presence of inter-alpha-inhibitor H4 heavy-chain during aspergillosis induced in an animal model.

    Science.gov (United States)

    Desoubeaux, Guillaume; Jourdan, Marie-Lise; Valera, Lionel; Jardin, Bénédicte; Hem, Sonia; Caille, Agnès; Cormier, Bénédicte; Marchand-Adam, Sylvain; Bailly, Éric; Diot, Patrice; Chandenier, Jacques

    2014-05-01

    Invasive pulmonary aspergillosis remains a matter of great concern in oncology/haematology, intensive care units and organ transplantation departments. Despite the availability of various diagnostic tools with attractive features, new markers of infection are required for better medical care. We therefore looked for potential pulmonary biomarkers of aspergillosis, by carrying out two-dimensional (2D) gel electrophoresis comparing the proteomes of bronchial-alveolar lavage fluids (BALF) from infected rats and from control rats presenting non-specific inflammation, both immunocompromised. A bioinformatic analysis of the 2D-maps revealed significant differences in the abundance of 20 protein spots (ANOVA P-valuevalue0.8). One of these proteins, identified by mass spectrometry, was considered of potential interest: inter-alpha-inhibitor H4 heavy-chain (ITIH4), characterised for the first time in this infectious context. Western blotting confirmed its overabundance in all infected BALF, particularly at early stages of murine aspergillosis. Further investigations were carried on rat serum, and confirmed that ITIH4 levels increased during experimental aspergillosis. Preliminary results in human samples strengthened this trend. To our knowledge, this is the first description of the involvement of ITIH4 in aspergillosis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. IOLOGICAL IMPORTANCE AND TOXICITY OF HEAVY METALS FOR BIOTA OF FRESHWATER BODIES (REVIEW

    Directory of Open Access Journals (Sweden)

    I. Hrytsyniak

    2014-06-01

    Full Text Available Purpose. To investigate the sources of scientific information on biological functions of heavy metals (Fe, Zn, Mn, Cu, Ni, Co, Pb, Cd and their negative effect on biota of fresh water bodies. Findings. A review of works of a variety of scientists showed that the majority of the studied heavy metals (Fe, Zn, Mn, Cum and Co played an important role in vital functions of freshwater organisms. The significance of other studied heavy metals (Ni, Pb, and Cd is probable or unknown. Besides biological importance, we also know about toxicity of heavy metals – a group of mineral polluting substances, which are the most distributed and dangerous for biota. Their negative effect includes drastic deterioration of conditions for existence of the majority of aquatic organisms, some species disappear, others reduce their number, components of trophic chains are lost, links in ecosystems become broken, and productivity of biocenoses decreases. Practical value. An array of generalized information will be useful for scientists who investigate freshwater ecosystems and effect of toxicants on them, in particular heavy metals.

  19. [The value of serum heavy/light chain immunoassay to assess therapeutic response in patients with multiple myeloma].

    Science.gov (United States)

    Yu, X C; Su, W; Zhuang, J L

    2018-04-14

    Objective: To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM). Methods: A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection. Results: ①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC. Conclusion: Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.

  20. Multi-element sewer slime impact pattern--a quantitative characteristic enabling identification of the source of heavy metal discharges into sewer systems.

    Science.gov (United States)

    Kintrup, J; Wünsch, G

    2001-11-01

    The capability of sewer slime to accumulate heavy metals from municipal wastewater can be exploited to identify the sources of sewage sludge pollution. Former investigations of sewer slime looked for a few elements only and could, therefore, not account for deviations of the enrichment efficiency of the slime or for irregularities from sampling. Results of ICP-MS multi element determinations were analyzed by multivariate statistical methods. A new dimensionless characteristic "sewer slime impact" is proposed, which is zero for unloaded samples. Patterns expressed in this data format specifically extract the information required to identify the type of pollution and polluter quicker and with less effort and cost than hitherto.

  1. Study of heavy metals in the grass-milk product chain by means of neutron activation and atomic absorption

    Energy Technology Data Exchange (ETDEWEB)

    Bruant, C; Bruant, J P; Neuburger, M; Vassal, L; Disant, C; Bittel, R; Fourcy, A

    1974-12-31

    with the heavy metals Hg, Cu, Zn, Pb, and Cd is studied. The first three metals were determined by neutron activation and tae last two by atomic absorption spectrophotometry. The chemical rature of these metals and their biological effect leads to different results from those obtained for tae principal fission products. As a rule the heavy metal concentrations at harvest are much lower than taat of the foods ingested by lactating cows. The cow plays the role of filter. If the concentration of these elements is considered in mu g/g of fresh material there is a reconcentration of these heavy metals in cream and cheese, probably cornected with their physico-chemical affinity for proteins. (JSR)

  2. Bone lesions in Chinese POEMS syndrome patients: imaging characteristics and clinical implications

    Directory of Open Access Journals (Sweden)

    Fengdan Wang

    2016-08-01

    Full Text Available Objective. Bone lesion is crucial for diagnosing and management of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin change (POEMS syndrome, a rare plasma cell disorder. This study is to compare the effectiveness of X-ray skeletal survey (SS and computed tomography (CT for detecting bone lesions in Chinese POEMS syndrome patients, and to investigate the relationship between bone lesion features and serum markers. Methods. SS and chest/abdomen/pelvic CT images of 38 Chinese patients (26 males, 12 females, aged 21–70 years with POEMS syndrome recruited at our medical center between January 2013 and January 2015 were retrospectively analyzed. Bone lesions identified by CT were further categorized according to the size (10 mm and appearance (osteosclerotic, lytic, mixed. The percentage of plasma cells in bone marrow smears, type of immunoglobulin, platelet (Plt, and levels of serum bone metabolic markers and inflammatory factors including alkaline phosphatase (ALP, calcium, phosphate, parathyroid hormone (PTH, beta-isomerized C-telopeptide (β-CTx, vascular endothelial growth factor (VEGF, and interleukin (IL-6 levels were also recorded. Results. Of the 38 POEMS syndrome patients, the immunoglobulin heavy chain isotypes were IgA in 25 patients (65.8%; 25/38 and IgG in 13 patients (34.2%; 13/38, and the light chain isotypes were λ in 35 patients (92.1%; 35/38 and κ in 3 patients (7.9%; 3/38. There were 23 patients with thrombocytosis. More patients with bone lesions were detected by CT than by SS (97.4% vs. 86.8%. The most commonly affected location was the pelvis (89.5%, followed by the spine, clavicle/scapula/sternum/ribs, skull, and long bones. Of the 38 POEMS syndrome patients, 35 (94.6% had osteosclerotic and 32 (86.5% had mixed lesions. Osteosclerotic lesions were typically scattered, variable in size, and plaque-like, whereas mixed lesions were pouch-shaped or soup bubble-like with a clear sclerotic margin and were

  3. Pattern statistics on Markov chains and sensitivity to parameter estimation

    Directory of Open Access Journals (Sweden)

    Nuel Grégory

    2006-10-01

    Full Text Available Abstract Background: In order to compute pattern statistics in computational biology a Markov model is commonly used to take into account the sequence composition. Usually its parameter must be estimated. The aim of this paper is to determine how sensitive these statistics are to parameter estimation, and what are the consequences of this variability on pattern studies (finding the most over-represented words in a genome, the most significant common words to a set of sequences,.... Results: In the particular case where pattern statistics (overlap counting only computed through binomial approximations we use the delta-method to give an explicit expression of σ, the standard deviation of a pattern statistic. This result is validated using simulations and a simple pattern study is also considered. Conclusion: We establish that the use of high order Markov model could easily lead to major mistakes due to the high sensitivity of pattern statistics to parameter estimation.

  4. Aspirin and salicylate bind to immunoglobulin heavy chain binding protein (BiP) and inhibit its ATPase activity in human fibroblasts.

    Science.gov (United States)

    Deng, W G; Ruan, K H; Du, M; Saunders, M A; Wu, K K

    2001-11-01

    Salicylic acid (SA), an endogenous signaling molecule of plants, possesses anti-inflammatory and anti-neoplastic actions in human. Its derivative, aspirin, is the most commonly used anti-inflammatory and analgesic drug. Aspirin and sodium salicylate (salicylates) have been reported to have multiple pharmacological actions. However, it is unclear whether they bind to a cellular protein. Here, we report for the first time the purification from human fibroblasts of a approximately 78 kDa salicylate binding protein with sequence identity to immunoglobulin heavy chain binding protein (BiP). The Kd values of SA binding to crude extract and to recombinant BiP were 45.2 and 54.6 microM, respectively. BiP is a chaperone protein containing a polypeptide binding site recognizing specific heptapeptide sequence and an ATP binding site. A heptapeptide with the specific sequence displaced SA binding in a concentration-dependent manner whereas a control heptapeptide did not. Salicylates inhibited ATPase activity stimulated by this specific heptapeptide but did not block ATP binding or induce BiP expression. These results indicate that salicylates bind specifically to the polypeptide binding site of BiP in human cells that may interfere with folding and transport of proteins important in inflammation.

  5. Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenic forms of Burkitt lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Neri, A.; Barriga, F.; Knowles, D.M.; Magrath, I.T.; Dalla-Favera, R.

    1988-04-01

    The authors show that endemic (eBL), sporadic (sBL), and acquired immunodeficiency syndrome-associated (AIDS-BL) forms of Burkitt lymphoma (BL) carrying t(8; 14) chromosomal translocations display different breakpoints within the immunoglobulin heavy-chain locus (IGH) on chromosome 14. In sBL (7 out of 11) and AIDS-BL (5 out of 6), the breakpoints occurred within or near the IGH ..mu.. switch (S/sub mu/) region on chromosome 14 and within the c-myc locus (MYC) on chromosome 8. In most eBL (13 out of 16) the breakpoints were mapped within or 5' to the IGH joining J/sub H/ region on chromosome 14 and outside the MYC locus on chromosome 8. Cloning and sequencing of the (8; 14) chromosomal junctions from two eBL cell lines and one eBL biopsy sample show that the recombination do not involve IGH-specific recombination signals on chromosome 14 or homologous sequences on chromosome 8, suggesting that these events are not likely to be mediated by the same mechanisms or enzymes as in IGH rearrangements. In general, these data have implications for the timing of occurrence of chromosomal translocations during B-cell differentiation in different BL types.

  6. The importance of subfragment 2 and C-terminus of myosin heavy chain for thick filament assembly in skeletal muscle cells.

    Science.gov (United States)

    Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Muroya, Susumu; Chikuni, Koichi; Hattori, Akihito; Nishimura, Takanori

    2015-04-01

    In skeletal muscle cells, myofibrillar proteins are highly organized into sarcomeres in which thick filaments interdigitate with thin filaments to generate contractile force. The size of thick filaments, which consist mainly of myosin molecules, is strictly controlled. However, little is known about the mechanisms by which myosin molecules assemble into thick filaments. Here, we assessed the ability of each domain of myosin heavy chain (Myh) to form thick filaments. We showed that exogenously expressed subfragment 2 (S2) + light meromyosin (LMM) of Myh was efficiently incorporated into thick filaments in muscle cells, although neither solely expressed S2 nor LMM targeted to thick filaments properly. In nonmuscle COS7 cells, S2+LMM formed more enlarged filaments/speckles than LMM. These results suggest that Myh filament formation is induced by S2 accompanying LMM. We further examined the effects of Myh C-terminus on thick filament assembly. C-terminal deletion mutants were incorporated not into entire thick filaments but rather into restricted regions of thick filaments. Our findings suggest that the elongation of myosin filaments to form thick filaments is regulated by S2 as well as C-terminus of LMM. © 2014 Japanese Society of Animal Science.

  7. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

    International Nuclear Information System (INIS)

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density

  8. Tumor necrosis factor-α attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Kou, Xingrui; Zhao, Qiudong; Zhao, Xue; Li, Rong; Wei, Lixin; Wu, Mengchao; Jing, Yingying; Deng, Weijie; Sun, Kai; Han, Zhipeng; Ye, Fei; Yu, Guofeng; Fan, Qingmin; Gao, Lu

    2013-01-01

    Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-α, which is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types. The basic objective of this study was to investigate the effects of TNF-α on the cell viability and apoptosis of hepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved. For this purpose, five different concentrations of TNF-α and two different serum settings (serum-cultured and serum-deprived) were used to investigate the effects of TNF-α on the cell viability and apoptosis of Hep3B and SMMC-7721 cells. TNF-α (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and autophagy conferred this process. BAY11-7082, a specific inhibitor of NF-κB, reversed the suppression of serum starvation-induced apoptosis by TNF-α. Moreover, TNF-α-induced NF-κB transactivation was suppressed by autophagy inhibitor 3-MA. In addition, TNF-α up-regulated Ferritin heavy chain (FHC) transiently by NF-κB activation and FHC levels were correlated with the TNF-α-induced protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells. Furthermore, FHC-mediated inhibition of apoptosis depended on suppressing ROS accumulation. Our findings suggested that autophagy conferred the TNF-α protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of the TNF-α/ NF-κB /FHC signaling pathway

  9. Cold exposure increases slow-type myosin heavy chain 1 (MyHC1) composition of soleus muscle in rats.

    Science.gov (United States)

    Mizunoya, Wataru; Iwamoto, Yohei; Sato, Yusuke; Tatsumi, Ryuichi; Ikeuchi, Yoshihide

    2014-03-01

    The aim of this study was to examine the effects of cold exposure on rat skeletal muscle fiber type, according to myosin heavy chain (MyHC) isoform and metabolism-related factors. Male Wistar rats (7 weeks old) were housed individually at 4 ± 2°C as a cold-exposed group or at room temperature (22 ± 2°C) as a control group for 4 weeks. We found that cold exposure significantly increased the slow-type MyHC1 content in the soleus muscle (a typical slow-type fiber), while the intermediate-type MyHC2A content was significantly decreased. In contrast to soleus, MyHC composition of extensor digitorum longus (EDL, a typical fast-type fiber) and gastrocnemius (a mix of slow-type and fast-type fibers) muscle did not change from cold exposure. Cold exposure increased mRNA expression of mitochondrial uncoupling protein 3 (UCP3) in both the soleus and EDL. Cold exposure also increased mRNA expression of myoglobin, peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and forkhead box O1 (FOXO1) in the soleus. Upregulation of UCP3 and PGC1α proteins were observed with Western blotting in the gastrocnemius. Thus, cold exposure increased metabolism-related factors in all muscle types that were tested, but MyHC isoforms changed only in the soleus. © 2013 Japanese Society of Animal Science.

  10. Measurement and Evaluation of Ecological Risk of Heavy Metals in Surface Sediments of Pars Special Economic Energy Zone

    OpenAIRE

    Arash Haghshenas; Masoud Hatami-manesh; Mohsen Mirzaei; MirMehrdad Mir Sanjari; Parisa Hossein Khezri

    2017-01-01

    Background: Today, heavy metals pollution in aquatic ecosystems is one of the most important global environmental problems. Because this metals have characteristics such as chemical stability, low degradability and bioaccumulation ability at different levels of the food chain cause the abundant ecological risks for organisms. Therefore, this study investigates the concentration of heavy metals (mercury, cadmium, lead, chromium, copper, nickel, zinc and iron) and ecological risk assessment of ...

  11. Distribution and behaviour of selected heavy metals and other elements in various components of the southern Baltic ecosystem

    International Nuclear Information System (INIS)

    Szefer, P.

    1998-01-01

    The concentrations and discrimination of selected heavy metals in biota from the southern Baltic indicate that a large group of the Baltic organisms bioaccumulates Fe and Pb but discriminates against U. There appears to be no significant transfer of heavy metals along successive levels of the food chain. The distribution of the heavy metals in the associated sediments is a result of the anthropogenic input of Zn, Pb, Cd, Ag, P and Cu. It is suggested that Pb is introduced to the Polish sector of the Baltic Sea mainly by atmospheric transport whereas other heavy-metal pollutants are introduced mainly from the Vistula River. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  12. Exploration of immunoglobulin transcriptomes from mice immunized with three-finger toxins and phospholipases A2 from the Central American coral snake, Micrurus nigrocinctus

    Directory of Open Access Journals (Sweden)

    Andreas H. Laustsen

    2017-01-01

    Full Text Available Snakebite envenomings represent a neglected public health issue in many parts of the rural tropical world. Animal-derived antivenoms have existed for more than a hundred years and are effective in neutralizing snake venom toxins when timely administered. However, the low immunogenicity of many small but potent snake venom toxins represents a challenge for obtaining a balanced immune response against the medically relevant components of the venom. Here, we employ high-throughput sequencing of the immunoglobulin (Ig transcriptome of mice immunized with a three-finger toxin and a phospholipase A2 from the venom of the Central American coral snake, Micrurus nigrocinctus. Although exploratory in nature, our indicate results showed that only low frequencies of mRNA encoding IgG isotypes, the most relevant isotype for therapeutic purposes, were present in splenocytes of five mice immunized with 6 doses of the two types of toxins over 90 days. Furthermore, analysis of Ig heavy chain transcripts showed that no particular combination of variable (V and joining (J gene segments had been selected in the immunization process, as would be expected after a strong humoral immune response to a single antigen. Combined with the titration of toxin-specific antibodies in the sera of immunized mice, these data support the low immunogenicity of three-finger toxins and phospholipases A2found in M. nigrocinctusvenoms, and highlight the need for future studies analyzing the complexity of antibody responses to toxins at the molecular level.

  13. Synthesis of total protein (TP) and myosin heavy chain (HC) isozymes in pressure overloaded rabbit hearts

    International Nuclear Information System (INIS)

    Nagai, R.; Martin, B.J.; Pritzl, N.; Zak, R.; Low, R.B.; Stirewalt, W.S.; Alpert, N.R.; Litten, R.Z.

