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Sample records for geer downmodulate secretion

  1. Glenn Extreme Environment Rig (GEER)

    NASA Image and Video Library

    2017-01-17

    NASA Glenn research engineers prepare our extreme environments chamber (GEER) for a test. GEER, which simulates the extreme conditions found in space, tests many devices that will explore Venus to see if they can withstand the punishing environment and temperatures over 800˚F.

  2. Glenn Extreme Environments Rig (GEER) Independent Review

    NASA Technical Reports Server (NTRS)

    Jankovsky, Robert S.; Smiles, Michael D.; George, Mark A.; Ton, Mimi C.; Le, Son K.

    2015-01-01

    The Chief of the Space Science Project Office at Glenn Research Center (GRC) requested support from the NASA Engineering and Safety Center (NESC) to satisfy a request from the Science Mission Directorate (SMD) Associate Administrator and the Planetary Science Division Chief to obtain an independent review of the Glenn Extreme Environments Rig (GEER) and the operational controls in place for mitigating any hazard associated with its operation. This document contains the outcome of the NESC assessment.

  3. Wild-type p53-mediated down-modulation of interleukin 15 and interleukin 15 receptors in human rhabdomyosarcoma cells.

    PubMed Central

    De Giovanni, C.; Nanni, P.; Sacchi, A.; Soddu, S.; Manni, I.; D'Orazi, G.; Bulfone-Paus, S.; Pohl, T.; Landuzzi, L.; Nicoletti, G.; Frabetti, F.; Rossi, I.; Lollini, P. L.

    1998-01-01

    We recently reported that rhabdomyosarcoma cell lines express and secrete interleukin 15 (IL-15), a tightly regulated cytokine with IL-2-like activity. To test whether the p53-impaired function that is frequently found in this tumour type could play a role in the IL-15 production, wild-type p53 gene was transduced in the human rhabdomyosarcoma cell line RD (which harbours a mutated p53 gene), and its effect on proliferation and expression of IL-15 was studied. Arrest of proliferation was induced by wild-type p53; increased proportions of G1-arrested cells and of apoptotic cells were observed. A marked down-modulation of IL-15 expression, at both the mRNA and protein level, was found in p53-transduced cells. Because a direct effect of IL-15 on normal muscle cells has been reported, the presence of IL-15 membrane receptors was studied by cytofluorometric analysis. Rhabdomyosarcoma cells showed IL-15 membrane receptors, which are down-modulated by wild-type p53 transfected gene. In conclusion, wild-type p53 transduction in human rhabdomyosarcoma cells induces the down-modulation of both IL-15 production and IL-15 receptor expression. Images Figure 3 PMID:9862562

  4. Efficient Nef-Mediated Downmodulation of TCR-CD3 and CD28 Is Associated with High CD4+ T Cell Counts in Viremic HIV-2 Infection

    PubMed Central

    Yu, Hangxing; Sauter, Daniel; Usmani, Shariq M.; Schmokel, Jan; Feldman, Jerome; Gruters, Rob A.; van der Ende, Marchina E.; Geyer, Matthias; Rowland-Jones, Sarah; Osterhaus, Albert D.

    2012-01-01

    The role of the multifunctional accessory Nef protein in the immunopathogenesis of HIV-2 infection is currently poorly understood. Here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load, >500 copies/ml) and 16 nonviremic (<500) HIV-2-infected individuals. On average, nef alleles from both groups were equally active in modulating CD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity. Thus, many HIV-2-infected individuals efficiently control the virus in spite of efficient Nef function. However, the potency of nef alleles in downmodulating TCR-CD3 and CD28 to suppress the activation and apoptosis of T cells correlated with high numbers of CD4+ T cells in viremic patients. No such correlations were observed in HIV-2-infected individuals with undetectable viral load. Further functional analyses showed that the Nef-mediated downmodulation of TCR-CD3 suppressed the induction of Fas, Fas-L, PD-1, and CTLA-4 cell surface expression as well as the secretion of gamma interferon (IFN-γ) by primary CD4+ T cells. Moreover, we identified a single naturally occurring amino acid variation (I132T) in the core domain of HIV-2 Nef that selectively disrupts its ability to downmodulate TCR-CD3 and results in functional properties highly reminiscent of HIV-1 Nef proteins. Taken together, our data suggest that the efficient Nef-mediated downmodulation of TCR-CD3 and CD28 help viremic HIV-2-infected individuals to maintain normal CD4+ T cell homeostasis by preventing T cell activation and by suppressing the induction of death receptors that may affect the functionality and survival of both virally infected and uninfected bystander cells. PMID:22345473

  5. Efficient Nef-mediated downmodulation of TCR-CD3 and CD28 is associated with high CD4+ T cell counts in viremic HIV-2 infection.

    PubMed

    Khalid, Mohammad; Yu, Hangxing; Sauter, Daniel; Usmani, Shariq M; Schmokel, Jan; Feldman, Jerome; Gruters, Rob A; van der Ende, Marchina E; Geyer, Matthias; Rowland-Jones, Sarah; Osterhaus, Albert D; Kirchhoff, Frank

    2012-05-01

    The role of the multifunctional accessory Nef protein in the immunopathogenesis of HIV-2 infection is currently poorly understood. Here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load, >500 copies/ml) and 16 nonviremic (<500) HIV-2-infected individuals. On average, nef alleles from both groups were equally active in modulating CD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity. Thus, many HIV-2-infected individuals efficiently control the virus in spite of efficient Nef function. However, the potency of nef alleles in downmodulating TCR-CD3 and CD28 to suppress the activation and apoptosis of T cells correlated with high numbers of CD4(+) T cells in viremic patients. No such correlations were observed in HIV-2-infected individuals with undetectable viral load. Further functional analyses showed that the Nef-mediated downmodulation of TCR-CD3 suppressed the induction of Fas, Fas-L, PD-1, and CTLA-4 cell surface expression as well as the secretion of gamma interferon (IFN-γ) by primary CD4(+) T cells. Moreover, we identified a single naturally occurring amino acid variation (I132T) in the core domain of HIV-2 Nef that selectively disrupts its ability to downmodulate TCR-CD3 and results in functional properties highly reminiscent of HIV-1 Nef proteins. Taken together, our data suggest that the efficient Nef-mediated downmodulation of TCR-CD3 and CD28 help viremic HIV-2-infected individuals to maintain normal CD4(+) T cell homeostasis by preventing T cell activation and by suppressing the induction of death receptors that may affect the functionality and survival of both virally infected and uninfected bystander cells.

  6. Down-modulation of receptors for phorbol ester tumor promoter in primary epidermal cells

    SciTech Connect

    Solanki, V.; Slaga, T.J.

    1982-01-01

    The specific (20-/sup 3/H)phorbol 12,13-dibutyrate ((/sup 3/H)PDBu) binding to intact epidermal cells displayed the phenomenon of down-modulation, i.e., the specific binding of (/sup 3/H)PDBu to its receptors on primary epidermal cells reached a maximum within 1 h and steadily declined thereafter. The apparent down-modulation of radiolabel resulted from a partial loss in the total number of receptors; the affinity of receptors for the ligand was essentially unchanged. A number of agents such as chloroquine, methylamine, or arginine which are known to prevent clustering, down-modulation, and/or internalization of several hormone receptors did not affect the down-modulation of phorbol ester receptors. Furthermore, cycloheximide had no effect either on down-modulation or on the binding capacity of cells. The surface binding capacity of down-modulated cells following a 90-min incubation with unlabeled ligand was almost returned to normal within 1 h. The effect of the antidepressant drug chlorpromazine, which is known to interact with calmodulin, on (/sup 3/H)PDBu binding was also investigated. Our data indicate that the effect of chlorpromazine on (/sup 3/H)PDBu binding is probably unrelated to its calmodulin-binding activity.

  7. Endotoxin down-modulates granulocyte colony-stimulating factor receptor (CD114) on human neutrophils.

    PubMed

    Hollenstein, U; Homoncik, M; Stohlawetz, P J; Marsik, C; Sieder, A; Eichler, H G; Jilma, B

    2000-07-01

    During infection, the development of nonresponsiveness to granulocyte colony-stimulating factor (G-CSF) may be influenced by the down-modulation of G-CSF receptor (G-CSFR) by cytokines. This down-modulation was studied during experimental human endotoxemia. Healthy volunteers received either 2 ng/kg endotoxin (lipopolysaccharide [LPS], n=20) or placebo (n=10) in a randomized, controlled trial. Endotoxin infusion increased the mean fluorescence intensity of the neutrophil activation marker CD11b >300% after 1 h (P<.001 vs. placebo). LPS infusion down-modulated G-CSFR expression in as early as 60 min (-17%; P=.001 vs. placebo). Down-modulation was almost maximal at 90 min and persisted for 6 h (-50% from baseline; P<.0001 vs. placebo). Plasma levels of G-CSF started to increase only after G-CSFR down-modulation had occurred and peaked 37-fold above baseline at 4 h (P<.0001 vs. placebo). In conclusion, LPS down-modulates G-CSFR expression in humans, which may render neutrophils less responsive to the effects of G-CSF and, thereby, compromise host defense mechanisms.

  8. Anasa tristis (De Geer) (Heteroptera: Coreidae) Tran-scriptional Response to Bacterial Elicitation

    USDA-ARS?s Scientific Manuscript database

    The Squash bug, Anasa tristis (De Geer), is a major pest of squash, pumpkin, and other cucurbits throughout North America. A. tristis is a piercing/sucking feeder which causes extensive foliar wilting, fruit scarring, and in addition transmits plant pathogens. Current biological control agents ava...

  9. Functional immunomics of the squash bug, Anasa tristis (De Geer) (Heteroptera: Coreidae)

    USDA-ARS?s Scientific Manuscript database

    The Squash bug, Anasa tristis (De Geer), is a major piercing/sucking pest of cucurbits causing extensive damage to plants and fruits, and transmitting phytopathogens. There are few effective biological control agents or cultural practices for controlling this highly destructive pest. A promising n...

  10. Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells

    PubMed Central

    Vogel, Stephanie; Grabski, Elena; Buschjäger, Daniela; Klawonn, Frank; Döring, Marius; Wang, Junxi; Fletcher, Erika; Bechmann, Ingo; Witte, Torsten; Durisin, Martin; Schraven, Burkhart; Mangsbo, Sara M.; Schönfeld, Kurt; Czeloth, Niklas; Kalinke, Ulrich

    2015-01-01

    Treatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fcγ receptor mediated cell-cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64+ monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients’ inflamed joints that comprised enhanced numbers of CD64+ cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64+ cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64+ cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single FcγR, but also the immunological environment that is appropriate to support such interactions. PMID:26670584

  11. Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64(+) cells.

    PubMed

    Vogel, Stephanie; Grabski, Elena; Buschjäger, Daniela; Klawonn, Frank; Döring, Marius; Wang, Junxi; Fletcher, Erika; Bechmann, Ingo; Witte, Torsten; Durisin, Martin; Schraven, Burkhart; Mangsbo, Sara M; Schönfeld, Kurt; Czeloth, Niklas; Kalinke, Ulrich

    2015-12-16

    Treatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fcγ receptor mediated cell-cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64(+) monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients' inflamed joints that comprised enhanced numbers of CD64(+) cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64(+) cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64(+) cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single FcγR, but also the immunological environment that is appropriate to support such interactions.

  12. Surveillance Definitions of Infections in Long-Term Care Facilities: Revisiting the McGeer Criteria

    PubMed Central

    Stone, Nimalie D.; Ashraf, Muhammad S.; Calder, Jennifer; Crnich, Christopher J.; Crossley, Kent; Drinka, Paul J.; Gould, Carolyn V.; Juthani-Mehta, Manisha; Lautenbach, Ebbing; Loeb, Mark; MacCannell, Taranisia; Malani, Preeti N.; Mody, Lona; Mylotte, Joseph M.; Nicolle, Lindsay E.; Roghmann, Mary-Claire; Schweon, Steven J.; Simor, Andrew E.; Smith, Philip W.; Stevenson, Kurt B.; Bradley, Suzanne F.

    2012-01-01

    (See the commentary by Moro, on pages 978–980.) Infection surveillance definitions for long-term care facilities (ie, the McGeer Criteria) have not been updated since 1991. An expert consensus panel modified these definitions on the basis of a structured review of the literature. Significant changes were made to the criteria defining urinary tract and respiratory tract infections. New definitions were added for norovirus gastroenteritis and Clostridum difficile infections. PMID:22961014

  13. Surveillance definitions of infections in long-term care facilities: revisiting the McGeer criteria.

    PubMed

    Stone, Nimalie D; Ashraf, Muhammad S; Calder, Jennifer; Crnich, Christopher J; Crossley, Kent; Drinka, Paul J; Gould, Carolyn V; Juthani-Mehta, Manisha; Lautenbach, Ebbing; Loeb, Mark; Maccannell, Taranisia; Malani, Preeti N; Mody, Lona; Mylotte, Joseph M; Nicolle, Lindsay E; Roghmann, Mary-Claire; Schweon, Steven J; Simor, Andrew E; Smith, Philip W; Stevenson, Kurt B; Bradley, Suzanne F

    2012-10-01

    (See the commentary by Moro, on pages 978-980 .) Infection surveillance definitions for long-term care facilities (ie, the McGeer Criteria) have not been updated since 1991. An expert consensus panel modified these definitions on the basis of a structured review of the literature. Significant changes were made to the criteria defining urinary tract and respiratory tract infections. New definitions were added for norovirus gastroenteritis and Clostridum difficile infections.

  14. The infestation of Dermestes ater (De Geer) on a human corpse in Malaysia.

    PubMed

    Kumara, T K; Abu Hassan, A; Che Salmah, M R; Bhupinder, S

    2009-04-01

    A human corpse at an advanced stage of decomposition was found in a house in the residential area of Bukit Mertajam, Penang, Malaysia. Entomological specimens were collected during the post-mortem and the live specimens were subsequently reared at room temperature. The time of death was estimated to have been 14 days previous to the discovery of the body based on the police investigation. Both adult and larvae of the beetle Dermestes ater (De Geer) were found to be infesting the corpse and from the stage of decomposition of the body and the estimated time of death it would appear that infestation may have begun at a relatively early stage of decomposition.

  15. Effect of diet and refugia on development of Dermestes maculatus DeGeer reared in a laboratory

    USDA-ARS?s Scientific Manuscript database

    The hide beetle (Dermestes maculatus DeGeer) is a Dermestid beetle that can infest a wide variety of stored products, including pet foods and animal feeds, dried foods, and grains products with high protein content. Although there is published information concerning the biology and habits of D. macu...

  16. A new species of Cephalobium (Rhabditida, Cephalobiidae), a parasite of Anurogryllus muticus (De Geer) (Orthoptera, Gryllidae) in Argentina.

    PubMed

    Camino, Nora B; Maiztegui, Bárbara

    2002-10-01

    Cephalobium odontolateralis n. sp. (Nematoda, Cephalobiidae) is described and illustrated from the nymphs of Anurogryllus muticus (De Geer) (Orthoptera, Gryllidae) from Buenos Aires province, Argentina. It is characterized by a lateral large tooth in the stoma and by the arrangement and number of the genital papillae in the male; there are 6 pairs of postanal papillae, but none is preanal.

  17. Development of Mass Rearing Methods, and Novel Methods For Control of the Squash Bug, Anasa Tristis (De Geer) (Heteroptera: Coreidae)

    USDA-ARS?s Scientific Manuscript database

    The Squash bug, Anasa tristis (De Geer), a major pest of squash, pumpkin, watermelon, cucumber and cantaloupe, uses piercing-sucking mouthparts to imbibe plant fluids. The severity of plant damage resulting from squash bug feeding causes extensive damage to stems resulting in wilting, fruit discolo...

  18. Kodamaea ohmeri (Ascomycota: Saccharomycotina) presence in commercial Bombus impatiens Cresson and feral Bombus pensylvanicus DeGeer (Hymenoptera: Apidae) colonies

    USDA-ARS?s Scientific Manuscript database

    In this study, eight commercial and three feral bumble bee (Bombus impatiens Cresson and Bombus pensylvanicus DeGeer respectively, Hymenoptera: Apidae) colonies were tested for the presence of Kodamaea ohmeri (Ascomycota: Saccharomycotina), a yeast known to attract small hive beetles (SHB) (Aethina ...

  19. RNase L down-modulation of the RNA Binding Protein, HuR, and cellular growth

    PubMed Central

    Al-Ahmadi, Wijdan; Al-Ghamdi, Maha; al-Haj, Latifa; Al-Mohanna, Futwan A.; Silverman, Robert H.; Khabar, Khalid S. A.

    2010-01-01

    Ribonuclease L (RNase L) is an intracellular enzyme that is vital in innate immunity, but also is a tumor suppressor candidate. Here, we show that over-expression of RNase L decreases cellular growth and down-modulates the RNA binding protein, HuR, a regulator of cell cycle progression and tumorigenesis. The effect is temporal, occurring in specific cell cycle phases and correlated with the cytoplasmic localization of RNase L. Both cellular growth and HuR were increased in RNASEL-null mouse fibroblast lines when compared to wild type cells. Moreover, the stability of HuR mRNA was enhanced in RNASEL-null cells. The HuR 3′UTR, which harbor U-rich and AU-rich elements, was potently responsive to RNase L over-expression when compared to control 3′UTR. Our results may offer a new explanation to the tumor suppressor role of RNase L. PMID:19252527

  20. Systemic inflammatory response and downmodulation of peripheral CD25+Foxp3+ T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer.

    PubMed

    Fietta, Anna Maria; Morosini, Monica; Passadore, Ileana; Cascina, Alessandro; Draghi, Paola; Dore, Roberto; Rossi, Sandro; Pozzi, Ernesto; Meloni, Federica

    2009-07-01

    Radiofrequency thermal ablation (RFTA) is a local tumor-destructing technique that can potentially modulate the host immune response through mechanisms that are not clearly defined. We assessed whether RFTA could affect multiple systemic inflammatory and immunological parameters, including CD25+Foxp+ cells, in patients with primary or metastatic lung tumors. Three days after RFTA, a moderate and temporary systemic inflammatory response developed, as demonstrated by the increase in peripheral neutrophils and monocytes and in plasma levels of proinflammatory chemokines (MIP-1alpha, MIP-1beta, eotaxin, and interleukin[IL]-8) and acute phase reactants (complement C3 and C4, serum amyloid, alpha1 antichymotrypsin, and C-reactive protein). Moreover, we found a concomitant release of the anti-inflammatory factor IL-10. Thirty days after RFTA, a significant reduction in CD25+Foxp3+ counts with an increase in CD4+ T-cell proliferation and number of interferon-gamma-secreting cells was observed. The reduction in CD25+Foxp3+ cells lasted up to 90 days after treatment. The use of RFTA in lung cancer patients has an immunomodulatory activity: it induces a self-limiting systemic inflammation early and later a reduction of circulating CD25+Foxp3+ Tregs. In addition to tumor ablation, downmodulation of this regulatory subset might be an important mechanism involved in the long-term clinical efficacy of RFTA.

  1. Biological Strategies of Dermestes maculatus DeGeer (Coleoptera: Dermestidae) at Larval Stages in Different Temperatures.

    PubMed

    Zanetti, N I; Visciarelli, E C; Centeno, N D

    2016-12-01

    The intraspecific variation in larval instars is a widely distributed phenomenon amongst holometabolous insects. Several factors can affect the number of instars, such as temperature, humidity, and density. Only a few references could be found in the literature because the invariability in the number of larval instars is considered normal, and the issue has raised little to no interest. Despite this, no study to date has intended to assess or focus on the larval development. Here, we analyzed the effect of different rearing temperature on the larval stage of Dermestes maculatus DeGeer (Coleoptera: Dermestidae). The results indicated that at all temperatures, L5 represented a decisive point for individuals as well as the other later larval instars, because the next step to follow was to pupate or molt to the next larval instar. Furthermore, there were mainly two populations, L5 and L6, although in different proportions according to temperature. We also found that at a greater number of instars, the larval development at all temperatures lasted longer. Moreover, the exponential model was the best adjustment in the developmental time of all populations as well as for the accumulated developmental time of L1-L4. Thus, we conclude that random factors such as genetics could probably cause interspecific variability in D. maculatus larval development.

  2. Karyosystematics of Triatoma rubrofasciata (De Geer, 1773) (Hemiptera: Reduviidae: Triatominae).

    PubMed

    Alevi, Kaio Cesar Chaboli; Borsatto, Kelly Cristine; Moreira, Felipe Ferraz Figueiredo; Jurberg, José; De Azeredo-Oliveir, Maria Tercília Vilela

    2015-08-03

    Triatoma rubrofasciata (De Geer) is the first species of triatomine described, and little is known on its vector biology. Studies are restricted to starvation resistance, interspecific morphometric variability, morphometry of testis follicles, coloration of the testicular peritoneal sheath, ultrastructure of the male accessory glands, phylogeny and cytogenetics. Thus, this study aims to address the karyosystematics of T. rubrofasciata and the possible events related to karyotype evolution of this species. Four adult males were analyzed cytogenetically. The analysis of meiotic metaphases of T. rubrofasciata allowed to confirm the karyotype of species, out more, 2n = 25 (22A + X1X2Y). This number is very important for taxonomic and evolutionary inferences on the species, because of the 88 triatomine species with described karyotype, only T. rubrofasciata exhibits 25 chromosomes. Based on the hypothesis of the karyotype 2n = 22 (20A + XY) as ancestral for triatomines, we propose three evolutionary hypotheses for the emergence of the karyotype of T rubrofasciata, all supported by agmatoploidy events (fission). Basically the hypotheses are 1) fission for a pair of autosomes, resulting in 22 autosomes and later fission of sex chromosome X; 2) fission of pair of autosomes and the sex chromosome X concomitantly; 3) fission of sex chromosome X and subsequently fission of pair of autosomes. Thus, this study highlights for the first time the importance of the number of chromosomes of T. rubrofasciata as characteristic diagnosis in Triatominae subfamily and describes three evolutionary hypotheses that possibly led the emergence of karyotype of this insect of global importance.

  3. Functional Immunomics of the Squash Bug, Anasa tristis (De Geer) (Heteroptera: Coreidae)

    PubMed Central

    Shelby, Kent S.

    2013-01-01

    The Squash bug, Anasa tristis (De Geer), is a major piercing/sucking pest of cucurbits, causing extensive damage to plants and fruits, and transmitting phytopathogens. No genomic resources to facilitate field and laboratory studies of this pest were available; therefore the first de novo exome for this destructive pest was assembled. RNA was extracted from insects challenged with bacterial and fungal immunoelicitors, insects fed on different cucurbit species, and insects from all life stages from egg to adult. All treatments and replicates were separately barcoded for subsequent analyses, then pooled for sequencing in a single lane using the Illumina HiSeq2000 platform. Over 211 million 100-base tags generated in this manner were trimmed, filtered, and cleaned, then assembled into a de novo reference transcriptome using the Broad Institute Trinity assembly algorithm. The assembly was annotated using NCBIx NR, BLAST2GO, KEGG and other databases. Of the >130,000 total assemblies 37,327 were annotated identifying the sequences of candidate gene silencing targets from immune, endocrine, reproductive, cuticle, and other physiological systems. Expression profiling of the adult immune response was accomplished by aligning the 100-base tags from each biological replicate from each treatment and controls to the annotated reference assembly of the A. tristis transcriptome. PMID:26462532

  4. Effects of food deprivation on the development of Coleomegilla maculata (De Geer) (Coleoptera: Coccinellidae).

    PubMed

    Santos-Cividanes, T M; Anjos, A C R dos; Cividanes, F J; Dias, P C

    2011-01-01

    The lady beetle Coleomegilla maculata (De Geer) is a natural enemy of several insect pests and feeds on pollen and nectar to survive periods when prey is scarce. The effect of the feeding interval on the development, survival, fecundity, and longevity of C. maculata was determined. Newly hatched larvae of C. maculata were reared individually and fed with eggs of the Mediterranean flour moth Anagasta kuehniella (Zeller) at intervals of one, two, and three days under controlled conditions (23 ± 1ºC; 60 ± 10% RH; 12 h phtophase). The duration of larval instars and the total larval stage was prolonged as the feeding interval increased. The larval period lasted on average 9.2 ± 0.19 days when the larvae were fed daily with prey, and 14.6 ± 0.48 days when food was offered at three-day intervals. There was an inverse relationship between food intervals, survival, and weight of larvae and adults of the coccinellid. Survival rate of larvae fed daily was 76.8%, while the rate was 50.0% and 23.4% for larvae fed every two and three days, respectively. Coleomegilla maculata showed fecundity of 781.1 ± 149.02, 563.4 ± 80.81 and 109.0 ± 103.0 eggs when fed daily and at intervals of two and three days, respectively.

  5. Climate change impacts on groundwater resources: modelled deficits in a chalky aquifer, Geer basin, Belgium

    NASA Astrophysics Data System (ADS)

    Brouyère, Serge; Carabin, Guy; Dassargues, Alain

    An integrated hydrological model (MOHISE) was developed in order to study the impact of climate change on the hydrological cycle in representative water basins in Belgium. This model considers most hydrological processes in a physically consistent way, more particularly groundwater flows which are modelled using a spatially distributed, finite-element approach. Thanks to this accurate numerical tool, after detailed calibration and validation, quantitative interpretations can be drawn from the groundwater model results. Considering IPCC climate change scenarios, the integrated approach was applied to evaluate the impact of climate change on the water cycle in the Geer basin in Belgium. The groundwater model is described in detail, and results are discussed in terms of climate change impact on the evolution of groundwater levels and groundwater reserves. From the modelling application on the Geer basin, it appears that, on a pluri-annual basis, most tested scenarios predict a decrease in groundwater levels and reserves in relation to variations in climatic conditions. However, for this aquifer, the tested scenarios show no enhancement of the seasonal changes in groundwater levels. Un modèle hydrologique intégré (MOHISE) a été développé afin d'étudier l'impact du changement climatique sur le cycle hydrologique de bassins versants représentatifs de Belgique. Ce modèle prend en compte tous les processus hydrologiques d'une manière physiquement consistante, plus particulièrement les écoulements souterrains qui sont modélisés par une approche spatialement distribuée aux éléments finis. Grâce à cet outil numérique précis, après une calibration et une validation détaillées, des interprétations quantitatives peuvent être réalisées à partir des résultats du modèle de nappe. Considérant des scénarios de changements climatiques de l'IPCC, l'approche intégrée a été appliquée pour évaluer l'impact du changement climatique sur le cycle de l

  6. Vinblastine-dependent down-modulation of TNF receptors in human osteosarcoma cells is mediated by protein kinase C activity.

    PubMed

    Boscoboinik, D; Galeotti, T; Azzi, A

    1994-02-28

    The binding of tumor necrosis factor (TNF) to a human osteogenic sarcoma cell line (Saos-2) was investigated. These cells express two types of receptors as determined by specific monoclonal antibodies. Vinblastine induced a down-modulation of these receptors weaker than the one produced by phorbol esters or okadaic acid treatment. On exposure of cells to 10 microM vinblastine for two hours an approximately 55-65% diminution of TNF binding was observed, but only 20% reduction occurred under long-term vinblastine treatment. TNF receptor down-modulation induced by vinblastine was partially prevented by protein kinase C inhibitors or protein kinase C depletion. It is suggested that the regulation of TNF binding to each one of its receptors in Saos-2 cells always occurs in a phosphorylation-dependent manner.

  7. Whole transcriptome analysis of the poultry red mite Dermanyssus gallinae (De Geer, 1778).

    PubMed

    Schicht, Sabine; Qi, Weihong; Poveda, Lucy; Strube, Christina

    2014-03-01

    SUMMARY Although the poultry red mite Dermanyssus gallinae (De Geer, 1778) is the major parasitic pest in poultry farming causing substantial economic losses every year, nucleotide data are rare in the public databases. Therefore, de novo sequencing covering the transcriptome of D. gallinae was carried out resulting in a dataset of 232 097 singletons and 42 130 contiguous sequences (contigs) which were subsequently clustered into 24 140 isogroups consisting of 35 788 isotigs. After removal of sequences possibly originating from bacteria or the chicken host, 267 464 sequences (231 657 singletons, 56 contigs and 35 751 isotigs) remained, of which 10·3% showed homology to proteins derived from other organisms. The most significant Blast top-hit species was the mite Metaseiulus occidentalis followed by the tick Ixodes scapularis. To gain functional knowledge of D. gallinae transcripts, sequences were mapped to Gene Ontology terms, Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways and parsed to InterProScan. The transcriptome dataset provides new insights in general mite genetics and lays a foundation for future studies on stage-specific transcriptomics as well as genomic, proteomic, and metabolomic explorations and might provide new perspectives to control this parasitic mite by identifying possible drug targets or vaccine candidates. It is also worth noting that in different tested species of the class Arachnida no 28S rRNA was detectable in the rRNA profile, indicating that 28S rRNA might consists of two separate, hydrogen-bonded fragments, whose (heat-induced) disruption may led to co-migration with 18S rRNA.

  8. Distinctive downmodulation of plasmacytoid dendritic cell functions by vitamin D3 analogue calcipotriol.

    PubMed

    Suzuki, Takahiro; Tatsuno, Kazuki; Ito, Taisuke; Sakabe, Jun-Ichi; Funakoshi, Atsuko; Tokura, Yoshiki

    2016-10-01

    In relation to Th17 cell actions, interferon (IFN)-α production by plasmacytoid dendritic cells (pDCs) are involved in the pathogenesis of psoriasis. Vitamin D3 analogues are widely used in the treatment of psoriasis, however, their actions on pDCs are not well understood. To investigate the effects of Vitamin D3 analogue calcipotriol (CAL) on pDCs, focusing on the cytokine production and chemotactic activity. We compared in mice the effects of CAL, cyclosporine A (CyA), and triamcinolone acetonide (TA) on the cytokine production by pDCs (IFN-α), conventional DCs (TNF-α), and γd T cells (IL-17A). pDCs isolated from mouse spleen cells were stimulated with CpG-ODN in the presence or absence of each drug for 48h. Purified splenic conventional DCs (cDCs) and lymph node γδ T cells were stimulated with CpG-ODN or with anti-CD3/CD28 antibody, respectively. IFN-α, TNF-α and IL-17A in the 48-h culture supernatants were quantified by ELISA. We also studied the ability of CAL to inhibit the chemotaxis of freshly isolated pDCs toward chemerin and VEGF-A, representative chemoattractants of pDCs, by a real-time monitoring method, EZ-Taxiscan. To assess the effect of CAL on pDC accumulation in vivo, we painted CAL ointment to the mouse skin inflamed by topical application of imiquimod cream (IMQ) for 4 consecutive days. In the skin samples, we enumerated 440c(+) pDCs by immunohistochemistry and evaluated the mRNA expression of cytokines by real-time PCR. CAL significantly inhibited CpG-enhanced pDC IFN-α production at a comparable level to T cell IL-17A production, whereas its effect on cDC TNF-α production was minimal. Accordingly, CAL suppressed the CpG-augmented expression of TLR9 and MyD88. On the contrary, CyA strongly suppressed the production of TNF-α and IL-17A, but not IFN-α. TA inhibited the production of all the cytokines tested. The effect of CAL on the chemotactic activity of pDCs was also evaluated, demonstrating a significant downmodulation by exposure

  9. Ebola Virus Glycoproteins Induce Global Surface Protein Down-Modulation and Loss of Cell Adherence

    PubMed Central

    Simmons, Graham; Wool-Lewis, Rouven J.; Baribaud, Frédéric; Netter, Robert C.; Bates, Paul

    2002-01-01

    The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293T cells. In this study we provide evidence that GPs from the other pathogenic subtypes, Sudan and Côte d'Ivoire, as well as from Reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than Zaire GP. Sequential removal of regions of potential O-linked glycosylation at the C terminus of GP1 led to a step-wise reduction in cell detachment without obviously affecting GP function, suggesting that such modifications are involved in inducing the detachment phenotype. While causing cell rounding and detachment in 293T cells, Ebola virus GP did not cause an increase in cell death. Indeed, following transient expression of GP, cells were able to readhere and continue to divide. Also, the rounding effect was not limited to 293T cells. Replication-deficient adenovirus vectors expressing Ebola virus GP induced the loss of cell adhesion in a range of cell lines and primary cell types, including those with proposed relevance to Ebola virus infection in vivo, such as endothelial cells and macrophages. In both transfected 293T and adenovirus-infected Vero cells, a reduction in cell surface expression of adhesion molecules such as integrin β1 concurrent with the loss of cell adhesion was observed. A number of other cell surface molecules, however, including major histocompatibility complex class I and the epidermal growth factor receptor, were also down-modulated, suggesting a global mechanism for surface molecule down-regulation. PMID:11836430

  10. Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence.

    PubMed

    Simmons, Graham; Wool-Lewis, Rouven J; Baribaud, Frédéric; Netter, Robert C; Bates, Paul

    2002-03-01

    The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293T cells. In this study we provide evidence that GPs from the other pathogenic subtypes, Sudan and Côte d'Ivoire, as well as from Reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than Zaire GP. Sequential removal of regions of potential O-linked glycosylation at the C terminus of GP1 led to a step-wise reduction in cell detachment without obviously affecting GP function, suggesting that such modifications are involved in inducing the detachment phenotype. While causing cell rounding and detachment in 293T cells, Ebola virus GP did not cause an increase in cell death. Indeed, following transient expression of GP, cells were able to readhere and continue to divide. Also, the rounding effect was not limited to 293T cells. Replication-deficient adenovirus vectors expressing Ebola virus GP induced the loss of cell adhesion in a range of cell lines and primary cell types, including those with proposed relevance to Ebola virus infection in vivo, such as endothelial cells and macrophages. In both transfected 293T and adenovirus-infected Vero cells, a reduction in cell surface expression of adhesion molecules such as integrin beta1 concurrent with the loss of cell adhesion was observed. A number of other cell surface molecules, however, including major histocompatibility complex class I and the epidermal growth factor receptor, were also down-modulated, suggesting a global mechanism for surface molecule down-regulation.

  11. The 22 March 2014 Oso Landslide, Snohomish County, Washington: Findings of the GEER Reconnaissance Investigation

    NASA Astrophysics Data System (ADS)

    Wartman, J.; Keaton, J. R.; Scott, A.; Benoit, J.; delaChapelle, J.; Gilbert, R.; Montgomery, D. R.

    2014-12-01

    We report the findings of the NSF-supported Geotechnical Extreme Events Reconnaissance (GEER) investigation of the Oso Landslide. Our findings are principally based on data collected during a four-day team reconnaissance across the entire landslide area, but also draw upon other data sources including lidar surveys, high-resolution imagery, geologic mapping, precipitation data, and seismic records. The Oso Landslide claimed 43 lives, making it the deadliest landslide disaster in U.S. history. The landslide occurred within a thick sequence of glacial sediments that were deposited into the North Fork Stillaguamish River valley during the last glacial advance. Geomorphic evidence suggests that the valley in the vicinity of Oso Landslide has experienced multiple large landslides over at least the past 6,000 years. Intense three-week rainfall that immediately preceded the event very probably played an important role in triggering the landslide; however, many other factors likely contributed to destabilization of the landslide mass. These include: (i) alteration of the local groundwater recharge and hydrogeological regime due to previous landsliding and, possibly, land use practices, (ii) weakening and alteration of the landslide mass due to previous landsliding and other natural geologic processes, and (iii) changes in stress distribution resulting from removal and deposition of material from earlier landsliding. During our field reconnaissance we identified six distinctive landslide zones and several subzones that are characterized by different geomorphic expression resulting from deformation styles, geologic materials, vegetation, and sequence of deposition. Based on the reconnaissance observations and other available data, we hypothesize that the landslide occurred in two major stages. The first stage of movement is interpreted to be a remobilization of the 2006 slide mass and headward extension that included part or all of the forested slope of an ancient landslide

  12. Membrane-type 6 matrix metalloproteinase regulates the activation-induced downmodulation of CD16 in human primary NK cells.

    PubMed

    Peruzzi, Giovanna; Femnou, Laurette; Gil-Krzewska, Aleksandra; Borrego, Francisco; Weck, Jennifer; Krzewski, Konrad; Coligan, John E

    2013-08-15

    CD16 (FcγRIIIa), the low-affinity receptor for IgG, expressed by the majority of human NK cells, is a potent activating receptor that facilitates Ab-dependent cell-mediated cytotoxicity (ADCC). ADCC dysfunction has been linked to cancer progression and poor prognosis for chronic infections, such as HIV; thus, understanding how CD16 expression is regulated by NK cells has clinical relevance. Importantly, CD16 cell-surface expression is downmodulated following NK cell activation and, in particular, exposure to stimulatory cytokines (IL-2 or IL-15), likely owing to the action of matrix metalloproteinases (MMPs). In this article, we identify membrane-type 6 (MT6) MMP (also known as MMP25) as a proteinase responsible for CD16 downmodulation. IL-2-induced upregulation of MT6/MMP25 cell-surface expression correlates with CD16 downmodulation. MT6/MMP25, sequestered in intracellular compartments in unstimulated NK cells, translocates to the cell surface after stimulation; moreover, it polarizes to the effector-target cell interface of the CD16-mediated immunological synapse. siRNA-mediated disruption of MT6/MMP25 expression enhances the ADCC capacity of NK cells, emphasizing the important functional role of MT6/MMP25 in the regulation of ADCC activity. Thus, this study uncovers a previously unknown role of MT6/MMP25 in human NK cells, and suggests that inhibition of MT6/MMP25 activity could improve ADCC efficacy of therapeutically administered NK cells that require IL-2 for culture and expansion.

  13. CCR5 susceptibility to ligand-mediated down-modulation differs between human T lymphocytes and myeloid cells.

    PubMed

    Fox, James M; Kasprowicz, Richard; Hartley, Oliver; Signoret, Nathalie

    2015-07-01

    CCR5 is a chemokine receptor expressed on leukocytes and a coreceptor used by HIV-1 to enter CD4(+) T lymphocytes and macrophages. Stimulation of CCR5 by chemokines triggers internalization of chemokine-bound CCR5 molecules in a process called down-modulation, which contributes to the anti-HIV activity of chemokines. Recent studies have shown that CCR5 conformational heterogeneity influences chemokine-CCR5 interactions and HIV-1 entry in transfected cells or activated CD4(+) T lymphocytes. However, the effect of CCR5 conformations on other cell types and on the process of down-modulation remains unclear. We used mAbs, some already shown to detect distinct CCR5 conformations, to compare the behavior of CCR5 on in vitro generated human T cell blasts, monocytes and MDMs and CHO-CCR5 transfectants. All human cells express distinct antigenic forms of CCR5 not detected on CHO-CCR5 cells. The recognizable populations of CCR5 receptors exhibit different patterns of down-modulation on T lymphocytes compared with myeloid cells. On T cell blasts, CCR5 is recognized by all antibodies and undergoes rapid chemokine-mediated internalization, whereas on monocytes and MDMs, a pool of CCR5 molecules is recognized by a subset of antibodies and is not removed from the cell surface. We demonstrate that this cell surface-retained form of CCR5 responds to prolonged treatment with more-potent chemokine analogs and acts as an HIV-1 coreceptor. Our findings indicate that the regulation of CCR5 is highly specific to cell type and provide a potential explanation for the observation that native chemokines are less-effective HIV-entry inhibitors on macrophages compared with T lymphocytes.

  14. Infections in Australian Aged-Care Facilities: Evaluating the Impact of Revised McGeer Criteria for Surveillance of Urinary Tract Infections.

    PubMed

    Bennett, Noleen J; Johnson, Sandra A; Richards, Michael J; Smith, Mary A; Worth, Leon J

    2016-05-01

    Our survey of 112 Australian aged-care facilities demonstrated the prevalence of healthcare-associated infections to be 2.9%. Urinary tract infections (UTIs) defined by McGeer criteria comprised 35% of all clinically defined UTIs. To estimate the infection burden in these facilities where microbiologic testing is not routine, modified surveillance criteria for UTIs are necessary.

  15. Lineament Domain of Regional Strike-Slip Corridor: Insight from the Neogene Transtensional De Geer Transform Fault in NW Spitsbergen

    NASA Astrophysics Data System (ADS)

    Cianfarra, P.; Salvini, F.

    2015-05-01

    Lineaments on regional scale images represent controversial features in tectonic studies. Published models explain the presence of the lineament domains in most geodynamic environments as resulting from the enhanced erosion along strikes normal to the upper crustal regional extension. Despite their success in many tectonic frameworks, these models fail to explain the existing lineament domains in the regional strike-slip corridors that separate regional blocks, including the transform faults. The present paper investigates the lineament distribution in such environments, and specifically presents the results from a study along the shear corridor of the De Geer Transform Fault in the North Atlantic, responsible for the separation and drifting away between Northern Greenland and the Svalbard Archipelago since Oligocene times. The study spans from satellite image analysis and outcrop scale investigations to a more regional analysis on a digital bathymetric model of the North Atlantic-Arctic Ocean. Lineaments were automatically detected in the spectral band 8 (0.52-0.9 μm) of a Landsat 7 image (15 m/pixel resolution). A total of 320 image lineaments were extracted from both the regional and the local scale investigations and statistically analyzed. Results from the multi-scalar lineament analyses revealed the existence of a main N-S lineament domain regionally persistent from the De Geer corridor to the western margin of northern Spitsbergen where it relates to the youngest, post-Oligocene, tectonics observed onshore. This is confirmed by field observations showing that the N-S faults represent the youngest brittle deformation system and systematically cut the deformations associated with the building of the Tertiary West Spitsbergen fold and thrust belt. The N-S lineament domain is the result of the activity of a larger, regional scale tectonic feature, NW-SE oriented and responsible for the localized extension within its deformation corridor, the De Geer Transform

  16. Zoledronic acid causes γδ T cells to target monocytes and down-modulate inflammatory homing

    PubMed Central

    Fowler, Daniel W; Copier, John; Dalgleish, Angus G; Bodman-Smith, Mark D

    2014-01-01

    Zoledronic acid (ZA) is a potential immunotherapy for cancer because it can induce potent γδ T-cell-mediated anti-tumour responses. Clinical trials are testing the efficacy of intravenous ZA in cancer patients; however, the effects of systemic ZA on the activation and migration of peripheral γδ T cells remain poorly understood. We found that γδ T cells within ZA-treated peripheral blood mononuclear cells were degranulating, as shown by up-regulated expression of CD107a/b. Degranulation was monocyte dependent because CD107a/b expression was markedly reduced in the absence of CD14+ cells. Consistent with monocyte-induced degranulation, we observed γδ T-cell-dependent induction of monocyte apoptosis, as shown by phosphatidylserine expression on monocytes and decreased percentages of monocytes in culture. Despite the prevailing paradigm that ZA promotes tumour homing in γδ T cells, we observed down-modulation of their tumour homing capacity, as shown by decreased expression of the inflammatory chemokine receptors CCR5 and CXCR3, and reduced migration towards the inflammatory chemokine CCL5. Taken together our data suggest that ZA causes γδ T cells to target monocytes and down-modulate the migratory programme required for inflammatory homing. This study provides novel insight into how γδ T cells interact with monocytes and the possible implications of systemic use of ZA in cancer. PMID:24912747

  17. Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications

    PubMed Central

    2012-01-01

    Background Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity. Results We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells. Conclusions Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells. PMID:22316211

  18. CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef.

    PubMed Central

    Chen, B K; Gandhi, R T; Baltimore, D

    1996-01-01

    The human immunodeficiency virus type 1 (HIV-1) genes vpu, env, and nef have all been implicated in modulating the levels of cell surface CD4 on infected cells. To quantitatively assess the relative contribution of each gene product to the regulation of CD4 during HIV infection of Jurkat T cells and peripheral blood mononuclear cells, we have developed an infectious HIV reporter system which expresses different combinations of these genes. To distinguish infected cells in the early or late stages of infection from uninfected cells, these viruses were designed to express human placental alkaline phosphatase with the kinetics of either early or late viral genes. Flow cytometry to detect placental alkaline phosphatase and CD4 in infected cells showed that vpu, env, and nef are independently capable of down-modulation of CD4. As predicted by their respective expression patterns, nef down-modulated CD4 rapidly during the early phase of virus infection whereas vpu and env functioned late in the infection. In both Jurkat cells and peripheral blood mononuclear cells, a combination of the three genes was more efficient than any one or two genes, demonstrating that all three genes are required to achieve maximal CD4 down-modulation. In primary cells, down-modulation of CD4 was less efficient than in Jurkat cells and there was a stronger dependence on nef function for reducing cell surface CD4. HIV therefore has three genes that are able to independently down-modulate CD4; together, they can eliminate the bulk of cell surface CD4. PMID:8709227

  19. Human CD6 Down-Modulation following T-Cell Activation Compromises Lymphocyte Survival and Proliferative Responses

    PubMed Central

    Carrasco, Esther; Escoda-Ferran, Cristina; Climent, Núria; Miró-Julià, Cristina; Simões, Inês T.; Martínez-Florensa, Mario; Sarukhan, Adelaida; Carreras, Esther; Lozano, Francisco

    2017-01-01

    Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3− (Tact) and FoxP3+ (Treg) T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T cells with activated (CD25+) or effector memory (effector memory T cell, CD45RA−CCR7−) phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA−CCR7+) counterparts. CD6lo/− T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses. PMID:28713387

  20. Human CD6 Down-Modulation following T-Cell Activation Compromises Lymphocyte Survival and Proliferative Responses.

    PubMed

    Carrasco, Esther; Escoda-Ferran, Cristina; Climent, Núria; Miró-Julià, Cristina; Simões, Inês T; Martínez-Florensa, Mario; Sarukhan, Adelaida; Carreras, Esther; Lozano, Francisco

    2017-01-01

    Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3(-) (Tact) and FoxP3(+) (Treg) T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4(+) and CD8(+) T cells with activated (CD25(+)) or effector memory (effector memory T cell, CD45RA(-)CCR7(-)) phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA(-)CCR7(+)) counterparts. CD6(lo/-) T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6(hi) T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses.

  1. [Secret medicines].

    PubMed

    Bonnemain, H

    2001-01-01

    Secret medicines had two characteristics: their formula remained unknown and they were prepared by many kinds of people. Before 1728 there were no general laws about these secret medicines but only peculiar rules. From 1728 to 1778, the King edicted rigorous rules in order to limit the number of secret medicines. Between 1778 and 1789, the law became more definite and the Royal Society of Medicine gave advices. The Law of Germinal An-XI forbid secret medicines but since 1805, some compromises took place. Slowly, secret medicines were replaced by pharmaceutics and new set of laws.

  2. Human immunodeficiency virus type 1 Nef-induced down-modulation of CD4 is due to rapid internalization and degradation of surface CD4.

    PubMed Central

    Rhee, S S; Marsh, J W

    1994-01-01

    Human immunodeficiency virus type 1 (HIV-1) Nef is a myristylated protein with a relative molecular mass of 27 kDa, is localized to the cytoplasmic surfaces of cellular membranes, and has been reported to down-modulate CD4 in human T cells. To understand the mechanism of HIV-1 Nef-mediated down-modulation of cell surface CD4, we expressed Nef protein in human T-cell line VB. Expression of HIV-1 Nef protein down-modulated surface CD4 molecules. In pulse-chase experiments, CD4 molecules in Nef-expressing cells were synthesized at normal levels. However, the bulk of newly synthesized CD4 protein was degraded with a half-life of approximately 6 h, compared with the 24-h half-life in control cells. This Nef-induced acceleration of CD4 turnover was inhibited by lysosomotropic agents NH4Cl and chloroquine as well as by the protease inhibitor leupeptin. Surface CD4 biotinylation experiments demonstrated that CD4 molecules in Nef-expressing T cells are transported to the plasma membrane with normal kinetics but are then rapidly internalized. Therefore, HIV-1 Nef-induced down-modulation of CD4 is due to rapid internalization of surface CD4 and subsequent degradation by an acid-dependent process, potentially lysosomal. Additionally, in a Nef-expressing cell, we find accelerated dissociation of the T-cell tyrosine kinase p56lck and CD4 but only after the complex reaches the plasma membrane. This implies that HIV-1 Nef protein might play a role in triggering a series of T-cell activation-like events, which contribute to p56lck dissociation and internalization of surface CD4 molecules. Images PMID:8035515

  3. CD4 and MHC class I down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates

    PubMed Central

    Gray, Lachlan R.; Gabuzda, Dana; Cowley, Daniel; Ellett, Anne; Chiavaroli, Lisa; Wesselingh, Steven L.; Churchill, Melissa J.; Gorry, Paul R.

    2015-01-01

    HIV-1 nef undergoes adaptive evolution in the CNS, reflecting altered requirements for HIV-1 replication in macrophages/microglia and brain-specific immune selection pressures. The role of Nef in HIV-1 neurotropism and the pathogenesis of HIV-associated dementia (HAD) is unclear. In this study, we characterized 82 nef alleles cloned from brain, CSF, spinal cord and blood/lymphoid tissue-derived HIV-1 isolates from 7 subjects with HAD. CNS isolate-derived nef alleles were genetically compartmentalized and had reduced sequence diversity compared to those from lymphoid tissue isolates. Defective nef alleles predominated in a brain-derived isolate from one of the 7 subjects (MACS2-br). The ability of Nef to down-modulate CD4 and MHC class 1 (MHC-1) was generally conserved among nef alleles from both CNS and lymphoid tissues. However, the potency of CD4 and MHC-1 down-modulation was variable, which was associated with sequence alterations known to influence these Nef functions. These results suggest that CD4 and MHC-1 down-modulation are highly conserved functions among nef alleles from CNS- and lymphoid tissue-derived HIV-1 isolates that may contribute to viral replication and escape from immune surveillance in the CNS. PMID:21165790

  4. Two year study of CO2, CH4 and N2O dynamics and fluxes in four rivers in Belgium (Meuse, Ourthe, Geer and Blanc Gravier)

    NASA Astrophysics Data System (ADS)

    Borges, Alberto V.; Darchambeau, François; Beulen, Aurore

    2013-04-01

    Two rivers and two streams close to the city of Liège in Belgium (Meuse, Ourthe, Geer and Blanc Gravier) were sampled to describe the dynamics of CO2, CH4 and N2O (for the first time in Belgium for freshwaters). The four systems were chosen to cover a gradient of size (stream to river) and of human influence (mainly forested to mainly agricultural watersheds). The study covers the period from February 2011 to March 2013 with weekly sampling in surface waters. The variables were very contrasted in the four systems, the Geer showing a strong enrichment in nitrogen NH4+ et NO2-) and phosphorous in relation to the other three systems. The O2 concentrations were much lower, and the concentration of CH4, N2O and pCO2 were much higher in the Geer than in other three systems. The concentrations in CH4, N2O and pCO2 were higher in the Ourthe than in the Meuse and than in the Blanc Gravier. Marked seasonal variations were observed in the 4 systems. In general the concentration of CH4, N2O and pCO2 were higher in summer than in winter. This is related on one hand to the increase of temperature in summer that stimulates bacterial activity. Also in summer, the availability of organic matter for bacterial activity is higher after the spring phytoplankton blooms and also from allochthnous inputs from the watersheds. The increase of temperature and bacterial consumption of O2 in the water column leads to a lesser O2 penetration in the sediments that could stimulate benthic anaerobic processes among which methanogenesis and denitrification, leading to an increase of CH4 and N2O in the water column. Also, the production of N2O by denitrification strongly increases at low O2. During low water, the increase of residence time of the water mass and the decrease of current (decrease of degasing) allow an accumulation of CO2, CH4 and N2O in the water column. On the contrary during high water, dilution and increase of current (increase of degasing) lead to a decrease of concentrations

  5. Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile.

    PubMed

    Elia, Angela Rita; Cappello, Paola; Puppo, Maura; Fraone, Tiziana; Vanni, Cristina; Eva, Alessandra; Musso, Tiziana; Novelli, Francesco; Varesio, Luigi; Giovarelli, Mirella

    2008-12-01

    Dendritic cells (DCs) are the most potent antigen-presenting cells and fine-tune the immune response. We have investigated hypoxia's effects on the differentiation and maturation of DCs from human monocytes in vitro, and have shown that it affects DC functions. Hypoxic immature DCs (H-iDCs) significantly fail to capture antigens through down-modulation of the RhoA/Ezrin-Radixin-Moesin pathway and the expression of CD206. Moreover, H-iDCs released higher levels of CXCL1, VEGF, CCL20, CXCL8, and CXCL10 but decreased levels of CCL2 and CCL18, which predict a different ability to recruit neutrophils rather than monocytes and create a proinflammatory and proangiogenic environment. By contrast, hypoxia has no effect on DC maturation. Hypoxic mature DCs display a mature phenotype and activate both allogeneic and specific T cells like normoxic mDCs. This study provides the first demonstration that hypoxia inhibits antigen uptake by DCs and profoundly changes the DC chemokine expression profile and may have a critical role in DC differentiation, adaptation, and activation in inflamed tissues.

  6. Concomitant helminth infection downmodulates the Vaccinia virus-specific immune response and potentiates virus-associated pathology.

    PubMed

    Gazzinelli-Guimarães, Pedro Henrique; de Freitas, Lorena Falabella Daher; Gazzinelli-Guimarães, Ana Clara; Coelho, Fabiana; Barbosa, Fernando Sérgio; Nogueira, Denise; Amorim, Chiara; Dhom-Lemos, Lucas de Carvalho; Oliveira, Luciana Maria; da Silveira, Alexandre Barcelos; da Fonseca, Flávio Guimarães; Bueno, Lilian Lacerda; Fujiwara, Ricardo Toshio

    2017-01-01

    The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8(+) T cells, the marked reduction of circulating CD4(+) T cells producing IFN-γ, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host. On the other hand, when evaluating the impact of the co-infection on the parasitic burden, co-infected mice presented a marked decrease in the total number of migrating Ascaris lung-stage larvae in comparison with Ascaris mono-infection. Taken together, our major findings suggest that Ascaris and VACV co-infection may potentiate the virus-associated pathology by the downmodulation of the VACV-specific immune response. Moreover, this study provides new evidence of how helminth parasites may influence the course of a coincident viral infection.

  7. In vitro pediculicidal activity of herbal shampoo base on Thai local plants against head louse (Pediculus humanus capitis De Geer).

