Sample records for spa encoding protein

  1. Molecular cloning and characterization of the spaB gene of Streptococcus sobrinus.

    PubMed

    Holt, R G; Perry, S E

    1990-07-01

    A gene of Streptococcus sobrinus 6715 (serotype g) designated spaB and encoding a surface protein antigen was isolated from a cosmid gene bank. A 5.4 kb HindIII/AvaI DNA fragment containing the gene was inserted into plasmid pBR322 to yield plasmid pXI404. Analysis of plasmid-encoded gene products showed that the 5.4 kb fragment of pXI404 encoded a 195 kDa protein. Southern blot experiments revealed that the 5.4 kb chromosomal insert DNA had sequence similarity with genomic DNA of S. sobrinus 6715, S. sobrinus B13 (serotype d) and Streptococcus cricetus HS6 (serotype a). The recombinant SpaB protein (rSpaB) was purified and monospecific antiserum was prepared. With immunological techniques and the anti-rSpaB serum, we have shown: (1) that the rSpaB protein has physico-chemical and antigenic identity with the S. sobrinus SpaB protein, (2) the presence of cross-reactive proteins in the extracellular protein of serotypes a and d of the mutans group of streptococci and (3) that the SpaB protein is expressed on the surface of mutans streptococcal serotypes a, d and g.

  2. Molecular basis of surface anchored protein A deficiency in the Staphylococcus aureus strain Wood 46.

    PubMed

    Balachandran, Manasi; Giannone, Richard J; Bemis, David A; Kania, Stephen A

    2017-01-01

    Protein A in Staphylococcus aureus is encoded by the spa (staphylococcal protein A) gene and binds to immunoglobulin (Ig). The S. aureus strain Wood 46 has been variously reported as protein A-deficient and/or spa negative and used as a control in animal models of staphylococcal infections. The results of this study indicate that Wood 46 has normal spa expression but transcribes very low levels of the srtA gene which encodes the sortase A (SrtA) enzyme. This is consistent with unique mutations in the srtA promoter. In this study, a low level of sortase A explains deficient anchoring of proteins with an LPXTG motif, such as protein A, fibrinogen-binding protein and fibronectin-binding proteins A and B on to the peptidoglycan cell wall. The activity of secreted protein A is an important consideration for use of Wood 46 in functional experiments and animal models.

  3. Molecular basis of surface anchored protein A deficiency in the Staphylococcus aureus strain Wood 46

    PubMed Central

    Balachandran, Manasi; Giannone, Richard J.; Bemis, David A.

    2017-01-01

    Protein A in Staphylococcus aureus is encoded by the spa (staphylococcal protein A) gene and binds to immunoglobulin (Ig). The S. aureus strain Wood 46 has been variously reported as protein A-deficient and/or spa negative and used as a control in animal models of staphylococcal infections. The results of this study indicate that Wood 46 has normal spa expression but transcribes very low levels of the srtA gene which encodes the sortase A (SrtA) enzyme. This is consistent with unique mutations in the srtA promoter. In this study, a low level of sortase A explains deficient anchoring of proteins with an LPXTG motif, such as protein A, fibrinogen-binding protein and fibronectin-binding proteins A and B on to the peptidoglycan cell wall. The activity of secreted protein A is an important consideration for use of Wood 46 in functional experiments and animal models. PMID:28859130

  4. Molecular basis of surface anchored protein A deficiency in the Staphylococcus aureus strain Wood 46

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Balachandran, Manasi; Giannone, Richard J.; Bemis, David A.

    Protein A in Staphylococcus aureus is encoded by the spa (staphylococcal protein A) gene and binds to immunoglobulin (Ig). The S. aureus strain Wood 46 has been variously reported as protein A-deficient and/or spa negative and used as a control in animal models of staphylococcal infections. The results of this study indicate that Wood 46 has normal spa expression but transcribes very low levels of the srtA gene which encodes the sortase A (SrtA) enzyme. This is consistent with unique mutations in the srtA promoter. In this study, a low level of sortase A explains deficient anchoring of proteins withmore » an LPXTG motif, such as protein A, fibrinogen-binding protein and fibronectin-binding proteins A and B on to the peptidoglycan cell wall. The activity of secreted protein A is an important consideration for use of Wood 46 in functional experiments and animal models.« less

  5. Molecular basis of surface anchored protein A deficiency in the Staphylococcus aureus strain Wood 46

    DOE PAGES

    Balachandran, Manasi; Giannone, Richard J.; Bemis, David A.; ...

    2017-08-31

    Protein A in Staphylococcus aureus is encoded by the spa (staphylococcal protein A) gene and binds to immunoglobulin (Ig). The S. aureus strain Wood 46 has been variously reported as protein A-deficient and/or spa negative and used as a control in animal models of staphylococcal infections. The results of this study indicate that Wood 46 has normal spa expression but transcribes very low levels of the srtA gene which encodes the sortase A (SrtA) enzyme. This is consistent with unique mutations in the srtA promoter. In this study, a low level of sortase A explains deficient anchoring of proteins withmore » an LPXTG motif, such as protein A, fibrinogen-binding protein and fibronectin-binding proteins A and B on to the peptidoglycan cell wall. The activity of secreted protein A is an important consideration for use of Wood 46 in functional experiments and animal models.« less

  6. Cross-reactivity between the immunodominant determinant of the antigen I component of Streptococcus sobrinus SpaA protein and surface antigens from other members of the Streptococcus mutans group.

    PubMed

    Goldschmidt, R M; Curtiss, R

    1990-07-01

    Most members of the Streptococcus mutans group of microorganisms specify a major cell surface-associated protein, SpaA, that is defined by its antigenic properties. The region of the spaA gene from Streptococcus sobrinus 6715 encoding the immunodominant determinant of the major antigenic component (antigen I) of the SpaA protein has recently been characterized. This study examined whether recognition of the immunodominant determinant is independent of the immunized animal host and whether antibodies elicited by the immunodominant determinant cross-react with cell surface proteins from S. mutans of various serotypes. Mouse and rabbit antisera to the undenatured SpaA protein reacted similarly both with the immunodominant determinant and with other antigenic structures of the protein in Western immunoblots with SpaA polypeptides that were specified by spaA gene fragments expressed in recombinant Escherichia coli. This suggests that the antibody responses of inbred and outbred animals were similar. Furthermore, antibodies raised against both the S. sobrinus SpaA immunodominant determinant expressed by recombinant E. coli and the purified protein from S. sobrinus displayed similar strain specificities and protein band profiles towards cells surface proteins from S. mutans of various serotypes in immunodot and Western blot analyses, respectively. This suggests that for S. sobrinus serotype g, the immune response against the SpaA protein is governed by the immunodominant determinant of antigen I. In addition, it indicates that the SpaA protein domain containing the immunodominant determinant overlaps the domain conferring cross-reactivity to cell surface proteins of S. mutans of various serotypes.

  7. Phenotypical Analysis of the Lactobacillus rhamnosus GG Fimbrial spaFED Operon: Surface Expression and Functional Characterization of Recombinant SpaFED Pili in Lactococcus lactis

    PubMed Central

    Kant, Ravi; Palva, Airi; von Ossowski, Ingemar

    2014-01-01

    A noticeable genomic feature of many piliated Gram-positive bacterial species is the presence of more than one pilus-encoding operon. Paradigmatically, the gut-adapted Lactobacillus rhamnosus GG strain contains two different fimbrial operons in its genome. However, whereas one of these operons (called spaCBA) is encoding for the functionally mucus-/collagen-binding SpaCBA pilus, for the other operon (called spaFED) any native expression of the SpaFED-called pili is still the subject of some uncertainty. Irrespective of such considerations, we decided it would be of relevance or interest to decipher the gross structure of this pilus type, and as well assess its functional capabilities for cellular adhesion and immunostimulation. For this, and by following the approach we had used previously to explicate the immuno-properties of SpaCBA pili, we constructed nisin-inducible expression clones producing either wild-type or SpaF pilin-deleted surface-assembled L. rhamnosus GG SpaFED pili on Lactococcus lactis cells. Using these piliated lactococcal constructs, we found that the pilin-polymerized architecture of a recombinant-produced SpaFED pilus coincides with sequence-based functional predictions of the related pilins, and in fact is prototypical of those other sortase-dependent pilus-like structures thus far characterized for piliated Gram-positive bacteria. Moreover, we confirmed that among the different pilin subunits encompassing spaFED operon-encoded pili, the SpaF pilin is a main adhesion determinant, and when present in the assembled structure can mediate pilus binding to mucus, certain extracellular matrix proteins, and different gut epithelial cell lines. However, somewhat unexpectedly, when recombinant SpaFED pili are surface-attached, we found that they could not potentiate the existing lactococcal cell-induced immune responses so elicited from intestinal- and immune-related cells, but rather instead, they could dampen them. Accordingly, we have now provided the first phenotypical description of a spaFED pilus operon, and with that furthered the functional understanding of surface piliation for a particular gut-commensalic genre of piliated Gram-positive bacteria. PMID:25415357

  8. Phenotypical analysis of the Lactobacillus rhamnosus GG fimbrial spaFED operon: surface expression and functional characterization of recombinant SpaFED pili in Lactococcus lactis.

    PubMed

    Rintahaka, Johanna; Yu, Xia; Kant, Ravi; Palva, Airi; von Ossowski, Ingemar

    2014-01-01

    A noticeable genomic feature of many piliated Gram-positive bacterial species is the presence of more than one pilus-encoding operon. Paradigmatically, the gut-adapted Lactobacillus rhamnosus GG strain contains two different fimbrial operons in its genome. However, whereas one of these operons (called spaCBA) is encoding for the functionally mucus-/collagen-binding SpaCBA pilus, for the other operon (called spaFED) any native expression of the SpaFED-called pili is still the subject of some uncertainty. Irrespective of such considerations, we decided it would be of relevance or interest to decipher the gross structure of this pilus type, and as well assess its functional capabilities for cellular adhesion and immunostimulation. For this, and by following the approach we had used previously to explicate the immuno-properties of SpaCBA pili, we constructed nisin-inducible expression clones producing either wild-type or SpaF pilin-deleted surface-assembled L. rhamnosus GG SpaFED pili on Lactococcus lactis cells. Using these piliated lactococcal constructs, we found that the pilin-polymerized architecture of a recombinant-produced SpaFED pilus coincides with sequence-based functional predictions of the related pilins, and in fact is prototypical of those other sortase-dependent pilus-like structures thus far characterized for piliated Gram-positive bacteria. Moreover, we confirmed that among the different pilin subunits encompassing spaFED operon-encoded pili, the SpaF pilin is a main adhesion determinant, and when present in the assembled structure can mediate pilus binding to mucus, certain extracellular matrix proteins, and different gut epithelial cell lines. However, somewhat unexpectedly, when recombinant SpaFED pili are surface-attached, we found that they could not potentiate the existing lactococcal cell-induced immune responses so elicited from intestinal- and immune-related cells, but rather instead, they could dampen them. Accordingly, we have now provided the first phenotypical description of a spaFED pilus operon, and with that furthered the functional understanding of surface piliation for a particular gut-commensalic genre of piliated Gram-positive bacteria.

  9. Overcoming codon-usage bias in heterologous protein expression in Streptococcus gordonii.

    PubMed

    Lee, Song F; Li, Yi-Jing; Halperin, Scott A

    2009-11-01

    One of the limitations facing the development of Streptococcus gordonii into a successful vaccine vector is the inability of this bacterium to express high levels of heterologous proteins. In the present study, we have identified 12 codons deemed as rare codons in S. gordonii and seven other streptococcal species. tRNA genes encoding 10 of the 12 rare codons were cloned into a plasmid. The plasmid was transformed into strains of S. gordonii expressing the fusion protein SpaP/S1, the anti-complement receptor 1 (CR1) single-chain variable fragment (scFv) antibody, or the Toxoplasma gondii cyclophilin C18 protein. These three heterologous proteins contained high percentages of amino acids encoded by rare codons. The results showed that the production of SpaP/S1, anti-CR1 scFv and C18 increased by 2.7-, 120- and 10-fold, respectively, over the control strains. In contrast, the production of the streptococcal SpaP protein without the pertussis toxin S1 fragment was not affected by tRNA gene supplementation, indicating that the increased production of SpaP/S1 protein was due to the ability to overcome the limitation caused by rare codons required for the S1 fragment. The increase in anti-CR1 scFv production was also observed in Streptococcus mutans following tRNA gene supplementation. Collectively, the findings in the present study demonstrate for the first time, to the best of our knowledge, that codon-usage bias exists in Streptococcus spp. and the limitation of heterologous protein expression caused by codon-usage bias can be overcome by tRNA supplementation.

  10. Regulation of translation by upstream translation initiation codons of surfactant protein A1 splice variants

    PubMed Central

    Tsotakos, Nikolaos; Silveyra, Patricia; Lin, Zhenwu; Thomas, Neal; Vaid, Mudit

    2014-01-01

    Surfactant protein A (SP-A), a molecule with roles in lung innate immunity and surfactant-related functions, is encoded by two genes in humans: SFTPA1 (SP-A1) and SFTPA2 (SP-A2). The mRNAs from these genes differ in their 5′-untranslated regions (5′-UTR) due to differential splicing. The 5′-UTR variant ACD′ is exclusively found in transcripts of SP-A1, but not in those of SP-A2. Its unique exon C contains two upstream AUG codons (uAUGs) that may affect SP-A1 translation efficiency. The first uAUG (u1) is in frame with the primary start codon (p), but the second one (u2) is not. The purpose of this study was to assess the impact of uAUGs on SP-A1 expression. We employed RT-qPCR to determine the presence of exon C-containing SP-A1 transcripts in human RNA samples. We also used in vitro techniques including mutagenesis, reporter assays, and toeprinting analysis, as well as in silico analyses to determine the role of uAUGs. Exon C-containing mRNA is present in most human lung tissue samples and its expression can, under certain conditions, be regulated by factors such as dexamethasone or endotoxin. Mutating uAUGs resulted in increased luciferase activity. The mature protein size was not affected by the uAUGs, as shown by a combination of toeprint and in silico analysis for Kozak sequence, secondary structure, and signal peptide and in vitro translation in the presence of microsomes. In conclusion, alternative splicing may introduce uAUGs in SP-A1 transcripts, which in turn negatively affect SP-A1 translation, possibly affecting SP-A1/SP-A2 ratio, with potential for clinical implication. PMID:25326576

  11. Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells

    PubMed Central

    Mandlik, Anjali; Swierczynski, Arlene; Das, Asis; Ton-That, Hung

    2010-01-01

    Summary Adherence to host tissues mediated by pili is pivotal in the establishment of infection by many bacterial pathogens. Corynebacterium diphtheriae assembles on its surface three distinct pilus structures. The function and the mechanism of how various pili mediate adherence, however, have remained poorly understood. Here we show that the SpaA-type pilus is sufficient for the specific adherence of corynebacteria to human pharyngeal epithelial cells. The deletion of the spaA gene, which encodes the major pilin forming the pilus shaft, abolishes pilus assembly but not adherence to pharyngeal cells. In contrast, adherence is greatly diminished when either minor pilin SpaB or SpaC is absent. Antibodies directed against either SpaB or SpaC block bacterial adherence. Consistent with a direct role of the minor pilins, latex beads coated with SpaB or SpaC protein bind specifically to pharyngeal cells. Therefore, tissue tropism of corynebacteria for pharyngeal cells is governed by specific minor pilins. Importantly, immunoelectron microscopy and immunofluorescence studies reveal clusters of minor pilins that are anchored to cell surface in the absence of a pilus shaft. Thus, the minor pilins may also be cell wall anchored in addition to their incorporation into pilus structures that could facilitate tight binding to host cells during bacterial infection. PMID:17376076

  12. Quantitative Expression Analysis of SpA, FnbA and Rsp Genes in Staphylococcus aureus: Actively Associated in the Formation of Biofilms.

    PubMed

    Yeswanth, Sthanikam; Chaudhury, Abhijit; Sarma, Potukuchi Venkata Gurunadha Krishna

    2017-12-01

    In Staphylococcus aureus, adherence and secretory proteins play chief role in the formation of biofilms. This mode of growth exhibits resistance to a variety of antibiotics and spreads its infections. In the present study, secretary and adherence proteins, Protein-A, Fibronectin-binding protein-A (FnbA) and Rsp (a transcription regulator encoding proteolytic property) expression levels were evaluated at different stages of growth in S. aureus ATCC12600 a drug-sensitive strain and multidrug-resistant strains of S. aureus. Initially, the SpA, FnbA and Rsp genes of S. aureus ATCC12600 were cloned, sequenced, expressed and characterized. The proteolytic property of recombinant Rsp was conspicuously shown when this pathogen was grown in aerobic conditions correlating with reduced biofilm units. In anaerobic mode of growth, S. aureus exhibited a higher expression of SpA and FnbA in early and mid adherence phases and finally stabilized at 48 h of incubation. This expression was more pronounced in methicillin-resistant strains (LMV1-8 and D1-4) of S. aureus. In all these stages, Rsp gene expression was at the lowest level and these results concur with the increased biofilm units. The results of the present study explain proteins chiefly contribute in the formation of biofilms.

  13. SP-A binding sites on bovine alveolar macrophages.

    PubMed

    Plaga, S; Plattner, H; Schlepper-Schaefer, J

    1998-11-25

    Surfactant protein A (SP-A) binding to bovine alveolar macrophages was examined in order to characterize SP-A binding proteins on the cell surface and to isolate putative receptors from these cells that could be obtained in large amounts. Human SP-A, unlabeled or labeled with gold particles, was bound to freshly isolated macrophages and analyzed with ELISA or the transmission electron microscope. Binding of SP-A was inhibited by Ca2+ chelation, by an excess of unlabeled SP-A, or by the presence of 20 mg/ml mannan. We conclude that bovine alveolar macrophages expose binding sites for SP-A that are specific and that depend on Ca2+ and on mannose residues. For isolation of SP-A receptors with homologous SP-A as ligand we isolated SP-A from bovine lung lavage. SDS-PAGE analysis of the purified SP-A showed a protein of 32-36 kDa. Functional integrity of the protein was demonstrated. Bovine SP-A bound to Dynabeads was used to isolate SP-A binding proteins. From the fractionated and blotted proteins of the receptor preparation two proteins bound SP-A in a Ca2+-dependent manner, a 40-kDa protein showing mannose dependency and a 210-kDa protein, showing no mannose sensitivity. Copyright 1998 Academic Press.

  14. Type III Pilus of Corynebacteria: Pilus Length Is Determined by the Level of Its Major Pilin Subunit

    PubMed Central

    Swierczynski, Arlene; Ton-That, Hung

    2006-01-01

    Multiple pilus gene clusters have been identified in several gram-positive bacterial genomes sequenced to date, including the Actinomycetales, clostridia, streptococci, and corynebacteria. The genome of Corynebacterium diphtheriae contains three pilus gene clusters, two of which have been previously characterized. Here, we report the characterization of the third pilus encoded by the spaHIG cluster. By using electron microscopy and biochemical analysis, we demonstrate that SpaH forms the pilus shaft, while SpaI decorates the structure and SpaG is largely located at the pilus tip. The assembly of the SpaHIG pilus requires a specific sortase located within the spaHIG pilus gene cluster. Deletion of genes specific for the synthesis and polymerization of the other two pilus types does not affect the SpaHIG pilus. Moreover, SpaH but not SpaI or SpaG is essential for the formation of the filament. When expressed under the control of an inducible promoter, the amount of the SpaH pilin regulates pilus length; no pili are assembled from an SpaH precursor that has an alanine in place of the conserved lysine of the SpaH pilin motif. Thus, the spaHIG pilus gene cluster encodes a pilus structure that is independently assembled and antigenically distinct from other pili of C. diphtheriae. We incorporate these findings in a model of sortase-mediated pilus assembly that may be applicable to many gram-positive pathogens. PMID:16923899

  15. Type III pilus of corynebacteria: Pilus length is determined by the level of its major pilin subunit.

    PubMed

    Swierczynski, Arlene; Ton-That, Hung

    2006-09-01

    Multiple pilus gene clusters have been identified in several gram-positive bacterial genomes sequenced to date, including the Actinomycetales, clostridia, streptococci, and corynebacteria. The genome of Corynebacterium diphtheriae contains three pilus gene clusters, two of which have been previously characterized. Here, we report the characterization of the third pilus encoded by the spaHIG cluster. By using electron microscopy and biochemical analysis, we demonstrate that SpaH forms the pilus shaft, while SpaI decorates the structure and SpaG is largely located at the pilus tip. The assembly of the SpaHIG pilus requires a specific sortase located within the spaHIG pilus gene cluster. Deletion of genes specific for the synthesis and polymerization of the other two pilus types does not affect the SpaHIG pilus. Moreover, SpaH but not SpaI or SpaG is essential for the formation of the filament. When expressed under the control of an inducible promoter, the amount of the SpaH pilin regulates pilus length; no pili are assembled from an SpaH precursor that has an alanine in place of the conserved lysine of the SpaH pilin motif. Thus, the spaHIG pilus gene cluster encodes a pilus structure that is independently assembled and antigenically distinct from other pili of C. diphtheriae. We incorporate these findings in a model of sortase-mediated pilus assembly that may be applicable to many gram-positive pathogens.

  16. Nucleotide Polymorphism in the Wheat Transcriptional Activator Spa Influences Its Pattern of Expression and Has Pleiotropic Effects on Grain Protein Composition, Dough Viscoelasticity, and Grain Hardness[W][OA

    PubMed Central

    Ravel, Catherine; Martre, Pierre; Romeuf, Isabelle; Dardevet, Mireille; El-Malki, Redouane; Bordes, Jacques; Duchateau, Nathalie; Brunel, Dominique; Balfourier, François; Charmet, Gilles

    2009-01-01

    Storage protein activator (SPA) is a key regulator of the transcription of wheat (Triticum aestivum) grain storage protein genes and belongs to the Opaque2 transcription factor subfamily. We analyzed the sequence polymorphism of the three homoeologous Spa genes in hexaploid wheat. The level of polymorphism in these genes was high particularly in the promoter. The deduced protein sequences of each homoeolog and haplotype show greater than 93% identity. Two major haplotypes were studied for each Spa gene. The three Spa homoeologs have similar patterns of expression during grain development, with a peak in expression around 300 degree days after anthesis. On average, Spa-B is 10 and seven times more strongly expressed than Spa-A and Spa-D, respectively. The haplotypes are associated with significant quantitative differences in Spa expression, especially for Spa-A and Spa-D. Significant differences were found in the quantity of total grain nitrogen allocated to the gliadin protein fractions for the Spa-A haplotypes, whereas the synthesis of glutenins is not modified. Genetic association analysis between Spa and dough viscoelasticity revealed that Spa polymorphisms are associated with dough tenacity, extensibility, and strength. Except for Spa-A, these associations can be explained by differences in grain hardness. No association was found between Spa markers and the average single grain dry mass or grain protein concentration. These results demonstrate that in planta Spa is involved in the regulation of grain storage protein synthesis. The associations between Spa and dough viscoelasticity and grain hardness strongly suggest that Spa has complex pleiotropic functions during grain development. PMID:19828671

  17. Differential effects of human SP-A1 and SP-A2 variants on phospholipid monolayers containing surfactant protein B

    PubMed Central

    Wang, Guirong; Taneva, Svetla; Keough, Kevin M.W.; Floros, Joanna

    2010-01-01

    Summary Surfactant protein A (SP-A), the most abundant protein in the lung alveolar surface, has multiple activities, including surfactant-related functions. SP-A is required for the formation of tubular myelin and the lung surface film. The human SP-A locus consists of two functional SP-A genes, SP-A1 and SP-A2, with a number of alleles characterized for each gene. We have found that the human in vitro expressed variants, SP-A1 (6A2) and SP-A2 (1A0), and the coexpressed SP-A1/SP-A2 (6A2/1A0) protein have a differential influence on the organization of phospholipid monolayers containing surfactant protein B (SP-B). Lipid films containing SP-B and SP-A2 (1A0) showed surface features similar to those observed in lipid films with SP-B and native human SP-A. Fluorescence images revealed the presence of characteristic fluorescent probe-excluding clusters coexisting with the traditional lipid liquid-expanded and liquid-condensed phase. Images of the films containing SP-B and SP-A1 (6A2) showed different distribution of the proteins. The morphology of lipid films containing SP-B and the coexpressed SP-A1/SP-A2 (6A2/1A0) combined features of the individual films containing the SP-A1 or SP-A2 variant. The results indicate that human SP-A1 and SP-A2 variants exhibit differential effects on characteristics of phospholipid monolayers containing SP-B. This may differentially impact surface film activity. PMID:17678872

  18. Functional Analysis of the Lactobacillus casei BL23 Sortases

    PubMed Central

    Muñoz-Provencio, Diego; Rodríguez-Díaz, Jesús; Collado, María Carmen; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2012-01-01

    Sortases are a class of enzymes that anchor surface proteins to the cell wall of Gram-positive bacteria. Lactobacillus casei BL23 harbors four sortase genes, two belonging to class A (srtA1 and srtA2) and two belonging to class C (srtC1 and srtC2). Class C sortases were clustered with genes encoding their putative substrates that were homologous to the SpaEFG and SpaCBA proteins that encode mucus adhesive pili in Lactobacillus rhamnosus GG. Twenty-three genes encoding putative sortase substrates were identified in the L. casei BL23 genome with unknown (35%), enzymatic (30%), or adhesion-related (35%) functions. Strains disrupted in srtA1, srtA2, srtC1, and srtC2 and an srtA1 srtA2 double mutant were constructed. The transcription of all four sortase encoding genes was detected, but only the mutation of srtA1 resulted in a decrease in bacterial surface hydrophobicity. The β-N-acetyl-glucosaminidase and cell wall proteinase activities of whole cells diminished in the srtA1 mutant and, to a greater extent, in the srtA1 srtA2 double mutant. Cell wall anchoring of the staphylococcal NucA reporter protein fused to a cell wall sorting sequence was also affected in the srtA mutants, and the percentages of adhesion to Caco-2 and HT-29 intestinal epithelial cells were reduced for the srtA1 srtA2 strain. Mutations in srtC1 or srtC2 result in an undetectable phenotype. Together, these results suggest that SrtA1 is the housekeeping sortase in L. casei BL23 and SrtA2 would carry out redundant or complementary functions that become evident when SrtA1 activity is absent. PMID:23042174

  19. A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.

    PubMed

    Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-12-01

    The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. © 2015 John Wiley & Sons Ltd.

  20. A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence

    PubMed Central

    Reardon-Robinson, Melissa E.; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2016-01-01

    Summary The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. PMID:26294390

  1. Molecular characterization of endocarditis-associated Staphylococcus aureus.

    PubMed

    Nethercott, Cara; Mabbett, Amanda N; Totsika, Makrina; Peters, Paul; Ortiz, Juan C; Nimmo, Graeme R; Coombs, Geoffrey W; Walker, Mark J; Schembri, Mark A

    2013-07-01

    Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninety-seven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted.

  2. Molecular Characterization of Endocarditis-Associated Staphylococcus aureus

    PubMed Central

    Nethercott, Cara; Mabbett, Amanda N.; Totsika, Makrina; Peters, Paul; Ortiz, Juan C.; Nimmo, Graeme R.; Coombs, Geoffrey W.

    2013-01-01

    Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninety-seven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted. PMID:23616460

  3. The blue light-induced interaction of cryptochrome 1 with COP1 requires SPA proteins during Arabidopsis light signaling.

    PubMed

    Holtkotte, Xu; Ponnu, Jathish; Ahmad, Margaret; Hoecker, Ute

    2017-10-01

    Plants constantly adjust their growth, development and metabolism to the ambient light environment. Blue light is sensed by the Arabidopsis photoreceptors CRY1 and CRY2 which subsequently initiate light signal transduction by repressing the COP1/SPA E3 ubiquitin ligase. While the interaction between cryptochromes and SPA is blue light-dependent, it was proposed that CRY1 interacts with COP1 constitutively, i.e. also in darkness. Here, our in vivo co-immunoprecipitation experiments suggest that CRY1 and CRY2 form a complex with COP1 only after seedlings were exposed to blue light. No association between COP1 and CRY1 or CRY2 was observed in dark-grown seedlings. Thus, our results suggest that cryptochromes bind the COP1/SPA complex after photoactivation by blue light. In a spa quadruple mutant that is devoid of all four SPA proteins, CRY1 and COP1 did not interact in vivo, neither in dark-grown nor in blue light-grown seedlings. Hence, SPA proteins are required for the high-affinity interaction between CRY1 and COP1 in blue light. Yeast three-hybrid experiments also show that SPA1 enhances the CRY1-COP1 interaction. The coiled-coil domain of SPA1 which is responsible for COP1-binding was necessary to mediate a CRY1-SPA1 interaction in vivo, implying that-in turn-COP1 may be necessary for a CRY1-SPA1 complex formation. Hence, SPA1 and COP1 may act cooperatively in recognizing and binding photoactivated CRY1. In contrast, the blue light-induced association between CRY2 and COP1 was not dependent on SPA proteins in vivo. Similarly, ΔCC-SPA1 interacted with CRY2, though with a much lower affinity than wild-type SPA1. In total, our results demonstrate that CRY1 and CRY2 strongly differ in their blue light-induced interaction with the COP1/SPA complex.

  4. Surfactant-Associated Protein A Provides Critical Immunoprotection in Neonatal Mice▿

    PubMed Central

    George, Caroline L. S.; Goss, Kelli L.; Meyerholz, David K.; Lamb, Fred S.; Snyder, Jeanne M.

    2008-01-01

    The collectins surfactant-associated protein A (SP-A) and SP-D are components of innate immunity that are present before birth. Both proteins bind pathogens and assist in clearing infection. The significance of SP-A and SP-D as components of the neonatal immune system has not been investigated. To determine the role of SP-A and SP-D in neonatal immunity, wild-type, SP-A null, and SP-D null mice were bred in a bacterium-laden environment (corn dust bedding) or in a semisterile environment (cellulose fiber bedding). When reared in the corn dust bedding, SP-A null pups had significant mortality (P < 0.001) compared to both wild-type and SP-D null pups exposed to the same environment. The mortality of the SP-A null pups was associated with significant gastrointestinal tract pathology but little lung pathology. Moribund SP-A null newborn mice exhibited Bacillus sp. and Enterococcus sp. peritonitis. When the mother or newborn produced SP-A, newborn survival was significantly improved (P < 0.05) compared to the results when there was a complete absence of SP-A in both the mother and the pup. Significant sources of SP-A likely to protect a newborn include the neonatal lung and gastrointestinal tract but not the lactating mammary tissue of the mother. Furthermore, exogenous SP-A delivered by mouth to newborn SP-A null pups with SP-A null mothers improved newborn survival in the corn dust environment. Therefore, a lack of SP-D did not affect newborn survival, while SP-A produced by either the mother or the pup or oral exogenous SP-A significantly reduced newborn mortality associated with environmentally induced infection in SP-A null newborns. PMID:17967856

  5. Staphylococcal poisoning foodborne outbreak: epidemiological investigation and strain genotyping.

    PubMed

    Gallina, S; Bianchi, D M; Bellio, A; Nogarol, C; Macori, G; Zaccaria, T; Biorci, F; Carraro, E; Decastelli, L

    2013-12-01

    In June 2011, an outbreak of Staphylococcus aureus enterotoxin food poisoning gastroenteritis occurred in Turin, Italy, following a catered dinner party at a private home. Within a few hours, 26 of the 47 guests experienced gastrointestinal illness, and 9 were hospitalized. A retrospective cohort study using a standardized questionnaire was carried out, and the risk ratios for each food item were calculated. The analysis indicated consumption of seafood salad as the most probable cause of the outbreak (risk ratio = 11.72; 95 % confidence interval, 1.75 to 78.54). Biological samples were collected from four of the hospitalized guests (stool and vomit), nasal mucosa swabs from three food handlers employed with the caterer, and available food residuals. All stool and vomit samples tested positive for enterotoxigenic S. aureus. As residues of the seafood salad were no longer available for sampling, suspected contamination could not be verified. However, no other food was found contaminated by S. aureus or its enterotoxins. All isolates from the biological samples were characterized at the genomic level by means of two multiplex PCR protocols to determine the presence of genes encoding staphylococcal enterotoxins, pulsed-field gel electrophoresis and staphylococcal protein A gene (spa) typing to describe their genetic profiles. All the isolates presented genes encoding SEA and SEI; the pulsed-field gel electrophoresis genetic profiles revealed the same pulsotype in the microorganism isolated from the hospitalized guests as in one of the isolates from a food handler's nasal mucosa, and the spa typing analysis reported two closely related spa types (t701 and t267), implicating the food handler as the most likely outbreak source.

  6. Role of surfactant protein A (SP-A)/lipid interactions for SP-A functions in the lung.

    PubMed

    Casals, C

    2001-01-01

    Surfactant protein A (SP-A), an oligomeric glycoprotein, is a member of a group of proteins named collectins that contain collagen-like and Ca(2+)-dependent carbohydrate recognition domains. SP-A interacts with a broad range of amphipathic lipids (glycerophospholipids, sphingophospholipids, glycosphingolipids, lipid A, and lipoglycans) that are present in surfactant or microbial membranes. This review summarizes SP-A/lipid interaction studies regarding the lipid system used (i.e., phospholipid vesicles, phospholipid monolayers, and lipids immobilized on silica or adsorbed on a solid support). The effect of calcium, ionic strength, and pH on the binding of SP-A to lipids and the subsequent lipid aggregation process is discussed. Current evidence suggests that hydrophobic-binding forces are involved in the peripherical association of SP-A to membranes. It is also proposed that fluid and liquid-ordered phase coexistence in surfactant membranes might favor partition of SP-A into those membranes. The binding of SP-A to surfactant membranes containing hydrophobic surfactant peptides makes possible the formation of a membrane reservoir in the alveolar fluid that is protected by SP-A against inactivation and improves the rate of surfactant film formation. In addition, the interaction of SP-A with membranes might enhance the affinity of SP-A for terminal carbohydrates of glycolipids or glycoproteins on the surface of invading microorganisms.

  7. Binding sites for interaction of peroxiredoxin 6 with surfactant protein A

    PubMed Central

    Krishnaiah, Saikumari Y; Dodia, Chandra; Sorokina, Elena M; Li, Haitao; Feinstein, Sheldon I; Fisher, Aron B

    2016-01-01

    Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A2 (PLA2) activities. This protein participates in the degradation and remodeling of internalized dipalmitoylphosphatidylcholine (DPPC), the major phospholipid component of lung surfactant. We have shown previously that the PLA2 activity of Prdx6 is inhibited by the lung surfactant-associated protein called surfactant protein A (SP-A) through direct protein-protein interaction. Docking of SPA and Prdx6 was modeled using the ZDOCK (zlab.bu.edu) program in order to predict molecular sites for binding of the two proteins. The predicted peptide sequences were evaluated for binding to the opposite protein using isothermal titration calorimetry and circular dichroism measurement followed by determination of the effect of the SP-A peptide on the PLA2 activity of Prdx6. The sequences 195EEEAKKLFPK204.in the Prdx6 helix and 83DEELQTELYEIKHQIL99 in SP-A were identified as the sites for hydrophobic interaction and H+-bonding between the 2 proteins. Treatment of mouse endothelial cells with the SP-A peptide inhibited their recovery from lipid peroxidation associated with oxidative stress indicating inhibition of Prdx6 activity by the peptide in the intact cell. PMID:26723227

  8. Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity.

    PubMed

    Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

    2012-09-25

    Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity.

  9. Sex differences in the acute in vivo effects of different human SP-A variants on the mouse alveolar macrophage proteome

    PubMed Central

    Phelps, David S.; Umstead, Todd M.; Floros, Joanna

    2014-01-01

    Surfactant protein A (SP-A) is involved in lung innate immunity. Humans have two SP-A genes, SFTPA1 and SFTPA2, each with several variants. We examined the in vivo effects of treatment with specific SP-A variants on the alveolar macrophage (AM) proteome from SP-A knockout (KO) mice. KO mice received either SP-A1, SP-A2, or both. AM were collected and their proteomes examined with 2D-DIGE. We identified 90 proteins and categorized them as related to actin/cytoskeleton, oxidative stress, protease balance/chaperones, regulation of inflammation, and regulatory/developmental processes. SP-A1 and SP-A2 had different effects on the AM proteome and these effects differed between sexes. In males more changes occurred in the oxidative stress, protease/chaperones, and inflammation groups with SP-A2 treatment than with SP-A1. In females most SP-A1-induced changes were in the actin/cytoskeletal and oxidative stress groups. We conclude that after acute SP-A1 and SP-A2 treatment, sex-specific differences were observed in the AM proteomes from KO mice, and that these sex differences differ in response to SP-A1 and SP-A2. Females are more responsive to SP-A1, whereas the gene-specific differences in males were minimal. These observations not only demonstrate the therapeutic potential of exogenous SP-A, but also illustrate sex- and gene-specific differences in the response to it. PMID:24954098

  10. Binding sites for interaction of peroxiredoxin 6 with surfactant protein A.

    PubMed

    Krishnaiah, Saikumari Y; Dodia, Chandra; Sorokina, Elena M; Li, Haitao; Feinstein, Sheldon I; Fisher, Aron B

    2016-04-01

    Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A2 (PLA2) activities. This protein participates in the degradation and remodeling of internalized dipalmitoylphosphatidylcholine (DPPC), the major phospholipid component of lung surfactant. We have shown previously that the PLA2 activity of Prdx6 is inhibited by the lung surfactant-associated protein called surfactant protein A (SP-A) through direct protein-protein interaction. Docking of SPA and Prdx6 was modeled using the ZDOCK (zlab.bu.edu) program in order to predict molecular sites for binding of the two proteins. The predicted peptide sequences were evaluated for binding to the opposite protein using isothermal titration calorimetry and circular dichroism measurement followed by determination of the effect of the SP-A peptide on the PLA2 activity of Prdx6. The sequences 195EEEAKKLFPK204.in the Prdx6 helix and 83DEELQTELYEIKHQIL99 in SP-A were identified as the sites for hydrophobic interaction and H(+)-bonding between the 2 proteins. Treatment of mouse endothelial cells with the SP-A peptide inhibited their recovery from lipid peroxidation associated with oxidative stress indicating inhibition of Prdx6 activity by the peptide in the intact cell. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and regulate intercellular connectivity

    PubMed Central

    Lai, Julian; Koh, Chuan Hock; Tjota, Monika; Pieuchot, Laurent; Raman, Vignesh; Chandrababu, Karthik Balakrishna; Yang, Daiwen; Wong, Limsoon; Jedd, Gregory

    2012-01-01

    Like animals and plants, multicellular fungi possess cell-to-cell channels (septal pores) that allow intercellular communication and transport. Here, using a combination of MS of Woronin body-associated proteins and a bioinformatics approach that identifies related proteins based on composition and character, we identify 17 septal pore-associated (SPA) proteins that localize to the septal pore in rings and pore-centered foci. SPA proteins are not homologous at the primary sequence level but share overall physical properties with intrinsically disordered proteins. Some SPA proteins form aggregates at the septal pore, and in vitro assembly assays suggest aggregation through a nonamyloidal mechanism involving mainly α-helical and disordered structures. SPA loss-of-function phenotypes include excessive septation, septal pore degeneration, and uncontrolled Woronin body activation. Together, our data identify the septal pore as a complex subcellular compartment and focal point for the assembly of unstructured proteins controlling diverse aspects of intercellular connectivity. PMID:22955885

  12. [Differentiation of spa types and staphylococcal cassette chromosome mec (SCCmec) in clinical methicillin-resistant Staphylococcus aureus isolated in medical sites of Gdańsk region].

    PubMed

    Kasprzyk, Joanna; Piechowicz, Lidia; Wiśniewska, Katarzyna; Dziewit, Łukasz; Bronk, Marek; Świeć, Krystyna

    2015-01-01

    Methicillin-resistant Staphylococcus aureus bacteria are one of the key etiological factors of hospital-acquired and community-acquired infections. MRSA strains have an ability of causing a broad spectrum infections: from a relatively mild skin infections to severe life-threatening systemic infections. They are characterized by multi-drug resistance, virulence of a number of factors, may clonally spread within the hospitals and between hospitals. The study embraced a number of 75 isolates of MRSA isolated from patients of 7 medical sites of the Gdansk region within the period of six months (June to December 2013). Strains have derived from various clinical materials, both of hospitalized patients (n=59) and outpatient (n=16). The isolates were tested for the susceptibility to antimicrobial agents accordance with the guidelines EUCAST. To estimate of the variability of occurrence of S. aureus clones used were standard spa gene, consisting in the amplified polymorphic region of the X gene encoding the protein A gene (spa). After receiving the results, a spa types were identified using international database Ridom Spa Server (www.spaserver.ridom.de). To determine the polymorphism cassette carrying the inecA gene from MRSA strains, used typing five major chromosomal cassette SCCmec (I-V) by multiplex PCR. MRSA population genetic analysis carried out on the basis of typing SCCmec cassettes and spa gene has showed a predominance of strains with SCCmec type II casette (46.7%) and SCCmec IV casette (38.7%). Less frequently detected were strains containing SCCmec I cassette (12.0%) and SCCmec III cassette (2.6%). Spa typing revealed the presence of 13 gene types in MRSA. The most frequently observed spa types were: t151 (24.0%), t003 (16.0%) in strains of the SCCmec II cassette and t437 (16.0%) and t008 (14.8%) in the isolates with SCCmec cassette IV, whereas staphylococcus with the type of spa t011 (12.0%) had SCCmec cassette I. In our population most frequent strains cassette SCCmec II (46.7%), in most representing types of spa t151 (51.4%) and t003 (34.3%), generally resistant not only to β-lactam antibiotics, but as erythromycin, clindamycin and norfloxacin (82.8%), the more frequently they were isolated from patients than a hospital outpatient centers. The strains SCCmec IV that represent the majority of outpatient centers (68.8%), the most represented type t437 (41.4%) and often occurred in hospital centers.

  13. Soy Protein Microparticles for Enhanced Oral Ibuprofen Delivery: Preparation, Characterization, and In Vitro Release Evaluation.

    PubMed

    Anaya Castro, Maria Antonieta; Alric, Isabelle; Brouillet, Fabien; Peydecastaing, Jérôme; Fullana, Sophie Girod; Durrieu, Vanessa

    2018-04-01

    The objective of this work was to evaluate soy protein isolate (SPI) and acylated soy protein (SPA) as spray-drying encapsulation carriers for oral pharmaceutical applications. SPI acylation was performed by the Schotten-Baumann reaction. SPA, with an acylation rate of 41%, displayed a decrease in solubility in acidic conditions, whereas its solubility was unaffected by basic conditions. The drug encapsulation capacities of both SPI and SPA were tested with ibuprofen (IBU) as a model poorly soluble drug. IBU-SPI and IBU-SPA particles were obtained by spray-drying under eco-friendly conditions. Yields of 70 to 87% and microencapsulation efficiencies exceeding 80% were attained for an IBU content of 20 to 40% w/w, confirming the excellent microencapsulation properties of SPI and the suitability of the chemical modification. The in vitro release kinetics of IBU were studied in simulated gastrointestinal conditions (pH 1.2 and pH 6.8, 37°C). pH-sensitive release patterns were observed, with an optimized low rate of release in simulated gastric fluid for SPA formulations, and a rapid and complete release in simulated intestinal fluid for both formulations, due to the optimal pattern of pH-dependent solubility for SPA and the molecular dispersion of IBU in soy protein. These results demonstrate that SPI and SPA are relevant for the development of pH-sensitive drug delivery systems for the oral route.

  14. Surfactant protein A is expressed in the central nervous system of rats with experimental autoimmune encephalomyelitis, and suppresses inflammation in human astrocytes and microglia

    PubMed Central

    Yang, Xue; Yan, Jun; Feng, Juan

    2017-01-01

    The collectin surfactant protein-A (SP-A), a potent host defense molecule, is well recognized for its role in the maintenance of pulmonary homeostasis and the modulation of inflammatory responses. While previous studies have detected SP-A in numerous extrapulmonary tissues, there is still a lack of information regarding its expression in central nervous system (CNS) and potential effects in neuroinflammatory diseases, such as multiple sclerosis (MS). The present study used experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS, to investigate the expression of SP-A in the CNS at different stages of disease progression. In addition, in vitro experiments with lipopolysaccharide (LPS)-stimulated human astrocytes and microglia were performed to investigate the potential role of SP-A in the modulation of CNS inflammatory responses. The results of the present study demonstrated widespread distribution of SP-A in the rat CNS, and also identified specific expression patterns of SP-A at different stages of EAE. In vitro, the current study revealed that treatment of human astrocytes and microglia with LPS promoted SP-A expression in a dose-dependent manner. Furthermore, exogenous SP-A protein significantly decreased Toll-like receptor 4 and nuclear factor-κB expression, and reduced interleukin-1β and tumor necrosis factor-α levels. The results of the current study indicate a potential role for SP-A in the modulation of CNS inflammatory responses. PMID:28393255

  15. [Clinical significance of levels of lung surfactant protein A in serum, in various lung diseases].

    PubMed

    Abe, S; Honda, Y; Ando, M; Saita, N; Kida, K; Jinno, S; Kondo, A; Kuroki, Y; Akino, T

    1995-11-01

    To assess the utility of measuring lung surfactant protein A (SP-A) in serum, a newly developed SP-A kit (Teijin TDR-30) was used at four facilities to measure serum SP-A levels in patients with various lung diseases. Serum SP-A levels in healthy volunteers were 24.6 +/- 9.6 ng/ml (mean +/- SD). serum SP-A levels did not differ significantly between different age groups (thirties through seventies). A cut-off level of 43.8 ng/ml was calculated, based on the values of the healthy volunteers. The serum SP-A levels in patients with idiopathic interstitial pneumonia (IIP: 67.9 +/- 42.5 ng/ml), pulmonary alveolar proteinosis (PAP: 7.0 +/- 45.7 ng/ml), and collagen disease with interstitial pneumonia (CDIP: 55.3 +/- 37.9 ng/ml) were significantly higher than those in healthy volunteers. When calculated with the cut-off value stated above, the positive rate of diagnosis for IIP was 71.4%. SP-A levels correlated closely with the clinical course; SP-A levels rose significantly during exacerbations of IIP. Measurement of SP-A in serum is useful for the diagnosis of IIP, PAP, and CDIP, and for monitoring exacerbations of IIP.

  16. Unprecedented Abundance of Protein Tyrosine Phosphorylation Modulates Shigella flexneri Virulence.

    PubMed

    Standish, Alistair James; Teh, Min Yan; Tran, Elizabeth Ngoc Hoa; Doyle, Matthew Thomas; Baker, Paul J; Morona, Renato

    2016-10-09

    Evidence is accumulating that protein tyrosine phosphorylation plays a crucial role in the ability of important human bacterial pathogens to cause disease. While most works have concentrated on its role in the regulation of a major bacterial virulence factor, the polysaccharide capsule, recent studies have suggested a much broader role for this post-translational modification. This prompted us to investigate protein tyrosine phosphorylation in the human pathogen Shigella flexneri. We first completed a tyrosine phosphoproteome, identifying 905 unique tyrosine phosphorylation sites on at least 573 proteins (approximately 15% of all proteins). This is the most tyrosine-phosphorylated sites and proteins in a single bacterium identified to date, substantially more than the level seen in eukaryotic cells. Most had not previously been identified and included proteins encoded by the virulence plasmid, which is essential for S. flexneri to invade cells and cause disease. In order to investigate the function of these phosphorylation sites in important virulence factors, phosphomimetic and ablative mutations were constructed in the type 3 secretion system ATPase Spa47 and the master virulence regulator VirB. This revealed that tyrosine residues phosphorylated in our study are critical for Spa47 and VirB activity, and tyrosine phosphorylation likely regulates their functional activity and subsequently the virulence of this major human pathogen. This study suggests that tyrosine phosphorylation plays a critical role in regulating a wide variety of virulence factors in the human pathogen S. flexneri and serves as a base for future studies defining its complete role. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Surfactant protein A (SP-A) inhibits agglomeration and macrophage uptake of toxic amine modified nanoparticles.

    PubMed

    McKenzie, Zofi; Kendall, Michaela; Mackay, Rose-Marie; Whitwell, Harry; Elgy, Christine; Ding, Ping; Mahajan, Sumeet; Morgan, Cliff; Griffiths, Mark; Clark, Howard; Madsen, Jens

    2015-01-01

    The lung provides the main route for nanomaterial exposure. Surfactant protein A (SP-A) is an important respiratory innate immune molecule with the ability to bind or opsonise pathogens to enhance phagocytic removal from the airways. We hypothesised that SP-A, like surfactant protein D, may interact with inhaled nanoparticulates, and that this interaction will be affected by nanoparticle (NP) surface characteristics. In this study, we characterise the interaction of SP-A with unmodified (U-PS) and amine-modified (A-PS) polystyrene particles of varying size and zeta potential using dynamic light scatter analysis. SP-A associated with both 100 nm U-PS and A-PS in a calcium-independent manner. SP-A induced significant calcium-dependent agglomeration of 100 nm U-PS NPs but resulted in calcium-independent inhibition of A-PS self agglomeration. SP-A enhanced uptake of 100 nm U-PS into macrophage-like RAW264.7 cells in a dose-dependent manner but in contrast inhibited A-PS uptake. Reduced association of A-PS particles in RAW264.7 cells following pre-incubation of SP-A was also observed with coherent anti-Stokes Raman spectroscopy. Consistent with these findings, alveolar macrophages (AMs) from SP-A(-/-) mice were more efficient at uptake of 100 nm A-PS compared with wild type C57Bl/6 macrophages. No difference in uptake was observed with 500 nm U-PS or A-PS particles. Pre-incubation with SP-A resulted in a significant decrease in uptake of 100 nm A-PS in macrophages isolated from both groups of mice. In contrast, increased uptake by AMs of U-PS was observed after pre-incubation with SP-A. Thus we have demonstrated that SP-A promotes uptake of non-toxic U-PS particles but inhibits the clearance of potentially toxic A-PS particles by blocking uptake into macrophages.

  18. MxiN Differentially Regulates Monomeric and Oligomeric Species of the Shigella Type Three Secretion System ATPase Spa47.

    PubMed

    Case, Heather B; Dickenson, Nicholas E

    2018-04-17

    Shigella rely entirely on the action of a single type three secretion system (T3SS) to support cellular invasion of colonic epithelial cells and to circumvent host immune responses. The ATPase Spa47 resides at the base of the Shigella needle-like type three secretion apparatus (T3SA), supporting protein secretion through the apparatus and providing a likely means for native virulence regulation by Shigella and a much needed target for non-antibiotic therapeutics to treat Shigella infections. Here, we show that MxiN is a differential regulator of Spa47 and that its regulatory impact is determined by the oligomeric state of the Spa47 ATPase, with which it interacts. In vitro and in vivo characterization shows that interaction of MxiN with Spa47 requires the six N-terminal residues of Spa47 that are also necessary for stable Spa47 oligomer formation and activation. This interaction with MxiN negatively influences the activity of Spa47 oligomers while upregulating the ATPase activity of monomeric Spa47. Detailed kinetic analyses of monomeric and oligomeric Spa47 in the presence and absence of MxiN uncover additional mechanistic insights into the regulation of Spa47 by MxiN, suggesting that the MxiN/Spa47 species resulting from interaction with monomeric and oligomeric Spa47 are functionally distinct and that both could be involved in Shigella T3SS regulation. Uncovering regulation of Spa47 by MxiN addresses an important gap in the current understanding of how Shigella controls T3SA activity and provides the first description of differential T3SS ATPase regulation by a native T3SS protein.

  19. Metabolic activity, urease production, antibiotic resistance and virulence in dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus.

    PubMed

    Vandecandelaere, Ilse; Van Nieuwerburgh, Filip; Deforce, Dieter; Coenye, Tom

    2017-01-01

    In this paper, the metabolic activity in single and dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus isolates was investigated. Our results demonstrated that there was less metabolic activity in dual species biofilms compared to S. aureus biofilms. However, this was not observed if S. aureus and S. epidermidis were obtained from the same sample. The largest effect on metabolic activity was observed in biofilms of S. aureus Mu50 and S. epidermidis ET-024. A transcriptomic analysis of these dual species biofilms showed that urease genes and genes encoding proteins involved in metabolism were downregulated in comparison to monospecies biofilms. These results were subsequently confirmed by phenotypic assays. As metabolic activity is related to acid production, the pH in dual species biofilms was slightly higher compared to S. aureus Mu50 biofilms. Our results showed that S. epidermidis ET-024 in dual species biofilms inhibits metabolic activity of S. aureus Mu50, leading to less acid production. As a consequence, less urease activity is required to compensate for low pH. Importantly, this effect was biofilm-specific. Also S. aureus Mu50 genes encoding virulence-associated proteins (Spa, SplF and Dps) were upregulated in dual species biofilms compared to monospecies biofilms and using Caenorhabditis elegans infection assays, we demonstrated that more nematodes survived when co-infected with S. epidermidis ET-024 and S. aureus mutants lacking functional spa, splF or dps genes, compared to nematodes infected with S. epidermidis ET-024 and wild- type S. aureus. Finally, S. epidermidis ET-024 genes encoding resistance to oxacillin, erythromycin and tobramycin were upregulated in dual species biofilms and increased resistance was subsequently confirmed. Our data indicate that both species in dual species biofilms of S. epidermidis and S. aureus influence each other's behavior, but additional studies are required necessary to elucidate the exact mechanism(s) involved.

  20. Metabolic activity, urease production, antibiotic resistance and virulence in dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus

    PubMed Central

    Vandecandelaere, Ilse; Van Nieuwerburgh, Filip; Deforce, Dieter

    2017-01-01

    In this paper, the metabolic activity in single and dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus isolates was investigated. Our results demonstrated that there was less metabolic activity in dual species biofilms compared to S. aureus biofilms. However, this was not observed if S. aureus and S. epidermidis were obtained from the same sample. The largest effect on metabolic activity was observed in biofilms of S. aureus Mu50 and S. epidermidis ET-024. A transcriptomic analysis of these dual species biofilms showed that urease genes and genes encoding proteins involved in metabolism were downregulated in comparison to monospecies biofilms. These results were subsequently confirmed by phenotypic assays. As metabolic activity is related to acid production, the pH in dual species biofilms was slightly higher compared to S. aureus Mu50 biofilms. Our results showed that S. epidermidis ET-024 in dual species biofilms inhibits metabolic activity of S. aureus Mu50, leading to less acid production. As a consequence, less urease activity is required to compensate for low pH. Importantly, this effect was biofilm-specific. Also S. aureus Mu50 genes encoding virulence-associated proteins (Spa, SplF and Dps) were upregulated in dual species biofilms compared to monospecies biofilms and using Caenorhabditis elegans infection assays, we demonstrated that more nematodes survived when co-infected with S. epidermidis ET-024 and S. aureus mutants lacking functional spa, splF or dps genes, compared to nematodes infected with S. epidermidis ET-024 and wild- type S. aureus. Finally, S. epidermidis ET-024 genes encoding resistance to oxacillin, erythromycin and tobramycin were upregulated in dual species biofilms and increased resistance was subsequently confirmed. Our data indicate that both species in dual species biofilms of S. epidermidis and S. aureus influence each other’s behavior, but additional studies are required necessary to elucidate the exact mechanism(s) involved. PMID:28263995

  1. Septal secretion of protein A in Staphylococcus aureus requires SecA and lipoteichoic acid synthesis

    PubMed Central

    Yu, Wenqi; Missiakas, Dominique

    2018-01-01

    Surface proteins of Staphylococcus aureus are secreted across septal membranes for assembly into the bacterial cross-wall. This localized secretion requires the YSIRK/GXXS motif signal peptide, however the mechanisms supporting precursor trafficking are not known. We show here that the signal peptide of staphylococcal protein A (SpA) is cleaved at the YSIRK/GXXS motif. A SpA signal peptide mutant defective for YSIRK/GXXS cleavage is also impaired for septal secretion and co-purifies with SecA, SecDF and LtaS. SecA depletion blocks precursor targeting to septal membranes, whereas deletion of secDF diminishes SpA secretion into the cross-wall. Depletion of LtaS blocks lipoteichoic acid synthesis and abolishes SpA precursor trafficking to septal membranes. We propose a model whereby SecA directs SpA precursors to lipoteichoic acid-rich septal membranes for YSIRK/GXXS motif cleavage and secretion into the cross-wall. PMID:29757141

  2. Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations.

    PubMed

    Goh, Boon Chong; Wu, Huixing; Rynkiewicz, Michael J; Schulten, Klaus; Seaton, Barbara A; McCormack, Francis X

    2016-07-05

    Surfactant protein A (SP-A) is a collagenous C-type lectin (collectin) that is critical for pulmonary defense against inhaled microorganisms. Bifunctional avidity of SP-A for pathogen-associated molecular patterns (PAMPs) such as lipid A and for dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant membranes lining the air-liquid interface of the lung, ensures that the protein is poised for first-line interactions with inhaled pathogens. To improve our understanding of the motifs that are required for interactions with microbes and surfactant structures, we explored the role of the tyrosine-rich binding surface on the carbohydrate recognition domain of SP-A in the interaction with DPPC and lipid A using crystallography, site-directed mutagenesis, and molecular dynamics simulations. Critical binding features for DPPC binding include a three-walled tyrosine cage that binds the choline headgroup through cation-π interactions and a positively charged cluster that binds the phosphoryl group. This basic cluster is also critical for binding of lipid A, a bacterial PAMP and target for SP-A. Molecular dynamics simulations further predict that SP-A binds lipid A more tightly than DPPC. These results suggest that the differential binding properties of SP-A favor transfer of the protein from surfactant DPPC to pathogen membranes containing appropriate lipid PAMPs to effect key host defense functions.

  3. [Development of a SPA-ELISA method for detecting anti-coronavirus IgG antibodies in serum samples from fulvous fruit bats].

    PubMed

    Zhou, Jie; Liao, Yu-xue; Chen, Zhong; Li, Yu-chun; Gao, Lu-Lu; Chen, Yi-xiong; Cai, Lian-gong; Chen, Qing; Yu, Shou-yi

    2008-05-01

    To develop an simple and sensitive method for detecting anti-coronavirus IgG antibodies in bat sera based on enzyme-linked immunosorbent assay (ELISA). A commercial ELISA kit for detecting SARS-CoV antibody was modified for detecting coronavirus antibodies in bat serum samples. The second antibody in the kit was replaced with horseradish peroxidase-conjugated protein-A (HRP-SPA) based on the characteristics of binding between Staphylococcus aureus protein A (SPA) and mammal IgG Fc fragment. The sera of 55 fulvous fruit bats (Rousettus dasymallus) were tested using the SPA-ELISA. The test results of the positive and negative controls in the kit and the serum samples from convalescent ;patient were consistent with expectation. Coronavirus antibody was detected in 2 out of the 55 bat serum samples. Serum neutralization test confirmed the validity of the SPA-ELISA method. This SPA-ELISA method is applicable for detecting coronavirus antibody in bat sera.

  4. Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from Shigella flexneri.

    PubMed

    Burgess, Jamie L; Jones, Heather B; Kumar, Prashant; Toth, Ronald T; Middaugh, C Russell; Antony, Edwin; Dickenson, Nicholas E

    2016-05-01

    Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents. © 2016 The Protein Society.

  5. spa typing for epidemiological surveillance of Staphylococcus aureus.

    PubMed

    Hallin, Marie; Friedrich, Alexander W; Struelens, Marc J

    2009-01-01

    The spa typing method is based on sequencing of the polymorphic X region of the protein A gene (spa), present in all strains of Staphylococcus aureus. The X region is constituted of a variable number of 24-bp repeats flanked by well-conserved regions. This single-locus sequence-based typing method combines a number of technical advantages, such as rapidity, reproducibility, and portability. Moreover, due to its repeat structure, the spa locus simultaneously indexes micro- and macrovariations, enabling the use of spa typing in both local and global epidemiological studies. These studies are facilitated by the establishment of standardized spa type nomenclature and Internet shared databases.

  6. Nanoparticles modulate surfactant protein A and D mediated protection against influenza A infection in vitro

    PubMed Central

    McKenzie, Zofi; Kendall, Michaela; Mackay, Rose-Marie; Tetley, Teresa D.; Morgan, Cliff; Griffiths, Mark; Clark, Howard W.; Madsen, Jens

    2015-01-01

    Numerous epidemiological and toxicological studies have indicated that respiratory infections are exacerbated following enhanced exposure to airborne particulates. Surfactant protein A (SP-A) and SP-D form an important part of the innate immune response in the lung and can interact with nanoparticles to modulate the cellular uptake of these particles. We hypothesize that this interaction will also affect the ability of these proteins to combat infections. TT1, A549 and differentiated THP-1 cells, representing the predominant cell types found in the alveolus namely alveolar type I (ATI) epithelial cells, ATII cells and macrophages, were used to examine the effect of two model nanoparticles, 100 nm amine modified (A-PS) and unmodified polystyrene (U-PS), on the ability of SP-A and SP-D to neutralize influenza A infections in vitro. Pre-incubation of low concentrations of U-PS with SP-A resulted in a reduction of SP-A anti-influenza activity in A549 cells, whereas at higher concentrations there was an increase in SP-A antiviral activity. This differential pattern of U-PS concentration on surfactant protein mediated protection against IAV was also shown with SP-D in TT1 cells. On the other hand, low concentrations of A-PS particles resulted in a reduction of SP-A activity in TT1 cells and a reduction in SP-D activity in A549 cells. These results indicate that nanoparticles can modulate the ability of SP-A and SP-D to combat viral challenges. Furthermore, the nanoparticle concentration, surface chemistry and cell type under investigation are important factors in determining the extent of these modulations. PMID:25533100

  7. Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition

    PubMed Central

    Condon, Jennifer C.; Jeyasuria, Pancharatnam; Faust, Julie M.; Mendelson, Carole R.

    2004-01-01

    Parturition is timed to begin only after the developing embryo is sufficiently mature to survive outside the womb. It has been postulated that the signal for the initiation of parturition arises from the fetus although the nature and source of this signal remain obscure. Herein, we provide evidence that this signal originates from the maturing fetal lung. In the mouse, secretion of the major lung surfactant protein, surfactant protein A (SP-A), was first detected in amniotic fluid (AF) at 17 days postcoitum, rising progressively to term (19 days postcoitum). Expression of IL-1β in AF macrophages and activation of NF-κB in the maternal uterus increased with the gestational increase in SP-A. SP-A stimulated IL-1β and NF-κB expression in cultured AF macrophages. Studies using Rosa 26 Lac-Z (B6;129S-Gt(rosa)26Sor) (Lac-Z) mice revealed that fetal AF macrophages migrate to the uterus with the gestational increase in AF SP-A. Intraamniotic (i.a.) injection of SP-A caused preterm delivery of fetuses within 6-24 h. By contrast, injection of an SP-A antibody or NF-κB inhibitor into AF delayed labor by >24 h. We propose that augmented production of SP-A by the fetal lung near term causes activation and migration of fetal AF macrophages to the maternal uterus, where increased production of IL-1β activates NF-κB, leading to labor. We have revealed a response pathway that ties augmented surfactant production by the maturing fetal lung to the initiation of labor. We suggest that SP-A secreted by the fetal lung serves as a hormone of parturition. PMID:15044702

  8. The spa typing of methicillin-resistant Staphylococcus aureus isolates by High Resolution Melting (HRM) analysis.

    PubMed

    Fasihi, Yasser; Fooladi, Saba; Mohammadi, Mohammad Ali; Emaneini, Mohammad; Kalantar-Neyestanaki, Davood

    2017-09-06

    Molecular typing is an important tool for control and prevention of infection. A suitable molecular typing method for epidemiological investigation must be easy to perform, highly reproducible, inexpensive, rapid and easy to interpret. In this study, two molecular typing methods including the conventional PCR-sequencing method and high resolution melting (HRM) analysis were used for staphylococcal protein A (spa) typing of 30 Methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from clinical samples. Based on PCR-sequencing method results, 16 different spa types were identified among the 30 MRSA isolates. Among the 16 different spa types, 14 spa types separated by HRM method. Two spa types including t4718 and t2894 were not separated from each other. According to our results, spa typing based on HRM analysis method is very rapid, easy to perform and cost-effective, but this method must be standardized for different regions, spa types, and real-time machinery.

  9. Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications.

    PubMed

    Lugogo, Njira; Francisco, Dave; Addison, Kenneth J; Manne, Akarsh; Pederson, William; Ingram, Jennifer L; Green, Cynthia L; Suratt, Benjamin T; Lee, James J; Sunday, Mary E; Kraft, Monica; Ledford, Julie G

    2018-03-01

    Eosinophils are prominent in some patients with asthma and are increased in the submucosa in a subgroup of obese patients with asthma (OAs). Surfactant protein A (SP-A) modulates host responses to infectious and environmental insults. We sought to determine whether SP-A levels are altered in OAs compared with a control group and to determine the implications of these alterations in SP-A levels in asthmatic patients. Bronchoalveolar lavage fluid from 23 lean, 12 overweight, and 20 obese subjects were examined for SP-A. Mouse tracheal epithelial cells grown at an air-liquid interface were used for mechanistic studies. SP-A -/- mice were challenged in allergen models, and exogenous SP-A therapy was given after the last challenge. Eosinophils were visualized and quantitated in lung parenchyma by means of immunostaining. Significantly less SP-A (P = .002) was detected in samples from OAs compared with those from control subjects. A univariable regression model found SP-A levels were significantly negatively correlated with body mass index (r = -0.33, P = .014), whereas multivariable modeling demonstrated that the correlation depended both on asthma status (P = .017) and the interaction of asthma and body mass index (P = .008). Addition of exogenous TNF-α to mouse tracheal epithelial cells was sufficient to attenuate SP-A and eotaxin secretion. Allergen-challenged SP-A -/- mice that received SP-A therapy had significantly less tissue eosinophilia compared with mice receiving vehicle. SP-A functions as an important mediator in resolving tissue and lavage fluid eosinophilia in allergic mouse models. Decreased levels of SP-A in OAs, which could be due to increased local TNF-α levels, might lead to impaired eosinophil resolution and could contribute to the eosinophilic asthma phenotype. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Human lung surfactant protein A exists in several different oligomeric states: oligomer size distribution varies between patient groups.

    PubMed Central

    Hickling, T. P.; Malhotra, R.; Sim, R. B.

    1998-01-01

    BACKGROUND: Lung surfactant protein A (SP-A) is a complex molecule composed of up to 18 polypeptide chains. In vivo, SP-A probably binds to a wide range of inhaled materials via the interaction of surface carbohydrates with the lectin domains of SP-A and mediates their interaction with cells as part of a natural defense system. Multiplicity of lectin domains gives high-affinity binding to carbohydrate-bearing surfaces. MATERIALS AND METHODS: Gel filtration analyses were performed on bronchoalveolar lavage (BAL) fluid samples from three patient groups: pulmonary alveolar proteinosis (n = 12), birch pollen allergy (n = 11), and healthy volunteers (n = 4). Sucrose density gradient centrifugation was employed to determine molecular weights of SP-A oligomers. SP-A was solubilized from the lipid phase to compare oligomeric state with that of water soluble SP-A. RESULTS: SP-A exists as fully assembled complexes with 18 polypeptide chains, but it is also consistently found in smaller oligomeric forms. This is true for both the water- and lipid-soluble fractions of SP-A. CONCLUSION: The three patient groups analyzed show a shift towards lower oligomeric forms of SP-A in the following sequence: healthy-pulmonary alveolar proteinosis-pollen allergy. Depolymerization would be expected to lead to loss of binding affinity for carbohydrate-rich surfaces, with loss or alteration of biological function. While there are many complex factors involved in the establishment of an allergy, it is possible that reduced participation of SP-A in clearing a potential allergen from the lungs could be an early step in the chain of events. Images Fig. 4 FIG. 6 Fig. 7 Fig. 8 PMID:9606179

  11. Characterization and complete genome sequences of L. rhamnosus DSM 14870 and L. gasseri DSM 14869 contained in the EcoVag® probiotic vaginal capsules.

    PubMed

    Marcotte, Harold; Krogh Andersen, Kasper; Lin, Yin; Zuo, Fanglei; Zeng, Zhu; Larsson, Per Göran; Brandsborg, Erik; Brønstad, Gunnar; Hammarström, Lennart

    2017-12-01

    Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869 were previously isolated from the vaginal epithelial cells (VEC) of healthy women and selected for the development of the vaginal EcoVag ® probiotic capsules. EcoVag ® was subsequently shown to provide long-term cure and reduce relapse of bacterial vaginosis (BV) as an adjunct to antibiotic therapy. To identify genes potentially involved in probiotic activity, we performed genome sequencing and characterization of the two strains. The complete genome analysis of both strains revealed the presence of genes encoding functions related to adhesion, exopolysaccharide (EPS) biosynthesis, antimicrobial activity, and CRISPR adaptive immunity but absence of antibiotic resistance genes. Interesting features of L. rhamnosus DSM 14870 genome include the presence of the spaCBA-srtC gene encoding spaCBA pili and interruption of the gene cluster encoding long galactose-rich EPS by integrases. Unique to L. gasseri DSM 14869 genome was the presence of a gene encoding a putative (1456 amino acid) new adhesin containing two rib/alpha-like repeats. L. rhamnosus DSM 14870 and L. gasseri DSM 14869 showed acidification of the culture medium (to pH 3.8) and a strong adhesion capability to the Caco-2 cell line and VEC. L. gasseri DSM 14869 could produce a thick (40nm) EPS layer and hydrogen peroxide. L. rhamnosus DSM 14870 was shown to produce SpaCBA pili and a 20nm EPS layer, and could inhibit the growth of Gardnerella vaginalis, a bacterium commonly associated with BV. The genome sequences provide a basis for further elucidation of the molecular basis for their probiotic functions. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Lung effector memory and activated CD4+ T cells display enhanced proliferation in surfactant protein A-deficient mice during allergen-mediated inflammation.

    PubMed

    Pastva, Amy M; Mukherjee, Sambuddho; Giamberardino, Charles; Hsia, Bethany; Lo, Bernice; Sempowski, Gregory D; Wright, Jo Rae

    2011-03-01

    Although many studies have shown that pulmonary surfactant protein (SP)-A functions in innate immunity, fewer studies have addressed its role in adaptive immunity and allergic hypersensitivity. We hypothesized that SP-A modulates the phenotype and prevalence of dendritic cells (DCs) and CD4(+) T cells to inhibit Th2-associated inflammatory indices associated with allergen-induced inflammation. In an OVA model of allergic hypersensitivity, SP-A(-/-) mice had greater eosinophilia, Th2-associated cytokine levels, and IgE levels compared with wild-type counterparts. Although both OVA-exposed groups had similar proportions of CD86(+) DCs and Foxp3(+) T regulatory cells, the SP-A(-/-) mice had elevated proportions of CD4(+) activated and effector memory T cells in their lungs compared with wild-type mice. Ex vivo recall stimulation of CD4(+) T cell pools demonstrated that cells from the SP-A(-/-) OVA mice had the greatest proliferative and IL-4-producing capacity, and this capability was attenuated with exogenous SP-A treatment. Additionally, tracking proliferation in vivo demonstrated that CD4(+) activated and effector memory T cells expanded to the greatest extent in the lungs of SP-A(-/-) OVA mice. Taken together, our data suggested that SP-A influences the prevalence, types, and functions of CD4(+) T cells in the lungs during allergic inflammation and that SP deficiency modifies the severity of inflammation in allergic hypersensitivity conditions like asthma.

  13. Inhibition of Virulence Gene Expression in Staphylococcus aureus by Novel Depsipeptides from a Marine Photobacterium

    PubMed Central

    Mansson, Maria; Nielsen, Anita; Kjærulff, Louise; Gotfredsen, Charlotte H.; Wietz, Matthias; Ingmer, Hanne; Gram, Lone; Larsen, Thomas O.

    2011-01-01

    During a global research expedition, more than five hundred marine bacterial strains capable of inhibiting the growth of pathogenic bacteria were collected. The purpose of the present study was to determine if these marine bacteria are also a source of compounds that interfere with the agr quorum sensing system that controls virulence gene expression in Staphylococcus aureus. Using a gene reporter fusion bioassay, we recorded agr interference as enhanced expression of spa, encoding Protein A, concomitantly with reduced expression of hla, encoding α-hemolysin, and rnaIII encoding RNAIII, the effector molecule of agr. A marine Photobacterium produced compounds interfering with agr in S. aureus strain 8325-4, and bioassay-guided fractionation of crude extracts led to the isolation of two novel cyclodepsipeptides, designated solonamide A and B. Northern blot analysis confirmed the agr interfering activity of pure solonamides in both S. aureus strain 8325-4 and the highly virulent, community-acquired strain USA300 (CA-MRSA). To our knowledge, this is the first report of inhibitors of the agr system by a marine bacterium. PMID:22363239

  14. Analysis of genes involved in biosynthesis of the lantibiotic subtilin.

    PubMed Central

    Klein, C; Kaletta, C; Schnell, N; Entian, K D

    1992-01-01

    Lantibiotics are peptide-derived antibiotics with high antimicrobial activity against pathogenic gram-positive bacteria. They are ribosomally synthesized and posttranslationally modified (N. Schnell, K.-D. Entian, U. Schneider, F. Götz, H. Zähner, R. Kellner, and G. Jung, Nature [London] 333:276-278, 1988). The most important lantibiotics are subtilin and the food preservative nisin, which both have a very similar structure. By using a hybridization probe specific for the structural gene of subtilin, spaS, the DNA region adjacent to spaS was isolated from Bacillus subtilis. Sequence analysis of a 4.9-kb fragment revealed several open reading frames with the same orientation as spaS. Downstream of spaS, no reading frames were present on the isolated XbaI fragment. Upstream of spaS, three reading frames, spaB, spaC, and spaT, were identified which showed strong homology to genes identified near the structural gene of the lantibiotic epidermin. The SpaT protein derived from the spaT sequence was homologous to hemolysin B of Escherichia coli, which indicated its possible function in subtilin transport. Gene deletions within spaB and spaC revealed subtilin-negative mutants, whereas spaT gene disruption mutants still produced subtilin. Remarkably, the spaT mutant colonies revealed a clumpy surface morphology on solid media. After growth on liquid media, spaT mutant cells agglutinated in the mid-logarithmic growth phase, forming longitudinal 3- to 10-fold-enlarged cells which aggregated. Aggregate formation preceded subtilin production and cells lost their viability, possibly as a result of intracellular subtilin accumulation. Our results clearly proved that reading frames spaB and spaC are essential for subtilin biosynthesis whereas spaT mutants are probably deficient in subtilin transport. Images PMID:1539969

  15. Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response.

    PubMed

    Carreto-Binaghi, Laura Elena; Aliouat, El Moukhtar; Taylor, Maria Lucia

    2016-06-01

    Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which are also known as pulmonary collectins, have an important function in the host's lung immune response; they act as opsonins for different pathogens via a C-terminal carbohydrate recognition domain and enhance the attachment to phagocytic cells or show their own microbicidal activity by increasing the cellular membrane permeability. Interactions between the pulmonary collectins and bacteria or viruses have been extensively studied, but this is not the same for fungal pathogens. SP-A and SP-D bind glucan and mannose residues from fungal cell wall, but there is still a lack of information on their binding to other fungal carbohydrate residues. In addition, both their relation with immune cells for the clearance of these pathogens and the role of surfactant proteins' regulation during respiratory fungal infections remain unknown. Here we highlight the relevant findings associated with SP-A and SP-D in those respiratory mycoses where the fungal infective propagules reach the lungs by the airways.

  16. Staphylococcus aureus from the German general population is highly diverse.

    PubMed

    Becker, Karsten; Schaumburg, Frieder; Fegeler, Christian; Friedrich, Alexander W; Köck, Robin

    2017-01-01

    This prospective cohort study evaluates colonization dynamics and molecular characteristics of methicillin-susceptible and - resistant Staphylococcus aureus (MSSA/MRSA) in a German general population. Nasal swabs of 1878 non-hospitalized adults were screened for S. aureus. Participants were screened thrice in intervals of 6-8 months. Isolates were characterized by spa and agr typing, mecA and mecC possession, respectively, and PCRs targeting virulence factors. 40.9% of all participants carried S. aureus at least once while 0.7% of the participants carried MRSA (mainly spa t011). MSSA isolates (n=1359) were associated with 331 different spa types; t084 (7.7%), t091 (6.1%) and t012 (71, 5.2%) were predominant. Of 206 participants carrying S. aureus at all three sampling time points, 14.1% carried the same spa type continuously; 5.3% carried different spa types with similar repeat patterns, but 80.6% carried S. aureus with unrelated spa types. MSSA isolates frequently harboured genes encoding enterotoxins (sec: 16.6%, seg: 63.1%, sei: 64.5%) and toxic shock syndrome toxin (tst: 17.5%), but rarely Panton-Valentine leukocidin (lukS-PV/lukF-PV: 0.2%). MSSA colonizing human nares in the community are clonally highly diverse. Among those constantly carrying S. aureus, clonal lineages changed over time. The proportion of persistent S. aureus carriers was lower than reported elsewhere. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Mapping of Monoclonal Antibody Binding Sites on CNBr Fragments of the S- Layer Protein Antigens of Rickettsia Typhi and Rickettsia Prowazekii

    DTIC Science & Technology

    1992-01-01

    proita:ekii SPA each constitutes 10-15% of the total Research and Development Command. Research Task No cellular protein and is readily released by...modification. Selected in spaP (Carl et al., 1990). A stretch of amino acid which subsets of eucaryotic cellular proteins and bears some sequence...Publish- in procaryotes . J. Bacteriol. 170, 2891-2897. ing House of the Slovak Academy of Sciences, Bratislava. Streuli C. H. and Griffin B. E. (1987

  18. Molecular typing of methicillin-resistant Staphylococcus aureus: Comparison of PCR-based open reading frame typing, multilocus sequence typing, and Staphylococcus protein A gene typing.

    PubMed

    Ogihara, Shinji; Saito, Ryoichi; Sawabe, Etsuko; Kozakai, Takahiro; Shima, Mari; Aiso, Yoshibumi; Fujie, Toshihide; Nukui, Yoko; Koike, Ryuji; Hagihara, Michio; Tohda, Shuji

    2018-04-01

    The recently developed PCR-based open reading frame typing (POT) method is a useful molecular typing tool. Here, we evaluated the performance of POT for molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) isolates and compared its performance to those of multilocus sequence typing (MLST) and Staphylococcus protein A gene typing (spa typing). Thirty-seven MRSA isolates were collected between July 2012 and May 2015. MLST, spa typing, and POT were performed, and their discriminatory powers were evaluated using Simpson's index analysis. The MRSA isolates were classified into 11, 18, and 33 types by MLST, spa typing, and POT, respectively. The predominant strains identified by MLST, spa typing, and POT were ST8 and ST764, t002, and 93-191-127, respectively. The discriminatory power of MLST, spa typing, and POT was 0.853, 0.875, and 0.992, respectively, indicating that POT had the highest discriminatory power. Moreover, the results of MLST and spa were available after 2 days, whereas that of POT was available in 5 h. Furthermore, POT is rapid and easy to perform and interpret. Therefore, POT is a superior molecular typing tool for monitoring nosocomial transmission of MRSA. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

    PubMed Central

    Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

    2015-01-01

    Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

  20. Correlation between antitumor activity of protein A and in vivo formation of defined high molecular weight complexes with immunoglobulin G in BALB/c mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Das, C.; Langone, J.J.

    1987-04-15

    The purpose of this study was to test the hypothesis that antitumor activity of staphylococcal protein A (SpA) is related to the composition of complexes formed in vivo with IgG. BALB/c mice were inoculated intradermally with 10(6) Meth A fibrosarcoma cells on day 0 and treated i.v. on days 3 and 7 with between 1 and 405 micrograms of SpA. The 45- and 15-micrograms doses significantly inhibited tumor growth and enhanced survival time compared to saline controls in four of four and two of four experiments, respectively. Sucrose gradient ultracentrifugation was used to show that serum from tumor-bearing or normalmore » mice given 45 or 15 micrograms of /sup 125/I-labeled SpA contained only high molecular weight ((IgG)2SpA)2 complexes for up to 24 h after injection, whereas serum from mice given higher ineffective doses (135 and 405 micrograms) contained low molecular weight (IgG)(SpA) complexes over the first 1-4 h. Serum from mice undergoing successful therapy with 45 micrograms of unlabeled SpA also contained only ((IgG)2SpA)2 complexes. In contrast, when mice with large tumors (120-150 mm2) were treated on days 16 and 20, only the 135- and 405-micrograms doses significantly inhibited further tumor growth. Serum from mice with 16-day tumors contained only ((IgG)2SpA)2 complexes even after 5 min and when 135 or 405 micrograms of 125I-SpA was given. This result is consistent with significantly higher levels of total and SpA-reactive IgG in serum from these mice compared to normal mice or mice with 3-day tumors. Our results demonstrate a correlation between antitumor activity of SpA and in vivo formation of ((IgG)2SpA)2 complexes in an established animal model, and help to define the mechanism of SpA action at the molecular level.« less

  1. Synthesis of β-arabinofuranoside glycolipids, studies of their binding to surfactant protein-A and effect on sliding motilities of M. smegmatis.

