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Sample records for 6-kda early secreted

  1. Trading secrets: Jews and the early modern quest for clandestine knowledge.

    PubMed

    Jütte, Daniel

    2012-12-01

    This essay explores the significance and function of secrecy and secret sciences in Jewish-Christian relations and in Jewish culture in the early modern period. It shows how the trade in clandestine knowledge and the practice of secret sciences became a complex, sometimes hazardous space for contact between Jews and Christians. By examining this trade, the essay clarifies the role of secrecy in the early modern marketplace of knowledge. The attribution of secretiveness to Jews was a widespread topos in early modern European thought. However, relatively little is known about the implications of such beliefs in science or in daily life. The essay pays special attention to the fact that trade in secret knowledge frequently offered Jews a path to the center of power, especially at court. Furthermore, it becomes clear that the practice of secret sciences, the trade in clandestine knowledge, and a mercantile agenda were often inextricably interwoven. Special attention is paid to the Italian-Jewish alchemist, engineer, and entrepreneur Abramo Colorni (ca. 1544-1599), whose career illustrates the opportunities provided by the marketplace of secrets at that time. Much scholarly (and less scholarly) attention has been devoted to whether and what Jews "contributed" to what is commonly called the "Scientific Revolution." This essay argues that the question is misdirected and that, instead, we should pay more attention to the distinctive opportunities offered by the early modern economy of secrecy. PMID:23488236

  2. Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion

    PubMed Central

    Kenny, Hilary A.; Chiang, Chun-Yi; White, Erin A.; Schryver, Elizabeth M.; Habis, Mohammed; Romero, Iris L.; Ladanyi, Andras; Penicka, Carla V.; George, Joshy; Matlin, Karl; Montag, Anthony; Wroblewski, Kristen; Yamada, S. Diane; Mazar, Andrew P.; Bowtell, David; Lengyel, Ernst

    2014-01-01

    Ovarian cancer (OvCa) metastasizes to organs in the abdominal cavity, such as the omentum, which are covered by a single layer of mesothelial cells. Mesothelial cells are generally thought to be “bystanders” to the metastatic process and simply displaced by OvCa cells to access the submesothelial extracellular matrix. Here, using organotypic 3D cultures, we found that primary human mesothelial cells secrete fibronectin in the presence of OvCa cells. Moreover, we evaluated the tumor stroma of 108 human omental metastases and determined that fibronectin was consistently overexpressed in these patients. Blocking fibronectin production in primary mesothelial cells in vitro or in murine models, either genetically (fibronectin 1 floxed mouse model) or via siRNA, decreased adhesion, invasion, proliferation, and metastasis of OvCa cells. Using a coculture model, we determined that OvCa cells secrete TGF-β1, which in turn activates a TGF-β receptor/RAC1/SMAD-dependent signaling pathway in the mesothelial cells that promotes a mesenchymal phenotype and transcriptional upregulation of fibronectin. Additionally, blocking α5 or β1 integrin function with antibodies reduced metastasis in an orthotopic preclinical model of OvCa metastasis. These findings indicate that cancer-associated mesothelial cells promote colonization during the initial steps of OvCa metastasis and suggest that mesothelial cells actively contribute to metastasis. PMID:25202979

  3. Parietal endoderm secreted S100A4 promotes early cardiomyogenesis in embryoid bodies

    SciTech Connect

    Stary, Martina; Schneider, Mikael; Sheikh, Soren P.; Weitzer, Georg . E-mail: georg.weitzer@meduniwien.ac.at

    2006-05-05

    Cardiomyogenesis is influenced by factors secreted by anterior-lateral and extra-embryonic endoderm. Differentiation of embryonic stem cells in embryoid bodies allows to study the influence of growth factors on cardiomyogenesis. By these means SPARC was identified as a new factor enhancing cardiomyogenesis [M. Stary, W. Pasteiner, A. Summer, A. Hrdina, A. Eger, G. Weitzer, Parietal endoderm secreted SPARC promotes early cardiomyogenesis in vitro, Exp. Cell Res. 310 (2005) 331-341]. Here we report a similar and new function for S100A4, a calcium-binding protein of the EF-hand type. S100A4 is secreted by parietal endoderm and promotes early differentiation and proliferation of cardiomyocytes. Oligomeric S100A4 supports cardiomyogenesis in a concentration-dependent manner, whereas inhibition of autocrine S100A4 severely attenuates cardiomyogenesis. S100A4 specifically influences transcription in differentiating cardiomyocytes, as evident from increased expression of cardiac transcription factor genes nkx2.5 and mef2C. These data suggest that S100A4, like SPARC, plays a supportive role in early in vitro cardiomyogenesis.

  4. Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve intestina...

  5. Foetal programming and cortisol secretion in early childhood: A meta-analysis of different programming variables.

    PubMed

    Pearson, Jessica; Tarabulsy, George M; Bussières, Eve-Line

    2015-08-01

    It is widely recognized that different events may take place in the intrauterine environment that may influence later developmental outcome. Scholars have long postulated that maternal prenatal stress, alcohol or drug use, and cigarette smoking may impact foetal formation of the hypothalamus-pituitary-adrenal (HPA) axis, which may later influence different aspects of early childhood socioemotional and cognitive development. However, results linking each of these factors with child cortisol secretion have been mixed. The current meta-analysis examined the relation between each of these programming variables and child cortisol secretion in studies conducted up to December 31st, 2012. Studies were included if they were conducted prior to child age 60 months, and if they reported an index of effect size linking either maternal prenatal stress, alcohol or drug use, or cigarette smoking with an index of child cortisol secretion. In total, 19 studies (N=2260) revealed an average effect size of d=.36 (p<.001). Moderator analyses revealed that greater effect sizes could be traced to maternal alcohol use, to the use of retrospective research methodology, where mothers are questioned after childbirth regarding programming variables, and to the use of baseline measures of cortisol secretion, as opposed to recovery measures. Discussion focuses on processes that link the environment to foetal development and how both are linked to later adaptation. PMID:26209745

  6. Cortisol Secretion and Change in Sleep Problems in Early Childhood: Moderation by Maternal Overcontrol

    PubMed Central

    Kiel, Elizabeth J.; Hummel, Alexandra C.; Luebbe, Aaron M.

    2015-01-01

    Childhood sleep problems are prevalent and relate to a wide range of negative psychological outcomes. However, it remains unclear how biological processes, such as HPA activity, may predict sleep problems over time in childhood in the context of certain parenting environments. Fifty-one mothers and their 18–20 month-old toddlers participated in a short-term longitudinal study assessing how shared variance among morning levels, diurnal change, and nocturnal change in toddlers’ cortisol secretion predicted change in sleep problems in the context of maternal overprotection and critical control. A composite characterized by low variability in, and, to a lesser extent, high morning values of cortisol, predicted increasing sleep problems from age 2 to age 3 when mothers reported high critical control. Results suggest value in assessing shared variance among different indices of cortisol secretion patterns and the interaction between cortisol and the environment in predicting sleep problems in early childhood. PMID:25766262

  7. School-Based Early Childhood Centers: Secrets of Success from Early Innovators.

    ERIC Educational Resources Information Center

    Jewett, Janet L.; Katzev, Aphra

    School-based early childhood centers have the potential for responding effectively to a broad range of child and family needs and to society's demands for more effective schools. They have four defining features: (1) implementation of quality programs and developmentally appropriate practices for young children through age eight; (2) families as…

  8. Identification of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival.

    PubMed

    Döhmer, Peter H; Valguarnera, Ezequiel; Czibener, Cecilia; Ugalde, Juan E

    2014-03-01

    Brucella abortus, the aetiological agent of bovine brucellosis, is an intracellular pathogen whose virulence is completely dependent on a type IV secretion system. This secretion system translocates effector proteins into the host cell to modulate the intracellular fate of the bacterium in order to establish a secure niche were it actively replicates. Although much has been done in understanding how this secretion system participates in the virulence process, few effector proteins have been identified to date. We describe here the identification of a type IV secretion substrate (SepA) that is only present in Brucella spp. and has no detectable homology to known proteins. This protein is secreted in a virB-dependent manner in a two-step process involving a periplasmic intermediate and secretion is necessary for its function. The deletion mutant showed a defect in the early stages of intracellular replication in professional and non-professional phagocytes although it invades the cells more efficiently than the wild-type parental strain. Our results indicate that, even though the mutant was more invasive, it had a defect in excluding the lysosomal marker Lamp-1 and was inactivated more efficiently during the early phases of the intracellular life cycle. PMID:24119283

  9. Identification of ABCC8 as a contributory gene to impaired early-phase insulin secretion in NZO mice.

    PubMed

    Andrikopoulos, Sofianos; Fam, Barbara C; Holdsworth, Anita; Visinoni, Sherley; Ruan, Zheng; Stathopoulos, Maria; Thorburn, Anne W; Joannides, Christos N; Cancilla, Michael; Balmer, Lois; Proietto, Joseph; Morahan, Grant

    2016-01-01

    Type 2 diabetes (T2D) is associated with defective insulin secretion, which in turn contributes to worsening glycaemic control and disease progression. The genetic cause(s) associated with impaired insulin secretion in T2D are not well elucidated. Here we used the polygenic New Zealand Obese (NZO) mouse model, which displays all the cardinal features of T2D including hyperglycaemia to identify genes associated with β-cell dysfunction. A genome-wide scan identified a major quantitative trait locus (QTL) on chromosome 7 associated with defective glucose-mediated insulin secretion. Using congenic strains, the locus was narrowed to two candidate genes encoding the components of the KATP channel: Abcc8 (SUR1) and Kcnj11 (Kir6.2). The NZO Abcc8 allele was associated with a ∼211 bp deletion in its transcript and reduced expression of SUR1. Transgenic NZO mice were generated that expressed the WT Abcc8/Kcnj11 genes and displayed significant improvements in early-phase glucose-mediated insulin secretion and glucose tolerance, confirming Abcc8 as a causative gene. Importantly, we showed that despite improving β-cell function in the NZO transgenic mice, there was no enhancement of insulin sensitivity or body weight. This study provides evidence for a role of Abcc8 in early-phase glucose-mediated insulin secretion and validates this gene as a contributor to β-cell dysfunction in T2D. PMID:26493453

  10. Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity.

    PubMed

    McMillen, I C; Edwards, L J; Duffield, J; Muhlhausler, B S

    2006-03-01

    A series of epidemiological, clinical and experimental studies have shown that there are associations between the fetal and neonatal nutritional environment and the amount and distribution of adipose tissue in adult life. This review considers the evidence for these relationships and discusses the potential impact of the prenatal nutritional experience on the development of the endocrine and neuroendocrine systems that regulate energy balance, with a particular emphasis on the role of the adipocyte-derived hormone, leptin. In the rodent, leptin derived from the mother may exert an important influence on the development of the appetite regulatory neural network and on the subsequent regulation of leptin synthesis and the risk for obesity in the offspring. In species such as the human and sheep, there is also recent evidence that the synthesis and secretion of adipocyte-derived hormones, such as leptin, are regulated in fetal life. Furthermore, the hypothalamic neuropeptides that regulate energy intake and expenditure in adult life are also present within the fetal brain and may be regulated by the prevailing level of maternal and hence fetal nutrient and hormonal signals, including leptin. This work is important in determining those initiating mechanisms within the 'fat-brain' axis in early life that precede the development of adult obesity. PMID:16514185

  11. The marine bacteria Shewanella frigidimarina NCIMB400 upregulates the type VI secretion system during early biofilm formation.

    PubMed

    Linares, Denis; Jean, Natacha; Van Overtvelt, Perrine; Ouidir, Tassadit; Hardouin, Julie; Blache, Yves; Molmeret, Maëlle

    2016-02-01

    Shewanella sp. are facultative anaerobic Gram-negative bacteria, extensively studied for their electron transfer ability. Shewanella frigidimarina has been detected and isolated from marine environments, and in particular, from biofilms. However, its ability to adhere to surfaces and form a biofilm is poorly understood. In this study, we show that the ability to adhere and to form a biofilm of S. frigidimarina NCIMB400 is significantly higher than that of Shewanella oneidensis in our conditions. We also show that this strain forms a biofilm in artificial seawater, whereas in Luria-Bertani, this capacity is reduced. To identify proteins involved in early biofilm formation, a proteomic analysis of sessile versus planktonic membrane-enriched fractions allowed the identification of several components of the same type VI secretion system gene cluster: putative Hcp1 and ImpB proteins as well as a forkhead-associated domain-containing protein. The upregulation of Hcp1 a marker of active translocation has been confirmed using quantitative reverse transcription polymerase chain reaction. Our data demonstrated the presence of a single and complete type VI secretion system in S. frigidimarina NCIMB400 genome, upregulated in sessile compared with planktonic conditions. The fact that three proteins including the secreted protein Hcp1 have been identified may suggest that this type VI secretion system is functional. PMID:26617163

  12. HrcQ Provides a Docking Site for Early and Late Type III Secretion Substrates from Xanthomonas

    PubMed Central

    Lorenz, Christian; Hausner, Jens; Büttner, Daniela

    2012-01-01

    Pathogenicity of many Gram-negative bacteria depends on a type III secretion (T3S) system which translocates bacterial effector proteins into eukaryotic cells. The membrane-spanning secretion apparatus is associated with a cytoplasmic ATPase complex and a predicted cytoplasmic (C) ring structure which is proposed to provide a substrate docking platform for secreted proteins. In this study, we show that the putative C ring component HrcQ from the plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria is essential for bacterial pathogenicity and T3S. Fractionation studies revealed that HrcQ localizes to the cytoplasm and associates with the bacterial membranes under T3S-permissive conditions. HrcQ binds to the cytoplasmic T3S-ATPase HrcN, its predicted regulator HrcL and the cytoplasmic domains of the inner membrane proteins HrcV and HrcU. Furthermore, we observed an interaction between HrcQ and secreted proteins including early and late T3S substrates. HrcQ might therefore act as a general substrate acceptor site of the T3S system and is presumably part of a larger protein complex. Interestingly, the N-terminal export signal of the T3S substrate AvrBs3 is dispensable for the interaction with HrcQ, suggesting that binding of AvrBs3 to HrcQ occurs after its initial targeting to the T3S system. PMID:23226460

  13. Sex-dependent differences in the effect of early weaning on the chosen hormones secretion in sheep during the postnatal transition to puberty--preliminary results.

    PubMed

    Cieślak, M; Chmielewska, N; Romanowicz, K; Młynarczuk, J; Wańkowska, M

    2015-01-01

    The influence of early weaning on the cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH) secretion in lambs of both sexes and testosterone (T4) level in male lambs during the postnatal transition to puberty was investigated by radioimmunoassay. It was hypothesized that this influence is long-term and sexually dimorphic. Hence, the effect of weaning at 5 weeks of age in comparison with the weaning at 9 weeks of age on hormone concentra- tions in peripheral blood plasma of 5-, 9-, 12-, and 16-week-old lambs of both sexes was investigated. The cortisol concentrations were greater (P < 0.05) in control and early weaned female lambs than in male lambs at investigated stages. Weaning at 5 weeks of age resulted in the lover (P < 0.05) cortisol secretion in male lambs in contrast to the greater (P < 0.05) cortisol secretion in female lambs at 16 weeks of age. Weaning at 5 weeks of age stimulated (P < 0.001) the FSH secretion, but reduced (P < 0.001) the LH, GH and T4 secretion in 16-week-old male lambs. In female lambs early weaning inhibited (P < 0.05) the FSH secretion at 9 weeks of age, LH secretion after 9 weeks of age and GH secretion after 12 weeks of age. Thus, early weaning results in the sexually dimorphic stress reaction that is more potent and long-lasting in female in contrast to male lambs. This maternal deprivation stress contributes to the inhibition of LH and GH secretion in lambs of both sexes and T4 secretion in male lambs during the postnatal transition to puberty. PMID:25928912

  14. Secretion of inhibin beta A by endoderm cultured from early embryonic chicken.

    PubMed

    Kokan-Moore, N P; Bolender, D L; Lough, J

    1991-07-01

    Although several reports have indicated a role for endoderm in the regulation of heart development, the mechanism remains unknown. To begin characterization of endoderm-secreted proteins, explants from postgastrulation (Hamburger-Hamilton stage 5/6-8) chicken embryos were cultured in defined medium. Fluorography of SDS-PAGE gels revealed a pattern of synthesized, secreted proteins that was independent of time in culture or embryonic stage when explants were removed. Approximately 10 labeled bands were detected, the most prominent of which migrated at 17, 25, and 200 kDa. ELISA analysis revealed that while acidic and basic fibroblast growth factor-like antigens were barely detectable, fibronectin and inhibin beta A were very reactive. Western blot analysis verified the presence of fibronectin and, most remarkably, inhibin beta A, activin dimers of which have recently been implicated in Xenopus mesoderm induction (Smith, Price, Van Nimmen, and Huylebrock (1990). Nature 345, 729.) PMID:2060706

  15. Recombinant porcine epidermal growth factor-secreting Lactococcus lactis promotes the growth performance of early-weaned piglets

    PubMed Central

    2014-01-01

    Background Epidermal growth factor (EGF) is an important growth factor in regulation of cell proliferation, differentiation, survival and apoptosis. Studies showed that food-grade Lactococcus lactis (L. lactis) and NICE expression system have superior performance in exogenous protein expression. This study aimed to construct and express porcine EGF (pEGF), and use L. lactis as vehicle for producing and delivering pEGF. Furthermore, investigating biological activity of pEGF and exploring applications feasibility of combination effects of L. lactis and pEGF on early weaned piglets’ production. Results A recombinant Lactococcus lactis which produced and secreted pEGF at 1000 ng/ml in culture supernatant was generated. Secreted pEGF was a fully biologically active protein, as demonstrated by its capacity to stimulate L929 mouse fibroblast cell line proliferation in vitro. For in vivo study, forty piglets were randomly allocated to control, antibiotic control, empty vector-expressing L. lactis (LL-EV) and pEGF-secreting L. lactis (LL-pEGF). After 14 d of rearing, final body weight and average daily gain in LL-pEGF were greater (P < 0.05, 8.95 vs. 8.37 kg, 206.1 vs. 157.7 g/day, respectively) than those in control, but no significant differences between LL-pEGF, LL-EV and antibiotic control. Overall period average daily feed intake was higher in LL-pEGF, LL-EV and antibiotic control than in control (P < 0.05, 252.9, 255.6, 250.0, 207.3 g/day, respectively). No significant difference was observed on ADFI/ADG. LL-pEGF increased villous height in the duodenum, jejunum and ileum than in control and LL-EV (P < 0.05). Sucrase in the 3 intestinal segments, aminopeptidase A in the duodenum and Jejunum, aminopeptidase N and dipeptidase IV in the duodenum in LL-pEGF were higher than those in control (P < 0.05). Furthermore, Escherichia coli and Enterococcus counts decreased in the ileum and Lactobacillus increased in the ileum and cecum digesta in LL-pEGF compare with the

  16. The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

    PubMed

    Jiménez-Guerrero, Irene; Pérez-Montaño, Francisco; Monreal, José Antonio; Preston, Gail M; Fones, Helen; Vioque, Blanca; Ollero, Francisco Javier; López-Baena, Francisco Javier

    2015-07-01

    Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain. PMID:25775271

  17. [Oxytocin and syndrome of inappropriate secretion of antidiuretic neonatal hormone. Case report of early severe hyponatremia and literature review].

    PubMed

    Aldana-Valenzuela, Carlos; Prieto-Pantoja, José Alfredo; Hernández-Acevedo, Angélica

    2010-12-01

    This is a clinical case presentation of a full term newborn infant who suffered severe hyponatremia and early seizures, associated with maternal fluid overload with electrolyte free solutions and high doses of oxytocin for labor augmentation. Although this condition has been recognized since the 1960's with isolated reports, this particular case has features that needs further investigation, not only for the unsually severe hyponatremia, but most importantly we think, for the prominent signs of fluid retention, the infant had, that suggest excessive antidiuretic activity probably due to oxytocin. These findings are consistent with syndrome of inappropriate secretion of antidiuretic hormone. Although until now there is no proof that oxytocin by itself produces this syndrome. We think the association is possible in certain clinical circumstances, such as those found in this case. We also, briefly discussed the pathophysiology of perinatal hyponatremia, the neonatal treatment of this condition and the current guidelines for the women in labor. Hyponatremia should not be considered a benign condition, since in the neonate, it may affect brain function. PMID:21961376

  18. Profiles of mRNA expression for genes involved in implantation, early and middle phases of secretion stage in human endometrium.

    PubMed

    Maslova, M A; Smol'nikova, V Yu; Savilova, A M; Burmenskaya, O V; Bystritskii, A A; Tabolova, V K; Korneeva, I E; Demura, T A; Donnikov, A E

    2015-04-01

    The expression of mRNA of 36 genes involved in implantation was studied by reverse transcription and real-time PCR. Significant differences in mRNA expression during the early and middle stages of the secretion phase were detected for genes mmp7, vegf, il2m, il1β, il8, il18, tnfα, il10, tgfβ, igfbp2, etc. PMID:25894777

  19. SMAD1/5 Signaling in the Early Equine Placenta Regulates Trophoblast Differentiation and Chorionic Gonadotropin Secretion

    PubMed Central

    Cabrera-Sharp, Victoria; Read, Jordan E.; Richardson, Stephanie; Kowalski, Alycia A.; Antczak, Douglas F.; Cartwright, Judith E.; Mukherjee, Abir

    2014-01-01

    TGFβ superfamily proteins, acting via SMAD (Sma- and Mad-related protein)2/3 pathways, regulate placental function; however, the role of SMAD1/5/8 pathway in the placenta is unknown. This study investigated the functional role of bone morphogenetic protein (BMP)4 signaling through SMAD1/5 in terminal differentiation of primary chorionic gonadotropin (CG)-secreting trophoblast. Primary equine trophoblast cells or placental tissues were isolated from day 27–34 equine conceptuses. Detected by microarray, RT-PCR, and quantitative RT-PCR, equine chorionic girdle trophoblast showed increased gene expression of receptors that bind BMP4. BMP4 mRNA expression was 20- to 60-fold higher in placental tissues adjacent to the chorionic girdle compared with chorionic girdle itself, suggesting BMP4 acts primarily in a paracrine manner on the chorionic girdle. Stimulation of chorionic girdle-trophoblast cells with BMP4 resulted in a dose-dependent and developmental stage-dependent increase in total number and proportion of terminally differentiated binucleate cells. Furthermore, BMP4 treatment induced non-CG-secreting day 31 chorionic girdle trophoblast cells to secrete CG, confirming a specific functional response to BMP4 stimulation. Inhibition of SMAD2/3 signaling combined with BMP4 treatment further enhanced differentiation of trophoblast cells. Phospho-SMAD1/5, but not phospho-SMAD2, expression as determined by Western blotting was tightly regulated during chorionic girdle trophoblast differentiation in vivo, with peak expression of phospho-SMAD1/5 in vivo noted at day 31 corresponding to maximal differentiation response of trophoblast in vitro. Collectively, these experiments demonstrate the involvement of BMP4-dependent pathways in the regulation of equine trophoblast differentiation in vivo and primary trophoblast differentiation in vitro via activation of SMAD1/5 pathway, a previously unreported mechanism of TGFβ signaling in the mammalian placenta. PMID:24848867

  20. Inhibition of P450 aromatase enhances gonadotropin secretion in early and midpubertal boys: evidence for a pituitary site of action of endogenous E.

    PubMed

    Wickman, S; Dunkel, L

    2001-10-01

    In early pubertal boys, E concentrations are very low. We studied the role and site of action of endogenous E in the regulation of gonadotropin secretion in early and midpubertal boys by inhibiting the action of E with a potent and specific P450 aromatase inhibitor, letrozole. A total of 35 boys who were referred to us because of suspicion of delayed puberty were included in the study. The boys were in either early or midpuberty, and they composed 3 groups: 10 boys did not receive any treatment, 12 boys received T alone, and 13 boys received T and letrozole. In the untreated group during the 5-month follow-up, no changes were observed in 17beta-E2, T, basal gonadotropin, or inhibin B concentrations or in the GnRH-induced gonadotropin responses. In the T-treated group during the 5-month treatment, the T concentration increased by 55% (P < 0.05), and the 17beta-E2 concentration increased by 130% (P < 0.02). Concurrently, basal gonadotropin concentrations were suppressed, but the GnRH-induced gonadotropin responses and the inhibin B concentration remained unchanged. In the T- plus letrozole-treated group during the 5-month treatment, an increase in T concentration of 606% was observed (P < 0.001), but the 17beta-E2 concentration remained unchanged. The changes in the 17beta-E2 concentration within 5 months in the untreated and the T- plus letrozole-treated groups were different (P < 0.02), indicating significant inhibition of endogenous E synthesis during letrozole treatment. During the T plus letrozole treatment, basal gonadotropin concentration, the GnRH-induced LH response, and inhibin B concentration increased, and the GnRH-induced FSH response did not change significantly. Serum nocturnal gonadotropin pulses were determined in 5 boys treated with T and in 5 boys treated with T plus letrozole. In the T- plus letrozole-treated group, the nocturnal LH pulse amplitude increased, and the LH pulse frequency and interpulse interval remained unchanged. In conclusion, in

  1. A novel phage element of Salmonella enterica serovar Enteritidis P125109 contributes to accelerated type III secretion system 2-dependent early inflammation kinetics in a mouse colitis model.

    PubMed

    Vishwakarma, Vikalp; Periaswamy, Balamurugan; Bhusan Pati, Niladri; Slack, Emma; Hardt, Wolf-Dietrich; Suar, Mrutyunjay

    2012-09-01

    Salmonella enterica subsp. I serovar Enteritidis exhibits type III secretion system 2 (TTSS2)-dependent early colonization and inflammation kinetics faster than those of closely related S. enterica serovar Typhimurium. To investigate the accelerated TTSS-2-dependent pathogenic potential of S. Enteritidis, we focused on its genome. Results of a previously published comparative genomic study revealed the presence of mutually exclusive genes in both serovars. In this study, we investigated the roles of six S. Enteritidis-specific genes in vivo by using differential fluorescence induction (DFI) through putative gene-specific promoters. The promoter construct associated with the gene locus SEN1140 induced green fluorescent protein (GFP) expression in the gut lumen, lamina propria, mesenteric lymph nodes, and related systemic organs. To further investigate the potential role of SEN1140, we compared a SEN1140 deletion mutant with S. Typhimurium in a TTSS1-deficient background. Interestingly, the S. Enteritidis mutant lacking SEN1140 did not show the unique TTSS-2-dependent early colonization and inflammation kinetic phenotype of S. Typhimurium. Consistent with this result, complementation of SEN1140 restored the TTSS-2-dependent accelerated inflammatory potential of S. Enteritidis. This report presents a suitable screening strategy that uses a combination of DFI, fluorescence-activated cell sorting, quantitative PCR, and wild-type isogenic tagged-strain techniques to explore the unique roles of S. Enteritidis-specific genes in bacterial pathogenesis. PMID:22753379

  2. 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.

  3. Role of exosomes in the reproductive tract Oviductosomes mediate interactions of oviductal secretion with gametes/early embryo.

    PubMed

    Al-Dossary, Amal A; Martin-Deleon, Patricia A

    2016-01-01

    The oviductal epithelial membrane releases into the luminal environment extracellular vesicles (EVs) which are pleomorphic in nature and fall into two categories: exosomes and microvesicles. Both of these membrane vesicles are referred to as Oviductosomes (OVS), and to date have been identified in the murine and bovine species. Bovine EVs derived in vivo and from in vitro culture show differences in their protein cargo which includes CD9 and HSC70 biochemical markers and fertility-modulating proteins such as oviduct-specific glycoprotein (OVGP) and Plasma Membrane Ca(2+) ATPase 4 (PMCA4). PMCA4, an essential multifunctional sperm protein, is hormonally-regulated with elevated levels seen in proestrus/estrus. OVS deliver PMCA4 to sperm via a fusogenic mechanism involving the interaction between CD9 and integrins which are present on their surfaces. Studies of OVS are needed to determine the components of their cargoes and their interaction with oocytes and the very early embryo. Based on our present knowledge of their interaction with sperm, they are expected to play pivotal roles in regulating fertility and promise to inform the current IVF practice. PMID:27100506

  4. DNA methylation analysis of secreted frizzled-related protein 2 gene for the early detection of colorectal cancer in fecal DNA

    PubMed Central

    Babaei, Hadi; Mohammadi, Mohsen; Salehi, Rasoul

    2016-01-01

    Background: The early detection of colorectal cancer (CRC) with high sensitivity screening is essential for the reduction of cancer-specific mortality. Abnormally methylated genes that are responsible for the pathogenesis of cancers can be used as biomarkers for the detection of CRC. The methylation status of the secreted frizzled-related protein 2 (SFRP2) gene was evaluated for their use as a marker in the noninvasive detection of CRC. Materials and Methods: Methylation-specific polymerase chain reaction was performed to analyze the promoter CpG methylation of SFRP2 in the fecal DNA of 25 patients with CRC and 25 individuals exhibiting normal colonoscopy results. Results: Promoter methylation levels of SFRP2 in CRC patients and in healthy controls were 60% and 8%, respectively. Methylation of the SFRP2 promoter in fecal DNA is associated with the presence of colorectal tumors. Conclusion: Hence, the detection of aberrantly methylated DNA in fecal samples may present a promising, noninvasive screening method for CRC.