    PubMed

    Rassami, Watcharawit; Soonwera, Mayura

    2013-04-01

    Head lice infestation, a worldwide head infestation caused Pediculus humanus capitis De Geer, is an important public health problem in Thailand. Several chemical pediculicides have lost in efficacy due to increasing resistance of lice against insecticide. Therefore, non-toxic alternative products, such as natural products from plants, e.g. plant extract pediculicides, are needed for head lice control. The aims of this study were to evaluate the potential of pediculicidal activity of herbal shampoo base on three species of Thai local plants (Accacia concinna (Willd.) DC, Averrhoa bilimbi Linn. and Tamarindus indica Linn.) against head lice and to compare them with carbaryl shampoo (Hafif shampoo®; 0.6% w/v carbaryl) and non-treatment control in order to assess their in vitro. Doses of 0.12 and 0.25 ml/cm2 of each herbal shampoo were applied to filter paper, and ten head lice were place on the filter paper. The mortalities of head lice on the filter paper were recorded at 1, 5, 10, 30 and 60 min by sterio-microscope. All herbal shampoos at 0.25 ml/cm2 were more effective pediculicide than carbaryl shampoo with 100% mortality at 5 min. The median lethal time (LT50) of all herbal shampoos at 0.25 ml/cm2 showed no significant differences over at 0.12 ml/cm2 (P<0.01). The most effective pediculicide was T. indica extract shampoo, followed by Av. bilimbi extract shampoo and Ac. concinna extract shampoo, with LT50 values<1.0 min. Our data showed that all herbal shampoos have high potential of pediculicide to head lice treatments for schoolchildren.

  8. Laboratory evaluation of a native strain of Beauveria bassiana for controlling Dermanyssus gallinae (De Geer, 1778) (Acari: Dermanyssidae).

    PubMed

    Immediato, Davide; Camarda, Antonio; Iatta, Roberta; Puttilli, Maria Rita; Ramos, Rafael Antonio Nascimento; Di Paola, Giancarlo; Giangaspero, Annunziata; Otranto, Domenico; Cafarchia, Claudia

    2015-09-15

    The poultry red mite, Dermanyssus gallinae (De Geer, 1778) (Acari: Dermanyssidae) is one of the most economically important ectoparasites of laying hens worldwide. Chemical control of this mite may result in environmental and food contamination, as well as the development of drug resistance. High virulence of Beauveria bassiana sensu lato strains isolated from naturally infected hosts or from their environment has been demonstrated toward many arthropod species, including ticks. However, a limited number of studies have assessed the use of B. bassiana for the control of D. gallinae s.l. and none of them have employed native strains. This study reports the pathogenicity of a native strain of B. bassiana (CD1123) against nymphs and adults of D. gallinae. Batches of nymph and adult mites (i.e., n=720 for each stage) for treated groups (TGs) were placed on paper soaked with a 0.1% tween 80 suspension of B. bassiana (CIS, 10(5), 10(7) and 10(9) conidia/ml), whilst 240 untreated control mites for each stage (CG) were exposed only to 0.1% tween 80. The mites in TG showed a higher mortality at all stages (p<0.01) when compared to CG, depending on the time of exposure and the conidial concentration. A 100% mortality rate was recorded using a CIS of 10(9) conidia/ml 12 days post infection (DPI) in adults and 14 DPI in nymphs. B. bassiana suspension containing 10(9) conidia/ml was highly virulent towards nymph and adult stages of D. gallinae, therefore representing a possible promising natural product to be used in alternative or in combination to other acaricidal compounds currently used for controlling the red mite.

  9. The Secrets of Acinetobacter Secretion.

    PubMed

    Weber, Brent S; Kinsella, Rachel L; Harding, Christian M; Feldman, Mario F

    2017-02-16

    Infections caused by the bacterial pathogen Acinetobacter baumannii are a mounting concern for healthcare practitioners as widespread antibiotic resistance continues to limit therapeutic treatment options. The biological processes used by A. baumannii to cause disease are not well defined, but recent research has indicated that secreted proteins may play a major role. A variety of mechanisms have now been shown to contribute to protein secretion by A. baumannii and other pathogenic species of Acinetobacter, including a type II secretion system (T2SS), a type VI secretion system (T6SS), autotransporter, and outer membrane vesicles (OMVs). In this review, we summarize the current knowledge of secretion systems in Acinetobacter species, and highlight their unique aspects that contribute to the pathogenicity and persistence of these emerging pathogens.

  10. Necator americanus and helminth co-infections: further down-modulation of hookworm-specific type 1 immune responses.

    PubMed

    Geiger, Stefan Michael; Alexander, Neal Douglas Edward; Fujiwara, Ricardo Toshio; Brooker, Simon; Cundill, Bonnie; Diemert, David Joseph; Correa-Oliveira, Rodrigo; Bethony, Jeffrey Michael

    2011-09-01

    Helminth co-infection in humans is common in tropical regions of the world where transmission of soil-transmitted helminths such as Ascaris lumbricoides, Trichuris trichiura, and the hookworms Necator americanus and Ancylostoma duodenale as well as other helminths such as Schistosoma mansoni often occur simultaneously. We investigated whether co-infection with another helminth(s) altered the human immune response to crude antigen extracts from either different stages of N. americanus infection (infective third stage or adult) or different crude antigen extract preparations (adult somatic and adult excretory/secretory). Using these antigens, we compared the cellular and humoral immune responses of individuals mono-infected with hookworm (N. americanus) and individuals co-infected with hookworm and other helminth infections, namely co-infection with either A. lumbricoides, Schistosoma mansoni, or both. Immunological variables were compared between hookworm infection group (mono- versus co-infected) by bootstrap, and principal component analysis (PCA) was used as a data reduction method. Contrary to several animal studies of helminth co-infection, we found that co-infected individuals had a further downmodulated Th1 cytokine response (e.g., reduced INF-γ), accompanied by a significant increase in the hookworm-specific humoral immune response (e.g. higher levels of IgE or IgG4 to crude antigen extracts) compared with mono- infected individuals. Neither of these changes was associated with a reduction of hookworm infection intensity in helminth co-infected individuals. From the standpoint of hookworm vaccine development, these results are relevant; i.e., the specific immune response to hookworm vaccine antigens might be altered by infection with another helminth.

  11. Down-modulation of Bcl-2 sensitizes PTEN-mutated prostate cancer cells to starvation and taxanes.

    PubMed

    Calastretti, Angela; Gatti, Giuliana; Quaresmini, Carolina; Bevilacqua, Annamaria

    2014-10-01

    The critical role of PTEN in regulating the PI3K/Akt/mTOR signaling pathway raises the possibility that targeting downstream effectors of the PI3K pathway, such as Bcl-2, might be an effective anti-proliferative strategy for PTEN-deficient prostate cancer cells. Four prostate cancer cell lines (LNCaP, PC3, DU145, 22Rv1) were assayed for their levels of total Akt and Ser473 phosphorylated Akt (p-Akt) by Western Blotting; their growth rates and sensitivity to different doses of paclitaxel were determined by cell counts after Trypan Blue dye exclusion assay. Cells were subjected to different combinations of starvation (growth factors and/or aminoacids withdrawal), paclitaxel treatment and Bcl-2 silencing by siRNA. Cell viability was evaluated by Trypan Blue dye exclusion assay, Propidium Iodide (PI) and Annexin-V/PI staining. We assessed the sensitivity of different prostate cancer cell lines to starvation and we observed a differential response correlated to the levels of Akt activation. The four prostate cancer cell lines also showed different sensitivity to taxol treatments; LNCaP and 22Rv1 cells were more resistant to paclitaxel than DU145 and PC3 cells. Combining taxol with growth factors and aminoacids deprivation leaded to a more than additive reduction of cell viability compared to single treatments in PTEN-mutant LNCaP cells. Down-modulation of anti-apoptotic Bcl-2 protein by siRNA sensitized LNCaP cells to taxanes and starvation induced cell death. Silencing Bcl-2 in PTEN-mutated prostate cancer cells enhances the apoptotic effects of combined starvation and taxol treatments, indicating that inhibition of Bcl-2 may be of significant value in PTEN-mutant tumor therapy. © 2014 Wiley Periodicals, Inc.

  12. Vpu Downmodulates Two Distinct Targets, Tetherin and Gibbon Ape Leukemia Virus Envelope, through Shared Features in the Vpu Cytoplasmic Tail

    PubMed Central

    Stephens, Edward B.; Johnson, Marc C.

    2012-01-01

    During human immunodeficiency virus-1 (HIV-1) assembly, the host proteins CD4 (the HIV-1 receptor) and tetherin (an interferon stimulated anti-viral protein) both reduce viral fitness. The HIV-1 accessory gene Vpu counteracts both of these proteins, but it is thought to do so through two distinct mechanisms. Modulation of CD4 likely occurs through proteasomal degradation from the endoplasmic reticulum. The exact mechanism of tetherin modulation is less clear, with possible roles for degradation and alteration of protein transport to the plasma membrane. Most investigations of Vpu function have used different assays for CD4 and tetherin. In addition, many of these investigations used exogenously expressed Vpu, which could result in variable expression levels. Thus, few studies have investigated these two Vpu functions in parallel assays, making direct comparisons difficult. Here, we present results from a rapid assay used to simultaneously investigate Vpu-targeting of both tetherin and a viral glycoprotein, gibbon ape leukemia virus envelope (GaLV Env). We previously reported that Vpu modulates GaLV Env and prevents its incorporation into HIV-1 particles through a recognition motif similar to that found in CD4. Using this assay, we performed a comprehensive mutagenic scan of Vpu in its native proviral context to identify features required for both types of activity. We observed considerable overlap in the Vpu sequences required to modulate tetherin and GaLV Env. We found that features in the cytoplasmic tail of Vpu, specifically within the cytoplasmic tail hinge region, were required for modulation of both tetherin and GaLV Env. Interestingly, these same regions features have been determined to be critical for CD4 downmodulation. We also observed a role for the transmembrane domain in the restriction of tetherin, as previously reported, but not of GaLV Env. We propose that Vpu may target both proteins in a mechanistically similar manner, albeit in different cellular

  13. AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress

    PubMed Central

    Rasool, R U; Nayak, D; Chakraborty, S; Faheem, M M; Rah, B; Mahajan, P; Gopinath, V; Katoch, A; Iqra, Z; Yousuf, S K; Mukherjee, D; Kumar, L D; Nargotra, A; Goswami, A

    2017-01-01

    The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT. The molecular dynamics studies identified important interactions, which may be responsible for the AKT inhibition and efficacy of 3-AWA towards AKT binding pocket. Interestingly, the p21 deceleration was rescued by incubating the cells with 3-AWA in the presence of an ER stress inhibitor, Salubrinal. Furthermore, we demonstrated that p21 expression decreases solitarily in Par-4+/+ MEFs; albeit, ER stress-induced JNK activation was observed in both Par-4+/+ and Par-4−/− MEFs. Par-4 knockdown or overexpression studies established that ectopic Par-4 along with ER stress are not sufficient to downregulate p21 in PC-3 cells but are adequate for DU-145 cells and that the ER stress inflicted activation of JNK, inhibition of AKT and Par-4 induction are all crucial to p21 downmodulation by 3-AWA. By using isogenic cell lines, such as HCT-116 p53+/+ and HCT-116 p53−/−, we found that deceleration in p21 expression due to ER stress is p53 independent. Moreover, in orthotopic carcinogen-induced rat colorectal carcinoma model, we found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil. PMID:28530706

  14. Vpu downmodulates two distinct targets, tetherin and gibbon ape leukemia virus envelope, through shared features in the Vpu cytoplasmic tail.

    PubMed

    Lucas, Tiffany M; Janaka, Sanath K; Stephens, Edward B; Johnson, Marc C

    2012-01-01

    During human immunodeficiency virus-1 (HIV-1) assembly, the host proteins CD4 (the HIV-1 receptor) and tetherin (an interferon stimulated anti-viral protein) both reduce viral fitness. The HIV-1 accessory gene Vpu counteracts both of these proteins, but it is thought to do so through two distinct mechanisms. Modulation of CD4 likely occurs through proteasomal degradation from the endoplasmic reticulum. The exact mechanism of tetherin modulation is less clear, with possible roles for degradation and alteration of protein transport to the plasma membrane. Most investigations of Vpu function have used different assays for CD4 and tetherin. In addition, many of these investigations used exogenously expressed Vpu, which could result in variable expression levels. Thus, few studies have investigated these two Vpu functions in parallel assays, making direct comparisons difficult. Here, we present results from a rapid assay used to simultaneously investigate Vpu-targeting of both tetherin and a viral glycoprotein, gibbon ape leukemia virus envelope (GaLV Env). We previously reported that Vpu modulates GaLV Env and prevents its incorporation into HIV-1 particles through a recognition motif similar to that found in CD4. Using this assay, we performed a comprehensive mutagenic scan of Vpu in its native proviral context to identify features required for both types of activity. We observed considerable overlap in the Vpu sequences required to modulate tetherin and GaLV Env. We found that features in the cytoplasmic tail of Vpu, specifically within the cytoplasmic tail hinge region, were required for modulation of both tetherin and GaLV Env. Interestingly, these same regions features have been determined to be critical for CD4 downmodulation. We also observed a role for the transmembrane domain in the restriction of tetherin, as previously reported, but not of GaLV Env. We propose that Vpu may target both proteins in a mechanistically similar manner, albeit in different cellular

  15. Modeling the impact of the nitrate contamination on groundwater at the groundwater body scale : The Geer basin case study (Invited)

    NASA Astrophysics Data System (ADS)

    Brouyere, S.; Orban, P.; Hérivaux, C.

    2009-12-01

    In the next decades, groundwater managers will have to face regional degradation of the quantity and quality of groundwater under pressure of land-use and socio-economic changes. In this context, the objectives of the European Water Framework Directive require that groundwater be managed at the scale of the groundwater body, taking into account not only all components of the water cycle but also the socio-economic impact of these changes. One of the main challenges remains to develop robust and efficient numerical modeling applications at such a scale and to couple them with economic models, as a support for decision support in groundwater management. An integrated approach between hydrogeologists and economists has been developed by coupling the hydrogeological model SUFT3D and a cost-benefit economic analysis to study the impact of agricultural practices on groundwater quality and to design cost-effective mitigation measures to decrease nitrate pressure on groundwater so as to ensure the highest benefit to the society. A new modeling technique, the ‘Hybrid Finite Element Mixing Cell’ approach has been developed for large scale modeling purposes. The principle of this method is to fully couple different mathematical and numerical approaches to solve groundwater flow and solute transport problems. The mathematical and numerical approaches proposed allows an adaptation to the level of local hydrogeological knowledge and the amount of available data. In combination with long time series of nitrate concentrations and tritium data, the regional scale modelling approach has been used to develop a 3D spatially distributed groundwater flow and solute transport model for the Geer basin (Belgium) of about 480 km2. The model is able to reproduce the spatial patterns of nitrate concentrations together nitrate trends with time. The model has then been used to predict the future evolution of nitrate trends for two types of scenarios: (i) a “business as usual scenario

  16. B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway.

    PubMed

    Milillo, M Ayelén; Velásquez, Lis N; Trotta, Aldana; Delpino, M Victoria; Marinho, Fábio V; Balboa, Luciana; Vermeulen, Mónica; Espindola, Sonia L; Rodriguez-Rodrigues, Nahuel; Fernández, Gabriela C; Oliveira, Sergio Costa; Giambartolomei, Guillermo H; Barrionuevo, Paula

    2017-08-01

    Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to persist and establish a chronic infection inside its host. We have previously reported that the infection of human monocytes/macrophages with B. abortus inhibits the IFN-γ-induced MHC-I cell surface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial viability and results from the capacity of B. abortus to retain the MHC-I molecules within the Golgi apparatus. Furthermore, we recently demonstrated that epidermal growth factor receptor (EGFR) pathway is involved in this phenomenon and that this is an early event during infection. However, the components and mechanisms whereby B. abortus is able to down-modulate MHC-I remained to be elucidated. In this study we demonstrated that the down-modulation of MHC-I expression is not mediated by well-known Brucella virulence factors but instead by B. abortus RNA, a PAMP associated to viability (vita-PAMP). Surprisingly, completely degraded RNA was also able to inhibit MHC-I expression to the same extent as intact RNA. Accordingly, B. abortus RNA and its degradation products were able to mimic the MHC-I intracellular retention within the Golgi apparatus observed upon infection. We further demonstrated that TLR8, a single-stranded RNA and RNA degradation products sensor, was involved in MHC-I inhibition. On the other hand, neutralization of the EGFR reversed the MHC-I inhibition, suggesting a connection between the TLR8 and EGFR pathways. Finally, B. abortus RNA-treated macrophages display diminished capacity of antigen presentation to CD8+ T cells. Overall, our results indicate that the vita-PAMP RNA as well as its degradation products constitute novel virulence factors whereby B. abortus, by a TLR8-dependent mechanism and through the EGFR pathway, inhibits the IFN-γ-induced MHC-I surface expression on human monocytes/macrophages. Thus, bacteria can hide within infected cells and avoid the

  17. Downmodulation of CCR7 by HIV-1 Vpu results in impaired migration and chemotactic signaling within CD4⁺ T cells.

    PubMed

    Ramirez, Peter W; Famiglietti, Marylinda; Sowrirajan, Bharatwaj; DePaula-Silva, Ana Beatriz; Rodesch, Christopher; Barker, Edward; Bosque, Alberto; Planelles, Vicente

    2014-06-26

    The chemokine receptor CCR7 plays a crucial role in the homing of central memory and naive T cells to peripheral lymphoid organs. Here, we show that the HIV-1 accessory protein Vpu downregulates CCR7 on the surface of CD4(+) T cells. Vpu and CCR7 were found to specifically interact and colocalize within the trans-Golgi network, where CCR7 is retained. Downmodulation of CCR7 did not involve degradation or endocytosis and was strictly dependent on Vpu expression. Stimulation of HIV-1-infected primary CD4(+) T cells with the CCR7 ligand CCL19 resulted in reduced mobilization of Ca(2+), reduced phosphorylation of Erk1/2, and impaired migration toward CCL19. Specific amino acid residues within the transmembrane domain of Vpu that were previously shown to be critical for BST-2 downmodulation (A14, A18, and W22) were also necessary for CCR7 downregulation. These results suggest that BST-2 and CCR7 may be downregulated via similar mechanisms.

  18. Glacial landforms on German Bank, Scotian Shelf: evidence for Late Wisconsinan ice-sheet dynamics and implications for the formation of De Geer moraines

    USGS Publications Warehouse

    Todd, Brian J.; Valentine, Page C.; Longva, Oddvar; Shaw, John

    2007-01-01

    The extent and behaviour of the southeast margin of the Laurentide Ice Sheet in Atlantic Canada is of significance in the study of Late Wisconsinan ice sheet-ocean interactions. Multibeam sonar imagery of subglacial, ice-marginal and glaciomarine landforms on German Bank, Scotian Shelf, provides evidence of the pattern of glacial-dynamic events in the eastern Gulf of Maine. Northwest-southeast trending drumlins and megaflutes dominate northern German Bank. On southern German Bank, megaflutes of thin glacial deposits create a distinct northwest-southeast grain. Lobate regional moraines (>10km long) are concave to the northwest, up-ice direction and strike southwest-northeast, normal to the direction of ice flow. Ubiquitous, overlying De Geer moraines (

  19. Scanning electron microscopy of foreleg tarsal sense organs of the poultry red mite, Dermanyssus gallinae (DeGeer) (Acari:Dermanyssidae).

    PubMed

    Cruz, M D Soler; Robles, M C Vega; Jespersen, J B; Kilpinen, O; Birkett, M; Dewhirst, S; Pickett, J

    2005-01-01

    Scanning electron microscopy (SEM) studies on the poultry red mite, Dermanyssus gallinae (DeGeer), showed that the tip of the foreleg tarsus of both sexes and early instar stages (larvae, protonymph and deutonymph) bears a cluster of 10 blunt peg-type sensillae. Diversity in size, shape and surface features of the wall of these sensillae characterize the sensilla complex (sensory field). Two short setae (1 and 2) with smooth walls lack detectable pores, whereas three medium-sized setae (4, 5 and 8) bear pores in the wall. Four medium or long setae (3, 6, 7 and 9) have longitudinal grooves or ribs in the wall, whilst one seta (10) possesses both pores and grooves in the wall. Based on the morphology, it is suggested that the porous setae could be olfactory receptors, and the grooved setae could be mechanoreceptors.

  20. Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60.

    PubMed

    Arapović, Jurica; Lenac Rovis, Tihana; Reddy, Anil Butchi; Krmpotić, Astrid; Jonjić, Stipan

    2009-11-01

    Both human and mouse cytomegalovirus (CMV) encode proteins that inhibit the activation of NK cells by down-regulating the cellular ligands for activating NK cell receptor, NKG2D. MCMV proteins m145, m152 and m155 interfere with the expression of all known NKG2D ligands, MULT-1, RAE-1 family members and H60, respectively, whereas m138 affects the expression of MULT-1 and H60. Here we show that m152 affects the maturation of newly synthesized RAE-1 molecules, but is not sufficient to prevent surface expression of RAE-1varepsilon. We have identified m138 as a main inhibitor of the surface expression of RAE-1varepsilon. In contrast to m152, m138 affects the surface-resident protein leading to its endocytosis, which can be prevented by a dynamin inhibitor. Moreover, we demonstrated that m138 does not need other viral proteins to down-modulate the expression of RAE-1varepsilon.

  1. Downmodulation of vaccine-induced immunity and protection against the intracellular bacterium Francisella tularensis by the inhibitory receptor FcγRIIB.

    PubMed

    Franz, Brian J; Li, Ying; Bitsaktsis, Constantine; Iglesias, Bibiana V; Pham, Giang; Sunagar, Raju; Kumar, Sudeep; Gosselin, Edmund J

    2015-01-01

    Fc gamma receptor IIB (FcγRIIB) is the only Fc gamma receptor (FcγR) which negatively regulates the immune response, when engaged by antigen- (Ag-) antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of FcγRIIB on immune protection against Francisella tularensis (Ft), a Category A biothreat agent. We utilized inactivated Ft (iFt) as an immunogen. Naïve and iFt-immunized FcγRIIB knockout (KO) or wildtype (WT) mice were challenged with Ft-live vaccine strain (LVS). While no significant difference in survival between naïve FcγRIIB KO versus WT mice was observed, iFt-immunized FcγRIIB KO mice were significantly better protected than iFt-immunized WT mice. Ft-specific IgA in serum and bronchial alveolar lavage, as well as IFN-γ, IL-10, and TNF-α production by splenocytes harvested from iFt-immunized FcγRIIB KO, were also significantly elevated. In addition, iFt-immunized FcγRIIB KO mice exhibited a reduction in proinflammatory cytokine levels in vivo at 5 days after challenge, which correlates with increased survival following Ft-LVS challenge in published studies. Thus, these studies demonstrate for the first time the ability of FcγRIIB to regulate vaccine-induced IgA production and downmodulate immunity and protection. The immune mechanisms behind the above observations and their potential impact on vaccine development are discussed.

  2. Infanticide secrets

    PubMed Central

    Barr, Jennieffer A.; Beck, Cheryl T.

    2008-01-01

    ABSTRACT OBJECTIVE To explore thoughts of infanticide that did not lead to the act among mothers with postpartum depression. DESIGN A phenomenologic hermeneutic study in which women were invited to share their experiences of having thoughts of infanticide. SETTING Community setting in a large metropolitan city, Brisbane, Australia. PARTICIPANTS Fifteen women who had been diagnosed as clinically depressed with postpartum onset whose babies were 12 months of age or younger. METHOD Audiotaped, in-depth interviews were transcribed verbatim. Thematic analysis commenced immediately after the first interview, and data collection continued until saturation was achieved. A questioning approach that reflected hermeneutics was facilitated by use of journals by the researchers. MAIN FINDINGS Six themes emerged from the data: imagined acts of infanticide, the experience of horror, distorted sense of responsibility, consuming negativity, keeping secrets, and managing the crisis. CONCLUSION Women who experienced nonpsychotic depression preferred not to disclose their thoughts of infanticide to health professionals, including trusted general practitioners or psychiatrists. These women were more likely to mention their suicidal thoughts than their infanticidal thoughts in order to obtain health care. General practitioners and other health professionals should directly ask about whether a woman has been experiencing thoughts of harming herself or her baby, regardless of the reason why she has presented. PMID:19074717

  3. Formation and structure of the ephippium (resting egg case) in relation to molting and egg laying in the water flea Daphnia pulex De Geer (Cladocera: Daphniidae).

    PubMed

    Hiruta, Chizue; Tochinai, Shin

    2014-07-01

    Resting eggs produced by daphnid species in response to environmental deterioration play an important role in colonizing new habitats or in re-establishing extinct populations. Females lay resting eggs into the space within the dorsal part of their carapace and form an egg case called the ephippium to protect them. Previous studies mainly reported the morphology of the completely formed ephippium and/or the forming ephippium of an uncertain stage. To understand ephippium formation and to clarify key transitions in the formation of resting eggs, we examined the structure and formation of the ephippium in the water flea Daphnia pulex De Geer (Cladocera: Daphniidae) by stereomicroscopy, histology, and scanning electron microscopy. The females used in this study produced resting eggs by obligate parthenogenesis. We divided ephippium formation into four stages based on two molts and a single ovulation, as follows. Stage I begins 13 min after molting in adult females that do not ovulate. In Stage II, immediately after the first molt, a protuberance appears beneath the neck region and the carapace begins to thicken. In Stage III, the resting eggs ovulate and the carapace in the area of the forming ephippium becomes much thicker than the normal carapace and accumulates dark pigmentation. In Stage IV, following the second molt, the female sheds the ephippium with the enclosed resting eggs and forms a new carapace. These stages will provide a useful reference for future studies on resting egg formation. © 2014 Wiley Periodicals, Inc.

  4. Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

    PubMed Central

    Almeida, Caroline de Souza; Andrade-Oliveira, Vinicius; Câmara, Niels Olsen Saraiva; Jacysyn, Jacqueline F.; Faquim-Mauro, Eliana L.

    2015-01-01

    Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a

  5. Interleukin-10 Stimulates Coxiella burnetii Replication in Human Monocytes through Tumor Necrosis Factor Down-Modulation: Role in Microbicidal Defect of Q Fever

    PubMed Central

    Ghigo, Eric; Capo, Christian; Raoult, Didier; Mege, Jean-Louis

    2001-01-01

    Coxiella burnetii, an obligate intracellular bacterium, is the agent of Q fever. The chronic form of the disease is associated with the overproduction of interleukin-10 and deficient C. burnetii killing by monocytes. We hypothesized that the replication of C. burnetii inside monocytes requires a macrophage-deactivating cytokine such as interleukin-10. In the absence of interleukin-10, C. burnetii survived but did not replicate in monocytes. C. burnetii replication (measured 15 days) was induced in interleukin-10-treated monocytes. This effect of interleukin-10 is specific since transforming growth factor β1 had no effect on bacterial replication. C. burnetii replication involves the down-modulation of tumor necrosis factor (TNF) release. First, interleukin-10 suppressed C. burnetii-stimulated production of TNF. Second, the addition of recombinant TNF to interleukin-10-treated monocytes inhibited bacterial replication. Third, the incubation of infected monocytes with neutralizing anti-TNF antibodies favored C. burnetii replication. On the other hand, deficient C. burnetii killing by monocytes from patients with chronic Q fever involves interleukin-10. Indeed, C. burnetii replication was observed in monocytes from patients with Q fever endocarditis, but not in those from patients with acute Q fever. Bacterial replication was inhibited by neutralizing anti-interleukin-10 antibodies. As monocytes from patients with endocarditis overproduced interleukin-10, the defective bacterial killing is likely related to endogenous interleukin-10. These results suggest that interleukin-10 enables monocytes to support C. burnetii replication and to favor the development of chronic Q fever. PMID:11254592

  6. Regulation of protein secretion by ... protein secretion?

    PubMed

    Atmakuri, Krishnamohan; Fortune, Sarah M

    2008-09-11

    Mycobacterium tuberculosis (Mtb) requires an alternative protein secretion system, ESX1, for virulence. Recently, Raghavan et al. (2008) reported a new regulatory circuit that may explain how ESX1 activity is controlled during infection. Mtb appears to regulate ESX1 by modulating transcription of associated genes rather than structural components of the secretion system itself.

  7. GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A

    PubMed Central

    Barcala Tabarrozzi, Andres E.; Andreone, Luz; Deckers, Julie; Castro, Carla N.; Gimeno, María L.; Ariolfo, Laura; Berguer, Paula M.; Antunica-Noguerol, María; Liberman, Ana C.; Vettorazzi, Sabine; Tuckermann, Jan P.; De Bosscher, Karolien; Perone, Marcelo J.

    2016-01-01

    Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted. PMID:27857212

  8. FTY720 Shows Promising In vitro and In vivo Preclinical Activity by Downmodulating Cyclin D1 and Phospho-Akt in Mantle Cell Lymphoma

    PubMed Central

    Liu, Qing; Alinari, Lapo; Chen, Ching-Shih; Yan, Fengting; Dalton, James T.; Lapalombella, Rosa; Zhang, Xiaoli; Mani, Rajeswaran; Lin, Teresa; Byrd, John C.; Baiocchi, Robert A.; Muthusamy, Natarajan

    2014-01-01

    Purpose Despite the progress that has been made in the treatment of mantle cell lymphoma (MCL), all patients invariably relapse with the currently available therapies. Because of the absence of curative therapy for MCL, we explored FTY720 as a novel agent against MCL. Experimental Design The cytotoxic effect of FTY720 in primary MCL tumor cells and cell lines were evaluated in vitro. The effects of FTY720 on caspase activation, generation of reactive oxygen species, and modulation of Cyclin D1 and Akt, which are implied in the pathogenesis of MCL, were investigated. The in vivo efficacy of FTY720 was evaluated in a Jeko-severe combined immunodeficient xenograft model of human MCL. Results FTY720 mediated time- and dose-dependent cytotoxicity in primary MCL tumor cells and MCL cell lines in vitro. FTY720-induced cytotoxicity occured independent of caspase activation but dependent on the generation of ROS in MCL. In addition, FTY720 treatment resulted in the time-dependent downmodulation of Cyclin D1 and accumulation of cells in G0-G1 and G2-M phases of the cell cycle with concomitant decrease in S-phase entry. Furthermore, concentrations of FTY720 that induced cytotoxicity led to decreased phospho-Akt in primary MCL cells and cell lines. Most importantly, the in vivo therapeutic activity of FTY720 was shown in severe combined immunodeficient mice engrafted with the Jeko MCL cell line. Conclusions These results provide the first evidence for a potential use of FTY720 in targeting key pathways that are operable in the pathogenesis of MCL and warrant further investigation of FTY720 in clinical trials to treat patients with MCL. PMID:20460491

  9. Determinants of acid secretion.

    PubMed

    Khanna, M U; Abraham, P

    1990-09-01

    Acid secretion is regulated by hormonal factors acting peripherally and centrally, as well as neural factors. Gastrin and histamine are the two most important peripheral hormonal stimulants, while the vagus is the predominant nerve affecting acid secretion. Meal related acid secretion occurs in three phases: cephalic, gastric and intestinal. Acid secretion is stimulated in the first two phases while it is inhibited in the intestinal phase. Proteins are potent acid stimulants but carbohydrates and fats are inhibitors. Tea, coffee, milk and alcohol are acid stimulants; on the other hand the damaging influence of spices on the stomach may not be related to increased acid secretion. Psychological stress has a variable effect. The effect of Helicobacter pylori infection on acid secretion is being elucidated. Many drugs modifying acid secretion are available and are useful in the treatment of acid peptic disease.

  10. P2X7 receptor activation downmodulates Na(+)-dependent high-affinity GABA and glutamate transport into rat brain cortex synaptosomes.

    PubMed

    Barros-Barbosa, A R; Lobo, M G; Ferreirinha, F; Correia-de-Sá, P; Cordeiro, J M

    2015-10-15

    Sodium-dependent high-affinity amino-acid transporters play crucial roles in terminating synaptic transmission in the central nervous system (CNS). However, there is lack of information about the mechanisms underlying the regulation of amino-acid transport by fast-acting neuromodulators, like ATP. Here, we investigated whether activation of the ATP-sensitive P2X7 receptor modulates Na(+)-dependent high-affinity γ-aminobutyric acid (GABA) and glutamate uptake into nerve terminals (synaptosomes) of the rat cerebral cortex. Radiolabeled neurotransmitter accumulation was evaluated by liquid scintillation spectrometry. The cell-permeant sodium-selective fluorescent indicator, SBFI-AM, was used to estimate Na(+) influx across plasma membrane. 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP, 3-300 μM), a prototypic P2X7 receptor agonist, concentration-dependently decreased [(3)H]GABA (14%) and [(14)C]glutamate (24%) uptake; BzATP decreased transport maximum velocity (Vmax) without affecting the Michaelis constant (Km) values. The selective P2X7 receptor antagonist, A-438079 (3 μM), prevented inhibition of [(3)H]GABA and [(14)C]glutamate uptake by BzATP (100 μM). The inhibitory effect of BzATP coincided with its ability to increase intracellular Na(+) and was mimicked by Na(+) ionophores, like gramicidin and monensin. Increases in intracellular Na(+) (with veratridine or ouabain) or substitution of extracellular Na(+) by N-methyl-D-glucamine (NMDG)(+) all decreased [(3)H]GABA and [(14)C]glutamate uptake and attenuated BzATP effects. Uptake inhibition by BzATP (100 μM) was also attenuated by calmidazolium, which selectively inhibits Na(+) currents through the P2X7 receptor pore. In conclusion, disruption of the Na(+) gradient by P2X7 receptor activation downmodulates high-affinity GABA and glutamate uptake into rat cortical synaptosomes. Interference with amino-acid transport efficacy may constitute a novel target for therapeutic management of cortical excitability.

  11. Authentication Without Secrets

    SciTech Connect

    Pierson, Lyndon G.; Robertson, Perry J.

    2015-11-01

    This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integrity of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.

  12. Further karyosystematic studies of the Boreonectes griseostriatus (De Geer) group of sibling species (Coleoptera, Dytiscidae)–characterisation of B. emmerichi (Falkenström, 1936) and additional European data

    PubMed Central

    Angus, Robert B.; Angus, Elizabeth M.; Jia, Fenglong; Chen, Zhen-ning; Zhang, Ying

    2015-01-01

    Abstract A lectotype is designated for the Tibetan species Deronectes emmerichi Falkenström, 1936 (Currently Boreonectes emmerichi (Falkenström)), and its habitus, as well as the median lobe and parameres of its aedeagus, are figured along with additional comparative material. Material of Boreonectes emmerichi from Sikkim (BMNH) represents the first record of a Boreonectes Angus, 2010 species from India. The karyotype of Boreonectes emmerichi is described as having 26 pairs of autosomes plus sex chromosomes which are X0 (♂), XX (♀). The karyotype is most like that of Boreonectes macedonicus (Géuorguiev, 1959), but with slight differences. Additional chromosomal information is given for Boreonectes griseostriatus griseostriatus (De Geer, 1774) in the French Alps, Boreonectes griseostriatus strandi (Brinck, 1943) on the Kola Peninsula, Boreonectes multilineatus (Falkenström, 1922) in the Pyrenees and Boreonectes ibericus (Dutton & Angus, 2007) in the Spanish Picos de Europa. PMID:25893080

  13. Further karyosystematic studies of the Boreonectesgriseostriatus (De Geer) group of sibling species (Coleoptera, Dytiscidae)-characterisation of B.emmerichi (Falkenström, 1936) and additional European data.

    PubMed

    Angus, Robert B; Angus, Elizabeth M; Jia, Fenglong; Chen, Zhen-Ning; Zhang, Ying

    2015-01-01

    A lectotype is designated for the Tibetan species Deronectesemmerichi Falkenström, 1936 (Currently Boreonectesemmerichi (Falkenström)), and its habitus, as well as the median lobe and parameres of its aedeagus, are figured along with additional comparative material. Material of Boreonectesemmerichi from Sikkim (BMNH) represents the first record of a Boreonectes Angus, 2010 species from India. The karyotype of Boreonectesemmerichi is described as having 26 pairs of autosomes plus sex chromosomes which are X0 (♂), XX (♀). The karyotype is most like that of Boreonectesmacedonicus (Géuorguiev, 1959), but with slight differences. Additional chromosomal information is given for Boreonectesgriseostriatusgriseostriatus (De Geer, 1774) in the French Alps, Boreonectesgriseostriatusstrandi (Brinck, 1943) on the Kola Peninsula, Boreonectesmultilineatus (Falkenström, 1922) in the Pyrenees and Boreonectesibericus (Dutton & Angus, 2007) in the Spanish Picos de Europa.

  14. Secrets to success.

    PubMed

    Sorrel, Amy Lynn

    2014-02-01

    A new national study reveals what it takes for physician practices to stay financially viable. Several Texas practices, among those rated as "better performers," share their secrets to success. One of those secrets, a physician says, is "hiring good people and getting out of their way."

  15. Noise and gastric secretion.

    PubMed

    Tomei, F; Papaleo, B; Baccolo, T P; Persechino, B; Spanò, G; Rosati, M V

    1994-09-01

    In view of the increasing incidence of diseases such as gastritis and ulcers in workers exposed to noise, we assessed whether noise does in fact affect gastric secretion. Then, considering the conflicting findings published on the effects of noise on gastric secretion, we also investigated whether the response was related to differences in baseline secretion, and whether it was further modified by a hydroalcoholic meal. We studied 50 dyspeptic subjects engaged in various types of work but not occupationally exposed to noise. They were exposed to a "pink noise" stimulus of 95 dB administered through earphones, lasting 15 minutes. Gastric secretion sometimes remained unchanged, sometimes increased, or sometimes even decreased in relation to the baseline hydrochloric acid secretion. The hydroalcoholic meal did not generally modify the effects of noise. These findings might help explain the differences in previous reports on this question.

  16. The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells.

    PubMed

    Arriola Benitez, Paula Constanza; Rey Serantes, Diego; Herrmann, Claudia Karina; Pesce Viglietti, Ayelén Ivana; Vanzulli, Silvia; Giambartolomei, Guillermo Hernán; Comerci, Diego José; Delpino, María Victoria

    2015-12-14

    The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway.

  17. The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells

    PubMed Central

    Arriola Benitez, Paula Constanza; Rey Serantes, Diego; Herrmann, Claudia Karina; Pesce Viglietti, Ayelén Ivana; Vanzulli, Silvia; Giambartolomei, Guillermo Hernán; Comerci, Diego José

    2015-01-01

    The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway. PMID:26667834

  18. The Presence of a vpu Gene and the Lack of Nef-Mediated Downmodulation of T Cell Receptor-CD3 Are Not Always Linked in Primate Lentiviruses ▿ †

    PubMed Central

    Schmökel, Jan; Sauter, Daniel; Schindler, Michael; Leendertz, Fabian H.; Bailes, Elizabeth; Dazza, Marie-Christine; Saragosti, Sentob; Bibollet-Ruche, Frederic; Peeters, Martine; Hahn, Beatrice H.; Kirchhoff, Frank

    2011-01-01

    Nef is an accessory protein critical for the ability of human and simian immunodeficiency viruses (HIV and SIV) to replicate efficiently in their respective hosts. Previous analyses of members of 15 different primate lentivirus lineages revealed a link between Nef function and the presence of a vpu gene. In particular, Nef proteins of all vpu-containing viruses had lost their ability to downmodulate the T cell (TCR-CD3) receptor. Here we examined Nef proteins from eight additional SIV lineages, including SIVgor, SIVwrc, SIVolc, SIVgri, SIVdrl, SIVlho, SIVden, and SIVasc, from western lowland gorillas, western red colobus monkeys, olive colobus monkeys, grivet monkeys, drills, L'Hoest's monkeys, Dent's mona monkeys, and red-tailed monkeys, respectively. We found that except for the nef gene of SIVdrl, all of them were efficiently expressed and modulated CD4, major histocompatibility complex class I (MHC-I), CD28, CXCR4, and Ii cell surface expression and/or enhanced viral infectivity and replication. Furthermore, the Nef proteins of SIVgri, SIVlho, SIVwrc, SIVolc, and SIVgor antagonized tetherin. As expected, the Nef protein of SIVgor, which carries vpu, failed to downmodulate CD3, whereas those of SIVwrc, SIVgri, SIVlho, and SIVasc, which lack vpu, were capable of performing this function. Surprisingly, however, the Nef protein of the vpu-containing SIVden strain retained the ability to downmodulate TCR-CD3, whereas that of SIVolc, which does not contain vpu, was unable to perform this function. Although the SIVden Vpu is about 20 amino acids shorter than other Vpu proteins, it degrades CD4 and antagonizes tetherin. Our data show that there are exceptions to the link between the presence of a vpu gene and nef alleles deficient in CD3 modulation, indicating that host properties also affect the selective pressure for Nef-mediated disruption of TCR-CD3 signaling. Our results are also further evidence that tetherin antagonism is a common function of primate lentivirus

  19. TSH secreting pituitary adenoma.

    PubMed

    Jha, S; Kumar, S

    2009-07-01

    Thyrotropin (TSH) secreting pituitary adenomas are a very rare cause of hyperthyroidism. They typically present with signs and symptoms of hyperthyroidism and rarely can be asymptomatic. TSH secreting tumors account for 1 percent of all pituitary adenoma. They are a rare cause of thyrotoxicosis in which adenomas completely or partially lose feedback regulation of thyroid hormones and lead to sustained stimulation of thyroid gland. The most definitive treatment of thyrotropin (TSH)-secreting pituitary adenomas is transsphenoidal removal of tumor after restoring euthyroidism. We report a case of pituitary adenoma associated with elevated serum free thyroid hormones and non-suppressed TSH levels.

  20. Six secrets of champagne

    NASA Astrophysics Data System (ADS)

    Liger-Belair, Gérard

    2015-12-01

    Popping open a bottle of champagne is one of life's great delights, but how much do you really know about the science behind this greatest of wines? Gérard Liger-Belair reveals his six favourite champagne secrets.

  1. Type VI secretion system.

    PubMed

    Salomon, Dor; Orth, Kim

    2015-03-30

    Bacteria employ a variety of tools to survive in a competitive environment. Salomon and Orth describe one such tool-the Type 6 Secretion Systems used by bacteria to deliver a variety of toxins into competing cells.

  2. Secret quality of love.

    PubMed

    Strachan-Hall, Elaine

    2016-09-01

    Many of us can recite three Donabedian dimensions of the quality of care of structure, process and outcome. Recently, I was introduced to another of Avedis Donabedian's quotes about the 'secret quality of love'.

  3. Haemophilus paragallinarum secretes metalloproteases.

    PubMed

    Rivero-García, P C; Cruz, C Vázquez; Alonso, P Sánchez; Vaca, S; Negrete-Abascal, E

    2005-10-01

    Haemophilus paragallinarum secretes metalloproteases into different culture media lacking serum. Secreted proteins, concentrated by precipitation with 70% ammonium sulphate ((NH(4))(2)SO(4)) or methanol, displayed proteolytic activity at >100 kDa molecular mass in 10% polyacrylamide gels co-polymerized with porcine gelatin (0.1%). They were active in a broad pH range (4-9); pH 7.5 being the optimum. Protease activity was inhibited by 20 mmol EDTA/L and reactivated by calcium. The proteolytic activity was heat-stable at 40, 50, and 60 degrees C, but its activity diminished at 70 degrees C or higher. Secreted proteins partially degraded chicken immunoglobulin G (IgG) and cross-reacted with a polyclonal serum against a high molecular mass protease secreted by Actinobacillus pleuropneumoniae. Extracellular proteases could play a role in infectious coryza caused by H. paragallinarum.

  4. Efficient quantum secret sharing

    NASA Astrophysics Data System (ADS)

    Qin, Huawang; Dai, Yuewei

    2016-05-01

    An efficient quantum secret sharing scheme is proposed, in which the dealer generates some single particles and then uses the operations of quantum-controlled-not and Hadamard gate to encode a determinate secret into these particles. The participants get their shadows by performing the single-particle measurements on their particles, and even the dealer cannot know their shadows. Compared to the existing schemes, our scheme is more practical within the present technologies.

  5. My4+/LeuM3- molecule and CD19 antigen are down-modulate by low affinity Fc gamma receptor II (CD32) stimulation on CD56-positive B-lymphoma cells.

    PubMed

    Ikemoto, T; Nakagawa, T; Hatanaka, M; Hasegawa, M; Kageyama, T; Hirano, M; Shimizu, A

    2000-09-01

    My4+/LeuM3- molecule is recognized by My4, but not by LeuM3, both well known mAbs to CD14. In a previous study we showed that the My4+/LeuM3- molecule on a human monoblastic cell line, U937, is not CD14, but another cell surface antigen. The roles and functions of the My4+/LeuM3- molecule remained unknown. We now report that specific stimulation of Fc gammaR with aggregated IgG or anti-Fc gammaRII antibody down-modulated the My4+/LeuM3- molecules, as well as CD19, in a case of CD56-positive B cell lymphoma. Stimulation of Fc gammaR with anti-mu antibody, which induced concomitant stimulation of sIg, did not induce down-modulation of either molecule. Stimulation of CR2 (CD21), a protein which is functionally or physically associated with CD19, with anti-CR2 (CD21) mAbs also had no effect. The modulation occurred specifically on CD56-positive B-lymphoma cells, since My4+/LeuM3(-)-positive, CD56-negative B-lymphoma cells did not respond to the stimulation. These results suggest that CD19 and My4+/LeuM3- molecules are functionally or physically associated with Fc gammaR II on CD56 positive B-lymphoma cells defined as being at a terminal B cell differentiation stage.

  6. Control of renin secretion.

    PubMed

    Abe, Y; Iwao, H; Okahara, T; Yamamoto, K

    1977-03-01

    The present study was designed to examine the interrelationship between the intrarenal vascular receptor and the sympathetic nerve, beta-adrenergic system, for renin secretion in the anesthetized dog. 1) A reduction in renal arterial pressure from a control pressure to 100 mmHg changed neither ther flow rates of all cortex zones nor renin secretion. Further reduction of renal arterial pressure to 75 mmHg resulted in a significant increase of renin secretion and a decrease of blood flow in the outer cortex. Intrarenal arterial infusion of norepinephrine at a control pressure increased a renin secretion. However, norepinephrine infusion at a reduced pressure suppressed the renin release with a recovery of the vascular resistance to the control level. These results suggest that the changes in the degree of blood flow and pressure in the renal afferent arterioles are not essential for the renin secretion,but renin secretion by the pressure reduction might be related to the autoregulatory capacity of afferent arterioles in the outer cortex. 2) At 5 min of hemorrhagic period (75 mmHg) arterial PRA elevated in control, and phenoxybenzamine and propranolol treated groups and any significant difference in responses was not observed among groups. However, at 60 min of hemorrhagic hypotensive period PRA in control and phenoxybenzamine treated groups further increased, but PRA in propranolol treated group was not alter from its 15 min value. These results indicated that the roles of vascular receptor and renal sympathetic nervous sytem in receptor and renal sympathetic nervous system in renin secretion might be separated, and that the renal sympathetic nervous system did not relate to the early response of renin release, but related to the late response. 3) Intrarenal arterial infusion of cAMP and DbcAMP resulted in a significant increase of renin release. In addition, CaC12 solution was infuesed into the renal artery and a significant rise in renal venous PRA was observed

  7. Multiparty quantum secret sharing

    SciTech Connect

    Zhang Zhanjun; Li Yong; Man Zhongxiao

    2005-04-01

    Based on a quantum secure direct communication (QSDC) protocol [Phys. Rev. A 69 052319 (2004)], we propose a (n,n)-threshold scheme of multiparty quantum secret sharing of classical messages (QSSCM) using only single photons. We take advantage of this multiparty QSSCM scheme to establish a scheme of multiparty secret sharing of quantum information (SSQI), in which only all quantum information receivers collaborate can the original qubit be reconstructed. A general idea is also proposed for constructing multiparty SSQI schemes from any QSSCM scheme.

  8. Porphyromonas gingivalis fimbriae dampen P2X7-dependent IL-1β secretion

    PubMed Central

    Morandini, Ana Carolina; Ramos-Junior, Erivan S.; Potempa, Jan; Nguyen, Ky-Anh; Oliveira, Ana Carolina; Bellio, Maria; Ojcius, David M.; Scharfstein, Julio; Coutinho-Silva, Robson

    2014-01-01

    Porphyromonas gingivalis is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-IL-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP. Here, we investigated the role of Pg fimbriae in eATP-induced IL-1β release. Bone marrow derived macrophages (BMDMs) from wild type (WT) or P2X7-deficient mice were infected with Pg (strain 381) or isogenic fimbriae deficient (strain DPG3) with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent of K+ efflux and Ca2+-iPLA2 activity. Accordingly, non-fimbriated Pg failed to inhibit apoptosis via eATP/P2X7-pathway. Furthermore, Pg-driven stimulation of IL-1β was TLR2- and MyD88-dependent, and irrespective of fimbriae expression. Fimbriae-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of Pg stimulation which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a markedly foci formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by Pg fimbriae in a P2X7-dependent manner. PMID:24925032

  9. Salivary Gland Secretion.

    ERIC Educational Resources Information Center

    Dorman, H. L.; And Others

    1981-01-01

    Describes materials and procedures for an experiment utilizing a live dog to demonstrate: (1) physiology of the salivary gland; (2) parasympathetic control of the salivary gland; (3) influence of varying salivary flow rates on sodium and potassium ions, osmolarity and pH; and (4) salivary secretion as an active process. (DS)

  10. Analysis of secreted proteins.

    PubMed

    Severino, Valeria; Farina, Annarita; Chambery, Angela

    2013-01-01

    Most biological processes including growth, proliferation, differentiation, and apoptosis are coordinated by tightly regulated signaling pathways, which also involve secreted proteins acting in an autocrine and/or paracrine manner. In addition, extracellular signaling molecules affect local niche biology and influence the cross-talking with the surrounding tissues. The understanding of this molecular language may provide an integrated and broader view of cellular regulatory networks under physiological and pathological conditions. In this context, the profiling at a global level of cell secretomes (i.e., the subpopulations of a proteome secreted from the cell) has become an active area of research. The current interest in secretome research also deals with its high potential for the biomarker discovery and the identification of new targets for therapeutic strategies. Several proteomic and mass spectrometry platforms and methodologies have been applied to secretome profiling of conditioned media of cultured cell lines and primary cells. Nevertheless, the analysis of secreted proteins is still a very challenging task, because of the technical difficulties that may hamper the subsequent mass spectrometry analysis. This chapter describes a typical workflow for the analysis of proteins secreted by cultured cells. Crucial issues related to cell culture conditions for the collection of conditioned media, secretome preparation, and mass spectrometry analysis are discussed. Furthermore, an overview of quantitative LC-MS-based approaches, computational tools for data analysis, and strategies for validation of potential secretome biomarkers is also presented.

  11. Secrets of Successful Homeschooling

    ERIC Educational Resources Information Center

    Rivero, Lisa

    2011-01-01

    Parents who homeschool gifted children often find the daily practice of home education very different from what they had imagined. Gifted children are complex in both personality and learning styles. Parents who say that homeschooling works well for their gifted children have learned from others or discovered on their own several secrets that make…

  12. Trade-Secret Dispute.

    ERIC Educational Resources Information Center

    Blumenstyk, Goldie

    1994-01-01

    A Michigan court has ruled that a Wayne State University (Michigan) chemistry professor appropriated a trade secret from a Massachusetts chemist for whom he was consulting and incorporated it into his own patent application, violating a written agreement. The university contends its pursuit of the patent was not improper. (MSE)

  13. Salivary Gland Secretion.

    ERIC Educational Resources Information Center

    Dorman, H. L.; And Others

    1981-01-01

    Describes materials and procedures for an experiment utilizing a live dog to demonstrate: (1) physiology of the salivary gland; (2) parasympathetic control of the salivary gland; (3) influence of varying salivary flow rates on sodium and potassium ions, osmolarity and pH; and (4) salivary secretion as an active process. (DS)

  14. US weapons secrets revealed

    SciTech Connect

    Norris, R.S.; Arkin, W.M.

    1993-03-01

    Extraordinary details have only recently been revealed about the struggle over the control of early U.S. nuclear weapons and their initial deployments abroad. The information comes from a newly declassified top secret report, part of a larger study, The History of the Strategic Arms Competition, 1945-1972, commissioned by Defense Secretary James R. Schlisinger in summer 1974.

  15. Secrets of Successful Homeschooling

    ERIC Educational Resources Information Center

    Rivero, Lisa

    2011-01-01

    Parents who homeschool gifted children often find the daily practice of home education very different from what they had imagined. Gifted children are complex in both personality and learning styles. Parents who say that homeschooling works well for their gifted children have learned from others or discovered on their own several secrets that make…

  16. Physiology of bile secretion

    PubMed Central

    Esteller, Alejandro

    2008-01-01

    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology. PMID:18837079

  17. Are Secrets Immoral? The Construction of Secrets in Everyday Conversation.

    ERIC Educational Resources Information Center

    Gunthner, Susanne; Luckmann, Thomas

    1998-01-01

    Investigates the communicative treatment of secrets, presenting examples from recorded communicative interactions in a wide range of social milieus and settings in which the participants revealed knowledge of secrets, tried to dig out old secrets without appearing to be doing so, and occasionally, appeared to be hiding some items of knowledge from…

  18. Wrapped up in Covers: Preschoolers' Secrets and Secret Hiding Places

    ERIC Educational Resources Information Center

    Corson, Kimberly; Colwell, Malinda J.; Bell, Nancy J.; Trejos-Castillo, Elizabeth

    2014-01-01

    In this qualitative study, interviews about children's secret hiding places were conducted with 3-5-year-olds (n?=?17) in a university sponsored preschool programme using art narratives. Since prior studies indicate that children understand the concept of a secret as early as five and that they associate secrets with hiding places, the purpose of…

  19. Wrapped up in Covers: Preschoolers' Secrets and Secret Hiding Places

    ERIC Educational Resources Information Center

    Corson, Kimberly; Colwell, Malinda J.; Bell, Nancy J.; Trejos-Castillo, Elizabeth

    2014-01-01

    In this qualitative study, interviews about children's secret hiding places were conducted with 3-5-year-olds (n?=?17) in a university sponsored preschool programme using art narratives. Since prior studies indicate that children understand the concept of a secret as early as five and that they associate secrets with hiding places, the purpose of…

  20. Extracellular secretion of recombinant proteins

    SciTech Connect

    Linger, Jeffrey G.; Darzins, Aldis

    2014-07-22

    Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

  1. Telling stories: keeping secrets.

    PubMed

    Jensen, Joan M

    2009-01-01

    This article addresses the reticence of some farm women to share their experiences with historians and how that desire to keep secrets collides with the desire by scholars to tell the stories of these women. It argues that scholars must continue to struggle with the issue of which stories to tell publicly and which to keep private. The author discusses her own experience telling stories about rural women in the 1970s and the need to give voice to the heritage of rural women, especially of groups that have feared revealing their experiences. She offers examples of historians of rural women who have successfully worked with formerly silenced populations and urges historians to continue to tell stories about these lives, to reevaluate what has been already learned, to ask new questions, and to discuss which secrets need to be shared.