    1986-01-01

    Pulmonary artery banding (PO) leads to a rapid increase in right ventricular (RV) weight as well as a shift toward β myosin isozyme. They determined: (1) the contributions of changes in the capacity (RNA content) and efficiency of total protein synthesis to the increase in RV weight; and (2) the relative contributions of translational and pretranslational mechanisms to the shift in myosin HC isotypes. The rates of synthesis in vivo of TP, α- and β-HC were measured by a constant infusion technique using 3 H-leucine. TP synthesis was 7 +/- 2(SD) mg/day in control (RV:367 +/- 70 mg) and was increased by 2.6 fold at day 2 and 2.9 fold at day 4 following PO (p < 0.01). RV RNA content was increased by 83% at day 2 and 103% at day 4 PO (p < 0.05). The efficiency of synthesis (rate/RNA) was also significantly higher at these time points (1.4- and 1.3-fold). β-HC synthesis was 0.6 +/- 0.2 mg/day in control and increased by 2.6 fold at day 2 and 3.5 fold at day 4 following PO. In contrast, the rate of synthesis of α-HC was unchanged. The relative rates of β-HC to total HC synthesis was correlated linearly with the relative levels of β-myosin mRNA as measured by S1 nuclease mapping. They conclude that increases in the proportion of β-HC myosin following PO is due to increases in the relative amount of β-myosin mRNA and therefore involves modulation of a pretranslational mechanism

  14. Heavy rare earths, permanent magnets, and renewable energies: An imminent crisis

    International Nuclear Information System (INIS)

    Smith Stegen, Karen

    2015-01-01

    This article sounds the alarm that a significant build-out of efficient lighting and renewable energy technologies may be endangered by shortages of rare earths and rare earth permanent magnets. At the moment, China is the predominant supplier of both and its recent rare earth industrial policies combined with its own growing demand for rare earths have caused widespread concern. To diversify supplies, new mining—outside of China—is needed. But what many observers of the “rare earth problem” overlook is that China also dominates in (1) the processing of rare earths, particularly the less abundant heavy rare earths, and (2) the supply chains for permanent magnets. Heavy rare earths and permanent magnets are critical for many renewable energy technologies, and it will require decades to develop new non-Chinese deposits, processing capacity, and supply chains. This article clarifies several misconceptions, evaluates frequently proposed solutions, and urges policy makers outside of China to undertake measures to avert a crisis, such as greater support for research and development and for the cultivation of intellectual capital. - Highlights: • Rare earths are needed for many efficient lighting and renewable energy technologies. • The industries for rare earths and permanent magnets are dominated by China. • China's reliability is compromised, necessitating non-Chinese mining and processing. • Recycling, substitution and reducing rare earth content are long-term solutions only. • Policy makers should support development of supply chains and intellectual capital

  15. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats (the 3rd report)

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Wang, Xiao Dong; Nagaoka, Shunji; Nojima, Kumie

    2005-01-01

    The effects of acute exposure of heavy ion on the properties of spinal motoneurons and their innervating muscle fibers were investigated. A 15, 20, 40, 50, or 70 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in 8-week-old male rats. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of spinal motoneurons innervating the soleus and plantaris muscles were analyzed by a computer-assisted image processing system. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no differences in the number of spinal motoneurons innervating the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in spinal motoneurons of the heavy-ion-exposed rats at the dose levels of 40, 50, and 70 Gy. There were no differences in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. It is concluded that more than 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there are no influences on the properties of muscle fibers which they innervate. (author)

  16. Expression and characterization of recombinant single-chain salmon class I MHC fused with beta2-microglobulin with biological activity

    DEFF Research Database (Denmark)

    Zhao, Heng; Stet, René J M; Skjødt, Karsten

    2008-01-01

    Heterodimeric class I major histocompatibility complex (MHC) molecules consist of a putative 45-kDa heavy chain and a 12-kDa beta2-microglobulin (beta2m) light chain. The knowledge about MHC genes in Atlantic salmon accumulated during the last decade has allowed us to generate soluble and stable ...... MHC class I molecules with biological activity. We report here the use of a bacterial expression system to produce the recombinant single-chain MHC molecules based on a specific allele Sasa-UBA*0301. This particular allele was selected because previous work has shown its association...... antibodies were successfully produced against both the MHC class I heavy chain and beta(2)m, and showed binding to the recombinant molecule. The recombinant complex Sasabeta2mUBA*0301 was expressed and isolated; the production was scaled up by adjusting to its optimal conditions. Subsequently......, the recombinant proteins were purified by affinity chromatography using mAb against beta2m and alpha3. Eluates were analyzed by Western blot and refolded by the removal of denaturant. The correct folding was confirmed by measuring its binding capacity against mAb produced to recognize the native form of MHC...

  17. Immune recognition of botulinum neurotoxin B: antibody-binding regions on the heavy chain of the toxin.

    Science.gov (United States)

    Dolimbek, Behzod Z; Steward, Lance E; Aoki, K Roger; Atassi, M Zouhair

    2008-02-01

    The purpose of this work was to map the continuous regions recognized by human, horse and mouse anti-botulinum neurotoxin B (BoNT/B) antibodies (Abs). We synthesized a panel of sixty 19-residue peptides (peptide C31 was 24 residues) that overlapped consecutively by 5 residues and together encompassed the entire heavy chain of BoNT/B (H/B, residues 442-1291). Abs from the three host species recognized similar, but not identical, peptides. There were also peptides recognized by two or only by one host species. Where a peptide was recognized by Abs of more than one host species, these Abs were at different levels among the species. Human, horse and mouse Abs bound, although in different amounts, to regions within peptides 736-754, 778-796, 848-866, 932-950, 974-992, 1058-1076 and 1128-1146. Human and horse Abs bound to peptides 890-908 and 1170-1188. Human and mouse Abs recognized peptides 470-488/484-502 overlap, 638-656, 722-740, 862-880, 1030-1048, 1072-1090, 1240-1258 and 1268-1291. We concluded that the antigenic regions localized with the three antisera are quite similar, exhibiting in some cases a small shift to the left or to the right. This is consistent with what is known about protein immune recognition. In the three-dimensional structure, the regions recognized on H/B by anti-BoNT/B Abs occupied surface locations and analysis revealed no correlation between these surface locations and surface electrostatic potential, hydrophilicity, hydrophobicity, or temperature factor. A region that bound mouse Abs overlapped with a recently defined site on BoNT/B that binds to mouse and rat synaptotagmin II, thus providing a molecular explanation for the blocking (protecting) activity of these Abs. The regions thus localized afford candidates for incorporation into a synthetic vaccine design.

  18. Muscle fiber type specific induction of slow myosin heavy chain 2 gene expression by electrical stimulation

    International Nuclear Information System (INIS)

    Crew, Jennifer R.; Falzari, Kanakeshwari; DiMario, Joseph X.

    2010-01-01

    Vertebrate skeletal muscle fiber types are defined by a broad array of differentially expressed contractile and metabolic protein genes. The mechanisms that establish and maintain these different fiber types vary throughout development and with changing functional demand. Chicken skeletal muscle fibers can be generally categorized as fast and fast/slow based on expression of the slow myosin heavy chain 2 (MyHC2) gene in fast/slow muscle fibers. To investigate the cellular and molecular mechanisms that control fiber type formation in secondary or fetal muscle fibers, myoblasts from the fast pectoralis major (PM) and fast/slow medial adductor (MA) muscles were isolated, allowed to differentiate in vitro, and electrically stimulated. MA muscle fibers were induced to express the slow MyHC2 gene by electrical stimulation, whereas PM muscle fibers did not express the slow MyHC2 gene under identical stimulation conditions. However, PM muscle fibers did express the slow MyHC2 gene when electrical stimulation was combined with inhibition of inositol triphosphate receptor (IP3R) activity. Electrical stimulation was sufficient to increase nuclear localization of expressed nuclear-factor-of-activated-T-cells (NFAT), NFAT-mediated transcription, and slow MyHC2 promoter activity in MA muscle fibers. In contrast, both electrical stimulation and inhibitors of IP3R activity were required for these effects in PM muscle fibers. Electrical stimulation also increased levels of peroxisome-proliferator-activated receptor-γ co-activator-1 (PGC-1α) protein in PM and MA muscle fibers. These results indicate that MA muscle fibers can be induced by electrical stimulation to express the slow MyHC2 gene and that fast PM muscle fibers are refractory to stimulation-induced slow MyHC2 gene expression due to fast PM muscle fiber specific cellular mechanisms involving IP3R activity.

  19. Processing-Dependent and Clonal Contamination Patterns of Listeria monocytogenes in the Cured Ham Food Chain Revealed by Genetic Analysis.

    Science.gov (United States)

    Morganti, Marina; Scaltriti, Erika; Cozzolino, Paolo; Bolzoni, Luca; Casadei, Gabriele; Pierantoni, Marco; Foni, Emanuela; Pongolini, Stefano

    2016-02-01

    The quantitative and qualitative patterns of environmental contamination by Listeria monocytogenes were investigated in the production chain of dry-cured Parma ham. Standard arrays of surfaces were sampled in processing facilities during a single visit per plant in the three compartments of the food chain, i.e., ham production (19 plants) and postproduction, which was divided into deboning (43 plants) and slicing (25 plants) steps. The numbers of sampled surfaces were 384 in ham production, with 25 positive for L. monocytogenes, and 1,084 in postproduction, with 83 positives. Statistical analysis of the prevalence of contaminated surfaces showed that in ham production, contamination was higher at the beginning of processing and declined significantly toward the end, while in postproduction, prevalence rose toward the end of processing. Prevalence was higher in the deboning facilities than in slicing facilities and was dependent on the type of surface (floor/drainage > clothing > equipment). The qualitative pattern of contamination was investigated through an analysis of the survey isolates and a set of isolates derived from routine monitoring, including longitudinal isolations. Pulsed-field gel electrophoresis (PFGE) and whole-genome single-nucleotide polymorphism (SNP) analysis revealed a remarkable clonality of L. monocytogenes within plants, with the detection of 16 plant-specific clones out of 17 establishments with multiple isolates. Repeated detections of clonal isolates >6 months apart were also observed. Six was the maximum number of between-isolate differences in core SNPs observed within these clones. Based on the same six-SNP threshold, three clusters of clonal isolates, shared by six establishments, were also identified. The spread of L. monocytogenes within and between plants, as indicated by its clonal behavior, is a matter of concern for the hygienic management of establishments. Copyright © 2016, American Society for Microbiology. All Rights

  20. Mixed-valent and heavy fermions and related systems: Technical progress report, October 1, 1987-September 14, 1988

    International Nuclear Information System (INIS)

    Schlottmann, P.

    1988-01-01

    This paper discusses Ce-impurities in LaB 6 and LaAL 2 , critical behavior of ferromagnetic Heisenberg chains; integrable SU(2)---invariant model; soluble narrow-band model with possible relevance to heavy-fermions and resonating valence bonds, soluble variant of the two-impurity Anderson model; De Haas-van Alphen effect in the Anderson lattice for large orbital degeneracy; interactions mediated by spin-fluctuations in He 3 ; mixed-valence and heavy-fermion systems and high-temperature superconductivity

  1. A Longitudinal Investigation of Heavy Drinking and Physical Dating Violence in Men and Women

    OpenAIRE

    Stappenbeck, Cynthia A.; Fromme, Kim

    2010-01-01

    Examinations of heavy drinking and dating violence have typically focused on either female victimization or male perpetration; yet recent findings indicate that mutual aggression is the most common pattern of dating violence. The current study investigated the relation between heavy drinking and dating violence for both men and women. Participants (N = 2,247) completed surveys that assessed their heavy drinking and dating violence frequency across the first three years of college. Findings in...

  2. Antibiogram and heavy metal tolerance of bullfrog bacteria in Malaysia

    OpenAIRE

    Tee, L.W.; Najiah, M.

    2011-01-01

    Bacterial isolates from 30 farmed bullfrogs (Lithobates catesbeianus) weighing 500-600 g at Johore, Malaysia with external clinical signs of ulcer, red leg and torticollis were tested for their antibiograms and heavy metal tolerance patterns. A total of 17 bacterial species with 77 strains were successfully isolated and assigned to 21 antibiotics and 4 types of heavy metal (Hg2+, Cr6+, Cd2+, Cu2+). Results revealed that bacteria were resistant against lincomycin (92%), oleandomycin (72.7%) an...

  3. Synthesis and crystal structure of the isotypic rare earth thioborates Ce[BS3], Pr[BS3], and Nd[BS3

    International Nuclear Information System (INIS)

    Hunger, Jens; Borna, Marija; Kniep, Ruediger

    2010-01-01

    The orthothioborates Ce[BS 3 ], Pr[BS 3 ] and Nd[BS 3 ] were prepared from mixtures of the rare earth (RE) metals together with amorphous boron and sulfur summing up to the compositions CeB 3 S 6 , PrB 5 S 9 and NdB 3 S 6 . The following preparation routes were used: solid state reactions with maximum temperatures of 1323 K and high-pressure high-temperature syntheses at 1173 K and 3 GPa. Pr[BS 3 ] and Nd[BS 3 ] were also obtained from rare earth chlorides RECl 3 and sodium thioborate Na 2 B 2 S 5 by metathesis type reactions at maximum temperatures of 1073 K. The crystal structure of the title compounds was determined from X-ray powder diffraction data. The thioborates are isotypic and crystallize in the orthorhombic spacegroup Pna2 1 (No. 33; Z=4; Ce: a=7.60738(6)A, b=6.01720(4)A, c=8.93016(6)A; Pr: a=7.56223(4)A, b=6.00876(2)A, c=8.89747(4)A; Nd: a=7.49180(3)A, b=6.00823(2)A, c=8.86197(3)A) . The crystal structures contain isolated [BS 3 ] 3- groups with boron in trigonal-planar coordination. The sulfur atoms form the vertices of undulated kagome nets, which are stacked along [100] according to the sequence ABAB. Within these nets every second triangle is occupied by boron and the large hexagons are centered by rare earth ions, which are surrounded by overall nine sulfur species. - Abstract: Graphical Abstract Legend (TOC Figure): Table of Contents Figure The isotypic orthothioborates Ce[BS 3 ], Pr[BS 3 ] and Nd[BS 3 ] were prepared using different preparation routes. The crystal structure of the title compounds was determined from X-ray powder diffraction data. The crystal structures contain isolated [BS 3 ] 3- groups with boron in trigonal-planar coordination. The sulfur atoms form the vertices of corrugated kagome nets (sketched with blue dotted lines), which are stacked along [100] according to the sequence ABAB. Within these nets every second triangle is occupied by boron and the large hexagons are centered by rare earth ions, which are surrounded by

  4. Heavy alcohol use and suicidal behavior among people who use illicit drugs: A cohort study.

    Science.gov (United States)

    Kennedy, Mary Clare; Marshall, Brandon D L; Hayashi, Kanna; Nguyen, Paul; Wood, Evan; Kerr, Thomas

    2015-06-01

    People who use illicit drugs (PWUD) are known to experience high rates of suicidal behavior. While heavy alcohol use has been associated with suicide risk, its impact on the suicidal behavior of PWUD has not been well characterized. Therefore, we examined the relationship between heavy alcohol use and suicidal behavior among PWUD in Vancouver, Canada. Data are derived from two prospective cohort studies of PWUD in Vancouver, Canada, from 2005 to 2013. Participants completed questionnaires that elicited information regarding sociodemographics, drug use patterns, and mental health problems, including suicidal behavior. We used recurrent event survival analyses to estimate the independent association between at-risk/heavy drinking (based on National Institute of Alcohol Abuse and Alcoholism [NIAAA] criteria) and risk of incident, self-reported suicide attempts. Of 1757 participants, 162 participants (9.2%) reported 227 suicide attempts over the 8-year study period, resulting in an incidence rate of 2.5 cases per 100 person-years. After adjusting for potential confounders, including intensive illicit drug use patterns, heavy alcohol use (adjusted hazard ratio [AHR] = 1.97; 95% confidence interval [CI] = 1.39, 2.78) was positively associated with an increased risk of suicidal behavior. We observed a high burden of suicidal behavior among a community-recruited sample of PWUD. Heavy alcohol use predicted a higher risk of suicide attempt, independent of other drug use patterns. These findings demonstrate the need for evidence-based interventions to address suicide risk among PWUD, particularly those who are heavy consumers of alcohol. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. The heavy top quark and supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Hall, L.J. [Lawrence Berkeley Lab., CA (United States)]|[Univ. of California, Berkeley, CA (United States)

    1997-01-01

    Three aspects of supersymmetric theories are discussed: electroweak symmetry breaking, the issues of flavor, and gauge unification. The heavy top quark plays an important, sometimes dominant, role in each case. Additional symmetries lead to extensions of the Standard Model which can provide an understanding for many of the outstanding problems of particle physics. A broken supersymmetric extension of spacetime allows electroweak symmetry breaking to follow from the dynamics of the heavy top quark; an extension of isospin provides a constrained framework for understanding the pattern of quark and lepton masses; and a grand unified extension of the Standard Model gauge group provides an elegant understanding of the gauge quantum numbers of the components of a generation. Experimental signatures for each of these additional symmetries are discussed.

  6. The heavy top quark and supersymmetry

    International Nuclear Information System (INIS)

    Hall, L.J.; Univ. of California, Berkeley, CA

    1996-01-01

    Three aspects of supersymmetric theories are discussed: electroweak symmetry breaking, the issues of flavor, and gauge unification. The heavy top quark plays an important, sometimes dominant, role in each case. Additional symmetries lead to extensions of the standard model which can provide an understanding for many of the outstanding problems of particle physics. A broken supersymmetric extension of spacetime allows electroweak symmetry breaking to follow from the dynamics of the heavy top quark; an extension of isospin provides a constrained framework for understanding the pattern of quark and lepton masses; and a grand unified extension of the standard model gauge group provides an elegant understanding of the gauge quantum numbers of the components of a generation. Experimental signatures for each of these additional symmetries are discussed

  7. The heavy top quark and supersymmetry

    International Nuclear Information System (INIS)

    Hall, L.J.