  5. The 6-Kilodalton Early Secreted Antigenic Target-Responsive, Asymptomatic Contacts of Tuberculosis Patients Express Elevated Levels of Interleukin-4 and Reduced Levels of Gamma Interferon

    PubMed Central

    Demissie, Abebech; Wassie, Liya; Abebe, Markos; Aseffa, Abraham; Rook, Graham; Zumla, Alimuddin; Andersen, Peter; Doherty, T. Mark

    2006-01-01

    It is well known that the majority of healthy individuals exposed to Mycobacterium tuberculosis do not become clinically ill. We have previously shown that in recently exposed healthy contacts of tuberculosis (TB) patients, a strong immune response to the M. tuberculosis 6-kDa early secreted antigenic target (ESAT-6) virulence factor correlated with a higher risk of subsequent disease, although the mechanism was unclear at that time. Inspired by recent reports that elevated expression of interleukin-4 (IL-4) in health care workers exposed to M. tuberculosis also correlated with a higher risk of their subsequently developing disease, we examined expression of IL-4, its competitive antagonist IL-4δ2, and gamma interferon (IFN-γ) in healthy household contacts of TB patients from Ethiopia. We then compared cytokine expression to their recognition of ESAT-6 (which is largely restricted to members of the tuberculosis complex and which serves as a reliable marker of infection) or to Ag85A (an antigen that is conserved among the mycobacteria and serves as a nonspecific control). Our study shows that in these recently exposed individuals, there is a correlation between a strong response to ESAT-6 and elevated expression of IL-4. Further, elevated expression of IL-4 is associated with lower expression of its antagonistic splice variant IL-4δ2 and with the Th1 cytokine IFN-γ, suggesting that in these at-risk individuals, immunity is skewed away from a protective Th1 response, even before the development of clinical symptoms. PMID:16622219

  6. Sustained Decrease of Early-Phase Insulin Secretion in Japanese Women with Gestational Diabetes Mellitus Who Developed Impaired Glucose Tolerance and Impaired Fasting Glucose Postpartum

    PubMed Central

    Katayama, Hiroko; Tachibana, Daisuke; Hamuro, Akihiro; Misugi, Takuya; Motoyama, Koka; Morioka, Tomoaki; Fukumoto, Shinya; Emoto, Masanori; Inaba, Masaaki; Koyama, Masayasu

    2015-01-01

    OBJECTIVE The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design. PATIENTS AND METHODS Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors. RESULTS Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. CONCLUSIONS Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves. PMID:26688669

  7. Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner.

    PubMed

    Chatterjee, Samit; Dwivedi, Ved Prakash; Singh, Yogesh; Siddiqui, Imran; Sharma, Pawan; Van Kaer, Luc; Chattopadhyay, Debprasad; Das, Gobardhan

    2011-11-01

    Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG) has been used as a tuberculosis (TB) vaccine since its development in 1921. BCG induces robust T helper 1 (Th1) immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb) infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6), expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1) exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1). However, TLR-2 knockout (TLR-2⁻/⁻) animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a) in dendritic cells (DCs), whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy. PMID:22102818

  8. Secret Places.

    ERIC Educational Resources Information Center

    Ridolfi, Kerry

    1997-01-01

    Argues that children are as deep as the ocean, with secret places inside of them waiting to be opened. Notes that it is powerful for students to learn they can make sense of the world through words, and describes inviting them into poetry as they read poetry, create poetry packets, and write and revise poems. (SR)

  9. 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…

  10. The product of Kaposi's sarcoma-associated herpesvirus immediate early gene K4.2 regulates immunoglobulin secretion and calcium homeostasis by interacting with and inhibiting pERP1.

    PubMed

    Wong, Lai-Yee; Brulois, Kevin; Toth, Zsolt; Inn, Kyung-Soo; Lee, Sun-Hwa; O'Brien, Kathryn; Lee, Hyera; Gao, Shou-Jiang; Cesarman, Ethel; Ensser, Armin; Jung, Jae U

    2013-11-01

    Chaperones are proteins that assist the noncovalent folding and assembly of macromolecular polypeptide chains, ultimately preventing the formation of nonfunctional or potentially toxic protein aggregates. Plasma cell-induced-endoplasmic reticulum (ER)-resident protein 1 (pERP1) is a cellular chaperone that is preferentially expressed in marginal-zone B cells and is highly upregulated during plasma cell differentiation. While initially identified as a dedicated factor for the assembly of secreted IgM, pERP1 has since been implicated in suppressing calcium mobilization, and its expression is misregulated in multiple tumors. A number of herpesvirus immediate early gene products play important roles in the regulation of viral gene expression and/or evasion of host immune responses. Here, we report that the Kaposi's sarcoma-associated herpesvirus (KSHV) immediate early viral gene K4.2 encodes an endoplasmic reticulum-localized protein that interacts with and inhibits pERP1. Consequently, K4.2 expression interfered with immunoglobulin secretion by delaying the kinetics of immunoglobulin assembly and also led to increased responsiveness of B-cell receptor signal transduction by enhancing phosphotyrosine signals and intracellular calcium fluxes. Furthermore, K4.2 expression also appeared to contribute to maximal lytic replication by enhancing viral glycoprotein expression levels and ultimately promoting infectious-virus production. Finally, immunohistochemistry analysis showed that pERP1 expression was readily detected in KSHV-positive cells from multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) lesions, suggesting that pERP1 may have potential roles in the KSHV life cycle and malignancy. In conclusion, our data suggest that K4.2 participates in lytic replication by enhancing calcium flux and viral glycoprotein expression, but also by interfering with immunoglobulin assembly to potentially dampen the adaptive immune response. PMID:23986581

  11. The Chlamydia trachomatis Type III Secretion Chaperone Slc1 Engages Multiple Early Effectors, Including TepP, a Tyrosine-phosphorylated Protein Required for the Recruitment of CrkI-II to Nascent Inclusions and Innate Immune Signaling

    PubMed Central

    Chen, Yi-Shan; Bastidas, Robert J.; Saka, Hector A.; Carpenter, Victoria K.; Richards, Kristian L.; Plano, Gregory V.; Valdivia, Raphael H.

    2014-01-01

    Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted infections, employs a type III secretion (T3S) system to deliver effector proteins into host epithelial cells to establish a replicative vacuole. Aside from the phosphoprotein TARP, a Chlamydia effector that promotes actin re-arrangements, very few factors mediating bacterial entry and early inclusion establishment have been characterized. Like many T3S effectors, TARP requires a chaperone (Slc1) for efficient translocation into host cells. In this study, we defined proteins that associate with Slc1 in invasive C. trachomatis elementary bodies (EB) by immunoprecipitation coupled with mass spectrometry. We identified Ct875, a new Slc1 client protein and T3S effector, which we renamed TepP (Translocated early phosphoprotein). We provide evidence that T3S effectors form large molecular weight complexes with Scl1 in vitro and that Slc1 enhances their T3S-dependent secretion in a heterologous Yersinia T3S system. We demonstrate that TepP is translocated early during bacterial entry into epithelial cells and is phosphorylated at tyrosine residues by host kinases. However, TepP phosphorylation occurs later than TARP, which together with the finding that Slc1 preferentially engages TARP in EBs leads us to postulate that these effectors are translocated into the host cell at different stages during C. trachomatis invasion. TepP co-immunoprecipitated with the scaffolding proteins CrkI-II during infection and Crk was recruited to EBs at entry sites where it remained associated with nascent inclusions. Importantly, C. trachomatis mutants lacking TepP failed to recruit CrkI-II to inclusions, providing genetic confirmation of a direct role for this effector in the recruitment of a host factor. Finally, endocervical epithelial cells infected with a tepP mutant showed altered expression of a subset of genes associated with innate immune responses. We propose a model wherein TepP acts downstream of TARP

  12. Early secreted antigenic target of 6 kDa (ESAT-6) protein of Mycobacterium tuberculosis induces interleukin-8 (IL-8) expression in lung epithelial cells via protein kinase signaling and reactive oxygen species.

    PubMed

    Boggaram, Vijay; Gottipati, Koteswara R; Wang, Xisheng; Samten, Buka

    2013-08-30

    Early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis is critical for the virulence and pathogenicity of M. tuberculosis. IL-8, a major chemotactic cytokine for neutrophils and T lymphocytes, plays important roles in the development of lung injury. To further understand the role of ESAT-6 in lung pathology associated with tuberculosis development, we studied the effects of ESAT-6 on the regulation of IL-8 expression in lung epithelial cells. ESAT-6 induced IL-8 expression by increasing IL-8 gene transcription and mRNA stability. ESAT-6 induction of IL-8 promoter activity was dependent on nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) binding and sensitive to pharmacological inhibition of PKC and ERK and p38 MAPK pathways. ESAT-6 activated ERK and p38 MAPK phosphorylation and rapidly induced reactive oxygen species (ROS) production. Dimethylthiourea but not mannitol inhibited IL-8 induction by ESAT-6, further supporting the involvement of ROS in the induction of IL-8 expression. Exposure of mice to ESAT-6 induced localized inflammatory cell aggregate formation with characteristics of early granuloma concomitant with increased keratinocyte chemoattractant CXCL1 staining in bronchiolar and alveolar type II epithelial cells and alveolar macrophages. Our studies have identified a signal transduction pathway involving ROS, PKC, ERK, and p38 MAPKs and NF-κB and AP-1 in the ESAT-6 induction of IL-8 expression in lung epithelial cells. This has important implications for the understanding of lung innate immune responses to tuberculosis and the pathogenesis of lung injury in tuberculosis. PMID:23867456

  13. 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.

  14. Prostaglandin F2α Stimulates the Expression and Secretion of Transforming Growth Factor B1 Via Induction of the Early Growth Response 1 Gene (EGR1) in the Bovine Corpus Luteum

    PubMed Central

    Hou, Xiaoying; Arvisais, Edward W.; Jiang, Chao; Chen, Dong-bao; Roy, Shyamal K.; Pate, Joy L.; Hansen, Thomas R.; Rueda, Bo R.; Davis, John S.

    2008-01-01

    In most mammals, prostaglandin F2α (PGF2α) is believed to be a trigger that induces the regression of the corpus luteum (CL), whereby progesterone synthesis is inhibited, the luteal structure involutes, and the reproductive cycle resumes. Studies have shown that the early growth response 1 (EGR1) protein can induce the expression of proapoptotic proteins, suggesting that EGR1 may play a role in luteal regression. Our hypothesis is that EGR1 mediates the actions of PGF2α by inducing the expression of TGF β1 (TGFB1), a key tissue remodeling protein. The levels of EGR1 mRNA and protein were up-regulated in the bovine CL during PGF2α-induced luteolysis in vivo and in PGF2α-treated luteal cells in vitro. Using chemical and genetic approaches, the RAF/MAPK kinase (MEK) 1/ERK pathway was identified as a proximal signaling event required for the induction of EGR1 in PGF2α-treated cells. Treatment with PGF2α increased the expression of TGFB1 mRNA and protein as well as the binding of EGR1 protein to TGFB1 promoter in bovine luteal cells. The effect of PGF2α on TGFB1 expression was mimicked by a protein kinase C (PKC)/RAF/MEK1/ERK activator or adenoviral-mediated expression of EGR1. The stimulatory effect of PGF2α on TGFB1 mRNA and TGFB1 protein secretion was inhibited by blockade of MEK1/ERK signaling and by adenoviral-mediated expression of NAB2, an EGR1 binding protein that inhibits EGR1 transcriptional activity. Treatment of luteal cells with TGFB1 reduced progesterone secretion, implicating TGFB1 in luteal regression. These studies demonstrate that PGF2α stimulates the expression of EGR1 and TGFB1 in the CL. We suggest that EGR1 plays a role in the expression of genes whose cognate proteins coordinate luteal regression. PMID:17916653

  15. Tubular Secretion in CKD.

    PubMed

    Suchy-Dicey, Astrid M; Laha, Thomas; Hoofnagle, Andrew; Newitt, Rick; Sirich, Tammy L; Meyer, Timothy W; Thummel, Ken E; Yanez, N David; Himmelfarb, Jonathan; Weiss, Noel S; Kestenbaum, Bryan R

    2016-07-01

    Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation. PMID:26614381

  16. The type III secreted effector DspE is required early in Solanum tuberosum leaf infection by Pectobacterium carotovorum to elicit cell death, and requires Wx(3-6)D/E motifs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pectobacterium species are enterobacterial plant-pathogens that cause soft rot disease in diverse plant species. Unlike hemi-biotrophic plant pathogenic bacteria, the type III secretion system (T3SS) of Pectobacterium carotovorum subsp. carotovorum (P. carotovorum) appears to secrete only one effect...

  17. 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." PMID:24500918

  18. 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'. PMID:27581908

  19. 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.

  20. 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.

  1. Bradykinin metabolism in rat and sheep nasal secretions.

    PubMed

    Chung, F Y; Donovan, M D

    1995-07-01

    The nasal secretions are the first barrier that nasally administered drugs encounter. Therefore, the characterization of peptide metabolism in the nasal secretions is essential to predict nasal peptide bioavailability. Metabolism of bradykinin was measured in rat and sheep nasal secretions to estimate the extent of degradation of nasally administered peptide compounds. A single-pass, in situ nasal perfusion technique was employed to collect secretions for the investigation of peptide metabolism in rat nasal secretions. The protein content, mucin concentration, and degree of bradykinin metabolism in perfusate aliquots collected over a 2-h period showed that the early perfusate fractions contained most of the active secretory materials. Evidence of continuous mucus secretion and plasma extravasation was found in the nasal perfusate throughout the entire collection period. Sheep nasal secretions were collected with a cotton pledget inserted into the nasal cavity. Bradykinin and its fragments were degraded by carboxypeptidases and endopeptidases present in both rat and sheep nasal secretions. Hydrolysis of Phe5-Ser6 was the major metabolism pathway of bradykinin in the rat nasal perfusate, whereas in sheep nasal secretions, hydrolysis of the Pro7-Phe8 and Phe8-Arg9 bonds also occurred. Evidence of angiotensin converting enzyme, carboxypeptide N, and aminopeptidase activity was identified in the rat nasal perfusate with specific substrates and inhibitors. The activity of these and other enzymes in the nasal secretions may significantly limit the bioavailability of nasally administered peptide drugs prior to their exposure to the nasal mucosal tissues. PMID:7562432

  2. Bronchial secretion concentrations of tobramycin.

    PubMed

    Alexander, M R; Schoell, J; Hicklin, G; Kasik, J E; Coleman, D

    1982-02-01

    The mean concentrations of tobramycin in bronchial secretions from patients with pneumonia were almost two times greater than secretions from patients free of lung infection. Mean tobramycin bronchial secretion to serum concentration ratios also were higher when obtained from infected lungs (0.66 versus 0.17) These data suggest that lung infection enhances the concentrations of tobramycin in bronchial secretions. PMID:7065524

  3. Fueling type III secretion

    PubMed Central

    Lee, Pei-Chung

    2015-01-01

    Type III secretion systems are complex nanomachines that export proteins from the bacterial cytoplasm across the cell envelope in a single step. They are at the core of the machinery used to assemble the bacterial flagellum, and the needle complex many Gram-negative pathogens use to inject effector proteins into host cells and cause disease. Several models have been put forward to explain how this export is energized, and the mechanism has been the subject of considerable debate. Here we present an overview of these models and discuss their relative merits. Recent evidence suggests that the proton motive force is the primary energy source for type III secretion, although contribution from refolding of secreted proteins has not been ruled out. The mechanism, by which the proton motive force is converted to protein export, remains enigmatic. PMID:25701111

  4. Ovarian tumors secreting insulin.

    PubMed

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  5. Dynamics of protein secretion during adipocyte differentiation.

    PubMed

    Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Muroya, Susumu; Nishimura, Takanori

    2016-08-01

    The major functions of adipocytes include both lipid storage and the production of secretory factors. However, the type of proteins released from mouse 3T3-L1 cells during adipocyte differentiation remains poorly understood. We examined the dynamics of secreted proteins during adipocyte differentiation using mass spectrometry (MS) combined with an iTRAQ (®) labeling method that enables the simultaneous analysis of relative protein expression levels. A total of 215 proteins were identified and quantified from approximately 10 000 MS/MS spectra. Of these, approximately 38% were categorized as secreted proteins based on gene ontology classification. Adipokine secretion levels were increased with the progression of differentiation. By contrast, levels of fibril collagen components, such as subunits of type I and III collagens, were decreased during differentiation. Basement membrane components attained their peak levels at day 4 when small lipid droplets accumulated in differentiated 3T3-L1 cells. Simultaneously, peak levels of collagen microfibril components that comprise type V and VI collagen subunits were also observed. Our data demonstrated that extracellular matrix components were predominantly released during the early and middle stages of adipocyte differentiation, with a subsequent increase in the secretion of adipokines. This suggests that 3T3-L1 cells secrete adipokines after their ECM is constructed during adipocyte differentiation. PMID:27516960

  6. 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.

  7. 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…

  8. 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)

  9. 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)

  10. 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

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

    PubMed Central

    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.

    2016-01-01

    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. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is 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. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain 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 patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not. PMID:26894971

  12. Secret neutrino interactions: a pseudoscalar model

    NASA Astrophysics Data System (ADS)

    Archidiacono, Maria; Hannestad, Steen; Sloth Hansen, Rasmus; Tram, Thomas

    2016-05-01

    Neutrino oscillation experiments point towards the existence of additional mostly sterile neutrino mass eigenstates in the eV mass range. At the same time, such sterile neutrinos are disfavoured by cosmology (Big Bang Nucleosynthesis, Cosmic Microwave Background and Large Scale Structure), unless they can be prevented from being thermalised in the early Universe. To this aim, we introduce a model of sterile neutrino secret interactions mediated by a new light pseudoscalar: The new interactions can accomodate sterile neutrinos in the early Universe, providing a good fit to all the up to date cosmological data.

  13. 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.

  14. A Secret Support Network

    ERIC Educational Resources Information Center

    Wasley, Paula

    2007-01-01

    This article describes Hanover College's Early Alert Team, an early-alert program that seeks to identify students' academic, social, or personal troubles as soon as they surface. The team's five members gather information about students from all corners of the campus and then devise strategies to help them. The early-alert system has not only…

  15. Blockade by NNC 55-0396, mibefradil, and nickel of calcium and exocytotic signals in chromaffin cells: implications for the regulation of hypoxia-induced secretion at early life.

    PubMed

    Fernández-Morales, José C; Fernando Padín, J; Vestring, Stefan; Musial, Diego C; de Diego, Antonio-Miguel G; García, Antonio G

    2015-03-15

    Adrenal chromaffin cells (CCs) express high-voltage activated calcium channels (high-VACCs) of the L, N and PQ subtypes; in addition, T-type low-VACCs are also expressed during embryo and neonatal life. Effects of the more frequently used T channel blockers NNC 55-0396 (NNC), mibefradil, and Ni2+ on the whole-cell Ba2+ current (IBa), the K+-elicited [Ca2+]c transients and catecholamine secretion have been studied in adult bovine CCs (BCCs) and rat embryo CCs (RECCs). NNC, mibefradil, and Ni2+ blocked BCC IBa with IC50 of 1.8, 4.9 and 70 μM, while IC50 to block IBa in RECCs were 2.1, 4.4 and 41 μM. Pronounced blockade of K+-elicited [Ca2+]c transients and secretion was also elicited by the three agents. However, the hypoxia-induced secretion (HIS) of catecholamine in RECCs was blocked substantially (75%) with thresholds concentrations of NCC (IC20 to block IBa); this was not the case for mibefradil and Ni2+ that required higher concentrations to block the HIS response. Thus, out of the three compounds, NNC seemed to be an adequate pharmacological tool to discern the contribution of T channels to the HIS response, without a contamination with high-VACC blockade. PMID:25622555

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Ghrelin and gastric acid secretion

    PubMed Central

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-induced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion. PMID:19009648

  2. Protecting Trade Secrets in Canada.

    PubMed

    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

  3. 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.

  4. 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.

  5. 4-Bromophenacyl Bromide Specifically Inhibits Rhoptry Secretion during Toxoplasma Invasion

    PubMed Central

    Ravindran, Sandeep; Lodoen, Melissa B.; Verhelst, Steven H. L.; Bogyo, Matthew; Boothroyd, John C.

    2009-01-01

    Toxoplasma gondii is a eukaryotic parasite of the phylum Apicomplexa that is able to infect a wide variety of host cells. During its active invasion process it secretes proteins from discrete secretory organelles: the micronemes, rhoptries and dense granules. Although a number of rhoptry proteins have been shown to be involved in important interactions with the host cell, very little is known about the mechanism of secretion of any Toxoplasma protein into the host cell. We used a chemical inhibitor of phospholipase A2s, 4-bromophenacyl bromide (4-BPB), to look at the role of such lipases in the secretion of Toxoplasma proteins. We found that 4-BPB was a potent inhibitor of rhoptry secretion in Toxoplasma invasion. This drug specifically blocked rhoptry secretion but not microneme secretion, thus effectively showing that the two processes can be de-coupled. It affected parasite motility and invasion, but not attachment or egress. Using propargyl- or azido-derivatives of the drug (so-called click chemistry derivatives) and a series of 4-BPB-resistant mutants, we found that the drug has a very large number of target proteins in the parasite that are involved in at least two key steps: invasion and intracellular growth. This potent compound, the modified “click-chemistry” forms of it, and the resistant mutants should serve as useful tools to further study the processes of Toxoplasma early invasion, in general, and rhoptry secretion, in particular. PMID:19956582

  6. 4-Bromophenacyl bromide specifically inhibits rhoptry secretion during Toxoplasma invasion.

    PubMed

    Ravindran, Sandeep; Lodoen, Melissa B; Verhelst, Steven H L; Bogyo, Matthew; Boothroyd, John C

    2009-01-01

    Toxoplasma gondii is a eukaryotic parasite of the phylum Apicomplexa that is able to infect a wide variety of host cells. During its active invasion process it secretes proteins from discrete secretory organelles: the micronemes, rhoptries and dense granules. Although a number of rhoptry proteins have been shown to be involved in important interactions with the host cell, very little is known about the mechanism of secretion of any Toxoplasma protein into the host cell. We used a chemical inhibitor of phospholipase A2s, 4-bromophenacyl bromide (4-BPB), to look at the role of such lipases in the secretion of Toxoplasma proteins. We found that 4-BPB was a potent inhibitor of rhoptry secretion in Toxoplasma invasion. This drug specifically blocked rhoptry secretion but not microneme secretion, thus effectively showing that the two processes can be de-coupled. It affected parasite motility and invasion, but not attachment or egress. Using propargyl- or azido-derivatives of the drug (so-called click chemistry derivatives) and a series of 4-BPB-resistant mutants, we found that the drug has a very large number of target proteins in the parasite that are involved in at least two key steps: invasion and intracellular growth. This potent compound, the modified "click-chemistry" forms of it, and the resistant mutants should serve as useful tools to further study the processes of Toxoplasma early invasion, in general, and rhoptry secretion, in particular. PMID:19956582

  7. 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…

  8. 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

  9. Exemption 4: Trade Secrets under the Freedom of Information Act.

    ERIC Educational Resources Information Center

    Selby, Holly E.

    Exemption 4 of the Freedom of Information Act (FOIA) protects from disclosure by government agencies privileged and confidential trade secrets and commercial or financial information. Based on early Exemption 4 litigation, courts have devised a "substantial competitive harm test" to decide whether requested information should be covered by the…

  10. emm1/sequence type 28 strains of group A streptococci that express covR at early stationary phase are associated with increased growth and earlier SpeB secretion.

    PubMed

    Chiang-Ni, Chuan; Zheng, Po-Xing; Ho, Yueh-Ren; Wu, Hsiu-Mei; Chuang, Woei-Jer; Lin, Yee-Shin; Lin, Ming-T; Liu, Ching-Chuan; Wu, Jiunn-Jong

    2009-10-01

    Streptococcus pyogenes (group A streptococcus [GAS]) is a versatile human pathogen, and emm1/sequence type 28 (ST28) is the most frequently isolated type from GAS infections. The emm1/ST28 strain is associated with necrotizing fasciitis and streptococcal toxic shock syndrome. Growth-phase regulation is one of the important regulatory mechanisms in GAS, which controls gene expression at restricted phases of growth. CovRS, a two-component regulatory system, is considered the regulator of streptococcal pyrogenic exotoxin B (SpeB) and is thought to be activated in the exponential phase of growth. In the present study, Northern hybridization analysis showed that 52% of the analyzed GAS strains expressed covR at the exponential phase, but 48% of the strains expressed covR at the early stationary phase of growth. Strains transcribing covR at the early stationary phase showed better growth and earlier SpeB expression than the other group of strains. Multilocus sequence typing and pulsed-field gel electrophoresis analysis showed only emm1/ST28 strains (which comprise a clonal cluster) were expressing covR at the early stationary phase of growth, indicating that emm1/ST28 strains have special characteristics which may be related to their worldwide distribution. PMID:19710271

  11. 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.

  12. 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.

  13. Secret Public Key Protocols Revisited

    NASA Astrophysics Data System (ADS)

    Lim, Hoon Wei; Paterson, Kenneth G.

    Password-based protocols are important and popular means of providing human-to-machine authentication. The concept of secret public keys was proposed more than a decade ago as a means of securing password-based authentication protocols against off-line password guessing attacks, but was later found vulnerable to various attacks. In this paper, we revisit the concept and introduce the notion of identity-based secret public keys. Our new identity-based approach allows secret public keys to be constructed in a very natural way using arbitrary random strings, eliminating the structure found in, for example, RSA or ElGamal keys. We examine identity-based secret public key protocols and give informal security analyses, indicating that they are secure against off-line password guessing and other attacks.

  14. 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. PMID:25140334

  15. 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

  16. Papain reduces gastric acid secretion induced by histamine and other secretagogues in anesthetized rats.

    PubMed

    Cho, C H; Han, P W

    1984-04-01

    We studied the effect of papain on rats' gastric acid secretion and found that: 1. Feeding of latex of unripe papaya fruit significantly reduced gastric acid secretion induced by methacholine; 2. Feeding of crystalline papain in doses of 3.2 mg/kg reduced gastric acid secretion induced by histamine, methacholine and tetragastrin; 3. The reduction of gastric acid secretion was observed as early as 2 hours after papain feeding, lasted up to 48 hours, and waned within 96 hours; 4. Intraperitoneal injection of papain had no effect on acid secretion. These results led us to believe tha the effect of papain on gastric acid secretion is a local one acting directly on the gastric mucosa, and this local effect of a single dose of papain is reversible, causing no permanent damage to the mucosa. PMID:6400589

  17. The physiology of salivary secretion.

    PubMed

    Proctor, Gordon B

    2016-02-01

    Saliva in the mouth is a biofluid produced mainly by three pairs of major salivary glands--the submandibular, parotid and sublingual glands--along with secretions from many minor submucosal salivary glands. Salivary gland secretion is a nerve-mediated reflex and the volume of saliva secreted is dependent on the intensity and type of taste and on chemosensory, masticatory or tactile stimulation. Long periods of low (resting or unstimulated) flow are broken by short periods of high flow, which is stimulated by taste and mastication. The nerve-mediated salivary reflex is modulated by nerve signals from other centers in the central nervous system, which is most obvious as hyposalivation at times of anxiety. An example of other neurohormonal influences on the salivary reflex is the circadian rhythm, which affects salivary flow and ionic composition. Cholinergic parasympathetic and adrenergic sympathetic autonomic nerves evoke salivary secretion, signaling through muscarinic M3 and adrenoceptors on salivary acinar cells and leading to secretion of fluid and salivary proteins. Saliva gland acinar cells are chloride and sodium secreting, and the isotonic fluid produced is rendered hypotonic by salivary gland duct cells as it flows to the mouth. The major proteins present in saliva are secreted by salivary glands, creating viscoelasticity and enabling the coating of oral surfaces with saliva. Salivary films are essential for maintaining oral health and regulating the oral microbiome. Saliva in the mouth contains a range of validated and potential disease biomarkers derived from epithelial cells, neutrophils, the microbiome, gingival crevicular fluid and serum. For example, cortisol levels are used in the assessment of stress, matrix metalloproteinases-8 and -9 appear to be promising markers of caries and periodontal disease, and a panel of mRNA and proteins has been proposed as a marker of oral squamous cell carcinoma. Understanding the mechanisms by which components enter

  18. Glucose regulation of glucagon secretion.

    PubMed

    Gylfe, Erik; Gilon, Patrick

    2014-01-01

    Glucagon secreted by pancreatic α-cells is the major hyperglycemic hormone correcting acute hypoglycaemia (glucose counterregulation). In diabetes the glucagon response to hypoglycaemia becomes compromised and chronic hyperglucagonemia appears. There is increasing awareness that glucagon excess may underlie important manifestations of diabetes. However opinions differ widely how glucose controls glucagon secretion. The autonomous nervous system plays an important role in the glucagon response to hypoglycaemia. But it is clear that glucose controls glucagon secretion also by mechanisms involving direct effects on α-cells or indirect effects via paracrine factors released from non-α-cells within the pancreatic islets. The present review discusses these mechanisms and argues that different regulatory processes are involved in a glucose concentration-dependent manner. Direct glucose effects on the α-cell and autocrine mechanisms are probably most significant for the glucagon response to hypoglycaemia. During hyperglycaemia, when secretion from β- and δ-cells is stimulated, paracrine inhibitory factors generate pulsatile glucagon release in opposite phase to pulsatile release of insulin and somatostatin. High concentrations of glucose have also stimulatory effects on glucagon secretion that tend to balance and even exceed the inhibitory influence. The latter actions might underlie the paradoxical hyperglucagonemia that aggravates hyperglycaemia in persons with diabetes. PMID:24367972

  19. Pancreatic Polypeptide Inhibits Somatostatin Secretion

    PubMed Central

    Kim, Wook; Fiori, Jennifer L.; Shin, Yu-Kyong; Okun, Eitan; Kim, Jung Seok; Rapp, Peter R.; Egan, Josephine M.