  2. Generalized quantum secret sharing

    SciTech Connect

    Singh, Sudhir Kumar; Srikanth, R.

    2005-01-01

    We explore a generalization of quantum secret sharing (QSS) in which classical shares play a complementary role to quantum shares, exploring further consequences of an idea first studied by Nascimento, Mueller-Quade, and Imai [Phys. Rev. A 64, 042311 (2001)]. We examine three ways, termed inflation, compression, and twin thresholding, by which the proportion of classical shares can be augmented. This has the important application that it reduces quantum (information processing) players by replacing them with their classical counterparts, thereby making quantum secret sharing considerably easier and less expensive to implement in a practical setting. In compression, a QSS scheme is turned into an equivalent scheme with fewer quantum players, compensated for by suitable classical shares. In inflation, a QSS scheme is enlarged by adding only classical shares and players. In a twin-threshold scheme, we invoke two separate thresholds for classical and quantum shares based on the idea of information dilution.

  3. Proactive quantum secret sharing

    NASA Astrophysics Data System (ADS)

    Qin, Huawang; Dai, Yuewei

    2015-11-01

    A proactive quantum secret sharing scheme is proposed, in which the participants can update their key shares periodically. In an updating period, one participant randomly generates the EPR pairs, and the other participants update their key shares and perform the corresponding unitary operations on the particles of the EPR pairs. Then, the participant who generated the EPR pairs performs the Bell-state measurement and updates his key share according to the result of the Bell-state measurement. After an updating period, each participant can change his key share, but the secret is changeless, and the old key shares will be useless even if they have been stolen by the attacker. The proactive property of our scheme is very useful to resist the mobile attacker.

  4. Cell secretion: an update

    PubMed Central

    Jeremic, A

    2008-01-01

    This past decade has witnessed the publication of a flurry of scientific papers and reports on the subject of cell secretion, following discovery of a permanent plasma membrane structure termed ‘porosome’ and its determination as the universal secretory machinery in cells. This discovery has led to a paradigm shift in our understanding of the secretory process, demonstrating that membrane-bound secretory vesicles transiently dock and fuse at the porosome base to release their contents to the cell exterior. The regulated release of intravesicular contents during cell secretion is governed by dilation of the porosome opening to the outside, and the extent of vesicle swelling. In agreement, a great number of articles have been written and studies performed, which are briefly discussed in this article. PMID:18363838

  5. Secret Key Crypto Implementations

    NASA Astrophysics Data System (ADS)

    Bertoni, Guido Marco; Melzani, Filippo

    This chapter presents the algorithm selected in 2001 as the Advanced Encryption Standard. This algorithm is the base for implementing security and privacy based on symmetric key solutions in almost all new applications. Secret key algorithms are used in combination with modes of operation to provide different security properties. The most used modes of operation are presented in this chapter. Finally an overview of the different techniques of software and hardware implementations is given.

  6. Bile Formation and Secretion

    PubMed Central

    Boyer, James L.

    2014-01-01

    Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile duct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (~1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bile ducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bile duct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions. PMID:23897680

  7. Catechin secretion and phytotoxicity

    PubMed Central

    Kaushik, Shail

    2010-01-01

    Research indicates that the invasiveness of Centaurea stoebe is attributed to the stronger allelopathic effects on the native North American species than on the related European species, which is one of the unquestionable aspects of the “novel weapons hypothesis (NWH).” Studies originating from controlled to field conditions have shown that C. stoebe utilizes its biochemical potential to exert its invasiveness. The roots of C. stoebe secrete a potent phytotoxin, catechin, which has a detrimental effect on the surrounding plant species. Although, studies on catechin secretion and phytotoxicity represent one of the most well studied systems describing negative plant-plant interactions, it has also sparked controversies lately due to its phytotoxicity dosages and secretion effluxes. Previous reports negate the phytotoxic and pro-oxidant nature of catechin.1–3 In our recent study we have shown that catechin is highly phytotoxic against Arabidopsis thaliana and Festuca idahoensis. We also show that (±) catechin applied to roots of A. thaliana induces reactive oxygen species (ROS) confirming the pro-oxidant nature of catechin. In addition, activation of signature cell death genes such as acd2 and cad1 post catechin treatment in A. thaliana ascertains the phytotoxic nature of catechin. PMID:21057643

  8. Down-Modulation of Lung Immune Responses by Interleukin-10 and Transforming Growth Factor β (TGF-β) and Analysis of TGF-β Receptors I and II in Active Tuberculosis

    PubMed Central

    Bonecini-Almeida, M. Glória; Ho, John L.; Boéchat, Neio; Huard, Richard C.; Chitale, Sadhana; Doo, Howard; Geng, Jiayuan; Rego, Lorena; Lazzarini, Luiz Claudio Oliveira; Kritski, AfrÂnio L.; Johnson, Warren D.; McCaffrey, Timothy A.; Silva, José R. Lapa e

    2004-01-01

    Immune factors influencing progression to active tuberculosis (TB) remain poorly defined. In this study, we investigated the expression of immunoregulatory cytokines and receptors by using lung bronchoalveolar lavage cells obtained from patients with pulmonary TB, patients with other lung diseases (OLD patients), and healthy volunteers (VOL) by using reverse transcriptase PCR, a transforming growth factor β (TGF-β) bioactivity assay, and an enzyme immunoassay. TB patients were significantly more likely than OLD patients to coexpress TGF-β receptor I (RI) and RII mRNA, as well as interleukin-10 (IL-10) mRNA (thereby indicating the state of active gene transcription in the alveolar cells at harvest). In contrast, gamma interferon (IFN-γ) and IL-2 mRNA was seen in both TB and OLD patients. Likewise, significantly elevated pulmonary steady-state protein levels of IL-10, IFN-γ, and bioactive TGF-β were found in TB patients versus those in OLD patients and VOL. These data suggest that the combined production of the immunosuppressants IL-10 and TGF-β, as well as coexpression of TGF-β RI and RII (required for cellular response to TGF-β), may act to down-modulate host anti-Mycobacterium tuberculosis immunity and thereby allow uncontrolled bacterial replication and overt disease. Delineating the underlying mechanisms of M. tuberculosis-triggered expression of these immune elements may provide a molecular-level understanding of TB immunopathogenesis. PMID:15102771

  9. Autotransporter protein secretion.

    PubMed

    Tame, Jeremy R H

    2011-12-01

    Autotransporter proteins are a large family of virulence factors secreted from Gram-negative bacteria by a unique mechanism. First described in the 1980s, these proteins have a C-terminal region that folds into a β-barrel in the bacterial outer membrane. The so-called passenger domain attached to this barrel projects away from the cell surface and may be liberated from the cell by self-cleavage or surface proteases. Although the majority of passenger domains have a similar β-helical structure, they carry a variety of sub-domains, allowing them to carry out widely differing functions related to pathogenesis. Considerable biochemical and structural characterisation of the barrel domain has shown that 'autotransporters' in fact require a conserved and essential protein complex in the outer membrane for correct folding. Although the globular domains of this complex projecting into the periplasmic space have also been structurally characterised, the overall secretion pathway of the autotransporters remains highly puzzling. It was presumed for many years that the passenger domain passed through the centre of the barrel domain to reach the cell surface, driven at least in part by folding. This picture is complicated by conflicting data, and there is currently little hard information on the true nature of the secretion intermediates. As well as their medical importance therefore, autotransporters are proving to be an excellent system to study the folding and membrane insertion of outer membrane proteins in general. This review focuses on structural aspects of autotransporters; their many functions in pathogenesis are beyond its scope.

  10. Immunoglobulin in intestinal secretions.

    PubMed

    Cutropia de Guirao, C

    1977-12-01

    The objective of the present investigation is the study and interpretation of the role played by the immunoglobulins, especially IgA, during acute diarrhea in children. IgA, IGG and IgM values in serum and IgA in intestinal secretions were studied in a group of children (between 3 months and 5 years of age) during diarrhea, convalescence and in normals. The method of simple radial immunodiffusion according to Mancini was employed. IgA is the immunoglobulin which suffers the greastest alteration in acute diarrhea. The precipitation halos (the average values), were lower during the diarrhea than in convalescence and in normals.

  11. Brucella abortus down-regulates MHC class II by the IL-6-dependent inhibition of CIITA through the downmodulation of IFN regulatory factor-1 (IRF-1).

    PubMed

    Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Fernández, Pablo; Pozner, Roberto G; Lang, Roland; Balboa, Luciana; Giambartolomei, Guillermo H; Barrionuevo, Paula

    2017-03-01

    Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4(+) T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B. abortus is able to down-regulate the expression of MHC-II, remained to be elucidated. In this study, we demonstrated that B. abortus infection inhibits the IFN-γ-induced transcription of MHC-II, transactivator (CIITA) and MHC-II genes. Accordingly, we observed that the synthesis of MHC-II proteins was also diminished. B. abortus was not only able to reduce the expression of mature MHC-II, but it also inhibited the expression of invariant chain (Ii)-associated immature MHC-II molecules. Outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, diminished the expression of MHC-II and CIITA transcripts to the same extent as B. abortus infection. IL-6 contributes to these down-regulatory phenomena. In addition, B. abortus and its lipoproteins, through IL-6 secretion, induced the transcription of the negative regulators of IFN-γ signaling, suppressor of cytokine signaling (SOCS)-1 and -3, without interfering with STAT1 activation. Yet, B. abortus lipoproteins via IL-6 inhibit the expression of IFN regulatory factor 1 (IRF-1), a critical regulatory transcription factor for CIITA induction. Overall, these results indicate that B. abortus inhibits the expression of MHC-II molecules at very early points in their synthesis and in this way, may prevent recognition by T cells establishing a chronic infection.

  12. Protecting Trade Secrets in Canada

    PubMed Central

    Courage, Noel; Calzavara, Janice

    2015-01-01

    Patents in the life sciences industries are a key form of intellectual property (IP), particularly for products such as brand-name drugs and medical devices. However, trade secrets can also be a useful tool for many types of innovations. In appropriate cases, trade secrets can offer long-term protection of IP for a lower financial cost than patenting. This type of protection must be approached with caution as there is little room for error when protecting a trade secret. Strong agreements and scrupulous security can help to protect the secret. Once a trade secret is disclosed to the public, it cannot be restored as the owner's property; however, if the information is kept from the public domain, the owner can have a property right of unlimited duration in the information. In some situations patents and trade secrets may be used cooperatively to protect innovation, particularly for manufacturing processes. PMID:25986591

  13. Protecting Trade Secrets in Canada.

    PubMed

    Courage, Noel; Calzavara, Janice

    2015-05-18

    Patents in the life sciences industries are a key form of intellectual property (IP), particularly for products such as brand-name drugs and medical devices. However, trade secrets can also be a useful tool for many types of innovations. In appropriate cases, trade secrets can offer long-term protection of IP for a lower financial cost than patenting. This type of protection must be approached with caution as there is little room for error when protecting a trade secret. Strong agreements and scrupulous security can help to protect the secret. Once a trade secret is disclosed to the public, it cannot be restored as the owner's property; however, if the information is kept from the public domain, the owner can have a property right of unlimited duration in the information. In some situations patents and trade secrets may be used cooperatively to protect innovation, particularly for manufacturing processes.

  14. General secretion signal for the mycobacterial type VII secretion pathway

    PubMed Central

    Daleke, Maria H.; Ummels, Roy; Bawono, Punto; Heringa, Jaap; Vandenbroucke-Grauls, Christina M. J. E.; Luirink, Joen; Bitter, Wilbert

    2012-01-01

    Mycobacterial pathogens use specialized type VII secretion (T7S) systems to transport crucial virulence factors across their unusual cell envelope into infected host cells. These virulence factors lack classical secretion signals and the mechanism of substrate recognition is not well understood. Here we demonstrate that the model T7S substrates PE25/PPE41, which form a heterodimer, are targeted to the T7S pathway ESX-5 by a signal located in the C terminus of PE25. Site-directed mutagenesis of residues within this C terminus resulted in the identification of a highly conserved motif, i.e., YxxxD/E, which is required for secretion. This motif was also essential for the secretion of LipY, another ESX-5 substrate. Pathogenic mycobacteria have several different T7S systems and we identified a PE protein that is secreted by the ESX-1 system, which allowed us to compare substrate recognition of these two T7S systems. Surprisingly, this ESX-1 substrate contained a C-terminal signal functionally equivalent to that of PE25. Exchange of these C-terminal secretion signals between the PE proteins restored secretion, but each PE protein remained secreted via its own ESX secretion system, indicating that an additional signal(s) provides system specificity. Remarkably, the YxxxD/E motif was also present in and required for efficient secretion of the ESX-1 substrates CFP-10 and EspB. Therefore, our data show that the YxxxD/E motif is a general secretion signal that is present in all known mycobacterial T7S substrates or substrate complexes. PMID:22733768

  15. Salmonella-secreted Virulence Factors

    SciTech Connect

    Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

    2011-05-01

    In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

  16. Expansible quantum secret sharing network

    NASA Astrophysics Data System (ADS)

    Sun, Ying; Xu, Sheng-Wei; Chen, Xiu-Bo; Niu, Xin-Xin; Yang, Yi-Xian

    2013-08-01

    In the practical applications, member expansion is a usual demand during the development of a secret sharing network. However, there are few consideration and discussion on network expansibility in the existing quantum secret sharing schemes. We propose an expansible quantum secret sharing scheme with relatively simple and economical quantum resources and show how to split and reconstruct the quantum secret among an expansible user group in our scheme. Its trait, no requirement of any agent's assistant during the process of member expansion, can help to prevent potential menaces of insider cheating. We also give a discussion on the security of this scheme from three aspects.

  17. Down-modulation of SEL1L, an Unfolded Protein Response and Endoplasmic Reticulum-associated Degradation Protein, Sensitizes Glioma Stem Cells to the Cytotoxic Effect of Valproic Acid*

    PubMed Central

    Cattaneo, Monica; Baronchelli, Simona; Schiffer, Davide; Mellai, Marta; Caldera, Valentina; Saccani, Gloria Jotti; Dalpra, Leda; Daga, Antonio; Orlandi, Rosaria; DeBlasio, Pasquale; Biunno, Ida

    2014-01-01

    Valproic acid (VPA), an histone deacetylase inhibitor, is emerging as a promising therapeutic agent for the treatments of gliomas by virtue of its ability to reactivate the expression of epigenetically silenced genes. VPA induces the unfolded protein response (UPR), an adaptive pathway displaying a dichotomic yin yang characteristic; it initially contributes in safeguarding the malignant cell survival, whereas long-lasting activation favors a proapoptotic response. By triggering UPR, VPA might tip the balance between cellular adaptation and programmed cell death via the deregulation of protein homeostasis and induction of proteotoxicity. Here we aimed to investigate the impact of proteostasis on glioma stem cells (GSC) using VPA treatment combined with subversion of SEL1L, a crucial protein involved in homeostatic pathways, cancer aggressiveness, and stem cell state maintenance. We investigated the global expression of GSC lines untreated and treated with VPA, SEL1L interference, and GSC line response to VPA treatment by analyzing cell viability via MTT assay, neurosphere formation, and endoplasmic reticulum stress/UPR-responsive proteins. Moreover, SEL1L immunohistochemistry was performed on primary glial tumors. The results show that (i) VPA affects GSC lines viability and anchorage-dependent growth by inducing differentiative programs and cell cycle progression, (ii) SEL1L down-modulation synergy enhances VPA cytotoxic effects by influencing GSCs proliferation and self-renewal properties, and (iii) SEL1L expression is indicative of glioma proliferation rate, malignancy, and endoplasmic reticulum stress statuses. Targeting the proteostasis network in association to VPA treatment may provide an alternative approach to deplete GSC and improve glioma treatments. PMID:24311781

  18. Down-modulation of SEL1L, an unfolded protein response and endoplasmic reticulum-associated degradation protein, sensitizes glioma stem cells to the cytotoxic effect of valproic acid.

    PubMed

    Cattaneo, Monica; Baronchelli, Simona; Schiffer, Davide; Mellai, Marta; Caldera, Valentina; Saccani, Gloria Jotti; Dalpra, Leda; Daga, Antonio; Orlandi, Rosaria; DeBlasio, Pasquale; Biunno, Ida

    2014-01-31

    Valproic acid (VPA), an histone deacetylase inhibitor, is emerging as a promising therapeutic agent for the treatments of gliomas by virtue of its ability to reactivate the expression of epigenetically silenced genes. VPA induces the unfolded protein response (UPR), an adaptive pathway displaying a dichotomic yin yang characteristic; it initially contributes in safeguarding the malignant cell survival, whereas long-lasting activation favors a proapoptotic response. By triggering UPR, VPA might tip the balance between cellular adaptation and programmed cell death via the deregulation of protein homeostasis and induction of proteotoxicity. Here we aimed to investigate the impact of proteostasis on glioma stem cells (GSC) using VPA treatment combined with subversion of SEL1L, a crucial protein involved in homeostatic pathways, cancer aggressiveness, and stem cell state maintenance. We investigated the global expression of GSC lines untreated and treated with VPA, SEL1L interference, and GSC line response to VPA treatment by analyzing cell viability via MTT assay, neurosphere formation, and endoplasmic reticulum stress/UPR-responsive proteins. Moreover, SEL1L immunohistochemistry was performed on primary glial tumors. The results show that (i) VPA affects GSC lines viability and anchorage-dependent growth by inducing differentiative programs and cell cycle progression, (ii) SEL1L down-modulation synergy enhances VPA cytotoxic effects by influencing GSCs proliferation and self-renewal properties, and (iii) SEL1L expression is indicative of glioma proliferation rate, malignancy, and endoplasmic reticulum stress statuses. Targeting the proteostasis network in association to VPA treatment may provide an alternative approach to deplete GSC and improve glioma treatments.

  19. Study Guide: Seven Simple Secrets

    ERIC Educational Resources Information Center

    Satterfield, Nancy; Breaux, Annette; Whitaker, Todd

    2007-01-01

    This study guide has been developed to accompany the "Seven Simple Secrets" book written by Dr. Todd Whitaker and Annette Breaux. "Seven Simple Secrets" focuses on those attributes that have been found to help teachers be their absolute best in their daily challenges of teaching and improving student learning. The study guide is divided into the…

  20. Study Guide: Seven Simple Secrets

    ERIC Educational Resources Information Center

    Satterfield, Nancy; Breaux, Annette; Whitaker, Todd

    2007-01-01

    This study guide has been developed to accompany the "Seven Simple Secrets" book written by Dr. Todd Whitaker and Annette Breaux. "Seven Simple Secrets" focuses on those attributes that have been found to help teachers be their absolute best in their daily challenges of teaching and improving student learning. The study guide is divided into the…

  1. Protein secretion in Bacillus species.

    PubMed Central

    Simonen, M; Palva, I

    1993-01-01

    Bacilli secrete numerous proteins into the environment. Many of the secretory proteins, their export signals, and their processing steps during secretion have been characterized in detail. In contrast, the molecular mechanisms of protein secretion have been relatively poorly characterized. However, several components of the protein secretion machinery have been identified and cloned recently, which is likely to lead to rapid expansion of the knowledge of the protein secretion mechanism in Bacillus species. Comparison of the presently known export components of Bacillus species with those of Escherichia coli suggests that the mechanism of protein translocation across the cytoplasmic membrane is conserved among gram-negative and gram-positive bacteria differences are found in steps preceding and following the translocation process. Many of the secretory proteins of bacilli are produced industrially, but several problems have been encountered in the production of Bacillus heterologous secretory proteins. In the final section we discuss these problems and point out some possibilities to overcome them. PMID:8464403

  2. Adipocytes Secrete Leukotrienes

    PubMed Central

    Mothe-Satney, Isabelle; Filloux, Chantal; Amghar, Hind; Pons, Catherine; Bourlier, Virginie; Galitzky, Jean; Grimaldi, Paul A.; Féral, Chloé C.; Bouloumié, Anne; Van Obberghen, Emmanuel; Neels, Jaap G.

    2012-01-01

    Leukotrienes (LTs) are potent proinflammatory mediators, and many important aspects of innate and adaptive immune responses are regulated by LTs. Key members of the LT synthesis pathway are overexpressed in adipose tissue (AT) during obesity, resulting in increased LT levels in this tissue. We observed that several mouse adipocyte cell lines and primary adipocytes from mice and humans both can secrete large amounts of LTs. Furthermore, this production increases with a high-fat diet (HFD) and positively correlates with adipocyte size. LTs produced by adipocytes play an important role in attracting macrophages and T cells in in vitro chemotaxis assays. Mice that are deficient for the enzyme 5-lipoxygenase (5-LO), and therefore lack LTs, exhibit a decrease in HFD-induced AT macrophage and T-cell infiltration and are partially protected from HFD-induced insulin resistance. Similarly, treatment of HFD-fed wild-type mice with the 5-LO inhibitor Zileuton also results in a reduction of AT macrophages and T cells, accompanied by a decrease in insulin resistance. Together, these findings suggest that LTs represent a novel target in the prevention or treatment of obesity-associated inflammation and insulin resistance. PMID:22688342

  3. Secrets of succulence.

    PubMed

    Males, Jamie

    2017-03-24

    Succulent plants are iconic components of the florae of many terrestrial ecosystems, but despite having caused fascination and prompted investigation for centuries, they still harbour many secrets in terms of physiological function and evolution. Tackling these mysteries is important, as this will not only provide insights into the dynamics and details of the convergent evolution of a major adaptive syndrome, but also inform efforts to conserve endangered biodiversity and utilize the unique physiological characteristics of succulents for biofuel and biomass production. Here I review advances in the phylogeny and organismal biology of succulent plants, and discuss how insights from recent work in the wider fields of plant hydraulics and photosynthetic physiology may relate to succulents. The potential for the exploration of mechanistic relationships between anatomical structure and physiological function to improve our understanding of the constraints that have shaped the evolution of succulence is highlighted. Finally, attention is drawn to how new methodologies and technologies provide exciting opportunities to address the wide range of outstanding questions in succulent plant biology.

  4. Helicobacter pylori in lacrimal secretions.

    PubMed

    Batioglu-Karaaltin, Aysegul; Saatci, Ozlem; Akpinar, Meltem; Celik, Melih Ozgür; Develioglu, Omer; Yigit, Ozgur; Külekçi, Mehmet; Akarsubaşı, Alper Tunga

    2016-03-01

    The aim of this study was to investigate the presence of Helicobacter pylori in human lacrimal and nasal secretions. Eighty patients with complaints of dyspepsia who had undergone endoscopies and gastric antrum biopsies were included in the study. A total of five specimens, including 2 lacrimal secretion samples, 2 nasal mucosal swab samples, and 1 gastric antrum biopsy, were collected from each patient and investigated with polymerase chain reaction (PCR) methods consisting of the urease enzyme coding gene GlmM (UreC) and the H pylori-specific 16S rRNA coding gene. The Reflux Symptom Index and ophthalmologic complaints of the patients were recorded. The detected positivity rates of the H pylori 16S rRNA coding gene in gastric biopsies and nasal mucous and lacrimal secretions were 55, 11.2, and 20%, respectively. The patients were grouped as gastric-antrum-biopsy-negative (Group I [n = 36]) and -positive (Group II [n = 44). In Group II, H pylori positivity in the lacrimal and nasal mucous secretions was 36.3 and 18%, respectively. A comparison between the groups in terms of H pylori presence in nasal mucous and lacrimal secretions yielded statistically significant differences (p = 0.0001, p = 0.003). The simultaneous presence of H pylori in nasal mucous and lacrimal secretions was 13.6% in Group II. H pylori positivity in nasal mucous and lacrimal secretions had a positive moderate correlation (r = 0.40; p = 0.0003). The present study is the first report on the presence of H pylori in lacrimal secretions through nested PCR, which suggested the presence of a number of mechanisms for H pylori transmission to lacrimal secretions.

  5. Secret Key Generation via a Modified Quantum Secret Sharing Protocol

    SciTech Connect

    Smith IV, Amos M; Evans, Philip G; Lawrie, Benjamin J; Legre, Matthieu; Lougovski, Pavel; Ray, William R; Williams, Brian P; Qi, Bing; Grice, Warren P

    2015-01-01

    We present and experimentally show a novel protocol for distributing secret information between two and only two parties in a N-party single-qubit Quantum Secret Sharing (QSS) system. We demonstrate this new algorithm with N = 3 active parties over 6km of telecom. ber. Our experimental device is based on the Clavis2 Quantum Key Distribution (QKD) system built by ID Quantique but is generalizable to any implementation. We show that any two out of the N parties can build secret keys based on partial information from each other and with collaboration from the remaining N > 2 parties. This algorithm allows for the creation of two-party secret keys were standard QSS does not and signicantly reduces the number of resources needed to implement QKD on a highly connected network such as the electrical grid.

  6. Secret key generation via a modified quantum secret sharing protocol

    NASA Astrophysics Data System (ADS)

    Smith, A. M.; Evans, P. G.; Lawrie, B.; Legré, M.; Lougovski, P.; Ray, W.; Williams, B. P.; Qi, B.; Grice, W. P.

    2015-05-01

    We present and experimentally show a novel protocol for distributing secret information between two and only two parties in a N-party single-qubit Quantum Secret Sharing (QSS) system. We demonstrate this new algorithm with N = 3 active parties over ~6km of telecom. fiber. Our experimental device is based on the Clavis2 Quantum Key Distribution (QKD) system built by ID Quantique but is generalizable to any implementation. We show that any two out of the N parties can build secret keys based on partial information from each other and with collaboration from the remaining N - 2 parties. This algorithm allows for the creation of two-party secret keys were standard QSS does not and significantly reduces the number of resources needed to implement QKD on a highly connected network such as the electrical grid.

  7. Secrets and disclosures: how young children handle secrets.

    PubMed

    Anagnostaki, Lida; Wright, Michael J; Papathanasiou, Athanasia

    2013-01-01

    The authors examined the influence of content and verbal cues on young children's understanding of secret information and of its disclosure. Participants were 209 5- and 6-year-old children in an experiment where a puppet, named Zinc, was the protagonist. Children were asked to whom Zinc would disclose a list of pieces of information, some of which are considered secrets. Children could choose between Zinc's friend, a nonfriend, both friend and nonfriend, or nobody. Participants were divided in 2 experiment groups: In the first group a prior verbal cue was given to the participants that some information might be secret, whereas in the second group no prior cue was presented. Results showed that young children, similar to older individuals, differentiated between secrets and nonsecrets partly on the basis of content, and chose to withhold secrets more than nonsecrets or to share secrets more with friends than with nonfriends, following the restrictive self-disclosure pattern. In contrast, young children did not withhold nonsecret information, but they shared it with friends and nonfriends. However, when given verbal cues regarding potential secrecy of the information, young children chose more restrictive disclosure patterns for all types of content.

  8. Proposal for quantum rational secret sharing

    NASA Astrophysics Data System (ADS)

    Maitra, Arpita; De, Sourya Joyee; Paul, Goutam; Pal, Asim K.

    2015-08-01

    A rational secret sharing scheme is a game in which each party responsible for reconstructing a secret tries to maximize his or her utility by obtaining the secret alone. Quantum secret sharing schemes, derived either from quantum teleportation or from quantum error correcting code, do not succeed when we assume rational participants. This is because all existing quantum secret sharing schemes consider that the secret is reconstructed by a party chosen by the dealer. In this paper, for the first time, we propose a quantum secret sharing scheme which is resistant to rational parties. The proposed scheme is fair (everyone gets the secret), is correct, and achieves strict Nash equilibrium.

  9. Adrenal gland hormone secretion (image)

    MedlinePlus

    The adrenal gland secretes steroid hormones such as cortisol and aldosterone. It also makes precursors that can be converted to ... steroids (androgen, estrogen). A different part of the adrenal gland makes adrenaline (epinephrine). When the glands produce more ...

  10. An Image Secret Sharing Method

    DTIC Science & Technology

    2006-07-01

    M. E. Hellman, “On secret sharing systems,” vol. IT-29, no. 1, pp. 35–41, Jan. 1983. [10] K. Kurosawa , K. Okada, K. Sakano, W. Ogata, and S. Tsujii...Ed., Berlin, Germany, 1994, pp. 1–12. [14] W. Ogata and K. Kurosawa , “Some ba- sic properties of general nonperfect secret sharing schemes,” J.UCS

  11. Nonlinear Secret Image Sharing Scheme

    PubMed Central

    Shin, Sang-Ho; Yoo, Kee-Young

    2014-01-01

    Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2⁡m⌉ bit-per-pixel (bpp), respectively. PMID:25140334

  12. [Pancreatic secretion in domestic sprue].

    PubMed

    Otte, M; Thurmayr, G R; Dageförde, J; Thurmayr, R; Forell, M M

    1985-02-15

    Pancreatic function was determined (using the secretin-pancreozymin test) before the use of gluten-free diet in 22 patients with endemic (celiac) sprue. Water and bicarbonate secretion were within normal limits, if anything there was a trend to high-normal values. Remarkable and apparently characteristic for celiac sprue was the only slight contraction of the gallbladder after intravenous injection of submaximal doses of cholecystokinin-pancreozymin (CCK). Secretion of the 3 enzymes amylase, lipase and trypsin was decreased in about one third of cases, the difference relating both to the concentrations and the amount secreted, compared with normal control values was significant (P greater than 0.01). But in no case was the reduced enzyme secretion so marked that one would expect maldigestion. Multivariate non-linear discriminance analysis demonstrated that pancreatic secretion in sprue is quite distinct from that in healthy subjects and those with chronic pancreatitis. It is assumed that there is a pattern of exocrine pancreatic secretion typical for sprue.

  13. Nonlinear secret image sharing scheme.

    PubMed

    Shin, Sang-Ho; Lee, Gil-Je; Yoo, Kee-Young

    2014-01-01

    Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2 m⌉ bit-per-pixel (bpp), respectively.

  14. Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus

    PubMed Central

    Hewitson, James P.; Nguyen, D. Linh; van Diepen, Angela; Smit, Cornelis H.; Koeleman, Carolien A.; McSorley, Henry J.; Murray, Janice; Maizels, Rick M.; Hokke, Cornelis H.

    2016-01-01

    Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory–secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. We used MALDI-TOF-MS and LC–MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory–secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1–4GlcNAc) structure, respectively. We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory–secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory–secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory–secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host. PMID:26688390

  15. QUANTITATIVE STUDIES OF PROSTATIC SECRETION

    PubMed Central

    Huggins, Charles; Masina, M. H.; Eichelberger, Lillian; Wharton, James D.

    1939-01-01

    A simple isolation of the prostate enabled quantitative collection of prostatic secretion in dogs over periods of months. The secretory stimulant was pilocarpine and 2 similar amounts injected with a 6 hour interval gave smaller amounts at the second testing, suggesting a fatigue effect. The prostate was not absolutely refractory since doubling the amount of alkaloid injected at the second test increased the volume to equal or exceed the preliminary secretion. The depression effect had disappeared at 24 hours. In normal dogs the secretory curves were essentially regular, with occasional prolonged rises or depressions. The amount of secretion did not bear a direct relationship to the weight of the gland in adult dogs. The germinal epithelium of the testis underwent atrophy during the first few weeks of cage life while the prostatic secretion was maintained, showing that the atrophy was differential and did not involve the cells producing the androgenic hormone. The atrophy was reversible and all dogs kept for more than 4 months showed restoration of the germ cells. A few dogs developed atrophy of the germinal cells with cessation of prostatic secretion for many weeks but with final recovery. Removal of the suprarenal glands with suprarenal insufficiency did not produce sterility. The distribution of electrolytes in the prostatic secretion differed from that in the serum-transudate system, although the concentration of osmotically active substances was the same, being made up almost entirely of sodium and chloride. The distribution was not affected by the different physiological procedures used in this study. Protein concentrations were less than 1 per cent. The rate of prostatic atrophy following castration was determined, and cessation of secretion occurred in 7 to 23 days. The restoration of prostatic fluid in castrate dogs following daily injections of testosterone propionate followed a smooth curve to form a plateau which was interrupted occasionally by

  16. QUANTITATIVE STUDIES OF PROSTATIC SECRETION

    PubMed Central

    Huggins, Charles; Sommer, John Lambert

    1953-01-01

    The prostate of the dog was relocated permanently in the perineum where its size could be measured and correlated with the output of prostatic secretion during many months. The secretion of a submaxillary gland obtained through a fistula was utilized as an internal biologic standard of the effects of pilocarpine, the secretory stimulus employed, because the amount and route of administration of the alkaloid are critical factors in inducing secretion. Prostatic secretion was found to be profoundly affected by androgenic and estrogenic compounds, in contrast to salivation. The curves of the secretory response of the prostate and submaxillary glands to pilocarpine proved to be similar and a mathematical formula has been constructed to represent them. When testosterone propionate was administered in increasing quantities for periods of weeks at each level, the volume of the prostate increased in a series of flattened curves. This volume, under the conditions mentioned, was found to stand in a simple arithmetic relationship to the amount of testosterone propionate administered. Moderate quantities of testosterone propionate masked the effects of small amounts of stilbestrol on the prostate. The reverse was also true and the critical amounts of these compounds were defined. The amounts of stilbestrol were determined which lowered the quantity of prostatic secretion resulting from the simultaneous administration of moderate amounts of testosterone propionate in castrate dogs, the result being a level and flat secretory curve which was maintained for many weeks. We designate this effect the plateau phenomenon. When this amount of estrogen was continued, and the dosage of testosterone propionate greatly augmented, the prostatic secretion did not increase in volume. Very slight increases above the critical amount of stilbestrol, however, caused the secretory curve to fall to new and still lower levels though the secretion was never completely suppressed. The acid phosphatase

  17. Quantum strongly secure ramp secret sharing

    NASA Astrophysics Data System (ADS)

    Zhang, Paul; Matsumoto, Ryutaroh

    2015-02-01

    Quantum secret sharing is a scheme for encoding a quantum state (the secret) into multiple shares and distributing them among several participants. If a sufficient number of shares are put together, then the secret can be fully reconstructed. If an insufficient number of shares are put together however, no information about the secret can be revealed. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an unqualified set, that cannot fully reconstruct the secret. By allowing this, the size of a share can be drastically reduced. This paper introduces a quantum analog of classical strong security in ramp secret sharing schemes. While the ramp secret sharing scheme still leaks partial information about the secret to unqualified sets of participants, the strong security condition ensures that qudits with critical information can no longer be leaked.

  18. Glucose Suppression of Glucagon Secretion

    PubMed Central

    Le Marchand, Sylvain J.; Piston, David W.

    2010-01-01

    Glucagon is released from α-cells present in intact pancreatic islets at glucose concentrations below 4 mm, whereas higher glucose levels inhibit its secretion. The mechanisms underlying the suppression of α-cell secretory activity are poorly understood, but two general types of models have been proposed as follows: direct inhibition by glucose or paracrine inhibition from non-α-cells within the islet of Langerhans. To identify α-cells for analysis, we utilized transgenic mice expressing fluorescent proteins targeted specifically to these cells. Measurements of glucagon secretion from pure populations of flow-sorted α-cells show that contrary to its effect on intact islets, glucose does stimulate glucagon secretion from isolated α-cells. This observation argues against a direct inhibition of glucagon secretion by glucose and supports the paracrine inhibition model. Imaging of cellular metabolism by two-photon excitation of NAD(P)H autofluorescence indicates that glucose is metabolized in α-cells and that glucokinase is the likely rate-limiting step in this process. Imaging calcium dynamics of α-cells in intact islets reveals that inhibiting concentrations of glucose increase the intracellular calcium concentration and the frequency of α-cell calcium oscillations. Application of candidate paracrine inhibitors leads to reduced glucagon secretion but did not decrease the α-cell calcium activity. Taken together, the data suggest that suppression occurs downstream from α-cell calcium signaling, presumably at the level of vesicle trafficking or exocytotic machinery. PMID:20231269

  19. Secret sharing using biometric traits

    NASA Astrophysics Data System (ADS)

    Kholmatov, Alisher; Yanikoglu, Berrin; Savas, Erkay; Levi, Albert

    2006-04-01

    In biometric based authentication, biometric traits of a person are matched against his/her stored biometric profile and access is granted if there is sufficient match. However, there are other access scenarios, which require participation of multiple previously registered users for a successful authentication or to get an access grant for a certain entity. For instance, there are cryptographic constructs generally known as secret sharing schemes, where a secret is split into shares and distributed amongst participants in such a way that it is reconstructed/revealed only when the necessary number of share holders come together. The revealed secret can then be used for encryption or authentication (if the revealed key is verified against the previously registered value). In this work we propose a method for the biometric based secret sharing. Instead of splitting a secret amongst participants, as is done in cryptography, a single biometric construct is created using the biometric traits of the participants. During authentication, a valid cryptographic key is released out of the construct when the required number of genuine participants present their biometric traits.

  20. Thyroid hormones and renin secretion.

    PubMed

    Ganong, W F

    Circulating angiotensin is produced by the action of renin from the kidneys on circulating angiotensinogen. There are other renin-angiotensin systems in various organs in the body, and recent observations raise the intriguing possibility that angiotensin II is produced by a totally intracellular pathway in the juxtaglomerular cells, the gonadotrops of the anterior pituitary, neurons, in the brain, salivary duct cells, and neuroblastoma cells. Circulating angiotensin II levels depend in large part on the plasma concentration of angiotensinogen, which is hormonally regulated, and on the rate of renin secretion. Renin secretion is regulated by an intrarenal baroreceptor mechanism, a macula densa mechanism, angiotensin II, vasopressin, and the sympathetic nervous system. The increase in renin secretion produced by sympathetic discharge is mediated for the most part by beta-adrenergic receptors, which are probably located on the juxtaglomerular cells. Hyperthyroidism would be expected to be associated with increased renin secretion in view of the increased beta-adrenergic activity in this condition, and hypothyroidism would be associated with decreased plasma renin activity due to decreased beta-adrenergic activity. Our recent research on serotonin-mediated increases in renin secretion that depend on the integrity of the dorsal raphe nucleus and the mediobasal hypothalamus has led us to investigate the effect of the pituitary on the renin response to p-chloroamphetamine. The response is potentiated immediately after hypophysectomy, but 22 days after the operation, it is abolished. This slowly developing decrease in responsiveness may be due to decreased thyroid function.

  1. Oscillatory control of insulin secretion.

    PubMed

    Tengholm, Anders; Gylfe, Erik

    2009-01-15

    Pancreatic beta-cells possess an inherent ability to generate oscillatory signals that trigger insulin release. Coordination of the secretory activity among beta-cells results in pulsatile insulin secretion from the pancreas, which is considered important for the action of the hormone in the target tissues. This review focuses on the mechanisms underlying oscillatory control of insulin secretion at the level of the individual beta-cell. Recent studies have demonstrated that oscillations of the cytoplasmic Ca(2+) concentration are synchronized with oscillations in beta-cell metabolism, intracellular cAMP concentration, phospholipase C activity and plasma membrane phosphoinositide lipid concentrations. There are complex interdependencies between the different messengers and signalling pathways that contribute to amplitude regulation and shaping of the insulin secretory response to nutrient stimuli and neurohormonal modulators. Several of these pathways may be important pharmacological targets for improving pulsatile insulin secretion in type 2 diabetes.

  2. On family secrets and -K.

    PubMed

    Orgad, Yariv

    2014-08-01

    In this paper I present a novel interpretation of family secrets. Leaning on Bion's concept of -K, the constitution of secrecy is interpreted in terms of family dynamics that actively prevent knowledge formation and mental growth. Family secrets are interpreted as a destructive process that attacks the family's truth-generating-space - the shared semiotic space within which meanings are constituted through family relationships. The paper explores the microstructure interpersonal process of -K through the analysis of Mike Leigh's movie, Secrets and Lies. Two scenes in the movie are used to demonstrate how -K is worked out in the form of a specific intersubjective semiotic endeavor that unconsciously blocks the process of meaning-making.

  3. Metalloproteases secreted by Actinobacillus suis.

    PubMed

    Negrete-Abascal, Erasmo; Pacheco, Sergio Vaca; Paniagua, Gloria L; Méndez, Alma Pérez; Caballero, Jorge Ibarra; Márquez, Víctor M Pérez; Tenorio, Víctor R

    2004-07-01

    Actinobacillus suis secretes metalloproteases into its medium. These secreted proteins, when concentrated by precipitation with 70% (NH4)2SO4 or methanol, displayed proteolytic activity at >200 kDa molecular mass bands in 10% polyacrylamide gels copolymerized with bovine casein (1%). They showed activity in a broad pH range (from pH 5 to pH 10) and were inhibited by 20 mM EDTA or EGTA, but could be reactivated by calcium. They were found heat stable at 40 degrees C, 50 degrees C, 60 degrees C, and 70 degrees C, but their activity diminished at 80 degrees C or higher. They degraded pig and bovine IgG and cross-reacted with a polyclonal serum against a high molecular mass secreted protease from A. pleuropneumoniae. Extracellular proteases could play a role in diseases caused by A. suis.

  4. Secrets and Disclosures: How Young Children Handle Secrets

    ERIC Educational Resources Information Center

    Anagnostaki, Lida; Wright, Michael J.; Papathanasiou, Athanasia

    2013-01-01

    The authors examined the influence of content and verbal cues on young children's understanding of secret information and of its disclosure. Participants were 209 5- and 6-year-old children in an experiment where a puppet, named Zinc, was the protagonist. Children were asked to whom Zinc would disclose a list of pieces of information, some of…

  5. Secrets and Disclosures: How Young Children Handle Secrets

    ERIC Educational Resources Information Center

    Anagnostaki, Lida; Wright, Michael J.; Papathanasiou, Athanasia

    2013-01-01

    The authors examined the influence of content and verbal cues on young children's understanding of secret information and of its disclosure. Participants were 209 5- and 6-year-old children in an experiment where a puppet, named Zinc, was the protagonist. Children were asked to whom Zinc would disclose a list of pieces of information, some of…

  6. News Note: Tracking Secret Satellite

    NASA Astrophysics Data System (ADS)

    Roberts, Greg

    2015-06-01

    The fourth flight of the secret US Air Force mini-shuttle, also known as the X-37B or OTV-4 (Orbital Test Vehicle) was launched by ULA (United Launch Alliance) atop an ATLAS V rocket from Cape Canaveral on the 20th May 2015 at 15.05UT. This article describes amateur efforts to find its orbit.

  7. FOIA: What's a Trade Secret?

    ERIC Educational Resources Information Center

    Hawker, Curtis

    The Freedom of Information Act (FOIA) was amended in 1974 in order to restrict government control and to facilitate the public's access to information. However, part of the FOIA bans federal officials from disclosing "trade secrets" and commercial or financial information obtained in confidential circumstances. This exemption has…

  8. FOIA: What's a Trade Secret?

    ERIC Educational Resources Information Center

    Hawker, Curtis

    The Freedom of Information Act (FOIA) was amended in 1974 in order to restrict government control and to facilitate the public's access to information. However, part of the FOIA bans federal officials from disclosing "trade secrets" and commercial or financial information obtained in confidential circumstances. This exemption has…

  9. The Year of Secret Assignments

    ERIC Educational Resources Information Center

    Moriarty, Jaclyn

    2004-01-01

    The path to "novelist" was a convoluted one for Moriarty, who began writing fiction as doctoral student at Cambridge University. Her interest in young adults stems from an appreciation for the "troubles, strengths, and surprises of that age group." Now, in a uniquely formatted book titled "The Year of Secret Assignments," we peek inside the mind…

  10. Seven Simple Secrets: What the Best Teachers Know and Do!

    ERIC Educational Resources Information Center

    Breaux, Annette L.; Whitaker, Todd

    2006-01-01

    Implementing the secrets presented in this book will change your life both in and out of the classroom. But most importantly, implementing these secrets will enhance the lives of every student you teach. The following are contained in this book: Secret One: The Secret of Planning; Secret Two: The Secret of Classroom Management; Secret Three: The…

  11. Seven Simple Secrets: What the Best Teachers Know and Do!

    ERIC Educational Resources Information Center

    Breaux, Annette L.; Whitaker, Todd

    2006-01-01

    Implementing the secrets presented in this book will change your life both in and out of the classroom. But most importantly, implementing these secrets will enhance the lives of every student you teach. The following are contained in this book: Secret One: The Secret of Planning; Secret Two: The Secret of Classroom Management; Secret Three: The…

  12. Tamper-proof secret image-sharing scheme for identifying cheated secret keys and shared images

    NASA Astrophysics Data System (ADS)

    Chen, Chien-Chang; Liu, Chong-An

    2013-01-01

    A (t,n) secret image-sharing scheme shares a secret image to n participants, and the t users recover the image. During the recovery procedure of a conventional secret image-sharing scheme, cheaters may use counterfeit secret keys or modified shared images to cheat other users' secret keys and shared images. A cheated secret key or shared image leads to an incorrect secret image. Unfortunately, the cheater cannot be identified. We present an exponent and modulus-based scheme to provide a tamper-proof secret image-sharing scheme for identifying cheaters on secret keys or shared images. The proposed scheme allows users to securely select their secret key. This assignment can be performed over networks. Modulus results of each shared image is calculated to recognize cheaters of a shared image. Experimental results indicate that the proposed scheme is excellent at identifying cheated secret keys and shared images.

  13. Metagenomic sequencing of expressed prostate secretions.

    PubMed

    Smelov, Vitaly; Arroyo Mühr, L Sara; Bzhalava, Davit; Brown, Lyndon J; Komyakov, Boris; Dillner, Joakim

    2014-12-01

    To investigate which microorganisms may be present in expressed prostate secretions (EPS) metagenomic sequencing (MGS) was applied to prostate secretion samples from five men with prostatitis and five matched control men as well as to combined expressed prostate secretion and urine from six patients with prostate cancer and six matched control men. The prostate secretion samples contained a variety of bacterial sequences, mostly belonging to the Proteobacteria phylum. The combined prostate secretion and urine samples were dominated by abundant presence of the JC polyomavirus, representing >20% of all detected metagenomic sequence reads. There were also other viruses detected, for example, human papillomavirus type 81. All combined prostate secretion and urine samples were also positive for Proteobacteria. In summary, MGS of expressed prostate secretion is informative for detecting a variety of bacteria and viruses, suggesting that a more large-scale use of MGS of prostate secretions may be useful in medical and epidemiological studies of prostate infections.

  14. [Thyrotropin-secreting pituitary adenomas].

    PubMed

    Caron, Philippe

    2009-01-01

    TSH-secreting pituitary adenomas represent 0.5 to 1% of all pituitary adenomas. They are recognized with increasing frequency due to the measurement of TSH level in patients with hyperthyroidism, the ultra sensitive TSH assays and the improvement in pituitary imaging. Patients present mild or moderate signs of hyperthyroidism. Hormonal evaluation shows increased free thyroid hormone concentration with detectable, normal or increased serum TSH level, raising the differential diagnosis with pituitary resistance to thyroid hormone syndrome. Magnetic resonance imaging reveals pituitary adenomas in most patients. Transphenoidal surgery remains the treatment of choice in patients with TSH-secreting pituitary microadenomas, while long-acting somatostatin analogs seem to be an alternative medical treatment to surgery in patients with macroadenomas or invasive pituitary tumors.

  15. Stimulation of incretin secreting cells

    PubMed Central

    Pais, Ramona; Gribble, Fiona M.; Reimann, Frank

    2016-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system through transporters and G-protein coupled receptors (GPCRs) present on their surface to ultimately culminate in hormone release. Some of the molecules described below such as sodium coupled glucose transporter 1 (SGLT1), G-protein coupled receptor (GPR) 119 and GPR40 are targets of novel therapeutics designed to enhance endogenous gut hormone release. Synthetic ligands at these receptors aimed at treating obesity and type 2 diabetes are currently under investigation. PMID:26885360

  16. 29 CFR 1903.9 - Trade secrets.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 5 2012-07-01 2012-07-01 false Trade secrets. 1903.9 Section 1903.9 Labor Regulations... INSPECTIONS, CITATIONS AND PROPOSED PENALTIES § 1903.9 Trade secrets. (a) Section 15 of the Act provides: “All... inspection or proceeding under this Act which contains or which might reveal a trade secret referred to...

  17. 22 CFR 1421.15 - Secret ballot.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Secret ballot. 1421.15 Section 1421.15 Foreign Relations FOREIGN SERVICE LABOR RELATIONS BOARD; FEDERAL LABOR RELATIONS AUTHORITY; GENERAL COUNSEL OF THE... THIS SUBCHAPTER § 1421.15 Secret ballot. Secret ballot means the expression by ballot, voting...

  18. 29 CFR 401.11 - Secret ballot.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Secret ballot. 401.11 Section 401.11 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.11 Secret ballot. Secret ballot means the expression...

  19. 29 CFR 1903.9 - Trade secrets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 5 2011-07-01 2011-07-01 false Trade secrets. 1903.9 Section 1903.9 Labor Regulations... INSPECTIONS, CITATIONS AND PROPOSED PENALTIES § 1903.9 Trade secrets. (a) Section 15 of the Act provides: “All... inspection or proceeding under this Act which contains or which might reveal a trade secret referred to...

  20. 29 CFR 1202.4 - Secret ballot.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 4 2012-07-01 2012-07-01 false Secret ballot. 1202.4 Section 1202.4 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.4 Secret ballot. In conducting such investigation, the Board is authorized to take a secret ballot of the employees involved,...

  1. 29 CFR 452.97 - Secret ballot.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 2 2013-07-01 2013-07-01 false Secret ballot. 452.97 Section 452.97 Labor Regulations... OF 1959 Election Procedures; Rights of Members § 452.97 Secret ballot. (a) A prime requisite of elections regulated by title IV is that they be held by secret ballot among the members or in...

  2. 29 CFR 401.11 - Secret ballot.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 2 2014-07-01 2014-07-01 false Secret ballot. 401.11 Section 401.11 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.11 Secret ballot. Secret ballot means the expression...

  3. 29 CFR 1202.4 - Secret ballot.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Secret ballot. 1202.4 Section 1202.4 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.4 Secret ballot. In conducting such investigation, the Board is authorized to take a secret ballot of the employees involved,...

  4. 5 CFR 2421.15 - Secret ballot.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Secret ballot. 2421.15 Section 2421.15... FEDERAL LABOR RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 2421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine or otherwise, but in no event by proxy, of...

  5. 29 CFR 1202.4 - Secret ballot.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 4 2013-07-01 2013-07-01 false Secret ballot. 1202.4 Section 1202.4 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.4 Secret ballot. In conducting such investigation, the Board is authorized to take a secret ballot of the employees involved,...

  6. 29 CFR 401.11 - Secret ballot.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 2 2013-07-01 2013-07-01 false Secret ballot. 401.11 Section 401.11 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.11 Secret ballot. Secret ballot means the expression...

  7. 22 CFR 1421.15 - Secret ballot.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Secret ballot. 1421.15 Section 1421.15 Foreign Relations FOREIGN SERVICE LABOR RELATIONS BOARD; FEDERAL LABOR RELATIONS AUTHORITY; GENERAL COUNSEL OF THE... THIS SUBCHAPTER § 1421.15 Secret ballot. Secret ballot means the expression by ballot, voting...

  8. 5 CFR 2421.15 - Secret ballot.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Secret ballot. 2421.15 Section 2421.15... FEDERAL LABOR RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 2421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine or otherwise, but in no event by proxy, of...

  9. 22 CFR 1421.15 - Secret ballot.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Secret ballot. 1421.15 Section 1421.15 Foreign Relations FOREIGN SERVICE LABOR RELATIONS BOARD; FEDERAL LABOR RELATIONS AUTHORITY; GENERAL COUNSEL OF THE... THIS SUBCHAPTER § 1421.15 Secret ballot. Secret ballot means the expression by ballot, voting...

  10. 29 CFR 401.11 - Secret ballot.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 2 2012-07-01 2012-07-01 false Secret ballot. 401.11 Section 401.11 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.11 Secret ballot. Secret ballot means the expression...

  11. 22 CFR 1421.15 - Secret ballot.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Secret ballot. 1421.15 Section 1421.15 Foreign Relations FOREIGN SERVICE LABOR RELATIONS BOARD; FEDERAL LABOR RELATIONS AUTHORITY; GENERAL COUNSEL OF THE... THIS SUBCHAPTER § 1421.15 Secret ballot. Secret ballot means the expression by ballot, voting...

  12. Quantum secret sharing with qudit graph states

    SciTech Connect

    Keet, Adrian; Fortescue, Ben; Sanders, Barry C.; Markham, Damian

    2010-12-15

    We present a unified formalism for threshold quantum secret sharing using graph states of systems with prime dimension. We construct protocols for three varieties of secret sharing: with classical and quantum secrets shared between parties over both classical and quantum channels.

  13. 5 CFR 2421.15 - Secret ballot.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Secret ballot. 2421.15 Section 2421.15... FEDERAL LABOR RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 2421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine or otherwise, but in no event by proxy, of...

  14. 29 CFR 1202.4 - Secret ballot.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 4 2011-07-01 2011-07-01 false Secret ballot. 1202.4 Section 1202.4 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.4 Secret ballot. In conducting such investigation, the Board is authorized to take a secret ballot of the employees involved,...