    PubMed

    Naresh, Kottari; Avaji, Prakash Gouda; Maiti, Krishnagopal; Bharati, Binod K; Syal, Kirtimaan; Chatterji, Dipankar; Jayaraman, Narayanaswamy

    2012-04-01

    Surfactant protein A (SP-A), which is a lung innate immune system component, is known to bind glycolipids present at the cell surface of a mycobacterial pathogen. Lipoarabinomannan (LAM), a component of mycobacterial thick, waxy cell wall, is one of the glycolipid ligands for SP-A. In order to assess binding of synthetic glycolipids with SP-A and the glycosidic linkage preferences for the interaction, β-arabinofuranoside trisaccharide glycolipids constituted with β-(1→2), β-(1→3) and β-(1→2), β-(1→5) linkages relevant to LAM were synthesized through chemical glycosylations. The efficacies of synthetic glycolipids to interact with SP-A were assessed by using the surface plasmon resonance (SPR) technique, from which association-dissociation rate constants and equilibrium binding constants were derived. The equilibrium binding constants of the interaction of two constitutionally varying β-arabinofuranoside glycolipids with SP-A were found to be in the millimolar range. A comparison of the results with few α-anomeric arabinofuranoside glycolipids showed that glycolipids with β-anomeric linkages were having relatively lower equilibrium binding constants than those with α-anomeric linkages in binding to the protein, whereas oligosaccharides alone, without lipidic chains, exhibited higher equilibrium binding constants. Further, the synthetic compounds inhibited the growth of mycobacteria and affected sliding motilities of the bacteria, although to an extent relatively lesser than that of synthetic compounds constituted with α-anomeric linkages.

  2. The Blue Light-Dependent Polyubiquitination and Degradation of Arabidopsis Cryptochrome2 Requires Multiple E3 Ubiquitin Ligases.

    PubMed

    Liu, Qing; Wang, Qin; Liu, Bin; Wang, Wei; Wang, Xu; Park, Joon; Yang, Zhenming; Du, Xinglin; Bian, Mingdi; Lin, Chentao

    2016-10-01

    Cryptochromes are blue light receptors regulated by light-dependent ubiquitination and degradation in both plant and animal lineages. The Arabidopsis genome encodes two cryptochromes, CRY1 and CRY2, of which CRY2 undergoes blue light-dependent ubiquitination and 26S proteasome-dependent degradation. The molecular mechanism regulating blue light-dependent proteolysis of CRY2 is still not fully understood. We found that the F-box proteins ZEITLUPE (ZTL) and Lov Kelch Protein2 (LKP2), which mediate blue light suppression of degradation of the CRY2 signaling partner CIB1, are not required for the blue light-dependent CRY2 degradation. We further showed that the previously reported function of the COP1-SPA1 protein complex in blue light-dependent CRY2 degradation is more likely to be attributable to its cullin 4 (CUL4)-based E3 ubiquitin ligase activity than its activity as the cryptochrome signaling partner. However, the blue light-dependent CRY2 degradation is only partially impaired in the cul4 mutant, the cop1-5 null mutant and the spa1234 quadruple mutant, suggesting a possible involvement of additional E3 ubiquitin ligases in the regulation of CRY2. Consistent with this hypothesis, we demonstrated that the blue light-dependent CRY2 degradation is significantly impaired in the temperature-sensitive cul1 mutant allele (axr6-3), especially under the non-permissive temperature. Based on these and other results presented, we propose that photoexcited CRY2 undergoes Lys48-linked polyubiquitination catalyzed by the CUL4- and CUL1-based E3 ubiquitin ligases. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Fever as an initial manifestation of spondyloarthritis: A retrospective study.

    PubMed

    Byun, Se Jin; Bae, William Han; Jung, Seung Min; Lee, Sang-Won; Park, Yong-Beom; Song, Jason Jungsik

    2017-01-01

    We aimed to evaluate a wide spectrum of clinical features of adult patients with spondyloarthritis (SpA) whose initial manifestation was fever, using the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. We retrospectively collected the electronic medical records of hospitalized SpA patients who initially presented to the Severance Hospital (Seoul, Korea) with fever from January 2010 to May 2016. As a control group, we also recruited one-hundred consecutive patients who were diagnosed with SpA in our outpatient clinic. Clinical features and laboratory findings were compared in two patient groups. There were 26 patients who had fever as initial presentation of SpA (reactive arthritis 50%, undifferentiated SpA 26.9%, ankylosing spondylitis 15.4%, enteropathic arthritis 3.8%, psoriatic arthritis 3.8%). Peripheral SpA was more common in febrile SpA patients than in control SpA patients (65.4% vs 24.0%, p<0.001). Febrile SpA patients were less frequently HLA-B27 positive than control SpA patients (52.2% vs 77.0%, p<0.05). At baseline, systemic inflammatory markers were significantly higher in the febrile SpA patients (white blood cell count, 11.57 vs 7.81 cells/μL, p<0.001; erythrocyte sedimentation rate, 69.2 vs 41.0 mm/h, p<0.001; C-reactive protein, 109.6 vs 15.3 mg/L, p<0.001). The proportion of patients treated with systemic steroids was significantly higher in febrile SpA patients (57.7% vs. 11.0%, p<0.001). The proportion of patients who visited rheumatology specialty was significantly lower in febrile SpA patients than in control SpA patients (7.7% vs 59.0%, p<0.001). Various subgroups of SpA can be presented with fever as an initial manifestation. Febrile SpA patients demonstrated higher systemic inflammation and a lower chance to visit rheumatology in early stage. When evaluating febrile patients with any clinical features of SpA, clinicians are advised to consider performing SpA-focused evaluation including HLA-B27 or a simple sacroiliac joint radiograph.

  4. Function of cell-cycle regulators in predicting silent pituitary adenoma progression following surgical resection

    PubMed Central

    Park, Sung Hyun; Jang, Ji Hwan; Lee, Young Min; Kim, Joon Soo; Kim, Kyu Hong; Kim, Young Zoon

    2017-01-01

    The present study investigated the use of cell-cycle regulators for predicting the progression of silent pituitary adenoma (SPA) following surgical resection, via immunohistochemical analysis of tumor samples obtained by surgical resection. The medical records of patients diagnosed with SPA between January 2000 and December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was performed on sections of the archived, paraffin-embedded tissues obtained by surgery, with all tissues stained for cell-cycle regulatory proteins p16, p15, p21, cyclin-dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and cyclin D1, as well as E3 ubiquitin-protein ligase mib1 (MIB-1) antigen and p53. The primary end-point was to investigate the expression of cell-cycle regulatory proteins in SPA. The secondary end-point was to estimate the progression-free survival of patients with SPA following surgical resection and to identify its association with the expression of cell-cycle regulatory proteins. Of the 127 SPA samples, 44 (34.6%) were from patients with progression during a mean follow-up period of 62.4 months (range, 24.2–118.9 months). Immunohistochemical overexpression was identified in 61 samples (48.0%) for p16, 38 samples (29.9%) for p15, 19 samples (15.0%) for p21, 49 samples (38.6%) for CDK4, 17 samples (13.4%) for CDK6, 57 samples (44.9%) for pRb and in 65 samples (51.2%) for cyclin D1. Multivariate analysis revealed that null cell adenoma [95% confidence interval (CI), 0.276–0.808], somatotroph SPAs (95% CI, 1.296–3.121), corticotroph SPAs (95% CI, 1.811–4.078), pluripotent SPAs (95% CI, 2.264–5.194), decreased expression of p16 (95% CI, 2.724–5.588), overexpression of pRb (95% CI, 2.557–5.333), cyclin D1 (95% CI, 1.894–4.122) and MIB-1 (95% CI, 1.561–4.133), increased mitotic index (95% CI, 1.228–4.079), increased p53 expression (95% CI, 1.307–4.065) and invasion into the cavernous sinus (95% CI, 3.842–7.502) predicted SPA progression following resection. The results of the present study suggested that specific cell-cycle regulators, including p16, cyclin D1 and pRb, were associated with SPA progression. PMID:29344143

  5. Unveiling the pan-genome of the SXT/R391 family of ICEs: molecular characterisation of new variable regions of SXT/R391-like ICEs detected in Pseudoalteromonas sp. and Vibrio scophthalmi.

    PubMed

    Rodríguez-Blanco, Arturo; Lemos, Manuel L; Osorio, Carlos R

    2016-08-01

    Integrating conjugative elements (ICEs) of the SXT/R391 family have been identified in fish-isolated bacterial strains collected from marine aquaculture environments of the northwestern Iberian Peninsula. Here we analysed the variable regions of two ICEs, one preliminarily characterised in a previous study (ICEVscSpa3) and one newly identified (ICEPspSpa1). Bacterial strains harboring these ICEs were phylogenetically assigned to Vibrio scophthalmi and Pseudoalteromonas sp., thus constituting the first evidence of SXT/R391-like ICEs in the genus Pseudoalteromonas to date. Variable DNA regions, which confer element-specific properties to ICEs of this family, were characterised. Interestingly, the two ICEs contained 29 genes not found in variable DNA insertions of previously described ICEs. Most notably, variable gene content for ICEVscSpa3 showed similarity to genes potentially involved in housekeeping functions of replication, nucleotide metabolism and transcription. For these genes, closest homologues were found clustered in the genome of Pseudomonas psychrotolerans L19, suggesting a transfer as a block to ICEVscSpa3. Genes encoding antibiotic resistance, restriction modification systems and toxin/antitoxin systems were absent from hotspots of ICEVscSpa3. In contrast, the variable gene content of ICEPspSpa1 included genes involved in restriction/modification functions in two different hotspots and genes related to ICE maintenance. The present study unveils a relatively large number of novel genes in SXT/R391-ICEs, and demonstrates the major role of ICE elements as contributors to horizontal gene transfer.

  6. Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats

    PubMed Central

    Li, Nan; Hu, Yang; Zhang, Yuan; Xu, Jin-Fu; Li, Xia; Ren, Jie; Su, Bo; Yuan, Wei-Zhong; Teng, Xin-Rong; Zhang, Rong-Xuan; Jiang, Dian-hua; Mulet, Xavier; Li, Hui-Ping

    2013-01-01

    Objective Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model. Methods DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. Results The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. Conclusions The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice. PMID:23516459

  7. In vitro reconstitution of sortase-catalyzed pilus polymerization reveals structural elements involved in pilin cross-linking.

    PubMed

    Chang, Chungyu; Amer, Brendan R; Osipiuk, Jerzy; McConnell, Scott A; Huang, I-Hsiu; Hsieh, Van; Fu, Janine; Nguyen, Hong H; Muroski, John; Flores, Erika; Ogorzalek Loo, Rachel R; Loo, Joseph A; Putkey, John A; Joachimiak, Andrzej; Das, Asis; Clubb, Robert T; Ton-That, Hung

    2018-06-12

    Covalently cross-linked pilus polymers displayed on the cell surface of Gram-positive bacteria are assembled by class C sortase enzymes. These pilus-specific transpeptidases located on the bacterial membrane catalyze a two-step protein ligation reaction, first cleaving the LPXTG motif of one pilin protomer to form an acyl-enzyme intermediate and then joining the terminal Thr to the nucleophilic Lys residue residing within the pilin motif of another pilin protomer. To date, the determinants of class C enzymes that uniquely enable them to construct pili remain unknown. Here, informed by high-resolution crystal structures of corynebacterial pilus-specific sortase (SrtA) and utilizing a structural variant of the enzyme (SrtA 2M ), whose catalytic pocket has been unmasked by activating mutations, we successfully reconstituted in vitro polymerization of the cognate major pilin (SpaA). Mass spectrometry, electron microscopy, and biochemical experiments authenticated that SrtA 2M synthesizes pilus fibers with correct Lys-Thr isopeptide bonds linking individual pilins via a thioacyl intermediate. Structural modeling of the SpaA-SrtA-SpaA polymerization intermediate depicts SrtA 2M sandwiched between the N- and C-terminal domains of SpaA harboring the reactive pilin and LPXTG motifs, respectively. Remarkably, the model uncovered a conserved TP(Y/L)XIN(S/T)H signature sequence following the catalytic Cys, in which the alanine substitutions abrogated cross-linking activity but not cleavage of LPXTG. These insights and our evidence that SrtA 2M can terminate pilus polymerization by joining the terminal pilin SpaB to SpaA and catalyze ligation of isolated SpaA domains in vitro provide a facile and versatile platform for protein engineering and bio-conjugation that has major implications for biotechnology.

  8. Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A*

    PubMed Central

    Sever-Chroneos, Zvjezdana; Krupa, Agnieszka; Davis, Jeremy; Hasan, Misbah; Yang, Ching-Hui; Szeliga, Jacek; Herrmann, Mathias; Hussain, Muzafar; Geisbrecht, Brian V.; Kobzik, Lester; Chroneos, Zissis C.

    2011-01-01

    Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap+) but not Eap-deficient (Eap−) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap+ S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap+ but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap+ S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap− S. aureus was impaired. Macrophages express two isoforms: SP-R210L and SP-R210S. The results show that WT alveolar macrophages are distinguished by expression of SP-R210L, whereas SR-A−/− alveolar macrophages are deficient in SP-R210L expressing only SP-R210S. Accordingly, SR-A−/− mice were highly susceptible to both Eap+ and Eap− S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210L mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A. PMID:21123169

  9. Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus involves binding of SP-A to the staphylococcal adhesin eap and the macrophage receptors SP-A receptor 210 and scavenger receptor class A.

    PubMed

    Sever-Chroneos, Zvjezdana; Krupa, Agnieszka; Davis, Jeremy; Hasan, Misbah; Yang, Ching-Hui; Szeliga, Jacek; Herrmann, Mathias; Hussain, Muzafar; Geisbrecht, Brian V; Kobzik, Lester; Chroneos, Zissis C

    2011-02-11

    Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap(+)) but not Eap-deficient (Eap(-)) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap(+) S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap(+) but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap(+) S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap(-) S. aureus was impaired. Macrophages express two isoforms: SP-R210(L) and SP-R210(S). The results show that WT alveolar macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-) alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S). Accordingly, SR-A(-/-) mice were highly susceptible to both Eap(+) and Eap(-) S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210(L) mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A.

  10. Air Pollution and Epigenetics: Effects on SP-A and Innate Host Defense in the Lung

    PubMed Central

    Silveyra, Patricia; Floros, Joanna

    2013-01-01

    Summary An appropriate immune and inflammatory response is key to defend against harmful agents present in the environment such as pathogens, allergens, and inhaled pollutants, including ozone and particulate matter. Air pollution is a serious public health concern worldwide, and cumulative evidence revealed that air pollutants contribute to epigenetic variation in several genes, and this in turn can contribute to disease susceptibility. Several groups of experts have recently reviewed findings on epigenetics and air pollution [1–6]. Surfactant proteins play a central role in pulmonary host defense by mediating pathogen clearance, modulating allergic responses and facilitating the resolution of lung inflammation. Recent evidence indicates that surfactant proteins are subject to epigenetic regulation under hypoxia and other conditions. Oxidative stress caused by ozone, and exposure to particulate matter have been shown to affect the expression of surfactant protein A (SP-A), an important lung host defense molecule, as well as alter its functions. In this review, we discuss recent findings in the fields of epigenetics and air pollution effects on innate immunity, with focus on SP-A, and the human SP-A variants in particular. Their function may be differentially affected by pollutants and specifically by ozone-induced oxidative stress, and this in turn may differentially affect susceptibility to lung disease. PMID:22553125

  11. The protective effect of different airway humidification liquids to lung after tracheotomy in traumatic brain injury: The role of pulmonary surfactant protein-A (SP-A).

    PubMed

    Su, Xinyang; Li, Zefu; Wang, Meilin; Li, Zhenzhu; Wang, Qingbo; Lu, Wenxian; Li, Xiaoli; Zhou, Youfei; Xu, Hongmei

    2016-02-10

    The purpose of this study was to establish a rat model of a brain injury with tracheotomy and compared the wetting effects of different airway humidification liquids, afterward, the best airway humidification liquid was selected for the clinical trial, thus providing a theoretical basis for selecting a proper airway humidification liquid in a clinical setting. Rats were divided into a sham group, group A (0.9% NaCl), group B (0.45% NaCl), group C (0.9% NaCl+ambroxol) and group D (0.9% NaCl+Pulmicort). An established rat model of traumatic brain injury with tracheotomy was used. Brain tissue samples were taken to determine water content, while lung tissue samples were taken to determine wet/dry weight ratio (W/D), histological changes and expression levels of SP-A mRNA and SP-A protein. 30 patients with brain injury and tracheotomy were selected and divided into two groups based on the airway humidification liquid instilled in the trachea tube, 0.45% NaCl and 0.9% NaCl+ambroxol. Blood was then extracted from the patients to measure the levels of SP-A, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The difference between group C and other groups in lung W/D and expression levels of SP-A mRNA and SP-A protein was significant (P<0.05). In comparison, the histological changes showed that the lung tissue damage was smallest in group C compared to the three other groups. Aspect of patients, 0.45% NaCl group and 0.9% NaCl+ambroxol group were significantly different in the levels of SP-A, IL-6, IL-8 and TNF-α (P<0.01). In the present study, 0.9% NaCl+ambroxol promote the synthesis and secretion of pulmonary surfactant, and has anti-inflammatory and antioxidant effects, which inhibit the release of inflammatory factors and cytokines, making it an ideal airway humidification liquid. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Surface Plasmon Resonance Investigations of Bioselective Element Based on the Recombinant Protein A for Immunoglobulin Detection

    NASA Astrophysics Data System (ADS)

    Bakhmachuk, A.; Gorbatiuk, O.; Rachkov, A.; Dons'koi, B.; Khristosenko, R.; Ushenin, I.; Peshkova, V.; Soldatkin, A.

    2017-02-01

    The developed surface plasmon resonance (SPR) biosensor based on the recombinant Staphylococcal protein A with an additional cysteine residue (SPA-Cys) used as a biorecognition component showed a good selectivity and sensitivity for the immunoglobulin detection. The developed biosensor with SPA-Cys-based bioselective element can also be used as a first step of immunosensor creation. The successful immobilization of SPA-Cys on the nanolayer gold sensor surface of the SPR spectrometer was performed. The efficiency of blocking nonspecific sorption sites on the sensor surface with milk proteins, gelatin, BSA, and HSA was studied, and a rather high efficiency of using gelatin was confirmed. The SPR biosensor selectively interacted with IgG and did not interact with the control proteins. The linear dependence of the sensor response on the IgG concentration in the range from 2 to 10 μg/ml was shown. Using the calibration curve, the IgG concentration was measured in the model samples. The determined concentrations are in good agreement ( r 2 = 0.97) with the given concentration of IgG.

  13. Distribution of surfactant protein A in rat lung.

    PubMed

    Doyle, I R; Barr, H A; Nicholas, T E

    1994-10-01

    Although surfactant protein A (SP-A) is an integral component of alveolar surfactant, its relative abundance in lamellar bodies, regarded as the intracellular storage organelles for surfactant, remains contentious. We have previously shown that lamellar bodies, isolated from rat lung by upward flotation on a sucrose gradient, can be subfractionated into classic-appearing lamellar bodies (Lb-A) and a vesicular fraction (Lb-B), which we have speculated may be a second release form of surfactant. In the present study, we have used two-dimensional protein electrophoresis and immunochemical analysis to clarify the origin and the composition of these two subcellular fractions. In addition, we have examined the hypothesis that the secretion of SP-A and surfactant phospholipids occurs by independent pathways by examining the distribution of SP-A, total protein, and disaturated phospholipids (DSP) in the tubular myelin-rich (Alv-1) and tubular myelin-poor (Alv-2) fractions separated from lavaged material and in Lb-A and Lb-B isolated from both lung homogenate and purified alveolar type II cells. Our findings indicate that Lb-B is derived from type II cells, although they do not indicate whether it is a secretory form of surfactant, a reuptake vesicle, or a mixture of both. We found that the lung has a large tissue pool of immunoreactive SP-A. The %SP-A/DSP of total lamellar bodies isolated from type II cells was 0.96 +/- 0.1 (mean +/- SE), intermediate between that in Lb-A (1.67 +/- 0.13) and in Lb-B (0.65 +/- 0.04). In contrast, the %SP-A/DSP was 11.16 +/- 0.84 in whole lung homogenate and 13.14 +/- 1.71 in whole type II cells. In the alveolar compartment, the %SP-A/DSP was 17.38 +/- 3.40 in Alv-1, 6.34 +/- 0.31 in Alv-2, and 10.49 +/- 1.43 in macrophages, values an order of magnitude greater than found with the lamellar bodies. Our results indicate that only a relatively small portion of alveolar SP-A is derived from lamellar bodies, and we suggest that secretion of SP-A and DSP occurs via independent pathways.

  14. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haque, Rizwanul; Umstead, Todd M.; Ponnuru, Padmavathi

    Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, andmore » 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure.« less

  15. Quantification of surfactant proteins in tears of patients suffering from dry eye disease compared to healthy subjects.

    PubMed

    Posa, Andreas; Paulsen, Friedrich; Dietz, Richard; Garreis, Fabian; Sander, Ralph; Schicht, Martin; Sel, Saadettin; Scholz, Michael; Hammer, Christian M; Bräuer, Lars

    2018-03-01

    To quantify and compare the amounts of surfactant proteins SP-A, SP-B, SP-C and SP-D in the tear fluid collected from patients with dry eye syndrome and from individuals with a healthy ocular surface. Schirmer strips were used to collect tear fluid from both eyes of 241 volunteers (99 men, 142 women; age range: 18-87 years). Dry eye syndrome was diagnosed by ophthalmologists in 125 patients, whereas the healthy control group comprised 116 individuals. The total protein concentration was determined via Bradford assay. The relative concentration of surfactant proteins SP-A through -D was measured by enzyme-linked immuno-sorbent assay (ELISA). The mean relative concentrations of SP-A, SP-C and SP-D were significantly higher in the dry eye group as compared to the healthy controls (p<0.05, one-way ANOVA). SP-B was also detected at a higher concentration in the dry eye group, but the difference to the control group was not statistically significant. The upregulation of SP-A and SP-D in the dry eye group is probably related to these proteins' known antimicrobial and immunomodulatory effects at the ocular surface. It may represent a pathophysiological response to the inflammatory condition of the ocular surface in dry eye. The upregulation of SP-B and SP-C may represent an effort of the lacrimal system to reduce surface tension and thus to counteract the increased tendency of the tear film to tear in dry eye. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Streptococcus mutans genes that code for extracellular proteins in Escherichia coli K-12.

    PubMed

    Holt, R G; Abiko, Y; Saito, S; Smorawinska, M; Hansen, J B; Curtiss, R

    1982-10-01

    Chromosomal DNA from Streptococcus mutans 6715 (serotype g) was cloned into Escherichia coli K-12 by using the cosmid pJC74 cloning vector and a bacteriophage lambda in vitro packaging system. Rabbit antiserum against S. mutans extracellular proteins was used for immunological screening of the clone bank. Twenty-one clones produced weak to strong precipitin bands around the colonies, but only after the lambda c1857 prophage was induced by being heated to lyse the E. coli cells. None of the clones expressed enzyme activity for several known S. mutans extracellular enzymes. One of these clones contained a 45-kilobase recombinant plasmid designated pYA721. An 8.5-kilobase fragment of S. mutans DNA from pYA721 was isolated and recloned into the BamHI restriction site of the plasmid vector pACYC184 to construct pYA726. pYA726 contained all, or nearly all, of the gene for a surface protein antigen (the spaA protein) of S. mutans 6715. This was deduced from immunological studies in which extracts of cells harboring pYA726 reacted with antisera against both purified 6715 spaA protein (about 210,000 daltons) and the immunologically similar antigen I/II of serotype c strains of S. mutans. In addition, the S. mutans spaA protein was found to possess at least one antigenic determinant not present on the protein specified by pYA726. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of E. coli clone extracts revealed that pYA726 produced a polypeptide with a molecular mass of about 180,000 daltons which was predominantly found in the periplasmic space of E. coli cells. Antisera to the spaA protein of S. mutans reacted with extracellular protein from representative strains of S. mutans serotypes a, c, d, e, f, and g, but not b.

  17. The Staphylococcus aureus protein-coding gene gdpS modulates sarS expression via mRNA-mRNA interaction.

    PubMed

    Chen, Chuan; Zhang, Xu; Shang, Fei; Sun, Haipeng; Sun, Baolin; Xue, Ting

    2015-08-01

    Staphylococcus aureus is an important Gram-positive pathogen responsible for numerous diseases ranging from localized skin infections to life-threatening systemic infections. The virulence of S. aureus is essentially determined by a wide spectrum of factors, including cell wall-associated proteins and secreted toxins that are precisely controlled in response to environmental changes. GGDEF domain protein from Staphylococcus (GdpS) is the only conserved staphylococcal GGDEF domain protein that is involved not in c-di-GMP synthesis but in the virulence regulation of S. aureus NCTC8325. Our previous study showed that the inactivation of gdpS generates an extensive change of virulence factors together with, in particular, a major Spa (protein A) surface protein. As reported, sarS is a direct positive regulator of spa. The decreased transcript levels of sarS in the gdpS mutant compared with the parental NCTC8325 strain suggest that gdpS affects spa through interaction with sarS. In this study, site mutation and complementary experiments showed that the translation product of gdpS was not involved in the regulation of transcript levels of sarS. We found that gdpS functioned through direct RNA-RNA base pairing with the 5' untranslated region (5'UTR) of sarS mRNA and that a putative 18-nucleotide region played a significant role in the regulatory process. Furthermore, the mRNA half-life analysis of sarS in the gdpS mutant showed that gdpS positively regulates the mRNA levels of sarS by contributing to the stabilization of sarS mRNA, suggesting that gdpS mRNA may regulate spa expression in an RNA-dependent pathway. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Based Upon Repeat Pattern (BURP): an algorithm to characterize the long-term evolution of Staphylococcus aureus populations based on spa polymorphisms.

    PubMed

    Mellmann, Alexander; Weniger, Thomas; Berssenbrügge, Christoph; Rothgänger, Jörg; Sammeth, Michael; Stoye, Jens; Harmsen, Dag

    2007-10-29

    For typing of Staphylococcus aureus, DNA sequencing of the repeat region of the protein A (spa) gene is a well established discriminatory method for outbreak investigations. Recently, it was hypothesized that this region also reflects long-term epidemiology. However, no automated and objective algorithm existed to cluster different repeat regions. In this study, the Based Upon Repeat Pattern (BURP) implementation that is a heuristic variant of the newly described EDSI algorithm was investigated to infer the clonal relatedness of different spa types. For calibration of BURP parameters, 400 representative S. aureus strains with different spa types were characterized by MLST and clustered using eBURST as "gold standard" for their phylogeny. Typing concordance analysis between eBURST and BURP clustering (spa-CC) were performed using all possible BURP parameters to determine their optimal combination. BURP was subsequently evaluated with a strain collection reflecting the breadth of diversity of S. aureus (JCM 2002; 40:4544). In total, the 400 strains exhibited 122 different MLST types. eBURST grouped them into 23 clonal complexes (CC; 354 isolates) and 33 singletons (46 isolates). BURP clustering of spa types using all possible parameter combinations and subsequent comparison with eBURST CCs resulted in concordances ranging from 8.2 to 96.2%. However, 96.2% concordance was reached only if spa types shorter than 8 repeats were excluded, which resulted in 37% excluded spa types. Therefore, the optimal combination of the BURP parameters was "exclude spa types shorter than 5 repeats" and "cluster spa types into spa-CC if cost distances are less than 4" exhibiting 95.3% concordance to eBURST. This algorithm identified 24 spa-CCs, 40 singletons, and excluded only 7.8% spa types. Analyzing the natural population with these parameters, the comparison of whole-genome micro-array groupings (at the level of 0.31 Pearson correlation index) and spa-CCs gave a concordance of 87.1%; BURP spa-CCs vs. manually grouped spa types resulted in 95.7% concordance. BURP is the first automated and objective tool to infer clonal relatedness from spa repeat regions. It is able to extract an evolutionary signal rather congruent to MLST and micro-array data.

  19. A spindle pole antigen gene MoSPA2 is important for polar cell growth of vegetative hyphae and conidia, but is dispensable for pathogenicity in Magnaporthe oryzae.

    PubMed

    Li, Chao; Yang, Jun; Zhou, Wei; Chen, Xiao-Lin; Huang, Jin-Guang; Cheng, Zhi-Hua; Zhao, Wen-Sheng; Zhang, Yan; Peng, You-Liang

    2014-11-01

    Spa2 is an important component of the multiprotein complex polarisome, which is involved in the establishment, maintenance, termination of polarized cell growth and is important for defining tip growth of filamentous fungi. In this study, we isolated an insertional mutant of the rice blast fungus Magnaporthe oryzae that formed smaller colony and conidia compared with the wild type. In the mutant, a spindle pole antigen gene MoSPA2 was disrupted by the integration of an exogenous plasmid. Targeted gene deletion and complementation assays demonstrated the gene disruption was responsible for the defects of the insertional mutant. Interestingly, the MoSpa2-GFP fusion protein was found to accumulate as a spot at hyphal tips, septa of hyphae and conidial tip cells where germ tubes are usually produced, but not in appressoria, infection hyphae or at the septa of conidia. Furthermore, the deletion mutants of MoSPA2 exhibited slower hyphal tip growth, more hyphal branches, and smaller size of conidial tip cells. However, MoSPA2 is not required for plant infection. These results indicate that MoSPA2 is required for vegetative hyphal growth and maintaining conidium morphology and that spotted accumulation of MoSpa2 is important for its functions during cell polar growth.

  20. Protein a Immunoadsorption May Hamper the Decision to Transplant Due to Interference With CDC Crossmatch Results.

    PubMed

    Koefoed-Nielsen, Pernille; Bistrup, Claus; Christiansen, Mette

    2017-06-01

    Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers. From 2012 to 2013, we experienced seven patients desensitized using SPA IA, initially presenting negative cytotoxic complement dependent (CDC) T-cell crossmatches but positive B and T cell flowcytometric crossmatch, who despite significant DSA reduction developed weakly positive CDC T-cell crossmatch shortly prior to transplantation. We hypothesised that leached SPA during IA could be the cause, as the complication was not observed in patients who received plasma exchanges. We found that the positive CDC was not donor specific and SPA column material incubated with control serum reproduced a positive CDC T-cell crossmatch. Finally, we detected leached SPA in one of the patient samples using a highly sensitive time-resolved fluorescent assay. In conclusion, the results emphasize the importance of carefully considering CDC crossmatch results subsequent to IA, before a planned transplantation is either postponed or cancelled. J. Clin. Apheresis 32:163-169, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Conversion from CUL4-based COP1–SPA E3 apparatus to UVR8–COP1–SPA complexes underlies a distinct biochemical function of COP1 under UV-B

    PubMed Central

    Huang, Xi; Ouyang, Xinhao; Yang, Panyu; Lau, On Sun; Chen, Liangbi; Wei, Ning; Deng, Xing Wang

    2013-01-01

    The evolutionarily conserved CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) is a RING and WD40 protein that functions as a substrate receptor of CULLIN4–DAMAGED DNA BINDING PROTEIN 1 (CUL4–DDB1)–based E3 ubiquitin ligases in both plants and animals. In Arabidopsis, COP1 is a central repressor of photomorphogenesis in the form of COP1–SUPPRESSOR OF PHYA (SPA) complex(es). CUL4–DDB1–COP1–SPA suppresses the photomorphogenic program by targeting the transcription factor ELONGATED HYPOCOTYL 5 for degradation. Intriguingly, under photomorphogenic UV-B light, COP1 reverses its repressive role and promotes photomorphogenesis. However, the mechanism by which COP1 is functionally switched is still obscure. Here, we demonstrate that UV-B triggers the physical and functional disassociation of the COP1–SPA core complex(es) from CUL4–DDB1 and the formation of a unique complex(es) containing the UV-B receptor UV RESISTANCE LOCUS 8 (UVR8). The establishment of this UV-B–dependent COP1 complex(es) is associated with its positive modulation of ELONGATED HYPOCOTYL 5 stability and activity, which sheds light on the mechanism of COP1’s promotive action in UV-B–induced photomorphogenesis. PMID:24067658

  2. Effect of Cys85 on biochemical properties and biological function of human SP-A variants

    PubMed Central

    Wang, Guirong; Myers, Catherine; Mikerov, Anatoly; Floros, Joanna

    2008-01-01

    Four “core” amino acid differences within the collagen-like domain distinguish the human surfactant proteins A1 (SP-A1) variants from the SP-A2 variants. One of these, cysteine 85 that could form intermolecular disulfide bonds, is present in SP-A1 (Cys85) and absent in SP-A2 (Arg85). We hypothesized that residue85 affects both structure and function of SP-A1 and SP-A2 variants. To test this, wild type (WT) variants, 6A2 of SP-A1 and 1A0 of SP-A2, and their mutants (6A2(C85R) and 1A0(R85C)), were generated and studied. We found: 1) Residue85 affected the binding ability to mannose and the oligomerization pattern of SP-As. The 1A0(R85C) and 6A2(C85R) patterns were similar and/or resembled those of WT 6A2 and 1A0, respectively. 2) Both SP-A WT and mutants differentially induced rough LPS and Pseudomonas aeruginosa aggregation in the following order: 1A0 > 6A2 > 6A2(C85R) > 1A0(R85C) for Re-LPS aggregation, and 1A0 > 6A2 = 6A2(C85R) = 1A0(R85C) for bacterial aggregation. 3) SP-A WT and mutants enhanced phagocytosis of P. aeruginosa by rat alveolar macrophages. Their phagocytic index order was: 6A2(C85R) > 1A0 > 6A2 = 1A0(R85C). The activity of mutant 1A0(C85R) was significantly lower from WT 1A0 but similar to 6A2. Compared to WT 6A2, the 6A2(C85R) mutant exhibited a significantly higher activity. These results indicate that SP-A variant/mutant with Arg85 exhibits higher ability to enhance bacterial phagocytosis than that with Cys85. Residue85 plays a important role in the structure and function of SP-A, and is a major factor for the differences between SP-A1 and SPA2 variants. PMID:17580966

  3. Application of Visible and Near-Infrared Hyperspectral Imaging to Determine Soluble Protein Content in Oilseed Rape Leaves

    PubMed Central

    Zhang, Chu; Liu, Fei; Kong, Wenwen; He, Yong

    2015-01-01

    Visible and near-infrared hyperspectral imaging covering spectral range of 380–1030 nm as a rapid and non-destructive method was applied to estimate the soluble protein content of oilseed rape leaves. Average spectrum (500–900 nm) of the region of interest (ROI) of each sample was extracted, and four samples out of 128 samples were defined as outliers by Monte Carlo-partial least squares (MCPLS). Partial least squares (PLS) model using full spectra obtained dependable performance with the correlation coefficient (rp) of 0.9441, root mean square error of prediction (RMSEP) of 0.1658 mg/g and residual prediction deviation (RPD) of 2.98. The weighted regression coefficient (Bw), successive projections algorithm (SPA) and genetic algorithm-partial least squares (GAPLS) selected 18, 15, and 16 sensitive wavelengths, respectively. SPA-PLS model obtained the best performance with rp of 0.9554, RMSEP of 0.1538 mg/g and RPD of 3.25. Distribution of protein content within the rape leaves were visualized and mapped on the basis of the SPA-PLS model. The overall results indicated that hyperspectral imaging could be used to determine and visualize the soluble protein content of rape leaves. PMID:26184198

  4. A natural human monoclonal antibody targeting Staphylococcus Protein A protects against Staphylococcus aureus bacteremia

    PubMed Central

    Varshney, Avanish K.; Sunley, Kevin M.; Bowling, Rodney A.; Kwan, Tzu-Yu; Mays, Heather R.; Rambhadran, Anu; Zhang, Yanfeng; Martin, Rebecca L.; Cavalier, Michael C.; Simard, John

    2018-01-01

    Staphylococcus aureus can cause devastating and life-threatening infections. With the increase in multidrug resistant strains, novel therapies are needed. Limited success with active and passive immunization strategies have been attributed to S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their Fc region, neutralizing effector function. The organism can thus shield itself with a protective coat of serum antibodies and render humoral immunity ineffective. The present antibody reactivity was derived from an individual with natural anti-SpA antibody titers. The monoclonal antibody is of an IgG3 subclass, which differs critically from other immunoglobulin subclasses since its Fc is not bound by SpA. Moreover, it targets a unique epitope on SpA that allows it to bind in the presence of serum antibodies. Consequently, the antibody opsonizes S. aureus and maintains effector function to enable natural immune mediated clearance. The data presented here provide evidence that 514G3 antibody is able to successfully rescue mice from S. aureus mediated bacteremia. PMID:29364906

  5. Correlation of the protein structure and gelling properties in dried egg white products.

    PubMed

    Handa, A; Hayashi, K; Shidara, H; Kuroda, N

    2001-08-01

    The relationship between protein structure and aggregation, as well as heat-induced gelling properties, of seven dried egg white (DEW) products was investigated. Strong correlations were found between average molecular weight and hydrophobicity plus surface SH groups of DEW-soluble protein aggregate (SPA). This suggests that hydrophobic interactions and disulfide bond formation between protein molecules were involved in the aggregation. The average molecular weight of DEW products with alkaline pHs was relatively higher than those with neutral pHs and the same degree of protein unfolding, probably because of more disulfide bond formation between protein molecules. In addition, strong correlations were found between hydrophobicity, surface SH groups plus average molecular weight of DEW-SPA, and physical properties of the gels from DEW products. These data indicated that controlling the aggregation of DEW proteins in the dry state is crucial to controlling the gelling properties of DEW.

  6. Prognostic significance of surfactant protein A, surfactant protein D, Clara cell protein 16, S100 protein, trefoil factor 3, and prostatic secretory protein 94 in idiopathic pulmonary fibrosis, sarcoidosis, and chronic pulmonary obstructive disease.

    PubMed

    Doubková, Martina; Karpíšek, Michal; Mazoch, Jiri; Skřičková, Jana; Doubek, Michael

    2016-10-07

    Identification of serum and bronchoalveolar lavage fluid (BALF) biomarkers may facilitate diagnosis and prognostication in various lung disorders. Serum and BALF levels of surfactant protein A (SP-A), surfactant protein D (SP-D), Clara cell protein 16 (CC16), S100 protein, trefoil factor 3 (TFF3), and prostatic secretory protein 94 (PSP94) were evaluated in 94 consecutive patients (idiopathic pulmonary fibrosis (IPF; n=18), sarcoidosis (n=25), chronic obstructive pulmonary disease (COPD; n=51)), and in 155 healthy controls. Biomarkers were measured at diagnosis and compared with disease characteristics. Both uniparametric and multiparametric analyses were used. Seven significant correlations were found: 1) BALF PSP94 level correlated with prognosis of sarcoidosis (P=0.035); 2) BALF SP-D level with pulmonary functions in IPF (P=0.032); 3) BALF SP-D and TFF3 with IPF mortality (P=0.049 and 0.017, respectively); 4) serum TFF3 level with COPD mortality (P=0.006,); 5) serum SP-A with pulmonary functions impairment in IPF (P=0.011); 6) serum SP-D level was associated with HRCT interstitial score in IPF (P=0.0346); and 7) serum SP-A was associated with staging of COPD according to spirometry (P<0.001). Moreover, our analysis showed that some biomarker levels differed significantly among the diseases: 1) BALF SP-D level differed between sarcoidosis and IPF; 2) serum SP-A level differed among IPF, sarcoidosis, COPD and was also different from healthy controls; 3) serum S100A6, S100A11 levels differed among IPF, sarcoidosis, COPD from healthy controls 4) serum SP-D, CC16, TFF-3 levels distinguished IPF patients from healthy controls; and 5) serum CC16, TFF3, PSP94 distinguished COPD patients from healthy controls. Our study shows that some of selected biomarkers should have prognostic value in the analysed lung disorders. On the other hand, these biomarkers do not appear to be unequivocally suitable for differential diagnosis of these disorders.

  7. Assessing the potential for raw meat to influence human colonization with Staphylococcus aureus.

    PubMed

    Carrel, Margaret; Zhao, Chang; Thapaliya, Dipendra; Bitterman, Patrick; Kates, Ashley E; Hanson, Blake M; Smith, Tara C

    2017-09-07

    The role of household meat handling and consumption in the transfer of Staphylococcus aureus (S. aureus) from livestock to consumers is not well understood. Examining the similarity of S. aureus colonizing humans and S. aureus in meat from the stores in which those individuals shop can provide insight into the role of meat in human S. aureus colonization. S. aureus isolates were collected from individuals in rural and urban communities in Iowa (n = 3347) and contemporaneously from meat products in stores where participants report purchasing meat (n = 913). The staphylococcal protein A (spa) gene was sequenced for all isolates to determine a spa type. Morisita indices and Permutational Multivariate Analysis of Variance Using Distance Matrices (PERMANOVA) were used to determine the relationship between spa type composition among human samples and meat samples. spa type composition was significantly different between households and meat sampled from their associated grocery stores. spa types found in meat were not significantly different regardless of the store or county in which they were sampled. spa types in people also exhibit high similarity regardless of residential location in urban or rural counties. Such findings suggest meat is not an important source of S. aureus colonization in shoppers.

  8. Fetal-to-maternal signaling in the timing of birth.

    PubMed

    Mendelson, Carole R; Montalbano, Alina P; Gao, Lu

    2017-06-01

    Preterm birth remains the major cause of neonatal morbidity and mortality throughout the world. This is due, in part, to our incomplete understanding of the mechanisms that underlie the maintenance of pregnancy and the initiation of parturition at term. In this article, we review our current knowledge of the complex, interrelated and concerted mechanisms whereby progesterone maintains myometrial quiescence throughout most of pregnancy, as well as those that mediate the upregulation of the inflammatory response and decline in progesterone receptor function leading to parturition. Herein, we review findings that demonstrate a role of the fetus in the timing of birth. Specifically, we focus on our own studies indicating that maturation of the fetal lung and enhanced secretion of the surfactant components, surfactant protein A (SP-A) and the potent inflammatory glycerophospholipid, platelet-activating factor (PAF), initiate a signaling cascade culminating in parturition. Our studies suggest an essential role of steroid receptor coactivators, SRC-1 and SRC-2, which activate expression of genes encoding SP-A and LPCAT1. LPCAT1 is a key enzyme in the synthesis of PAF, as well as DPPC, a highly surface-active glycerophospholipid component of surfactant. Thus, we describe a novel pathway through which the fetus contributes to the initiation of labor by signaling the mother when its lungs have achieved sufficient maturity for survival in an aerobic environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation.

    PubMed

    Burgess, Jamie L; Burgess, R Alan; Morales, Yalemi; Bouvang, Jenna M; Johnson, Sean J; Dickenson, Nicholas E

    2016-12-09

    Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation*

    PubMed Central

    Burgess, Jamie L.; Burgess, R. Alan; Morales, Yalemi; Bouvang, Jenna M.; Johnson, Sean J.; Dickenson, Nicholas E.

    2016-01-01

    Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. PMID:27770024

  11. A Comparative Pan-Genome Perspective of Niche-Adaptable Cell-Surface Protein Phenotypes in Lactobacillus rhamnosus

    PubMed Central

    Kant, Ravi; Sigvart-Mattila, Pia; Paulin, Lars; Mecklin, Jukka-Pekka; Saarela, Maria; Palva, Airi; von Ossowski, Ingemar

    2014-01-01

    Lactobacillus rhamnosus is a ubiquitously adaptable Gram-positive bacterium and as a typical commensal can be recovered from various microbe-accessible bodily orifices and cavities. Then again, other isolates are food-borne, with some of these having been long associated with naturally fermented cheeses and yogurts. Additionally, because of perceived health benefits to humans and animals, numerous L. rhamnosus strains have been selected for use as so-called probiotics and are often taken in the form of dietary supplements and functional foods. At the genome level, it is anticipated that certain genetic variances will have provided the niche-related phenotypes that augment the flexible adaptiveness of this species, thus enabling its strains to grow and survive in their respective host environments. For this present study, we considered it functionally informative to examine and catalogue the genotype-phenotype variation existing at the cell surface between different L. rhamnosus strains, with the presumption that this might be relatable to habitat preferences and ecological adaptability. Here, we conducted a pan-genomic study involving 13 genomes from L. rhamnosus isolates with various origins. In using a benchmark strain (gut-adapted L. rhamnosus GG) for our pan-genome comparison, we had focused our efforts on a detailed examination and description of gene products for certain functionally relevant surface-exposed proteins, each of which in effect might also play a part in niche adaptability among the other strains. Perhaps most significantly of the surface protein loci we had analyzed, it would appear that the spaCBA operon (known to encode SpaCBA-called pili having a mucoadhesive phenotype) is a genomic rarity and an uncommon occurrence in L. rhamnosus. However, for any of the so-piliated L. rhamnosus strains, they will likely possess an increased niche-specific fitness, which functionally might presumably be manifested by a protracted transient colonization of the gut mucosa or some similar microhabitat. PMID:25032833

  12. Increased expression of human leucocyte antigen class I free heavy chains on monocytes of patients with spondyloarthritis and cells transfected with HLA-B27.

    PubMed

    Ding, Jin; Feng, Yuan; Zheng, Zhao Hui; Li, Xue Yi; Wu, Zhen Biao; Zhu, Ping

    2015-02-01

    Human leucocyte antigen (HLA)-B27 expression is correlated with spondyloarthritis (SpA), but its role in disease pathogenesis remains unclear. The aim of the study was to determine whether HLA-B27 free heavy chain (FHC) contributes to SpA pathogenesis. Flow cytometry was used to analyse the FHC expression on CD3+ and CD14+ cells in the peripheral blood (PB) and synovial fluid (SF) from SpA patients, healthy controls, and rheumatoid arthritis (RA) patients. Human monocytic U937 cell lines stably expressing enhanced green fluorescence protein (EGFP)/HLA-B27, EGFP/HLA-A2 or EGFP alone were created to further investigate the relation between HLA-B27 and FHC expression. The relative FHC level on CD14+ PB cells was significantly higher in SpA patients than in controls, but lower than on the SF cells of SpA patients. No significant correlation was found for relative FHC expression with HLA-B27 or β2-microglobulin expression. HLA-B27-transfected U937 cells expressed higher FHC levels than either EGFP/HLA-A2- or EGFP-transfected cells. HLA class I FHC expression was significantly increased on monocytes of SpA patients and HLA-B27-transfected cells, implying that FHC, perhaps mostly derived from HLA-B27, plays an important role in SpA pathogenesis. © 2014 John Wiley & Sons Ltd.

  13. CdTe quantum dots: aqueous phase synthesis, stability studies and protein conjugation for development of biosensors

    NASA Astrophysics Data System (ADS)

    Borse, Vivek; Sadawana, Mayur; Srivastava, Rohit

    2016-04-01

    Synthesis of quantum dots (QDs) in aqueous medium is advantageous as compared to the organic solvent mediated synthesis, as the aqueous synthesis is less toxic, reagent effective, easily reproducible and importantly, synthesized QDs have biological compatibility. The QDs should be aqueous in nature for use in cell imaging, drug labeling, tracking and delivery. Structural modifications are necessary to enable their use in biosensing application. In this work, mercaptopropionic acid capped cadmium telluride QDs (MPA-CdTe QDs) were synthesized by hydrothermal method and characterized by various techniques. Water and various biochemical buffers were used to study the fluorescence intensity stability of the QDs at different physicochemical conditions. QDs stored in 4° C showed excellent stability of fluorescence intensity values as compared to the samples stored at room temperature. Staphylococcal protein A (SPA) was conjugated with the QDs (SPA-QDs) and characterized using UV and fluorescence spectroscopy, zeta potential, HRTEM, FTIR, and AFM. Blue shift was observed in the fluorescence emission spectra that may be due to reduction in the surface charge as carboxyl groups on QDs were replaced by amino groups of SPA. This SPA conjugated to QDs enables binding of the C-terminal of antibodies on its surface allowing N-terminal binding site remain free to bind with antigenic biomarkers. Thus, the biosensor i.e. antibody bound on SPA-QDs would bind to the antigenic biomarkers in sample and the detection system could be developed. As QDs have better fluorescence properties than organic dyes, this biosensor will provide high sensitivity and quantitative capability in diagnostics.

  14. Mice Deficient in Surfactant Protein A (SP-A) and SP-D or in TLR2 Manifest Delayed Parturition and Decreased Expression of Inflammatory and Contractile Genes

    PubMed Central

    Montalbano, Alina P.; Hawgood, Samuel

    2013-01-01

    Previously we obtained compelling evidence that the fetus provides a critical signal for the initiation of term labor through developmental induction of surfactant protein (SP)-A expression by the fetal lung and secretion into amniotic fluid (AF). We proposed that interactions of AF macrophage (Mφ) Toll-like receptors (TLRs) with SP-A, at term, or bacterial components, at preterm, result in their activation and migration to the pregnant uterus. Herein the timing of labor in wild-type (WT) C57BL/6 mice was compared with mice homozygous null for TLR2, SP-A, SP-D, or doubly deficient in SP-A and SP-D. Interestingly, TLR2−/− females manifested a significant (P < 0.001) delay in timing of labor compared with WT as well as reduced expression of the myometrial contraction-associated protein (CAP) gene, connexin-43, and Mφ marker, F4/80, at 18.5 d postcoitum (dpc). Whereas in first pregnancies, SP-A−/−, SP-D−/−, and SP-A/D−/− females delivered at term (∼19.5 dpc), in second pregnancies, parturition was delayed by approximately 12 h in SP-A−/− (P = 0.07) and in SP-A/D−/− (P <0.001) females. Myometrium of SP-A/D−/− females expressed significantly lower levels of IL-1β, IL-6, and CAP genes, connexin-43, and oxytocin receptor at 18.5 dpc compared with WT. F4/80+ AF Mφs from TLR2−/− and SP-A/D−/− mice expressed significantly lower levels of both proinflammatory and antiinflammatory activation markers (e.g. IL-1β, IL-6, ARG1, YM1) compared with gestation-matched WT AF Mφs. These novel findings suggest that the pulmonary collectins acting via TLR2 serve a modulatory role in the timing of labor; their relative impact may be dependent on parity. PMID:23183169

  15. Cap-independent translation of human SP-A 5′-UTR variants: a double-loop structure and cis-element contribution

    PubMed Central

    Wang, Guirong; Guo, Xiaoxuan; Silveyra, Patricia; Kimball, Scot R.; Floros, Joanna

    2009-01-01

    Human surfactant protein A (hSP-A), a molecule of innate immunity and surfactant-related functions, consists of two functional genes, SP-A1 and SP-A2. SP-A expression is regulated by several factors including environmental stressors. SP-A1 and SP-A2 5′-untranslated region (5′-UTR) splice variants have a differential impact on translation efficiency and mRNA stability. To study whether these variants mediate internal ribosome entry site (IRES) activity (i.e., cap-independent translation), we performed transient transfection experiments in H441 cells with constructs containing one SP-A1 (A′D′, AB′D′, or A′CD′) or SP-A2 (ABD) 5′-UTR splice variant between the Renilla and firefly luciferase genes of a bicistronic reporter vector. We found that 1) variants A′D′, ABD, and AB′D′ exhibit significantly higher IRES activities than negative control (no SP-A 5′-UTR) and A′CD′ has no activity; the order of highest IRES activity was ABD > A′D′ > AB′D; 2) IRES activity of ABD significantly increased in response to diesel particulate matter (20 μg/ml) but not in response to ozone (1 ppm for 1 h); 3) deletion mutants of ABD revealed regulatory elements associated with IRES activity; one at the end of exon A attenuated activity, whereas a region containing a short adenosine-rich motif in the second half of exon B and the start of exon D enhanced activity; 4) elimination of a predicted double-loop structure or increase in free energy significantly reduced IRES activity; 5) elimination of one or both double-loop structures in A′D′ did not affect cap-dependent translation activity. Thus several factors, including cis-elements and secondary structure type and stability, are required for hSP-A 5′-UTR variant-mediated cap-independent translation. PMID:19181744

  16. Predominance of Three Closely Related Methicillin-Resistant Staphylococcus aureus Clones Carrying a Unique ccrC-Positive SCCmec type III and the Emergence of spa t304 and t690 SCCmec type IV pvl+ MRSA Isolates in Kinta Valley, Malaysia.

    PubMed

    Ho, Wai-Yew; Choo, Quok-Cheong; Chew, Choy-Hoong

    2017-03-01

    We investigated the epidemiology and clonality of 175 nonrepetitive methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical specimens collected between 2011 and 2012 in Kinta Valley in Malaysia. Molecular tools such as polymerase chain reaction, pulsed-field gel electrophoresis, and staphylococcal protein A (spa) typing were used. Our study revealed the predominance of three closely related ermA + SCCmec type III pulsotypes belonging to spa type t037 (Brazilian-Hungarian clone), which were deficient in the locus F, but positive for the ccrC gene in majority (65.7%) of the MRSA infections in this region. The first evidence of SCCmec type II MRSA in the country, belonging to spa type t2460, was also noted. Although the carriage of pvl gene was uncommon (8.6%) and mostly confined to either SCCmec type IV or SCCmec type V isolates, most of these isolates belonged to spa types t345 or t657, which are associated with the Bengal-Bay CA-MRSA clone. Interestingly, spa t304 and t690 SCCmec type IV pvl + were also detected among the MRSA isolates. Data from this study show the rise of uncommon clones among MRSA isolates in Malaysia.

  17. Piliation of Lactobacillus rhamnosus GG Promotes Adhesion, Phagocytosis, and Cytokine Modulation in Macrophages

    PubMed Central

    Vargas García, Cynthia E.; Petrova, Mariya; Claes, Ingmar J. J.; De Boeck, Ilke; Verhoeven, Tine L. A.; Dilissen, Ellen; von Ossowski, Ingemar; Palva, Airi; Bullens, Dominique M.; Vanderleyden, Jos

    2015-01-01

    Recently, spaCBA-encoded pili on the cell surface of Lactobacillus rhamnosus GG were identified to be key molecules for binding to human intestinal mucus and Caco-2 intestinal epithelial cells. Here, we investigated the role of the SpaCBA pilus of L. rhamnosus GG in the interaction with macrophages in vitro by comparing the wild type with surface mutants. Our results show that SpaCBA pili play a significant role in the capacity for adhesion to macrophages and also promote bacterial uptake by these phagocytic cells. Interestingly, our data suggest that SpaCBA pili also mediate anti-inflammatory effects by induction of interleukin-10 (IL-10) mRNA and reduction of interleukin-6 (IL-6) mRNA in a murine RAW 264.7 macrophage cell line. These pili appear to mediate these effects indirectly by promoting close contact with the macrophages, facilitating the exertion of anti-inflammatory effects by other surface molecules via yet unknown mechanisms. Blockage of complement receptor 3 (CR3), previously identified to be a receptor for streptococcal pili, significantly decreased the uptake of pilus-expressing strains in RAW 264.7 cells, while the expression of IL-10 and IL-6 mRNA by these macrophages was not affected by this blocking. On the other hand, blockage of Toll-like receptor 2 (TLR2) significantly reduced the expression of IL-6 mRNA irrespective of the presence of pili. PMID:25576613

  18. DECREASED PRODUCTION OF SURFACTANT PROTEINS AFTER DIESEL EXHAUST EXPOSURE INCREASES SUSCEPTIBILITY TO INFLUENZA INFECTION

    EPA Science Inventory

    Pulmonary surfactant proteins A and D (SP-A and SP-D), termed collectins, enhance the opsonization of foreign particles and pathogens by phagocytic cells. Inhaled pollutants such as diesel exhaust (DE) have a possible role in suppressing the production of surfactant proteins whic...

  19. A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kang, Hae Joo; Paterson, Neil G.; Kim, Chae Un

    2014-05-01

    Two crystal structures of the major pilin SpaD from C. diphtheriae have been determined at 1.87 and 2.5 Å resolution. The N-terminal domain is found to contain an isopeptide bond that forms slowly over time in the recombinant protein. Given its structural context, this provides insight into the relationship between internal isopeptide-bond formation and pilus assembly. The Gram-positive organism Corynebacterium diphtheriae, the cause of diphtheria in humans, expresses pili on its surface which it uses for adhesion and colonization of its host. These pili are covalent protein polymers composed of three types of pilin subunit that are assembled by specificmore » sortase enzymes. A structural analysis of the major pilin SpaD, which forms the polymeric backbone of one of the three types of pilus expressed by C. diphtheriae, is reported. Mass-spectral and crystallographic analysis shows that SpaD contains three internal Lys–Asn isopeptide bonds. One of these, shown by mass spectrometry to be located in the N-terminal D1 domain of the protein, only forms slowly, implying an energy barrier to bond formation. Two crystal structures, of the full-length three-domain protein at 2.5 Å resolution and of a two-domain (D2-D3) construct at 1.87 Å resolution, show that each of the three Ig-like domains contains a single Lys–Asn isopeptide-bond cross-link, assumed to give mechanical stability as in other such pili. Additional stabilizing features include a disulfide bond in the D3 domain and a calcium-binding loop in D2. The N-terminal D1 domain is more flexible than the others and, by analogy with other major pilins of this type, the slow formation of its isopeptide bond can be attributed to its location adjacent to the lysine used in sortase-mediated polymerization during pilus assembly.« less

  20. Streptococcus mutans SpaP binds to RadD of Fusobacterium nucleatum ssp. polymorphum.

    PubMed

    Guo, Lihong; Shokeen, Bhumika; He, Xuesong; Shi, Wenyuan; Lux, Renate

    2017-10-01

    Adhesin-mediated bacterial interspecies interactions are important elements in oral biofilm formation. They often occur on a species-specific level, which could determine health or disease association of a biofilm community. Among the key players involved in these processes are the ubiquitous fusobacteria that have been recognized for their ability to interact with numerous different binding partners. Fusobacterial interactions with Streptococcus mutans, an important oral cariogenic pathogen, have previously been described but most studies focused on binding to non-mutans streptococci and specific cognate adhesin pairs remain to be identified. Here, we demonstrated differential binding of oral fusobacteria to S. mutans. Screening of existing mutant derivatives indicated SpaP as the major S. mutans adhesin specific for binding to Fusobacterium nucleatum ssp. polymorphum but none of the other oral fusobacteria tested. We inactivated RadD, a known adhesin of F. nucleatum ssp. nucleatum for interaction with a number of gram-positive species, in F. nucleatum ssp. polymorphum and used a Lactococcus lactis heterologous SpaP expression system to demonstrate SpaP interaction with RadD of F. nucleatum ssp. polymorphum. This is a novel function for SpaP, which has mainly been characterized as an adhesin for binding to host proteins including salivary glycoproteins. In conclusion, we describe an additional role for SpaP as adhesin in interspecies adherence with RadD-SpaP as the interacting adhesin pair for binding between S. mutans and F. nucleatum ssp. polymorphum. Furthermore, S. mutans attachment to oral fusobacteria appears to involve species- and subspecies-dependent adhesin interactions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Molecular epidemiology of Staphylococcus aureus bacteremia in a single large Minnesota medical center in 2015 as assessed using MLST, core genome MLST and spa typing.

    PubMed

    Park, Kyung-Hwa; Greenwood-Quaintance, Kerryl E; Uhl, James R; Cunningham, Scott A; Chia, Nicholas; Jeraldo, Patricio R; Sampathkumar, Priya; Nelson, Heidi; Patel, Robin

    2017-01-01

    Staphylococcus aureus is a leading cause of bacteremia in hospitalized patients. Whether or not S. aureus bacteremia (SAB) is associated with clonality, implicating potential nosocomial transmission, has not, however, been investigated. Herein, we examined the epidemiology of SAB using whole genome sequencing (WGS). 152 SAB isolates collected over the course of 2015 at a single large Minnesota medical center were studied. Staphylococcus protein A (spa) typing was performed by PCR/Sanger sequencing; multilocus sequence typing (MLST) and core genome MLST (cgMLST) were determined by WGS. Forty-eight isolates (32%) were methicillin-resistant S. aureus (MRSA). The isolates encompassed 66 spa types, clustered into 11 spa clonal complexes (CCs) and 10 singleton types. 88% of 48 MRSA isolates belonged to spa CC-002 or -008. Methicillin-susceptible S. aureus (MSSA) isolates were more genotypically diverse, with 61% distributed across four spa CCs (CC-002, CC-012, CC-008 and CC-084). By MLST, there was 31 sequence types (STs), including 18 divided into 6 CCs and 13 singleton STs. Amongst MSSA isolates, the common MLST clones were CC5 (23%), CC30 (19%), CC8 (15%) and CC15 (11%). Common MRSA clones were CC5 (67%) and CC8 (25%); there were no MRSA isolates in CC45 or CC30. By cgMLST analysis, there were 9 allelic differences between two isolates, with the remaining 150 isolates differing from each other by over 40 alleles. The two isolates were retroactively epidemiologically linked by medical record review. Overall, cgMLST analysis resulted in higher resolution epidemiological typing than did multilocus sequence or spa typing.

  2. ABI domain containing proteins contribute to surface protein display and cell division in Staphylococcus aureus

    PubMed Central

    Frankel, Matthew B.; Wojcik, Brandon; DeDent, Andrea C.; Missiakas, Dominique M.; Schneewind, Olaf

    2012-01-01

    Summary The human pathogen Staphyloccocus aureus requires cell wall anchored surface proteins to cause disease. During cell division, surface proteins with YSIRK signal peptides are secreted into the cross wall, a layer of newly synthesized peptidoglycan between separating daughter cells. The molecular determinants for the trafficking of surface proteins are, however, still unknown. We screened mutants with non-redundant transposon insertions by fluorescence-activated cell sorting for reduced deposition of protein A (SpA) into the staphylococcal envelope. Three mutants, each of which harbored transposon insertions in genes for transmembrane proteins, displayed greatly reduced envelope abundance of SpA and surface proteins with YSIRK signal peptides. Characterization of the corresponding mutations identified three transmembrane proteins with abortive infectivity (ABI) domains, elements first described in lactococci for their role in phage exclusion. Mutations in genes for ABI domain proteins, designated spdA, spdB and spdC (surface protein display), diminish the expression of surface proteins with YSIRK signal peptides, but not of precursor proteins with conventional signal peptides. spdA, spdB and spdC mutants display an increase in the thickness of cross walls and in the relative abundance of staphylococci with cross walls, suggesting that spd mutations may represent a possible link between staphylococcal cell division and protein secretion. PMID:20923422

  3. ABI domain-containing proteins contribute to surface protein display and cell division in Staphylococcus aureus.

    PubMed

    Frankel, Matthew B; Wojcik, Brandon M; DeDent, Andrea C; Missiakas, Dominique M; Schneewind, Olaf

    2010-10-01

    The human pathogen Staphylococcus aureus requires cell wall anchored surface proteins to cause disease. During cell division, surface proteins with YSIRK signal peptides are secreted into the cross-wall, a layer of newly synthesized peptidoglycan between separating daughter cells. The molecular determinants for the trafficking of surface proteins are, however, still unknown. We screened mutants with non-redundant transposon insertions by fluorescence-activated cell sorting for reduced deposition of protein A (SpA) into the staphylococcal envelope. Three mutants, each of which harboured transposon insertions in genes for transmembrane proteins, displayed greatly reduced envelope abundance of SpA and surface proteins with YSIRK signal peptides. Characterization of the corresponding mutations identified three transmembrane proteins with abortive infectivity (ABI) domains, elements first described in lactococci for their role in phage exclusion. Mutations in genes for ABI domain proteins, designated spdA, spdB and spdC (surface protein display), diminish the expression of surface proteins with YSIRK signal peptides, but not of precursor proteins with conventional signal peptides. spdA, spdB and spdC mutants display an increase in the thickness of cross-walls and in the relative abundance of staphylococci with cross-walls, suggesting that spd mutations may represent a possible link between staphylococcal cell division and protein secretion. © 2010 Blackwell Publishing Ltd.

  4. Genotypes and oxacillin resistance of Staphylococcus aureus from chicken and chicken meat in Poland.

    PubMed

    Krupa, P; Bystroń, J; Bania, J; Podkowik, M; Empel, J; Mroczkowska, A

    2014-12-01

    The genotypes and oxacillin resistance of 263 Staphylococcus aureus isolates cultured from chicken cloacae (n = 138) and chicken meat (n = 125) was analyzed. Fifteen spa types were determined in the studied S. aureus population. Among 5 staphylococcal protein A gene (spa) types detected in S. aureus from chicken, t002, t3478, and t13620 were the most frequent. Staphylococcus aureus isolates from meat were assigned to 14 spa types. Among them, the genotypes t002, t056, t091, t3478, and t13620 were dominant. Except for 4 chicken S. aureus isolates belonging to CC398, the remaining 134 isolates were clustered into multilocus sequence clonal complex (CC) 5. Most of meat-derived isolates were assigned to CC5, CC7, and CC15, and to the newly described spa-CC12954 complex belonging to CC1. Except for t011 (CC398), all other spa types found among chicken isolates were also present in isolates from meat. Four S. aureus isolated from chicken and one from meat were identified as methicillin-resistant S. aureus (MRSA) with oxacillin minimum inhibitory concentrations from 16 to 64 μg/mL. All MRSA were assigned to spa types belonging to ST398, and included 4 animal spa t011 SCCmecV isolates and 1 meat-derived spa t899, SCCmecIV isolate. Borderline oxacillin-resistant S. aureus (BORSA) isolates, shown to grow on plates containing 2 to 3 μg/mL of oxacillin, were found within S. aureus isolates from chicken (3 isolates) and from meat (19 isolates). The spa t091 and t084 dominated among BORSA from chicken meat, whereas t548 and t002 were found within animal BORSA. We report for the first time the presence of MRSA in chicken in Poland. We demonstrate that MRSA CC398 could be found in chicken meat indicating potential of introduction of animal-associated genotypes into the food chain. We also report for the first time the possibility of transmission of BORSA isolates from chicken to meat. ©2014 Poultry Science Association Inc.

  5. Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity

    PubMed Central

    Toussirot, Éric; Saas, Philippe; Deschamps, Marina; Pouthier, Fabienne; Perrot, Lucille; Perruche, Sylvain; Chabod, Jacqueline; Tiberghien, Pierre; Wendling, Daniel

    2009-01-01

    Introduction Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied. Methods Sera from 165 patients with SpA were evaluated for sCTLA-4 measurements. Results were compared with those from 71 patients with rheumatoid arthritis (RA) and 88 healthy subjects. In 32 patients with SpA, 22 patients with RA and 15 healthy controls, we analyzed the intracellular CTLA-4 expression in CD4+ T cells, CD8+ T cells, activated (HLA-DR+Foxp3-) CD4+ T cells, CD4+ regulatory (CD25+Foxp3+) T cells and in CD3 negative cells by flow cytometry. Expression of the full length (coding for membrane CTLA-4) and spliced form (coding for sCTLA-4) of CTLA-4 transcripts in PBL were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR). Results High levels of sCTLA-4 were found in the SpA group compared to the RA group and healthy controls (P < 0.0001). Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI (r = 0.42, P < 0.0001) and C-reactive protein (CRP) levels (r = 0.17, P = 0.037). In contrast to RA patients, SpA patients did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested. Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA (P = 0.0014) in PBL. Conclusions SpA patients exhibit high levels of circulating sCTLA-4 that may result from an alternative splicing of CTLA-4 transcripts. This may influence immune activation and regulation in SpA. PMID:19570209

  6. Evaluation of IgY capture ELISA for sensitive detection of alpha hemolysin of Staphylococcus aureus without staphylococcal protein A interference.

    PubMed

    Reddy, Prakash Kudumala; Shekar, Aravind; Kingston, Joseph Jeyabalaji; Sripathy, Murali Harishchandra; Batra, Harshvardhan

    2013-05-31

    Staphylococcal protein A (Spa) secreted by all Staphylococcus aureus strains is the major hindrance in development of specific immunoassays for detecting S. aureus antigens, because of its characteristic feature of binding to Fc region of most mammalian immunoglobulins and also to Fab region of certain classes of mammalian immunoglobulins. Immunoglobulin Y (IgY) is the avian equivalent of mammalian IgG which does not have any affinity to Spa. In the present study we report that using chicken egg yolk IgY over mammalian IgG as capture antibody prevents both soluble and surface bound protein A from causing false positives quantified by chicken anti-protein A antibodies. This was demonstrated by development of sandwich ELISA for detection of alpha hemolysin toxin from culture supernatants of S. aureus strains with anti alpha hemolysin IgY as capture and rabbit anti alpha hemolysin IgG as revealing antibody. This indirect sandwich ELISA was evaluated onto a large number of S. aureus isolates recovered from clinical sources for alpha hemolysin secretion. Results of sandwich ELISA were compared with PCR and Western blot analysis. The immunoassay is highly specific and has high sensitivity of detecting less than 1 ng/ml. This procedure is highly effective in eliminating Spa interference and can be extended to detection of other important superantigen toxins of S. aureus. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

    PubMed Central

    Hu, Fengqi; Ding, Guohua; Zhang, Zhiyong; Gatto, Louis A.; Hawgood, Samuel; Poulain, Francis R.; Cooney, Robert N.; Wang, Guirong

    2015-01-01

    To investigate the effects of surfactant proteins A and D (SP-A, SP-D) in urinary tract infection (UTI), SP-A and SP-D double knockout (SP-A/D KO) and wild type (WT) C57BL/6 female mice were infected with uropathogenic Escherichia coli by intravesical inoculation. Compared with WT mice SP-A/D KO mice showed increased susceptibility to UTI as evidenced by higher bacterial CFU, more infiltrating neutrophils and severe pathological changes. Keratinocyte-derived chemokine increased in the kidney of WT mice but not in SP-A/D KO mice 24 h post-infection. Compared to control, level of IL-17 was elevated in the kidney of infected WT and SP-A/D KO mice and the level of IL-17 was higher in the infected SP-A/D KO mice than infected WT mice 24 and 48 h post-infection. Basal level of p38 MAPK phosphorylation in SP-A/D KO mice was higher compared to WT mice. Phosphorylated-p38 level was elevated in the kidney of WT mice post-infection but not in SP-A/D KO mice. Furthermore, in vitro growth of uropathogenic E. coli was inhibited by SP-A and SP-D. We conclude that SP-A and SP-D function as mediators of innate immunity by inhibiting bacterial growth and modulating renal inflammation in part by regulating p38 MAPK-related pathway in murine UTI. PMID:26511057

  8. Leptin Promotes Fetal Lung Maturity and Upregulates SP-A Expression in Pulmonary Alveoli Type-II Epithelial Cells Involving TTF-1 Activation

    PubMed Central

    Huang, Hui; Wang, Zhen-Hua; Cheng, Rui; Cai, Wei-Bin

    2013-01-01

    The placental hormone leptin has important functions in fetal and neonatal growth, and prevents depressed respiration in leptin-deficient mice. The effect of leptin on respiratory distress suffered by low birth weight and premature infants has been studied. However, it is unclear how leptin enhances lung maturity in the fetus and ameliorates neonatal respiratory distress. In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR). Mean birth weight and lung wet weight were higher in the leptin-treated group than in the PBS-treated group, indicating promotion of fetal growth. Leptin upregulated the intracellular expression and extracellular secretion of surfactant protein (SP) A in type-II alveolar epithelial cells (AECs) in vivo and in vitro. Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1 (TTF-1), a nuclear transcription essential for branching morphogenesis of the lung and expression of SP-A in type-II AECs. Knockdown of TTF-1 by RNA interference indicated that TTF-1 may play a vital role in leptin-induced SP-A expression. These results suggest that leptin may have great therapeutic potential for the treatment of FGR, and leptin-mediated SP-A induction and lung maturity of the fetus are TTF-1 dependent. PMID:23894445

  9. Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage.

    PubMed

    Cole, A L; Muthukrishnan, G; Chong, C; Beavis, A; Eade, C R; Wood, M P; Deichen, M G; Cole, A M

    2016-11-01

    Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Out of 15 studies, 10 resulted in rapid clearance (9±6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not interleukin (IL)-17. Nasal SA persistence corresponded with elevated baseline levels of macrophage inflammatory protein-1β, IL-1β, and IL-6, no induction of inflammatory factors after inoculation, and decreased IL-1 receptor antagonist/IL-1β ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (ΔSpA) strains were cleared faster than wild type only in participants with upregulated inflammatory markers after inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. ΔSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial codeterminant of SA nasal carriage.

  10. Polymorphisms of human leukocyte antigen B*27 on clinical phenotype of spondyloarthritis in Chinese.

    PubMed

    Ma, Hai-Jun; Yin, Qing-Feng; Liu, Yun; Wu, Yin; Zhu, Tie-Chui; Guo, Ming-Hao

    2018-02-01

    In recent years, an ever-increasing number of alleles of human leukocyte antigen B*27 (HLA-B*27) have been identified. This study aimed to establish an updated method for HLA-B*27 subtyping, and to investigate the impact of HLA-B*27 polymorphisms on the clinical phenotype of spondyloarthritis (SpA). Overall, 184 SpA patients were recruited for analyzing diversity of HLA-B*27 via an updated high-resolution polymerase chain reaction amplification with sequence specific primers (PCR-SSP). The prevalence of HLA-B*27 was 94.0%, and four subtypes were identified including HLA-B*2704 (77.5%), B*2705 (20.2%), B*2707 (1.7%), and B*2724 (0.6%). There was an obvious male predominance (P=.05) and markedly elevated C-reaction protein (CRP) in B*27 positive SpA (P<.01). In multivariate linear regression analysis, the elevated CRP was positively associated with HLA-B*27 positivity (regression coefficient B=46.1, P=.0003), grade of sacroiliitis (B=47.5, P=.0032), and male gender (B=20.4, P=.0041). Notably, a male predilection was also found in B*2705 positive SpA while B*2707 was associated with older age, higher positive family history, and higher prevalence of extra-articular features (all P<.05). In this study, an updated PCR-SSP technique to identify increasing alleles of HLA-B*27 was developed and their different effects on clinical manifestations of SpA were demonstrated. Genotyping of HLA-B*27 would shed light on our understanding of the pathogenesis of SpA. © 2017 Wiley Periodicals, Inc.

  11. Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli.

    PubMed

    Hu, Fengqi; Ding, Guohua; Zhang, Zhiyong; Gatto, Louis A; Hawgood, Samuel; Poulain, Francis R; Cooney, Robert N; Wang, Guirong

    2016-01-01

    To investigate the effects of surfactant proteins A and D (SP-A and SP-D, respectively) in urinary tract infection (UTI), SP-A and SP-D double knockout (SP-A/D KO) and wild type (WT) C57BL/6 female mice were infected with uropathogenic Escherichia coli by intravesical inoculation. Compared with WT mice SP-A/D KO mice showed increased susceptibility to UTI, as evidenced by higher bacterial CFU, more infiltrating neutrophils and severe pathological changes. Keratinocyte-derived chemokine increased in the kidney of WT mice but not in SP-A/D KO mice 24 h post-infection. Compared with control, the level of IL-17 was elevated in the kidney of infected WT and SP-A/D KO mice and the level of IL-17 was higher in the infected SP-A/D KO mice than in infected WT mice 24 and 48 h post-infection. The basal level of p38 MAPK phosphorylation in SP-A/D KO mice was higher than in WT mice. The phosphorylated p38 level was elevated in the kidney of WT mice post infection but not in SP-A/D KO mice. Furthermore, in vitro growth of uropathogenic E. coli was inhibited by SP-A and SP-D. We conclude that SP-A and SP-D function as mediators of innate immunity by inhibiting bacterial growth and modulating renal inflammation in part by regulating p38 MAPK-related pathway in murine UTI. © The Author(s) 2015.

  12. Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis.

    PubMed

    Visan, Lucian; Sanchez, Violette; Kania, Margaux; de Montfort, Aymeric; de la Maza, Luis M; Ausar, Salvador Fernando

    2016-09-01

    Chlamydia trachomatis is one of the most common sexually transmitted pathogens and the development of an effective vaccine is highly desirable. The Major Outer Membrane Protein (MOMP) is one of the most abundant and immunogenic chlamydial proteins. Here we investigated the effects of phosphate substitution on the physicochemical and immunochemical properties of an experimental vaccine composed of serovar E recombinant MOMP (rMOMP) and a proprietary adjuvant system SPA08, consisting of aluminum oxyhydroxide (AlOOH) containing the TLR4 agonist E6020. An increase in phosphate substitution in the AlOOH component of the adjuvant markedly decreased the adsorptive coefficient and adsorptive capacity for both Ser E rMOMP and E6020. In vaccine formulations used for immunizations, phosphate substitution induced a decrease in the % adsorption of Ser E rMOMP without affecting the % adsorption of E6020. Immunogenicity studies in CD1 mice showed that an increase in phosphate substitution of the SPA08 adjuvant resulted in an increase in Ser E rMOMP-specific serum total IgG and IgG1 but not IgG2a titers. The degree of phosphate substitution in SPA08 also significantly increased in vitro neutralization concomitant with a decrease in proinflammatory cytokines secreted by Ser E rMOMP-restimulated splenocytes. Taken together, the results of these studies suggest that the degree of phosphate substitution in AlOOH greatly affects the adsorption of E6020 and Ser E rMOMP to AlOOH resulting in significant effects on vaccine-induced cellular and humoral responses.

  13. The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome

    PubMed Central

    2009-01-01

    Background Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A) plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s) responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood. Methods We employed 2-dimensional difference gel electrophoresis (2D-DIGE), a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL) proteomes in wild type (WT) and SP-A knockout (KO) mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups. Results We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours) there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice. Conclusion We postulate that SP-A plays a role in reactive oxidant scavenging in WT mice and that its absence in the KO mice in the presence or absence of ozone exposure results in more pronounced, and presumably chronic, oxidative stress. PMID:19323824

  14. Specific capture and detection of Staphylococcus aureus with high-affinity modified aptamers to cell surface components

    PubMed Central

    Baumstummler, A; Lehmann, D; Janjic, N; Ochsner, UA

    2014-01-01

    Slow off-rate modified aptamer (SOMAmer) reagents were generated to several Staphylococcus aureus cell surface-associated proteins via SELEX with multiple modified DNA libraries using purified recombinant or native proteins. High-affinity binding agents with sub-nanomolar Kd's were obtained for staphylococcal protein A (SpA), clumping factors (ClfA, ClfB), fibronectin-binding proteins (FnbA, FnbB) and iron-regulated surface determinants (Isd). Further screening revealed several SOMAmers that specifically bound to Staph. aureus cells from all strains that were tested, but not to other staphylococci or other bacteria. SpA and ClfA SOMAmers proved useful for the selective capture and enrichment of Staph. aureus cells, as shown by culture and PCR, leading to improved limits of detection and efficient removal of PCR inhibitors. Detection of Staph. aureus cells was enhanced by several orders of magnitude when the bacterial cell surface was coated with SOMAmers followed by qPCR of the SOMAmers. Furthermore, fluorescence-labelled SpA SOMAmers demonstrated their utility as direct detection agents in flow cytometry. Significance and Impact of the Study Monitoring for microbial contamination of food, water, nonsterile products or the environment is typically based on culture, PCR or antibodies. Aptamers that bind with high specificity and affinity to well-conserved cell surface epitopes represent a promising novel type of reagents to detect bacterial cells without the need for culture or cell lysis, including for the capture and enrichment of bacteria present at low cell densities and for the direct detection via qPCR or fluorescent staining. PMID:24935714

  15. Novel bacteriophages containing a genome of another bacteriophage within their genomes.

    PubMed

    Swanson, Maud M; Reavy, Brian; Makarova, Kira S; Cock, Peter J; Hopkins, David W; Torrance, Lesley; Koonin, Eugene V; Taliansky, Michael

    2012-01-01

    A novel bacteriophage infecting Staphylococus pasteuri was isolated during a screen for phages in Antarctic soils. The phage named SpaA1 is morphologically similar to phages of the family Siphoviridae. The 42,784 bp genome of SpaA1 is a linear, double-stranded DNA molecule with 3' protruding cohesive ends. The SpaA1 genome encompasses 63 predicted protein-coding genes which cluster within three regions of the genome, each of apparently different origin, in a mosaic pattern. In two of these regions, the gene sets resemble those in prophages of Bacillus thuringiensis kurstaki str. T03a001 (genes involved in DNA replication/transcription, cell entry and exit) and B. cereus AH676 (additional regulatory and recombination genes), respectively. The third region represents an almost complete genome (except for the short terminal segments) of a distinct bacteriophage, MZTP02. Nearly the same gene module was identified in prophages of B. thuringiensis serovar monterrey BGSC 4AJ1 and B. cereus Rock4-2. These findings suggest that MZTP02 can be shuttled between genomes of other bacteriophages and prophages, leading to the formation of chimeric genomes. The presence of a complete phage genome in the genome of other phages apparently has not been described previously and might represent a 'fast track' route of virus evolution and horizontal gene transfer. Another phage (BceA1) nearly identical in sequence to SpaA1, and also including the almost complete MZTP02 genome within its own genome, was isolated from a bacterium of the B. cereus/B. thuringiensis group. Remarkably, both SpaA1 and BceA1 phages can infect B. cereus and B. thuringiensis, but only one of them, SpaA1, can infect S. pasteuri. This finding is best compatible with a scenario in which MZTP02 was originally contained in BceA1 infecting Bacillus spp, the common hosts for these two phages, followed by emergence of SpaA1 infecting S. pasteuri.