    2014-01-01

    Pancreatic polypeptide (PP) is a major agonist for neuropeptide Y4 receptors (NPY4R). While NPY4R has been identified in various tissues, the cells on which it is expressed and its function in those cells has not been clearly delineated. Here we report that NPY4R is present in all somatostatin-containing cells of tissues that we tested, including pancreatic islets, duodenum, hippocampus, and hypothalamus. Its agonism by PP decreases somatostatin secretion from human islets. Mouse embryonic hippocampal (mHippo E18) cells expressed NPY4Rs and their activation by PP consistently decreased somatostatin secretion. Furthermore, central injection of PP in mice induced c-Fos immunoreactivity in somatostatin-containing cells in the hippocampus compared with PBS-injected mice. In sum, our results identify PP as a pivotal modulator of somatostatin secretion. PMID:25019573

  20. Multiparty Quantum Remote Secret Conference

    NASA Astrophysics Data System (ADS)

    Li, Xi-Han; Li, Chun-Yan; Deng, Fu-Guo; Zhou, Ping; Liang, Yu-Jie; Zhou, Hong-Yu

    2007-01-01

    We present two schemes for multiparty quantum remote secret conference in which each legitimate conferee can read out securely the secret message announced by another, but a vicious eavesdropper can get nothing about it. The first one is based on the same key shared efficiently and securely by all the parties with Greenberger-Horne-Zeilinger (GHZ) states, and each conferee sends his secret message to the others with one-time pad crypto-system. The other one is based on quantum encryption with a quantum key, a sequence of GHZ states shared among all the conferees and used repeatedly after confirming their security. Both these schemes are optimal as their intrinsic efficiency for qubits approaches the maximal value.

  1. 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. PMID:24902493

  2. Suppression of insulin production and secretion by a decretin hormone.

    PubMed

    Alfa, Ronald W; Park, Sangbin; Skelly, Kathleen-Rose; Poffenberger, Gregory; Jain, Nimit; Gu, Xueying; Kockel, Lutz; Wang, Jing; Liu, Yinghua; Powers, Alvin C; Kim, Seung K

    2015-02-01

    Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia, and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila ortholog of Neuromedin U receptors (NMURs), in insulin-producing cells phenocopied limostatin deficiency and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output. PMID:25651184

  3. Suppression of Insulin Production and Secretion by a Decretin Hormone

    PubMed Central

    Alfa, Ronald W.; Park, Sangbin; Skelly, Kathleen-Rose; Poffenberger, Gregory; Jain, Nimit; Gu, Xueying; Kockel, Lutz; Wang, Jing; Liu, Yinghua; Powers, Alvin C.; Kim, Seung K.

    2015-01-01

    SUMMARY Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila orthologue of Neuromedin U receptors (NMUR), in insulin-producing cells phenocopied limostatin deficiency, and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β-cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output. PMID:25651184

  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. YscU/FlhB of Yersinia pseudotuberculosis Harbors a C-terminal Type III Secretion Signal.

    PubMed

    Login, Frédéric H; Wolf-Watz, Hans

    2015-10-23

    All type III secretion systems (T3SS) harbor a member of the YscU/FlhB family of proteins that is characterized by an auto-proteolytic process that occurs at a conserved cytoplasmic NPTH motif. We have previously demonstrated that YscUCC, the C-terminal peptide generated by auto-proteolysis of Yersinia pseudotuberculosis YscU, is secreted by the T3SS when bacteria are grown in Ca(2+)-depleted medium at 37 °C. Here, we investigated the secretion of this early T3S-substrate and showed that YscUCC encompasses a specific C-terminal T3S signal within the 15 last residues (U15). U15 promoted C-terminal secretion of reporter proteins like GST and YopE lacking its native secretion signal. Similar to the "classical" N-terminal secretion signal, U15 interacted with the ATPase YscN. Although U15 is critical for YscUCC secretion, deletion of the C-terminal secretion signal of YscUCC did neither affect Yop secretion nor Yop translocation. However, these deletions resulted in increased secretion of YscF, the needle subunit. Thus, these results suggest that YscU via its C-terminal secretion signal is involved in regulation of the YscF secretion. PMID:26338709

  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. The secret of the universe.

    NASA Astrophysics Data System (ADS)

    Asimov, I.

    The author turns his attention to such questions as: How near is the nearest star? How heavy is the Sun? How does the Doppler effect work? and countless others. In addition, he provides an explanation of how mankind first became engaged in business and commerce, and advances his own unique theory on the secret of the universe.

  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 resulted in a…

  9. 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…

  10. 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.

  11. Acute allograft rejection and immunosuppression: influence on endogenous melatonin secretion.

    PubMed

    Cardell, Markus; Jung, Florian Johannes; Zhai, Wei; Hillinger, Sven; Welp, Andre; Manz, Bernhard; Weder, Walter; Korom, Stephan

    2008-04-01

    Melatonin displays a dose-dependent immunoregulatory effect in vitro and in vivo. Exogenous high-dose melatonin therapy exerted an immunosuppressive effect, abrogating acute rejection (AR), significantly prolonging transplant survival. Endogenous melatonin secretion, in response to heterotopic rat cardiac allograft transplantation (Tx), was investigated during the AR response and under standardized immunosuppressive maintenance therapy with cyclosporin A (CsA) and rapamycin (RPM). Recipients of syngeneic transplants, and recipients of allogeneic grafts, either untreated or receiving immunosuppressive therapy constituted the experimental groups. Endogenous circadian melatonin levels were measured at 07:00, 19:00, and 24:00 hr, using a novel radioimmunoassay (RIA) procedure, under standardized 12-hr-light/dark-conditions (light off: 19:00 hr; light on: 07:00 hr), before and after Tx. Neither the operative trauma, nor the challenge with a perfused allograft or the AR response influenced endogenous melatonin peak secretion. Immunosuppressive therapy with CsA led to a significant increase in peak secretion, measured for days 7 (212 +/- 40.7 pg/mL; P < 0.05), 14 (255 +/- 13.9 pg/mL; P < 0.001), and 21 (219 +/- 34 pg/mL; P < 0.01) after Tx, as compared with naïve animals (155 +/- 25.8 pg/mL). In contrast, treatment with RPM significantly decreased the melatonin peak post-Tx up to day 7 (87 +/- 25.2 pg/mL; P < 0.001), compared with naïve animals (155 +/- 25.8 pg/mL). These findings imply a robust nature of the endogenous circadian melatonin secretion kinetics, even against the background of profound allogeneic stimuli. Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin secretion, indicating a specific secondary action of these drugs. Further studies are necessary to disclose the long-term effect of immunosuppressive therapy on circadian melatonin secretion in transplant recipients. PMID:18339121

  12. Uncoupling of Secretion From Growth in Some Hormone Secretory Tissues

    PubMed Central

    2014-01-01

    Context: Most syndromes with benign primary excess of a hormone show positive coupling of hormone secretion to size or proliferation in the affected hormone secretory tissue. Syndromes that lack this coupling seem rare and have not been examined for unifying features among each other. Evidence Acquisition: Selected clinical and basic features were analyzed from original reports and reviews. We examined indices of excess secretion of a hormone and indices of size of secretory tissue within the following three syndromes, each suggestive of uncoupling between these two indices: familial hypocalciuric hypercalcemia, congenital diazoxide-resistant hyperinsulinism, and congenital primary hyperaldosteronism type III (with G151E mutation of the KCNJ5 gene). Evidence Synthesis: Some unifying features among the three syndromes were different from features present among common tumors secreting the same hormone. The unifying and distinguishing features included: 1) expression of hormone excess as early as the first days of life; 2) normal size of tissue that oversecretes a hormone; 3) diffuse histologic expression in the hormonal tissue; 4) resistance to treatment by subtotal ablation of the hormone-secreting tissue; 5) causation by a germline mutation; 6) low potential of the same mutation to cause a tumor by somatic mutation; and 7) expression of the mutated molecule in a pathway between sensing of a serum metabolite and secretion of hormone regulating that metabolite. Conclusion: Some shared clinical and basic features of uncoupling of secretion from size in a hormonal tissue characterize three uncommon states of hormone excess. These features differ importantly from features of common hormonal neoplasm of that tissue. PMID:25004249

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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.

  10. 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...

  11. 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...

  12. 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,...

  13. 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,...

  14. 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,...

  15. 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...

  16. 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,...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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,...

  2. 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... 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...

  3. 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...

  4. Stimulation of incretin secreting cells.

    PubMed

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

    2016-02-01

    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

  5. 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

  6. 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

  7. 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. PMID:26360835

  8. Factors affecting maximal acid secretion

    PubMed Central

    Desai, H. G.

    1969-01-01

    The mechanisms by which different factors affect the maximal acid secretion of the stomach are discussed with particular reference to nationality, sex, age, body weight or lean body mass, procedural details, mode of calculation, the nature, dose and route of administration of a stimulus, the synergistic action of another stimulus, drugs, hormones, electrolyte levels, anaemia or deficiency of the iron-dependent enzyme system, vagal continuity and parietal cell mass. PMID:4898322

  9. Transporter-mediated biofuel secretion.

    PubMed

    Doshi, Rupak; Nguyen, Tuan; Chang, Geoffrey

    2013-05-01

    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

  10. 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

  11. Is quantum secret sharing different to the sharing of a quantum secret?

    NASA Astrophysics Data System (ADS)

    Lance, Andrew M.; Symul, Thomas; Bowen, Warwick P.; Tyc, Tomas; Sanders, Barry C.; Lam, Ping Koy

    2004-02-01

    We present an experimental scheme to perform continuous variable (2,3) threshold quantum secret sharing on the quadratures amplitudes of bright light beams. It requires a pair of entangled light beams and an electro-optic feedforward loop for the reconstruction of the secret. We examine the efficacy of quantum secret sharing in terms of fidelity, as well as the signal transfer coefficients and the conditional variances of the reconstructed output state. We show that, in the ideal limit, perfect secret reconstruction is possible. We discuss two different definitions of quantum secret sharing: the sharing of a quantum secret and the sharing of a classical secret with quantum resources.

  12. Experimental quantum secret sharing using telecommunication fiber

    NASA Astrophysics Data System (ADS)

    Bogdanski, Jan; Rafiei, Nima; Bourennane, Mohamed

    2008-12-01

    We report quantum secret sharing experiment in telecommunication fiber in five-party implementation. The quantum secret sharing experiment has been based on a single qubit protocol, which has opened the door to practical secret sharing implementation over fiber 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. The secret sharing protocol has been implemented in an interferometric fiber optics setup with phase encoding and demonstrated for three, four, and five parties. The experimental setup measurements have shown feasibility and scalability of secure multiparty quantum communication over commercial telecom fiber networks.

  13. Prkar1a in the regulation of insulin secretion.

    PubMed

    Hussain, M A; Stratakis, C; Kirschner, L

    2012-09-01

    The incidence of type 2 diabetes mellitus (T2DM) is rapidly increasing worldwide with significant consequences on individual quality of life as well as economic burden on states' healthcare costs. While origins of the pathogenesis of T2DM are poorly understood, an early defect in glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is considered a hallmark of T2DM. Upon a glucose stimulus, insulin is secreted in a biphasic manner with an early first-phase burst of insulin, which is followed by a second, more sustained phase of insulin output. First phase insulin secretion is diminished early in T2DM as well is in subjects who are at risk of developing T2DM. An effective treatment of T2DM with incretin hormone glucagon-like peptide-1 (GLP-1) or its long acting peptide analogue exendin-4 (E4), restores first-phase and augments second-phase glucose stimulated insulin secretion. This effect of incretin action occurs within minutes of GLP-1/E4 infusion in T2DM humans. An additional important consideration is that incretin hormones augment GSIS only above a certain glucose threshold, which is slightly above the normal glucose range. This ensures that incretin hormones stimulate GSIS only when glucose levels are high, while they are ineffective when insulin levels are below a certain threshold. Activation of the GLP-1 receptor, which is highly expressed on pancreatic β-cells, stimulates 2 -distinct intracellular signaling pathways: a) the cAMP-protein kinase A branch and b) the cAMP-EPAC2 (EPAC=exchange protein activated by cAMP) branch. While the EPAC2 branch is considered to mediate GLP-1 effects on first-phase GSIS, the PKA branch is necessary for the former branch to be active. However, how these 2 branches interplay and converge and how their effects on insulin secretion and insulin vesicle exocytosis are coordinated is poorly understood.Thus, at the outset of our studies we have a poorly understood intracellular interplay of cAMP-dependent signaling

  14. Transient fusion and selective secretion of vesicle proteins in Phytophthora nicotianae zoospores.

    PubMed

    Zhang, Weiwei; Blackman, Leila M; Hardham, Adrienne R

    2013-01-01

    Secretion of pathogen proteins is crucial for the establishment of disease in animals and plants. Typically, early interactions between host and pathogen trigger regulated secretion of pathogenicity factors that function in pathogen adhesion and host penetration. During the onset of plant infection by spores of the Oomycete, Phytophthora nicotianae, proteins are secreted from three types of cortical vesicles. Following induction of spore encystment, two vesicle types undergo full fusion, releasing their entire contents onto the cell surface. However, the third vesicle type, so-called large peripheral vesicles, selectively secretes a small Sushi domain-containing protein, PnCcp, while retaining a large glycoprotein, PnLpv, before moving away from the plasma membrane. Selective secretion of PnCcp is associated with its compartmentalization within the vesicle periphery. Pharmacological inhibition of dynamin function, purportedly in vesicle fission, by dynasore treatment provides evidence that selective secretion of PnCcp requires transient fusion of the large peripheral vesicles. This is the first report of selective protein secretion via transient fusion outside mammalian cells. Selective secretion is likely to be an important aspect of plant infection by this destructive pathogen. PMID:24392285

  15. 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.

  16. Synchronous connections: nursing's little secret.

    PubMed

    Krejci, J W

    1995-07-01

    As nurses prepare for their place in health care reform, it is becoming more important than ever to be clear about the unique contribution nurses make to health care outcomes. In our technology-driven society, however, some of nursing's most powerful contributions go unacknowledged. An unexpected finding of a study on nurse experts' perceptions of synchrony revealed that nurses themselves frequently do not document or even dialog about important contributions if they cannot be captured within the dominant paradigm of high-technology care. The article describes nurses "little secret" that must be exposed. PMID:7640383

  17. Controlling secretion to limit chemoresistance.

    PubMed

    Georgilis, Athena; Gil, Jesús

    2016-08-15

    The tumor microenvironment influences cancer progression and therapy outcome by mechanisms not yet fully understood. In this issue of Genes & Development, Bent and colleagues (pp. 1811-1821) show how chemotherapy causes endothelial senescence. Interestingly, senescent endothelial cells do not mount a typical senescence-associated secretory phenotype but instead acutely secrete IL-6, promoting chemoresistance. This study unveils a physiological switch involving PI3K/AKT/mTOR signaling that restrains the senescence secretory responses to limit the detrimental consequences of persistent inflammation. PMID:27601527

  18. 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.

  19. Modulation of the NMDA Receptor Through Secreted Soluble Factors.

    PubMed

    Cerpa, Waldo; Ramos-Fernández, Eva; Inestrosa, Nibaldo C

    2016-01-01

    Synaptic activity is a critical determinant in the formation and development of excitatory synapses in the central nervous system (CNS). The excitatory current is produced and regulated by several ionotropic receptors, including those that respond to glutamate. These channels are in turn regulated through several secreted factors that function as synaptic organizers. Specifically, Wnt, brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF), and transforming growth factor (TGF) particularly regulate the N-methyl-D-aspartate receptor (NMDAR) glutamatergic channel. These factors likely regulate early embryonic development and directly control key proteins in the function of important glutamatergic channels. Here, we review the secreted molecules that participate in synaptic organization and discuss the cell signaling behind of this fine regulation. Additionally, we discuss how these factors are dysregulated in some neuropathologies associated with glutamatergic synaptic transmission in the CNS. PMID:25429903

  20. Human Mammospheres Secrete Hormone-Regulated Active Extracellular Vesicles

    PubMed Central

    Rodriguez-Suarez, Eva; Gil, David; Royo, Felix; Elortza, Felix; Falcon-Perez, Juan M.; Vivanco, Maria dM.

    2014-01-01

    Breast cancer is a leading cause of cancer-associated death worldwide. One of the most important prognostic factors for survival is the early detection of the disease. Recent studies indicate that extracellular vesicles may provide diagnostic information for cancer management. We demonstrate the secretion of extracellular vesicles by primary breast epithelial cells enriched for stem/progenitor cells cultured as mammospheres, in non-adherent conditions. Using a proteomic approach we identified proteins contained in these vesicles whose expression is affected by hormonal changes in the cellular environment. In addition, we showed that these vesicles are capable of promoting changes in expression levels of genes involved in epithelial-mesenchymal transition and stem cell markers. Our findings suggest that secreted extracellular vesicles could represent potential diagnostic and/or prognostic markers for breast cancer and support a role for extracellular vesicles in cancer progression. PMID:24404144

  1. Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates

    PubMed Central

    Farnell, Edward; Rousseau, Karine; Thornton, David J.; Bowyer, Paul; Herrick, Sarah E.

    2012-01-01

    The ubiquitous filamentous fungus Aspergillus fumigatus secretes a number of allergens with protease activity and has been linked to a variety of allergic conditions such as Severe Asthma with Fungal Sensitization (SAFS) and Allergic Bronchopulmonary Aspergillosis (ABPA). However, it is unclear which allergen proteases are being secreted during fungal invasion and whether the local biological environment regulates their expression. Understanding the dynamic expression of allergen proteases during growth of A. fumigatus may lead to further characterisation of the pathogenesis of these disorders as well as improved standardisation in the commercial production of these allergens. Secretion of proteases during germination and early growth of A. fumigatus was investigated in response to various complex protein sources (pig lung homogenate, mucin or casein). Protease inhibitor studies demonstrated that A. fumigatus (AF293 strain) secretes predominately serine proteases during growth in pig lung based medium and mainly metalloproteases during growth in casein based medium but suppressed protease secretion in unmodified Vogel's minimal medium and secreted both types in mucin based medium. Analysis of gene transcription and protein identification by mass spectrometry showed that the matrix metalloprotease, Mep/Asp f 5 and the serine protease, Alp1/Asp f 13, were upregulated and secreted during growth in pig lung medium, whereas Alp1 was predominately expressed and secreted in mucin based medium. In casein medium, the matrix metalloprotease, Lap1, was also upregulated and secreted in addition to Mep and Alp1. These findings suggest that A. fumigatus is able to detect different complex proteins available as substrates in its environment and regulate protease secretion accordingly. There is a requirement for the standardisation of A. fumigatus allergen extracts used both in clinical diagnosis of A. fumigatus allergy and in research studies. PMID:22954343

  2. 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

  3. Motilin stimulates pepsinogen secretion in Suncus murinus.

    PubMed

    Goswami, Chayon; Tanaka, Toru; Jogahara, Takamichi; Sakai, Takafumi; Sakata, Ichiro

    2015-07-01

    Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in suncus. PMID:25957475

  4. Calcium signaling and secretion in cholangiocytes

    PubMed Central

    Guerra, Mateus T.; Nathanson, Michael H.

    2015-01-01

    Alcoholic hepatitis affects up to one-third of individuals who abuse alcohol and can be associated with high mortality. Although this disorder is characterized by hepatocellular damage, steatosis and neutrophil infiltration, recent evidence suggests that cholestasis or impaired bile secretion may be a frequent occurrence as well. Bile secretion results from the concerted activity of hepatocytes and cholangiocytes, the epithelial cells that line the bile ducts. Hepatocytes secrete bile acids and conjugated products into the bile canaliculi, which then are modified by cholangiocytes through secretion of bicarbonate and water to give rise to the final secreted bile. Here the molecular mechanisms regulating bile secretion in cholangiocytes are reviewed. Moreover, we discuss how the expression of intracellular Ca2+ channels might be regulated in cholangiocytes, plus evidence that components of the Ca2+ signaling machinery are altered in a range of cholestatic diseases of the bile ducts. PMID:26100660

  5. Calcium signaling and secretion in cholangiocytes.

    PubMed

    Guerra, Mateus T; Nathanson, Michael H

    2015-07-01

    Alcoholic hepatitis affects up to one-third of individuals who abuse alcohol and can be associated with high mortality. Although this disorder is characterized by hepatocellular damage, steatosis and neutrophil infiltration, recent evidence suggests that cholestasis or impaired bile secretion may be a frequent occurrence as well. Bile secretion results from the concerted activity of hepatocytes and cholangiocytes, the epithelial cells that line the bile ducts. Hepatocytes secrete bile acids and conjugated products into the bile canaliculi, which then are modified by cholangiocytes through secretion of bicarbonate and water to give rise to the final secreted bile. Here the molecular mechanisms regulating bile secretion in cholangiocytes are reviewed. Moreover, we discuss how the expression of intracellular Ca(2+) channels might be regulated in cholangiocytes, plus evidence that components of the Ca(2+) signaling machinery are altered in a range of cholestatic diseases of the bile ducts. PMID:26100660

  6. Neonaticides following "secret" pregnancies: seven case reports.

    PubMed Central

    Saunders, E

    1989-01-01

    Seven neonaticides were reported during a 14-month period in the State of Iowa. This is an alarming number considering that only one such case was reported in the previous year. The majority of cases involved the birth of a live infant to an adolescent who had reportedly kept her pregnancy secret from family and friends. The death of the infants resulted from exposure or drowning. Efforts were made by the mother to hide or dispose of her infant's body. Basic information about each of the reported cases is presented, as well as the sentences given the adult mothers charged with the crime of child endangerment. The dynamics of these cases are reviewed in the context of earlier studies dealing with the phenomenon of neonaticide. Infanticide has deep roots in several cultures. It was practiced in some primitive societies and was decreed a capital offense as early as 1643. Its occurrence recently prompts suggestions for activities by professionals to prevent these tragedies. More research and further attention to this problem is warranted. PMID:2502808

  7. Secret sharing based on quantum Fourier transform

    NASA Astrophysics Data System (ADS)

    Yang, Wei; Huang, Liusheng; Shi, Runhua; He, Libao

    2013-07-01

    Secret sharing plays a fundamental role in both secure multi-party computation and modern cryptography. We present a new quantum secret sharing scheme based on quantum Fourier transform. This scheme enjoys the property that each share of a secret is disguised with true randomness, rather than classical pseudorandomness. Moreover, under the only assumption that a top priority for all participants (secret sharers and recovers) is to obtain the right result, our scheme is able to achieve provable security against a computationally unbounded attacker.

  8. Thymidine secretion by hybridoma and myeloma cells

    SciTech Connect

    Spilsberg, Bjorn . E-mail: bjorn.spilsberg@biokjemi.uio.no; Rise, Frode; Petersen, Dirk; Nissen-Meyer, Jon

    2006-03-31

    Secretion of thymidine appeared to be a common property of hybridoma and myeloma cells, but not of other cell types, which were tested. Of three hybridoma cell lines tested, all secreted thymidine in amounts resulting in the accumulation of thymidine to concentrations of 10-20 {mu}M in the culture medium. Also three of five myeloma cell lines that were analyzed secrete thymidine, but none of the other cell types that were studied. Thymidine was purified to homogeneity (4 mg purified from 3 l of culture medium) and identified as such by nuclear magnetic resonance spectroscopy. The cells that secreted thymidine showed high resistance to the growth inhibitory effect of thymidine.

  9. 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.

  10. 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.

  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. Characterization of secreted proteins in HepG2 and LO2 cells by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Lin, Juqiang; Ruan, Qiuyong; Liao, Fadian; Lin, Jinyong; Huang, Zufang; Liu, Nenrong; Chen, Rong

    2014-11-01

    Secreted proteins, the promising source of biomarkers for early detection and diagnosis of cancer, have received considerable attention. Raman spectroscopy and principal component analysis (PCA) were used to characterize the secreted proteins collected from the cell cultures of human hepatoma cell line HepG2 and normal human liver cell line LO2 in this paper. We found the major difference of secreted proteins Raman spectra between HepG2 and LO2 cells were in the range of 1200cm-1-1800cm-1. Compared with LO2 cells, some significant changes based on secondary structure of secreted proteins in HepG2 cells were observed, including the increase in the relative intensity of the band at 1004cm-1, 1445cm-1, 1674cm-1 and the decrease at 1074cm-1. These variations of Raman bands indicated that the species and conformation of secreted proteins in HepG2 cells changed. The measured Raman spectra of the two groups were separated into two distinct clusters with no overlap and high specificity and sensitivity by PCA. These results show that the combination of Raman spectroscopy and PCA analysis may be a powerful tool for distinguishing the secreted proteins between human hepatoma cells and normal human liver cells, provide a new thought to analyze the secreted proteins from cancer cells and find a novel cancer biomarker.

  13. Structural analysis of toad oviductal mucosa in relation to jelly components secretion throughout the reproductive cycle.

    PubMed

    Crespo, Claudia Alejandra; Ramos, Inés; Medina, Marcela Fátima; Cisint, Susana Beatriz; Iruzubieta Villagra, Ana Lucrecia; Fernández, Silvia Nélida

    2014-05-01

    In amphibians, the components of the jelly coats that surround the oocytes at the time of fertilization and coordinate gamete interaction are secreted by the oviduct. We analysed the histological variations in the mucosa of the oviductal pars convoluta (PC) of Rhinella arenarum during the reproductive cycle and its relationship with secretion. During the preovulatory period, the mucosa reaches a high degree of morphological and functional development, with a large number of epithelial (ESC) and glandular secretory cells (GSC) loaded with contents that are secreted into the oviductal lumen. During the ovulatory period, the secretory cells (SC) of both layers present maximum secretory activity through apocrinia and merocrinia. While the ESC located at the tips of the folds release their content directly in contact with the oocytes, the GSC secrete material from the bottom of the epithelial folds that, by interaction with the secretion of the ESC in the lateral faces, form a product with a certain degree of organization. Secretion is a continuous process with formation of coats of increasing complexity from the intermediate proximal zone (IPZ) to the pars convoluta (pc) itself, and the passage of the oocyte is a requisite for the organization of the jelly coats around the gamete. During the early postovulatory period, although there is a marked decrease in the number and volume of the SC, the ESC still release material into the oviductal lumen. In the late postovulatory period the morphological characteristics of the PC begin to recovery although there is no evidence of secretion. PMID:23174084

  14. ESX/type VII secretion systems of mycobacteria: Insights into evolution, pathogenicity and protection.

    PubMed

    Simeone, Roxane; Bottai, Daria; Frigui, Wafa; Majlessi, Laleh; Brosch, Roland

    2015-06-01

    Pathogenesis of Mycobacterium tuberculosis depends on the secretion of key virulence factors, such as the 6 kDa early secreted antigenic target ESAT-6 (EsxA) and its protein partner, the 10 kDa culture filtrate protein CFP-10 (EsxB), via the ESX-1 secretion system. ESX-1 represents the prototype system of the recently named type VII secretion systems that exist in a range of actinobacteria. The M. tuberculosis genome harbours a total of five gene clusters potentially coding for type VII secretion systems, designated ESX-1 - ESX-5, with ESX-4 being the most ancient system from which other ESX systems seem to have evolved by gene duplication and gene insertion events. The five ESX systems show similarity in gene content and gene order but differ in function. ESX-1 and ESX-5 are both crucial virulence determinants of M. tuberculosis, but with different mechanisms. While ESX-1 is implicated in the lysis of the host cell phagosomes, ESX-5 is involved in secretion of the mycobacteria specific PE and PPE proteins and cell wall stability. Research on type VII secretion systems has thus become a large and competitive research topic that is tightly linked to studies of host-pathogen interaction of pathogenic mycobacteria. Insights into this matter are of relevance for redrawing the patho-evolution of M. tuberculosis, which might help improving current strategies for prevention, diagnostics and therapy of tuberculosis as well as elucidating the virulence mechanisms employed by this important human pathogen. PMID:25732627

  15. Effect of Naloxon on Counter Insulin Hormone Secretion in Insulin-Induced Hypoglycemia

    PubMed Central

    Ju, Yeong Shil; Kim, Sung Woon; Yang, In Myung; Kim, Jin Woo; Kim, Young Seol; Choi, Young Kil

    1987-01-01

    To investigate the normal physiologic role of endogenous opiates in glucose homeostasis and as a preliminary study for clarifying the association of endogenous opites with pathophysilogy of NIDDM, we obseved the changes in the secretion of counter-insulin hormones in response to insulin-induced hypoglycemia with or without naloxone. The results were as follows: Blood glucose was decreased significantly more rapidly with naloxone infusion than after insulin alone, which seems to play a role in the early responses of ACTH and GH.Not only was the more rapid response of ACTH and GH, but also the prolonged secretion of ACTH and Cortisol were observed after administration of insulin and naloxone. We concluded that endogenous opiates may be involved in the feedback regulation of secretion of ACTH and GH during hypoglycemia either at hypophysis or hypothalamus, and involved in glucose homeostasis via a certain direct mechanism other than regulation of counter hormone secretion. PMID:2856480

  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. Cortactin enhances exosome secretion without altering cargo.