  15. 29 CFR 1202.4 - Secret ballot.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 4 2014-07-01 2014-07-01 false Secret ballot. 1202.4 Section 1202.4 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.4 Secret ballot. In conducting such investigation, the Board is authorized to take a secret ballot of the employees involved,...

  16. 22 CFR 1421.15 - Secret ballot.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Secret ballot. 1421.15 Section 1421.15 Foreign Relations FOREIGN SERVICE LABOR RELATIONS BOARD; FEDERAL LABOR RELATIONS AUTHORITY; GENERAL COUNSEL OF THE... THIS SUBCHAPTER § 1421.15 Secret ballot. Secret ballot means the expression by ballot, voting...

  17. 29 CFR 452.97 - Secret ballot.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 2 2012-07-01 2012-07-01 false Secret ballot. 452.97 Section 452.97 Labor Regulations... OF 1959 Election Procedures; Rights of Members § 452.97 Secret ballot. (a) A prime requisite of elections regulated by title IV is that they be held by secret ballot among the members or in...

  18. 29 CFR 1903.9 - Trade secrets.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 5 2013-07-01 2013-07-01 false Trade secrets. 1903.9 Section 1903.9 Labor Regulations... INSPECTIONS, CITATIONS AND PROPOSED PENALTIES § 1903.9 Trade secrets. (a) Section 15 of the Act provides: “All... inspection or proceeding under this Act which contains or which might reveal a trade secret referred to...

  19. 29 CFR 1903.9 - Trade secrets.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 5 2014-07-01 2014-07-01 false Trade secrets. 1903.9 Section 1903.9 Labor Regulations... INSPECTIONS, CITATIONS AND PROPOSED PENALTIES § 1903.9 Trade secrets. (a) Section 15 of the Act provides: “All... inspection or proceeding under this Act which contains or which might reveal a trade secret referred to...

  20. 29 CFR 401.11 - Secret ballot.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 2 2011-07-01 2011-07-01 false Secret ballot. 401.11 Section 401.11 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.11 Secret ballot. Secret ballot means the expression...

  1. 29 CFR 452.97 - Secret ballot.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 2 2011-07-01 2011-07-01 false Secret ballot. 452.97 Section 452.97 Labor Regulations... OF 1959 Election Procedures; Rights of Members § 452.97 Secret ballot. (a) A prime requisite of elections regulated by title IV is that they be held by secret ballot among the members or in...

  2. 5 CFR 2421.15 - Secret ballot.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Secret ballot. 2421.15 Section 2421.15... FEDERAL LABOR RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 2421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine or otherwise, but in no event by proxy, of...

  3. 29 CFR 452.97 - Secret ballot.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 2 2014-07-01 2014-07-01 false Secret ballot. 452.97 Section 452.97 Labor Regulations... OF 1959 Election Procedures; Rights of Members § 452.97 Secret ballot. (a) A prime requisite of elections regulated by title IV is that they be held by secret ballot among the members or in...

  4. 5 CFR 2421.15 - Secret ballot.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Secret ballot. 2421.15 Section 2421.15... FEDERAL LABOR RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 2421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine or otherwise, but in no event by proxy, of...

  5. 29 CFR 452.97 - Secret ballot.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Secret ballot. 452.97 Section 452.97 Labor Regulations... OF 1959 Election Procedures; Rights of Members § 452.97 Secret ballot. (a) A prime requisite of elections regulated by title IV is that they be held by secret ballot among the members or in...

  6. Anticounterfeit holographic marks with secret codes

    NASA Astrophysics Data System (ADS)

    Liu, Shou; Zhang, Xiangsu; Lai, Hongkai

    1993-11-01

    The paper introduces the methods of making secret codes in the holograms for the purpose of anti-counterfeiting, especially the production of two kinds of visual holographic secret codes. The optical arrangements for recording are presented, and the effective results from using the visual secret codes into holographic trade marks are reported.

  7. A Resilient Quantum Secret Sharing Scheme

    NASA Astrophysics Data System (ADS)

    Maitra, Arpita; Paul, Goutam

    2015-02-01

    A resilient secret sharing scheme is supposed to generate the secret correctly even after some shares are damaged. In this paper, we show how quantum error correcting codes can be exploited to design a resilient quantum secret sharing scheme, where a quantum state is shared among more than one parties.

  8. Renal tubular secretion of pramipexole.

    PubMed

    Knop, Jana; Hoier, Eva; Ebner, Thomas; Fromm, Martin F; Müller, Fabian

    2015-11-15

    The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2-K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK-MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12μM and 5.5μM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. A dopamine-secreting pheochromocytoma.

    PubMed

    Yasunari, K; Kohno, M; Minami, M; Kano, H; Ohhira, M; Nakamura, K; Yoshikawa, J

    2000-01-01

    We describe a patient with pheochromocytoma, which secretes dopamine. He was admitted to hospital because of chronic diarrhea. After surgical resection of the tumor, dramatic cessation of the diarrhea and blood pressure elevation were observed. Decreased expression of dopamine beta-hydroxylase in the tumor was considered a possible mechanism of producing a pathophysiological concentration of dopamine. This case shows that excessive excretion of dopamine, a vasodilative hormone, may affect blood pressure.

  10. Native Small Airways Secrete Bicarbonate

    PubMed Central

    Quinton, Paul M.

    2014-01-01

    Since the discovery of Cl− impermeability in cystic fibrosis (CF) and the cloning of the responsible channel, CF pathology has been widely attributed to a defect in epithelial Cl− transport. However, loss of bicarbonate (HCO3−) transport also plays a major, possibly more critical role in CF pathogenesis. Even though HCO3− transport is severely affected in the native pancreas, liver, and intestines in CF, we know very little about HCO3− secretion in small airways, the principle site of morbidity in CF. We used a novel, mini-Ussing chamber system to investigate the properties of HCO3− transport in native porcine small airways (∼ 1 mm φ). We assayed HCO3− transport across small airway epithelia as reflected by the transepithelial voltage, conductance, and equivalent short-circuit current with bilateral 25-mM HCO3− plus 125-mM NaGlu Ringer’s solution in the presence of luminal amiloride (10 μM). Under these conditions, because no major transportable anions other than HCO3− were present, we took the equivalent short-circuit current to be a direct measure of active HCO3− secretion. Applying selective agonists and inhibitors, we show constitutive HCO3− secretion in small airways, which can be stimulated significantly by β-adrenergic– (cAMP) and purinergic (Ca2+) -mediated agonists, independently. These results indicate that two separate components for HCO3− secretion, likely via CFTR- and calcium-activated chloride channel–dependent processes, are physiologically regulated for likely roles in mucus clearance and antimicrobial innate defenses of small airways. PMID:24224935

  11. Electronic enhancement of tear secretion

    NASA Astrophysics Data System (ADS)

    Brinton, Mark; Lim Chung, Jae; Kossler, Andrea; Kook, Koung Hoon; Loudin, Jim; Franke, Manfred; Palanker, Daniel

    2016-02-01

    Objective. To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion. Approach. We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz). Main results. Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm-2 with 170-680 μs pulses) than the damage threshold (3.5 μC mm-2 with 1 ms pulses). Significance. Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and

  12. Transporter-mediated biofuel secretion

    PubMed Central

    Doshi, Rupak; Nguyen, Tuan; Chang, Geoffrey

    2013-01-01

    Engineering microorganisms to produce biofuels is currently among the most promising strategies in renewable energy. However, harvesting these organisms for extracting biofuels is energy- and cost-intensive, limiting the commercial feasibility of large-scale production. Here, we demonstrate the use of a class of transport proteins of pharmacological interest to circumvent the need to harvest biomass during biofuel production. We show that membrane-embedded transporters, better known to efflux lipids and drugs, can be used to mediate the secretion of intracellularly synthesized model isoprenoid biofuel compounds to the extracellular milieu. Transporter-mediated biofuel secretion sustainably maintained an approximate three- to fivefold boost in biofuel production in our Escherichia coli test system. Because the transporters used in this study belong to the ubiquitous ATP-binding cassette protein family, we propose their use as “plug-and-play” biofuel-secreting systems in a variety of bacteria, cyanobacteria, diatoms, yeast, and algae used for biofuel production. This investigation showcases the potential of expressing desired membrane transport proteins in cell factories to achieve the export or import of substances of economic, environmental, or therapeutic importance. PMID:23613592

  13. Transporter-mediated biofuel secretion.

    PubMed

    Doshi, Rupak; Nguyen, Tuan; Chang, Geoffrey

    2013-05-07

    Engineering microorganisms to produce biofuels is currently among the most promising strategies in renewable energy. However, harvesting these organisms for extracting biofuels is energy- and cost-intensive, limiting the commercial feasibility of large-scale production. Here, we demonstrate the use of a class of transport proteins of pharmacological interest to circumvent the need to harvest biomass during biofuel production. We show that membrane-embedded transporters, better known to efflux lipids and drugs, can be used to mediate the secretion of intracellularly synthesized model isoprenoid biofuel compounds to the extracellular milieu. Transporter-mediated biofuel secretion sustainably maintained an approximate three- to fivefold boost in biofuel production in our Escherichia coli test system. Because the transporters used in this study belong to the ubiquitous ATP-binding cassette protein family, we propose their use as "plug-and-play" biofuel-secreting systems in a variety of bacteria, cyanobacteria, diatoms, yeast, and algae used for biofuel production. This investigation showcases the potential of expressing desired membrane transport proteins in cell factories to achieve the export or import of substances of economic, environmental, or therapeutic importance.

  14. QUANTITATIVE STUDIES OF PROSTATIC SECRETION

    PubMed Central

    Huggins, Charles; Clark, Philip Johnson

    1940-01-01

    Cystic hyperplasia of the prostate occurs spontaneously in senile dogs only when they possess physiologically effective amounts of androgenic hormone. The cysts are closely grouped and radially arranged in a conical manner with the base of the cone at the periphery of the gland. Flattened and columnar epithelium, varying from about 5 to 25µ are seen in each cyst. The cysts communicate with the urethra by way of ducts. Both normal and cystic prostates undergo marked atrophy when the testes are removed, the chief difference 3 months after orchiectomy being the persistence of slightly dilated clefts and spaces at the site of the former cysts in the senile state. In the castrate dog whose prostate gland is being reconstructed as result of the influence of daily injections of androgen, certain doses of estrogen prevent increase of secretion and still larger doses greatly depress the output of the gland. In dogs so treated by daily injections of testosterone propionate, 10 mg., the amount of secretion is maintained from day to day at a level by daily injections of stilbestrol, 0.4 to 0.6 mg. and greatly depressed by doses of 1 to 1.5 mg. When the larger amounts of estrogen are used, together with androgen, squamous metaplasia occurs in the posterior lobe of the prostate while the epithelium of the acini decreases in height to cuboidal or low columnar form; these histological signs of activity of both androgen and estrogen on the prostate show that inhibition of the male hormone by stilbestrol is incomplete at these ratios. In dogs with either normal or cystic prostate glands, the prostate decreases in size when estrogen is injected in amounts to depress prostatic secretion profoundly. The gland is maintained in an atrophic state and overdosage avoided by controlled periodic injections of stilbestrol until secretion is reduced to the minimum, followed by free intervals, the estrogen being again administered when secretion measurably increases. The shrinkage is related to

  15. Secretion of Protective Antigens by Tissue-Stage Nematode Larvae Revealed by Proteomic Analysis and Vaccination-Induced Sterile Immunity

    PubMed Central

    Hewitson, James P.; Ivens, Al C.; Harcus, Yvonne; Filbey, Kara J.; McSorley, Henry J.; Murray, Janice; Bridgett, Stephen; Ashford, David; Dowle, Adam A.; Maizels, Rick M.

    2013-01-01

    Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES) products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4) larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel repertoire of H

  16. Unconventional Pathways of Secretion Contribute to Inflammation

    PubMed Central

    Daniels, Michael J. D.; Brough, David

    2017-01-01

    In the conventional pathway of protein secretion, leader sequence-containing proteins leave the cell following processing through the endoplasmic reticulum (ER) and Golgi body. However, leaderless proteins also enter the extracellular space through mechanisms collectively known as unconventional secretion. Unconventionally secreted proteins often have vital roles in cell and organism function such as inflammation. Amongst the best-studied inflammatory unconventionally secreted proteins are interleukin (IL)-1β, IL-1α, IL-33 and high-mobility group box 1 (HMGB1). In this review we discuss the current understanding of the unconventional secretion of these proteins and highlight future areas of research such as the role of nuclear localisation. PMID:28067797

  17. Studies into secretions of Tetrahymena: enzymes secreted into inorganic medium.

    PubMed

    Kovács, P; Karsa, J; Csaba, G

    1992-01-01

    The peptides secreted by Tetrahymena cells into inorganic medium were chromatographed. Six fractions showing a marked enzyme-like activity were examined for influence on certain physiological parameters of Tetrahymena. The enzymatically active fractions increased the phagocytic activity of Tetrahymena and decreased its binding capacity for lectins and hormone (insulin), but enhanced insulin imprinting at primary interaction. It remains to be clarified whether these effects were due to the enzymatic or other components of the fractions investigated, or to lack of the compensatory influence of the fractions not studied.

  18. Semiquantum secret sharing using entangled states

    SciTech Connect

    Li Qin; Chan, W. H.; Long Dongyang

    2010-08-15

    Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but one of them cannot. The presented protocols are also shown to be secure against eavesdropping.

  19. Unconventional protein secretion: an evolving mechanism

    PubMed Central

    Malhotra, Vivek

    2013-01-01

    The process by which proteins are secreted without entering the classical endoplasmic reticulum (ER)–Golgi complex pathway, in eukaryotic cells, is conveniently called unconventional protein secretion. Recent studies on one such protein called Acb1 have revealed a number of components involved in its secretion. Interestingly, conditions that promote the secretion of Acb1 trigger the biogenesis of a new compartment called CUPS (Compartment for Unconventional Protein Secretion). CUPS form near the ER exit site but lack ER-specific proteins. Other proteins that share some of the features common with the secretion of Acb1 are interleukin-1β and tissue transglutaminase. Here I will review recent advances made in the field and propose a new model for unconventional protein secretion. PMID:23665917

  20. LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis.

    PubMed

    Reina, Laura D; O'Bryant, Deanna M; Matson, Jyl S; Nilles, Matthew L

    2008-02-08

    LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2-6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

  1. LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

    PubMed Central

    Reina, Laura D; O'Bryant, Deanna M; Matson, Jyl S; Nilles, Matthew L

    2008-01-01

    Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion. PMID:18261225

  2. Russian scientists save American secrets

    SciTech Connect

    Sagdeev, R.

    1993-05-01

    Many have feared that the collapse of the Soviet Union has created new opportunities for would-be nuclear proliferators. Until recently, those dangers have seemed mainly theoretical. However, the former Soviet world was recently on the brink of breaching the Nuclear Non-Proliferation Treaty (NPT) from an unexpected corner -- the KGB. This article discusses the irony that a move to publicize Russia's files on early Soviet espionage activities in the United States would originate from the KGB. It is of note that a publication of such secrets could have been useful to countries currently trying to develop a basic nuclear bomb.

  3. Donor insemination: the secret experiment.

    PubMed

    Rushbrooke, Rupert

    2004-03-01

    This paper gives an overview of the research that has been done into people created by donor insemination (DI) (note 1), shows how the secretive way DI is carried out makes objective knowledge of their situation impossible to obtain and describes how doctors support this secrecy. It argues that DI is a social experiment whose potential justifications are implicit theories that have either been falsified or are unfalsifiable, and that consequently DI is conducted unscientifically and unethically. In conclusion, it questions the integrity of the industry and the institutions that support it, and considers where we should go from here.

  4. Matroids and quantum-secret-sharing schemes

    SciTech Connect

    Sarvepalli, Pradeep; Raussendorf, Robert

    2010-05-15

    A secret-sharing scheme is a cryptographic protocol to distribute a secret state in an encoded form among a group of players such that only authorized subsets of the players can reconstruct the secret. Classically, efficient secret-sharing schemes have been shown to be induced by matroids. Furthermore, access structures of such schemes can be characterized by an excluded minor relation. No such relations are known for quantum secret-sharing schemes. In this paper we take the first steps toward a matroidal characterization of quantum-secret-sharing schemes. In addition to providing a new perspective on quantum-secret-sharing schemes, this characterization has important benefits. While previous work has shown how to construct quantum-secret-sharing schemes for general access structures, these schemes are not claimed to be efficient. In this context the present results prove to be useful; they enable us to construct efficient quantum-secret-sharing schemes for many general access structures. More precisely, we show that an identically self-dual matroid that is representable over a finite field induces a pure-state quantum-secret-sharing scheme with information rate 1.

  5. The evidence for secretion clearance techniques.

    PubMed

    Hess, D R

    2001-11-01

    Many acute and chronic respiratory diseases are associated with increased respiratory secretions in the airways. Narrative reviews and a few systematic reviews of secretion clearance techniques have been published. These reviews raise concerns regarding the lack of evidence to support the various secretion clearance techniques. I conducted a comprehensive MEDLINE search of the following subjects: chest physical therapy, chest physiotherapy, postural drainage, forced expiratory technique, autogenic drainage, high-frequency chest wall compression, flutter device and secretions, positive expiratory pressure and secretions, intrapulmonary percussion, mechanical in-exsufflation and secretions. This was followed by a comprehensive search of cross-references to identify additional studies. The results of this review are reported herein. There are a number of methodological limitations of the literature reporting studies of the use of secretion clearance techniques. Most of the studies were small, most used crossover designs, and few used sham therapy. Many studies were limited to short-term outcomes such as sputum clearance with a single treatment session. Despite the clinical observation that retained secretions are detrimental to respiratory function and despite anecdotal associations between secretion clearance and improvements in respiratory function, there is a dearth of high-level evidence to support any secretion clearance technique.

  6. A gastric acid secretion model.

    PubMed Central

    de Beus, A M; Fabry, T L; Lacker, H M

    1993-01-01

    A theory of gastric acid production and self-protection is formulated mathematically and examined for clinical and experimental correlations, implications, and predictions using analytic and numerical techniques. In our model, gastric acid secretion in the stomach, as represented by an archetypal gastron, consists of two chambers, circulatory and luminal, connected by two different regions of ion exchange. The capillary circulation of the gastric mucosa is arranged in arterial-venous arcades which pass from the gastric glands up to the surface epithelial lining of the lumen; therefore the upstream region of the capillary chamber communicates with oxyntic cells, while the downstream region communicates with epithelial cells. Both cell types abut the gastric lumen. Ion currents across the upstream region are calculated from a steady-state oxyntic cell model with active ion transport, while the downstream ion fluxes are (facilitated) diffusion driven or secondarily active. Water transport is considered iso-osmotic. The steady-state model is solved in closed form for low gastric lumen pH. A wide variety of previously performed static and dynamic experiments on ion and CO2 transport in the gastric lumen and gastric blood supply are for the first time correlated with each other for an (at least) semiquantitative test of current concepts of gastric acid secretion and for the purpose of model verification. Agreement with the data is reported with a few outstanding and instructive exceptions. Model predictions and implications are also discussed. Images FIGURE 1 PMID:8396457

  7. Liquid secretion properties of airway submucosal glands

    PubMed Central

    Ballard, Stephen T; Inglis, Sarah K

    2004-01-01

    The tracheobronchial submucosal glands secrete liquid that is important for hydrating airway surfaces, supporting mucociliary transport, and serving as a fluid matrix for numerous secreted macromolecules including the gel-forming mucins. This review details the essential structural elements of airway glands and summarizes what is currently known regarding the ion transport processes responsible for producing the liquid component of gland secretion. Liquid secretion most likely arises from serous cells and is principally under neural control with muscarinic agonists, substance P, and vasoactive intestinal peptide (VIP) functioning as effective secretogogues. Liquid secretion is driven by the active transepithelial secretion of both Cl− and HCO3− and at least a portion of this process is mediated by the cystic fibrosis transmembrane conductance regulator (CFTR), which is highly expressed in glands. The potential role of submucosal glands in cystic fibrosis lung disease is discussed. PMID:14660706

  8. Normal and abnormal secretion by haemopoietic cells

    PubMed Central

    STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M

    2001-01-01

    The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687

  9. Secretion by numbers: protein traffic in prokaryotes

    PubMed Central

    Economou, Anastasias; Christie, Peter J.; Fernandez, Rachel C.; Palmer, Tracy; Plano, Greg V.; Pugsley, Anthony P.

    2013-01-01

    Summary Almost all aspects of protein traffic in bacteria were covered at the ASM-FEMS meeting on the topic in Iraklio, Crete in May 2006. The studies presented ranged from mechanistic analysis of specific events leading proteins to their final destinations to the physiological roles of the targeted proteins. Among the highlights from the meeting that are reviewed here are the molecular dynamics of SecA protein, membrane protein insertion, type III secretion needles and chaperones, type IV secretion, the two partner and autosecretion systems, the ‘secretion competent state’, and the recently discovered type VI secretion system. PMID:17020575

  10. Efficient multiparty quantum-secret-sharing schemes

    SciTech Connect

    Xiao Li; Deng Fuguo; Long Guilu; Pan Jianwei

    2004-05-01

    In this work, we generalize the quantum-secret-sharing scheme of Hillery, Buzek, and Berthiaume [Phys. Rev. A 59, 1829 (1999)] into arbitrary multiparties. Explicit expressions for the shared secret bit is given. It is shown that in the Hillery-Buzek-Berthiaume quantum-secret-sharing scheme the secret information is shared in the parity of binary strings formed by the measured outcomes of the participants. In addition, we have increased the efficiency of the quantum-secret-sharing scheme by generalizing two techniques from quantum key distribution. The favored-measuring-basis quantum-secret-sharing scheme is developed from the Lo-Chau-Ardehali technique [H. K. Lo, H. F. Chau, and M. Ardehali, e-print quant-ph/0011056] where all the participants choose their measuring-basis asymmetrically, and the measuring-basis-encrypted quantum-secret-sharing scheme is developed from the Hwang-Koh-Han technique [W. Y. Hwang, I. G. Koh, and Y. D. Han, Phys. Lett. A 244, 489 (1998)] where all participants choose their measuring basis according to a control key. Both schemes are asymptotically 100% in efficiency, hence nearly all the Greenberger-Horne-Zeilinger states in a quantum-secret-sharing process are used to generate shared secret information.

  11. Physiology of Epithelial Chloride and Fluid Secretion

    PubMed Central

    Frizzell, Raymond A.; Hanrahan, John W.

    2012-01-01

    Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epithelial anion and fluid secretion, their regulation, and how these processes are altered in CF disease to account for organ-specific secretory phenotypes. PMID:22675668

  12. Stimulation of leptin secretion by insulin

    PubMed Central

    Tsai, Minglun; Asakawa, Akihiro; Amitani, Haruka; Inui, Akio

    2012-01-01

    Leptin has a crucial role in regulating food intake and maintaining metabolic homeostasis. Although little is known about the process of leptin secretion, insulin, which has an important role in the metabolism of glucose and lipids, is believed to regulate leptin secretion through a posttranscriptional mechanism in the short term, and via glucose metabolism in the long term. The gastric mucosa secretes leptin, but this mechanism has not been completely elucidated. Understanding the mechanism of insulin-regulated leptin secretion could lead to the development of new treatment methods for obesity and its comorbidities, which are serious public health concerns. PMID:23565488

  13. Random Secretion of Growth Hormone in Humans

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

    1996-08-01

    In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

  14. Metabolic control of renin secretion

    PubMed Central

    Gevorgyan, Haykanush; Lam, Lisa; Riquier-Brison, Anne

    2015-01-01

    One emerging topic in renin–angiotensin system (RAS) research is the direct local control of renin synthesis and release by endogenous metabolic intermediates. During the past few years, our laboratory has characterized the localization and signaling of the novel metabolic receptor GPR91 in the normal and diabetic kidney and established GPR91 as a new, direct link between high glucose and RAS activation in diabetes. GPR91 (also called SUCNR1) binds tricarboxylic acid (TCA) cycle intermediate succinate which can rapidly accumulate in the local tissue environment when energy supply and demand are out of balance. In a variety of physiological and pathological conditions associated with metabolic stress, succinate signaling via GPR91 appears to be an important mediator or modulator of renin secretion. This review summarizes our current knowledge on the control of renin release by molecules of endogenous metabolic pathways with the main focus on succinate/GPR91. PMID:22729752

  15. Metabolic control of renin secretion.

    PubMed

    Peti-Peterdi, János; Gevorgyan, Haykanush; Lam, Lisa; Riquier-Brison, Anne

    2013-01-01

    One emerging topic in renin-angiotensin system (RAS) research is the direct local control of renin synthesis and release by endogenous metabolic intermediates. During the past few years, our laboratory has characterized the localization and signaling of the novel metabolic receptor GPR91 in the normal and diabetic kidney and established GPR91 as a new, direct link between high glucose and RAS activation in diabetes. GPR91 (also called SUCNR1) binds tricarboxylic acid (TCA) cycle intermediate succinate which can rapidly accumulate in the local tissue environment when energy supply and demand are out of balance. In a variety of physiological and pathological conditions associated with metabolic stress, succinate signaling via GPR91 appears to be an important mediator or modulator of renin secretion. This review summarizes our current knowledge on the control of renin release by molecules of endogenous metabolic pathways with the main focus on succinate/GPR91.

  16. Noninvasive clearance of airway secretions.

    PubMed

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  17. [Mucoprotein secretion in calculous gallbladder].

    PubMed

    Fernández Lobato, R; Ortega, L; Balibrea, J L; Torres, A J; García-Calvo, M; Alvarez Sánchez, J A

    1994-05-01

    Secretion of mucoproteins or mucine (MP) have been studied as possible markers in several pathological conditions of the digestive tract, such us colonic polyposis or gastric dysplasia. In the gallbladder (VB) it has been established that form the core of crystalization for the calculi. A study in 100 gallbladders have been made based on the utility of the analysis of the qualitative and quantitative modifications of MP in lithogenesis. It was been determined by histochemical techniques the three main types of MP (neutral, low and high sulphated acid) to evaluate the alterations in the process of lithiasis. Results show a high production of the MP in VB with lithiasis, presenting in 97% a mixed composition of MP (48.9% of 2 types, and 3 types in 46%), without a predominating type in this pathology.

  18. Protein secretion pathways in Bacillus subtilis: implication for optimization of heterologous protein secretion.

    PubMed

    Ling Lin Fu; Zi Rong Xu; Wei Fen Li; Jiang Bing Shuai; Ping Lu; Chun Xia Hu

    2007-01-01

    The absence of an outer membrane in Bacillus subtilis can simplify the protein secretion pathways and allow the organism to secrete high levels of extracellular proteins. Of the three known secretory routes, Sec-SRP pathway can direct the majority of secretory proteins into the growth medium. Alternatively, a small number of exoproteins with specific functions are secreted via Tat pathway or ABC transporters in B. subtilis. The discriminating function of precursor proteins among these pathways is largely attributed to the distinct structure of their cleavable signal peptides. Individual secretion machinery components with their special functions are involved in the total flow of proteins from the cytoplasm to the medium. Notably, multiple regulators with signal transduction functions can affect expression of secretion machinery as well as their post-transcriptional actions for protein secretion, resulting in the complicated networks in B. subtilis. Ultimately, according to the available knowledge of secretion machinery, several approaches aimed at optimizing protein secretion are discussed.

  19. Unitary reconstruction of secret for stabilizer-based quantum secret sharing

    NASA Astrophysics Data System (ADS)

    Matsumoto, Ryutaroh

    2017-08-01

    We propose a unitary procedure to reconstruct quantum secret for a quantum secret sharing scheme constructed from stabilizer quantum error-correcting codes. Erasure correcting procedures for stabilizer codes need to add missing shares for reconstruction of quantum secret, while unitary reconstruction procedures for certain class of quantum secret sharing are known to work without adding missing shares. The proposed procedure also works without adding missing shares.

  20. Type VI secretion system: secretion by a contractile nanomachine

    PubMed Central

    Basler, Marek

    2015-01-01

    The type VI secretion systems (T6SS) are present in about a quarter of all Gram-negative bacteria. Several key components of T6SS are evolutionarily related to components of contractile nanomachines such as phages and R-type pyocins. The T6SS assembly is initiated by formation of a membrane complex that binds a phage-like baseplate with a sharp spike, and this is followed by polymerization of a long rigid inner tube and an outer contractile sheath. Effectors are preloaded onto the spike or into the tube during the assembly by various mechanisms. Contraction of the sheath releases an unprecedented amount of energy, which is used to thrust the spike and tube with the associated effectors out of the effector cell and across membranes of both bacterial and eukaryotic target cells. Subunits of the contracted sheath are recycled by T6SS-specific unfoldase to allow for a new round of assembly. Live-cell imaging has shown that the assembly is highly dynamic and its subcellular localization is in certain bacteria regulated with a remarkable precision. Through the action of effectors, T6SS has mainly been shown to contribute to pathogenicity and competition between bacteria. This review summarizes the knowledge that has contributed to our current understanding of T6SS mode of action. PMID:26370934

  1. Family Secrets: The Bioethics of Genetic Testing

    ERIC Educational Resources Information Center

    Markowitz, Dina G.; DuPre, Michael J.; Holt, Susan; Chen, Shaw-Ree; Wischnowski, Michael

    2006-01-01

    This article discusses "Family Secrets," a problem-based learning (PBL) curriculum module that focuses on the bioethical implications of genetic testing. In high school biology classrooms throughout New York State, students are using "Family Secrets" to learn about DNA testing; Huntington's disease (HD); and the ethical, legal,…

  2. "The Secret Garden": A Literary Journey.

    ERIC Educational Resources Information Center

    Jordan, Anne Devereaux

    1998-01-01

    Outlines the life of Frances Hodgson Burnett, author of "The Secret Garden." Argues that it not only tells an enthralling tale, but takes readers on a journey through the history of English literature. Discusses the gothic tradition and romanticism of "The Secret Garden." Lists classic elements in the book and offers five ideas…

  3. 29 CFR 1903.9 - Trade secrets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Trade secrets. 1903.9 Section 1903.9 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR INSPECTIONS, CITATIONS AND PROPOSED PENALTIES § 1903.9 Trade secrets. (a) Section 15 of the Act provides: “All information reported to or otherwise obtained...

  4. Comment on "Proactive quantum secret sharing"

    NASA Astrophysics Data System (ADS)

    Gao, Gan; Wang, Yue

    2017-03-01

    In the paper, Qin and Dai (Quantum Inf Process 14:4237-4244, 2015) proposed a proactive quantum secret sharing scheme. We study the security of the proposed scheme and find that it is not secure. In the distribution phase of the proposed scheme, two dishonest participants may collaborate to eavesdrop the secret of the dealer without introducing any error.

  5. "The Secret Garden": A Literary Journey.

    ERIC Educational Resources Information Center

    Jordan, Anne Devereaux

    1998-01-01

    Outlines the life of Frances Hodgson Burnett, author of "The Secret Garden." Argues that it not only tells an enthralling tale, but takes readers on a journey through the history of English literature. Discusses the gothic tradition and romanticism of "The Secret Garden." Lists classic elements in the book and offers five ideas…

  6. Transepithelial bicarbonate secretion: lessons from the pancreas.

    PubMed

    Park, Hyun Woo; Lee, Min Goo

    2012-10-01

    Many cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelia secrete bicarbonate (HCO(3)(-))-containing fluids. Recent evidence suggests that defects in epithelial bicarbonate secretion are directly involved in the pathogenesis of cystic fibrosis, in particular by building up hyperviscous mucus in the ductal structures of the lung and pancreas. Pancreatic juice is one of the representative fluids that contain a very high concentration of bicarbonate among bodily fluids that are secreted from CFTR-expressing epithelia. We introduce up-to-date knowledge on the basic principles of transepithelial bicarbonate transport by showing the mechanisms involved in pancreatic bicarbonate secretion. The model of pancreatic bicarbonate secretion described herein may also apply to other exocrine epithelia. As a central regulator of bicarbonate transport at the apical membrane, CFTR plays an essential role in both direct and indirect bicarbonate secretion. The major role of CFTR in bicarbonate secretion would be variable depending on the tissue and cell type. For example, in epithelial cells that produce a low concentration of bicarbonate-containing fluid (up to 80 mm), either CFTR-dependent Cl(-)/HCO(3)(-) exchange or CFTR anion channel with low bicarbonate permeability would be sufficient to generate such fluid. However, in cells that secrete high-bicarbonate-containing fluids, a highly selective CFTR bicarbonate channel activity is required. Therefore, understanding the molecular mechanism of transepithelial bicarbonate transport and the role of CFTR in each specific epithelium will provide therapeutic strategies to recover from epithelial defects induced by hyposecretion of bicarbonate in cystic fibrosis.

  7. Bacterial Secretion Systems – An overview

    PubMed Central

    Green, Erin R.; Mecsas, Joan

    2015-01-01

    CHAPTER SUMMARY Bacterial pathogens utilize a multitude of methods to invade mammalian hosts, damage tissue sites, and thwart the immune system from responding. One essential component of these strategies for many bacterial pathogens is the secretion of proteins across phospholipid membranes. Secreted proteins can play many roles in promoting bacterial virulence, from enhancing attachment to eukaryotic cells, to scavenging resources in an environmental niche, to directly intoxicating target cells and disrupting their functions. Many pathogens use dedicated protein secretion systems to secrete virulence factors from the cytosol of the bacteria into host cells or the host environment. In general, bacterial protein secretion apparatuses can be divided into different classes, based on their structures, functions, and specificity. Some systems are conserved in all classes of bacteria and secrete a broad array of substrates, while others are only found in a small number of bacterial species and/or are specific to only one or a few proteins. In this chapter, we review the canonical features of several common bacterial protein secretion systems, as well as their roles in promoting the virulence of bacterial pathogens. Additionally, we address recent findings that indicate that the innate immune system of the host can detect and respond to the presence of protein secretion systems during mammalian infection. PMID:26999395

  8. Family Secrets: The Bioethics of Genetic Testing

    ERIC Educational Resources Information Center

    Markowitz, Dina G.; DuPre, Michael J.; Holt, Susan; Chen, Shaw-Ree; Wischnowski, Michael

    2006-01-01

    This article discusses "Family Secrets," a problem-based learning (PBL) curriculum module that focuses on the bioethical implications of genetic testing. In high school biology classrooms throughout New York State, students are using "Family Secrets" to learn about DNA testing; Huntington's disease (HD); and the ethical, legal,…

  9. Toxins and Secretion Systems of Photorhabdus luminescens

    PubMed Central

    Rodou, Athina; Ankrah, Dennis O.; Stathopoulos, Christos

    2010-01-01

    Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae. Recent studies show the importance of this bacterium as an alternative source of insecticides, as well as an emerging human pathogen. Various toxins have been identified and characterized in this bacterium. These toxins are classified into four major groups: the toxin complexes (Tcs), the Photorhabdus insect related (Pir) proteins, the “makes caterpillars floppy” (Mcf) toxins and the Photorhabdus virulence cassettes (PVC); the mechanisms however of toxin secretion are not fully elucidated. Using bioinformatics analysis and comparison against the components of known secretion systems, multiple copies of components of all known secretion systems, except the ones composing a type IV secretion system, were identified throughout the entire genome of the bacterium. This indicates that Photorhabdus luminescens has all the necessary means for the secretion of virulence factors, thus it is capable of establishing a microbial infection. PMID:22069636

  10. Ionizing radiation in secret services' conspirative actions.

    PubMed

    Vogel, H; Lotz, P; Vogel, B

    2007-08-01

    The death of Litvinenko has been reported by the media. It has raised the question whether this case had been unique. The fall of the wall has allowed a glimpse in the planning and comporting of a secret service. Documents of the secret service of the former German democratic republic (GDR), books of defectors, and media reports about secret service actions with radiating substances have been analyzed. Since decades, secret services have been using radioactive nuclides and radiation for their tasks. Several killings with radiation have been reported. A complicated logistic had been developed. Only singular cases of the employment of radiating substances have become known. It is probable that the majority rests unknown. Government support seems necessary in secret services' conspirative actions with radiating substance.

  11. Toxins and secretion systems of Photorhabdus luminescens.

    PubMed

    Rodou, Athina; Ankrah, Dennis O; Stathopoulos, Christos

    2010-06-01

    Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae. Recent studies show the importance of this bacterium as an alternative source of insecticides, as well as an emerging human pathogen. Various toxins have been identified and characterized in this bacterium. These toxins are classified into four major groups: the toxin complexes (Tcs), the Photorhabdus insect related (Pir) proteins, the "makes caterpillars floppy" (Mcf) toxins and the Photorhabdus virulence cassettes (PVC); the mechanisms however of toxin secretion are not fully elucidated. Using bioinformatics analysis and comparison against the components of known secretion systems, multiple copies of components of all known secretion systems, except the ones composing a type IV secretion system, were identified throughout the entire genome of the bacterium. This indicates that Photorhabdus luminescens has all the necessary means for the secretion of virulence factors, thus it is capable of establishing a microbial infection.

  12. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems

    SciTech Connect

    Samudrala, Ram; Heffron, Fred; McDermott, Jason E.

    2009-04-24

    The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, after eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  13. The pathway of collagen secretion.

    PubMed

    Malhotra, Vivek; Erlmann, Patrik

    2015-01-01

    COPII vesicles mediate export of secretory cargo from the endoplasmic reticulum (ER). However, a standard COPII vesicle with a diameter of 60-90 nm is too small to export collagens that are composed of rigid triple helices of up to 400 nm in length. How do cells pack and secrete such bulky molecules? This issue is fundamentally important, as collagens constitute approximately 25% of our dry body weight and are essential for almost all cell-cell interactions. Recently, a potential mechanism for the biogenesis of mega-transport carriers was identified, involving packing collagens and increasing the size of COPII coats. Packing is mediated by TANGO1, which binds procollagen VII in the lumen and interacts with the COPII proteins Sec23/Sec24 on the cytoplasmic side of the ER. Cullin3, an E3 ligase, and its specific adaptor protein, KLHL12, ubiquitinate Sec31, which could increase the size of COPII coats. Recruitment of these proteins and their specific interactors into COPII-mediated vesicle biogenesis may be all that is needed for the export of bulky collagens from the ER. Nonetheless, we present an alternative pathway in which TANGO1 and COPII cooperate to export collagens without generating a mega-transport carrier.

  14. Glucagon secretion from pancreatic α-cells

    PubMed Central

    Briant, Linford; Salehi, Albert; Vergari, Elisa; Zhang, Quan; Rorsman, Patrik

    2016-01-01

    Type 2 diabetes involves a ménage à trois of impaired glucose regulation of pancreatic hormone release: in addition to impaired glucose-induced insulin secretion, the release of the hyperglycaemic hormone glucagon becomes dysregulated; these last-mentioned defects exacerbate the metabolic consequences of hypoinsulinaemia and are compounded further by hypersecretion of somatostatin (which inhibits both insulin and glucagon secretion). Glucagon secretion has been proposed to be regulated by either intrinsic or paracrine mechanisms, but their relative significance and the conditions under which they operate are debated. Importantly, the paracrine and intrinsic modes of regulation are not mutually exclusive; they could operate in parallel to control glucagon secretion. Here we have applied mathematical modelling of α-cell electrical activity as a novel means of dissecting the processes that underlie metabolic regulation of glucagon secretion. Our analyses indicate that basal hypersecretion of somatostatin and/or increased activity of somatostatin receptors may explain the loss of adequate counter-regulation under hypoglycaemic conditions, as well as the physiologically inappropriate stimulation of glucagon secretion during hyperglycaemia seen in diabetic patients. We therefore advocate studying the interaction of the paracrine and intrinsic mechanisms; unifying these processes may give a more complete picture of the regulation of glucagon secretion from α-cells than studying the individual parts. PMID:27044683

  15. Neurotrophin secretion: current facts and future prospects.

    PubMed

    Lessmann, Volkmar; Gottmann, Kurt; Malcangio, Marzia

    2003-04-01

    The proteins of the mammalian neurotrophin family (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5)) were originally identified as neuronal survival factors. During the last decade, evidence has accumulated implicating them (especially BDNF) in addition in the regulation of synaptic transmission and synaptogenesis in the CNS. However, a detailed understanding of the secretion of neurotrophins from neurons is required to delineate their role in regulating synaptic function. Some crucial questions that need to be addressed include the sites of neurotrophin secretion (i.e. axonal versus dendritic; synaptic versus extrasynaptic) and the neuronal and synaptic activity patterns that trigger the release of neurotrophins. In this article, we review the current knowledge in the field of neurotrophin secretion, focussing on activity-dependent synaptic release of BDNF. The modality and the site of neurotrophin secretion are dependent on the processing and subsequent targeting of the neurotrophin precursor molecules. Therefore, the available data regarding formation and trafficking of neurotrophins in the secreting neurons are critically reviewed. In addition, we discuss existing evidence that the characteristics of neurotrophin secretion are similar (but not identical) to those of other neuropeptides. Finally, since BDNF has been proposed to play a critical role as an intercellular synaptic messenger in long-term potentiation (LTP) in the hippocampus, we try to reconcile this possible role of BDNF in LTP with the recently described features of synaptic BDNF secretion.

  16. Secretion of phospholipase C by Pseudomonas aeruginosa.

    PubMed Central

    Stinson, M W; Hayden, C

    1979-01-01

    The conditions necessary for the secretion of phospholipase C (phosphatidylcholine cholinephosphohydrolase) by Pseudomonas aeruginosa were studied. Enzyme secretion by washed cell suspensions required a carbon source and ammonium, potassium, and calcium ions. The calcium requirement could be substituted by magnesium and strontium but not by copper, manganese, cobalt, or zinc. During growth in liquid medium, cells secreted phospholipase C during late logarithmic and early stationary phases. Secretion was repressed by the addition of inorganic phosphate but not by organic phosphates, glucose, or sodium succinate. Studies with tetracycline indicated that de novo protein synthesis was necessary for the secretion of phospholipase C and that the exoenzyme was not released from a preformed periplasmic pool. Similarly, extraction of actively secreting cells with 0.2 M MgCl2 at pH 8.4 solubilized large quantities of the periplasmic enzyme alkaline phosphatase but insignificant amounts of phospholipase C. Bacteria continued to secrete enzyme for nearly 45 min after the addition of inorganic phosphate or rifampin. Images PMID:114487

  17. Lycaenid Caterpillar Secretions Manipulate Attendant Ant Behavior.

    PubMed

    Hojo, Masaru K; Pierce, Naomi E; Tsuji, Kazuki

    2015-08-31

    Mutualistic interactions typically involve the exchange of different commodities between species. Nutritious secretions are produced by a number of insects and plants in exchange for services such as defense. These rewards are valuable metabolically and can be used to reinforce the behavior of symbiotic partners that can learn and remember them effectively. We show here novel effects of insect exocrine secretions produced by caterpillars in modulating the behavior of attendant ants in the food-for-defense interaction between lycaenid butterflies and ants. Reward secretions from the dorsal nectary organ (DNO) of Narathura japonica caterpillars function to reduce the locomotory activities of their attendant ants, Pristomyrmex punctatus workers. Moreover, workers that feed from caterpillar secretions are significantly more likely to show aggressive responses to eversion of the tentacle organs of the caterpillars. Analysis of the neurogenic amines in the brains of workers that consumed caterpillar secretions showed a significant decrease in levels of dopamine compared with controls. Experimental treatments in which reserpine, a known inhibitor of dopamine in Drosophila, was fed to workers similarly reduced their locomotory activity. We conclude that DNO secretions of lycaenid caterpillars can manipulate attendant ant behavior by altering dopaminergic regulation and increasing partner fidelity. Unless manipulated ants also receive a net nutritional benefit from DNO secretions, this suggests that similar reward-for-defense interactions that have been traditionally considered to be mutualisms may in fact be parasitic in nature. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The buffer capacity of airway epithelial secretions

    PubMed Central

    Kim, Dusik; Liao, Jie; Hanrahan, John W.

    2014-01-01

    The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 μl) volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO−3 is the major buffer. Peak buffer capacity (β) increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO−3 secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO−3 secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions. PMID:24917822

  19. Parathyroid hormone - Secretion and metabolism in vivo.

    NASA Technical Reports Server (NTRS)

    Habener, J. F.; Powell, D.; Murray, T. M.; Mayer, G. P.; Potts, J. T., Jr.

    1971-01-01

    Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood from patients with hyperparathyroidism, as well as from calves and from cattle. It was found that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically, dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

  20. [Secret drug tribulations and French legislation].

    PubMed

    Charlot, Colette

    2002-01-01

    From an official Montpellier prefecture paper of 18th century, we are interested in a secret drug from Provence origin: the Irroë powder. This purgative will pass from "secret" drug status to "patent" drug. It's notoriety will come from its arrival to Paris. The law of 21th germinal year XI, the decret of 25 prairial year XIII and this of 18th 1810 imposed to give the drug composition to an official status; that examined and permit it's sale. This secret will be produce for half century.

  1. Landmark discoveries in intracellular transport and secretion

    PubMed Central

    Paknikar, Kishore M

    2007-01-01

    Abstract Cellular protein transport and secretion is fundamental to the very existence of an organism, regulating important physiological functions such as reproduction, digestion, energy production, growth, neurotransmission, hormone release, water and ion transport, etc., all required for the survival and maintenance of homeostasis within an organism. Molecular understanding of transport and secretion of intracellular product has therefore been of paramount importance and aggressively investigated for over six decades. Only in the last 20 years, the general molecular mechanism of the process has come to light, following discovery of key proteins involved in ER-Golgi transport, and discovery of the ‘porosome’– the universal secretion machinery in cells. PMID:17635635

  2. Digestive Secretion of Dionaea muscipula (Venus's Flytrap).

    PubMed

    Scala, J; Iott, K; Schwab, D W; Semersky, F E

    1969-03-01

    The digestive fluid of Dionaea muscipula has been studied with respect to its protein content as a function of time after entrapment of protein material and some enzymes of the secretion. Maximum secretion of enzyme occurs within the first 3 days of the digestive cycle and protein reaches its maximum at 4 days. Phosphatase, proteinase, nuclease and amylase have been observed in the secretion. The enzymes have acid pH optima and the proteinase has a molecular weight of about 40,000.

  3. Parathyroid hormone - Secretion and metabolism in vivo.

    NASA Technical Reports Server (NTRS)

    Habener, J. F.; Powell, D.; Murray, T. M.; Mayer, G. P.; Potts, J. T., Jr.

    1971-01-01

    Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood from patients with hyperparathyroidism, as well as from calves and from cattle. It was found that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically, dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

  4. Isolating a Cell Maximally Secreting Acetylcholinesterase

    DTIC Science & Technology

    1985-04-01

    research is to isolate a cell line maximally secreting human acetylcholinesterase (AChE, acetylcholine hydrolase, EC 3.1.1.7). This positive...Figures 17-42 " ’ . . ! I I I 1 List of Figures for Annual Report 1. Secretion Levels of Human AChE for Various Cell Lines 2. Culture Data for Human ...secretion of AChE, the A-204 human rhabdomyosarcoma muscle cell line (described previously) has proven to be the most consistent secretor of enzyme (2-4

  5. Digestive Secretion of Dionaea muscipula (Venus's Flytrap)

    PubMed Central

    Scala, J.; Iott, K.; Schwab, D. W.; Semersky, F. E.

    1969-01-01

    The digestive fluid of Dionaea muscipula has been studied with respect to its protein content as a function of time after entrapment of protein material and some enzymes of the secretion. Maximum secretion of enzyme occurs within the first 3 days of the digestive cycle and protein reaches its maximum at 4 days. Phosphatase, proteinase, nuclease and amylase have been observed in the secretion. The enzymes have acid pH optima and the proteinase has a molecular weight of about 40,000. PMID:16657071

  6. Multimer recognition and secretion by the non-classical secretion pathway in Bacillus subtilis.

    PubMed

    Zhao, Liuqun; Chen, Jingqi; Sun, Jibin; Zhang, Dawei

    2017-03-09

    Non-classical protein secretion in bacteria is a common phenomenon. However, the selection principle for non-classical secretion pathways remains unclear. Here, our experimental data, to our knowledge, are the first to show that folded multimeric proteins can be recognized and excreted by a non-classical secretion pathway in Bacillus subtilis. We explored the secretion pattern of a typical cytoplasmic protein D-psicose 3-epimerase from Ruminococcus sp. 5_1_39BFAA (RDPE), and showed that its non-classical secretion is not simply due to cell lysis. Analysis of truncation variants revealed that the C- and N-terminus, and two hydrophobic domains, are required for structural stability and non-classical secretion of RDPE. Alanine scanning mutagenesis of the hydrophobic segments of RDPE revealed that hydrophobic residues mediated the equilibrium between its folded and unfolded forms. Reporter mCherry and GFP fusions with RDPE regions show that its secretion requires an intact tetrameric protein complex. Using cross-linked tetramers, we show that folded tetrameric RDPE can be secreted as a single unit. Finally, we provide evidence that the non-classical secretion pathway has a strong preference for multimeric substrates, which accumulate at the poles and septum region. Altogether, these data show that a multimer recognition mechanism is likely applicable across the non-classical secretion pathway.

  7. Multimer recognition and secretion by the non-classical secretion pathway in Bacillus subtilis

    PubMed Central

    Zhao, Liuqun; Chen, Jingqi; Sun, Jibin; Zhang, Dawei

    2017-01-01

    Non-classical protein secretion in bacteria is a common phenomenon. However, the selection principle for non-classical secretion pathways remains unclear. Here, our experimental data, to our knowledge, are the first to show that folded multimeric proteins can be recognized and excreted by a non-classical secretion pathway in Bacillus subtilis. We explored the secretion pattern of a typical cytoplasmic protein D-psicose 3-epimerase from Ruminococcus sp. 5_1_39BFAA (RDPE), and showed that its non-classical secretion is not simply due to cell lysis. Analysis of truncation variants revealed that the C- and N-terminus, and two hydrophobic domains, are required for structural stability and non-classical secretion of RDPE. Alanine scanning mutagenesis of the hydrophobic segments of RDPE revealed that hydrophobic residues mediated the equilibrium between its folded and unfolded forms. Reporter mCherry and GFP fusions with RDPE regions show that its secretion requires an intact tetrameric protein complex. Using cross-linked tetramers, we show that folded tetrameric RDPE can be secreted as a single unit. Finally, we provide evidence that the non-classical secretion pathway has a strong preference for multimeric substrates, which accumulate at the poles and septum region. Altogether, these data show that a multimer recognition mechanism is likely applicable across the non-classical secretion pathway. PMID:28276482

  8. Using Transcriptional Control To Increase Titers of Secreted Heterologous Proteins by the Type III Secretion System

    PubMed Central

    Metcalf, Kevin J.; Finnerty, Casey; Azam, Anum; Valdivia, Elias

    2014-01-01

    The type III secretion system (T3SS) encoded at the Salmonella pathogenicity island 1 (SPI-1) locus secretes protein directly from the cytosol to the culture media in a concerted, one-step process, bypassing the periplasm. While this approach is attractive for heterologous protein production, product titers are too low for many applications. In addition, the expression of the SPI-1 gene cluster is subject to native regulation, which requires culturing conditions that are not ideal for high-density growth. We used transcriptional control to increase the amount of protein that is secreted into the extracellular space by the T3SS of Salmonella enterica. The controlled expression of the gene encoding SPI-1 transcription factor HilA circumvents the requirement of endogenous induction conditions and allows for synthetic induction of the secretion system. This strategy increases the number of cells that express SPI-1 genes, as measured by promoter activity. In addition, protein secretion titer is sensitive to the time of addition and the concentration of inducer for the protein to be secreted and SPI-1 gene cluster. Overexpression of hilA increases secreted protein titer by >10-fold and enables recovery of up to 28 ± 9 mg/liter of secreted protein from an 8-h culture. We also demonstrate that the protein beta-lactamase is able to adopt an active conformation after secretion, and the increase in secreted titer from hilA overexpression also correlates to increased enzyme activity in the culture supernatant. PMID:25038096

  9. Insulin and Glucagon Secretion In Vitro

    NASA Technical Reports Server (NTRS)

    Rajan, Arun S.

    1998-01-01

    Long-duration space flight is associated with many physiological abnormalities in astronauts. In particular, altered regulation of the hormones insulin and glucagon may contribute to metabolic disturbances such as increased blood sugar levels, which if persistently elevated result in toxic effects. These changes are also observed in the highly prevalent disease diabetes, which affects 16 million Americans and consumes over $100 billion in annual healthcare costs. By mimicking the microgravity environment of space in the research laboratory using a NASA-developed bioreactor, one can study the physiology of insulin and glucagon secretion and determine if there are alterations in these cellular processes. The original specific objectives of the project included: (1) growing ('cell culture') of pancreatic islet beta and alpha cells that secrete insulin and glucagon respectively, in the NASA bioreactor; (2) examination of the effects of microgravity on insulin and glucagon secretion; and (3) study of molecular mechanisms of insulin and glucagon secretion if altered by microgravity.

  10. EPCRA Trade Secret Form Instructions (PDF)

    EPA Pesticide Factsheets

    Detail on what information is required for each section of the form. Only the specific chemical identity required to be disclosed in EPCRA sections 303, 311,312, and 313 submissions may be claimed trade secret on the EPCRA report.

  11. Applying secret sharing for HIS backup exchange.

    PubMed

    Kuroda, Tomohiro; Kimura, Eizen; Matsumura, Yasushi; Yamashita, Yoshinori; Hiramatsu, Haruhiko; Kume, Naoto; Sato, Atsushi

    2013-01-01

    To secure business continuity is indispensable for hospitals to fulfill its social responsibility under disasters. Although to back up the data of the hospital information system (HIS) at multiple remote sites is a key strategy of business continuity plan (BCP), the requirements to treat privacy sensitive data jack up the cost for the backup. The secret sharing is a method to split an original secret message up so that each individual piece is meaningless, but putting sufficient number of pieces together to reveal the original message. The secret sharing method eases us to exchange HIS backups between multiple hospitals. This paper evaluated the feasibility of the commercial secret sharing solution for HIS backup through several simulations. The result shows that the commercial solution is feasible to realize reasonable HIS backup exchange platform when template of contract between participating hospitals is ready.