    1997-01-01

    Three aspects of supersymmetric theories are discussed: electroweak symmetry breaking, the issues of flavor, and gauge unification. The heavy top quark plays an important, sometimes dominant, role in each case. Additional symmetries lead to extensions of the Standard Model which can provide an understanding for many of the outstanding problems of particle physics. A broken supersymmetric extension of spacetime allows electroweak symmetry breaking to follow from the dynamics of the heavy top quark; an extension of isospin provides a constrained framework for understanding the pattern of quark and lepton masses; and a grand unified extension of the Standard Model gauge group provides an elegant understanding of the gauge quantum numbers of the components of a generation. Experimental signatures for each of these additional symmetries are discussed

  8. Spatial Distribution and Mobility Assessment of Carcinogenic Heavy Metals in Soil Profiles Using Geostatistics and Random Forest, Boruta Algorithm

    Directory of Open Access Journals (Sweden)

    Asma Shaheen

    2018-03-01

    Full Text Available In third world countries, industries mainly cause environmental contamination due to lack of environmental policies or oversight during their implementation. The Sheikhupura industrial zone, which includes industries such as tanneries, leather, chemical, textiles, and colour and dyes, contributes massive amounts of untreated effluents that are released directly into drains and used for the irrigation of crops and vegetables. This practice causes not only soil contamination with an excessive amount of heavy metals, but is also considered a source of toxicity in the food chain, i.e., bioaccumulation in plants and ultimately in human body organs. The objective of this research study was to assess the spatial distribution of the heavy metals chromium (Cr, cadmium (Cd, and lead (Pb, at three depths of soil using geostatistics and the selection of significant contributing variables to soil contamination using the Random Forest (RF function of the Boruta Algorithm. A total of 60 sampling locations were selected in the study area to collect soil samples (180 samples at three depths (0–15 cm, 15–30 cm, and 60–90 cm. The soil samples were analysed for their physico-chemical properties, i.e., soil saturation, electrical conductivity (EC, organic matter (OM, pH, phosphorus (P, potassium (K, and Cr, Cd, and Pb using standard laboratory procedures. The data were analysed with comprehensive statistics and geostatistical techniques. The correlation coefficient matrix between the heavy metals and the physico-chemical properties revealed that electrical conductivity (EC had a significant (p ≤ 0.05 negative correlation with Cr, Cd, and Pb. The RF function of the Boruta Algorithm employed soil depth as a classifier and ranked the significant soil contamination parameters (Cr, Cd, Pb, EC, and P in relation to depth. The mobility factor indicated the leachate percentage of heavy metals at different vertical depths of soil. The spatial distribution pattern of

  9. B-Lymphoblastic Lymphomas Evolving from Follicular Lymphomas Co-Express Surrogate Light Chains and Mutated Gamma Heavy Chains.

    Science.gov (United States)

    Slot, Linda M; Hoogeboom, Robbert; Smit, Laura A; Wormhoudt, Thera A M; Biemond, Bart J; Oud, Monique E C M; Schilder-Tol, Esther J M; Mulder, André B; Jongejan, Aldo; van Kampen, Antoine H C; Kluin, Philip M; Guikema, Jeroen E J; Bende, Richard J; van Noesel, Carel J M

    2016-12-01

    Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma able to transform into germinal center-type diffuse large B-cell lymphoma. We describe four extraordinary cases of FL, which progressed to TdT + CD20 - precursor B-lymphoblastic lymphoma (B-LBL). Fluorescence in situ hybridization analysis showed that all four B-LBLs had acquired a MYC translocation on transformation. Comparative genomic hybridization analysis of one case demonstrated that in addition to 26 numerical aberrations that were shared between the FL and B-LBL, deletion of CDKN2A/B and 17q11, 14q32 amplification, and copy-neutral loss of heterozygosity of 9p were gained in the B-LBL cells. Whole-exome sequencing revealed mutations in FMN2, NEB, and SYNE1 and a nonsense mutation in KMT2D, all shared by the FL and B-LBL, and TNFRSF14, SMARCA2, CCND3 mutations uniquely present in the B-LBL. Remarkably, all four FL-B-LBL pairs expressed IgG. In two B-LBLs, evidence was obtained for ongoing rearrangement of IG light chain variable genes and expression of the surrogate light chain. IGHV mutation analysis showed that all FL-B-LBL pairs harbored identical or near-identical somatic mutations. From the somatic gene alterations found in the IG and non-IG genes, we conclude that the FLs and B-LBLs did not develop in parallel from early t(14;18)-positive IG-unmutated precursors, but that the B-LBLs developed from preexistent FL subclones that accumulated additional genetic damage. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. NEB view of development potential and markets for heavy crude oil. [Canada

    Energy Technology Data Exchange (ETDEWEB)

    Scotland, W A; Gutek, A M.H.

    1977-01-01

    The phased reduction in total crude oil and equivalent exports, from 911 Mpbd in 1974 to 465 Mbpd in 1976, has no doubt had a disruptive effect on the rate of development of heavy crude oil reserves. The effect could have become more series as total exports continued to drop. However, the separate licensing of heavy crude oil for export will allow heavy crude oil to enter available markets until the early 1980s. The construction of one or several upgrading facilities by the early 1980s, combined with growing domestic requirements for heavy crude oil feedstock, could make the disposition of heavy oil largely independent of the purchasing patterns of export markets. The prospect of increased market stability combined with increasing cash flows should provide an appropriate environment to optimize the role that heavy oil resources can play in Canada's future energy balance. (12 refs.)

  11. Multi-element sewer slime impact pattern - a quantitative characteristic enabling identification of the source of heavy metal discharges into sewer systems

    Energy Technology Data Exchange (ETDEWEB)

    Kintrup, J. [Chemistry Lab., Wessling GmbH, Hannover (Germany); Wuensch, G. [Lehrgebiet Analytische Chemie, Univ. Hannover (Germany)

    2001-11-01

    The capability of sewer slime to accumulate heavy metals from municipal wastewater can be exploited to identify the sources of sewage sludge pollution. Former investigations of sewer slime looked for a few elements only and could, therefore, not account for deviations of the enrichment efficiency of the slime or for irregularities from sampling. Results of ICP-MS multi element determinations were analyzed by multivariate statistical methods. A new dimensionless characteristic ''sewer slime impact'' is proposed, which is zero for unloaded samples. Patterns expressed in this data format specifically extract the information required to identify the type of pollution and polluter quicker and with less effort and cost than hitherto. (orig.)

  12. Role of kinesin heavy chain in Crumbs localization along the rhabdomere elongation in Drosophila photoreceptor.

    Directory of Open Access Journals (Sweden)

    Garrett P League

    Full Text Available BACKGROUND: Crumbs (Crb, a cell polarity gene, has been shown to provide a positional cue for the extension of the apical membrane domain, adherens junction (AJ, and rhabdomere along the growing proximal-distal axis during Drosophila photoreceptor morphogenesis. In developing Drosophila photoreceptors, a stabilized microtubule structure was discovered and its presence was linked to polarity protein localization. It was therefore hypothesized that the microtubules may provide trafficking routes for the polarity proteins during photoreceptor morphogenesis. This study has examined whether Kinesin heavy chain (Khc, a subunit of the microtubule-based motor Kinesin-1, is essential in polarity protein localization in developing photoreceptors. METHODOLOGY/PRINCIPAL FINDINGS: Because a genetic interaction was found between crb and khc, Crb localization was examined in the developing photoreceptors of khc mutants. khc was dispensable during early eye differentiation and development. However, khc mutant photoreceptors showed a range of abnormalities in the apical membrane domain depending on the position along the proximal-distal axis in pupal photoreceptors. The khc mutant showed a progressive mislocalization in the apical domain along the distal-proximal axis during rhabdomere elongation. The khc mutation also led to a similar progressive defect in the stabilized microtubule structures, strongly suggesting that Khc is essential for microtubule structure and Crb localization during distal to proximal rhabdomere elongation in pupal morphogenesis. This role of Khc in apical domain control was further supported by khc's gain-of-function phenotype. Khc overexpression in photoreceptors caused disruption of the apical membrane domain and the stabilized microtubules in the developing photoreceptors. CONCLUSIONS/SIGNIFICANCE: In summary, we examined the role of khc in the regulation of the apical Crb domain in developing photoreceptors. Since the rhabdomeres in

  13. Data on heavy metals and selected anions in the Persian popular herbal distillates

    Directory of Open Access Journals (Sweden)

    Mozhgan Keshtkar

    2016-09-01

    Full Text Available In this data article, we determined the concentration levels of heavy metals including Pb, Co, Cd, Mn, Mg, Fe and Cu as well as selected anions including NO3− , NO2−, PO4−3 and SO4−2 in the most used and popular herbal distillates in Iran. It is well known that heavy metals may pose a serious health hazard due to their bioaccumulation throughout the trophic chain (“Heavy metals (Cd, Cu, Ni and Pb content in two fish species of Persian Gulf in Bushehr Port, Iran” (Dobaradaran et al., 2013 [1]; “Comparative investigation of heavy metal, trace, and macro element contents in commercially valuable fish species harvested off from the Persian Gulf” (Abadi et al., 2015 [2] as well as some other environmental pollutions, “Assessment of sediment quality based on acid-volatile sulfide and simultaneously extracted metals in heavily industrialized area of Asaluyeh, Persian Gulf: concentrations, spatial distributions, and sediment bioavailability/toxicity” (Arfaeinia et al., 2016 [3]. The concentration levels of heavy metals and anions in herbal distillates samples were determined using flame atomic absorption spectrometry (FAAS, Varian AA240, Australia and a spectrophotometer (M501 Single Beam Scanning UV/VIS, UK respectively. Keywords: Daily intake, Herbal distillates, Heavy metals, Selected anions

  14. Cloning of skeletal myosin heavy chain gene family from adult pleopod muscle and whole larvae of shrimps.

    Science.gov (United States)

    Koyama, Hiroki; Piyapattanakorn, Sanit; Watabe, Shugo

    2013-06-01

    The physiological and biological properties of skeletal muscle in crustacea have not been well understood compared with those of vertebrates. The present study focused on myosin, the major protein in skeletal muscle, from shrimps. In our previous study, two full-length genes encoding myosin heavy chain (MHC), a large subunit of the myosin molecule, were cloned from abdominal fast skeletal muscle of kuruma Marsupenaeus japonicus, black tiger Penaeus monodon and Pacific white Penaeus vannamei shrimps, and named as MHCa and MHCb. In this study, we renamed these as MHC1 and MHC2, respectively, due to the presence of various isoforms newly identified. Partial MHC sequences were identified from pleopod muscle of these shrimps. Two MHCs, named MHC3 and MHC4, were identified from pleopod muscle of kuruma shrimp, whereas two MHCs, named MHC4 and MHC5, were cloned from Pacific white shrimp pleopod. MHC3 was cloned only from black tiger shrimp pleopod. Partial MHC sequences from zoea, mysis, and postlarvae of black tiger and Pacific white shrimps were also determined. The phylogenetic tree demonstrated that most MHCs from pleopod muscle and larval MHCs formed clades with MHC1 and MHC2, respectively. These MHCs were considered to be of fast type, since MHC1 and MHC2 are fast-type MHCs according to our previous study. MHC5 obtained from pleopod muscle of Pacific white shrimp in this study was monophyletic with American lobster Homarus americanus S2 slow tonic MHC previously reported, indicating that MHC5 from Pacific white shrimp is of slow type. Copyright © 2013 Wiley Periodicals, Inc.

  15. Prolonged Cre expression driven by the α-myosin heavy chain promoter can be cardiotoxic.

    Science.gov (United States)

    Pugach, Emily K; Richmond, Phillip A; Azofeifa, Joseph G; Dowell, Robin D; Leinwand, Leslie A

    2015-09-01

    Studying the importance of genetic factors in a desired cell type or tissue necessitates the use of precise genetic tools. With the introduction of bacteriophage Cre recombinase/loxP mediated DNA editing and promoter-specific Cre expression, it is feasible to generate conditional knockout mice in which particular genes are disrupted in a cell type-specific manner in vivo. In cardiac myocytes, this is often achieved through α-myosin heavy chain promoter (αMyHC)-driven Cre expression in conjunction with a loxP-site flanked gene of interest. Recent studies in other cell types demonstrate toxicity of Cre expression through induction of DNA damage. However, it is unclear to what extent the traditionally used αMyHC-Cre line [1] may exhibit cardiotoxicity. Further, the genotype of αMyHC-Cre(+/-) is not often included as a control group in cardiac myocyte-specific knockout studies. Here we present evidence that these αMyHC-Cre(+/-) mice show molecular signs of cardiac toxicity by 3months of age and exhibit decreased cardiac function by 6months of age compared to wild-type littermates. Hearts from αMyHC-Cre(+/-) mice also display evidence of fibrosis, inflammation, and DNA damage. Interestingly, some of the early functional changes observed in αMyHC-Cre(+/-) mice are sexually dimorphic. Given the high level of Cre recombinase expression resulting from expression from the αMyHC promoter, we asked if degenerate loxP-like sites naturally exist in the mouse genome and if so, whether they are affected by Cre in the absence of canonical loxP-sites. Using a novel bioinformatics search tool, we identified 619 loxP-like sites with 4 or less mismatches to the canonical loxP-site. 227 sites overlapped with annotated genes and 55 of these genes were expressed in cardiac muscle. Expression of ~26% of the 27 genes tested was disrupted in αMyHC-Cre(+/-) mice indicating potential targeting by Cre. Taken together, these results highlight both the importance of using αMyHC-Cre mice

  16. Evaluation of Heavy Metals Concentration and Sequential Extraction in Zahedan Compost

    Directory of Open Access Journals (Sweden)

    Safoora Javan

    2016-03-01

    Full Text Available Background: Producing compost out of municipal solid wastes and organic materials is one of the main ways to recycle organic materials which plays an important role in waste management. Compost can also bring some toxic substances such as heavy metals into the soil and food chain and these substances have negative effects on the living things. Methods: This research is a cross-sectional descriptive study which was carried out during two seasons of spring and summer on Zahedan vermicompost factory. There were 100 samples in the research and the rate of mobility of heavy metals of lead, cadmium, and nickel was measured through five-step sequential extraction method. Then the hazard of the metals was assessed too. Results: The results show that the highest rate of mobility is related to chromium and then cadmium and lead. Moreover, the risk assessment of heavy metals estimates the average risk of all three metals for the living things in the environment. Conclusion: Heavy metals of lead and cadmium and nickel in Zahedan compost are less than the standard that is set for Iran. 

  17. Study of the effect of heavy ion energy on the sensitivity of electronic devices

    International Nuclear Information System (INIS)

    Raine, M.

    2011-01-01

    This thesis studies the sensitivity of advanced electronic devices in radiative environments. The work deals with the detailed modeling of the deposited energy induced by heavy-ion in matter, and the influence of taking it into account in the tools simulating the response of irradiated devices. To do so, a simulation chain was developed, combining different calculation codes at various scales. In a first step, the particle-matter interaction code Geant4 is used to model the heavy ion track. These tracks are then implemented in a TCAD simulator, in order to study the response of elementary transistors to these detailed energy deposits. This step is completed with experimental measurements. Finally, the study is extended to the circuit level, by interfacing the heavy ion tracks with a SEE prediction tool. These different steps evidence the need for taking into account the radial extension of the ion track to all simulation levels, to adequately model the response of advanced devices under heavy ion irradiations. (author) [fr

  18. New semi-empirical formula for α-decay half-lives of the heavy and superheavy nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Manjunatha, H.C. [Government College for Women, Department of Physics, Kolar, Karnataka (India); Sridhar, K.N. [Government First Grade College, Department of Physics, Kolar, Karnataka (India)

    2017-07-15

    We have succesfully formulated the semi-empirical formula for α-decay half-lives of heavy and superheavy nuclei for different isotopes of the wide atomic-number range 94 < Z < 136. We have considered 2627 isotopes of heavy and superheavy nuclei for the fitting. The value produced by the present formula is compared with that of experiments and other eleven models, i.e. ImSahu, Sahu, Royer10, VS2, UNIV2, SemFIS2, WKB. Sahu16, Densov, VSS and Royer formula. This formula is exclusively for heavy and superheavy nuclei. α-decay is one of the dominant decay mode of superheavy nucleus. By identifying the α-decay mode superheavy nuclei can be detected. This formula helps in predicting the α-decay chains of superheavy nuclei. (orig.)

  19. Data on heavy metals and selected anions in the Persian popular herbal distillates.

    Science.gov (United States)

    Keshtkar, Mozhgan; Dobaradaran, Sina; Soleimani, Farshid; Karbasdehi, Vahid Noroozi; Mohammadi, Mohammad Javad; Mirahmadi, Roghayeh; Ghasemi, Fatemeh Faraji

    2016-09-01

    In this data article, we determined the concentration levels of heavy metals including Pb, Co, Cd, Mn, Mg, Fe and Cu as well as selected anions including [Formula: see text] , [Formula: see text], [Formula: see text] and [Formula: see text] in the most used and popular herbal distillates in Iran. It is well known that heavy metals may pose a serious health hazard due to their bioaccumulation throughout the trophic chain ("Heavy metals (Cd, Cu, Ni and Pb) content in two fish species of Persian Gulf in Bushehr Port, Iran" (Dobaradaran et al., 2013) [1]; "Comparative investigation of heavy metal, trace, and macro element contents in commercially valuable fish species harvested off from the Persian Gulf" (Abadi et al., 2015) [2]) as well as some other environmental pollutions, "Assessment of sediment quality based on acid-volatile sulfide and simultaneously extracted metals in heavily industrialized area of Asaluyeh, Persian Gulf: concentrations, spatial distributions, and sediment bioavailability/toxicity" (Arfaeinia et al., 2016) [3]. The concentration levels of heavy metals and anions in herbal distillates samples were determined using flame atomic absorption spectrometry (FAAS, Varian AA240, Australia) and a spectrophotometer (M501 Single Beam Scanning UV/VIS, UK) respectively.

  20. Pollution load index for heavy metals in Mian-Ab plain soil, Khuzestan, Iran.

    Science.gov (United States)

    Jorfi, Sahand; Maleki, Rohangiz; Jaafarzadeh, Neemat; Ahmadi, Mehdi

    2017-12-01

    Soil pollution by heavy metals is a major concern in agricultural area. Potential impact of heavy metals in agricultural soil on human health by accumulating in food chain demonstrated elsewhere. In this regard Mian-Ab plain as a major agricultural site of Khuzestan province considered for Arsenic, cadmium and lead concentration as the main potential toxic pollutants in soil. 50 topsoil samples were collected and analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Also Contamination level of selected heavy metals in Mian-Ab Plain, was assessed by single factor contaminant index (PI) and pollution load index (PLI). Results show mean concentration of arsenic, cadmium and lead were 2.52, 0.30 and 7.21 mg kg -1 . Base on PLI results 12 point (24%) of the studied area show moderately polluted and 38 point (76%) show unpolluted area.

  1. STATISTICAL ANALYSIS OF NOTATIONAL AFL DATA USING CONTINUOUS TIME MARKOV CHAINS

    Directory of Open Access Journals (Sweden)

    Denny Meyer

    2006-12-01

    Full Text Available Animal biologists commonly use continuous time Markov chain models to describe patterns of animal behaviour. In this paper we consider the use of these models for describing AFL football. In particular we test the assumptions for continuous time Markov chain models (CTMCs, with time, distance and speed values associated with each transition. Using a simple event categorisation it is found that a semi-Markov chain model is appropriate for this data. This validates the use of Markov Chains for future studies in which the outcomes of AFL matches are simulated

  2. Maturation of Shark Single-Domain (IgNAR) Antibodies: Evidence for Induced-Fit Binding

    Energy Technology Data Exchange (ETDEWEB)

    Stanfield, R.L.; Dooley, H.; Verdino, P.; Flajnik, M.F.; Wilson, I.A.; /Scripps Res. Inst. /Maryland U.