    PubMed

    Gangoda, Lahiru; Mathivanan, Suresh

    2016-07-18

    The role of cortactin, a regulator of late endosomal trafficking, in the biogenesis and secretion of exosomes is poorly understood. In this issue, Sinha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601025) elucidate the role of cortactin as a positive regulator of late endosomal docking and exosome secretion. PMID:27432895

  18. 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

  19. "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 for stimulating…

  20. 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, and social…

  1. Identification of secreted and cytosolic gelsolin in Drosophila.

    PubMed

    Stella, M C; Schauerte, H; Straub, K L; Leptin, M

    1994-05-01

    We have cloned the gene for Drosophila gelsolin. Two mRNAs are produced from this gene by differential splicing. The protein encoded by the longer mRNA has a signal peptide and its electrophoretic mobility when translated in vitro in the presence of microsomes is higher than when it is translated without microsomes. The protein translated from the shorter mRNA does not show this difference. This indicates that Drosophila like vertebrates has two forms of gelsolin, one secreted, the other cytoplasmic. The mRNA for both is present ubiquitously in the early embryo. Later, the cytoplasmic form is expressed in parts of the gut. The RNA for the secreted form is expressed in the fat body, and the secreted protein is abundant in extracellular fluid (hemolymph). The cytoplasmic form of gelsolin co-localizes with F-actin in the cortex of the cells in the embryo and in larval epithelia. However, during cellularization of the blastoderm it is reduced at the base of the cleavage furrow, a structure similar to the contractile ring in dividing cells. PMID:8175883

  2. Insulin secretion after injuries of differing severity in the rat.

    PubMed Central

    Frayn, K. N.

    1976-01-01

    The effects on insulin secretion of injuries of differing severity have been studied in the rat. The injuries used were dorsal scalds to 20% and 40% of the body surface area, and a 4-h period of bilateral hind-limb ischaemia. These injuries resulted in 48 h mortality rates of 0/10, 7/10 and 5/10 respectively. Rats were studied 1-5-2 h after scalding or removal of tourniquets. The blood glucose concentration was markedly raised after all these injuries, and the plasma insulin concentration was also raised, so that the insulin to glucose ratio in any group did not differ significantly from that in non-injured controls. Injection of glucose (0-5 g/kg i.v.) induced a rise in insulin concentration in all groups, although the insulin to glucose ratio after the lethal 40% scald was lower than in control rats. It was concluded that in the rat normal insulin secretion is maintained even after lethal injuries, although some suppression of the insulin response to exogenous glucose may occur. Insulin resistance is more important in the rat than impairment of insulin secretion even at an early stage after injury. PMID:782499

  3. Quantitative Proteomic Analysis of Burkholderia pseudomallei Bsa Type III Secretion System Effectors Using Hypersecreting Mutants

    PubMed Central

    Vander Broek, Charles W.; Chalmers, Kevin J.; Stevens, Mark P.; Stevens, Joanne M.

    2015-01-01

    Burkholderia pseudomallei is an intracellular pathogen and the causative agent of melioidosis, a severe disease of humans and animals. One of the virulence factors critical for early stages of infection is the Burkholderia secretion apparatus (Bsa) Type 3 Secretion System (T3SS), a molecular syringe that injects bacterial proteins, called effectors, into eukaryotic cells where they subvert cellular functions to the benefit of the bacteria. Although the Bsa T3SS itself is known to be important for invasion, intracellular replication, and virulence, only a few genuine effector proteins have been identified and the complete repertoire of proteins secreted by the system has not yet been fully characterized. We constructed a mutant lacking bsaP, a homolog of the T3SS “gatekeeper” family of proteins that exert control over the timing and magnitude of effector protein secretion. Mutants lacking BsaP, or the T3SS translocon protein BipD, were observed to hypersecrete the known Bsa effector protein BopE, providing evidence of their role in post-translational control of the Bsa T3SS and representing key reagents for the identification of its secreted substrates. Isobaric Tags for Relative and Absolute Quantification (iTRAQ), a gel-free quantitative proteomics technique, was used to compare the secreted protein profiles of the Bsa T3SS hypersecreting mutants of B. pseudomallei with the isogenic parent strain and a bsaZ mutant incapable of effector protein secretion. Our study provides one of the most comprehensive core secretomes of B. pseudomallei described to date and identified 26 putative Bsa-dependent secreted proteins that may be considered candidate effectors. Two of these proteins, BprD and BapA, were validated as novel effector proteins secreted by the Bsa T3SS of B. pseudomallei. PMID:25635268

  4. 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

  5. Non-classical protein secretion in bacteria

    PubMed Central

    Bendtsen, Jannick D; Kiemer, Lars; Fausbøll, Anders; Brunak, Søren

    2005-01-01

    Background We present an overview of bacterial non-classical secretion and a prediction method for identification of proteins following signal peptide independent secretion pathways. We have compiled a list of proteins found extracellularly despite the absence of a signal peptide. Some of these proteins also have known roles in the cytoplasm, which means they could be so-called "moon-lightning" proteins having more than one function. Results A thorough literature search was conducted to compile a list of currently known bacterial non-classically secreted proteins. Pattern finding methods were applied to the sequences in order to identify putative signal sequences or motifs responsible for their secretion. We have found no signal or motif characteristic to any majority of the proteins in the compiled list of non-classically secreted proteins, and conclude that these proteins, indeed, seem to be secreted in a novel fashion. However, we also show that the apparently non-classically secreted proteins are still distinguished from cellular proteins by properties such as amino acid composition, secondary structure and disordered regions. Specifically, prediction of disorder reveals that bacterial secretory proteins are more structurally disordered than their cytoplasmic counterparts. Finally, artificial neural networks were used to construct protein feature based methods for identification of non-classically secreted proteins in both Gram-positive and Gram-negative bacteria. Conclusion We present a publicly available prediction method capable of discriminating between this group of proteins and other proteins, thus allowing for the identification of novel non-classically secreted proteins. We suggest candidates for non-classically secreted proteins in Escherichia coli and Bacillus subtilis. The prediction method is available online. PMID:16212653

  6. 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.

  7. Secrets of the Wabar craters

    USGS Publications Warehouse

    Wynn, Jeffrey C.; Shoemaker, Eugene M.

    1997-01-01

    Focuses on the existence of craters in the Empty Quarter of Saudi Arabia created by the impact of meteors in early times. Mars Pathfinder and Mars Global Surveyor's encounter with impact craters; Elimination of craters in the Earth's surface by the action of natural elements; Impact sites' demand for careful scientific inspections; Location of the impact sites.

  8. Overexpression of des(1-3)hIGF-I in the mammary gland during prolonged lactation enhances milk yield and elevates prolactin secretion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During prolonged lactation, the mammary gland loses the capacity to synthesize and secrete the large amounts of milk that are produced during early lactation. This loss occurs despite the continued presence of a suckling stimulus and complete removal of mammary secretions. The decline in milk synthe...

  9. Identification of protein secretion systems and novel secreted proteins in Rhizobium leguminosarum bv. viciae

    PubMed Central

    Krehenbrink, Martin; Downie, J Allan

    2008-01-01

    Background Proteins secreted by bacteria play an important role in infection of eukaryotic hosts. Rhizobia infect the roots of leguminous plants and establish a mutually beneficial symbiosis. Proteins secreted during the infection process by some rhizobial strains can influence infection and modify the plant defence signalling pathways. The aim of this study was to systematically analyse protein secretion in the recently sequenced strain Rhizobium leguminosarum bv. viciae 3841. Results Similarity searches using defined protein secretion systems from other Gram-negative bacteria as query sequences revealed that R. l. bv. viciae 3841 has ten putative protein secretion systems. These are the general export pathway (GEP), a twin-arginine translocase (TAT) secretion system, four separate Type I systems, one putative Type IV system and three Type V autotransporters. Mutations in genes encoding each of these (except the GEP) were generated, but only mutations affecting the PrsDE (Type I) and TAT systems were observed to affect the growth phenotype and the profile of proteins in the culture supernatant. Bioinformatic analysis and mass fingerprinting of tryptic fragments of culture supernatant proteins identified 14 putative Type I substrates, 12 of which are secreted via the PrsDE, secretion system. The TAT mutant was defective for the symbiosis, forming nodules incapable of nitrogen fixation. Conclusion None of the R. l. bv. viciae 3841 protein secretion systems putatively involved in the secretion of proteins to the extracellular space (Type I, Type IV, Type V) is required for establishing the symbiosis with legumes. The PrsDE (Type I) system was shown to be the major route of protein secretion in non-symbiotic cells and to secrete proteins of widely varied size and predicted function. This is in contrast to many Type I systems from other bacteria, which typically secrete specific substrates encoded by genes often localised in close proximity to the genes encoding the

  10. Pancreatic calcium waves and secretion.

    PubMed

    Kasai, H

    1995-01-01

    Pancreatic acinar cells display stereotypic Ca2+ waves resulting from Ca2+ release from internal stores during stimulation. The Ca2+ waves are initiated at the luminal pole, and, at high agonist concentrations, spread towards the basal pole. Two key mechanisms behind the generation of Ca2+ waves have been identified. First, the Ca2+ waves are composite, mediated by three distinct Ca2+ release mechanisms with a polarized distribution: high-sensitivity inositol 1,4,5-trisphosphate (InsP3) receptors at a small trigger zone (T zone) in the secretory granule area, Ca(2+)-induced Ca2+ release channels in the granular area and low-sensitivity InsP3 receptors in the basal area. Second, InsP3 can readily diffuse in the cytosol, whereas rises in cytosolic Ca2+ concentration ([Ca2+]i) can be confined through strong buffering and sequestration of Ca2+. InsP3 is thus used as a long-range messenger to transmit agonist signals to the T zone, and [Ca2+]i rises at the T zone are used as a local switch. These mechanisms enable preferential activation of the T zone, irrespective of localization of stimuli and agonist receptors. The secretion of enzymes and fluid is a direct consequence of [Ca2+]i rises at the T zone. The Ca2+ waves and oscillations probably boost the T zone functions. PMID:7587613

  11. 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

  12. 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

  13. Energy source of flagellar type III secretion.

    PubMed

    Paul, Koushik; Erhardt, Marc; Hirano, Takanori; Blair, David F; Hughes, Kelly T

    2008-01-24

    Bacterial flagella contain a specialized secretion apparatus that functions to deliver the protein subunits that form the filament and other structures to outside the membrane. This apparatus is related to the injectisome used by many gram-negative pathogens and symbionts to transfer effector proteins into host cells; in both systems this export mechanism is termed 'type III' secretion. The flagellar secretion apparatus comprises a membrane-embedded complex of about five proteins, and soluble factors, which include export-dedicated chaperones and an ATPase, FliI, that was thought to provide the energy for export. Here we show that flagellar secretion in Salmonella enterica requires the proton motive force (PMF) and does not require ATP hydrolysis by FliI. The export of several flagellar export substrates was prevented by treatment with the protonophore CCCP, with no accompanying decrease in cellular ATP levels. Weak swarming motility and rare flagella were observed in a mutant deleted for FliI and for the non-flagellar type-III secretion ATPases InvJ and SsaN. These findings show that the flagellar secretion apparatus functions as a proton-driven protein exporter and that ATP hydrolysis is not essential for type III secretion. PMID:18216859

  14. Extracellular Enzyme Secretion by Pseudomonas lemoignei

    PubMed Central

    Stinson, M. W.; Merrick, J. M.

    1974-01-01

    The ability of succinate to repress the secretion of Pseudomonas lemoignei poly-β-hydroxybutyrate depolymerase was a function of pH. Repression only occurred when the pH of the medium was 7.0 or less. At a higher pH, lack of sensitivity to succinate concentration may have been due to a limited ability to transport succinate. Actively secreting cultures (at pH 7.4) continued to secrete enzyme for approximately 30 min after the pH was rapidly decreased to pH 6.8, even though sufficient succinate was present to repress enzyme synthesis. Similarly, after the addition of rifampin to secreting cultures, there was a 30-min delay before secretion was inhibited. Evidence is presented which suggests that continued secretion may be the result of depolymerase messenger ribonucleic acid accumulation within the cells. Studies with chloramphenicol indicated that de novo protein synthesis is necessary for the secretion of poly-β-hydroxybutyrate depolymerase and that exoenzyme is not released from a preformed pool. Studies with various inhibitors of protein synthesis indicated that synthesis of exoenzyme is 5 to 10 times more susceptible to inhibition than is the synthesis of cell-associated proteins. PMID:4152045

  15. 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. PMID:26234210

  16. Insulin signaling pathways in lepidopteran ecdysone secretion

    PubMed Central

    Smith, Wendy A.; Lamattina, Anthony; Collins, McKensie

    2014-01-01

    Molting and metamorphosis are stimulated by the secretion of ecdysteroid hormones from the prothoracic glands. Insulin-like hormones have been found to enhance prothoracic gland activity, providing a mechanism to link molting to nutritional state. In silk moths (Bombyx mori), the prothoracic glands are directly stimulated by insulin and the insulin-like hormone bombyxin. Further, in Bombyx, the neuropeptide prothoracicotropic hormone (PTTH) appears to act at least in part through the insulin-signaling pathway. In the prothoracic glands of Manduca sexta, while insulin stimulates the phosphorylation of the insulin receptor and Akt, neither insulin nor bombyxin II stimulate ecdysone secretion. Involvement of the insulin-signaling pathway in Manduca prothoracic glands was explored using two inhibitors of phosphatidylinositol-3-kinase (PI3K), LY294002 and wortmannin. PI3K inhibitors block the phosphorylation of Akt and 4EBP but have no effect on ecdysone secretion, or on the phosphorylation of the MAPkinase, ERK. Inhibitors that block phosphorylation of ERK, including the MEK inhibitor U0126, and high doses of the RSK inhibitor SL0101, effectively inhibit ecdysone secretion. The results highlight differences between the two lepidopteran insects most commonly used to directly study ecdysteroid secretion. In Bombyx, the PTTH and insulin-signaling pathways intersect; both insulin and PTTH enhance the phosphorylation of Akt and stimulate ecdysteroid secretion, and inhibition of PI3K reduces ecdysteroid secretion. By contrast, in Manduca, the action of PTTH is distinct from insulin. The results highlight species differences in the roles of translational regulators such as 4EBP, and members of the MAPkinase pathway such as ERK and RSK, in the regulation of insect ecdysone secretion, and in the impact of nutritionally-sensitive hormones such as insulin in the control of ecdysone secretion and molting. PMID:24550835

  17. 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.

  18. Islet Insulin Secretion Measurements in the Mouse.

    PubMed

    Hugill, Alison; Shimomura, Kenju; Cox, Roger D

    2016-01-01

    This article describes detailed protocols for in vitro measurements of insulin function and secretion in isolated mouse islets for the analysis of glucose homeostasis. We specify a method of enzyme digestion and hand picking to isolate and release the greatest number of high quality islets from the pancreas of the mouse. We describe an effective method for generating dynamic measurements of insulin secretion using a perifusion assay including a detailed protocol for constructing a peristaltic pump and tubing assembly. In addition we describe an alternative and simple technique for measuring insulin secretion using static incubation of isolated islets. © 2016 by John Wiley & Sons, Inc. PMID:27584553

  19. 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

  20. Interactions between Trypanosoma cruzi Secreted Proteins and Host Cell Signaling Pathways

    PubMed Central

    Watanabe Costa, Renata; da Silveira, Jose F.; Bahia, Diana

    2016-01-01

    Chagas disease is one of the prevalent neglected tropical diseases, affecting at least 6–7 million individuals in Latin America. It is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to vertebrate hosts by blood-sucking insects. After infection, the parasite invades and multiplies in the myocardium, leading to acute myocarditis that kills around 5% of untreated individuals. T. cruzi secretes proteins that manipulate multiple host cell signaling pathways to promote host cell invasion. The primary secreted lysosomal peptidase in T. cruzi is cruzipain, which has been shown to modulate the host immune response. Cruzipain hinders macrophage activation during the early stages of infection by interrupting the NF-kB P65 mediated signaling pathway. This allows the parasite to survive and replicate, and may contribute to the spread of infection in acute Chagas disease. Another secreted protein P21, which is expressed in all of the developmental stages of T. cruzi, has been shown to modulate host phagocytosis signaling pathways. The parasite also secretes soluble factors that exert effects on host extracellular matrix, such as proteolytic degradation of collagens. Finally, secreted phospholipase A from T. cruzi contributes to lipid modifications on host cells and concomitantly activates the PKC signaling pathway. Here, we present a brief review of the interaction between secreted proteins from T. cruzi and the host cells, emphasizing the manipulation of host signaling pathways during invasion. PMID:27065960

  1. Small-Conductance Ca2+-Activated Potassium Channels Negatively Regulate Aldosterone Secretion in Human Adrenocortical Cells.

    PubMed

    Yang, Tingting; Zhang, Hai-Liang; Liang, Qingnan; Shi, Yingtang; Mei, Yan-Ai; Barrett, Paula Q; Hu, Changlong

    2016-09-01

    Aldosterone, which plays a key role in maintaining water and electrolyte balance, is produced by zona glomerulosa cells of the adrenal cortex. Autonomous overproduction of aldosterone from zona glomerulosa cells causes primary hyperaldosteronism. Recent clinical studies have highlighted the pathological role of the KCNJ5 potassium channel in primary hyperaldosteronism. Our objective was to determine whether small-conductance Ca(2+)-activated potassium (SK) channels may also regulate aldosterone secretion in human adrenocortical cells. We found that apamin, the prototypic inhibitor of SK channels, decreased membrane voltage, raised intracellular Ca(2+) and dose dependently increased aldosterone secretion from human adrenocortical H295R cells. By contrast, 1-Ethyl-2-benzimidazolinone, an agonist of SK channels, antagonized apamin's action and decreased aldosterone secretion. Commensurate with an increase in aldosterone production, apamin increased mRNA expression of steroidogenic acute regulatory protein and aldosterone synthase that control the early and late rate-limiting steps in aldosterone biosynthesis, respectively. In addition, apamin increased angiotensin II-stimulated aldosterone secretion, whereas 1-Ethyl-2-benzimidazolinone suppressed both angiotensin II- and high K(+)-stimulated production of aldosterone in H295R cells. These findings were supported by apamin-modulation of basal and angiotensin II-stimulated aldosterone secretion from acutely prepared slices of human adrenals. We conclude that SK channel activity negatively regulates aldosterone secretion in human adrenocortical cells. Genetic association studies are necessary to determine whether mutations in SK channel subtype 2 genes may also drive aldosterone excess in primary hyperaldosteronism. PMID:27432863

  2. Modulating the expression level of secreted Wnt3 influences cerebellum development in zebrafish transgenics.

    PubMed

    Teh, Cathleen; Sun, Guangyu; Shen, Hongyuan; Korzh, Vladimir; Wohland, Thorsten

    2015-11-01

    The boundaries of brain regions are associated with the tissue-specific secretion of ligands from different signaling pathways. The dynamics of these ligands in vivo and the impact of its disruption remain largely unknown. Using light and fluorescence microscopy for the overall imaging of the specimen and fluorescence correlation spectroscopy (FCS) to determine Wnt3 dynamics, we demonstrated that Wnt3 regulates cerebellum development during embryogenesis using zebrafish wnt3 transgenics with either tissue-specific expression of an EGFP reporter or a functionally active fusion protein, Wnt3EGFP. The results suggest a state of dynamic equilibrium of Wnt3EGFP mobility in polarized neuroepithelial-like progenitors in the dorsal midline and cerebellar progenitors on the lateral side. Wnt3EGFP is secreted from the cerebellum as shown by measurements of its mobility in the ventricular cavity. The importance of Wnt secretion in brain patterning was validated with the Porcn inhibitor Wnt-C59 (C59), which, when applied early, reduced membrane-bound and secreted fractions of Wnt3EGFP and led to a malformed brain characterized by the absence of epithalamus, optic tectum and cerebellum. Likewise, interference with Wnt secretion later on during cerebellar development negatively impacted cerebellar growth and patterning. Our work, supported by quantitative analysis of protein dynamics in vivo, highlights the importance of membrane-localized and secreted Wnt3 during cerebellum development. PMID:26395493

  3. The ESAT-6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation.

    PubMed

    Tan, Tracy; Lee, Warren L; Alexander, David C; Grinstein, Sergio; Liu, Jun

    2006-09-01

    Virulence of Mycobacterium tuberculosis and related pathogenic mycobacteria requires the secretion of early secretory antigenic 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10), two small proteins that lack traditional signal sequences and are exported through an alternative secretion pathway encoded primarily by the RD1 genetic locus. Mutations affecting the synthesis or secretion of ESAT-6 or CFP-10 attenuate the virulence of M. tuberculosis in murine models of infection. However, the specific functions of these proteins and of their secretion system are currently unclear. In this study, we isolated a mutant of Mycobacterium marinum defective in the secretion of ESAT-6 and CFP-10. The mutation was localized within MM5446, which is orthologous to Rv3871 of M. tuberculosis H37Rv and encodes an ATPase that is a component of the ESAT-6/CFP-10 secretion system. The mutant bacteria were unable to replicate within J774 macrophages although their growth in 7H9 medium was equivalent to the parental strain. Phagosome maturation and acidification were analysed in infected macrophages by confocal and electron microscopy using the late endosome/lysosome marker LAMP-1, along with various fluid-phase markers such as rhodamine-dextran and ferritin and the acidotropic dye LysoTracker Red. These studies demonstrated that while the wild-type parental strain of M. marinum primarily resides in a poorly acidified, non-lysosomal compartment, a significantly higher percentage of the MM5446 mutant organisms are in acidified compartments. These results suggest that the ESAT-6/CFP-10 secretion system plays a role in preventing phagolysosomal fusion, a novel function that accounts for the ability of bacteria to survive inside host cells. This finding provides a mechanism by which the ESAT-6/CFP-10 secretion system potentiates the virulence of pathogenic mycobacteria. PMID:16922861

  4. Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscUCC

    PubMed Central

    Frost, Stefan; Ho, Oanh; Login, Frédéric H.; Weise, Christoph F.; Wolf-Watz, Hans; Wolf-Watz, Magnus

    2012-01-01

    Type III secretion system mediated secretion and translocation of Yop-effector proteins across the eukaryotic target cell membrane by pathogenic Yersinia is highly organized and is dependent on a switching event from secretion of early structural substrates to late effector substrates (Yops). Substrate switching can be mimicked in vitro by modulating the calcium levels in the growth medium. YscU that is essential for regulation of this switch undergoes autoproteolysis at a conserved N↑PTH motif, resulting in a 10 kDa C-terminal polypeptide fragment denoted YscUCC. Here we show that depletion of calcium induces intramolecular dissociation of YscUCC from YscU followed by secretion of the YscUCC polypeptide. Thus, YscUCC behaved in vivo as a Yop protein with respect to secretion properties. Further, destabilized yscU mutants displayed increased rates of dissociation of YscUCC in vitro resulting in enhanced Yop secretion in vivo at 30°C relative to the wild-type strain.These findings provide strong support to the relevance of YscUCC dissociation for Yop secretion. We propose that YscUCC orchestrates a block in the secretion channel that is eliminated by calcium depletion. Further, the striking homology between different members of the YscU/FlhB family suggests that this protein family possess regulatory functions also in other bacteria using comparable mechanisms. PMID:23185318

  5. 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 }

  6. 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

  7. 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.

  8. 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. PMID:24110653

  9. 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

  10. Removal of Duodenum Elicits GLP-1 Secretion

    PubMed Central

    Muscogiuri, Giovanna; Mezza, Teresa; Prioletta, Annamaria; Sorice, Gian Pio; Clemente, Gennaro; Sarno, Gerardo; Nuzzo, Gennaro; Pontecorvi, Alfredo; Holst, Jens J.; Giaccari, Andrea

    2013-01-01

    OBJECTIVE To evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects. RESEARCH DESIGN AND METHODS For evaluation of hormonal secretion and insulin sensitivity, 10 overweight patients without type 2 diabetes (age 61 ± 19.3 years and BMI 27.9 ± 5.3 kg/m2) underwent a mixed-meal test and a hyperinsulinemic-euglycemic clamp before and after pylorus-preserving pancreatoduodenectomy for ampulloma. RESULTS All patients experienced a reduction in insulin (P = 0.002), C-peptide (P = 0.0002), and gastric inhibitory peptide (GIP) secretion (P = 0.0004), while both fasting and postprandial glucose levels increased (P = 0.0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0.02 and 0.031). While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R2 = 0.56; P = 0.012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R2 = 0.46; P = 0.03) and C-peptide (R2 = 0.37; P = 0.04). Given that the remaining pancreas presumably has preserved intraislet anatomy, insulin secretory capacity, and α- and β-cell interplay, our data suggest that the increased glucagon secretion is related to decreased systemic insulin. CONCLUSIONS Pylorus-preserving pancreatoduodenectomy was associated with a decrease in GIP and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion. Rather, the hypoinsulinemia may have caused an increase in glucagon secretion. PMID:23393218

  11. 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.

  12. 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

  13. Development of secreted proteins as biotherapeutic agents.

    PubMed

    Bonin-Debs, Angelika L; Boche, Irene; Gille, Hendrik; Brinkmann, Ulrich

    2004-04-01

    As one of the most important classes of proteins, secreted factors account for about one-tenth of the human genome, 3000 - 4000 in total, including factors of signalling pathways, blood coagulation and immune defence, as well as digestive enzymes and components of the extracellular matrix. Secreted proteins are a rich source of new therapeutics and drug targets, and are currently the focus of major drug discovery programmes throughout the industry. Many of the most important novel drugs developed in biotechnology have resulted from the application of secreted proteins as therapeutics. Secreted proteins often circulate throughout the body and, therefore, have access to most organs and tissues. Because of that, many of the factors are themselves therapeutic agents. This paper gives an overview on the features and functions of human secreted proteins and peptides, as well as strategies by which to discover additional therapeutic proteins from the human 'secretome'. Furthermore, a variety of examples are provided for the therapeutic use of recombinant secreted proteins as 'biologicals', including features and applications of recombinant antibodies, erythropoietin, insulin, interferon, plasminogen activators, growth hormone and colony-stimulating factors. PMID:15102604

  14. 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.

  15. The cargo and the transport system: secreted proteins and protein secretion in Trichoderma reesei (Hypocrea jecorina).

    PubMed

    Saloheimo, Markku; Pakula, Tiina M

    2012-01-01

    Trichoderma reesei (Hypocrea jecorina) is an efficient cell factory for protein production that is exploited by the enzyme industry. Yields of over 100 g secreted protein l(-1) from industrial fermentations have been reported. In this review we discuss the spectrum of proteins secreted by T. reesei and the studies carried out on its protein secretion system. The major enzymes secreted by T. reesei under production conditions are those degrading plant polysaccharides, the most dominant ones being the major cellulases, as demonstrated by the 2D gel analysis of the secretome. According to genome analysis, T. reesei has fewer genes encoding enzymes involved in plant biomass degradation compared with other fungi with sequenced genomes. We also discuss other T. reesei secreted enzymes and proteins that have been studied, such as proteases, laccase, tyrosinase and hydrophobins. Investigation of the T. reesei secretion pathway has included molecular characterization of the pathway components functioning at different stages of the secretion process as well as analysis of the stress responses caused by impaired folding or trafficking in the pathway or by expression of heterologous proteins. Studies on the transcriptional regulation of the secretory pathway have revealed similarities, but also interesting differences, with other organisms, such as a different induction mechanism of the unfolded protein response and the repression of genes encoding secreted proteins under secretion stress conditions. PMID:22053009

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

    DOE PAGESBeta

    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

  17. The evolution of milk secretion and its ancient origins.

    PubMed

    Oftedal, O T

    2012-03-01

    Lactation represents an important element of the life history strategies of all mammals, whether monotreme, marsupial, or eutherian. Milk originated as a glandular skin secretion in synapsids (the lineage ancestral to mammals), perhaps as early as the Pennsylvanian period, that is, approximately 310 million years ago (mya). Early synapsids laid eggs with parchment-like shells intolerant of desiccation and apparently dependent on glandular skin secretions for moisture. Mammary glands probably evolved from apocrine-like glands that combined multiple modes of secretion and developed in association with hair follicles. Comparative analyses of the evolutionary origin of milk constituents support a scenario in which these secretions evolved into a nutrient-rich milk long before mammals arose. A variety of antimicrobial and secretory constituents were co-opted into novel roles related to nutrition of the young. Secretory calcium-binding phosphoproteins may originally have had a role in calcium delivery to eggs; however, by evolving into large, complex casein micelles, they took on an important role in transport of amino acids, calcium and phosphorus. Several proteins involved in immunity, including an ancestral butyrophilin and xanthine oxidoreductase, were incorporated into a novel membrane-bound lipid droplet (the milk fat globule) that became a primary mode of energy transfer. An ancestral c-lysozyme lost its lytic functions in favor of a role as α-lactalbumin, which modifies a galactosyltransferase to recognize glucose as an acceptor, leading to the synthesis of novel milk sugars, of which free oligosaccharides may have predated free lactose. An ancestral lipocalin and an ancestral whey acidic protein four-disulphide core protein apparently lost their original transport and antimicrobial functions when they became the whey proteins β-lactoglobulin and whey acidic protein, which with α-lactalbumin provide limiting sulfur amino acids to the young. By the late

  18. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the... the MSDS, provided that the operator— (1) Can support the claim that the chemical's identity is a... secret, (3) Indicates in the MSDS that the chemical's identity is withheld as a trade secret, and...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. Exocytosis and protein secretion in Trypanosoma

    PubMed Central

    2010-01-01

    Background Human African trypanosomiasis is a lethal disease caused by the extracellular parasite Trypanosoma brucei. The proteins secreted by T. brucei inhibit the maturation of dendritic cells and their ability to induce lymphocytic allogenic responses. To better understand the pathogenic process, we combined different approaches to characterize these secreted proteins. Results Overall, 444 proteins were identified using mass spectrometry, the largest parasite secretome described to date. Functional analysis of these proteins revealed a strong bias toward folding and degradation processes and to a lesser extent toward nucleotide metabolism. These features were shared by different strains of T. brucei, but distinguished the secretome from published T. brucei whole proteome or glycosome. In addition, several proteins had not been previously described in Trypanosoma and some constitute novel potential therapeutic targets or diagnostic markers. Interestingly, a high proportion of these secreted proteins are known to have alternative roles once secreted. Furthermore, bioinformatic analysis showed that a significant proportion of proteins in the secretome lack transit peptide and are probably not secreted through the classical sorting pathway. Membrane vesicles from secretion buffer and infested rat serum were purified on sucrose gradient and electron microscopy pictures have shown 50- to 100-nm vesicles budding from the coated plasma membrane. Mass spectrometry confirmed the presence of Trypanosoma proteins in these microvesicles, showing that an active exocytosis might occur beyond the flagellar pocket. Conclusions This study brings out several unexpected features of the secreted proteins and opens novel perspectives concerning the survival strategy of Trypanosoma as well as possible ways to control the disease. In addition, concordant lines of evidence support the original hypothesis of the involvement of microvesicle-like bodies in the survival strategy allowing

  5. 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

  6. Quantum Ramp Secret Sharing Scheme and Quantum Operations

    NASA Astrophysics Data System (ADS)

    Xiao, Heling; Wang, Huifeng; Wang, Bin

    2016-05-01

    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.