  12. How to Share a Quantum Secret

    SciTech Connect

    Cleve, R.; Gottesman, D.; Lo, H.

    1999-07-01

    We investigate the concept of quantum secret sharing. In a (k,thinspn) threshold scheme, a secret quantum state is divided into n shares such that any k of those shares can be used to reconstruct the secret, but any set of k{minus}1 or fewer shares contains absolutely no information about the secret. We show that the only constraint on the existence of threshold schemes comes from the quantum {open_quotes}no-cloning theorem,{close_quotes} which requires that n{lt}2k , and we give efficient constructions of all threshold schemes. We also show that, for k{le}n{lt}2k{minus}1 , then any (k,thinspn) threshold scheme {ital must} distribute information that is globally in a mixed state. {copyright} {ital 1999} {ital The American Physical Society }

  13. Secreting glandular trichomes: more than just hairs.

    PubMed

    Wagner, G J

    1991-07-01

    Secreting glandular plant trichome types which accumulate large quantities of metabolic products in the space between their gland cell walls and cuticle permit the plant to amass secretions in a compartment that is virtually outside the plant body. These structures not only accumulate and store what are often phytotoxic oils but they position these compounds as an apparent first line of defense at the surface of the plant. Recent advances in methods for isolation and study of trichome glands have allowed more precise analysis of gland cell metabolism and enzymology. Isolation of mutants with altered trichome phenotypes provides new systems for probing the genetic basis of trichome development. These advances and their continuation can pave the way for future attempts at modification of trichome secretion. The biochemical capability of glandular secreting trichomes and the potential for its future manipulation to exploit this external storage compartment is the focus of this review.

  14. Secreting Glandular Trichomes: More than Just Hairs

    PubMed Central

    Wagner, George J.

    1991-01-01

    Secreting glandular plant trichome types which accumulate large quantities of metabolic products in the space between their gland cell walls and cuticle permit the plant to amass secretions in a compartment that is virtually outside the plant body. These structures not only accumulate and store what are often phytotoxic oils but they position these compounds as an apparent first line of defense at the surface of the plant. Recent advances in methods for isolation and study of trichome glands have allowed more precise analysis of gland cell metabolism and enzymology. Isolation of mutants with altered trichome phenotypes provides new systems for probing the genetic basis of trichome development. These advances and their continuation can pave the way for future attempts at modification of trichome secretion. The biochemical capability of glandular secreting trichomes and the potential for its future manipulation to exploit this external storage compartment is the focus of this review. PMID:16668241

  15. Is keeping a secret or being a secretive person linked to psychological symptoms?

    PubMed

    Kelly, Anita E; Yip, Jonathan J

    2006-10-01

    This prospective study explored whether keeping a major secret, self-concealment (i.e., the predisposition to keep secrets), and social support at Time 1 predicted symptomatology levels 9 weeks later (Time 2) among a sample of 86 undergraduates. The results showed that the process of keeping a secret actually predicted fewer symptoms, whereas the personality variable of self-concealment predicted more symptoms at Time 2, even when the analyses controlled for social support. However, the predictive effects of both secret keeping and self-concealment were wiped out when the analyses statistically controlled for initial symptomatology, which was positively linked to self-concealment from the outset. These findings challenge conventional wisdom about the dangers of keeping a major secret and suggest that, instead, the kind of person who is secretive simply might be more vulnerable to symptoms.

  16. Progress in Studying Salt Secretion from the Salt Glands in Recretohalophytes: How Do Plants Secrete Salt?

    PubMed Central

    Yuan, Fang; Leng, Bingying; Wang, Baoshan

    2016-01-01

    To survive in a saline environment, halophytes have evolved many strategies to resist salt stress. The salt glands of recretohalophytes are exceptional features for directly secreting salt out of a plant. Knowledge of the pathway(s) of salt secretion in relation to the function of salt glands may help us to change the salt-tolerance of crops and to cultivate the extensive saline lands that are available. Recently, ultrastructural studies of salt glands and the mechanism of salt secretion, particularly the candidate genes involved in salt secretion, have been illustrated in detail. In this review, we summarize current researches on salt gland structure, salt secretion mechanism and candidate genes involved, and provide an overview of the salt secretion pathway and the asymmetric ion transport of the salt gland. A new model recretohalophyte is also proposed. PMID:27446195

  17. Percolation of secret correlations in a network

    SciTech Connect

    Leverrier, Anthony; Garcia-Patron, Raul

    2011-09-15

    In this work, we explore the analogy between entanglement and secret classical correlations in the context of large networks--more precisely, the question of percolation of secret correlations in a network. It is known that entanglement percolation in quantum networks can display a highly nontrivial behavior depending on the topology of the network and on the presence of entanglement between the nodes. Here we show that this behavior, thought to be of a genuine quantum nature, also occurs in a classical context.

  18. Peptides and neurotransmitters that affect renin secretion

    NASA Technical Reports Server (NTRS)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  19. A New Improving Quantum Secret Sharing Scheme

    NASA Astrophysics Data System (ADS)

    Xu, Ting-Ting; Li, Zhi-Hui; Bai, Chen-Ming; Ma, Min

    2017-01-01

    An improving quantum secret sharing scheme (IQSS scheme) was introduced by Nascimento et al. (Phys. Rev. A 64, 042311 (2001)), which was analyzed by the improved quantum access structure. In this paper, we propose a new improving quantum secret sharing scheme, and more quantum access structures can be realized by this scheme than the previous one. For example, we prove that any threshold and hypercycle quantum access structures can be realized by the new scheme.

  20. Secreted HSP Vaccine for Malaria Prophylaxis

    DTIC Science & Technology

    2015-10-01

    Award Number: W81XWH-13-2-0098 TITLE: Secreted HSP Vaccine for Malaria Prophylaxis PRINCIPAL INVESTIGATOR: Dr. Natasa Strbo CONTRACTING...REPORT DATE October 2015 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE Secreted HSP Vaccine for Malaria ...expected to provide prophylactic immunity for malaria by removing infected liver cells before sporozoites can replicate and spread to the erythrocyte

  1. A New Improving Quantum Secret Sharing Scheme

    NASA Astrophysics Data System (ADS)

    Xu, Ting-Ting; Li, Zhi-Hui; Bai, Chen-Ming; Ma, Min

    2017-04-01

    An improving quantum secret sharing scheme (IQSS scheme) was introduced by Nascimento et al. (Phys. Rev. A 64, 042311 (2001)), which was analyzed by the improved quantum access structure. In this paper, we propose a new improving quantum secret sharing scheme, and more quantum access structures can be realized by this scheme than the previous one. For example, we prove that any threshold and hypercycle quantum access structures can be realized by the new scheme.

  2. Transepithelial Bicarbonate Secretion: Lessons from the Pancreas

    PubMed Central

    Park, Hyun Woo; Lee, Min Goo

    2012-01-01

    Many cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelia secrete bicarbonate (HCO3−)-containing fluids. Recent evidence suggests that defects in epithelial bicarbonate secretion are directly involved in the pathogenesis of cystic fibrosis, in particular by building up hyperviscous mucus in the ductal structures of the lung and pancreas. Pancreatic juice is one of the representative fluids that contain a very high concentration of bicarbonate among bodily fluids that are secreted from CFTR-expressing epithelia. We introduce up-to-date knowledge on the basic principles of transepithelial bicarbonate transport by showing the mechanisms involved in pancreatic bicarbonate secretion. The model of pancreatic bicarbonate secretion described herein may also apply to other exocrine epithelia. As a central regulator of bicarbonate transport at the apical membrane, CFTR plays an essential role in both direct and indirect bicarbonate secretion. The major role of CFTR in bicarbonate secretion would be variable depending on the tissue and cell type. For example, in epithelial cells that produce a low concentration of bicarbonate-containing fluid (up to 80 mm), either CFTR-dependent Cl−/HCO3− exchange or CFTR anion channel with low bicarbonate permeability would be sufficient to generate such fluid. However, in cells that secrete high-bicarbonate-containing fluids, a highly selective CFTR bicarbonate channel activity is required. Therefore, understanding the molecular mechanism of transepithelial bicarbonate transport and the role of CFTR in each specific epithelium will provide therapeutic strategies to recover from epithelial defects induced by hyposecretion of bicarbonate in cystic fibrosis. PMID:23028131

  3. Peptides and neurotransmitters that affect renin secretion

    NASA Technical Reports Server (NTRS)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  4. Insulin secretion in children with growth retardation.

    PubMed

    Boscherini, B; Finocchi, G; Lostia, O; Mancuso, G; Montani, P; Pasquino, A M; Rezza, E; Rocchio, J; Taggi, F; Zorretta, D

    1977-12-30

    The effect of tolbutamide administration on insulin secretion was studied in 69 children with growth retardation. Diminished insulin secretion was found in all the patients, compared to the control group. This insulin deficit was most evident in patients with isolated, total GH deficiency and least evident in children with idiopathic short stature. Intermediate values were found in dwarfism due to isolated, partial GH deficiency. These results favour the hypothesis that hypoinsulinism contributes to the somatotropin deficiency in causing growth retardation.

  5. Alcohol and gastric acid secretion in humans.

    PubMed

    Chari, S; Teyssen, S; Singer, M V

    1993-06-01

    The secretory response of gastric acid to pure ethanol and alcoholic beverages may be different because the action of the non-ethanolic contents of the beverage may overwhelm that of ethanol. Pure ethanol in low concentrations (< 5% vol/vol) is a mild stimulant of acid secretion whereas at higher concentrations it has either no effect or a mildly inhibitory one. Pure ethanol given by any route does not cause release of gastrin in humans. Alcoholic beverages with low ethanol content (beer and wine) are strong stimulants of gastric acid secretion and gastrin release, the effect of beer being equal to the maximal acid output. Beverages with a higher ethanol content (whisky, gin, cognac) do not stimulate gastric acid secretion or release of gastrin. The powerful stimulants of gastric acid secretion present in beer, which are yet to be identified, are thermostable and anionic polar substances. The effect of chronic alcohol abuse on gastric acid secretion is not as predictable. Chronic alcoholic patients may have normal, enhanced, or diminished acid secretory capacity; hypochlorhydria being associated histologically with atrophic gastritis. There are no studies on the acute effect of alcohol intake on gastric acid secretion in chronic alcoholic patients. The acid stimulatory component of beer and wine needs to be characterised and its possible role in the causation of alcohol induced gastrointestinal diseases needs to be investigated.

  6. An unexpected knock on Corrigan's secret door.

    PubMed

    Woywodt, Alexander

    2010-10-01

    Corrigan's secret door describes a metaphorical escape route for busy physicians. The term was derived from the successful and exceptionally busy professional life of Irish physician Dominic John Corrigan (1802-80). It is claimed that Corrigan's outpatient clinic was so busy that he required a secret door in his consulting rooms to escape from the ever-growing queue of eager patients. The origins of this charming story are unknown, and the door may have never existed. However, at present, Corrigan's secret door is often quoted when busy physicians have their own little ways in surviving a stressful professional life. Generations of British-trained doctors have grown up with Corrigan's secret door, as it was featured in the introduction of the Oxford Handbook of Clinical Medicine. Accordingly, trainees as well as more senior doctors are often reminded that having a 'secret door' is vital in surviving in the medical profession. My own escape is through classical music and the violoncello, in particular. As the name implies, my own secret door is normally invisible to colleagues and patients. This little article is about a patient who found me out, and a reflection on the role of classical music and the cello in my professional life.

  7. A gatekeeper chaperone complex directs translocator secretion during type three secretion.

    PubMed

    Archuleta, Tara L; Spiller, Benjamin W

    2014-11-01

    Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ∼20 individual protein components that form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.

  8. A Gatekeeper Chaperone Complex Directs Translocator Secretion during Type Three Secretion

    PubMed Central

    Archuleta, Tara L.; Spiller, Benjamin W.

    2014-01-01

    Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ∼20 individual protein components that form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors. PMID:25375170

  9. A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion

    DOE PAGES

    Archuleta, Tara L.; Spiller, Benjamin W.; Kubori, Tomoko

    2014-11-06

    Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components thatmore » form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.« less

  10. A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion

    SciTech Connect

    Archuleta, Tara L.; Spiller, Benjamin W.; Kubori, Tomoko

    2014-11-06

    Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components that form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.

  11. SecretP: a new method for predicting mammalian secreted proteins.

    PubMed

    Yu, Lezheng; Guo, Yanzhi; Zhang, Zheng; Li, Yizhou; Li, Menglong; Li, Gongbing; Xiong, Wenjia; Zeng, Yuhong

    2010-04-01

    In contrast to a large number of classically secreted proteins (CSPs) and non-secreted proteins (NSPs), only a few proteins have been experimentally proved to enter non-classical secretory pathways. So it is difficult to identify non-classically secreted proteins (NCSPs), and no methods are available for distinguishing the three types of proteins simultaneously. In order to solve this problem, a data mining has been taken firstly, and mammalian proteins exported via ER-Golgi-independent pathways are collected through extensive literature searches. In this paper, a support vector machine (SVM)-based ternary classifier named SecretP is proposed to predict mammalian secreted proteins by using pseudo-amino acid composition (PseAA) and five additional features. When distinguishing the three types of proteins, SecretP yielded an accuracy of 88.79%. Evaluating the performance of our method by an independent test set of 92 human proteins, 76 of them are correctly predicted as NCSPs. When performed on another public independent data set, the prediction result of SecretP is comparable to those of other existing computational methods. Therefore, SecretP can be a useful supplementary tool for future secretome studies. The web server SecretP and all supplementary tables listed in this paper are freely available at http://cic.scu.edu.cn/bioinformatics/secretp/index.htm. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  12. YscP of Yersinia pestis Is a Secreted Component of the Yop Secretion System

    PubMed Central

    Payne, Patricia L.; Straley, Susan C.

    1999-01-01

    The Yersinia pestis low-Ca2+ response stimulon is responsible for the environmentally regulated expression and secretion of antihost proteins (V antigen and Yops). We have previously shown that yscO encodes a secreted core component of the Yop secretion (Ysc) mechanism. In this study, we constructed and characterized in-frame deletions in the adjacent gene, yscP, in the yscN–yscU operon. The ΔP1 mutation, which removed amino acids 246 to 333 of YscP, had no effect on Yop expression or secretion, and the mutant protein, YscP1, was secreted, as was YscP in the parent. In contrast, the ΔP2 strain expressed and secreted less of each Yop than did the parent under the inductive conditions of 37°C and the absence of Ca2+, with an exception being YopE, which was only minimally affected by the mutation. The YscP2 protein, missing amino acids 57 to 324 of YscP, was expressed but not secreted by the ΔP2 mutant. The effect of the ΔP2 mutation was at the level of Yop secretion because YopM and V antigen still showed limited secretion when overproduced in trans. Excess YscP also affected secretion: overexpression of YscP in the parent, in either yscP mutant, or in an lcrG mutant effectively shut off secretion. However, co-overexpression of YscO and YscP had no effect on secretion, and YscP overexpression in an lcrE mutant had little effect on Yop secretion, suggesting that YscP acts, in conjunction with YscO, at the level of secretion control of LcrE at the bacterial surface. These findings place YscP among the growing family of mobile Ysc components that both affect secretion and themselves are secreted by the Ysc. PMID:10217778

  13. Mediators of Ca2(+)-dependent secretion.

    PubMed Central

    Chaudhry, A; Rubin, R P

    1990-01-01

    Ca2+, an obligatory mediator of the secretory process, acts in concert with other second messengers that further amplify or inhibit the secretory response. In this overview, we will consider the relative roles of diacylglycerol (DAG), arachidonic acid, and cyclic AMP (cAMP) in modulating Ca2(+)-dependent secretion in nonexcitable cells. DAG, a product of phospholipase C (PLC)-catalyzed breakdown of phosphoinositides, stimulates protein kinase C. Ca2+ ionophores and phorbol esters (or DAG analogues) elicit a synergistic secretory response in the exocrine pancreas and parotid gland. These findings suggest that the complete activation of secretion requires stimulation of both Ca2(+)-dependent and protein kinase C-dependent pathways. Hydrolysis of phospholipids can also lead to the liberation of arachidonic acid in secretory cells. Endogenously generated arachidonic acid inhibits polyphosphoinositide synthesis in exocrine pancreas, leading to inhibition of agonist-induced IP3 formation, Ca2(+)-mobilization and amylase secretion. By contrast, arachidonic acid and its metabolites stimulate PLC in the rabbit peritoneal neutrophil, causing Ca2(+)-mobilization and lysosomal enzyme secretion. Arachidonic acid can thus serve as a positive or negative feedback regulator of secretion induced by Ca2(+)-mobilizing agonists. Finally, in the parotid gland, stimulation of amylase secretion by norepinephrine, the physiological mediator, which stimulates both the alpha and beta adrenoceptors, requires the interaction of both Ca2+ and cAMP pathways to produce a full secretory response. These studies, taken together, indicate that phosphoinositide and cAMP-dependent pathways play coordinate roles in signal transduction, leading to the Ca2(+)-mediated secretion. PMID:2161754

  14. Sagnac secret sharing over telecom fiber networks.

    PubMed

    Bogdanski, Jan; Ahrens, Johan; Bourennane, Mohamed

    2009-01-19

    We report the first Sagnac quantum secret sharing (in three-and four-party implementations) over 1550 nm single mode fiber (SMF) networks, using a single qubit protocol with phase encoding. Our secret sharing experiment has been based on a single qubit protocol, which has opened the door to practical secret sharing implementation over fiber telecom channels and in free-space. The previous quantum secret sharing proposals were based on multiparticle entangled states, difficult in the practical implementation and not scalable. Our experimental data in the three-party implementation show stable (in regards to birefringence drift) quantum secret sharing transmissions at the total Sagnac transmission loop distances of 55-75 km with the quantum bit error rates (QBER) of 2.3-2.4% for the mean photon number micro?= 0.1 and 1.7-2.1% for micro= 0.3. In the four-party case we have achieved quantum secret sharing transmissions at the total Sagnac transmission loop distances of 45-55 km with the quantum bit error rates (QBER) of 3.0-3.7% for the mean photon number micro= 0.1 and 1.8-3.0% for micro?= 0.3. The stability of quantum transmission has been achieved thanks to our new concept for compensation of SMF birefringence effects in Sagnac, based on a polarization control system and a polarization insensitive phase modulator. The measurement results have showed feasibility of quantum secret sharing over telecom fiber networks in Sagnac configuration, using standard fiber telecom components.

  15. Milk secretion: The role of SNARE proteins.

    PubMed

    Truchet, Sandrine; Chat, Sophie; Ollivier-Bousquet, Michèle

    2014-03-01

    During lactation, polarized mammary epithelial secretory cells (MESCs) secrete huge quantities of the nutrient molecules that make up milk, i.e. proteins, fat globules and soluble components such as lactose and minerals. Some of these nutrients are only produced by the MESCs themselves, while others are to a great extent transferred from the blood. MESCs can thus be seen as a crossroads for both the uptake and the secretion with cross-talks between intracellular compartments that enable spatial and temporal coordination of the secretion of the milk constituents. Although the physiology of lactation is well understood, the molecular mechanisms underlying the secretion of milk components remain incompletely characterized. Major milk proteins, namely caseins, are secreted by exocytosis, while the milk fat globules are released by budding, being enwrapped by the apical plasma membrane. Prolactin, which stimulates the transcription of casein genes, also induces the production of arachidonic acid, leading to accelerated casein transport and/or secretion. Because of their ability to form complexes that bridge two membranes and promote their fusion, SNARE (Soluble N-ethylmaleimide-Sensitive Factor Attachment Protein Receptor) proteins are involved in almost all intracellular trafficking steps and exocytosis. As SNAREs can bind arachidonic acid, they could be the effectors of the secretagogue effect of prolactin in MESCs. Indeed, some SNAREs have been observed between secretory vesicles and lipid droplets suggesting that these proteins could not only orchestrate the intracellular trafficking of milk components but also act as key regulators for both the coupling and coordination of milk product secretion in response to hormones.

  16. Regulation of atrial natriuretic peptide (ANP) secretion

    SciTech Connect

    Ruskoaho, H.; Toth, M.; Lang, R.E.; Unger, Th.; Garten, D.

    1986-03-05

    To investigate the role of calcium, protein kinase C and adenylate cyclase in the ANP secretion, the secretory responses from isolated perfused rat hearts to a calcium channel activator, Bay k8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluomethylphenyl)-2-pyridine-5-carboxylate), the calcium ionophore (A23187), the phorbol ester (12-0-tetradecanoylphorbol-13-acetate, TPA), and to forskolin were studied. ANP in perfusate was measured by radioimmunoassay 10 min before and during the infusion (30 min) of various agents at 2 min intervals. A23187 (5.7 x 10/sup -7/) induced a sharp increase, whereas TPA (0.15 - 1.6 x 10/sup -7/) caused a slowly progressive increase in ANP secretion. 4a-phorbol-12,13-didecanoate, a non-active phorbol ester, had no effect on ANP secretion. Bay k8644 (4 x 10/sup -7/) and forskolin (1 x 10/sup -6/) alone caused small but sustained increase in ANP secretion. The combination of TPA with Bay k8644, forskolin or A23187 stimulated ANP secretion higher than the calculated additive value for each agent. Dibuturyl-cAMP (1.6 x 10/sup -4/) pretreatment also enhanced TPA-induced ANP release. 8-Bromo-cGMP (1.3 x 10/sup -4/) and sodium nitroprusside (9 x 10/sup -5/) alone had no effect, but both attenuated the TPA-induced ANP secretion. The results suggest that atrial cardiocytes possess at least two different secretory pathways for ANP secretion, which are probably dependent on protein kinase C and cyclic AMP.

  17. Interactive Cytokine Regulation of Synoviocyte Lubricant Secretion

    PubMed Central

    Blewis, Megan E.; Lao, Brian J.; Schumacher, Barbara L.; Bugbee, William D.; Firestein, Gary S.

    2010-01-01

    Cytokine regulation of synovial fluid (SF) lubricants, hyaluronan (HA), and proteoglycan 4 (PRG4) is important in health, injury, and disease of synovial joints, and may also provide powerful regulation of lubricant secretion in bioreactors for articulating tissues. This study assessed lubricant secretion rates by human synoviocytes and the molecular weight (MW) of secreted lubricants in response to interleukin (IL)-1β, IL-17, IL-32, transforming growth factor-beta 1 (TGF-β1), and tumor necrosis factor-alpha (TNF-α), applied individually and in all combinations. Lubricant secretion rates were assessed using ELISA and binding assays, and lubricant MW was assessed using gel electrophoresis and Western blotting. HA secretion rates were increased ∼40-fold by IL-1β, and increased synergistically to ∼80-fold by the combination of IL-1β + TGF-β1 or TNF-α + IL-17. PRG4 secretion rates were increased ∼80-fold by TGF-β1, and this effect was counterbalanced by IL-1β and TNF-α. HA MW was predominantly <1 MDa for controls and individual cytokine stimulation, but was concentrated at >3 MDa after stimulation by IL-1β + TGF-β1 + TNF-α to resemble the distribution in human SF. PRG4 MW was unaffected by cytokines and similar to that in human SF. These results contribute to an understanding of the relationship between SF cytokine and lubricant content in health, injury, and disease, and provide approaches for using cytokines to modulate lubricant secretion rates and MW to help achieve desired lubricant composition of fluid in bioreactors. PMID:19908966

  18. Interactive cytokine regulation of synoviocyte lubricant secretion.

    PubMed

    Blewis, Megan E; Lao, Brian J; Schumacher, Barbara L; Bugbee, William D; Sah, Robert L; Firestein, Gary S

    2010-04-01

    Cytokine regulation of synovial fluid (SF) lubricants, hyaluronan (HA), and proteoglycan 4 (PRG4) is important in health, injury, and disease of synovial joints, and may also provide powerful regulation of lubricant secretion in bioreactors for articulating tissues. This study assessed lubricant secretion rates by human synoviocytes and the molecular weight (MW) of secreted lubricants in response to interleukin (IL)-1beta, IL-17, IL-32, transforming growth factor-beta 1 (TGF-beta1), and tumor necrosis factor-alpha (TNF-alpha), applied individually and in all combinations. Lubricant secretion rates were assessed using ELISA and binding assays, and lubricant MW was assessed using gel electrophoresis and Western blotting. HA secretion rates were increased approximately 40-fold by IL-1beta, and increased synergistically to approximately 80-fold by the combination of IL-1beta + TGF-beta1 or TNF-alpha + IL-17. PRG4 secretion rates were increased approximately 80-fold by TGF-beta1, and this effect was counterbalanced by IL-1beta and TNF-alpha. HA MW was predominantly <1 MDa for controls and individual cytokine stimulation, but was concentrated at >3 MDa after stimulation by IL-1beta + TGF-beta1 + TNF-alpha to resemble the distribution in human SF. PRG4 MW was unaffected by cytokines and similar to that in human SF. These results contribute to an understanding of the relationship between SF cytokine and lubricant content in health, injury, and disease, and provide approaches for using cytokines to modulate lubricant secretion rates and MW to help achieve desired lubricant composition of fluid in bioreactors.

  19. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Provisions for withholding trade secrets. 47.81... withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the... trade secret, (2) Identifies the chemical in a way that it can be referred to without disclosing...

  20. 5 CFR 1312.27 - Top secret control.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of...

  1. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the...

  2. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the...

  3. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the...

  4. 5 CFR 1312.27 - Top secret control.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of...

  5. 5 CFR 1312.27 - Top secret control.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of...

  6. 5 CFR 1312.27 - Top secret control.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of...

  7. 5 CFR 1312.27 - Top secret control.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of...

  8. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the...

  9. Quantum Ramp Secret Sharing Scheme and Quantum Operations

    NASA Astrophysics Data System (ADS)

    Xiao, Heling; Wang, Huifeng; Wang, Bin

    2016-09-01

    In order to improve the efficiency of quantum secret sharing, quantum ramp secret sharing schemes were proposed (Ogawa et al., Phys. Rev. A 72, 032318 [2005]), which had a trade-off between security and coding efficiency. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an intermediate set, which cannot fully reconstruct the secret. This paper revisits the size of a share in the quantum ramp secret scheme based on a relation between the quantum operations and the coherent information. We also propose an optimal quantum ramp secret sharing scheme.

  10. Effects of endothelin family on ANP secretion.

    PubMed

    Yuan, Kuichang; Park, Byung Mun; Choi, Young Tae; Kim, Jong Hun; Cho, Kyung Woo; Kim, Suhn Hee

    2016-08-01

    The endothelins (ET) peptide family consists of ET-1, ET-2, ET-3, and sarafotoxin (s6C, a snake venom) and their actions appears to be different among isoforms. The aim of this study was to compare the secretagogue effect of ET-1 on atrial natriuretic peptide (ANP) secretion with ET-3 and evaluate its physiological meaning. Isolated nonbeating atria from male Sprague-Dawley rats were used to evaluate stretch-activated ANP secretion in response to ET-1, ET-2, ET-3, and s6C. Changes in mean blood pressure (MAP) were measured during acute injection of ET-1 and ET-3 with and without natriuretic peptide receptor-A antagonist (A71915) in anesthetized rats. Changes in atrial volume induced by increased atrial pressure from o to 1, 2, 4, or 6cm H2O caused proportional increases in mechanically-stimulated extracellular fluid (ECF) translocation and stretch-activated ANP secretion. ET-1 (10nM) augmented basal and stretch-activated ANP secretion in terms of ECF translocation, which was blocked by the pretreatment with ETA receptor antagonist (BQ123, 1μM) but not by ETB receptor antagonist (BQ788, 1μM). ETA receptor antagonist itself suppressed stretch-activated ANP secretion. As compared to ET-1- induced ANP secretion (3.2-fold by 10nM), the secretagogue effects of ANP secretion by ET-2 was similar (2.8-fold by 10nM) and ET-3 and s6C were less potent (1.7-fold and 1.5-fold by 100nM, respectively). Acute injection of ET-1 or ET-3 increased mean blood pressure (MAP), which was augmented in the presence of natriuretic peptide receptor-A antagonist. Therefore, we suggest that the order of secretagogue effect of ET family on ANP secretion was ET-1≥ET-2>ET-3>s6C and ET-1-induced ANP secretion negatively regulates the pressor effect of ET-1. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Characterization of Nops, nodulation outer proteins, secreted via the type III secretion system of NGR234.

    PubMed

    Marie, Corinne; Deakin, William J; Viprey, Virginie; Kopciñska, Joanna; Golinowski, Wladyslaw; Krishnan, Hari B; Perret, Xavier; Broughton, William J

    2003-09-01

    The nitrogen-fixing symbiotic bacterium Rhizobium species NGR234 secretes, via a type III secretion system (TTSS), proteins called Nops (nodulation outer proteins). Abolition of TTSS-dependent protein secretion has either no effect or leads to a change in the number of nodules on selected plants. More dramatically, Nops impair nodule development on Crotalaria juncea roots, resulting in the formation of nonfixing pseudonodules. A double mutation of nopX and nopL, which code for two previously identified secreted proteins, leads to a phenotype on Pachyrhizus tuberosus differing from that of a mutant in which the TTSS is not functional. Use of antibodies and a modification of the purification protocol revealed that NGR234 secretes additional proteins in a TTSS-dependent manner. One of them was identified as NopA, a small 7-kDa protein. Single mutations in nopX and nopL were also generated to assess the involvement of each Nop in protein secretion and nodule formation. Mutation of nopX had little effect on NopL and NopA secretion but greatly affected the interaction of NGR234 with many plant hosts tested. NopL was not necessary for the secretion of any Nops but was required for efficient nodulation of some plant species. NopL may thus act as an effector protein whose recognition is dependent upon the hosts' genetic background.

  12. Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

    ERIC Educational Resources Information Center

    Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

    2013-01-01

    It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

  13. Secrets and the Sociological Imagination: Using PostSecret.com to Illustrate Sociological Concepts

    ERIC Educational Resources Information Center

    Noy, Shiri

    2014-01-01

    Introductory sociology classes afford instructors an opportunity to expose students, often from a variety of backgrounds and majors, to the sociological imagination. In this article, I describe how the use of secrets from a popular website, PostSecret.com, can help teach students about the sociological imagination and incorporate biographical…

  14. Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

    ERIC Educational Resources Information Center

    Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

    2013-01-01

    It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

  15. Secrets and the Sociological Imagination: Using PostSecret.com to Illustrate Sociological Concepts

    ERIC Educational Resources Information Center

    Noy, Shiri

    2014-01-01

    Introductory sociology classes afford instructors an opportunity to expose students, often from a variety of backgrounds and majors, to the sociological imagination. In this article, I describe how the use of secrets from a popular website, PostSecret.com, can help teach students about the sociological imagination and incorporate biographical…

  16. 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...

  17. Role of adipose secreted factors and kisspeptin in the metabolic control of gonadotropin secretion and puberty

    USDA-ARS?s Scientific Manuscript database

    Factors secreted by adipose tissue continue to be discovered. Evidence indicates a strong link between neural influences and adipocyte expression and secretion of a wide array of cytokines, neurotrophic factors, growth factors, binding proteins, and neuropeptides. These “adipokines” are linked to im...

  18. Analysis of anal secretions from phlaeothripine thrips.

    PubMed

    Suzuki, Takahisa; Haga, Kazuo; Tsutsumi, Tadaaki; Matsuyama, Shigeru

    2004-02-01

    The anal secretions of 16 phlaeothripine thrips species (Thysanoptera: Phlaeothripidae) were studied, including a reinvestigation of three species previously reported. A total of 37 components were detected, including hydrocarbons, acetates, terpenes, carboxylic acids, a quinone, an aromatic compound, and a pyranone compound. The secretions of all species were composed of some of these components, with Xylaplothrips inquilinus possessing as many as 11 components. Of these components, (Z)-9-octadecene, (Z)-9-nonadecene, nonadecadiene, octanoic acid, decanoic acid, geranial, neral, alpha-pinene, beta-pinene, caryophyllene, 2-hydroxy-6-methylbenzaldehyde, and two unidentified monoterpenes [UK-I (M+136) and UK-II (M+168)] were detected for the first time. The chemicals were species-specific; four Liothrips species and three Holothrips species could be distinguished from each other and their congeners by the GC profiles of the ether extracts of their anal secretions. The anal secretions of gall-inducing thrips commonly contained terpenes. of which citral (a mixture of geranial and neral) and beta-acaridial repelled ants or had antifungal activity. The findings suggest that these terpenes play a defensive role and prevent galls from fungal infestation. 3-Butanoyl-4-hydroxy-6-methyl-2H-pyran-2-one, found from three Holothrips spp., caused paralysis in ants. Chemical analysis of anal secretion components is a useful method for the classification of tubuliferan species that are difficult to distinguish on the basis of morphological characters.

  19. Fast-weighted secret image sharing

    NASA Astrophysics Data System (ADS)

    Lin, Sian-Jheng; Chen, Lee Shu-Teng; Lin, Ja-Chen

    2009-07-01

    Thien and Lin [Comput. and Graphics 26(5), 765-770 (2002)] proposed a threshold scheme to share a secret image among n shadows: any t of the n shadows can recover the secret, whereas t-1 or fewer shadows cannot. However, in real life, certain managers probably play key roles to run a company and thus need special authority to recover the secret in managers' meeting. (Each manager's shadow should be more powerful than an ordinary employee's shadow.) In Thien and Lin's scheme, if a company has less than t managers, then manager's meeting cannot recover the secret, unless some managers were given multiple shadows in advance. But this compromise causes managers inconvenience because too many shadows were to be kept daily and carried to the meeting. To solve this dilemma, a weighted sharing method is proposed: each of the shadows has a weight. The secret is recovered if and only if the total weights (rather than the number) of received shadows is at least t. The properties of GF(2r) are utilized to accelerate sharing speed. Besides, the method is also a more general approach to polynomial-based sharing. Moreover, for convenience, each person keeps only one shadow and only one shadow index.

  20. Functional anatomy and physiology of gastric secretion.

    PubMed

    Schubert, Mitchell L

    2015-11-01

    This review summarizes the past year's literature regarding the neuroendocrine and intracellular regulation of gastric acid secretion, discussing both basic and clinical aspects. Gastric acid facilitates the digestion of protein as well as the absorption of iron, calcium, vitamin B12, and certain medications. High acidity kills ingested microorganisms and limits bacterial overgrowth, enteric infection, and possibly spontaneous bacterial peritonitis. The main stimulants of acid secretion are gastrin, released from antral gastrin cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons. Ghrelin and coffee also stimulate acid secretion whereas somatostatin, cholecystokinin, glucagon-like peptide-1, and atrial natriuretic peptide inhibit acid secretion. Although 95% of parietal cells are contained within the oxyntic mucosa (fundus and body), 50% of human antral glands contain parietal cells. Proton pump inhibitors are considered well tolerated drugs, but concerns have been raised regarding dysbiosis, atrophic gastritis, hypergastrinemia, hypomagnesemia, and enteritis/colitis. Our understanding of the functional anatomy and physiology of gastric secretion continues to advance. Such knowledge is crucial for improved management of acid-peptic disorders, prevention and management of neoplasia, and the development of novel medications.

  1. Pancreatic Bicarbonate Secretion Involves Two Proton Pumps*

    PubMed Central

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.; Haanes, Kristian A.; Krabbe, Simon; Nitschke, Roland; Hede, Susanne E.

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H+/HCO3− transporters, which depend on gradients created by the Na+/K+-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H+-K+-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H+-K+ pump inhibitors and ion substitutions. Gastric and non-gastric H+-K+ pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H+/HCO3− and fluid transport shows that the H+-K+ pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H+-K+ pumps in pathophysiology. PMID:20978133

  2. Shared secrets versus secrets kept private are linked to better adolescent adjustment.

    PubMed

    Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

    2013-02-01

    It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch adolescents showed that, in line with hypotheses, shared secrets (1) were kept by more adolescents than private secrets, (2) were not linked to maladjustment and (3) were linked to higher interpersonal functioning. Whereas private secrecy was associated with increased delinquency, physical complaints, depressive mood, loneliness, and with lower quality relationships, shared secrecy was associated only with more interpersonal competence. Moreover, sharing a secret was specifically linked to a higher quality relationship with the confidant, and sharing with parents was linked with less delinquency, whereas sharing with a best friend was linked with less loneliness and more interpersonal competence.

  3. Experimental demonstration of four-party quantum secret sharing.

    PubMed

    Gaertner, S; Kurtsiefer, C; Bourennane, M; Weinfurter, H

    2007-01-12

    Secret sharing is a multiparty cryptographic task in which some secret information is split into several pieces which are distributed among the participants such that only an authorized set of participants can reconstruct the original secret. Similar to quantum key distribution, in quantum secret sharing, the secrecy of the shared information relies not on computational assumptions, but on laws of quantum physics. Here, we present an experimental demonstration of four-party quantum secret sharing via the resource of four-photon entanglement.

  4. Experimental Demonstration of Four-Party Quantum Secret Sharing

    NASA Astrophysics Data System (ADS)

    Gaertner, S.; Kurtsiefer, C.; Bourennane, M.; Weinfurter, H.

    2007-01-01

    Secret sharing is a multiparty cryptographic task in which some secret information is split into several pieces which are distributed among the participants such that only an authorized set of participants can reconstruct the original secret. Similar to quantum key distribution, in quantum secret sharing, the secrecy of the shared information relies not on computational assumptions, but on laws of quantum physics. Here, we present an experimental demonstration of four-party quantum secret sharing via the resource of four-photon entanglement.

  5. A light-triggered protein secretion system.

    PubMed

    Chen, Daniel; Gibson, Emily S; Kennedy, Matthew J

    2013-05-13

    Optical control of protein interactions has emerged as a powerful experimental paradigm for manipulating and studying various cellular processes. Tools are now available for controlling a number of cellular functions, but some fundamental processes, such as protein secretion, have been difficult to engineer using current optical tools. Here we use UVR8, a plant photoreceptor protein that forms photolabile homodimers, to engineer the first light-triggered protein secretion system. UVR8 fusion proteins were conditionally sequestered in the endoplasmic reticulum, and a brief pulse of light triggered robust forward trafficking through the secretory pathway to the plasma membrane. UVR8 was not responsive to excitation light used to image cyan, green, or red fluorescent protein variants, allowing multicolor visualization of cellular markers and secreted protein cargo as it traverses the cellular secretory pathway. We implemented this novel tool in neurons to demonstrate restricted, local trafficking of secretory cargo near dendritic branch points.

  6. Penetration of pefloxacin into bronchial secretions.

    PubMed Central

    Bonmarchand, G; Grès, J J; Lerebours, G; Massari, P; Mayoux, J J; Montay, A; Leroy, J

    1989-01-01

    Twelve patients, intubated for acute exacerbation of chronic obstructive pulmonary disease, received six intravenous doses of 400 mg of pefloxacin at 12-h intervals. Samples of blood and bronchial secretions were taken simultaneously, before the injection and at 0.5, 3, 6, 9, and 12 h after the end of the sixth infusion. There was a large variation in pefloxacin levels in both serum and bronchial secretions. The mean concentrations of pefloxacin in bronchial secretions ranged from 6.51 to 11.1 micrograms/ml and were higher than the corresponding concentrations in serum at all times. Of 61 bronchial specimens, 48 (79%) contained more than 8 micrograms of the antibiotic per ml. PMID:2729932

  7. Lactation and the physiology of prolactin secretion

    PubMed Central

    McNeilly, A. S.

    1975-01-01

    Prolactin in man appears to form an essential part of the complex of hormones necessary for milk secretion and lactation. Levels of prolactin during pregnancy gradually increase towards term, and remain elevated for up to 6 weeks post partum. The lactogenic effects of prolactin appear to be blocked at the mammary gland by the elevated levels of fetoplacental steroids secreted during pregnancy. The immediate decline in steroid levels at delivery removes this block to prolactin and milk secretion ensues. The amenorrhoea associated with both puerperal lactation and galactorrhoea appears to reflect failure of cyclical discharge of gonadotrophins and anovulation. This appears to be due to peripheral inhibition of steroidogenesis by the elevated levels of prolactin associated with these situations. No consistent changes in circulating levels of prolactin occur during the menstrual cycle, but changes in prolactin levels within the follicular fluid of the developing ovarian follicle indicate a specific and permissive role of prolactin in steroidogenesis. PMID:1197152

  8. The 'Secret' of success part 1.

    PubMed

    Busby, Mike

    2011-03-01

    Practice success is defined across the four'dimensions' of oral health, patient satisfaction, job satisfaction and financial profit. It is suggested that the 'secret' of success in dental practice is to make patient (customer) satisfaction the primary focus. Not a very earth shattering or surprising'secret' perhaps! This is hardly a new idea, and not a concept restricted to dental practice. This principle applies to all businesses. This series of articles reviews evidence from across a broad spectrum of publications: from populist business publications through to refereed scientific papers, this'secret' seems to be confirmed. The evidence for which aspects of our service are most important in achieving patient satisfaction (and therefore success) is explored. Good oral health outcomes for patients are defined as the primary purpose of dental practice and, therefore, an essential dimension of success. The link between positive patient perceptions of general care and their own oral health to practice success is explored.

  9. The 'secret' of success. Part 2.

    PubMed

    Busby, Mike

    2011-04-01

    Practice success is defined across the four 'dimensions' of oral health, patient satisfaction, job satisfaction and financial profit. It is suggested that the 'secret' of success in dental practice is to make patient (customer) satisfaction the primary focus. Not a very earth shattering or surprising 'secret' perhaps! This is hardly a new idea, and not a concept restricted to dental practice. This principle applies to all businesses. This series of articles reviews evidence from across a broad spectrum of publications: from populist business publications through to refereed scientific papers, this 'secret' seems to be confirmed. The evidence for which aspects of our service are most important in achieving patient satisfaction (and therefore success) is explored. Good oral health outcomes for patients are defined as the primary purpose of dental practice and, therefore, an essential dimension of success. The link between positive patient perceptions of general care and their own oral health to practice success is explored.

  10. The 'secret' of success. Part 3.

    PubMed

    Busby, Mike

    2011-05-01

    Practice success is defined across the four 'dimensions' of oral health, patient satisfaction, job satisfaction and financial profit. It is suggested that the 'secret' of success in dental practice is to make patient (customer) satisfaction the primary focus. Not a very earth shattering or surprising 'secret' perhaps! This is hardly a new idea, and not a concept restricted to dental practice. This principle applies to all businesses. This series of articles reviews evidence from across a broad spectrum of publications: from populist business publications through to refereed scientific papers, this 'secret' seems to be confirmed. The evidence for which aspects of our service are most important in achieving patient satisfaction (and therefore success) is explored. Good oral health outcomes for patients are defined as the primary purpose of dental practice and, therefore, an essential dimension of success. The link between positive patient perceptions of general care and his/her own oral health to practice success is explored.

  11. Nutrient detection by incretin hormone secreting cells

    PubMed Central

    Diakogiannaki, Eleftheria; Gribble, Fiona M.; Reimann, Frank

    2012-01-01

    The hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulintropic polypeptide (GIP) are secreted after a meal. Like other enteroendocrine hormones they help to orchestrate the bodies' response to the availability of newly absorbable nutrients and are noteworthy as they stimulate postprandial insulin secretion, underlying what is known as the incretin effect. GLP-1-mimetics are now widely used in the treatment of type 2 diabetes and advantages over older insulinotropic therapies include weight loss. An alternative treatment regime might be the recruitment of endogenous GLP-1, however, very little is known about the physiological control of enteroendocrine responses. This review focuses on the molecular mechanisms to detect nutrient arrival in the gut that have been implicated within the incretin secreting cells. PMID:22182802

  12. Regulation and secretion of Xanthomonas virulence factors.

    PubMed

    Büttner, Daniela; Bonas, Ulla

    2010-03-01

    Plant pathogenic bacteria of the genus Xanthomonas cause a variety of diseases in economically important monocotyledonous and dicotyledonous crop plants worldwide. Successful infection and bacterial multiplication in the host tissue often depend on the virulence factors secreted including adhesins, polysaccharides, LPS and degradative enzymes. One of the key pathogenicity factors is the type III secretion system, which injects effector proteins into the host cell cytosol to manipulate plant cellular processes such as basal defense to the benefit of the pathogen. The coordinated expression of bacterial virulence factors is orchestrated by quorum-sensing pathways, multiple two-component systems and transcriptional regulators such as Clp, Zur, FhrR, HrpX and HpaR. Furthermore, virulence gene expression is post-transcriptionally controlled by the RNA-binding protein RsmA. In this review, we summarize the current knowledge on the infection strategies and regulatory networks controlling secreted virulence factors from Xanthomonas species.

  13. A pilot study of pepsin in tracheal and oral secretions.

    PubMed

    Schallom, Marilyn; Tricomi, Sally M; Chang, Yie-Hwa; Metheny, Norma A

    2013-09-01

    Because reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, it is reasonable to hypothesize that the detection of pepsin (the major gastric enzyme in gastric juice) in oral secretions may provide a relatively noninvasive method of predicting risk for aspiration. To describe the incidence of pepsin in oral and tracheal secretions collected concurrently from a sample of 50 gastric-fed patients undergoing mechanical ventilation. An exploratory descriptive design with a convenience sample from 4 medical and surgical intensive care units. An oral secretion and a tracheal secretion were collected concurrently from each patient (yielding a sample of 50 oral and 50 tracheal secretions). The tracheal secretions were obtained via the inline suction system with an attached sputum trap; oral secretions were obtained via a Yankauer suction tip with an attached sputum trap. All specimens were assayed for pepsin by the Western blot method. Oral secretions from 10 patients (20%) and tracheal secretions from 2 patients (4%) were pepsin-positive. Both patients with pepsin-positive tracheal secretions also had pepsin-positive oral secretions. Pepsin was not found in the tracheal secretions from the remaining 8 patients with pepsin-positive oral secretions. Although reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, individual reflux events do not necessarily lead to aspiration. Thus, it is reasonable that we found pepsin 5 times more often in oral secretions than in tracheal secretions.

  14. Apocrine secretion--fact or artifact?

    PubMed

    Aumüller, G; Wilhelm, B; Seitz, J

    1999-09-01

    In this review, the history of apocrine secretion and the essential categories are briefly mentioned and fused into a more generally applicable terminology. Using the coagulating gland of the male rat as a model, the mechanisms of apocrine secretion, the participation of the cytoskeleton in the formation of the apocrine blebs ("aposomes") and the structure of the secretory proteins, as well as the hormonal regulation of their biosynthesis are described. Apocrine secreted proteins share the following peculiarities: (i) Their biosynthesis and post-translational modification (including an unusual form of glycosylation) take place in the cytoplasm. (ii) Intracellular transport proceeds without participation of the endomembrane system, the Golgi apparatus and secretion granules. (iii) Blood serum derived transsudated albumin entering the secretory cells functions as a carrier of the apocrine-released proteins. Some common molecular features are specific for the apocrine-synthesized proteins studied so far by our group: (a) Their primary sequence is synthesized without a signal peptide. (b) Their N-terminus is blocked by acetylation. (c) The substituting glycanes are neither O- nor N-linked. (d) At least one of the apocrine-synthesized proteins (secretory transglutaminase) contains a glycerol-phosphoinositol (GPI-) anchor. There are a number of still open questions in apocrine secretion, pertaining to (I) the intracellular transport and targeting of the proteins, (II) the coordination of simultaneously occurring apocrine and merocrine secretion in several of the apocrine glands, (III) the biosynthesis of the apical membrane proteins surrounding the aposomes and (IV) the repair mechanisms of the apical cell pole following the release of the aposomes. In conclusion, apocrine release is not an artifact but rather an alternative extrusion mechanism of soluble and membrane-associated proteins, usually linked with sex- or reproductive-related glands, such as the prostate, the

  15. Noncholinergic control of adrenal catecholamine secretion.

    PubMed Central

    Livett, B G; Marley, P D

    1993-01-01

    It has been known for over 70 years that adrenal catecholamine secretion can be modulated or elicited by noncholinergic neurotransmitters and hormones. However, our understanding of the cellular mechanisms by which these agents produce their effects and the physiological conditions under which they act are not well characterised. Here we briefly review the mechanisms by which one such agent (the neuropeptide substance P) modulates the cholinergic secretory response of adrenal chromaffin cells, and another agent (angiotensin II) elicits catecholamine secretion independently of the cholinergic innervation. PMID:7507911

  16. Secret Sharing Comparison by Transformation and Rotation

    NASA Astrophysics Data System (ADS)

    Reistad, Tord Ingolf; Toft, Tomas

    Given any linear secret sharing scheme with a multiplication protocol, we show that a given set of players holding shares of two values a, b in {mathbb Z}p for some prime p, it is possible to compute a sharing of ρ such that ρ = (a < b) with only eight rounds and 29ℓ + 36log2(ℓ) invocations of the multiplication protocol, where ℓ = log(p). The protocol is unconditionally secure against active/adaptive adversaries when the underlying secret sharing scheme has these properties. The proposed protocol is an improvement in the sense that it requires fewer rounds and less invocations of the multiplication protocol than previous solutions.

  17. THE HYPOPHYSIS AND SECRETION OF INSULIN

    PubMed Central

    Houssay, B. A.; Foglia, V. G.; Smyth, F. S.; Rietti, C. T.; Houssay, A. B.

    1942-01-01

    The ability of the pancreas, from various types of dogs, to correct diabetic hyperglycemia has been studied (Table XI). The pancreas from one animal was united by a vascular union with the neck blood vessels of another dog which had been pancreatectomized for 20 hours. The time necessary to reduce the blood sugar level to 120 mg. per cent was determined. 1. Pancreas from 6 hypophysectomized dogs produced a normal insulin secretion, showing that an anterior pituitary hormone is not necessary for its production or maintenance. 2. In 14 of 17 normal dogs given anterior pituitary extract for 3 or more consecutive days and presenting diabetes (fasting blood sugar 150 mg. per cent or more) the pancreas showed diminished insulin production. 3. In animals which remained diabetic after discontinuing the injections of hypophyseal extract, the pancreas islands were markedly pathologic and the insulin secretion was practically nil. 4. When hyperglycemia existed on the 2nd to 5th day but fell later, the insulin secretion of 5 dogs was normal in 2, supernormal in 1, and less than normal in 2. Histologic examination showed a restoration of beta cells. 5. In 14 dogs resistant to the diabetogenic action of anterior pituitary extract, as shown by little or no change in blood sugar, the pancreatic secretion of insulin was normal in 6 cases, supernormal in 3, and subnormal in 5 cases. Clear signs of hyperfunction of B cells were observed. In 6 resistant animals a high blood sugar (150 mg. per cent) appeared shortly before transplanting, but insulin secretion was normal in 4, supernormal in 1, and subnormal in 1 case. 6. With one injection of extract and 1 day of hyperglycemia the capacity of the pancreas to secrete insulin was not altered. 7. A high blood sugar level lasting 4 days does not alter the islets. The hypophyseal extract acts, therefore, by some other mechanism. In normal dogs, the continuous intravenous infusion of glucose for 4 days maintained the blood sugar at levels as

  18. Experimental single qubit quantum secret sharing.

    PubMed

    Schmid, Christian; Trojek, Pavel; Bourennane, Mohamed; Kurtsiefer, Christian; Zukowski, Marek; Weinfurter, Harald

    2005-12-02

    We present a simple and practical protocol for the solution of a secure multiparty communication task, the secret sharing, and its proof-of-principle experimental realization. In this protocol, a secret is split among several parties in a way that its reconstruction requires the collaboration of the participating parties. In our scheme the parties solve the problem by sequential transformations on a single qubit. In contrast with recently proposed schemes involving multiparticle Greenberger-Horne-Zeilinger states, the approach demonstrated here is much easier to realize and scalable in practical applications.

  19. Differential-phase-shift quantum secret sharing.

    PubMed

    Inoue, K; Ohashi, T; Kukita, T; Watanebe, K; Hayashi, S; Honjo, T; Takesue, H

    2008-09-29

    A quantum secret sharing (QSS) protocol based on a differential-phase-shift scheme is proposed, which quantum mechanically provides a full secret key to one party and partial keys to two other parties. A weak coherent pulse train is utilized instead of individual photons as in conventional schemes. Compared with previous QSS protocols, the present one features a simple setup, is suitable for fiber transmission, and offers the possibility for a high key creation rate. An experiment is also carried out to demonstrate the operation.

  20. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    DOE PAGES

    Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; ...

    2016-02-15

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significantmore » peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.« less

  1. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    SciTech Connect

    Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; Seiler, Roland; Fleischmann, Achim; Bagryanova, Lora; Kim, Sara R.; Chia, David; Goodglick, Lee; Shimizu, Yoshiko; Rosser, Charles J.; Gao, Yuqian; Liu, Alvin Y.

    2016-02-15

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significant peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.

  2. Unique substrates secreted by the type VI secretion system of Francisella tularensis during intramacrophage infection.

    PubMed

    Bröms, Jeanette E; Meyer, Lena; Sun, Kun; Lavander, Moa; Sjöstedt, Anders

    2012-01-01

    Gram-negative bacteria have evolved sophisticated secretion machineries specialized for the secretion of macromolecules important for their life cycles. The Type VI secretion system (T6SS) is the most widely spread bacterial secretion machinery and is encoded by large, variable gene clusters, often found to be essential for virulence. The latter is true for the atypical T6SS encoded by the Francisella pathogenicity island (FPI) of the highly pathogenic, intracellular bacterium Francisella tularensis. We here undertook a comprehensive analysis of the intramacrophage secretion of the 17 FPI proteins of the live vaccine strain, LVS, of F. tularensis. All were expressed as fusions to the TEM β-lactamase and cleavage of the fluorescent substrate CCF2-AM, a direct consequence of the delivery of the proteins into the macrophage cytosol, was followed over time. The FPI proteins IglE, IglC, VgrG, IglI, PdpE, PdpA, IglJ and IglF were all secreted, which was dependent on the core components DotU, VgrG, and IglC, as well as IglG. In contrast, the method was not directly applicable on F. novicida U112, since it showed very intense native β-lactamase secretion due to FTN_1072. Its role was proven by ectopic expression in trans in LVS. We did not observe secretion of any of the LVS substrates VgrG, IglJ, IglF or IglI, when tested in a FTN_1072 deficient strain of F. novicida, whereas IglE, IglC, PdpA and even more so PdpE were all secreted. This suggests that there may be fundamental differences in the T6S mechanism among the Francisella subspecies. The findings further corroborate the unusual nature of the T6SS of F. tularensis since almost all of the identified substrates are unique to the species.