    2007-07-13

    Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts with antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.

  3. Optimization of heavy metals total emission, case study: Bor (Serbia)

    Science.gov (United States)

    Ilić, Ivana; Bogdanović, Dejan; Živković, Dragana; Milošević, Novica; Todorović, Boban

    2011-07-01

    The town of Bor (Serbia) is one of the most polluted towns in southeastern Europe. The copper smelter which is situated in the centre of the town is the main pollutant, mostly because of its old technology, which leads to environmental pollution caused by higher concentrations of SO 2 and PM 10. These facts show that the word is about a very polluted region in Europe which, apart from harming human health in the region itself, poses a particular danger for wider area of southeastern Europe. Optimization of heavy metal's total emission was undertaken because years of long contamination of the soil with heavy metals of anthropogenic origin created a danger that those heavy metals may enter the food chains of animals and people, which can lead to disastrous consequences. This work represents the usage of Geographic Information System (GIS) for establishing a multifactor assessment model to quantitatively divide polluted zones and for selecting control sites in a linear programming model, combined with PROMETHEE/GAIA method, Screen View modeling system, and linear programming model. The results show that emissions at some control sites need to be cut for about 40%. In order to control the background of heavy metal pollution in Bor, the ecological environment must be improved.

  4. Engineering electronic states of periodic and quasiperiodic chains by buckling

    Science.gov (United States)

    Mukherjee, Amrita; Nandy, Atanu; Chakrabarti, Arunava

    2017-07-01

    The spectrum of spinless, non-interacting electrons on a linear chain that is buckled in a non-uniform, quasiperiodic manner is investigated within a tight binding formalism. We have addressed two specific cases, viz., a perfectly periodic chain wrinkled in a quasiperiodic Fibonacci pattern, and a quasiperiodic Fibonacci chain, where the buckling also takes place in a Fibonacci pattern. The buckling brings distant neighbors in the parent chain to close proximity, which is simulated by a tunnel hopping amplitude. It is seen that, in the perfectly ordered case, increasing the strength of the tunnel hopping (that is, bending the segments more) absolutely continuous density of states is retained towards the edges of the band, while the central portion becomes fragmented and host subbands of narrowing widths containing extended, current carrying states, and multiple isolated bound states formed as a result of the bending. A switching ;on; and ;off; of the electronic transmission can thus be engineered by buckling. On the other hand, in the second example of a quasiperiodic Fibonacci chain, imparting a quasiperiodic buckling is found to generate continuous subband(s) destroying the usual multifractality of the energy spectrum. We present exact results based on a real space renormalization group analysis, that is corroborated by explicit calculation of the two terminal electronic transport.

  5. Bridging the gap between university and industry: experiences with a senior level undergraduate supply chain course

    NARCIS (Netherlands)

    Steenhuis, H.J.; de Bruijn, E.J.

    2005-01-01

    Teaching operations and supply chain management courses can be challenging especially because textbook materials and “real” life experiences don’t always coincide. At Eastern Washington University a new approach has been introduced with a heavy emphasis on practical knowledge, i.e. oriented towards

  6. Microbial and Plant-Assisted Bioremediation of Heavy Metal Polluted Environments: A Review

    Directory of Open Access Journals (Sweden)

    Omena Bernard Ojuederie

    2017-12-01

    Full Text Available Environmental pollution from hazardous waste materials, organic pollutants and heavy metals, has adversely affected the natural ecosystem to the detriment of man. These pollutants arise from anthropogenic sources as well as natural disasters such as hurricanes and volcanic eruptions. Toxic metals could accumulate in agricultural soils and get into the food chain, thereby becoming a major threat to food security. Conventional and physical methods are expensive and not effective in areas with low metal toxicity. Bioremediation is therefore an eco-friendly and efficient method of reclaiming environments contaminated with heavy metals by making use of the inherent biological mechanisms of microorganisms and plants to eradicate hazardous contaminants. This review discusses the toxic effects of heavy metal pollution and the mechanisms used by microbes and plants for environmental remediation. It also emphasized the importance of modern biotechnological techniques and approaches in improving the ability of microbial enzymes to effectively degrade heavy metals at a faster rate, highlighting recent advances in microbial bioremediation and phytoremediation for the removal of heavy metals from the environment as well as future prospects and limitations. However, strict adherence to biosafety regulations must be followed in the use of biotechnological methods to ensure safety of the environment.

  7. Microbial and Plant-Assisted Bioremediation of Heavy Metal Polluted Environments: A Review

    Science.gov (United States)

    Ojuederie, Omena Bernard

    2017-01-01

    Environmental pollution from hazardous waste materials, organic pollutants and heavy metals, has adversely affected the natural ecosystem to the detriment of man. These pollutants arise from anthropogenic sources as well as natural disasters such as hurricanes and volcanic eruptions. Toxic metals could accumulate in agricultural soils and get into the food chain, thereby becoming a major threat to food security. Conventional and physical methods are expensive and not effective in areas with low metal toxicity. Bioremediation is therefore an eco-friendly and efficient method of reclaiming environments contaminated with heavy metals by making use of the inherent biological mechanisms of microorganisms and plants to eradicate hazardous contaminants. This review discusses the toxic effects of heavy metal pollution and the mechanisms used by microbes and plants for environmental remediation. It also emphasized the importance of modern biotechnological techniques and approaches in improving the ability of microbial enzymes to effectively degrade heavy metals at a faster rate, highlighting recent advances in microbial bioremediation and phytoremediation for the removal of heavy metals from the environment as well as future prospects and limitations. However, strict adherence to biosafety regulations must be followed in the use of biotechnological methods to ensure safety of the environment. PMID:29207531

  8. Optimal Distributed Controller Synthesis for Chain Structures: Applications to Vehicle Formations

    OpenAIRE

    Khorsand, Omid; Alam, Assad; Gattami, Ather

    2012-01-01

    We consider optimal distributed controller synthesis for an interconnected system subject to communication constraints, in linear quadratic settings. Motivated by the problem of finite heavy duty vehicle platooning, we study systems composed of interconnected subsystems over a chain graph. By decomposing the system into orthogonal modes, the cost function can be separated into individual components. Thereby, derivation of the optimal controllers in state-space follows immediately. The optimal...

  9. The Battle for Heavy Water Three physicists' heroic exploits

    CERN Multimedia

    2002-01-01

    Up until the end of the 1970s you could still catch a glimpse of his massive silhouette in the corridors of CERN. Lew Kowarksi, one of the pioneers of the Laboratory, was not only a great physicist; he was also a genuine hero of World War II. In 1940, along with Frédéric Joliot and Hans von Halban, Lew Kowarski managed to get the entire world supply of heavy water away to safety from the Nazis after a fantastic escape from occupied France. At the end of the war, the three physicists played themselves in a film about their adventures entitled 'la Bataille de l'eau lourde'. This film, which has been loaned to us by the French National Film Library, will be shown at CERN for the first time next Thursday. At the beginning of the war, heavy water (D20, two atoms of deuterium and one oxygen atom) was of strategic importance. In 1939 Frédéric Joliot, aided by Hans von Halban and Lew Kowarski, demonstrated the nuclear chain reaction and the moderator role that heavy water plays in it. A few weeks before the inv...

  10. PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissues: diagnostic value of immunoglobulin kappa and lambda light chain gene rearrangement investigation.

    Science.gov (United States)

    Amara, Khaled; Trimeche, Mounir; Ziadi, Sonia; Sriha, Badreddine; Mokni, Moncef; Korbi, Sadok

    2006-01-01

    Polymerase chain reaction (PCR)-based analysis, employed for detecting immunoglobulin heavy chain (IgH) gene rearrangements, has become a diagnostic tool widely used in the investigation of B-cell lymphomas, but the overall sensitivity of these methods does not exceed 80%, notably in germinal center (GC) and post-GC B-cell origin lymphomas. Many PCR strategies devised for detecting immunoglobulin light chain (IgL) gene rearrangements have been developed to enhance the clonality detection rates. However, the feasibility of these methods in routine clinical diagnosis using paraffin-embedded tissues has not yet been investigated sufficiently. We studied a large series of 108 cases of B-cell lymphomas, as well as 20 reactive lymphoid tissues using degenerate primers to amplify immunoglobulin kappa (Igkappa) and lambda (Iglambda) light chain genes. B-cell clonality was further investigated using semi-nested PCR for IgH gene rearrangements. B-cell clonality was detected in 74%, 56.5%, and 43.5% of cases using IgH, Igkappa, and Iglambda PCR, respectively. By combining these methods, the clonality detection rate increased to 93.5%. Only polyclonal patterns were noted in reactive lymphoid samples. We concluded that in addition to the established methods for IgH analysis, a PCR-based approach for IgL gene rearrangements analysis improves the clonality detection rate in over 90% of B-cell lymphoma cases using routine histological specimens with poor preservation of the genomic DNA.

  11. Monitoring of Heavy Metal Concentration in Groundwater of Qorveh County, Kurdistan Province, Iran

    Directory of Open Access Journals (Sweden)

    Nafiseh Yousefi

    2016-07-01

    Full Text Available Background & Aims of the Study: Nowadays, the quality of water is a very important concern. High levels of heavy metals in drinking water may cause some health problems such as cancer. The aim of this study is determination of some heavy metal concentrations in groundwater of some parts of Qorveh county, Kurdistan, Iran. Materials & Methods: In this study 25 water samples were analyzed, using Inductively Coupled Plasma for determining the concentrations of iron, chromium, copper and zinc. As a case study, the groundwater contamination in some parts of Qorveh county, Kurdistan, Iran, was investigated and compared to the maximum contaminant level specified by the World Health Organization (WHO and Iranian Standard Institute (IS: 1053, using ANOVA test. Results: Obtained results showed that in some cases the concentration of heavy metals were above WHO and IS: 1053. Conclusions: Heavy metals contamination can enter the food chain and cause various health problems. Thus, according to the obtained results, it is necessary to launch water management programs in the study area.

  12. Heavy baryon transitions and the heavy quark effective theory

    International Nuclear Information System (INIS)

    Hussain, F.

    1992-01-01

    Heavy baryon decays are studied in the context of the Bethe-Salpeter approach to the heavy quark effective theory. A drastic reduction, in the number of independent form factors, is found. Results are presented both for heavy to heavy and heavy to light baryon decays. (orig.)

  13. Isomyosin expression patterns during rat heart morphogenesis: an immunohistochemical study

    NARCIS (Netherlands)

    de Groot, I. J.; Lamers, W. H.; Moorman, A. F.

    1989-01-01

    An immunohistochemical study of cardiac alpha and beta myosin heavy chain (MHC) expression during rat heart morphogenesis was performed. In tubular hearts (embryonic days, ED10-11) coexpression of both cardiac alpha and beta MHC was found throughout the heart, except for the left free wall of the

  14. Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease.

    Science.gov (United States)

    Nitschke, Felix; Sullivan, Mitchell A; Wang, Peixiang; Zhao, Xiaochu; Chown, Erin E; Perri, Ami M; Israelian, Lori; Juana-López, Lucia; Bovolenta, Paola; Rodríguez de Córdoba, Santiago; Steup, Martin; Minassian, Berge A

    2017-07-01

    Lafora disease (LD) is a fatal progressive epilepsy essentially caused by loss-of-function mutations in the glycogen phosphatase laforin or the ubiquitin E3 ligase malin. Glycogen in LD is hyperphosphorylated and poorly hydrosoluble. It precipitates and accumulates into neurotoxic Lafora bodies (LBs). The leading LD hypothesis that hyperphosphorylation causes the insolubility was recently challenged by the observation that phosphatase-inactive laforin rescues the laforin-deficient LD mouse model, apparently through correction of a general autophagy impairment. We were for the first time able to quantify brain glycogen phosphate. We also measured glycogen content and chain lengths, LBs, and autophagy markers in several laforin- or malin-deficient mouse lines expressing phosphatase-inactive laforin. We find that: (i) in laforin-deficient mice, phosphatase-inactive laforin corrects glycogen chain lengths, and not hyperphosphorylation, which leads to correction of glycogen amounts and prevention of LBs; (ii) in malin-deficient mice, phosphatase-inactive laforin confers no correction; (iii) general impairment of autophagy is not necessary in LD We conclude that laforin's principle function is to control glycogen chain lengths, in a malin-dependent fashion, and that loss of this control underlies LD. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  15. Low-pressure evolution of arc magmas in thickened crust: The San Pedro-Linzor volcanic chain, Central Andes, Northern Chile

    Science.gov (United States)

    Godoy, Benigno; Wörner, Gerhard; Kojima, Shoji; Aguilera, Felipe; Simon, Klaus; Hartmann, Gerald

    2014-07-01

    Magmatism at Andean Central Volcanic Zone (CVZ), or Central Andes, is strongly influenced by differentiation and assimilation at high pressures that occurred at lower levels of the thick continental crust. This is typically shown by high light to heavy rare earth element ratios (LREE/HREE) of the erupted lavas at this volcanic zone. Increase of these ratios with time is interpreted as a change to magma evolution in the presence of garnet during evolution of Central Andes. Such geochemical signals could be introduced into the magmas be high-pressure fractionation with garnet on the liquidus and/or assimilation from crustal rocks with a garnet-bearing residue. However, lavas erupted at San Pedro-Linzor volcanic chain show no evidence of garnet fractionation in their trace element patterns. This volcanic chain is located in the active volcanic arc, between 22°00‧S and 22°30‧S, over a continental crust ˜70 km thick. Sampled lavas show Sr/Y and Sm/Yb ratios Chile. We relate our geochemical observations to shallow crustal evolution of primitive magmas involving a high degree of assimilation of upper continental crust. We emphasize that low pressure AFC- (Assimilation Fractional Crystallization) type evolution of the San Pedro-Linzor volcanic chain reflects storage, fractionation, and contamination of mantle-derived magmas at the upper felsic crust (<40 km depth). The ascent of mantle-derived magmas to mid-crustal levels is related with the extensional regime that has existed in this zone of arc-front offset since Late-Miocene age, and the relatively thin portion of mafic lower crust observed below the volcanic chain.

  16. Heavy metal incorporated helium ion active hybrid non-chemically amplified resists: Nano-patterning with low line edge roughness

    Directory of Open Access Journals (Sweden)

    Pulikanti Guruprasad Reddy

    2017-08-01

    Full Text Available Helium (He ion lithography is being considered as one of the most promising and emerging technology for the manufacturing of next generation integrated circuits (ICs at nanolevel. However, He-ion active resists are rarely reported. In this context, we are introducing a new non-chemically amplified hybrid resist (n-CAR, MAPDSA-MAPDST, for high resolution He-ion beam lithography (HBL applications. In the resist architecture, 2.15 % antimony is incorporated as heavy metal in the form of antimonate. This newly developed resists has successfully used for patterning 20 nm negative tone features at a dose of 60 μC/cm2. The resist offered very low line edge roughness (1.27±0.31 nm for 20 nm line features. To our knowledge, this is the first He-ion active hybrid resist for nanopatterning. The contrast (γ and sensitivity (E0 of this resist were calculated from the contrast curve as 0.73 and 7.2 μC/cm2, respectively.

  17. Heavy metal incorporated helium ion active hybrid non-chemically amplified resists: Nano-patterning with low line edge roughness

    Science.gov (United States)

    Reddy, Pulikanti Guruprasad; Thakur, Neha; Lee, Chien-Lin; Chien, Sheng-Wei; Pradeep, Chullikkattil P.; Ghosh, Subrata; Tsai, Kuen-Yu; Gonsalves, Kenneth E.

    2017-08-01

    Helium (He) ion lithography is being considered as one of the most promising and emerging technology for the manufacturing of next generation integrated circuits (ICs) at nanolevel. However, He-ion active resists are rarely reported. In this context, we are introducing a new non-chemically amplified hybrid resist (n-CAR), MAPDSA-MAPDST, for high resolution He-ion beam lithography (HBL) applications. In the resist architecture, 2.15 % antimony is incorporated as heavy metal in the form of antimonate. This newly developed resists has successfully used for patterning 20 nm negative tone features at a dose of 60 μC/cm2. The resist offered very low line edge roughness (1.27±0.31 nm) for 20 nm line features. To our knowledge, this is the first He-ion active hybrid resist for nanopatterning. The contrast (γ) and sensitivity (E0) of this resist were calculated from the contrast curve as 0.73 and 7.2 μC/cm2, respectively.

  18. Health risks of heavy metals in contaminated soils and food crops irrigated with wastewater in Beijing, China

    International Nuclear Information System (INIS)

    Khan, S.; Cao, Q.; Zheng, Y.M.; Huang, Y.Z.; Zhu, Y.G.

    2008-01-01

    Consumption of food crops contaminated with heavy metals is a major food chain route for human exposure. We studied the health risks of heavy metals in contaminated food crops irrigated with wastewater. Results indicate that there is a substantial buildup of heavy metals in wastewater-irrigated soils, collected from Beijing, China. Heavy metal concentrations in plants grown in wastewater-irrigated soils were significantly higher (P ≤ 0.001) than in plants grown in the reference soil, and exceeded the permissible limits set by the State Environmental Protection Administration (SEPA) in China and the World Health Organization (WHO). Furthermore, this study highlights that both adults and children consuming food crops grown in wastewater-irrigated soils ingest significant amount of the metals studied. However, health risk index values of less than 1 indicate a relative absence of health risks associated with the ingestion of contaminated vegetables. - Long-term wastewater irrigation leads to buildup of heavy metals in soils and food crops

  19. Sperm, nuclear, phospholipid, and red blood cell antibodies and isotype RF in infertile couples and patients with autoimmune rheumatic diseases.

    Science.gov (United States)

    Fichorova, R; Nakov, L; Baleva, M; Nikolov, K; Gegova, I

    1996-12-01

    To determine if measuring of nonorgan-specific autoantibodies is useful for better understanding and management of unexplained infertility. Sera were obtained from 70 infertile couples, 57 rheumatic patients, and 76 fertile donors. Sperm antibodies (SA) were detected by the tests of Kibrick and Friberg, anti-histones, anti-cardiolipin antibodies, and RF isotypes by ELISA, antinuclear antibodies by indirect immunofluorescence, and anti-red blood cell antibodies by Capture-R. Multiple autoimmune reactivity (both partners positive and/or more than one type of autoantibody involved), higher than naturally occurring in fertile individuals, was found in 55% of the idiopathically infertile couples. IgA-RF was the dominant autoimmune marker. SA revealed similar rates in patients with rheumatic diseases and in infertiles with or without other autoantibodies. Although no single autoimmunity marker could predict occurrence of SA, the coincidence of enhanced polyclonal autoimmunity in both partners of infertile couples might potentiate their negative effect on reproduction.