  7. 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.

  8. Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis.

    PubMed

    Nielsen, Sebastian R; Quaranta, Valeria; Linford, Andrea; Emeagi, Perpetua; Rainer, Carolyn; Santos, Almudena; Ireland, Lucy; Sakai, Takao; Sakai, Keiko; Kim, Yong-Sam; Engle, Dannielle; Campbell, Fiona; Palmer, Daniel; Ko, Jeong Heon; Tuveson, David A; Hirsch, Emilio; Mielgo, Ainhoa; Schmid, Michael C

    2016-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is a devastating metastatic disease for which better therapies are urgently needed. Macrophages enhance metastasis in many cancer types; however, the role of macrophages in PDAC liver metastasis remains poorly understood. Here we found that PDAC liver metastasis critically depends on the early recruitment of granulin-secreting inflammatory monocytes to the liver. Mechanistically, we demonstrate that granulin secretion by metastasis-associated macrophages (MAMs) activates resident hepatic stellate cells (hStCs) into myofibroblasts that secrete periostin, resulting in a fibrotic microenvironment that sustains metastatic tumour growth. Disruption of MAM recruitment or genetic depletion of granulin reduced hStC activation and liver metastasis. Interestingly, we found that circulating monocytes and hepatic MAMs in PDAC patients express high levels of granulin. These findings suggest that recruitment of granulin-expressing inflammatory monocytes plays a key role in PDAC metastasis and may serve as a potential therapeutic target for PDAC liver metastasis. PMID:27088855

  9. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis

    PubMed Central

    Zhou, Weiying; Fong, Miranda Y.; Min, Yongfen; Somlo, George; Liu, Liang; Palomares, Melanie R.; Yu, Yang; Chow, Amy; O’Connor, Sean Timothy Francis; Chin, Andrew R.; Yen, Yun; Wang, Yafan; Marcusson, Eric G.; Chu, Peiguo; Wu, Jun; Wu, Xiwei; Li, Arthur Xuejun; Li, Zhuo; Gao, Hanlin; Ren, Xiubao; Boldin, Mark P.; Lin, Pengnian Charles; Wang, Shizhen Emily

    2014-01-01

    SUMMARY Cancer-secreted miRNAs are emerging mediators of cancer–host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in non-metastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. MiR-105 can be detected in the circulation at the pre-metastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer. PMID:24735924

  10. Platelet C1- inhibitor. A secreted alpha-granule protein.

    PubMed Central

    Schmaier, A H; Smith, P M; Colman, R W

    1985-01-01

    In order to characterize which proteins of the contact phase of coagulation interact with platelets, human platelets were studied immunochemically and functionally to determine if they contain C1- inhibitor. By means of monospecific antibody to C1- inhibitor, a competitive enzyme-linked immunosorbent assay (CELISA) was developed to measure directly platelet C1- inhibitor. With the CELISA, from 33 to 115 ng of C1- inhibitor antigen per 10(8) platelets from 15 normal donors was quantified in lysates of washed human platelets solubilized in nonionic detergent. The mean concentration in 10(8) platelets was 62 +/- 33 ng (SD). Plasma C1- inhibitor either in the platelet suspension medium or on the surface of the platelets could account for only from 6.5 to 16% of the total antigen measured in the solubilized platelets. Upon functional studies, platelets contained 84 +/- 36 ng (SD) of C1- inhibitor activity in 10(8) platelets. As assessed by the CELISA, platelet C1- inhibitor antigen was immunochemically identical to plasma and purified C1- inhibitor. In contrast, the mean concentration of platelet C1- inhibitor antigen in platelets from four patients with classical hereditary angioedema was 8.3 ng/10(8) platelets (range, 5.3 to 11.3 ng/10(8) platelets). 25 and 31% of the total platelet C1- inhibitor was secreted without cell lysis from normal platelets after exposure to collagen (20 micrograms/ml) and thrombin (1 U/ml), respectively, and this secretion was blocked by metabolic inhibitors. Platelet subcellular fractionation showed that platelet C1- inhibitor resided mostly in alpha-granules, similar to the location of platelet fibrinogen. Thus, human platelets contained C1- inhibitor, which became available by platelet secretion. The identification of platelet C1- inhibitor suggests that platelets may modulate the activation of the proteins of early blood coagulation and the classical complement pathways. Images PMID:3965505

  11. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Inhibition of apolipoprotein B and triglyceride secretion in human hepatoma cells (HepG2).

    PubMed

    Haghpassand, M; Wilder, D; Moberly, J B

    1996-07-01

    Apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins, is assembled into a lipoprotein particle via a complex, multistep process. Recent studies indicate that triglyceride-rich lipoprotein assembly requires the activity of the heterodimeric protein, microsomal triglyceride transfer protein (MTP). We identified a novel inhibitor of apolipoprotein B secretion using the human hepatoma cell line, HepG2. CP-10447, a derivative of the hypnotic drug methaqualone (Quaalude), inhibited apoB secretion from HepG2 cells with an IC50 of approximately 5 microM. CP-10447 also inhibited apoB secretion from Caco-2 cells, a model of intestinal lipoprotein production. In experiments using [3H]glycerol as a precursor for triglyceride synthesis, CP-10447 (20 microM) inhibited radiolabeled triglyceride secretion by approximately 83% (P < 0.0001) in HepG2 cells and 76% (P < 0.05) in Caco-2 cells with no effect on radiolabel incorporation into cellular triglyceride, indicating that CP-10447 inhibited triglyceride secretion without affecting triglyceride synthesis. RNA solution hybridization assay indicated that CP-10447 did not affect apoB or apoA-I mRNA levels. Pulse-chase experiments in HepG2 cells confirmed that CP-10447 inhibited the secretion of apoB (not its synthesis) without affecting secretion of total proteins or albumin and suggested that CP-10447 stimulates the early intracellular degradation of apoB in the endoplasmic reticulum (ER). Further studies demonstrated that CP-10447 is a potent inhibitor of human liver microsomal triglyceride transfer activity (IC50 approximately 1.7 microM) in an in vitro assay containing artificial liposomes and partially purified human MTP. These data suggest that CP-10447 may inhibit apoB and triglyceride secretion by inhibiting MTP activity and stimulating the early ER degradation of apoB. CP-10447 should provide a useful tool for further study of the mechanisms of apoB secretion and triglyceride

  15. 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. PMID:27208702

  16. 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

  17. Biochemical Methods to Analyze Wnt Protein Secretion.

    PubMed

    Glaeser, Kathrin; Boutros, Michael; Gross, Julia Christina

    2016-01-01

    Wnt proteins act as potent morphogens in various aspects of embryonic development and adult tissue homeostasis. However, in addition to its physiological importance, aberrant Wnt signaling has been linked to the onset and progression of different types of cancer. On the cellular level, the secretion of Wnt proteins involves trafficking of lipid-modified Wnts from the endoplasmic reticulum (ER) to Golgi and further compartments via the Wnt cargo receptor evenness interrupted. Others and we have recently shown that Wnt proteins are secreted on extracellular vesicles (EVs) such as microvesicles and exosomes. Although more details about specific regulation of Wnt secretion steps are emerging, it remains largely unknown how Wnt proteins are channeled into different release pathways such as lipoprotein particles, EVs and cytonemes. Here, we describe protocols to purify and quantify Wnts from the supernatant of cells by either assessing total Wnt proteins in the supernatant or monitoring Wnt proteins on EVs. Purified Wnts from the supernatant as well as total cellular protein content can be investigated by immunoblotting. Additionally, the relative activity of canonical Wnts in the supernatant can be assessed by a dual-luciferase Wnt reporter assay. Quantifying the amount of secreted Wnt proteins and their activity in the supernatant of cells allows the investigation of intracellular trafficking events that regulate Wnt secretion and the role of extracellular modulators of Wnt spreading. PMID:27590148

  18. Cyclic AMP-induced K+ secretion occurs independently of Cl- secretion in rat distal colon.

    PubMed

    Sandle, Geoffrey I; Rajendran, Vazhaikkurichi M

    2012-08-01

    cAMP induces both active Cl(-) and active K(+) secretion in mammalian colon. It is generally assumed that a mechanism for K(+) exit is essential to maintain cells in the hyperpolarized state, thus favoring a sustained Cl(-) secretion. Both Kcnn4c and Kcnma1 channels are located in colon, and this study addressed the questions of whether Kcnn4c and/or Kcnma1 channels mediate cAMP-induced K(+) secretion and whether cAMP-induced K(+) secretion provides the driving force for Cl(-) secretion. Forskolin (FSK)-enhanced short-circuit current (indicator of net electrogenic ion transport) and K(+) fluxes were measured simultaneously in colonic mucosa under voltage-clamp conditions. Mucosal Na(+) orthovanadate (P-type ATPase inhibitor) inhibited active K(+) absorption normally present in rat distal colon. In the presence of mucosal Na(+) orthovanadate, serosal FSK induced both K(+) and Cl(-) secretion. FSK-induced K(+) secretion was 1) not inhibited by either mucosal or serosal 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34; a Kcnn4 channel blocker), 2) inhibited (92%) by mucosal iberiotoxin (Kcnma1 channel blocker), and 3) not affected by mucosal cystic fibrosis transmembrane conductance regulator inhibitor (CFTR(inh)-172). By contrast, FSK-induced Cl(-) secretion was 1) completely inhibited by serosal TRAM-34, 2) not inhibited by either mucosal or serosal iberiotoxin, and 3) completely inhibited by mucosal CFTR(inh)-172. These results indicate that cAMP-induced colonic K(+) secretion is mediated via Kcnma1 channels located in the apical membrane and most likely contributes to stool K(+) losses in secretory diarrhea. On the other hand, cAMP-induced colonic Cl(-) secretion requires the activity of Kcnn4b channels located in the basolateral membrane and is not dependent on the concurrent activation of apical Kcnma1 channels. PMID:22648950

  19. Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management.

    PubMed

    Amlashi, Fatemeh G; Tritos, Nicholas A

    2016-06-01

    Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas. PMID:26792794

  20. Protein Secretion and the Endoplasmic Reticulum

    PubMed Central

    Benham, Adam M.

    2012-01-01

    In a complex multicellular organism, different cell types engage in specialist functions, and as a result, the secretory output of cells and tissues varies widely. Whereas some quiescent cell types secrete minor amounts of proteins, tissues like the pancreas, producing insulin and other hormones, and mature B cells, producing antibodies, place a great demand on their endoplasmic reticulum (ER). Our understanding of how protein secretion in general is controlled in the ER is now quite sophisticated. However, there remain gaps in our knowledge, particularly when applying insight gained from model systems to the more complex situations found in vivo. This article describes recent advances in our understanding of the ER and its role in preparing proteins for secretion, with an emphasis on glycoprotein quality control and pathways of disulfide bond formation. PMID:22700933

  1. 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

  2. A light-triggered protein secretion system

    PubMed Central

    Chen, Daniel; Gibson, Emily S.

    2013-01-01

    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. PMID:23671313

  3. CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations.

    PubMed

    Arce, Sergio; Luger, Elke; Muehlinghaus, Gwendolin; Cassese, Giuliana; Hauser, Anja; Horst, Alexander; Lehnert, Katja; Odendahl, Marcus; Hönemann, Dirk; Heller, Karl-Dieter; Kleinschmidt, Harald; Berek, Claudia; Dörner, Thomas; Krenn, Veit; Hiepe, Falk; Bargou, Ralf; Radbruch, Andreas; Manz, Rudolf A

    2004-06-01

    Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Several subpopulations of IgG-secreting cells were identified among the cells isolated from tonsils and bone marrow, particularly differing in the expression levels of CD9, CD19, and CD38. CD38 low IgG-secreting cells were present exclusively in the tonsils. A major fraction of these cells appeared to be early plasma cell precursors, as upon activation of B cells in vitro, IgG secretion preceded up-regulation of CD38, and on tonsillar sections, IgG-containing, CD38 low cells with a plasmacytoid phenotype were found in follicles, where plasma cell differentiation starts. A unitary phenotype of migratory peripheral blood IgG-secreting cells suggests that all bone marrow plasma cell populations share a common precursor cell. These data are compatible with a multistep model for plasma cell differentiation and imply that a common CD38 low IgG-secreting precursor gives rise to a diverse plasma cell compartment. PMID:15020647

  4. Rescue fantasies and the secret benefactor.

    PubMed

    Gillman, R D

    1992-01-01

    The concept of rescue fantasies is traced from Freud's earliest idea of the rescue of the mother as the fallen woman to later ideas of ambivalent rescue of the father, siblings, and children. Clinical vignettes from work with children and adults illustrate these points as well as reparative rescue fantasies in response to trauma and narcissistic hurt. The contemporary family romance myth of the secret benefactor as rescuer is described. An analytic case presentation explores the narcissistic-masochistic and the positive and negative oedipal meanings of the secret benefactor rescue fantasy. Application to countertransference enactments in the analyst is suggested. PMID:1289936

  5. Comment on "Dynamic quantum secret sharing"

    NASA Astrophysics Data System (ADS)

    Liao, Ci-Hong; Yang, Chun-Wei; Hwang, Tzonelish

    2013-10-01

    Hsu et al. (Quantum Inf Process 12:331-344,2013) proposed a dynamic quantum secret sharing (DQSS) protocol using the entanglement swapping of Bell states for an agent to easily join (or leave) the system. In 2013, Wang and Li (Quantum Inf Process 12(5):1991-1997, 2013) proposed a collusion attack on Hsu et al.'s DQSS protocol. Nevertheless, this study points out a new security issue on Hsu et al.'s DQSS protocol regarding to the honesty of a revoked agent. Without considering this issue, the DQSS protocol could be failed to provide secret sharing function.

  6. 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

  7. Pancreatic enzyme secretion during intravenous fat infusion.

    PubMed

    Burns, G P; Stein, T A

    1987-01-01

    The nutritional support of patients with pancreatic and high gastrointestinal fistulas and severe pancreatitis frequently involves intravenous fat infusion. There are conflicting reports on the effect of intravenous fat on pancreatic exocrine secretion. In 10 dogs with chronic pancreatic fistulas, pancreatic juice was collected during secretin (n = 10) or secretin + cholecystokinin (n = 4) stimulation, with and without intravenous fat infusion (5 g/hr). The hormonal-stimulated secretion of lipase, amylase, trypsin, total protein, bicarbonate, and water was unchanged during fat infusion. This study supports the use of intravenous fat as a nutritional source when it is desirable to avoid stimulation of the pancreas. PMID:2434670

  8. Growth hormone secreting pituitary adenoma with admixed gangliocytoma and ganglioglioma.

    PubMed

    Jukes, Alistair; Allan, Rodney; Rawson, Robert; Buckland, Michael E

    2016-09-01

    Pituitary adenomas are the most common tumours found in the sellar region and, when both functioning and non-functioning adenomas are combined, account for 7-15% of primary brain tumours in adults. Rarely, admixed or discrete groups of cells comprising two or more tumour subtypes are seen; the so-called 'collision tumour'. We present a case of a 54-year-old-woman with a growth hormone-secreting pituitary adenoma admixed with both ganglioglioma and gangliocytoma. The possible mechanisms by which this may occur include a pre-existing gangliocytoma promoting the development of pituitary adenoma by hypersecretion of releasing hormones or aberrant migration of hypothalamic neurons in early embryogenesis. PMID:27068013

  9. 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. PMID:26014472

  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. Structure of a Type IV Secretion System

    PubMed Central

    Rivera-Calzada, Angel; Braun, Nathalie; Connery, Sarah; Dujeancourt, Annick; Lu, Fang; Redzej, Adam; Fronzes, Rémi; Orlova, Elena V.; Waksman, Gabriel

    2014-01-01

    Bacterial type IV secretion (T4S) systems translocate virulence factors into eukaryotic cells1,2, distribute genetic material between bacteria, and have shown potential as a tool for the genetic modification of human cells3. Given the complex choreography of the substrate through the secretion apparatus4, the molecular mechanism of the T4S system has proven difficult to dissect in the absence of structural data for the entire machinery. Here we use electron microscopy (EM) to reconstruct the T4S system encoded by the Escherichia coli R388 conjugative plasmid. We show that eight proteins assemble in an intricate stoichiometric relationship to form a ~3 megadalton (MDa) nanomachine that spans the entire cell envelope. The structure comprises an outer membrane-associated core complex1 connected by a central stalk to a substantial inner membrane complex that is dominated by a battery of twelve VirB4 ATPase subunits organised as side by side hexameric barrels. Our results show a secretion system with markedly different architecture, and consequently mechanism, to other known bacterial secretion systems1,4-6. PMID:24670658

  12. 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…

  13. Penetration of cefotaxime into respiratory secretions.

    PubMed Central

    Fick, R B; Alexander, M R; Prince, R A; Kasik, J E

    1987-01-01

    The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h after receiving four doses of cefotaxime (2 g intravenously every 6 h). In 11 patients, cefotaxime levels measured by high-pressure liquid chromatography in bronchial secretions were below detectable limits (less than 0.5 mg/liter); however, levels of desacetyl cefotaxime exceeded 1.5 mg/liter in 9 of these 11 patients (range, 1.6 to 10 mg/liter). Concentrations of desacetyl cefotaxime in lung secretions (6.9 +/- 0.85 [standard error] mg/liter) was 77% of mean levels of desacetyl cefotaxime in plasma (8.9 +/- 1.26 mg/liter). In summary, concentrations of desacetyl cefotaxime in bronchial secretions are markedly higher than those of cefotaxime. PMID:3606080

  14. 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.…

  15. Site of Fluid Secretion in Small Airways.

    PubMed

    Flores-Delgado, Guillermo; Lytle, Christian; Quinton, Paul M

    2016-03-01

    The secretion and management of readily transportable airway surface liquid (ASL) along the respiratory tract is crucial for the clearance of debris and pathogens from the lungs. In proximal large airways, submucosal glands (SMGs) can produce ASL. However, in distal small airways, SMGs are absent, although the lumens of these airways are, uniquely, highly plicated. Little is known about the production and maintenance of ASL in small airways, but using electrophysiology, we recently found that native porcine small airways simultaneously secrete and absorb. How these airways can concurrently transport ASL in opposite directions is puzzling. Using high expression of the Na-K-2Cl cotransport (NKCC) 1 protein (SLC12a2) as a phenotypic marker for fluid secretory cells, immunofluorescence microscopy of porcine small airways revealed two morphologically separated sets of luminal epithelial cells. NKCC1 was abundantly expressed by most cells in the contraluminal regions of the pleats but highly expressed very infrequently by cells in the luminal folds of the epithelial plications. In larger proximal airways, the acini of SMGs expressed NKCC1 prominently, but cells expressing NKCC1 in the surface epithelium were sparse. Our findings indicate that, in the small airway, cells in the pleats of the epithelium secrete ASL, whereas, in the larger proximal airways, SMGs mainly secrete ASL. We propose a mechanism in which the locations of secretory cells in the base of pleats and of absorptive cells in luminal folds physically help maintain a constant volume of ASL in small airways. PMID:26562629

  16. 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…

  17. 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,…

  18. Regulated Mucin Secretion from Airway Epithelial Cells

    PubMed Central

    Adler, Kenneth B.; Tuvim, Michael J.; Dickey, Burton F.

    2013-01-01

    Secretory epithelial cells of the proximal airways synthesize and secrete gel-forming polymeric mucins. The secreted mucins adsorb water to form mucus that is propelled by neighboring ciliated cells, providing a mobile barrier which removes inhaled particles and pathogens from the lungs. Several features of the intracellular trafficking of mucins make the airway secretory cell an interesting comparator for the cell biology of regulated exocytosis. Polymeric mucins are exceedingly large molecules (up to 3 × 106 Da per monomer) whose folding and initial polymerization in the ER requires the protein disulfide isomerase Agr2. In the Golgi, mucins further polymerize to form chains and possibly branched networks comprising more than 20 monomers. The large size of mucin polymers imposes constraints on their packaging into transport vesicles along the secretory pathway. Sugar side chains account for >70% of the mass of mucins, and their attachment to the protein core by O-glycosylation occurs in the Golgi. Mature polymeric mucins are stored in large secretory granules ∼1 μm in diameter. These are translocated to the apical membrane to be positioned for exocytosis by cooperative interactions among myristoylated alanine-rich C kinase substrate, cysteine string protein, heat shock protein 70, and the cytoskeleton. Mucin granules undergo exocytic fusion with the plasma membrane at a low basal rate and a high stimulated rate. Both rates are mediated by a regulated exocytic mechanism as indicated by phenotypes in both basal and stimulated secretion in mice lacking Munc13-2, a sensor of the second messengers calcium and diacylglycerol (DAG). Basal secretion is induced by low levels of activation of P2Y2 purinergic and A3 adenosine receptors by extracellular ATP released in paracrine fashion and its metabolite adenosine. Stimulated secretion is induced by high levels of the same ligands, and possibly by inflammatory mediators as well. Activated receptors are coupled to

  19. Monosodium Urate Activates Src/Pyk2/PI3 Kinase and Cathepsin Dependent Unconventional Protein Secretion From Human Primary Macrophages*

    PubMed Central

    Välimäki, Elina; Miettinen, Juho J.; Lietzén, Niina; Matikainen, Sampsa; Nyman, Tuula A.

    2013-01-01

    Monosodium urate (MSU) is an endogenous danger signal that is crystallized from uric acid released from injured cells. MSU is known to activate inflammatory response in macrophages but the molecular mechanisms involved have remained uncharacterized. Activated macrophages start to secrete proteins to activate immune response and to recruit other immune cells to the site of infection and/or tissue damage. Secretome characterization after activation of innate immune system is essential to unravel the details of early phases of defense responses. Here, we have analyzed the secretome of human primary macrophages stimulated with MSU using quantitative two-dimensional gel electrophoresis based proteomics as well as high-throughput qualitative GeLC-MS/MS approach combining protein separation by SDS-PAGE and protein identification by liquid chromatography-MS/MS. Both methods showed that MSU stimulation induced robust protein secretion from lipopolysaccharide-primed human macrophages. Bioinformatic analysis of the secretome data showed that MSU stimulation strongly activates unconventional, vesicle mediated protein secretion. The unconventionally secreted proteins included pro-inflammatory cytokines like IL-1β and IL-18, interferon-induced proteins, and danger signal proteins. Also active forms of lysosomal proteases cathepsins were secreted on MSU stimulation, and cathepsin activity was essential for MSU-induced unconventional protein secretion. Additionally, proteins associated to phosphorylation events including Src family tyrosine kinases were increased in the secretome of MSU-stimulated cells. Our functional studies demonstrated that Src, Pyk2, and PI3 kinases act upstream of cathepsins to activate the overall protein secretion from macrophages. In conclusion, we provide the first comprehensive characterization of protein secretion pathways activated by MSU in human macrophages, and reveal a novel role for cathepsins and Src, Pyk2, PI3 kinases in the activation of

  20. Measurement of endotracheal tube secretions volume by micro computed tomography (MicroCT) scan: an experimental and clinical study

    PubMed Central

    2014-01-01

    Background Biofilm accumulates within the endotracheal tube (ETT) early after intubation. Contaminated secretions in the ETT are associated with increased risk for microbial dissemination in the distal airways and increased resistance to airflow. We evaluated the effectiveness of micro computed tomography (MicroCT) for the quantification of ETT inner volume reduction in critically ill patients. Methods We injected a known amount of gel into unused ETT to simulate secretions. We calculated the volume of gel analyzing MicroCT scans for a length of 20 cm. We then collected eleven ETTs after extubation of critically ill patients, recording clinical and demographical data. We assessed the amount of secretions by MicroCT and obtained ETT microbiological cultures. Results Gel volumes assessed by MicroCT strongly correlated with injected gel volumes (p < 0.001, r2 = 0.999). MicroCT revealed the accumulation of secretions on all the ETTs (median 0.154, IQR:0.02-0.837 mL), corresponding to an average cross-sectional area reduction of 1.7%. The amount of secretions inversely correlated with patients’ age (p = 0.011, rho = −0.727) but not with days of intubation, SAPS2, PaO2/FiO2 assessed on admission. Accumulation of secretions was higher in the cuff region (p = 0.003). Microbial growth occurred in cultures from 9/11 ETTs, and did not correlate with secretions amount. In 7/11 cases the same microbes were identified also in tracheal aspirates. Conclusions MicroCT appears as a feasible and precise technique to measure volume of secretions within ETTs after extubation. In patients, secretions tend to accumulate in the cuff region, with high variability among patients. PMID:24678963

  1. 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. PMID:7846688

  2. 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

  3. Early years.

    PubMed

    2011-04-01

    Healthcare professionals in Scotland who are involved in early years work now have an additional resource in the shape of NHS Scotland's Maternal and Early Years website, aimed at practitioners at all levels. The site includes evidence updates, news and events, and can be accessed at www.maternal-and-early-years.org.uk. PMID:27368523

  4. [Early Intervention.

    ERIC Educational Resources Information Center

    Pawl, Jeree, Ed.

    1992-01-01

    This newsletter focuses on the theme of early intervention which infants and young children with special needs in nine brief articles: "Early Intervention: A Matter of Context" (Samuel J. Meisels); "Early Intervention Research: Asking and Answering Meaningful Questions" (Jack P. Shonkoff); "From Case Management to Service Coordination: Families,…

  5. Early Intervention.

    ERIC Educational Resources Information Center

    Abery, Brian, Ed.; McConnell, Scott, Ed.

    1989-01-01

    This "feature issue" focuses on early intervention with handicapped children, with an emphasis on: Project EDGE (Expanding Developmental Growth through Education), an early intervention research project initiated in 1968; strategies for developing family-friendly early intervention services; and progress reports from various states and programs.…

  6. 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

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

    PubMed

    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

  8. 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)

  9. 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.

  10. Secretions and structures of the head of Sagitta setosa (Chaetognatha)

    NASA Astrophysics Data System (ADS)

    Kapp, Helga; Mathey, Juliane

    1989-03-01

    The different secretions of the mouth, the vestibular organs, and the vestibular pits of chaetognaths are shown on scanning electron micrographs of the head of Sagitta setosa. The secreting organs are described and the functions of the secretions are discussed. In addition, the secretion under the praeputium, a pit between the two rows of anterior teeth, and the surface structure of the teeth are described.

  11. 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.

  12. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name... MSDS, provided that the operator— (1) Can support the claim that the chemical's identity is a trade...) Indicates in the MSDS that the chemical's identity is withheld as a trade secret, and (4) Discloses in...

  13. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name... MSDS, provided that the operator— (1) Can support the claim that the chemical's identity is a trade...) Indicates in the MSDS that the chemical's identity is withheld as a trade secret, and (4) Discloses in...

  14. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name... MSDS, provided that the operator— (1) Can support the claim that the chemical's identity is a trade...) Indicates in the MSDS that the chemical's identity is withheld as a trade secret, and (4) Discloses in...

  15. 30 CFR 47.81 - Provisions for withholding trade secrets.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name... MSDS, provided that the operator— (1) Can support the claim that the chemical's identity is a trade...) Indicates in the MSDS that the chemical's identity is withheld as a trade secret, and (4) Discloses in...

  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. 32 CFR 9.9 - Protection of State secrets.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Protection of State secrets. 9.9 Section 9.9... § 9.9 Protection of State secrets. Nothing in this part shall be construed to authorize disclosure of state secrets to any person not authorized to receive them....

  18. 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...

  19. 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...

  20. 32 CFR 9.9 - Protection of State secrets.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Protection of State secrets. 9.9 Section 9.9... § 9.9 Protection of State secrets. Nothing in this part shall be construed to authorize disclosure of state secrets to any person not authorized to receive them....

  1. 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...

  2. 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...

  3. 32 CFR 9.9 - Protection of State secrets.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Protection of State secrets. 9.9 Section 9.9... § 9.9 Protection of State secrets. Nothing in this part shall be construed to authorize disclosure of state secrets to any person not authorized to receive them....

  4. 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...