  3. Unique Substrates Secreted by the Type VI Secretion System of Francisella tularensis during Intramacrophage Infection

    PubMed Central

    Bröms, Jeanette E.; Sjöstedt, Anders

    2012-01-01

    Gram-negative bacteria have evolved sophisticated secretion machineries specialized for the secretion of macromolecules important for their life cycles. The Type VI secretion system (T6SS) is the most widely spread bacterial secretion machinery and is encoded by large, variable gene clusters, often found to be essential for virulence. The latter is true for the atypical T6SS encoded by the Francisella pathogenicity island (FPI) of the highly pathogenic, intracellular bacterium Francisella tularensis. We here undertook a comprehensive analysis of the intramacrophage secretion of the 17 FPI proteins of the live vaccine strain, LVS, of F. tularensis. All were expressed as fusions to the TEM β-lactamase and cleavage of the fluorescent substrate CCF2-AM, a direct consequence of the delivery of the proteins into the macrophage cytosol, was followed over time. The FPI proteins IglE, IglC, VgrG, IglI, PdpE, PdpA, IglJ and IglF were all secreted, which was dependent on the core components DotU, VgrG, and IglC, as well as IglG. In contrast, the method was not directly applicable on F. novicida U112, since it showed very intense native β-lactamase secretion due to FTN_1072. Its role was proven by ectopic expression in trans in LVS. We did not observe secretion of any of the LVS substrates VgrG, IglJ, IglF or IglI, when tested in a FTN_1072 deficient strain of F. novicida, whereas IglE, IglC, PdpA and even more so PdpE were all secreted. This suggests that there may be fundamental differences in the T6S mechanism among the Francisella subspecies. The findings further corroborate the unusual nature of the T6SS of F. tularensis since almost all of the identified substrates are unique to the species. PMID:23185631

  4. Activation of the basolateral membrane Cl− conductance essential for electrogenic K+ secretion suppresses electrogenic Cl− secretion

    PubMed Central

    He, Quanhua; Halm, Susan T.; Zhang, Jin; Halm, Dan R.

    2010-01-01

    Adrenaline activates transient Cl−-secretion and sustained K+-secretion across isolated distal colonic mucosa of guinea pig. The Ca++-activated Cl− channel inhibitor CaCCinh-A01 [30μM] significantly reduced electrogenic K+-secretion, detected as short-circuit current (Isc). This inhibition supported the cell model for K+-secretion in which basolateral membrane Cl− channels provide an exit pathway for Cl− entering the cell via Na+/K+/2Cl−-cotransporters. CaCCinh-A01 inhibited both Isc and transepithelial conductance in a concentration dependent manner, IC50 = 6.3μM. GlyH-101, another Cl− channel inhibitor, also reduced sustained adrenaline-activated Isc (IC50 = 9.4μM). Adrenaline activated whole-cell Cl− current in isolated intact colonic crypts, confirmed by ion substitution. This adrenaline-activated whole-cell Cl− current also was inhibited by CaCCinh-A01 or GlyH-101. In contrast to K+-secretion, CaCCinh-A01 augmented the electrogenic Cl−-secretion activated by adrenaline as well as that activated by PGE2. Synergistic Cl−-secretion activated by cholinergic/PGE2 stimulation was insensitive to CaCCinh-A01. Colonic expression of the Ca++-activated Cl− channel protein Tmem16A was supported by RT-PCR detection of Tmem16A-mRNA, by immuno-blot with a Tmem16A-antibody, and by immuno-fluorescence detection in lateral membranes of epithelial cells. Alternative splices of Tmem16A were detected for exons that are involved in channel activation. Inhibition of K+-secretion and augmentation of Cl−-secretion by CaCCinh-A01 supports a common colonic cell model for these two ion secretory processes, such that activation of basolateral membrane Cl− channels contributes to the production of electrogenic K+-secretion and limits the rate of Cl−-secretion. Maximal physiological Cl−-secretion occurs only for synergistic activation mechanisms that close these basolateral membrane Cl− channels. PMID:21169331

  5. The Best-Kept Secret in Town

    ERIC Educational Resources Information Center

    Perna, Mark C.

    2006-01-01

    In this article, the author describes how he has toured many impressive schools over the years and has heard one familiar statement that amazes him: "We are the best-kept secret in town." How can a school exist for any significant period of time and be virtually unknown to the community it serves? The truth is that if one considers his school to…

  6. Eccrine sweat gland development and sweat secretion.

    PubMed

    Cui, Chang-Yi; Schlessinger, David

    2015-09-01

    Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca(2+) -dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers - for example InsP3 and Ca(2+) - and downstream ion channels/transporters in the framework of a Na(+) -K(+) -Cl(-) cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid-base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined.

  7. Analysis of assembly of secreted mucins.

    PubMed

    Johansson, Malin E V; Hansson, Gunnar C

    2012-01-01

    Studies of assembly and secretion of gel-forming mucins are complex. The pulse-chase methods for mucins described here include metabolic radiolabeling and labeling in animals with azido-GalNAc. The labeled mucins are analyzed by composite agarose-polyacrylamide gel electrophoresis and autoradiography or by mucus-preserving tissue fixation and Click-iT(®) chemistry.

  8. Secret Codes, Remainder Arithmetic, and Matrices.

    ERIC Educational Resources Information Center

    Peck, Lyman C.

    This pamphlet is designed for use as enrichment material for able junior and senior high school students who are interested in mathematics. No more than a clear understanding of basic arithmetic is expected. Students are introduced to ideas from number theory and modern algebra by learning mathematical ways of coding and decoding secret messages.…

  9. Secret Shopping as User Experience Assessment Tool

    ERIC Educational Resources Information Center

    Boyce, Crystal M.

    2015-01-01

    Secret shopping is a form of unobtrusive evaluation that can be accomplished with minimal effort, but still produce rich results. With as few as 11 shoppers, the author was able to identify trends in user satisfaction with services provided across two entry-level desks at Illinois Wesleyan University's The Ames Library. The focus of this secret…

  10. Secrets of Mlearning Failures: Confronting Reality

    ERIC Educational Resources Information Center

    Cochrane, Thomas

    2012-01-01

    Having implemented and evaluated over 35 mlearning projects in a variety of contexts in higher education over the past 6 years the researcher is ready to share the untold secret: not all mlearning projects succeed! This article critiques three of the researcher's mlearning projects that can be classed as "failures" and compares them to successful…

  11. Containing the secret of child sexual abuse.

    PubMed

    McElvaney, Rosaleen; Greene, Sheila; Hogan, Diane

    2012-04-01

    This study reports a grounded theory study of the process of how children tell of their experiences of child sexual abuse from the perspectives of young people and their parents. Individual interviews were conducted with 22 young people aged 8 to 18, and 14 parents. A theoretical model was developed that conceptualises the process of disclosure as one of containing the secret of child sexual abuse. Three key dynamics were identified: the active withholding of the secret on the part of the child, the experience of a 'pressure cooker effect' reflecting a conflict between the wish to tell and the wish to keep the secret, and the confiding itself which often occurs in the context of an intimacy being shared. Children's experiences of disclosure were multidetermined and suggest the need for multifaceted and multisystemic approaches to prevention and intervention. The need for the secret to be contained, individually and interpersonally in appropriate safeguarding and therapeutic contexts needs to be respected in helping children tell.

  12. Secret Shopping as User Experience Assessment Tool

    ERIC Educational Resources Information Center

    Boyce, Crystal M.

    2015-01-01

    Secret shopping is a form of unobtrusive evaluation that can be accomplished with minimal effort, but still produce rich results. With as few as 11 shoppers, the author was able to identify trends in user satisfaction with services provided across two entry-level desks at Illinois Wesleyan University's The Ames Library. The focus of this secret…

  13. Secrets of Mlearning Failures: Confronting Reality

    ERIC Educational Resources Information Center

    Cochrane, Thomas

    2012-01-01

    Having implemented and evaluated over 35 mlearning projects in a variety of contexts in higher education over the past 6 years the researcher is ready to share the untold secret: not all mlearning projects succeed! This article critiques three of the researcher's mlearning projects that can be classed as "failures" and compares them to successful…

  14. Eccrine sweat gland development and sweat secretion

    PubMed Central

    Cui, Chang-Yi; Schlessinger, David

    2017-01-01

    Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca2+-dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers – for example InsP3 and Ca2+ – and downstream ion channels/transporters in the framework of a Na+-K+-Cl− cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid–base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined. PMID:26014472

  15. Metabolic priming by a secreted fungal effector.

    PubMed

    Djamei, Armin; Schipper, Kerstin; Rabe, Franziska; Ghosh, Anupama; Vincon, Volker; Kahnt, Jörg; Osorio, Sonia; Tohge, Takayuki; Fernie, Alisdair R; Feussner, Ivo; Feussner, Kirstin; Meinicke, Peter; Stierhof, York-Dieter; Schwarz, Heinz; Macek, Boris; Mann, Matthias; Kahmann, Regine

    2011-10-05

    Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation.

  16. Trade Secrets for Crafting a Conceptual Article.

    ERIC Educational Resources Information Center

    Salamone, Paul R.

    1993-01-01

    The author clarifies the distinction between a sound conceptual article and a literature review, outlines the creative process as it applies to written work, and provides "trade secrets" for novice writers on how to enhance their literary creativity and how to confront and solve writing problems. (Author/SR)

  17. The secret of the blue fog

    NASA Astrophysics Data System (ADS)

    Henrich, Oliver; Marenduzzo, Davide

    2017-04-01

    Why certain liquids turn blue when cooled was a mystery that stumped scientists for more than a century. As Oliver Henrich and Davide Marenduzzo explain, solving the secret of the “blue fog” proved to be an intellectual tour de force - and one that could lead to new types of display devices

  18. The Best Kept Secret in Gifted Education

    ERIC Educational Resources Information Center

    Alvino, James

    2004-01-01

    It is perhaps one of the best-kept secrets in educating gifted high school youth, and yet for 45 years, Hugh O'Brian Youth Leadership (HOBY) has been going strong, "Motivating Tomorrow's Leaders Today." After spending nine inspirational days in 1958 with Albert Schweitzer (Nobel Prize physician and philosopher) at his clinic in the African jungle,…

  19. Gastric inhibitory polypeptide secretion after radical pancreatoduodenectomy.

    PubMed Central

    Miyata, M; Nakao, K; Tanaka, Y; Sakamoto, T; Hamaji, M; Taketani, H; Kawashima, Y

    1984-01-01

    To elucidate the role of gastric inhibitory polypeptide (GIP) in the alteration of insulin secretion following pancreatoduodenal resection, in which the main sources of GIP are removed, plasma levels of GIP were measured for 180 minutes after oral glucose administration, both before and after radical pancreatoduodenectomy in nine patients with periampullary cancer. Fasting plasma levels of GIP remained much the same before and after surgery, and were not different from those in normal controls. The levels of GIP after glucose ingestion were significantly greater in the preoperative patients than in normal controls throughout 180 minutes. After pancreatoduodenectomy, the postglucose levels significantly diminished but remained within normal limits. Changes in plasma levels of insulin early after glucose ingestion in these patients, however, were significantly less both before and after surgery than in normal controls, and were not concomitant with the initial increase in plasma GIP. On the other hand, plasma levels of insulin greatly increased immediately after glucose ingestion in accordance with a rapid elevation of plasma GIP in 11 gastrectomized patients in whom the duodenum and the pancreas were preserved intact and who served as the control group. Thus, the diminution in GIP secretion following pancreatoduodenectomy may relate to the lack of main sources of this gut hormone and not to factors involved in the reconstruction of the alimentary tract. We conclude that the impaired insulin secretion following oral glucose ingestion in patients before and after pancreatoduodenectomy does not relate to the secretion of GIP. PMID:6367676

  20. The Best Kept Secret in Gifted Education

    ERIC Educational Resources Information Center

    Alvino, James

    2004-01-01

    It is perhaps one of the best-kept secrets in educating gifted high school youth, and yet for 45 years, Hugh O'Brian Youth Leadership (HOBY) has been going strong, "Motivating Tomorrow's Leaders Today." After spending nine inspirational days in 1958 with Albert Schweitzer (Nobel Prize physician and philosopher) at his clinic in the African jungle,…

  1. A mathematical model of insulin secretion.

    PubMed

    Shannon, A G; Hogg, J M; Ollerton, R L; Luzio, S; Owens, D R

    1994-01-01

    Diabetes mellitus is a chronic state of excessive blood glucose levels (hyperglycaemia), which may result from many environmental and genetic factors, often acting jointly. The major regulator of glucose concentration in the blood is insulin. It is known that about 50% of the insulin is taken up by the liver on passing through it after secretion from the pancreas. The precise value of this fractional uptake is not known, so the prehepatic insulin secretion rates cannot be readily estimated from the plasma insulin concentration levels. By utilizing the equimolar secretion of insulin and connecting peptide (C-peptide) from the pancreas, a noninvasive method has been formulated. This was based on a compartmental model which involved the pancreas, liver, and plasma. The resulting differential equation yielded a gamma variate solution which could be readily linearized. The model was then tested on 56 normal (51 nonobese and 5 obese) subjects, and three groups of subjects with diabetes who could be labelled as mild, moderate, and severe (based on the fasting plasma glucose concentration) with 83, 88, and 64 subjects respectively. We have focused on the human patient environment of the clinician to produce a distinct model which gave a consistent pattern within all four groups with good fits between observed and theoretical values of the plasma insulin levels. The consequent rates for insulin secretion were consistent across the groups and were clinically meaningful.

  2. ACTH-secreting 'apudoma' of gallbladder.

    PubMed Central

    Spence, R W; Burns-Cox, C J

    1975-01-01

    The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side. Images Fig 1 Fig 2 PMID:168130

  3. Calcium, carbonic anhydrase and gastric acid secretion.

    PubMed

    Puscas, I; Coltau, M; Baican, M; Domuta, G; Hecht, A

    2001-01-01

    Previous data concerning the action of calcium (Ca) on gastric acid secretion (GAS) indicated that calcium ions increase GAS elicited by gastrin released through a vagal mechanism, and also by a direct effect on parietal cells. Our research showed that the stimulating effect of calcium on gastric acid secretion can be antagonized by verapamil administration, which reduces gastric acid secretion . In the present study we followed the effect induced by administration of calcium and Ca-chelating agents (disodium EDTA) on gastric acid secretion and on carbonic anhydrase (CA) activity. We selected two groups of healthy volunteers: Group I (n=21) received a single i.v. dose of CaCl2 (15 mg/kg b.w.), whereas Group II (n=22) received a single i.v. dose of disodium EDTA (5 mg/kg b.w.). We determined blood calcium before and after treatment, gastric acid secretion at 2 hours. erythrocyte CA II activity, and CA IV activity in membrane parietal cells, which were isolated from gastric mucosa obtained by endoscopic biopsy. Assessment of carbonic anhydrase activity was achieved by the stopped-flow method. In Group I calcium administration increased blood calcium, HCl output, CA II and CA IV activity as compared to initial values. In Group II, disodium EDTA reduced blood calcium, HCl output, CA II and CA IV activity as compared to initial values. The results demonstrated that increased blood calcium and GAS values after calcium administration correlated with the increase of erythrocyte CA II and parietal cell CA IV activity, while disodium EDTA induced a reversed process. Our results also show that cytosolic CA II and membrane CA IV values are sensitive to calcium changes and they directly depend on these levels. Our data suggest that intra- and extracellular pH changes induced by carbonic anhydrase might account for the modulation of the physiological and pathological secretory processes in the organism.

  4. Insulin reciprocally regulates glucagon secretion in humans.

    PubMed

    Cooperberg, Benjamin A; Cryer, Philip E

    2010-11-01

    We tested the hypothesis that an increase in insulin per se, i.e., in the absence of zinc, suppresses glucagon secretion during euglycemia and that a decrease in insulin per se stimulates glucagon secretion during hypoglycemia in humans. We measured plasma glucagon concentrations in patients with type 1 diabetes infused with the zinc-free insulin glulisine on three occasions. Glulisine was infused with clamped euglycemia (∼95 mg/dl [5.3 mmol/l]) from 0 to 60 min on all three occasions. Then, glulisine was discontinued with clamped euglycemia or with clamped hypoglycemia (∼55 mg/dl [3.0 mmol/l]) or continued with clamped hypoglycemia from 60 to 180 min. Plasma glucagon concentrations were suppressed by -13 ± 3, -9 ± 3, and -12 ± 2 pg/ml (-3.7 ± 0.9, -2.6 ± 0.9, and -3.4 ± 0.6 pmol/l), respectively, (all P < 0.01) during zinc-free hyperinsulinemic euglycemia over the first 60 min. Glucagon levels remained suppressed following a decrease in zinc-free insulin with euglycemia (-14 ± 3 pg/ml [-4.0 ± 0.9 pmol/l]) and during sustained hyperinsulinemia with hypoglycemia (-14 ± 2 pg/ml [-4.0 ± 0.6 pmol/l]) but increased to -3 ± 3 pg/ml (-0.9 ± 0.9 pmol/l) (P < 0.01) following a decrease in zinc-free insulin with hypoglycemia over the next 120 min. These data indicate that an increase in insulin per se suppresses glucagon secretion and a decrease in insulin per se, in concert with a low glucose concentration, stimulates glucagon secretion. Thus, they document that insulin is a β-cell secretory product that, in concert with glucose and among other signals, reciprocally regulates α-cell glucagon secretion in humans.

  5. SecretEPDB: a comprehensive web-based resource for secreted effector proteins of the bacterial types III, IV and VI secretion systems

    PubMed Central

    An, Yi; Wang, Jiawei; Li, Chen; Revote, Jerico; Zhang, Yang; Naderer, Thomas; Hayashida, Morihiro; Akutsu, Tatsuya; Webb, Geoffrey I.; Lithgow, Trevor; Song, Jiangning

    2017-01-01

    Bacteria translocate effector molecules to host cells through highly evolved secretion systems. By definition, the function of these effector proteins is to manipulate host cell biology and the sequence, structural and functional annotations of these effector proteins will provide a better understanding of how bacterial secretion systems promote bacterial survival and virulence. Here we developed a knowledgebase, termed SecretEPDB (Bacterial Secreted Effector Protein DataBase), for effector proteins of type III secretion system (T3SS), type IV secretion system (T4SS) and type VI secretion system (T6SS). SecretEPDB provides enriched annotations of the aforementioned three classes of effector proteins by manually extracting and integrating structural and functional information from currently available databases and the literature. The database is conservative and strictly curated to ensure that every effector protein entry is supported by experimental evidence that demonstrates it is secreted by a T3SS, T4SS or T6SS. The annotations of effector proteins documented in SecretEPDB are provided in terms of protein characteristics, protein function, protein secondary structure, Pfam domains, metabolic pathway and evolutionary details. It is our hope that this integrated knowledgebase will serve as a useful resource for biological investigation and the generation of new hypotheses for research efforts aimed at bacterial secretion systems. PMID:28112271

  6. Secretion of slow-folding proteins by a Type 1 secretion system.

    PubMed

    Schwarz, Christian K W; Lenders, Michael H H; Smits, Sander H J; Schmitt, Lutz

    2012-01-01

    Protein production through dedicated secretion systems might offer an potential alternative to the conventional cytoplasmical expression. The application of Type 1 secretion systems of Gram-negative bacteria, however, where often not successful in the past for a wide range of proteins. Recently, two studies using the E. coli maltose binding protein (MalE) and the rat intestinal fatty acid binding protein (IFABP) revealed a rational to circumvent these limitations. Here, wild-type passenger proteins were not secreted, while folding mutants with decreased folding kinetics were efficiently exported to the extracellular space. Subsequently, an one-step purification protocol yielded homogeneous and active protein. Taken together, theses two studies suggest that the introduction of slow-folding mutations into a protein sequence might be the key to use Type 1 secretion systems for the biotechnological production of proteins.

  7. Properties of Duvernoy's secretions from opisthoglyphous and aglyphous colubrid snakes.

    PubMed

    Weinstein, S A; Kardong, K V

    1994-10-01

    Relatively little attention has been given to the biological properties of Duvernoy's secretions produced by opisthoglyphous and some aglyphous colubrid snakes. A review is presented of literature pertaining to these secretions. Most detailed analyses of Duvernoy's secretions and their biological properties have been performed since the late 1970s. The dispholidines, Dispholidus typus and Thelotornis sp., and the natricines, Rhabdophis tigrinus and R. subminiata, have received the most attention due to the high toxicity of their secretions and their medical importance. These species produce secretions with variably strong prothrombin-activating activity, defibrinating activity, and hemorrhagic potential. Boigines, and natricines other than Rhabdophis, produce secretions of low to moderate toxicity and are variably hemorrhagic and proteolytic. Xenodontines and homalopsines similarly show hemorrhagic potential with low to moderate toxicity. Neurotoxic activity has been reported only from secretions of the boigines, Boiga blandingi and B. irregularis and the xenodontine, Heterodon platyrhinos. These species produce secretions containing postsynaptically acting components. Analyses of some of these secretions have shown that enzymes common to many ophidian venoms such as phospholipases A and L-amino acid oxidase are uncommon in the colubrid secretions studied. This may be due to few studies assaying for multiple enzyme activities and/or the unavailability of many secretion samples for study. Methods of secretion extraction, storage, and assay are discussed. Projected future research and the adaptive implications of Duvernoy's secretions are considered.

  8. Somatomammotrophic cells in GH-secreting and PRL-secreting human pituitary adenomas.

    PubMed

    Bassetti, M; Brina, M; Spada, A; Giannattasio, G

    1989-11-01

    A morphological study has been carried out on 20 GH-secreting adenomas removed from acromegalic normoprolactinemic patients, on 29 PRL-secreting adenomas removed from hyperprolactinemic patients without signs of acromegaly and on one normal human anterior pituitary gland collected at autopsy. The protein A-gold immunoelectron microscopic technique has been utilized in order to verify the presence of mixed cells producing both GH and PRL (somatomammotrophs) in these pituitary tissues. In the normal pituitary a considerable number of somatomammotrophs (15-20%) was found, thus supporting the idea that these cells are normal components of the human anterior pituitary gland. In 10 GH-secreting adenomas and in 10 PRL-secreting adenomas somatomammotrophs were present in a variable number (from 4 to 20% of the whole cell population in GH adenomas and from 1 to 47% in PRL tumors). It can be concluded therefore that these cells, largely present in all GH/PRL-secreting adenomas, can also be found in GH-secreting and PRL-secreting tumors without clinical evidence of a mixed secretion. Adenomatous somatomammotrophs displayed ultrastructural features of adenomatous somatotrophs and mammotrophs (prominent Golgi complexes, abundant rough endoplasmic reticulum, irregular nuclei). The size and the number of granules were variable. In some cells GH and PRL were stored in distinct secretory granules, in others in mixed granules or both in mixed and distinct granules, thus suggesting that in adenomatous somatomammotrophs the efficiency of the mechanisms of sorting of the two hormones varies from one cell to another.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. SepD/SepL-Dependent Secretion Signals of the Type III Secretion System Translocator Proteins in Enteropathogenic Escherichia coli

    PubMed Central

    Deng, Wanyin; Yu, Hong B.; Li, Yuling

    2015-01-01

    ABSTRACT The type III protein secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE) is essential for the pathogenesis of attaching/effacing bacterial pathogens, including enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium. These pathogens use the T3SS to sequentially secrete three categories of proteins: the T3SS needle and inner rod protein components; the EspA, EspB, and EspD translocators; and many LEE- and non-LEE-encoded effectors. SepD and SepL are essential for translocator secretion, and mutations in either lead to hypersecretion of effectors. However, how SepD and SepL control translocator secretion and secretion hierarchy between translocators and effectors is poorly understood. In this report, we show that the secreted T3SS components, the translocators, and both LEE- and non-LEE-encoded effectors all carry N-terminal type III secretion and translocation signals. These signals all behave like those of the effectors and are sufficient for mediating type III secretion and translocation by wild-type EPEC and hypersecretion by the sepD and sepL mutants. Our results extended previous observations and suggest that the secretion hierarchy of the different substrates is determined by a signal other than the N-terminal secretion signal. We identified a domain located immediately downstream of the N-terminal secretion signal in the translocator EspB that is required for SepD/SepL-dependent secretion. We further demonstrated that this EspB domain confers SepD/SepL- and CesAB-dependent secretion on the secretion signal of effector EspZ. Our results thus suggest that SepD and SepL control and regulate secretion hierarchy between translocators and effectors by recognizing translocator-specific export signals. IMPORTANCE Many bacterial pathogens use a syringe-like protein secretion apparatus, termed the type III protein secretion system (T3SS), to secrete and inject numerous proteins directly into

  10. Involvement of type VI secretion system in secretion of iron chelator pyoverdine in Pseudomonas taiwanensis

    PubMed Central

    Chen, Wen-Jen; Kuo, Tzu-Yen; Hsieh, Feng-Chia; Chen, Pi-Yu; Wang, Chang-Sheng; Shih, Yu-Ling; Lai, Ying-Mi; Liu, Je-Ruei; Yang, Yu-Liang; Shih, Ming-Che

    2016-01-01

    Rice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive rice diseases worldwide. Therefore, in addition to breeding disease-resistant rice cultivars, it is desirable to develop effective biocontrol agents against Xoo. Here, we report that a soil bacterium Pseudomonas taiwanensis displayed strong antagonistic activity against Xoo. Using matrix-assisted laser desorption/ionization imaging mass spectrometry, we identified an iron chelator, pyoverdine, secreted by P. taiwanensis that could inhibit the growth of Xoo. Through Tn5 mutagenesis of P. taiwanensis, we showed that mutations in genes that encode components of the type VI secretion system (T6SS) as well as biosynthesis and maturation of pyoverdine resulted in reduced toxicity against Xoo. Our results indicated that T6SS is involved in the secretion of endogenous pyoverdine. Mutations in T6SS component genes affected the secretion of mature pyoverdine from the periplasmic space into the extracellular medium after pyoverdine precursor is transferred to the periplasm by the inner membrane transporter PvdE. In addition, we also showed that other export systems, i.e., the PvdRT-OpmQ and MexAB-OprM efflux systems (for which there have been previous suggestions of involvement) and the type II secretion system (T2SS), are not involved in pyoverdine secretion. PMID:27605490

  11. Molecular Mechanisms of Insulin Secretion and Insulin Action.

    ERIC Educational Resources Information Center

    Flatt, Peter R.; Bailey, Clifford J.

    1991-01-01

    Information and current ideas on the factors regulating insulin secretion, the mechanisms underlying the secretion and biological actions of insulin, and the main characteristics of diabetes mellitus are presented. (Author)

  12. Molecular Mechanisms of Insulin Secretion and Insulin Action.

    ERIC Educational Resources Information Center

    Flatt, Peter R.; Bailey, Clifford J.

    1991-01-01

    Information and current ideas on the factors regulating insulin secretion, the mechanisms underlying the secretion and biological actions of insulin, and the main characteristics of diabetes mellitus are presented. (Author)

  13. Sympathetic regulation of estradiol secretion from the ovary.

    PubMed

    Uchida, Sae

    2015-01-01

    It is well known that hormone secretion from endocrine glands is regulated by hierarchical feedback mechanisms. However, although Cannon revealed in the 1920s that sympathoadrenal medullary function increased during emergency situations, no studies on the autonomic nervous regulation of hormone secretion have been undertaken for many years. In the past 40 years, the autonomic nervous regulation of insulin secretion from the pancreas, gastrin secretion from the stomach, glucocorticoid secretion from the adrenal cortex, etc., has been demonstrated. Estradiol secretion from the ovary is strongly controlled by the hypothalamic-pituitary-ovarian axis, and its possible regulation by autonomic nerves has been largely unnoticed. Some histological studies have revealed rich adrenergic sympathetic innervation in the ovary. Recently, it has been demonstrated that the activation of the sympathetic nerves to the ovary directly reduces estradiol secretion from the ovary. This article reviews physiological and morphological studies, primarily in rats, on the sympathetic regulation of estradiol secretion from the ovary.

  14. Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

    SciTech Connect

    Lee, Je Min; Lee, Sang-Jik; Rose, Jocelyn K.C.; Yeam, Inhwa; Kim, Byung-Dong

    2014-04-18

    Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.

  15. Efficient Robust Storage Using Secret Tokens

    NASA Astrophysics Data System (ADS)

    Dobre, Dan; Majuntke, Matthias; Serafini, Marco; Suri, Neeraj

    We present algorithms that reduce the time complexity and improve the scalability of robust storage for unauthenticated data. Robust storage ensures progress under every condition (wait-freedom) and never returns an outdated value (regularity) nor a forged value (Byzantine fault tolerance). The algorithms use secret tokens, which are values randomly selected by the clients and attached to the data written into the storage. Tokens are secret because they cannot be predicted by the attacker before they are used, and thus revealed, by the clients. Our algorithms do not rely on unproven cryptographic assumptions as algorithms based on self-verifying data. They are optimally-resilient, and ensure that reads complete in two communication rounds if readers do not write into the storage, or in one communication round otherwise.

  16. A switchable yeast display/secretion system

    PubMed Central

    Van Deventer, James A.; Kelly, Ryan L.; Rajan, Saravanan; Wittrup, K. Dane; Sidhu, Sachdev S.

    2015-01-01

    Display technologies such as yeast and phage display offer powerful alternatives to traditional immunization-based antibody discovery, but require conversion of displayed proteins into soluble form prior to downstream characterization. Here we utilize amber suppression to implement a yeast-based switchable display/secretion system that enables the immediate production of soluble, antibody-like reagents at the end of screening efforts. Model selections in the switchable format remain efficient, and library screening in the switchable format yields renewable sources of affinity reagents exhibiting nanomolar binding affinities. These results confirm that this system provides a seamless link between display-based screening and the production and evaluation of soluble forms of candidate binding proteins. Switchable display/secretion libraries provide a cloning-free, accessible approach to affinity reagent generation. PMID:26333274

  17. A switchable yeast display/secretion system.

    PubMed

    Van Deventer, James A; Kelly, Ryan L; Rajan, Saravanan; Wittrup, K Dane; Sidhu, Sachdev S

    2015-10-01

    Display technologies such as yeast and phage display offer powerful alternatives to traditional immunization-based antibody discovery, but require conversion of displayed proteins into soluble form prior to downstream characterization. Here we utilize amber suppression to implement a yeast-based switchable display/secretion system that enables the immediate production of soluble, antibody-like reagents at the end of screening efforts. Model selections in the switchable format remain efficient, and library screening in the switchable format yields renewable sources of affinity reagents exhibiting nanomolar binding affinities. These results confirm that this system provides a seamless link between display-based screening and the production and evaluation of soluble forms of candidate binding proteins. Switchable display/secretion libraries provide a cloning-free, accessible approach to affinity reagent generation.

  18. Pituitary tumours: TSH-secreting adenomas.

    PubMed

    Beck-Peccoz, Paolo; Persani, Luca; Mannavola, Deborah; Campi, Irene

    2009-10-01

    Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last years, the diagnosis has been facilitated by the routine use of ultra-sensitive TSH immunometric assays. Failure to recognise the presence of a TSHoma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumour volume to further expand. The diagnosis mainly rests on dynamic testing, such as T3 suppression tests and TRH, which are useful in differentiating TSHomas from the syndromes of thyroid hormone resistance. The first therapeutical approach to TSHomas is the pituitary neurosurgery. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogues, such as octreotide and lanreotide, which are effective in reducing TSH secretion in more than 90% of patients with consequent normalisation of FT4 and FT3 levels and restoration of the euthyroid state.

  19. Management of oral secretions in neurological disease.

    PubMed

    McGeachan, Alexander J; Mcdermott, Christopher J

    2017-04-01

    Sialorrhoea is a common and problematic symptom that arises from a range of neurological conditions associated with bulbar or facial muscle dysfunction. Drooling can significantly affect quality of life due to both physical complications such as oral chapping, and psychological complications such as embarrassment and social isolation. Thicker, tenacious oral and pharyngeal secretions may result from the drying management approach to sialorrhoea. The management of sialorrhoea in neurological diseases depends on the underlying pathology and severity of symptoms. Interventions include anticholinergic drugs, salivary gland-targeted radiotherapy, salivary gland botulinum toxin and surgical approaches. The management of thick secretions involves mainly conservative measures such as pineapple juice as a lytic agent, cough assist, saline nebulisers and suctioning or mucolytic drugs like carbocisteine. Despite a current lack of evidence and variable practice, management of sialorrhoea should form a part of the multidisciplinary approach needed for long-term neurological conditions.

  20. Regulation of renal potassium secretion: molecular mechanisms.

    PubMed

    Welling, Paul A

    2013-05-01

    A new understanding of renal potassium balance has emerged as the molecular underpinnings of potassium secretion have become illuminated, highlighting the key roles of apical potassium channels, renal outer medullary potassium channel (ROMK) and Big Potassium (BK), in the aldosterone-sensitive distal nephron and collecting duct. These channels act as the final-regulated components of the renal potassium secretory machinery. Their activity, number, and driving forces are precisely modulated to ensure potassium excretion matches dietary potassium intake. Recent identification of the underlying regulatory mechanisms at the molecular level provides a new appreciation of the physiology and reveals a molecular insight to explain the paradoxic actions of aldosterone on potassium secretion. Here, we review the current state of knowledge in the field.

  1. [Synthesis and regulation of growth hormone secretion].

    PubMed

    Miyachi, Y; Yakushiji, F; Terazono, T

    1993-10-01

    Human growth hormone (hGH) is a single chain, 22 kd-protein with two intramolecular disulfide bonds. The hGH gene is located on chromosome 17 at band q22-q24 and has four introns separating five coding exons. The expression of hGH is restricted to the pituitary and regulated by GHF-1 which binds to the hGH promoter acting in concert with several other more ubiquitous DNA binding proteins. The secretion of hGH is regulated by GH releasing hormone (GRH) and somatostatin. GRH controls GH synthesis by stimulating transcription of GH mRNA while somatostatin determines the timing and amplitude of GH pulses. Pulsatile GH secretion is influenced by a number of neurogenic, metabolic and hormonal factors.

  2. The secretion, components, and properties of saliva.

    PubMed

    Carpenter, Guy H

    2013-01-01

    Saliva has one of the most difficult roles to perform in the body. It must facilitate the taste and detection of foods nutritious to the body but also defend the mucosa from infection by the ever-present microbiota present in the mouth. It achieves these roles by having a complex composition and versatile physical properties. The protein and ion components make a solution that is 99% water into a viscoelastic solution capable of many roles, such as acting as a lubricant and an antimicrobial, preventing the dissolution of teeth, aiding digestion, and facilitating taste. This review describes the neural regulation of salivary secretion in terms of fluid, protein, and ion secretion. It then describes some of the components and physical properties of saliva and attempts to relate them to the functions that saliva must perform.

  3. [The symbolic power of bodily secretions].

    PubMed

    Isaksen, Lise Widding

    2002-01-10

    Are ethical and political questions discussed more in aesthetic than in social terms? Political debates in contemporary art are often expressed through the use of symbolic power structures that are related to bodily secretions and products. By visualizing the less delicate parts of the organic body, contemporary artists focus on the vulnerability of the human body and its illness and pain. If human suffering is aestheticized: is this a question of form or a question of creating a cultural cover-up? Bodily secretions are associated with a range of complex social and cultural meanings and symbols. Metaphors related to body products may function as markers of ethnic, religious, social and sexual differences. In postmodern cultural criticism, the symbolic power of body metaphors is of great importance.

  4. Tachykinin receptors mediating airway marcomolecular secretion

    SciTech Connect

    Gentry, S.E. )

    1991-01-01

    Three tachykinin receptor types, termed NK1, NK2, and NK3, can be distinguished by the relative potency of various peptides in eliciting tissue responses. Airway macromolecular secretion is stimulated by the tachykinin substance P (SP). The purposes of this study were to determine the tachykinin receptor subtype responsible for this stimulation, and to examine the possible involvement of other neurotransmitters in mediating this effect. Ferret tracheal explants maintained in organ culture were labeled with {sup 3}H-glucosamine, a precursor of high molecular weight glycoconjugates (HMWG) which are released by airway secretory cells. Secretion of labeled HMWG then was determined in the absence and presence of the tachykinins SP, neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY), and eledoisin (ELE). To evaluate the possible contribution of other mediators, tachykinin stimulation was examined in the presence of several receptor blockers.

  5. Milk protein concentrations in galactorrhoeic mammary secretions.

    PubMed

    Yap, P L; Pryde, E A; McClelland, D B

    1980-02-01

    Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA) or single radial immunodiffusion (IgG, lactoferrin, lysozyme and albumin) in the mammayr secretions of one nulliparous and three parous female patients with galactorrhoea due to hyperprolactinaemia. Concentrations of all the proteins studied were found to be similar to the concentrations observed in post-partum colostrum. In particular, secretory IgA was the only form of IgA detected in galactorrhoeic secretions. It is suggested that hyperprolactinaemia alone can result in increased mammary synthesis of the milk proteins since the steroid changes associated with a full-term pregnancy and delivery of the placenta did not immediately precede the galactorrhoea in three of the four patients studied.

  6. Effect of diazepam on unstimulated and on stimulated gastric secretion.

    PubMed

    Bennett, P N; Davies, P; Frigo, G M; Weerasinghe, W M; Lennard-Jones, J E

    1975-01-01

    The effect of intravenous diazepam on unstimulated and on pentagastrin-stimulated gastric secretion has been studied in normal subjects. No significant effect of diazapam was found on pentagastrin-stimulated gastric secretion. Unstimulated secretion was reduced by diazepam. This action of diazepam may be useful in peptic ulcer therapy.

  7. Trade Secrets in Life Science and Pharmaceutical Companies

    PubMed Central

    Nealey, Tara; Daignault, Ronald M.; Cai, Yu

    2015-01-01

    Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through “improper means” is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today’s interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees’ careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. PMID:25414378

  8. Information Theoretic Secret Key Generation: Structured Codes and Tree Packing

    ERIC Educational Resources Information Center

    Nitinawarat, Sirin

    2010-01-01

    This dissertation deals with a multiterminal source model for secret key generation by multiple network terminals with prior and privileged access to a set of correlated signals complemented by public discussion among themselves. Emphasis is placed on a characterization of secret key capacity, i.e., the largest rate of an achievable secret key,…

  9. 10 CFR 1016.34 - Accountability for Secret Restricted Data.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall...

  10. 40 CFR 209.23 - Trade secrets and privileged information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Trade secrets and privileged... secrets and privileged information. In the presentation, admission, disposition, and use of evidence, the administrative law judge shall preserve the confidentiality of trade secrets and other privileged commercial...

  11. 40 CFR 209.23 - Trade secrets and privileged information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Trade secrets and privileged... secrets and privileged information. In the presentation, admission, disposition, and use of evidence, the administrative law judge shall preserve the confidentiality of trade secrets and other privileged commercial...

  12. 40 CFR 209.23 - Trade secrets and privileged information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Trade secrets and privileged... secrets and privileged information. In the presentation, admission, disposition, and use of evidence, the administrative law judge shall preserve the confidentiality of trade secrets and other privileged commercial...

  13. 40 CFR 209.23 - Trade secrets and privileged information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Trade secrets and privileged... secrets and privileged information. In the presentation, admission, disposition, and use of evidence, the administrative law judge shall preserve the confidentiality of trade secrets and other privileged commercial...

  14. 10 CFR 1016.34 - Accountability for Secret Restricted Data.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall...

  15. 40 CFR 209.23 - Trade secrets and privileged information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Trade secrets and privileged... secrets and privileged information. In the presentation, admission, disposition, and use of evidence, the administrative law judge shall preserve the confidentiality of trade secrets and other privileged commercial...

  16. 10 CFR 1016.34 - Accountability for Secret Restricted Data.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall...

  17. Trade secrets in life science and pharmaceutical companies.

    PubMed

    Nealey, Tara; Daignault, Ronald M; Cai, Yu

    2014-11-20

    Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through "improper means" is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today's interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees' careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft.

  18. 10 CFR 1016.34 - Accountability for Secret Restricted Data.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall...

  19. Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion

    DTIC Science & Technology

    2014-10-01

    Exosome Secretion PRINCIPAL INVESTIGATOR: Christine Vogel CONTRACTING ORGANIZATION: New York University, New York, NY 10012...30 Sep 2013 - 29 Sep 2014 4. TITLE AND SUBTITLE Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5a. CONTRACT...NUMBER Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5b. GRANT NUMBER W81XWH-13-1-0467 5c. PROGRAM ELEMENT

  20. Information Theoretic Secret Key Generation: Structured Codes and Tree Packing

    ERIC Educational Resources Information Center

    Nitinawarat, Sirin

    2010-01-01

    This dissertation deals with a multiterminal source model for secret key generation by multiple network terminals with prior and privileged access to a set of correlated signals complemented by public discussion among themselves. Emphasis is placed on a characterization of secret key capacity, i.e., the largest rate of an achievable secret key,…

  1. Hoopoes color their eggs with antimicrobial uropygial secretions

    NASA Astrophysics Data System (ADS)

    Soler, Juan J.; Martín-Vivaldi, M.; Peralta-Sánchez, J. M.; Arco, L.; Juárez-García-Pelayo, N.

    2014-09-01

    Uropygial gland secretions are used as cosmetics by some species of birds to color and enhance properties of feathers and teguments, which may signal individual quality. Uropygial secretions also reach eggshells during incubation and, therefore, may influence the coloration of birds' eggs, a trait that has attracted the attention of evolutionary biologists for more than one century. The color of hoopoe eggs typically changes along incubation, from bluish-gray to greenish-brown. Here, we test experimentally the hypothesis that dark uropygial secretion of females is responsible for such drastic color change. Moreover, since uropygial secretion of hoopoes has antimicrobial properties, we also explore the association between color and antimicrobial activity of the uropygial secretion of females. We found that eggs stayed bluish-gray in nests where female access to the uropygial secretion was experimentally blocked. Furthermore, experimental eggs that were maintained in incubators and manually smeared with uropygial secretion experienced similar color changes that naturally incubated eggs did, while control eggs that were not in contact with the secretions did not experience such color changes. All these results strongly support the hypothesis that female hoopoes use their uropygial gland secretion to color the eggs. Moreover, saturation of the uropygial secretion was associated with antimicrobial activity against Bacillus licheniformis. Given the known antimicrobial potential of uropygial secretions of birds, this finding opens the possibility that in scenarios of sexual selection, hoopoes in particular and birds in general signal antimicrobial properties of their uropygial secretion by mean of changes in egg coloration along incubation.

  2. Hoopoes color their eggs with antimicrobial uropygial secretions.

    PubMed

    Soler, Juan J; Martín-Vivaldi, M; Peralta-Sánchez, J M; Arco, L; Juárez-García-Pelayo, N

    2014-09-01

    Uropygial gland secretions are used as cosmetics by some species of birds to color and enhance properties of feathers and teguments, which may signal individual quality. Uropygial secretions also reach eggshells during incubation and, therefore, may influence the coloration of birds' eggs, a trait that has attracted the attention of evolutionary biologists for more than one century. The color of hoopoe eggs typically changes along incubation, from bluish-gray to greenish-brown. Here, we test experimentally the hypothesis that dark uropygial secretion of females is responsible for such drastic color change. Moreover, since uropygial secretion of hoopoes has antimicrobial properties, we also explore the association between color and antimicrobial activity of the uropygial secretion of females. We found that eggs stayed bluish-gray in nests where female access to the uropygial secretion was experimentally blocked. Furthermore, experimental eggs that were maintained in incubators and manually smeared with uropygial secretion experienced similar color changes that naturally incubated eggs did, while control eggs that were not in contact with the secretions did not experience such color changes. All these results strongly support the hypothesis that female hoopoes use their uropygial gland secretion to color the eggs. Moreover, saturation of the uropygial secretion was associated with antimicrobial activity against Bacillus licheniformis. Given the known antimicrobial potential of uropygial secretions of birds, this finding opens the possibility that in scenarios of sexual selection, hoopoes in particular and birds in general signal antimicrobial properties of their uropygial secretion by mean of changes in egg coloration along incubation.

  3. Unconventional protein secretion (UPS) pathways in plants.

    PubMed

    Ding, Yu; Robinson, David G; Jiang, Liwen

    2014-08-01

    As in yeast and mammalian cells, novel unconventional protein secretion (UPS) or unconventional membrane trafficking pathways are now known to operate in plants. UPS in plants is generally associated with stress conditions such as pathogen attack, but little is known about its underlying mechanism and function. Here, we present an update on the current knowledge of UPS in the plants in terms of its transport pathways, possible functions and its relationship to autophagy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Human adipocytes secrete mineralocorticoid-releasing factors.

    PubMed

    Ehrhart-Bornstein, M; Lamounier-Zepter, V; Schraven, A; Langenbach, J; Willenberg, H S; Barthel, A; Hauner, H; McCann, S M; Scherbaum, W A; Bornstein, S R

    2003-11-25

    Obesity has become an epidemic problem in western societies, contributing to metabolic diseases, hypertension, and cardiovascular disease. Overweight and obesity are frequently associated with increased plasma levels of aldosterone. Recent evidence suggests that human fat is a highly active endocrine tissue. Therefore, we tested the hypothesis that adipocyte secretory products directly stimulate adrenocortical aldosterone secretion. Secretory products from isolated human adipocytes strongly stimulated steroidogenesis in human adrenocortical cells (NCI-H295R) with a predominant effect on mineralocorticoid secretion. Aldosterone secretion increased 7-fold during 24 h of incubation. This stimulation was comparable to maximal stimulation of these cells with forskolin (2 x 10(-5) M). On the molecular level, there was a 10-fold increase in the expression of steroid acute regulatory peptide mRNA. This effect was independent of adipose angiotensin II as revealed by the stimulatory effect of fat cell-conditioned medium even in the presence of the angiotensin type 1 receptor antagonist, valsartan. None of the recently defined adipocytokines accounted for the effect. Mineralocorticoid-stimulating activity was heat sensitive and could be blunted by heating fat cell-conditioned medium to 99 degrees C. Centrifugal filtration based on molecular mass revealed at least two releasing factors: a heat sensitive fraction (molecular mass >50 kDa) representing 60% of total activity, and an inactive fraction (molecular mass <50 kDa). However, the recovery rate increased to 92% when combining these two fractions, indicating the interaction of at least two factors. In conclusion, human adipocytes secrete potent mineralocorticoid-releasing factors, suggesting a direct link between obesity and hypertension.

  5. America's Secret Educational Weapon: Community Colleges

    ERIC Educational Resources Information Center

    Magrath, C. Peter

    2008-01-01

    The U.S. has a powerful weapon in its educational arsenal: its community colleges. Yet these institutions, according to the author, are so often overlooked in discussions of the future of U.S. society and the U.S. work force that they might as well be deemed "top secret." More than 1,200 community colleges enroll some 47% of all undergraduates.…

  6. Thermal requirements of Dermanyssus gallinae (De Geer, 1778) (Acari: Dermanyssidae).

    PubMed

    Tucci, Edna Clara; do Prado, Angelo P; de Araújo, Raquel Pires

    2008-01-01

    The thermal requirements for development of Dermanyssus gallinae were studied under laboratory conditions at 15, 20, 25, 30 and 35 degrees C, a 12h photoperiod and 60-85% RH. The thermal requirements for D. gallinae were as follows. Preoviposition: base temperature 3.4 degrees C, thermal constant (k) 562.85 degree-hours, determination coefficient (R(2)) 0.59, regression equation: Y= -0.006035 + 0.001777x. Egg: base temperature 10.60 degrees C, thermal constant (k) 689.65 degree-hours, determination coefficient (R(2)) 0.94, regression equation: Y= -0.015367 + 0.001450x. Larva: base temperature 9.82 degrees C, thermal constant (k) 464.91 degree-hours, determination coefficient (R(2)) 0.87, regression equation: Y= -0.021123 + 0.002151x. Protonymph: base temperature 10.17 degrees C, thermal constant (k) 504.49 degree-hours, determination coefficient (R(2)) 0.90, regression equation: Y= -0.020152 + 0.001982x. Deutonymph: base temperature 11.80 degrees C, thermal constant (k) 501.11 degree-hours, determination coefficient (R(2)) 0.99, regression equation: Y= -0.023555 + 0.001996x. The results obtained showed that 15 to 42 generations of Dermanyssus gallinae may occur during the year in the State of São Paulo, as estimated based on isotherm charts. Dermanyssus gallinae may develop continually in the State of São Paulo, with a population decrease in the winter. There were differences between the developmental stages of D. gallinae in relation to thermal requirements.

  7. A Trade Secret Model for Genomic Biobanking

    PubMed Central

    Conley, John M.; Kenan, William Rand; Mitchell, Robert; Cadigan, R. Jean; Davis, Arlene M.; Dobson, Allison W.; Gladden, Ryan Q.

    2012-01-01

    Genomic biobanks present ethical challenges that are qualitatively unique and quantitatively unprecedented. Many critics have questioned whether the current system of informed consent can be meaningfully applied to genomic biobanking. Proposals for reform have come from many directions, but have tended to involve incremental change in current informed consent practice. This paper reports on our efforts to seek new ideas and approaches from those whom informed consent is designed to protect: research subjects. Our model emerged from semi-structured interviews with healthy volunteers who had been recruited to join either of two biobanks (some joined, some did not), and whom we encouraged to explain their concerns and how they understood the relationship between specimen contributors and biobanks. These subjects spoke about their DNA and the information it contains in ways that were strikingly evocative of the legal concept of the trade secret. They then described the terms and conditions under which they might let others study their DNA, and there was a compelling analogy to the commonplace practice of trade secret licensing. We propose a novel biobanking model based on this trade secret concept, and argue that it would be a practical, legal, and ethical improvement on the status quo. PMID:23061589

  8. Dragon's blood secretion and its ecological significance.

    PubMed

    Jura-Morawiec, Joanna; Tulik, Mirela

    Dragon's blood is the name given to a red exudate produced by some plant species belonging to the genera Daemonorops, Dracaena, Croton and Pterocarpus. These are endemic to various parts of the globe. It is classified as a resin or latex depending on its mode of secretion and its chemical composition, which is species specific. This red substance functions in defence and is produced (a) constitutively and stored in preformed anatomical structures, or (b) by induction in response to traumatic events, such as mechanical injury, pathogen attack or invasion by insects. Apart from its defensive role in plants, dragon's blood is also a valuable natural resource renowned since antiquity for its diverse medicinal properties and uses in art. Despite the great importance of dragon's blood, our knowledge of the biological basis for its secretion is still incomplete. This review summarizes recent advances in the study of the anatomical basis for its secretion, and discusses its classification and ecological function. Bringing some clarity to these issues may also help in the commercial sourcing of dragon's blood.

  9. A trade secret model for genomic biobanking.

    PubMed

    Conley, John M; Mitchell, Robert; Cadigan, R Jean; Davis, Arlene M; Dobson, Allison W; Gladden, Ryan Q

    2012-01-01

    Genomic biobanks present ethical challenges that are qualitatively unique and quantitatively unprecedented. Many critics have questioned whether the current system of informed consent can be meaningfully applied to genomic biobanking. Proposals for reform have come from many directions, but have tended to involve incremental change in current informed consent practice. This paper reports on our efforts to seek new ideas and approaches from those whom informed consent is designed to protect: research subjects. Our model emerged from semi-structured interviews with healthy volunteers who had been recruited to join either of two biobanks (some joined, some did not), and whom we encouraged to explain their concerns and how they understood the relationship between specimen contributors and biobanks. These subjects spoke about their DNA and the information it contains in ways that were strikingly evocative of the legal concept of the trade secret. They then described the terms and conditions under which they might let others study their DNA, and there was a compelling analogy to the commonplace practice of trade secret licensing. We propose a novel biobanking model based on this trade secret concept, and argue that it would be a practical, legal, and ethical improvement on the status quo.

  10. Validation of the secretion severity rating scale.

    PubMed

    Pluschinski, Petra; Zaretsky, Eugen; Stöver, Timo; Murray, Joseph; Sader, Robert; Hey, Christiane

    2016-10-01

    Accumulation of secretions within the hypopharynx, aditus laryngis, and trachea is one characteristic of severe dysphagia and is of high clinical and therapeutic relevance. For the graduation of the secretion severity level, a secretion scale was provided by Murray et al. in 1996. The purpose of the study presented here is the validation of this scale by analyzing the intra-rater and inter-rater reliability as well as concurrent validity. For examination of reliability and validity, a reference standard was defined by two expert clinicians who reviewed 40 video recordings of fiberendoscopic swallowing evaluations, with 10 videos for each severity grade. These videos were rated and rerated independently and blinded by 4 ENT-residents with an interval of 4 weeks. Both the intra-rater (Kendall's τ > 0.847***) and inter-rater reliability (Kendall's W > 0.951***) were highly significant and can be considered good or very good. Correlation of the median of all ratings with the reference standard was close to the highest possible value 1 (τ = 0.984***). The scale was proved to be a reliable and valid instrument for graduation of one of the principal symptoms of oropharyngeal dysphagia and is recommended as an evidence-based instrument for standardized fiberoptic endoscopic evaluation of swallowing.

  11. Secret Sharing of a Quantum State.

    PubMed

    Lu, He; Zhang, Zhen; Chen, Luo-Kan; Li, Zheng-Da; Liu, Chang; Li, Li; Liu, Nai-Le; Ma, Xiongfeng; Chen, Yu-Ao; Pan, Jian-Wei

    2016-07-15

    Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

  12. Cell-secreted signals shape lymphoma identity.

    PubMed

    Gloghini, Annunziata; Bongarzone, Italia

    2015-10-01

    Sequencing data show that both specific genes and a number of signaling pathways are recurrently mutated in various types of lymphoma. DNA sequencing analyses of lymphoma have identified several aberrations that might affect the interaction between malignant cells and the tumor microenvironment. Microenvironmental functions are essential to lymphoma; they provide survival and proliferation signals and license immune evasion. It is plausible that interventions that aim to destroy tumor-microenvironment interactions may improve responses to therapeutics. Accordingly, the identification of extrinsic factors and their downstream intracellular signaling targets has led to much progress in understanding tumor-microenvironment interactions. Lymphoma cells are differently influenced by cells' interactions with components of their microenvironment; these cell extrinsic factors include soluble and immobilized factors, the extracellular matrix, and signals presented by neighboring cells. Soluble factors, which are often cell-secreted autocrine and paracrine factors, comprise a significant fraction of targetable molecules. To begin to understand how intercellular communication is conducted in lymphoma, a first order of study is deciphering the soluble factors secreted by malignant cells and microenvironmental cells. These soluble factors are shed into the interstitial fluid in lymphoma and can be conveniently explored using mass spectrometry. Protein components can be detected and quantified, thus enabling the routine navigation of the soluble part of the microenvironment. Elucidating functional and signaling states affords a new paradigm for understanding cancer biology and devising new therapies. This review summarizes knowledge in this field and discusses the utility of studying tumor-secreted factors.