  16. Molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with bacteremia based on MLST, SCCmec, spa, and agr locus types analysis.

    PubMed

    Goudarzi, Mehdi; Seyedjavadi, Sima Sadat; Nasiri, Mohammad Javad; Goudarzi, Hossein; Sajadi Nia, Raheleh; Dabiri, Hossein

    2017-03-01

    The widespread emergence of methicillin resistant Staphylococcus aureus, as a common cause of nosocomial infections, is becoming a serious concern in global public health. The objective of the present study was to investigate antimicrobial susceptibility pattern, frequency of virulence genes and molecular characteristics of methicillin-resistant Staphylococcus aureus strains isolated from patients with bacteremia. A total of 128 methicillin-resistant Staphylococcus aureus isolates were collected during February 2015 to January 2016. In vitro antimicrobial susceptibility of the isolates was assessed using the disk diffusion method. Conventional PCR was performed for the detection of adhesion (can, bbp, ebp, fnbB, fnbA, clfB, clfA) and toxin (etb, eta, pvl, tst) encoding genes, determining the agr type, SCCmec, MLST and spa typing of the isolates. All the methicillin-resistant Staphylococcus aureus isolates were found to be sensitive to linezolid, teicoplanin, and vancomycin. Resistance to the tested antibiotics varied from 97.7% for penicillin to 24.2% for mupirocin. The rate of multi drug resistance (MDR) in the present study was 97.7%. The most commonly detected toxin and adhesion genes were tst (58.6%), and clfB (100%), respectively. The majority of SCCmec III isolates were found in agr group I while SCCmec IV and II isolates were distributed among agr group III. Multilocus Sequence Typing (MLST) of the MRSA isolates showed five different sequence types: ST239 (43%), ST22 (39.8%), ST585 (10.9%), ST45 (3.9%) and ST240 (2.3%). All of the pvl positive strains belonged to ST22-SCCmec IV/t790 clone and were MDR. Among different 7 spa types, the most common were t790 (27.3%), t037 (21.9%), and t030 (14.1%). spa types t016, t924 and spa type t383 were reported for the first time from Asia and Iran, respectively. It was shown that spa types circulating in the studied hospitals varied which support the need to perform future surveillance studies in order to understand methicillin-resistant Staphylococcus aureus distribution and thus more effective infection control. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. The efficacy and safety of etanercept in patients with rheumatoid arthritis and spondyloarthropathy on hemodialysis.

    PubMed

    Senel, Soner; Kisacik, Bunyamin; Ugan, Yunus; Kasifoglu, Timucin; Tunc, Ercan; Cobankara, Veli

    2011-10-01

    We aimed to evaluate the efficacy and safety of long-term use of etanercept therapy in patients with spondyloarthropathy (SpA) and rheumatoid arthritis (RA) on hemodialysis (HD). Selected RA or SpA patients treated with etanercept under HD were retrospectively evaluated. Etanercept-related adverse events were closely recorded for all patients. At the follow-up, erythrocyte sedimentation rate and C-reactive protein levels were monitored. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for SpA patients and Disease Activity Score (DAS28) for RA patients were measured at every 3 or 6 months. In total five end-stage renal disease (ESRD) patients were enrolled to the study. The causes of ESRD in the study subjects were amyloidosis (n = 2), analgesic nephropathy (n = 2), and nephrolithiasis (n = 1). Three were diagnosed as SpA and two were RA. All patients used etanercept. The median age was 39 years (range 22-72 years). The median disease duration was 12 years (range 2-20 years). The median follow-up after etanercept therapy was 18 months (range 5-33 months). DAS28 score decreased after the treatment and did not increase during follow-up in RA patients. BASDAI score decreased after the treatment during follow-up in three patients with SpA. At the follow-up, only one patient was diagnosed with septic arthritis. As a result of our study, etanercept treatment in RA and SpA patients on HD seems to be safe, well tolerated, and effective in most of the patients. Above all, due to impaired host defense in patients with ESRD, enhanced risk of infections should be kept in mind during follow-up period and larger trials are needed to prove the safety of etanercept in HD patients.

  18. Staphylococcus aureus isolated from wastewater treatment plants in Tunisia: occurrence of human and animal associated lineages.

    PubMed

    Ben Said, Meriam; Abbassi, Mohamed Salah; Gómez, Paula; Ruiz-Ripa, Laura; Sghaier, Senda; Ibrahim, Chourouk; Torres, Carmen; Hassen, Abdennaceur

    2017-08-01

    The objective was to characterize Staphylococcus aureus isolated from two wastewater treatment plants (WWTPs) located in Tunis City (Tunisia), during the period 2014-2015. Genetic lineages, antibiotic resistance mechanisms and virulence factors were determined for the recovered isolates. S. aureus isolates were recovered from 12 of the 62 wastewater samples tested (19.35%), and one isolate/sample was characterized, all of them being methicillin-susceptible (MSSA). Six spa types (t587, t674, t224, t127, t701 and t1534) were found among the 12 isolates, and the spa-t587, associated with the new sequence type ST3245, was the most predominant one (7 isolates). The remaining isolates were assigned to five clonal complexes (CC5, CC97, CC1, CC6 and CC522) according to the sequence-type determined and/or the spa-type detected. S. aureus isolates were ascribed to agrI (n = 3), agrII (n = 7) and agrIII (n = 1); however, one isolate was non-typeable. S. aureus showed resistance to (number of isolates): penicillin (12), erythromycin (7), tetracycline (one) and clindamycin (one). Among the virulence factors investigated, only one isolate harboured the tst gene, encoding the TSST-1 (toxic shock syndrome toxin 1). Despite the low number of studied isolates, the present study reports the occurrence of both human- and animal-associated S. aureus clonal complexes in WWTPs in Tunisia.

  19. Cost-Effectiveness and Efficacy of spa, SCCmec, and PVL Genotyping of Methicillin-Resistant Staphylococcus aureus as Compared to Pulsed-Field Gel Electrophoresis

    PubMed Central

    Li, Vincent; Chui, Linda; Louie, Lisa; Simor, Andrew; Golding, George R.; Louie, Marie

    2013-01-01

    Pulsed-field gel electrophoresis (PFGE) is a valuable molecular typing assay used for methicillin-resistant Staphylococcus aureus (MRSA) surveillance and genotyping. However, there are several limitations associated with PFGE. In Alberta, Canada, the significant increase in the number of MRSA isolates submitted to the Provincial Laboratory for Public Health (ProvLab) for PFGE typing led to the need for an alternative genotyping method. In this study, we describe the transition from PFGE to Staphylococcus protein A (spa), Staphylococcal cassette chromosome (SCCmec), and Panton-Valentine leukocidin (PVL) typing. A total of 1915 clinical MRSA isolates collected from 2005 to 2009 were used to develop and validate an algorithm for assigning PFGE epidemic types using spa, SCCmec, and PVL typing and the resulting data was used to populate a new Alberta MRSA typing database. An additional 12620 clinical MRSA isolates collected from 2010 to 2012 as part of ongoing routine molecular testing at ProvLab were characterized using the new typing algorithm and the Alberta MRSA typing database. Switching to spa, SCCmec, and PVL from PFGE typing substantially reduced hands-on and turn-around times while maintaining historical PFGE epidemic type designations. This led to an approximate $77,000 reduction in costs from 2010 to 2012. PFGE typing is still required for a small subset of MRSA isolates that have spa types that are rare, novel, or associated with more than one PFGE epidemic type. PMID:24244440

  20. Molecular Characterization of Methicillin-Resistant Staphylococcus aureus Isolates, Isolated from a Burn Hospital in Southwest Iran in 2006 and 2014.

    PubMed

    Ghaznavi-Rad, Ehsanollah; Ekrami, Alireza

    2018-01-01

    Incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing every year, especially in burn patients with a high rate of morbidity and mortality. Molecular and epidemiologic studies are useful practices for understanding the relatedness of isolates in a single patient or a hospital. This study aimed at determining molecular characterizations of isolates collected in 2006 and 2014 using S. aureus -specific staphylococcal protein A (Spa) typing and Multilocus Sequence Typing (MLST) methods. Totally, 71 MRSA isolates were collected during the last two studies (2006 and 2014) from burn patients at Taleghani Burn Centre. After confirmation, all isolates were analysed using MLST and Spa typing methods. We reported the emergence of Spa type t021, ST-30-IV MRSA isolates, which were PVL-positive in 14.6% of the cases and t12366, ST-8-IV isolates, which were PVL-negative in 9.8% of the cases. In 2014 study, Spa typing of MRSA isolates revealed five different spa types. Overall, in two studies, t037, ST-239, SCC mec III, and CC8 were predominant clones and they were reported in 63% of the cases. The predominance of ST-239 in this region during the last eight years is a major concern. It also has a disturbing impact on the management of staphylococcal infections. Moreover, the SCC mec type IV strain is able to disseminate rapidly in hospital environments, demanding an improvement in infection-control policy.

  1. Human Staphylococcus aureus lineages among Zoological Park residents in Greece

    PubMed Central

    Drougka, E.; Foka, A.; Posantzis, D.; Giormezis, N.; Anastassiou, E.D.; Petinaki, E.; Spiliopoulou, I.

    2015-01-01

    Staphylococcus aureus is a part of the microbiota flora in many animal species. The clonal spread of S. aureus among animals and personnel in a Zoological Park was investigated. Samples were collected from colonized and infected sites among 32 mammals, 11 birds and eight humans. The genes mecA, mecC, lukF/lukS-PV (encoding Panton-Valentine leukocidin, PVL) and tst (toxic shock syndrome toxin-1) were investigated by PCR. Clones were defined by Multilocus Sequence Typing (MLST), spa type and Pulsed-Field Gel Electrophoresis (PFGE). Seven S. aureus isolates were recovered from four animals and one from an employee. All were mecA, mecC and tst–negative, whereas, one carried the PVL genes and was isolated from an infected Squirrel monkey. Clonal analysis revealed the occurrence of seven STs, eight PFGE and five spa types including ones of human origin. Even though a variety of genotypes were identified among S. aureus strains colonizing zoo park residents, our results indicate that colonization with human lineages has indeed occurred. PMID:26623381

  2. The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles.

    PubMed

    Ruge, Christian A; Schaefer, Ulrich F; Herrmann, Jennifer; Kirch, Julian; Cañadas, Olga; Echaide, Mercedes; Pérez-Gil, Jesús; Casals, Cristina; Müller, Rolf; Lehr, Claus-Michael

    2012-01-01

    The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different intrinsic surface properties.

  3. Clinical and biochemical effects of a 3-week program of diet combined with spa therapy in obese and diabetic patients: a pilot open study.

    PubMed

    Fioravanti, Antonella; Adamczyk, Przemysław; Pascarelli, Nicola Antonio; Giannitti, Chiara; Urso, Renato; Tołodziecki, Michał; Ponikowska, Irena

    2015-07-01

    Obesity is a major risk factor for arterial hypertension, coronary artery disease, dyslipidemias, and type 2 diabetes. Spa therapy has long been used for treating obesity and its comorbidities. Enlargement of adipose tissue has been linked to a dysregulation of adipokine secretion and adipose tissue inflammation. Adipokines are currently investigated as potential drug targets in these conditions. Our primary aim was to assess the clinical efficacy of a 3-week program of diet combined with spa therapy in obese patients with and without type 2 diabetes. The secondary aim was to examine whether this combined program influences the response of serum levels of leptin, adiponectin, visfatin, and high-sensitivity C-reactive protein. Fifty obese males were enrolled and 21 of these featured a type 2 diabetes. During the 3-week period of the study, the patients were on a 1,000-kcal diet and were involved in mineral bath and total body's mud-pack applications (15 procedures). Patients were assessed at baseline and at the end of the therapy for clinical and biochemical parameters (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glycemia, and adipokines). We showed that a 3-week program of spa therapy in obese patients induced significant decrease of body weight, body mass index, triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, glycemia, and serum levels of leptin and high-sensitivity C-reactive protein. So, a cycle of mud-bath therapy associated with a controlled diet may be a promising treatment for obesity and type 2 diabetes decreasing body weight and many risk factors for atherosclerosis and metabolic syndrome.

  4. Clinical and biochemical effects of a 3-week program of diet combined with spa therapy in obese and diabetic patients: a pilot open study

    NASA Astrophysics Data System (ADS)

    Fioravanti, Antonella; Adamczyk, Przemysław; Pascarelli, Nicola Antonio; Giannitti, Chiara; Urso, Renato; Tołodziecki, Michał; Ponikowska, Irena

    2015-07-01

    Obesity is a major risk factor for arterial hypertension, coronary artery disease, dyslipidemias, and type 2 diabetes. Spa therapy has long been used for treating obesity and its comorbidities. Enlargement of adipose tissue has been linked to a dysregulation of adipokine secretion and adipose tissue inflammation. Adipokines are currently investigated as potential drug targets in these conditions. Our primary aim was to assess the clinical efficacy of a 3-week program of diet combined with spa therapy in obese patients with and without type 2 diabetes. The secondary aim was to examine whether this combined program influences the response of serum levels of leptin, adiponectin, visfatin, and high-sensitivity C-reactive protein. Fifty obese males were enrolled and 21 of these featured a type 2 diabetes. During the 3-week period of the study, the patients were on a 1,000-kcal diet and were involved in mineral bath and total body's mud-pack applications (15 procedures). Patients were assessed at baseline and at the end of the therapy for clinical and biochemical parameters (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glycemia, and adipokines). We showed that a 3-week program of spa therapy in obese patients induced significant decrease of body weight, body mass index, triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, glycemia, and serum levels of leptin and high-sensitivity C-reactive protein. So, a cycle of mud-bath therapy associated with a controlled diet may be a promising treatment for obesity and type 2 diabetes decreasing body weight and many risk factors for atherosclerosis and metabolic syndrome.

  5. Ovariectomized Highly Fit Rats Are Protected against Diet-Induced Insulin Resistance.

    PubMed

    Park, Young-Min; Kanaley, Jill A; Zidon, Terese M; Welly, Rebecca J; Scroggins, Rebecca J; Britton, Steven L; Koch, Lauren G; Thyfault, John P; Booth, Frank W; Padilla, Jaume; Vieira-Potter, Victoria J

    2016-07-01

    In the absence of exercise training, rats selectively bred for high intrinsic aerobic capacity (high-capacity running (HCR)) are protected against ovariectomy (OVX)-induced insulin resistance (IR) and obesity compared with those bred for low intrinsic aerobic capacity (low-capacity running (LCR)). This study determined whether OVX HCR rats remain protected with exposure to high-fat diet (HFD) compared with OVX LCR rats. Female HCR and LCR rats (n = 36; age, 27-33 wk) underwent OVX and were randomized to a standard chow diet (NC, 5% kcal fat) or HFD (45% kcal fat) ad libitum for 11 wk. Total energy expenditure, resting energy expenditure, spontaneous physical activity (SPA), and glucose tolerance were assessed midway, whereas fasting circulating metabolic markers, body composition, adipose tissue distribution, and skeletal muscle adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial markers were assessed at sacrifice. Both HCR and LCR rats experienced HFD-induced increases in total and visceral adiposity after OVX. Despite similar gains in adiposity, HCR rats were protected from HFD-induced IR and reduced total energy expenditure observed in LCR rats (P < 0.05). This metabolic protection was likely attributed to a compensatory increase in SPA and associated preservation of skeletal muscle AMPK activity in HCR; however, HFD significantly reduced SPA and AMPK activity in LCR (P < 0.05). In both lines, HFD reduced citrate synthase activity, gene expression of markers of mitochondrial biogenesis (tFAM, NRF1, and PGC-1α), and protein levels of mitochondrial oxidative phosphorylation complexes I, II, IV, and V in skeletal muscle (all P < 0.05). After OVX, HCR and LCR rats differentially respond to HFD such that HCR increase while LCR decrease SPA. This "physical activity compensation" likely confers protection from HFD-induced IR and reduced energy expenditure in HCR rats.

  6. Specific capture and detection of Staphylococcus aureus with high-affinity modified aptamers to cell surface components.

    PubMed

    Baumstummler, A; Lehmann, D; Janjic, N; Ochsner, U A

    2014-10-01

    Slow off-rate modified aptamer (SOMAmer) reagents were generated to several Staphylococcus aureus cell surface-associated proteins via SELEX with multiple modified DNA libraries using purified recombinant or native proteins. High-affinity binding agents with sub-nanomolar Kd 's were obtained for staphylococcal protein A (SpA), clumping factors (ClfA, ClfB), fibronectin-binding proteins (FnbA, FnbB) and iron-regulated surface determinants (Isd). Further screening revealed several SOMAmers that specifically bound to Staph. aureus cells from all strains that were tested, but not to other staphylococci or other bacteria. SpA and ClfA SOMAmers proved useful for the selective capture and enrichment of Staph. aureus cells, as shown by culture and PCR, leading to improved limits of detection and efficient removal of PCR inhibitors. Detection of Staph. aureus cells was enhanced by several orders of magnitude when the bacterial cell surface was coated with SOMAmers followed by qPCR of the SOMAmers. Furthermore, fluorescence-labelled SpA SOMAmers demonstrated their utility as direct detection agents in flow cytometry. Significance and impact of the study: Monitoring for microbial contamination of food, water, nonsterile products or the environment is typically based on culture, PCR or antibodies. Aptamers that bind with high specificity and affinity to well-conserved cell surface epitopes represent a promising novel type of reagents to detect bacterial cells without the need for culture or cell lysis, including for the capture and enrichment of bacteria present at low cell densities and for the direct detection via qPCR or fluorescent staining. © 2014 Soma Logic, Inc. published by John Wiley & Sons Ltd On behalf of the society for Applied Microbiology.

  7. MRSA clonal complex 22 strains harboring toxic shock syndrome toxin (TSST-1) are endemic in the primary hospital in Gaza, Palestine.

    PubMed

    Al Laham, Nahed; Mediavilla, José R; Chen, Liang; Abdelateef, Nahed; Elamreen, Farid Abu; Ginocchio, Christine C; Pierard, Denis; Becker, Karsten; Kreiswirth, Barry N

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in both community and healthcare-related settings worldwide. Current knowledge regarding the epidemiology of S. aureus and MRSA in Gaza is based on a single community-based carriage study. Here we describe a cross-sectional analysis of 215 clinical isolates collected from Al-Shifa Hospital in Gaza during 2008 and 2012. All isolates were characterized by spa typing, SCCmec typing, and detection of genes encoding Panton-Valentine leukocidin (PVL) and toxic shock syndrome toxin (TSST-1). Representative genotypes were also subjected to multilocus sequence typing (MLST). Antibiotic susceptibility testing was performed using VITEK2 and MicroScan. MRSA represented 56.3% of all S. aureus strains, and increased in frequency from 2008 (54.8%) to 2012 (58.4%). Aside from beta-lactams, resistance was observed to tetracycline, erythromycin, clindamycin, gentamicin, and fluoroquinolones. Molecular typing identified 35 spa types representing 17 MLST clonal complexes (CC), with spa 998 (Ridom t223, CC22) and spa 70 (Ridom t044, CC80) being the most prevalent. SCCmec types I, III, IV, V and VI were identified among MRSA isolates, while type II was not detected. PVL genes (lukF/S-PV) were detected in 40.0% of all isolates, while the TSST-1 gene (tst) was detected in 27.4% of all isolates, with surprisingly high frequency within CC22 (70.4%). Both PVL and TSST-1 genes were found in several isolates from 2012. Molecular typing of clinical isolates from Gaza hospitals revealed unusually high prevalence of TSST-1 genes among CC22 MRSA, which is noteworthy given a recent community study describing widespread carriage of a CC22 MRSA clone known as the 'Gaza strain'. While the latter did not address TSST-1, tst-positive spa 998 (Ridom t223) has been detected in several neighboring countries, and described as endemic in an Italian NICU, suggesting international spread of a 'Middle Eastern variant' of pandemic CC22 strain EMRSA-15.

  8. Typing of Panton-Valentine Leukocidin-Encoding Phages and lukSF-PV Gene Sequence Variation in Staphylococcus aureus from China.

    PubMed

    Zhao, Huanqiang; Hu, Fupin; Jin, Shu; Xu, Xiaogang; Zou, Yuhan; Ding, Baixing; He, Chunyan; Gong, Fang; Liu, Qingzhong

    2016-01-01

    Panton-Valentine leukocidin (PVL, encoded by lukSF-PV genes), a bi-component and pore-forming toxin, is carried by different staphylococcal bacteriophages. The prevalence of PVL in Staphylococcus aureus has been reported around the globe. However, the data on PVL-encoding phage types, lukSF-PV gene variation and chromosomal phage insertion sites for PVL-positive S. aureus are limited, especially in China. In order to obtain a more complete understanding of the molecular epidemiology of PVL-positive S. aureus, an integrated and modified PCR-based scheme was applied to detect the PVL-encoding phage types. Phage insertion locus and the lukSF-PV variant were determined by PCR and sequencing. Meanwhile, the genetic background was characterized by staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene polymorphisms typing, pulsed-field gel electrophoresis (PFGE) typing, accessory gene regulator (agr) locus typing and multilocus sequence typing (MLST). Seventy eight (78/1175, 6.6%) isolates possessed the lukSF-PV genes and 59.0% (46/78) of PVL-positive strains belonged to CC59 lineage. Eight known different PVL-encoding phage types were detected, and Φ7247PVL/ΦST5967PVL (n = 13) and ΦPVL (n = 12) were the most prevalent among them. While 25 (25/78, 32.1%) isolates, belonging to ST30, and ST59 clones, were unable to be typed by the modified PCR-based scheme. Single nucleotide polymorphisms (SNPs) were identified at five locations in the lukSF-PV genes, two of which were non-synonymous. Maximum-likelihood tree analysis of attachment sites sequences detected six SNP profiles for attR and eight for attL, respectively. In conclusion, the PVL-positive S. aureus mainly harbored Φ7247PVL/ΦST5967PVL and ΦPVL in the regions studied. lukSF-PV gene sequences, PVL-encoding phages, and phage insertion locus generally varied with lineages. Moreover, PVL-positive clones that have emerged worldwide likely carry distinct phages.

  9. Secretion of Ipa proteins by Shigella flexneri: inducer molecules and kinetics of activation.

    PubMed Central

    Bahrani, F K; Sansonetti, P J; Parsot, C

    1997-01-01

    The type III Mxi-Spa secretion machinery of Shigella flexneri is responsible for secretion of Ipa proteins, which are involved in the entry of bacteria into epithelial cells. Ipa proteins accumulate within bacteria growing in laboratory media, and their secretion is activated upon contact of bacteria with eukaryotic cells. In this study, we have identified a group of chemical compounds, including Congo red, Evans blue, and direct orange, which are able to induce secretion of Ipa proteins by bacteria suspended in phosphate-buffered saline. Parameters of kinetics of activation of Ipa secretion by Congo red were determined by measuring by enzyme-linked immunosorbent assay the amount of IpaC secreted and by investigating the increase in susceptibility of Ipa proteins to proteinase K degradation. Ipa secretion occurred at 37 degrees C, was obtained with 5 to 10 microM Congo red, and was complete within 30 min. In addition, activation of Ipa secretion by Congo red was observed with bacteria harvested throughout the exponential phase of growth but not with bacteria in the stationary phase. The interactions of Congo red and Congo red-related compounds with the Mxi-Spa secretion apparatus might be specific hydrophobic interactions similar to those involved in binding of Congo red to amyloid proteins. PMID:9316999

  10. Wireless poly(dimethylsiloxane) quartz-crystal-microbalance biosensor chip fabricated by nanoimprint lithography for micropump integration aiming at application in lab-on-a-chip

    NASA Astrophysics Data System (ADS)

    Kato, Fumihito; Noguchi, Hiroyuki; Kodaka, Yukinari; Oshida, Naoya; Ogi, Hirotsugu

    2018-07-01

    We developed a quartz-crystal-microbalance (QCM) biosensor chip that operates wirelessly via electromagnetic waves, using poly(dimethylsiloxane) (PDMS). An AT-cut quartz oscillator (22–30 µm) is packaged in a microchannel, where it is supported by micropillars without mechanical fixing. As a result, the quartz oscillator is little affected by the thermal stress caused by the difference in the thermal expansion coefficients of the components, and the leakage of the vibration energy of the quartz oscillator is reduced. Consequently, high-frequency (∼56 MHz) measurement with a stable baseline (±∼2 ppm) is realized. We succeeded in repeatedly monitoring the binding reaction between immunoglobulin G (IgG) and Staphylococcus aureus protein A (SPA) with the quartz oscillator on which SPA molecules were immobilized nonspecifically. In addition, the affinity between SPA and IgG was calculated from the association and dissociation curves, and the usefulness of our wireless PDMS QCM biosensor was demonstrated.

  11. Balneotherapy in Psoriasis Rehabilitation

    PubMed Central

    PÉTER, IVÁN; JAGICZA, ANNA; AJTAY, ZÉNÓ; BONCZ, IMRE; KISS, ISTVÁN; SZENDI, KATALIN; KUSTÁN, PÉTER; NÉMETH, BALÁZS

    2017-01-01

    Background/Aim: This study aimed to report a balneotherapy-based psoriasis rehabilitation protocol and assess its effectivity. Patients and Methods: Eighty psoriatic patients who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and high sensitivity C-reactive protein (CRP) were determined on admission and before discharge. Results: The mean PASI score and CRP level –determined on admission and before discharge– decreased significantly after the 3-week-long rehabilitation 7.15±7.3 vs. 2.62±3.05 (p<0.001) and 4.1±3.8 vs. 3.5±3.1 (p=0.026). A negative correlation was found between PASI delta and the number of spa therapies received (r=–0.228). Conclusion: After completing the 3-week-long spa therapy based rehabilitation, both PASI score and CRP levels showed improvement of psoriasis. The complex spa therapy used during the rehabilitation is an effective tool to reduce the symptoms of psoriasis and improve the patient’s well-being. PMID:29102940

  12. Balneotherapy in Psoriasis Rehabilitation.

    PubMed

    Péter, Iván; Jagicza, Anna; Ajtay, Zénó; Boncz, Imre; Kiss, István; Szendi, Katalin; Kustán, Péter; Németh, Balázs

    2017-01-01

    This study aimed to report a balneotherapy-based psoriasis rehabilitation protocol and assess its effectivity. Eighty psoriatic patients who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and high sensitivity C-reactive protein (CRP) were determined on admission and before discharge. The mean PASI score and CRP level -determined on admission and before discharge-decreased significantly after the 3-week-long rehabilitation 7.15±7.3 vs. 2.62±3.05 (p<0.001) and 4.1±3.8 vs. 3.5±3.1 (p=0.026). A negative correlation was found between PASI delta and the number of spa therapies received (r=-0.228). After completing the 3-week-long spa therapy based rehabilitation, both PASI score and CRP levels showed improvement of psoriasis. The complex spa therapy used during the rehabilitation is an effective tool to reduce the symptoms of psoriasis and improve the patient's well-being. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Virulence properties of methicillin-susceptible Staphylococcus aureus food isolates encoding Panton-Valentine Leukocidin gene.

    PubMed

    Sudagidan, Mert; Aydin, Ali

    2010-04-15

    In this study, three Panton-Valentine Leukocidin gene carrying methicillin-susceptible Staphylococcus aureus (MSSA) strains (M1-AAG42B, PY30C-b and YF1B-b) were isolated from different food samples in Kesan-Edirne, Turkey. These strains were characterized on the basis of MLST type, spa type, virulence factor gene contents, antibiotic susceptibilities against 21 antibiotics and biofilm formation. The genetic relatedness of the strains was determined by PFGE. In addition, the complete gene sequences of lukS-PV and lukF-PV were also investigated. All strains were found to be susceptible to tested antibiotics and they were mecA negative. Three strains showed the same PFGE band pattern, ST152 clonal type and t355 spa type. In the detection of virulence factor genes, sea, seb, sec, sed, see, seg, seh, sei, sej, sek, sel, sem, sen, seo, sep, seq, seu, eta, etb, set1, geh and tst genes were not detected. All strains showed the positive results for alpha- and beta-haemolysin genes (hla and hlb), protease encoding genes (sspA, sspB and aur), lukE and lukD leukocidin genes (lukED). The strains were found to be non-biofilm formers. By this study, the virulence properties of the strains were described and this is one of the first reports regarding PVL-positive MSSA strains from food. (c) 2010 Elsevier B.V. All rights reserved.

  14. Histological findings and immunohistochemical surfactant protein A (SP-A) expression in asphyxia: its application in the diagnosis of drowning.

    PubMed

    Pérez-Cárceles, M D; Sibón, A; Vizcaya, M A; Osuna, E; Gómez-Zapata, M; Luna, A; Martínez-Díaz, F

    2008-09-01

    The histopathological alterations that permit the diagnosis of death by asphyxia are very unspecific, although pulmonary alterations are of great importance in this respect. The postmortem diagnosis of drowning, particularly, continues to be one of the most difficult in forensic pathology. The aim of this study is to jointly evaluate microscopic findings and immunohistochemical surfactant protein A (SP-A) expression in the upper and lower lobes of lungs in different causes of death, and their possible application to the diagnosis of drowning. We studied 120 cadavers from subjects with a mean age of 48.73 years (SD 19.45; range 2-86 years), and with a mean post-mortem interval of 30 hours (SD 39.59; range 3-216 hours). According to the scene, cause and circumstances of death, and autopsy findings, cases were classified into groups as follows: (a) drowning (n=47); (b) other asphyxia (n=44) and (c) other causes (n=29). In the upper and lower lobes of lungs, histological studies of H&E staining and immunohistochemical surfactant protein A expression were made. The presence and severity of congestion, haemorrhage and oedema, together with immunohistochemical SP-A expression, may have a diagnostic value in differentiating asphyxia and drowning from other causes of death, and drowning from other types of asphyxia. Our findings suggest that both lobes should be investigated to establish the diagnosis, although the findings in the upper lobe might be the most important for differentiating the exact cause of death.

  15. Two Novel Antioxidant Nonapeptides from Protein Hydrolysate of Skate (Raja porosa) Muscle

    PubMed Central

    Hu, Fa-Yuan; Chi, Chang-Feng; Wang, Bin; Deng, Shang-Gui

    2015-01-01

    In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity of SMH. Under the optimum conditions of pH 7.0, enzymolysis temperature 60 °C, enzyme/substrate ratio (E/S) 2%, and enzymolysis time 5 h, EC50 of SMH on HO· was 2.14 ± 0.17 mg/mL. Using ultrafiltration, gel filtration chromatography, and RP-HPLC, two novel antioxidant nonapeptides (SP-A and SP-B) were isolated from SMH and their amino acid sequences were found to be APPTAYAQS (SP-A) and NWDMEKIWD (SP-B) with calculated molecular masses of 904.98 Da and 1236.38 Da, respectively. Both showed strong antioxidant activities. SP-A and SP-B exhibited good scavenging activities on HO· (EC50 0.390 and 0.176 mg/mL), DPPH· (EC50 0.614 and 0.289 mg/mL), and O2−· (EC50 0.215 and 0.132 mg/mL) in a dose-dependent manner. SP-B was also effective against lipid peroxidation in the model system. The aromatic (2Trp), acidic (2Asp and Glu), and basic (Lys) amino acid residues within the sequences of SP-B might account for its pronounced antioxidant activity. The results of this study suggested that protein hydrolysate and peptides from skate muscle might be effective as food additives for retarding lipid peroxidation occurring in foodstuffs. PMID:25854645

  16. Two novel antioxidant nonapeptides from protein hydrolysate of skate (Raja porosa) muscle.

    PubMed

    Hu, Fa-Yuan; Chi, Chang-Feng; Wang, Bin; Deng, Shang-Gui

    2015-04-03

    In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity of SMH. Under the optimum conditions of pH 7.0, enzymolysis temperature 60 °C, enzyme/substrate ratio (E/S) 2%, and enzymolysis time 5 h, EC50 of SMH on HO· was 2.14 ± 0.17 mg/mL. Using ultrafiltration, gel filtration chromatography, and RP-HPLC, two novel antioxidant nonapeptides (SP-A and SP-B) were isolated from SMH and their amino acid sequences were found to be APPTAYAQS (SP-A) and NWDMEKIWD (SP-B) with calculated molecular masses of 904.98 Da and 1236.38 Da, respectively. Both showed strong antioxidant activities. SP-A and SP-B exhibited good scavenging activities on HO· (EC50 0.390 and 0.176 mg/mL), DPPH· (EC50 0.614 and 0.289 mg/mL), and O2-· (EC50 0.215 and 0.132 mg/mL) in a dose-dependent manner. SP-B was also effective against lipid peroxidation in the model system. The aromatic (2Trp), acidic (2Asp and Glu), and basic (Lys) amino acid residues within the sequences of SP-B might account for its pronounced antioxidant activity. The results of this study suggested that protein hydrolysate and peptides from skate muscle might be effective as food additives for retarding lipid peroxidation occurring in foodstuffs.

  17. Molecular characterisation of methicillin-resistant Staphylococcus aureus (MRSA) isolated at a large referral hospital in Zambia.

    PubMed

    Samutela, Mulemba Tillika; Kalonda, Annie; Mwansa, James; Lukwesa-Musyani, Chileshe; Mwaba, John; Mumbula, Enoch Mulowa; Mwenya, Darlington; Simulundu, Edgar; Kwenda, Geoffrey

    2017-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is globally recognized as an important public health problem. Whereas comprehensive molecular typing data of MRSA strains is available, particularly in Europe, North America and Australia, similar information is very limited in sub-Saharan Africa including Zambia. In this study, thirty two clinical isolates of Staphylococcus aureus , collected at a large referral hospital in Lusaka, Zambia between June 2009 and December 2012 were analysed by Staphylococcal cassette chromosome mec (SCCmec), Staphylococcus protein A gene typing (spa) and detection of the Panton-Valentine Leukocidin genes (pvl) . Three SCC mec types were identified namely SCC mec type IV (65.6%), SCCmec type III (21.9%), SCC mec type I (3.1%). Nine point four percent (9.4%) of the isolates were untypable. Five spa types, which included a novel type, were detected and the most prevalent spa type was t064 (40.6%). Other spa types included spa types t2104 (31.3%), t355 (3.1%) and t1257 (21.9%). The pvl genes were detected in 3 out of 32 isolates. These molecular typing data indicated that the MRSA strains collected in Lusaka were diverse. Although the source of these MRSA was not established, these results stress the need for assessing infection prevention and control procedures at this health-care facility in order to curtail possible nosocomial infections. Furthermore, country-wide surveillance of MRSA in both the community and health-care facilities is recommended for infection prevention and control. To our knowledge, this represents the first study to characterise MRSA using molecular tools in Zambia.

  18. Modeling heat stress under different environmental conditions.

    PubMed

    Carabaño, M J; Logar, B; Bormann, J; Minet, J; Vanrobays, M-L; Díaz, C; Tychon, B; Gengler, N; Hammami, H

    2016-05-01

    Renewed interest in heat stress effects on livestock productivity derives from climate change, which is expected to increase temperatures and the frequency of extreme weather events. This study aimed at evaluating the effect of temperature and humidity on milk production in highly selected dairy cattle populations across 3 European regions differing in climate and production systems to detect differences and similarities that can be used to optimize heat stress (HS) effect modeling. Milk, fat, and protein test day data from official milk recording for 1999 to 2010 in 4 Holstein populations located in the Walloon Region of Belgium (BEL), Luxembourg (LUX), Slovenia (SLO), and southern Spain (SPA) were merged with temperature and humidity data provided by the state meteorological agencies. After merging, the number of test day records/cows per trait ranged from 686,726/49,655 in SLO to 1,982,047/136,746 in BEL. Values for the daily average and maximum temperature-humidity index (THIavg and THImax) ranges for THIavg/THImax were largest in SLO (22-74/28-84) and shortest in SPA (39-76/46-83). Change point techniques were used to determine comfort thresholds, which differed across traits and climatic regions. Milk yield showed an inverted U-shaped pattern of response across the THI scale with a HS threshold around 73 THImax units. For fat and protein, thresholds were lower than for milk yield and were shifted around 6 THI units toward larger values in SPA compared with the other countries. Fat showed lower HS thresholds than protein traits in all countries. The traditional broken line model was compared with quadratic and cubic fits of the pattern of response in production to increasing heat loads. A cubic polynomial model allowing for individual variation in patterns of response and THIavg as heat load measure showed the best statistical features. Higher/lower producing animals showed less/more persistent production (quantity and quality) across the THI scale. The estimated correlations between comfort and THIavg values of 70 (which represents the upper end of the THIavg scale in BEL-LUX) were lower for BEL-LUX (0.70-0.80) than for SPA (0.83-0.85). Overall, animals producing in the more temperate climates and semi-extensive grazing systems of BEL and LUX showed HS at lower heat loads and more re-ranking across the THI scale than animals producing in the warmer climate and intensive indoor system of SPA. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. 78 FR 77565 - Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Previously Held by Agusta S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Previously Held by Agusta S.p.A.) Helicopters... directive (AD): 2013-25-09 AGUSTAWESTLAND S.P.A. (TYPE CERTIFICATE FORMERLY HELD BY AGUSTA S.P.A... airworthiness directive (AD) for certain AgustaWestland S.p.A. (Agusta) Model AB139 and AW139 helicopters. This...

  20. Effects of water deficit on breadmaking quality and storage protein compositions in bread wheat (Triticum aestivum L.).

    PubMed

    Zhou, Jiaxing; Liu, Dongmiao; Deng, Xiong; Zhen, Shoumin; Wang, Zhimin; Yan, Yueming

    2018-03-12

    Water deficiency affects grain proteome dynamics and storage protein compositions, resulting in changes in gluten viscoelasticity. In this study, the effects of field water deficit on wheat breadmaking quality and grain storage proteins were investigated. Water deficiency produced a shorter grain-filling period, a decrease in grain number, grain weight and grain yield, a reduced starch granule size and increased protein content and glutenin macropolymer contents, resulting in superior dough properties and breadmaking quality. Reverse phase ultra-performance liquid chromatography analysis showed that the total gliadin and glutenin content and the accumulation of individual components were significantly increased by water deficiency. Two-dimensional gel electrophoresis detected 144 individual storage protein spots with significant accumulation changes in developing grains under water deficit. Comparative proteomic analysis revealed that water deficiency resulted in significant upregulation of 12 gliadins, 12 high-molecular-weight glutenin subunits and 46 low-molecular-weight glutenin subunits. Quantitative real-time polymerase chain reaction analysis revealed that the expression of storage protein biosynthesis-related transcription factors Dof and Spa was upregulated by water deficiency. The present results illustrated that water deficiency leads to increased accumulation of storage protein components and upregulated expression of Dof and Spa, resulting in an improvement in glutenin strength and breadmaking quality. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  1. Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage

    PubMed Central

    Cole, Amy L.; Muthukrishnan, Gowrishankar; Chong, Christine; Beavis, Ashley; Eade, Colleen R.; Wood, Matthew P.; Deichen, Michael G.; Cole, Alexander M.

    2016-01-01

    Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Ten out of 15 studies resulted in rapid clearance (9±6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not IL-17. Nasal SA persistence corresponded with elevated baseline levels of MIP-1β, IL-1β, and IL-6, no induction of inflammatory factors post-inoculation, and decreased IL-1RA:IL-1β ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (ΔSpA) strains were cleared faster than wild-type only in participants with upregulated inflammatory markers post-inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. ΔSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial co-determinant of SA nasal carriage. PMID:26838052

  2. First Report of cfr-Carrying Plasmids in the Pandemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Staphylococcal Cassette Chromosome mec Type IV Clone

    PubMed Central

    Shore, Anna C.; Lazaris, Alexandros; Kinnevey, Peter M.; Brennan, Orla M.; Brennan, Gráinne I.; O'Connell, Brian; Feßler, Andrea T.; Schwarz, Stefan

    2016-01-01

    Linezolid is often the drug of last resort for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Linezolid resistance is mediated by mutations in 23S rRNA and genes for ribosomal proteins; cfr, encoding phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPSA) resistance; its homologue cfr(B); or optrA, conferring oxazolidinone and phenicol resistance. Linezolid resistance is rare in S. aureus, and cfr is even rarer. This study investigated the clonality and linezolid resistance mechanisms of two MRSA isolates from patients in separate Irish hospitals. Isolates were subjected to cfr PCR, PhLOPSA susceptibility testing, 23S rRNA PCR and sequencing, DNA microarray profiling, spa typing, pulsed-field gel electrophoresis (PFGE), plasmid curing, and conjugative transfer. Whole-genome sequencing was used for single-nucleotide variant (SNV) analysis, multilocus sequence typing, L protein mutation identification, cfr plasmid sequence analysis, and optrA and cfr(B) detection. Isolates M12/0145 and M13/0401 exhibited linezolid MICs of 64 and 16 mg/liter, respectively, and harbored identical 23S rRNA and L22 mutations, but M12/0145 exhibited the mutation in 2/6 23S rRNA alleles, compared to 1/5 in M13/0401. Both isolates were sequence type 22 MRSA staphylococcal cassette chromosome mec type IV (ST22-MRSA-IV)/spa type t032 isolates, harbored cfr, exhibited the PhLOPSA phenotype, and lacked optrA and cfr(B). They differed by five PFGE bands and 603 SNVs. Isolate M12/0145 harbored cfr and fexA on a 41-kb conjugative pSCFS3-type plasmid, whereas M13/0401 harbored cfr and lsa(B) on a novel 27-kb plasmid. This is the first report of cfr in the pandemic ST22-MRSA-IV clone. Different cfr plasmids and mutations associated with linezolid resistance in genotypically distinct ST22-MRSA-IV isolates highlight that prudent management of linezolid use is essential. PMID:26953212

  3. Role of collectins and complement protein C1q in pregnancy and parturition.

    PubMed

    Madhukaran, Shanmuga Priyaa; Alhamlan, Fatimah S; Kale, Kavita; Vatish, Manu; Madan, Taruna; Kishore, Uday

    2016-11-01

    Collectins such as surfactant proteins SP-A, SP-D, and mannan-binding lectin (MBL), as well as complement protein C1q are evolutionarily conserved innate immune molecules. They are known to opsonize a range of microbial pathogens (bacteria, fungi, virus, and parasites) and trigger effector clearance mechanisms involving phagocytosis and/or complement activation. Collectins and C1q have also attracted attention in studies involving pregnancy as they are expressed in the female reproductive tissues during pregnancy; a unique state of immune suppression with increased susceptibility to infectious diseases. Recent studies are beginning to unravel their functional significance in implantation, placentation, pregnancy maintenance and parturition in normal and adverse pregnancies. Collectins and C1q, expressed in gestational tissues during pregnancy, might alter the status of mother's immune response to the allogenic fetus and the microenvironment, thereby serving as important regulators of fetus-mother interaction. Here, we discuss the functional roles that have been assigned to SP-A, SP-D, MBL and C1q in pregnancy and parturition. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. 78 FR 41888 - Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Previously Held by Agusta S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ...-0604; Directorate Identifier 2012-SW-110-AD] RIN 2120-AA64 Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Previously Held by Agusta S.p.A.) Helicopters AGENCY: Federal Aviation... (AD): AgustaWestland S.p.A. (Type Certificate Formerly Held By Agusta S.p.A.) Helicopters: Docket No...

  5. 78 FR 54596 - Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Formerly Held by Agusta S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-05

    ...-0751; Directorate Identifier 2012-SW-051-AD] RIN 2120-AA64 Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Formerly Held by Agusta S.p.A) (Agusta) Helicopters AGENCY: Federal Aviation... airworthiness directive (AD): Agustawestland S.p.A. (Type Certificate Formerly Held by Augsta S.p.A) (Agusta...

  6. spa Typing and Multilocus Sequence Typing Show Comparable Performance in a Macroepidemiologic Study of Staphylococcus aureus in the United States

    PubMed Central

    O'Hara, F. Patrick; Suaya, Jose A.; Ray, G. Thomas; Baxter, Roger; Brown, Megan L.; Mera, Robertino M.; Close, Nicole M.; Thomas, Elizabeth

    2016-01-01

    A number of molecular typing methods have been developed for characterization of Staphylococcus aureus isolates. The utility of these systems depends on the nature of the investigation for which they are used. We compared two commonly used methods of molecular typing, multilocus sequence typing (MLST) (and its clustering algorithm, Based Upon Related Sequence Type [BURST]) with the staphylococcal protein A (spa) typing (and its clustering algorithm, Based Upon Repeat Pattern [BURP]), to assess the utility of these methods for macroepidemiology and evolutionary studies of S. aureus in the United States. We typed a total of 366 clinical isolates of S. aureus by these methods and evaluated indices of diversity and concordance values. Our results show that, when combined with the BURP clustering algorithm to delineate clonal lineages, spa typing produces results that are highly comparable with those produced by MLST/BURST. Therefore, spa typing is appropriate for use in macroepidemiology and evolutionary studies and, given its lower implementation cost, this method appears to be more efficient. The findings are robust and are consistent across different settings, patient ages, and specimen sources. Our results also support a model in which the methicillin-resistant S. aureus (MRSA) population in the United States comprises two major lineages (USA300 and USA100), which each consist of closely related variants. PMID:26669861

  7. spa Typing and Multilocus Sequence Typing Show Comparable Performance in a Macroepidemiologic Study of Staphylococcus aureus in the United States.

    PubMed

    O'Hara, F Patrick; Suaya, Jose A; Ray, G Thomas; Baxter, Roger; Brown, Megan L; Mera, Robertino M; Close, Nicole M; Thomas, Elizabeth; Amrine-Madsen, Heather

    2016-01-01

    A number of molecular typing methods have been developed for characterization of Staphylococcus aureus isolates. The utility of these systems depends on the nature of the investigation for which they are used. We compared two commonly used methods of molecular typing, multilocus sequence typing (MLST) (and its clustering algorithm, Based Upon Related Sequence Type [BURST]) with the staphylococcal protein A (spa) typing (and its clustering algorithm, Based Upon Repeat Pattern [BURP]), to assess the utility of these methods for macroepidemiology and evolutionary studies of S. aureus in the United States. We typed a total of 366 clinical isolates of S. aureus by these methods and evaluated indices of diversity and concordance values. Our results show that, when combined with the BURP clustering algorithm to delineate clonal lineages, spa typing produces results that are highly comparable with those produced by MLST/BURST. Therefore, spa typing is appropriate for use in macroepidemiology and evolutionary studies and, given its lower implementation cost, this method appears to be more efficient. The findings are robust and are consistent across different settings, patient ages, and specimen sources. Our results also support a model in which the methicillin-resistant S. aureus (MRSA) population in the United States comprises two major lineages (USA300 and USA100), which each consist of closely related variants.

  8. AIP mutations in Brazilian patients with sporadic pituitary adenomas: a single-center evaluation

    PubMed Central

    Kasuki, Leandro; de Azeredo Lima, Carlos Henrique; Ogino, Liana; Camacho, Aline H S; Chimelli, Leila; Korbonits, Márta

    2017-01-01

    Aryl hydrocarbon receptor-interacting protein (AIP) gene mutations (AIPmut) are the most frequent germline mutations found in apparently sporadic pituitary adenomas (SPA). Our aim was to evaluate the frequency of AIPmut among young Brazilian patients with SPA. We performed an observational cohort study between 2013 and 2016 in a single referral center. AIPmut screening was carried out in 132 SPA patients with macroadenomas diagnosed up to 40 years or in adenomas of any size diagnosed until 18 years of age. Twelve tumor samples were also analyzed. Leukocyte DNA and tumor tissue DNA were sequenced for the entire AIP-coding region for evaluation of mutations. Eleven (8.3%) of the 132 patients had AIPmut, comprising 9/74 (12%) somatotropinomas, 1/38 (2.6%) prolactinoma, 1/10 (10%) corticotropinoma and no non-functioning adenomas. In pediatric patients (≤18 years), AIPmut frequency was 13.3% (2/15). Out of the 5 patients with gigantism, two had AIPmut, both truncating mutations. The Y268* mutation was described in Brazilian patients and the K273Rfs*30 mutation is a novel mutation in our patient. No somatic AIP mutations were found in the 12 tumor samples. A tumor sample from an acromegaly patient harboring the A299V AIPmut showed loss of heterozygosity. In conclusion, AIPmut frequency in SPA Brazilian patients is similar to other populations. Our study identified two mutations exclusively found in Brazilians and also shows, for the first time, loss of heterozygosity in tumor DNA from an acromegaly patient harboring the A299V AIPmut. Our findings corroborate previous observations that AIPmut screening should be performed in young patients with SPA. PMID:29074612

  9. The regulation of the Z- and G-box containing promoters by light signaling components, SPA1 and MYC2, in Arabidopsis.

    PubMed

    Gangappa, Sreeramaiah N; Maurya, Jay P; Yadav, Vandana; Chattopadhyay, Sudip

    2013-01-01

    Although many transcription factors and regulatory proteins have been identified and functionally characterized in light signaling pathways, photoperception to transcription remains largely fragmented. The Z-box is one of the LREs (Light responsive elements) that plays important role in the regulation of transcription during light-controlled Arabidopsis seedling development. The involvement of photoreceptors in the modulation of the activity of the Z-box containing promoters has been demonstrated. However, the role of downstream signaling components such as SPA1 and MYC2/ZBF1, which are functionally interrelated, remains unknown. In this study, we have investigated the regulation of the Z-box containing synthetic and native promoters by SPA1 and MYC2 by using stable transgenic lines. Our studies suggest that SPA1 negatively regulates the expression of CAB1 native promoter. MYC2 negatively regulates the activity of Z- and/or G-box containing synthetic as well as native promoters irrespective of light quality. Moreover, MYC2 negatively regulates the expression of Z/G-NOS101-GUS even in the darkness. Furthermore, analyses of tissue specific expression in adult plants suggest that MYC2 strongly regulates the activity of Z- and G-box containing promoters specifically in leaves and stems. In roots, whereas MYC2 positively regulates the activity of the Z-box containing synthetic promoter, it does not seem to control the activity of the G-box containing promoters. Taken together, these results provide insights into SPA1- and MYC2-mediated transcriptional regulation of the Z- and G-box containing promoters in light signaling pathways.

  10. Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition

    PubMed Central

    Gao, Lu; Rabbitt, Elizabeth H.; Condon, Jennifer C.; Renthal, Nora E.; Johnston, John M.; Mitsche, Matthew A.; Chambon, Pierre; Xu, Jianming; O’Malley, Bert W.; Mendelson, Carole R.

    2015-01-01

    The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A–deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2–deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2–deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2–deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2–dependent production of SP-A and PAF is crucial for this process. PMID:26098214

  11. Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition.

    PubMed

    Gao, Lu; Rabbitt, Elizabeth H; Condon, Jennifer C; Renthal, Nora E; Johnston, John M; Mitsche, Matthew A; Chambon, Pierre; Xu, Jianming; O'Malley, Bert W; Mendelson, Carole R

    2015-07-01

    The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A-deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2-deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2-deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2-deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2-dependent production of SP-A and PAF is crucial for this process.

  12. Developmental Decline in the MicroRNA 199a (miR-199a)/miR-214 Cluster in Human Fetal Lung Promotes Type II Cell Differentiation by Upregulating Key Transcription Factors.

    PubMed

    Mishra, Ritu; Benlhabib, Houda; Guo, Wei; Lerma Cervantes, Connie B; Mendelson, Carole R

    2018-06-01

    The major surfactant protein, SP-A (a product of the SFTPA gene), serves as a marker of type II pneumocyte differentiation and surfactant synthesis. SFTPA expression in cultured human fetal lung (HFL) epithelial cells is upregulated by hormones that increase cyclic AMP (cAMP) and activate TTF-1/NKX2.1 and NF-κB. To further define mechanisms for type II cell differentiation and induction of SP-A, we investigated roles of microRNAs (miRNAs). Using microarray to identify differentially expressed miRNAs in HFL epithelial cells during type II cell differentiation in culture, we observed that members of the miRNA 199a (miR-199a)/miR-214 cluster were significantly downregulated during differentiation. Validated and predicted targets of miR-199a-3p/miR-199a-5p and miR-214, which serve roles in type II cell differentiation (COX-2, NF-κB p50/p65, and CREB1), and the CREB1 target, C/EBPβ, were coordinately upregulated. Accordingly, overexpression of miR-199a-5p, miR-199a-3p, or miR-214 mimics in cultured HFL epithelial cells decreased COX-2, NF-κB p50/p65, CREB1, and C/EBPβ proteins, with an associated inhibition of SP-A expression. Interestingly, overexpression of the EMT factor, ZEB1, which declines during cAMP-induced type II cell differentiation, increased pri-miR-199a and reduced the expression of the targets NF-κB/p50 and COX-2. Collectively, these findings suggest that the developmental decline in miR-199a/miR-214 in HFL causes increased expression of critical targets that enhance type II cell differentiation and SP-A expression. Copyright © 2018 American Society for Microbiology.

  13. Vancomycin modifies the expression of the agr system in multidrug-resistant Staphylococcus aureus clinical isolates

    PubMed Central

    Cázares-Domínguez, Vicenta; Ochoa, Sara A.; Cruz-Córdova, Ariadnna; Rodea, Gerardo E.; Escalona, Gerardo; Olivares, Alma L.; Olivares-Trejo, José de Jesús; Velázquez-Guadarrama, Norma; Xicohtencatl-Cortes, Juan

    2015-01-01

    Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called agr (accessory gene regulator) and sar (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on hld and spa gene expression during the exponential and post-exponential growth phases in multidrug-resistant (MDR) S. aureus. Methods: Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis (PFGE). Polymorphisms of agr and SCCmec (staphylococcal cassette chromosome mec) were analyzed by multiplex polymerase chain reaction (PCR). The expression levels of hld and spa were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining. Results: In total, 60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR S. aureus isolates were distributed in subcluster 10, with >90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the agrII and the cassette SCCmec II polymorphisms was found. Our data showed significant increases in hld expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in spa expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR S. aureus isolates were challenged with vancomycin. Conclusion: The polymorphism agrII, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR S. aureus. Additionally, under our study conditions, vancomycin modified hld and spa expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of these virulence factors. PMID:25999924

  14. Immunohistochemical investigation of a pulmonary surfactant in fatal mechanical asphyxia.

    PubMed

    Zhu, B L; Ishida, K; Fujita, M Q; Maeda, H

    2000-01-01

    We evaluated the usefulness of pulmonary surfactant protein A (SP-A) as a practical diagnostic marker of fatal mechanical asphyxia in forensic autopsy cases. A total of 27 cases of asphyxia were examined histologically and immunohistochemically and compared with a control group consisting of 16 cases of poisoning (n = 9) and peracute death (n = 7). Both groups showed histological findings of local atelectasis and local emphysema, congestion, intra-alveolar and interstitial edema in most cases and pulmonary hemorrhages in some cases. The mechanical asphyxia group showed a significantly increased intensity of SP-A staining in the intra-alveolar space accompanied by many massive aggregates in approximately 60% of cases, which was not found in the control group. These structures may be interpreted as aggregates of pulmonary surfactant released from the alveolar wall due to enhanced secretion caused by strong forced breathing or over-excitement of the autonomic nervous system by mechanical asphyxia. The results of our investigation suggest the practical usefulness of the immunohistochemical detection of SP-A in distinguishing mechanical asphyxia from other types of hypoxia.

  15. An immuno-biosensor system based on quartz crystal microbalance for avian influenza virus detection

    NASA Astrophysics Data System (ADS)

    Liu, Shengping; Chen, Guoming; Zhou, Qi; Wei, Yunlong

    2007-12-01

    For the quick detection of Avian Influenza Virus (AIV), a biosensor based on Quartz Crystal Microbalance (QCM) was fabricated according to the specific bonding principle between antibody and antigen. Staphylococcal Protein A (SPA) was extracted from Staphylococcus and purified. Then SPA was coated on the surface of QCM for immobilizing AIV monoclonal antibodies. The use of AIV monoclonal antibody could enhance the specificity of the immuno-biosensor. A multi-channel piezoelectricity detection system for the immuno-biosensor was developed. The system can work for the quick detection of AIV antigen in the case of the entirely aqueous status owe to one special oscillating circuit designed in this work. The optimum conditions of SPA coating and AIV monoclonal antibody immobilization were investigated utilizing the multi-channel detection system. The preliminary application of the immuno-biosensor system for detection of AIV was evaluated. Results indicate that the immuno-biosensor system can detect the AIV antigens with a linear range of 3-200ng/ml. The system can accomplish the detection of AIV antigens around 40 minutes.

  16. Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species.

    PubMed

    Justiz-Vaillant, A A; Akpaka, P E; McFarlane-Anderson, N; Smikle, M F

    2013-01-01

    The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera). These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins.

  17. Detection of Nitrogen Content in Rubber Leaves Using Near-Infrared (NIR) Spectroscopy with Correlation-Based Successive Projections Algorithm (SPA).

    PubMed

    Tang, Rongnian; Chen, Xupeng; Li, Chuang

    2018-05-01

    Near-infrared spectroscopy is an efficient, low-cost technology that has potential as an accurate method in detecting the nitrogen content of natural rubber leaves. Successive projections algorithm (SPA) is a widely used variable selection method for multivariate calibration, which uses projection operations to select a variable subset with minimum multi-collinearity. However, due to the fluctuation of correlation between variables, high collinearity may still exist in non-adjacent variables of subset obtained by basic SPA. Based on analysis to the correlation matrix of the spectra data, this paper proposed a correlation-based SPA (CB-SPA) to apply the successive projections algorithm in regions with consistent correlation. The result shows that CB-SPA can select variable subsets with more valuable variables and less multi-collinearity. Meanwhile, models established by the CB-SPA subset outperform basic SPA subsets in predicting nitrogen content in terms of both cross-validation and external prediction. Moreover, CB-SPA is assured to be more efficient, for the time cost in its selection procedure is one-twelfth that of the basic SPA.

  18. Comparison of the DiversiLab Repetitive Element PCR System with spa Typing and Pulsed-Field Gel Electrophoresis for Clonal Characterization of Methicillin-Resistant Staphylococcus aureus▿

    PubMed Central

    Babouee, B.; Frei, R.; Schultheiss, E.; Widmer, A. F.; Goldenberger, D.

    2011-01-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become an increasing problem worldwide in recent decades. Molecular typing methods have been developed to identify clonality of strains and monitor spread of MRSA. We compared a new commercially available DiversiLab (DL) repetitive element PCR system with spa typing, spa clonal cluster analysis, and pulsed-field gel electrophoresis (PFGE) in terms of discriminatory power and concordance. A collection of 106 well-defined MRSA strains from our hospital was analyzed, isolated between 1994 and 2006. In addition, we analyzed 6 USA300 strains collected in our institution. DL typing separated the 106 MRSA isolates in 10 distinct clusters and 8 singleton patterns. Clustering analysis into spa clonal complexes resulted in 3 clusters: spa-CC 067/548, spa-CC 008, and spa-CC 012. The discriminatory powers (Simpson's index of diversity) were 0.982, 0.950, 0.846, and 0.757 for PFGE, spa typing, DL typing, and spa clonal clustering, respectively. DL typing and spa clonal clustering showed the highest concordance, calculated by adjusted Rand's coefficients. The 6 USA300 isolates grouped homogeneously into distinct PFGE and DL clusters, and all belonged to spa type t008 and spa-CC 008. Among the three methods, DL proved to be rapid and easy to perform. DL typing qualifies for initial screening during outbreak investigation. However, compared to PFGE and spa typing, DL typing has limited discriminatory power and therefore should be complemented by more discriminative methods in isolates that share identical DL patterns. PMID:21307215

  19. Early Disease Activity or Clinical Response as Predictors of Long‐Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis

    PubMed Central

    Deodhar, A.; Fleischmann, R.; Mease, P. J.; Rudwaleit, M.; Nurminen, T.; Davies, O.

    2017-01-01

    Objective Early identification of patients unlikely to achieve good long‐term disease control with anti–tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat‐to‐target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol. Methods The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week‐48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C‐reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID‐axSpA and RAPID‐PsA trial data. Results A clear relationship between disease activity from week 2 to 12 and achievement of week‐48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week‐48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week‐12 ASDAS inactive disease. For PsA, week‐48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28‐CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week‐48 outcomes, though to a lesser extent than disease activity. Conclusion Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long‐term treatment goals. PMID:27696727

  20. An Electrochemiluminescence Immunosensor Based on Gold-Magnetic Nanoparticles and Phage Displayed Antibodies

    PubMed Central

    Mu, Xihui; Tong, Zhaoyang; Huang, Qibin; Liu, Bing; Liu, Zhiwei; Hao, Lanqun; Dong, Hua; Zhang, Jinping; Gao, Chuan

    2016-01-01

    Using the multiple advantages of the ultra-highly sensitive electrochemiluminescence (ECL) technique, Staphylococcus protein A (SPA) functionalized gold-magnetic nanoparticles and phage displayed antibodies, and using gold-magnetic nanoparticles coated with SPA and coupled with a polyclonal antibody (pcAb) as magnetic capturing probes, and Ru(bpy)32+-labeled phage displayed antibody as a specific luminescence probe, this study reports a new way to detect ricin with a highly sensitive and specific ECL immunosensor and amplify specific detection signals. The linear detection range of the sensor was 0.0001~200 µg/L, and the limit of detection (LOD) was 0.0001 µg/L, which is 2500-fold lower than that of the conventional ELISA technique. The gold-magnetic nanoparticles, SPA and Ru(bpy)32+-labeled phage displayed antibody displayed different amplifying effects in the ECL immunosensor and can decrease LOD 3-fold, 3-fold and 20-fold, respectively, compared with the ECL immunosensors without one of the three effects. The integrated amplifying effect can decrease the LOD 180-fold. The immunosensor integrates the unique advantages of SPA-coated gold-magnetic nanoparticles that improve the activity of the functionalized capturing probe, and the amplifying effect of the Ru(bpy)32+-labeled phage displayed antibodies, so it increases specificity, interference-resistance and decreases LOD. It is proven to be well suited for the analysis of trace amounts of ricin in various environmental samples with high recovery ratios and reproducibility. PMID:26927130

  1. 78 FR 37162 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ...-0518; Directorate Identifier 2009-SW-021-AD] RIN 2120-AA64 Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A) (Agusta) Helicopters AGENCY: Federal Aviation....p.A. (Type Certificate Currently Held By Agustawestland S.p.A.) (Agusta): Docket No. FAA-2013-0518...

  2. 77 FR 73273 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A.) (Agusta.... Helicopters (Type Certificate Currently Held By AgustaWestland S.P.A.) (Agusta): Amendment 39-17281; Docket No... ``Mail'' address between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. Examining the...

  3. Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

    PubMed

    Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

    2015-03-01

    We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. MITLL 2015 Language Recognition Evaluation System Description

    DTIC Science & Technology

    2016-01-27

    912 8.18 qsl-rus Russian 2021 37.80 ara-ary Maghrebi 919 46.91 spa-car Carib. Spa. 194 30.59 ara-arz Egyptian 440 97.27 spa-eur Eur. Spa. 366 8.55...qsl-pol Polish 695 32.14 ara-arb MSA 912 8.18 qsl-rus Russian 2021 37.80 ara-ary Maghrebi 919 46.91 spa-car Carib. Spa. 194 30.59 ara-arz Egyptian ...BOTTLENECK I-VECTOR SYSTEM (BNF1) The Deep Neural Network architecture that we used for this system was composed of seven hidden layers. The sixth

  5. A synoptic study of Sudden Phase Anomalies (SPA's) effecting VLF navigation and timing

    NASA Technical Reports Server (NTRS)

    Swanson, E. R.; Kugel, C. P.

    1973-01-01

    Sudden phase anomalies (SPA's) observed on VLF recordings are related to sudden ionospheric disturbances due to solar flares. Results are presented for SPA statistics on 500 events observed in New York during the ten year period 1961 to 1970. Signals were at 10.2kHz and 13.6kHz emitted from the OMEGA transmitters in Hawaii and Trinidad. A relationship between SPA frequency and sun spot number was observed. For sun spot number near 85, about one SPA per day will be observed somewhere in the world. SPA activity nearly vanishes during periods of low sun spot number. During years of high solar activity, phase perturbations observed near noon are dominated by SPA effects beyond the 95th percentile. The SPA's can be represented by a rapid phase run-off which is approximately linear in time, peaking in about 6 minutes, and followed by a linear recovery. Typical duration is 49 minutes.

  6. Cell-specific modulation of surfactant proteins by ambroxol treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seifart, Carola; Clostermann, Ursula; Seifart, Ulf

    2005-02-15

    Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNAmore » content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.« less

  7. Try Them-You'll Like Them

    ERIC Educational Resources Information Center

    Norton, Darryl E.

    1975-01-01

    The author discusses the role of speech pathology assistants (SPA), responding to speech pathologists fears regarding SPA's, describing the National Association for Hearing and Speech Action SPA training program, and pointing out the duties of SPA's and their benefits to speech pathologists. (LS)

  8. Longitudinal Change of Self-Perceptions of Aging and Mortality

    PubMed Central

    2014-01-01

    Objective. To understand the association between self-perceptions of aging (SPA) and mortality in late life. Method. The sample (n = 1,507) was drawn from the Australian Longitudinal Study of Aging (baseline age = 65–103 years). We used joint growth curve and survival models on 5 waves of data for a period of 16 years to investigate the random intercept and slope of SPA for predicting all-cause mortality. Results. The unadjusted model revealed that poor SPA at baseline, as well as decline in SPA, increased the risk of mortality (SPA intercept hazard ratio [HR] = 1.21, 95% confidence interval [CI] = 1.13, 1.31; SPA slope HR = 1.17, 95% CI = 1.02, 1.33). This relationship remained significant for the SPA intercept after adjusting for other risk factors including demographics, physical health, cognitive functioning, and well-being. Conclusion. These findings suggest that a single measurement of SPA in late life may be very informative of future long-term vulnerability to health decline and mortality. Furthermore, a dynamic measure of SPA may be indicative of adaptation to age-related changes. This supports a “self-fulfilling” hypothesis, whereby SPA is a lens through which age-related changes are interpreted, and these interpretations can affect future health and health behaviors. PMID:23419867

  9. Optically active substituted polyacetylene@carbon nanotube hybrids: Preparation, characterization and infrared emissivity property study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bu, Xiaohai; Zhou, Yuming, E-mail: ymzhou@seu.edu.cn; Zhang, Tao

    Optically active substituted polyacetylene@multiwalled carbon nanotubes (SPA@MWCNTs) nanohybrids were fabricated by wrapping helical SPA copolymers onto the surface of modified nanotubes through ester bonding linkage. SPA copolymer based on chiral phenylalanine and serine was pre-polymerized by a rhodium zwitterion catalyst in THF, and evidently proved to possess strong optical activity and adopt a predominately one-handed helical conformation. Various characterizations including Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and transmission electron microscopy (TEM) demonstrated that the SPA had been covalently grafted onto the nanotubes without destroying their original graphite structure. The wrapped SPA was found tomore » exhibit an enhancement in thermal stability and still maintained considerable optical activity after grafting. The infrared emissivity property of the nanohybrids at 8–14 μm was investigated in addition. The results indicated that the SPA@MWCNTs hybrid matrix could possess a much lower infrared emissivity value (ε=0.707) than raw MWCNTs, which might be due to synergistic effect of the unique helical conformation of optically active SPA and strengthened interfacial interaction between the organic polymers and inorganic nanoparticles. - Graphical abstract: Optically active SPA@MWCNTs nanohybrids with low infrared emissivity. - Highlights: • Synthesis of optically active SPA copolymer derived from serine and phenylalanine. • Preparation and characterization of optically active SPA@MWCNTs nanohybrids. • Application study of the SPA@MWCNTs nanohybrids (ε=0.707) in lowering the infrared emissivity.« less

  10. Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

    PubMed

    Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

    2009-03-11

    Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.

  11. Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages.

    PubMed

    Unverdorben, Laura; Haufe, Thomas; Santoso, Laura; Hofmann, Simone; Jeschke, Udo; Hutter, Stefan

    2016-04-28

    Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas.

  12. Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages

    PubMed Central

    Unverdorben, Laura; Haufe, Thomas; Santoso, Laura; Hofmann, Simone; Jeschke, Udo; Hutter, Stefan

    2016-01-01

    Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas. PMID:27136536

  13. Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins

    PubMed Central

    Berlon, Nicholas R.; Qi, Robert; Sharma-Kuinkel, Batu K.; Joo, Hwang-Soo; Park, Lawrence P.; George, Dennis; Thaden, Joshua T.; Messina, Julia A.; Maskarinec, Stacey A.; Mueller-Premru, Manica; Athan, Eugene; Tattevin, Pierre; Pericas, Juan M.; Woods, Christopher W.; Otto, Michael; Fowler, Vance G.

    2016-01-01

    Summary Background Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes. Methods 177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal–Wallis tests as appropriate. Results Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p < 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p < 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMα1-4, PSMβ1, and δ-toxin than other isolates (p < 0.001). These findings persisted when USA300 isolates were excluded from analysis. PMID:26079275

  14. A systematic review of quality-of-life domains and items relevant to patients with spondyloarthritis.

    PubMed

    Kwan, Yu Heng; Fong, Warren; Tan, Victoria Ie Ching; Lui, Nai Lee; Malhotra, Rahul; Østbye, Truls; Thumboo, Julian

    2017-10-01

    To summarize, from the literature, quality-of-life (QoL) domains and items relevant to patients with spondyloarthritis (SpA), and to determine if commonly used SpA patient-reported outcome (PRO) instruments include the identified domains. We used PRISMA statement for systematic review and searched Medline ® , Embase ® , and PsycInfo ® using relevant keywords. In addition, hand searches of references of the included articles were conducted. All articles were reviewed for inclusion by 2 independent reviewers. QoL domains and items relevant to patients with axial or peripheral SpA were extracted and presented using the adapted World Health Organization Quality-of-Life (WHOQOL) domain framework. SpA PROs were assessed to determine if they included the domains identified. We retrieved 14,343 articles, of which 34 articles fulfilled inclusion criteria for review. Twenty-five articles were conducted in the European population. Domains such as negative feelings and activities of daily living were found to be present in 28 and 27 articles, respectively. SpA impacted QoL in all domains of the adapted WHOQOL framework. Domains that differed between types of SpA were financial resources, general levels of independence and medication side effects. Embarrassment, self-image, and premature ageing were items that differed by geographical setting. PROs to capture domains for peripheral SpA were similar for axial SpA. We found that a wide range of domains and items of QoL were relevant to patients with SpA with minimal differences between patients with axial and peripheral SpA. Clinicians may consider using peripheral SpA PROs to measure QoL of patients with axial SpA. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. 77 FR 36257 - Notice of Implementation of Determination Under Section 129 of the Uruguay Round Agreements Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-18

    ... (``Divella''), Pasta Zara SpA 1 and Pasta Zara SpA 2 (collectively, ``Pasta Zara''), Pastificio Di Martino... Antidumping Duty Administrative Review, 75 FR 11116 (March 10, 2010). Divella,\\10\\ Pasta Zara, Certain Pasta... Pasta from Italy (2006/07) F. Divella S.p.A 2.83 0.00 Pasta Zara S.p.A. 1 and Pasta Zara 9.71 0.00 S.p.A...

  16. Effect of spa therapy with saline balneotherapy on oxidant/antioxidant status in patients with rheumatoid arthritis: a single-blind randomized controlled trial

    NASA Astrophysics Data System (ADS)

    Karagülle, Mine; Kardeş, Sinan; Karagülle, Oğuz; Dişçi, Rian; Avcı, Aslıhan; Durak, İlker; Karagülle, Müfit Zeki

    2017-01-01

    Oxidative stress has been shown to play a contributory role in the pathogenesis of rheumatoid arthritis (RA). Recent studies have provided evidence for antioxidant properties of spa therapy. The purpose of this study is to investigate whether spa therapy with saline balneotherapy has any influence on the oxidant/antioxidant status in patients with RA and to assess clinical effects of spa therapy. In this investigator-blind randomized controlled trial, we randomly assigned 50 patients in a 1:1 ratio to spa therapy plus standard drug treatment (spa group) or standard drug treatment alone (control group). Spa group followed a 2-week course of spa therapy regimen consisting of a total of 12 balneotherapy sessions in a thermal mineral water pool at 36-37 °C for 20 min every day except Sunday. All clinical and biochemical parameters were assessed at baseline and after spa therapy (2 weeks). The clinical parameters were pain intensity, patient global assessment, physician global assessment, Health Assessment Questionnaire disability index (HAQ-DI), Disease Activity Score for 28-joints based on erythrocyte sedimentation rate (DAS28-4[ESR]). Oxidative status parameters were malondialdehyde (MDA), nonenzymatic superoxide radical scavenger activity (NSSA), antioxidant potential (AOP), and superoxide dismutase (SOD). The NSSA levels were increased significantly in the spa group ( p = 0.003) but not in the control group ( p = 0.509); and there was a trend in favor of spa therapy for improvements in NSSA levels compared to control ( p = 0.091). Significant clinical improvement was found in the spa group compared to the control in terms of patient global assessment ( p = 0.011), physician global assessment ( p = 0.043), function (HAQ-DI) ( p = 0.037), disease activity (DAS28-4[ESR]) (0.044) and swollen joint count (0.009), and a trend toward improvement in pain scores (0.057). Spa therapy with saline balneotherapy exerts antioxidant effect in patients with RA as reflected by the increase in NSSA levels after spa therapy; whether this antioxidant effect contributes to the clinical improvements observed remains to be verified.

  17. Effect of spa therapy with saline balneotherapy on oxidant/antioxidant status in patients with rheumatoid arthritis: a single-blind randomized controlled trial.

    PubMed

    Karagülle, Mine; Kardeş, Sinan; Karagülle, Oğuz; Dişçi, Rian; Avcı, Aslıhan; Durak, İlker; Karagülle, Müfit Zeki

    2017-01-01

    Oxidative stress has been shown to play a contributory role in the pathogenesis of rheumatoid arthritis (RA). Recent studies have provided evidence for antioxidant properties of spa therapy. The purpose of this study is to investigate whether spa therapy with saline balneotherapy has any influence on the oxidant/antioxidant status in patients with RA and to assess clinical effects of spa therapy. In this investigator-blind randomized controlled trial, we randomly assigned 50 patients in a 1:1 ratio to spa therapy plus standard drug treatment (spa group) or standard drug treatment alone (control group). Spa group followed a 2-week course of spa therapy regimen consisting of a total of 12 balneotherapy sessions in a thermal mineral water pool at 36-37 °C for 20 min every day except Sunday. All clinical and biochemical parameters were assessed at baseline and after spa therapy (2 weeks). The clinical parameters were pain intensity, patient global assessment, physician global assessment, Health Assessment Questionnaire disability index (HAQ-DI), Disease Activity Score for 28-joints based on erythrocyte sedimentation rate (DAS28-4[ESR]). Oxidative status parameters were malondialdehyde (MDA), nonenzymatic superoxide radical scavenger activity (NSSA), antioxidant potential (AOP), and superoxide dismutase (SOD). The NSSA levels were increased significantly in the spa group (p = 0.003) but not in the control group (p = 0.509); and there was a trend in favor of spa therapy for improvements in NSSA levels compared to control (p = 0.091). Significant clinical improvement was found in the spa group compared to the control in terms of patient global assessment (p = 0.011), physician global assessment (p = 0.043), function (HAQ-DI) (p = 0.037), disease activity (DAS28-4[ESR]) (0.044) and swollen joint count (0.009), and a trend toward improvement in pain scores (0.057). Spa therapy with saline balneotherapy exerts antioxidant effect in patients with RA as reflected by the increase in NSSA levels after spa therapy; whether this antioxidant effect contributes to the clinical improvements observed remains to be verified.

  18. Adhesion by pathogenic corynebacteria.

    PubMed

    Rogers, Elizabeth A; Das, Asis; Ton-That, Hung

    2011-01-01

    Pathogenic members of the genus Corynebacterium cause a wide range of serious infections in humans including diphtheria. Adhesion to host cells is a crucial step during infection. In Corynebacterium diphtheriae, adhesion is mediated primarily by filamentous structures called pili or fimbriae that are covalently attached to the bacterial cell wall. C. diphtheriae produces three distinct pilus structures, SpaA-, SpaD- and SpaH-type pili. Similar to other types, the prototype SpaA pilus consists of SpaA forming the pilus shaft and two minor pilins SpaB and SpaC located at the base and at the tip, respectively. The minor pilins SpaB/SpaC are critical for bacterial binding to human pharyngeal cells, and thus represent the major adhesins of corynebacteria. Like pili of many other gram-positive microbes, the assembly of corynebacterial pili occurs by a two-step mechanism, whereby pilins are covalently polymerized by a transpeptidase enzyme named pilin-specific sortase and the generated pilus polymer is subsequently anchored to the cell wall peptidoglycan via the base pilin by the housekeeping sortase or a non-polymerizing sortase. This chapter reviews the current knowledge of corynebacterial adhesion, with a specific focus on pilus structures, their assembly, and the mechanism of adhesion mediated by pili.

  19. Construction of type-II QC-LDPC codes with fast encoding based on perfect cyclic difference sets

    NASA Astrophysics Data System (ADS)

    Li, Ling-xiang; Li, Hai-bing; Li, Ji-bi; Jiang, Hua

    2017-09-01

    In view of the problems that the encoding complexity of quasi-cyclic low-density parity-check (QC-LDPC) codes is high and the minimum distance is not large enough which leads to the degradation of the error-correction performance, the new irregular type-II QC-LDPC codes based on perfect cyclic difference sets (CDSs) are constructed. The parity check matrices of these type-II QC-LDPC codes consist of the zero matrices with weight of 0, the circulant permutation matrices (CPMs) with weight of 1 and the circulant matrices with weight of 2 (W2CMs). The introduction of W2CMs in parity check matrices makes it possible to achieve the larger minimum distance which can improve the error- correction performance of the codes. The Tanner graphs of these codes have no girth-4, thus they have the excellent decoding convergence characteristics. In addition, because the parity check matrices have the quasi-dual diagonal structure, the fast encoding algorithm can reduce the encoding complexity effectively. Simulation results show that the new type-II QC-LDPC codes can achieve a more excellent error-correction performance and have no error floor phenomenon over the additive white Gaussian noise (AWGN) channel with sum-product algorithm (SPA) iterative decoding.

  20. Spa Goers' Repeated Visits for Health and Wellness and the Influential Factors: An Exploratory Study of the UK Spa Goers.