  5. 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...

  6. 32 CFR 9.9 - Protection of State secrets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Protection of State secrets. 9.9 Section 9.9... § 9.9 Protection of State secrets. Nothing in this part shall be construed to authorize disclosure of state secrets to any person not authorized to receive them....

  7. 32 CFR 9.9 - Protection of State secrets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Protection of State secrets. 9.9 Section 9.9... § 9.9 Protection of State secrets. Nothing in this part shall be construed to authorize disclosure of state secrets to any person not authorized to receive them....

  8. 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...

  9. 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...

  10. 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... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall...

  11. 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,…

  12. Trade secrets in life science and pharmaceutical companies.

    PubMed

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

    2015-04-01

    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

  13. Secretion of flavins by three species of methanotrophic bacteria.

    PubMed

    Balasubramanian, Ramakrishnan; Levinson, Benjamin T; Rosenzweig, Amy C

    2010-11-01

    We detected flavins in the growth medium of the methanotrophic bacterium Methylocystis species strain M. Flavin secretion correlates with growth stage and increases under iron starvation conditions. Two other methanotrophs, Methylosinus trichosporium OB3b and Methylococcus capsulatus (Bath), secrete flavins, suggesting that flavin secretion may be common to many methanotrophic bacteria. PMID:20833792

  14. Proteomic Analysis of Schistosoma mansoni Egg Secretions

    PubMed Central

    Cass, Cynthia L.; Johnson, Jeffrey R.; Califf, Lindsay L.; Xu, Tao; Hernandez, Hector J.; Stadecker, Miguel J.; Yates, John R.; Williams, David L.

    2007-01-01

    Schistosomiasis remains a largely neglected, global health problem. The morbid pathology of the disease stems from the host's inflammatory response to parasite eggs trapped in host tissues. Long term host/parasite survival is dependent upon the successful modulation of the acute pathological response, which is induced by egg antigens. In this study, using Multidimensional Protein Identification Technology, we identified the Schistosoma mansoni egg secretome consisting of 188 proteins. Notably we identified proteins involved in redox balance, molecular chaperoning and protein folding, development and signaling, scavenging and metabolic pathways, immune response modulation, and 32 novel, previously uncharacterized schistosome proteins. We localized a subset of previously-characterized schistosome proteins identified in egg secretions in this study, to the surface of live S. mansoni eggs using the circumoval precipitin reaction. The identification of proteins actively secreted by live schistosome eggs provides important new information for understanding immune modulation and the pathology of schistosomiasis. PMID:17644200

  15. The SNARE Machinery in Mast Cell Secretion

    PubMed Central

    Lorentz, Axel; Baumann, Anja; Vitte, Joana; Blank, Ulrich

    2012-01-01

    Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators – stored in granules – as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion. PMID:22679448

  16. The secret life of dust [Book Review

    NASA Astrophysics Data System (ADS)

    Muller, Richard A.

    The Secret Life of Dust by Hannah Holmes is not a quick read. I frequently paused to reach for a pen to mark interesting pages, to write down surprising facts, or to tell my spouse about some wonderful story I had just read. This is not a book to rush through; it is a book to sink into, and it is densely packed with information. Holmes does not glorify dust, but she certainly finds it fascinating, little appreciated, and much misunderstood. The Secret Life of Dust is her attempt to open our eyes to something that is too small to see easily but too large to catch the attention of most physicists or chemists. Dust is everywhere, and it is far more important than most of us realize.

  17. Opioid control of gonadotrophin secretion in humans.

    PubMed

    Genazzani, A R; Genazzani, A D; Volpogni, C; Pianazzi, F; Li, G A; Surico, N; Petraglia, F

    1993-11-01

    Hypothalamus-pituitary-axis (HPA) is constantly under the modulatory effect of many substances, such as neurotransmitters, neuromodulators and steroid hormones. Recently, the involvement of endogenous opioid peptides (EOP) in the control of the neuroendocrine mechanism modulating gonadotrophin secretion has been supported by several authors. It has been demonstrated that acute morphine administration decreases luteinizing hormone (LH) plasma levels and this is due to an inhibitory modulation on gonadotrophin releasing hormone discharge from the hypothalamic neurons. EOP are usually increased by stressful situations. In stress-induced amenorrhoea, the presence of low LH plasma levels and an abnormal LH pulsatile secretion has been related to an increased opioid activity, thus supporting the integrative role of opioids between hormonal and neuronal afferences of brain. PMID:8276950

  18. Analysis of secreted proteins using SILAC.

    PubMed

    Henningsen, Jeanette; Blagoev, Blagoy; Kratchmarova, Irina

    2014-01-01

    Secreted proteins serve a crucial role in the communication between cells, tissues, and organs. Proteins released to the extracellular environment exert their function either locally or at distant points of the organism. Proteins are secreted in a highly dynamic fashion by cells and tissues in the body responding to the stimuli and requirements presented by the extracellular milieu. Characterization of secretomes derived from various cell types has been performed using different quantitative mass spectrometry-based proteomics strategies, several of them taking advantage of labeling with stable isotopes. Here, we describe the use of Stable Isotope Labeling by Amino acids in Cell culture (SILAC) for the quantitative analysis of the skeletal muscle secretome during myogenesis. PMID:25059621

  19. Neuroserpin, an axonally secreted serine protease inhibitor.

    PubMed Central

    Osterwalder, T; Contartese, J; Stoeckli, E T; Kuhn, T B; Sonderegger, P

    1996-01-01

    We have identified and chromatographically purified an axonally secreted glycoprotein of CNS and PNS neurons. Several peptides derived from it were microsequenced. Based on these sequences, a fragment of the corresponding cDNA was amplified and used as a probe to isolate a full length cDNA from a chicken brain cDNA library. Because the deduced amino acid sequence qualified the protein as a novel member of the serpin family of serine protease inhibitors, we called it neuroserpin. Analysis of the primary structural features further characterized neuroserpin as a heparin-independent, functional inhibitor of a trypsin-like serine protease. In situ hybridization revealed a predominantly neuronal expression during the late stages of neurogenesis and in the adult brain in regions which exhibit synaptic plasticity. Thus, neuroserpin might function as an axonally secreted regulator of the local extracellular proteolysis involved in the reorganization of the synaptic connectivity during development and synapse plasticity in the adult. Images PMID:8670795

  20. 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.…

  1. Paliperidone Induced Hypoglycemia by Increasing Insulin Secretion.

    PubMed

    Omi, Tsubasa; Riku, Keisen; Fukumoto, Motoyuki; Kanai, Koji; Omura, Yumi; Takada, Hiromune; Matunaga, Hidenori

    2016-01-01

    We report the case of a 41-year-old woman with schizophrenia who developed persistent hypoglycemia following paliperidone administration. After discontinuing paliperidone, the hypoglycemia resolved, but symptoms of diabetes emerged. Therefore, it appears that the hypoglycemia induced by paliperidone may mask symptoms of diabetes. Paliperidone may induce hypoglycemia by increasing insulin secretion. This report could help elucidate the relationship between atypical antipsychotics and glucose metabolism. PMID:27478670

  2. Paliperidone Induced Hypoglycemia by Increasing Insulin Secretion

    PubMed Central

    Riku, Keisen; Fukumoto, Motoyuki; Kanai, Koji; Omura, Yumi; Matunaga, Hidenori

    2016-01-01

    We report the case of a 41-year-old woman with schizophrenia who developed persistent hypoglycemia following paliperidone administration. After discontinuing paliperidone, the hypoglycemia resolved, but symptoms of diabetes emerged. Therefore, it appears that the hypoglycemia induced by paliperidone may mask symptoms of diabetes. Paliperidone may induce hypoglycemia by increasing insulin secretion. This report could help elucidate the relationship between atypical antipsychotics and glucose metabolism. PMID:27478670

  3. 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

  4. The accelerating effect of negative pressure wound therapy with Prevena™ on the healing of a closed wound with persistent serous secretion.

    PubMed

    Altintas, Burak; Biber, Roland; Brem, Matthias H

    2015-12-01

    Negative pressure wound therapy has been lately used on closed incisions in the immediate postoperative period to accelerate wound healing. However, there are no data in the literature regarding the use of this type of therapy for wounds with persistent secretion in the early postoperative care. We present the first report of persistent postoperative serous wound secretion in a patient after femoral nailing treated successfully with Prevena™ (KCI), a closed incision negative pressure management system (CINPWT). PMID:24393137

  5. Continuous measurements of ATP secretion in vivo.

    PubMed

    Smith, J B; Burke, S E; Lefer, A M; Freilich, A

    1984-01-01

    Blood was withdrawn continuously from femoral veins of anesthetized rabbits at a rate of 0.07 ml/min. Sodium citrate was pumped into the blood to prevent coagulation, and luciferin-luciferase reagent was added to permit the continuous detection of extracellular ATP. Subsequently, the red blood cells were lysed and the platelet count was recorded continuously. Injection of platelet activating factor or collagen into rabbit ear veins caused an almost immediate but short-lived increase in extracellular ATP with a simultaneous but more prolonged decrease in the platelet count. Although both the endoperoxide analog 9,11-azo-PGH2 and ADP also decreased the platelet count, little extracellular ATP was detected after the azo-PGH2 and none after ADP. These studies demonstrate that those agents that cause platelet secretion from rabbit platelets in vitro also cause secretion in vivo. The method described should be useful in evaluating the capacity of antithrombotic drugs to modify platelet secretion in vivo. PMID:24277184

  6. 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. PMID:27472103

  7. 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.

  8. An Ectopic ACTH Secreting Metastatic Parotid Tumour.

    PubMed

    Dacruz, Thomas; Kalhan, Atul; Rashid, Majid; Obuobie, Kofi

    2016-01-01

    A 60-year old woman presented with features of Cushing's syndrome (CS) secondary to an ectopic adrenocorticotropic hormone (ACTH) secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5-10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC) and neuroendocrine tumours (NET) account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH. PMID:26904316

  9. 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

  10. Electrophysiology of chloride-secreting epithelia.

    PubMed

    Frizzell, R A; Welsh, M J; Smith, P L

    1981-01-01

    A primary event in the stimulation of cyclic AMP-mediated active Cl secretion across epithelial tissues is an increase in the Cl permeability of the apical cell membrane. A rapid reduction in apical cell membrane resistance to Cl movement permits Cl to leave the cell down its electrochemical potential difference across this barrier. Since cell Cl activity is not markedly influenced by changes in the rate of Cl secretion, the cyclic nucleotide may also increase the ease with which Cl gains access to the secretory cells across the basolateral membrane. This Cl entry process appears to be mediated by NaCl co-transport since the maintenance of a high cell Cl activity depends upon the presence of sodium in the serosal bathing solution. Increased Cl entry across the basolateral membrane would promote enhanced Na entry into the cell and a secondary stimulation of active Na extrusion from cell to serosal solution. Increased Na-K-pump activity and/or a change in the K permeability of the basolateral membrane may be responsible for the augmented conductive ion flow across this barrier which accompanies the stimulation of active Cl secretion. PMID:6116284

  11. An Ectopic ACTH Secreting Metastatic Parotid Tumour

    PubMed Central

    Dacruz, Thomas; Kalhan, Atul; Rashid, Majid; Obuobie, Kofi

    2016-01-01

    A 60-year old woman presented with features of Cushing's syndrome (CS) secondary to an ectopic adrenocorticotropic hormone (ACTH) secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5–10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC) and neuroendocrine tumours (NET) account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH. PMID:26904316

  12. Secreted Aspartic Proteinase Family of Candida tropicalis

    PubMed Central

    Zaugg, Christophe; Borg-von Zepelin, Margarete; Reichard, Utz; Sanglard, Dominique; Monod, Michel

    2001-01-01

    Medically important yeasts of the genus Candida secrete aspartic proteinases (Saps), which are of particular interest as virulence factors. Like Candida albicans, Candida tropicalis secretes in vitro one dominant Sap (Sapt1p) in a medium containing bovine serum albumin (BSA) as the sole source of nitrogen. Using the gene SAPT1 as a probe and under low-stringency hybridization conditions, three new closely related gene sequences, SAPT2 to SAPT4, encoding secreted proteinases were cloned from a C. tropicalis λEMBL3 genomic library. All bands identified by Southern blotting of EcoRI-digested C. tropicalis genomic DNA with SAPT1 could be assigned to a specific SAP gene. Therefore, the SAPT gene family of C. tropicalis is likely to contain only four members. Interestingly, the SAPT2 and SAPT3 gene products, Sapt2p and Sapt3p, which have not yet been detected in C. tropicalis cultures in vitro, were produced as active recombinant enzymes with the methylotrophic yeast Pichia pastoris as an expression system. As expected, reverse transcriptase PCR experiments revealed a strong SAPT1 signal with RNA extracted from cells grown in BSA medium. However, a weak signal was obtained with all other SAPT genes under several conditions tested, showing that these SAPT genes could be expressed at a basic level. Together, these experiments suggest that the gene products Sapt2p, Sapt3p, and Sapt4p could be produced under conditions yet to be described in vitro or during infection. PMID:11119531

  13. Overtrained horses alter their resting pulsatile growth hormone secretion

    PubMed Central

    de Graaf-Roelfsema, E.; Veldhuis, P. P.; Keizer, H. A.; van Ginneken, M. M. E.; van Dam, K. G.; Johnson, M. L.; Barneveld, A.; Menheere, P. P. C. A.; van Breda, E.; Wijnberg, I. D.; van der Kolk, J. H.

    2009-01-01

    The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern. PMID:19494168

  14. Nilotinib exacerbates diabetes mellitus by decreasing secretion of endogenous insulin.

    PubMed

    Ito, Yoshikiyo; Miyamoto, Toshihiro; Chong, Yong; Maki, Toshinobu; Akashi, Koichi; Kamimura, Tomohiko

    2013-01-01

    We report a 74-year-old female with chronic myelogenous leukemia (CML) in accelerated phase with pre-existing severe type 2 diabetes (T2D) and hemorrhagic gastric ulcers who was successfully treated with nilotinib. We first considered second-generation tyrosine kinase inhibitors for the treatment of this patient, as they elicit a superior response compared with imatinib. We next selected nilotinib, rather than dasatinib, since the increased risk of bleeding associated with dasatinib represented a greater risk of fatality than aggravation of T2D with nilotinib. After improvement of hemorrhagic gastric ulcers and T2D with exogenous insulin therapy, we began nilotinib administration; insulin dose was increased to maintain her glucose levels whereas urine C-peptide level decreased. Conversely, when nilotinib was discontinued due to liver dysfunction, the dosage of injected insulin was decreased and urine C-peptide levels increased. After re-starting nilotinib, the required dose of insulin gradually increased again, and urine C-peptide level decreased, indicating that nilotinib may have impaired secretion of endogenous insulin. The patient obtained a complete cytogenetic response after 3 months of nilotinib treatment. Her T2D has since been well controlled by insulin therapy. To our knowledge, this is the first report that nilotinib treatment for patients with severe T2D may induce a reversible decrease in endogenous insulin secretion, although the precise underlying mechanisms remain unknown. We highly recommend sufficient screening and early intervention with exogenous insulin therapy for diabetic CML patients who receive nilotinib. PMID:23179903

  15. 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…

  16. Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.

    PubMed

    Ahlkvist, Linda; Omar, Bilal; Valeur, Anders; Fosgerau, Keld; Ahrén, Bo

    2016-03-01

    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose±GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased β-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of β-cell function during development of type 2 diabetes. PMID:26698567

  17. Live attenuated Salmonella vaccines against Mycobacterium tuberculosis with antigen delivery via the type III secretion system.

    PubMed

    Juárez-Rodríguez, María Dolores; Arteaga-Cortés, Lourdes T; Kader, Rebin; Curtiss, Roy; Clark-Curtiss, Josephine E

    2012-02-01

    Tuberculosis remains a global health threat, and there is dire need to develop a vaccine that is safe and efficacious and confers long-lasting protection. In this study, we constructed recombinant attenuated Salmonella vaccine (RASV) strains with plasmids expressing fusion proteins consisting of the 80 amino-terminal amino acids of the type 3 secretion system effector SopE of Salmonella and the Mycobacterium tuberculosis antigens early secreted antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10). We demonstrated that the SopE-mycobacterial antigen fusion proteins were translocated into the cytoplasm of INT-407 cells in cell culture assays. Oral immunization of mice with RASV strains synthesizing SopE-ESAT-6-CFP-10 fusion proteins resulted in significant protection of the mice against aerosol challenge with M. tuberculosis H37Rv that was similar to the protection afforded by immunization with Mycobacterium bovis bacillus Calmette-Guérin (BCG) administered subcutaneously. In addition, oral immunization with the RASV strains specifying these mycobacterial antigens elicited production of significant antibody titers to ESAT-6 and production of ESAT-6- or CFP-10-specific gamma interferon (IFN-γ)-secreting and tumor necrosis factor alpha (TNF-α)-secreting splenocytes. PMID:22144486

  18. 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.

  19. Efficient Multi Secret Sharing with Generalized Access Structures

    NASA Astrophysics Data System (ADS)

    VP, Binu; A, Sreekumar

    2014-03-01

    Multi-secret sharing is an extension of secret sharing technique where several secrets are shared between the participants, each according to a specified access structure. The secrets can be reconstructed according to the access structure by participants using their private shares.Each participant has to hold a single share, additional information are made available in a public bulletin board.The scheme is computationally efficient and also each participant can verify the shares of the other participants and also the reconstructed secret.The scheme does not need any secure channel also.

  20. Autoproteolysis and intramolecular dissociation of Yersinia YscU precedes secretion of its C-terminal polypeptide YscU(CC).

    PubMed

    Frost, Stefan; Ho, Oanh; Login, Frédéric H; Weise, Christoph F; Wolf-Watz, Hans; Wolf-Watz, Magnus

    2012-01-01

    Type III secretion system mediated secretion and translocation of Yop-effector proteins across the eukaryotic target cell membrane by pathogenic Yersinia is highly organized and is dependent on a switching event from secretion of early structural substrates to late effector substrates (Yops). Substrate switching can be mimicked in vitro by modulating the calcium levels in the growth medium. YscU that is essential for regulation of this switch undergoes autoproteolysis at a conserved N↑PTH motif, resulting in a 10 kDa C-terminal polypeptide fragment denoted YscU(CC). Here we show that depletion of calcium induces intramolecular dissociation of YscU(CC) from YscU followed by secretion of the YscU(CC) polypeptide. Thus, YscU(CC) behaved in vivo as a Yop protein with respect to secretion properties. Further, destabilized yscU mutants displayed increased rates of dissociation of YscU(CC)in vitro resulting in enhanced Yop secretion in vivo at 30°C relative to the wild-type strain.These findings provide strong support to the relevance of YscU(CC) dissociation for Yop secretion. We propose that YscU(CC) orchestrates a block in the secretion channel that is eliminated by calcium depletion. Further, the striking homology between different members of the YscU/FlhB family suggests that this protein family possess regulatory functions also in other bacteria using comparable mechanisms. PMID:23185318

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

    PubMed

    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 Ca(2+) 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 Ca(2+) concentration raising the question of the driving force of substrate secretion by T1SS in general. PMID:27616645

  2. The role of jasmonates in floral nectar secretion.

    PubMed

    Radhika, Venkatesan; Kost, Christian; Boland, Wilhelm; Heil, Martin

    2010-01-01

    Plants produce nectar in their flowers as a reward for their pollinators and most of our crops depend on insect pollination, but little is known on the physiological control of nectar secretion. Jasmonates are well-known for their effects on senescence, the development and opening of flowers and on plant defences such as extrafloral nectar. Their role in floral nectar secretion has, however, not been explored so far. We investigated whether jasmonates have an influence on floral nectar secretion in oil-seed rape, Brassica napus. The floral tissues of this plant produced jasmonic acid (JA) endogenously, and JA concentrations peaked shortly before nectar secretion was highest. Exogenous application of JA to flowers induced nectar secretion, which was suppressed by treatment with phenidone, an inhibitor of JA synthesis. This effect could be reversed by additional application of JA. Jasmonoyl-isoleucine and its structural mimic coronalon also increased nectar secretion. Herbivory or addition of JA to the leaves did not have an effect on floral nectar secretion, demonstrating a functional separation of systemic defence signalling from reproductive nectar secretion. Jasmonates, which have been intensively studied in the context of herbivore defences and flower development, have a profound effect on floral nectar secretion and, thus, pollination efficiency in B. napus. Our results link floral nectar secretion to jasmonate signalling and thereby integrate the floral nectar secretion into the complex network of oxylipid-mediated developmental processes of plants. PMID:20174464

  3. 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. PMID:26168358

  4. Isotonic secretion via frog skin glands in vitro. Water secretion is coupled to the secretion of sodium ions.

    PubMed

    Nielsen, R

    1990-05-01

    In isolated frog skin at least three different types of cells are engaged in the transepithelial ion and water transport; these are the granular cells, the mitochondria-rich cells and the glandular cells. The experiments presented were carried out on isolated frog skin bathed in Cl- or NO3- Ringer's solution, where the active transepithelial Na+ uptake via the granular cells was blocked by amiloride. Transepithelial current and water flow were measured. When a negative current was passed across the skins (the skins were clamped at -100 mV), the current was mainly carried by a net influx of Cl- via the mitochondria-rich cells. The current had no effect on the transepithelial water movement. This finding indicates that there is nearly no coupling between the Cl- flux and the movement of water via the mitochondria-rich cells. Prostaglandin E2 activates the glandular cells of the exocrine glands in the skin. When prostaglandin E2 was added under these experimental conditions (the skins were clamped at -100 mV, with amiloride in the apical bathing solution, and the glandular secretion of ions was blocked by the use of NO3- Ringer's solution), then the transepithelial current became more negative. This change in current was mainly due to an increase in the Na+ efflux via the glands. Thus PGE2 increase the Na+ conductance of the skin glands. Together with this increase in the Na+ efflux a highly significant increase in the water secretion was observed. The water movement (secretion) across the skin was under these conditions coupled to the PGE2-induced efflux of Na+, and when one Na+ was pulled from the basolateral to the apical solution via this pathway 215 molecules of water followed. This must be due to electro-osmosis (friction between ions and water) or current-induced local osmosis. PMID:2356751

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

    DOE PAGESBeta

    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 (singlemore » photon detectors, lasers and dark ber connections) needed to implement QKD on the grid.« less

  6. 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.

  7. 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

  8. Proteomics of protein secretion by Aggregatibacter actinomycetemcomitans.

    PubMed

    Zijnge, Vincent; Kieselbach, Thomas; Oscarsson, Jan

    2012-01-01

    The extracellular proteome (secretome) of periodontitis-associated bacteria may constitute a major link between periodontitis and systemic diseases. To obtain an overview of the virulence potential of Aggregatibacter actinomycetemcomitans, an oral and systemic human pathogen implicated in aggressive periodontitis, we used a combined LC-MS/MS and bioinformatics approach to characterize the secretome and protein secretion pathways of the rough-colony serotype a strain D7S. LC-MS/MS revealed 179 proteins secreted during biofilm growth. Further to confirming the release of established virulence factors (e.g. cytolethal distending toxin [CDT], and leukotoxin [LtxA]), we identified additional putative virulence determinants in the secretome. These included DegQ, fHbp, LppC, Macrophage infectivity protein (MIP), NlpB, Pcp, PotD, TolB, and TolC. This finding indicates that the number of extracellular virulence-related proteins is much larger than previously demonstrated, which was also supported by in silico analysis of the strain D7S genome. Moreover, our LC-MS/MS and in silico data revealed that at least Type I, II, and V secretion are actively used to excrete proteins directly into the extracellular space, or via two-step pathways involving the Sec/Tat systems for transport across the inner membrane, and outer membrane factors, secretins and auto-transporters, respectively for delivery across the outer membrane. Taken together, our results provide a molecular basis for further elucidating the role of A. actinomycetemcomitans in periodontal and systemic diseases. PMID:22848560

  9. Sebocytes differentially express and secrete adipokines.

    PubMed

    Kovács, Dóra; Lovászi, Marianna; Póliska, Szilárd; Oláh, Attila; Bíró, Tamás; Veres, Imre; Zouboulis, Christos C; Ståhle, Mona; Rühl, Ralph; Remenyik, Éva; Törőcsik, Dániel

    2016-03-01

    In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines [adiponectin, interleukin (IL) 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol-binding protein 4 (RBP4) and monocyte chemoattractant protein 1 (MCP1)] in sebaceous glands of healthy and various disease-affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion [by using Toll-like receptor (TLR)2 and 4 activators], or by 13-cis retinoic acid (13CRA; also known as isotretinoin), a key anti-acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines. PMID:26476096

  10. 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.

  11. [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. PMID:2559451

  12. Quantum secret sharing using product states

    SciTech Connect

    Hsu, L.-Y.; Li, C.-M.

    2005-02-01

    This study proposes quantum secret sharing protocols using product states. The first two protocols adopt the quantum key distribution protocol using product states [Guo et al.Phys. Rev. A 64, 042301 (2001)]. In these two protocols, the sender does not reveal any information about the qutrits until confirming that each receiver has received a qutrit. This study also considers the security and some possible eavesdropping strategies. In the third proposed protocol, three-level Bell states are exploited for qutrit preparation via nonlocality swapping.

  13. Endoderm induction by the organizer-secreted factors chordin and noggin in Xenopus animal caps.

    PubMed Central

    Sasai, Y; Lu, B; Piccolo, S; De Robertis, E M

    1996-01-01

    Spemann's organizer has potent neural inducing and mesoderm dorsalizing activities in the Xenopus gastrula. A third activity, the organizer's ability to induce a secondary gut, has been difficult to analyze experimentally due to the lack of early gene markers. Here we introduce endodermin, a pan-endodermal gene marker, and use it to demonstrate that chordin (Chd), a protein secreted by the organizer region, is able to induce endodermal differentiation in Xenopus. The ability of chd, as well as that of noggin, to induce endoderm in animal cap explants is repressed by the ventralizing factor BMP-4. When FGF signaling is blocked by a dominant-negative FGF receptor in chd-injected animal caps, neural induction is inhibited and most of the explant is induced to become endoderm. The results suggest that proteins secreted by the organizer, acting together with known peptide growth factors, regulate differentiation of the endodermal germ layer. Images PMID:8887546

  14. Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion

    PubMed Central

    Krtková, Jana; Thomas, Elizabeth B.; Alas, Germain C. M.; Schraner, Elisabeth M.; Behjatnia, Habib R.; Hehl, Adrian B.

    2016-01-01

    ABSTRACT Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia’s sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-RacCA) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-RacCA-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis. PMID:27555307

  15. The Rab11 Effector Protein FIP1 Regulates Adiponectin Trafficking and Secretion

    PubMed Central

    Moreno-Navarrete, Jose Maria; Fernandez-Real, Jose Manuel; Mora, Silvia

    2013-01-01

    Adiponectin is an adipokine secreted by white adipocytes involved in regulating insulin sensitivity in peripheral tissues. Secretion of adiponectin in adipocytes relies on the endosomal system, however, the intracellular machinery involved in mediating adiponectin release is unknown. We have previously reported that intracellular adiponectin partially compartmentalizes with rab 5 and rab11, markers for the early/sorting and recycling compartments respectively. Here we have examined the role of several rab11 downstream effector proteins (rab11 FIPs) in regulating adiponectin trafficking and secretion. Overexpression of wild type rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed in HEK293 cells, whereas overexpression of rab11 FIP2 or FIP4 had no effect. Furthermore shRNA-mediated depletion of FIP1 enhanced adiponectin release whereas knock down of FIP5 decreased adiponectin secretion. Knock down of FIP3 had no effect. In 3T3L1 adipocytes, endogenous FIP1 co-distributed intracellularly with endogenous adiponectin and FIP1 depletion enhanced adiponectin release without altering insulin-mediated trafficking of the glucose transporter Glut4. While adiponectin receptors internalized with transferrin receptors, there were no differences in transferrin receptor recycling between wild type and FIP1 depleted adipocytes. Consistent with its inhibitory role, FIP1 expression was decreased during adipocyte differentiation, by treatment with thiazolidinediones, and with increased BMI in humans. In contrast, FIP1 expression increased upon exposure of adipocytes to TNFα. In all, our findings identify FIP1 as a novel protein involved in the regulation of adiponectin trafficking and release. PMID:24040321

  16. Physiology and endocrinology symposium: evidence that oviduct secretions influence sperm function: a retrospective view for livestock.

    PubMed

    Killian, G

    2011-05-01

    The mammalian oviduct has long been recognized as an organ essential for successful reproduction. Bovine, ovine, porcine, and equine animal models have offered clear advantages for oviduct study related to gamete physiology, fertilization, and early embryonic development. Livestock species are amenable to surgical alteration of the reproductive tract, estrous cycle manipulation, gamete cryopreservation, and AI, as well as in vitro fertilization and embryo production. Although most reproductive technology developed for livestock was intended to benefit production animal agriculture, these techniques are a treasure trove of tools for researchers to better understand how the oviduct influences gamete function. Oviduct secretions obtained from in vitro tissue cultures or via indwelling oviduct catheters have been used for analyses to define the protein, lipid, carbohydrate, enzyme, and electrolyte compositions of the secretions during the estrous cycle or in response to hormone treatment. Oviduct secretions or components purified from them have also been used in in vitro assays to assess their ability to bind to sperm, influence sperm viability, motility, sperm capacitation, the acrosome reaction, sperm-egg binding, and egg penetration, as well as subsequent embryonic development. Compelling data have emerged which show that the composition of secretions differs during the estrous cycle and that their composition differs whether they originate from the ampullary or isthmic regions of the oviduct. These differences in composition are functionally relevant and associated with different responses by sperm. Evidence indicatess that oviduct-specific glycoproteins, glycosaminoglycans, carbohydrates, norepinepherine, catecholamines, heat-shock protein, and osteopontin are components of the oviductal milieu that have the capacity to modulate sperm function. Future research on the livestock oviduct will likely define the role that oviduct secretions have in modulating sperm

  17. Russian/Soviet weapons secrets revealed

    SciTech Connect

    Norris, R.S.