  13. [Prostaglandins, insulin secretion and diabetes mellitus].

    PubMed

    Giugliano, D; Torella, R; Scheen, A J; Lefebvre, P J; D'Onofrio, F

    1988-12-01

    The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase derivatives, mainly PGE2, reduce the insulin response to glucose whereas lipo-oxygenase derivatives, mainly 15-HPETE, stimulate insulin secretion. So, for instance, drugs that increase prostaglandins synthesis as colchicine or furosemide inhibit insulin secretion while non steroid anti-inflammator drugs, mainly salicylates, which inhibit cyclo-oxygenase, enhance the insulin response to various stimuli. In type-2 (non insulin-dependent) diabetes, an increased sensitivity to endogenous prostaglandins has been proposed as a possible cause for the insulin secretion defect which characterizes this disease. Play in favor of this hypothesis the fact that the administration of PGE inhibits the insulin response to arginine in type-2 diabetics but not in normal subject and the fact that the administration of salicylates could improve the insulin response to glucose in some of these patients.

  14. Secret Sharing of a Quantum State

    NASA Astrophysics Data System (ADS)

    Lu, He; Zhang, Zhen; Chen, Luo-Kan; Li, Zheng-Da; Liu, Chang; Li, Li; Liu, Nai-Le; Ma, Xiongfeng; Chen, Yu-Ao; Pan, Jian-Wei

    2016-07-01

    Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

  15. Floral and vegetative cues in oil-secreting and non-oil-secreting Lysimachia species

    PubMed Central

    Schäffler, I.; Balao, F.; Dötterl, S.

    2012-01-01

    Background and Aims Unrelated plants pollinated by the same group or guild of animals typically evolve similar floral cues due to pollinator-mediated selection. Related plant species, however, may possess similar cues either as a result of pollinator-mediated selection or as a result of sharing a common ancestor that possessed the same cues or traits. In this study, visual and olfactory floral cues in Lysimachia species exhibiting different pollination strategies were analysed and compared, and the importance of pollinators and phylogeny on the evolution of these floral cues was determined. For comparison, cues of vegetative material were examined where pollinator selection would not be expected. Methods Floral and vegetative scents and colours in floral oil- and non-floral oil-secreting Lysimachia species were studied by chemical and spectrophotometric analyses, respectively, compared between oil- and non-oil-secreting species, and analysed by phylogenetically controlled methods. Key Results Vegetative and floral scent was species specific, and variability in floral but not vegetative scent was lower in oil compared with non-oil species. Overall, oil species did not differ in their floral or vegetative scent from non-oil species. However, a correlation was found between oil secretion and six floral scent constituents specific to oil species, whereas the presence of four other floral compounds can be explained by phylogeny. Four of the five analysed oil species had bee-green flowers and the pattern of occurrence of this colour correlated with oil secretion. Non-oil species had different floral colours. The colour of leaves was similar among all species studied. Conclusions Evidence was found for correlated evolution between secretion of floral oils and floral but not vegetative visual and olfactory cues. The cues correlating with oil secretion were probably selected by Macropis bees, the specialized pollinators of oil-secreting Lysimachia species, and may have

  16. Adopting Frank Warren's PostSecret Art Project to Illustrate the Role of Secrets in Interpersonal Communication

    ERIC Educational Resources Information Center

    Paxman, Christina G.

    2013-01-01

    The exploration of secrets summons the adage that ''what someone doesn't know won't hurt them.'' While this phrase implies that keeping secrets can be advantageous, it also foreshadows another consideration: secrets have the propensity to hurt others (Caughlin, Scott, Miller, & Hefner, 2009). Despite this, the act…

  17. Adopting Frank Warren's PostSecret Art Project to Illustrate the Role of Secrets in Interpersonal Communication

    ERIC Educational Resources Information Center

    Paxman, Christina G.

    2013-01-01

    The exploration of secrets summons the adage that ''what someone doesn't know won't hurt them.'' While this phrase implies that keeping secrets can be advantageous, it also foreshadows another consideration: secrets have the propensity to hurt others (Caughlin, Scott, Miller, & Hefner, 2009). Despite this, the act…

  18. Distinct Action of Flavonoids, Myricetin and Quercetin, on Epithelial Cl− Secretion: Useful Tools as Regulators of Cl− Secretion

    PubMed Central

    Sun, Hongxin; Niisato, Naomi; Nishio, Kyosuke; Hamilton, Kirk L.; Marunaka, Yoshinori

    2014-01-01

    Epithelial Cl− secretion plays important roles in water secretion preventing bacterial/viral infection and regulation of body fluid. We previously suggested that quercetin would be a useful compound for maintaining epithelial Cl− secretion at a moderate level irrespective of cAMP-induced stimulation. However, we need a compound that stimulates epithelial Cl− secretion even under cAMP-stimulated conditions, since in some cases epithelial Cl− secretion is not large enough even under cAMP-stimulated conditions. We demonstrated that quercetin and myricetin, flavonoids, stimulated epithelial Cl− secretion under basal conditions in epithelial A6 cells. We used forskolin, which activates adenylyl cyclase increasing cytosolic cAMP concentrations, to study the effects of quercetin and myricetin on cAMP-stimulated epithelial Cl− secretion. In the presence of forskolin, quercetin diminished epithelial Cl− secretion to a level similar to that with quercetin alone without forskolin. Conversely, myricetin further stimulated epithelial Cl− secretion even under forskolin-stimulated conditions. This suggests that the action of myricetin is via a cAMP-independent pathway. Therefore, myricetin may be a potentially useful compound to increase epithelial Cl− secretion under cAMP-stimulated conditions. In conclusion, myricetin would be a useful compound for prevention from bacterial/viral infection even under conditions that the amount of water secretion driven by cAMP-stimulated epithelial Cl− secretion is insufficient. PMID:24818160

  19. Evaluation of facial skin type by sebum secretion: discrepancies between subjective descriptions and sebum secretion.

    PubMed

    Youn, Sang Woong; Kim, Soo Jung; Hwang, In A; Park, Kyoung Chan

    2002-08-01

    Facial skin is usually classified as dry, normal, and oily in the cosmetics field. However, there is no standard objective method for classifying facial skin. We measured sebum excretion with Sebumeter at four sites on the face. Based on the amount of sebum secretion, we reclassified skin type according to the guidelines provided by the manufacturer. The mean of sebum excretion (mean facial sebum excretion; MFSE) was also calculated. People secrete varying amounts of sebum at different skin sites. Reclassification of skin type based on sebum secretion revealed that most participants underestimated the amount of facial sebum excretion. When sebum secretion amounts were compared, a statistically significant difference was apparent between the oily and dry skin types. However, there were no statistical differences between oily and normal, and normal and dry skin. We showed that subjective skin type does not match the amount of sebum secreted. Thus, this simple and subjective classification is of very limited use and it should be re-evaluated by using an objective and standardized measuring tool.

  20. In vivo quantification of the secretion rates of the hemolysin A Type I secretion system

    PubMed Central

    Lenders, Michael H. H.; Beer, Tobias; Smits, Sander H. J.; Schmitt, Lutz

    2016-01-01

    Type 1 secretion systems (T1SS) of Gram-negative bacteria secrete a broad range of substrates into the extracellular space. Common to all substrates is a C-terminal secretion sequence and nonapeptide repeats in the C-terminal part that bind Ca2+ in the extracellular space, to trigger protein folding. Like all T1SS, the hemolysin A (HlyA) T1SS of Escherichia coli consists of an ABC transporter, a membrane fusion protein and an outer membrane protein allowing the one step translocation of the substrate across both membranes. Here, we analyzed the secretion rate of the HlyA T1SS. Our results demonstrate that the rate is independent of substrate-size and operates at a speed of approximately 16 amino acids per transporter per second. We also demonstrate that the rate is independent of the extracellular Ca2+ concentration raising the question of the driving force of substrate secretion by T1SS in general. PMID:27616645

  1. Verifiable Quantum ( k, n)-threshold Secret Key Sharing

    NASA Astrophysics Data System (ADS)

    Yang, Yu-Guang; Teng, Yi-Wei; Chai, Hai-Ping; Wen, Qiao-Yan

    2011-03-01

    Based on Lagrange interpolation formula and the post-verification mechanism, we show how to construct a verifiable quantum ( k, n) threshold secret key sharing scheme. Compared with the previous secret sharing protocols, ours has the merits: (i) it can resist the fraud of the dealer who generates and distributes fake shares among the participants during the secret distribution phase; Most importantly, (ii) It can check the cheating of the dishonest participant who provides a false share during the secret reconstruction phase such that the authorized group cannot recover the correct secret.

  2. The semantics of secrecy: young children's classification of secret content.

    PubMed

    Anagnostaki, Lida; Wright, Michael J; Bourchier-Sutton, Alison J

    2010-01-01

    The authors explored whether young children can distinguish potential secrets from nonsecrets by their content, as can older children, adolescents, and adults. Ninety children, 4, 5, and 6 years old, rated the secrecy of items from an adult-validated list of personal information about an age- and gender-appropriate puppet. Two factors of the children's data corresponded to the adult categories of nonsecrets and secrets, and a third factor corresponded to surprises. All ages rated surprises as significantly more secret than nonsecret items; however, the surprise items contained linguistic cues to secrecy. A tendency to rate nonsecrets as secret decreased with age, but only the 6-year-olds rated secrets other than surprises as significantly more secret than nonsecrets. Thus, children acquire the implicit rules defining secret content from a somewhat later age than that reported for the cognitive or behavioral capacities for secrecy.

  3. Mechanisms of bicarbonate secretion: lessons from the airways.

    PubMed

    Bridges, Robert J

    2012-08-01

    Early studies showed that airway cells secrete HCO(3)(-) in response to cAMP-mediated agonists and HCO(3)(-) secretion was impaired in cystic fibrosis (CF). Studies with Calu-3 cells, an airway serous model with high expression of CFTR, also show the secretion of HCO(3)(-) when cells are stimulated with cAMP-mediated agonists. Activation of basolateral membrane hIK-1 K(+) channels inhibits HCO(3)(-) secretion and stimulates Cl(-) secretion. CFTR mediates the exit of both HCO(3)(-) and Cl(-) across the apical membrane. Entry of HCO(3)(-) on a basolateral membrane NBC or Cl(-) on the NKCC determines which anion is secreted. Switching between these two secreted anions is determined by the activity of hIK-1 K(+) channels.

  4. Mechanisms of Bicarbonate Secretion: Lessons from the Airways

    PubMed Central

    Bridges, Robert J.

    2012-01-01

    Early studies showed that airway cells secrete HCO3− in response to cAMP-mediated agonists and HCO3− secretion was impaired in cystic fibrosis (CF). Studies with Calu-3 cells, an airway serous model with high expression of CFTR, also show the secretion of HCO3− when cells are stimulated with cAMP-mediated agonists. Activation of basolateral membrane hIK-1 K+ channels inhibits HCO3− secretion and stimulates Cl− secretion. CFTR mediates the exit of both HCO3− and Cl− across the apical membrane. Entry of HCO3− on a basolateral membrane NBC or Cl− on the NKCC determines which anion is secreted. Switching between these two secreted anions is determined by the activity of hIK-1 K+ channels. PMID:22908201

  5. [Secret remedies in France until abolition in 1926].

    PubMed

    Warolin, Christian

    2002-01-01

    Secret remedies are preparations or medicines whose composition is not disclosed by the inventor in order to protect his invention or to deceive the public. Secret remedies have always existed. From time immemorial the communities of apothecaries in Paris or in the provinces were opposed to quack doctors or healers who sold inactive mixtures. The 1352 Royal Edict forbade preparations of secret remedies. However, in the 17th century secret remedies were authorized through commission letters or warrants. In the 18th century regulations were implemented to control secret trade. The famous 11 April 1803 Law called the Germinal Law banned the sale of secret remedies but its severity was softened through successive decrees based on divergent interpretations of the regulations. The final banning of secret remedies was pronounced by a decree on 13 July 1926.

  6. Developmental and nutritional regulation of isoflavone secretion from soybean roots.

    PubMed

    Sugiyama, Akifumi; Yamazaki, Yumi; Yamashita, Kazuaki; Takahashi, Seiji; Nakayama, Toru; Yazaki, Kazufumi

    2015-01-01

    Isoflavones play important roles in plant-microbe interactions in rhizospheres. Soybean roots secrete daidzein and genistein to attract rhizobia. Despite the importance of isoflavones in plant-microbe interactions, little is known about the developmental and nutritional regulation of isoflavone secretion from soybean roots. In this study, soybeans were grown in hydroponic culture, and isoflavone contents in tissues, isoflavone secretion from the roots, and the expression of isoflavone conjugates hydrolyzing beta-glucosidase (ICHG) were investigated. Isoflavone contents did not show strong growth-dependent changes, while secretion of daidzein from the roots dramatically changed, with higher secretion during vegetative stages. Coordinately, the expression of ICHG also peaked at vegetative stages. Nitrogen deficiency resulted in 8- and 15-fold increases in secretion of daidzein and genistein, respectively, with no induction of ICHG. Taken together, these results suggest that large amounts of isoflavones were secreted during vegetative stages via the hydrolysis of (malonyl)glucosides with ICHG.

  7. Mechanisms and regulation of neurotrophin synthesis and secretion.

    PubMed

    Al-Qudah, Mohammad A; Al-Dwairi, Ahmed

    2016-10-01

    Neurotrophins are secreted proteins that are synthesized as pre-pro-neurotrophins on the rough endoplasmic reticulum, which are subsequently processed and then secreted as mature proteins. During synthesis, neurotrophins are sorted in the trans-Golgi apparatus into 2 pathways of secretion; the constitutive and the regulated pathways. Neurotrophins in the constitutive pathway are secreted cautiously without any trigger, while in the regulated pathway of secretion an external stimulus elevates the calcium concentration intracellularly leading to neurotrophin release. The regulation of sorting and secretion of neurotrophins is critical for several processes in the body, such as synaptic plasticity, neurodegenerative disorders, demyelination disease, and inflammation. The purpose of this review is to summarize the current mechanisms of neurotrophin sorting and secretion.

  8. Two-Party secret key distribution via a modified quantum secret sharing protocol

    DOE PAGES

    Grice, Warren P.; Evans, Philip G.; Lawrie, Benjamin; ...

    2015-01-01

    We present and demonstrate a method of distributing secret information based on N-party single-qubit Quantum Secret Sharing (QSS) in a modied plug-and-play two-party Quantum Key Distribution (QKD) system with N 2 intermediate nodes and compare it to both standard QSS and QKD. Our setup is based on the Clavis2 QKD system built by ID Quantique but is generalizable to any implementation. We show that any two out of N parties can build a secret key based on partial information from each other and with collaboration from the remaining N 2 parties. This method signicantly reduces the number of resources (singlemore » photon detectors, lasers and dark ber connections) needed to implement QKD on the grid.« less

  9. Two-party secret key distribution via a modified quantum secret sharing protocol.

    PubMed

    Grice, W P; Evans, P G; Lawrie, B; Legré, M; Lougovski, P; Ray, W; Williams, B P; Qi, B; Smith, A M

    2015-03-23

    We present and demonstrate a novel protocol for distributing secret keys between two and only two parties based on N-party single-qubit Quantum Secret Sharing (QSS). We demonstrate our new protocol with N = 3 parties using phase-encoded photons. We show that any two out of N parties can build a secret key based on partial information from each other and with collaboration from the remaining N - 2 parties. Our implementation allows for an accessible transition between N-party QSS and arbitrary two party QKD without modification of hardware. In addition, our approach significantly reduces the number of resources such as single photon detectors, lasers and dark fiber connections needed to implement QKD.

  10. Two-Party secret key distribution via a modified quantum secret sharing protocol

    SciTech Connect

    Grice, Warren P.; Evans, Philip G.; Lawrie, Benjamin; Legré, M.; Lougovski, P.; Ray, William R.; Williams, Brian P.; Qi, B.; Smith, A. M.

    2015-01-01

    We present and demonstrate a method of distributing secret information based on N-party single-qubit Quantum Secret Sharing (QSS) in a modied plug-and-play two-party Quantum Key Distribution (QKD) system with N 2 intermediate nodes and compare it to both standard QSS and QKD. Our setup is based on the Clavis2 QKD system built by ID Quantique but is generalizable to any implementation. We show that any two out of N parties can build a secret key based on partial information from each other and with collaboration from the remaining N 2 parties. This method signicantly reduces the number of resources (single photon detectors, lasers and dark ber connections) needed to implement QKD on the grid.

  11. A Pilot Study of Pepsin in Tracheal and Oral Secretions

    PubMed Central

    Schallom, Marilyn; Tricomi, Sally M.; Chang, Yie-Hwa; Metheny, Norma A.

    2013-01-01

    Background Because reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, it is reasonable to hypothesize that the detection of pepsin (the major gastric enzyme in gastric juice) in oral secretions may provide a relatively non-invasive method to predict risk for aspiration. Objective The purpose of this pilot study was to describe the incidence of pepsin in oral and tracheal secretions collected concurrently from a sample of 50 mechanically ventilated, gastric-fed patients. Methods The study used an exploratory descriptive design with a convenience sample from four medical and surgical intensive care units. A single oral and tracheal secretion was collected concurrently from each patient (yielding a sample of 50 oral and 50 tracheal secretions). The tracheal secretions were obtained via the inline suction system with an attached sputum trap; oral secretions were obtained via a yankauer suction tip with an attached sputum trap. All specimens were assayed for pepsin by the Western Blot method. Results Oral secretions from ten patients (20%) were pepsin-positive while tracheal secretions from two patients (4%) were pepsin-positive. Both patients with pepsin-positive tracheal secretions also had pepsin-positive oral secretions. Pepsin was not found in the tracheal secretions from the remaining eight patients with pepsin-positive oral secretions. Conclusions Although reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, individual reflux events do not necessarily lead to aspiration. Thus, it is reasonable that we found pepsin 5-times more often in oral secretions than in tracheal secretions. PMID:23996420

  12. Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

    PubMed Central

    Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El

    2016-01-01

    Purpose: To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. Materials and Methods: From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Results: Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Conclusion: Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma. PMID:27306775

  13. Will They or Won't They? Secret Telling in Interpersonal Interactions.

    PubMed

    Kowalski, Robin Marie; Morgan, Chad Alan; Whittaker, Elizabeth; Zaremba, Brittany; Frazee, Laura; Dean, Jessica

    2015-01-01

    This study investigated predictors of within-gender secret telling. Eighty-eight participants were exposed to either a "positive" or a "negative" secret about another individual. Just under 20% of participants told the secret. Conscientiousness, secret condition, empathy, and the conscientiousness by secret condition interaction had effects on the rate of secret telling, χ(2) (5,82) = 17.78, p = .003, AIC = 80.60. Conscientiousness had a negative effect on secret telling among participants that told the "negative" secret.

  14. Yersinia enterocolitica type III secretion: evidence for the ability to transport proteins that are folded prior to secretion.

    PubMed

    Wilharm, Gottfried; Lehmann, Verena; Neumayer, Wibke; Trcek, Janja; Heesemann, Jürgen

    2004-07-12

    Pathogenic Yersinia species (Y. enterocolitica, Y. pestis, Y. pseudotuberculosis) share a type three secretion system (TTSS) which allows translocation of effector proteins (called Yops) into host cells. It is believed that proteins are delivered through a hollow needle with an inner diameter of 2-3 nm. Thus transport seems to require substrates which are essentially unfolded. Recent work from different groups suggests that the Yersinia TTSS cannot accommodate substrates which are folded prior to secretion. It was suggested that folding is prevented either by co-translational secretion or by the assistance of specific Yop chaperones (called Sycs). In this study we have fused YopE secretion signals of various length to the mouse dihydrofolate reductase (DHFR) in order to analyse the DHFR folding state prior to secretion. We could demonstrate that secretion-deficient as well as secretion-competent YopE-DHFR fusions complexed to SycE can be efficiently purified from Yersinia cytosol by affinity chromatography using methotrexate-agarose. This implies the folding of the DHFR fusion moiety despite SycE binding and contradicts the previously presented model of folding inhibition by chaperone binding. Secretion-deficient YopE-DHFR fusions caused severe jamming of the TTSS. This observation contradicts the co-translational secretion model. We present evidence that the Yersinia TTSS is familiar with the processing of transport substrates which are folded prior to secretion. We therefore predict that an unfoldase is involved in type III secretion.

  15. [Cushing syndrome due to ectopic ACTH secretion].

    PubMed

    Mendonça, B B; Madureira, G; Bloise, W; Albergaria, A; Halpern, A; Liberman, B; Villares, S M; Batista, M C; Avancini, V F; Nitterdorfi, C T

    1989-01-01

    The authors studied 8 patients (4 males and 4 females) with Cushing's syndrome due to ectopic ACTH secretion. Chronological age ranged from 15 to 45 years and duration of the disease ranged from 3 to 48 months. All patients presented typical signs of Cushing's syndrome, blood hypertension, and four of them had hyperpigmentation of the skin. Five patients had fasting hyperglycemia and all patients but one had serum hypokalemia (serum K = 2.2 to 3.9mEq/l). The circadian rhythm of cortisol was absent in all patients and basal cortisol levels were elevated in all patients but one. Basal ACTH levels evaluated in 7 patients were elevated in 6 (29 to 1050 pg/ml-MRC). One patient presented normal depression of urinary 17-OH after two days of dexamethasone and normal increase of urinary 17-OH and serum 11-dexycortisol after methyrapone. Four patients had carcinoid tumor (3 thymic and 1 bronchial), two had pancreatic islets cell tumors, one had bilateral pheochromocytoma and medular carcinoma of the thyroid, and one had oat cell carcinoma of the lung and medular carcinoma of the thyroid. Thoracic X-rays identified the ectopic ACTH secretion tumor in four cases, all confirmed by CT scan. Abdominal CT showed a difuse enlargement of the adrenals in seven cases and bilateral nodules in one case (pheochromocytomas). Six patients died within 3 years of the diagnosis. The authors concluded that clinical and hormonal findings could mislead the findings of ACTH ectopic secretion and Cushing's disease, and suggest that thoracic X-rays and CT scans of the skull, thorax, and abdome should be done in all cases of Cushing's syndrome.

  16. Proteomic analysis of human meibomian gland secretions

    PubMed Central

    Tsai, P S; Evans, J E; Green, K M; Sullivan, R M; Schaumberg, D A; Richards, S M; Dana, M R; Sullivan, D A

    2006-01-01

    Background/aim Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study's aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. Methods Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform‐methanol mixture. Samples were partitioned in a biphasic system and non‐lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by µ‐capillary reverse phase chromatography and the effluent examined by nano‐electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. Results The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the α2‐macroglobulin receptor, IgA α chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD‐SP21 (also termed high affinity IgE receptor β subunit), and TrkC tyrosine kinase. Conclusions These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease. PMID:16488965

  17. Secret Objective Standoff: International Safeguards Educational Exercise

    SciTech Connect

    Okowita, Samantha L

    2014-01-01

    The International Safeguards Regime, being so multi-faceted, can be overwhelming to those first introduced to its many components. The organizers and lecturers of workshops and courses on nonproliferation often provide a series of independent lectures and must somehow demonstrate the cohesive and effective nature of the system. An exercise titled The Secret Objective Standoff was developed to complement lectures with hands-on learning to assist participants in bringing all the many components (IAEA agreements, export controls, treaty obligations, international diplomacy, etc.) of the International Safeguards Regime together. This exercise divides participants into teams that are assigned the role of either a country or the IAEA and asks that they fully immerse themselves in their roles. The teams are then randomly assigned three unique and secret objectives that are intended to represent realistic and current geopolitical scenarios. Through construction, trading, or hoarding of four resources (experts, technology, money, and uranium), the teams have a finite number of turns to accomplish their objectives. Each turn has three phases random dispersal of resources, a timed discussion where teams can coordinate and strategize with others, and an action phase. During the action phase, teams inform the moderator individually and secretly what they will be doing that turn. The exercise has been tested twice with Oak Ridge National Laboratory personnel, and has been conducted with outside participants twice, in each case the experience was well received by both participants and instructors. This exercise provides instructors the ability to modify the exercise before or during game play to best fit their educational goals. By offering a range of experiences, from an in-depth look at specific components to a generalized overview, this exercise is an effective tool in helping participants achieve a full understanding the International Safeguards Regime.

  18. Adrenergic and cromolyn sodium modulation of ECL cell histamine secretion.

    PubMed

    Lawton, G P; Tang, L H; Miu, K; Gilligan, C J; Absood, A; Modlin, I M

    1995-01-01

    The histamine secreting enterochromaffin-like (ECL) cell is now recognized as the principal regulator of gastric acid secretion. Histamine is not only a primary modulator of acid secretion, but may be of relevance in gastritis and as a mitogen in gastric neoplasia. Study of the ECL cell has been limited since no pure preparation was available. We therefore developed a pure isolated ECL cell preparation with a purity of 90-95% as determined by total histamine content and chromogranin immunofluorescence. Trypan blue exclusion demonstrated > 95% viability. While gastrin and acetylcholine are known modulators of acid secretion, the role of adrenergic neurotransmitters has not been clearly delineated. The purpose of this study was to examine adrenergic modulation of ECL cell histamine release. To further define the inhibitory mechanisms of histamine secretion, we evaluated the mast cell histamine inhibitor sodium cromoglycate. Histamine secretion was determined by radioimmunoassay. Basal secretion was 0.6 +/- 0.2 nmol/10(3) cells. Gastrin stimulated histamine secretion with an EC50 of 3 x 10(-10) M. Octopamine (alpha-adrenergic agonist) (10(-11)-10(-4) M) failed to stimulate histamine secretion. Isoproterenol (beta-adrenergic agonist) stimulated histamine secretion (EC50, 6 x 10(-8) M) and was inhibited by propranolol (IC50 5 x 10(-10) M).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Gliding motility and polarized slime secretion.

    PubMed

    Yu, Rosa; Kaiser, Dale

    2007-01-01

    Myxococcus leaves a trail of slime on agar as it moves. A filament of slime can be seen attached to the end of a cell, but it is seen only at one end at any particular moment. To identify genes essential for A motility, transposon insertion mutations with defective A motility were studied. Fifteen of the 33 mutants had totally lost A motility. All these mutant cells had filaments of slime emerging from both ends, indicating that bipolar secretion prevents A motility. The remaining 18 A motility mutants, also produced by gene knockout, secreted slime only from one pole, but they swarmed at a lower rate than A(+) and are called 'partial' gliding mutants, or pgl. For each pgl mutant, the reduction in swarm expansion rate was directly proportional to the reduction in the coefficient of elasticotaxis. The pgl mutants have a normal reversal frequency and normal gliding speed when they move. But their probability of movement per unit time is lower than pgl(+) cells. Many of the pgl mutants are produced by transposon insertions in glycosyltransferase genes. It is proposed that these glycosyltransferases carry out the synthesis of a repeat unit polysaccharide that constitutes the slime.

  20. The Versatile Type VI Secretion System

    PubMed Central

    Alteri, Christopher J.; Mobley, Harry L.T.

    2016-01-01

    Summary Bacterial Type VI Secretion Systems (T6SS) function as contractile nanomachines to puncture target cells and deliver lethal effectors. In the ten years since the discovery of the T6SS, much has been learned about the structure and function of this versatile protein secretion apparatus. Most of the conserved protein components that comprise the T6SS apparatus itself have been identified and ascribed specific functions. In addition, numerous effector proteins that are translocated by the T6SS have been identified and characterized. These protein effectors usually represent toxic cargoes that are delivered by the attacker cell to a target cell. The field is beginning to better understand the lifestyle or physiology that dictates when bacteria normally express their T6SS. In this Chapter, we consider what is known about the structure and regulation of the T6SS, the numerous classes of antibacterial effector T6SS substrates, and how the action of the T6SS relates to a given lifestyle or behavior in certain bacteria. PMID:27227310

  1. Determinants of parathormone secretion in primary hyperparathyroidism.

    PubMed

    Paillard, M; Gardin, J P; Borensztein, P; Prigent, A

    1989-01-01

    We studied the effects of acute modifications in plasma calcium on parathormone (PTH) secretion in 23 patients with primary hyperparathyroidism (PHPT). In 12 patients, PTH hypersecretion was autonomous, and basal plasma calcium concentration was positively correlated with maximal serum PTH(1-84) reached during Na2EDTA infusions. In 11 patients, PTH hypersecretion remained suppressible, but with elevated set point value, and basal plasma calcium concentration was positively correlated with set point. Thus, the degree of hypercalcemia seems mainly determined by the magnitude of maximal PTH secretion and set point error in autonomous and suppressible PHPT, respectively. We have previously suggested that high serum calcitriol levels might chronically inhibit PTH hypersecretion in PHPT. We showed that hyperparathyroid patients with renal stone presentation exhibited an abnormally high value of circulating calcitriol and a moderately elevated PTH activity, while patients with severe bone disease presentation displayed a low to normal calcitriol value and a dramatically increased PTH activity. The hypothesis was supported by a recent study from our Unit in one hyperparathyroid patient with severe bone disease and normal serum calcitriol level. Increment of serum calcitriol after daily intravenous Rocaltrol for 5 days directly suppressed PTH hypersecretion without change in plasma ionized calcium.

  2. Gastric lipase secretion in children with gastritis.

    PubMed

    Tomasik, Przemyslaw J; Wędrychowicz, Andrzej; Rogatko, Iwona; Zając, Andrzej; Fyderek, Krzysztof; Sztefko, Krystyna

    2013-07-29

    Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14) and the control group including healthy adolescents (n = 14). Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005) and the control group (p < 0.005). Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003) and the HPG group (p < 0.01). We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

  3. Mechanism by which cyproheptadine inhibits insulin secretion.

    PubMed Central

    Donatsch, P.; Lowe, D. A.; Richardson, B. P.; Taylor, P.

    1980-01-01

    1 Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion. 2 D-Glucose and tolbutamide, both of which require extracellular Ca2+ to produce insulin release, failed to evoke a secretory response from islets pretreated with cyproheptadine. Conversely veratridine, the calcium ionophore A23187 and theophylline, all of which are capable of mobilizing sufficient intracellular Ca2+ to evoke insulin secretion in the absence of extracellular Ca2+, produced similar responses from cyproheptadine pretreated and control islets. 3 Cyproheptadine completely inhibited Ca2+ uptake induced by D-glucose and high Ko+, two agents which depolarize the islet beta-cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+-Ca2+ counter transport) was only slightly reduced. 4 A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine. 5 These results suggest that cyproheptadine inhibits depolarization-dependent calcium entry into pancreatic beta-cells. PMID:7002245

  4. Dopamine-Secreting Paraganglioma in the Retroperitoneum.

    PubMed

    Matsuda, Yusuke; Kimura, Noriko; Yoshimoto, Takanobu; Sekiguchi, Yoshihiro; Tomoishi, Junzo; Kasahara, Ichiro; Hara, Yoshihito; Ogawa, Yoshihiro

    2017-03-01

    Pheochromocytomas and paragangliomas, which exclusively produce dopamine, are very rare. Herein, we report for the first time a Japanese case of an exclusively dopamine-producing paraganglioma accompanied by detailed immunohistochemical analyses. A 70-year-old Japanese woman was referred to our hospital for functional examination of her left retroperitoneal mass. Her adrenal functions were normal, except for excessive dopamine secretion. After the tumorectomy, her dopamine level normalized. The histopathological diagnosis of the tumor was paraganglioma; this was confirmed by positive immunostaining of chromogranin A (CgA), tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), and succinate dehydrogenase gene subunit B (SDHB). However, the immunostaining of CgA in the tumor cells showed peculiar dot-like staining located corresponding to Golgi complex in the perinuclear area, rather than the diffuse cytoplasmic staining usually observed in epinephrine- or norepinephrine-producing functional pheochromocytomas and paragangliomas. The immunohistochemical results suggested that the tumor cells had sparse neuroendocrine granules in the cytoplasm, resulting in inhibition of catecholamine synthesis from dopamine to norepinephrine in neurosecretory granules. This may be the mechanism responsible for exclusive dopamine secretion in the present case.

  5. [Thyrotropin--TSH secreting pituitary tumor].

    PubMed

    Zieliński, Grzegorz; Podgórski, Jan K; Warczyńska, Agnieszka; Koziarski, Andrzej; Zgliczyński, Wojciech

    2002-01-01

    Thyrotropin-releasing pituitary tumors represent 0.9 to 2.8% of all pituitary adenomas. They cause secondary or central hyperthyroidism. The diagnosis of these tumors has been increasing in the past 20 years. It was produced by introduction of the sensitive immunoradio-metric assay of TSH and better radiological imaging (magnetic resonance imaging). TSH--secreting pituitary adenomas are aggressive and invasive neoplasms. Most reports describe a poor outcome after pharmacological therapy, surgery and radiation therapy. Presently the diagnosis of thyrotropin-secreting pituitary tumor is based on the lack of: a. inhibition of TSH levels in the presence of increased free thyroid hormones; b. response of TSH to stimulation with TRH; c. and presence of a abnormal, neoplastic(adenomatous) intrasellar or parasellar mass. Surgical excision (selective adenomectomy) by the transsphenoidal route is the first treatment. Craniotomy should be reserved for parasellar tumors with significant lateral extension. Pharmacological pretreatment with long acting somatostatin analogues is recently a standard before surgery. This medical treatment of the TSH-omas is effective in reducing TSH and free thyroid hormone plasma levels. Administration of the somatostatin analogues causing tumor mass shrinkage and changes consistency. This pretreatment is effective therapy and improves surgical outcome especially in patients harbouring macroadenomas. Radiotherapy is noncurative and produces long term complications (hypopituitarism). Authors present and discuss current cure criteria of TSH-omas with reference to their clinical experience.

  6. Managing prolactin-secreting adenomas during pregnancy

    PubMed Central

    Imran, Syed Ali; Ur, Ehud; Clarke, David B.

    2007-01-01

    OBJECTIVE To determine an appropriate approach to managing prolactin-secreting adenomas of varying severity in pregnant women. SOURCES OF INFORMATION MEDLINE was searched using the key words “hyperprolactinemia,” “prolactinoma,” “pregnancy,” and “management.” Experience from a multidisciplinary tertiary care centre was also reviewed. Recommendations are based on mostly levels II and III evidence. MAIN MESSAGE With appropriate management, most women with hyperprolactinemia can achieve pregnancy. Although most women with prolactin-secreting adenomas during pregnancy need only careful observation, others might require medical treatment or even surgical evacuation. Ideally, such patients should be managed by multidisciplinary teams. In the absence of such teams, most pregnant women with small tumours can be managed safely by their primary physicians. Those with large tumours should be referred to specialists. CONCLUSION Family physicians play an important role in managing women with prolactinomas during pregnancy. Knowledge of current approaches to management is crucial in determining when and how to refer these patients. PMID:17872715

  7. Secretion of clostridium cellulase by E. coli

    DOEpatents

    Yu, Ida Kuo

    1998-01-01

    A gene, encoding an endocellulase from a newly isolated mesophilic Clostridium strain IY-2 which can digest bamboo fibers, cellulose, rice straw, and sawdust, was isolated by shotgun cloning in an E. coli expression plasmid pLC2833. E. coli positive clones were selected based on their ability to hydrolyze milled bamboo fibers and cellulose present in agar plates. One clone contained a 2.8 kb DNA fragment that was responsible for cellulase activity. Western blot analyses indicated that the positive clone produced a secreted cellulase with a mass of about 58,000 daltons that was identical in size to the subunit of one of the three major Clostridium cellulases. The products of cellulose digestion by this cloned cellulase were cellotetraose and soluble higher polymers. The cloned DNA contained signal sequences capable of directing the secretion of heterologous proteins from an E. coli host. The invention describes a bioprocess for the treatment of cellulosic plant materials to produce cellular growth substrates and fermentation end products suitable for production of liquid fuels, solvents, and acids.

  8. Kinetic regulation of coated vesicle secretion

    PubMed Central

    Foret, Lionel; Sens, Pierre

    2008-01-01

    The secretion of vesicles for intracellular transport often relies on the aggregation of specialized membrane-bound proteins into a coat able to curve cell membranes. The nucleation and growth of a protein coat is a kinetic process that competes with the energy-consuming turnover of coat components between the membrane and the cytosol. We propose a generic kinetic description of coat assembly and the formation of coated vesicles and discuss its implication to the dynamics of COP vesicles that traffic within the Golgi and with the endoplasmic reticulum. We show that stationary coats of fixed area emerge from the competition between coat growth and the recycling of coat components, in a fashion resembling the treadmilling of cytoskeletal filaments. We further show that the turnover of coat components allows for a highly sensitive switching mechanism between a quiescent and a vesicle producing membrane, upon a slowing down of the exchange kinetics. We claim that the existence of this switching behavior, also triggered by factors, such as the presence of cargo and variation of the membrane mechanical tension, allows for efficient regulation of vesicle secretion. We propose a model, supported by different experimental observations, in which vesiculation of secretory membranes is impaired by the energy-consuming desorption of coat proteins, until the presence of cargo or other factors triggers a dynamical switch into a vesicle producing state. PMID:18824695

  9. The Yersinia pestis type III secretion needle plays a role in the regulation of Yop secretion.

    PubMed

    Torruellas, Julie; Jackson, Michael W; Pennock, Jeffry W; Plano, Gregory V

    2005-09-01

    Activation of bacterial virulence-associated type III secretion systems (T3SSs) requires direct contact between a bacterium and a eukaryotic cell. In Yersinia pestis, the cytosolic LcrG protein and a cytosolic YopN-TyeA complex function to block T3S in the presence of extracellular calcium and prior to contact with a eukaryotic cell. The mechanism by which the bacterium senses extracellular calcium and/or cell contact and transmits these signals to the cytosolic compartment is unknown. We report here that YscF, a small protein that polymerizes to form the external needle of the T3SS, is essential for the calcium-dependent regulation of T3S. Alanine-scanning mutagenesis was used to identify YscF mutants that secrete virulence proteins in the presence and absence of calcium and prior to contact with a eukaryotic cell. Interestingly, one of the YscF mutants that exhibited constitutive T3S was unable to translocate secreted proteins across the eukaryotic plasma membrane. These data indicate that the YscF needle is a multifunctional structure that participates in virulence protein secretion, in translocation of virulence proteins across eukaryotic membranes and in the cell contact- and calcium-dependent regulation of T3S.

  10. Trade Secret Law and Information Systems: Can Your Students Keep a Secret?

    ERIC Educational Resources Information Center

    Willey, Lorrie; Ford, Janet C.; White, Barbara Jo; Clapper, Danial L.

    2011-01-01

    The impact of intellectual property (IP) law on information systems (IS) professionals in business cannot be overstated. The IS 2010 model curriculum guidelines for undergraduate IS programs stress the importance of information security and knowledge about IP. While copyright and patents are the most well-known types of IP, another, trade secrets,…

  11. Inside the Chamber of Secrets of the Type III Secretion System.

    PubMed

    Cascales, Eric

    2017-03-09

    The bacterial type III secretion system is a specialized machine that injects effectors into eukaryotic cells to manipulate the host cell physiology. In this issue of Cell, Hu et al. use cryo-electron tomography to reveal an unprecedented level of details regarding the architecture of this machine and the conformational changes that occur during its assembly.

  12. Trade Secret Law and Information Systems: Can Your Students Keep a Secret?

    ERIC Educational Resources Information Center

    Willey, Lorrie; Ford, Janet C.; White, Barbara Jo; Clapper, Danial L.

    2011-01-01

    The impact of intellectual property (IP) law on information systems (IS) professionals in business cannot be overstated. The IS 2010 model curriculum guidelines for undergraduate IS programs stress the importance of information security and knowledge about IP. While copyright and patents are the most well-known types of IP, another, trade secrets,…

  13. [Regulation and self-regulation of the pancreas secretion].

    PubMed

    Korot'ko, G F; Voskanian, S E

    2001-01-01

    A review of modern experimental and clinical research, including own author's data, on regulation of the periodical and postprandial external pancreas secretion and of the secretion phases. Focus on self-regulation of pancreas exosecretion with the pancreatic enzymes based on the principle of negative feedback, and on mechanisms of the feedback inhibition of pancreatic secretion. Description of the selective and generalised inhibition of secretion of pancreatic enzymes, the role of this mechanism in emergency adaptation of the fermental spectrum of the pancreas secretion in response to the nutritional composition and properties of the duodenal chemus. In conclusion, the experimental and clinical data are presented on use of intraduodenal injection of trypsin as a generalised inhibitor of pancreas secretion in case of acute pancreatitis.

  14. Insulin secretion from beta cells within intact islets: location matters.

    PubMed

    Hoang Do, Oanh; Thorn, Peter

    2015-04-01

    The control of hormone secretion is central to body homeostasis, and its dysfunction is important in many diseases. The key cellular steps that lead to hormone secretion have been identified, and the stimulus-secretion pathway is understood in outline for many endocrine cells. In the case of insulin secretion from pancreatic beta cells, this pathway involves the uptake of glucose, cell depolarization, calcium entry, and the triggering of the fusion of insulin-containing granules with the cell membrane. The wealth of information on the control of insulin secretion has largely been obtained from isolated single-cell studies. However, physiologically, beta cells exist within the islets of Langerhans, with structural and functional specializations that are not preserved in single-cell cultures. This review focuses on recent work that is revealing distinct aspects of insulin secretion from beta cells within the islet.

  15. Identification of secreted bacterial proteins by noncanonical amino acid tagging.

    PubMed

    Mahdavi, Alborz; Szychowski, Janek; Ngo, John T; Sweredoski, Michael J; Graham, Robert L J; Hess, Sonja; Schneewind, Olaf; Mazmanian, Sarkis K; Tirrell, David A

    2014-01-07

    Pathogenic microbes have evolved complex secretion systems to deliver virulence factors into host cells. Identification of these factors is critical for understanding the infection process. We report a powerful and versatile approach to the selective labeling and identification of secreted pathogen proteins. Selective labeling of microbial proteins is accomplished via translational incorporation of azidonorleucine (Anl), a methionine surrogate that requires a mutant form of the methionyl-tRNA synthetase for activation. Secreted pathogen proteins containing Anl can be tagged by azide-alkyne cycloaddition and enriched by affinity purification. Application of the method to analysis of the type III secretion system of the human pathogen Yersinia enterocolitica enabled efficient identification of secreted proteins, identification of distinct secretion profiles for intracellular and extracellular bacteria, and determination of the order of substrate injection into host cells. This approach should be widely useful for the identification of virulence factors in microbial pathogens and the development of potential new targets for antimicrobial therapy.

  16. Substrate recognition by the Yersinia type III protein secretion machinery.

    PubMed

    Ramamurthi, Kumaran S; Schneewind, Olaf

    2003-11-01

    Type III secretion is the designation given to those protein secretion pathways, primarily in pathogenic Gram-negative bacteria, whose secretion machinery components share an amino acid sequence homology to components of the flagellar basal body. In Yersinia spp., these secretion machineries inject virulence proteins called Yops into the cytosol of target macrophages in an effort to evade phagocytic killing. To date, a clear mechanism by which Yops are recognized by the type III secretion machinery has not been elucidated. Unlike most, if not all, previously characterized protein sorting pathways, the information that identifies Yops as substrates for secretion seems not to be wholly encoded within the Yop peptide sequence. In fact, it appears that at least some of this information is contained within yop mRNAs. This review summarizes recent observations that have been made in this unusual field and proposes models by which proteins may be initiated into this pathway.

  17. [Research progress on musk secretion mechanism of forest musk deer].

    PubMed

    Jie, Hang; Feng, Xiao-Lan; Zhao, Gui-Jun; Zeng, De-Jun; Zhang, Cheng-Lu; Chen, Qiang

    2014-12-01

    Forest musk deer (Moschus berezovskii), a rare wild medicinal animal, is listed under the category of the state key protected wildlife list of China. Musk, secreted by the musk glands, is with high economic and medicinal value and used as precious traditional medicine in China. In order to meet the needs of musk in Chinese traditional medicine, forest musk deer farming was conducted in 1950s, but the research progress on musk secretion mechanism was slow. Therefore, by reviewing the histological and anatomical structure of forest musk deer musk gland, the relationship between sex hormones and the musk secretion process, and the molecular mechanism of the musk secretion, the existing problems in investigating the musk secretion mechanism were analyzed and the development trends in this field were also discussed, in order to provide a reference for further studies on the musk secretion mechanism and improve musk production of forest musk deer.

  18. Functional changes in acid secretion produced by duodenogastric reflux.

    PubMed Central

    Thomas, W E

    1980-01-01

    The effects of duodenal reflux on gastric secretion have been examined in dogs. Acid secretion during pentagastrin stimulation increased by 68% in animals with chronic diversion of duodenal contents into the stomach. This increased acid secretion did not occur when bile alone was diverted into the stomach and could be abolished by vagotomy. The hypersecretion observed with pentagastrin did not occur when histamine was the stimulus, which suggests that it was not due solely to a trophic effect on parietal cells. PMID:7429304

  19. Secure direct communication based on secret transmitting order of particles

    SciTech Connect

    Zhu Aidong; Zhang Shou; Xia Yan; Fan Qiubo

    2006-02-15

    We propose the schemes of quantum secure direct communication based on a secret transmitting order of particles. In these protocols, the secret transmitting order of particles ensures the security of communication, and no secret messages are leaked even if the communication is interrupted for security. This strategy of security for communication is also generalized to a quantum dialogue. It not only ensures the unconditional security but also improves the efficiency of communication.

  20. Secret Sharing Schemes from Linear Codes over Finite Rings

    NASA Astrophysics Data System (ADS)

    Qian, Jianfa; Ma, Wenping

    An important concept in secret sharing scheme is the access structure. However, determining the access structure of the secret sharing scheme based on a linear code is a very difficult problem. In this work, we provide a method to construct a class of two-weight linear codes over finite rings. Based on the two-weight codes, we present an access structure of a secret sharing scheme.

  1. Short-term regulation of adiponectin secretion in rat adipocytes.

    PubMed

    Szkudelski, T; Nogowski, L; Szkudelska, K

    2011-01-01

    Adiponectin belongs to the group of biologically active substances secreted by adipocytes and referred to as adipokines. Disturbances in its secretion and/or action are thought to be involved in the pathogenesis of some metabolic diseases. However, regulation of adiponectin secretion is poorly elucidated. In the present study, short-term regulation of adiponectin secretion in primary rat adipocytes was investigated. Isolated rat adipocytes were incubated in Krebs-Ringer buffer containing 5 mM glucose and insulin alone or in the combination with epinephrine, dibutyryl-cAMP, adenosine A(1) receptor antagonist (DPCPX), palmitate, 2-bromopalmitate or inhibitor of mitochondrial electron transport (rotenone). Adipocyte exposure for 2 h to insulin (1-100 nM) significantly increased secretion of adiponectin compared with secretion observed without insulin. Furthermore, secretion of adiponectin from adipocytes incubated with glucose and insulin was reduced by 1 and 2 microM epinephrine, but not by 0.25 and 0.5 microM epinephrine. Under similar conditions, 1 and 2 mM dibutyryl-cAMP substantially diminished secretion of adiponectin, whereas 0.5 mM dibutyryl-cAMP was ineffective. Secretion of adiponectin was found to be effectively decreased by DPCPX. Moreover, adipocyte exposure to rotenone also resulted in a substantial diminution of secretory response of adipocytes incubated for 2 h with glucose and insulin. It was also demonstrated that palmitate and 2-bromopalmitate (0.06-0.5 mM) failed to affect secretion of leptin. The obtained results indicated that in short-term regulation of adiponectin secretion, insulin and epinephrine exert the opposite effects. These effects appeared as early as after 2 h of exposure. Moreover, deprivation of energy or blockade of adenosine action substantially decreased secretion of adiponectin.

  2. Trade-secret protection in utility rate cases

    SciTech Connect

    Massella, I.M.

    1982-07-08

    A closed hearing of the Ohio Public Utility Commission put a statute protecting private trade secrets in conflict with protecting the public's right to know. A first step in resolving the controversy over constitutional protections against a forced disclosure of proprietary secrets and the legal problems of balancing public and private interests is identifying those trade secrets that are protectible business information, developing a protective order, and enforcing that order. (DCK)

  3. How to secretly share the treasure map of the captain?

    NASA Astrophysics Data System (ADS)

    Islam, N.; Puech, W.; Brouzet, R.

    2010-01-01

    In this paper we present a new approach for sharing a secret image between l users exploiting additive homomorphic property of Paillier algorithm. With a traditional approach, when a dealer wants to share an image between l players, the secret image must be sequentially encrypted l + 1 times using l + 1 keys (secret or public keys). When the dealer and the l players want to extract the secret image, they must decrypt sequentially, keeping the same order of the encryption step, by using l + 1 keys (secret or private). With the proposed approach, during the encryption step, each player encrypts his own secret image using the same public key given by the dealer, the dealer encrypts the secret image to be shared with the same key and then the l secret encrypted images plus the encrypted image to be shared are multiplied between them to get a scrambled image. After this step, the dealer can securely use the private key to decrypt this scrambled image to get a new scrambled image which corresponds to the addition of the l + 1 original images because of the additive homomorphic property of Paillier algorithm. When the l players want to extract the secret image, they do not need the dealer and to use keys. Indeed, with our approach, to extract the secret image, the l players need only to subtract their own secret image from the scrambled image. In this paper we illustrate our approach with an example of a captain who wants to share a secret treasure map between l pirates. Experimental results and security analysis show the effectiveness of the proposed scheme.

  4. ERAD-icating mutant insulin promotes functional insulin secretion.

    PubMed

    Moore, Daniel J

    2017-01-18

    Overexpression of a chaperone protein liberates functional insulin from a misfolded mutant partner to improve insulin secretion. Copyright © 2017, American Association for the Advancement of Science.

  5. BetaHCG secretion by a pulmonary adenocarcinoma

    PubMed Central

    2013-01-01

    We report a rare case of metastatic non-small-cell lung cancer in a 43-year-old woman with a history of smoking. The tumor secreted human chorionic gonadotropin and its beta subunit (BetaHCG). The patient presented with amenorrhea, a positive pregnancy test and chest pain. A physical examination and investigations revealed no pregnancy, and it was determined that a paraneoplastic syndrome stemming from a pulmonary tumor was responsible for the secretion of BetaHCG. This secretion decreased with tumor response to chemotherapy. Only a few reports of paraneoplastic BetaHCG secretion can be found in the literature for several different cancers. PMID:24034807

  6. A Brevibacillus choshinensis system that secretes cytoplasmic proteins.

    PubMed

    Horne, Irene; Williams, Michelle; Sutherland, Tara D; Russell, Robyn J; Oakeshott, John G

    2004-01-01

    Brevibacillus choshinensis has previously been shown to be a useful strain for the secretion of heterologous proteins via the Sec secretory pathway. This pathway involves the secretion of proteins prior to folding, whereas the alternative TAT (twin-arginine translocation) pathway enables pre-folded proteins to be secreted. We have modified the signal peptide of the Brevibacillus expression vector pNCMO2 to accommodate a Sec avoidance signal as well as the twin arginines required for secretion via the TAT system. Use of this modified signal peptide with the phosphotriesterase OpdA enabled B. choshinensis transformants to express and secrete the enzyme in an active and substantially pure form. The system was also used successfully to secrete two cytoplasmic proteins, the phosphotriesterase HocA from Pseudomonas monteilii and the phenylcarbamate-degrading enzyme, PCD, from Arthrobacter oxydans. The inhibitors carbonyl cyanide m-chlorophenyl hydrazine and sodium azide were used to confirm that secretion was occurring via the TAT secretion pathway. The modified B. choshinensis system we have developed may have general utility in secreting a wide range of heterologous proteins in active and conveniently processed form.

  7. A secret image sharing scheme for light images

    NASA Astrophysics Data System (ADS)

    Wu, Kuang-Shyr

    2013-12-01

    In this study, a new ( r, n)-threshold secret image sharing scheme with low information overhead for images is provided, which has a low distortion rate, and is more applicable for light images. A secret image is encoded into n noise-like shadow images to satisfy the condition that any r of the n shares can be used to reveal the secret image, and no information on the secret can be revealed from any r - 1 or fewer shares. The size of the shadow images is relatively small. The experimental results show the effectiveness of the proposed scheme.

  8. Diadenosine tetraphosphate contributes to carbachol-induced tear secretion.

    PubMed

    Fonseca, Begoña; Martínez-Águila, Alejandro; Díaz-Hernández, Miguel; Pintor, Jesús

    2015-03-01

    The purpose of this study is to investigate if the cholinergic stimulation by carbachol on tear secretion is a direct process or if it is also mediated by purinergic mechanisms. Experiments were performed in New Zealand male rabbits. The amount of tear secretion was measured with Schirmer's test and then analyzed by a HPLC protocol in order to study the nucleotide levels. Animal eyes were instilled with carbachol (a cholinergic agonist), pirenzepine, gallamine and 4-DAMP (muscarinic antagonists), PPADS, suramin and reactive blue 2 (purinergic antagonists), and a P2Y2 receptor small interfering RNA (siRNA). Tear secretion increased with the instillation of carbachol, approximately 84 % over control values 20 min after the instillation and so did Ap4A and ATP release. When we applied carbachol in the presence of muscarinic antagonists, tear volume only increased to 4 % with atropine, 12 % in the case of pirenzepine, 3 % with gallamine, and 8 % with 4-DAMP. In the presence of carbachol and purinergic antagonists, tear secretion was increased to 12 % (all values compared to basal tear secretion). By analyzing tear secretion induced with carbachol in presence of a P2Y2 receptor siRNA, we found that tear secretion was diminished to 60 %. The inhibition of tear secretion in the presence of carbachol and purinergic antagonists or P2Y2 siRNA occurred with no apparent change in the tear amount of Ap4A. These experiments demonstrated the participation of Ap4A in lacrimal secretion process.