    PubMed

    Choi, Myungsuk; Poade, Donna; Sohn, Minsung; Choi, Mankyu

    2016-01-01

    Dissemination of spa services across the globe and its market saturation drive demand for differentiated communication methods. This study aims to explore the influential factors on spa goers' repeated visits and their practical applications in the health and wellness spa industry. The identified factors were used as the measurement variables to examine the relation with spa goers' repeated visits. The proposed concept was tested by a mixed method combining a self-administered questionnaire and semistructured interview with 54 survey participants and 6 interviewees. It was meaningful to use a sample of the UK spa goers from the southwest region since global spa trends stem from the EU spas, and the United Kingdom is one of the market leaders. The data were analyzed using frequency, percentage, multiple logistic regression analysis, and coding process. The survey findings demonstrated that the most significant influential factor on the repeated spa visits is a memorable experience of which showed 13.7 times higher probability than the reference up-to-date facility. The details of memorable experiences were discovered throughout the interviews that include the rediscovery of self, feeling of connectedness, recharge for positive emotions, self-reward through escapism, and experience of noncommercialized local products and attractions. Therefore, using experiential marketing methods can be effective spa service marketing.

  1. Uveitis in Spondyloarthritis: An Overview.

    PubMed

    Cantini, Fabrizio; Nannini, Carlotta; Cassarà, Emanuele; Kaloudi, Olga; Niccoli, Laura

    2015-11-01

    Autoimmune anterior uveitis (AU) accounts for at least half of the cases of noninfectious uveitis, and similarly to spondyloarthritis (SpA), its occurrence is related to HLA-B27 positivity. AU is significantly more frequently found in HLA-B27-positive subjects with SpA and is characterized by unilateral eye involvement, marked tendency to recur with involvement of both eyes in alternate fashion, and has good prognosis in the majority of cases. The estimated frequency of SpA in patients with AU is around 50%, whereas AU in SpA has been reported in at least 30% of cases. Across the SpA disease spectrum, AU has a frequency peak of 33.4% in patients with ankylosing spondylitis, while the estimated prevalence in psoriatic arthritis (PsA) and inflammatory bowel disease-associated SpA is 2%-25%, and 25%, respectively. In early PsA, the frequency of AU has been found in 9% of patients. The wide range of prevalence reported in PsA may be explained by the variable sets of classification criteria used for patient selection and the different length of followup. AU may precede the clinical features of SpA, may be present at diagnosis, or may complicate the SpA clinical course. However, the occurrence of AU in SpA as well as AU flares has been reduced through treatment of SpA with anti-tumor necrosis factor-α agents.

  2. Sparse regressions for predicting and interpreting subcellular localization of multi-label proteins.

    PubMed

    Wan, Shibiao; Mak, Man-Wai; Kung, Sun-Yuan

    2016-02-24

    Predicting protein subcellular localization is indispensable for inferring protein functions. Recent studies have been focusing on predicting not only single-location proteins, but also multi-location proteins. Almost all of the high performing predictors proposed recently use gene ontology (GO) terms to construct feature vectors for classification. Despite their high performance, their prediction decisions are difficult to interpret because of the large number of GO terms involved. This paper proposes using sparse regressions to exploit GO information for both predicting and interpreting subcellular localization of single- and multi-location proteins. Specifically, we compared two multi-label sparse regression algorithms, namely multi-label LASSO (mLASSO) and multi-label elastic net (mEN), for large-scale predictions of protein subcellular localization. Both algorithms can yield sparse and interpretable solutions. By using the one-vs-rest strategy, mLASSO and mEN identified 87 and 429 out of more than 8,000 GO terms, respectively, which play essential roles in determining subcellular localization. More interestingly, many of the GO terms selected by mEN are from the biological process and molecular function categories, suggesting that the GO terms of these categories also play vital roles in the prediction. With these essential GO terms, not only where a protein locates can be decided, but also why it resides there can be revealed. Experimental results show that the output of both mEN and mLASSO are interpretable and they perform significantly better than existing state-of-the-art predictors. Moreover, mEN selects more features and performs better than mLASSO on a stringent human benchmark dataset. For readers' convenience, an online server called SpaPredictor for both mLASSO and mEN is available at http://bioinfo.eie.polyu.edu.hk/SpaPredictorServer/.

  3. Interethnic Variations and Clinical Features of Spondyloarthropathies in a Middle Eastern Country.

    PubMed

    Quraishi, Mohammed Kamil; Badsha, Humeira; Khan, Bhavna; Shahzeb, Muhammad; Hegde, Srilakshmi; Mofti, Ayman; Ooi, Kong Kok

    2018-01-01

    The study aimed to demonstrate the interethnic differences and clinical features of Spondyloarthropathy(SpA) patients in a diverse Middle Eastern Country. A retrospective review of medical records to collect the required data was conducted for SpA patients at two study institutions in the United Arab Emirates. Of 141 SpA patients found, 88 AS(Ankylosing Spondylitis) patients and 53 'other SpA' patients were identified. Males constituted 81% of AS and 55% of 'other SpA' patients. Patients with AS and 'other SpA' had a mean age of symptom onset of 28 and 34 years, respectively.49% and 40% of AS and 'other SpA' patients had a history of Anti-TNF therapy usage. Enthesitis and Uveitis were noted in 16% and 18% of AS patients whilst 53% and 11% in 'other SpA' patients, respectively.Caucasian, Indian Subcontinent and Arabs constituted 93% of our cohort. Mean age of onset of symptoms in the Indian Subcontinent 'other SpA' group was much greater than the other two ethnicities. Duration of symptoms to diagnosis was 3.5 and 4 years in AS and other SpA patients' respectively. HLA-B27 positivity was found in 53%, 80% and 93% of Arab, Indian Subcontinent and Caucasian AS patients, respectively, whilst seen in 50%, 25% and 33% of the same respective ethnicties in 'other SpA' patients. This study on 141 patients is the largest to analyse inter-ethnic variations in SpA patients in the region. Our cohort shows a short delay in diagnosis with a relatively higher Anti-TNF usage.

  4. 76 FR 71246 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes AGENCY: Federal Aviation Administration (FAA... directive (AD) for Piaggio Aero Industries S.p.A. Model P-180 airplanes. This AD results from mandatory.... For service information identified in this AD, contact Piaggio Aero Industries S.p.A. Airworthiness...

  5. Identification of minor inner-membrane components of the Shigella type III secretion system 'needle complex'.

    PubMed

    Zenk, Sebastian F; Stabat, David; Hodgkinson, Julie L; Veenendaal, Andreas K J; Johnson, Steven; Blocker, Ariel J

    2007-08-01

    Type III secretion systems (T3SSs or secretons) are central virulence factors of many Gram-negative bacteria, used to inject protein effectors of virulence into eukaryotic host cells. Their overall morphology, consisting of a cytoplasmic region, an inner- and outer-membrane section and an extracellular needle, is conserved in various species. A portion of the secreton, containing the transmembrane regions and needle, has been isolated biochemically and termed the 'needle complex' (NC). However, there are still unsolved questions concerning the nature and relative arrangement of the proteins assembling the NC. Until these are resolved, the mode of function of the NC cannot be clarified. This paper describes an affinity purification method that enables highly efficient purification of Shigella NCs under near-physiological conditions. Using this method, three new minor components of the NC were identified by mass spectrometry: IpaD, a known component of the needle tip complex, and two predicted components of its central inner-membrane export apparatus, Spa40 and Spa24. A further minor component of the NC, MxiM, is only detected by immunoblotting. MxiM is a 'pilotin'-type protein for the outer-membrane 'secretin' ring formed of MxiD. As expected, it localized to the outer rim of the upper ring of NCs, validating the other findings.

  6. 78 FR 44042 - Airworthiness Directives; Agusta S.p.A. Helicopters (Type Certificate Currently Held By...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ...-0643; Directorate Identifier 2012-SW-096-AD] RIN 2120-AA64 Airworthiness Directives; Agusta S.p.A. Helicopters (Type Certificate Currently Held By AgustaWestland S.P.A) (AgustaWestland) AGENCY: Federal... (Type Certificate Currently Held By Agustawestland S.p.A) (AgustaWestland): Docket No. FAA-2013-0643...

  7. Seasonal variation of lipid-lowering effects of complex spa therapy.

    PubMed

    Strauss-Blasche, G; Ekmekcioglu, C; Leibetseder, V; Marktl, W

    2003-04-01

    It has been shown that spa therapy has a lipid-lowering effect. Also, seasonal variations in spa therapy effects have been found for some outcome measures. The aim of the present study is to investigate whether the lipid-lowering effects of spa therapy as a complex health intervention also are subject to seasonal variation. The effect of 3-week resident spa therapy at the Austrian spa Bad Tatzmannsdorf was studied in 395 patients with moderate musculoskeletal chronic pain over a time of 2 years. Spa therapy included balneotherapy, exercise therapy, and dietary measures. Total cholesterol (CHOL), HDL, LDL, triglycerides (TG), and the CHOL/HDL ratio were assessed at the beginning and end of therapy. Spa therapy was associated with a decrease of CHOL, HDL, and LDL (p < 0.001). TG and CHOL/HDL did not change. The decrease of lipids was smaller for older patients, females, and normal weight individuals. CHOL decrease showed a seasonal variation independent of weight loss (p = 0.04), being largest in fall (-6.1%) and smallest in spring (-2.4%). CHOL and CHOL/HDL for obese individuals showed the greatest decrease in winter (-10% for CHOL, -9% for CHOL/HDL ratio), whereas corresponding measures increased for normal-weight subjects. The lipid-lowering effect of spa therapy could be confirmed; it is partly moderated by season. The results suggest that the effect of some components of spa therapy such as exercise therapy, diet, and relaxation may be subject to seasonal variation. Copyright 2003 S. Karger GmbH, Freiburg

  8. Induced static asymmetry of the pelvis is associated with functional asymmetry of the lumbo-pelvo-hip complex.

    PubMed

    Gnat, Rafał; Saulicz, Edward

    2008-03-01

    This study evaluates the hypothesis that triggering and eliminating induced static pelvic asymmetry (SPA) may be followed by immediate change in functional asymmetry of the lumbo-pelvo-hip complex. Repeated measures experimental design with 2 levels of independent variable, that is, induced SPA triggered and induced SPA eliminated, was implemented. Three series of measurements were performed, that is, baseline, after triggering SPA, and after eliminating SPA. A group of 84 subjects with no initial symptoms of SPA was studied. Different forms of mechanical stimulation were applied aiming to induce SPA, and the 2 manual stretching-manipulating techniques were performed aiming to eliminate it. A hand inclinometer was used to measure SPA in standing posture. Selected ranges of motion of the hip joints and lumbar spine were used to depict functional asymmetry of the lumbo-pelvo-hip complex. The functional asymmetry indices for individual movements were calculated. Repeated measures design of analysis of variance, dependent data Student t test, and linear Pearson's correlation test were used. Assessment of the SPA showed its significant increase between baseline and series 2 measurements, with a subsequent significant decrease between series 2 and series 3 measurements. Values of the functional asymmetry indices changed accordingly, that is, they increased significantly between series 1 and series 2 and had returned to their initial level in series 3 measurements. Induced SPA shows considerable association with functional asymmetry of the lumbo-pelvo-hip complex.

  9. Altered gut transcriptome in spondyloarthropathy

    PubMed Central

    Laukens, D; Peeters, H; Cruyssen, B V; Boonefaes, T; Elewaut, D; De Keyser, F; Mielants, H; Cuvelier, C; Veys, E M; Knecht, K; Van Hummelen, P; Remaut, E; Steidler, L; De Vos, M; Rottiers, P

    2006-01-01

    Background Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn's disease. Inflammation is manifested clinically in Crohn's disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn's disease. Aims To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn's disease and to examine global gene expression in non‐inflamed colon biopsy specimens and screen patients for differentially expressed genes. Methods Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn's disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn's disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass‐based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn's disease and 10 controls. Results 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn's disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn's disease. Conclusion The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn's disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn's disease in patients with SpA can be considered. PMID:16476712

  10. Regional Impact of Population Aging on Changes in Individual Self-perceptions of Aging: Findings From the German Ageing Survey.

    PubMed

    Wolff, Julia K; Beyer, Ann-Kristin; Wurm, Susanne; Nowossadeck, Sonja; Wiest, Maja

    2018-01-18

    The importance of self-perceptions of aging (SPA) for health and longevity is well documented. Comparably little is known about factors that contribute to SPA. Besides individual factors, the context a person lives in may shape SPA. Research has so far focused on country-level differences in age stereotypes, indicating that rapid population aging accompanies more negative age stereotypes. The present study expands previous research by investigating the impact of district-specific population aging within one country on different facets of SPA. Based on a large representative survey in Germany, the study investigates changes in SPA as ongoing development as well as the SPA of physical loss over a 12-year period in adults aged 40+. The study uses several indicators of population aging (e.g., population development, average age, greying index), to identify four clusters differing in their pace of population aging. Based on three-level latent change models, these clusters were compared in their impact on changes in SPA. Compared to districts with an average rate of population aging, the study shows that persons living in regions with a fast population aging rate (C1) hold more negative SPA in both facets (ps = .01). Districts with slow population aging (C2) have significantly higher SPA ongoing development (p = .03). The study underlines the importance for regional differences in population aging on the development of SPA. In particular, societies should be aware that fast population aging may result in more negative SPA. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Spa therapy together with supervised self-mobilisation improves pain, function and quality of life in patients with chronic shoulder pain: a single-blind randomised controlled trial

    NASA Astrophysics Data System (ADS)

    Chary-Valckenaere, Isabelle; Loeuille, Damien; Jay, Nicolas; Kohler, François; Tamisier, Jean-Noë; Roques, Christian-François; Boulange, Michel; Gay, Gérard

    2018-02-01

    To determine whether spa therapy has a beneficial effect on pain and disability in patients with chronic shoulder pain, this single-blind randomised controlled clinical trial included patients with chronic shoulder pain due to miscellaneous conditions attending one of four spa centres as outpatients. Patients were randomised into two groups: spa therapy (18 days of standardised treatment combining thermal therapy together with supervised mobilisation in a thermal pool) and controls (spa therapy delayed for 6 months: `immediate versus delayed treatment' paradigm). All patients continued usual treatments during the 6-month follow-up period. The main endpoint was the mean change in the French-Quick DASH (F-QD) score at 6 months. The effect size of spa therapy was calculated, and the proportion of patients reaching minimal clinically important improvement (MCII) was compared. Secondary endpoints were the mean change in SF-36, treatment use and tolerance. One hundred eighty-six patients were included (94 patients as controls, 92 in the spa group) and analysed by intention to treat. At 6 months, the mean change in the F-QD score was statistically significantly greater among spa therapy patients than controls (- 32.6 versus - 8.15%; p < 0.001) with an effect size of 1.32 (95%CI: 0.97-1.68). A significantly greater proportion of spa therapy patients reached MCII (59.3 versus 17.9%). Spa therapy was well tolerated with a significant impact on SF-36 components but not on drug intake. Spa therapy provided a statistically significant benefit on pain, function and quality of life in patients with chronic shoulder pain after 6 months compared with usual care.

  12. Formation of South Pole-Aitken Basin as the Result of an Oblique Impact: Implications for Melt Volume and Source of Exposed Materials

    NASA Technical Reports Server (NTRS)

    Petro, N. E.

    2012-01-01

    The South Pole-Aitken Basin (SPA) is the largest, deepest, and oldest identified basin on the Moon and contains surfaces that are unique due to their age, composition, and depth of origin in the lunar crust [1-3] (Figure 1). SPA has been a target of interest as an area for robotic sample return in order to determine the age of the basin and the composition and origin of its interior [3-6]. As part of the investigation into the origin of SPA materials there have been several efforts to estimate the likely provenance of regolith material in central SPA [5, 6]. These model estimates suggest that, despite the formation of basins and craters following SPA, the regolith within SPA is dominated by locally derived material. An assumption inherent in these models has been that the locally derived material is primarily SPA impact-melt as opposed to local basement material (e.g. unmelted lower crust). However, the definitive identification of SPA derived impact melt on the basin floor, either by remote sensing [2, 7] or via photogeology [8] is extremely difficult due to the number of subsequent impacts and volcanic activity [3, 4]. In order to identify where SPA produced impact melt may be located, it is important to constrain both how much melt would have been produced in a basin forming impact and the likely source of such melted material. Models of crater and basin formation [9, 10] present clear rationale for estimating the possible volumes and sources of impact melt produced during SPA formation. However, if SPA formed as the result of an oblique impact [11, 12], the volume and depth of origin of melted material could be distinct from similar material in a vertical impact [13].

  13. Spa therapy adjunct to pharmacotherapy is beneficial in rheumatoid arthritis: a crossover randomized controlled trial

    NASA Astrophysics Data System (ADS)

    Karagülle, Mine; Kardeş, Sinan; Dişçi, Rian; Karagülle, Müfit Zeki

    2018-02-01

    This study aims to investigate whether 2-week spa therapy, as an adjunct to usual pharmacological therapy, has any beneficial effect in patients with rheumatoid arthritis (RA). In this single-blind crossover study, 50 patients were randomly assigned in a 1:1 manner to receive usual pharmacological therapy plus 2-week spa therapy or usual pharmacological therapy alone (period 1.6 months); after a 9-month washout, patients were crossed over to the opposite assignment (period 2.6 months). Spa therapy program included a daily saline balneotherapy session at 36-37 °C for 20 min except Sundays. The clinical outcomes were evaluated at baseline, after spa therapy (2 weeks) and 3 and 6 months after the spa therapy in both period and were pain (Visual Analogue Scale (VAS)), patient and physician global assessments (VAS), Health Assessment Questionnaire (HAQ), and Disease Activity Score (DAS28). Spa therapy was superior to control therapy in improving all the assessed clinical outcomes at the end of the spa therapy. This superiority persisted significantly in physician global assessment ( p = 0.010) and with a trend in favor of spa group in patient global assessment ( p = 0.058), function ( p = 0.092), and disease activity ( p = 0.098) at 3 months. Statistically significant improvements were found in spa therapy compared to control in disease activity ( p = 0.006) and patient ( p = 0.020) and physician global ( p = 0.011) assessments, and a trend toward improvements in pain ( p = 0.069) and swollen joints ( p = 0.070) at 6 months. A 2-week spa therapy adjunct to usual pharmacological therapy provided beneficial clinical effects compared to usual pharmacological therapy alone, in RA patients treated with traditional disease-modifying antirheumatic drugs. These beneficial effects may last for 6 months.

  14. Spa therapy together with supervised self-mobilisation improves pain, function and quality of life in patients with chronic shoulder pain: a single-blind randomised controlled trial

    NASA Astrophysics Data System (ADS)

    Chary-Valckenaere, Isabelle; Loeuille, Damien; Jay, Nicolas; Kohler, François; Tamisier, Jean-Noë; Roques, Christian-François; Boulange, Michel; Gay, Gérard

    2018-06-01

    To determine whether spa therapy has a beneficial effect on pain and disability in patients with chronic shoulder pain, this single-blind randomised controlled clinical trial included patients with chronic shoulder pain due to miscellaneous conditions attending one of four spa centres as outpatients. Patients were randomised into two groups: spa therapy (18 days of standardised treatment combining thermal therapy together with supervised mobilisation in a thermal pool) and controls (spa therapy delayed for 6 months: `immediate versus delayed treatment' paradigm). All patients continued usual treatments during the 6-month follow-up period. The main endpoint was the mean change in the French-Quick DASH (F-QD) score at 6 months. The effect size of spa therapy was calculated, and the proportion of patients reaching minimal clinically important improvement (MCII) was compared. Secondary endpoints were the mean change in SF-36, treatment use and tolerance. One hundred eighty-six patients were included (94 patients as controls, 92 in the spa group) and analysed by intention to treat. At 6 months, the mean change in the F-QD score was statistically significantly greater among spa therapy patients than controls (- 32.6 versus - 8.15%; p < 0.001) with an effect size of 1.32 (95%CI: 0.97-1.68). A significantly greater proportion of spa therapy patients reached MCII (59.3 versus 17.9%). Spa therapy was well tolerated with a significant impact on SF-36 components but not on drug intake. Spa therapy provided a statistically significant benefit on pain, function and quality of life in patients with chronic shoulder pain after 6 months compared with usual care.

  15. Role for imaging in spondyloarthritis.

    PubMed

    Ran, Jun; Morelli, John N; Xie, Ruyi; Zhang, Xiaoli; Liang, Xiaoqing; Liu, Xuanlin; Li, Xiaoming

    2017-09-01

    Despite major progress in the imaging diagnosis of spondyloarthritis (SpA), the relative advantages of various available imaging techniques remain unclear. The aim of this study is to assess the current use of imaging in the diagnosis of SpA and to provide suitable recommendations for the use of imaging as an outcome measure as defined in the Assessment in SpondyloArthritis international Society (ASAS) criteria. A systematic literature search regarding imaging in SpA was performed. Articles were assessed by two reviewers to identify and summarized key information pertaining to imaging in SpA. The search identified 180 relevant articles. Conventional radiography (CR) (17 articles), ultrasound (US) (26 articles), conventional computed tomography (CT) (13 articles), spectral computed tomography (spectral CT) (2 articles), bone scintigraphy (24 articles), and magnetic resonance imaging (MRI) were assessed (98 articles). Sacroiliitis and enthesitis were the major imaging findings in SpA. Multiple studies assessed the feasibility, validity, or differences among imaging modalities for the diagnosis of SpA; however, comprehensive assessments were not available due to a paucity of prospective imaging studies. CR is a widely available, inexpensive initial approach to evaluate patients with suspected SpA. CT enables assessment of structural changes from chronic sacroiliitis including bony erosions, subchondral sclerosis, joint space narrowing, and ankyloses; however, both CR and CT modalities are insensitive for demonstrating early enthesitis and sacroiliitis in SpA. US mainly identifies appendicular enthesitis but is more limited with respect to the sacroiliac joints. Bone scintigraphy can identify sacroiliac joint lesions and semi-quantitatively assess active sacroiliitis. MRI optimally evaluates not only early enthesitis and sacroiliitis of SpA but also chronic structural changes to the sacroiliac joints. More than one modality may be required for diagnostic and assessment of SpA depending upon disease characteristics and evolution. CR is a suitable initial examination while MRI is able to detect both early and late changes of SpA. A combination of CR and MRI is recommended for the diagnosis and assessment of SpA.

  16. Lunar Reconnaissance Orbiter Camera Observations Relating to Science and Landing Site Selection in South Pole-Aitken Basin for a Robotic Sample Return Mission

    NASA Technical Reports Server (NTRS)

    Jolliff, B. L.; Clegg-Watkins, R. N.; Petro, N. E.; Lawrence, S. L.

    2016-01-01

    The Moon's South Pole-Aitken basin (SPA) is a high priority target for Solar System exploration, and sample return from SPA is a specific objective in NASA's New Frontiers program. Samples returned from SPA will improve our understanding of early lunar and Solar System events, mainly by placing firm timing constraints on SPA formation and the post-SPA late-heavy bombardment (LHB). Lunar Reconnaissance Orbiter Camera (LROC) images and topographic data, especially Narrow Angle Camera (NAC) scale (1-3 mpp) morphology and digital terrain model (DTM) data are critical for selecting landing sites and assessing landing hazards. Rock components in regolith at a given landing site should include (1) original SPA impact-melt rocks and breccia (to determine the age of the impact event and what materials were incorporated into the melt); (2) impact-melt rocks and breccia from large craters and basins (other than SPA) that represent the post-SPA LHB interval; (3) volcanic basalts derived from the sub-SPA mantle; and (4) older, "cryptomare" (ancient buried volcanics excavated by impact craters, to determine the volcanic history of SPA basin). All of these rock types are sought for sample return. The ancient SPA-derived impact-melt rocks and later-formed melt rocks are needed to determine chronology, and thus address questions of early Solar System dynamics, lunar history, and effects of giant impacts. Surface compositions from remote sensing are consistent with mixtures of SPA impactite and volcanic materials, and near infrared spectral data distinguish areas with variable volcanic contents vs. excavated SPA substrate. Estimating proportions of these rock types in the regolith requires knowledge of the surface deposits, evaluated via morphology, slopes, and terrain ruggedness. These data allow determination of mare-cryptomare-nonmare deposit interfaces in combination with compositional and mineralogical remote sensing to establish the types and relative proportions of materials expected at a given site. Remote sensing compositions, e.g., FeO, also constrain the relative abundances of components. Landing-site assessments use crater and boulder distributions, and slope and terrain rugge

  17. Genetic mapping of common bunt resistance and plant height QTL in wheat.

    PubMed

    Singh, Arti; Knox, Ron E; DePauw, R M; Singh, A K; Cuthbert, R D; Kumar, S; Campbell, H L

    2016-02-01

    Breeding for field resistance to common bunt in wheat will need to account for multiple genes and epistatic and QTL by environment interactions. Loci associated with quantitative resistance to common bunt are co-localized with other beneficial traits including plant height and rust resistance. Common bunt, also known as stinking smut, is caused by seed borne fungi Tilletia tritici (Bjerk.) Wint. [syn. Tilletia caries (DC.) Tul.] and Tilletia laevis Kühn [syn. Tilletia foetida (Wallr.) Liro.]. Common bunt is known to cause grain yield and quality losses in wheat due to bunt ball formation and infestation of the grain. The objectives of this research were to identify and map quantitative trait loci (QTL) for common bunt resistance, to study the epistatic interactions between the identified QTL, and investigate the co-localization of bunt resistance with plant height. A population of 261 doubled haploid lines from the cross Carberry/AC Cadillac and checks were genotyped with polymorphic genome wide microsatellite and DArT(®) markers. The lines were grown in 2011, 2012, and 2013 in separate nurseries for common bunt incidence and height evaluation. AC Cadillac contributed a QTL (QCbt.spa-6D) for common bunt resistance on chromosome 6D at markers XwPt-1695, XwPt-672044, and XwPt-5114. Carberry contributed QTL for bunt resistance on chromosomes 1B (QCbt.spa-1B at XwPt743523) 4B (QCbt.spa-4B at XwPt-744434-Xwmc617), 4D (QCbt.spa-4D at XwPt-9747), 5B (QCbt.spa-5B at XtPt-3719) and 7D (QCbt.spa-7D at Xwmc273). Significant epistatic interactions were identified for percent bunt incidence between QCbt.spa-1B × QCbt.spa-4B and QCbt.spa-1B × QCbt.spa-6D, and QTL by environment interaction between QCbt.spa-1B × QCbt.spa-6D. Plant height QTL were found on chromosomes 4B (QPh.spa-4B) and 6D (QPh.spa-6D) that co-located with bunt resistance QTL. The identification of previously unreported common bunt resistance QTL (on chromosomes 4B, 4D and 7D), and new understanding of QTL × QTL interactions will facilitate marker-assisted breeding for common bunt resistance.

  18. 75 FR 2580 - Carolina Coastal Railway, Inc.-Acquisition and Operation Exemption-North Carolina State Ports...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... North Carolina State Ports Authority (SPA) and to operate approximately 0.87 miles of SPA's rail lines... by SPA (or previously owned or leased by North Carolina Ports Railway Commission), in Carteret County... SPA to the PCS Phosphate Company, Inc., rail car dump and the ``Fishmeal'' spur on the area commonly...

  19. 78 FR 67015 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by Agusta Westland...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by Agusta Westland) Helicopters AGENCY... Sec. 39.13 by adding the following new airworthiness directive (AD): 2013-22-16 Agusta S.P.A. (Type... new airworthiness directive (AD) for certain Agusta S.p.A. (Agusta) Model AW139 helicopters. This AD...

  20. Hydrochemical Investigation of the Balikli Spa (Kangal Fish Spring), Sivas, Turkey

    NASA Astrophysics Data System (ADS)

    Kaçaroǧlu, Fikret

    2010-05-01

    Balıklı Spa (Kangal Fish Spring) is situated to the northeast of Kangal district centre, Sivas, Turkey. Balıklı Spa is of a particular place amongst the other thermal baths found in Turkey and is used in the treatment of psoriasis. The temperature and discharge of the Balıklı Spa water range between 33.6 and 35.4 oC and 145-220 L/s, respectively. The discharge of the Çermik Stream measured downstream of the Balıklı Spa is in the range of 150-660 L/s, and is mostly supplied by Balıklı Spa. Total dissolved solids (TDS) of the Balıklı Spa and Çermik Stream waters range between 348 and 395 mg/L and 278 and 377 mg/L, respectively. Dominant ions of these waters are Ca, Mg and HCO3, and they are classified as calcium bicarbonate type waters. In terms of balneological classification Balıklı Spa is "acrotothermal water". Secondary and minor element (B, Cr, Mn, Fe, Cu, Zn, As, Se, Sr, Sb, Ba, Hg, Pb) concentrations in the investigated waters are below 1 mg/L. The stable isotope (oxygen-18 and deuterium) composition of the Balıklı Spa water suggests that the origin of the thermal water is meteoric water.

  1. Formation of trihalomethanes as disinfection byproducts in herbal spa pools.

    PubMed

    Fakour, Hoda; Lo, Shang-Lien

    2018-04-09

    Herbal spa treatments are favorite recreational activities throughout the world. The water in spas is often disinfected to control pathogenic microorganisms and guarantee hygiene. However, chlorinated water may cause the formation of disinfection byproducts (DBPs). Although there have been many studies on DBP formation in swimming pools, the role of organic matter derived from herbal medicines applied in herbal spa water has been largely neglected. Accordingly, the present study investigated the effect of herbal medicines on the formation of trihalomethanes (THMs) in simulated herbal spa water. Water samples were collected from a spa pool, and then, disinfection and herbal addition experiments were performed in a laboratory. The results showed that the organic molecules introduced by the herbal medicines are significant precursors to the formation of THMs in spa pool water. Since at least 50% of THMs were produced within the first six hours of the reaction time, the presence of herbal medicines in spa water could present a parallel route for THM exposure. Therefore, despite the undeniable benefits of herbal spas, the effect of applied herbs on DBP formation in chlorinated water should be considered to improve the water quality and health benefits of spa facilities.

  2. Rapid detection of mecA and spa by the loop-mediated isothermal amplification (LAMP) method.

    PubMed

    Koide, Y; Maeda, H; Yamabe, K; Naruishi, K; Yamamoto, T; Kokeguchi, S; Takashiba, S

    2010-04-01

    To develop a detection assay for staphylococcal mecA and spa by using loop-mediated isothermal amplification (LAMP) method. Staphylococcus aureus and other related species were subjected to the detection of mecA and spa by both PCR and LAMP methods. The LAMP successfully amplified the genes under isothermal conditions at 64 degrees C within 60 min, and demonstrated identical results with the conventional PCR methods. The detection limits of the LAMP for mecA and spa, by gel electrophoresis, were 10(2) and 10 cells per tube, respectively. The naked-eye inspections were possible with 10(3) and 10 cells for detection of mecA and spa, respectively. The LAMP method was then applied to sputum and dental plaque samples. The LAMP and PCR demonstrated identical results for the plaque samples, although frequency in detection of mecA and spa by the LAMP was relatively lower for the sputum samples when compared to the PCR methods. Application of the LAMP enabled a rapid detection assay for mecA and spa. The assay may be applicable to clinical plaque samples. The LAMP offers an alternative detection assay for mecA and spa with a great advantage of the rapidity.

  3. Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs.

    PubMed

    Meeker, Daniel G; Jenkins, Samir V; Miller, Emily K; Beenken, Karen E; Loughran, Allister J; Powless, Amy; Muldoon, Timothy J; Galanzha, Ekaterina I; Zharov, Vladimir P; Smeltzer, Mark S; Chen, Jingyi

    2016-04-08

    Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species as "ESKAPE pathogens" on the basis of the rapidly decreasing availability of useful antibiotics. This emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens. In this study, we used Staphylococcus aureus ( S. aureus ) as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic (daptomycin) can be incorporated into polydopamine-coated gold nanocages (AuNC@PDA) and that daptomycin-loaded AuNC@PDA can be conjugated to antibodies targeting a species-specific surface protein (staphylococcal protein A; Spa) as a means of achieving selective delivery of the nanoconstructs directly to the bacterial cell surface. Targeting specificity was confirmed by demonstrating a lack of binding to mammalian cells, reduced photothermal and antibiotic killing of the Spa-negative species Staphylococcus epidermidis , and reduced killing of S. aureus in the presence of unconjugated anti-Spa antibodies. We demonstrate that laser irradiation at levels within the current safety standard for use in humans can be used to achieve both a lethal photothermal effect and controlled release of the antibiotic, thus resulting in a degree of therapeutic synergy capable of eradicating viable S. aureus cells. The system was validated using planktonic bacterial cultures of both methicillin-sensitive and methicillin-resistant S. aureus strains and subsequently shown to be effective in the context of an established biofilm, thus indicating that this approach could be used to facilitate the effective treatment of intrinsically resistant biofilm infections.

  4. Detrended Topographic Data of the South-pole Aitken Basin (SPA): Comparisons with Apollo 16 and Schiller-Schickard as Indications of the Formation and Evolution of the Spa Interior

    NASA Technical Reports Server (NTRS)

    Petro, N. E.; Hollibaugh-Baker, D.; Jolliff, B. L.

    2017-01-01

    Data from recent lunar orbital missions have provided critical insight into the surface composition, morphology, and geologic history of the Moon. A key region that has benefited from this new data is the South Pole-Aitken Basin (SPA), a key area for future sample return]. A key area of investigation of SPA has been the characterization of its surface, detailing the interior composition, geologic evolution, and possible exposure of deep-seated materials. Recently we have applied a number of datasets to ascertain the origin of surfaces in central SPA and identify units that represent the ancient SPA-derived impact melt and those that represent volcanic activity. Here we apply a technique that utilizes high-resolution topographic data to remove local slopes to highlight subtle topographic variations. Such detrended data allows us to characterize units that are either ancient (SPA impact melt) or that represent subsequent volcanic activity.

  5. Highly stable aptamers selected from a 2'-fully modified fGmH RNA library for targeting biomaterials.

    PubMed

    Friedman, Adam D; Kim, Dongwook; Liu, Rihe

    2015-01-01

    When developed as targeting ligands for the in vivo delivery of biomaterials to biological systems, RNA aptamers immediately face numerous obstacles, in particular nuclease degradation and post-selection 2' modification. This study aims to develop a novel class of highly stable, 2'-fully modified RNA aptamers that are ideal for the targeted delivery of biomaterials. We demonstrated the facile transcription of a fGmH (2'-F-dG, 2'-OMe-dA/dC/dU) RNA library with unexpected hydrophobicity, the direct selection of aptamers from a fGmH RNA library that bind Staphylococcus aureus Protein A (SpA) as a model target, and the superior nuclease and serum stability of these aptamers compared to 2'-partially modified RNA variants. Characterizations of fGmH RNA aptamers binding to purified SpA and to endogenous SpA present on the surface of S. aureus cells demonstrate fGmH RNA aptamer selectivity and stability. Significantly, fGmH RNA aptamers were able to functionalize, stabilize, and specifically deliver aggregation-prone silver nanoparticles (AgNPs) to S. aureus with SpA-dependent antimicrobial effects. This study describes a novel aptamer class with considerable potential to improve the in vivo applicability of nucleic acid-based affinity molecules to biomaterials.

  6. Clinical and Imaging Signs of Spondyloarthritis in First-Degree Relatives of HLA-B27-Positive Ankylosing Spondylitis Patients: The Pre-Spondyloarthritis (Pre-SpA) Cohort Study.

    PubMed

    Turina, Maureen C; de Winter, Janneke J; Paramarta, Jacky E; Gamala, Mihaela; Yeremenko, Nataliya; Nabibux, Marita N; Landewé, Robert; Baeten, Dominique L

    2016-10-01

    To investigate whether seemingly healthy first-degree relatives of patients with ankylosing spondylitis (AS) have clinical, laboratory, or imaging features of spondyloarthritis (SpA). First-degree relatives (ages 18-40 years) of HLA-B27-positive AS patients were included in the pre-spondyloarthritis (Pre-SpA) cohort, a prospective inception cohort study. Clinical, biologic, and imaging features were recorded. First-degree relatives were classified according to several sets of SpA classification criteria. We report baseline features of 51 first-degree relatives included in this study. Twenty-nine (57%) had back pain, 2 (4%) had psoriasis, 1 (2%) had inflammatory bowel disease, and 1 (2%) had uveitis. Three (6%) had low-grade sacroiliitis, 1 (2%) had cervical syndesmophytes on radiography, and 10 (20%) had bone marrow edema on magnetic resonance imaging of the sacroiliiac joints. Seventeen of 51 first-degree relatives (33%) fulfilled SpA classification criteria: 7 (14%) fulfilled both Assessment of SpondyloArthritis international Society (ASAS) axial SpA and European Spondylarthropathy Study Group (ESSG) classification criteria, 6 (12%) fulfilled only ASAS axial SpA classification criteria, and 4 (8%) fulfilled only ESSG classification criteria; 3 (6%) also fulfilled the Amor criteria. None fulfilled other SpA classification criteria. First-degree relatives fulfilling the ASAS axial SpA and/or ESSG classification criteria had more frequent inflammatory back pain, had a higher level of disease activity, and had more psoriasis. No differences were found in parameters of inflammation, peripheral and extraarticular disease other than psoriasis, and HLA-B27 positivity between those who did and those who did not fulfill the ASAS axial SpA and/or ESSG classification criteria. Four first-degree relatives (12%) who did not fulfill the ASAS axial SpA and/or ESSG classification criteria had imaging abnormalities suggestive of SpA. A substantial proportion of seemingly healthy first-degree relatives of HLA-B27-positive AS patients have clinical and/or imaging abnormalities suggestive of SpA. Thirty-three percent could be classified as having SpA. Further follow-up will show which first-degree relatives will develop clinically manifest SpA. © 2016, American College of Rheumatology.

  7. 78 FR 58868 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by Agusta Westland S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-25

    ... Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by Agusta Westland S.p.A) (Agusta... Office between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The AD docket contains... standard maintenance regulations. For helicopters with T/R hub and blade assembly, part number (P/N) 109...

  8. Moonrise: Sampling the South Pole-Aitken Basin to Address Problems of Solar System Significance

    NASA Technical Reports Server (NTRS)

    Zeigler, R. A.; Jolliff, B. L.; Korotev, R. L.; Shearer, C. K.

    2016-01-01

    A mission to land in the giant South Pole-Aitken (SPA) Basin on the Moon's southern farside and return a sample to Earth for analysis is a high priority for Solar System Science. Such a sample would be used to determine the age of the SPA impact; the chronology of the basin, including the ages of basins and large impacts within SPA, with implications for early Solar System dynamics and the magmatic history of the Moon; the age and composition of volcanic rocks within SPA; the origin of the thorium signature of SPA with implications for the origin of exposed materials and thermal evolution of the Moon; and possibly the magnetization that forms a strong anomaly especially evident in the northern parts of the SPA basin. It is well known from studies of the Apollo regolith that rock fragments found in the regolith form a representative collection of many different rock types delivered to the site by the impact process (Fig. 1). Such samples are well documented to contain a broad suite of materials that reflect both the local major rock formations, as well as some exotic materials from far distant sources. Within the SPA basin, modeling of the impact ejection process indicates that regolith would be dominated by SPA substrate, formed at the time of the SPA basin-forming impact and for the most part moved around by subsequent impacts. Consistent with GRAIL data, the SPA impact likely formed a vast melt body tens of km thick that took perhaps several million years to cool, but that nonetheless represents barely an instant in geologic time that should be readily apparent through integrated geochronologic studies involving multiple chronometers. It is anticipated that a statistically significant number of age determinations would yield not only the age of SPA but also the age of several prominent nearby basins and large craters within SPA. This chronology would provide a contrast to the Imbrium-dominated chronology of the nearside Apollo samples and an independent test of the timing of the lunar cataclysm.

  9. Production of bioinspired and rationally designed polymer hydrogels for controlled delivery of therapeutic proteins

    NASA Astrophysics Data System (ADS)

    Kim, Sung Hye

    Hydrogel systems for controlled delivery therapeutic growth factors have been developed in a wide spectrum of strategies: these systems aim for the release of growth factors via a passive diffusion, electrostatic interaction, degradation of hydrogels, and responsiveness to external stimuli. Heparin, a highly sulfated glycosaminoglycan (GAG), was employed for a targeted delivery system of vascular endothelial growth factor (VEGF) to endothelial cells overexpressing a relevant receptor VEGFR-2. Addition of dimeric VEGF to 4-arm star-shaped poly(ethylene glycol) (PEG) immobilized with low-molecular weight heparin (LMWH) afforded a non-covalently assembled hydrogel via interaction between heparin and VEGF, with storage modulus 10 Pa. The release of VEGF and hydrogel erosion reached maximum 100 % at day 4 in the presence of VEGFR-2 overexpressing pocine aortic endothelial cell (PAE/KDR), while those of 80% were achieved via passive release at day 5 in the presence of PAE cell lacking VEGFR-2 or in the absence of cell, indicating that the release of VEGF was in targeted manner toward cell receptor. The proliferation of PAE/KDR in the presence of [PEG-LMWH/VEGF] hydrogel was greater by ca. 30% at day 4 compared to that of PAE, confirming that the release of VEGF was in response to the cellular demand. The phosphorylation fraction of VEGFR-2 on PAE/KDR was greater in the presence of [PEG-LMWH/VEGF] hydrogel, increasing from 0.568 at day 1 to 0.790 at day 4, whereas it was maintained at 0.230 at day 4 in the presence of [PEG-LMWH] hydrogel. This study has proven that this hydrogel, assembled via bio-inspired non-covalent interaction, liberating VEGFon celluar demand to target cell, eroding upon VEGF release, and triggering endothelial cell proliferation, could be used in multiple applications including targeted delivery and angiogenesis. Heparin has been widely exploited in growth factor delivery systems owing to its ability to bind many growth factors through the flexible patterns of functional groups. However, heterogeneity in the composition and in the polydispersity of heparin has been problematic in controlled delivery system and thus motivated the development of homogeneous heparin mimics. Peptides of appropriate sequence and chemical function have therefore recently emerged as potential replacements for heparin in select applications. Studied was the assessment of the binding affinities of multiple sulfated peptides (SPs) for a set of heparin-binding peptides (HBPs) and for VEGF; these binding partners have application in the selective immobilization of proteins and in hydrogel formation through non-covalent interactions. Sulfated peptides were produced via solid-phase methods, and their affinity for the HBPs and VEGF was assessed via affinity liquid chromatography (ALC), surface plasmon resonance (SPR), and in select cases, isothermal titration calorimetry (ITC). The shortest peptide, SPa, showed the highest affinity binding of HBPs and VEGF165 in both ALC and SPR measurements, with slight exceptions. Of the investigated HBPs, a peptide based on the heparin-binding domain of human platelet factor 4 showed greatest binding affinities toward all of the SPs, consistent with its stronger binding to heparin. The affinity between SPa and PF4ZIP was indicated via SPR ( KD = 5.27 muM) and confirmed via ITC (KD = 8.09 muM). The binding by SPa of both VEGF and HBPs suggests its use as a binding partner to multiple species, and the use of these interactions in assembly of materials. Given that the peptide sequences can be varied to control binding affinity and selectivity, opportunities are also suggested for the production of a wider array of matrices with selective binding and release properties useful for biomaterials applications. Hydrogel consisting of SPa was formed via a covalent Michael Addition reaction between maleimide- and thiol-terminated multi-arm PEGs and Cys-SPa. The mechanical property of hydrogel was tunable from ca. 186 to 1940 Pa. by varing the cross-linking density, suggesting its flexible applications depending on matrix needs. The non-anti-coagulative property of SPa, assessed via activated partial thromboplastin time (APTT) and HeptestRTM in comparison to LMWH, implied its usefulness in applications without excessive bleeding. The VEGF released from [PEG-SPa] hydrogel showed up to ca. 400% greater bioactivity on proliferation of human umbilical vein endothelical cell (HUVEC) compared to the VEGF incubated in solution for the same period: this was significantly higher than that of [PEG] hydrogel (ca. 280%), suggesting the SPa may protect the bioactivity of VEGF when bound. The release of dual growth factor, i.e. VEGF and fibroblast growth factor-2 (FGF-2), were investigated on [PEG-SPa] hydrogel: the release of bFGF was lower than that of VEGF due to weaker binding affinity to matrix-bound SPa. The HUVEC culture on dual growth factor loaded [PEG-SPa] showed that the synergistic effects of dual system in select concentrations, suggesting the opportunity of manipulating cell responses. Given that sulfated peptides for various binding targets with desired affinity can be identified, applications are suggested in multiple growth factors delivery where an integrated action of multiple growth factors is required, such as angiogenesis.

  10. Spa therapy for elderly: a retrospective study of 239 older patients with osteoarthritis.

    PubMed

    Karagülle, Mine; Kardeş, Sinan; Dişçi, Rian; Gürdal, Hatice; Karagülle, Müfit Zeki

    2016-10-01

    Very few studies tested the effectiveness of spa therapy in older patients with osteoarthritis. Therefore, we aimed to evaluate the short-term effects of spa therapy in patients aged 65 years and older with generalized, knee, hip, and cervical and lumbar spine osteoarthritis. In an observational retrospective study design at the Medical Ecology and Hydroclimatology Department of Istanbul Medical Faculty, we analyzed the records of 239 patients aged over 65 years with the diagnosis of all types of osteoarthritis who were prescribed a spa therapy course in some spa resorts in Turkey between 7 March 2002 and 31 December 2012. They travelled to a spa resort where they stayed at a thermal spa hotel and followed the usual therapy packages for 2 weeks. Patients were assessed by an experienced physician within a week before the spa journey and within a week after the completion of the spa therapy. Compared with baseline in whole sample, statistically significant improvements were observed in pain (visual analog scale, VAS), patient and physician global assessments (VAS), Health Assessment Questionnaire disability index (HAQ-DI), Lequesne algofunctional index (LAFI) for knee, Western Ontario and McMaster Universities index (WOMAC), Waddell disability index (WDI), and Neck Pain and Disability Scale (NPAD). According to Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Set of Responder Criteria, responder rate were 63.8 % (51/80) in generalized, 52 % (13/25) in knee, 50 % (2/4) in hip, 66.7 % (8/12) in lumbar, and 100 % (6/6) in cervical osteoarthritis subgroups. Spa therapy improved pain and physical functional status in older patients with osteoarthritis, especially generalized osteoarthritis and multiple joint osteoarthritis with involvement of knee. This improvement was clinically important in majority of the patients. To confirm the results of this preliminary study, there is a need of a randomized controlled clinical study comparing spa therapy with usual care in the elderly population with osteoarthritis.

  11. Spa therapy for elderly: a retrospective study of 239 older patients with osteoarthritis

    NASA Astrophysics Data System (ADS)

    Karagülle, Mine; Kardeş, Sinan; Dişçi, Rian; Gürdal, Hatice; Karagülle, Müfit Zeki

    2016-10-01

    Very few studies tested the effectiveness of spa therapy in older patients with osteoarthritis. Therefore, we aimed to evaluate the short-term effects of spa therapy in patients aged 65 years and older with generalized, knee, hip, and cervical and lumbar spine osteoarthritis. In an observational retrospective study design at the Medical Ecology and Hydroclimatology Department of Istanbul Medical Faculty, we analyzed the records of 239 patients aged over 65 years with the diagnosis of all types of osteoarthritis who were prescribed a spa therapy course in some spa resorts in Turkey between 7 March 2002 and 31 December 2012. They travelled to a spa resort where they stayed at a thermal spa hotel and followed the usual therapy packages for 2 weeks. Patients were assessed by an experienced physician within a week before the spa journey and within a week after the completion of the spa therapy. Compared with baseline in whole sample, statistically significant improvements were observed in pain (visual analog scale, VAS), patient and physician global assessments (VAS), Health Assessment Questionnaire disability index (HAQ-DI), Lequesne algofunctional index (LAFI) for knee, Western Ontario and McMaster Universities index (WOMAC), Waddell disability index (WDI), and Neck Pain and Disability Scale (NPAD). According to Outcome Measures in Rheumatology—Osteoarthritis Research Society International (OMERACT-OARSI) Set of Responder Criteria, responder rate were 63.8 % (51/80) in generalized, 52 % (13/25) in knee, 50 % (2/4) in hip, 66.7 % (8/12) in lumbar, and 100 % (6/6) in cervical osteoarthritis subgroups. Spa therapy improved pain and physical functional status in older patients with osteoarthritis, especially generalized osteoarthritis and multiple joint osteoarthritis with involvement of knee. This improvement was clinically important in majority of the patients. To confirm the results of this preliminary study, there is a need of a randomized controlled clinical study comparing spa therapy with usual care in the elderly population with osteoarthritis.

  12. Diagnosis and Management of Late-Onset Spondyloarthritis: Implications of Treat-to-Target Recommendations.

    PubMed

    Toussirot, Éric

    2015-07-01

    Spondyloarthritis (SpA) is usually observed in young patients while onset in the elderly is less common. Late-onset forms of SpA may become more common due to longer life expectancy. The clinical spectrum of late-onset SpA is as broad as in young people, with a predominance of peripheral SpA over pure axial disease. The Assessment of SpondyloArthritis international Society (ASAS) has developed new criteria for axial or peripheral SpA that allow patients aged under 45 years at the time of disease onset to be identified. These criteria are not theoretically adapted for the classification of patients with late-onset disease but they are useful for the diagnosis. Similarly, magnetic resonance imaging (MRI) is now widely used for the early recognition of sacroiliitis or spinal inflammation in SpA, and sacroiliitis as evidenced by MRI is included in the ASAS criteria for axial SpA. Nevertheless, the utility of sacroiliac joint and/or spine inflammation as detected by MRI has mostly been described in young patients with ankylosing spondylitis, SpA, or inflammatory back pain, but not in the elderly. The management of SpA is now more focused on remission or, alternatively, low disease activity, according to the treat-to-target recommendations. Such an optimized approach to therapy is thought to improve patient outcomes and ultimately long-term quality of life. The same principles of treatment should apply in the elderly, but require certain adjustments, especially with biological agents. Tumor necrosis factor-α blocking agents are very effective in SpA, but seem slightly less effective in the elderly and are associated with an increased risk of infection in this population. A careful and rigorous evaluation is thus required before initiating these agents in elderly subjects.

  13. Student peer assessment in evidence-based medicine (EBM) searching skills training: an experiment

    PubMed Central

    Eldredge, Jonathan D.; Bear, David G.; Wayne, Sharon J.; Perea, Paul P.

    2013-01-01

    Background: Student peer assessment (SPA) has been used intermittently in medical education for more than four decades, particularly in connection with skills training. SPA generally has not been rigorously tested, so medical educators have limited evidence about SPA effectiveness. Methods: Experimental design: Seventy-one first-year medical students were stratified by previous test scores into problem-based learning tutorial groups, and then these assigned groups were randomized further into intervention and control groups. All students received evidence-based medicine (EBM) training. Only the intervention group members received SPA training, practice with assessment rubrics, and then application of anonymous SPA to assignments submitted by other members of the intervention group. Results: Students in the intervention group had higher mean scores on the formative test with a potential maximum score of 49 points than did students in the control group, 45.7 and 43.5, respectively (P = 0.06). Conclusions: SPA training and the application of these skills by the intervention group resulted in higher scores on formative tests compared to those in the control group, a difference approaching statistical significance. The extra effort expended by librarians, other personnel, and medical students must be factored into the decision to use SPA in any specific educational context. Implications: SPA has not been rigorously tested, particularly in medical education. Future, similarly rigorous studies could further validate use of SPA so that librarians can optimally make use of limited contact time for information skills training in medical school curricula. PMID:24163593

  14. Inhibition of TNF-{alpha}-mediated inflammatory responses by a benzodioxolylacetylamino-linked benzothiazole analog in human fibroblast-like synoviocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Young-Rae; Jin, Guo Hua; Lee, Sang-Myeong

    Highlights: {yields} We synthesized SPA0537, a benzothiazole analog. {yields} SPA0537 is a potent NF-{kappa}B inhibitor. {yields} SPA0537 suppresses the production of proinflammatory mediators in human rheumatoid fibroblast-like synoviocytes. {yields} SPA0537 is effective at suppressing osteoclast differentiation. -- Abstract: The pathologic processes of rheumatoid arthritis are mediated by a number of cytokines, chemokines, and matrix metalloproteinases, the expressions of which are controlled by NF-{kappa}B. This study was performed to explore the effects of a benzothiazole analog, SPA0537, on the control of the NF-{kappa}B activation pathway. We also investigated whether SPA0537 had any anti-inflammatory effects in human rheumatoid fibroblast-like synoviocytes (FLS). SPA0537more » inhibited the nuclear translocation and the DNA binding of NF-{kappa}B subunits, which correlated with the inhibitory effects on IKK phosphorylation and I{kappa}B{alpha} degradation in TNF-{alpha}-stimulated rheumatoid FLS. These events further suppressed chemokine production, matrix metalloproteinase secretion, and TNF-{alpha}-induced cell proliferation. In addition, SPA0537 inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor (MCSF) and receptor activator of the NF-{kappa}B ligand (RANKL) in bone marrow macrophages. These findings suggest that SPA0537 exerts anti-inflammatory effects in rheumatoid FLS through the inhibition of the NF-{kappa}B pathway. Therefore, it may have therapeutic value for the treatment of rheumatoid arthritis.« less

  15. Preparation and characterization of superporous agarose-reticulated vitreous carbon electrodes as platforms for electrochemical bioassays.

    PubMed

    Rao, Ashwin K; Creager, Stephen E

    2008-08-01

    Three-dimensional flow-through electrodes were fabricated using superporous agarose (SPA) and reticulated vitreous carbon (RVC) composite materials that were suitable as a platform for sandwich assays. These SPA-RVC composite electrodes were fabricated by fitting a SPA-RVC composite cylinder inside a graphite tube and subsequently fixing the graphite tube onto a polypropylene micropipette tip. The electrode design allows for ease in reagent/washing steps involved in sandwich assay protocols and could easily be made portable. The electrode materials were characterized with respect to pore-size distribution, total free volume, ligament and bulk densities of the RVC, and physical structural characteristics. Coulometric detection of redox molecules such as K(3)Fe(CN)(6) and 4-aminophenol was possible using SPA-RVC electrodes by the trapping of these redox molecules inside the SPA-RVC electrodes. Avidin affinity molecules were covalently immobilized onto the SPA matrix inside the RVC electrodes by periodate-activation followed by reductive amination. The amount of avidin immobilized inside the SPA-RVC electrodes was (5+/-0.06)x10(-11) mol, which was determined by saturating the avidin sites with biotinylated fluorescein (b-fluo) and subsequently determining the amount of immobilized b-fluo via a standard addition method using fluorescence spectroscopy. Non-specific binding of labeled enzymes such as biotinylated alkaline phosphatase (b-ALP) onto the SPA-RVC electrodes without avidin capture sites was determined to be less than 1% compared to the specific binding of b-ALP on avidinylated SPA-RVC electrodes.

  16. A pilot study to evaluate the effects of floatation spa treatment on patients with osteoarthritis.

    PubMed

    Hill, S; Eckett, M J; Paterson, C; Harkness, E F

    1999-12-01

    To conduct a preliminary investigation of the effects on floatation spa therapy on quality of life in patients with osteoarthritis to see if controlled trials are warranted. Uncontrolled clinical trial. Private floatation spa therapy centre. Fourteen patients with chronic osteoarthritis of the weight-bearing joints, of whom four dropped out. Six weekly sessions of floatation spa therapy. SF36, AIMS2 and MYMOP quality-of-life questionnaires. All patients improved. Differences between baseline and discharge scores showed statistically significant improvement for MYMOP, but not AIMS2 or SF-36. Controlled trials of floatation spa therapy for patients with osteoarthritis are warranted.

  17. The successive projection algorithm as an initialization method for brain tumor segmentation using non-negative matrix factorization.

    PubMed

    Sauwen, Nicolas; Acou, Marjan; Bharath, Halandur N; Sima, Diana M; Veraart, Jelle; Maes, Frederik; Himmelreich, Uwe; Achten, Eric; Van Huffel, Sabine

    2017-01-01

    Non-negative matrix factorization (NMF) has become a widely used tool for additive parts-based analysis in a wide range of applications. As NMF is a non-convex problem, the quality of the solution will depend on the initialization of the factor matrices. In this study, the successive projection algorithm (SPA) is proposed as an initialization method for NMF. SPA builds on convex geometry and allocates endmembers based on successive orthogonal subspace projections of the input data. SPA is a fast and reproducible method, and it aligns well with the assumptions made in near-separable NMF analyses. SPA was applied to multi-parametric magnetic resonance imaging (MRI) datasets for brain tumor segmentation using different NMF algorithms. Comparison with common initialization methods shows that SPA achieves similar segmentation quality and it is competitive in terms of convergence rate. Whereas SPA was previously applied as a direct endmember extraction tool, we have shown improved segmentation results when using SPA as an initialization method, as it allows further enhancement of the sources during the NMF iterative procedure.

  18. In vitro interaction between SURFACEN® and surfactant protein A against Leishmania amazonensis.

    PubMed

    de Guevara, Yuliannis Lugones Ladrón; Hidalgo, Odalys Blanco; Faure, Roberto; Fidalgo, Lianet Monzote

    2013-01-01

    Leishmaniasis is caused by a parasite of the Leishmania genus, affecting more than 12 million people in 98 countries. The control of leishmaniasis remains a serious problem. There are currently no vaccines for leishmaniasis. The drugs available are toxic, expensive and frequently ineffective. The in vitro activity of SURFACEN® and SP-A against Leishmania amazonensis was evaluated. The combination of both products resulted in a synergic pharmacology effect, demonstrated by a fractional inhibitory concentration index <0.5. A more effective combination was a SURFACEN/SP-A ratio of 4:1, using a method of fixed ratio. The therapeutic effect of SURFACEN and SP-A as antileishmanial compounds was demonstrated, with a potentiation of activity when they were incubated in conjunction. Our results propose an exploration of these products in order to design new formulations against the Leishmania parasite. © 2014 S. Karger AG, Basel.

  19. Fetal-to-maternal signaling to initiate parturition

    PubMed Central

    Reinl, Erin L.; England, Sarah K.

    2015-01-01

    Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition. PMID:26098207

  20. Bombesin-like peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation.

    PubMed

    Emanuel, R L; Torday, J S; Mu, Q; Asokananthan, N; Sikorski, K A; Sunday, M E

    1999-11-01

    Previously, we have shown that bombesin-like peptide (BLP) promotes fetal lung development in rodents and humans but mediates postnatal lung injury in hyperoxic baboons. The present study analyzed the normal ontogeny of BLP and BLP receptors as well as the effects of BLP on cultured normal fetal baboon lungs. Transcripts encoding gastrin-releasing peptide (GRP), a pulmonary BLP, were detectable on gestational day 60 (ED60), peaked on approximately ED90, and then declined before term (ED180). Numbers of BLP-immunopositive neuroendocrine cells peaked from ED80 to ED125 and declined by ED160, preceding GRP-receptor mRNAs detected from ED125 until birth. BLP (0.1-10 nM) stimulated type II cell differentiation in organ cultures as assessed by [(3)H]choline incorporation into surfactant phospholipids, electron microscopy, and increased surfactant protein (SP) A- and/or SP-C-immunopositive cells and SP-A mRNA. BLP also induced neuroendocrine differentiation on ED60. Cell proliferation was induced by GRP, peaking on ED90. Similarly, blocking BLP degradation stimulated lung growth and maturation, which was completely reversed by a BLP-specific antagonist. The dissociation between GRP and GRP-receptor gene expression during ontogeny suggests that novel BLP receptors and/or peptides might be implicated in these responses.

  1. More than Just IQ: A Longitudinal Examination of Self-Perceived Abilities as Predictors of Academic Performance in a Large Sample of UK Twins

    ERIC Educational Resources Information Center

    Chamorro-Premuzic, Tomas; Harlaar, Nicole; Greven, Corina U.; Plomin, Robert

    2010-01-01

    This paper examines the longitudinal causal relationship between self-perceived abilities (SPA) and academic achievement (Ach) while controlling for cognitive ability (CA). In all, 5957 UK school children were assessed on SPA, Ach and CA at ages 9 and 12. Results indicated that SPA and Ach at age 9 independently affected both SPA and Ach at age…

  2. The Relationship of Gender and Self-Efficacy on Social Physique Anxiety among College Students.

    PubMed

    Rothberger, Sara M; Harris, Brandonn S; Czech, Daniel R; Melton, Bridget

    The anxiety or fear associated with physique evaluation is defined as Social Physique Anxiety (SPA). Numerous studies have examined this construct, yet a gap exists exploring this phenomenon among current college students with SPA, self-efficacy, and gender concurrently. Therefore, the purposes of this study included quantitatively analyzing the association between SPA, gender, and self-efficacy. Participants included 237 students at a Southeastern university participating in jogging, body conditioning, or weight training courses. Analysis of Variance yielded a significant main effect for self-efficacy as well, as those with lower self-efficacy displayed higher levels of SPA ( p < 0.001). Stepwise regression analysis indicated self-efficacy and gender were both significant predictors of SPA. This information could aid in creating interventions designed to decrease the prevalence of SPA and increase levels of self-efficacy among the current college student population.

  3. Transgenic cells with increased plastoquinone levels and methods of use

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sayre, Richard T.; Subramanian, Sowmya; Cahoon, Edgar

    Disclosed herein are transgenic cells expressing a heterologous nucleic acid encoding a prephenate dehydrogenase (PDH) protein, a heterologous nucleic acid encoding a homogentisate solanesyl transferase (HST) protein, a heterologous nucleic acid encoding a deoxyxylulose phosphate synthase (DXS) protein, or a combination of two or more thereof. In particular examples, the disclosed transgenic cells have increased plastoquinone levels. Also disclosed are methods of increasing cell growth rates or production of biomass by cultivating transgenic cells expressing a heterologous nucleic acid encoding a PDH protein, a heterologous nucleic acid encoding an HST protein, a heterologous nucleic acid encoding a DXS protein, ormore » a combination of two or more thereof under conditions sufficient to produce cell growth or biomass.« less

  4. Distribution of the Most Prevalent Spa Types among Clinical Isolates of Methicillin-Resistant and -Susceptible Staphylococcus aureus around the World: A Review

    PubMed Central

    Asadollahi, Parisa; Farahani, Narges Nodeh; Mirzaii, Mehdi; Khoramrooz, Seyed Sajjad; van Belkum, Alex; Asadollahi, Khairollah; Dadashi, Masoud; Darban-Sarokhalil, Davood

    2018-01-01

    Background: Staphylococcus aureus, a leading cause of community-acquired and nosocomial infections, remains a major health problem worldwide. Molecular typing methods, such as spa typing, are vital for the control and, when typing can be made more timely, prevention of S. aureus spread around healthcare settings. The current study aims to review the literature to report the most common clinical spa types around the world, which is important for epidemiological surveys and nosocomial infection control policies. Methods: A search via PubMed, Google Scholar, Web of Science, Embase, the Cochrane library, and Scopus was conducted for original articles reporting the most prevalent spa types among S. aureus isolates. The search terms were “Staphylococcus aureus, spa typing.” Results: The most prevalent spa types were t032, t008 and t002 in Europe; t037 and t002 in Asia; t008, t002, and t242 in America; t037, t084, and t064 in Africa; and t020 in Australia. In Europe, all the isolates related to spa type t032 were MRSA. In addition, spa type t037 in Africa and t037and t437 in Australia also consisted exclusively of MRSA isolates. Given the fact that more than 95% of the papers we studied originated in the past decade there was no option to study the dynamics of regional clone emergence. Conclusion: This review documents the presence of the most prevalent spa types in countries, continents and worldwide and shows big local differences in clonal distribution. PMID:29487578

  5. The Molecular Epidemiology of the Highly Virulent ST93 Australian Community Staphylococcus aureus Strain

    PubMed Central

    Coombs, Geoffrey W.; Goering, Richard V.; Chua, Kyra Y. L.; Monecke, Stefan; Howden, Benjamin P.; Stinear, Timothy P.; Ehricht, Ralf; O’Brien, Frances G.; Christiansen, Keryn J.

    2012-01-01

    In Australia the PVL - positive ST93-IV [2B], colloquially known as “Queensland CA-MRSA” has become the dominant CA-MRSA clone. First described in the early 2000s, ST93-IV [2B] is associated with skin and severe invasive infections including necrotizing pneumonia. A singleton by multilocus sequence typing (MLST) eBURST analysis ST93 is distinct from other S aureus clones. To determine if the increased prevalence of ST93-IV [2B] is due to the widespread transmission of a single strain of ST93-IV [2B] the genetic relatedness of 58 S. aureus ST93 isolated throughout Australia over an extended period were studied in detail using a variety of molecular methods including pulsed-field gel electrophoresis, spa typing, MLST, microarray DNA, SCCmec typing and dru typing. Identification of the phage harbouring the lukS-PV/lukF-PV Panton Valentine leucocidin genes, detection of allelic variations in lukS-PV/lukF-PV, and quantification of LukF-PV expression was also performed. Although ST93-IV [2B] is known to have an apparent enhanced clinical virulence, the isolates harboured few known virulence determinants. All PVL-positive isolates carried the PVL-encoding phage ΦSa2USA and the lukS-PV/lukF-PV genes had the same R variant SNP profile. The isolates produced similar expression levels of LukF-PV. Although multiple rearrangements of the spa sequence have occurred, the core genome in ST93 is very stable. The emergence of ST93-MRSA is due to independent acquisitions of different dru-defined type IV and type V SCCmec elements in several spa-defined ST93-MSSA backgrounds. Rearrangement of the spa sequence in ST93-MRSA has subsequently occurred in some of these strains. Although multiple ST93-MRSA strains were characterised, little genetic diversity was identified for most isolates, with PVL-positive ST93-IVa [2B]-t202-dt10 predominant across Australia. Whether ST93-IVa [2B] t202-dt10 arose from one PVL-positive ST93-MSSA-t202, or by independent acquisitions of SCCmec-IVa [2B]-dt10 into multiple PVL-positive ST93-MSSA-t202 strains is not known. PMID:22900085

  6. Discriminatory Indices of Typing Methods for Epidemiologic Analysis of Contemporary Staphylococcus aureus Strains.

    PubMed

    Rodriguez, Marcela; Hogan, Patrick G; Satola, Sarah W; Crispell, Emily; Wylie, Todd; Gao, Hongyu; Sodergren, Erica; Weinstock, George M; Burnham, Carey-Ann D; Fritz, Stephanie A

    2015-09-01

    Historically, a number of typing methods have been evaluated for Staphylococcus aureus strain characterization. The emergence of contemporary strains of community-associated S. aureus, and the ensuing epidemic with a predominant strain type (USA300), necessitates re-evaluation of the discriminatory power of these typing methods for discerning molecular epidemiology and transmission dynamics, essential to investigations of hospital and community outbreaks. We compared the discriminatory index of 5 typing methods for contemporary S. aureus strain characterization. Children presenting to St. Louis Children's Hospital and community pediatric practices in St. Louis, Missouri (MO), with community-associated S. aureus infections were enrolled. Repetitive sequence-based PCR (repPCR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal protein A (spa), and staphylococcal cassette chromosome (SCC) mec typing were performed on 200 S. aureus isolates. The discriminatory index of each method was calculated using the standard formula for this metric, where a value of 1 is highly discriminatory and a value of 0 is not discriminatory. Overall, we identified 26 distinct strain types by repPCR, 17 strain types by PFGE, 30 strain types by MLST, 68 strain types by spa typing, and 5 strain types by SCCmec typing. RepPCR had the highest discriminatory index (D) of all methods (D = 0.88), followed by spa typing (D = 0.87), MLST (D = 0.84), PFGE (D = 0.76), and SCCmec typing (D = 0.60). The method with the highest D among MRSA isolates was repPCR (D = 0.64) followed by spa typing (D = 0.45) and MLST (D = 0.44). The method with the highest D among MSSA isolates was spa typing (D = 0.98), followed by MLST (D = 0.93), repPCR (D = 0.92), and PFGE (D = 0.89). Among isolates designated USA300 by PFGE, repPCR was most discriminatory, with 10 distinct strain types identified (D = 0.63). We identified 45 MRSA isolates which were classified as identical by PFGE, MLST, spa typing, and SCCmec typing (USA300, ST8, t008, SCCmec IV, respectively); within this collection, there were 5 distinct strain types identified by repPCR. The typing methods yielded comparable discriminatory power for S. aureus characterization overall; when discriminating among USA300 isolates, repPCR retained the highest discriminatory power. This property is advantageous for investigations conducted in the era of contemporary S. aureus infections.

  7. Discriminatory Indices of Typing Methods for Epidemiologic Analysis of Contemporary Staphylococcus aureus Strains

    PubMed Central

    Rodriguez, Marcela; Hogan, Patrick G.; Satola, Sarah W.; Crispell, Emily; Wylie, Todd; Gao, Hongyu; Sodergren, Erica; Weinstock, George M.; Burnham, Carey-Ann D.; Fritz, Stephanie A.

    2015-01-01

    Abstract Historically, a number of typing methods have been evaluated for Staphylococcus aureus strain characterization. The emergence of contemporary strains of community-associated S. aureus, and the ensuing epidemic with a predominant strain type (USA300), necessitates re-evaluation of the discriminatory power of these typing methods for discerning molecular epidemiology and transmission dynamics, essential to investigations of hospital and community outbreaks. We compared the discriminatory index of 5 typing methods for contemporary S. aureus strain characterization. Children presenting to St. Louis Children's Hospital and community pediatric practices in St. Louis, Missouri (MO), with community-associated S. aureus infections were enrolled. Repetitive sequence-based PCR (repPCR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal protein A (spa), and staphylococcal cassette chromosome (SCC) mec typing were performed on 200 S. aureus isolates. The discriminatory index of each method was calculated using the standard formula for this metric, where a value of 1 is highly discriminatory and a value of 0 is not discriminatory. Overall, we identified 26 distinct strain types by repPCR, 17 strain types by PFGE, 30 strain types by MLST, 68 strain types by spa typing, and 5 strain types by SCCmec typing. RepPCR had the highest discriminatory index (D) of all methods (D = 0.88), followed by spa typing (D = 0.87), MLST (D = 0.84), PFGE (D = 0.76), and SCCmec typing (D = 0.60). The method with the highest D among MRSA isolates was repPCR (D = 0.64) followed by spa typing (D = 0.45) and MLST (D = 0.44). The method with the highest D among MSSA isolates was spa typing (D = 0.98), followed by MLST (D = 0.93), repPCR (D = 0.92), and PFGE (D = 0.89). Among isolates designated USA300 by PFGE, repPCR was most discriminatory, with 10 distinct strain types identified (D = 0.63). We identified 45 MRSA isolates which were classified as identical by PFGE, MLST, spa typing, and SCCmec typing (USA300, ST8, t008, SCCmec IV, respectively); within this collection, there were 5 distinct strain types identified by repPCR. The typing methods yielded comparable discriminatory power for S. aureus characterization overall; when discriminating among USA300 isolates, repPCR retained the highest discriminatory power. This property is advantageous for investigations conducted in the era of contemporary S. aureus infections. PMID:26376402

  8. Health tourism in a Czech health spa.

    PubMed

    Speier, Amy R

    2011-04-01

    This paper is about the changing shape of health tourism in a Czech spa town. The research focuses on balneotherapy as a traditional Czech healing technique, which involves complex drinking and bathing therapies, as it is increasingly being incorporated into the development of a Czech health tourism industry. Today, the health tourism industry in Mariánske Lázne is attempting to 'harmoniously' combine three elements--balneology, travel and business activities. One detects subtle shifts and consequent incongruities as doctors struggle for control over the medical portion of spa hotels. At the same time, marketing groups are creating new packages for a general clientele, and the implementation of these new packages de-medicalizes balneotherapy. Related to the issue of the doctor's authority in the spa, the changes occurring with the privatization of tourism entails the entrance of 'tourists' to Mariánske Lázne who are not necessarily seeking spa treatment but who are still staying at spa hotels. There is a general consensus among spa doctors and employees that balneotherapy has become commodified. Thus, while balneotherapy remains a traditional form of therapy, the commercial context in which it exists has created a new form of health tourism.

  9. Volume of Impact Melt Generated by the Formation of the South Pole-Aitken Basin

    NASA Technical Reports Server (NTRS)

    Petro, Noah E.

    2011-01-01

    The South Pole-Aitken Basin (SPA) is the largest, deepest, and oldest identified basin on the Moon and as such contains surfaces that are unique due to their age, composition, and depth of origin in the lunar crust [1-5] (Figure 1). SPA has been a target of intense interest as an area for robotic sample return in order to determine the age of the basin and the composition and origin of its interior [6-8]. In response to this interest there have been several efforts to estimate the likely provenance of regolith material within central SPA [9-12]. These model estimates suggest that, despite the formation of basins and craters following SPA, the regolith within SPA is dominated by locally derived material. An assumption of these models has been that the locally derived material is primarily SPA impact-melt as opposed to local basement material (e.g. unmelted lower crust). However, the definitive identification of SPA derived impact melt on the basin floor, either by remote sensing [5, 13] or via photogeology [2, 14] is extremely difficult due to the number of subsequent impacts and volcanic activity [4].

  10. A multicenter randomized controlled trial evaluating balneotherapy in patients with advanced chronic venous insufficiency.

    PubMed

    Carpentier, Patrick H; Blaise, Sophie; Satger, Bernadette; Genty, Céline; Rolland, Carole; Roques, Christian; Bosson, Jean-Luc

    2014-02-01

    Apart from compression therapy, physical therapy has scarcely been evaluated in the treatment of chronic venous disorders (CVDs). Spa treatment is a popular way to administer physical therapy for CVDs in France, but its efficacy has not yet been assessed in a large trial. The objective was to assess the efficacy of spa therapy for patients with advanced CVD (CEAP clinical classes C4-C5). This was a single-blind (treatment concealed to the investigators) randomized, multicenter, controlled trial (French spa resorts). Inclusion criteria were primary or post-thrombotic CVD with skin changes but no active ulcer (C4a, C4b, or C5). The treated group had the usual 3-week spa treatment course soon after randomization; the control group had spa treatment after the 1-year comparison period. All patients continued their usual medical care including wearing compression stockings. Treatment consisted of four balneotherapy sessions per day for 6 days a week. Follow-up was performed at 6, 12 and 18 months by independent blinded investigators. The main outcome criterion was the incidence of leg ulcers at 12 months. Secondary criteria were a modified version of the Venous Clinical Severity Score, a visual analog scale for leg symptoms, and the Chronic Venous Insufficiency Questionnaire 2 and EuroQol 5D quality-of-life autoquestionnaires. Four hundred twenty-five subjects were enrolled: 214 in the treatment group (Spa) and 211 in the control group (Ctr); they were similar at baseline regarding their demographic characteristics, the severity of the CVD, and the outcome variables. At 1 year, the incidence of leg ulcers was not statistically different (Spa: +9.3%; 95% confidence interval [CI], +5.6 - +14.3; Ctr: +6.1%; 95% CI, +3.2 - +10.4), whereas the Venous Clinical Severity Score improved significantly in the treatment group (Spa: -1.2; 95% CI, -1.6 - -0.8; Ctr: -0.6; 95% CI, -1.0 - -0.2; P = .04). A significant difference favoring spa treatment was found regarding symptoms after 1 year (Spa: -0.03; 95% CI, -0.57 - +0.51; Ctr: +0.87; 95% CI,+0.46 - +1.26; P = .009). EuroQol 5D improved in the treatment group (Spa: +0.01; 95% CI, -0.02 - +0.04) while it worsened (Ctr: -0.07; 95% CI, -0.10 - -0.04) in the control group (P < .001). A similar pattern was found for the Chronic Venous Insufficiency Questionnaire 2 scale (Spa: -2.0; 95% CI, -4.4 - +0.4; Ctr: +2.4; 95% CI, +0.2 - +4.7; P = .008). The control patients showed similar improvements in clinical severity, symptoms, and quality of life after their own spa treatment (day 547). In this study, the incidence of leg ulcers was not reduced after a 3-week spa therapy course. Nevertheless, our study demonstrates that spa therapy provides a significant and substantial improvement in clinical status, symptoms, and quality of life of patients with advanced venous insufficiency for at least 1 year. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  11. SPArking Interest in the Long Noncoding RNA World: A New Class of 5' SnoRNA-Stabilized LncRNA that Influences Alternative Splicing.

    PubMed

    Li, Ruohan; Fox, Archa H

    2016-11-03

    Delving deeply into the locus deleted in Prader-Willi syndrome, in this issue of Molecular Cell, Wu et al. (2016) identify SPA RNAs, a new class of 5' snoRNA-capped lncRNAs that sequester RNA binding proteins and influence alternative splicing. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Isolation, pathogenicity and disinfection of Staphylococcus aureus carried by insects in two public hospitals of Vitória da Conquista, Bahia, Brazil.

    PubMed

    Oliveira, Pollianna S; Souza, Simone G; Campos, Guilherme B; da Silva, Danilo C C; Sousa, Daniel S; Araújo, Suerda P F; Ferreira, Laiziane P; Santos, Verena M; Amorim, Aline T; Santos, Angelita M O G; Timenetsky, Jorge; Cruz, Mariluze P; Yatsuda, Regiane; Marques, Lucas M

    2014-01-01

    Currently, hospital infection is a serious public health problem, and several factors may influence the occurrence of these infections, including the presence of insects, which are carriers of multidrug-resistant bacterial species. The aim of this study was to isolate staphylococci carried by insects in two public hospitals of Vitoria da Conquista, Bahia and to identify the resistance profile, pathogenicity and efficacy of disinfection of the premises. A total of 91 insects were collected in 21 strategic points of these hospitals, and 32 isolated strains of Staphylococcus aureus were isolated. Based on antibiogram and Minimum Inhibitory Concentration results, 95% of these strains were susceptible to oxacillin. These strains were also evaluated for the presence of resistance genes encoding resistance to oxacillin/methicillin by polymerase chain reaction, but the sample was negative for this gene. Pathogenicity tests were performed in vitro biofilm formation induced by glucose, where it was found that eight (27.58%) strains were classified as biofilm producers and 21 (72.4%) as stronger producers. In addition, we performed PCR for their virulence genes: Sea (enterotoxin A), SEB (B), Sec (C), PVL (Panton-Valentine Leukocidin), ClfA (clumping factor A) and Spa (protein A). Of these, Sea, Spa PVL were positive in 7 (21.8%), 2 (6.3%) and 1 (3.1%) samples, respectively. The analysis of cytokine induction in the inflammatory response of J774 macrophages by isolates from the two hospitals did not show statistical difference at the levels of IL-6, TNF-α, IL-1 and IL-10 production. In addition, we verified the antimicrobial activity of disinfecting agents on these strains, quaternary ammonium, 0.5% sodium hypochlorite, 1% sodium hypochlorite, 2% sodium hypochlorite, 2% glutaraldehyde, Lysoform(®), 70% alcohol solution of chlorhexidine digluconate, 2% peracetic acid, and 100% vinegar. Resistance was seen in only for the following two disinfectants: 70% alcohol in 31 (96.8%) samples tested and vinegar in 30 (93.8%) samples. The study demonstrated the presence of resistant and pathogenic organisms conveyed by insects, thus suggesting improvement in efforts to control these vectors. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  13. Drug survival of the first course of anti-TNF agents in patients with rheumatoid arthritis and seronegative spondyloarthritis: analysis from the MonitorNet database.

    PubMed

    Scirè, Carlo A; Caporali, Roberto; Sarzi-Puttini, Piercarlo; Frediani, Bruno; Di Franco, Manuela; Tincani, Angela; Sinigaglia, Luigi; Sfriso, Paolo; Tirri, Rosella; Bellis, Emanuela; Delsante, Giovanni; Porru, Giovanni; Salaffi, Fausto; Giuggioli, Dilia; Rossini, Maurizio; Todoerti, Monica; Bazzichi, Laura; Govoni, Marcello; Gerli, Roberto; Raschetti, Roberto; Minisola, Giovanni; Montecucco, Carlomaurizio; Todesco, Silvano

    2013-01-01

    To compare drug survival of different anti-TNF drugs (infliximab, INF, etanercept, ETA, and adalimumab, ADA) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) by analysing data collected from an Italian multicenter observational cohort study. All patients with RA or SpA registered in the MonitorNet database who started their first course of anti-TNF therapy were included. Overall drug survival was measured, along with specific reasons of discontinuation (inefficacy or adverse events). A first set of analyses using RA as reference category assessed the relationship between diagnosis and drug survival. A second set of analyses stratified by diagnosis (RA and SpA) used INF as reference drug. Adjustment for confounders was performed. The results are presented as adjusted hazard ratios (adjHR) and 95% confidence intervals (95%CI). 2640 RA patients and 1220 SpA patients with a median follow-up of 17 months (IQR 7.2-33.4) were included in the analyses. Patients with a diagnosis of SpA showed a lower risk of drug discontinuation with an adjHR (95%CI) of 0.81 (0.73, 0.90). In SpA, the subset of patients with ankylosing spondylitis (AS) showed the best survival on treatment. In RA, both ETA and ADA showed a significantly lower probability of withdrawal when compared to INF [adjHR (95%CI) 0.46 (0.38, 0.56) and 0.68 (0.57, 0.81), respectively]. Similar results were found in SpA. Drug survival for SpA is longer than that in RA mainly due to the AS subgroup. In both RA and SpA, ETA and ADA showed a better retention on treatment when compared to INF.