  20. The Effect of the Shape of Atomic Potential on the Diffraction Pattern ...

    African Journals Online (AJOL)

    We have simulated the diffraction patterns of both periodic and quasiperiodic monatomic chains using the code Laue (written by Silsbee and Drager) and investigated the effects of the shape of the atomic potential. Three fundamental differences between the diffraction patterns of periodic and quasiperiodic monatomic chain ...

  1. Markov chain analysis of the rainfall patterns of five geographical locations in the south eastern coast of Ghana

    Directory of Open Access Journals (Sweden)

    Meshach Tettey

    2017-08-01

    Full Text Available Abstract This study develops an objective rainfall pattern assessment through Markov chain analysis using daily rainfall data from 1980 to 2010, a period of 30 years, for five cities or towns along the south eastern coastal belt of Ghana; Cape Coast, Accra, Akuse, Akatsi and Keta. Transition matrices were computed for each town and each month using the conditional probability of rain or no rain on a particular day given that it rained or did not rain on the previous day. The steady state transition matrices and the steady state probability vectors were also computed for each town and each month. It was found that, the rainy or dry season pattern observed using the monthly steady state rainfall vectors tended to reflect the monthly rainfall time series trajectory. Overall, the probability of rain on any day was low to average: Keta 0.227, Akuse 0.382, Accra 0.467, Cape Coast, 0.50 and Akatsi 0.50. In particular, for Accra, the rainy season was observed to be in the months of May to June and September to October. We also determined that the probability of rainfall generally tended to increase from east to west along the south eastern coast of Ghana.

  2. Evaluation of biochars from different stock materials as carriers of bacterial strain for remediation of heavy metal-contaminated soil.

    Science.gov (United States)

    Wang, Ting; Sun, Hongwen; Ren, Xinhao; Li, Bing; Mao, Hongjun

    2017-09-21

    Two kinds of biochars, one derived from corn straw and one from pig manure, were studied as carriers of a mutant genotype from Bacillus subtilis (B38) for heavy metal contaminated soil remediation. After amendment with biochar, the heavy metal bioavailability decreased. Moreover, the heavy metal immobilization ability of the biochar was enhanced by combining it with B38. The simultaneous application of B38 and pig manure-derived biochar exhibited a superior effect on the promotion of plant growth and the immobilization of heavy metals in soil. The plant biomass increased by 37.9% and heavy metal concentrations in the edible part of lettuce decreased by 69.9-96.1%. The polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) profiles revealed that pig manure-derived biochar could enhance the proliferation of both exotic B38 and native microbes. These results suggest that B38 carried by pig manure-derived biochar may be a promising candidate for the remediation of soils contaminated by multiple heavy metals.

  3. Diversity of heavy metal resistant bacteria from Kalimas Surabaya: A phylogenetic taxonomy approach

    Science.gov (United States)

    Zulaika, Enny; Utomo, Andry Prio; Prima, Adisya; Alami, Nur Hidayatul; Kuswytasari, Nengah Dwianita; Shovitri, Maya; Sembiring, Langkah

    2017-06-01

    Bacterial resistance to heavy metal is a genetic and physiological adaptation to the environment which contaminated by heavy metal. Kalimas is an important river in Surabaya that is contaminated by some heavy metals and probably as a habitat for heavy metal resistance bacteria. Bacterial resistance to heavy metals are different for each species, and their diversity can be studied by phylogenetic taxonomy approach. Isolates screening was done using nutrient agar which contained 1 mg/L HgCl2, CdCl2 and K2Cr2O7. Bacterial viability were observed by nutrient broth which contained 10 mg/L HgCl2, 30 mg/L CdCl2 and 50 mg/L K2Cr2O7. Isolates that resistant to heavy metal and viable after exposure to heavy metal were identified using 16S rRNA gene marker by Polymerase Chain Reaction (PCR). Phylogenetic tree reconstruction was done by the neighbor-joining algorithm. Genetic assignment showed isolates that resist and viable after exposure of Hg, Cd and Cr are Bacillus S1, SS19 and DA11. Based on BLAST analysis from NCBI gene bank, 16S rRNA sequences, those isolates were similar with the member of Bacillus cereus. Depend on 16S rRNA nucleotide alignment by the neighbor-joining algorithm, Bacillus S1, SS19 and DA11 were belong to Bacillus cereus sensu-lato group.

  4. Heavy leptons

    International Nuclear Information System (INIS)

    Smith, C.H.L.

    1977-01-01

    The possibility that a new lepton may exist is discussed under the headings; theoretical reasons for the introduction of heavy leptons, classification of heavy leptons (ortho and paraleptons), discrimination between different types of lepton, decays of charged heavy leptons, production of charged heavy leptons (in e + e - storage rings, neutrino production, photoproduction, and hadroproduction), neutral heavy leptons, and hadroleptons. (U.K.)

  5. Themes and challenges in making supply chains socially sustainable

    DEFF Research Database (Denmark)

    Abbasi, Maisam

    2014-01-01

    Purpose Purpose of this paper is to explore and classify pattern of the currently discussed themes and challenges in making supply chains socially sustainable. Design/methodology/approach The methodology was based on a systematic review of the existing literature in order to explore what major...... themes and challenges have been discussed as well as the significant gaps where opportunities for further research can be found. Findings In total five categories of themes were identified, namely goods/service-centric, human-centric, organization-centric, corporate-centric, and management...... holistic view of the pattern of currently discussed themes and challenges may be beneficial in increasing the absorptive capacity of industrial and business practitioners when they design and operationalize innovative strategies in developing sustainable supply chains. Originality/value This paper may...

  6. Thyroid hormone partially corrects the effect of diabetes on mysoin heavy chain RNAs in the rat ventricle

    International Nuclear Information System (INIS)

    Barrieux, A.; Dillmann, W.H.

    1986-01-01

    The relative abundance of the 2 cardiac myosin heavy chains (MHH-α and MHC-β) and their corresponding RNAs is similarly affected by hypothyroidism and diabetes in the rat ventricle. Since circulating levels of thyroid hormone (T 3 ) are significantly decreased in diabetes the decreased RNA-α and increased RNA-β associated with diabetes may be related to T 3 deficiency. Chronically diabetic rats were injected with T 3 , insulin (I), or both and sacrificed between 1 and 12 hrs after injection, MHC RNA was quantified by hybridization of total RNA to a [ 32 P]-cDNA MHC-α probe. Total MHC RNA was measured by retention of S1-resistant label on DE-81 while RNA-α and RNA-β were quantified by separation of intact (α) and partially digested (β) probe by gel electrophoresis. Total MHC RNA was not changed by T 3 or I (.9-1.2 ng/μg of cellular RNA). T 3 and I elicited a very rapid increase in RNA-α (18% in untreated to 38% (I) and 47% (T 3 within 1 hr). I administered either 7 hr before or 1 hr after T 3 did not modify the RNA-α increase observed after T 3 alone. However, the response of diabetic rats to T 3 was markedly different from that of hypothyroid rats. Conclusions: 1) T 3 in diabetic rats does not mimick the effect of T 3 in hypothyroid rats; it may simply impose a hyperthyroid state on the existing diabetes and 2) since neither T 3 nor I are able to increase RNA-α to control levels within 12 hrs, neither hormone is sufficient to regulate the expression of MHC RNAs

  7. Heavy Flavor Physics in Heavy-Ion Collisions with STAR Heavy Flavor Tracker

    International Nuclear Information System (INIS)

    Yifei Zhang

    2010-01-01

    Heavy quarks are a unique tool to probe the strongly interacting matter created in relativistic heavy-ion collisions at RHIC energies. Due to their large mass, energetic heavy quarks are predicted to lose less energy than light quarks by gluon radiation when they traverse a Quark-Gluon Plasma. In contrast, recent measurements of non-photonic electrons from heavy quark decays at high transverse momentum (p T ) show a jet quenching level similar to that of the light hadrons. Heavy quark are produced mainly at early stage in heavy-ion collisions, thus they are proposed to probe the QCD medium and to be sensitive to bulk medium properties. Ultimately, their flow behavior may help establish whether light quarks thermalize. But due to the absence of the measurement of B-mesons and precise measurement of D-mesons, it is difficult to separate bottom and charm contributions experimentally in current non-photonic electron measurements for both spectra and elliptic flow v 2 . Therefore, topological reconstruction of D-mesons and identification of electrons from charm and bottom decays are crucial to understand the heavy flavor production and their in medium properties. The Heavy Flavor Tracker (HFT) is a micro-vertex detector utilizing active pixel sensors and silicon strip technology. The HFT will significantly extend the physics reach of the STAR experiment for precise measurement of charmed and bottom hadrons. We present a study on the open charm nuclear modification factor, elliptic flow v 2 and λ c measurement as well as the measurement of bottom mesons via a semi-leptonic decay. (author)

  8. China's Rare Earth Supply Chain: Illegal Production, and Response to new Cerium Demand

    Science.gov (United States)

    Nguyen, Ruby Thuy; Imholte, D. Devin

    2016-07-01

    As the demand for personal electronic devices, wind turbines, and electric vehicles increases, the world becomes more dependent on rare earth elements. Given the volatile, Chinese-concentrated supply chain, global attempts have been made to diversify supply of these materials. However, the overall effect of supply diversification on the entire supply chain, including increasing low-value rare earth demand, is not fully understood. This paper is the first attempt to shed some light on China's supply chain from both demand and supply perspectives, taking into account different Chinese policies such as mining quotas, separation quotas, export quotas, and resource taxes. We constructed a simulation model using Powersim Studio that analyzes production (both legal and illegal), production costs, Chinese and rest-of-world demand, and market dynamics. We also simulated new demand of an automotive aluminum-cerium alloy in the US market starting from 2018. Results showed that market share of the illegal sector has grown since 2007-2015, ranging between 22% and 25% of China's rare earth supply, translating into 59-65% illegal heavy rare earths and 14-16% illegal light rare earths. There will be a shortage in certain light and heavy rare earths given three production quota scenarios and constant demand growth rate from 2015 to 2030. The new simulated Ce demand would require supply beyond that produced in China. Finally, we illustrate revenue streams for different ore compositions in China in 2015.

  9. Kinetic chain abnormalities in the athletic shoulder.

    Science.gov (United States)

    Sciascia, Aaron; Thigpen, Charles; Namdari, Surena; Baldwin, Keith

    2012-03-01

    Overhead activities require the shoulder to be exposed to and sustain repetitive loads. The segmental activation of the body's links, known as the kinetic chain, allows this to occur effectively. Proper muscle activation is achieved through generation of energy from the central segment or core, which then transfers the energy to the terminal links of the shoulder, elbow, and hand. The kinetic chain is best characterized by 3 components: optimized anatomy, reproducible efficient motor patterns, and the sequential generation of forces. However, tissue injury and anatomic deficits such as weakness and/or tightness in the leg, pelvic core, or scapular musculature can lead to overuse shoulder injuries. These injuries can be prevented and maladaptations can be detected with a thorough understanding of biomechanics of the kinetic chain as it relates to overhead activity.

  10. Treatment patterns and healthcare resource utilization and costs in heavy menstrual bleeding: a Japanese claims database analysis.

    Science.gov (United States)

    Akiyama, Sayako; Tanaka, Erika; Cristeau, Olivier; Onishi, Yoshie; Osuga, Yutaka

    2018-06-01

    Heavy menstrual bleeding (HMB) is a highly prevalent condition, characterized by excessive menstrual blood loss and cramping, that interferes with activities of daily life. The aim of this study was to investigate treatment patterns in HMB in Japan, and to assess healthcare resource utilization and costs among women newly-diagnosed with the condition. This study retrospectively analyzed health insurance data available in the Japan Medical Data Center (JMDC) database on women aged 18-49 years who were newly-diagnosed with primary or secondary HMB. Treatment patterns were analyzed, and healthcare utilization and costs were evaluated and compared to matched controls. The study included a total of 635 patients, 210 with primary HMB and 425 with secondary HMB. In the primary HMB cohort, 60.0% of patients received one or more pharmacological or surgical treatments, compared with 76.2% in the secondary HMB cohort. The most commonly prescribed medications in all patients were hemostatic agents (28.7%), traditional Chinese medicine (TCM) (12.1%), and low-dose estrogen progestins (LEPs) (10.1%). After adjustment for patient baseline characteristics, healthcare costs were 1.93-times higher in primary HMB cases (p < .0001) and 4.44-times higher in secondary HMB cases (p < .0001) vs healthy controls. Outpatient care was the main cost driver. The main limitations of this study are related to its retrospective nature, and the fact that only reimbursed medications were captured in the source database. A substantial proportion of HMB patients did not receive the recommended treatments. Healthcare costs were considerably increased in the presence of an HMB diagnosis.

  11. Accumulation of heavy metals in Medicago sativa L. and Trifolium pratense L. at the contaminated fluvisol

    Directory of Open Access Journals (Sweden)

    Jakšić Snežana P.

    2013-01-01

    Full Text Available Recently, heavy metals concentrations increased in some agricultural areas due to the consequences of anthropogenic impacts. The aim of this study was to determine the level of heavy metals (As, Cr, Ni and Pb in Medicago sativa L. and Trifolium pratense L. grown on fluvisol, in order to obtain information on safety of these nutrients. The total content of Pb, As, Cr and Ni in the samples of fluvisol was above the maximum allowable amount. The content of heavy metals in Medicago sativa L. and Trifolium pratense L. was below the critical and toxic concentrations in all samples originating from contaminated soil. It was concluded that the accumulation of heavy metals in plants did not depend only on the total content in soil, but also the affinity of the plant, and individual and interactive effects of various soil properties. No statistically significant differences in the accumulation of heavy metals between Medicago sativa L. and Trifolium pratense L were observed. It is necessary to further control of heavy metals in the investigated area, in order to prevent their entry into the food chain and provide healthy food.

  12. Short- and medium-chain chlorinated paraffins in biota from the European Arctic -- differences in homologue group patterns.

    Science.gov (United States)

    Reth, Margot; Ciric, Anita; Christensen, Guttorm N; Heimstad, Eldbjørg S; Oehme, Michael

    2006-08-15

    Congener and homologue group patterns of chlorinated paraffins (CPs) in biota can be influenced by different processes, but these are not well studied yet. Short- (SCCPs) and medium-chain chlorinated paraffins (MCCPs) were quantified in liver from Arctic char and seabirds (little auk and kittiwake) collected at Bear Island (European Arctic) as well as in cod from Iceland and Norway. CP concentrations were between 5 and 88 ng/g wet weight (ww) for SCCPs and between 5 and 55 ng/g ww for MCCPs with one exception of 370 ng/g measured in a liver sample from little auk. The SCCP homologue group patterns were compared with those of technical mixtures and of SCCPs present in cod liver from the Baltic Sea. The latter showed a more common SCCP homologue distribution (sum of C(11) and C(12)>60%) in contrast to cod liver from the Northwest of Europe, which had a high abundance of C(10) and C(12) congeners. Seabirds from Bear Island contained an equally distributed SCCP homologue group pattern. In Arctic char, the SCCP distribution was closer to technical products, but with a high proportion (average of 18.9%) of C(10) congeners. A comparison of C(10)/C(12) ratios confirmed the higher abundance of C(10) congeners in samples from higher latitudes. For the first time, MCCPs could be detected in Arctic samples. The average proportion of C(14) congeners was 65.8%. The C(14)/C(15) abundance ratio was similar to technical mixtures. High-chlorinated CPs (Cl(>7)) were also detectable. The average chlorine content of the SCCPs was 61.9% (59.0-63.3%), and that of the MCCPs 55.8% (54.5-57.4%).

  13. Molecular design of high performance zwitterionic liquids for enhanced heavy-oil recovery processes.

    Science.gov (United States)

    Martínez-Magadán, J M; Cartas-Rosado, A R; Oviedo-Roa, R; Cisneros-Dévora, R; Pons-Jiménez, M; Hernández-Altamirano, R; Zamudio-Rivera, L S

    2018-03-01

    Branched gemini zwitterionic liquids, which contain two zwitterionic moieties of linked quaternary-ammonium and carboxylate groups, are proposed as chemicals to be applied in the Enhanced Oil Recovery (EOR) from fractured carbonate reservoirs. The zwitterionic moieties are bridged between them through an alkyl chain containing 12 ether groups, and each zwitterionic moiety has attached a long alkyl tail including a CC double bond. A theoretical molecular mechanism over which EOR could rest, consisting on both the disaggregation of heavy oil and the reservoir-rock wettability alteration, was suggested. Results show that chemicals can both reduce the viscosity and remove heavy-oil molecules from the rock surface. Copyright © 2018. Published by Elsevier Inc.

  14. Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG

    Science.gov (United States)

    Fischer, Nicolas; Elson, Greg; Magistrelli, Giovanni; Dheilly, Elie; Fouque, Nicolas; Laurendon, Amélie; Gueneau, Franck; Ravn, Ulla; Depoisier, Jean-François; Moine, Valery; Raimondi, Sylvain; Malinge, Pauline; Di Grazia, Laura; Rousseau, François; Poitevin, Yves; Calloud, Sébastien; Cayatte, Pierre-Alexis; Alcoz, Mathias; Pontini, Guillemette; Fagète, Séverine; Broyer, Lucile; Corbier, Marie; Schrag, Delphine; Didelot, Gérard; Bosson, Nicolas; Costes, Nessie; Cons, Laura; Buatois, Vanessa; Johnson, Zoe; Ferlin, Walter; Masternak, Krzysztof; Kosco-Vilbois, Marie

    2015-01-01

    Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a κλ-body, is assembled by co-expressing one heavy chain and two different light chains, one κ and one λ. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the κλ-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies. PMID:25672245

  15. Transgenerational inheritance of modified DNA methylation patterns and enhanced tolerance induced by heavy metal stress in rice (Oryza sativa L.).