  9. SepD/SepL-dependent secretion signals of the type III secretion system translocator proteins in enteropathogenic Escherichia coli.

    PubMed

    Deng, Wanyin; Yu, Hong B; Li, Yuling; Finlay, B Brett

    2015-04-01

    The type III protein secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE) is essential for the pathogenesis of attaching/effacing bacterial pathogens, including enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium. These pathogens use the T3SS to sequentially secrete three categories of proteins: the T3SS needle and inner rod protein components; the EspA, EspB, and EspD translocators; and many LEE- and non-LEE-encoded effectors. SepD and SepL are essential for translocator secretion, and mutations in either lead to hypersecretion of effectors. However, how SepD and SepL control translocator secretion and secretion hierarchy between translocators and effectors is poorly understood. In this report, we show that the secreted T3SS components, the translocators, and both LEE- and non-LEE-encoded effectors all carry N-terminal type III secretion and translocation signals. These signals all behave like those of the effectors and are sufficient for mediating type III secretion and translocation by wild-type EPEC and hypersecretion by the sepD and sepL mutants. Our results extended previous observations and suggest that the secretion hierarchy of the different substrates is determined by a signal other than the N-terminal secretion signal. We identified a domain located immediately downstream of the N-terminal secretion signal in the translocator EspB that is required for SepD/SepL-dependent secretion. We further demonstrated that this EspB domain confers SepD/SepL- and CesAB-dependent secretion on the secretion signal of effector EspZ. Our results thus suggest that SepD and SepL control and regulate secretion hierarchy between translocators and effectors by recognizing translocator-specific export signals. Many bacterial pathogens use a syringe-like protein secretion apparatus, termed the type III protein secretion system (T3SS), to secrete and inject numerous proteins directly into the host cells to

  10. Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

    PubMed

    Guttu, K; Røsok, B; Gislason, H; Fändriks, L; Svanes, K; Grønbech, J E

    1991-04-01

    In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.

  11. Alternative protein secretion: The Mam1 ABC transporter supports secretion of M-factor linked GFP in fission yeast

    SciTech Connect

    Kjaerulff, Soren

    2005-12-30

    To examine whether the fission yeast Mam1 ABC transporter can be used for secretion of heterologous proteins, thereby bypassing the classical secretion pathway, we have analyzed chimeric forms of the M-factor precursor. It was demonstrated that GFP can be exported when fused to both the amino-terminal prosequence from mfm1 and a CaaX motif. This secretion was dependent on the Mam1 transporter and not the classical secretion pathway. The secretion efficiency of GFP, however, was relatively low and most of the reporter protein was trapped in the vacuolar membranes. Our findings suggest that the Mam1 ABC protein is a promiscuous peptide transporter that can accommodate globular proteins of a relatively large size. Furthermore, our results help in defining the sequences required for processing and secretion of natural M-factor.

  12. A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins.

    PubMed

    Tejeda-Dominguez, Farid; Huerta-Cantillo, Jazmin; Chavez-Dueñas, Lucia; Navarro-Garcia, Fernando

    2017-03-28

    The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic Escherichia coli (EPEC) autotransporter, and YopH, a protein detected on the surface of Yersinia, require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore. Interestingly, this novel mechanism does not exclude the injection model (i.e., EspF) operating through the T3SS conduit; therefore, T3SS can be functioning as an internal conduit or as an external railway, which can be used to reach the translocator pore, and this mechanism appears to be conserved among different T3SS-dependent pathogens.IMPORTANCE The type 3 secretion system is essential for injection of virulence factors, which are delivered directly into the cytosol of the host cells for usurping and subverting host processes. Recent studies have shown that these effectors proteins indeed travel inside an "injectisome" conduit through a single step of translocation by connecting the bacterium and host cell cytoplasms. However, all findings are not compatible with this model. For example, both YopH, a protein detected on the surface of Yersinia, and EspC, an autotransporter protein secreted by enteropathogenic E. coli, require a functional T3

  13. Secreted fungal aspartic proteases: A review.

    PubMed

    Mandujano-González, Virginia; Villa-Tanaca, Lourdes; Anducho-Reyes, Miguel Angel; Mercado-Flores, Yuridia

    2016-01-01

    The aspartic proteases, also called aspartyl and aspartate proteases or acid proteases (E.C.3.4.23), belong to the endopeptidase family and are characterized by the conserved sequence Asp-Gly-Thr at the active site. These enzymes are found in a wide variety of microorganisms in which they perform important functions related to nutrition and pathogenesis. In addition, their high activity and stability at acid pH make them attractive for industrial application in the food industry; specifically, they are used as milk-coagulating agents in cheese production or serve to improve the taste of some foods. This review presents an analysis of the characteristics and properties of secreted microbial aspartic proteases and their potential for commercial application. Copyright © 2016 Asociación Española de Micología. Published by Elsevier Espana. All rights reserved.

  14. How to hide a secret direction

    NASA Astrophysics Data System (ADS)

    Bagan, E.; Calsamiglia, J.; Demkowicz-Dobrzański, R.; Munoz-Tapia, R.

    2007-08-01

    We present a procedure that uses a multipartite quantum state to communicate a secret spatial direction when there is no shared reference frame between the preparer and the group of recipients. The procedure guarantees that the recipients can determine the direction if they perform joint measurements on the state, but fail to do so if they restrict themselves to local operations and classical communication (LOCC). We calculate the fidelity for joint measurements, give bounds on the fidelity achievable by LOCC, and prove that there is a non-vanishing gap between the two of them, even in the limit of infinitely many copies. The robustness of the procedure under particle loss is also studied. Additionally, we find bounds on the probability of discriminating by LOCC between the invariant subspaces of total angular momentum N/2 and N/2-1 in a system of N elementary spins.

  15. Polyamines are Inhibitors of Gastric Acid Secretion

    NASA Astrophysics Data System (ADS)

    Ray, Tushar K.; Nandi, Jyotirmoy; Pidhorodeckyj, Nykolai; Meng-Ai, Zhou

    1982-03-01

    The naturally occurring organic polycations such as spermine and spermidine inhibit histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro; spermine is much more potent than spermidine. Unlike the H2 receptor antagonists, the polyamines are completely ineffective from the nutrient side and are effective only from the secretory side of the chambered mucosa. The polyamine effects could be reversed by increasing K+ concentration in the secretory solution. Studies with isolated gastric microsomal vesicles demonstrate that the polyamines do not inhibit the gastric H+,K+-ATPase but greatly decrease the ATPase-mediated uptake of H+ under appropriate conditions. For the latter effects the presence of polyamine within the vesicle interior was found to be essential. Our data strongly suggest an uncoupling of the gastric H+,K+-ATPase system by the polyamines. The therapeutic potential of these and similar compounds in the treatment of hyperacidity and peptic ulcer is discussed.

  16. Gastric acid secretion: changes during a century.

    PubMed

    Di Mario, Francesco; Goni, Elisabetta

    2014-12-01

    The advances in knowledge of gastric physiology within the past century have been the most exciting and important in this area of interest for many decades. The aim of this presentation consists of a comprehensive review of the extensive recent literature on this topic in order to highlight milestones in the field of gastric physiology, in particular in gastric acid secretion, gastric pathophysiology, acid-related diseases and use of acid regulatory drugs. Moreover, in the 21st century there have been many epidemiologic changes as well as a decrease of Helicobacter pylori infection and gastric cancer together with an increase of gastroesophageal reflux disease and the related increase of pomp proton inhibitor wide use.

  17. TSH-secreting adenoma improved with cabergoline.

    PubMed

    Mouton, F; Faivre-Defrance, F; Cortet-Rudelli, C; Assaker, R; Soto-Ares, G; Defoort-Dhellemmes, S; Blond, S; Wemeau, J-L; Vantyghem, M-C

    2008-06-01

    TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.

  18. Secretion of proteases from Pasteurella multocida isolates.

    PubMed

    Negrete-Abascal, E; Tenorio, V R; de la Garza, M

    1999-01-01

    The capability of Pasteurella multocida to secrete proteases to the culture medium and their characterization were studied in five animal isolates (bovine, chicken, sheep, and two from pig). All the isolates produced proteases in a wide range of molecular mass. It is suggested that they are neutral metalloproteases, since they were optimally active between pH 6 and 7, inhibited by chelating agents but not by other protease inhibitors, and reactivated by calcium. Proteases from isolates were able to degrade IgG. Several proteins from supernatants of cultures precipitated with 70% (NH4)2SO4 of all the P. multocida isolates were recognized by a polyclonal antiserum raised against a purified protease from Actinobacillus pleuropneumoniae. Protease production might play an important role during tissue colonization and in P. multocida diseases.

  19. Secretion from Myeloid Cells: Secretory Lysosomes.

    PubMed

    Griffiths, Gillian M

    2016-08-01

    Many cells of the myeloid lineage use an unusual secretory organelle to deliver their effector mechanisms. In these cells, the lysosomal compartment is often modified not only to fulfill the degradative functions of a lysosome but also as a mechanism for secreting additional proteins that are found in the lysosomes of each specialized cell type. These extra proteins vary from one cell type to another according to the specialized function of the cell. For example, mast cells package histamine; cytotoxic T cells express perforin; azurophilic granules in neutrophils express antimicrobial peptides, and platelets von Willebrand factor. Upon release, these very different proteins can trigger inflammation, cell lysis, microbial death, and clotting, respectively, and hence deliver the very different effector mechanisms of these different myeloid cells.

  20. Precursor in cotranslational secretion of diphtheria toxin.

    PubMed Central

    Smith, W P; Tai, P C; Murphy, J R; Davis, B D

    1980-01-01

    By extracellular labeling of peptides of intact Corynebacterium diphtheriae, followed by fractionation of the cells and chain completion by isolated polysomes, it is shown that diphtheria toxin is formed and secreted cotranslationally by membrane-bound polysomes; free polysomes from none. Moreover, when the chains on these polysomes were completed in vitro, in the absence of membrane they were found to include not only diphtheria toxin of a molecular weight of 62,000, but also a larger precursor of a molecular weight of 68,000. The precursor was identified by several properties: immune precipitation; conversion into toxin fragments A and B; adenosine diphosphate ribosyl-transferase activity after activation with trypsin; and cleavage to 62,000 daltons by membrane enzymes. The precursor yields an N-terminal A fragment with a broadened molecular weight distribution, compared with that from authentic toxin, thus supporting the expectation that the extra segment of the precursor is N-terminal. PMID:6243620

  1. Marker for type VI secretion system effectors

    PubMed Central

    Salomon, Dor; Kinch, Lisa N.; Trudgian, David C.; Guo, Xiaofeng; Klimko, John A.; Grishin, Nick V.; Mirzaei, Hamid; Orth, Kim

    2014-01-01

    Bacteria use diverse mechanisms to kill, manipulate, and compete with other cells. The recently discovered type VI secretion system (T6SS) is widespread in bacterial pathogens and used to deliver virulence effector proteins into target cells. Using comparative proteomics, we identified two previously unidentified T6SS effectors that contained a conserved motif. Bioinformatic analyses revealed that this N-terminal motif, named MIX (marker for type six effectors), is found in numerous polymorphic bacterial proteins that are primarily located in the T6SS genome neighborhood. We demonstrate that several MIX-containing proteins are T6SS effectors and that they are not required for T6SS activity. Thus, we propose that MIX-containing proteins are T6SS effectors. Our findings allow for the identification of numerous uncharacterized T6SS effectors that will undoubtedly lead to the discovery of new biological mechanisms. PMID:24927539

  2. Secreted and Transmembrane Wnt Inhibitors and Activators

    PubMed Central

    Cruciat, Cristina-Maria; Niehrs, Christof

    2013-01-01

    Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand–receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step. With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling. Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease. PMID:23085770

  3. Type VI Secretion Effectors: Methodologies and Biology

    PubMed Central

    Lien, Yun-Wei; Lai, Erh-Min

    2017-01-01

    The type VI secretion system (T6SS) is a nanomachine deployed by many Gram-negative bacteria as a weapon against eukaryotic hosts or prokaryotic competitors. It assembles into a bacteriophage tail-like structure that can transport effector proteins into the environment or target cells for competitive survival or pathogenesis. T6SS effectors have been identified by a variety of approaches, including knowledge/hypothesis-dependent and discovery-driven approaches. Here, we review and discuss the methods that have been used to identify T6SS effectors and the biological and biochemical functions of known effectors. On the basis of the nature and transport mechanisms of T6SS effectors, we further propose potential strategies that may be applicable to identify new T6SS effectors. PMID:28664151

  4. Nutrient regulation of insulin secretion and action.

    PubMed

    Newsholme, Philip; Cruzat, Vinicius; Arfuso, Frank; Keane, Kevin

    2014-06-01

    Pancreatic β-cell function is of critical importance in the regulation of fuel homoeostasis, and metabolic dysregulation is a hallmark of diabetes mellitus (DM). The β-cell is an intricately designed cell type that couples metabolism of dietary sources of carbohydrates, amino acids and lipids to insulin secretory mechanisms, such that insulin release occurs at appropriate times to ensure efficient nutrient uptake and storage by target tissues. However, chronic exposure to high nutrient concentrations results in altered metabolism that impacts negatively on insulin exocytosis, insulin action and may ultimately lead to development of DM. Reduced action of insulin in target tissues is associated with impairment of insulin signalling and contributes to insulin resistance (IR), a condition often associated with obesity and a major risk factor for DM. The altered metabolism of nutrients by insulin-sensitive target tissues (muscle, adipose tissue and liver) can result in high circulating levels of glucose and various lipids, which further impact on pancreatic β-cell function, IR and progression of the metabolic syndrome. Here, we have considered the role played by the major nutrient groups, carbohydrates, amino acids and lipids, in mediating β-cell insulin secretion, while also exploring the interplay between amino acids and insulin action in muscle. We also focus on the effects of altered lipid metabolism in adipose tissue and liver resulting from activation of inflammatory processes commonly observed in DM pathophysiology. The aim of this review is to describe commonalities and differences in metabolism related to insulin secretion and action, pertinent to the development of DM. © 2014 Society for Endocrinology.

  5. Electrogenic bicarbonate secretion by prairie dog gallbladder.

    PubMed

    Moser, A James; Gangopadhyay, A; Bradbury, N A; Peters, K W; Frizzell, R A; Bridges, R J

    2007-06-01

    Pathological rates of gallbladder salt and water transport may promote the formation of cholesterol gallstones. Because prairie dogs are widely used as a model of this event, we characterized gallbladder ion transport in animals fed control chow by using electrophysiology, ion substitution, pharmacology, isotopic fluxes, impedance analysis, and molecular biology. In contrast to the electroneutral properties of rabbit and Necturus gallbladders, prairie dog gallbladders generated significant short-circuit current (I(sc); 171 +/- 21 microA/cm(2)) and lumen-negative potential difference (-10.1 +/- 1.2 mV) under basal conditions. Unidirectional radioisotopic fluxes demonstrated electroneutral NaCl absorption, whereas the residual net ion flux corresponded to I(sc). In response to 2 microM forskolin, I(sc) exceeded 270 microA/cm(2), and impedance estimates of the apical membrane resistance decreased from 200 Omega.cm(2) to 13 Omega.cm(2). The forskolin-induced I(sc) was dependent on extracellular HCO(3)(-) and was blocked by serosal 4,4'-dinitrostilben-2,2'-disulfonic acid (DNDS) and acetazolamide, whereas serosal bumetanide and Cl(-) ion substitution had little effect. Serosal trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chroman and Ba(2+) reduced I(sc), consistent with the inhibition of cAMP-dependent K(+) channels. Immunoprecipitation and confocal microscopy localized cystic fibrosis transmembrane conductance regulator protein (CFTR) to the apical membrane and subapical vesicles. Consistent with serosal DNDS sensitivity, pancreatic sodium-bicarbonate cotransporter protein pNBC1 expression was localized to the basolateral membrane. We conclude that prairie dog gallbladders secrete bicarbonate through cAMP-dependent apical CFTR anion channels. Basolateral HCO(3)(-) entry is mediated by DNDS-sensitive pNBC1, and the driving force for apical anion secretion is provided by K(+) channel activation.

  6. Pyrilamine inhibits nicotine-induced catecholamine secretion.

    PubMed

    Kim, Dong-Chan; Yun, So Jeong; Park, Yong-Soo; Jun, Dong-Jae; Kim, Dongjin; Jiten Singh, N; Kim, Sanguk; Kim, Kyong-Tai

    2014-07-01

    Function of nicotine, which induces activation of all parts of the body including our brain, has been receiving much attention for a long period of time and also been actively studied by researchers for its pharmacological actions in the central nervous system. The modulation of nicotine concentration and the inhibition of nicotine binding on target receptors in the brain are the key factors for smoking addiction therapy. In previous studies showed that influx of nicotine at the blood-brain barrier was through the pyrilamine-sensitive organic cation transporters. But the direct interacting mechanism of pyrilamine on the nicotine binding target receptors has not yet been clarified. The aim of the present study is to investigate the direct binding mechanisms of a pyrilamine on the nicotinic acetylcholine receptors (nAChRs). We found that pyrilamine shares the same ligand binding pocket of nicotine (NCT) on nAChRs but interacts with more amino acid residues than NCT does. The extended part of pyrilamine interacts with additional residues in the ligand binding pocket of nAChRs which are located nearby the entrance of the binding pocket. The catecholamine (CA) secretion induced by nAChR agonist (NCT') was significantly inhibited by the pyrilamine pretreatment. Real time carbon-fiber amperometry confirmed the inhibition of the NCT'-induced exocytosis by pyrilamine in a single cell level. We also found that pyrilamine inhibited the NCT'-induced [Ca(2+)]i. In contrast, pyrilamine did not affect the increase in calcium induced by high K(+). Overall, these data suggest that pyrilamine directly docks into the ligand binding site of nAChRs and specifically inhibits the nAChR-mediated effects thereby causing inhibition of CA secretion. Therefore, pyrilamine may play an important role to explore new treatments to aid smoking cessation.

  7. Renal tubular secretion of glutathione (GSH)

    SciTech Connect

    Scott, R.D.; Curthoys, N.P.

    1986-05-01

    The rapid turnover of renal GSH may require its secretion into the tubular lumen. Renal clearance of plasma GSH was measured in rats anesthetized with Inactin and infused with (/sup 3/H)inulin. Renal ..gamma..-glutamyltranspeptidase (..gamma..GT) was then inactivated (> 97%) by infusion of acivicin and samples were collected for 6-7 h. By 4.5 h arterial and urinary GSH increased from 5..mu..M and 1.3 n mol/h to 23 ..mu..M and 2400-7000 nmol/h, respectively. The ratio of urinary GSH to filtered load increased from < 0.01 to 0.7-2.6. When renal GSH was decreased to 30% of normal by pretreating rats with buthionine sulfoximine (BSO), the subsequent inactivation of ..gamma..GT caused only a slight increase in arterial GSH and urinary GSH increased to only 400-600 nmol/h (60-70% of filtered load). The amount of GSH filtered by the kidney was reduced by initially treating a rat with acivicin and 3 h later infusing purified ..gamma..GT (0.2 mg/h) to degrade plasma GSH. Just before infusion of ..gamma..GT, arterial GSH was 23 ..mu..M and urinary GSH was equal to 90% of the filtered load. At 1 h after infusion of ..gamma..GT, arterial GSH decreased to 0.3 ..mu..M, whereas urinary GSH remained elevated (1200-1800 nmol/h) and now equalled 10-20 times the filtered load. When similar experiments were carried out in BSO treated rats, maximal urinary GSH was reduced to 200 nmol/h, a value that was still 10 times the filtered load. Therefore, secreted GSH constitutes a significant portion of the GSH that is normally catabolized within the tubular lumen.

  8. Vitamin D, Insulin Secretion, Sensitivity, and Lipids

    PubMed Central

    Grimnes, Guri; Figenschau, Yngve; Almås, Bjørg; Jorde, Rolf

    2011-01-01

    OBJECTIVE Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies. The intention was to compare insulin sensitivity (the primary end point) and secretion and lipids in subjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels. RESEARCH DESIGN AND METHODS Participants were recruited from a population-based study (the Tromsø Study) based on their serum 25(OH)D measurements. A 3-h hyperglycemic clamp was performed, and the participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D3 or identical-looking placebo twice weekly for 6 months. A final hyperglycemic clamp was then performed. RESULTS The 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA1c and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups. CONCLUSIONS Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile. PMID:21911741

  9. An Engineered Yeast Efficiently Secreting Penicillin

    PubMed Central

    Gidijala, Loknath; Kiel, Jan A. K. W.; Douma, Rutger D.; Seifar, Reza M.; van Gulik, Walter M.; Bovenberg, Roel A. L.; Veenhuis, Marten; van der Klei, Ida J.

    2009-01-01

    This study aimed at developing an alternative host for the production of penicillin (PEN). As yet, the industrial production of this β-lactam antibiotic is confined to the filamentous fungus Penicillium chrysogenum. As such, the yeast Hansenula polymorpha, a recognized producer of pharmaceuticals, represents an attractive alternative. Introduction of the P. chrysogenum gene encoding the non-ribosomal peptide synthetase (NRPS) δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) in H. polymorpha, resulted in the production of active ACVS enzyme, when co-expressed with the Bacillus subtilis sfp gene encoding a phosphopantetheinyl transferase that activated ACVS. This represents the first example of the functional expression of a non-ribosomal peptide synthetase in yeast. Co-expression with the P. chrysogenum genes encoding the cytosolic enzyme isopenicillin N synthase as well as the two peroxisomal enzymes isopenicillin N acyl transferase (IAT) and phenylacetyl CoA ligase (PCL) resulted in production of biologically active PEN, which was efficiently secreted. The amount of secreted PEN was similar to that produced by the original P. chrysogenum NRRL1951 strain (approx. 1 mg/L). PEN production was decreased over two-fold in a yeast strain lacking peroxisomes, indicating that the peroxisomal localization of IAT and PCL is important for efficient PEN production. The breakthroughs of this work enable exploration of new yeast-based cell factories for the production of (novel) β-lactam antibiotics as well as other natural and semi-synthetic peptides (e.g. immunosuppressive and cytostatic agents), whose production involves NRPS's. PMID:20016817

  10. Calmodulin antagonists inhibit secretion in Paramecium

    PubMed Central

    1983-01-01

    Secretion in Paramecium is Ca2+-dependent and involves exocytic release of the content of the secretory organelle, known as the trichocyst. The content, called the trichocyst matrix, undergoes a Ca2+-induced reordering of its paracrystalline structure during release, and we have defined three stages in this expansion process. The stage I, or fully condensed trichocyst, is the 4 microns-long membrane-bounded form existing prior to stimulation. Stage II, the partially expanded trichocyst, we define as an intermediate stage in the transition, preceding stage III, the fully expanded extruded form which is a 20-40 microns-long needlelike structure. These stages have been used to assay the effects of trifluoperazine (TFP) and W-7, calmodulin (CaM) antagonists, on trichocyst matrix expansion in vivo. TFP and W-7 are shown to reversibly block matrix release induced by picric acid. Ultra- structural examination reveals that one effect of this inhibition is reflected in the organelles themselves, which are prevented from undergoing the stage I-stage II transition by preincubation in 14 microM TFP or 35 microM W-7 before fixation. This inhibition of expansion by TFP can be moderated but not abolished by high extracellular Ca2+ (5 mM). The moderation by high Ca2+ can be eliminated by raising TFP concentration to 20 microM. A possible explanation for the ability to titrate the inhibition in this manner is that TFP is acting to block expansion by binding to the Ca2+-CaM complex. Brief exposure of cells to the Ca2+ ionophore A23187 and 5 mM Ca2+ following TFP treatment promotes matrix expansion, although in 14 microM TFP a residual level of inhibition remains. These results suggest that, following stimulation, CaM regulates secretion in Paramecium, possibly by controlling the Ca2+-dependent matrix expansion which accompanies exocytosis in these cells. PMID:6403556

  11. An engineered yeast efficiently secreting penicillin.

    PubMed

    Gidijala, Loknath; Kiel, Jan A K W; Douma, Rutger D; Seifar, Reza M; van Gulik, Walter M; Bovenberg, Roel A L; Veenhuis, Marten; van der Klei, Ida J

    2009-12-15

    This study aimed at developing an alternative host for the production of penicillin (PEN). As yet, the industrial production of this beta-lactam antibiotic is confined to the filamentous fungus Penicillium chrysogenum. As such, the yeast Hansenula polymorpha, a recognized producer of pharmaceuticals, represents an attractive alternative. Introduction of the P. chrysogenum gene encoding the non-ribosomal peptide synthetase (NRPS) delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) in H. polymorpha, resulted in the production of active ACVS enzyme, when co-expressed with the Bacillus subtilis sfp gene encoding a phosphopantetheinyl transferase that activated ACVS. This represents the first example of the functional expression of a non-ribosomal peptide synthetase in yeast. Co-expression with the P. chrysogenum genes encoding the cytosolic enzyme isopenicillin N synthase as well as the two peroxisomal enzymes isopenicillin N acyl transferase (IAT) and phenylacetyl CoA ligase (PCL) resulted in production of biologically active PEN, which was efficiently secreted. The amount of secreted PEN was similar to that produced by the original P. chrysogenum NRRL1951 strain (approx. 1 mg/L). PEN production was decreased over two-fold in a yeast strain lacking peroxisomes, indicating that the peroxisomal localization of IAT and PCL is important for efficient PEN production. The breakthroughs of this work enable exploration of new yeast-based cell factories for the production of (novel) beta-lactam antibiotics as well as other natural and semi-synthetic peptides (e.g. immunosuppressive and cytostatic agents), whose production involves NRPS's.

  12. Type II secretion in Yersinia—a secretion system for pathogenicity and environmental fitness

    PubMed Central

    von Tils, Dominik; Blädel, Inga; Schmidt, M. Alexander; Heusipp, Gerhard

    2012-01-01

    In Yersinia species, type III secretion (T3S) is the most prominent and best studied secretion system and a hallmark for the infection process of pathogenic Yersinia species. Type II secretion (T2S), on the other hand, is less well-characterized, although all Yersinia species, pathogenic as well as non-pathogenic, possess one or even two T2S systems. The only Yersinia strain in which T2S has so far been studied is the human pathogenic strain Y. enterocolitica 1b. Mouse infection experiments showed that at least one of the two T2S systems of Y. enterocolitica 1b, termed Yts1, is involved in dissemination and colonization of deeper tissues like liver and spleen. Interestingly, in vitro studies revealed a complex regulation of the Yts1 system, which is mainly active at low temperatures and high Mg2+-levels. Furthermore, the functional characterization of the proteins secreted in vitro indicates a role of the Yts1 machinery in survival of the bacteria in an environmental habitat. In silico analyses identified Yts1 homologous systems in bacteria that are known as plant symbionts or plant pathogens. Thus, the recent studies point to a dual function of the Yts1 T2S systems, playing a role in virulence of humans and animals, as well as in the survival of the bacteria outside of the mammalian host. In contrast, the role of the second T2S system, Yts2, remains ill defined. Whereas the T3S system and its virulence-mediating role has been intensively studied, it might now be time to also focus on the T2S system and its role in the Yersinia lifestyle, especially considering that most of the Yersinia isolates are not found in infected humans but have been gathered from various environmental samples. PMID:23248779

  13. Identification of Porphyromonas gingivalis proteins secreted by the Por secretion system.

    PubMed

    Sato, Keiko; Yukitake, Hideharu; Narita, Yuka; Shoji, Mikio; Naito, Mariko; Nakayama, Koji

    2013-01-01

    The Gram-negative bacterium Porphyromonas gingivalis possesses a number of potential virulence factors for periodontopathogenicity. In particular, cysteine proteinases named gingipains are of interest given their abilities to degrade host proteins and process other virulence factors such as fimbriae. Gingipains are translocated on the cell surface or into the extracellular milieu by the Por secretion system (PorSS), which consists of a number of membrane or periplasmic proteins including PorK, PorL, PorM, PorN, PorO, PorP, PorQ, PorT, PorU, PorV (PG27, LptO), PorW and Sov. To identify proteins other than gingipains secreted by the PorSS, we compared the proteomes of P. gingivalis strains kgp rgpA rgpB (PorSS-proficient strain) and kgp rgpA rgpB porK (PorSS-deficient strain) using two-dimensional gel electrophoresis and peptide-mass fingerprinting. Sixteen spots representing 10 different proteins were present in the particle-free culture supernatant of the PorSS-proficient strain but were absent or faint in that of the PorSS-deficient strain. These identified proteins possessed the C-terminal domains (CTDs), which had been suggested to form the CTD protein family. These results indicate that the PorSS is used for secretion of a number of proteins other than gingipains and that the CTDs of the proteins are associated with the PorSS-dependent secretion. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  14. Production, secretion, and stability of human secreted alkaline phosphatase in tobacco NT1 cell suspension cultures.

    PubMed

    Becerra-Arteaga, Alejandro; Mason, Hugh S; Shuler, Michael L

    2006-01-01

    Tobacco NT1 cell suspension cultures secreting active human secreted alkaline phosphatase (SEAP) were generated for the first time as a model system to study recombinant protein production, secretion, and stability in plant cell cultures. The SEAP gene encodes a secreted form of the human placental alkaline phosphatase (PLAP). During batch culture, the highest level of active SEAP in the culture medium (0.4 U/mL, corresponding to approximately 27 mg/L) was observed at the end of the exponential growth phase. Although the level of active SEAP decreased during the stationary phase, the activity loss did not appear to be due to SEAP degradation (based on Western blots) but due to SEAP denaturation. The protein-stabilizing agents polyvinylpirrolidone (PVP) and bacitracin were added extracellularly to test for their ability to reduce the loss of SEAP activity during the stationary phase. Bacitracin (100 mg/L) was the most effective treatment at sustaining activity levels for up to 17 days post-subculture. Commercially available human placental alkaline phosphatase (PLAP) was used to probe the mechanism of SEAP deactivation. Experiments with PLAP in sterile and conditioned medium corroborated the denaturation of SEAP by factors generated by cell growth and not due to simple proteolysis. We also show for the first time that the factors promoting activity loss are heat labile at 95 degrees C but not at 70 degrees C, and they are not inactivated after a 5 day incubation period under normal culture conditions (27 degrees C). In addition, there were no significant changes in pH or redox potential when comparing sterile and cell-free conditioned medium during PLAP incubation, indicating that these factors were unimportant.

  15. A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders.

    PubMed

    Mumford, Andrew D; Frelinger, Andrew L; Gachet, Christian; Gresele, Paolo; Noris, Patrizia; Harrison, Paul; Mezzano, Diego

    2015-07-01

    Measurement of platelet granule release to detect inherited platelet secretion disorders (IPSDs) is essential for the evaluation of patients with abnormal bleeding and is necessary to distinguish which granule sub-types are affected and whether there is abnormal granule bio-synthesis or secretion. The radioactive serotonin incorporation and release assay, described before 1970, is still considered the "gold standard" test to assess platelet δ-granule release, although is unsuitable for clinical diagnostic laboratories. Luciferin-based assays, such as lumiaggregometry, are the most widely performed alternatives, although these methods do not distinguish defects in δ-granule biosynthesis from defects in secretion. Platelet α-granule release is commonly evaluated using flow cytometry by measuring surface exposure of P-selectin after platelet activation. However, this assay has poor sensitivity for some α-granule disorders. Only few studies have been published with more recently developed assays and no critical reviews on these methods are available. In this review, we describe the rationale for developing robust and accurate laboratory tests of platelet granule release and describe the characteristics of the currently available tests. We identify an unmet need for further systematic evaluation of new assays and for standardisation of methodologies for clinical diagnostic laboratories.

  16. Yersinia enterocolitica type III secretion-translocation system: channel formation by secreted Yops.

    PubMed Central

    Tardy, F; Homblé, F; Neyt, C; Wattiez, R; Cornelis, G R; Ruysschaert, J M; Cabiaux, V

    1999-01-01

    'Type III secretion' allows extracellular adherent bacteria to inject bacterial effector proteins into the cytosol of their animal or plant host cells. In the archetypal Yersinia system the secreted proteins are called Yops. Some of them are intracellular effectors, while YopB and YopD have been shown by genetic analyses to be dedicated to the translocation of these effectors. Here, the secretion of Yops by Y.enterocolitica was induced in the presence of liposomes, and some Yops, including YopB and YopD, were found to be inserted into liposomes. The proteoliposomes were fused to a planar lipid membrane to characterize the putative pore-forming properties of the lipid-bound Yops. Electrophysiological experiments revealed the presence of channels with a 105 pS conductance and no ionic selectivity. Channels with those properties were generated by mutants devoid of the effectors and by lcrG mutants, as well as by wild-type bacteria. In contrast, mutants devoid of YopB did not generate channels and mutants devoid of YopD led to current fluctuations that were different from those observed with wild-type bacteria. The observed channel could be responsible for the translocation of Yop effectors. PMID:10581252

  17. Yersinia enterocolitica type III secretion-translocation system: channel formation by secreted Yops.

    PubMed

    Tardy, F; Homblé, F; Neyt, C; Wattiez, R; Cornelis, G R; Ruysschaert, J M; Cabiaux, V

    1999-12-01

    'Type III secretion' allows extracellular adherent bacteria to inject bacterial effector proteins into the cytosol of their animal or plant host cells. In the archetypal Yersinia system the secreted proteins are called Yops. Some of them are intracellular effectors, while YopB and YopD have been shown by genetic analyses to be dedicated to the translocation of these effectors. Here, the secretion of Yops by Y.enterocolitica was induced in the presence of liposomes, and some Yops, including YopB and YopD, were found to be inserted into liposomes. The proteoliposomes were fused to a planar lipid membrane to characterize the putative pore-forming properties of the lipid-bound Yops. Electrophysiological experiments revealed the presence of channels with a 105 pS conductance and no ionic selectivity. Channels with those properties were generated by mutants devoid of the effectors and by lcrG mutants, as well as by wild-type bacteria. In contrast, mutants devoid of YopB did not generate channels and mutants devoid of YopD led to current fluctuations that were different from those observed with wild-type bacteria. The observed channel could be responsible for the translocation of Yop effectors.

  18. A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins

    PubMed Central

    Tejeda-Dominguez, Farid; Huerta-Cantillo, Jazmin; Chavez-Dueñas, Lucia

    2017-01-01

    ABSTRACT The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic Escherichia coli (EPEC) autotransporter, and YopH, a protein detected on the surface of Yersinia, require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore. Interestingly, this novel mechanism does not exclude the injection model (i.e., EspF) operating through the T3SS conduit; therefore, T3SS can be functioning as an internal conduit or as an external railway, which can be used to reach the translocator pore, and this mechanism appears to be conserved among different T3SS-dependent pathogens. PMID:28351918

  19. 10 CFR 1016.34 - Accountability for Secret Restricted Data.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Accountability for Secret Restricted Data. 1016.34 Section 1016.34 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) SAFEGUARDING OF RESTRICTED DATA Control of Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents...

  20. New Construction of Group Secret Handshakes Based on Pairings

    NASA Astrophysics Data System (ADS)

    Zhou, Lan; Susilo, Willy; Mu, Yi

    In a secret handshake protocol, an honest member in the group will never reveal his group affiliation unless the other party is a valid member of the same group. However, most prior work of secret handshake are for 2-party secret handshakes. Tsudik and Xu extended the notion of secret handshake to a multi-party setting in 2005. Unfortunately, this seminal work is rather inefficient, since they consider a generic construction of such a scheme. Following this work, Jarecki et al. proposed an efficient solution to multi-party secret handshake. The aim of this paper is twofold. Firstly, we show that Jarecki et al.'s scheme has some drawbacks and therefore the scheme does not fulfill the security requirements of secret handshake. Secondly, we present a new construction of the group secret handshake scheme. In a group secret handshake protocol, a valid member in the group should never reveals his group affiliation unless all the other parties are valid members of the same group. In other words, if a handshake among this group of parties fails, the identities of every involved parties will not be disclosed. We then show that our scheme is secure under the bilinear Diffie-Hellman assumption and decisional bilinear Diffie-Hellman assumption in the random oracle model.

  1. Secrets and Misperceptions: The Creation of Self-Fulfilling Illusions

    PubMed Central

    Cowan, Sarah K.

    2015-01-01

    This study examines who hears what secrets, comparing two similar secrets-one that is highly stigmatized and one that is less so. Using a unique survey representative of American adults and intake forms from a medical clinic, I document marked differences in who hears these secrets. People who are sympathetic to the stigmatizing secret are more likely to hear of it than those who may react negatively. This is a consequence of people not just selectively disclosing their own secrets but selectively sharing others’ as well. As a result, people in the same social network will be exposed to and influenced by different information about those they know and hence experience that network differently. When people effectively exist in networks tailored by others not to offend, then the information they hear tends to be that of which they already approve. Were they to hear secrets they disapproved of, then their attitudes might change, but they are less likely to hear those secrets. As such, the patterns of secret hearing contribute to a stasis in public opinion. PMID:26082932

  2. Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets.

    PubMed

    Reissaus, Christopher A; Piston, David W

    2017-04-01

    Misregulated hormone secretion from the islet of Langerhans is central to the pathophysiology of diabetes. Although insulin plays a key role in glucose regulation, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from α-cells are still unclear. We used pseudoislets reconstituted from dispersed islet cells to study α-cells with and without various indirect effects from other islet cells. Dispersed islet cells secrete aberrant levels of glucagon and insulin at basal and elevated glucose levels. When cultured, murine islet cells reassociate to form pseudoislets, which recover normal glucose-regulated hormone secretion, and human islet cells follow a similar pattern. We created small (∼40-µm) pseudoislets using all of the islet cells or only some of the cell types, which allowed us to characterize novel aspects of regulated hormone secretion. The recovery of regulated glucagon secretion from α-cells in small pseudoislets depends upon the combined action of paracrine factors, such as insulin and somatostatin, and juxtacrine signals between EphA4/7 on α-cells and ephrins on β-cells. Although these signals modulate different pathways, both appear to be required for proper inhibition of glucagon secretion in response to glucose. This improved understanding of the modulation of glucagon secretion can provide novel therapeutic routes for the treatment of some individuals with diabetes. © 2017 by the American Diabetes Association.

  3. Quantum secret sharing schemes and reversibility of quantum operations

    SciTech Connect

    Ogawa, Tomohiro; Sasaki, Akira; Iwamoto, Mitsugu; Yamamoto, Hirosuke

    2005-09-15

    Quantum secret sharing schemes encrypting a quantum state into a multipartite entangled state are treated. The lower bound on the dimension of each share given by Gottesman [Phys. Rev. A 61, 042311 (2000)] is revisited based on a relation between the reversibility of quantum operations and the Holevo information. We also propose a threshold ramp quantum secret sharing scheme and evaluate its coding efficiency.

  4. Secrets and Misperceptions: The Creation of Self-Fulfilling Illusions.

    PubMed

    Cowan, Sarah K

    2014-11-01

    This study examines who hears what secrets, comparing two similar secrets-one that is highly stigmatized and one that is less so. Using a unique survey representative of American adults and intake forms from a medical clinic, I document marked differences in who hears these secrets. People who are sympathetic to the stigmatizing secret are more likely to hear of it than those who may react negatively. This is a consequence of people not just selectively disclosing their own secrets but selectively sharing others' as well. As a result, people in the same social network will be exposed to and influenced by different information about those they know and hence experience that network differently. When people effectively exist in networks tailored by others not to offend, then the information they hear tends to be that of which they already approve. Were they to hear secrets they disapproved of, then their attitudes might change, but they are less likely to hear those secrets. As such, the patterns of secret hearing contribute to a stasis in public opinion.

  5. Childhood's Secrets: Intimacy, Privacy, and the Self Reconsidered.

    ERIC Educational Resources Information Center

    Van Manen, Max; Levering, Bas

    The prevailing view of secrets as undesirable or unhealthy is challenged in this exploration of the meaning and significance of secrecy. As a crucial dimension of human development, secrets lead to a child's awareness of inner space and external worlds. This in turn leads to the development of a sense of self, personal responsibility, autonomy,…

  6. The Availability of "Trade Secret" Protection for University Research.

    ERIC Educational Resources Information Center

    Shockley, Pat

    1994-01-01

    Instances in which federal patent or copyright law may be too rigid or limited to protect university research are discussed, and the applicability of trade-secrets law is assessed, particularly under the Freedom of Information Act. Differential treatment of trade secrets under state laws is considered. (MSE)

  7. The Availability of "Trade Secret" Protection for University Research.

    ERIC Educational Resources Information Center

    Shockley, Pat

    1994-01-01

    Instances in which federal patent or copyright law may be too rigid or limited to protect university research are discussed, and the applicability of trade-secrets law is assessed, particularly under the Freedom of Information Act. Differential treatment of trade secrets under state laws is considered. (MSE)

  8. Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium

    SciTech Connect

    Pratt, A.D.; Clancy, G.; Welsh, M.J.

    1986-08-01

    Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium the authors found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. The observation that mucosal 8-phenyletheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.

  9. Nightshade Wound Secretion: The World's Simplest Extrafloral Nectar?

    PubMed

    Heil, Martin

    2016-08-01

    Wounded nightshade leaves secrete a sugary liquid that, like extrafloral nectar (EFN), attracts ants as defence against herbivores. The secretion of these droplets requires no detectable nectary tissue, showing how little it takes to produce a functioning nectary. Easy de novo formation of extrafloral nectaries explains their 'scattered' phylogenetic distribution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Extrafloral nectar secretion from wounds of Solanum dulcamara.

    PubMed

    Lortzing, Tobias; Calf, Onno W; Böhlke, Marlene; Schwachtje, Jens; Kopka, Joachim; Geuß, Daniel; Kosanke, Susanne; van Dam, Nicole M; Steppuhn, Anke

    2016-04-25

    Plants usually close wounds rapidly to prevent infections and the loss of valuable resources such as assimilates(1). However, herbivore-inflicted wounds on the bittersweet nightshade Solanum dulcamara appear not to close completely and produce sugary wound secretions visible as droplets. Many plants across the plant kingdom secrete sugary nectar from extrafloral nectaries(2) to attract natural enemies of herbivores for indirect defence(3,4). As ants forage on wound edges of S. dulcamara in the field, we hypothesized that wound secretions are a form of extrafloral nectar (EFN). We show that, unlike EFN from known nectaries, wound secretions are neither associated with any specific structure nor restricted to certain locations. However, similar to EFN, they are jasmonate-inducible and the plant controls their chemical composition. Wound secretions are attractive for ants, and application of wound secretion mimics increases ant attraction and reduces herbivory on S. dulcamara plants in a natural population. In greenhouse experiments, we reveal that ants can defend S. dulcamara from two of its native herbivores, slugs and flea beetle larvae. Since nectar is defined by its ecological function as a sugary secretion involved in interactions with animals(5), such 'plant bleeding' could be a primitive mode of nectar secretion exemplifying an evolutionary origin of structured extrafloral nectaries.

  11. Lateral nasal gland secretion in the anaesthetized dog.

    PubMed Central

    Wells, U; Widdicombe, J G

    1986-01-01

    The effects of pharmacological and nervous stimuli on the flow of secretion from the dog lateral nasal gland following catheterization are described. Drugs were injected close-arterially into the arterial supply to the nose, or intravenously. Cholinergic agonists (pilocarpine, methacholine), given intravenously (I.V.) or intra-arterially (I.A.), and stimulation of the vidian nerve produced a copious flow of secretion which was blocked by atropine. The adrenoceptor agonists phenylephrine (alpha) and salbutamol (beta 2), given I.V. or I.A., and stimulation of the vagosympathetic nerve produced a small but consistent flow of secretion. Histamine (50 micrograms), substance P (0.1 micrograms) and prostaglandin E1 (1-5 micrograms), injected I.A., produced small flows of secretion. Bradykinin (25 ng-50 micrograms), 5-hydroxytryptamine (100 ng-50 micrograms) and vasoactive intestinal peptide (VIP) (10 ng-50 micrograms) did not cause secretion. The total protein content, the composition of secretions as revealed by sodium dodecyl sulphate-polyacrylamide agarose gel electrophoresis, and changes in [Na] and [K] in relation to flow of secretion are described. Differences in ion and protein concentrations, and in protein composition, are described for vidian nerve-induced and vagosympathetically induced secretions. Electron microscopy revealed that the gland contains serous cells in the secretory region, and ducts morphologically similar to the intercalated, striated and excretory ducts of salivary glands. Images Fig. 5 Fig. 6 PMID:3746694

  12. Enhanced secretion of natto phytase by Bacillus subtilis.

    PubMed

    Tsuji, Shogo; Tanaka, Kosei; Takenaka, Shinji; Yoshida, Ken-ichi

    2015-01-01

    Phytases comprise a group of phosphatases that trim inorganic phosphates from phytic acid (IP6). In this study, we aimed to achieve the efficient secretion of phytase by Bacillus subtilis. B. subtilis laboratory standard strain 168 and its derivatives exhibit no phytase activity, whereas a natto starter secretes phytase actively. The natto phytase gene was cloned into strain RIK1285, a protease-defective derivative of 168, to construct a random library of its N-terminal fusions with 173 different signal peptides (SPs) identified in the 168 genome. The library was screened to assess the efficiency of phytase secretion based on clear zones around colonies on plates, which appeared when IP6 was hydrolyzed. The pbp SP enhanced the secretion of the natto phytase most efficiently, i.e. twice that of the original SP. Thus, the secreted natto phytase was purified and found to remove up to 3 phosphates from IP6.

  13. Secretion Systems Used by Bacteria to Subvert Host Functions.

    PubMed

    Rapisarda, Chiara; Fronzes, Rémi

    2017-09-06

    In this review we examine the use of secretion systems by bacteria to subvert host functions. Bacteria have evolved multiple systems to interact with and overcome their eukaryotic host and other prokaryotes. Secretion systems are required for the release of several effectors through the bacterial membrane(s) into the extracellular space or directly into the cytoplasm of the host. We review the secretion systems of Gram-positive and Gram-negative bacteria and describe briefly the structural composition of the seven secretion systems that have been associated with increased virulence through subversion of host functions. Some of the effects of such systems on eukaryotic host processes have been studied extensively. We also describe the best-characterized effectors of each secretion system to give an overview of the molecular mechanisms employed by bacteria to hide from the immune system and convert eukaryotic cells into optimal ecological niches for their replication.

  14. Secret key distillation from shielded two-qubit states

    SciTech Connect

    Bae, Joonwoo

    2010-05-15

    The quantum states corresponding to a secret key are characterized using the so-called private states, where the key part consisting of a secret key is shielded by the additional systems. Based on the construction, it was shown that a secret key can be distilled from bound entangled states. In this work, I consider the shielded two-qubit states in a key-distillation scenario and derive the conditions under which a secret key can be distilled using the recurrence protocol or the two-way classical distillation, advantage distillation together with one-way postprocessing. From the security conditions, it is shown that a secret key can be distilled from bound entangled states in a much wider range. In addition, I consider the case that in which white noise is added to quantum states and show that the classical distillation protocol still works despite a certain amount of noise although the recurrence protocol does not.

  15. J774 macrophages secrete antibiotics via organic anion transporters.

    PubMed

    Cao, C X; Silverstein, S C; Neu, H C; Steinberg, T H

    1992-02-01

    Mouse macrophages and J774 macrophage-like cells express probenecid-inhibitable organic anion transporters that remove anionic dyes from the cells' cytoplasmic matrix and secrete these dyes into the extracellular medium. The present studies show that these transporters also secrete antibiotics from J774 macrophages. Penicillin G permeates J774 cells poorly, but after it was introduced into the cell cytoplasm, it was secreted in a probenecid-inhibitable fashion. The quinolone norfloxacin enters macrophages readily. Probenecid retarded the secretion of intracellular norfloxacin by J774 cells and enhanced norfloxacin accumulation three- to fourfold. Thus the intracellular accumulation of norfloxacin is regulated in part by organic anion transporters that secrete norfloxacin (and penicillin G) from J774 cells. This transport process may have clinical significance, as fluoroquinolones inhibit growth of intracellular pathogens such as mycobacteria and Brucella organisms in vitro but fail to arrest infections with these organisms in vivo.

  16. STUDIES ON THE DEVELOPMENT OF TOXICITY IN INTESTINAL SECRETION

    PubMed Central

    Davis, David M.; Stone, Harvey B.

    1917-01-01

    1. Intestinal secretion, collected by the method described in this paper, is non-toxic when fresh. 2. This secretion, when heated immediately to 90–95°C. and kept sterile, remains non-toxic. 3. This secretion, when not heated, remains non-toxic when kept under chloroform and toluene, even if incubated at 37°C. 4. This secretion, when not heated, but collected in a sterile flask, becomes toxic upon incubating 18 hours, producing symptoms like those of closed loop fluid. 5. The secretion, when treated with chloroform and toluene, and later incubated for 18 hours, after these preservatives have been removed by distillation at 60°C., does not produce lesions typical of closed loop fluid. PMID:19868174

  17. Quantum secret sharing with identity authentication based on Bell states

    NASA Astrophysics Data System (ADS)

    Abulkasim, Hussein; Hamad, Safwat; Khalifa, Amal; El Bahnasy, Khalid

    Quantum secret sharing techniques allow two parties or more to securely share a key, while the same number of parties or less can efficiently deduce the secret key. In this paper, we propose an authenticated quantum secret sharing protocol, where a quantum dialogue protocol is adopted to authenticate the identity of the parties. The participants simultaneously authenticate the identity of each other based on parts of a prior shared key. Moreover, the whole prior shared key can be reused for deducing the secret data. Although the proposed scheme does not significantly improve the efficiency performance, it is more secure compared to some existing quantum secret sharing scheme due to the identity authentication process. In addition, the proposed scheme can stand against participant attack, man-in-the-middle attack, impersonation attack, Trojan-horse attack as well as information leaks.

  18. Cropping and noise resilient steganography algorithm using secret image sharing

    NASA Astrophysics Data System (ADS)

    Juarez-Sandoval, Oswaldo; Fierro-Radilla, Atoany; Espejel-Trujillo, Angelina; Nakano-Miyatake, Mariko; Perez-Meana, Hector

    2015-03-01

    This paper proposes an image steganography scheme, in which a secret image is hidden into a cover image using a secret image sharing (SIS) scheme. Taking advantage of the fault tolerant property of the (k,n)-threshold SIS, where using any k of n shares (k≤n), the secret data can be recovered without any ambiguity, the proposed steganography algorithm becomes resilient to cropping and impulsive noise contamination. Among many SIS schemes proposed until now, Lin and Chan's scheme is selected as SIS, due to its lossless recovery capability of a large amount of secret data. The proposed scheme is evaluated from several points of view, such as imperceptibility of the stegoimage respect to its original cover image, robustness of hidden data to cropping operation and impulsive noise contamination. The evaluation results show a high quality of the extracted secret image from the stegoimage when it suffered more than 20% cropping or high density noise contamination.

  19. Threshold secret sharing scheme based on phase-shifting interferometry.

    PubMed

    Deng, Xiaopeng; Shi, Zhengang; Wen, Wei

    2016-11-01

    We propose a new method for secret image sharing with the (3,N) threshold scheme based on phase-shifting interferometry. The secret image, which is multiplied with an encryption key in advance, is first encrypted by using Fourier transformation. Then, the encoded image is shared into N shadow images based on the recording principle of phase-shifting interferometry. Based on the reconstruction principle of phase-shifting interferometry, any three or more shadow images can retrieve the secret image, while any two or fewer shadow images cannot obtain any information of the secret image. Thus, a (3,N) threshold secret sharing scheme can be implemented. Compared with our previously reported method, the algorithm of this paper is suited for not only a binary image but also a gray-scale image. Moreover, the proposed algorithm can obtain a larger threshold value t. Simulation results are presented to demonstrate the feasibility of the proposed method.

  20. Regulation of insulin secretion and proinsulin biosynthesis by succinate.

    PubMed

    Attali, Veronique; Parnes, Marcela; Ariav, Yafa; Cerasi, Erol; Kaiser, Nurit; Leibowitz, Gil

    2006-11-01

    Succinate stimulates insulin secretion and proinsulin biosynthesis. We studied the effects of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-modulating pathways on glucose- and succinate-stimulated insulin secretion and proinsulin biosynthesis in the rat and the insulin-resistant Psammomys obesus. Disruption of the anaplerotic pyruvate/malate shuttle by phenylacetic acid inhibited glucose- and succinate-stimulated insulin secretion and succinate-stimulated proinsulin biosynthesis in both species. In contrast, phenylacetic acid failed to inhibit glucose-stimulated proinsulin biosynthesis in P. obesus islets. Inhibition of the NADPH-consuming enzyme neuronal nitric oxide synthase (nNOS) with l-N(G)-nitro-l-arginine methyl ester or with N(G)-monomethyl-l-arginine(G) doubled succinate-stimulated insulin secretion in rat islets, suggesting that succinate- and nNOS-derived signals interact to regulate insulin secretion. In contrast, nNOS inhibition had no effect on succinate-stimulated proinsulin biosynthesis in both species. In P. obesus islets, insulin secretion was not stimulated by succinate in the absence of glucose, whereas proinsulin biosynthesis was increased 5-fold. Conversely, under stimulating glucose levels, succinate doubled insulin secretion, indicating glucose-dependence. Pyruvate ester and inhibition of nNOS partially mimicked the permissive effect of glucose on succinate-stimulated insulin secretion, suggesting that anaplerosis-derived signals render the beta-cells responsive to succinate. We conclude that beta-cell anaplerosis via pyruvate carboxylase is important for glucose- and succinate-stimulated insulin secretion and for succinate-stimulated proinsulin biosynthesis. In P. obesus, pyruvate/malate shuttle dependent and independent pathways that regulate proinsulin biosynthesis coexist; the latter can maintain fuel stimulated biosynthetic activity when the succinate-dependent pathway is inhibited. nNOS signaling is a negative regulator