  14. Intervening on spontaneous physical activity to prevent weight regain in older adults: design of a randomized, clinical trial.

    PubMed

    Nicklas, Barbara J; Gaukstern, Jill E; Legault, Claudine; Leng, Iris; Rejeski, W Jack

    2012-03-01

    There is a need to identify evidenced-based obesity treatments that are effective in maintaining lost weight. Weight loss results in reductions in energy expenditure, including spontaneous physical activity (SPA) which is defined as energy expenditure resulting primarily from unstructured mobility-related activities that occur during daily life. To date, there is little research, especially randomized, controlled trials, testing strategies that can be adopted and sustained to prevent declines in SPA that occur with weight loss. Self-monitoring is a successful behavioral strategy to facilitate behavior change, so a provocative question is whether monitoring SPA-related energy expenditure would override these reductions in SPA, and slow weight regain. This study is a randomized trial in older, obese men and women designed to test the hypothesis that adding a self-regulatory intervention (SRI), focused around self-monitoring of SPA, to a weight loss intervention will result in less weight and fat mass regain following weight loss than a comparable intervention that lacks this self-regulatory behavioral strategy. Participants (n=72) are randomized to a 5-month weight loss intervention with or without the addition of a behavioral component that includes an innovative approach to promoting increased SPA. Both groups then transition to self-selected diet and exercise behavior for a 5-month follow-up. Throughout the 10-month period, the SRI group is provided with an intervention designed to promote a SPA level that is equal to or greater than each individual's baseline SPA level, allowing us to isolate the effects of the SPA self-regulatory intervention component on weight and fat mass regain. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Adenosine A1 Receptors in Mouse Pontine Reticular Formation Depress Breathing, Increase Anesthesia Recovery Time, and Decrease Acetylcholine Release

    PubMed Central

    Gettys, George C.; Liu, Fang; Kimlin, Ed; Baghdoyan, Helen A.; Lydic, Ralph

    2012-01-01

    Background Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. Methods Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N6-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and time to recovery of righting response (RoRR) was quantified after PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), or SPA and DPCPX. Results First, SPA significantly decreased respiratory rate (−18%), tidal volume (−12%) and minute ventilation (−16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). DPCPX alone caused a concentration-dependent increase in acetylcholine, decrease in RoRR, and decrease in breathing rate. Coadministration of SPA and DPCPX blocked the SPA-induced decrease in acetylcholine and increase in RoRR. Conclusions Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing. PMID:23263018

  16. The value of SPaCE in delivering patient feedback.

    PubMed

    Clapham, Laura; Allan, Laura; Stirling, Kevin

    2016-02-01

    The use of simulated patients (SPs) within undergraduate medical curricula is an established and valued learning opportunity. Within the context of simulation, it is imperative to capture feedback from all participants within the simulation activity. The Simulated Patient Candidate Evaluation (SPaCE) tool was developed to deliver SP feedback following a simulation activity. SpaCE is a closed feedback tool that allows SPs to rate a student's performance, using a five-point Likert scale, in three domains: attitude; interaction skills; and management. This research study examined the value of the SPaCE tool and how it contributes to the overall feedback that a student receives. Classical test theory was used to determine the reliability of the SPaCE tool. An evaluation of all SP responses was conducted to observe trends in scoring patterns for each question. Qualitative data were collected via a free-text questionnaire and subsequent focus group discussion. It is imperative to capture feedback from all participants within the simulation activity Classical test theory determined that the SPaCE tool had a reliability co-efficient of 0.89. A total of 13 SPs replied to the questionnaire. A thematic analysis of all questionnaire data identified that the SPaCE tool provides a structure that allows patient feedback to be given effectively following a simulation activity. These themes were discussed further with six SPs who attended the subsequent focus group session. The SPaCE tool has been shown to be a reliable closed feedback tool that allows SPs to discriminate between students, based on their performance. The next stage in the development of the SPaCE tool is to test the wider applicability of this feedback tool. © 2015 John Wiley & Sons Ltd.

  17. Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial

    PubMed Central

    Forestier, R; Desfour, H; Tessier, J-M; Françon, A; Foote, A M; Genty, C; Rolland, C; Roques, C-F; Bosson, J-L

    2010-01-01

    Objective To determine whether spa therapy, plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment, in the management of knee osteoarthritis. Methods Large multicentre randomised prospective clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria, attending French spa resorts as outpatients between June 2006 and April 2007. Zelen randomisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating. The main endpoint criteria were patient self-assessed. All patients continued usual treatments and performed daily standardised home exercises. The spa therapy group also received 18 days of spa therapy (massages, showers, mud and pool sessions). Main Endpoint The number of patients achieving minimal clinically important improvement (MCII) at 6 months, defined as ≥19.9 mm on the visual analogue pain scale and/or ≥9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery. Results The intention to treat analysis included 187 controls and 195 spa therapy patients. At 6 months, 99/195 (50.8%) spa group patients had MCII and 68/187 (36.4%) controls (χ2=8.05; df=1; p=0.005). However, no improvement in quality of life (Short Form 36) or patient acceptable symptom state was observed at 6 months. Conclusion For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone, and is well tolerated. Trial registration number NCT00348777. PMID:19734131

  18. [Balneotherapy and spa therapy of rheumatic diseases in Turkey: a systematic review].

    PubMed

    Karagülle, M Z; Karagülle, M

    2004-02-01

    Turkey has a lot of thermal and mineral springs and is looking back on a still vivid tradition of spa therapy and balneotherapy, applied especially for the treatment of rheumatic diseases. This tradition is predominantly empiric and intuitive, however, it has assumed some important aspects of modern balneotherapeutic methods as well. This article is aimed at presenting the characteristics of traditional and modern balneological and spa therapy forms in Turkey. The studies which have been conducted between 1990 and 2000 in different spas in Turkey on the efficacy and effectiveness of spa therapy and balneotherapy for rheumatic diseases have been searched and analyzed independent of their design. A descriptive evaluation of the studies was carried out. A total of 15 published studies have been found and analyzed. The investigations have been carried out in 8 different spa resorts in Turkey. In these studies the effectiveness and efficacy of different balneological and spa therapies on a variety of rheumatic diseases (from osteoarthritis to fibromyalgia and from rheumatoid arthritis to low back pain) could be shown. Nearly all studied balneotherapeutic modalities were applied as bathing cures. Only in one study peloid therapy was applied. Balneotherapeutic therapy was applied in a modern and traditional way, and both open and stationary spa therapy forms were used at the same time. The review has shown the effectiveness of the investigated spa therapy and balneotherapy forms. It could be concluded that nearly all forms of spa therapy and balneotherapy used for the treatment of rheumatic diseases in Turkey are effective. A definitive conclusion, however, is not possible because of the heterogeneity of the study designs, methodological flaws, and the publication bias. In future good quality randomized controlled trials are needed. Copyright 2004 S. Karger GmbH, Freiburg

  19. Adenosine A(1) receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release.

    PubMed

    Gettys, George C; Liu, Fang; Kimlin, Ed; Baghdoyan, Helen A; Lydic, Ralph

    2013-02-01

    Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and the time to recovery of righting response (RoRR) was quantified after a PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine, or SPA and 1, 3-dipropyl-8-cyclopentylxanthine. First, SPA significantly decreased respiratory rate (-18%), tidal volume (-12%), and minute ventilation (-16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). 1, 3-dipropyl-8-cyclopentylxanthine alone caused a concentration-dependent increase in acetylcholine, a decrease in RoRR, and a decrease in breathing rate. Coadministration of SPA and 1, 3-dipropyl-8-cyclopentylxanthine blocked the SPA-induced decrease in acetylcholine and increase in RoRR. Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing.

  20. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    PubMed

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  1. Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics

    PubMed Central

    Hazen, Tracy H.; Leonard, Susan R.; Lampel, Keith A.; Lacher, David W.

    2016-01-01

    Enteroinvasive Escherichia coli (EIEC) is a unique pathovar that has a pathogenic mechanism nearly indistinguishable from that of Shigella species. In contrast to isolates of the four Shigella species, which are widespread and can be frequent causes of human illness, EIEC causes far fewer reported illnesses each year. In this study, we analyzed the genome sequences of 20 EIEC isolates, including 14 first described in this study. Phylogenomic analysis of the EIEC genomes demonstrated that 17 of the isolates are present in three distinct lineages that contained only EIEC genomes, compared to reference genomes from each of the E. coli pathovars and Shigella species. Comparative genomic analysis identified genes that were unique to each of the three identified EIEC lineages. While many of the EIEC lineage-specific genes have unknown functions, those with predicted functions included a colicin and putative proteins involved in transcriptional regulation or carbohydrate metabolism. In silico detection of the Shigella virulence plasmid (pINV), which is essential for the invasion of host cells, demonstrated that a form of pINV was present in nearly all EIEC genomes, but the Mxi-Spa-Ipa region of the plasmid that encodes the invasion-associated proteins was absent from several of the EIEC isolates. The comparative genomic findings in this study support the hypothesis that multiple EIEC lineages have evolved independently from multiple distinct lineages of E. coli via the acquisition of the Shigella virulence plasmid and, in some cases, the Shigella pathogenicity islands. PMID:27271741

  2. Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics.

    PubMed

    Hazen, Tracy H; Leonard, Susan R; Lampel, Keith A; Lacher, David W; Maurelli, Anthony T; Rasko, David A

    2016-08-01

    Enteroinvasive Escherichia coli (EIEC) is a unique pathovar that has a pathogenic mechanism nearly indistinguishable from that of Shigella species. In contrast to isolates of the four Shigella species, which are widespread and can be frequent causes of human illness, EIEC causes far fewer reported illnesses each year. In this study, we analyzed the genome sequences of 20 EIEC isolates, including 14 first described in this study. Phylogenomic analysis of the EIEC genomes demonstrated that 17 of the isolates are present in three distinct lineages that contained only EIEC genomes, compared to reference genomes from each of the E. coli pathovars and Shigella species. Comparative genomic analysis identified genes that were unique to each of the three identified EIEC lineages. While many of the EIEC lineage-specific genes have unknown functions, those with predicted functions included a colicin and putative proteins involved in transcriptional regulation or carbohydrate metabolism. In silico detection of the Shigella virulence plasmid (pINV), which is essential for the invasion of host cells, demonstrated that a form of pINV was present in nearly all EIEC genomes, but the Mxi-Spa-Ipa region of the plasmid that encodes the invasion-associated proteins was absent from several of the EIEC isolates. The comparative genomic findings in this study support the hypothesis that multiple EIEC lineages have evolved independently from multiple distinct lineages of E. coli via the acquisition of the Shigella virulence plasmid and, in some cases, the Shigella pathogenicity islands. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Highly Stable Aptamers Selected from a 2′-Fully Modified fGmH RNA Library for Targeting Biomaterials

    PubMed Central

    Friedman, Adam D.; Kim, Dongwook; Liu, Rihe

    2014-01-01

    When developed as targeting ligands for the in vivo delivery of biomaterials to biological systems, RNA aptamers immediately face numerous obstacles, in particular nuclease degradation and post-selection 2′ modification. This study aims to develop a novel class of highly stable, 2′-fully modified RNA aptamers that are ideal for the targeted delivery of biomaterials. We demonstrated the facile transcription of a fGmH (2′-F-dG, 2′-OMe-dA/dC/dU) RNA library with unexpected hydrophobicity, the direct selection of aptamers from a fGmH RNA library that bind Staphylococcus aureus Protein A (SpA) as a model target, and the superior nuclease and serum stability of these aptamers compared to 2′-partially modified RNA variants. Characterizations of fGmH RNA aptamers binding to purified SpA and to endogenous SpA present on the surface of S. aureus cells demonstrate fGmH RNA aptamer selectivity and stability. Significantly, fGmH RNA aptamers were able to functionalize, stabilize, and further deliver aggregation-prone silver nanoparticles (AgNPs) to S. aureus with SpA-dependent antimicrobial effects. This study describes a novel aptamer class with considerable potential to improve the in vivo applicability of nucleic acid-based affinity molecules to biomaterials. PMID:25443790

  4. Clinical and anti-aging effect of mud-bathing therapy for patients with fibromyalgia.

    PubMed

    Maeda, Toyoki; Kudo, Yoshihiro; Horiuchi, Takahiko; Makino, Naoki

    2017-12-06

    Spa bathing is known as a medical treatment for certain diseases causing chronic pains. Spa water contains mineral components which lower the specific heat of the water, resulting in a higher efficiency to warm body-core temperature. This phenomenon yields pain-relieving effect for rheumatoid arthritis, low back pain, sciatic neuralgia, fibromyalgia, etc. Here we introduce medical and biological effects of mud-spa-bathing therapy for fibromyalgia other than pain relief, the changes of blood examination data, and the telomere length of circulating leukocytes. The enrolled 7 patients with fibromyalgia syndrome were hospitalized and were subject to daily mud bathing at 40 °C for 10 min for about a month. Then, their subjective pain was reduced to about a quarter in average. They also showed lowered serum triglyceride and C-reactive protein level, maintaining the levels of aspartate transaminase and creatine phosphokinase, and increases of the red blood cell count, the serum albumin level, and the serum LDL-cholesterol level in comparison with cases without mud-bathing therapy, suggesting that mud bathing prevents inflammation and muscle atrophy and improves nutritional condition in fibromyalgia. In addition, the analysis of telomere length of peripheral leukocytes revealed a trend of negative correlation between telomere shortening and laboratory data change of hemoglobin and serum albumin. These telomeric changes can be explained hypothetically by an effect of mud bathing extending life-span of circulating leukocytes.

  5. May spa therapy be a valid opportunity to treat hand osteoarthritis? A review of clinical trials and mechanisms of action

    NASA Astrophysics Data System (ADS)

    Fortunati, Nicola Angelo; Fioravanti, Antonella; Seri, Gina; Cinelli, Simone; Tenti, Sara

    2016-01-01

    Osteoarthritis (OA) is the most common form of arthritis and its current treatment includes non-pharmacological and pharmacological modalities. Spa therapy represents a popular treatment for many rheumatic diseases. The aim of this review was to summarize the currently available information on clinical effects and mechanisms of action of spa therapy in OA of the hand. We conducted a search of the literature to extract articles describing randomized clinical trials (RCTs) in hand OA published in the period 1952-2015. We identified three assessable articles reporting RCTs on spa therapy in hand OA. Data from these clinical trials support a beneficial effect of spa therapy on pain, function and quality of life in hand OA. Spa therapy seems to have a role in the treatment of hand OA. However, additional RCTs are necessary to clarify the mechanisms of action and the effects of the application of thermal treatments.

  6. The Role of Aspiration Level in Risky Choice: A Comparison of Cumulative Prospect Theory and SP/A Theory.

    PubMed

    Lopes; Oden

    1999-06-01

    In recent years, descriptive models of risky choice have incorporated features that reflect the importance of particular outcome values in choice. Cumulative prospect theory (CPT) does this by inserting a reference point in the utility function. SP/A (security-potential/aspiration) theory uses aspiration level as a second criterion in the choice process. Experiment 1 compares the ability of the CPT and SP/A models to account for the same within-subjects data set and finds in favor of SP/A. Experiment 2 replicates the main finding of Experiment 1 in a between-subjects design. The final discussion brackets the SP/A result by showing the impact on fit of both decreasing and increasing the number of free parameters. We also suggest how the SP/A approach might be useful in modeling investment decision making in a descriptively more valid way and conclude with comments on the relation between descriptive and normative theories of risky choice. Copyright 1999 Academic Press.

  7. Balneotherapy and coenzyme Q10 in clinical and experimental medicine.

    PubMed

    Gvozdjakova, Anna; Kucharska, Jarmila; Sykora, L'ubomir; Singh, Ram B

    2014-01-01

    Balneotherapy or Spa therapy is used in neurological, cardiovascular, musculoskeletal, dermatological and gynecological diseases, in infertility as well as in metabolic disturbances. Beneficial effects of balneotherapy at the metabolic level is not fully understood. Authors have documented enhancement of antioxidants concentrations (coenzyme Q10- CoQ(10-OX) and alpha-tocopherol) of women with gynecological diseases by treatment with natural mineral water (Spa Lucky balneotherapy, Slovakia). In an experiment with rats, drinking of Spa Lucky mineral water decreased oxidative stress and enhanced concentrations of antioxidants CoQ(9-OX), CoQ(10-OX) in the myocardium, and alpha-tocopherol in uterus, ovaries and myocardium. Drinking of Spa Lucky water by rats stimulated myocardial mitochondrial respiration and energy production, and diminished skeletal muscle mitochondrial function. Simultaneous ingestion of coenzyme Q10 with drinking spa water returned mitochondrial parameters to the values of the control group. This pilot study helps explain the role of antioxidants, oxidative stress and mitochondrial energy production in beneficial effects of Spa Lucky balneotherapy.

  8. G-protein-coupled receptor-2-interacting protein-1 is required for endothelial cell directional migration and tumor angiogenesis via cortactin-dependent lamellipodia formation.

    PubMed

    Majumder, Syamantak; Sowden, Mark P; Gerber, Scott A; Thomas, Tamlyn; Christie, Christine K; Mohan, Amy; Yin, Guoyong; Lord, Edith M; Berk, Bradford C; Pang, Jinjiang

    2014-02-01

    Recent evidence suggests G-protein-coupled receptor-2-interacting protein-1 (GIT1) overexpression in several human metastatic tumors, including breast, lung, and prostate. Tumor metastasis is associated with an increase in angiogenesis. We have showed previously that GIT1 is required for postnatal angiogenesis during lung development. However, the functional role of GIT1 in pathological angiogenesis during tumor growth is unknown. In the present study, we show inhibition of angiogenesis in matrigel implants as well as reduced tumor angiogenesis and melanoma tumor growth in GIT1-knockout mice. We demonstrate that this is a result of impaired directional migration of GIT1-depleted endothelial cells toward a vascular endothelial growth factor gradient. Cortactin-mediated lamellipodia formation in the leading edge is critical for directional migration. We observed a significant reduction in cortactin localization and lamellipodia formation in the leading edge of GIT1-depleted endothelial cells. We specifically identified that the Spa homology domain (aa 250-420) of GIT1 is required for GIT1-cortactin complex localization to the leading edge. The mechanisms involved extracellular signal-regulated kinases 1 and 2-mediated Cortactin-S405 phosphorylation and activation of Rac1/Cdc42. Finally, using gain of function studies, we show that a constitutively active mutant of cortactin restored directional migration of GIT1-depleted cells. Our data demonstrated that a GIT1-cortactin association through GIT1-Spa homology domain is required for cortactin localization to the leading edge and is essential for endothelial cell directional migration and tumor angiogenesis.

  9. Development of a new pentaplex real-time PCR assay for the identification of poly-microbial specimens containing Staphylococcus aureus and other staphylococci, with simultaneous detection of staphylococcal virulence and methicillin resistance markers.

    PubMed

    Okolie, Charles E; Wooldridge, Karl G; Turner, David P; Cockayne, Alan; James, Richard

    2015-06-01

    Staphylococcus aureus strains harbouring genes encoding virulence and antibiotic resistance are of public health importance. In clinical samples, pathogenic S. aureus is often mixed with putatively less pathogenic coagulase-negative staphylococci (CoNS), both of which can harbour mecA, the gene encoding staphylococcal methicillin-resistance. There have been previous attempts at distinguishing MRSA from MRCoNS, most of which were based on the detection of one of the pathognomonic markers of S. aureus, such as coa, nuc or spa. That approach might suffice for discrete colonies and mono-microbial samples; it is inadequate for identification of clinical specimens containing mixtures of S. aureus and CoNS. In the present study, a real-time pentaplex PCR assay has been developed which simultaneously detects markers for bacteria (16S rRNA), coagulase-negative staphylococcus (cns), S. aureus (spa), Panton-Valentine leukocidin (pvl) and methicillin resistance (mecA). Staphylococcal and non-staphylococcal bacterial strains (n = 283) were used to validate the new assay. The applicability of this test to clinical samples was evaluated using spiked blood cultures (n = 43) containing S. aureus and CoNS in mono-microbial and poly-microbial models, which showed that the 5 markers were all detected as expected. Cycling completes within 1 h, delivering 100% specificity, NPV and PPV with a detection limit of 1.0 × 10(1) to 3.0 × 10(1) colony forming units (CFU)/ml, suggesting direct applicability in routine diagnostic microbiology. This is the most multiplexed real-time PCR-based PVL-MRSA assay and the first detection of a unique marker for CoNS without recourse to the conventional elimination approach. There was no evidence that this new assay produced invalid/indeterminate test results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome.

    PubMed

    Henderson, William R; Barnbrook, Julian; Dominelli, Paolo B; Griesdale, Donald Eg; Arndt, Tara; Molgat-Seon, Yannick; Foster, Glen; Ackland, Gareth L; Xu, James; Ayas, Najib T; Sheel, Andrew W

    2014-12-01

    The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). The present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration. The mean (± SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 ± 0.27 μM/well) was approximately 15% of the value found for the background control (6.30 ± 0.37 μM/well; p < 0.001). Elastance of the respiratory system (E RS) and the lung (E L) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (E CW) did not change in SPA-treated animals. There were no differences in E RS, E L, or E CW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis). In this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation.

  11. Nasal Carriage of Staphylococcus aureus among Children in the Ashanti Region of Ghana.

    PubMed

    Eibach, Daniel; Nagel, Michael; Hogan, Benedikt; Azuure, Clinton; Krumkamp, Ralf; Dekker, Denise; Gajdiss, Mike; Brunke, Melanie; Sarpong, Nimako; Owusu-Dabo, Ellis; May, Jürgen

    2017-01-01

    Nasal carriage with Staphylococcus aureus is a common risk factor for invasive infections, indicating the necessity to monitor prevalent strains, particularly in the vulnerable paediatric population. This surveillance study aims to identify carriage rates, subtypes, antimicrobial susceptibilities and virulence markers of nasal S. aureus isolates collected from children living in the Ashanti region of Ghana. Nasal swabs were obtained from children < 15 years of age on admission to the Agogo Presbyterian Hospital between April 2014 and January 2015. S. aureus isolates were characterized by their antimicrobial susceptibility, the presence of genes encoding for Panton-Valentine leukocidin (PVL) and toxic shock syndrome toxin-1 (TSST-1) and further differentiated by spa-typing and multi-locus-sequence-typing. Out of 544 children 120 (22.1%) were colonized with S. aureus, with highest carriage rates during the rainy seasons (27.2%; p = 0.007), in females aged 6-8 years (43.7%) and males aged 8-10 years (35.2%). The 123 isolates belonged to 35 different spa-types and 19 sequence types (ST) with the three most prevalent spa-types being t355 (n = 25), t84 (n = 18), t939 (n = 13), corresponding to ST152, ST15 and ST45. Two (2%) isolates were methicillin-resistant S. aureus (MRSA), classified as t1096 (ST152) and t4454 (ST45), and 16 (13%) were resistant to three or more different antimicrobial classes. PVL and TSST-1 were detected in 71 (58%) and 17 (14%) isolates respectively. S. aureus carriage among Ghanaian children seems to depend on age, sex and seasonality. While MRSA rates are low, the high prevalence of PVL is of serious concern as these strains might serve not only as a source for severe invasive infections but may also transfer genes, leading to highly virulent MRSA clones.

  12. Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin.

    PubMed

    Palaniyar, Nades; Nadesalingam, Jeya; Clark, Howard; Shih, Michael J; Dodds, Alister W; Reid, Kenneth B M

    2004-07-30

    Collectins are a family of innate immune proteins that contain fibrillar collagen-like regions and globular carbohydrate recognition domains (CRDs). The CRDs of these proteins recognize various microbial surface-specific carbohydrate patterns, particularly hexoses. We hypothesized that collectins, such as pulmonary surfactant proteins (SPs) SP-A and SP-D and serum protein mannose-binding lectin, could recognize nucleic acids, pentose-based anionic phosphate polymers. Here we show that collectins bind DNA from a variety of origins, including bacteria, mice, and synthetic oligonucleotides. Pentoses, such as arabinose, ribose, and deoxyribose, inhibit the interaction between SP-D and mannan, one of the well-studied hexose ligands for SP-D, and biologically relevant d-forms of the pentoses are better competitors than the l-forms. In addition, DNA and RNA polymer-related compounds, such as nucleotide diphosphates and triphosphates, also inhibit the carbohydrate binding ability of SP-D, or approximately 60 kDa trimeric recombinant fragments of SP-D that are composed of the alpha-helical coiled-coil neck region and three CRDs (SP-D(n/CRD)) or SP-D(n/CRD) with eight GXY repeats (SPD(GXY)(8)(n/CRD)). Direct binding and competition studies suggest that collectins bind nucleic acid via their CRDs as well as by their collagen-like regions, and that SP-D binds DNA more effectively than do SP-A and mannose-binding lectin at physiological salt conditions. Furthermore, the SP-D(GXY)(8)(n/CRD) fragments co-localize with DNA, and the protein competes the interaction between propidium iodide, a DNA-binding dye, and apoptotic cells. In conclusion, we show that collectins are a new class of proteins that bind free DNA and the DNA present on apoptotic cells by both their globular CRDs and collagen-like regions. Collectins may therefore play an important role in decreasing the inflammation caused by DNA in lungs and other tissues.

  13. 33 CFR 117.571 - Spa Creek.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Spa Creek. 117.571 Section 117.571 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Maryland § 117.571 Spa Creek. The S181 bridge, mile 4.0, at...

  14. 33 CFR 117.571 - Spa Creek.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Spa Creek. 117.571 Section 117.571 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Maryland § 117.571 Spa Creek. The S181 bridge, mile 4.0, at...

  15. 78 FR 49662 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-15

    ... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA... airworthiness directive (AD) for PIAGGIO AERO INDUSTRIES S.p.A. Model P-180 airplanes. The rescinded AD resulted... to develop on affected type design airplanes. DATES: This AD is effective September 19, 2013...

  16. Stochastic multiresonance for a fractional linear oscillator with time-delayed kernel and quadratic noise

    NASA Astrophysics Data System (ADS)

    Guo, Feng; Wang, Xue-Yuan; Zhu, Cheng-Yin; Cheng, Xiao-Feng; Zhang, Zheng-Yu; Huang, Xu-Hui

    2017-12-01

    The stochastic resonance for a fractional oscillator with time-delayed kernel and quadratic trichotomous noise is investigated. Applying linear system theory and Laplace transform, the system output amplitude (SPA) for the fractional oscillator is obtained. It is found that the SPA is a periodical function of the kernel delayed-time. Stochastic multiplicative phenomenon appears on the SPA versus the driving frequency, versus the noise amplitude, and versus the fractional exponent. The non-monotonous dependence of the SPA on the system parameters is also discussed.

  17. Prevalence of spondyloarthritis symptom in inflammatory bowel disease patients: A questionnaire survey.

    PubMed

    Kamo, Kenta; Shuto, Toshihide; Haraguchi, Akihisa

    2015-05-01

    We clarified the prevalence of spondyloarthritis (SpA) symptom in inflammatory bowel disease (IBD). We performed the questionnaire survey of SpA symptom in IBD patients on their office visit. One hundred and thirty seven patients were evaluated. The SpA features group included 46 (33.6%) patients (32 Men). Among them there were 22 Crohn's disease (CD) patients and 24 ulcerative colitis (UC) patients. The patients had a mean age of 48.3 years with a mean disease duration of 12.3 years. Non-SpA group (66.4%) included 91 patients (49 Men). Among them there were 27 CD patients and 64 UC patients. The patients had a mean age of 43.3 years with a mean disease duration of 9.2 years. In univariate analysis, the SpA group (33.6%) had longer disease duration than non-SpA group (p < 0.05). However, age at onset and sex were not significantly different among the groups. Multivariate analysis showed that disease duration was independently associated with SpA symptom (OR, 1.05; 95% CI, 1-1.09; p = 0.036). The prevalence of SpA symptom was relatively higher than what we had expected. Physicians should consider SpA when they observe IBD patients with arthralgia, and refer them to an appropriate department if needed.

  18. Pulling Marbles from a Bag: Deducing the Regional Impact History of the SPA Basin from Impact Melt Rocks

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara A.; Coker, R. F.

    2009-01-01

    The South Pole-Aitken (SPA) basin is an important target for absolute age-dating. Vertical and lateral impact mixing ensures that regolith within SPA will contain rock fragments from SPA itself, local impact craters, and faraway giant basins. About 20% of the regolith at any given site is foreign [1, 2], but much of this material will be cold ejecta, not impact melt. We calculated the fraction of contributed impact melt using scaling laws to estimate the amount and provenance of impact melt, demonstrating that SPA melt is the dominant impact melt rock (>70%) likely to be present. We also constructed a statistical model to illustrate how many randomly-selected impact-melt fragments would need to be dated, and with what accuracy, to confidently reproduce the impact history of a site. A detailed impact history becomes recognizable after a few hundred to a thousand randomly-selected marbles, however, it will be useful to have more information (e.g. compositional, mineralogical, remote sensing) to group fragments. These exercises show that SPA melt has a high probability of being present in a scoop sample and that dating of a few hundred to a thousand impact-melt fragments will yield the impact history of the SPA basin.

  19. Willingness of patients with ankylosing spondylitis to pay for inpatient treatment is influenced by the treatment environment and expectations of improvement.

    PubMed

    Boonen, A; Severens, J L; van Tubergen, A; Landewé, R; Bonsel, G; van der Heijde, D; van der Linden, Sj

    2005-11-01

    To assess the willingness to pay (WTP) for treatment in a spa resort of patients with ankylosing spondylitis (AS) and to assess if the experience of a spa influences the WTP. 120 patients participating in a randomised trial comparing 3 weeks' treatment in a spa resort in Austria or in the Netherlands with a control group completed a WTP questionnaire before and after spa treatment. Patients indicated on a payment card the maximal co-payment they wanted to contribute for three scenarios that included (a) two levels of improvement in pain and stiffness and (b) two treatment environments: a rehabilitation hospital and a spa resort. At baseline, patients wanted to contribute more for the same improvement after treatment in a spa resort compared with a rehabilitation hospital (p<0.003), and were prepared to pay more when expected effects were higher (p<0.001). No differences were found between men and women, pain, or income. After the trial none of the treatment groups showed a change in their WTP. The WTP of patients with AS for inpatient treatment is influenced by the treatment environment and the expected improvement. Experiencing treatment in a spa resort does not influence the co-payment.

  20. Spa Treatment (Balneotherapy) for Fibromyalgia—A Qualitative-Narrative Review and a Historical Perspective

    PubMed Central

    Ablin, Jacob N.; Buskila, Dan

    2013-01-01

    Aim. To perform a narrative review of spa therapy for management of the fibromyalgia syndrome (FMS), evaluating this traditional time-honored form of therapy in a historical perspective. Methods. Medline was searched using the terms “Spa therapy,” “Balneotherapy,” and “Fibromyalgia” between 1990 (year of ACR fibromyalgia criteria publication) and April 2013. The Cochrane database was also searched. Publications relating to the implementation of spa therapy and related practices over the centuries were identified through references, searched, and reviewed. Results. Reports of balneotherapy were described from diverse locations throughout Europe and Asia, and various forms of water-related therapy have been incorporated for many musculoskeletal indications. In the management of FMS, spa therapy has generally been shown to be well accepted and moderately effective for symptom reduction. Conclusion. While achieving high-quality evidence-based conclusions is difficult for complex natural therapies such as spa therapy, the existing evidence indicates a positive effect in management of FMS. In view of the long history of this modality in the management of rheumatic pain as well as the inherent difficulties related to pharmacological treatment, the role of spa therapy should currently be recognized as part of a therapeutic program for FMS. PMID:23983795

  1. Social physique anxiety and physical activity behaviour of male and female exercisers.

    PubMed

    Portman, Robert M; Bradbury, Jane; Lewis, Kiara

    2018-03-01

    Despite females consistently reporting greater social physique anxiety (SPA), previous literature has yet to demonstrate whether SPA gender differences are linked to the way males and females perform physical activity. This study investigated an association between SPA and physical activity frequency, history of exercise, and physical activity intensity. Participants were represented by currently active users (N = 33 males; N = 31 females) of an on-campus university-run gym and completed a background physical activity questionnaire and the nine-item Social Physique Anxiety Scale. Participants also performed an exercise session at a self-selected level of exertion, with the intensity of each session measured via heart rate monitor. SPA was not associated with physical activity frequency, history of exercise (length of gym membership), or intensity for male and female exercisers. With respect to male participants, females reported higher SPA and a preference for performing higher intensity physical activity. Females and males also indicated a preference for performing aerobic and anaerobic physical activity respectively. Our findings suggest the experience of SPA does not deter body-conscious individuals from the performance of regular physical activity. Findings also suggest the discrepancy in male and female SPA is not linked to differences in the way physical activity is performed.

  2. Effects of voluntary exercise on spontaneous physical activity and food consumption in mice: Results from an artificial selection experiment.

    PubMed

    Copes, Lynn E; Schutz, Heidi; Dlugosz, Elizabeth M; Acosta, Wendy; Chappell, Mark A; Garland, Theodore

    2015-10-01

    We evaluated the effect of voluntary exercise on spontaneous physical activity (SPA) and food consumption in mice from 4 replicate lines bred for 57 generations for high voluntary wheel running (HR) and from 4 non-selected control (C) lines. Beginning at ~24 days of age, mice were housed in standard cages or in cages with attached wheels. Wheel activity and SPA were monitored in 1-min intervals. Data from the 8th week of the experiment were analyzed because mice were sexually mature and had plateaued in body mass, weekly wheel running distance, SPA, and food consumption. Body mass, length, and masses of the retroperitoneal fat pad, liver, and heart were recorded after the 13th week. SPA of both HR and C mice decreased with wheel access, due to reductions in both duration and average intensity of SPA. However, total activity duration (SPA+wheel running; min/day) was ~1/3 greater when mice were housed with wheels, and food consumption was significantly increased. Overall, food consumption in both HR and C mice was more strongly affected by wheel running than by SPA. Duration of wheel running had a stronger effect than average speed, but the opposite was true for SPA. With body mass as a covariate, chronic wheel access significantly reduced fat pad mass and increased heart mass in both HR and C mice. Given that both HR and C mice housed with wheels had increased food consumption, the energetic cost of wheel running was not fully compensated by concomitant reductions in SPA. The experiment demonstrates that both duration and intensity of both wheel running and SPA were significant predictors of food consumption. This sort of detailed analysis of the effects of different aspects of physical activity on food consumption has not previously been reported for a non-human animal, and it sets the stage for longitudinal examination of energy balance and its components in rodent models. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Molecular investigation of Staphylococcus aureus isolated from the patients, personnel, air and environment of an ICU in a hospital in Tehran.

    PubMed

    Mirzaii, Mehdi; Emaneini, Mohammad; Jabalameli, Fereshteh; Halimi, Shahnaz; Taherikalani, Morovat

    2015-01-01

    The aim of this study was to determine the prevalence and characteristics of Staphylococcus aureus isolates from the patients, staff, air and environments of an ICU in a hospital in Tehran. During this study, 37 S. aureus isolates were collected and analyzed via the spa typing method. Of the 37 S. aureus isolates, 35 (94%) were methicillin resistant (MRSA), 28 (76%) were identified as SCCmec types III or IIIA, four (10%) were identified as SCCmec types I or IA and three (8%) were identified a SCCmec type IV. All of the MRSA isolates were resistant to oxacillin and contained mecA. The isolates were all spa typed and found to comprise 11 spa types, including t7688, t7689, and t7789, which have not previously been reported. The spa type t7688 was isolated from the hands of two ICU personnel. The spa type t7689 was observed among five isolates from the air and the environment. The spa type t7789 was observed among three isolates from the patients, ventilators and the air. The majority of the isolates (43%) belonged to spa types t030 and t037. Our results revealed that MRSA strains that were isolated from the air, the environment of the ICU and the patients who were colonized or infected with MRSA often exhibited the same spa and SCCmec types. These results also reveal that the isolates from the patients and environment were usually indistinguishable. Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  4. Mortality in American Veterans with the HLA-B27 gene.

    PubMed

    Walsh, Jessica A; Zhou, Xi; Clegg, Daniel O; Teng, Chiachen; Cannon, Grant W; Sauer, Brian

    2015-04-01

    To compare survival in American veterans with and without the HLA-B27 (B27) gene. Mortality was evaluated in a national cohort of veterans with clinically available B27 test results between October 1, 1999, and December 31, 2011. The primary outcome was the mortality difference between B27-positive and B27-negative veterans, adjusted for age, sex, race, and diagnoses codes for diseases that may have influenced both B27 testing and mortality, including psoriasis, inflammatory bowel disease, spondyloarthritis (SpA), and other types of inflammatory arthritis. The secondary outcomes were the adjusted mortality HR for B27+ and B27- veterans, in subgroups with and without SpA. Among veterans with available B27 test results, 27,652 (84.7%) were B27- and 4978 (15.3%) were B27+. The mean followup time was 4.6 years. Mortality was higher in the B27+ group than in the B27- group (HR 1.15, 95% CI 1.03-1.27). Mortality was also higher in the B27+ subgroups with SpA (HR 1.35, 95% CI 1.06-1.72) and without SpA (HR 1.11, 95% CI 0.99-1.24), but the difference was significant only in the subgroup with SpA. B27 positivity was associated with an increased mortality rate in a cohort of veterans clinically selected for B27 testing, after adjustment for SpA. In the subgroup with SpA, the mortality rate was associated with B27 positivity, and in the subgroup without SpA, there was a nonsignificant association between B27+ and mortality.

  5. 2014 Update of the Canadian Rheumatology Association/spondyloarthritis research consortium of Canada treatment recommendations for the management of spondyloarthritis. Part I: principles of the management of spondyloarthritis in Canada.

    PubMed

    Rohekar, Sherry; Chan, Jon; Tse, Shirley M L; Haroon, Nigil; Chandran, Vinod; Bessette, Louis; Mosher, Dianne; Flanagan, Cathy; Keen, Kevin J; Adams, Karen; Mallinson, Michael; Thorne, Carter; Rahman, Proton; Gladman, Dafna D; Inman, Robert D

    2015-04-01

    The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA). A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference. A survey was sent to the membership of the CRA to obtain an extended review that was used to finalize the recommendations. Guidelines for the management of SpA were created. Part I focuses on the principles of management of SpA in Canada and includes 6 general management principles, 5 ethical considerations, target groups for treatment recommendations, 2 wait time recommendations, and recommendations for disease monitoring. Also included are 6 modifications for application to juvenile SpA. These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that the implementation of these recommendations will promote best practices in the treatment of SpA.

  6. Social physique anxiety and disturbed eating attitudes and behaviors in adolescents: moderating effects of sport, sport-related characteristics, and gender.

    PubMed

    Lanfranchi, Marie-Christine; Maïano, Christophe; Morin, Alexandre J S; Therme, Pierre

    2015-02-01

    The involvement of adolescents presenting high levels of social physique anxiety (SPA) in sport practice has been hypothesized as potentially problematic in terms of being associated with disturbed eating attitudes and behaviors (DEAB). Indeed, sport practice itself has been reported to be associated with higher levels of SPA and DEAB, and sport settings may sometimes promote unhealthy life habits. Nevertheless, current studies are few and present several limitations. The objective of the present study was to examine these relationships among adolescents involved or not in various types (i.e., leanness and individual) and contexts (i.e., organized and competitive) of sport practice. The sample included 766 French adolescents (337 boys and 429 girls), aged between 11 and 18 years, involved (n = 335) or not (n = 431) in sport practice. SPA and DEAB were assessed using French adaptations of the SPA scale and the Eating Attitudes Test-26. The results reveal a significant and positive association between SPA and the DEAB scales. Furthermore, they show a positive relationship between SPA and (a) vomiting-purging behaviors in adolescents involved in individual sports and (b) generic DEAB (i.e., a subscale covering fear of getting fat, food preoccupation, and eating-related guilt), particularly in adolescents involved in individual sports. The relationship between SPA and DEAB does not differ according to adolescents' involvement in sport practice or according to their involvement in organized, competitive, or leanness sport practice more specifically. However, higher levels of SPA and DEAB were observed in adolescents involved in individual sports.

  7. Superporous agarose--reticulated vitreous carbon electrodes for electrochemical sandwich bioassays.

    PubMed

    Rao, Ashwin K; Creager, Stephen E

    2008-11-03

    We report on the use of flow-through electrodes fabricated from a composite of superporous agarose (SPA) and reticulated vitreous carbon (RVC) for carrying out sandwich bioassays via a model sandwich assay scheme. The flow-through design of the SPA-RVC electrodes allows for ease in solution handling with the use of micropipettors while allowing sandwich assays to be performed on the SPA matrix inside the RVC. A sandwich bioassay was devised for detecting biotinylated bovine serum albumin (b-BSA) as a proof-of-concept scheme to demonstrate applicability of SPA-RVC electrodes to carry out sandwich assays. In this bioassay scheme, SPA-RVC electrodes with avidin molecules immobilized on the SPA matrix were incubated with low quantities of b-BSA followed by incubation with avidinylated alkaline phosphatase (av-ALP). This construct creates a sandwich bioassay whereby b-BSA is sandwiched between the two avidin complexes. Av-ALP labels captured on the bound b-BSA catalytically hydrolyze conversion of 4-aminophenylphosphate (PAPP) to electrochemically active 4-aminophenol (PAP) which is then voltammetrically detected inside the RVC. The lower concentration detection limit for b-BSA was 0.32+/-0.1 ng mL(-1) and the absolute detection limit was 32+/-10 pg. Non-specific binding of av-ALP enzyme labels onto the avidin-activated SPA-RVC electrodes was low. Catalytic generation of PAP by non-specifically bound av-ALP occurs at a rate less than 2% of that for PAP generation by av-ALP in [(SPA-av)-(b-BSA-b)-(av-ALP)] sandwich constructs.

  8. Protein A immunoadsorption therapy in HIV-related immune thrombocytopenia: a preliminary report.

    PubMed

    Bertram, J H; Snyder, H W; Gill, P S; Shulman, I; Henry, D H; Jenkins, D; Kiprov, D D

    1988-12-01

    Nine homosexual patients with immune thrombocytopenia were treated with autologous plasma that had been perfused over silica-immobilized Staphylococcus aureus protein A (SpA). Pretreatment platelet counts ranged from 10,000 to 98,000 cells/mm3 (mean: 54,000 cells/mm3). Six patients responded to therapy. Platelets increased by a mean of 95,000 cells/mm3 (p less than 0.007) and reached normal levels (greater than 150,000 cells/mm3) in four patients. Increased platelet counts are presently sustained in these four individuals after 5 months of follow-up. Increases in platelet counts significantly correlated with decreases in platelet-associated IgG (PAIgG), platelet-directed IgG (PDIgG), and immune complexes (CIC). PAIgG and PDIgG declined by a mean of 67% (p less than 0.003) and 58% (p less than 0.007), respectively. CIC decreased by a mean of 37% (p = 0.02). Complement was concomitantly activated in all four examined patients. C3a and C5a increased 23-fold and 2.6-fold, respectively, while total hemolytic complement decreased by 50%. Activated complement components and removal of CIC and IgG thus may contribute to the platelet-enhancing activity of SpA immunoadsorption therapy.

  9. Fabrication and characterization of a chemically oxidized-nanostructured porous silicon based biosensor implementing orienting protein A.

    PubMed

    Naveas, Nelson; Hernandez-Montelongo, Jacobo; Pulido, Ruth; Torres-Costa, Vicente; Villanueva-Guerrero, Raúl; Predestinación García Ruiz, Josefa; Manso-Silván, Miguel

    2014-03-01

    Nanostructured porous silicon (PSi) elicits as a very attractive material for future biosensing systems due to its high surface area, biocompatibility and well-established fabrication methods. In order to engineer its performance as a biosensor transducer platform, the density of immunoglobulins properly immobilized and oriented onto the surface needs to be optimized. In this work we fabricated and characterized a novel biosensing system focusing on the improvement of the biofunctionalization cascade. The system consists on a chemically oxidized PSi platform derivatized with 3-aminopropyltriethoxysilane (APTS) that is coupled to Staphylococcus protein A (SpA). The chemical oxidation has previously demonstrated to enhance the biofunctionalization process and here "by implementing SpA" a molecularly oriented immunosensor is achieved. The biosensor system is characterized in terms of its chemical composition, wettability and optical reflectance. Finally, this system is successfully exploited to develop a biosensor for detecting asymmetric dimethylarginine (ADMA), an endogenous molecule involved in cardiovascular diseases. Therefore, this work is relevant from the point of view of design and optimization of the biomolecular immobilization cascade on PSi surfaces with the added value of contribution to the development of new assays for detecting ADMA with a view on prevention of cardiovascular diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Molecular characterization of nasal methicillin resistant Staphylococcus aureus isolates from workers of an automaker company in southeast Iran.

    PubMed

    Sobhanipoor, Mohammad Hossein; Ahmadrajabi, Roya; Karmostaji, Afsaneh; Saffari, Fereshteh

    2017-10-01

    Colonization of methicillin resistant Staphylococccus aureus (MRSA) can occur more commonly in healthy people who live in close together or are in close physical contact with each other. Having knowledge about the molecular characteristics of these strains provides considerable discernment into the epidemiology of this important microorganism. A total of 806 nasal swabs were collected from healthy workers of an automaker company in the southeast of Iran and were analyzed to detect MRSA isolates. Multilocus sequence typing (MLST), spa typing, and detection of staphylococcal cassette chromosome mec (SCCmec) were performed. The presence of genes encoding Panton-Valentine Leukocidin (PVL) and Arginine Catabolic Mobile Element (ACME) were also investigated. Carriage rate of S. aureus was 20%. Among 10 identified MRSA, no acme was found while high prevalence of pvl (60%) was of great concern. Seven different spa types including five new ones were identified. The most frequent sequence type was the novel one; ST 3373 (n = 3), followed by each of ST22, ST88, ST859 (n = 2) and ST1955 (n = 1). MRSA isolates were clustered into two main clonal complexes; CC22 (n = 6) and CC88 (n = 4). Low genetic diversity with the dominance of CC22, SCCmecIV was found. Distribution of previously found hospital-associated MRSA was demonstrated among our isolates. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  11. 76 FR 54403 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... Federal holidays. For service information identified in this proposed AD, contact Piaggio Aero Industries... Service Information Piaggio Aero Industries S.p.A. has issued Mandatory Service Bulletin No. 80-0304... Accomplishment Instructions of Piaggio Aero Industries S.p.A. Mandatory Service Bulletin No. 80-0304, dated July...

  12. 77 FR 67764 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-14

    ... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA... directive (AD) for certain Piaggio Aero Industries S.p.A. Model P-180 airplanes. That AD currently requires...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service...

  13. 78 FR 69597 - Airworthiness Directives; Piaggio Aero Industries S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... Industries S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT... (AD) for Piaggio Aero Industries S.p.A Model P-180 airplanes that would supersede an existing AD. This... proposed AD, contact Piaggio Aero Industries S.p.A-Airworthiness Office, Via Luigi Cibrario, 4-16154 Genova...

  14. Social Physique Anxiety in Adolescence: An Exploration of Influences, Coping Strategies, and Health Behaviors

    ERIC Educational Resources Information Center

    Sabiston, C. M.; Sedgwick, W. A.; Crocker, P. R. E.; Kowalski, K. C.; Mack, D. E.

    2007-01-01

    This study explored adolescent females' experiences of social physique anxiety (SPA) and related coping strategies. A final sample of 31 adolescent females ages 13 to 18 years discussed dealing with SPA during individual semistructured interviews. Resultant themes pertaining to the transactional experiences of SPA were coded using content…

  15. 7 CFR 2902.35 - Bathroom and spa cleaners.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Bathroom and spa cleaners. 2902.35 Section 2902.35... Items § 2902.35 Bathroom and spa cleaners. (a) Definition. Products that are designed to clean and/or prevent deposits on surfaces found in bathrooms and spas including, but not necessarily limited to, bath...

  16. The National Education Association's Educational Computer Service. An Assessment.

    ERIC Educational Resources Information Center

    Software Publishers Association, Washington, DC.

    The Educational Computer Service (ECS) of the National Education Association (NEA) evaluates and distributes educational software. An investigation of ECS was conducted by the Computer Education Committee of the Software Publishers Association (SPA) at the request of SPA members. The SPA found that the service, as it is presently structured, is…

  17. 78 FR 32363 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA... propose to rescind an airworthiness directive (AD) for PIAGGIO AERO INDUSTRIES S.p.A. Model P-180... or is not likely to develop on affected type design airplanes, and therefore the AD should be...

  18. A novel diagnostic method (spectral computed tomography of sacroiliac joints) for axial spondyloarthritis.

    PubMed

    Zhang, Ping; Yu, Kai Hu; Guo, Rui Min; Ran, Jun; Liu, Yao; Morelli, John; Runge, Val M; Li, Xiao Ming

    2016-08-01

    To evaluate the diagnostic value of spectral computed tomography (CT) of sacroiliac joints for axial spondyloarthritis (SpA). We retrospectively analyzed the records of 125 patients with low back pain (LBP) suspected of having SpA. Each patient underwent sacroiliac joint spectral CT examination. Water- and calcium-based material decomposition images were reconstructed. After 3-6 months of follow-up, 76 were diagnosed with SpA, and the remaining 49 patients were diagnosed with nonspecific LBP (nLBP). The slope of sacroiliac bone marrow HU (Hounsfield unit) curve (λHU), CT value, and bone marrow to normal muscle ratios of water and calcium concentrations in the ilium and sacrum were calculated and compared between nLBP and SpA patients. The iliac λHU was 8.26 ± 3.91 for nLBP and 9.81 ± 4.92 for SpA. The mean iliac ratios of water and calcium concentrations were 1.04 ± 0.03 and 21.67 ± 4.40, respectively, for nLBP, and 1.07 ± 0.04 and 111.5 ± 358.98, respectively, for SpA. The mean iliac CT values were 311.12 ± 86.52 HU for nLBP and 423.97 ± 127.51 HU for SpA. There were statistically significant differences in iliac ratios of water and calcium concentrations, CT value, and λHU between nLBP and SpA patients (p < 0.05). The sensitivity of iliac λHU was the highest. The diagnostic odds ratio of ratio of iliac calcium concentration was the highest, and its negative likelihood ratio was the lowest. Spectral CT not only shows bone erosion and sclerosis, but also shows and quantitatively measures bone marrow edema in the sacroiliac joints of SpA patients. Copyright © 2015. Published by Elsevier B.V.

  19. Prevalence of spondyloarthritis in reference to HLA-B27 in the French population: results of the GAZEL cohort.

    PubMed

    Costantino, Félicie; Talpin, Alice; Said-Nahal, Roula; Goldberg, Marcel; Henny, Joseph; Chiocchia, Gilles; Garchon, Henri-Jean; Zins, Marie; Breban, Maxime

    2015-04-01

    To estimate the prevalence of spondyloarthritis (SpA) in reference to HLA-B27 in the French population. In 1989, 20 625 employees of the French national gas and electricity company aged 35-50 years were enrolled in the GAZEL cohort. In 2010, 18 757 still active participants were screened by a questionnaire validated for the detection of SpA. Responders with available DNA were retained for further studies. Pelvic radiograph and HLA-B27 typing were performed in all the self-reported cases of SpA or psoriatic arthritis. Self-reported diagnosis was verified by a qualified rheumatologist. HLA-B27 determination was also performed in subjects without any SpA feature. The target population consisted of 6556 responders with available DNA. Their male:female ratio was 3.6 and their mean age was 65.5±3.3 years. A diagnosis of SpA was confirmed in 32 of the 72 self-reported cases, 75% of them being HLA-B27 positive. Estimated SpA prevalence adjusted for sex was 0.43% (95% CI 0.26% to 0.70%). HLA-B27 positivity rate in 2466 healthy controls was 6.9% (95% CI 5.9% to 7.9%). The relative risk of SpA in HLA-B27 positive individuals was 39 (95% CI 17 to 86). We estimated the prevalence of SpA in the French population in 2010 to 0.43%. With an estimated prevalence of 75.0% in SpA and 6.9% in healthy controls, HLA-B27 increased the disease risk 39-fold, as compared with HLA-B27 negative subjects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Survival of TNF antagonists in spondylarthritis is better than in rheumatoid arthritis. Data from the Spanish registry BIOBADASER

    PubMed Central

    Carmona, Loreto; Gómez-Reino, Juan J

    2006-01-01

    The aim of the present work is to compare drug survival and safety of infliximab, etanercept, and adalimumab (tumor necrosis factor [TNF] antagonists) in spondylarthritis (SpA) with those of rheumatoid arthritis (RA). To this purpose, we analysed the data in BIOBADASER (2000–2005), a drug registry launched in 2000 for long-term follow-up of the safety of these biologics in rheumatic diseases. The rates of drug discontinuation and adverse events (AEs) in SpA (n = 1,524) were estimated and compared with those of RA (n = 4,006). Cox regression analyses were used to adjust for independent factors. Total exposure to TNF antagonists for SpA was 2,430 patient-years and 7,865 for RA. Drug survival in SpA was significantly greater than in RA at 1, 2, and 3 years. The hazard ratio (HR) for discontinuation in SpA compared with RA was 0.66 (95% confidence interval [CI], 0.57–0.76) after adjustment for age, gender, and use of infliximab. The difference remained after controlling for the individual medication and its place in the sequence of treatment. There were fewer SpA patients with AEs (17%) than RA patients (26%; p < 0.001). The HR for AEs in SpA was 0.80 (95% CI, 0.70–0.91) compared with RA after adjustment for age, disease duration, and use of infliximab. In conclusion, due in part to a better safety profile, survival of TNF antagonists in SpA is better than in RA. TNF antagonists are at present a safe and effective therapeutic option for long-term treatment of patients with SpA failing to respond to traditional drugs. Because chronic therapy is necessary, continual review of this issue is necessary. PMID:16620398

  1. Whodunit? The Contribution of Interleukin (IL)-17/IL-22-Producing γδ T Cells, αβ T Cells, and Innate Lymphoid Cells to the Pathogenesis of Spondyloarthritis

    PubMed Central

    Reinhardt, Annika; Prinz, Immo

    2018-01-01

    γδ T cells, αβ T cells, and innate lymphoid cells (ILCs) are capable of producing interleukin (IL)-17A, IL-17F, and IL-22. Among these three families of lymphocytes, it is emerging that γδ T cells are, at least in rodents, the main source of these key pro-inflammatory cytokines. γδ T cells were implicated in multiple inflammatory and autoimmune diseases, including psoriasis, experimental autoimmune encephalomyelitis and uveitis, colitis, and rheumatoid arthritis. Recent findings pointed toward a central role of γδ T cells in the pathogenesis of spondyloarthritis (SpA), a group of inflammatory rheumatic diseases affecting the axial skeleton. SpA primarily manifests as inflammation and new bone formation at the entheses, which are connecting tendons or ligaments with bone. In SpA patients, joint inflammation is frequently accompanied by extra-articular manifestations, such as inflammatory bowel disease or psoriasis. In humans, genome-wide association studies could link the IL-23/IL-17 cytokine axis to SpA. Accordingly, antibodies targeting IL-23/IL-17 for SpA treatment already showed promising results in clinical studies. However, the contribution of IL-17-producing γδ T cells to SpA pathogenesis is certainly not an open-and-shut case. Indeed, the cell types that are chiefly involved in local inflammation in human SpA still remain largely unclear. Some studies focusing on blood or synovium from SpA patients reported augmented IL-17-producing and IL-23 receptor-expressing γδ T cells, but other cell types might contribute as well. Here, we summarize the current understanding of how γδ T cells, αβ T cells, and ILCs contribute to the pathogenesis of human and experimental SpA. PMID:29922283

  2. Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

    PubMed Central

    Hu, Yueming; Huang, He; Hui, Xinjie; Cheng, Xi; White, Aaron P.

    2016-01-01

    Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia. PMID:27217422

  3. Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression.

    PubMed

    Amaya, Ronny; Cancel, Limary M; Tarbell, John M

    2016-01-01

    Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle-SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA as well as reversal flow (OSI) are important parameters characterizing arterial susceptibility to disease.

  4. Variability in the prescription of non-biologic disease-modifying antirheumatic drugs for the treatment of spondyloarthritis in Spain.

    PubMed

    Silva-Fernández, Lucía; Pérez-Vicente, Sabina; Martín-Martínez, María Auxiliadora; López-González, Ruth

    2015-06-01

    To describe the variability in the prescription of non-biologic disease-modifying antirheumatic drugs (nbDMARDs) for the treatment of spondyloarthritis (SpA) in Spain and to explore which factors relating to the disease, patient, physician, and/or center contribute to these variations. A retrospective medical record review was performed using a probabilistic sample of 1168 patients with SpA from 45 centers distributed in 15/19 regions in Spain. The sociodemographic and clinical features and the use of drugs were recorded following a standardized protocol. Logistic regression, with nbDMARDs prescriptions as the dependent variable, was used for bivariable analysis. A multilevel logistic regression model was used to study variability. The probability of receiving an nbDMARD was higher in female patients [OR = 1.548; 95% confidence interval (CI): 1.208-1.984], in those with elevated C-reactive protein (OR = 1.039; 95% CI: 1.012-1.066) and erythrocyte sedimentation rate (OR = 1.012; 95% CI: 1.003-1.021), in those with a higher number of affected peripheral joints (OR = 12.921; 95% CI: 2.911-57.347), and in patients with extra-articular manifestations like dactylitis (OR = 2.997; 95% CI: 1.868-4.809), psoriasis (OR = 2.601; 95% CI: 1.870-3.617), and enthesitis (OR = 1.717; 95% CI: 1.224-2.410). There was a marked variability in the prescription of nbDMARDs for SpA patients, depending on the center (14.3%; variance 0.549; standard error 0.161; median odds ratio 2.366; p < 0.001). After adjusting for patient and center variables, this variability fell to 3.8%. A number of factors affecting variability in clinical practice, and which are independent of disease characteristics, are associated with the probability of SpA patients receiving nbDMARDs in Spain. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression

    PubMed Central

    Amaya, Ronny; Cancel, Limary M.; Tarbell, John M.

    2016-01-01

    Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle–SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA as well as reversal flow (OSI) are important parameters characterizing arterial susceptibility to disease. PMID:27846267

  6. Robust model-based analysis of single-particle tracking experiments with Spot-On

    PubMed Central

    Grimm, Jonathan B; Lavis, Luke D

    2018-01-01

    Single-particle tracking (SPT) has become an important method to bridge biochemistry and cell biology since it allows direct observation of protein binding and diffusion dynamics in live cells. However, accurately inferring information from SPT studies is challenging due to biases in both data analysis and experimental design. To address analysis bias, we introduce ‘Spot-On’, an intuitive web-interface. Spot-On implements a kinetic modeling framework that accounts for known biases, including molecules moving out-of-focus, and robustly infers diffusion constants and subpopulations from pooled single-molecule trajectories. To minimize inherent experimental biases, we implement and validate stroboscopic photo-activation SPT (spaSPT), which minimizes motion-blur bias and tracking errors. We validate Spot-On using experimentally realistic simulations and show that Spot-On outperforms other methods. We then apply Spot-On to spaSPT data from live mammalian cells spanning a wide range of nuclear dynamics and demonstrate that Spot-On consistently and robustly infers subpopulation fractions and diffusion constants. PMID:29300163

  7. Robust model-based analysis of single-particle tracking experiments with Spot-On.

    PubMed

    Hansen, Anders S; Woringer, Maxime; Grimm, Jonathan B; Lavis, Luke D; Tjian, Robert; Darzacq, Xavier

    2018-01-04

    Single-particle tracking (SPT) has become an important method to bridge biochemistry and cell biology since it allows direct observation of protein binding and diffusion dynamics in live cells. However, accurately inferring information from SPT studies is challenging due to biases in both data analysis and experimental design. To address analysis bias, we introduce 'Spot-On', an intuitive web-interface. Spot-On implements a kinetic modeling framework that accounts for known biases, including molecules moving out-of-focus, and robustly infers diffusion constants and subpopulations from pooled single-molecule trajectories. To minimize inherent experimental biases, we implement and validate stroboscopic photo-activation SPT (spaSPT), which minimizes motion-blur bias and tracking errors. We validate Spot-On using experimentally realistic simulations and show that Spot-On outperforms other methods. We then apply Spot-On to spaSPT data from live mammalian cells spanning a wide range of nuclear dynamics and demonstrate that Spot-On consistently and robustly infers subpopulation fractions and diffusion constants. © 2018, Hansen et al.

  8. The role of porcine reproductive and respiratory syndrome (PRRS) virus structural and non-structural proteins in virus pathogenesis.

    PubMed

    Music, Nedzad; Gagnon, Carl A

    2010-12-01

    Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating viral disease affecting the swine industry worldwide. The etiological agent, PRRS virus (PRRSV), possesses a RNA viral genome with nine open reading frames (ORFs). The ORF1a and ORF1b replicase-associated genes encode the polyproteins pp1a and pp1ab, respectively. The pp1a is processed in nine non-structural proteins (nsps): nsp1α, nsp1β, and nsp2 to nsp8. Proteolytic cleavage of pp1ab generates products nsp9 to nsp12. The proteolytic pp1a cleavage products process and cleave pp1a and pp1ab into nsp products. The nsp9 to nsp12 are involved in virus genome transcription and replication. The 3' end of the viral genome encodes four minor and three major structural proteins. The GP(2a), GP₃ and GP₄ (encoded by ORF2a, 3 and 4), are glycosylated membrane associated minor structural proteins. The fourth minor structural protein, the E protein (encoded by ORF2b), is an unglycosylated membrane associated protein. The viral envelope contains two major structural proteins: a glycosylated major envelope protein GP₅ (encoded by ORF5) and an unglycosylated membrane M protein (encoded by ORF6). The third major structural protein is the nucleocapsid N protein (encoded by ORF7). All PRRSV non-structural and structural proteins are essential for virus replication, and PRRSV infectivity is relatively intolerant to subtle changes within the structural proteins. PRRSV virulence is multigenic and resides in both the non-structural and structural viral proteins. This review discusses the molecular characteristics, biological and immunological functions of the PRRSV structural and nsps and their involvement in the virus pathogenesis.

  9. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

    PubMed Central

    Quiroz, Felipe García; Chilkoti, Ashutosh

    2015-01-01

    Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level. PMID:26390327

  10. 77 FR 35888 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service.... Relevant Service Information PIAGGIO AERO INDUSTRIES S.p.A. has issued Service Bulletin No. 80- 0318, dated... Instructions of Piaggio Aero Industries S.p.A. Mandatory Service Bulletin No. 80-0318, revision 2, dated March...

  11. 75 FR 7409 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ... INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of.... As a consequence, this new Airworthiness Directive (AD) requires a functional check of main and stand... AERO INDUSTRIES S.p.A. has issued Service Bulletin (Mandatory) N.: 80-0278, dated July 15, 2009. The...

  12. 78 FR 40443 - Submission for OMB Review; Comment Request-Virginia Graeme Baker Pool and Spa Safety Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-05

    ... Request--Virginia Graeme Baker Pool and Spa Safety Act; Compliance Form AGENCY: Consumer Product Safety... of an approval regarding a form used to verify whether pools and spas are in compliance with the Virginia Graeme Baker Pool and Spa Safety Act. No comments were received in response to that notice...

  13. The ribosome as a missing link in prebiotic evolution II: Ribosomes encode ribosomal proteins that bind to common regions of their own mRNAs and rRNAs.

    PubMed

    Root-Bernstein, Robert; Root-Bernstein, Meredith

    2016-05-21

    We have proposed that the ribosome may represent a missing link between prebiotic chemistries and the first cells. One of the predictions that follows from this hypothesis, which we test here, is that ribosomal RNA (rRNA) must have encoded the proteins necessary for ribosomal function. In other words, the rRNA also functioned pre-biotically as mRNA. Since these ribosome-binding proteins (rb-proteins) must bind to the rRNA, but the rRNA also functioned as mRNA, it follows that rb-proteins should bind to their own mRNA as well. This hypothesis can be contrasted to a "null" hypothesis in which rb-proteins evolved independently of the rRNA sequences and therefore there should be no necessary similarity between the rRNA to which rb-proteins bind and the mRNA that encodes the rb-protein. Five types of evidence reported here support the plausibility of the hypothesis that the mRNA encoding rb-proteins evolved from rRNA: (1) the ubiquity of rb-protein binding to their own mRNAs and autogenous control of their own translation; (2) the higher-than-expected incidence of Arginine-rich modules associated with RNA binding that occurs in rRNA-encoded proteins; (3) the fact that rRNA-binding regions of rb-proteins are homologous to their mRNA binding regions; (4) the higher than expected incidence of rb-protein sequences encoded in rRNA that are of a high degree of homology to their mRNA as compared with a random selection of other proteins; and (5) rRNA in modern prokaryotes and eukaryotes encodes functional proteins. None of these results can be explained by the null hypothesis that assumes independent evolution of rRNA and the mRNAs encoding ribosomal proteins. Also noteworthy is that very few proteins bind their own mRNAs that are not associated with ribosome function. Further tests of the hypothesis are suggested: (1) experimental testing of whether rRNA-encoded proteins bind to rRNA at their coding sites; (2) whether tRNA synthetases, which are also known to bind to their own mRNAs, are encoded by the tRNA sequences themselves; (3) and the prediction that archaeal and prokaryotic (DNA-based) genomes were built around rRNA "genes" so that rRNA-related sequences will be found to make up an unexpectedly high proportion of these genomes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Referral Patterns, Diagnosis, and Disease Management of Patients With Axial Spondyloarthritis

    PubMed Central

    van der Heijde, Désirée; Sieper, Joachim; Elewaut, Dirk; Deodhar, Atul; Pangan, Aileen L.; Dorr, Alexander P.

    2014-01-01

    Background Recognition, diagnosis, and management of axial spondyloarthritis (axial SpA) continue to advance. Objectives The objectives of this study were to compare referrals, diagnosis, and management of axial SpA in Western Europe (WE), North America (US and Canada), and the rest of world (RoW) in academic and community rheumatology practices and to identify areas for further education. Methods Rheumatologists responded online to the MAXIMA (Management of Axial SpA International and Multicentric Approaches) survey. Questions pertained to referral, diagnosis, and management of axial SpA. Results Rheumatologists (N = 809) from 56 countries completed the survey about patients with chronic back pain (≥3 months) starting before age 45 years. Responses from academic and community practice rheumatologists were generally similar. Most referrals were from primary care providers. Symptom duration of 3 years or more at referral was reported more frequently by WE and RoW than US respondents. More WE and RoW than US rheumatologists referred to the Assessment of SpondyloArthritis International Society criteria for axial SpA in clinical practice. Rheumatologists reported prescribing disease-modifying antirheumatic drugs for the management of axial SpA. Sulfasalazine was frequently prescribed across regions; methotrexate was more commonly prescribed by US rheumatologists compared with other regions. Conclusions Referral patterns, diagnosis, and disease management for axial SpA were similar among WE, North America, and RoW rheumatologists and in academic/community practices, although more WE and RoW rheumatologists referred to Assessment of SpondyloArthritis International Society criteria in clinical practice. Disease-modifying antirheumatic drugs were commonly prescribed for axial SpA patients, although it was unclear whether these were prescribed for axial or peripheral symptoms. PMID:25417676

  15. Referral patterns, diagnosis, and disease management of patients with axial spondyloarthritis: results of an international survey.

    PubMed

    van der Heijde, Désirée; Sieper, Joachim; Elewaut, Dirk; Deodhar, Atul; Pangan, Aileen L; Dorr, Alexander P

    2014-12-01

    Recognition, diagnosis, and management of axial spondyloarthritis (axial SpA) continue to advance. The objectives of this study were to compare referrals, diagnosis, and management of axial SpA in Western Europe (WE), North America (US and Canada), and the rest of world (RoW) in academic and community rheumatology practices and to identify areas for further education. Rheumatologists responded online to the MAXIMA (Management of Axial SpA International and Multicentric Approaches) survey. Questions pertained to referral, diagnosis, and management of axial SpA. Rheumatologists (N = 809) from 56 countries completed the survey about patients with chronic back pain (≥3 months) starting before age 45 years. Responses from academic and community practice rheumatologists were generally similar. Most referrals were from primary care providers. Symptom duration of 3 years or more at referral was reported more frequently by WE and RoW than US respondents. More WE and RoW than US rheumatologists referred to the Assessment of SpondyloArthritis International Society criteria for axial SpA in clinical practice. Rheumatologists reported prescribing disease-modifying antirheumatic drugs for the management of axial SpA. Sulfasalazine was frequently prescribed across regions; methotrexate was more commonly prescribed by US rheumatologists compared with other regions. Referral patterns, diagnosis, and disease management for axial SpA were similar among WE, North America, and RoW rheumatologists and in academic/community practices, although more WE and RoW rheumatologists referred to Assessment of SpondyloArthritis International Society criteria in clinical practice. Disease-modifying antirheumatic drugs were commonly prescribed for axial SpA patients, although it was unclear whether these were prescribed for axial or peripheral symptoms.

  16. Evolutionary Characteristics of Missing Proteins: Insights into the Evolution of Human Chromosomes Related to Missing-Protein-Encoding Genes.

    PubMed

    Xu, Aishi; Li, Guang; Yang, Dong; Wu, Songfeng; Ouyang, Hongsheng; Xu, Ping; He, Fuchu

    2015-12-04

    Although the "missing protein" is a temporary concept in C-HPP, the biological information for their "missing" could be an important clue in evolutionary studies. Here we classified missing-protein-encoding genes into two groups, the genes encoding PE2 proteins (with transcript evidence) and the genes encoding PE3/4 proteins (with no transcript evidence). These missing-protein-encoding genes distribute unevenly among different chromosomes, chromosomal regions, or gene clusters. In the view of evolutionary features, PE3/4 genes tend to be young, spreading at the nonhomology chromosomal regions and evolving at higher rates. Interestingly, there is a higher proportion of singletons in PE3/4 genes than the proportion of singletons in all genes (background) and OTCSGs (organ, tissue, cell type-specific genes). More importantly, most of the paralogous PE3/4 genes belong to the newly duplicated members of the paralogous gene groups, which mainly contribute to special biological functions, such as "smell perception". These functions are heavily restricted into specific type of cells, tissues, or specific developmental stages, acting as the new functional requirements that facilitated the emergence of the missing-protein-encoding genes during evolution. In addition, the criteria for the extremely special physical-chemical proteins were first set up based on the properties of PE2 proteins, and the evolutionary characteristics of those proteins were explored. Overall, the evolutionary analyses of missing-protein-encoding genes are expected to be highly instructive for proteomics and functional studies in the future.

  17. High and Low Activity Rats: Elevated intrinsic physical activity drives resistance to diet induced obesity in non-bred rats

    PubMed Central

    Perez-Leighton, Claudio E.; Boland, Kelsey; Billington, Charles; Kotz, Catherine M.

    2012-01-01

    Humans and rodents show large variability in their individual sensitivity to diet-induced obesity, which has been associated with differences in intrinsic spontaneous physical activity (SPA). Evidence from genetic and out-bred rat obesity models shows that higher activity of the orexin peptides results in higher intrinsic SPA and protection against diet-induced obesity. Based on this, we hypothesized that naturally occurring variation in SPA and orexin signaling activity is sufficient to drive differences in sensitivity to diet-induced obesity. We analyzed orexin activity and sensitivity to diet-induced obesity in non-manipulated male Sprague Dawley rats selected for high and low intrinsic SPA. Our results defined a new model of differential DIO sensitivity, the high-activity and low activity-rats, and suggest that naturally occurring variations in intrinsic SPA cause differences in energy expenditure that are mediated by orexin signaling and alter DIO sensitivity. PMID:23404834

  18. [Extensive treatment of teacher's voice disorders in health spa].

    PubMed

    Niebudek-Bogusz, Ewa; Marszałek, Sławomir; Woźnicka, Ewelina; Minkiewicz, Zofia; Hima, Joanna; Sliwińska-Kowalska, Mariola

    2010-01-01

    Treatment in a health spa with proper infrastructure and professional medical care can provide optimal conditions for intensive voice rehabilitation, especially for people with occupational voice disorders. The most numerous group of people with voice disorders are teachers. In Poland, they have an opportunity to take care of, or regain, their health during a one-year paid leave. The authors describe a multi-specialist model of extensive treatment of voice disorders in a health spa, including holistic and interdisciplinary procedures in occupational dysphonia. Apart from balneotherapy, the spa treatment includes vocal training exercises, relaxation exercises, elements of physiotherapy with the larynx manual therapy and psychological workshops. The voice rehabilitation organized already for two groups of teachers has been received with great satisfaction by this occupational group. The implementation of a model program of extensive treatment of voice disorders in a health spa should become one of the steps aimed at preventing occupational voice diseases.

  19. IL-23/IL-17 axis in spondyloarthritis-bench to bedside.

    PubMed

    Raychaudhuri, Siba P; Raychaudhuri, Smriti K

    2016-06-01

    Cytokines play a critical role in the pathogenesis of psoriatic arthritis, ankylosing spondylitis, and other types of spondyloarthritis (SpA). Besides IFN-γ and TNF-α; IL-23/IL-17 cytokines play a dominant role in the inflammatory and proliferative cascades of SpA. Recently, in a series of elegant experiments using mouse models and human tissues, it has been demonstrated that IL-23-induced Th17 cytokines (IL-17 and IL-22) can contribute to following pathologic events associated with SpA: development of psoriatic plaque, pannus formation in the joint, joint erosion, and new bone formation. In this review article, we have discussed the contributing role of the IL-23/IL-17 cytokine axis in the pathogenesis of PsA and AS. IL-23/IL-17-targeted therapies are very promising for SpA, and we have provided an outline about usefulness of these new groups of biologics in SpA.

  20. Transcriptomic analysis of Arabidopsis developing stems: a close-up on cell wall genes

    PubMed Central

    Minic, Zoran; Jamet, Elisabeth; San-Clemente, Hélène; Pelletier, Sandra; Renou, Jean-Pierre; Rihouey, Christophe; Okinyo, Denis PO; Proux, Caroline; Lerouge, Patrice; Jouanin, Lise

    2009-01-01

    Background Different strategies (genetics, biochemistry, and proteomics) can be used to study proteins involved in cell biogenesis. The availability of the complete sequences of several plant genomes allowed the development of transcriptomic studies. Although the expression patterns of some Arabidopsis thaliana genes involved in cell wall biogenesis were identified at different physiological stages, detailed microarray analysis of plant cell wall genes has not been performed on any plant tissues. Using transcriptomic and bioinformatic tools, we studied the regulation of cell wall genes in Arabidopsis stems, i.e. genes encoding proteins involved in cell wall biogenesis and genes encoding secreted proteins. Results Transcriptomic analyses of stems were performed at three different developmental stages, i.e., young stems, intermediate stage, and mature stems. Many genes involved in the synthesis of cell wall components such as polysaccharides and monolignols were identified. A total of 345 genes encoding predicted secreted proteins with moderate or high level of transcripts were analyzed in details. The encoded proteins were distributed into 8 classes, based on the presence of predicted functional domains. Proteins acting on carbohydrates and proteins of unknown function constituted the two most abundant classes. Other proteins were proteases, oxido-reductases, proteins with interacting domains, proteins involved in signalling, and structural proteins. Particularly high levels of expression were established for genes encoding pectin methylesterases, germin-like proteins, arabinogalactan proteins, fasciclin-like arabinogalactan proteins, and structural proteins. Finally, the results of this transcriptomic analyses were compared with those obtained through a cell wall proteomic analysis from the same material. Only a small proportion of genes identified by previous proteomic analyses were identified by transcriptomics. Conversely, only a few proteins encoded by genes having moderate or high level of transcripts were identified by proteomics. Conclusion Analysis of the genes predicted to encode cell wall proteins revealed that about 345 genes had moderate or high levels of transcripts. Among them, we identified many new genes possibly involved in cell wall biogenesis. The discrepancies observed between results of this transcriptomic study and a previous proteomic study on the same material revealed post-transcriptional mechanisms of regulation of expression of genes encoding cell wall proteins. PMID:19149885

  1. Targeted Quantitative Screening of Chromosome 18 Encoded Proteome in Plasma Samples of Astronaut Candidates.

    PubMed

    Kopylov, Artur T; Ilgisonis, Ekaterina V; Moysa, Alexander A; Tikhonova, Olga V; Zavialova, Maria G; Novikova, Svetlana E; Lisitsa, Andrey V; Ponomarenko, Elena A; Moshkovskii, Sergei A; Markin, Andrey A; Grigoriev, Anatoly I; Zgoda, Victor G; Archakov, Alexander I

    2016-11-04

    This work was aimed at estimating the concentrations of proteins encoded by human chromosome 18 (Chr 18) in plasma samples of 54 healthy male volunteers (aged 20-47). These young persons have been certified by the medical evaluation board as healthy subjects ready for space flight training. Over 260 stable isotope-labeled peptide standards (SIS) were synthesized to perform the measurements of proteins encoded by Chr 18. Selected reaction monitoring (SRM) with SIS allowed an estimate of the levels of 84 of 276 proteins encoded by Chr 18. These proteins were quantified in whole and depleted plasma samples. Concentration of the proteins detected varied from 10 -6 M (transthyretin, P02766) to 10 -11 M (P4-ATPase, O43861). A minor part of the proteins (mostly representing intracellular proteins) was characterized by extremely high inter individual variations. The results provide a background for studies of a potential biomarker in plasma among proteins encoded by Chr 18. The SRM raw data are available in ProteomeXchange repository (PXD004374).

  2. 75 FR 1407 - Tribal Consultation on Proposed Revisions to 25 CFR Parts 81 & 82

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... the date of January 14, 2010 for the meeting scheduled at the Pala Casino Resort and Spa in Pala... Pala Casino Resort and Spa in Pala, California. This notice changes the date to February 2, 2010, and.... * * * Pala Casino Resort and Spa, 11154 Hwy. 76, Pala, California 92059; Telephone: (877) 946-7252'' to read...

  3. 75 FR 65224 - Airworthiness Directives; Agusta S.p.A. Model A109E Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... Airworthiness Directives; Agusta S.p.A. Model A109E Helicopters AGENCY: Federal Aviation Administration (FAA... http://www.regulations.gov ; or in person at the Docket Management Facility between 9 a.m. and 5 p.m... installation for Agusta S.p.A. Model A109E helicopters. As published, the AD number shown in the third column...

  4. 75 FR 28673 - Carolina Coastal Railway, Inc.-Acquisition and Operation Exemption-Morehead & South Fork Railroad...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-21

    ... Railroad Co., Inc. (MHSF) with North Carolina State Ports Authority (SPA) and to operate approximately 0.87 miles of SPA's rail line. After the effective date of the exemption, CLNA filed a letter on February 16... agreement with SPA and therefore was not assigning a lease to CLNA. Instead, MHSF assigned a freight...

  5. The use of exer-learning games for rehabilitation in spa clinics at home.

    PubMed

    Lucht, Martina; Krausser, Kati; Joerg, Daniel; Schwandt, Tobias

    2012-01-01

    This paper examines benefits of the exer-learning concept HOPSCOTCH for rehabilitation in spa clinics and at home. It describes a specific application to motivate obese patients in spa clinics for exercise. Furthermore results of an empirical study are reported where HOPSCOTCH was implemented in two spa clinics for a period of four weeks. The results of the study have shown that the concept is very convincing, but mainly depends on the content of the application; however the idea of HOPSCOTCH appeared to have a high potential to be used as a therapeutic agent in terms of motivation for exercise.

  6. Effect of Hofmeister series salts on Absorptivity of aqueous solutions on Sodium polyacrylate

    NASA Astrophysics Data System (ADS)

    Korrapati, Swathi; Pullela, Phani Kumar; Vijayalakshmi, U.