    Science.gov (United States)

    Ou, Xiufang; Zhang, Yunhong; Xu, Chunming; Lin, Xiuyun; Zang, Qi; Zhuang, Tingting; Jiang, Lili; von Wettstein, Diter; Liu, Bao

    2012-01-01

    DNA methylation is sensitive and responsive to stressful environmental conditions. Nonetheless, the extent to which condition-induced somatic methylation modifications can impose transgenerational effects remains to be fully understood. Even less is known about the biological relevance of the induced epigenetic changes for potentially altered well-being of the organismal progenies regarding adaptation to the specific condition their progenitors experienced. We analyzed DNA methylation pattern by gel-blotting at genomic loci representing transposable elements and protein-coding genes in leaf-tissue of heavy metal-treated rice (Oryza sativa) plants (S0), and its three successive organismal generations. We assessed expression of putative genes involved in establishing and/or maintaining DNA methylation patterns by reverse transcription (RT)-PCR. We measured growth of the stressed plants and their unstressed progenies vs. the control plants. We found (1) relative to control, DNA methylation patterns were modified in leaf-tissue of the immediately treated plants, and the modifications were exclusively confined to CHG hypomethylation; (2) the CHG-demethylated states were heritable via both maternal and paternal germline, albeit often accompanying further hypomethylation; (3) altered expression of genes encoding for DNA methyltransferases, DNA glycosylase and SWI/SNF chromatin remodeling factor (DDM1) were induced by the stress; (4) progenies of the stressed plants exhibited enhanced tolerance to the same stress their progenitor experienced, and this transgenerational inheritance of the effect of condition accompanying heritability of modified methylation patterns. Our findings suggest that stressful environmental condition can produce transgenerational epigenetic modifications. Progenies of stressed plants may develop enhanced adaptability to the condition, and this acquired trait is inheritable and accord with transmission of the epigenetic modifications. We suggest

  16. Myeloma-Derived Light Chain Paired with a Diagnostic Monoclonal Antibody Hinders Immunoassay Performance.

    Science.gov (United States)

    Tu, Bailin; Tieman, Bryan; Moore, Jeffrey; Pan, You; Muerhoff, A Scott

    2017-06-01

    Monoclonal antibodies are widely used as the capture and detection reagents in diagnostic immunoassays. In the past, myeloma fusion partners expressing endogenous heavy and/or light chains were often used to generate hybridoma cell lines. As a result, mixed populations of antibodies were produced that can cause inaccurate test results, poor antibody stability, and significant lot-to-lot variability. We describe one such scenario where the P3U1 (P3X63Ag8U.1) myeloma fusion partner was used in the generation of a hybridoma producing protein induced vitamin K absence/antagonist-II (PIVKA II) antibody. The hybridoma produces three subpopulations of immunoglobulin as determined by ion exchange (IEx) chromatography that exhibit varying degrees of immunoreactivity (0%, 50%, or 100%) to the target antigen as determined by Surface Plasmon Resonance. To produce an antibody with the highest possible sensitivity and specificity, the antigen-specific heavy and light chain variable domains (VH and VL) were cloned from the hybridoma and tethered to murine IgG1 and kappa scaffolds. The resulting recombinant antibody was expressed in Chinese hamster ovary cells and is compatible for use in a diagnostic immunoassay.

  17. The social location of heavy episodic alcohol consumption in the Victorian population.

    Science.gov (United States)

    Matthews, Sharon; Dietze, Paul; Room, Robin; Chikritzhs, Tanya; Jolley, Damien

    2013-03-01

    To examine heavy episodic drinking across demographic subgroups to identify where heavy episodic drinking is socially located in an Australian state. Cross-sectional survey, 2483 adult Victorians using Computer Assisted Telephone Interviewing. Two measures of heavy drinking were used: (i) heavy episodic drinking-more than five standard drinks at least weekly; and (ii) typically heavy drinking-50% or more of all drinking occasions involving consumption of 5+ standard drinks. Associations between heavy episodic drinking and eight potential sociodemographic correlates (gender, age, education, income, marital status, ethnic origin, religion and geographical remoteness) were examined. There were few significant correlates of heavy episodic drinking apart from gender and age, once gender and age were controlled. Men were more likely to report heavy episodic drinking than women, but this was attenuated in the measure of typically heavy drinking, suggesting that women reporting heavy episodic drinking were more likely to typically drink that much when they drank. Younger people were more likely to report weekly heavy episodic drinking and more likely to report engaging in this pattern on at least half of their drinking occasions, and this was also true for those unmarried or in de facto relationships. Those of Asian background were less likely to report heavy drinking. In multivariate analysis, the remaining sociodemographic variables were largely unrelated to the drinking measures. The study clearly shows that the prevalence of heavy episodic drinking varies particularly across gender and age groups in Victoria. These variations appear to hold across key sociodemographic variables such as income and education. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  18. Characteristics of implicit chaining in cotton-top tamarins (Saguinus oedipus).

    Science.gov (United States)

    Locurto, Charles; Gagne, Matthew; Nutile, Lauren

    2010-07-01

    In human cognition there has been considerable interest in observing the conditions under which subjects learn material without explicit instructions to learn. In the present experiments, we adapted this issue to nonhumans by asking what subjects learn in the absence of explicit reinforcement for correct responses. Two experiments examined the acquisition of sequence information by cotton-top tamarins (Saguinus oedipus) when such learning was not demanded by the experimental contingencies. An implicit chaining procedure was used in which visual stimuli were presented serially on a touchscreen. Subjects were required to touch one stimulus to advance to the next stimulus. Stimulus presentations followed a pattern, but learning the pattern was not necessary for reinforcement. In Experiment 1 the chain consisted of five different visual stimuli that were presented in the same order on each trial. Each stimulus could occur at any one of six touchscreen positions. In Experiment 2 the same visual element was presented serially in the same five locations on each trial, thereby allowing a behavioral pattern to be correlated with the visual pattern. In this experiment two new tests, a Wild-Card test and a Running-Start test, were used to assess what was learned in this procedure. Results from both experiments indicated that tamarins acquired more information from an implicit chain than was required by the contingencies of reinforcement. These results contribute to the developing literature on nonhuman analogs of implicit learning.

  19. Exploring themes and challenges in developing sustainable supply chains – A complexity theory perspective

    DEFF Research Database (Denmark)

    Abbasi, Maisam

    identify, classify, and tackle the challenges that can hinder the execution of such strategies. To develop innovative strategies, the patterns of current trends and themes need to be learned and the missing ones need to be identified. The purpose of this research was to explore themes and challenges......To develop sustainable supply chains in a way that their negative environmental and social effects are minimized, shortand long-term targets should be set. The transformation of supply chains towards these targets calls for the development of innovative strategies and the need to continuously...... in developing sustainable supply chain activities from theoretical and empirical perspectives. Six research studies (RS) were designed and carried out. Two explored the patterns of the themes and challenges in making supply chains environmentally and socially sustainable in general (RS1, RS2). One explored...

  20. Peroxidase activity in Raphanus sativus and its relationship with soil heavy metals

    International Nuclear Information System (INIS)

    Alipour, H.; Zare Myvan, H.; Sharifi, M.

    2009-01-01

    Today heavy metals are important environmental pollutants which generated from human activities and are one of the most important environmental stresses that cause molecular damages to plants through reactive oxygen species formation such as H2O2. Heavy metals are absorbed and accumulated by plants thus are absorbed by human bodies through the food chain. Raphanus sativus is a herbaceous plant within the Brassicaceae family that has different varieties and is used as a food plant in different parts of Iran. Peroxidase is one of the most important enzyme in oxidoreductase super family that can metabolize H2O2. In this research we studied some growth parameters, peroxidase activity and their relationships with heavy metal content and other soil factors in three different populations of radish collected from Sari, Semnan and south of Tehran. After harvesting the plants shoots and roots Peroxidase activity was assayed spectrophotometrically at 470 nm. Our results showed total heavy metal content of shomal 3 station soil and radish plants was higher than other stations, so plants collected from this station had lowest root and shoot lengths, fresh weights, dry weights, protein content and leaf collrophyll content. The peroxidase activity in both leaves and roots of these plants was higher than plants of other stations Therefore our results showed that with increasing heavy metal concentrations in soils peroxidase activity increased.

  1. The identification of 'hotspots' of heavy metal pollution in soil-rice systems at a regional scale in eastern China.

    Science.gov (United States)

    Li, Wanlu; Xu, Binbin; Song, Qiujin; Liu, Xingmei; Xu, Jianming; Brookes, Philip C

    2014-02-15

    Chinese agricultural soils and crops are suffering from increasing damage from heavy metals, which are introduced from various pollution sources including agriculture, traffic, mining and especially the flourishing private metal recycling industry. In this study, 219 pairs of rice grain and corresponding soil samples were collected from Wenling in Zhejiang Province to identify the spatial relationship and pollution hotspots of Cd, Cu, Ni and Zn in the soil-rice system. The mean soil concentrations of heavy metals were 0.316 mg kg(-1) for Cd, 47.3 mg kg(-1) for Cu, 31.7 mg kg(-1) for Ni and 131 mg kg(-1) for Zn, and the metal concentrations in rice grain were 0.132 mg kg(-1) for Cd, 2.46 mg kg(-1) for Cu, 0.223 mg kg(-1) for Ni and 17.4 mg kg(-1) for Zn. The coefficient of variability (CV) of soil Cd, Cu and rice Cd were 147%, 146% and 180%, respectively, indicating an extensive variability. While the CVs of other metals ranged from 23.4% to 84.3% with a moderate variability. Kriging interpolation procedure and the Local Moran's I index detected the locations of pollution hotspots of these four metals. Cd and Cu had a very similar spatial pattern, with contamination hotspots located simultaneously in the northwestern part of the study area, and there were obvious hotspots for soil Zn in the north area, while in the northeast for soil Ni. The existence of hotspots may be due to industrialization and other anthropogenic activities. An Enrichment Index (EI) was employed to measure the uptake of heavy metals by rice. The results indicated that the accumulation and availability of heavy metals in the soil-rice system may be influenced by both soil heavy metal concentrations and soil physico-chemical properties. Cross-correlograms quantitatively illustrated that EIs were significantly correlated with soil properties. Soil pH and organic matter were the most important factors controlling the uptake of heavy metals by rice. As results, positive measures should be taken into

  2. Heavy baryons

    International Nuclear Information System (INIS)

    Koerner, J.G.

    1994-06-01

    We review the experimental and theoretical status of baryons containing one heavy quark. The charm and bottom baryon states are classified and their mass spectra are listed. The appropriate theoretical framework for the description of heavy baryons is the Heavy Quark Effective Theory, whose general ideas and methods are introduced and illustrated in specific examples. We present simple covariant expressions for the spin wave functions of heavy baryons including p-wave baryons. The covariant spin wave functions are used to determine the Heavy Quark Symmetry structure of flavour-changing current-induced transitions between heavy baryons as well as one-pion and one-photon transitions between heavy baryons of the same flavour. We discuss 1/m Q corrections to the current-induced transitions as well as the structure of heavy to light baryon transitions. Whenever possible we attempt to present numbers to compare with experiment by making use of further model-dependent assumptions as e.g. the constituent picture for light quarks. We highlight recent advances in the theoretical understanding of the inclusive decays of hadrons containing one heavy quark including polarization. For exclusive semileptonic decays we discuss rates, angular decay distributions and polarization effects. We provide an update of the experimental and theoretical status of lifetimes of heavy baryons and of exclusive nonleptonic two body decays of charm baryons. (orig.)

  3. Remarks on the fission barriers of super-heavy nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, S. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Goethe-Universitaet Frankfurt, Institut fuer Physik, Frankfurt (Germany); Heinz, S.; Mann, R.; Maurer, J.; Muenzenberg, G.; Barth, W.; Dahl, L.; Kindler, B.; Kojouharov, I.; Lang, R.; Lommel, B.; Runke, J.; Scheidenberger, C.; Tinschert, K. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Antalic, S. [Comenius University, Department of Nuclear Physics and Biophysics, Bratislava (Slovakia); Eberhardt, K.; Thoerle-Pospiech, P.; Trautmann, N. [Johannes Gutenberg-Universitaet Mainz, Mainz (Germany); Grzywacz, R. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); University of Tennessee, Knoxville, TN (United States); Hamilton, J.H. [Vanderbilt University, Department of Physics and Astronomy, Nashville, TN (United States); Henderson, R.A.; Kenneally, J.M.; Moody, K.J.; Shaughnessy, D.A.; Stoyer, M.A. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Miernik, K. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); University of Warsaw, Warsaw (Poland); Miller, D. [University of Tennessee, Knoxville, TN (United States); Morita, K. [RIKEN Nishina Center for Accelerator-Based Science, Wako, Saitama (Japan); Nishio, K. [Japan Atomic Energy Agency, Tokai, Ibaraki (Japan); Popeko, A.G.; Yeremin, A.V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Roberto, J.B.; Rykaczewski, K.P. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Uusitalo, J. [University of Jyvaeskylae, Department of Physics, Jyvaeskylae (Finland)

    2016-04-15

    Shell-correction energies of super-heavy nuclei are approximated by using Q{sub α} values of measured decay chains. Five decay chains were analyzed, which start at the isotopes {sup 285}Fl, {sup 294}118, {sup 291}Lv, {sup 292}Lv and {sup 293}Lv. The data are compared with predictions of macroscopic-microscopic models. Fission barriers are estimated that can be used to eliminate uncertainties in partial fission half-lives and in calculations of evaporation-residue cross-sections. In that calculations, fission probability of the compound nucleus is a major factor contributing to the total cross-section. The data also provide constraints on the cross-sections of capture and quasi-fission in the entrance channel of the fusion reaction. Arguments are presented that fusion reactions for synthesis of isotopes of elements 118 and 120 may have higher cross-sections than assumed so far. (orig.)

  4. Heavy quark effective theory and study of heavy hadron spectra

    International Nuclear Information System (INIS)

    Dong Yubing

    1995-01-01

    By employing the heavy quark effective theory, the spectra of heavy hadrons, such as heavy mesons (Q-barq), heavy baryons (QQq and Qqq) and heavy multiquark systems (Q-barQ-barqq) are studied systemically. The results are compared with the predictions for Q-barQ-barqq in potential model

  5. DISTRIBUTION OF HEAVY METALS AMONG THE COMPONENTS OF FRESHWATER ECOSYSTEMS (REVIEW

    Directory of Open Access Journals (Sweden)

    N. Kolesnyk

    2014-09-01

    Full Text Available Purpose. To review scientific sources on the distribution of heavy metals among the components of freshwater ecosystems. Findings. The review of the works of many scientists showed that heavy metals are widespread in the biotic and abiotic components of freshwater ecosystems. The article highlights the distribution of heavy metals in water, bottom sediments, natural food base, fish organs and tissues. It has been shown that as a result of global pollution of the ecosystem, the majority of Ukrainian rivers belong to polluted and very polluted. Of special interest are the studies of the distribution of heavy metals in phytoplankton, zooplankton, and zoobenthos because these components occupy a certain position in fish food chain. The presence of heavy metals in the natural food base showed that, on one hand, it could accumulate heavy metals in large amounts in such a way cleaning the water; and on the other hand, the heavy metals could migrate in the food web and contaminate fish. Ones of objects, which should be given attention when assessing toxicologic pollution, are aquatic plants, in particular phytoplankton. Studies showed that the accumulation of heavy metals in plants occurred first of all by their adsorption on the cellular wall. It explains the maximum adsorption of heavy metals by plants immediately after introduction of heavy metals into their culture. Fish as a rule occupy in the food web of water bodies one of the last places. They actively move in the aquatic environment and accumulating heavy metals at the same time they provide the most integrated and precise estimate of environmental pollution. By analyzing the distribution of heavy metals in fish organs and tissues, depending on their ability to accumulate them, it can be noted that the accumulation is the most intensive in such organs as gills, liver, and kidneys. Usually, their lowest content is observed in muscles that is important for human life because they are the main

  6. Inclusive b-jet production in heavy ion collisions at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinrui, E-mail: jinruih@lanl.gov; Kang, Zhong-Bo, E-mail: zkang@lanl.gov; Vitev, Ivan, E-mail: ivitev@lanl.gov

    2013-10-07

    Theoretical and experimental advances in understanding light jet production and modification in Pb + Pb reactions at √(s{sub NN})=2.76 TeV have been a highlight of the LHC heavy ion program. At the same time, the detailed mechanisms of heavy quark propagation and energy loss in dense QCD matter are not yet fully understood. With this motivation, we present theoretical predictions for the nuclear-induced attenuation of the differential cross section for inclusive b-jet production in heavy ion collisions at the LHC for comparison to upcoming data. We find that for transverse momenta p{sub T}≳75 GeV both hadronization and mass effects are negligible and this attenuation is comparable to the one observed for light jets. We discuss how the detailed b-jet quenching patterns can be used to gain new insight into the in-medium heavy flavor dynamics.

  7. Heavy metals contamination of soil and fodder: a possible risk to livestock

    International Nuclear Information System (INIS)

    Ahmad, K.; Shaheen, M.; Khan, Z.I.

    2013-01-01

    Heavy metals are significant ecological pollutant, principally in areas with sky-scraping anthropogenic stress. Their existence in the environment, soil and water, still in traces can cause severe tribulations to all organisms; heavy metal bioaccumulation in the food chain particularly can be extremely hazardous to animal and human health. Heavy metals generally come into the body by breathing and eating, ingestion being the most important route of contact to these elements in animals. The current study was conducted to examine lead (Pb), cadmium (Cd) and chromium (Cr) in the soil and fodders. Representative samples of soil were collected during two different seasons from two different sites, known as feeding sites for ruminants and analysed for heavy metals after wet digestion, using Atomic Absorption Spectrophotometer. The results showed that location and season had a significant effect (P>0.001) on soil and heavy metal concentrations. Soil and forage Pb, Cd, and Cr concentrations were higher in summer than in winter. From the results of the current study, it was determined that all the metals in soil were lower than deadly levels, posing no probable threat to both plant and animal life. There is an incessant need for monitoring the bioavailability of these heavy metals to grazing livestock, principally in summer season when these metals were found in relatively elevated concentrations, so that their possible toxic consequence to the grazing livestock can not be permitted. Agronomic practices, such as, manure and water managements as well as crop alternation system, can affect bioavailability and crop accretion of heavy metals, thus influencing the thresholds for assessing nutritional toxicity of heavy metals in the foodstuff. This study would be important for livestock owners and scientists working in extension services in Pakistan and other countries with same ecological condition. (author)

  8. Myosin heavy chain composition in the vastus lateralis muscle in relation to oxygen uptake and heart rate during cycling in humans.