    1993-04-01

    Russia's Ministry of Atomic Energy has opened a museum at the Arzamas-16 nuclear weapon design laboratory with an exhibit on some early weapons. This exhibit and recent articles in the Russian press provide previously unknown details on the early Soviet nuclear program. This article compiles some of this information to provide a refined record of the development of the H-bomb.

  18. Early development of the secretory cavity of peltate glands in Humulus lupulus L. (Cannabaceae).

    PubMed

    Kim, E S; Mahlberg, P G

    2000-10-31

    Early development of the secretory cavity of chemically fixed peltate glands in Humulus lupulus L. showed secretions with different densities, light, gray and dark, in the cytoplasm of disc cells and in the periplasmic space adjacent to the developing secretory cavity. Secretions were detected in the disc cell wall and subsequently in the developing secretory cavity under the subcuticular wall of the sheath. Light and gray secretions in the cavity possessed a membrane-like surface feature. Secretions were in contact with the irregular inner surface of the cuticle. Secretions contributed to the thickening of the cuticle, whereas the membrane-like surface feature contributed to a network of Cannabis striae distributed throughout the cuticle. This study supports an early development and organization of the secretory cavity in H. lupulus, parallel to those in Cannabis, and may represent common features for lipophilic glands in angiosperms. PMID:11101137

  19. Production and Secretion of the Polysaccharide Biodispersan of Acinetobacter calcoaceticus A2 in Protein Secretion Mutants.

    PubMed

    Elkeles, A; Rosenberg, E; Ron, E Z

    1994-12-01

    Biodispersan is an extracellular anionic polysaccharide produced by Acinetobacter calcoaceticus A2 that changes the surface properties of limestone and acts both as a dispersant and as a grinding aid (E. Rosenberg, C. Rubinovitz, A. Gottlieb, S. Rosenhak, and E. Z. Ron, Appl. Environ. Microbiol. 54:317-322, 1988; E. Rosenberg, C. Rubinovitz, R. Legmann, and E. Z. Ron, Appl. Environ. Microbiol. 54:323-326, 1988; E. Rosenberg, Z. Schwartz, A. Tenenbaum, C. Rubinovitz, R. Legmann, and E. Z. Ron, J. Dispersion Sci. Technol. 10:241-250, 1989). Extracellular fluid also contains a high concentration of secreted proteins that create problems in the purification and application of biodispersan. In order to obtain preparations of biodispersan that contained smaller amounts of protein, we selected mutants of strain A2 that were defective in protein secretion. These mutants produced equal, or even higher, levels of total biodispersan compared with those of the parental strain. Moreover, although there was a significant drop in the concentration of extracellular proteins in the medium, the secretion of biodispersan was unaffected. These results suggest that secretion mutants are potentially useful for the production of extracellular polysaccharides. PMID:16349473

  20. 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,…

  1. 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

  2. Loose excitation-secretion coupling in astrocytes.

    PubMed

    Vardjan, Nina; Parpura, Vladimir; Zorec, Robert

    2016-05-01

    Astrocytes play an important housekeeping role in the central nervous system. Additionally, as secretory cells, they actively participate in cell-to-cell communication, which can be mediated by membrane-bound vesicles. The gliosignaling molecules stored in these vesicles are discharged into the extracellular space after the vesicle membrane fuses with the plasma membrane. This process is termed exocytosis, regulated by SNARE proteins, and triggered by elevations in cytosolic calcium levels, which are necessary and sufficient for exocytosis in astrocytes. For astrocytic exocytosis, calcium is sourced from the intracellular endoplasmic reticulum store, although its entry from the extracellular space contributes to cytosolic calcium dynamics in astrocytes. Here, we discuss calcium management in astrocytic exocytosis and the properties of the membrane-bound vesicles that store gliosignaling molecules, including the vesicle fusion machinery and kinetics of vesicle content discharge. In astrocytes, the delay between the increase in cytosolic calcium activity and the discharge of secretions from the vesicular lumen is orders of magnitude longer than that in neurons. This relatively loose excitation-secretion coupling is likely tailored to the participation of astrocytes in modulating neural network processing. PMID:26358496

  3. 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.

  4. Cushing's syndrome due to ectopic ACTH secretion.

    PubMed

    Cieszyński, Łukasz; Berendt-Obołończyk, Monika; Szulc, Michał; Sworczak, Krzysztof

    2016-01-01

    Cushing's syndrome (CS) is defined as a constellation of clinical signs and symptoms occurring due to hypercortisolism. Cortisol excess may be endogenous or exogenous. The most common cause of CS is glucocorticoid therapy with supraphysiological (higher than in the case of substitution) doses used in various diseases (e.g. autoimmune). One possible CS cause is ectopic (extra-pituitary) ACTH secretion (EAS) by benign or malignant tumours. Since its first description in 1963, EAS aetiology has changed, i.e. as well as small cell lung cancer (SCLC), higher incidence in other malignancies has been reported. Ectopic ACTH secretion symptoms are usually similar to hypercortisolism symptoms due to other causes. A clinical suspicion of CS requires laboratory investigations. There is no single and specific laboratory test for making a CS diagnosis, and therefore multiple dynamic tests should be ordered. A combination of multiple laboratory noninvasive and invasive tests gives 100% sensitivity and 98% specificity for EAS diagnosis. If the EAS is caused by localised malignancy, surgery is the optimal treatment choice. Radical tumour excision may be performed in 40% of patients, and 80% of them are cured of the disease. The authors present an interesting clinical case of EAS, which is always a huge diagnostic challenge for clinicians. (Endokrynol Pol 2016; 67 (4): 458-464). PMID:27387249

  5. Early Days

    ERIC Educational Resources Information Center

    Mathematical Gazette, 1971

    1971-01-01

    Reprinted are articles related to the early years of The Mathematical Association of Great Britain. Some of the topics include reports from curriculum committees, tributes to persons associated with The Mathematical Association, and the teaching of mathematics. (CT)

  6. Sterile neutrinos with secret interactions—lasting friendship with cosmology

    NASA Astrophysics Data System (ADS)

    Chu, Xiaoyong; Dasgupta, Basudeb; Kopp, Joachim

    2015-10-01

    Sterile neutrinos with mass simeq 1 eV and order 10% mixing with active neutrinos have been proposed as a solution to anomalies in neutrino oscillation data, but are tightly constrained by cosmological limits. It was recently shown that these constraints are avoided if sterile neutrinos couple to a new MeV-scale gauge boson A'. However, even this scenario is restricted by structure formation constraints when A'-mediated collisional processes lead to efficient active-to-sterile neutrino conversion after neutrinos have decoupled. In view of this, we reevaluate in this paper the viability of sterile neutrinos with such ``secret'' interactions. We carefully dissect their evolution in the early Universe, including the various production channels and the expected modifications to large scale structure formation. We argue that there are two regions in parameter space—one at very small A' coupling, one at relatively large A' coupling—where all constraints from big bang nucleosynthesis (BBN), cosmic microwave background (CMB), and large scale structure (LSS) data are satisfied. Interestingly, the large A' coupling region is precisely the region that was previously shown to have potentially important consequences for the small scale structure of dark matter halos if the A' boson couples also to the dark matter in the Universe.

  7. Regulation of pigeon cropmilk secretion and parental behaviors by prolactin.

    PubMed

    Horseman, N D; Buntin, J D

    1995-01-01

    Prolactin stimulates the growth and development of specialized epithelial cells lining the cropsac of pigeons and doves (family Columbidae), leading to formation of "cropmilk," which is fed to the newly hatched squab. This system of milk feeding is unique among birds. To support the feeding of cropmilk, a complex array of behavioral adaptations are also supported by high levels of prolactin secretion in columbids during parenting. These specializations include elevated food intake (hyperphagia), nest attendance, and regurgitation feeding of the squab. Although prolactin is clearly important for these behavioral adaptations, the precise physiological and mechanistic bases for these behavioral effects remain controversial. The molecular mechanisms of prolactin action in the cropsac epithelium have been studied by cloning prolactin-induced genes, by cloning and expressing the pigeon prolactin receptor, and by analyzing the transcription factors that are activated after prolactin treatment. The avian (pigeon) prolactin receptor is a member of the cytokine receptor superfamily and uniquely contains a complete duplication of the extracellular ligand-binding domain. One of the early signal-transducing actions of prolactin in cropsac epithelium is the activation of signal transducer and activator of transcription (STAT) proteins via tyrosine phosphorylation. This fundamental signaling pathway is shared with mammalian prolactin target tissues. The convergent evolution of milk feeding and the behaviors that support parenting in columbids and mammals has depended on adaptation of both conserved mechanisms and divergent physiological processes. PMID:8527218

  8. Secrets in Primary Care: A Qualitative Exploration and Conceptual Model

    PubMed Central

    Biderman, Aya; Mitki, Revital; Borkan, Jeffrey M.

    2007-01-01

    Objective Secrets and issues of confidentiality are critical concerns in doctor–patient communication and fundamental aspects of every medical encounter. Nevertheless, the nature, content, prevalence, impact, and consequences of secrets in medicine have largely been unexplored. This study investigates the role of secrets in primary care. It describes the intuitive strategies used by primary care physicians to cope with secrets, provides a categorization system, and suggests a conceptual model. Design Focus groups of primary care physicians were the principal data collection method employed. Transcripts from 8 focus groups were analyzed using an “immersion–crystallization” framework involving cycles of concentrated textual review of data. Insights from this iterative process and from the literature were employed in the construction of contextual types, content categories, processes, and models. Participants Sixty-one family physicians and general practitioners in Israel with a wide variety of seniority, ethnic, religious, and immigration backgrounds. Setting Locations in the north, south, and center of Israel. Results Analysis revealed insights about definitions, prevalence, process, and content of secrets in primary care. The main content findings centered on categories of secrets such as propensity to secrecy, toxicity of secrets, and the special nature of secrets in family medicine. The main process findings regarded the life cycle of secrets and doctors’ coping strategies. Based on our findings and a review of the literature, a conceptual model of secrets in primary care is proposed. Conclusions The importance and impact of secrets are significant part of daily medical practice. Further research is needed to enhance physicians’ effective and ethical handling of secrets and secrecy in practice. PMID:17487521

  9. 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.

  10. Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells

    PubMed Central

    Cavet, M E; West, M; Simmons, N L

    1997-01-01

    Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic ciprofloxacin. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to competitive inhibition by sulphate, thiosulphate, oxalate, succinate and para-amino hippurate, probenecid (10 mM), taurocholate (100 μM) or bromosulphophthalein (100 μM). Similarly tetraethylammonium and N-′methylnicotinamide (10 mM) were without effect. Net secretion of ciprofloxacin was inhibited by the organic exchange inhibitor 4,4′-diisothiocyanostilbene-2-2′-disulphonic acid (DIDS, 400 μM). Net secretion of ciprofloxacin was partially inhibited by 100 μM verapamil, whilst net secretion of the P-glycoprotein substrate vinblastine was totally abolished under these conditions. Ciprofloxacin secretion was unaltered after preincubation of cells with two anti-P-glycoprotein antibodies (UIC2 and MRK16), which both significantly reduced secretory vinblastine flux (measured in the same cell batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretion in Caco-2 epithelia, and was not itself secreted by the P-glycoprotein expressing and vinblastine secreting dog kidney cell line, MDCK. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either cytosolic or medium pH, or dependent on the presence of medium Na+, Cl− or K+ in the bathing media. The substrate specificity of the ciprofloxacin secretory transport in Caco-2 epithelia is distinct from both the renal organic anion and cation transport. A role for P-glycoprotein in ciprofloxacin secretion may also be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil mediates secretion of ciprofloxacin by human intestinal Caco-2 epithelia. PMID:9283689

  11. Combinatorial insulin secretion dynamics of recombinant hepatic and enteroendocrine cells.

    PubMed

    Durvasula, Kiranmai; Thulé, Peter M; Sambanis, Athanassios

    2012-04-01

    One of the most promising cell-based therapies for combating insulin-dependent diabetes entails the use of genetically engineered non-β cells that secrete insulin in response to physiologic stimuli. A normal pancreatic β cell secretes insulin in a biphasic manner in response to glucose. The first phase is characterized by a transient stimulation of insulin to rapidly lower the blood glucose levels, which is followed by a second phase of insulin secretion to sustain the lowered blood glucose levels over a longer period of time. Previous studies have demonstrated hepatic and enteroendocrine cells to be appropriate hosts for recombinant insulin expression. Due to different insulin secretion kinetics from these cells, we hypothesized that a combination of the two cell types would mimic the biphasic insulin secretion of normal β cells with higher fidelity than either cell type alone. In this study, insulin secretion experiments were conducted with two hepatic cell lines (HepG2 and H4IIE) transduced with 1 of 3 adenoviruses expressing the insulin transgene and with a stably transfected recombinant intestinal cell line (GLUTag-INS). Insulin secretion was stimulated by exposing the cells to glucose only (hepatic cells), meat hydrolysate only (GLUTag-INS), or to a cocktail of the two secretagogues. It was found experimentally that the recombinant hepatic cells secreted insulin in a more sustained manner, whereas the recombinant intestinal cell line exhibited rapid insulin secretion kinetics upon stimulation. The insulin secretion profiles were computationally combined at different cell ratios to arrive at the combinatorial kinetics. Results indicate that combinations of these two cell types allow for tuning the first and second phase of insulin secretion better than either cell type alone. This work provides the basic framework in understanding the secretion kinetics of the combined system and advances it towards preclinical studies. PMID:22094821

  12. Combinatorial Insulin Secretion Dynamics of Recombinant Hepatic and Enteroendocrine Cells

    PubMed Central

    Durvasula, Kiranmai; Thulé, Peter M.; Sambanis, Athanassios

    2012-01-01

    One of the more promising cell-based therapies for combating insulin-dependent diabetes entails the use of genetically engineered non-β cells that secrete insulin in response to physiologic stimuli. A normal pancreatic β cell secretes insulin in a biphasic manner in response to glucose. The first phase is characterized by a transient stimulation of insulin to rapidly lower the blood glucose levels, which is followed by a second phase of insulin secretion to sustain the lowered blood glucose levels over a longer period of time. Previous studies have demonstrated hepatic and enteroendocrine cells to be appropriate hosts for recombinant insulin expression. Due to different insulin secretion kinetics from these cells, we hypothesized that a combination of the two cell types would mimic the biphasic insulin secretion of normal β cells with higher fidelity than either cell type alone. In this study, insulin secretion experiments were conducted with two hepatic cell lines (HepG2 and H4IIE) transduced with one of three adenoviruses expressing the insulin transgene and with a stably transfected recombinant intestinal cell line (GLUTag-INS). Insulin secretion was stimulated by exposing the cells to glucose only (hepatic cells), meat hydrolysate only (GLUTag-INS), or to a cocktail of the two secretagogues. It was found experimentally that the recombinant hepatic cells secreted insulin in a more sustained manner, whereas the recombinant intestinal cell line exhibited rapid insulin secretion kinetics upon stimulation. The insulin secretion profiles were computationally combined at different cell ratios to arrive at the combinatorial kinetics. Results indicate that combinations of these two cell types allow for tuning the first and second phase of insulin secretion better than either cell type alone. This work provides the basic framework in understanding the secretion kinetics of the combined system and advances it towards pre-clinical studies. PMID:22094821

  13. FLUID SECRETION BY SUBMUCOSAL GLANDS OF THE TRACHEOBRONCHIAL AIRWAYS

    PubMed Central

    Ballard, Stephen T.; Spadafora, Domenico

    2009-01-01

    Submucosal glands of the tracheobronchial airways provide the important functions of secreting mucins, antimicrobial substances, and fluid. This review focuses on the ionic mechanism and regulation of gland fluid secretion and examines the possible role of gland dysfunction in the lethal disease cystic fibrosis (CF). The fluid component of gland secretion is driven by the active transepithelial secretion of both Cl− and HCO3− by serous cells. Gland fluid secretion is neurally regulated with acetylcholine, substance P, and vasoactive intestinal peptide (VIP) playing prominent roles. The cystic fibrosis transmembrane conductance regulator (CFTR) is present in the apical membrane of gland serous cells and mediates the VIP-induced component of liquid secretion whereas the muscarinic component of liquid secretion appears to be at least partially CFTR-independent. Loss of CFTR function, which occurs in CF disease, reduces the capacity of glands to secrete fluid but not mucins. The possible links between the loss of fluid secretion capability and the complex airway pathology of CF are discussed. PMID:17707699

  14. Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage

    PubMed Central

    Dilwali, Sonam; Landegger, Lukas D.; Soares, Vitor Y. R.; Deschler, Daniel G.; Stankovic, Konstantina M.

    2015-01-01

    Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects’ degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs. PMID:26690506

  15. 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.

  16. A microdomain for protein secretion in Gram-positive bacteria.

    PubMed

    Rosch, Jason; Caparon, Michael

    2004-06-01

    Gram-positive bacteria face unique challenges in generating biologically active conformations for their exported proteins because they lack a dedicated compartment for folding secreted polypeptides. We have discovered that protein secretion by way of the general secretory (Sec) pathway in the important human pathogen Streptococcus pyogenes proceeds through a single microdomain. Unlike other mechanisms for asymmetry involving the Sec pathway, proteins destined for secretion are targeted to a single locus distal to either cell pole that has specialized to contain the Sec translocons. This subcellular organization may represent a paradigm for secretion common to other Gram-positive pathogens with profound implications for pathogenesis. PMID:15178803

  17. Protein secretion controlled by a synthetic gene in Escherichia coli.

    PubMed

    Blanchin-Roland, S; Masson, J M

    1989-03-01

    The inability of Escherichia coli to secrete proteins in growth medium is one of the major drawbacks in its use in genetic engineering. A synthetic gene, homologous to the one coding for the kil peptide of pColE1, was made and cloned under the control of the lac promoter, in order to obtain the inducible secretion of homologous or heterologous proteins by E. coli. The efficiency of this synthetic gene to promote secretion was assayed by analysing the production and secretion of two proteins, the R-TEM1 beta-lactamase, and the alpha-amylase from Bacillus licheniformis. This latter protein was expressed in E. coli from its gene either on the same plasmid as the kil gene or on a different plasmid. The primary effect of the induction of the kil gene is the overproduction of the secreted proteins. When expressed at a high level, the kil gene promotes the overproduction of all periplasmic proteins and the total secretion in the culture medium of both the beta-lactamase or the alpha-amylase. This secretion is semi-selective for most periplasmic proteins are not secreted. The kil peptide induces the secretion of homologous or heterologous proteins in two steps, first acting on the cytoplasmic membrane, then permeabilizing the outer membrane. This system, which is now being assayed at the fermentor scale, is the first example of using a synthetic gene to engineer a new property into a bacterial strain. PMID:2652141

  18. The ESX System in Bacillus subtilis Mediates Protein Secretion

    PubMed Central

    Chase, Michael R.; Sarracino, David A.; Fortune, Sarah M.; Burton, Briana M.

    2014-01-01

    Esat-6 protein secretion systems (ESX or Ess) are required for the virulence of several human pathogens, most notably Mycobacterium tuberculosis and Staphylococcus aureus. These secretion systems are defined by a conserved FtsK/SpoIIIE family ATPase and one or more WXG100 family secreted substrates. Gene clusters coding for ESX systems have been identified amongst many organisms including the highly tractable model system, Bacillus subtilis. In this study, we demonstrate that the B. subtilis yuk/yue locus codes for a nonessential ESX secretion system. We develop a functional secretion assay to demonstrate that each of the locus gene products is specifically required for secretion of the WXG100 virulence factor homolog, YukE. We then employ an unbiased approach to search for additional secreted substrates. By quantitative profiling of culture supernatants, we find that YukE may be the sole substrate that depends on the FtsK/SpoIIIE family ATPase for secretion. We discuss potential functional implications for secretion of a unique substrate. PMID:24798022

  19. Regulation of endogenous apolipoprotein E secretion by macrophages.

    PubMed

    Kockx, Maaike; Jessup, Wendy; Kritharides, Leonard

    2008-06-01

    Apolipoprotein E has critical roles in the protection against atherosclerosis and is understood to follow the classical constitutive secretion pathway. Recent studies have indicated that the secretion of apoE from macrophages is a regulated process of unexpected complexity. Cholesterol acceptors such as apolipoprotein A-I, high density lipoprotein, and phospholipid vesicles can stimulate apoE secretion. The ATP binding cassette transporter ABCA1 is involved in basal apoE secretion and in lipidating apoE-containing particles secreted by macrophages. However, the stimulation of apoE secretion by apoA-I is ABCA1-independent, indicating the existence of both ABCA1-dependent and -independent pathways of apoE secretion. The release of apoE under basal conditions is also regulated, requiring intact protein kinase A activity, intracellular calcium, and an intact microtubular network. Mathematical modeling of apoE turnover indicates that whereas some pools of apoE are committed to either secretion or degradation, other pools can be diverted from degradation toward secretion. Targeted inhibition or stimulation of specific apoE trafficking pathways will provide unique opportunities to regulate the biology of this important molecule. PMID:18388328

  20. Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate

    PubMed Central

    Platel, J.-C.; Boisseau, S.; Dupuis, A.; Brocard, J.; Poupard, A.; Savasta, M.; Villaz, M.; Albrieux, M.

    2005-01-01

    Before synaptogenesis, early excitability implicating voltage-dependent and transmitter-activated channels is known to be crucial for neuronal development. We previously showed that preplate (PP) neurons of the mouse neocortex express functional Na+ channels as early as embryonic day 12. In this study, we investigated the role of these Na+ channels in signaling during early development. In the neocortex of embryonic-day-13 mice, activation of Na+ channels with veratridine induced a large Ca2+ response throughout the neocortex, even in cell populations that lack the Na+ channel. This Na+-dependent Ca2+ activity requires external Ca2+ and is completely blocked by inhibitors of Na+/Ca2+ exchangers. Moreover, veratridine-induced Ca2+ increase coincides with a burst of exocytosis in the PP. In parallel, we show that Na+ channel stimulation enhances glutamate secretion in the neocortical wall. Released glutamate triggers further Ca2+ response in PP and ventricular zone, as indicated by the decreased response to veratridine in the presence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NMDA-receptor inhibitors. Therefore, the combined activation of the Na+ channel and the Na+/Ca2+ exchanger triggers Ca2+ signaling in the PP neurons, leading to glutamate secretion, which amplifies the signal and serves as an autocrine/paracrine transmitter before functional synapses are formed in the neocortex. Membrane depolarization induced by glycine receptors activation could be one physiological activator of this Na+ channel-dependent pathway. PMID:16357207

  1. The presence in salivary secretions of Glossina morsitans of stages of Trypanosoma (Trypanozoon) brucei other than those occurring in the salivary glands.

    PubMed

    Otieno, L H

    1978-01-01

    Using the bat wing membrane technique to study salivary secretions of Glossina morsitans infected with Trypanosoma (Trypanozoon) brucei, it was shown that flies extrude infected salivary secretions as early as day six after an infective blood meal. The non-salivary-gland stages of T. (T.) brucei were extruded intermittently and flies infected with such trypanosomes were not all destined to develop metacyclic infections. Once the salivary glands were involved, the trypanosomes appeared in the secretions each time the flies were tested. Some of the flies with gut infections, but no demonstrable salivary gland involvement, transmitted T. brucei to mice and it is suggested that these infections were intiated by some of the proventricular trypanosomes secreted with saliva. PMID:569915

  2. Evidence of Extrapancreatic Glucagon Secretion in Man.

    PubMed

    Lund, Asger; Bagger, Jonatan I; Wewer Albrechtsen, Nicolai J; Christensen, Mikkel; Grøndahl, Magnus; Hartmann, Bolette; Mathiesen, Elisabeth R; Hansen, Carsten P; Storkholm, Jan H; van Hall, Gerrit; Rehfeld, Jens F; Hornburg, Daniel; Meissner, Felix; Mann, Matthias; Larsen, Steen; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K

    2016-03-01

    Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from α-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy. PMID:26672094

  3. Secreted and transmembrane wnt inhibitors and activators.

    PubMed

    Cruciat, Cristina-Maria; Niehrs, Christof

    2013-03-01

    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

  4. 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.

  5. Neuroendocrine Regulation of Growth Hormone Secretion.

    PubMed

    Steyn, Frederik J; Tolle, Virginie; Chen, Chen; Epelbaum, Jacques

    2016-01-01

    This article reviews the main findings that emerged in the intervening years since the previous volume on hormonal control of growth in the section on the endocrine system of the Handbook of Physiology concerning the intra- and extrahypothalamic neuronal networks connecting growth hormone releasing hormone (GHRH) and somatostatin hypophysiotropic neurons and the integration between regulators of food intake/metabolism and GH release. Among these findings, the discovery of ghrelin still raises many unanswered questions. One important event was the application of deconvolution analysis to the pulsatile patterns of GH secretion in different mammalian species, including Man, according to gender, hormonal environment and ageing. Concerning this last phenomenon, a great body of evidence now supports the role of an attenuation of the GHRH/GH/Insulin-like growth factor-1 (IGF-1) axis in the control of mammalian aging. © 2016 American Physiological Society. Compr Physiol 6:687-735, 2016. PMID:27065166

  6. 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

  7. 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

    2009-01-01

    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. PMID:20016817

  8. 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.

  9. Unveiling Cell Surface and Type IV Secretion Proteins Responsible for Archaeal Rudivirus Entry

    PubMed Central

    Deng, Ling; He, Fei; Bhoobalan-Chitty, Yuvaraj; Martinez-Alvarez, Laura; Guo, Yang

    2014-01-01

    Sulfolobus mutants resistant to archaeal lytic virus Sulfolobus islandicus rod-shaped virus 2 (SIRV2) were isolated, and mutations were identified in two gene clusters, cluster sso3138 to sso3141 and cluster sso2386 and sso2387, encoding cell surface and type IV secretion proteins, respectively. The involvement of the mutations in the resistance was confirmed by genetic complementation. Blocking of virus entry into the mutants was demonstrated by the lack of early gene transcription, strongly supporting the idea of a role of the proteins in SIRV2 entry. PMID:24965447

  10. Secrets of platelet exocytosis – what do we really know about platelet secretion mechanisms?

    PubMed Central

    Golebiewska, Ewelina M; Poole, Alastair W

    2014-01-01

    Upon activation by extracellular matrix components or soluble agonists, platelets release in excess of 300 active molecules from intracellular granules. Those factors can both activate further platelets and mediate a range of responses in other cells. The complex microenvironment of a growing thrombus, as well as platelets' roles in both physiological and pathological processes, require platelet secretion to be highly spatially and temporally regulated to ensure appropriate responses to a range of stimuli. However, how this regulation is achieved remains incompletely understood. In this review we outline the importance of regulated secretion in thrombosis as well as in ‘novel’ scenarios beyond haemostasis and give a detailed summary of what is known about the molecular mechanisms of platelet exocytosis. We also discuss a number of theories of how different cargoes could be released in a tightly orchestrated manner, allowing complex interactions between platelets and their environment. PMID:24588354

  11. 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. PMID:23075153

  12. Secretion of a pneumococcal type II secretion system pilus correlates with DNA uptake during transformation

    PubMed Central

    Balaban, Murat; Bättig, Patrick; Muschiol, Sandra; Tirier, Stephan M.; Wartha, Florian; Normark, Staffan; Henriques-Normark, Birgitta

    2014-01-01

    Streptococcus pneumoniae is a major human pathogen that successfully adapts to the host environment via an efficient uptake system for free DNA liberated from other organisms in the upper respiratory tract, facilitating immune evasion and drug resistance. Although the initial signaling events leading to pneumococcal competence for DNA transformation and the fate of DNA when it has been taken up have been extensively studied, the actual mechanism by which DNA in the environment may traverse the thick capsular and cell wall layers remains unknown. Here we visualize that induction of competence results in the formation of a native morphologically distinct pilus structure on the bacterial surface. This plaited pilus is encoded by the competence (com)G locus, and, after assembly, it is rapidly released into the surrounding medium. Heterologous pneumococcal pilus expression in Escherichia coli was obtained by replacing the pulE-K putative pilin genes of the Klebsiella oxytoca type II secretion system with the complete comG locus. In the pneumococcus, the coordinated secretion of pili from the cells correlates to DNA transformation. A model for DNA transformation is proposed whereby pilus assembly “drills” a channel across the thick cell wall that becomes transiently open by secretion of the pilus, providing the entry port for exogenous DNA to gain access to DNA receptors associated with the cytoplasmic membrane. PMID:24550320

  13. Endocrine Determinants of Changes in Insulin Sensitivity and Insulin Secretion during a Weight Cycle in Healthy Men

    PubMed Central

    Karschin, Judith; Lagerpusch, Merit; Enderle, Janna; Eggeling, Ben; Müller, Manfred J.; Bosy-Westphal, Anja

    2015-01-01

    Objective Changes in insulin sensitivity (IS) and insulin secretion occur with perturbations in energy balance and glycemic load (GL) of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear. Methods In a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m2) followed 1wk of overfeeding (OF), 3wks of caloric restriction (CR) containing either 50% or 65% carbohydrate (CHO) and 2wks of refeeding (RF) with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI), insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose) and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion) were assessed. Results IS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05). Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05) whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05) and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only). After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant. Conclusion Weight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and

  14. 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,…

  15. 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.