    2017-11-01

    Sodium polyacrylate (SPA) is a popular super absorbent commonly used in children diapers, sanitary pads, adult diapers etc. The use of SPA is in force from past 30 years and the newer applications like as food preservant are evolving. SPA is recently discovered by our group for improvement of sensitivity of colorimetric agents. Though the discovery of improvement in sensitivity is phenomenal, the mechanism still remains a puzzle. A typical assay reagent contains colorimetric/fluorescent reagents, buffers, salts, stabilizers etc. These chemicals are known to influence the water absorptivity of SPA. If we were to perform chemical/biochemical assays on SPA absorbed reagents effect of salts and other excipients on colorimetric/fluorescence compounds absorbed on SPA is very important. The hofmeister series are standard for studying effect of salts on permeability, stability, aggregation, fluorescence quenching etc. We recently studied affect of urea, sodium chloride, ammonium sulfate, guanidine thiocayanate on fluorescence characteristics of fluorescence compounds and noted that except urea all other reagents have resulted in fluorescence quenching and urea had an opposite effect and increased the fluorescence intensity. This result was attributed to the different water structure around fluorescent in urea solution versus other chaotropic agents.

  7. Cancer Mortality in Low Radon Spa Area

    PubMed Central

    Suzuki, Yasuyo; Honjo, Satoshi; Kawamura, Hiroko; Koishi, Fumiko; Suzuki, Tomokazu; Hirohata, Tomio

    1994-01-01

    Recently lower mortality for cancers of all sites was reported among inhabitants in the Misasa spa area, where there is a high radon background. To clarify the effects of radon exposure on cancer mortality, the effects of a hot spring itself on cancer mortality was investigated in the Beppu spa area, which has only a low radon background, and adjacent control areas. For females, the mortalities for cancers of all sites, liver and lung were higher in Beppu than those for all Japan on the basis of the standardized mortality ratio (SMR), while the SMR for all cancers was lower in adjacent areas. For the male inhabitants in hoth areas the cancer mortalities of all sites were not significantly different from those of all Japan. When we directly compared the most typical spa areas in Beppu and an adjacent control area, a Poisson regression analysis did not show that the relative risk of dying from cancer of all sites was decreased in the spa areas. These results are thus consistent with the view that the lower cancer mortality in the Misasa spa area might be related to exposure to low levels of radon . PMID:7829388

  8. The Apollo peak-ring impact basin: Insights into the structure and evolution of the South Pole-Aitken basin

    NASA Astrophysics Data System (ADS)

    Potter, Ross W. K.; Head, James W.; Guo, Dijun; Liu, Jianzhong; Xiao, Long

    2018-05-01

    The 492 km-diameter Apollo impact basin post-dates, and is located at the inner edge of, the ∼2240 km-diameter South Pole-Aitken (SPA) basin, providing an opportunity to assess the SPA substructure and lateral heterogeneity. Gravity Recovery and Interior Laboratory gravity data suggest an average crustal thickness on the floor of SPA of ∼20 km and within the Apollo basin of ∼5 km, yet remote sensing data reveal no conclusive evidence for the presence of exposed mantle material. We use the iSALE shock physics code to model the formation of the Apollo basin and find that the observational data are best fit by the impact of a 40 km diameter body traveling at 15 km/s into 20-40 km thick crustal material. These results strongly suggest that the Apollo impact occurred on ejecta deposits and collapsed crustal material of the SPA basin and could help place constraints on the location, size and geometry of the SPA transient cavity. The peak ring in the interior of Apollo basin is plausibly interpreted to be composed of inwardly collapsed lower crustal material that experienced peak shock pressures in excess of 35 GPa, consistent with remote sensing observations that suggest shocked plagioclase. Proposed robotic and/or human missions to SPA and Apollo would present an excellent opportunity to test the predictions of this work and address many scientific questions about SPA basin evolution and structure.

  9. The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis.

    PubMed

    Yeremenko, Nataliya; Paramarta, Jacqueline E; Baeten, Dominique

    2014-07-01

    Various novel therapies for spondyloarthritis (SpA) are currently under development. In this review, we discuss the scientific rational to target the interleukin (IL)-23/IL-17 axis in SpA and give an overview of the proof-of-concept trials with drugs directed towards this axis. Cumulative evidence from genetics (e.g. the strong genetic association with the IL-23 receptor gene), in-vitro models (e.g. the increased IL-23 production upon HLA-B27 misfolding), human expression studies (e.g. the expansion of IL-17 producing innate cells in SpA) and animal models (e.g. the increased IL-17 production in HLA-B27 transgenic rats) strongly supports the involvement of the IL-23/IL-17 axis in the pathogenesis of SpA. Ustekinumab (a monoclonal antibody directed against the common p40 subunit of IL-23 and IL-12), secukinumab, ixekizumab (both monoclonal antibodies directed against IL-17A), and brodalumab a monoclonal antibody against the IL-17RA receptor) have been recently used in proof-of-concept and randomized trials in the ankylosing spondylitis and/or psoriatic arthritis subforms of SpA, with overall very promising clinical efficacy. The first results for novel drugs blocking key cytokines in the IL-23/IL-17 axis are promising in SpA and more novel compounds are upcoming. This will teach us more on the role of the IL-23/IL-17 axis in the pathophysiology of SpA.

  10. Meta-analysis of the effect of pregrazing pasture mass on pasture intake, milk production, and grazing behavior of dairy cows strip-grazing temperate grasslands.

    PubMed

    Pérez-Prieto, L A; Delagarde, R

    2012-09-01

    Grazing management is a key factor in pasture-based dairy systems, which can be improved given advanced knowledge of the effects of pregrazing pasture mass (PM) on the performance of dairy cows. The aim of this study was to quantify the effects of PM on the pasture intake, milk production, milk composition, and grazing behavior of strip- or rotational-grazing dairy cows, based on a meta-analysis of published research papers. A database was created that included experiments in which the effects of PM on pasture intake and milk production of dairy cows were studied. Papers were selected only if at least 2 PM were compared under similar experimental conditions, particularly the same pasture allowance (SPA). The final database included 15 papers with 27 PM comparisons. For analytical purposes, the database was subdivided into 3 subsets that varied according to the estimation height at which pasture allowance was determined; that is, where PM were compared at the SPA above ground level (SPA(0) subset), above 2 to 3 cm (SPA(3) subset), and above 4 to 5 cm (SPA(5) subset). Statistical analyses were conducted on the entire database (global analysis) and within each subset using linear model procedures. An interaction between PM and estimation height was found for pasture intake and milk production in the global analysis. On the basis of the predictive equations, pasture intake increased by 1.58 kg of dry matter/d per tonne increase in PM when PM were compared at SPA(0), was not affected by PM when PM were compared at SPA(3), and decreased by 0.65 kg of dry matter/d per tonne increase in PM when PM were compared at SPA(5). This is consistent with the effect of PM on milk production, which was positive and negative (1.04 and -0.79 kg/t of PM, respectively) when PM were compared at SPA(0) and SPA(5), respectively. Grazing time was only slightly affected by PM, irrespective of estimation height, because the effect of PM on pasture intake was mainly dependent on the variation in pasture intake rate. Pasture intake rate increased with increasing PM at SPA(0) but decreased with increasing PM at SPA(5). This meta-analysis clearly demonstrates that the effects of PM on pasture intake, milk production, and behavior of strip-grazing dairy cows depend largely on the height at which the PM and pasture allowance are measured. These results have methodological implications for future grazing research because it can be recommended that PM be compared at similar levels of pasture availability (i.e., at the same pasture allowance above 2 to 3 cm) to avoid possible misinterpretations of results. They also reveal the benefits of improving grazing management and intake prediction through modeling in pasture-based dairy systems. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Molecular mechanisms for protein-encoded inheritance

    PubMed Central

    Wiltzius, Jed J. W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

    2013-01-01

    Strains are phenotypic variants, encoded by nucleic acid sequences in chromosomal inheritance and by protein “conformations” in prion inheritance and transmission. But how is a protein “conformation” stable enough to endure transmission between cells or organisms? Here new polymorphic crystal structures of segments of prion and other amyloid proteins offer structural mechanisms for prion strains. In packing polymorphism, prion strains are encoded by alternative packings (polymorphs) of β-sheets formed by the same segment of a protein; in a second mechanism, segmental polymorphism, prion strains are encoded by distinct β-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring “conformations,” capable of encoding strains. These molecular mechanisms for transfer of information into prion strains share features with the familiar mechanism for transfer of information by nucleic acid inheritance, including sequence specificity and recognition by non-covalent bonds. PMID:19684598

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

    DOEpatents

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

    2017-08-08

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

  13. 77 FR 52688 - Initiation of Antidumping and Countervailing Duty Administrative Reviews and Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... Ltd SRF Limited Italy: Certain Pasta, A-475-818 7/1/11-6/30/12 Alberto Poiatti S.p.A Delverde Industrie Alimentari S.p.A Industria Alimentare Colavita, S.p.A Pasta Lensi S.r.L Pastificio Attilio Mastromauro-Pasta Granoro S.r.L Pastificio Gallo Natale & F. Ili S.r.L Fiamma Vesuviana S.r.L Pastificio...

  14. Maturity Assessment of Space Plug-and-Play Architecture

    DTIC Science & Technology

    2013-03-01

    SSM SPA Service Module SRL System Readiness Level TAT Time-at-Tone TRA Technology Readiness Assessment TRL Technology Readiness Level USB Universal...maturity assessment—the Technology Readiness Level (TRL) process, the Integration Readiness Level (IRL) process, and the System Readiness Level ( SRL ...is an important hallmark of the SPA concept, and makes possible the composability and scalability of system designs that employ it. 14 4. SPA

  15. RADON AND PROGENY SOURCED DOSE ASSESSMENT OF SPA EMPLOYEES IN BALNEOLOGICAL SITES.

    PubMed

    Uzun, Sefa Kemal; Demiröz, Işık

    2016-09-01

    This study was conducted in the scope of IAEA project with the name 'Establishing a Systematic Radioactivity Survey and Total Effective Dose Assessment in Natural Balneological Sites' (TUR/9/018), at the Health Physics department of Sarayköy Nuclear Research and Training Center (SANAEM). The aim of this study is estimation of radon and progeny sourced effective dose for the people who are working at the spa facilities by measuring radon activity concentration (RAC) at the ambient air of indoor spa pools and dressing rooms. As it is known, the source of the radon gas is the radium content of the earth crust. Therefore, thermal waters coming from ground may contain dissolved radon and the radon can diffuse water to air. So the ambient air of spa pools can contain serious RAC that depends on a lot of parameters. In this regard, RAC measurements were executed at the 70 spa facilities in Turkey. The measurements were done with both active and passive methods at ambient air of spa pools and dressing rooms. Thus, active measurements were carried out by using the Alphaguard(®) with diffusion mode during half an hour, and passive measurements were carried out by using the humidity resistive CR-39 radon detectors during 2 months. Results show that RAC values at ambient air of spa pools varies between 13 Bq m(-3) and 10 kBq m(-3) Because long-term measurements are more reliable, if it is available, for dose calculations passive radon measurements (with CR-39 detectors) at ambient air of spa pools and dressing rooms were used, otherwise active measurement results were used. With the measurement by the conversion coefficients of ICRP 65 and occupational data of the employees has got from questionary forms, effective dose values were calculated. According to the calculations, spa employees are exposed to annual average dose between 0.05 and 29 mSv because of radon and progeny. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Cartilage collagen type II seromarker patterns in axial spondyloarthritis and psoriatic arthritis: associations with disease activity, smoking and HLA-B27.

    PubMed

    Munk, Heidi Lausten; Gudmann, Natasja Staehr; Christensen, Anne Friesgaard; Ejstrup, Leif; Sorensen, Grith Lykke; Loft, Anne Gitte; Bay-Jensen, Anne C; Siebuhr, Anne Sofie; Junker, Peter

    2016-04-01

    The aim of the study was to assess the possible association between type II collagen turnover seromarkers and disease profile in patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). Outpatients with axial SpA (n = 110) or PsA (n = 101) underwent clinical examination including disease activity measures and HLA-B27 typing. The procollagen IIA N-terminal peptide (PIIANP) and a matrix metalloproteinase-generated type II collagen fragment (C2M) were quantified in serum by ELISA. C2M was higher in SpA than in controls, 0.41 versus 0.36 ng/ml (p = 0.004), while PIIANP did not differ between patients and healthy subjects, 2252 versus 2142 ng/ml (p = 0.13). However, DMARD-naïve SpA patients had higher PIIANP, 2461 ng/ml (p = 0.01) and C2M, 0.44 ng/ml (p = 0.0007) levels than controls, and PIIANP correlated with CRP (ρ = 0.34). C2M was lower in SpA smokers, 0.36 ng/ml versus non-smokers, 0.43 ng/ml (p = 0.02), while PIIANP was higher in HLA-B27 positive, 2312 ng/ml versus negative patients, 2021 ng/ml (p = 0.03). In PsA, PIIANP and C2M did not differ between patients and controls, but PIIANP was elevated in patients not receiving DMARDs, 2726 ng/ml. In PsA, PIIANP and C2M did not differ according to smoking and HLA-B27. Cartilage degradation assessed by C2M is increased in SpA irrespective of treatment but not in PsA. Cartilage synthesis reflected by PIIANP is increased in untreated SpA and PsA. PIIANP correlates with CRP in SpA while not in PsA. In DMARD-naïve SpA but not in PsA, HLA-B27 positivity and smoking are associated with a chondro-proliferative metabolic pattern.

  17. Continuous Aerobic Training in Individualized Intensity Avoids Spontaneous Physical Activity Decline and Improves MCT1 Expression in Oxidative Muscle of Swimming Rats.

    PubMed

    Scariot, Pedro P M; Manchado-Gobatto, Fúlvia de Barros; Torsoni, Adriana S; Dos Reis, Ivan G M; Beck, Wladimir R; Gobatto, Claudio A

    2016-01-01

    Although aerobic training has been shown to affect the lactate transport of skeletal muscle, there is no information concerning the effect of continuous aerobic training on spontaneous physical activity (SPA). Because every movement in daily life (i.e., SPA) is generated by skeletal muscle, we think that it is possible that an improvement of SPA could affect the physiological properties of muscle with regard to lactate transport. The aim of this study was to evaluate the effect of 12 weeks of continuous aerobic training in individualized intensity on SPA of rats and their gene expressions of monocarboxylate transporters (MCT) 1 and 4 in soleus (oxidative) and white gastrocnemius (glycolytic) muscles. We also analyzed the effect of continuous aerobic training on aerobic and anaerobic parameters using the lactate minimum test (LMT). Sixty-day-old rats were randomly divided into three groups: a baseline group in which rats were evaluated prior to initiation of the study; a control group (Co) in which rats were kept without any treatment during 12 weeks; and a chronic exercise group (Tr) in which rats swam for 40 min/day, 5 days/week at 80% of anaerobic threshold during 12 weeks. After the experimental period, SPA of rats was measured using a gravimetric method. Rats had their expression of MCTs determined by RT-PCR analysis. In essence, aerobic training is effective in maintaining SPA, but did not prevent the decline of aerobic capacity and anaerobic performance, leading us to propose that the decline of SPA is not fully attributed to a deterioration of physical properties. Changes in SPA were concomitant with changes in MCT1 expression in the soleus muscle of trained rats, suggestive of an additional adaptive response toward increased lactate clearance. This result is in line with our observation showing a better equilibrium on lactate production-remotion during the continuous exercise (LMT). We propose an approach to combat the decline of SPA of rats in their home cages. This new finding is worth for scientists who work with animal models to study the protective effects of exercise.

  18. Novel RepA-MCM proteins encoded in plasmids pTAU4, pORA1 and pTIK4 from Sulfolobus neozealandicus

    PubMed Central

    Greve, Bo; Jensen, Susanne; Phan, Hoa; Brügger, Kim; Zillig, Wolfram; She, Qunxin; Garrett, Roger A.

    2005-01-01

    Three plasmids isolated from the crenarchaeal thermoacidophile Sulfolobus neozealandicus were characterized. Plasmids pTAU4 (7,192 bp), pORA1 (9,689 bp) and pTIK4 (13,638 bp) show unusual properties that distinguish them from previously characterized cryptic plasmids of the genus Sulfolobus. Plasmids pORA1 and pTIK4 encode RepA proteins, only the former of which carries the novel polymerase–primase domain of other known Sulfolobus plasmids. Plasmid pTAU4 encodes a mini-chromosome maintenance protein homolog and no RepA protein; the implications for DNA replication are considered. Plasmid pORA1 is the first Sulfolobus plasmid to be characterized that does not encode the otherwise highly conserved DNA-binding PlrA protein. Another encoded protein appears to be specific for the New Zealand plasmids. The three plasmids should provide useful model systems for functional studies of these important crenarchaeal proteins. PMID:15876565

  19. The rice blast resistance gene Ptr encodes an atypical protein required for broad spectrum disease resistance

    USDA-ARS?s Scientific Manuscript database

    Plant resistance (R) genes typically encode proteins with nucleotide binding site-leucine rich repeat (NLR) domains. We identified a novel, broad-spectrum rice blast R gene, Ptr, encoding a non-NLR protein with four Armadillo repeats. Ptr was originally identified by fast neutron mutagenesis as a ...

  20. Alternative intronic promoters in development and disease.

    PubMed

    Vacik, Tomas; Raska, Ivan

    2017-05-01

    Approximately 20,000 mammalian genes are estimated to encode between 250 thousand and 1 million different proteins. This enormous diversity of the mammalian proteome is caused by the ability of a single-gene locus to encode multiple protein isoforms. Protein isoforms encoded by one gene locus can be functionally distinct, and they can even have antagonistic functions. One of the mechanisms involved in creating this proteome complexity is alternative promoter usage. Alternative intronic promoters are located downstream from their canonical counterparts and drive the expression of alternative RNA isoforms that lack upstream exons. These upstream exons can encode some important functional domains, and proteins encoded by alternative mRNA isoforms can be thus functionally distinct from the full-length protein encoded by canonical mRNA isoforms. Since any misbalance of functionally distinct protein isoforms is likely to have detrimental consequences for the cell and the whole organism, their expression must be precisely regulated. Misregulation of alternative intronic promoters is frequently associated with various developmental defects and diseases including cancer, and it is becoming increasingly clear that this phenomenon deserves more attention.

  1. [The topical problems of pediatric balneotherapy and the spa and health resort-based treatment of the children].

    PubMed

    Razumov, A N; Khan, M A

    2016-01-01

    This article is devoted to the topical problems of pediatric balneotherapy with special reference to the organization of the spa and health resort-based treatment of the children in the Russian Federation. The main issues discussed by the authors include the current state of health resort care for the children, the problem of statutory regulation of the activities of the children's spa and health resort facilities, the approaches to increasing the availability of the spa and health resort-based treatment for the children at the enhanced risk of the development of chronic diseases, disabilities, and tuberculosis. Also considered are the problems of the development of the regulatory framework for the medical rehabilitation of the children based at the spa and health resort facilities. The principal goals to be sought in climatotherapy, physiotherapy, balneotherapy, and pelotherapy in the pediatric context are outlined along with the further prospects for the development of the main areas of pediatric balneology.

  2. Sclerosing polycystic adenosis of the parotid gland presenting with a Warthin tumor.

    PubMed

    Tokyol, Ciğdem; Aktepe, Fatma; Hastürk, Güler Senyıldız; Yıldız, Hüseyin; Miman, Murat Cem

    2012-01-01

    Sclerosing polycystic adenosis (SPA) frequently presents as an isolated process, however it may involve adjacent benign salivary gland neoplasia. In this article, we present a 77-year-old female case with a 10-year history of a slow-growing mass of the left parotid gland of SPA presenting with a Warthin tumor. The patient underwent left superficial parotidectomy. The histopathological examination revealed SPA and multifocal Warthin tumor.

  3. Statistical Power Analysis with Microsoft Excel: Normal Tests for One or Two Means as a Prelude to Using Non-Central Distributions to Calculate Power

    ERIC Educational Resources Information Center

    Texeira, Antonio; Rosa, Alvaro; Calapez, Teresa

    2009-01-01

    This article presents statistical power analysis (SPA) based on the normal distribution using Excel, adopting textbook and SPA approaches. The objective is to present the latter in a comparative way within a framework that is familiar to textbook level readers, as a first step to understand SPA with other distributions. The analysis focuses on the…

  4. Application of a Cloud Model-Set Pair Analysis in Hazard Assessment for Biomass Gasification Stations.

    PubMed

    Yan, Fang; Xu, Kaili

    2017-01-01

    Because a biomass gasification station includes various hazard factors, hazard assessment is needed and significant. In this article, the cloud model (CM) is employed to improve set pair analysis (SPA), and a novel hazard assessment method for a biomass gasification station is proposed based on the cloud model-set pair analysis (CM-SPA). In this method, cloud weight is proposed to be the weight of index. In contrast to the index weight of other methods, cloud weight is shown by cloud descriptors; hence, the randomness and fuzziness of cloud weight will make it effective to reflect the linguistic variables of experts. Then, the cloud connection degree (CCD) is proposed to replace the connection degree (CD); the calculation algorithm of CCD is also worked out. By utilizing the CCD, the hazard assessment results are shown by some normal clouds, and the normal clouds are reflected by cloud descriptors; meanwhile, the hazard grade is confirmed by analyzing the cloud descriptors. After that, two biomass gasification stations undergo hazard assessment via CM-SPA and AHP based SPA, respectively. The comparison of assessment results illustrates that the CM-SPA is suitable and effective for the hazard assessment of a biomass gasification station and that CM-SPA will make the assessment results more reasonable and scientific.

  5. Successive Projections Algorithm-Multivariable Linear Regression Classifier for the Detection of Contaminants on Chicken Carcasses in Hyperspectral Images

    NASA Astrophysics Data System (ADS)

    Wu, W.; Chen, G. Y.; Kang, R.; Xia, J. C.; Huang, Y. P.; Chen, K. J.

    2017-07-01

    During slaughtering and further processing, chicken carcasses are inevitably contaminated by microbial pathogen contaminants. Due to food safety concerns, many countries implement a zero-tolerance policy that forbids the placement of visibly contaminated carcasses in ice-water chiller tanks during processing. Manual detection of contaminants is labor consuming and imprecise. Here, a successive projections algorithm (SPA)-multivariable linear regression (MLR) classifier based on an optimal performance threshold was developed for automatic detection of contaminants on chicken carcasses. Hyperspectral images were obtained using a hyperspectral imaging system. A regression model of the classifier was established by MLR based on twelve characteristic wavelengths (505, 537, 561, 562, 564, 575, 604, 627, 656, 665, 670, and 689 nm) selected by SPA , and the optimal threshold T = 1 was obtained from the receiver operating characteristic (ROC) analysis. The SPA-MLR classifier provided the best detection results when compared with the SPA-partial least squares (PLS) regression classifier and the SPA-least squares supported vector machine (LS-SVM) classifier. The true positive rate (TPR) of 100% and the false positive rate (FPR) of 0.392% indicate that the SPA-MLR classifier can utilize spatial and spectral information to effectively detect contaminants on chicken carcasses.

  6. Application of a Cloud Model-Set Pair Analysis in Hazard Assessment for Biomass Gasification Stations

    PubMed Central

    Yan, Fang; Xu, Kaili

    2017-01-01

    Because a biomass gasification station includes various hazard factors, hazard assessment is needed and significant. In this article, the cloud model (CM) is employed to improve set pair analysis (SPA), and a novel hazard assessment method for a biomass gasification station is proposed based on the cloud model-set pair analysis (CM-SPA). In this method, cloud weight is proposed to be the weight of index. In contrast to the index weight of other methods, cloud weight is shown by cloud descriptors; hence, the randomness and fuzziness of cloud weight will make it effective to reflect the linguistic variables of experts. Then, the cloud connection degree (CCD) is proposed to replace the connection degree (CD); the calculation algorithm of CCD is also worked out. By utilizing the CCD, the hazard assessment results are shown by some normal clouds, and the normal clouds are reflected by cloud descriptors; meanwhile, the hazard grade is confirmed by analyzing the cloud descriptors. After that, two biomass gasification stations undergo hazard assessment via CM-SPA and AHP based SPA, respectively. The comparison of assessment results illustrates that the CM-SPA is suitable and effective for the hazard assessment of a biomass gasification station and that CM-SPA will make the assessment results more reasonable and scientific. PMID:28076440

  7. Antibodies to VP1 of swine pasivirus in humans without evidence of transmission from a pig source.

    PubMed

    Arnold, Francoise; Hober, Didier; Chaussade, Hélène; Dumarest, Marine; Sané, Famara; Nowakowsjki, Mireille; Rigaud, Emma; Bellalou, Jacques; Desailloud, Rachel; Coursaget, Pierre; Eloit, Marc

    2015-08-01

    Swine pasivirus (SPaV1) is a recently described enteric virus close to human parechoviruses and highly prevalent in pigs. Antibodies to Escherichia coli-expressed VP1 of SpaV1 have been found in a majority of humans in China. The objectives were to estimate the antibody prevalence in a European country, to test if exposure to the virus was linked to pig products and if this exposure was a risk factor for the development of diabetes type 1. An ELISA test was developed and used to screen 842 healthy subjects with known exposure to pig products, 39 patients with diabetes type 1 and 20 controls. We identified a high seroprevalence (15.6%) reacting to VP1 of SPaV1 among healthy human subjects. Analysis of risk factors argues against cross-species transmission from pigs as the source of infection. Data also indicate that the presence of SPaV1 VP1-binding antibodies is not associated with diabetes type 1 in humans. Our results suggest that the seroreactivity frequently found in humans against SpaV1 is due to cross-reactivity with related antigen, perhaps a picornavirus, and that SpaV1 is not a zoonotic virus. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Supersonic Wing Optimization Using SpaRibs

    NASA Technical Reports Server (NTRS)

    Locatelli, David; Mulani, Sameer B.; Liu, Qiang; Tamijani, Ali Y.; Kapania, Rakesh K.

    2014-01-01

    This research investigates the advantages of using curvilinear spars and ribs, termed SpaRibs, to design a supersonic aircraft wing-box in comparison to the use of classic design concepts that employ straight spars and ribs. The objective is to achieve a more efficient load-bearing mechanism and to passively control the deformation of the structure under the flight loads. Moreover, the use of SpaRibs broadens the design space and allows for natural frequencies and natural mode shape tailoring. The SpaRibs concept is implemented in a new optimization MATLAB-based framework referred to as EBF3SSWingOpt. This optimization scheme performs both the sizing and the shaping of the internal structural elements, connecting the optimizer with the analysis software. The shape of the SpaRibs is parametrically defined using the so called Linked Shape method. Each set of SpaRibs is placed in a one by one square domain of the natural space. The set of curves is subsequently transformed in the physical space for creating the wing structure geometry layout. The shape of each curve of each set is unique; however, mathematical relations link the curvature in an effort to reduce the number of design variables. The internal structure of a High Speed Commercial Transport aircraft concept developed by Boeing is optimized subjected to stress, subsonic flutter and supersonic flutter constraints. The results show that the use of the SpaRibs allows for the reduction of the aircraft's primary structure weight without violating the constraints. A weight reduction of about 15 percent is observed.

  9. Spa therapy: can be a valid option for treating knee osteoarthritis?

    NASA Astrophysics Data System (ADS)

    Tenti, Sara; Cheleschi, Sara; Galeazzi, Mauro; Fioravanti, Antonella

    2015-08-01

    Osteoarthritis (OA) continues to be one of the leading causes of `years lived with disability' worldwide. Symptomatic knee OA is highly prevalent among people aged 50 years and over and is destined to become an ever more important healthcare problem. Current management of knee OA includes non-pharmacological and pharmacological treatments. Spa therapy is one of the most commonly used non-pharmacological approaches for OA in many European countries, as well as in Japan and Israel. Despite its long history and popularity, spa treatment is still the subject of debate and its role in modern medicine continues to be unclear. The objective of this review is to summarize the currently available information on clinical effects and mechanisms of action of spa therapy in knee OA. Various randomized controlled clinical trials (RCTs) were conducted to assess the efficacy and tolerability of balneotherapy and mud-pack therapy in patients with knee OA. Data from these clinical trials support a beneficial effect of spa therapy on pain, function and quality of life in knee OA that lasts over time, until 6-9 months after the treatment. The mechanisms by which immersion in mineral or thermal water or the application of mud alleviate suffering in OA are not fully understood. The net benefit is probably the result of a combination of factors, among which the mechanical, thermal and chemical effects are most prominent. In conclusion, spa therapy seems to have a role in the treatment of knee OA. Additional RCTs and further studies of mechanisms of action with high methodological quality are necessary to prove the effects of spa therapy.

  10. Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review

    NASA Astrophysics Data System (ADS)

    Antonelli, Michele; Donelli, Davide

    2018-06-01

    Balneotherapy and spa therapy are well-known practices, even though limited evidence has been produced about their biological effects. This systematic review primarily aims at assessing if balneotherapy, mud/peloid therapy, and spa therapy may influence cortisol levels. Secondarily, it aims at understanding if these interventions may improve stress resilience. PubMed/Medline, Embase, and Cochrane Library were searched for relevant articles in English or Italian about studies involving healthy and sub-healthy subjects or patients with a diagnosed disease about effects of balneotherapy, mud/peloid therapy, and spa therapy on serum and salivary cortisol levels. Fifteen studies involving 684 subjects were included. Five studies investigated biological effects of balneotherapy alone. Two of them reported significant changes of cortisol levels in healthy participants. The other three studies reported no significant variations in patients with rheumatic conditions. No studies investigated biological effects of mud/peloid therapy alone. Ten studies investigated biological effects of spa therapy with or without included mud/peloid therapy, and in all but two studies, significant variations of cortisol levels were reported. Our main findings suggest that balneotherapy may have the potential to influence cortisol levels in healthy subjects, in such a way as to improve stress resilience. Spa therapy with or without included mud/peloid therapy demonstrated the same potential to influence cortisol levels also in sub-healthy subjects and in patients with a diagnosed disease. Therefore, balneotherapy and spa therapy may be considered as useful interventions for the management of stress conditions. Further investigation is needed because of limited available data.

  11. Effectiveness of balneotherapy and spa therapy for the treatment of chronic low back pain: a review on latest evidence.

    PubMed

    Karagülle, Mine; Karagülle, Müfit Zeki

    2015-02-01

    In most European countries, balneotherapy and spa therapy are widely prescribed by physicians and preferred by European citizens for the treatment of musculoskeletal problems including chronic low back pain (LBP). We aimed to review and evaluate the recent evidence on the effectiveness of balneotherapy and spa therapy for patients with LBP. We comprehensively searched data bases for randomized controlled trials (RCTs) published in English between July 2005 and December 2013. We identified all trials testing balneotherapy or spa therapy for LBP that reported that the sequence of allocation was randomized. We finally included total of eight RCTs: two on balneotherapy and six on spa therapy. All reviewed trials reported that balneotherapy was superior in long term to tap water therapy in relieving pain and improving function and that spa therapy combining balneotherapy with mud pack therapy and/or exercise therapy, physiotherapy, and/or education was effective in the management of low back pain and superior or equally effective to the control treatments in short and long terms. We used Jadad scale to grade the methodological quality. Only three out of total eight had a score of above 3 indicating the good quality. The data from the RCTs indicates that overall evidence on effectiveness of balneotherapy and spa therapy in LBP is encouraging and reflects the consistency of previous evidence. However, the overall quality of trials is generally low. Better quality RCTs (well designed, conducted, and reported) are needed testing short- and long-term effects for relieving chronic back pain and proving broader beneficial effects.

  12. Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review.

    PubMed

    Antonelli, Michele; Donelli, Davide

    2018-02-18

    Balneotherapy and spa therapy are well-known practices, even though limited evidence has been produced about their biological effects. This systematic review primarily aims at assessing if balneotherapy, mud/peloid therapy, and spa therapy may influence cortisol levels. Secondarily, it aims at understanding if these interventions may improve stress resilience. PubMed/Medline, Embase, and Cochrane Library were searched for relevant articles in English or Italian about studies involving healthy and sub-healthy subjects or patients with a diagnosed disease about effects of balneotherapy, mud/peloid therapy, and spa therapy on serum and salivary cortisol levels. Fifteen studies involving 684 subjects were included. Five studies investigated biological effects of balneotherapy alone. Two of them reported significant changes of cortisol levels in healthy participants. The other three studies reported no significant variations in patients with rheumatic conditions. No studies investigated biological effects of mud/peloid therapy alone. Ten studies investigated biological effects of spa therapy with or without included mud/peloid therapy, and in all but two studies, significant variations of cortisol levels were reported. Our main findings suggest that balneotherapy may have the potential to influence cortisol levels in healthy subjects, in such a way as to improve stress resilience. Spa therapy with or without included mud/peloid therapy demonstrated the same potential to influence cortisol levels also in sub-healthy subjects and in patients with a diagnosed disease. Therefore, balneotherapy and spa therapy may be considered as useful interventions for the management of stress conditions. Further investigation is needed because of limited available data.

  13. Soft Pneumatic Actuator Fascicles for High Force and Reliability

    PubMed Central

    Robertson, Matthew A.; Sadeghi, Hamed; Florez, Juan Manuel

    2017-01-01

    Abstract Soft pneumatic actuators (SPAs) are found in mobile robots, assistive wearable devices, and rehabilitative technologies. While soft actuators have been one of the most crucial elements of technology leading the development of the soft robotics field, they fall short of force output and bandwidth requirements for many tasks. In addition, other general problems remain open, including robustness, controllability, and repeatability. The SPA-pack architecture presented here aims to satisfy these standards of reliability crucial to the field of soft robotics, while also improving the basic performance capabilities of SPAs by borrowing advantages leveraged ubiquitously in biology; namely, the structured parallel arrangement of lower power actuators to form the basis of a larger and more powerful actuator module. An SPA-pack module consisting of a number of smaller SPAs will be studied using an analytical model and physical prototype. Experimental measurements show an SPA pack to generate over 112 N linear force, while the model indicates the benefit of parallel actuator grouping over a geometrically equivalent single SPA scale as an increasing function of the number of individual actuators in the group. For a module of four actuators, a 23% increase in force production over a volumetrically equivalent single SPA is predicted and validated, while further gains appear possible up to 50%. These findings affirm the advantage of utilizing a fascicle structure for high-performance soft robotic applications over existing monolithic SPA designs. An example of high-performance soft robotic platform will be presented to demonstrate the capability of SPA-pack modules in a complete and functional system. PMID:28289573

  14. Soft Pneumatic Actuator Fascicles for High Force and Reliability.

    PubMed

    Robertson, Matthew A; Sadeghi, Hamed; Florez, Juan Manuel; Paik, Jamie

    2017-03-01

    Soft pneumatic actuators (SPAs) are found in mobile robots, assistive wearable devices, and rehabilitative technologies. While soft actuators have been one of the most crucial elements of technology leading the development of the soft robotics field, they fall short of force output and bandwidth requirements for many tasks. In addition, other general problems remain open, including robustness, controllability, and repeatability. The SPA-pack architecture presented here aims to satisfy these standards of reliability crucial to the field of soft robotics, while also improving the basic performance capabilities of SPAs by borrowing advantages leveraged ubiquitously in biology; namely, the structured parallel arrangement of lower power actuators to form the basis of a larger and more powerful actuator module. An SPA-pack module consisting of a number of smaller SPAs will be studied using an analytical model and physical prototype. Experimental measurements show an SPA pack to generate over 112 N linear force, while the model indicates the benefit of parallel actuator grouping over a geometrically equivalent single SPA scale as an increasing function of the number of individual actuators in the group. For a module of four actuators, a 23% increase in force production over a volumetrically equivalent single SPA is predicted and validated, while further gains appear possible up to 50%. These findings affirm the advantage of utilizing a fascicle structure for high-performance soft robotic applications over existing monolithic SPA designs. An example of high-performance soft robotic platform will be presented to demonstrate the capability of SPA-pack modules in a complete and functional system.

  15. Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review

    NASA Astrophysics Data System (ADS)

    Antonelli, Michele; Donelli, Davide

    2018-02-01

    Balneotherapy and spa therapy are well-known practices, even though limited evidence has been produced about their biological effects. This systematic review primarily aims at assessing if balneotherapy, mud/peloid therapy, and spa therapy may influence cortisol levels. Secondarily, it aims at understanding if these interventions may improve stress resilience. PubMed/Medline, Embase, and Cochrane Library were searched for relevant articles in English or Italian about studies involving healthy and sub-healthy subjects or patients with a diagnosed disease about effects of balneotherapy, mud/peloid therapy, and spa therapy on serum and salivary cortisol levels. Fifteen studies involving 684 subjects were included. Five studies investigated biological effects of balneotherapy alone. Two of them reported significant changes of cortisol levels in healthy participants. The other three studies reported no significant variations in patients with rheumatic conditions. No studies investigated biological effects of mud/peloid therapy alone. Ten studies investigated biological effects of spa therapy with or without included mud/peloid therapy, and in all but two studies, significant variations of cortisol levels were reported. Our main findings suggest that balneotherapy may have the potential to influence cortisol levels in healthy subjects, in such a way as to improve stress resilience. Spa therapy with or without included mud/peloid therapy demonstrated the same potential to influence cortisol levels also in sub-healthy subjects and in patients with a diagnosed disease. Therefore, balneotherapy and spa therapy may be considered as useful interventions for the management of stress conditions. Further investigation is needed because of limited available data.

  16. One year in review 2017: spondyloarthritis.

    PubMed

    Terenzi, Riccardo; Monti, Sara; Tesei, Giulia; Carli, Linda

    2018-01-01

    The term spondyloarthritis (SpA) represents a condition characterised by a broad spectrum of clinical manifestations, laboratory abnormalities and imaging features; in particular, SpA is an inflammatory condition in which both peripheral and axial joints might be affected. The majority of people with this disease have either psoriatic arthritis or axial spondyloarthritis, which includes ankylosing spondylitis. Less common subgroups are enteropathic SpA, which is associated with inflammatory bowel diseases (Crohn's disease and ulcerative colitis), reactive arthritis, which can occur in people following gastrointestinal or genitourinary infections and undifferentiated SpA, that does not meet the diagnostic criteria of the other subgroups at onset, but that may evolve to do so later. Very interestingly, much of the emerging data show how SpA, during its course, tends to associate with the development of some comorbidities; in particular, with cardiovascular diseases, diabetes mellitus, osteoporosis and depressive disorders. Healthcare professionals in non-specialist settings do not always recognise the signs and symptoms of SpA, particularly spinal symptoms, which may be mistakenly attributed to other causes of low back pain, thus leading to significant delays in diagnosis and treatment of the disease itself and of its related comorbidities, with consequent disease progression and disability, compromising the health-related quality of life of patients. In this paper we reviewed the literature of the past year (Medline search of articles published from 1st March 2016 to 28th February 2017) with the aim of approaching the spectrum of SpA from some different points of view, to try to give the reader an insight into this clinically challenging group of rheumatic pathologies.

  17. Sagittal Vertical Axias, Spinosacral Angle, Spinopelvic Angle, and T1 Pelvic Angle: Which Parameters May Effectively Predict the Quality of Life in Ankylosing Spondylitis Patients With Thoracolumbar Kyphosis?

    PubMed

    Zhang, Yun-Peng; Qian, Bang-Ping; Qiu, Yong; Qu, Zhe; Mao, Sai-Hu; Jiang, Jun; Zhu, Ze-Zhang

    2017-08-01

    This is a retrospective study. To identify the relationship between global sagittal alignment and health-related quality of life (HRQoL) in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis. Little data are available on correlation between global sagittal alignment and HRQoL in AS. A total of 107 AS patients were included in this study. The radiographic parameters were measured on lateral radiographs of the whole spine, including sagittal vertical axias (SVA), spinosacral angle (SSA), spinopelvic angle (SPA), and T1 pelvic angle (TPA). HRQoL was assessed using the oswestry disability index questionnaire, the bath ankylosing spondylitis disease activity index, the bath ankylosing spondylitis functional index, and short form-36 questionnaire. The patients were divided into 2 groups: group A (n=76, global kyphosis≤70 degrees), group B (n=31, global kyphosis>70 degrees). Statistical analysis was performed to identify significant differences between these 2 groups. In addition, correlation analysis and multiple regression analysis between radiologic parameters and clinical questionnaires were conducted. With respect to SVA, SSA, SPA, TPA, and HRQoL scores, significant differences were observed between 2 groups (P<0.05). Also, SVA, SSA, SPA, and TPA were significantly related to HRQoL. Multiple regression analysis revealed that SVA, SSA, SPA, and TPA were significant parameters in the prediction of HRQoL in AS patients with thoracolumbar kyphosis. Of note, HRQoL related much more to SSA and SPA than SVA and TPA. AS patients with moderate and severe deformity were demonstrated to be significantly different in terms of SVA, SSA, SPA, TPA, and HRQoL. Moreover, SVA, SSA, SPA, and TPA correlated with HRQoL significantly. In particular, SSA and SPA could better predict HRQoL than SVA and TPA in AS patients with thoracolumbar kyphosis.

  18. [Impact of SPA therapy with sulphureous mineral water on quality of life and psychological distress in chronic plaque psoriasis].

    PubMed

    Costantino, M; Filippelli, A

    2014-01-01

    The plaque psoriasis, one of the most common form of psoriasis, is a chronic inflammatory disease. This pathology can cause devastating effects on quality of life and social relations with significant physical and psychological distress. Currently among the therapeutic agents available for the treatment of psoriasis is including SPA therapy, whose mechanism of action is only partially known, as well as very few studies examined the impact of this therapy on the quality of life. On the basis of these considerations, the research analyzed the effectiveness of SPA bath therapy (BLT) and its impact on quality of life and psychological distress in patients suffering from chronic plaque psoriasis. The study was conducted on 35 patients with chronic plaque psoriasis: 23% male and 77% female; mean age:56 ± 19 years; age range:17-85 years. The subjects were treated, for 2 weeks, with sulphureous SPA bath therapy from Terme of Telese SpA (Benevento-Italy). At the beginning and at the end of the SPA treatment considered was evaluated: the itching symptom (using NRS scale); the PASI Index; the impact on quality of life (using SF-36 and DLQI questionnaires) and on psychological distress (using ZUNG -tests). At the end of the SPA treatment, the mean values ± SD, compared to baseline, have showed a significant (p <0.01) reduction in itching symptom (1.8 ± 1.1-->1.0 ± 1.0) and PASI score (4 ± 4-->1.7 ± 2) with an improvement in quality of life and psichological distress as demonstrated by SF-36, DLQI and ZUNG tests. The data of this research show that the sulphureous SPA bath therapy can be considered very useful in patients with mild-to-moderate psoriasis for the improving of the quality of life and social relationship.

  19. Validation of the Spanish Version of the Eating Assessment Tool-10 (EAT-10spa) in Colombia. A Blinded Prospective Cohort Study.

    PubMed

    Giraldo-Cadavid, Luis Fernando; Gutiérrez-Achury, Alejandra María; Ruales-Suárez, Karem; Rengifo-Varona, Maria Leonor; Barros, Camilo; Posada, Andrés; Romero, Carlos; Galvis, Ana María

    2016-06-01

    Dysphagia might affect 12 % of the general population, and its complications include pneumonia, malnutrition, social isolation, and death. No validated Spanish symptom survey exists to quantify dysphagia symptoms among Latin Americans. Therefore, we performed a prospective cohort study in a tertiary care university hospital to validate the Spanish version of the 10-Item Eating-Assessment-Tool (EAT-10spa) for use in Colombia. After an interdisciplinary committee of five bilingual specialists evaluated the EAT-10spa (translated and validated in Spain) and deemed it appropriate for the Colombian culture, its feasibility, reliability, validity, sensitivity to change, and diagnostic capacity were evaluated. As a reference standard, we used the flexible endoscopic evaluation of swallowing with sensory testing and a standardized clinical evaluation. All assessments were blinded. In total, 133 subjects were included (52 % women, mean age 55 years) and completed the EAT-10spa (median completion time: 2 min [IQR 1-3 min]), 39 % of whom had an elementary-level education. Cronbach's α coefficient: 0.91; test-retest intra-class correlation coefficient: 0.94. The Spearman's correlation coefficient of the EAT-10spa with the 8-point penetration-aspiration scale was 0.54 (P < 0.001). The area under the receiver-operating-characteristic-curve (AUC-ROC) for dysphagia and aspiration were 0.79 (P < 0.001) and 0.81 (P < 0.001), respectively. The best cut-off points for dysphagia and aspiration were EAT-10spa ≥2 (sensitivity 93.6 %, specificity 36.4 %) and EAT-10spa ≥4 (sensitivity 94.3 %, specificity 49.5 %), respectively. A reduction in the EAT-10 ≥3 was the best cut-off point for a clinically significant improvement (AUC-ROC 0.83; P < 0.0001). The EAT-10spa showed excellent psychometric properties and discriminatory capacity for use in Colombia.

  20. Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis.

    PubMed

    Tito, Raul Y; Cypers, Heleen; Joossens, Marie; Varkas, Gaëlle; Van Praet, Liesbet; Glorieus, Elien; Van den Bosch, Filip; De Vos, Martine; Raes, Jeroen; Elewaut, Dirk

    2017-01-01

    Dysbiosis of the intestinal microbiota has been widely established in inflammatory bowel disease (IBD). There is significant clinical and genetic overlap between spondyloarthritis (SpA) and IBD, and up to 50% of all patients with SpA exhibit microscopic signs of bowel inflammation, often bearing particular resemblance to early Crohn's disease, a subtype of IBD. This study was undertaken to assess the relationship between intestinal microbial composition, gut histology, and disease activity markers in SpA. Gene analysis by 16S ribosomal RNA amplicon sequencing was used to compare the microbial composition in ileal and colonic biopsy specimens from 27 patients with SpA (14 with microscopic bowel inflammation, 13 without) and 15 healthy control subjects (ileal samples from all 15 subjects and colonic samples from 6). Spearman's rank correlation tests were used to assess correlations of the microbial composition with disease activity measures. The intestinal inflammation status (histologically normal versus acute or chronic inflammation) was strongly associated with the mucosal microbiota profile of patients with SpA. In inflamed biopsy tissue, the detected bacterial community composition clustered separately from that in noninflamed biopsy tissue (P < 0.05 by permutational multivariate analysis of variance, using hierarchical clustering on Bray-Curtis distances). Interestingly, abundance of the genus Dialister was found to be positively correlated with the Ankylosing Spondylitis Disease Activity Score (Spearman's rho = 0.62, false discovery rate-corrected q < 0.01). This finding was further supported by the low frequency of Dialister observed in noninflamed ileal and colonic biopsy tissue from patients with SpA and healthy controls. These findings demonstrate a significant difference in the intestinal microbial composition in patients with SpA who have microscopic gut inflammation compared to those without microscopic gut inflammation. Moreover, Dialister may represent a potential microbial marker of disease activity in SpA. © 2016, American College of Rheumatology.

  1. Comparison of structured and unstructured physical activity training on predicted VO2max and heart rate variability in adolescents - a randomized control trial.

    PubMed

    Sharma, Vivek Kumar; Subramanian, Senthil Kumar; Radhakrishnan, Krishnakumar; Rajendran, Rajathi; Ravindran, Balasubramanian Sulur; Arunachalam, Vinayathan

    2017-05-01

    Physical inactivity contributes to many health issues. The WHO-recommended physical activity for adolescents encompasses aerobic, resistance, and bone strengthening exercises aimed at achieving health-related physical fitness. Heart rate variability (HRV) and maximal aerobic capacity (VO2max) are considered as noninvasive measures of cardiovascular health. The objective of this study is to compare the effect of structured and unstructured physical training on maximal aerobic capacity and HRV among adolescents. We designed a single blinded, parallel, randomized active-controlled trial (Registration No. CTRI/2013/08/003897) to compare the physiological effects of 6 months of globally recommended structured physical activity (SPA), with that of unstructured physical activity (USPA) in healthy school-going adolescents. We recruited 439 healthy student volunteers (boys: 250, girls: 189) in the age group of 12-17 years. Randomization across the groups was done using age and gender stratified randomization method, and the participants were divided into two groups: SPA (n=219, boys: 117, girls: 102) and USPA (n=220, boys: 119, girls: 101). Depending on their training status and gender the participants in both SPA and USPA groups were further subdivided into the following four sub-groups: SPA athlete boys (n=22) and girls (n=17), SPA nonathlete boys (n=95) and girls (n=85), USPA athlete boys (n=23) and girls (n=17), and USPA nonathlete boys (n=96) and girls (n=84). We recorded HRV, body fat%, and VO2 max using Rockport Walk Fitness test before and after the intervention. Maximum aerobic capacity and heart rate variability increased significantly while heart rate, systolic blood pressure, diastolic blood pressure, and body fat percentage decreased significantly after both SPA and USPA intervention. However, the improvement was more in SPA as compared to USPA. SPA is more beneficial for improving cardiorespiratory fitness, HRV, and reducing body fat percentage in terms of magnitude than USPA in adolescent individuals irrespective of their gender and sports activities.

  2. Comparative study of safety and outcomes of single-port access versus conventional laparoscopic colorectal surgery.

    PubMed

    Kanakala, V; Borowski, D W; Agarwal, A K; Tabaqchali, M A; Garg, D K; Gill, T S

    2012-12-01

    Single-port access (SPA) offers cosmetic advantages in addition to the well-recognised benefits of conventional multi-port laparoscopic (CL) surgery, and can be carried out using standard straight instruments. We report the outcomes of our early experience with SPA colorectal resections in comparison with CL surgery. We compared the following data, patient characteristics, operating time, morbidity, operative mortality, length of hospital stay and tumour variables, of patients who underwent SPA right, left, sigmoid and total colon resections, as well as high anterior resections and panproctocolectomies, with that of patients who underwent equivalent conventional laparoscopic (CL) operations. The 40 SPA and 78 CL patients studied underwent surgery between February 2008 and September 2011. There was no difference between the SPA and CL operations, as regards the patient's sex (55.0 vs. 62.8% males, p = 0.411), comorbidity (ASA I 10.0 vs. 12.8%; ASA II 57.5 vs. 59.0%; ASA III 32.5 vs. 25.6%; ASA IV 0 vs. 2.6%, p = 0.722) and body mass index (26.2 vs. 28.0 kg/m(2), p = 0.073). However, SPA patients were younger (mean age 54.1 vs. 64.8 years, p = 0.001), and malignancy was a less common indication for surgery (25.0 vs. 71.8%, p < 0.001). There were no conversions to open surgery, and one death occurred in the CL group (1.3%). Mean operating time (162 vs. 170 min, p = 0.547), median post-operative hospital stay (4 vs. 4 days, p = 0.255) and morbidity (7.5 vs. 12.8%, p = 0.538) were comparable. SPA laparoscopic surgery appears safe in the hands of experienced laparoscopic surgeons, with no increase in operating time, length of stay, morbidity and mortality. Selection of patients with indications for surgery for benign disease may be of importance to ensure an oncologically safe initial uptake of SPA colorectal practice.

  3. Spontaneous physical activity protects against fat mass gain

    PubMed Central

    Teske, Jennifer A.; Billington, Charles J.; Kuskowski, Michael A.; Kotz, Catherine M.

    2011-01-01

    It is unclear whether elevated spontaneous physical activity (SPA, very low-intensity physical activity) positively influences body composition long-term. Objective We determined whether SPA and caloric intake were differentially related to the growth curve trajectories of body weight, FM and FFM between obesity resistant and Sprague-Dawley rats at specific age intervals. Design and Subjects Body composition, SPA and caloric intake were measured in selectively-bred obesity resistant and out-bred Sprague-Dawley rats from 1-18 mo. Data from development throughout maturation were analyzed by longitudinal growth curve modeling to determine the rate and acceleration of body weight, fat mass (FM) and fat-free mass (FFM) gain. Results Obesity resistant rats had a lower rate of FM gain overall, a lower acceleration in body weight early in life, significantly greater SPA and lower cumulative caloric intake. Greater SPA in obesity resistant rats was significantly associated with a lower rate of FM gain overall and lower acceleration in body weight early in life. Obesity resistant rats lost less FFM compared to Sprague-Dawley rats despite that obesity resistant rats had a lower acceleration in FFM gain early in life. Obesity resistant rats gained less FM and more FFM per gram body weight and were less energy efficient than Sprague-Dawley rats. Caloric intake was significantly and positively related to body weight, FM and FFM gain in both groups. Circadian patterns of caloric intake were group and age-dependent. Our data demonstrate that elevated and sustained SPA during development and over the lifespan are related to the reduced the rate of FM gain and may preserve FFM. Conclusion These data support the idea that SPA level is a reproducible marker that reliably predicts propensity for obesity in rats, and that elevated levels of SPA maintained during the lifespan promote a lean phenotype. PMID:21610695

  4. Adenosine A1 Receptors in Mouse Pontine Reticular Formation Modulate Nociception Only in the Presence of Systemic Leptin

    PubMed Central

    Watson, Sarah L.; Watson, Christopher J.; Baghdoyan, Helen A.; Lydic, Ralph

    2014-01-01

    Human obesity is associated with increased leptin levels and pain, but the specific brain regions and neurochemical mechanisms underlying this association remain poorly understood. This study used adult male C57BL/6J (B6, n = 14) mice and leptin-deficient, obese B6.Cg-Lepob/J (obese, n = 10) mice to evaluate the hypothesis that nociception is altered by systemic leptin levels and by adenosine A1 receptors in the pontine reticular formation. Nociception was quantified as paw withdrawal latency (PWL) in s after onset of a thermal stimulus. PWL was converted to percent maximum possible effect (%MPE). After obtaining baseline PWL measures, the pontine reticular formation was microinjected with saline (control), three concentrations of the adenosine A1 receptor agonist N6-p-sulfophenyladenosine (SPA), or super-active mouse leptin receptor antagonist (SMLA) followed by SPA 15 min later, and PWL was again quantified. In obese, leptin-deficient mice, nociception was quantified before and during leptin replacement via subcutaneous osmotic pumps. SPA was administered into the pontine reticular formation of leptin-replaced mice and PWL testing was repeated. During baseline (before vehicle or SPA administration), PWL was significantly (p = 0.0013) lower in leptin-replaced obese mice than in B6 mice. Microinjecting SPA into the pontine reticular formation of B6 mice caused a significant (p = 0.0003) concentration-dependent increase in %MPE. SPA also significantly (p < 0.05) increased %MPE in B6 mice and in leptin-replaced obese mice, but not in leptin-deficient obese mice. Microinjection of the mouse super-active leptin antagonist (SMLA) into the pontine reticular formation before SPA did not alter PWL. The results show for the first time that pontine reticular formation administration of the adenosine A1 receptor agonist SPA produced antinociception only in the presence of systemic leptin. The concentration-response data support the interpretation that adenosine A1 receptors localized to the pontine reticular formation significantly alter nociception. PMID:24976513

  5. Adenosine A₁ receptors in mouse pontine reticular formation modulate nociception only in the presence of systemic leptin.

    PubMed

    Watson, S L; Watson, C J; Baghdoyan, H A; Lydic, R

    2014-09-05

    Human obesity is associated with increased leptin levels and pain, but the specific brain regions and neurochemical mechanisms underlying this association remain poorly understood. This study used adult male C57BL/6J (B6, n=14) mice and leptin-deficient, obese B6.Cg-Lep(ob)/J (obese, n=10) mice to evaluate the hypothesis that nociception is altered by systemic leptin levels and by adenosine A₁ receptors in the pontine reticular formation. Nociception was quantified as paw withdrawal latency (PWL) in s after onset of a thermal stimulus. PWL was converted to percent maximum possible effect (%MPE). After obtaining baseline PWL measures, the pontine reticular formation was microinjected with saline (control), three concentrations of the adenosine A₁ receptor agonist N(6)-p-sulfophenyladenosine (SPA), or super-active mouse leptin receptor antagonist (SMLA) followed by SPA 15 min later, and PWL was again quantified. In obese, leptin-deficient mice, nociception was quantified before and during leptin replacement via subcutaneous osmotic pumps. SPA was administered into the pontine reticular formation of leptin-replaced mice and PWL testing was repeated. During baseline (before vehicle or SPA administration), PWL was significantly (p=0.0013) lower in leptin-replaced obese mice than in B6 mice. Microinjecting SPA into the pontine reticular formation of B6 mice caused a significant (p=0.0003) concentration-dependent increase in %MPE. SPA also significantly (p<0.05) increased %MPE in B6 mice and in leptin-replaced obese mice, but not in leptin-deficient obese mice. Microinjection of SMLA into the pontine reticular formation before SPA did not alter PWL. The results show for the first time that pontine reticular formation administration of the adenosine A₁ receptor agonist SPA produced antinociception only in the presence of systemic leptin. The concentration-response data support the interpretation that adenosine A₁ receptors localized to the pontine reticular formation significantly alter nociception. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE PAGES

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; ...

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links V H3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High V H3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppressesmore » host B cell responses. Immunization with SpA KKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  7. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links V H3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High V H3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppressesmore » host B cell responses. Immunization with SpA KKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  8. Encoding of contextual fear memory requires de novo proteins in the prelimbic cortex

    PubMed Central

    Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu L.; Swarnkar, Supriya; Lora, Joan; Kadakkuzha, Beena M.; Liu, Xin-An; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.

    2016-01-01

    Background Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory. Methods Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex manipulation (n = 56) of Homer 3, a candidate identified from polyribosome profiling. Results We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA enriched in polyribosomes following CFC, in the PL constrained encoding of contextual fear memory. Conclusions Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC. PMID:28503670

  9. Randomized trial of balneotherapy associated with patient education in patients with advanced chronic venous insufficiency.

    PubMed

    Carpentier, Patrick H; Satger, Bernadette

    2009-01-01

    Except for compression therapy, physical therapy has scarcely been evaluated in the treatment of chronic venous disorders (CVD). Spa treatment is a popular way to administer physical therapy for CVD in France, but its efficacy has not been evaluated yet. This study aimed to assess the efficacy of balneotherapy associated with patient education, as performed in the spa resort of La Léchère, in patients with advanced chronic venous insufficiency (CEAP clinical classes C4/C5). The study was a randomized controlled trial, spa therapy being administered on top of the usual medical care. Evaluation was by a blinded independent investigator. Subjects were patients with primary or post-thrombotic CVD with skin changes but no active ulcer (C4a, C4b, or C5), living in Grenoble area, and willing to undergo a spa treatment course in La Léchère. The treated group had the three week spa treatment course in La Léchère, soon after randomization; the control group also had a spa treatment, but starting at day 365. The treatment consisted of four balneology sessions per day, six days a week during three weeks, and three educational workshops. An independent follow-up was performed in Grenoble hospital every three months for 15 months. The main outcome criterion was the severity of the skin changes, as evaluated by means of malleolar chromametry. Quality of life, as measured by the Chronic Venous Insufficiency Questionnaire 2 scale, a visual analog scale (VAS) for leg symptoms, and the occurrence of leg ulcers were used as secondary criteria. The year after spa treatment in the treated group was compared with the year before spa treatment in the control group. Fifty-nine subjects were enrolled (29 in the treatment group and 30 in the control group). No statistically significant difference between groups was found at study onset regarding age, sex, etiology, CEAP "C" class, and the outcome variables. After treatment, chromametry showed significantly decreased pigmentation and erythema in the treatment group compared with the controls (P < .01). Quality of life (P < .01) and symptoms (P < .001) also improved significantly. These differences remained significant after one year follow-up. The control patients improved similarly after their own spa treatment (day 450). This study shows that spa therapy, associating balneotherapy and patient education, is able to improve significantly the skin trophic changes of the CVD patients and their CVD related quality of life and symptoms. This effect is of large magnitude and remains significant one year after the treatment course.

  10. Burkholderia Mallei tssM Encodes a Secreted Deubiquitinase that is Expressed Inside Infected RAW 264.7 Murine Macrophages

    DTIC Science & Technology

    2008-10-13

    Furthermore, the encoded protein of this gene is only 30 kDa. A potential GTG start codon at position 625 also encodes a protein that is too small...horizontal bar and putative alternate translation initiation sites (ATG, GTG , and TTG) are indicated. The sizes and locations of the proteins encoded... gray line with rounded rectangles showing sequence features and motifs, including the Ala- and Pro-rich N-terminal region and the C-terminal Cys and

  11. East and West African milk products are reservoirs for human and livestock-associated Staphylococcus aureus.

    PubMed

    Jans, Christoph; Merz, Axel; Johler, Sophia; Younan, Mario; Tanner, Sabine A; Kaindi, Dasel Wambua Mulwa; Wangoh, John; Bonfoh, Bassirou; Meile, Leo; Tasara, Taurai

    2017-08-01

    Staphylococcus aureus frequently isolated from milk products in sub-Saharan Africa (SSA) is a major pathogen responsible for food intoxication, human and animal diseases. SSA hospital-derived strains are well studied but data on the population structure of foodborne S. aureus required to identify possible staphylococcal food poisoning sources is lacking. Therefore, the aim was to assess the population genetic structure, virulence and antibiotic resistance genes associated with milk-derived S. aureus isolates from Côte d'Ivoire, Kenya and Somalia through spa-typing, MLST, and DNA microarray analysis. Seventy milk S. aureus isolates from the three countries were assigned to 27 spa (7 new) and 23 (12 new) MLST sequence types. Milk-associated S. aureus of the three countries is genetically diverse comprising human and livestock-associated clonal complexes (CCs) predominated by the CC5 (n = 10) and CC30 (n = 9) isolates. Panton-Valentine leukocidin, toxic shock syndrome toxin and enterotoxin encoding genes were predominantly observed among human-associated CCs. Penicillin, fosfomycin and tetracycline, but not methicillin resistance genes were frequently detected. Our findings indicate that milk-associated S. aureus in SSA originates from human and animal sources alike highlighting the need for an overarching One Health approach to reduce S. aureus disease burdens through improving production processes, animal care and hygienic measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

    PubMed

    Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

    2015-08-01

    Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Oncoprotein AEG-1 is an endoplasmic reticulum RNA-binding protein whose interactome is enriched in organelle resident protein-encoding mRNAs.

    PubMed

    Hsu, Jack C-C; Reid, David W; Hoffman, Alyson M; Sarkar, Devanand; Nicchitta, Christopher V

    2018-05-01

    Astrocyte elevated gene-1 (AEG-1), an oncogene whose overexpression promotes tumor cell proliferation, angiogenesis, invasion, and enhanced chemoresistance, is thought to function primarily as a scaffolding protein, regulating PI3K/Akt and Wnt/β-catenin signaling pathways. Here we report that AEG-1 is an endoplasmic reticulum (ER) resident integral membrane RNA-binding protein (RBP). Examination of the AEG-1 RNA interactome by HITS-CLIP and PAR-CLIP methodologies revealed a high enrichment for endomembrane organelle-encoding transcripts, most prominently those encoding ER resident proteins, and within this cohort, for integral membrane protein-encoding RNAs. Cluster mapping of the AEG-1/RNA interaction sites demonstrated a normalized rank order interaction of coding sequence >5' untranslated region, with 3' untranslated region interactions only weakly represented. Intriguingly, AEG-1/membrane protein mRNA interaction sites clustered downstream from encoded transmembrane domains, suggestive of a role in membrane protein biogenesis. Secretory and cytosolic protein-encoding mRNAs were also represented in the AEG-1 RNA interactome, with the latter category notably enriched in genes functioning in mRNA localization, translational regulation, and RNA quality control. Bioinformatic analyses of RNA-binding motifs and predicted secondary structure characteristics indicate that AEG-1 lacks established RNA-binding sites though shares the property of high intrinsic disorder commonly seen in RBPs. These data implicate AEG-1 in the localization and regulation of secretory and membrane protein-encoding mRNAs and provide a framework for understanding AEG-1 function in health and disease. © 2018 Hsu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  14. Solenopsis invicta virus 3: mapping of structural proteins, ribosomal frameshifting, and similarities to Acyrthosiphon pisum virus and Kelp fly virus.

    PubMed

    Valles, Steven M; Bell, Susanne; Firth, Andrew E

    2014-01-01

    Solenopsis invicta virus 3 (SINV-3) is a positive-sense single-stranded RNA virus that infects the red imported fire ant, Solenopsis invicta. We show that the second open reading frame (ORF) of the dicistronic genome is expressed via a frameshifting mechanism and that the sequences encoding the structural proteins map to both ORF2 and the 3' end of ORF1, downstream of the sequence that encodes the RNA-dependent RNA polymerase. The genome organization and structural protein expression strategy resemble those of Acyrthosiphon pisum virus (APV), an aphid virus. The capsid protein that is encoded by the 3' end of ORF1 in SINV-3 and APV is predicted to have a jelly-roll fold similar to the capsid proteins of picornaviruses and caliciviruses. The capsid-extension protein that is produced by frameshifting, includes the jelly-roll fold domain encoded by ORF1 as its N-terminus, while the C-terminus encoded by the 5' half of ORF2 has no clear homology with other viral structural proteins. A third protein, encoded by the 3' half of ORF2, is associated with purified virions at sub-stoichiometric ratios. Although the structural proteins can be translated from the genomic RNA, we show that SINV-3 also produces a subgenomic RNA encoding the structural proteins. Circumstantial evidence suggests that APV may also produce such a subgenomic RNA. Both SINV-3 and APV are unclassified picorna-like viruses distantly related to members of the order Picornavirales and the family Caliciviridae. Within this grouping, features of the genome organization and capsid domain structure of SINV-3 and APV appear more similar to caliciviruses, perhaps suggesting the basis for a "Calicivirales" order.

  15. Achieving a golden mean: mechanisms by which coronaviruses ensure synthesis of the correct stoichiometric ratios of viral proteins.

    PubMed

    Plant, Ewan P; Rakauskaite, Rasa; Taylor, Deborah R; Dinman, Jonathan D

    2010-05-01

    In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed -1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the -1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream- to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by >4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a "golden mean" model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins.

  16. AGU section-wide electronic connections: A case history from SPA

    NASA Astrophysics Data System (ADS)

    Le, Guan; Russell, C. T.; Luhmann, J. G.

    In the spring of 1994 when the Internet was rapidly expanding and the World Wide Web was still developing,several of us serving in the SPA Section Executive Committee decided to launch an electronic newsletter and section Web site.The purpose of each was multifold. The newsletter would provide a way to rapidly disseminate items of recent interest, allowing widespread, immediate community response when warranted and a venue for advertising events of specific concern to SPA members and others with space physics connections. It would serve as an effective bulletin board for the exchange of useful information; for example, the launch of a spacecraft, the release of a special data set, or notes on honors bestowed upon SPA members.

  17. Protein synthesis in sperm: dialog between mitochondria and cytoplasm.

    PubMed

    Gur, Yael; Breitbart, Haim

    2008-01-30

    Ejaculated sperm are capable of using mRNAs transcripts for protein translation during the final maturation steps before fertilization. In a capacitation-dependent process, nuclear-encoded mRNAs are translated by mitochondrial-type ribosomes while the cytoplasmic translation machinery is not involved. Our findings suggest that new proteins are synthesized to replace degraded proteins while swimming and waiting in the female reproductive tract before fertilization, or produced due to the specific needs of the capacitating spermatozoa. In addition, a growing number of articles have reported evidence for the correlation of nuclear-encoded mRNA and protein synthesis in somatic mitochondria. It is known that all of the proteins necessary for the replication, transcription and translation of the genes encoded in mtDNA are now encoded in the nuclear genome. This genetic investment is far out of proportion to the number of proteins involved, as there have been multiple movements and duplications of genes. However, the evolutionary retention (or secondary uptake) of the mitochondrial machinery for translation of nuclear-encoded mRNAs may shed light on this paradox.

  18. Human AZU-1 gene, variants thereof and expressed gene products

    DOEpatents

    Chen, Huei-Mei; Bissell, Mina

    2004-06-22

    A human AZU-1 gene, mutants, variants and fragments thereof. Protein products encoded by the AZU-1 gene and homologs encoded by the variants of AZU-1 gene acting as tumor suppressors or markers of malignancy progression and tumorigenicity reversion. Identification, isolation and characterization of AZU-1 and AZU-2 genes localized to a tumor suppressive locus at chromosome 10q26, highly expressed in nonmalignant and premalignant cells derived from a human breast tumor progression model. A recombinant full length protein sequences encoded by the AZU-1 gene and nucleotide sequences of AZU-1 and AZU-2 genes and variant and fragments thereof. Monoclonal or polyclonal antibodies specific to AZU-1, AZU-2 encoded protein and to AZU-1, or AZU-2 encoded protein homologs.

  19. The Bean pod mottle virus RNA2-encoded 58-kilodalton protein P58 is required in cis for RNA2 accumulation

    USDA-ARS?s Scientific Manuscript database

    Bean pod mottle virus (BPMV) is a bipartite, positive sense (+) RNA plant virus in the Secoviridae family. Its RNA1 encodes proteins required for genome replication, whereas RNA2 primarily encodes proteins needed for virion assembly and cell-to-cell movement. However, the function of a 58 kilo-dalto...

  20. Characterization of the 5’- and 3’-terminal subgenomic RNAs produced by a capillovirus: evidence for a CP subgenomic RNA

    USDA-ARS?s Scientific Manuscript database

    The members of Capillovirus genus encode two overlapping open reading frames (ORFs): ORF1 encodes a large polyprotein containing the domains of replication-associated proteins plus a coat protein (CP), and ORF2 encodes a movement protein, located within ORF1 in a different reading frame. Organizatio...

  1. Protection of Mice from Fatal Measles Encephalitis by Vaccination with Vaccinia Virus Recombinants Encoding Either the Hemagglutinin or the Fusion Protein

    NASA Astrophysics Data System (ADS)

    Drillien, Robert; Spehner, Daniele; Kirn, Andre; Giraudon, Pascale; Buckland, Robin; Wild, Fabian; Lecocq, Jean-Pierre

    1988-02-01

    Vaccinia virus recombinants encoding the hemagglutinin or fusion protein of measles virus have been constructed. Infection of cell cultures with the recombinants led to the synthesis of authentic measles proteins as judged by their electrophoretic mobility, recognition by antibodies, glycosylation, proteolytic cleavage, and presentation on the cell surface. Mice vaccinated with a single dose of the recombinant encoding the hemagglutinin protein developed antibodies capable of both inhibiting hemagglutination activity and neutralizing measles virus, whereas animals vaccinated with the recombinant encoding the fusion protein developed measles neutralizing antibodies. Mice vaccinated with either of the recombinants resisted a normally lethal intracerebral inoculation of a cell-associated measles virus subacute sclerosing panencephalitis strain.

  2. Identification of a maize nucleic acid-binding protein (NBP) belonging to a family of nuclear-encoded chloroplast proteins.

    PubMed Central

    Cook, W B; Walker, J C

    1992-01-01

    A cDNA encoding a nuclear-encoded chloroplast nucleic acid-binding protein (NBP) has been isolated from maize. Identified as an in vitro DNA-binding activity, NBP belongs to a family of nuclear-encoded chloroplast proteins which share a common domain structure and are thought to be involved in posttranscriptional regulation of chloroplast gene expression. NBP contains an N-terminal chloroplast transit peptide, a highly acidic domain and a pair of ribonucleoprotein consensus sequence domains. NBP is expressed in a light-dependent, organ-specific manner which is consistent with its involvement in chloroplast biogenesis. The relationship of NBP to the other members of this protein family and their possible regulatory functions are discussed. Images PMID:1346929

  3. A novel dynamic flow immunochromatographic test (DFICT) using gold nanoparticles for the serological detection of Toxoplasma gondii infection in dogs and cats.

    PubMed

    Jiang, Wei; Liu, Yingchun; Chen, Yongjun; Yang, Qiufeng; Chun, Peter; Yao, Kailing; Han, Xiangan; Wang, Shaohui; Yu, Shengqing; Liu, Yongjie; Wang, Quan

    2015-10-15

    A novel dynamic flow immunochromatographic test (DFICT) is proposed for rapid assay utilizing Toxoplasma gondii as a model. The test is based on a proprietary technology that combines the principles of immunochromatography and fluid dynamics. Gold nanoparticles conjugated to staphylococcal protein A (SPA) were prepared in liquid form and used as signal vehicles. T. gondii-specific recombinant antigens and SPA were sprayed onto a nitrocellulose membrane in strips at positions designated as T and C, respectively. The DFICT is performed by applying a 100 µL aliquot of liquid gold-SPA conjugate to the reagent hole and a 5 μL aliquot of serum sample to the sample hole. The results were observable within 5 min by the naked eye. The lowest detectable limit of the assay was determined as the highest dilution (1:320) of positive serum. No cross-reaction of the antibodies with other related canine or feline pathogens was observed. The DFICT can be stored for 12 months at 4°C or 6 months with no loss of sensitivity or specificity. A high degree of consistency was observed between the DFICT and the standard ELISA kit, supporting the reliability of the novel test strip. The introduction of a liquid gold nanoparticle conjugate reagent provides this method with several attractive characteristics, such as ease of manufacture, low sample volume requirements, high selectivity and high efficiency. This method opens a novel pathway for rapid diagnostic screening and field analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Extensive Genetic Diversity Identified among Sporadic Methicillin-Resistant Staphylococcus aureus Isolates Recovered in Irish Hospitals between 2000 and 2012

    PubMed Central

    Kinnevey, Peter M.; Shore, Anna C.; Brennan, Grainne I.; Sullivan, Derek J.; Ehricht, Ralf; Monecke, Stefan

    2014-01-01

    Clonal replacement of predominant nosocomial methicillin-resistant Staphylococcus aureus (MRSA) strains has occurred several times in Ireland during the last 4 decades. However, little is known about sporadically occurring MRSA in Irish hospitals or in other countries. Eighty-eight representative pvl-negative sporadic MRSA isolates recovered in Irish hospitals between 2000 and 2012 were investigated. These yielded unusual pulsed-field gel electrophoresis and antibiogram-resistogram typing patterns distinct from those of the predominant nosocomial MRSA clone, ST22-MRSA-IV, during the study period. Isolates were characterized by spa typing and DNA microarray profiling for multilocus sequence type (MLST) clonal complex (CC) and/or sequence type (ST) and SCCmec type assignment, as well as for detection of virulence and antimicrobial resistance genes. Conventional PCR-based SCCmec subtyping was undertaken when necessary. Extensive diversity was detected, including 38 spa types, 13 MLST-CCs (including 18 STs among 62 isolates assigned to STs), and 25 SCCmec types (including 2 possible novel SCCmec elements and 7 possible novel SCCmec subtypes). Fifty-four MLST-spa-SCCmec type combinations were identified. Overall, 68.5% of isolates were assigned to nosocomial lineages, with ST8-t190-MRSA-IID/IIE ± SCCM1 predominating (17.4%), followed by CC779/ST779-t878-MRSA-ψSCCmec-SCC-SCCCRISPR (7.6%) and CC22/ST22-t032-MRSA-IVh (5.4%). Community-associated clones, including CC1-t127/t386/t2279-MRSA-IV, CC59-t216-MRSA-V, CC8-t008-MRSA-IVa, and CC5-t002/t242-MRSA-IV/V, and putative animal-associated clones, including CC130-t12399-MRSA-XI, ST8-t064-MRSA-IVa, ST398-t011-MRSA-IVa, and CC6-t701-MRSA-V, were also identified. In total, 53.3% and 47.8% of isolates harbored genes for resistance to two or more classes of antimicrobial agents and two or more mobile genetic element-encoded virulence-associated factors, respectively. Effective ongoing surveillance of sporadic nosocomial MRSA is warranted for early detection of emerging clones and reservoirs of virulence, resistance, and SCCmec genes. PMID:24395241

  5. Clonal Structure and Characterization of Staphylococcus aureus Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, spa Types, Clonal Complexes, and Genetic Markers

    PubMed Central

    Ilczyszyn, Weronika M.; Sabat, Artur J.; Akkerboom, Viktoria; Szkarlat, Anna; Klepacka, Joanna; Sowa-Sierant, Iwona; Wasik, Barbara; Kosecka-Strojek, Maja; Buda, Aneta; Miedzobrodzki, Jacek; Friedrich, Alexander W.

    2016-01-01

    The aim of current study was to examine clonal structure and genetic profile of invasive Staphylococcus aureus isolates recovered from infants and children treated at the Jagiellonian University Children’s Hospital of Krakow, Poland. The 107 invasive S. aureus isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, spa typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 S. aureus isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare-associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, spa-CC 002), CC45 (spa-CC 015), CC7 or CC15 (t084, t091, spa-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, spa types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including erm(A), sea (N315), egc-cluster, chp was significantly higher in isolates obtained from children in this age group. The spa types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas spa type t008, CC8 and presence of splE was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5 years, although the majority of invasive infections was associated with MSSA strains. Moreover, an association between age group of children from the study population and a specific strain genotype (spa type, clonal complex or genetic content) was observed among the patients. PMID:26992009

  6. [Uveitis in spondyloarthritis patients and its association with HLA-B27 histocompatibility antigen: prospective study].

    PubMed

    Razumova, I Yu; Godzenko, A A; Vorob'eva, O K; Guseva, I A

    2016-01-01

    to perform a prospective study of clinical presentation and course of uveitis in spondyloarthritis (SpA) patients as well as its association with the HLA-B27 histocompatibility antigen. The study included 219 patients with uveitis, all tested for HLA-B27 antigen and various infections (viral, bacterial, and parasitic) as well as examined for locomotive system involvement. The presence of the HLA-B27 antigen was determined in 142 (64.8%) out of 219 patients, of them 87 were diagnosed with an entity of the SpA group. The remaining 77 (35.2%) patients appeared to be HLA-B27-negative, but 13 were still diagnosed with an entity of the SpA group. There were 10 (4.6%) patients with 2 or more diseases from the SpA group («clinical decussation»). When comparing the two groups of HLA-B27-positive and negative patients having both SpA and uveitis, no statistically significant difference was found as to the age of onset, site, frequency of attacks, and uni- or bilateral involvement (p>0.05). We also performed a comparison of HLA-B27-positive and negative patients with no account to their SpA status and revealed a higher complication rate in those that were «negative» (p<0.0001), which can be explained by the fact that HLA-B27-negative patients often have autoimmune or infectious uveitis of different origin notable for long attacks and short remissions. Assessing the site and course of uveitis as well as HLA-B27 testing of uveitis patients has proved important for etiological diagnosis. Diseases of the SpA group have been shown to be 6.7 times more common in HLA-B27-positive patients as compared to HLA-B27-negative ones. Clinical presentation of uveitis in the presence of SpA in both HLA-B27-positive and negative patients resembles that of idiopathic uveitis - an independent HLA-B27-associated syndrome (р>0.05). Cases of «decussation» between entities of the SpA group are usually more severe in terms of clinical presentation and course of uveitis and are associated with a worse prognosis. Complications of uveitis are more likely to be found in non-SpA HLA-B27-negative patients (р<0.0001).

  7. South Pole-Aitken Sample Return Mission: Collecting Mare Basalts from the Far Side of the Moon

    NASA Technical Reports Server (NTRS)

    Gillis, J. J.; Jolliff, B. L.; Lucey, P. G.

    2003-01-01

    We consider the probability that a sample mission to a site within the South Pole-Aitken Basin (SPA) would return basaltic material. A sample mission to the SPA would be the first opportunity to sample basalts from the far side of the Moon. The near side basalts are more abundant in terms of volume and area than their far-side counterparts (16:1), and the basalt deposits within SPA represent approx. 28% of the total basalt surface area on the far side. Sampling far-side basalts is of particular importance because as partial melts of the mantle, they could have derived from a mantle that is mineralogically and chemically different than determined for the nearside, as would be expected if the magma ocean solidified earlier on the far side. For example, evidence to support the existence of high-Th basalts like those that appear to be common on the nearside in the Procellarum KREEP Terrane has been found. Although SPA is the deepest basin on the Moon, it is not extensively filled with mare basalt, as might be expected if similar amounts of partial melting occurred in the mantle below SPA as for basins on the near side. These observations may mean that mantle beneath the far-side crust is lower in Th and other heat producing elements than the nearside. One proposed location for a sample-return landing site is 60 S, 160 W. This site was suggested to maximize the science return with respect to sampling crustal material and SPA impact melt, however, basaltic samples would undoubtedly occur there. On the basis of Apollo samples, we should expect that basaltic materials would be found in the vicinity of any landing site within SPA, even if located away from mare deposits. For example, the Apollo 16 mission landed in an ancient highlands region 250-300 km away from the nearest mare-highlands boundary yet it still contains a small component of basaltic samples (20 lithic fragments ranging is size from <1 to .01 cm). A soil sample from the floor of SPA will likely contain an assortment of basaltic fragments from surrounding regions. In terms both of selecting the best landing sites and understanding the geologic context for returned samples, it is important to understand the compositional distribution of basalts within SPA basin.