    Science.gov (United States)

    Majerczak, J; Nieckarz, Z; Karasinski, J; Zoladz, J A

    2014-04-01

    In this study we examined the relationship between fast myosin heavy chain (MyHC2) content in the vastus lateralis and the rate of oxygen uptake (VO2) and heart rate (HR) increase during an incremental exercise in 38, young, healthy men. Prior to the exercise test, muscle biopsies were taken in order to evaluate the MyHC composition. It was found that during cycling performed below the lactate threshold (LT), a positive relationship between MyHC2 and the intercept of the oxygen uptake and power output (VO2-PO) relationship existed (r=0.49, P=0.002), despite no correlation between MyHC2 and the slope value of the VO2-PO relationship (r= -0.18, P=0.29). During cycling performed above the LT, MyHC2 correlated positively with the magnitude of the nonlinearity in the VO2-PO relationship; i.e. with the accumulated VO2'excess' (r=0.44, P=0.006) and peak VO2'excess' (r=0.44, P=0.006), as well as with the slope of the HR-PO relationship (r=0.49, P=0.002). We have concluded that a greater MyHC2 content in the vastus lateralis is accompanied by a higher oxygen cost of cycling during exercise performed below the LT. This seems to be related to the higher energy cost of the non-cross-bridge activities in the muscles possessing a greater proportion of MyHC2 content. In the case of heavy-intensity exercise, a higher MyHC2 content in the vastus lateralis is accompanied by greater non-linearity in the VO2-PO relationship, as well as a steeper increase in HR in the function of an increase of PO. This relationship can be explained by greater disturbances in metabolic stability in type II muscle fibres during exercise, resulting in a decrease of muscle mechanical efficiency and greater increase of heart rate at a given power output. Therefore, MyHC composition has an impact on the oxygen cost of cycling both below and above the LT.

  9. Value Chain Model Development of Tuna and Tuna Alike In Indonesia

    Directory of Open Access Journals (Sweden)

    Ateng Supriatna

    2014-11-01

    Full Text Available Sustainability of tuna and tuna alike fisheries depend on chain value system formed by stakeholders ranging from product fishing, processing/diversification, distribution, and marketing. The objective of this research was to create chain value system model of tuna and tuna alike fisheries, to predict the interaction pattern of stakeholders and to formulate the precise strategy to minimize the synergy resistance of chain value system development strategy of tuna and tuna alike fisheries. Structural Equation Modelling (SEM was applied to analyze the chain value model. The stakeholders/the players of tuna and tuna alike fisheries basically have positive interaction (CE>0.The negative interaction occured on retailers and consumers. Interaction of retailers with consumers is significant (p<0.05 0.01. Interaction pattern of fishermen, retailers, collectors, and exporters affected significantlly by pricing and the level of role played by the stakeholders. The strategy to minimize the sinergy resistance of chain value system development are respectivelly the strategy of involving the group of fishermen on products pricing (CE= 1,176 and P= 0,000, the strategy of involving the seller groups on products pricing (CE-PE=1,08, CE-PB= 0,766, CE EKS= 2,028 AND P= 0,000, and the strategy on guaranteeing flexible interaction between retailer and consumers (CE= 0,179 and p = 0,01.Keywords: tuna and tuna alike, interaction, tuna and tuna alike stakeholders, and value chain

  10. Heavy baryons in the heavy quark effective theory

    International Nuclear Information System (INIS)

    Koerner, J.G.; Thompson, G.

    1991-10-01

    We give a mini-review of recent results on current-induced transitions between heavy baryons (and between heavy and light baryons) in the light of the new spin and flavour symmetries of the Heavy Quark Effective Theory (HQET). We discuss the structure of the 1/m corrections to the heavy mass limit and outline a diagrammatic proof that there are no 0(1/m) correction to the Voloshin-Shifman normalization condition at zero recoil. (orig.)

  11. Remediation of heavy metal(loid)s contaminated soils--to mobilize or to immobilize?

    Science.gov (United States)

    Bolan, Nanthi; Kunhikrishnan, Anitha; Thangarajan, Ramya; Kumpiene, Jurate; Park, Jinhee; Makino, Tomoyuki; Kirkham, Mary Beth; Scheckel, Kirk

    2014-02-15

    Unlike organic contaminants, metal(loid)s do not undergo microbial or chemical degradation and persist for a long time after their introduction. Bioavailability of metal(loid)s plays a vital role in the remediation of contaminated soils. In this review, the remediation of heavy metal(loid) contaminated soils through manipulating their bioavailability using a range of soil amendments will be presented. Mobilizing amendments such as chelating and desorbing agents increase the bioavailability and mobility of metal(loid)s. Immobilizing amendments such of precipitating agents and sorbent materials decrease the bioavailabilty and mobility of metal(loid)s. Mobilizing agents can be used to enhance the removal of heavy metal(loid)s though plant uptake and soil washing. Immobilizing agents can be used to reduce the transfer to metal(loid)s to food chain via plant uptake and leaching to groundwater. One of the major limitations of mobilizing technique is susceptibility to leaching of the mobilized heavy metal(loid)s in the absence of active plant uptake. Similarly, in the case of the immobilization technique the long-term stability of the immobilized heavy metal(loid)s needs to be monitored. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Crystal structure and Mössbauer studies of the isotypic Fe6-cluster compounds RE15[Fe8C25], RE=Dy, Ho

    KAUST Repository

    Davaasuren, Bambar

    2015-05-01

    The carboferrates RE15[Fe8C25] (RE=Dy, Ho) were prepared from mixtures of the elements by arc-melting followed with subsequent annealing at 1373 K. The crystal structures were determined from single crystal X-ray diffraction data and revealed an isotypic relationship to Er15[Fe8C25] (hP48, P321). The main feature of the crystal structure is given by Fe6 cluster units characterized by covalent Fe-Fe bonding interactions. 57Fe Mössbauer spectra of Dy15[Fe8C25] were fitted by three subspectra with relative spectral weights of about 3:3:2 which is in general agreement with the crystal structure. Below 50 K, an onset of magnetic hyperfine fields at the three iron sites is observed which is supposed to be caused by dipolar fields arising from neighboring, slowly relaxing Dy magnetic moments.

  13. A novel variable antibody fragment dimerized by leucine zippers with enhanced neutralizing potency against rabies virus G protein compared to its corresponding single-chain variable antibody fragment.

    Science.gov (United States)

    Li, Zhuang; Cheng, Yue; Xi, Hualong; Gu, Tiejun; Yuan, Ruosen; Chen, Xiaoxu; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2015-12-01

    Fatal rabies can be prevented effectively by post-exposure prophylactic (PEP) with rabies immunoglobulin (RIG). Single-chain variable fragments (scFv), which are composed of a variable heavy chain (VH) and a variable light chain (VL) connected by a peptide linker, can potentially be used to replace RIG. However, in our previous study, a scFv (scFV57S) specific for the rabies virus (RV) G protein showed a lower neutralizing potency than that of its parent IgG due to lower stability and altered peptide assembly pattern. In monoclonal antibodies, the VH and VL interact non-covalently, while in scFvs the VH is connected covalently with the VL by the artificial linker. In this study, we constructed and expressed two peptides 57VL-JUN-HIS and 57VH-FOS-HA in Escherichia coli. The well-known Fos and Jun leucine zippers were utilized to dimerize VH and VL similarly to the IgG counterpart. The two peptides assembled to form zipFv57S in vitro. Due to the greater similarity in structure with IgG, the zipFv57S protein showed a higher binding ability and affinity resulting in notable improvement of in vitro neutralizing activity over its corresponding scFv. The zipFv57S protein was also found to be more stable and showed similar protective rate as RIG in mice challenged with a lethal dose of RV. Our results not only indicated zipFv57S as an ideal alternative for RIG in PEP but also offered a novel and efficient hetero-dimerization pattern of VH and VL leading to enhanced neutralizing potency. Copyright © 2015. Published by Elsevier Ltd.

  14. Reducing heavy alcohol consumption in young restaurant workers.

    Science.gov (United States)

    Broome, Kirk M; Bennett, Joel B

    2011-01-01

    Restaurant employees often have high rates of heavy drinking and problems with alcohol. This study evaluates reductions in drinking and associated problems at work, in connection with a new program for prevention and early intervention. The program, called Team Resilience, is designed for young restaurant workers. A cluster-randomized trial design was used, with 28 stores from a national casual-dining restaurant chain and 235 of their employees (54% male, 46% female). Fourteen stores received the Team Resilience training workshop, consisting of three 2-hour sessions held on 3 consecutive days. Sessions included group discussion, role-play and practice activities, and a learning game. Workers in trained stores reported significantly greater decreases in recurring heavy drinking (i.e., having five or more drinks on the same occasion, on 5 or more days in the past month) and work-related problems with alcohol than workers in control stores. In the intervention group, the odds of recurring heavy drinking declined by about one half and the number of work-related problem areas declined by one third following training. In addition, drinking behaviors and problems were tied to age and were most common among employees in their middle 20s. Findings support Team Resilience as an effective intervention for reducing drinking and associated problems among young restaurant workers, a population with substantial needs.

  15. The importance of heavy water in nuclear technology

    International Nuclear Information System (INIS)

    Gharib, A.G.

    2004-01-01

    Due to similarities of chemical and almost physical properties in H 2 O and D 2 O but differences in nuclear and particle peculiarities provide valuable application for D 2 O. To sustain a controlled chain reaction, the energy of neutrons produced by fission must be reduced through collisions with other nuclei, a process called moderation. A good moderator has a mass close to that of the neutron to maximize energy loss per collision and a very small neutron capture cross section to minimize unwanted nuclear reactions. Deuterium is far the best moderator, more than 80 times better than hydrogen and 30 times better than 12 C ir 18 O. Heavy water is almost as good as deuterium and has the distinct advantage of being a nonflammable liquid. Heavy water is also an excellent neutron reflector, and thus decreases the number of neutrons that escape the reactor core without participating in fission reactions. For this reason a feasibility study and subsequently a technical survey was carried out on engineering of a pilot scale plant. As the result of this studies, the know-how of heavy water production on basis of selected method including dual temperature isotopic exchange and distillation techniques developed. Subsequently the primary and almost detail engineering documents prepared on best knowledge of our own engineers without external contribution

  16. General analysis of weak decay form factors in heavy to heavy and heavy to light baryon transitions

    International Nuclear Information System (INIS)

    Hussain, F.; Liu Dongsheng; Kraemer, M.; Koerner, J.G.; Tawfiq, S.

    1992-01-01

    We present a complete analysis of the heavy to heavy and heavy to light baryon semi-leptonic decays in the heavy quark effective theory within the framework of a Bethe-Salpeter (BS) approach and demonstrate the equivalence of this approach to other work in the field. We present in a compact form the baryon BS amplitudes which incorporate the symmetries manifest in the heavy quark limit and which also show clearly the light quark dynamics. A similar form of the BS amplitude is presented for light baryons. Using the BS amplitudes, the heavy to heavy and heavy to light semi-leptonic baryon decays are considered. As expected there is a dramatic reduction in the number of form factors. An advantage of our BS approach is demonstrated where the form factors are written as loop integrals which in principle can be calculated. (orig.)

  17. CHAINS-PC, Decay Chain Atomic Densities

    International Nuclear Information System (INIS)

    1994-01-01

    1 - Description of program or function: CHAINS computes the atom density of members of a single radioactive decay chain. The linearity of the Bateman equations allows tracing of interconnecting chains by manually accumulating results from separate calculations of single chains. Re-entrant loops can be treated as extensions of a single chain. Losses from the chain are also tallied. 2 - Method of solution: The Bateman equations are solved analytically using double-precision arithmetic. Poles are avoided by small alterations of the loss terms. Multigroup fluxes, cross sections, and self-shielding factors entered as input are used to compute the effective specific reaction rates. The atom densities are computed at any specified times. 3 - Restrictions on the complexity of the problem: Maxima of 100 energy groups, 100 time values, 50 members in a chain

  18. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Scrideli

    2001-09-01

    Full Text Available CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%. There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%, presence of CALLA+ (81.2% versus 80% or risk group (62.5% versus 60%. Disease-free survival was similar in both groups, with no significant difference (p: 0.7695. CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

  19. Crystal structures of fac-trichloridotris(trimethylphosphane-κPrhodium(III monohydrate and fac-trichloridotris(trimethylphosphane-κPrhodium(III methanol hemisolvate: rhodium structures that are isotypic with their iridium analogs

    Directory of Open Access Journals (Sweden)

    Joseph S. Merola

    2015-02-01

    Full Text Available The crystal structures of two solvates of fac-trichloridotris(trimethylphosphane-κPrhodium(III are reported, i.e. one with water in the crystal lattice, fac-[RhCl3(Me3P3]·H2O, and one with methanol in the crystal lattice, fac-[RhCl3(Me3P3]·0.5CH3OH. These rhodium compounds exhibit distorted octahedral coordination spheres at the metal and are isotypic with the analogous iridium compounds previously reported by us [Merola et al. (2013. Polyhedron, 54, 67–73]. Comparison is made between the rhodium and iridium compounds, highlighting their isostructural relationships.

  20. Heavy metal transport in large river systems: heavy metal emissions and loads in the Rhine and Elbe river basins

    Science.gov (United States)

    Vink, Rona; Behrendt, Horst

    2002-11-01

    Pollutant transport and management in the Rhine and Elbe basins is still of international concern, since certain target levels set by the international committees for protection of both rivers have not been reached. The analysis of the chain of emissions of point and diffuse sources to river loads will provide policy makers with a tool for effective management of river basins. The analysis of large river basins such as the Elbe and Rhine requires information on the spatial and temporal characteristics of both emissions and physical information of the entire river basin. In this paper, an analysis has been made of heavy metal emissions from various point and diffuse sources in the Rhine and Elbe drainage areas. Different point and diffuse pathways are considered in the model, such as inputs from industry, wastewater treatment plants, urban areas, erosion, groundwater, atmospheric deposition, tile drainage, and runoff. In most cases the measured heavy metal loads at monitoring stations are lower than the sum of the heavy metal emissions. This behaviour in large river systems can largely be explained by retention processes (e.g. sedimentation) and is dependent on the specific runoff of a catchment. Independent of the method used to estimate emissions, the source apportionment analysis of observed loads was used to determine the share of point and diffuse sources in the heavy metal load at a monitoring station by establishing a discharge dependency. The results from both the emission analysis and the source apportionment analysis of observed loads were compared and gave similar results. Between 51% (for Hg) and 74% (for Pb) of the total transport in the Elbe basin is supplied by inputs from diffuse sources. In the Rhine basin diffuse source inputs dominate the total transport and deliver more than 70% of the total transport. The diffuse hydrological pathways with the highest share are erosion and urban areas.

  1. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  2. The Use of Electrical Resistivity Method to Mapping The Migration of Heavy Metals by Electrokinetic

    Science.gov (United States)

    Azhar, A. T. S.; Ayuni, S. A.; Ezree, A. M.; Nizam, Z. M.; Aziman, M.; Hazreek, Z. A. M.; Norshuhaila, M. S.; Zaidi, E.

    2017-08-01

    The presence of heavy metals contamination in soil environment highly needs innovative remediation. Basically, this contamination was resulted from ex-mining sites, motor workshop, petrol station, landfill and industrial sites. Therefore, soil treatment is very important due to metal ions are characterized as non-biodegradable material that may be harmful to ecological system, food chain, human health and groundwater sources. There are various techniques that have been proposed to eliminate the heavy metal contamination from the soil such as bioremediation, phytoremediation, electrokinetic remediation, solidification and stabilization. The selection of treatment needs to fulfill some criteria such as cost-effective, easy to apply, green approach and high remediation efficiency. Electrokinetic remediation technique (EKR) offers those solutions in certain area where other methods are impractical. While, electrical resistivity method offers an alternative geophysical technique for soil subsurface profiling to mapping the heavy metals migration by the influece of electrical gradient. Consequently, this paper presents an overview of the use of EKR to treat contaminated soil by using ERM method to verify their effectiveness to remove heavy metals.

  3. Radioactive contamination levels in the ambient medium and in the food chain - Quadriennial report 1972-1975

    International Nuclear Information System (INIS)

    1976-01-01

    In the period 1972-1975, the EURATOM-CEA Association continued its research in the following fields: human biology, study of iodine metabolism and its variability, study of the mineral composition of the human body. Transfers of contamination from sources of pollution to man - dry and moist deposits of iodine on grass - transfers of Cr, Zn and Cd in aquatic chains - transfers of heavy metals in marine chains - transfers of iodine and mercury from soil and sediments - transfers in foodstuffs during processing and distribution. Studies of the assessment of the radiological capacity of the environment and methods of assessing individual and collective doses [fr

  4. Discrete kink dynamics in hydrogen-bonded chains: The two-component model

    DEFF Research Database (Denmark)

    Karpan, V.M.; Zolotaryuk, Yaroslav; Christiansen, Peter Leth

    2004-01-01

    We study discrete topological solitary waves (kinks and antikinks) in two nonlinear diatomic chain models that describe the collective dynamics of proton transfers in one-dimensional hydrogen-bonded networks. The essential ingredients of the models are (i) a realistic (anharmonic) ion-proton inte......We study discrete topological solitary waves (kinks and antikinks) in two nonlinear diatomic chain models that describe the collective dynamics of proton transfers in one-dimensional hydrogen-bonded networks. The essential ingredients of the models are (i) a realistic (anharmonic) ion...... chain subject to a substrate with two optical bands), both providing a bistability of the hydrogen-bonded proton. Exact two-component (kink and antikink) discrete solutions for these models are found numerically. We compare the soliton solutions and their properties in both the one- (when the heavy ions...... principal differences, like a significant difference in the stability switchings behavior for the kinks and the antikinks. Water-filled carbon nanotubes are briefly discussed as possible realistic systems, where topological discrete (anti)kink states might exist....

  5. Impact of substrate contamination with mycotoxins, heavy metals and pesticides on the growth performance and composition of black soldier fly larvae (Hermetia illucens) for use in the feed and food value chain.