  8. Cytochrome b5 gene and protein of Candida tropicalis and methods relating thereto

    DOEpatents

    Craft, David L.; Madduri, Krishna M.; Loper, John C.

    2003-01-01

    A novel gene has been isolated which encodes cytochrome b5 (CYTb5) protein of the .omega.-hydroxylase complex of C. tropicalis 20336. Vectors including this gene, and transformed host cells are provided. Methods of increasing the production of a CYTb5 protein are also provided which involve transforming a host cell with a gene encoding this protein and culturing the cells. Methods of increasing the production of a dicarboxylic acid are also provided which involve increasing in the host cell the number of genes encoding this protein.

  9. Biologically Plausible, Human-Scale Knowledge Representation.

    PubMed

    Crawford, Eric; Gingerich, Matthew; Eliasmith, Chris

    2016-05-01

    Several approaches to implementing symbol-like representations in neurally plausible models have been proposed. These approaches include binding through synchrony (Shastri & Ajjanagadde, ), "mesh" binding (van der Velde & de Kamps, ), and conjunctive binding (Smolensky, ). Recent theoretical work has suggested that most of these methods will not scale well, that is, that they cannot encode structured representations using any of the tens of thousands of terms in the adult lexicon without making implausible resource assumptions. Here, we empirically demonstrate that the biologically plausible structured representations employed in the Semantic Pointer Architecture (SPA) approach to modeling cognition (Eliasmith, ) do scale appropriately. Specifically, we construct a spiking neural network of about 2.5 million neurons that employs semantic pointers to successfully encode and decode the main lexical relations in WordNet, which has over 100,000 terms. In addition, we show that the same representations can be employed to construct recursively structured sentences consisting of arbitrary WordNet concepts, while preserving the original lexical structure. We argue that these results suggest that semantic pointers are uniquely well-suited to providing a biologically plausible account of the structured representations that underwrite human cognition. Copyright © 2015 Cognitive Science Society, Inc.

  10. [Effects of drinking spa therapy on oxidative stress].

    PubMed

    Costantino, M; Giampaolo, C; Filippelli, A

    2012-01-01

    Data of literature have shown the correlation between oxidative stress and some diseases of gastrointestinal and metabolic relevance such as diabetes mellitus, gastric cancer, gastritis, etc.. Studies have also shown that sulfurous mineral water may be useful in the treatment of gastrointestinal diseases. The aim of our research was to evaluate the antioxidant effect of sulphurous mineral water, administered by drinking method, in type 2 diabetes mellitus, a chronic disease with a high social and economic impact. The study has been performed on 57 subjects (25% women and 75% males; mean age: 60 ± 1.1 years; BMI: 27 ± 0.4) affected by type 2 Diabetes Mellitus. The subjects were divided in four groups: A (subjected to glucose-lowering diet therapy), B (subjected to antihyperglycaemic therapy), C (exposed to glucose-lowering diet therapy + drinking SPA therapy) and D (exposed to antihyperglycaemic therapy + drinking SPA therapy). Drinking SPA treatment was effected with sulphurous mineral water from Terme of Telese SpA (Benevento - Italy) and the pharmacological treatment provided the use of hypoglycemic drugs normally used in diabetic disease. After two weeks of therapy with treatments considered were evaluated fasting blood glycaemia and plasma concentration of ROMs (reactive oxygen metabolites) (d-ROMs test-Diacron International srl®-Grosseto - Italy). The results of our study have shown a significant (p<0.05) reduction of the fasting blood glycaemia when to hypoglycemic drugs or diet therapy was associated the sulphurous drinking SPA therapy. It was also observed a reduction of plasma ROMs levels, significant (p <0.05) in group D versus group B. The data from this preliminary investigation suggest that the drinking SPA therapy with sulphurous mineral water, especially in combination with antidiabetic drug treatment, may be useful in type 2 diabetes mellitus for the improvement redox state of the organism.

  11. SpaRibs Geometry Parameterization for Wings with Multiple Sections using Single Design

    NASA Technical Reports Server (NTRS)

    De, Shuvodeep; Jrad, Mohamed; Locatelli, Davide; Kapania, Rakesh K.; Baker, Myles; Pak, Chan-Gi

    2017-01-01

    The SpaRibs topology of an aircraft wing has a significant effect on its structural behavior and stability as well as the flutter performance. The development of additive manufacturing techniques like Electron Beam Free Form Fabrication (EBF3) has made it feasible to manufacture aircraft wings with curvilinear spars, ribs (SpaRibs) and stiffeners. In this article a new global-local optimization framework for wing with multiple sections using curvilinear SpaRibs is described. A single design space is used to parameterize the SpaRibs geometry. This method has been implemented using MSC-PATRAN to create a broad range of SpaRibs topologies using limited number of parameters. It ensures C0 and C1 continuities in SpaRibs geometry at the junction of two wing sections with airfoil thickness gradient discontinuity as well as mesh continuity between all structural components. This method is advantageous in complex multi-disciplinary optimization due to its potential to reduce the number of design variables. For the global-local optimization the local panels are generated by an algorithm which is totally based on a set algebra on the connectivity matrix data. The great advantage of this method is that it is completely independent of the coordinates of the nodes of the finite element model. It is also independent of the order in which the elements are distributed in the FEM. The code is verified by optimizing of the CRM Baseline model at trim condition at Mach number equal to 0.85 for five different angle of attack (-2deg, 0deg,2deg,4deg and 6deg). The final weight of the wing is 19,090.61 lb. This value is comparable to that obtained by Qiang et al. 6 (19,269 lb).

  12. [Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations].

    PubMed

    Walczak, Katarzyna; Zmyślony, Marek

    2013-01-01

    Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers), Iran (5), China (4) and India (5). Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings). In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program.

  13. Molecular Characterization and Antimicrobial Susceptibility of Staphylococcus aureus Isolates from Clinical Infection and Asymptomatic Carriers in Southwest Nigeria

    PubMed Central

    Olasupo, Nurudeen A.; Egwari, Louis O.; Becker, Karsten

    2015-01-01

    Few reports from Africa suggest that resistance pattern, virulence factors and genotypes differ between Staphylococcus aureus from nasal carriage and clinical infection. We therefore compared antimicrobial resistance, selected virulence factors and genotypes of S. aureus from nasal carriage and clinical infection in Southwest Nigeria. Non-duplicate S. aureus isolates were obtained from infection (n = 217) and asymptomatic carriers (n = 73) during a cross sectional study in Lagos and Ogun States, Nigeria from 2010–2011. Susceptibility testing was performed using Vitek automated systems. Selected virulence factors were detected by PCR. The population structure was assessed using spa typing. The spa clonal complexes (spa-CC) were deduced using the Based Upon Repeat Pattern algorithm (BURP). Resistance was higher for aminoglycosides in clinical isolates while resistances to quinolones and tetracycline were more prevalent in carrier isolates. The Panton-Valentine leukocidin (PVL) was more frequently detected in isolates from infection compared to carriage (80.2 vs 53.4%; p<0.001, chi2-test). Seven methicillin resistant S. aureus isolates were associated with spa types t002, t008, t064, t194, t8439, t8440 and t8441. The predominant spa types among the methicillin-susceptible S. aureus isolates were t084 (65.5%), t2304 (4.4%) and t8435 (4.1%). spa-CC 084 was predominant among isolates from infection (80.3%, n = 167) and was significantly associated with PVL (OR = 7.1, 95%CI: 3.9–13.2, p<0.001, chi2- test). In conclusion, PVL positive isolates were more frequently detected among isolates from infection compared to carriage and are associated with spa-CC 084. PMID:26348037

  14. Has time come for a re-assessment of spa therapy? The NAIADE survey in Italy

    NASA Astrophysics Data System (ADS)

    Coccheri, S.; Gasbarrini, G.; Valenti, M.; Nappi, G.; di Orio, F.

    2008-01-01

    Goal of this study was to investigate whether appropriately applied spa therapy in several indications could be associated with a subsequent fall in the need for costly health services and missed working days due to sick-leave. The Naiade project was a multicenter observational, longitudinal, questionnaire-based study comparing an “entry” inquiry addressed to patients before an entry thermal cycle, and a “return” inquiry after 1 year. Routine statistical methods were used for comparisons. The study was carried out in 297 of the 340 certified Italian spa centers. Inquiries were managed by the spa doctor(s), with the collaboration of family doctors, and when necessary, hospitals, other health services, labour offices and employers. After exclusion of regular customers and of patients with acute disease phases or severe health conditions, 39,943 patients divided into eight diseases subgroups (rheumatic, respiratory, dermatologic, gynaecologic, otorhynologic, urinary, vascular and gastroenteric) underwent entry inquiry and appropriate spa treatment. Patients who returned for treatment after 1 year (“index year”) were 23,680 (59.2%) and received return inquiry. Outcomes considered were: frequency and duration of hospitalisation periods; missed working days; regular use of disease-specific drugs; and resort to “non-spa” rehabilitation therapies. The data collected at return inquiry were compared with those of entry inquiry. All the considered outcomes appeared to be significantly reduced in the index year in seven of the eight disease subgroups in comparison with the previous year. In conclusion, disease-appropriate spa treatments were followed by a reduction in the need of subsequent health interventions in most disease subgroups. The health promoting value of spa treatments should therefore undergo more rigorous assessment with randomised controlled studies.

  15. Luminol-dependent chemiluminescence in antibody-sensitized neutrophils stimulated with protein A-bearing staphylococci.

    PubMed

    Nishihara, S; Seki, K; Ikigai, H; Masuda, S

    1988-01-01

    When mouse polymorphonuclear leukocytes (PMNs) sensitized with rabbit antibody to mouse Ehrlich ascites tumor cells were stimulated by Staphylococcus aureus Cowan I cells, a conspicuous luminol-dependent chemiluminescence was observed in the absence of opsonin. The profile of the chemiluminescence (CL) response evoked by staphylococcal cells from antibody-sensitized PMNs had two peaks. An initial peak, observed within 1 min after stimulation, was sharp and high and a second peak, observed about 5 min after stimulation, was low and extended. The CL response of antibody-sensitized PMNs stimulated by S. aureus Cowan I cells was dose-dependently blocked by preincubation with soluble SpA. Cells of a mutant derived from S. aureus Cowan I strain with trace amounts of cell-bound SpA failed to stimulate the antibody-sensitized PMNs to generate the CL response. The antibody-sensitized PMNs were found to phagocytize SpA-bearing S. aureus cells even in the absence of opsonic serum. These results suggest that the observation presented here might provide a useful tool for the investigation of CL response of PMNs.

  16. Reduced Appendicular Lean Body Mass, Muscle Strength, and Size of Type II Muscle Fibers in Patients with Spondyloarthritis versus Healthy Controls: A Cross-Sectional Study.

    PubMed

    Røren Nordén, Kristine; Dagfinrud, Hanne; Løvstad, Amund; Raastad, Truls

    Introduction . The purpose of this study was to investigate body composition, muscle function, and muscle morphology in patients with spondyloarthritis (SpA). Methods . Ten male SpA patients (mean ± SD age 39 ± 4.1 years) were compared with ten healthy controls matched for sex, age, body mass index, and self-reported level of physical exercise. Body composition was measured by dual energy X-ray absorptiometry. Musculus quadriceps femoris (QF) strength was assessed by maximal isometric contractions prior to test of muscular endurance. Magnetic resonance imaging of QF was used to measure muscle size and calculate specific muscle strength. Percutaneous needle biopsy samples were taken from m. vastus lateralis . Results . SpA patients presented with significantly lower appendicular lean body mass (LBM) ( p = 0.02), but there was no difference in bone mineral density, fat mass, or total LBM. Absolute QF strength was significantly lower in SpA patients ( p = 0.03) with a parallel trend for specific strength ( p = 0.08). Biopsy samples from the SpA patients revealed significantly smaller cross-sectional area (CSA) of type II muscle fibers ( p = 0.04), but no difference in CSA type I fibers. Conclusions . Results indicate that the presence of SpA disease is associated with reduced appendicular LBM, muscle strength, and type II fiber CSA.

  17. Characterization of Staphylococcus aureus isolates from buffalo, bovine, ovine, and caprine milk samples collected in Rio de Janeiro State, Brazil.

    PubMed

    Aires-de-Sousa, Marta; Parente, Carlos E S R; Vieira-da-Motta, Olney; Bonna, Isabel C F; Silva, Denise A; de Lencastre, Hermínia

    2007-06-01

    Eighty-four staphylococcal isolates were obtained from milk samples from cows, sheep, goats, and buffalo with subclinical mastitis and from colonization samples from ostriches. The animals were hosted in 18 small dairy herds and an ostrich breeding located in 10 municipalities of the state of Rio de Janeiro, Brazil. Thirty isolates were identified as Staphylococcus aureus by biochemical and molecular techniques and were comparatively characterized by phenotypic and genotypic methods. The molecular characterization by pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST) revealed five clonal types (PFGE A, spa type t359, sequence type 747 [ST747]; PFGE B, spa type t1180, ST750; PFGE C, spa type t605, ST126; PFGE D, spa type t127, ST751; and PFGE F, spa type t002, ST5). None of the isolates harbored the Panton-Valentine leukocidin or exfoliative toxin D gene. The detection of major clone A (in 63% of the isolates) in different herds, among all animal species studied, and in infection and colonization samples evidenced its geographical spread among Rio de Janeiro State and no host preference among the animal species. Comparison with S. aureus from a human origin suggested that all but one clone found in the present study might be animal specific.

  18. Influence of amendments on soil arsenic fractionation and phytoavailability by Pteris vittata L.

    PubMed

    Yan, Xiulan; Zhang, Min; Liao, Xiaoyong; Tu, Shuxin

    2012-06-01

    Increasing availability of soil arsenic is of significance for accelerating phytoremediation efficiency of As-polluted sites. The effects of seven amendments, i.e., citrate, oxalate, EDTA, sodium polyacrylate (SPA), phosphate rock (PR), single superphosphate (SSP), and compost on fractionation and phytoavailability of soil As were investigated in lab culture experiment. The results showed that the addition of PR, SPA, EDTA or compost to soils significantly increased the concentration of NaHCO(3)-extractable As over a 120 d incubation period compared with the control (amendment-free) soil. Then, the four amendments were selected to add to As-contaminated soil growing Pteris vittata. It was concluded that As accumulation by the fern increased significantly under the treatments of PR and SPA by 25% and 31%, respectively. For As fractionation in soil, SPA increased Fe-As significantly by 51% and PR increased Ca-As significantly by 18%, while both the two amendments reduced occluded-As by 16% and 19%, respectively. Adding PR and SPA in soil increased the activities of urease and neutral phosphatase resulting from the improvement the fertility and physical structure of the soil, which benefits plant growth and As absorption of P. vittata. The results of the research revealed that both PR and SPA were effective amendments for improving phytoremediation of As-contaminated sites by P. vittata. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Resource or Hindrance? The benefits and costs of social support for functional difficulties and its implications for depressive symptoms.

    PubMed

    Sharifian, Neika; O'Brien, Erica L

    2018-02-09

    The impact of social support on the relationship between stress and well-being remains somewhat inconclusive, with work suggesting either null, buffering, or amplification effects. The current study investigated the conditions in which perceived social support is likely to act as a buffer or amplifier by considering individual differences in self-perceptions of aging. Using data from two subsamples of the Wisconsin Longitudinal Study (graduates: 70-74 years, siblings: 40-92 years), we examined how perceived social support (emotional versus instrumental) and self-perceptions of aging (SPA) moderated the effect of functional limitations on depressive symptoms (DS). Although emotional support positively predicted DS, its effects did not depend on SPA. Instrumental support was associated with both increases and decreases in well-being that were dependent upon SPA. Functional limitations predicted more DS at both low and high levels of instrumental support when SPA were negative. However, when SPA were positive, low levels of social support were found to decrease depressive symptoms, and high levels were found to increase depressive symptoms. The impact of social social may enhance or deteriorate well-being, depending on how it interacts with self-evaluative beliefs. Findings offer insights as to the boundary conditions associated with the (positive) effects of social support and SPA, and highlight the need for continued research on the mechanisms associated these effects.

  20. Molecular characterization and expression of the M6 gene of grass carp hemorrhage virus (GCHV), an aquareovirus.

    PubMed

    Qiu, T; Lu, R H; Zhang, J; Zhu, Z Y

    2001-07-01

    The complete nucleotide sequence of M6 gene of grass carp hemorrhage virus (GCHV) was determined. It is 2039 nucleotides in length and contains a single large open reading frame that could encode a protein of 648 amino acids with predicted molecular mass of 68.7 kDa. Amino acid sequence comparison revealed that the protein encoded by GCHV M6 is closely related to the protein mu1 of mammalian reovirus. The M6 gene, encoding the major outer-capsid protein, was expressed using the pET fusion protein vector in Escherichia coli and detected by Western blotting using chicken anti-GCHV immunoglobulin (IgY). The result indicates that the protein encoded by M6 may share a putative Asn-42-Pro-43 proteolytic cleavage site with mu1.

  1. The privatization of spa companies in Poland - An evaluation of policy assumptions and implementation.

    PubMed

    Szromek, Adam R; Romaniuk, Piotr; Hadzik, Andrzej

    2016-04-01

    The aim of this article is to present the course of privatization of spa companies in Poland during the period 2001-2011. We discuss assumptions of the privatization process, as well as actual implementation, having identified the process as chaotic and inconsistent with prior legal provisions. We found that in its applied form the process resulted in limitation of the therapeutic potential of spas, and reduction of the State's ability to implement health policy in a legally determined form. We also found that privatization potentially improved spa infrastructure standards and increases the tourist potential of spa resorts. We recommend that clear eligibility criteria are applied to institutions in the privatization process, as well as the provision of legal guarantees for access to spa services financed from public resources. Such guarantees should be made a public obligation, to ensure the availability of services for insured persons, and there should be an obligation to maintain a specific part of a given institution's potential for the needs of patients funded by public health insurance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. [Influencing factors on surgical duration of ovarian cystectomy by single-port access].

    PubMed

    Poizac, S; Ménager, N; Tourette, C; Gnisci, A; Estrade, J-P; Agostini, A

    2015-01-01

    To evaluate the factors influencing the operative duration of ovarian cystectomy by single-port access (SPA). Observational monocentric study from June 2010 to September 2012. Inclusive patients were patients with an indication of ovarian cystectomy may be done by laparoscopy. The procedures were performed by the SPA system LESS®. Factors evaluated were BMI of the patient, histological nature and size of the cyst. We performed 54 cystectomy in 49 patients. SPA surgery was successfully completed in 53 patients. The median operative time was statistically longer for endometriotic cysts than dermoid cysts or serous-mucinous cysts (P=0.003). Cases exceeding 60minutes were significantly higher in the endometriosis group (P=0.005). There wasn't correlation found between the BMI of the patient and operative time (P=0.5). The operating time wasn't increased according to the size of the cyst (P=0.9). Endometriotic cysts nature appears to be the only limiting factor of cystectomy by SPA. Further studies are needed to evaluate the factors that may limit the SPA actions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Dogs Identify Agents in Third-Party Interactions on the Basis of the Observed Degree of Contingency.

    PubMed

    Tauzin, Tibor; Kovács, Krisztina; Topál, József

    2016-08-01

    To investigate whether dogs could recognize contingent reactivity as a marker of agents' interaction, we performed an experiment in which dogs were presented with third-party contingent events. In the perfect-contingency condition, dogs were shown an unfamiliar self-propelled agent (SPA) that performed actions corresponding to audio clips of verbal commands played by a computer. In the high-but-imperfect-contingency condition, the SPA responded to the verbal commands on only two thirds of the trials; in the low-contingency condition, the SPA responded to the commands on only one third of the trials. In the test phase, the SPA approached one of two tennis balls, and then the dog was allowed to choose one of the balls. The proportion of trials on which a dog chose the object indicated by the SPA increased with the degree of contingency: Dogs chose the target object significantly above chance level only in the perfect-contingency condition. This finding suggests that dogs may use the degree of temporal contingency observed in third-party interactions as a cue to identify agents. © The Author(s) 2016.

  4. Luciferase Complementation Imaging Assay in Nicotiana benthamiana Leaves for Transiently Determining Protein-protein Interaction Dynamics.

    PubMed

    Sun, Kaiwen; Zheng, Yuyu; Zhu, Ziqiang

    2017-11-20

    Protein-protein interactions are fundamental mechanisms for relaying signal transduction in most cellular processes; therefore, identification of novel protein-protein interaction pairs and monitoring protein interaction dynamics are of particular interest for revealing how plants respond to environmental factors and/or developmental signals. A plethora of approaches have been developed to examine protein-protein interactions, either in vitro or in vivo. Among them, the recently established luciferase complementation imaging (LCI) assay is the simplest and fastest method for demonstrating in vivo protein-protein interactions. In this assay, protein A or protein B is fused with the amino-terminal or carboxyl-terminal half of luciferase, respectively. When protein A interacts with protein B, the two halves of luciferase will be reconstituted to form a functional and active luciferase enzyme. Luciferase activity can be recorded with a luminometer or CCD-camera. Compared with other approaches, the LCI assay shows protein-protein interactions both qualitatively and quantitatively. Agrobacterium infiltration in Nicotiana benthamiana leaves is a widely used system for transient protein expression. With the combination of LCI and transient expression, these approaches show that the physical interaction between COP1 and SPA1 was gradually reduced after jasmonate treatment.

  5. DNA encoding a DNA repair protein

    DOEpatents

    Petrini, John H.; Morgan, William Francis; Maser, Richard Scott; Carney, James Patrick

    2006-08-15

    An isolated and purified DNA molecule encoding a DNA repair protein, p95, is provided, as is isolated and purified p95. Also provided are methods of detecting p95 and DNA encoding p95. The invention further provides p95 knock-out mice.

  6. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    PubMed Central

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Martina; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-01-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit. PMID:25996248

  7. Analysis of in vitro interactions of protein tyrosine phosphatase 1B with insulin receptors.

    PubMed

    Wang, X Y; Bergdahl, K; Heijbel, A; Liljebris, C; Bleasdale, J E

    2001-02-28

    One strategy to treat the insulin resistance that is central to type II diabetes mellitus may be to maintain insulin receptors (IR) in the active (tyrosine phosphorylated) form. Because protein tyrosine phosphatase 1B (PTP1B) binds and subsequently dephosphorylates IR, inhibitors of PTP1B-IR binding are potential insulin 'sensitizers.' A Scintillation Proximity Assay (SPA) was developed to characterize and quantitate PTP1B-IR binding. Human IR were solubilized and captured on wheat germ agglutinin (WGA)-coated SPA beads. Subsequent binding of human, catalytically inactive [35S] PTP1B Cys(215)/Ser (PTP1B(C215S)) to the lectin-anchored IR results in scintillation from the SPA beads that can be quantitated. Binding of PTP1B to IR was pH- and divalent cation-sensitive. Ca(2+) and Mn(2+), but not Mg(2+), dramatically attenuated the loss of PTP1B-IR binding observed when pH was raised from 6.2 to 7.8. PTP1B binding to IR from insulin-stimulated cells was much greater than to IR from unstimulated cells and was inhibited by either an antiphosphotyrosine antibody or treatment of IR with alkaline phosphatase, suggesting that tyrosine phosphorylation of IR is required for PTP1B binding. Phosphopeptides modeled after various IR phosphotyrosine domains each only partially inhibited PTP1B-IR binding, indicating that multiple domains of IR are likely involved in binding PTP1B. However, competitive displacement of [35S]PTP1B(C215S) by PTP1B(C215S) fitted best to a single binding site with a K(d) in the range 100-1000 nM, depending upon pH and divalent cations. PNU-200898, a potent and selective inhibitor of PTP1B whose orientation in the active site of PTP1B has been solved, competitively inhibited catalysis and PTP1B-IR binding with equal potency. The results of this novel assay for PTP1B-IR binding suggest that PTP1B binds preferentially to tyrosine phosphorylated IR through its active site and that binding may be susceptible to therapeutic disruption by small molecules.

  8. Populus trichocarpa encodes small, effector-like secreted proteins that are highly induced during mutualistic symbiosis

    DOE PAGES

    Plett, Jonathan M.; Yin, Hengfu; Mewalal, Ritesh; ...

    2017-03-23

    During symbiosis, organisms use a range of metabolic and protein-based signals to communicate. Of these protein signals, one class is defined as ‘effectors’, i.e., small secreted proteins (SSPs) that cause phenotypical and physiological changes in another organism. To date, protein-based effectors have been described in aphids, nematodes, fungi and bacteria. Using RNA sequencing of Populus trichocarpa roots in mutualistic symbiosis with the ectomycorrhizal fungus Laccaria bicolor, we sought to determine if host plants also contain genes encoding effector-like proteins. We identified 417 plant-encoded putative SSPs that were significantly regulated during this interaction, including 161 SSPs specific to P. trichocarpa andmore » 15 SSPs exhibiting expansion in Populus and closely related lineages. We demonstrate that a subset of these SSPs can enter L. bicolor hyphae, localize to the nucleus and affect hyphal growth and morphology. Finally, we conclude that plants encode proteins that appear to function as effector proteins that may regulate symbiotic associations.« less

  9. Populus trichocarpa encodes small, effector-like secreted proteins that are highly induced during mutualistic symbiosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Plett, Jonathan M.; Yin, Hengfu; Mewalal, Ritesh

    During symbiosis, organisms use a range of metabolic and protein-based signals to communicate. Of these protein signals, one class is defined as ‘effectors’, i.e., small secreted proteins (SSPs) that cause phenotypical and physiological changes in another organism. To date, protein-based effectors have been described in aphids, nematodes, fungi and bacteria. Using RNA sequencing of Populus trichocarpa roots in mutualistic symbiosis with the ectomycorrhizal fungus Laccaria bicolor, we sought to determine if host plants also contain genes encoding effector-like proteins. We identified 417 plant-encoded putative SSPs that were significantly regulated during this interaction, including 161 SSPs specific to P. trichocarpa andmore » 15 SSPs exhibiting expansion in Populus and closely related lineages. We demonstrate that a subset of these SSPs can enter L. bicolor hyphae, localize to the nucleus and affect hyphal growth and morphology. Finally, we conclude that plants encode proteins that appear to function as effector proteins that may regulate symbiotic associations.« less

  10. Molecular comparison of the structural proteins encoding gene clusters of two related Lactobacillus delbrueckii bacteriophages.

    PubMed Central

    Vasala, A; Dupont, L; Baumann, M; Ritzenthaler, P; Alatossava, T

    1993-01-01

    Virulent phage LL-H and temperate phage mv4 are two related bacteriophages of Lactobacillus delbrueckii. The gene clusters encoding structural proteins of these two phages have been sequenced and further analyzed. Six open reading frames (ORF-1 to ORF-6) were detected. Protein sequencing and Western immunoblotting experiments confirmed that ORF-3 (g34) encoded the main capsid protein Gp34. The presence of a putative late promoter in front of the phage LL-H g34 gene was suggested by primer extension experiments. Comparative sequence analysis between phage LL-H and phage mv4 revealed striking similarities in the structure and organization of this gene cluster, suggesting that the genes encoding phage structural proteins belong to a highly conservative module. Images PMID:8497043

  11. Three copies of a single protein II-encoding sequence in the genome of Neisseria gonorrhoeae JS3: evidence for gene conversion and gene duplication.

    PubMed

    van der Ley, P

    1988-11-01

    Gonococci express a family of related outer membrane proteins designated protein II (P.II). These surface proteins are subject to both phase variation and antigenic variation. The P.II gene repertoire of Neisseria gonorrhoeae strain JS3 was found to consist of at least ten genes, eight of which were cloned. Sequence analysis and DNA hybridization studies revealed that one particular P.II-encoding sequence is present in three distinct, but almost identical, copies in the JS3 genome. These genes encode the P.II protein that was previously identified as P.IIc. Comparison of their sequences shows that the multiple copies of this P.IIc-encoding gene might have been generated by both gene conversion and gene duplication.

  12. Comparative differential gene expression analysis of nucleus-encoded proteins for Rafflesia cantleyi against Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Ng, Siuk-Mun; Lee, Xin-Wei; Wan, Kiew-Lian; Firdaus-Raih, Mohd

    2015-09-01

    Regulation of functional nucleus-encoded proteins targeting the plastidial functions was comparatively studied for a plant parasite, Rafflesia cantleyi versus a photosynthetic plant, Arabidopsis thaliana. This study involved two species of different feeding modes and different developmental stages. A total of 30 nucleus-encoded proteins were found to be differentially-regulated during two stages in the parasite; whereas 17 nucleus-encoded proteins were differentially-expressed during two developmental stages in Arabidopsis thaliana. One notable finding observed for the two plants was the identification of genes involved in the regulation of photosynthesis-related processes where these processes, as expected, seem to be present only in the autotroph.

  13. Diagnosis of the socionic temperament of personality and creating a psychological portrait of the Western European SPA and wellness tourists in Bulgaria

    NASA Astrophysics Data System (ADS)

    Stoyanova, Milena

    2017-03-01

    Human personality is a set of psychological characteristics that distinguishes it from others. However people can be classified as congenital personality types, interactions that are precisely defined. The aim of this article is to characterize the socionic temperament and psychological profile of the spa and wellness tourists in Bulgaria. The study is based on a survey of 460 tourists who visited Bulgarian spa centers in the summer and autumn of 2015.

  14. [Pseudomonas folliculitis after spa bath exposure].

    PubMed

    Uldall Pallesen, Kristine Appel; Andersen, Klaus Ejner; Mørtz, Charlotte Gotthard

    2012-06-25

    Pseudomonas aeruginosa is a rare cause of folliculitis. Pseudomonas folliculitis can develop after contact with contaminated water from swimming pools, hot tubs and spa baths. Systemic therapy may be indicated in patients with widespread lesions, systemic symptoms or in immunosuppressed patients. We describe a 23-year-old healthy woman who developed a pustular rash and general malaise after using a spa bath contaminated with Pseudomonas aeruginosa. Bacterial culture from a pustule confirmed Pseudomonas folliculitis and the patient was treated with ciprofloxacin with rapid good effect.

  15. The Andes hantavirus NSs protein is expressed from the viral small mRNA by a leaky scanning mechanism.

    PubMed

    Vera-Otarola, Jorge; Solis, Loretto; Soto-Rifo, Ricardo; Ricci, Emiliano P; Pino, Karla; Tischler, Nicole D; Ohlmann, Théophile; Darlix, Jean-Luc; López-Lastra, Marcelo

    2012-02-01

    The small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein. In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional nonstructural protein denominated NSs. In this study, we show that Andes hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is expressed in the context of an ANDV infection. Additionally, our results suggest that translation initiation from the NSs initiation codon is mediated by ribosomal subunits that have bypassed the upstream N protein initiation codon through a leaky scanning mechanism.

  16. The Andes Hantavirus NSs Protein Is Expressed from the Viral Small mRNA by a Leaky Scanning Mechanism

    PubMed Central

    Vera-Otarola, Jorge; Solis, Loretto; Soto-Rifo, Ricardo; Ricci, Emiliano P.; Pino, Karla; Tischler, Nicole D.; Ohlmann, Théophile; Darlix, Jean-Luc

    2012-01-01

    The small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein. In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional nonstructural protein denominated NSs. In this study, we show that Andes hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is expressed in the context of an ANDV infection. Additionally, our results suggest that translation initiation from the NSs initiation codon is mediated by ribosomal subunits that have bypassed the upstream N protein initiation codon through a leaky scanning mechanism. PMID:22156529

  17. Fusagene vectors: a novel strategy for the expression of multiple genes from a single cistron.

    PubMed

    Gäken, J; Jiang, J; Daniel, K; van Berkel, E; Hughes, C; Kuiper, M; Darling, D; Tavassoli, M; Galea-Lauri, J; Ford, K; Kemeny, M; Russell, S; Farzaneh, F

    2000-12-01

    Transduction of cells with multiple genes, allowing their stable and co-ordinated expression, is difficult with the available methodologies. A method has been developed for expression of multiple gene products, as fusion proteins, from a single cistron. The encoded proteins are post-synthetically cleaved and processed into each of their constituent proteins as individual, biologically active factors. Specifically, linkers encoding cleavage sites for the Golgi expressed endoprotease, furin, have been incorporated between in-frame cDNA sequences encoding different secreted or membrane bound proteins. With this strategy we have developed expression vectors encoding multiple proteins (IL-2 and B7.1, IL-4 and B7.1, IL-4 and IL-2, IL-12 p40 and p35, and IL-12 p40, p35 and IL-2 ). Transduction and analysis of over 100 individual clones, derived from murine and human tumour cell lines, demonstrate the efficient expression and biological activity of each of the encoded proteins. Fusagene vectors enable the co-ordinated expression of multiple gene products from a single, monocistronic, expression cassette.

  18. 42 CFR 447.76 - Public schedule.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... for approval a State plan amendment (SPA) to establish alternative premiums or cost sharing under... applicable State law, and must submit documentation with the SPA to demonstrate that this requirement was met...

  19. Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue.

    PubMed

    Rysnik, Oliwia; McHugh, Kirsty; van Duivenvoorde, Leonie; van Tok, Melissa; Guggino, Giuliana; Taurog, Joel; Kollnberger, Simon; Ciccia, Francesco; Baeten, Dominique; Bowness, Paul

    2016-06-01

    Human leukocyte antigen (HLA)-B27 (B27) is the strongest genetic factor associated with development of Ankylosing Spondylitis and other spondyloarthropathies (SpA), yet the role it plays in disease pathogenesis remains unclear. We investigated the expression of potentially pathogenic non-conventional heavy chain forms (NC) of B27 in synovial and intestinal tissues obtained from SpA patients. We also determined the presence of NC-B27 in joints, lymphoid and gastrointestinal tissue from B27 transgenic (TG(1)) rats with M.tuberculosis-induced SpA. Expression of NC-B27 in human SpA joints and gut and in (21-3 × 283-2)F1 HLA-B27/Huβ2m rat tissue was determined by immunohistochemistry, flow cytometry and confocal microscopy analysis using HC10 and HD6 antibodies. Both HC10- and HD6-reactive HLA molecules were present in synovial tissue from SpA patients. Both NC-B27 and KIR3DL2, a ligand for NC-B27, were expressed in inflamed terminal ileal tissues in patients with early SpA. Infiltrating cells in inflamed joint tissues isolated from B27 TG(1) rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG(1) rats prior to clinical arthritis. The expression of NC-B27 on B27 TG(1) rat CD11b/c(+), CD8α(+), cells from spleens and LNs increased with animal age and disease progression. Non-conventional HLA class 1 molecules are expressed on resident and infiltrating cells in both synovial and GI tissues in human SpA. NC-B27 expression in joints and lymphoid tissues from B27 TG(1) rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

    PubMed Central

    Smolen, Josef S; Braun, Jürgen; Dougados, Maxime; Emery, Paul; FitzGerald, Oliver; Helliwell, Philip; Kavanaugh, Arthur; Kvien, Tore K; Landewé, Robert; Luger, Thomas; Mease, Philip; Olivieri, Ignazio; Reveille, John; Ritchlin, Christopher; Rudwaleit, Martin; Schoels, Monika; Sieper, Joachim; de Wit, Martinus; Baraliakos, Xenofon; Betteridge, Neil; Burgos-Vargas, Ruben; Collantes-Estevez, Eduardo; Deodhar, Atul; Elewaut, Dirk; Gossec, Laure; Jongkees, Merryn; Maccarone, Mara; Redlich, Kurt; van den Bosch, Filip; Wei, James Cheng-Chung; Winthrop, Kevin; van der Heijde, Désirée

    2014-01-01

    Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9–10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA. PMID:23749611

  1. Isotope-Encoded Carboxyl Group Footprinting for Mass Spectrometry-Based Protein Conformational Studies

    NASA Astrophysics Data System (ADS)

    Zhang, Hao; Liu, Haijun; Blankenship, Robert E.; Gross, Michael L.

    2016-01-01

    We report an isotope-encoding method coupled with carboxyl-group footprinting to monitor protein conformational changes. The carboxyl groups of aspartic/glutamic acids and of the C-terminus of proteins can serve as reporters for protein conformational changes when labeled with glycine ethyl ester (GEE) mediated by carbodiimide. In the new development, isotope-encoded "heavy" and "light" GEE are used to label separately the two states of the orange carotenoid protein (OCP) from cyanobacteria. Two samples are mixed (1:1 ratio) and analyzed by a single LC-MS/MS experiment. The differences in labeling extent between the two states are represented by the ratio of the "heavy" and "light" peptides, providing information about protein conformational changes. Combining isotope-encoded MS quantitative analysis and carboxyl-group footprinting reduces the time of MS analysis and improves the sensitivity of GEE and other footprinting.

  2. Isotope-encoded Carboxyl Group Footprinting for Mass Spectrometry-based Protein Conformational Studies

    PubMed Central

    Zhang, Hao; Liu, Haijun; Blankenship, Robert E.; Gross, Michael L.

    2015-01-01

    We report an isotope-encoding method coupled with carboxyl-group footprinting to monitor protein conformational changes. The carboxyl groups of aspartic/glutamic acids and of the C-terminus of proteins can serve as reporters for protein conformational changes when labeled with glycine ethyl ester (GEE) mediated by carbodiimide. In the new development, isotope-encoded “heavy” and “light” GEE are used to label separately the two states of the Orange Carotenoid Protein (OCP) from cyanobacteria. Two samples are mixed (1:1 ratio) and analyzed by a single LC-MS/MS experiment. The differences in labeling extent between the two states are represented by the ratio of the “heavy” and “light” peptides, providing information about protein conformational changes. Combining isotope-encoded MS quantitative analysis and carboxyl-group footprinting reduces the time of MS analysis and improves the sensitivity of GEE and other footprinting. PMID:26384685

  3. Isotope-Encoded Carboxyl Group Footprinting for Mass Spectrometry-Based Protein Conformational Studies

    DOE PAGES

    Zhang, Hao; Liu, Haijun; Blankenship, Robert E.; ...

    2015-09-18

    Here, we report an isotope-encoding method coupled with carboxyl-group footprinting to monitor protein conformational changes. The carboxyl groups of aspartic/glutamic acids and of the C-terminus of proteins can serve as reporters for protein conformational changes when labeled with glycine ethyl ester (GEE) mediated by carbodiimide. In the new development, isotope-encoded “heavy” and “light” GEE are used to label separately the two states of the orange carotenoid protein (OCP) from cyanobacteria. Two samples are mixed (1:1 ratio) and analyzed by a single LC-MS/MS experiment. The differences in labeling extent between the two states are represented by the ratio of the “heavy”more » and “light” peptides, providing information about protein conformational changes. Combining isotope-encoded MS quantitative analysis and carboxyl-group footprinting reduces the time of MS analysis and improves the sensitivity of GEE and other footprinting.« less

  4. Characterization of virulence factor regulation by SrrAB, a two-component system in Staphylococcus aureus.

    PubMed

    Pragman, Alexa A; Yarwood, Jeremy M; Tripp, Timothy J; Schlievert, Patrick M

    2004-04-01

    Workers in our laboratory have previously identified the staphylococcal respiratory response AB (SrrAB), a Staphylococcus aureus two-component system that acts in the global regulation of virulence factors. This system down-regulates production of agr RNAIII, protein A, and toxic shock syndrome toxin 1 (TSST-1), particularly under low-oxygen conditions. In this study we investigated the localization and membrane orientation of SrrA and SrrB, transcription of the srrAB operon, the DNA-binding properties of SrrA, and the effect of SrrAB expression on S. aureus virulence. We found that SrrA is localized to the S. aureus cytoplasm, while SrrB is localized to the membrane and is properly oriented to function as a histidine kinase. srrAB has one transcriptional start site which results in either an srrA transcript or a full-length srrAB transcript; srrB must be cotranscribed with srrA. Gel shift assays of the agr P2, agr P3, protein A (spa), TSST-1 (tst), and srr promoters revealed SrrA binding at each of these promoters. Analysis of SrrAB-overexpressing strains by using the rabbit model of bacterial endocarditis demonstrated that overexpression of SrrAB decreased the virulence of the organisms compared to the virulence of isogenic strains that do not overexpress SrrAB. We concluded that SrrAB is properly localized and oriented to function as a two-component system. Overexpression of SrrAB, which represses agr RNAIII, TSST-1, and protein A in vitro, decreases virulence in the rabbit endocarditis model. Repression of these virulence factors is likely due to a direct interaction between SrrA and the agr, tst, and spa promoters.

  5. Environmental Staphylococcus aureus contamination in a Tunisian hospital.

    PubMed

    Gharsa, Haythem; Dziri, Raoudha; Klibi, Naouel; Chairat, Sarra; Lozano, Carmen; Torres, Carmen; Bellaaj, Ridha; Slama, Karim Ben

    2016-12-01

    One hundred hospital environment samples were obtained in 2012 in a Tunisian hospital and tested for Staphylococcus aureus recovery. Antimicrobial resistance profile and virulence gene content were determined. Multilocus-sequence-typing (MLST), spa-typing, agr-typing and SmaI-pulsed-field gel electrophoresis (PFGE) were performed. Two methicillin-resistant S. aureus (MRSA) isolates typed as: ST247-t052-SCCmecI-agrI were recovered from the intensive care unit (ICU). Ten samples contained methicillin-susceptible S. aureus (MSSA) and these samples were collected in different services, highlighting the presence of the tst gene encoding the toxic shock syndrome toxin as well as the lukED, hla, hlb, hld and hlg v virulence genes in some of the isolates. In conclusion, we have shown that the hospital environment could be a reservoir contributing to dissemination of virulent S. aureus and MRSA.

  6. Image quality improvement in megavoltage cone beam CT using an imaging beam line and a sintered pixelated array system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Breitbach, Elizabeth K.; Maltz, Jonathan S.; Gangadharan, Bijumon

    2011-11-15

    Purpose: To quantify the improvement in megavoltage cone beam computed tomography (MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line (IBL) with a carbon electron target and a detector system equipped with a novel sintered pixelated array (SPA) of translucent Gd{sub 2}O{sub 2}S ceramic scintillator. Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a-Si) flat panel imager, and the Kodak Lanex Fast-B (LFB) scintillator. The IBL produces a greater fluence of keV-range photons than the TBL, to whichmore » the detector response is more optimal, and the SPA is a more efficient scintillator than the LFB. Methods: A prototype IBL + SPA system was installed on a Siemens Oncor linear accelerator equipped with the MVision{sup TM} image guided radiation therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and measuring 40 cm by 10.96 cm in the crossplane and inplane directions, respectively, was installed in the flat panel imager. Head- and pelvis-sized phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at each dose was quantified using the contrast-to-noise ratio (CNR) and modulation transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate) cancer patients were imaged with the three imaging system configurations at multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively from the patient image data. Results: For head and neck and pelvis-sized phantom images, imaging doses of 3 cGy or greater, and relative electron densities of 1.09 and 1.48, the CNR average improvement factors for imaging system change of TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were 1.63 (p < 10{sup -8}), 1.64 (p < 10{sup -13}), 2.66 (p < 10{sup -9}), respectively. For all imaging doses, soft tissue contrast was more easily differentiated on IBL + SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA thoracic images were comparable to IBL + LFB images, but less noisy than TBL + LFB images at all imaging doses considered. The mean MTFs over all imaging doses were comparable, at within 3%, for all imaging system configurations for both the head- and pelvis-sized phantoms. Conclusions: Since CNR scales with the square root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL + SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38 and 0.37, respectively. MTFs were comparable between imaging system configurations. IBL + SPA patient image quality was always better than that of the TBL + LFB system and as good as or better than that of the IBL + LFB system, for a given dose.« less

  7. Nopaline-type Ti plasmid of Agrobacterium encodes a VirF-like functional F-box protein.

    PubMed

    Lacroix, Benoît; Citovsky, Vitaly

    2015-11-20

    During Agrobacterium-mediated genetic transformation of plants, several bacterial virulence (Vir) proteins are translocated into the host cell to facilitate infection. One of the most important of such translocated factors is VirF, an F-box protein produced by octopine strains of Agrobacterium, which presumably facilitates proteasomal uncoating of the invading T-DNA from its associated proteins. The presence of VirF also is thought to be involved in differences in host specificity between octopine and nopaline strains of Agrobacterium, with the current dogma being that no functional VirF is encoded by nopaline strains. Here, we show that a protein with homology to octopine VirF is encoded by the Ti plasmid of the nopaline C58 strain of Agrobacterium. This protein, C58VirF, possesses the hallmarks of functional F-box proteins: it contains an active F-box domain and specifically interacts, via its F-box domain, with SKP1-like (ASK) protein components of the plant ubiquitin/proteasome system. Thus, our data suggest that nopaline strains of Agrobacterium have evolved to encode a functional F-box protein VirF.

  8. First description of PVL-positive methicillin-resistant Staphylococcus aureus (MRSA) in wild boar meat.

    PubMed

    Kraushaar, Britta; Fetsch, Alexandra

    2014-09-01

    Staphylococcus aureus is an important food-borne pathogen due to the ability of enterotoxigenic strains to produce staphylococcal enterotoxins (SEs) in food. Methicillin-resistant S. aureus (MRSA) is also an important pathogen for humans, causing severe and hard to treat diseases in hospitals and in the community due to its multiresistance against antimicrobials. In particular, strains harbouring genes encoding for the Panton-Valentine leukocidin (PVL) toxin are of concern from a public health perspective as they are usually capable of causing severe skin and soft tissue infections (sSSTIs) and occasionally necrotizing pneumonia which is associated with high mortality. This is the first report on the detection of MRSA with genes encoding for PVL in wild boar meat. Among the 28 MRSA isolated from wild boar meat in the course of a national monitoring programme in Germany, seven harboured PVL-encoding genes. Six of the isolates were identical according to the results of spa-, MLST-, microarray- and PFGE-typing. They could be assigned to the epidemic MRSA clone USA300. Epidemiological investigations revealed that people handling the food were the most likely common source of contamination with these MRSA. These findings call again for suitable hygienic measures at all processing steps of the food production chain. The results of the study underline that monitoring along the food chain is essential to closely characterise the total burden of MRSA for public health. Copyright © 2014. Published by Elsevier B.V.

  9. Pulling Marbles from a Bag: Deducing the Regional Impact History of the SPA Basin from Impact-Melt Rocks

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara A.; Coker, Robert F.

    2010-01-01

    The South Pole Aitken (SPA) basin is the stratigraphically oldest identifiable lunar basin and is therefore one of the most important targets for absolute age-dating to help understand whether ancient lunar bombardment history smoothly declined or was punctuated by a cataclysm. A feasible near-term approach to this problem is to robotically collect a sample from near the center of the basin, where vertical and lateral mixing provided by post-basin impacts ensures that such a sample will be composed of small rock fragments from SPA itself, from local impact craters, and from faraway giant basins. The range of ages, intermediate spikes in the age distribution, and the oldest ages are all part of the definition of the absolute age and impact history recorded within the SPA basin.

  10. Structural physical approximation for the realization of the optimal singlet fraction with two measurements

    NASA Astrophysics Data System (ADS)

    Adhikari, Satyabrata

    2018-04-01

    Structural physical approximation (SPA) has been exploited to approximate nonphysical operation such as partial transpose. It has already been studied in the context of detection of entanglement and found that if the minimum eigenvalue of SPA to partial transpose is less than 2/9 then the two-qubit state is entangled. We find application of SPA to partial transpose in the estimation of the optimal singlet fraction. We show that the optimal singlet fraction can be expressed in terms of the minimum eigenvalue of SPA to partial transpose. We also show that the optimal singlet fraction can be realized using Hong-Ou-Mandel interferometry with only two detectors. Further we have shown that the generated hybrid entangled state between a qubit and a binary coherent state can be used as a resource state in quantum teleportation.

  11. New immune cells in spondyloarthritis: Key players or innocent bystanders?

    PubMed

    Venken, Koen; Elewaut, Dirk

    2015-12-01

    The central role of the inflammatory cytokines such as TNF-α, IL-23, and IL-17 in the disease pathogenesis of spondyloarthritis (SpA) is unquestionable, given the strong efficacy of anti-cytokine therapeutics used in the treatment of SpA patients. These cytokines are produced by a diverse range of immune cells, some extending beyond the typical spectrum of lineage-defined subsets. Recently, a number of specialized cells, such as innate-like T-cells, innate lymphoid cells (ILCs) and natural killer receptor (NKR)-expressing T cells, have been marked to be involved in SpA pathology. In this chapter, we will elaborate on the unique characteristics of these particular immune subsets and critically evaluate their potential contribution to SpA disease, taking into account their role in joint and gut pathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Intravenous superoxide dismutase as a protective agent to prevent impairment of lung function induced by high tidal volume ventilation.

    PubMed

    Wu, Nan-Chun; Liao, Fan-Ting; Cheng, Hao-Min; Sung, Shih-Hsien; Yang, Yu-Chun; Wang, Jiun-Jr

    2017-07-26

    Positive-pressure mechanical ventilation is essential in assisting patients with respiratory failure in the intensive care unit and facilitating oxygenation in the operating room. However, it was also recognized as a primary factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary oxidative stress and lung inflammation had been known to play important roles. Cu/Zn superoxide dismutase (SOD) is an important antioxidant, and possesses anti-inflammatory capacity. In this study, we aimed to study the efficacy of Cu/Zn SOD, administered intravenously during high tidal volume (HTV) ventilation, to prevent impairment of lung function. Thirty-eight male Sprague-Dawley rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV; 8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14). Lung function was evaluated both at baseline and after 5-h ventilation. Lung injury was assessed by histological examination, lung water and protein contents in the bronchoalveolar lavage fluid (BALF). Pulmonary oxidative stress was examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in BALF, and antioxidative activity by protein expression of glutathione peroxidase-1 (GPx-1) in the lung. Severity of lung inflammation was evaluated by white blood cell and differential count in BALF, and protein expression of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and mRNA expression of nuclear factor-κB (NF-κB) in the lung. We also examined protein expression of surfactant protein (SP)-A and D and we measured hourly changes in serum nitric oxide (NO) level. Five hours of LTV ventilation did not induce a major change in lung function, whereas 5 h of HTV ventilation induced apparent combined restrictive and obstructive lung disorder, together with increased pulmonary oxidative stress, decreased anti-oxidative activity and increased lung inflammation (P < 0.05). HTV ventilation also decreased SP-A and SP-D expression and suppressed serum NO level during the time course of ventilation. Cu/Zn SOD administered intravenously during HTV ventilation effectively reversed associated pulmonary oxidative stress and lung inflammation (P < 0.05); moreover, it preserved SP-A and SP-D expressions in the lung and increased serum nitric oxide (NO) level, enhancing vascular NO bioavailability. HTV ventilation can induce combined restrictive and obstructive lung disorders. Intravenous administration of Cu/Zn SOD during HTV ventilation can prevent lung function impairment and lung injury via reducing pulmonary oxidative stress and lung inflammation, preserving pulmonary surfactant expression, and enhancing vascular NO bioavailability.

  13. The mitochondrial gene encoding ribosomal protein S12 has been translocated to the nuclear genome in Oenothera.

    PubMed Central

    Grohmann, L; Brennicke, A; Schuster, W

    1992-01-01

    The Oenothera mitochondrial genome contains only a gene fragment for ribosomal protein S12 (rps12), while other plants encode a functional gene in the mitochondrion. The complete Oenothera rps12 gene is located in the nucleus. The transit sequence necessary to target this protein to the mitochondrion is encoded by a 5'-extension of the open reading frame. Comparison of the amino acid sequence encoded by the nuclear gene with the polypeptides encoded by edited mitochondrial cDNA and genomic sequences of other plants suggests that gene transfer between mitochondrion and nucleus started from edited mitochondrial RNA molecules. Mechanisms and requirements of gene transfer and activation are discussed. Images PMID:1454526

  14. Characterization of methicillin-resistant Staphylococcus aureus from residents and the environment in a long-term care facility.

    PubMed

    Ludden, C; Brennan, G; Morris, D; Austin, B; O'Connell, B; Cormican, M

    2015-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health concern associated with residence in a long-term care facility (LTCF). The aim of this prospective study was to characterize MRSA isolated from residents over a 1-year period and their physical environment over a 2-year period. MRSA was recovered from 17/64 residents (R) of a LTCF and from 42 environmental (E) sites. All isolates carried the mecA gene and lacked the mecC and Panton-Valentine leukocidin (PVL) genes. Thirteen spa types were identified with t032 being the most frequent (41% of total; n = 8R, 16E), followed by t727 (22% of total; n = 13E), and t8783 (10% of total; n = 6E). Five spa types were each represented by single isolates. Thirty-nine isolates were of spa types associated with the multilocus sequence type ST22 (t032, 41%; spa-CC22, 68%) and reflect the predominance of ST22 in Irish hospitals. The uncommon spa types t727, t8783, t1372, t3130, t10038 were present in the environment but not detected in residents and are infrequently observed in Ireland.

  15. Recommendations for the prescription of physical exercise for patients with spondyloarthritis.

    PubMed

    Flórez García, Mariano Tomás; Carmona, Loreto; Almodóvar, Raquel; Fernández de Las Peñas, César; García Pérez, Fernando; Pérez Manzanero, M Ángeles; García García, José Manuel; Soriano Segarra, Lidón; Jiménez Díaz, José Fernando; Mendoza Laiz, Nuria; de Miguel Mendieta, Eugenio; Torre Alonso, Juan Carlos; Linares Ferrando, Luis Francisco; Collantes Estévez, Eduardo; Sanz Sanz, Jesús; Zarco Montejo, Pedro

    2017-08-11

    To develop expert-based recommendations on physical activity and exercise for patients with spondyloarthritis (SpA). Two discussion groups, one of physical therapists, rehabilitation physicians, and professionals of physical activity and sports, and another of rheumatologists interested in SpA, were held to discuss the results of a survey of rheumatologists on exercise and two focus groups with patients on barriers to exercise. Preliminary recommendations were drafted. These were submitted to the opinion of the experts in both groups according to a two round Delphi methodology. Twenty one recommendations covering general aspects of exercise, adaptation to patient, how to deliver messages, pain management, and type of exercise and monitoring were issued. The level of agreement varied slightly between expert groups but it was high overall. Items with poor agreement were removed from the consensus. We present recommendations on when and how to prescribe and monitor exercise in patients with SpA based on the opinion of experts in exercise and in SpA. We must now test whether these recommendations are useful for clinical practice and have an effect on patients with SpA seen by rheumatologists. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  16. [Study on the early detection of Sclerotinia of Brassica napus based on combinational-stimulated bands].

    PubMed

    Liu, Fei; Feng, Lei; Lou, Bing-gan; Sun, Guang-ming; Wang, Lian-ping; He, Yong

    2010-07-01

    The combinational-stimulated bands were used to develop linear and nonlinear calibrations for the early detection of sclerotinia of oilseed rape (Brassica napus L.). Eighty healthy and 100 Sclerotinia leaf samples were scanned, and different preprocessing methods combined with successive projections algorithm (SPA) were applied to develop partial least squares (PLS) discriminant models, multiple linear regression (MLR) and least squares-support vector machine (LS-SVM) models. The results indicated that the optimal full-spectrum PLS model was achieved by direct orthogonal signal correction (DOSC), then De-trending and Raw spectra with correct recognition ratio of 100%, 95.7% and 95.7%, respectively. When using combinational-stimulated bands, the optimal linear models were SPA-MLR (DOSC) and SPA-PLS (DOSC) with correct recognition ratio of 100%. All SPA-LSSVM models using DOSC, De-trending and Raw spectra achieved perfect results with recognition of 100%. The overall results demonstrated that it was feasible to use combinational-stimulated bands for the early detection of Sclerotinia of oilseed rape, and DOSC-SPA was a powerful way for informative wavelength selection. This method supplied a new approach to the early detection and portable monitoring instrument of sclerotinia.

  17. Software Process Assessment (SPA)

    NASA Technical Reports Server (NTRS)

    Rosenberg, Linda H.; Sheppard, Sylvia B.; Butler, Scott A.

    1994-01-01

    NASA's environment mirrors the changes taking place in the nation at large, i.e. workers are being asked to do more work with fewer resources. For software developers at NASA's Goddard Space Flight Center (GSFC), the effects of this change are that we must continue to produce quality code that is maintainable and reusable, but we must learn to produce it more efficiently and less expensively. To accomplish this goal, the Data Systems Technology Division (DSTD) at GSFC is trying a variety of both proven and state-of-the-art techniques for software development (e.g., object-oriented design, prototyping, designing for reuse, etc.). In order to evaluate the effectiveness of these techniques, the Software Process Assessment (SPA) program was initiated. SPA was begun under the assumption that the effects of different software development processes, techniques, and tools, on the resulting product must be evaluated in an objective manner in order to assess any benefits that may have accrued. SPA involves the collection and analysis of software product and process data. These data include metrics such as effort, code changes, size, complexity, and code readability. This paper describes the SPA data collection and analysis methodology and presents examples of benefits realized thus far by DSTD's software developers and managers.

  18. High frequency of methicillin-resistant Staphylococcus aureus (MRSA) with SCCmec type III and spa type t030 in Karaj's teaching hospitals, Iran.

    PubMed

    Bayat, Bahareh; Zade, Masoumeh Hallaj; Mansouri, Samaneh; Kalantar, Enayat; Kabir, Kourosh; Zahmatkesh, Ehsan; Sepehr, Mohammad Noori; Naseri, Mohammmad Hassan; Darban-Sarokhalil, Davood

    2017-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the most important antibiotic-resistant pathogen in many parts of the world over the past decades. This cross-sectional study was conducted to investigate MRSA isolated between July 2013 and July 2014 in Karaj, Iran. All tested isolates were collected in teaching hospitals from personnel, patients, and surfaces and each MRSA was analyzed by SCCmec and spa typing. Antibiotic susceptibility testing was accomplished by disk diffusion method. Out of 49 MRSA isolates from the Karaj's teaching hospitals, 82%, 10%, and 6% of the isolates were SCCmec types III, II, and I, respectively. The main spa type in this study was spa t030 with frequency as high as 75.5% from intensive care unit (ICU) of the hospitals and high rate of resistance to rifampicin (53%) was found in MRSA isolates. In conclusion, high frequency of spa t030 with SCCmec type III and MRSA phenotype illustrated circulating of one of the antibiotic-resistant strains in ICU of Karaj's teaching hospitals and emphasizes the need for ongoing molecular surveillance, antibiotic susceptibility monitoring, and infection control.

  19. [Measurement of soil organic matter and available K based on SPA-LS-SVM].

    PubMed

    Zhang, Hai-Liang; Liu, Xue-Mei; He, Yong

    2014-05-01

    Visible and short wave infrared spectroscopy (Vis/SW-NIRS) was investigated in the present study for measurement of soil organic matter (OM) and available potassium (K). Four types of pretreatments including smoothing, SNV, MSC and SG smoothing+first derivative were adopted to eliminate the system noises and external disturbances. Then partial least squares regression (PLSR) and least squares-support vector machine (LS-SVM) models were implemented for calibration models. The LS-SVM model was built by using characteristic wavelength based on successive projections algorithm (SPA). Simultaneously, the performance of LSSVM models was compared with PLSR models. The results indicated that LS-SVM models using characteristic wavelength as inputs based on SPA outperformed PLSR models. The optimal SPA-LS-SVM models were achieved, and the correlation coefficient (r), and RMSEP were 0. 860 2 and 2. 98 for OM and 0. 730 5 and 15. 78 for K, respectively. The results indicated that visible and short wave near infrared spectroscopy (Vis/SW-NIRS) (325 approximately 1 075 nm) combined with LS-SVM based on SPA could be utilized as a precision method for the determination of soil properties.

  20. Achieving a Golden Mean: Mechanisms by Which Coronaviruses Ensure Synthesis of the Correct Stoichiometric Ratios of Viral Proteins▿

    PubMed Central

    Plant, Ewan P.; Rakauskaitė, Rasa; Taylor, Deborah R.; Dinman, Jonathan D.

    2010-01-01

    In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed −1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the −1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream- to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by >4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a “golden mean” model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins. PMID:20164235

  1. Fast simulation of electromagnetic and hadronic showers in SpaCal calorimeter at the H1 experiment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Raičević, Nataša, E-mail: raicevic@mail.desy.de; Glazov, Alexandre

    2016-03-25

    The fast simulation of showers induced by electrons (positrons) in the H1 lead/scintillating-fiber calorimeter, SpaCal, based on shower library technique has been presented previously. In this paper we show the results on linearity and uniformity of the reconstructed electron/positron cluster energy in electromagnetic section of Spacal for the simulations based on shower library and GFLASH shower parametrisation. The shapes of the clusters originating from photon and hadron candidates in SpaCal are analysed and experimental distributions compared with the two simulations.

  2. Ectromelia Virus BTB/kelch Proteins, EVM150 and EVM167, Interact with Cullin-3 Based Ubiquitin Ligases

    PubMed Central

    Wilton, Brianne A.; Campbell, Stephanie; Van Buuren, Nicholas; Garneau, Robyn; Furukawa, Manabu; Xiong, Yue; Barry., Michele

    2008-01-01

    Cellular proteins containing BTB and kelch domains have been shown to function as adapters for the recruitment of substrates to cullin-3-based ubiquitin ligases. Poxviruses are the only family of viruses known to encode multiple BTB/kelch proteins, suggesting that poxviruses may modulate the ubiquitin pathway through interaction with cullin-3. Ectromelia virus encodes four BTB/kelch proteins and one BTB-only protein. Here we demonstrate that two of the ectromelia virus encoded BTB/kelch proteins, EVM150 and EVM167, interacted with cullin-3. Similar to cellular BTB proteins, the BTB domain of EVM150 and EVM167 was necessary and sufficient for cullin-3 interaction. During infection, EVM150 and EVM167 localized to discrete cytoplasmic regions, which co-localized with cullin-3. Furthermore, EVM150 and EVM167 co-localized and interacted with conjugated ubiquitin, as demonstrated by confocal microscopy and co-immunoprecipitation. Our findings suggest that the ectromelia virus encoded BTB/kelch proteins, EVM150 and EVM167, interact with cullin-3 potentially functioning to recruit unidentified substrates for ubiquitination. PMID:18221766

  3. Characterization of a cDNA encoding a protein involved in formation of the skeleton during development of the sea urchin Lytechinus pictus.

    PubMed

    Livingston, B T; Shaw, R; Bailey, A; Wilt, F

    1991-12-01

    In order to investigate the role of proteins in the formation of mineralized tissues during development, we have isolated a cDNA that encodes a protein that is a component of the organic matrix of the skeletal spicule of the sea urchin, Lytechinus pictus. The expression of the RNA encoding this protein is regulated over development and is localized to the descendents of the micromere lineage. Comparison of the sequence of this cDNA to homologous cDNAs from other species of urchin reveal that the protein is basic and contains three conserved structural motifs: a signal peptide, a proline-rich region, and an unusual region composed of a series of direct repeats. Studies on the protein encoded by this cDNA confirm the predicted reading frame deduced from the nucleotide sequence and show that the protein is secreted and not glycosylated. Comparison of the amino acid sequence to databases reveal that the repeat domain is similar to proteins that form a unique beta-spiral supersecondary structure.

  4. Direct Repeat Unit (dru) Typing of Methicillin-Resistant Staphylococcus pseudintermedius from Dogs and Cats.

    PubMed

    Kadlec, Kristina; Schwarz, Stefan; Goering, Richard V; Weese, J Scott

    2015-12-01

    Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged in a remarkable manner as an important problem in dogs and cats. However, limited molecular epidemiological information is available. The aims of this study were to apply direct repeat unit (dru) typing in a large collection of well-characterized MRSP isolates and to use dru typing to analyze a collection of previously uncharacterized MRSP isolates. Two collections of MRSP isolates from dogs and cats were included in this study. The first collection comprised 115 well-characterized MRSP isolates from North America and Europe. The data for these isolates included multilocus sequence typing (MLST) and staphylococcal protein A gene (spa) typing results as well as SmaI macrorestriction patterns after pulsed-field gel electrophoresis (PFGE). The second collection was a convenience sample of 360 isolates from North America. The dru region was amplified by PCR, sequenced, and analyzed. For the first collection, the discriminatory indices of the typing methods were calculated. All isolates were successfully dru typed. The discriminatory power for dru typing (D = 0.423) was comparable to that of spa typing (D = 0.445) and of MLST (D = 0.417) in the first collection. Occasionally, dru typing was able to further discriminate between isolates that shared the same spa type. Among all 475 isolates, 26 different dru types were identified, with 2 predominant types (dt9a and dt11a) among 349 (73.4%) isolates. The results of this study underline that dru typing is a useful tool for MRSP typing, being an objective, standardized, sequence-based method that is relatively cost-efficient and easy to perform. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Molecular pathology of pulmonary surfactants and cytokines in drowning compared with other asphyxiation and fatal hypothermia.

    PubMed

    Miyazato, Takako; Ishikawa, Takaki; Michiue, Tomomi; Maeda, Hitoshi

    2012-07-01

    Drowning involves complex fatal factors, including asphyxiation and electrolyte/osmotic disturbances, as well as hypothermia in cold water. The present study investigated the molecular pathology of pulmonary injury due to drowning, using lung specimens from forensic autopsy cases of drowning (n = 21), acute mechanical asphyxia due to neck compression and smothering (n = 24), and hypothermia (cold exposure, n = 11), as well as those of injury (n = 23), intoxication (n = 13), fire fatality (n = 18), and acute cardiac death (n = 9) for comparison. TaqMan real-time reverse transcription polymerase chain reaction was used to quantify messenger RNA (mRNA) expressions of pulmonary surfactant-associated proteins A and D (SP-A and SP-D), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10. SP-A and SP-D mRNA levels were lower for drowning, mechanical asphyxiation, fire fatality, and acute cardiac deaths than for hypothermia and injury. TNF-α, IL-1β, and IL-10 mRNA levels were higher for drowning or for drowning and injury than for other groups; there was no significant difference between fire fatality, involving airway injury due to inhalation of hot/irritant gases, and other control groups. These observations suggest characteristic molecular biological patterns of pulmonary injury involving suppression of pulmonary surfactants and activation of early-phase mediators of inflammation in drowning, with high mRNA expression levels of pulmonary surfactants in fatal hypothermia; however, there was no significant difference among these markers in immunohistochemical detection, except for SP-A. These mRNA expressions can be used as markers of pulmonary injury to assist in investigations of the pathophysiology of drowning and fatal hypothermia in combination with other biochemical and biological markers.

  6. Trichoderma genes

    DOEpatents

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  7. Rebamipide prevents peripheral arthritis and intestinal inflammation by reciprocally regulating Th17/Treg cell imbalance in mice with curdlan-induced spondyloarthritis.

    PubMed

    Min, Hong-Ki; Kim, Jae-Kyung; Lee, Seon-Yeong; Kim, Eun-Kyung; Lee, Seung Hoon; Lee, Jennifer; Kwok, Seung-Ki; Cho, Mi-La; Park, Sung-Hwan

    2016-06-27

    Spondyloarthritis (SpA) usually manifests as arthritis of the axial and peripheral joints but can also result in extra-articular manifestations such as inflammatory bowel disease. Proinflammatory cytokine interleukin-17 (IL-17) plays a crucial role in the pathogenesis of SpA. Rebamipide inhibits signal transducer and activator of transcription 3 that controls IL-17 production and Th17 cell differentiation. This study examined the effect of rebamipide on SpA development. SKG ZAP-70(W163C) mice were immunized with curdlan to induce SpA features. The mice were then intraperitoneally injected with rebamipide or vehicle 3 times a week for 14 weeks and their clinical scores were evaluated. Histological scores of the paw and spine and the length of the gut were measured at sacrifice. Immunohistochemical staining of IL-17 and tumor necrosis factor-α (TNF-α) was performed using tissue samples isolated from the axial joints, peripheral joints, and gut. Spleen tissue samples were isolated from both rebamipide- or vehicle-treated mice with SpA at 14 weeks after curdlan injection to determine the effect of rebamipide on Th17 and regulatory T (Treg) cell differentiation. Rebamipide decreased the clinical and histological scores of the peripheral joints. The total length of the gut was preserved in rebamipide-treated mice. IL-17 and TNF-α expression in the spine, peripheral joints, and gut was lower in rebamipide-treated mice than in control mice. Th17 cell differentiation was suppressed whereas Treg cell differentiation was upregulated in the spleen of rebamipide-treated mice. Rebamipide exerted beneficial effects in mice with SpA by preventing peripheral arthritis and intestinal inflammation and by regulating Th17/Treg cell imbalance, suggesting that it can be used as a potential therapeutic agent for treating arthritis to SpA patients.

  8. Survivorship of standard versus modified posterior surgical approaches in metal-on-metal hip resurfacing.

    PubMed

    M Takamura, K; Maher, P; Nath, T; Su, E P

    2014-05-01

    Metal-on-metal hip resurfacing (MOMHR) is available as an alternative option for younger, more active patients. There are failure modes that are unique to MOMHR, which include loosening of the femoral head and fractures of the femoral neck. Previous studies have speculated that changes in the vascularity of the femoral head may contribute to these failure modes. This study compares the survivorship between the standard posterior approach (SPA) and modified posterior approach (MPA) in MOMHR. A retrospective clinical outcomes study was performed examining 351 hips (279 male, 72 female) replaced with Birmingham Hip Resurfacing (BHR, Smith and Nephew, Memphis, Tennessee) in 313 patients with a pre-operative diagnosis of osteoarthritis. The mean follow-up period for the SPA group was 2.8 years (0.1 to 6.1) and for the MPA, 2.2 years (0.03 to 5.2); this difference in follow-up period was statistically significant (p < 0.01). Survival analysis was completed using the Kaplan-Meier method. At four years, the Kaplan-Meier survival curve for the SPA was 97.2% and 99.4% for the MPA; this was statistically significant (log-rank; p = 0.036). There were eight failures in the SPA and two in the MPA. There was a 3.5% incidence of femoral head collapse or loosening in the SPA and 0.4% in the MPA, which represented a significant difference (p = 0.041). There was a 1.7% incidence of fractures of the femoral neck in the SPA and none in the MPA (p = 0.108). This study found a significant difference in survivorship at four years between the SPA and the MPA (p = 0.036). The clinical outcomes of this study suggest that preserving the vascularity of the femoral neck by using the MPA results in fewer vascular-related failures in MOMHRs. Cite this article: Bone Joint Res 2014;3:150-4. ©2014 The British Editorial Society of Bone & Joint Surgery.

  9. Survivorship of standard versus modified posterior surgical approaches in metal-on-metal hip resurfacing

    PubMed Central

    M. Takamura, K.; Maher, P.; Nath, T.; Su, E. P.

    2014-01-01

    Objectives Metal-on-metal hip resurfacing (MOMHR) is available as an alternative option for younger, more active patients. There are failure modes that are unique to MOMHR, which include loosening of the femoral head and fractures of the femoral neck. Previous studies have speculated that changes in the vascularity of the femoral head may contribute to these failure modes. This study compares the survivorship between the standard posterior approach (SPA) and modified posterior approach (MPA) in MOMHR. Methods A retrospective clinical outcomes study was performed examining 351 hips (279 male, 72 female) replaced with Birmingham Hip Resurfacing (BHR, Smith and Nephew, Memphis, Tennessee) in 313 patients with a pre-operative diagnosis of osteoarthritis. The mean follow-up period for the SPA group was 2.8 years (0.1 to 6.1) and for the MPA, 2.2 years (0.03 to 5.2); this difference in follow-up period was statistically significant (p < 0.01). Survival analysis was completed using the Kaplan–Meier method. Results At four years, the Kaplan–Meier survival curve for the SPA was 97.2% and 99.4% for the MPA; this was statistically significant (log-rank; p = 0.036). There were eight failures in the SPA and two in the MPA. There was a 3.5% incidence of femoral head collapse or loosening in the SPA and 0.4% in the MPA, which represented a significant difference (p = 0.041). There was a 1.7% incidence of fractures of the femoral neck in the SPA and none in the MPA (p = 0.108). Conclusion This study found a significant difference in survivorship at four years between the SPA and the MPA (p = 0.036). The clinical outcomes of this study suggest that preserving the vascularity of the femoral neck by using the MPA results in fewer vascular-related failures in MOMHRs. Cite this article: Bone Joint Res 2014;3:150–4 PMID:24842931

  10. Performance of the Assessment of Spondyloarthritis International Society criteria for the classification of spondyloarthritis in early spondyloarthritis clinics participating in the ESPERANZA programme.

    PubMed

    Tomero, Eva; Mulero, Juan; de Miguel, Eugenio; Fernández-Espartero, Cruz; Gobbo, Milena; Descalzo, Miguel A; Collantes-Estévez, Eduardo; Zarco, Pedro; Muñoz-Fernández, Santiago; Carmona, Loreto

    2014-02-01

    The objective of this study was to analyse the performance of the Assessment of SpondyloArthritis International Society (ASAS) criteria for the classification of SpA in early SpA clinics. We used a cross-sectional study of patients referred to early SpA units within the ESPERANZA programme (a Spanish nationwide health management programme designed to provide excellence in diagnosis and care for early SpA). Patients were eligible if they were <45 years of age and had any of the following: (i) a 2-year history of inflammatory back pain; (ii) back or joint pain with psoriasis, anterior uveitis, radiographic sacroiliitis, family history of SpA or positive HLA-B27; or (iii) asymmetric arthritis. We excluded patients for whom imaging (X-rays/MRI) or HLA-B27 results were not available. We analysed the performance (sensitivity and specificity) of different classification criteria sets, taking the rheumatologist's opinion as the gold standard. The analysis included 775 patients [mean age 33 (s.d. 7) years; 55% men; mean duration of symptoms 11 (s.d. 6) months]; SpA was diagnosed in 538 patients (69.5%). A total of 274 (67.9%) patients with chronic back pain met the ASAS axial criteria, 76 (56.3%) patients with arthritis but not chronic back pain fulfilled the ASAS criteria for peripheral SpA and 350 (65.1%) fulfilled all the ASAS criteria. The sensitivity and specificity of the ASAS criteria set were 65% and 93%, respectively (axial criteria: sensitivity 68%, specificity 95%). The sensitivity and specificity for the ESSG and Amor criteria were 58% and 90% and 59% and 86%, respectively. Despite performing better than the Amor or ESSG criteria, the ASAS criteria may be limited to detection of early forms, particularly in populations in which MRI is not extensively available or in populations with a low prevalence of HLA-B27.

  11. Association of human leukocyte A, B, and DR antigens in Colombian patients with diagnosis of spondyloarthritis.

    PubMed

    Santos, Ana M; Peña, Paola; Avila, Mabel; Briceño, Ignacio; Jaramillo, Carlos; Vargas-Alarcon, Gilberto; Rueda, Juan C; Saldarriaga, Eugenia-Lucia; Angarita, Jose-Ignacio; Martinez-Rodriguez, Nancy; Londono, John

    2017-04-01

    There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.

  12. High prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene in a semi-extensive red deer (Cervus elaphus hispanicus) farm in Southern Spain.

    PubMed

    Gómez, Paula; Lozano, Carmen; González-Barrio, David; Zarazaga, Myriam; Ruiz-Fons, Francisco; Torres, Carmen

    2015-06-12

    The objective was to determine the prevalence of Staphylococcus aureus nasal carriage in red deer of a semi-extensive farm and in humans in contact with the estate animals, and to characterize obtained isolates. Nasal swabs of 65 deer and 15 humans were seeded on mannitol-salt-agar and oxacillin-resistance-screening-agar-base. Isolates were identified by microbiological and molecular methods. Antimicrobial susceptibility profile was determined for 16 antibiotics by disk-diffusion and the presence of eight antibiotic resistance genes, seven virulence genes and genes of immune-evasion-cluster (IEC) was analyzed by PCR. S. aureus was typed by PFGE-SmaI, spa, agr, SCCmec and MLST. Isolates were detected in 16 deer (24.6%). Eleven S. aureus isolates were methicillin-resistant (MRSA), and five were methicillin-susceptible (MSSA). All MRSA harbored mecC gene and were agr-III/SCCmecXI/ST1945 (four spa-t843 and seven spa-t1535). All mecC-MRSA carried blaZ-SCCmecXI and etd2, were IEC-type-E, and belonged to the same PFGE pattern. The five MSSA were typed as spa-t2420/agr-I/ST133. Regarding humans, S. aureus was recovered from six samples (40%). The isolates were MSSA and were typed as spa-t002/agr-II, spa-t012/agr-III or spa-t822/agr-III and showed different IEC types (A, B, D and F). blaZ and erm(A) genes were detected, as well as cna and tst genes. As conclusion, red deer analyzed in this study are frequent carriers of mecC-MRSA CC130 (16.9%), they are characterized by few resistance and virulence determinants, and by the presence of IEC type-E. Deer could be a source of mecC-MRSA which could potentially be transmitted to other animals, or even to humans. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Global distribution and diversity of ovine-associated Staphylococcus aureus.

    PubMed

    Smith, Edward M; Needs, Polly F; Manley, Grace; Green, Laura E

    2014-03-01

    Staphylococcus aureus is an important pathogen of many species, including sheep, and impacts on both human and animal health, animal welfare, and farm productivity. Here we present the widest global diversity study of ovine-associated S. aureus to date. We analysed 97 S. aureus isolates from sheep and sheep products from the UK, Turkey, France, Norway, Australia, Canada and the USA using multilocus sequence typing (MLST) and spa typing. These were compared with 196 sheep isolates from Europe (n=153), Africa (n=28), South America (n=14) and Australia (n=1); 172 bovine, 68 caprine and 433 human S. aureus profiles. Overall there were 59 STs and 87 spa types in the 293 ovine isolates; in the 97 new ovine isolates there were 22 STs and 37 spa types, including three novel MLST alleles, four novel STs and eight novel spa types. Three main CCs (CC133, CC522 and CC700) were detected in sheep and these contained 61% of all isolates. Four spa types (t002, t1534, t2678 and t3576) contained 31% of all isolates and were associated with CC5, CC522, CC133 and CC522 respectively. spa types were consistent with MLST CCs, only one spa type (t1403) was present in multiple CCs. The three main ovine CCs have different but overlapping patterns of geographical dissemination that appear to match the location and timing of sheep domestication and selection for meat and wool production. CC133, CC522 and CC700 remained ovine-associated following the inclusion of additional host species. Ovine isolates clustered separately from human and bovine isolates and those from sheep cheeses, but closely with caprine isolates. As with cattle isolates, patterns of clonal diversification of sheep isolates differ from humans, indicative of their relatively recent host-jump. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  14. IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

    PubMed Central

    2013-01-01

    Introduction Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. Methods IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters. Results Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this antigen had low levels of IgG1, indicating an inverse association. Different IgG subclasses were produced against bacterial and human HSP60 in the same serum sample, IgG1 and IgG3, respectively, indicating that there was no cross-reaction. Conclusions A significant association was observed between axial SpA and the presence of IgG1/IgG3 antibodies to human HSP60 and of IgG1 to S. enterica Enteritidis and C. trachomatis. Generation of antibodies to human HSP60 was independent of the presence of antibodies to bacterial HSP60. No association was observed between clinical and MRI changes with antibodies over time. Altogether, such antibodies do not reflect the disease activity in these patients. This study has been approved by the Regional Research Ethics Committee of Central Jutland, Denmark. Trial registration numbers: 20050046 and 20100083 PMID:23705835

  15. Screening for ATM Mutations in an African-American Population to Identify a Predictor of Breast Cancer Susceptibility

    DTIC Science & Technology

    2006-07-01

    ATM genetic variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for each mutation examined. 15. SUBJECT...women without breast cancer. An additional objective is to determine the functional impact upon the protein encoded by the ATM gene for each mutation ...each ATM variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for mutations identified. Body STATEMENT

  16. The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis.

    PubMed

    Veale, Douglas J; McGonagle, Dennis; McInnes, Iain B; Krueger, James G; Ritchlin, Christopher T; Elewaut, Dirk; Kanik, Keith S; Hendrikx, Thijs; Berstein, Gabriel; Hodge, Jennifer; Telliez, Jean-Baptiste

    2018-04-03

    The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS.

  17. In Silico Identification of Epitopes in Mycobacterium avium subsp. paratuberculosis Proteins That Were Upregulated under Stress Conditions

    PubMed Central

    Gurung, Ratna B.; Purdie, Auriol C.; Begg, Douglas J.

    2012-01-01

    Johne's disease in ruminants is caused by Mycobacterium avium subsp. paratuberculosis. Diagnosis of M. avium subsp. paratuberculosis infection is difficult, especially in the early stages. To date, ideal antigen candidates are not available for efficient immunization or immunodiagnosis. This study reports the in silico selection and subsequent analysis of epitopes of M. avium subsp. paratuberculosis proteins that were found to be upregulated under stress conditions as a means to identify immunogenic candidate proteins. Previous studies have reported differential regulation of proteins when M. avium subsp. paratuberculosis is exposed to stressors which induce a response similar to dormancy. Dormancy may be involved in evading host defense mechanisms, and the host may also mount an immune response against these proteins. Twenty-five M. avium subsp. paratuberculosis proteins that were previously identified as being upregulated under in vitro stress conditions were analyzed for B and T cell epitopes by use of the prediction tools at the Immune Epitope Database and Analysis Resource. Major histocompatibility complex class I T cell epitopes were predicted using an artificial neural network method, and class II T cell epitopes were predicted using the consensus method. Conformational B cell epitopes were predicted from the relevant three-dimensional structure template for each protein. Based on the greatest number of predicted epitopes, eight proteins (MAP2698c [encoded by desA2], MAP2312c [encoded by fadE19], MAP3651c [encoded by fadE3_2], MAP2872c [encoded by fabG5_2], MAP3523c [encoded by oxcA], MAP0187c [encoded by sodA], and the hypothetical proteins MAP3567 and MAP1168c) were identified as potential candidates for study of antibody- and cell-mediated immune responses within infected hosts. PMID:22496492

  18. Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

    PubMed

    Kollmann, Christopher S; Bai, Xiaopeng; Tsai, Ching-Hsuan; Yang, Hongfang; Lind, Kenneth E; Skinner, Steven R; Zhu, Zhengrong; Israel, David I; Cuozzo, John W; Morgan, Barry A; Yuki, Koichi; Xie, Can; Springer, Timothy A; Shimaoka, Motomu; Evindar, Ghotas

    2014-04-01

    The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Is being in paid work beyond state pension age beneficial for health? Evidence from England using a life-course approach

    PubMed Central

    Corna, Laurie M; Worts, Diana; McDonough, Peggy; Sacker, Amanda; Price, Debora; Glaser, Karen

    2017-01-01

    Background Given the current policy emphasis in many Western societies on extending working lives, we investigated the health effects of being in paid work beyond state pension age (SPA). Until now, work has largely focused on the health of those who exit the labour force early. Methods Our data come from waves 2–4 of the English Longitudinal Study of Ageing, including the life history interview at wave 3. Using logistic and linear regression models, we assessed the longitudinal associations between being in paid work beyond SPA and 3 measures of health (depression, a latent measure of somatic health and sleep disturbance) among men aged 65–74 and women aged 60–69. Our analyses controlled for baseline health and socioeconomic characteristics, as well as for work histories and health in adulthood and childhood. Results Approximately a quarter of women and 15% of men were in paid work beyond SPA. Descriptive bivariate analyses suggested that men and women in paid work were more likely to report better health at follow-up. However, once baseline socioeconomic characteristics as well as adulthood and baseline health and labour market histories were accounted for, the health benefits of working beyond SPA were no longer significant. Conclusions Potential health benefits of working beyond SPA need to be considered in the light of the fact that those who report good health and are more socioeconomically advantaged are more likely to be working beyond SPA to begin with. PMID:27940656

  20. [Near infrared spectroscopy study on water content in turbine oil].

    PubMed

    Chen, Bin; Liu, Ge; Zhang, Xian-Ming

    2013-11-01

    Near infrared (NIR) spectroscopy combined with successive projections algorithm (SPA) was investigated for determination of water content in turbine oil. Through the 57 samples of different water content in turbine oil scanned applying near infrared (NIR) spectroscopy, with the water content in the turbine oil of 0-0.156%, different pretreatment methods such as the original spectra, first derivative spectra and differential polynomial least squares fitting algorithm Savitzky-Golay (SG), and successive projections algorithm (SPA) were applied for the extraction of effective wavelengths, the correlation coefficient (R) and root mean square error (RMSE) were used as the model evaluation indices, accordingly water content in turbine oil was investigated. The results indicated that the original spectra with different water content in turbine oil were pretreated by the performance of first derivative + SG pretreatments, then the selected effective wavelengths were used as the inputs of least square support vector machine (LS-SVM). A total of 16 variables selected by SPA were employed to construct the model of SPA and least square support vector machine (SPA-LS-SVM). There is 9 as The correlation coefficient was 0.975 9 and the root of mean square error of validation set was 2.655 8 x 10(-3) using the model, and it is feasible to determine the water content in oil using near infrared spectroscopy and SPA-LS-SVM, and an excellent prediction precision was obtained. This study supplied a new and alternative approach to the further application of near infrared spectroscopy in on-line monitoring of contamination such as water content in oil.

  1. Evaluation of serum prolidase activity and oxidative stress markers in men with BPH and prostate cancer.

    PubMed

    Kucukdurmaz, Faruk; Efe, Erkan; Çelik, Ahmet; Dagli, Hasan; Kılınc, Metin; Resim, Sefa

    2017-12-12

    Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are diseases of elderly men and are related to increased oxidative stress (OS). Although prolidase has a role in collagen metabolism, it is also used to evaluate OS in many diseases. However, there is a lack of data about serum prolidase activity (SPA) in prostate cancer. The aim of this study was to evaluate and compare SPA levels in males with BPH and PCa. Evaluation was made of a total of 81 men who underwent transrectal ultrasound guided prostate biopsy for a definitive diagnosis due to high PSA levels. Patients were separated into 2 groups as BPH and PCa patients. Pre-biopsy malondialdehyde (MDA), superoxide dismutase (SOD), PSA levels and serum prolidase activities (SPA) were compared between the groups and the correlations of SPA with the other parameters were also investigated in both groups. BPH was diagnosed in 51 patients and PCa in 30. The mean age of patients was similar in both groups as 63.25 ± 5.81 years in the BPH group 65.30 ± 7.35 years in the PCa group(p:0.081). The median MDA and SOD levels were insignificantly increased in the PCa patients. SPA values were similar in BPH and PCa patients. SPA did not correlate with age, PSA, MDA or SOD levels in either group. Our study results revealed that serum prolidase activity is similar in BPH and PCa cases and is not correlated with MDA, SOD or PSA levels.

  2. Assessing the Provenance of regolith components in the South Pole-Aitken Basin: Results from LRO, M3, GRAIL, and Ejecta Modeling

    NASA Astrophysics Data System (ADS)

    Petro, N. E.; Cohen, B. A.; Jolliff, B. L.; Moriarty, D. P.

    2016-12-01

    Results from recent lunar missions are reshaping our view of the lunar surface, the evolution of the Moon, and the scale of processes that have affected the Moon. From orbital remote sensing data we can investigate surface mineralogy at the 100s m scale as well as corresponding high-resolution images to evaluate the exposures of various compositions. Coupled with geophysical data from the GRAIL mission, we can now assess the effects of large impacts (>200 km in diameter). These data are essential for assessing the composition of the interior of the South Pole-Aitken Basin (SPA), a key destination for future sample return (Jolliff et al., this conference). Data from the Lunar Reconnaissance Orbiter (LRO) shows that variations in surface roughness and morphology are broad and likely reflect both the ancient age of the basin floor, as well as younger volcanic and impact-related resurfacing events. Data from the Moon Mineralogy Mapper also reveal compositional variations across the interior of the basin and reflect both ancient volcanic activity as well as surface exposures of deep-seated crustal (SPA substrate) materials. These datasets are critical for delineating variations in surface compositions, which indicate formation mechanisms (e.g., volcanic vs. impact-derived). We investigate the resurfacing history of SPA, focusing on integrating data from multiple instruments, as well as updated modeling into the origin of regolith components (in the form of ejecta from near and distant impact craters). Recent advances include determination of the inventory of large craters as well as improved estimates of the amount of ejecta from such craters. As with past estimates of basin ejecta distribution, the volume of ejecta introduced to SPA is relatively small and quickly becomes diluted within the regolith. In addition, the contribution of ejecta by smaller, local craters is shown to distribute a comparable amount of material within the basin. Much of the material distributed by these local craters is SPA substrate, with a small amount of re-melted material. In most locations within SPA, the amount of reworked SPA substrate by ballistic ejecta emplacement and mixing from impacts within the presumed transient cavity greatly exceeds the amount of material contributed by ballistic sedimentation from large craters outside of SPA.

  3. The performance of different classification criteria sets for spondyloarthritis in the worldwide ASAS-COMOSPA study.

    PubMed

    Bakker, Pauline; Moltó, Anna; Etcheto, Adrien; Van den Bosch, Filip; Landewé, Robert; van Gaalen, Floris; Dougados, Maxime; van der Heijde, Désirée

    2017-05-16

    In this study, we sought to compare the performance of spondyloarthritis (SpA) classification criteria sets in an international SpA cohort with patients included from five continents around the world. Data from the (ASAS) COMOrbidities in SPondyloArthritis (ASAS-COMOSPA) study were used. ASAS-COMOSPA is a multinational, cross-sectional study with consecutive patients diagnosed with SpA by rheumatologists worldwide. Patients were classified according to the European Spondyloarthropathy Study Group (ESSG), modified European Spondyloarthropathy Study Group (mESSG), Amor, modified Amor, Assessment of SpondyloArthritis international Society (ASAS) axial Spondyloarthritis (axSpA), ASAS peripheral spondyloarthritis (pSpA) and ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria. Overlap between the classification criteria sets was assessed for patients with and without back pain. Furthermore, patients fulfilling different arms of the ASAS axSpA criteria (imaging arm, clinical arm, both arms) were compared on the presence of SpA features. A total of 3942 patients (5 continents, 26 countries) were included. The mean age was 43.6 years, 65.0% were male, 56.2% were human leucocyte antigen B27-positive and 64.4% had radiographic sacroiliitis (based on modified New York criteria). Of the patients, 85.5% were classified by the ASAS SpA criteria (87.7% ASAS axSpA, 12.3% ASAS pSpA). Fulfilment of the Amor, ESSG and CASPAR criteria was present in 83.3%, 88.4% and 21.6% of patients, respectively. Of the patients with back pain (n = 3227), most were classified by all three of Amor, ESSG and ASAS axSpA criteria (71.4%). Patients fulfilling the imaging arm and the clinical arm of the ASAS axSpA criteria had similar presentations of SpA features. In patients without back pain, overlap between classification criteria sets was seen, although to a lesser extent. Most patients with a clinical diagnosis of axial SpA in the worldwide ASAS-COMOSPA study fulfil several classification criteria sets, and a substantial overlap between different criteria sets is seen, which suggests a high level of credibility of the criteria. Large inter-regional differences in the fulfilment of classification criteria were not found. Patients fulfilling the clinical arm were remarkably similar to patients fulfilling the imaging arm with respect to the presence of most SpA features.

  4. CIP1 polypeptides and their uses

    DOEpatents

    Foreman, Pamela [Los Altos, CA; Van Solingen, Pieter [Naaldwijk, NL; Goedegebuur, Frits [Vlaardingen, NL; Ward, Michael [San Francisco, CA

    2011-04-12

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  5. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hervey, IV, William Judson; Khalsa-Moyers, Gurusahai K; Lankford, Patricia K

    Protein enrichments of engineered, affinity-tagged (or bait ) fusion proteins with interaction partners are often laden with background, non-specific proteins, due to interactions that occur in vitro as an artifact of the technique. Furthermore, the in vivo expression of the bait protein may itself affect physiology or metabolism. In this study, intrinsic affinity purification challenges were investigated in a model protein complex, DNA-dependent RNA polymerase (RNAP), encompassing chromosome- and plasmid-encoding strategies for bait proteins in two different microbial species: Escherichia coli and Rhodopseudomonas palustris. Isotope ratio measurements of bait protein expression strains relative to native, wild-type strains were performed bymore » liquid chromatography tandem mass spectrometry (LC-MS-MS) to assess bait protein expression strategies in each species. Authentic interacting proteins of RNAP were successfully discerned from artifactual co-isolating proteins by the isotopic differentiation of interactions as random or targeted (I-DIRT) method (A. J. Tackett et al. J. Proteome Res. 2005, 4 (5), 1752-1756). To investigate broader effects of bait protein production in the bacteria, we compared proteomes from strains harboring a plasmid that encodes an affinity-tagged subunit (RpoA) of the RNAP complex with the corresponding wild-type strains using stable isotope metabolic labeling. The ratio of RpoA abundance in plasmid strains versus wild type was 0.8 for R. palustris and 1.7 for E. coli. While most other proteins showed no appreciable difference, proteins significantly increased in abundance in plasmid-encoded bait-expressing strains of both species included the plasmid encoded antibiotic resistance protein, GenR and proteins involved in amino acid biosynthesis. Together, these local, complex-specific and more global, whole proteome isotopic abundance ratio measurements provided a tool for evaluating both in vivo and in vitro effects of plasmid-encoding strategies for bait protein expression. This approach has the potential for enabling discovery of protein-protein interactions among the growing number of sequenced microbial species without the need for development of chromosomal insertion systems.« less

  6. Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy

    PubMed Central

    Cecconi, Massimiliano; Parodi, Maria I.; Formisano, Francesco; Spirito, Paolo; Autore, Camillo; Musumeci, Maria B.; Favale, Stefano; Forleo, Cinzia; Rapezzi, Claudio; Biagini, Elena; Davì, Sabrina; Canepa, Elisabetta; Pennese, Loredana; Castagnetta, Mauro; Degiorgio, Dario; Coviello, Domenico A.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is mainly associated with myosin, heavy chain 7 (MYH7) and myosin binding protein C, cardiac (MYBPC3) mutations. In order to better explain the clinical and genetic heterogeneity in HCM patients, in this study, we implemented a target-next generation sequencing (NGS) assay. An Ion AmpliSeq™ Custom Panel for the enrichment of 19 genes, of which 9 of these did not encode thick/intermediate and thin myofilament (TTm) proteins and, among them, 3 responsible of HCM phenocopy, was created. Ninety-two DNA samples were analyzed by the Ion Personal Genome Machine: 73 DNA samples (training set), previously genotyped in some of the genes by Sanger sequencing, were used to optimize the NGS strategy, whereas 19 DNA samples (discovery set) allowed the evaluation of NGS performance. In the training set, we identified 72 out of 73 expected mutations and 15 additional mutations: the molecular diagnosis was achieved in one patient with a previously wild-type status and the pre-excitation syndrome was explained in another. In the discovery set, we identified 20 mutations, 5 of which were in genes encoding non-TTm proteins, increasing the diagnostic yield by approximately 20%: a single mutation in genes encoding non-TTm proteins was identified in 2 out of 3 borderline HCM patients, whereas co-occuring mutations in genes encoding TTm and galactosidase alpha (GLA) altered proteins were characterized in a male with HCM and multiorgan dysfunction. Our combined targeted NGS-Sanger sequencing-based strategy allowed the molecular diagnosis of HCM with greater efficiency than using the conventional (Sanger) sequencing alone. Mutant alleles encoding non-TTm proteins may aid in the complete understanding of the genetic and phenotypic heterogeneity of HCM: co-occuring mutations of genes encoding TTm and non-TTm proteins could explain the wide variability of the HCM phenotype, whereas mutations in genes encoding only the non-TTm proteins are identifiable in patients with a milder HCM status. PMID:27600940

  7. Molecular cloning of low-temperature-inducible ribosomal proteins from soybean.

    PubMed

    Kim, Kee-Young; Park, Seong-Whan; Chung, Young-Soo; Chung, Chung-Han; Kim, Jung-In; Lee, Jai-Heon

    2004-05-01

    Three ribosomal protein genes induced by low-temperature treatment were isolated from soybean. GmRPS13 (742 bp) encodes a 17.1 kDa protein which has 95% identity with the 40S ribosomal protein S13 of Panax ginseng (AB043974). GmRPS6 (925 bp) encodes a 28.1 kDa protein which has 94% identity with the 40S ribosomal protein S6 of Asparagus officinalis (AJ277533). GmRPL37 (494 bp) encodes a 10.7 kDa protein which has 85% identity with the 60S ribosomal protein L37 of Arabidopsis thaliana (AF370216). The expression of these ribosomal protein genes started to increase 3 d after low-temperature treatment, whereas the cold-stress protein src1 was highly induced from the first day. Such late response of these ribosomal protein genes may be due to secondary signals during cold adaptation. The induction of ribosomal protein genes might enhance the translation process or help proper ribosome functioning under low-temperature conditions.

  8. Medical spa marketing.

    PubMed

    Sadick, Neil S; Dinkes, Adam; Oskin, Larry

    2008-07-01

    Medical spas are different. We are not just selling medical and dermatology services; we are offering clients viable new solutions to their skin care, body care, and hair care challenges. Traditional medical marketing becomes blurred today, as the expansion and acceptance of medical spas helps you to effectively compete with traditional skin care clinics, salons, and spas, while offering more therapeutic treatments from professionally licensed doctors, nurses, aestheticians, massage therapists, spa professionals, and medical practitioners. We recommend that you make the choice to successfully and competitively become a market-driven medical spa with an annual strategic plan, rather than an operationally driven business.

  9. [On the development of a system of medical weather forecast for the Caucasian Mineral Waters spa-and-resort complex].

    PubMed

    Povolotskaia, N P; Efimova, N V; Zherlitsina, L I; Kirilenko, A A; Kortunova, Z V; Golitsin, G S; Senik, I A; Rubinshteĭn, K G

    2010-01-01

    A system of medical weather forecast for the Caucasian Mineral Waters spa-and-resort complex has been modified and updated based on the results of long-term observations of weather conditions in the region of interest with special reference to the bioclimatic regime, atmospheric circulation, aerosol pollution of the near-ground air, ultraviolet radiation, heliomagnetic activity, and meteopathic effects. This system provides a basis for the timely emergency meteopreventive treatment of meteodependent patients and therefore can be instrumental in enhancing efficiency of spa-and-resort rehabilitative therapy.

  10. Authenticity assessment of banknotes using portable near infrared spectrometer and chemometrics.

    PubMed

    da Silva Oliveira, Vanessa; Honorato, Ricardo Saldanha; Honorato, Fernanda Araújo; Pereira, Claudete Fernandes

    2018-05-01

    Spectra recorded using a portable near infrared (NIR) spectrometer, Soft Independent Modeling of Class Analogy (SIMCA) and Linear Discriminant Analysis (LDA) associated to Successive Projections Algorithm (SPA) models were applied to identify counterfeit and authentic Brazilian Real (R$20, R$50 and R$100) banknotes, enabling a simple field analysis. NIR spectra (950-1650nm) were recorded from seven different areas of the banknotes (two with fluorescent ink, one over watermark, three with intaglio printing process and one over the serial numbers with typography printing). SIMCA and SPA-LDA models were built using 1st derivative preprocessed spectral data from one of the intaglio areas. For the SIMCA models, all authentic (300) banknotes were correctly classified and the counterfeits (227) were not classified. For the two classes SPA-LDA models (authentic and counterfeit currencies), all the test samples were correctly classified into their respective class. The number of selected variables by SPA varied from two to nineteen for R$20, R$50 and R$100 currencies. These results show that the use of the portable near-infrared with SIMCA or SPA-LDA models can be a completely effective, fast, and non-destructive way to identify authenticity of banknotes as well as permitting field analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Comparative analysis of two different models of swimming applied to pregnant rats born small for pregnant age.

    PubMed

    Corvino, Silvana B; Damasceno, Débora C; Sinzato, Yuri K; Netto, Aline O; Macedo, Nathália C D; Zambrano, Elena; Volpato, Gustavo T

    2017-01-01

    The aim of this study was to compare two models of swimming applied to pregnant rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult female rats to develop an inadequate intrauterine environment, leading to birth of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to different swimming programs. The exercise program 1 (Ex1) consisted of swimming for 15 minutes, followed by 15 minutes of rest and another 15 minutes of swimming, 3 days a week before and during pregnancy. Another program (Ex2) was applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The pregnant rats presented no interference on body weight and glycemia. The rats submitted to Ex2 model showed decreased insulin and blood glucose levels by oral glucose tolerance test, and reduction in area under curve values. The offspring from dams submitted to both exercise protocols presented an increased rate of newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of 60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth-restricted females. However, this protocol employed at pregnancy leads to intrauterine growth restriction.

  12. Staphylococcus aureus innate immune evasion is lineage-specific: a bioinfomatics study.

    PubMed

    McCarthy, Alex J; Lindsay, Jodi A

    2013-10-01

    Staphylococcus aureus is a major human pathogen, and is targeted by the host innate immune system. In response, S. aureus genomes encode dozens of secreted proteins that inhibit complement, chemotaxis and neutrophil activation resulting in successful evasion of innate immune responses. These proteins include immune evasion cluster proteins (IEC; Chp, Sak, Scn), staphylococcal superantigen-like proteins (SSLs), phenol soluble modulins (PSMs) and several leukocidins. Biochemical studies have indicated that genetic variants of these proteins can have unique functions. To ascertain the scale of genetic variation in secreted immune evasion proteins, whole genome sequences of 88 S. aureus isolates, representing 25 clonal complex (CC) lineages, in the public domain were analysed across 43 genes encoding 38 secreted innate immune evasion protein complexes. Twenty-three genes were variable, with between 2 and 15 variants, and the variants had lineage-specific distributions. They include genes encoding Eap, Ecb, Efb, Flipr/Flipr-like, Hla, Hld, Hlg, Sbi, Scin-B/C and 13 SSLs. Most of these protein complexes inhibit complement, chemotaxis and neutrophil activation suggesting that isolates from each S. aureus lineage respond to the innate immune system differently. In contrast, protein complexes that lyse neutrophils (LukSF-PVL, LukMF, LukED and PSMs) were highly conserved, but can be carried on mobile genetic elements (MGEs). MGEs also encode proteins with narrow host-specificities arguing that their acquisition has important roles in host/environmental adaptation. In conclusion, this data suggests that each lineage of S. aureus evades host immune responses differently, and that isolates can adapt to new host environments by acquiring MGEs and the immune evasion protein complexes that they encode. Cocktail therapeutics that targets multiple variant proteins may be the most appropriate strategy for controlling S. aureus infections. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Transmission over UWB channels with OFDM system using LDPC coding

    NASA Astrophysics Data System (ADS)

    Dziwoki, Grzegorz; Kucharczyk, Marcin; Sulek, Wojciech

    2009-06-01

    Hostile wireless environment requires use of sophisticated signal processing methods. The paper concerns on Ultra Wideband (UWB) transmission over Personal Area Networks (PAN) including MB-OFDM specification of physical layer. In presented work the transmission system with OFDM modulation was connected with LDPC encoder/decoder. Additionally the frame and bit error rate (FER and BER) of the system was decreased using results from the LDPC decoder in a kind of turbo equalization algorithm for better channel estimation. Computational block using evolutionary strategy, from genetic algorithms family, was also used in presented system. It was placed after SPA (Sum-Product Algorithm) decoder and is conditionally turned on in the decoding process. The result is increased effectiveness of the whole system, especially lower FER. The system was tested with two types of LDPC codes, depending on type of parity check matrices: randomly generated and constructed deterministically, optimized for practical decoder architecture implemented in the FPGA device.

  14. Recombinant constructs of Borrelia burgdorferi

    DOEpatents

    Dattwyler, Raymond J.; Gomes-Solecki, Maria J. C.; Luft, Benjamin J.; Dunn, John J.

    2007-02-20

    Novel chimeric nucleic acids, encoding chimeric Borrelia proteins comprising OspC or an antigenic fragment thereof and OspA or an antigenic fragment thereof, are disclosed. Chimeric proteins encoded by the nucleic acid sequences are also disclosed. The chimeric proteins are useful as vaccine immunogens against Lyme borreliosis, as well as for immunodiagnostic reagents.

  15. Recombinant HT{sub m4} gene, protein and assays

    DOEpatents

    Lim, B.; Adra, C.N.; Lelias, J.M.

    1996-09-03

    The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

  16. Recombinant HT.sub.m4 gene, protein and assays

    DOEpatents

    Lim, Bing; Adra, Chaker N.; Lelias, Jean-Michel

    1996-01-01

    The invention relates to a recombinant DNA molecule which encodes a HT.sub.m4 protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT.sub.m4 protein and a recombinant HT.sub.m4 protein. The invention also relates to a method for detecting the presence of a hereditary atopy.

  17. A member of a new plant gene family encoding a meprin and TRAF homology (MATH) domain-containing protein is involved in restriction of long distance movement of plant viruses

    PubMed Central

    Cosson, Patrick; Sofer, Luc; Schurdi-Levraud, Valérie

    2010-01-01

    Restriction of long distance movement of several potyviruses in Arabidopsis thaliana is controlled by at least three dominant restricted TEV movement (RTM) genes, named RTM1, RTM2 and RTM3 and acts as a non-conventional resistance. RTM1 encodes a protein belonging to the jacalin family and RTM2 encodes a protein which has similarities to small heat shock proteins. The recent cloning of RTM3 which encodes a protein belonging to an unknown protein family of 29 members that has a meprin and TRAF homology (MATH) domain in its N-terminal region and a coiled-coil (CC) domain at its C-terminal end is an important breakthrough for a better understanding of this resistance process. Not only the third gene involved in this resistance has been identified and has allowed revealing a new gene family in plant but the discovery that the RTM3 protein interacts directly with RTM1 strongly suggests that the RTM proteins form a multimeric complex. However, these data also highlight striking similarities of the RTM resistance with the well known R-gene mediated resistance. PMID:20930558

  18. Nosocomial outbreak of staphyloccocal scalded skin syndrome in neonates in England, December 2012 to March 2013.

    PubMed

    Paranthaman, K; Bentley, A; Milne, L M; Kearns, A; Loader, S; Thomas, A; Thompson, F; Logan, M; Newitt, S; Puleston, R

    2014-08-21

    Staphylococcal scalded skin syndrome (SSSS) is a blistering skin condition caused by exfoliative toxin-producing strains of Staphylococcus aureus. Outbreaks of SSSS in maternity settings are rarely reported. We describe an outbreak of SSSS that occurred among neonates born at a maternity unit in England during December 2012 to March 2013. Detailed epidemiological and microbiological investigations were undertaken. Eight neonates were found to be infected with the outbreak strain of S. aureus, of spa type t346, representing a single pulsotype. All eight isolates contained genes encoding exfoliative toxin A (eta) and six of them contained genes encoding toxin B (etb). Nasal swabs taken during targeted staff screening yielded a staphylococcal carriage rate of 21% (17/80), but none contained the outbreak strain. Mass screening involving multi-site swabbing and pooled, enrichment culture identified a healthcare worker (HCW) with the outbreak strain. This HCW was known to have a chronic skin condition and their initial nasal screen was negative. The outbreak ended when they were excluded from work. This outbreak highlights the need for implementing robust swabbing and culture methodswhen conventional techniques are unsuccessful in identifying staff carrier(s). This study adds to the growing body of evidence on the role of HCWs in nosocomial transmission of S. aureus.

  19. Four rice seed cDNA clones belonging to the alpha-amylase/trypsin inhibitor gene family encode potential rice allergens.

    PubMed

    Alvarez, A M; Fukuhara, E; Nakase, M; Adachi, T; Aoki, N; Nakamura, R; Matsuda, T

    1995-07-01

    Four rice seed proteins encoded by cDNAs belonging to the alpha-amylase/trypsin inhibitor gene family were overexpressed as TrpE-fusion proteins in E. coli. The expressed rice proteins were detected by SDS-PAGE as major proteins in bacterial cell lysates. Western blot analyses showed that all the recombinant proteins were immunologically reactive to rabbit polyclonal antibodies and to a mouse monoclonal antibody (25B9) specific for a previously isolated rice allergen of 16 kDa. Some truncated proteins from deletion mutants of the cDNAs retained their reactivity to the specific antibodies. These results suggest that the cDNAs encode potential rice allergens and that some epitopes of the recombinant proteins are still immunoreactive when they are expressed as their fragments.

  20. RNA-guided transcriptional regulation

    DOEpatents

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  1. Molecular cloning and nucleotide sequences of the genes for two essential proteins constituting a novel enzyme system for heptaprenyl diphosphate synthesis.

    PubMed

    Koike-Takeshita, A; Koyama, T; Obata, S; Ogura, K

    1995-08-04

    The genes encoding two dissociable components essential for Bacillus stearothermophilus heptaprenyl diphosphate synthase (all-trans-hexparenyl-diphosphate:isopentenyl-diphosphate hexaprenyl-trans-transferase, EC 2.5.1.30) were cloned, and their nucleotide sequences were determined. Sequence analyses revealed the presence of three open reading frames within 2,350 base pairs, designated as ORF-1, ORF-2, and ORF-3 in order of nucleotide sequence, which encode proteins of 220, 234, and 323 amino acids, respectively. Deletion experiments have shown that expression of the enzymatic activity requires the presence of ORF-1 and ORF-3, but ORF-2 is not essential. As a result, this enzyme was proved genetically to consist of two different protein compounds with molecular masses of 25 kDa (Component I) and 36 kDa (Component II), encoded by two of the three tandem genes. The protein encoded by ORF-1 has no similarity to any protein so far registered. However, the protein encoded by ORF-3 shows a 32% similarity to the farnesyl diphosphate synthase of the same bacterium and has seven highly conserved regions that have been shown typical in prenyltransferases (Koyama, T., Obata, S., Osabe, M., Takeshita, A., Yokoyama, K., Uchida, M., Nishino, T., and Ogura, K. (1993) J. Biochem. (Tokyo) 113, 355-363).

  2. Amino acid sequence of the smaller basic protein from rat brain myelin

    PubMed Central

    Dunkley, Peter R.; Carnegie, Patrick R.

    1974-01-01

    1. The complete amino acid sequence of the smaller basic protein from rat brain myelin was determined. This protein differs from myelin basic proteins of other species in having a deletion of a polypeptide of 40 amino acid residues from the centre of the molecule. 2. A detailed comparison is made of the constant and variable regions in a group of myelin basic proteins from six species. 3. An arginine residue in the rat protein was found to be partially methylated. The ratio of methylated to unmethylated arginine at this position differed from that found for the human basic protein. 4. Three tryptic peptides were isolated in more than one form. The differences between the two forms of each peptide are discussed in relation to the electrophoretic heterogeneity of myelin basic proteins, which is known to occur at alkaline pH values. 5. Detailed evidence for the amino acid sequence of the protein has been deposited as Supplementary Publication SUP 50029 at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1973) 131, 5. PMID:4141893

  3. 78 FR 65161 - Airworthiness Directives; Agusta S.p.A. (Type Certificate Currently Held by AgustaWestland S.p.A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... engine speeds during steady-state operations. These actions are intended to alert pilots to avoid certain... alert pilots to avoid certain engine speeds during steady-state operations, prevent failure of the third...

  4. Using the South Pole-Aitken (SPA) Impact Melt Composition to Infer Upper Mantle Mineralogy and Timing of Potential Mantle Overturn

    NASA Astrophysics Data System (ADS)

    Kring, D. A.; Needham, D. H.

    2018-05-01

    Observed melt composition within the SPA basin are consistent with an impact prior to mantle overturn, when the upper mantle contained clinopyroxene rather than olivine. Potentially, the impact triggered mantle overturn.

  5. Meta-omic signatures of microbial metal and nitrogen cycling in marine oxygen minimum zones

    PubMed Central

    Glass, Jennifer B.; Kretz, Cecilia B.; Ganesh, Sangita; Ranjan, Piyush; Seston, Sherry L.; Buck, Kristen N.; Landing, William M.; Morton, Peter L.; Moffett, James W.; Giovannoni, Stephen J.; Vergin, Kevin L.; Stewart, Frank J.

    2015-01-01

    Iron (Fe) and copper (Cu) are essential cofactors for microbial metalloenzymes, but little is known about the metalloenyzme inventory of anaerobic marine microbial communities despite their importance to the nitrogen cycle. We compared dissolved O2, NO3−, NO2−, Fe and Cu concentrations with nucleic acid sequences encoding Fe and Cu-binding proteins in 21 metagenomes and 9 metatranscriptomes from Eastern Tropical North and South Pacific oxygen minimum zones and 7 metagenomes from the Bermuda Atlantic Time-series Station. Dissolved Fe concentrations increased sharply at upper oxic-anoxic transition zones, with the highest Fe:Cu molar ratio (1.8) occurring at the anoxic core of the Eastern Tropical North Pacific oxygen minimum zone and matching the predicted maximum ratio based on data from diverse ocean sites. The relative abundance of genes encoding Fe-binding proteins was negatively correlated with O2, driven by significant increases in genes encoding Fe-proteins involved in dissimilatory nitrogen metabolisms under anoxia. Transcripts encoding cytochrome c oxidase, the Fe- and Cu-containing terminal reductase in aerobic respiration, were positively correlated with O2 content. A comparison of the taxonomy of genes encoding Fe- and Cu-binding vs. bulk proteins in OMZs revealed that Planctomycetes represented a higher percentage of Fe genes while Thaumarchaeota represented a higher percentage of Cu genes, particularly at oxyclines. These results are broadly consistent with higher relative abundance of genes encoding Fe-proteins in the genome of a marine planctomycete vs. higher relative abundance of genes encoding Cu-proteins in the genome of a marine thaumarchaeote. These findings highlight the importance of metalloenzymes for microbial processes in oxygen minimum zones and suggest preferential Cu use in oxic habitats with Cu > Fe vs. preferential Fe use in anoxic niches with Fe > Cu. PMID:26441925

  6. Meta-omic signatures of microbial metal and nitrogen cycling in marine oxygen minimum zones.

    PubMed

    Glass, Jennifer B; Kretz, Cecilia B; Ganesh, Sangita; Ranjan, Piyush; Seston, Sherry L; Buck, Kristen N; Landing, William M; Morton, Peter L; Moffett, James W; Giovannoni, Stephen J; Vergin, Kevin L; Stewart, Frank J

    2015-01-01

    Iron (Fe) and copper (Cu) are essential cofactors for microbial metalloenzymes, but little is known about the metalloenyzme inventory of anaerobic marine microbial communities despite their importance to the nitrogen cycle. We compared dissolved O2, NO[Formula: see text], NO[Formula: see text], Fe and Cu concentrations with nucleic acid sequences encoding Fe and Cu-binding proteins in 21 metagenomes and 9 metatranscriptomes from Eastern Tropical North and South Pacific oxygen minimum zones and 7 metagenomes from the Bermuda Atlantic Time-series Station. Dissolved Fe concentrations increased sharply at upper oxic-anoxic transition zones, with the highest Fe:Cu molar ratio (1.8) occurring at the anoxic core of the Eastern Tropical North Pacific oxygen minimum zone and matching the predicted maximum ratio based on data from diverse ocean sites. The relative abundance of genes encoding Fe-binding proteins was negatively correlated with O2, driven by significant increases in genes encoding Fe-proteins involved in dissimilatory nitrogen metabolisms under anoxia. Transcripts encoding cytochrome c oxidase, the Fe- and Cu-containing terminal reductase in aerobic respiration, were positively correlated with O2 content. A comparison of the taxonomy of genes encoding Fe- and Cu-binding vs. bulk proteins in OMZs revealed that Planctomycetes represented a higher percentage of Fe genes while Thaumarchaeota represented a higher percentage of Cu genes, particularly at oxyclines. These results are broadly consistent with higher relative abundance of genes encoding Fe-proteins in the genome of a marine planctomycete vs. higher relative abundance of genes encoding Cu-proteins in the genome of a marine thaumarchaeote. These findings highlight the importance of metalloenzymes for microbial processes in oxygen minimum zones and suggest preferential Cu use in oxic habitats with Cu > Fe vs. preferential Fe use in anoxic niches with Fe > Cu.

  7. Detection of hepatitis B virus X product using an open reading frame Escherichia coli expression vector.

    PubMed Central

    Elfassi, E; Haseltine, W A; Dienstag, J L

    1986-01-01

    The genome of the hepatitis B virus (HBV) contains a sequence, designated X, capable of encoding a protein of 154 amino acids. To determine whether the putative protein synthesized from this region is antigenic, we examined the sera of HBV-infected patients for the ability to react with a hybrid protein that contained 133 amino acids encoded by the X region and portions of the bacterial ompF and beta-galactosidase genes. Some HBV-positive sera tested contained antibodies that specifically recognized the hybrid protein. All sera were from patients diagnosed as suffering from chronic active hepatitis. We conclude that the X region of HBV encodes a protein and that this protein is antigenic in some patients. Images PMID:3515347

  8. Cytoprophet: a Cytoscape plug-in for protein and domain interaction networks inference.

    PubMed

    Morcos, Faruck; Lamanna, Charles; Sikora, Marcin; Izaguirre, Jesús

    2008-10-01

    Cytoprophet is a software tool that allows prediction and visualization of protein and domain interaction networks. It is implemented as a plug-in of Cytoscape, an open source software framework for analysis and visualization of molecular networks. Cytoprophet implements three algorithms that predict new potential physical interactions using the domain composition of proteins and experimental assays. The algorithms for protein and domain interaction inference include maximum likelihood estimation (MLE) using expectation maximization (EM); the set cover approach maximum specificity set cover (MSSC) and the sum-product algorithm (SPA). After accepting an input set of proteins with Uniprot ID/Accession numbers and a selected prediction algorithm, Cytoprophet draws a network of potential interactions with probability scores and GO distances as edge attributes. A network of domain interactions between the domains of the initial protein list can also be generated. Cytoprophet was designed to take advantage of the visual capabilities of Cytoscape and be simple to use. An example of inference in a signaling network of myxobacterium Myxococcus xanthus is presented and available at Cytoprophet's website. http://cytoprophet.cse.nd.edu.

  9. [Ph-Sensor Properties of a Fluorescent Protein from Dendronephthya sp].

    PubMed

    Pakhomov, A A; Chertkova, R V; Martynov, V I

    2015-01-01

    Genetically encoded biosensors based on fluorescent proteins are now widely applicable for monitoring pH changes in live cells. Here, we have shown that a fluorescent protein from Dendronephthya sp. (DendFP) exhibits a pronounced pH-sensitivity. Unlike most of known genetically encoded pH-sensors, fluorescence of the protein is not quenched upon medium acidification, but is shifting from the red to green spectral range. Therefore, quantitative measurements of intracellular pH are feasible by ratiometric comparison of emission intensities in the red and green spectral ranges, which makes DendFP advantageous compared with other genetically encoded pH-sensors.

  10. Molecular cloning and characterization of alpha - galactosidase gene from Glaciozyma antarctica

    NASA Astrophysics Data System (ADS)

    Moheer, Reyad Qaed Al; Bakar, Farah Diba Abu; Murad, Abdul Munir Abdul

    2015-09-01

    Psychrophilic enzymes are proteins produced by psychrophilic organisms which recently are the limelight for industrial applications. A gene encoding α-galactosidase from a psychrophilic yeast, Glaciozyma antarctica PI12 which belongs to glycoside hydrolase family 27, was isolated and analyzed using several bioinformatic tools. The cDNA of the gene with the size of 1,404-bp encodes a protein with 467 amino acid residues. Predicted molecular weight of protein was 48.59 kDa and hence we name the gene encoding α-galactosidase as GAL48. We found that the predicted protein sequences possessed signal peptide sequence and are highly conserved among other fungal α-galactosidase.

  11. Improving the quality of colonoscopy bowel preparation using a smart phone application: a randomized trial.

    PubMed

    Lorenzo-Zúñiga, Vicente; Moreno de Vega, Vicente; Marín, Ingrid; Barberá, Marta; Boix, Jaume

    2015-07-01

    Getting ready for a colonoscopy is difficult and involves many steps. Information given to patients is very important for adherence to treatment. We created a novel smart phone application (SPA) aimed to increase bowel preparation quality and patient satisfaction. We carried out a prospective, endoscopist-blinded, randomized, controlled trial. We enrolled 260 outpatient (58% female, age range 21-75 years) owners of a smartphone. Patients were allocated to two different protocols: instructions provided by SPA (SPA group; n = 108) or written instructions with visual aids (control group; n = 152). All procedures were carried out in the afternoon and patients received the same purgative regimen (2 L polyethylene glycol (PEG) solution plus ascorbic acid), in a full-dose same-day regimen. The study was designed to detect an improvement in quality of bowel preparation using the Harefield Cleansing Scale (HCS) scale. Effect of protocol on patient satisfaction was assessed with a specific questionnaire at the time of colonoscopy. Proportion of patients who obtained successful bowel preparation for colonoscopy (HCS A or B) was significantly higher in the SPA group than in the control group (100% vs 96.1%, respectively; P = 0.037). Mean global HCS scores were similar in both groups. Patient-reported tolerability and overall experience with the prescribed bowel preparation were significantly higher for the SPA group than for the control group. Successful cleansing and patient acceptability with the use of SPA were superior to written instructions in outpatients submitted for colonoscopy using 2 L PEG solution plus ascorbic acid. © 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

  12. Is being in paid work beyond state pension age beneficial for health? Evidence from England using a life-course approach.

    PubMed

    Di Gessa, Giorgio; Corna, Laurie M; Platts, Loretta G; Worts, Diana; McDonough, Peggy; Sacker, Amanda; Price, Debora; Glaser, Karen

    2017-05-01

    Given the current policy emphasis in many Western societies on extending working lives, we investigated the health effects of being in paid work beyond state pension age (SPA). Until now, work has largely focused on the health of those who exit the labour force early. Our data come from waves 2-4 of the English Longitudinal Study of Ageing, including the life history interview at wave 3. Using logistic and linear regression models, we assessed the longitudinal associations between being in paid work beyond SPA and 3 measures of health (depression, a latent measure of somatic health and sleep disturbance) among men aged 65-74 and women aged 60-69. Our analyses controlled for baseline health and socioeconomic characteristics, as well as for work histories and health in adulthood and childhood. Approximately a quarter of women and 15% of men were in paid work beyond SPA. Descriptive bivariate analyses suggested that men and women in paid work were more likely to report better health at follow-up. However, once baseline socioeconomic characteristics as well as adulthood and baseline health and labour market histories were accounted for, the health benefits of working beyond SPA were no longer significant. Potential health benefits of working beyond SPA need to be considered in the light of the fact that those who report good health and are more socioeconomically advantaged are more likely to be working beyond SPA to begin with. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Assessing the quality of study reports on spa therapy based on randomized controlled trials by the spa therapy checklist (SPAC).

    PubMed

    Kamioka, Hiroharu; Tsutani, Kiichiro; Maeda, Masaharu; Hayasaka, Shinya; Okuizum, Hiroyasu; Goto, Yasuaki; Okada, Shinpei; Kitayuguchi, Jun; Abe, Takafumi

    2014-11-01

    The purpose of this study was to assess the quality of study reports on spa therapy based on randomized controlled trials by the spa therapy and balneotherapy checklist (SPAC), and to show the relationship between SPAC score and the characteristics of publication. We searched the following databases from 1990 up to September 30, 2013: MEDLINE via PubMed, CINAHL, Web of Science, Ichushi Web, Global Health Library, the Western Pacific Region Index Medicus, PsycINFO, and the Cochrane Database of Systematic Reviews. We used the SPAC to assess the quality of reports on spa therapy and balneotherapy trials (SPAC) that was developed using the Delphi consensus method. Fifty-one studies met all inclusion criteria. Forty studies (78%) were about "Diseases of the musculoskeletal system and connective)". The total SPAC score (full-mark; 19 pts) was 10.8 ± 2.3 pts (mean ± SD). The items for which a description was lacking (very poor; <50%) in many studies were as follows: "locations of spa facility where the data were collected"; "pH"; "scale of bathtub"; "presence of other facility and exposure than bathing (sauna, steam bath, etc.)"; "qualification and experience of care provider"; "Instructions about daily life" and "adherence". We clarified that there was no relationship between the publish period, languages, and the impact factor (IF) for the SPAC score. In order to prevent flawed description, SPAC could provide indispensable information for researchers who are going to design a research protocol according to each disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Educational needs in patients with spondyloarthritis in Sweden - a mixed-methods study.

    PubMed

    Haglund, Emma; Bremander, Ann; Bergman, Stefan; Larsson, Ingrid

    2017-08-02

    There is a demand for a flexible and individually tailored patient education to meet patients' specific needs and priorities, but this area has seldom been studied in patients with spondyloarthritis (SpA), a family of inflammatory rheumatic diseases. The aim of the present study was to identify needs and priorities in patient education in patients with SpA. A second aim was to investigate patients' experiences and preferences of receiving patient education. Data collection included a questionnaire survey with the Educational Needs Assessment Tool (ENAT) and interviews, using a mixed-methods design. Patients were identified through a specialist clinic register. Descriptive data are presented as mean with standard deviation, or frequencies. Chi-square test and independent-samples t-test were used for group comparisons. A manifest qualitative conventional content analysis was conducted to explore patients' experiences and needs in patient education, based on two focus groups (n = 6) and five individual interviews. Almost half (43%) of the 183 SpA patients had educational needs, particularly regarding aspects of self-help, feelings, and the disease process. More educational needs were reported by women and in patients with higher disease activity, while duration of disease did not affect the needs. The qualitative analysis highlighted the importance of obtaining a guiding, reliable, and easily available patient education for management of SpA. Individual contacts with healthcare professionals were of importance, but newer media were also requested. There are considerable educational needs in patients with SpA, and education concerning self-help, feelings, and the diseases process were raised as important issues. Healthcare professionals need to consider the importance of presenting varied formats of education based on the experiences and preferences of patients with SpA.

  15. Counting Costs under Severe Financial Constraints: A Cost-of-Illness Analysis of Spondyloarthropathies in a Tertiary Hospital in Greece.

    PubMed

    Tsifetaki, Niki; Migkos, Michail P; Papagoras, Charalampos; Voulgari, Paraskevi V; Athanasakis, Kostas; Drosos, Alexandros A

    2015-06-01

    To investigate the total annual direct cost of patients with spondyloarthritis (SpA) in Greece. Retrospective study with 156 patients diagnosed and followed up in the rheumatology clinic of the University Hospital of Ioannina. Sixty-four had ankylosing spondylitis (AS) and 92 had psoriatic arthritis (PsA). Health resource use for each patient was elicited through a retrospective chart review that documented the use of monitoring visits, medications, laboratory/diagnostic tests, and inpatient stays for the previous year from the date that the review took place. Costs were calculated from a third-party payer perspective and are reported in 2014 euros. The mean ± SD annual direct cost for the patients with SpA reached €8680 ± 6627. For the patients with PsA and AS, the cost was estimated to be €8097 ± 6802 and €9531 ± 6322, respectively. The major cost was medication, which represented 88.9%, 88.2%, and 89.3% of the mean total direct cost for SpA, AS, and PsA, respectively. The annual amount of the scheduled tests for all patients corresponded to 7.5%, and for those performed on an emergency basis, 1.1%. Further, the cost for scheduled and emergency hospitalization, as well as the cost of scheduled visits to an outpatient clinic, corresponded to 2.5% of the mean total annual direct cost for the patients with SpA. SpA carries substantial financial cost, especially in the era of new treatment options. Adequate access and treatment for patients with SpA remains a necessity, even in times of fiscal constraint. Thus, the recommendations of the international scientific organizations should be considered when administering high-cost drugs such as biological treatments.

  16. SPA (Solus per Aqua) service industry: An entrepeneurship opportunity to beauty education department

    NASA Astrophysics Data System (ADS)

    Marwiyah, Apriyani, Delta

    2018-03-01

    Beauty industry grows vastly in the scope of regional, national, or international. Beauty industry includes Spa service. It becomes one of the choices where the urban citizen can use it to release their stress and relax their mind. This business grows as the development of technology. Spa industry should be able to provide the best service for physical and mental therapy, it will make the user of the service can be freed from their business and stress in the respective time to be healthies, more beautiful, and able to do their activity maximally. Spa treatment consists of hair creambath, facial treatment, manicure-pedicure, scrub treatment, foot spa, aromatherapy, and body treatment with traditional cosmetics which are easy to get in Indonesia. Beauty education is one of the programs in Home Economics Department of Engineering Faculty of UNNES. This program was established to produce graduates in beauty fields as Vocational High School teachers with bachelor (S1) qualification. The graduates suppose to be excellent, professional, skillful, and care to the environment, culture, and social condition around them. It prepares them as teachers of beauty (in formal and non- formal education). Besides, it also prepared them to have professional competence in production fields of beauty service with adaptive, creative, and innovative which can be entrepreneurs who are able to create job vacancies for others. Beauty education used KKNI- based curriculum, which is oriented to Industry and Working Fields with UNNES' Conservation basis. It provided the students a chance to practive their knowledge in working internship program, study field trip, and teaching practice program. The industry of Spa service provides a big chance to become an entrepreneur, create a working field, and help the government reduce unemployment number, whether from beauty education graduates or from vocational high school students

  17. Is HLA-B27 increased in patients diagnosed with undifferentiated arthritis? Results from the Leiden early arthritis cohort.

    PubMed

    van Gaalen, Floris; van den Berg, Rosaline; Verhoog, Inge; Schonkeren, Joris; van der Helm-van Mil, Annette; Huizinga, Tom; van der Heijde, Désirée M

    2014-10-01

    Undifferentiated arthritis (UA) is a common form of arthritis. According to the Assessment of Spondyloarthritis international Society (ASAS) criteria for peripheral spondyloarthritis (pSpA), HLA-B27 can be used to help classify patients with pSpA. We tested whether HLA-B27 is increased in patients diagnosed with UA. Prevalence of HLA-B27 was compared between healthy controls and patients with UA. SpA features were compared between HLA-B27-positive and -negative UA, and SpA. We found 10.1% of UA (38/375) versus 7.2% (403/5584) of controls were HLA-B27-positive (OR 1.5, 95% CI 1.0-2.1; p = 0.037). HLA-B27-positive patients with UA had more SpA features than HLA-B27-negative patients (mean 1.6, SD 1.0, and 0.9 SD 0.6; p < 0.001), but patients with SpA had significantly more SpA features (mean 4.5, SD 1.5; p < 0.001). Family history and preceding infection were features more common in HLA-B27-positive than in HLA-B27-negative UA (15.8% vs 1.3%, p = 0.04 and 15.8% vs 2.6%, p = 0.04). After HLA-B27 testing, 21 additional patients (5.6%) with UA could potentially have been classified with pSpA according to the ASAS criteria. HLA-B27 is more common in patients with UA than in controls. However, the yield of HLA-B27 testing in UA is low. Our results suggest that HLA-B27 testing should be reserved for patients with additional SpA features.

  18. Centre-related variability in hospital admissions of patients with spondyloarthritis.

    PubMed

    Andrés, Mariano; Sivera, Francisca; Pérez-Vicente, Sabina; Carmona, Loreto; Vela, Paloma

    2016-09-01

    The aim of this study was to explore the variability in hospital admissions of patients with spondyloarthritis (SpA) in Spain, and the centre factors that may influence that variability. Descriptive cross-sectional study, part of the emAR II study, performed in Spain (2009-2010). Health records of patients with a diagnosis of SpA and at least one visit to the rheumatology units within the previous 2 years were reviewed. Variables related to hospital admissions, to the SpA, and to the patient and centre were collected. A multilevel logistic regression analysis of random intercept with non-random slopes was performed to assess variability between centres. From 45 centres, 1168 patients' health records were reviewed. Main SpA forms were ankylosing spondylitis (55.2 %) and psoriatic arthritis (22.2 %). A total of 248 admissions were registered for 196 patients (19.2 %, n = 1020). An adjusted variability of 17.6 % in hospitalizations between centres was noted. The following hospital-related factors showed a significant association with admissions: the total number of admissions of the centre, the existence of electronic admission, and the availability of ultrasound in rheumatology. However, these factors only explained 42.9 % of the inter-centre variability. The risk of a patient with SpA of being admitted could double (median OR 2.09), depending on the hospital where the patient was being managed. Hospital admissions of patients with SpA varied between hospitals due to centre characteristics. Further studies are needed to ascertain which specific factors may be causing the variation, as studied variables explained less than half of the variability.

  19. Subchronic perinatal asphyxia increased anxiety-and depression-like behaviors in the rat offspring.

    PubMed

    Sedláčková, Natália; Krajčiová, Martina; Koprdová, Romana; Ujházy, Eduard; Brucknerová, Ingrid; Mach, Mojmír

    2014-01-01

    Perinatal asphyxia is one of the major cause of mortality in newborns and cause of neurological disorders in adulthood. Brain damage is of the most concern due to high sensitivity of nervous system to suboptimal intrauterine oxygen condition. The aim of this study was to assess effect of subchronic prenatal asphyxia (SPA) during sensitive stages of brain maturation on behavioral changes in rats, as a method of prenatal programming of anxiety and depression-like behavior. Pregnant Wistar/DV females were exposed to environment containing lower oxygen (10.5% O2) during sensitive stages of brain maturation (day 19-20 of gestation) for 4h a day and anxiety- and depression-like behaviors in offspring were assessed using battery of behavioral tests--Open field (OF), Elevated plus maze (EPM), Light/dark test (L/D), Forced swim test (FST), and Stress induced hyperthermia (SIH). OF did not induced changes of locomotor and exploration activities. The anxiety-like behavior was induced by SPA in EPM and L/D. These results were significant in males SPA group only. The higher response to the stress stimulus in SIH was recorded in both males and females SPA group. The intensity of climbing on the walls of cylinder in FST in males SPA group was significantly decreased indicating depression-like behavior in adulthood. In conclusion, we found out that perinatal asphyxia on 19th and 20th day of gestation caused anxiety- and depression-like behaviors in the rat offspring. Our model of SPA has proved to be useful to study the conditions of asphyxia during pregnancy, and could be suitable model for studies uncovering the mechanisms of prenatal programming of psychiatric diseases.

  20. Validity and reliability of the Short Form 36 Health Surveys (SF-36) among patients with spondyloarthritis in Singapore.

    PubMed

    Kwan, Yu Heng; Fong, Warren Weng Seng; Lui, Nai Lee; Yong, Si Ting; Cheung, Yin Bun; Malhotra, Rahul; Østbye, Truls; Thumboo, Julian

    2016-12-01

    The Short Form 36 Health Survey (SF-36) is a popular health-related quality of life (HrQoL) tool. However, few studies have assessed its psychometric properties in patients with spondyloarthritis (SpA). We therefore aimed to assess the reliability and validity of the SF-36 in patients with SpA in Singapore. Cross-sectional data from a registry of 196 SpA patients recruited from a dedicated tertiary referral clinic in Singapore from 2011 to 2014 was used. Analyses were guided by the COnsensus-based Standards for the selection of health Measurement INstruments framework. Internal consistency reliability was assessed using Cronbach's alpha. Construct validity was assessed through 33 a priori hypotheses by correlations of the eight subscales and two summary scores of SF-36 with other health outcomes. Known-group construct validity was assessed by comparison of the means of the subscales and summary scores of the SF-36 of SpA patients and the general population of Singapore using student's t tests. Among 196 patients (155 males (79.0 %), median (range) age: 36 (17-70), 166 Chinese (84.6 %)), SF-36 scales showed high internal consistency ranging from 0.88 to 0.90. Convergent construct validity was supported as shown by fulfillment of all hypotheses. Divergent construct validity was supported, as SF-36 MCS was not associated with PGA, pain and HAQ. Known-group construct validity showed SpA patients had lower scores of 3.8-12.5 when compared to the general population at p < 0.001. This study supports the SF-36 as a valid and reliable measure of HrQoL for use in patients with SpA at a single time point.

  1. Comparison of medicine availability measurements at health facilities: evidence from Service Provision Assessment surveys in five sub-Saharan African countries.

    PubMed

    Choi, Yoonjoung; Ametepi, Paul

    2013-07-09

    With growing emphasis on health systems strengthening in global health, various health facility assessment methods have been used increasingly to measure medicine and commodity availability. However, few studies have systematically compared estimates of availability based on different definitions. The objective of this study was to compare estimates of medicine availability based on different definitions. A secondary data analysis was conducted using data from the Service Provision Assessment (SPA)--a nationally representative sample survey of health facilities--conducted in five countries: Kenya SPA 2010, Namibia SPA 2009, Rwanda SPA 2007, Tanzania SPA 2006, and Uganda SPA 2007. For 32 medicines, percent of facilities having the medicine were estimated using five definitions: four for current availability and one for six-month period availability. 'Observed availability of at least one valid unit' was used as a reference definition, and ratios between the reference and each of the other four estimates were calculated. Summary statistics of the ratios among the 32 medicines were calculated by country. The ratios were compared further between public and non-public facilities within each country. Across five countries, compared to current observed availability of at least one valid unit, 'reported availability without observation' was on average 6% higher (ranging from 3% in Rwanda to 8% in Namibia), 'observed availability where all units were valid' was 11% lower (ranging from 2% in Tanzania to 19% in Uganda), and 'six-month period availability' was 14% lower (ranging from 5% in Namibia to 25% in Uganda). Medicine availability estimates vary substantially across definitions, and need to be interpreted with careful consideration of the methods used.

  2. The genomic structure of the human Charcot-Leyden crystal protein gene is analogous to those of the galectin genes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dyer, K.D.; Handen, J.S.; Rosenberg, H.F.

    The Charcot-Leyden crystal (CLC) protein, or eosinophil lysophospholipase, is a characteristic protein of human eosinophils and basophils; recent work has demonstrated that the CLC protein is both structurally and functionally related to the galectin family of {beta}-galactoside binding proteins. The galectins as a group share a number of features in common, including a linear ligand binding site encoded on a single exon. In this work, we demonstrate that the intron-exon structure of the gene encoding CLC is analogous to those encoding the galectins. The coding sequence of the CLC gene is divided into four exons, with the entire {beta}-galactoside bindingmore » site encoded by exon III. We have isolated CLC {beta}-galactoside binding sites from both orangutan (Pongo pygmaeus) and murine (Mus musculus) genomic DNAs, both encoded on single exons, and noted conservation of the amino acids shown to interact directly with the {beta}-galactoside ligand. The most likely interpretation of these results suggests the occurrence of one or more exon duplication and insertion events, resulting in the distribution of this lectin domain to CLC as well as to the multiple galectin genes. 35 refs., 3 figs.« less

  3. Identification of the cleavage sites of the RNA2-encoded polyproteins for two members of the genus Torradovirus by N-terminal sequencing of the virion capsid proteins.

    PubMed

    Ferriol, I; Silva Junior, D M; Nigg, J C; Zamora-Macorra, E J; Falk, B W

    2016-11-01

    Torradoviruses, family Secoviridae, are emergent bipartite RNA plant viruses. RNA1 is ca. 7kb and has one open reading frame (ORF) encoding for the protease, helicase and RNA-dependent RNA polymerase (RdRp). RNA2 is ca. 5kb and has two ORFs. RNA2-ORF1 encodes for a putative protein with unknown function(s). RNA2-ORF2 encodes for a putative movement protein and three capsid proteins. Little is known about the replication and polyprotein processing strategies of torradoviruses. Here, the cleavage sites in the RNA2-ORF2-encoded polyproteins of two torradoviruses, Tomato marchitez virus isolate M (ToMarV-M) and tomato chocolate spot virus, were determined by N-terminal sequencing, revealing that the amino acid (aa) at the -1 position of the cleavage sites is a glutamine. Multiple aa sequence comparison confirmed that this glutamine is conserved among other torradoviruses. Finally, site-directed mutagenesis of conserved aas in the ToMarV-M RdRp and protease prevented substantial accumulation of viral coat proteins or RNAs. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. DNA-encoded libraries - an efficient small molecule discovery technology for the biomedical sciences.

    PubMed

    Kunig, Verena; Potowski, Marco; Gohla, Anne; Brunschweiger, Andreas

    2018-06-27

    DNA-encoded compound libraries are a highly attractive technology for the discovery of small molecule protein ligands. These compound collections consist of small molecules covalently connected to individual DNA sequences carrying readable information about the compound structure. DNA-tagging allows for efficient synthesis, handling and interrogation of vast numbers of chemically synthesized, drug-like compounds. They are screened on proteins by an efficient, generic assay based on Darwinian principles of selection. To date, selection of DNA-encoded libraries allowed for the identification of numerous bioactive compounds. Some of these compounds uncovered hitherto unknown allosteric binding sites on target proteins; several compounds proved their value as chemical biology probes unraveling complex biology; and the first examples of clinical candidates that trace their ancestry to a DNA-encoded library were reported. Thus, DNA-encoded libraries proved their value for the biomedical sciences as a generic technology for the identification of bioactive drug-like molecules numerous times. However, large scale experiments showed that even the selection of billions of compounds failed to deliver bioactive compounds for the majority of proteins in an unbiased panel of target proteins. This raises the question of compound library design.

  5. A High-Resolution Gene Map of the Chloroplast Genome of the Red Alga Porphyra purpurea.

    PubMed Central

    Reith, M; Munholland, J

    1993-01-01

    Extensive DNA sequencing of the chloroplast genome of the red alga Porphyra purpurea has resulted in the detection of more than 125 genes. Fifty-eight (approximately 46%) of these genes are not found on the chloroplast genomes of land plants. These include genes encoding 17 photosynthetic proteins, three tRNAs, and nine ribosomal proteins. In addition, nine genes encoding proteins related to biosynthetic functions, six genes encoding proteins involved in gene expression, and at least five genes encoding miscellaneous proteins are among those not known to be located on land plant chloroplast genomes. The increased coding capacity of the P. purpurea chloroplast genome, along with other characteristics such as the absence of introns and the conservation of ancestral operons, demonstrate the primitive nature of the P. purpurea chloroplast genome. In addition, evidence for a monophyletic origin of chloroplasts is suggested by the identification of two groups of genes that are clustered in chloroplast genomes but not in cyanobacteria. PMID:12271072

  6. 76 FR 36980 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation... Management Facility between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The AD docket...-P ...

  7. Seeking 'energy' vs. pain relief in spas in Brazil (Caldas da Imperatriz) and Portugal (Termas da Sulfurea).

    PubMed

    Quintela, Maria Manuel

    2011-04-01

    This paper is a comparative ethnography of the therapeutic practices at two different spa locations: Caldas da Imperatriz, SC, Brazil, and Termas da Sulfurea in Cabeco de Vide, Portugal. The comparison reveals the existence of contrasting 'explanatory models' held by the spa-goers as well as by the official medical systems. In the Portuguese context this model is highly medicalized; in the Brazilian case, spa treatments are viewed as 'alternative' or 'complementary' therapy and are also related to religious philosophies. Each model corresponds to a different idiom expressing certain experiences and world views, one focusing on 'pains' (dores) and the other on 'energy' (energia), the former leading to the rationale of 'curing', the latter to the notion of 'energizing'. In this paper the author intends to analyze and contrast the categories found in these models, which originate from different conceptions of health, illness and healing for Brazilian and Portuguese spa-goers.

  8. Transition metal ions mediated tyrosine based short peptide amphiphile nanostructures inhibit bacterial growth.

    PubMed

    Joshi, Khashti Ballabh; Singh, Ramesh; Mishra, Narendra Kumar; Kumar, Vikas; Vinayak, Vandana

    2018-05-17

    We report the design and synthesis of biocompatible small peptide based molecule for the controlled and targeted delivery of the encapsulated bioactive metal ions via transforming their internal nanostructures. Tyrosine based short peptide amphiphile (sPA) was synthesized which self-assembled into β-sheet like secondary structures. The self assembly of the designed sPA was modulated by using different bioactive transition metal ions which is confirmed by spectroscopic and microscopic techniques. These bioactive metal ions conjugated sPA hybrid structures are further used to develop antibacterial materials. It is due to the excellent antibacterial activity of zinc ions that the growth of clinically relevant bacteria such as E. Coli was inhibited in the presence of zinc-sPA conjugate. The bacterial test demonstrated that owing to high biocompatibility with bacterial cell, the designed sPA worked as metal ions delivery agent and therefore it can show great potential in locally addressing bacterial infections. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Mars Science Laboratory Sample Acquisition, Sample Processing and Handling Subsystem: A Description of the Sampling Functionality

    NASA Astrophysics Data System (ADS)

    Jandura, L.; Burke, K.; Kennedy, B.; Melko, J.; Okon, A.; Sunshine, D.

    2009-12-01

    The Sample Acquisition/Sample Processing and Handling (SA/SPaH) subsystem for the Mars Science Library (MSL) is a rover-based sampling system scheduled to launch in 2011. The SA/SPaH consists of a powdering drill and a scooping, sieving, and portioning device mounted on a turret at the end of a robotic arm. Also on the turret is a dust removal tool for clearing the surface of scientific targets, and two science instruments mounted on vibration isolators. The SA/SPaH can acquire powder from rocks at depths of 20 to 50 mm and can also pick up loose regolith with its scoop. The acquired sample is sieved and portioned and delivered to one of two instruments inside the rover for analysis. The functionality of the system will be described along with the targets the system can acquire and the sample that can be delivered. Top View of the SA/SPaH on the Rover

  10. Safety of treatment options for spondyloarthritis: a narrative review.

    PubMed

    D'Angelo, Salvatore; Carriero, Antonio; Gilio, Michele; Ursini, Francesco; Leccese, Pietro; Palazzi, Carlo

    2018-05-01

    Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents). Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed. Readers will be provided with a comprehensive overview on frequent and rare adverse events associated with each drug listed in current SpA treatment recommendations. Expert opinion: The overall safety profile of such molecules is good and serious adverse events are rare but need to be promptly recognized and treated. However, the monitoring of adverse events is a major challenge for clinicians because it is not adequately addressed by current treatment recommendations. A tailored treatment is crucial and rheumatologists must accurately select patients in order to identify those more susceptible to develop adverse events.

  11. Secretion Trap Tagging of Secreted and Membrane-Spanning Proteins Using Arabidopsis Gene Traps

    Treesearch

    Andrew T. Groover; Joseph R. Fontana; Juana M. Arroyo; Cristina Yordan; W. Richard McCombie; Robert A. Martienssen

    2003-01-01

    Secreted and membrane-spanning proteins play fundamental roles in plant development but pose challenges for genetic identification and characterization. We describe a "secretion trap" screen for gene trap insertions in genes encoding proteins routed through the secretory pathway. The gene trap transposon encodes a ß-glucuronidase reporter enzyme...

  12. Identification of an opd (organophosphate degradation) gene in an Agrobacterium isolate.

    PubMed

    Horne, Irene; Sutherland, Tara D; Harcourt, Rebecca L; Russell, Robyn J; Oakeshott, John G

    2002-07-01

    We isolated a bacterial strain, Agrobacterium radiobacter P230, which can hydrolyze a wide range of organophosphate (OP) insecticides. A gene encoding a protein involved in OP hydrolysis was cloned from A. radiobacter P230 and sequenced. This gene (called opdA) had sequence similarity to opd, a gene previously shown to encode an OP-hydrolyzing enzyme in Flavobacterium sp. strain ATCC 27551 and Brevundimonas diminuta MG. Insertional mutation of the opdA gene produced a strain lacking the ability to hydrolyze OPs, suggesting that this is the only gene encoding an OP-hydrolyzing enzyme in A. radiobacter P230. The OPH and OpdA proteins, encoded by opd and opdA, respectively, were overexpressed and purified as maltose-binding proteins, and the maltose-binding protein moiety was cleaved and removed. Neither protein was able to hydrolyze the aliphatic OP malathion. The kinetics of the two proteins for diethyl OPs were comparable. For dimethyl OPs, OpdA had a higher k(cat) than OPH. It was also capable of hydrolyzing the dimethyl OPs phosmet and fenthion, which were not hydrolyzed at detectable levels by OPH.

  13. Methicillin-resistant Staphylococcus aureus (MRSA) is associated with low within-herd prevalence of intra-mammary infections in dairy cows: Genotyping of isolates.

    PubMed

    Luini, M; Cremonesi, P; Magro, G; Bianchini, V; Minozzi, G; Castiglioni, B; Piccinini, R

    2015-08-05

    Staphylococcus aureus is one of the most common mastitis-causing pathogens worldwide. In the last decade, livestock-associated methicillin-resistant S. aureus (LA-MRSA) infections have been described in several species, included the bovines. Hence, this paper investigates the diffusion of MRSA within Italian dairy herds; the strains were further characterized using a DNA microarray, which detects 330 different sequences, including the methicillin-resistance genes mecA and mecC and SCCmec typing. The analysis of overall patterns allows the assignment to Clonal Complexes (CC). Overall 163 S. aureus isolates, collected from quarter milk samples in 61 herds, were tested. MRSA strains were further processed using spa typing. Fifteen strains (9.2%), isolated in 9 herds (14.75%), carried mecA, but none harboured mecC. MRSA detection was significantly associated (P<0.011) with a within-herd prevalence of S. aureus intra-mammary infections (IMI) ≤5%. Ten MRSA strains were assigned to CC398, the remaining ones to CC97 (n=2), CC1 (n=2) or CC8 (n=1). In 3 herds, MRSA and MSSA co-existed: CC97-MRSA with CC398-MSSA, CC1-MRSA with CC8-MSSA and CC398-MRSA with CC126-MSSA. The results of spa typing showed an overall similar profile of the strains belonging to the same CC: t127-CC1, t1730-CC97, t899 in 8 out of 10 CC398. In the remaining 2 isolates a new spa type, t14644, was identified. The single CC8 was a t3092. The SCCmec cassettes were classified as type IV, type V or type IV/V composite. All or most strains harboured the genes encoding the β-lactamase operon and the tetracycline resistance. Streptogramin resistance gene was related to CC398. Enterotoxin and leukocidin genes were carried only by CC1, CC8 and CC97-MRSA. The persistence of MRSA clones characterized by broader host range, in epidemiologically unrelated areas and in dairy herds with low prevalence of S. aureus IMI, might enhance the risk for adaptation to human species. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Nucleic acid encoding DS-CAM proteins and products related thereto

    DOEpatents

    Korenberg, Julie R.

    2005-11-01

    In accordance with the present invention, there are provided Down Syndrome-Cell Adhesion Molecule (DS-CAM) proteins. Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention DS-CAM proteins can be employed in a variety of ways, for example, for the production of anti-DS-CAM antibodies thereto, in therapeutic compositions and methods employing such proteins and/or antibodies. DS-CAM proteins are also useful in bioassays to identify agonists and antagonists thereto.

  15. Fetal head circumference and subpubic angle are independent risk factors for unplanned cesarean and operative delivery.

    PubMed

    Rizzo, Giuseppe; Aiello, Elisa; Bosi, Costanza; D'Antonio, Francesco; Arduini, Domenico

    2017-08-01

    The aim of this study was to ascertain whether combined ultrasound assessment of fetal head circumference (HC) and maternal subpubic angle (SPA) prior to the onset of labor may predict the likelihood of an unplanned operative delivery (UOD) in nulliparous women at term. Prospective cohort study of singleton pregnancies in cephalic presentation. Pregnancies experiencing UOD secondary to fetal distress were excluded. HC was assessed transabdominally and SPA values were obtained from a reconstructed coronal plane on three-dimensional (3D) ultrasound performed translabially at 36-38 weeks of gestation. Maternal characteristics, HC expressed as multiple of median, and SPA were compared according to the mode of delivery. Logistic regression and receiver operating characteristics curve analyses were used to analyze the data. 597 pregnancies were included in the study. Spontaneous vaginal delivery occurred in 70.2% of the cases and UOD was required in 29.8%. There was no difference in pregnancy characteristics and birthweight between women who had a spontaneous vaginal birth compared with UOD. The HC multiple of median was larger (1.00 ± 0.02 vs. 1.03 ± 0.02, p ≤ 0.0001), whereas SPA was narrower in the UOD group (124.02 ± 13.64 vs. 102.61 ± 16.13, p ≤ 0.0001). At logistic regression, SPA (OR 0.91, 95% CI 0.89-0.93), HC multiple of median (OR 1.13, 95% CI 1.09-1.17) and maternal height (OR 0.95, 95% CI 0.92-0.99) were independently associated with UOD. When combined, the diagnostic accuracy of a predictive model integrating HC, SPA and maternal height was highly predictive of UOD with an area under the curve of 0.904 (95% CI 0.88-0.93). Ultrasound assessment of fetal HC and maternal SPA after 36 weeks of gestation can identify a subset of women at higher risk of UOD during labor, for whom early planned delivery might be beneficial. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  16. Real-life effectiveness of spa therapy in rheumatic and musculoskeletal diseases: a retrospective study of 819 patients

    NASA Astrophysics Data System (ADS)

    Karagülle, Mine; Kardeş, Sinan; Karagülle, Müfit Zeki

    2017-11-01

    The objective of this study is to determine the use and efficacy of spa therapy in patients with a wide spectrum of rheumatic and musculoskeletal diseases under real-life clinical practice circumstances. In this retrospective observational study at the Medical Ecology and Hydroclimatology Department of Istanbul Faculty of Medicine, the records of all adult patients with rheumatic and musculoskeletal diseases who were prescribed a spa therapy in various health resorts in Turkey between 2002 and 2012 were analyzed. Patients sojourned to and stayed at a health resort and followed a usual 2-week course of spa therapy. The patients were examined within a week before and after the spa therapy at the department by the physicians and outcome measures were pain intensity (visual analog scale, VAS), patient's general evaluation (VAS), physician's general evaluation (VAS), Health Assessment Questionnaire (HAQ), Lequesne's Functional Index (LFI), Western Ontario and McMaster Universities Index (WOMAC), Waddell Index (WI), Neck Pain and Disability Scale (NPDS), Shoulder Disability Questionnaire (SDQ), Fibromyalgia Impact Questionnaire (FIQ), and Beck's Depression Inventory (BDI). In total, 819 patients were included in the analysis. The diagnoses were 536 osteoarthritis; 115 fibromyalgia; 50 lumbar disc herniation; 34 cervical disc herniation; 23 nonspecific low back pain; 22 ankylosing spondylitis; 16 rheumatoid arthritis; 9 rotator cuff tendinitis; and 14 other conditions/diseases including scoliosis, stenosing flexor tenosynovitis, congenital hip dislocation in adult, Behçet's disease, de Quervain tendinopathy, psoriatic arthritis, osteoporosis, fracture rehabilitation, and diffuse idiopathic skeletal hyperostosis. Statistically significant decrease in pain scores was found in all patients except hip osteoarthritis ( p = 0.063) and rheumatoid arthritis ( p = 0.134) subgroups; and statistically significant improvement in function in all patients except hip osteoarthritis ( p = 0.068), rheumatoid arthritis ( p = 0.111), and rotator cuff tendinitis ( p = 0.078) subgroups. In daily clinical practice, spa therapy is prescribed and practiced mainly for osteoarthritis, then fibromyalgia, lumbar/cervical disc herniation, and nonspecific low back pain; and less for ankylosing spondylitis, rheumatoid arthritis, and rotator cuff tendinitis. The study results suggest that real-life spa therapy may be effective in a variety of rheumatic and musculoskeletal diseases by improving pain and function.

  17. Establishment of right ventricle-pulmonary artery continuity as the first-stage palliation in older infants with pulmonary atresia with ventricular septal defect may be preferable to use of an arterial shunt.

    PubMed

    Zheng, Shuai; Yang, Keming; Li, Kun; Li, Shoujun

    2014-07-01

    Right ventricle-pulmonary artery (RV-PA) conduit and systemic-to-pulmonary artery (S-PA) shunt in younger infants for the first-stage palliation with pulmonary atresia with ventricular septal defect (PAVSD) obtained good results. However, the pulmonary arteries (PA) grow slow in older infants undergoing an S-PA shunt. We compared the clinical outcomes of the two procedures in older infants with PAVSD. A total of 48 patients with PAVSD underwent the first-stage palliative procedure between January 2010 and July 2012. Patients were divided into the RV-PA group and the S-PA group based on whether they had an RV-PA conduit (n = 24) or an S-PA shunt (n = 24). The early and late outcomes were compared between groups. There was no significant difference in in-hospital mortality, mechanical ventilation time, paediatric intensive care unit stay and hospital stay between groups (all P > 0.05). The RV-PA conduits were associated with better PA growth compared with the S-PA shunts (P < 0.001). The RV-PA group had a higher rate of second-stage biventricular surgery compared with the S-PA group (P = 0.03). The early outcomes among different conduits of the RV-PA conduit were not different (all P > 0.05). A positive correlation was found between the size of conduits and body weight (R(2) = 0.684, P < 0.001). In older infants with PAVSD who underwent the first-stage palliative procedure, early outcomes showed no difference between the RV-PA conduit group and the S-PA shunt group. The RV-PA conduits were associated with better growth of the PA and higher rates of second-stage biventricular repair. Autologous pericardium is a good choice for RV-PA conduits, and there is a correlation between body weight and size of conduit. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  18. Comprehensive investigation of clinicopathologic features, oncogenic driver mutations and immunohistochemical markers in peripheral lung squamous cell carcinoma.

    PubMed

    Zhang, Yang; Zheng, Difan; Li, Yuan; Pan, Yunjian; Sun, Yihua; Chen, Haiquan

    2017-11-01

    Although the majority of lung squamous cell carcinomas (SQCC) arise in central airways, the prevalence of peripheral (p) SQCC is increasing. This study aimed to have a comprehensive investigation of clinicopathologic features, status of common driver mutations and immunophenotypes of p-SQCC compared to central (c) SQCC. A total of 261 p-SQCC were compared to 444 c-SQCC for clinicopathologic characteristics. Comprehensive mutational analysis of EGFR, KRAS, HER2, BRAF, PIK3CA, DDR2, AKT1, ALK, ROS1, RET and FGFRs were performed. TTF1, CK7, Napsin A and PE10 protein expression were analyzed through immunohistochemistry (IHC). TTF1, CK7, CK8, SPA and TP63 gene expression levels were measured by quantitative real-time PCR. Compared to c-SQCC, p-SQCC were associated with female (14.2% vs . 4.5%, P<0.001), never-smokers (22.6% vs . 13.3%, P=0.001), older age at diagnosis (64.9 vs . 59.5 years, P<0.001) and lower pathologic stage (P<0.001). The frequency of EGFR mutations was significantly higher in p-SQCC than c-SQCC (6.2% vs . 2.2%, P=0.040). Positive protein expression of TTF1 (P=0.010) and CK7 (P=0.001) was significantly more prevalent in p-SQCC. p-SQCC had significantly higher gene expression of SPA (P=0.003), whereas c-SQCC showed higher gene expression of TP63 (P=0.028). Lung p-SQCC had distinctive clinicopathologic characteristics and molecular features compared to c-SQCC, but showed some similarity with adenocarcinoma (ADC).

  19. Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

    PubMed Central

    Gentry-Weeks, C R; Hultsch, A L; Kelly, S M; Keith, J M; Curtiss, R

    1992-01-01

    Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the Asd+ vector pYA292, and the construct was introduced into the avirulent delta cya delta crp delta asd S. typhimurium chi 3987 for oral immunization of birds. The gene encoding the 21-kDa protein was expressed equivalently in B. avium 197, delta asd E. coli chi 6097, and S. typhimurium chi 3987 and was localized primarily in the cytoplasmic membrane and outer membrane. In preliminary studies on oral inoculation of turkey poults with S. typhimurium chi 3987 expressing the gene encoding the B. avium 21-kDa protein, it was determined that a single dose of the recombinant Salmonella vaccine failed to elicit serum antibodies against the 21-kDa protein and challenge with wild-type B. avium 197 resulted in colonization of the trachea and thymus with B. avium 197. Images PMID:1447140

  20. Does it really matter that people zip through ads? Testing the effectiveness of simultaneous presentation advertising in an IDTV environment.

    PubMed

    Nam, Yoonjae; Kwon, Kyonghee H; Lee, Sungjoon

    2010-04-01

    In an IDTV environment, which facilitates self-scheduling, skipping advertisements by zipping is an emerging ad-avoidance behavior. This study explores whether an alternative ad format, called simultaneous presentation advertising (SPA), may overcome the limitations of classical sequential advertising (CSA) in controlling zipping behavior and increasing the effectiveness of ads. The experiment revealed that SPA is more effective than CSA in reducing zipping and increasing recall, but SPA was more intrusive and produced a negative product image. There was no difference regarding cognitive avoidance. This work discusses the implications of these findings in the interactive media environment.

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