    Science.gov (United States)

    Purschke, Benedict; Scheibelberger, Rafaela; Axmann, Sonja; Adler, Andreas; Jäger, Henry

    2017-08-01

    Edible insects have emerged as an alternative and sustainable source of high-quality, animal-derived protein and fat for livestock production or direct human nutrition. During the production of insects, substrate quality is a key parameter to assure optimal insect biomass gain as well as the safety of feed and food derived from commercially reared insects. Therefore, the influence of a realistic substrate contamination scenario on growth performance and accumulation behaviour of black soldier fly larvae (BSFL; Hermetia illucens L.) was investigated. Newly hatched larvae were fed on a corn-based substrate spiked with heavy metals (As, Cd, Cr, Hg, Ni, Pb), mycotoxins (aflatoxins B1/B2/G2, deoxynivalenol, ochratoxin A, zearalenone) and pesticides (chlorpyrifos, chlorpyrifos-methyl, pirimiphos-methyl) under defined breeding conditions (10 days, 28°C, 67% relative humidity). The extent of contaminants' bioaccumulation in the larval tissue as well as the effect on growing determinants were examined. The applied heavy metal substrate contamination was shown to impair larval growing indicated by significantly lower post-trial larval mass and feed conversion ratio (FCR). Cd and Pb accumulation factors of 9 and 2, respectively, were determined, while the concentrations of other heavy metals in the larvae remained below the initial substrate concentration. In contrast, mycotoxins and pesticides have neither been accumulated in the larval tissue nor significantly affected the growing determinants in comparison with the control. The use of BSFL as livestock feed requires contaminant monitoring - especially for Cd and Pb - in the substrates as well as in feedstuff containing BSFL to ensure feed and food safety along the value chain.

  6. Bacterial mediated alleviation of heavy metal stress and decreased accumulation of metals in plant tissues: Mechanisms and future prospects.

    Science.gov (United States)

    Etesami, Hassan

    2018-01-01

    Heavy metal pollution of agricultural soils is one of main concerns causing some of the different ecological and environmental problems. Excess accumulation of these metals in soil has changed microbial community (e.g., structure, function, and diversity), deteriorated soil, decreased the growth and yield of plant, and entered into the food chain. Plants' tolerance to heavy metal stress needs to be improved in order to allow growth of crops with minimum or no accumulation of heavy metals in edible parts of plant that satisfy safe food demands for the world's rapidly increasing population. It is well known that PGPRs (plant growth-promoting rhizobacteria) enhance crop productivity and plant resistance to heavy metal stress. Many recent reports describe the application of heavy metal resistant-PGPRs to enhance agricultural yields without accumulation of metal in plant tissues. This review provides information about the mechanisms possessed by heavy metal resistant-PGPRs that ameliorate heavy metal stress to plants and decrease the accumulation of these metals in plant, and finally gives some perspectives for research on these bacteria in agriculture in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Visually driven chaining of elementary swim patterns into a goal-directed motor sequence: a virtual reality study of zebrafish prey capture

    Directory of Open Access Journals (Sweden)

    Chintan A Trivedi

    2013-05-01

    Full Text Available Prey capture behavior critically depends on rapid processing of sensory input in order to track, approach and catch the target. When using vision, the nervous system faces the problem of extracting relevant information from a continuous stream of input in order to detect and categorize visible objects as potential prey and to select appropriate motor patterns for approach. For prey capture, many vertebrates exhibit intermittent locomotion, in which discrete motor patterns are chained into a sequence, interrupted by short periods of rest. Here, using high-speed recordings of full-length prey capture sequences performed by freely swimming zebrafish larvae in the presence of a single paramecium, we provide a detailed kinematic analysis of first and subsequent swim bouts during prey capture. Using Fourier analysis, we show that individual swim bouts represent an elementary motor pattern. Changes in orientation are directed towards the target on a graded scale and are implemented by an asymmetric tail bend component superimposed on this basic motor pattern. To further investigate the role of visual feedback on the efficiency and speed of this complex behavior, we developed a closed-loop virtual reality setup in which minimally restrained larvae recapitulated interconnected swim patterns closely resembling those observed during prey capture in freely moving fish. Systematic variation of stimulus properties showed that prey capture is initiated within a narrow range of stimulus size and velocity. Furthermore, variations in the delay and location of swim-triggered visual feedback showed that the reaction time of secondary and later swims is shorter for stimuli that appear within a narrow spatio-temporal window following a swim. This suggests that the larva may generate an expectation of stimulus position, which enables accelerated motor sequencing if the expectation is met by appropriate visual feedback.

  8. Visually driven chaining of elementary swim patterns into a goal-directed motor sequence: a virtual reality study of zebrafish prey capture

    Science.gov (United States)

    Trivedi, Chintan A.; Bollmann, Johann H.

    2013-01-01

    Prey capture behavior critically depends on rapid processing of sensory input in order to track, approach, and catch the target. When using vision, the nervous system faces the problem of extracting relevant information from a continuous stream of input in order to detect and categorize visible objects as potential prey and to select appropriate motor patterns for approach. For prey capture, many vertebrates exhibit intermittent locomotion, in which discrete motor patterns are chained into a sequence, interrupted by short periods of rest. Here, using high-speed recordings of full-length prey capture sequences performed by freely swimming zebrafish larvae in the presence of a single paramecium, we provide a detailed kinematic analysis of first and subsequent swim bouts during prey capture. Using Fourier analysis, we show that individual swim bouts represent an elementary motor pattern. Changes in orientation are directed toward the target on a graded scale and are implemented by an asymmetric tail bend component superimposed on this basic motor pattern. To further investigate the role of visual feedback on the efficiency and speed of this complex behavior, we developed a closed-loop virtual reality setup in which minimally restrained larvae recapitulated interconnected swim patterns closely resembling those observed during prey capture in freely moving fish. Systematic variation of stimulus properties showed that prey capture is initiated within a narrow range of stimulus size and velocity. Furthermore, variations in the delay and location of swim triggered visual feedback showed that the reaction time of secondary and later swims is shorter for stimuli that appear within a narrow spatio-temporal window following a swim. This suggests that the larva may generate an expectation of stimulus position, which enables accelerated motor sequencing if the expectation is met by appropriate visual feedback. PMID:23675322

  9. Natural Radionuclides and Heavy Metals Pollution in Seawater at Kuala Langat Coastal Area

    International Nuclear Information System (INIS)

    Sabarina Md Yunus; Zaini Hamzah; Ab Khalik Hj Wood; Ahmad Saat

    2015-01-01

    Rapid industrial developments along the Langat river basin play an important role in contributing to the increases of pollution loading at Kuala Langat coastal area. The major pollutant sources in this area may be originating from human activities such as industrial discharge, domestic sewage, construction, agriculture and pig farming near the tributaries that affects the water quality. In addition, Langat and Semenyih rivers flow through the mining and ex-mining area, which is related to the source of natural radionuclides contamination. Heavy metals in the aquatic environment and more likely to enter the food chain. This study is focusing to the levels of radionuclides and heavy metals in seawater. The samples were collected using appropriate water sampler, which is then acidified until pH 2 and filtered using cellulose acetate 0.45 μm. The concentration of these radionuclides and heavy metals were determined using Inductive Coupled Plasma Mass Spectrometer (ICPMS) after dilution. In general, the radionuclides and heavy metals concentrations are lower than Malaysia Marine Water Quality Standard (MMWQS) except for few locations where the concentration levels above the standards. The higher concentration of pollutant in the seawater may have a toxic effect on sensitive plants and living organisms. The results of pollution levels of these radionuclides and heavy metals were also compared with other studies. (author)

  10. Study of the applicability of Markov chain Monte Carlo methods to the statistical separation of electron sources via the impact parameter for ALICE

    Energy Technology Data Exchange (ETDEWEB)

    Wittner, Manuel [Physikalisches Institut, Universitaet Heidelberg, Heidelberg (Germany); Collaboration: ALICE-Collaboration

    2015-07-01

    One particularly interesting measurement detected by the ALICE set-up at the LHC are electrons from charm and beauty hadron decays. Heavy quarks originate from initial hard scattering processes and thus experience the whole history of a heavy ion collision. Therefore, they are valuable probes to study the mechanisms of energy loss and hadronization in the hot and dense state of matter, that is expected to be formed in a heavy-ion collision at LHC. One important task is the distinction of the different electron sources, for which a method was developed. Hereby, the impact parameter distribution of the measurement data is compared with impact parameter distributions for the individual sources, which are created through Monte Carlo simulations. Afterwards, a maximum likelihood fit is applied. However, creating a posterior distribution of the likelihood according to Bayes' theorem and sampling it with Markov Chain Monte Carlo algorithms provides several advantages, e.g. a mathematically correct estimation of the uncertainties or the usage of prior knowledge. Hence for the first time in this particular problem, a Markov Chain Monte Carlo algorithm, namely the Metropolis algorithm, was implemented and investigated for its applicability in heavy flavor physics. First studies indicate its great usefulness in this field of physics.

  11. A Typology of Power in Global Value Chains

    DEFF Research Database (Denmark)

    Dallas, Mark; Ponte, Stefano; Sturgeon, Timothy

    ‘Power’ has been a foundational concept in examining global value chains and production networks for understanding patterns and dynamics in the global political economy. Yet, in most GVC scholarship, power is not explicitly defined and is applied as a unitary concept, rather than as having multiple...

  12. Predicting heavy episodic drinking using an extended temporal self-regulation theory.

    Science.gov (United States)

    Black, Nicola; Mullan, Barbara; Sharpe, Louise

    2017-10-01

    Alcohol consumption contributes significantly to the global burden from disease and injury, and specific patterns of heavy episodic drinking contribute uniquely to this burden. Temporal self-regulation theory and the dual-process model describe similar theoretical constructs that might predict heavy episodic drinking. The aims of this study were to test the utility of temporal self-regulation theory in predicting heavy episodic drinking, and examine whether the theoretical relationships suggested by the dual-process model significantly extend temporal self-regulation theory. This was a predictive study with 149 Australian adults. Measures were questionnaires (self-report habit index, cues to action scale, purpose-made intention questionnaire, timeline follow-back questionnaire) and executive function tasks (Stroop, Tower of London, operation span). Participants completed measures of theoretical constructs at baseline and reported their alcohol consumption two weeks later. Data were analysed using hierarchical multiple linear regression. Temporal self-regulation theory significantly predicted heavy episodic drinking (R 2 =48.0-54.8%, ptheory and the extended temporal self-regulation theory provide good prediction of heavy episodic drinking. Intention, behavioural prepotency, planning ability and inhibitory control may be good targets for interventions designed to decrease heavy episodic drinking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Network analysis of pig movements: Loyalty patterns and contact chains of different holding types in Denmark

    DEFF Research Database (Denmark)

    Schulz, Jana; Boklund, Anette; Hisham Beshara Halasa, Tariq

    2017-01-01

    proportion of holdings in the largest strongly connected component. All production sites showed low levels of in-going contact chains and we observed a high level of out-going contact chain for breeding and multiplier herds. Except for livestock auctions, all transit sites also showed low levels of out......-going contact chains. Our results reflect the pyramidal structure of the underlying network. Based on the considered disease, the time frame for the calculation of network measurements needs to be adapted. Using these adapted values for loyalty and contact chains might help to identify holdings with high...... in the connection between holdings dealing with pigs, such as breeding and multiplier herds, production herds, slaughterhouses or traders. Pig movements, which occurred between 1st January 2006 and 31st December 2015 in Denmark, were summarized to investigate temporal trends such as the number of active holdings...

  14. A heavy load for heavy ions

    CERN Multimedia

    2003-01-01

    On 25 September, the two large coils for the dipole magnet of ALICE, the LHC experiment dedicated to heavy ions, arrived at Point 2 on two heavy load trucks after a 1200 km journey from their assembly in Vannes, France.

  15. Process for removing heavy metal compounds from heavy crude oil

    Science.gov (United States)

    Cha, Chang Y.; Boysen, John E.; Branthaver, Jan F.

    1991-01-01

    A process is provided for removing heavy metal compounds from heavy crude oil by mixing the heavy crude oil with tar sand; preheating the mixture to a temperature of about 650.degree. F.; heating said mixture to up to 800.degree. F.; and separating tar sand from the light oils formed during said heating. The heavy metals removed from the heavy oils can be recovered from the spent sand for other uses.

  16. Heavy-ion radiography and heavy-ion computed tomography

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Holley, W.R.; McFarland, E.W.; Tobias, C.a.

    1982-02-01

    Heavy-ion projection and CT radiography is being developed into a safe, low-dose, noninvasive radiological procedure that can quantitate and image small density differences in human tissues. The applications to heavy-ion mammography and heavy-ion CT imaging of the brain in clinical patients suggest their potential value in cancer diagnosis

  17. Contamination features and health risk of soil heavy metals in China

    International Nuclear Information System (INIS)

    Chen, Haiyang; Teng, Yanguo; Lu, Sijin; Wang, Yeyao; Wang, Jinsheng

    2015-01-01

    China faces a big challenge of environmental deterioration amid its rapid economic development. To comprehensively identify the contamination characteristics of heavy metals in Chinese soils on a national scale, data set of the first national soil pollution survey was employed to evaluate the pollution levels using several pollution indicators (pollution index, geoaccumulation index and enrichment factor) and to quantify their exposure risks posed to human health with the risk assessment model recommended by the US Environmental Protection Agency. The results showed that, due to the drastically increased industrial operations and fast urban expansion, Chinese soils were contaminated by heavy metals in varying degrees. As a whole, the exposure risk levels of soil metals in China were tolerable or close to acceptable. Comparatively speaking, children and adult females were the relatively vulnerable populations for the non-carcinogenic and carcinogenic risks, respectively. Cadmium and mercury have been identified as the priority control metals due to their higher concentrations in soils or higher health risks posed to the public, as well as, arsenic, lead, chromium and nickel. Spatial distribution pattern analysis implied that the soil metal pollutions in southern provinces of China were relatively higher than that in other provinces, which would be related to the higher geochemical background in southwest regions and the increasing human activities in southeast areas. Meanwhile, it should be noticed that Beijing, the capital of China, also has been labeled as the priority control province for its higher mercury concentration. These results will provide basic information for the improvement of soil environment management and heavy metal pollution prevention and control in China. - Highlights: • Soil contamination with heavy metals in China was systematically studied. • Spatial distribution patterns of heavy metals in Chinese soils were identified. • Monte

  18. Contamination features and health risk of soil heavy metals in China

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Haiyang [Engineering Research Center of Groundwater Pollution Control and Remediation, Ministry of Education, Beijing 100875 (China); College of Water Sciences, Beijing Normal University, Beijing 100875 (China); Teng, Yanguo, E-mail: Teng1974@163.com [Engineering Research Center of Groundwater Pollution Control and Remediation, Ministry of Education, Beijing 100875 (China); College of Water Sciences, Beijing Normal University, Beijing 100875 (China); Lu, Sijin; Wang, Yeyao [China National Environmental Monitoring Center, Beijing 100012 (China); Wang, Jinsheng [Engineering Research Center of Groundwater Pollution Control and Remediation, Ministry of Education, Beijing 100875 (China); College of Water Sciences, Beijing Normal University, Beijing 100875 (China)

    2015-04-15

    China faces a big challenge of environmental deterioration amid its rapid economic development. To comprehensively identify the contamination characteristics of heavy metals in Chinese soils on a national scale, data set of the first national soil pollution survey was employed to evaluate the pollution levels using several pollution indicators (pollution index, geoaccumulation index and enrichment factor) and to quantify their exposure risks posed to human health with the risk assessment model recommended by the US Environmental Protection Agency. The results showed that, due to the drastically increased industrial operations and fast urban expansion, Chinese soils were contaminated by heavy metals in varying degrees. As a whole, the exposure risk levels of soil metals in China were tolerable or close to acceptable. Comparatively speaking, children and adult females were the relatively vulnerable populations for the non-carcinogenic and carcinogenic risks, respectively. Cadmium and mercury have been identified as the priority control metals due to their higher concentrations in soils or higher health risks posed to the public, as well as, arsenic, lead, chromium and nickel. Spatial distribution pattern analysis implied that the soil metal pollutions in southern provinces of China were relatively higher than that in other provinces, which would be related to the higher geochemical background in southwest regions and the increasing human activities in southeast areas. Meanwhile, it should be noticed that Beijing, the capital of China, also has been labeled as the priority control province for its higher mercury concentration. These results will provide basic information for the improvement of soil environment management and heavy metal pollution prevention and control in China. - Highlights: • Soil contamination with heavy metals in China was systematically studied. • Spatial distribution patterns of heavy metals in Chinese soils were identified. • Monte

  19. Levels and distribution patterns of short chain chlorinated paraffins in sewage sludge of wastewater treatment plants in China.

    Science.gov (United States)

    Zeng, Lixi; Wang, Thanh; Ruan, Ting; Liu, Qian; Wang, Yawei; Jiang, Guibin

    2012-01-01

    Short chain chlorinated paraffins (SCCPs) are listed as persistent organic pollutant candidates in the Stockholm Convention and are receiving more and more attentions worldwide. In general, concentrations of contaminants in sewage sludge can give an important indication on their pollution levels at a local/regional basis. In this study, SCCPs were investigated in sewage sludge samples collected from 52 wastewater treatment plants in China. Concentrations of total SCCPs (ΣSCCPs) in sludge were in the range of 0.80-52.7 μg/g dry weight (dw), with a mean value of 10.7 μg/g dw. Most of SCCPs in the sludge samples showed a similar congener distribution patterns, and C(11) and Cl(7,8) were identified as the dominant carbon and chlorine congener groups. Significant linear relationships were found among different SCCP congener groups (r(2) ≥ 0.9). High concentrations of SCCPs in sewage sludge imply that SCCPs are widely present in China. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. A field study on heavy metals phytoattenuation potential of monocropping and intercropping of maize and/or legumes in weakly alkaline soils.

    Science.gov (United States)

    Zhu, Saiyong; Ma, Xinwang; Guo, Rui; Ai, Shiwei; Liu, Bailin; Zhang, Wenya; Zhang, Yingmei

    2016-10-02

    The study focused on the phytoattenuation effects of monocropping and intercropping of maize (Zea mays) and/or legumes on Cu, Zn, Pb, and Cd in weakly alkaline soils. Nine growth stages of monocropping maize were chosen to study the dynamic process of extraction of heavy metals. The total content of heavy metals extracted by the aerial part of monocropped maize increased in a sigmoidal pattern over the effective accumulative temperature. The biggest biomass, highest extraction content, and lowest heavy metals bioaccumulation level occurred at physiological maturity. Among the different planting patterns, including monocropping and intercropping of maize and/or soybean (Glycine max), pea (Pisum sativum), and alfalfa (Medicago sativa), the extraction efficiency of Cu, Zn, Pb, and Cd varied greatly. Only intercropping of maize and soybean yielded relatively higher extraction efficiency for the four metals with no significant difference in the total biomass. Moreover, the heavy metals concentrations in dry biomass from all the planting patterns in the present study were within China's national legal thresholds for fodder use. Therefore, slightly polluted alkaline soils can be safely used through monocropping and intercropping of maize and/or legumes for a range of purposes. In particular, this study indicated that intercropping improves soil ecosystems polluted by heavy metals compared with monocropping.