  16. 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

    2016-01-01

    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. PMID:27243650

  17. Localization of growth and secretion of proteins in Aspergillus niger.

    PubMed

    Wösten, H A; Moukha, S M; Sietsma, J H; Wessels, J G

    1991-08-01

    Hyphal growth and secretion of proteins in Aspergillus niger were studied using a new method of culturing the fungus between perforated membranes which allows visualization of both parameters. At the colony level the sites of occurrence of growth and general protein secretion were correlated. In 4-d-old colonies both growth and secretion were localized at the periphery of the colony, whereas in a 5-d-old colony growth and secretion also occurred in a more central zone of the colony where conidiophore differentiation was observed. However, in both cases glucoamylase secretion was mainly detected at the periphery of the colonies. At the hyphal level immunogold labelling showed glucoamylase secretion at the tips of leading hyphae only. Microautoradiography after labelling with N-acetylglucosamine showed that these hyphae were probably all growing. Glucoamylase secretion could not be demonstrated immediately after a temperature shock which stopped growth. These results indicate that glucoamylase secretion is located at the tips of growing hyphae only. PMID:1955876

  18. 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. PMID:27375224

  19. Type VI Secretion: not just for pathogenesis anymore

    PubMed Central

    Jani, Andrea J.; Cotter, Peggy A.

    2010-01-01

    Summary Type VI Secretion Systems (T6SS) have been studied primarily in the context of pathogenic bacterial-host interactions. Recent data suggest, however, that these versatile secretion systems may also function to promote commensal or mutualistic relationships between bacteria and eukaryotes, or to mediate cooperative or competitive interactions between bacteria. PMID:20638635

  20. 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

  1. 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)

  2. Complete Tumor Resection for a Hepatocellular Carcinoma Secreting Parathyroid Hormone-related Peptide.

    PubMed

    Kim, Eun Kyoung; Kim, Jin Su; Shin, Ki Chul; Lee, Gil Tae; Han, Chul Ju; Kim, Sang Beom; Ku, Yun Hyi

    2015-08-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We report a 71-year-old man who presented with symptoms of vague abdominal discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging studies revealed a large HCC without metastasis. The laboratory findings showed elevated serum calcium level, low intact parathyroid hormone (iPTH) level and elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC and paraneoplastic hypercalcemia. After emergency management of the hypercalcemia, the patient underwent an extended right hemihepatectomy with cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH-rP, and iPTH levels. This case demonstrates that the rare phenomenon of life-threatening hypercalcemia caused by HCC should not be overlooked. These symptoms offer a good opportunity to diagnose HCC early. Radical tumor resection makes it possible to cure patients with PTH-rP-secreting HCC. PMID:26289247

  3. Proteomics informed by transcriptomics identifies novel secreted proteins in Dermacentor andersoni saliva

    SciTech Connect

    Mudenda, Lwiindi; Aguilar Pierle, Sebastian; Turse, Joshua E.; Scoles, Glen A.; Purvine, Samuel O.; Nicora, Carrie D.; Clauss, Therese RW; Ueti, Massaro W.; Brown, Wendy C.; Brayton, Kelly A.

    2014-08-07

    Dermacentor andersoni, known as the Rocky Mountain wood tick, is found in the western United States and transmits pathogens that cause diseases of veterinary and public health importance including Rocky Mountain spotted fever, tularemia, Colorado tick fever and bovine anaplasmosis. Tick saliva is known to modulate both innate and acquired immune responses, enabling ticks to feed for several days without detection. During feeding ticks subvert host defences such as hemostasis and inflammation, which would otherwise result in coagulation, wound repair and rejection of the tick. Molecular characterization of the proteins and pharmacological molecules secreted in tick saliva offers an opportunity to develop tick vaccines as an alternative to the use of acaricides, as well as new anti-inflammatory drugs. We performed proteomics informed by transcriptomics to identify D. andersoni saliva proteins that are secreted during feeding. The transcript data generated a database of 21,797 consensus sequences, which we used to identify 677 proteins secreted in the saliva of D. andersoni ticks fed for 2 and 5 days, following proteomic investigations of whole saliva using mass spectrometry. Salivary gland transcript levels of unfed ticks were compared with 2 and 5 day fed ticks to identify genes upregulated early during tick feeding. We cross-referenced the proteomic data with the transcriptomic data to identify 157 proteins of interest for immunomodulation and blood feeding. Proteins of unknown function as well as known immunomodulators were identified.

  4. Drosophila sec10 is required for hormone secretion but not general exocytosis or neurotransmission.

    PubMed

    Andrews, Hillary K; Zhang, Yong Q; Trotta, Nick; Broadie, Kendal

    2002-12-01

    The sec6/8, or exocyst, complex is implicated in trafficking of secretory vesicles to fusion sites in the plasma membrane. Genetic analyses have been done primarily in yeast, where mutation of the eight protein subunits similarly disrupts polarized vesicle fusion. The goal of this study was to assay the sec6/8 complex in Drosophila, and specifically to test its widely hypothesized functions in synaptogenesis and neurotransmission. We used a transgenic RNAi approach to remove the most highly conserved complex component, Drosophila sec10 (dSec10). Ubiquitous dSec10 RNAi resulted in early postembryonic lethality, demonstrating that dSec10 is essential. Surprisingly, tissue-specific dSec10 RNAi revealed no essential requirement in nervous system, musculature, gut or epidermis. Assays of polarized secretion in all these tissues failed to reveal any role for dSec10. In particular, the neuromuscular synapse showed no defects in morphogenesis or vesicle trafficking/fusion underlying neurotransmission. The essential requirement for dSec10 was restricted to the ring gland, the Drosophila organ specialized for endocrine function. The developmental arrest of dSec10 RNAi animals was partially rescued by feeding ecdysone, suggesting dSec10 mediates steroid hormone secretion. We conclude that dSec10 has no detectable role in most forms of polarized trafficking/exocytosis, including neurotransmission, but rather is essential for endocrine secretion. PMID:12453153

  5. Changes in the sialylation and sulfation of secreted thyrotropin in congenital hypothyroidism

    SciTech Connect

    Gyves, P.W.; Gesundheit, N.; Thotakura, N.R.; Stannard, B.S.; DeCherney, G.S.; Weintraub, B.D. )

    1990-05-01

    The authors have examined the oligosaccharide structure of secreted thyrotropin (TSH) in perinatal and mature rats with congenital primary hypothyroidism. Rat pituitaries from euthyroid control animals and those rendered hypothyroid by methimazole treatment were incubated with ({sup 3}H)glucosamine in vitro. Secreted TSH was purified, and oligosaccharides were enzymatically released and characterized by anion-exchange HPLC. In perinatal hypothyroid animals compared with control animals, oligosaccharides from TSH {alpha} and {beta} subunits contained more species with three or more negative charges. Moreover, perinatal hypothyroid animals demonstrated a dramatic increase in the ratio of sialylated to sulfated species within oligosaccharides of the same negative charge. In mature hypothyroid 9-week-old animals compared with control animals, changes were less pronounced, suggesting that endocrine regulation of oligosaccharide structure is dependent upon the maturational state of the animal. Together, these data provide direct evidence and characterization of specific changes in the structure of a secreted pituitary glycoprotein hormone occurring as a result of in vivo endocrine alterations during early development. Moreover, they provide a potential structural basis to explain the delayed clearance of both TSH and the gonadotropins with end-organ deficiency, which may have important implications for the in vivo biological activities of these hormones.

  6. The Secretion of Areolar (Montgomery's) Glands from Lactating Women Elicits Selective, Unconditional Responses in Neonates

    PubMed Central

    Doucet, Sébastien; Soussignan, Robert; Sagot, Paul; Schaal, Benoist

    2009-01-01

    Background The communicative meaning of human areolae for newborn infants was examined here in directly exposing 3-day old neonates to the secretion from the areolar glands of Montgomery donated by non related, non familiar lactating women. Methodology/Principal Findings The effect of the areolar stimulus on the infants' behavior and autonomic nervous system was compared to that of seven reference stimuli originating either from human or non human mammalian sources, or from an arbitrarily-chosen artificial odorant. The odor of the native areolar secretion intensified more than all other stimuli the infants' inspiratory activity and appetitive oral responses. These responses appeared to develop independently from direct experience with the breast or milk. Conclusion/Significance Areolar secretions from lactating women are especially salient to human newborns. Volatile compounds carried in these substrates are thus in a position to play a key role in establishing behavioral and physiological processes pertaining to milk transfer and production, and, hence, to survival and to the early engagement of attachment and bonding. PMID:19851461

  7. Synthesis and secretion of light-chain immunoglobulin in two successive cycles of synchronized plasmacytoma cells

    PubMed Central

    1976-01-01

    Suspension-cultured mouse plasmacytoma cells (MPC-11) were accumulated in the late G1 phase by exposure to isoleucine-deficient medium for 20- 24 h. The arrested culture was fed with complete medium enabling the cells to continue the cell cycle synchronously, undergo mitosis, and enter a second cycle of growth. This method of synchronization left the protein-synthesizing ability intact as judged by the polysome profile and the capacity of the cells to incorporate labeled amino acids into protein after the restoration of isoleucine. After incubation in isoleucine-deficient medium and the addition of isoleucine to the culture, cells entered the S phase after a short lag, as judged by [3H]thymidine incorporation into nucleic acid and by spectrophotometric measurement of nuclear DNA. The cells were in mitosis between 12 and 18 h as judged by the increase in cell count and analysis of cell populations on albumin gradients. Synthesis and secretion of light- chain immunoglobulin were maximal in the late G1/early S phase of the first cycle. During late S phase, G2 phase, and mitosis, both synthesis and secretion were observed to be at a low level; however, immediately after motosis the cells which then entered the G1 phase apparently commenced synthesis of light chain immunoglobulin straight away, although secretion of labeled material remained at a low level. PMID:812877

  8. Proteomics informed by transcriptomics identifies novel secreted proteins in Dermacentor andersoni saliva.

    PubMed

    Mudenda, Lwiindi; Pierlé, Sebastián Aguilar; Turse, Joshua E; Scoles, Glen A; Purvine, Samuel O; Nicora, Carrie D; Clauss, Therese R W; Ueti, Massaro W; Brown, Wendy C; Brayton, Kelly A

    2014-11-01

    Dermacentor andersoni, known as the Rocky Mountain wood tick, is found in the western United States and transmits pathogens that cause diseases of veterinary and public health importance including Rocky Mountain spotted fever, tularemia, Colorado tick fever and bovine anaplasmosis. Tick saliva is known to modulate both innate and acquired immune responses, enabling ticks to feed for several days without detection. During feeding ticks subvert host defences such as hemostasis and inflammation, which would otherwise result in coagulation, wound repair and rejection of the tick. Molecular characterization of the proteins and pharmacological molecules secreted in tick saliva offers an opportunity to develop tick vaccines as an alternative to the use of acaricides, as well as new anti-inflammatory drugs. We performed proteomics informed by transcriptomics to identify D. andersoni saliva proteins that are secreted during feeding. The transcript data generated a database of 21,797 consensus sequences, which we used to identify 677 proteins secreted in the saliva of D. andersoni ticks fed for 2 and 5days, following proteomic investigations of whole saliva using mass spectrometry. Salivary gland transcript levels of unfed ticks were compared with 2 and 5day fed ticks to identify genes upregulated early during tick feeding. We cross-referenced the proteomic data with the transcriptomic data to identify 157 proteins of interest for immunomodulation and blood feeding. Proteins of unknown function as well as known immunomodulators were identified. PMID:25110293

  9. Early Math.

    ERIC Educational Resources Information Center

    Van Nuys, Ute Elisabeth

    1986-01-01

    Presents reviews of the following mathematics software designed to teach young children counting, number recognition, visual discrimination, matching, addition, and subtraction skills; Stickybear Numbers, Learning with Leeper, Getting Ready to Read and Add, Counting Parade, Early Games for Young Children, Charlie Brown's 1,2,3's, Let's Go Fishing,…

  10. 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.

  11. 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.

  12. New Explorations with Waste Materials in Early Childhood Education

    ERIC Educational Resources Information Center

    Uyanik, Ozgun; Inal, Gozde; Calisandemir, Fatma; Can-Yasar, Munevver; Kandir, Adalet

    2011-01-01

    Creativity is innately brought with secret power which can emerge at any time throughout life and be enhanced if fostered. Properly designed art activities serve as a potential for emergence and the enhancement of children's creativities in their early childhood educations. Those children who cannot express their emotions through oral language or…

  13. Cabergoline inhibits prolactin secretion and accelerates involution in dairy cows after dry-off.

    PubMed

    Boutinaud, M; Isaka, N; Lollivier, V; Dessauge, F; Gandemer, E; Lamberton, P; De Prado Taranilla, A I; Deflandre, A; Sordillo, L M

    2016-07-01

    Dairy cattle require a dry period between successive lactations to ensure optimal milk production. Because prolactin (PRL) is necessary for the initiation and maintenance of milk production, strategies that can inhibit PRL secretion might hasten the involution process. The objective of this study was to determine the effect of the PRL release inhibitor cabergoline on markers of mammary gland involution during the early dry period. To assess the effect of cabergoline treatment on mammary gland involution, 14 Holstein dairy cows in late lactation were treated with either a single i.m. administration of 5.6mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n=7) or placebo (n=7) at the time of dry-off. Blood samples and mammary secretion samples were collected 6d before dry-off and again 1, 2, 3, 4, 8, and 14d following the abrupt cessation of lactation. Blood samples were used to determine plasma PRL concentrations. Mammary secretion samples were used to determine somatic cell count, milk fat, lactose, true protein content, and concentrations of α-lactalbumin, lactoferrin, and citrate. Following the cessation of lactation, changes in mammary secretion composition indicated diminished milk synthesis, including reduced concentrations of α-lactalbumin, citrate, and lactose. In contrast, milk somatic cell count, percent total protein, percent fat content, and lactoferrin concentrations significantly increased as involution progressed. Cabergoline treatment decreased the plasma PRL concentrations during the first week of dry-off, compared with the control treatment. No significant differences in citrate, α-lactalbumin, or protein content were observed between treatment groups. The most dramatic changes in secretion composition as a consequence of cabergoline treatment occurred during the first week of the dry period, when lactose concentrations and the citrate:lactoferrin molar ratio were lower and lactoferrin concentrations higher than in the control

  14. Mechanism and Synergism in Epithelial Fluid and Electrolyte Secretion

    PubMed Central

    Hong, Jeong Hee; Park, Seonghee; Shcheynikov, Nikolay; Muallem, Shmuel

    2014-01-01

    A central function of epithelia is the control of the volume and electrolyte composition of bodily fluids through vectorial transport of electrolytes and the obligatory H2O. In exocrine glands fluid and electrolyte secretion is carried out by both acinar and duct cells, with the portion of fluid secreted by each cell type vary among glands. All acinar cells secrete isotonic, plasma-like fluid, while the duct determines the final electrolyte composition of the fluid by absorbing most of the Cl− and secreting HCO3−. The key transporters mediating acinar fluid and electrolyte secretion are the basolateral Na+/K+/2Cl− cotransporter, the luminal Ca2+-activated Cl− channel ANO1 and basolateral and luminal Ca2+-activated K+ channels. Ductal fluid and HCO3− secretion are mediated by the basolateral membrane Na+-HCO3− cotransporter NBCe1-B and the luminal membrane Cl−/HCO3− exchanger slc26a6 and the Cl− channel CFTR. The function of the transporters is regulated by multiple inputs, which in the duct include major regulation by the WNK/SPAK pathway that inhibit secretion and the IRBIT/PP1 pathway that antagonize the effects of the WNK/SPAK pathway to both stimulate and coordinate the secretion. The function of these regulatory pathways in secretory glands acinar cells is yet to be examined. An important concept in biology is synergism among signaling pathways to generate the final physiological response that ensures regulation with high fidelity and guards against cell toxicity. While synergism is observed in all epithelial functions, the molecular mechanism mediating the synergism is not known. Recent work reveals a central role for IRBIT as a third messenger that integrates and synergizes the function of the Ca2+ and cAMP signaling pathways in activation of epithelial fluid and electrolyte secretion. These concepts are discussed in this review using secretion by the pancreatic and salivary gland ducts as model systems. PMID:24240699

  15. Molecular genetic manipulation of Pichia pastoris SEC4 governs cell growth and glucoamylase secretion

    SciTech Connect

    Liu, S.-H.; Chou, W.-I; Lin, S.-C.; Sheu, C.-C.; Chang, Margaret Dah-Tsyr . E-mail: dtchang@life.nthu.edu.tw

    2005-11-04

    We have previously engineered a recombinant Pichia pastoris GS115 transformant, MSPGA-7, harboring seven copies of glucoamylase (GA) fused with modified signal peptide. High yield secretion of GA was achieved as an extra copy of SEC4 was integrated to the transformant. To elucidate the physiological role of SEC4, a dominant-negative mutant of SEC4, SEC4 {sub S28N}, was overexpressed under the control of alchohol oxidase 1 (AOX1) promoter in P. pastoris strain MSPGA-7 as well as a set of host cells harboring multi-copy of wild type SEC4. We found that SEC4 {sub S28N} mutation in the key guanine nucleotide binding domain reduced guanine nucleotide binding affinity, hence it blocked the transport of vesicles required for targeting and fusion to the plasma membrane. The inhibitory levels of cell growth and GA secretion were correlated with the dosage of SEC4 {sub S28N} gene. In addition, overexpression of SEC4 driven by AOX1 promoter in MSPGA-7 improved the secretory production of GA, but demonstrated the delay of cell growth by increased gene dosage of SEC4. Interestingly, a limited level of Sec4p did not disturb the cell growth. It was because expression of only one copy of SEC4 resulted in delay of cell growth at an early stage while still maintaining high level Sec4p at long-term incubation. Accordingly, as glyceraldehyde-3-phosphate dehydrogenase promoter was used to substitute AOX1 promoter to drive the SEC4 expression, enhanced GA secretion but not inhibition of cell growth was achieved. Taken together, our results demonstrate that SEC4 is essential for P. pastoris in regulating cell growth and heterologous protein secretion in a dosage-dependent manner.

  16. Molecular genetic manipulation of Pichia pastoris SEC4 governs cell growth and glucoamylase secretion.

    PubMed

    Liu, Shi-Hwei; Chou, Wei-I; Lin, Shu-Chuan; Sheu, Chia-Chin; Chang, Margaret Dah-Tsyr

    2005-11-01

    We have previously engineered a recombinant Pichia pastoris GS115 transformant, MSPGA-7, harboring seven copies of glucoamylase (GA) fused with modified signal peptide. High yield secretion of GA was achieved as an extra copy of SEC4 was integrated to the transformant. To elucidate the physiological role of SEC4, a dominant-negative mutant of SEC4, SEC4(S28N), was overexpressed under the control of alchohol oxidase 1 (AOX1) promoter in P. pastoris strain MSPGA-7 as well as a set of host cells harboring multi-copy of wild type SEC4. We found that SEC4(S28N) mutation in the key guanine nucleotide binding domain reduced guanine nucleotide binding affinity, hence it blocked the transport of vesicles required for targeting and fusion to the plasma membrane. The inhibitory levels of cell growth and GA secretion were correlated with the dosage of SEC4(S28N) gene. In addition, overexpression of SEC4 driven by AOX1 promoter in MSPGA-7 improved the secretory production of GA, but demonstrated the delay of cell growth by increased gene dosage of SEC4. Interestingly, a limited level of Sec4p did not disturb the cell growth. It was because expression of only one copy of SEC4 resulted in delay of cell growth at an early stage while still maintaining high level Sec4p at long-term incubation. Accordingly, as glyceraldehyde-3-phosphate dehydrogenase promoter was used to substitute AOX1 promoter to drive the SEC4 expression, enhanced GA secretion but not inhibition of cell growth was achieved. Taken together, our results demonstrate that SEC4 is essential for P. pastoris in regulating cell growth and heterologous protein secretion in a dosage-dependent manner. PMID:16176807

  17. The Historical Legacy of a Secret Society at Duke University (1913-1971): Cultural Hegemony and the Tenacious Ideals of the "Big Man on Campus"

    ERIC Educational Resources Information Center

    Barr, Krispin Wagoner

    2013-01-01

    Collegiate secret societies, as distinguished from Greek-letter fraternal organizations, enjoyed prominence within many American campus communities from the early nineteenth century through the mid-twentieth century (Baird, 1879; Hitchcock, 1863; Slosson, 1910; Veysey, 1965). The establishment of these elite groups preceded the maturation of…

  18. Uncovering the Secret of Shock Wave Lithotripsy

    NASA Astrophysics Data System (ADS)

    Zhong, P.

    Shock wave lithotripsy (SWL) is an engineering innovation that has revolutionized the treatment of kidney stone disease since the early 1980s [1] - [3]. Today, SWL is the first-line therapy for millions of patients worldwide with renal and upper urinary stones [3, 4].

  19. Early Risers

    ERIC Educational Resources Information Center

    Asquith, Chistina

    2002-01-01

    In this article, the author features Bard High School Early College, the first public school in the country to offer a free, full-time college curriculum--and all the credits that go with it--to high schoolers. In Bard's four-year program, students race through high school requirements in 9th and 10th grades, then take college courses in 11th and…

  20. Secreted Metalloprotease Gene Family of Microsporum canis

    PubMed Central

    Brouta, Frédéric; Descamps, Frédéric; Monod, Michel; Vermout, Sandy; Losson, Bertrand; Mignon, Bernard

    2002-01-01

    Keratinolytic proteases secreted by dermatophytes are likely to be virulence-related factors. Microsporum canis, the main agent of dermatophytosis in dogs and cats, causes a zoonosis that is frequently reported. Using Aspergillus fumigatus metalloprotease genomic sequence (MEP) as a probe, three genes (MEP1, MEP2, and MEP3) were isolated from an M. canis genomic library. They presented a quite-high percentage of identity with both A. fumigatus MEP and Aspergillus oryzae neutral protease I genes. At the amino acid level, they all contained an HEXXH consensus sequence, confirming that these M. canis genes (MEP genes) encode a zinc-containing metalloprotease gene family. Furthermore, MEP3 was found to be the gene encoding a previously isolated M. canis 43.5-kDa keratinolytic metalloprotease, and was successfully expressed as an active recombinant enzyme in Pichia pastoris. Reverse transcriptase nested PCR performed on total RNA extracted from the hair of M. canis-infected guinea pigs showed that at least MEP2 and MEP3 are produced during the infection process. This is the first report describing the isolation of a gene family encoding potential virulence-related factors in dermatophytes. PMID:12228297

  1. Choice of measurement as the secret

    NASA Astrophysics Data System (ADS)

    Liu, Bin; Gao, Fei; Qin, Su-Juan; Huang, Wei; Liu, Feng; Wen, Qiao-Yan

    2014-04-01

    Recently, Kalev et al. [A. Kalev, A. Mann, and M. Revzen, Phys. Rev. Lett. 110, 260502 (2013)., 10.1103/PhysRevLett.110.260502] proposed a quantum (public) communication protocol with an interesting encoding style, where the signal is encoded in the choice of the measurement basis of one of the communicating parties (Bob) and Bob's measurement results are irrelevant for the communication. As we know, one of the main advantages of quantum technique in communication over the classical one is the higher security. Therefore, as Kalev et al. have mentioned in their paper, an interesting open question is whether one could and how to utilize this new encoding style to design a secure communication protocol, i.e., translate the choice of measurement into the secret. Here we propose a quantum key distribution protocol, which is a secure communication protocol, with this encoding style, where Bob's measurement results are still irrelevant. Furthermore, the security of the proposed protocol in the zero-error case has been proved.

  2. Analysis of eight out genes in a cluster required for pectic enzyme secretion by Erwinia chrysanthemi: sequence comparison with secretion genes from other gram-negative bacteria.

    PubMed Central

    Lindeberg, M; Collmer, A

    1992-01-01

    Many extracellular proteins produced by Erwinia chrysanthemi require the out gene products for transport across the outer membrane. In a previous report (S. Y. He, M. Lindeberg, A. K. Chatterjee, and A. Collmer, Proc. Natl. Acad. Sci. USA 88:1079-1083, 1991) cosmid pCPP2006, sufficient for secretion of Erwinia chrysanthemi extracellular proteins by Escherichia coli, was partially sequenced, revealing four out genes sharing high homology with pulH through pulK from Klebsiella oxytoca. The nucleotide sequence of eight additional out genes reveals homology with pulC through pulG, pulL, pulM, pulO, and other genes involved in secretion by various gram-negative bacteria. Although signal sequences and hydrophobic regions are generally conserved between Pul and Out proteins, four out genes contain unique inserts, a pulN homolog is not present, and outO appears to be transcribed separately from outC through outM. The sequenced region was subcloned, and an additional 7.6-kb region upstream was identified as being required for secretion in E. coli. out gene homologs were found on Erwinia carotovora cosmid clone pAKC651 but were not detected in E. coli. The outC-through-outM operon is weakly induced by polygalacturonic acid and strongly expressed in the early stationary phase. The out and pul genes are highly similar in sequence, hydropathic properties, and overall arrangement but differ in both transcriptional organization and the nature of their induction. Images PMID:1429461

  3. The Evolution of the Secreted Regulatory Protein Progranulin.

    PubMed

    Palfree, Roger G E; Bennett, Hugh P J; Bateman, Andrew

    2015-01-01

    Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i): the origins of metazoan progranulins (ii): the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii): the evolution of granulin module architectures of vertebrate progranulins (iv): the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl-terminus. Polypeptide

  4. The Evolution of the Secreted Regulatory Protein Progranulin

    PubMed Central

    Palfree, Roger G. E.; Bennett, Hugh P. J.; Bateman, Andrew

    2015-01-01

    Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i): the origins of metazoan progranulins (ii): the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii): the evolution of granulin module architectures of vertebrate progranulins (iv): the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl-terminus. Polypeptide

  5. Insulin secretion as a determinant of pancreatic cancer risk.

    PubMed

    McCarty, M F

    2001-08-01

    New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. PMID:11461162

  6. Type V Protein Secretion Pathway: the Autotransporter Story

    PubMed Central

    Henderson, Ian R.; Navarro-Garcia, Fernando; Desvaux, Mickaël; Fernandez, Rachel C.; Ala'Aldeen, Dlawer

    2004-01-01

    Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function. PMID:15590781

  7. Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages.

    PubMed

    Soliman, D M; Twigg, H L

    1992-10-01

    Studies suggest smokers have decreased alveolar macrophage (AM) accessory cell (AC) function and a reduced incidence of immune-mediated lung diseases such as sarcoidosis. Impaired AM secretion of cytokines important in T-cell immune responses could explain this observation. We investigated production and secretion of interleukin-1 (IL-1) and interleukin-6 (IL-6) in smokers and nonsmokers. Lipopolysaccharide-induced AM IL-1 secretion in smokers was significantly reduced compared with nonsmoker AM. However, intracellular IL-1 in smoker AM was higher than in nonsmokers, suggesting that reduced IL-1 secretion was due to impaired release rather than reduced production. Smoker AM secreted significantly less bioactive IL-6 measured in a bioassay compared with nonsmoker AM. Intracellular IL-6 was virtually undetectable in both groups. In some smokers IL-6 production determined by immunoprecipitation was reduced. However, as a group antigenic IL-6 secretion determined by enzyme-linked immunoabsorbent assay was similar in smokers and nonsmokers, suggesting that smoker AM may cosecrete an inhibitor of IL-6 bioactivity. Indeed, AM supernatants from smokers inhibited B9 proliferation in response to maximal recombinant IL-6 stimulation, whereas supernatants from nonsmokers did not. We conclude that AM from smokers secrete less cytokines important in T-cell proliferation than AM from nonsmokers and suggest that for IL-6 this impairment is related to both decreased production of antigenic protein as well as cosecretion of an IL-6 inhibitor. PMID:1415725

  8. The behavior of pollination drop secretion in Ginkgo biloba L.

    PubMed Central

    Jin, Biao; Jiang, Xiaoxue; Wang, Di; Zhang, Lei; Wan, Yinglang; Wang, Li

    2012-01-01

    Pollination drop (PD) secretion plays a critical role in wind pollination in many gymnosperms. We conducted detailed investigations on PD secretion in Ginkgo biloba, and found that PDs could not form when the micropyle was removed, but were able to form after removal of the shoot, leaves, ovular stalk, or ovular collar. The duration and volume of the PD increased under high relative humidity, but addition of salt or sugar did not affect PD secretion, its size, or its duration. Morphological and anatomical observations showed that many secretion cells at the nucellus tip contributed to secreting the PD after the formation of pollen chamber. Under laboratory conditions, the PD persisted for approximately 10 d if not pollinated, and re-formed five times after it was removed, with the total volume of PDs reaching approximately 0.4 μL. These results suggested that PDs can be continuously secreted by the tip of the nucellus cells during the pollination stage to increase the chance of capturing pollen from the air. Importantly, PD secretion is an independent behavior of the ovule and PDs were produced apoplastically. PMID:22899081

  9. Mutations alter secretion of fukutin-related protein.

    PubMed

    Lu, Pei J; Zillmer, Allen; Wu, XiaoHua; Lochmuller, Hanns; Vachris, Judy; Blake, Derek; Chan, Yiumo Michael; Lu, Qi L

    2010-02-01

    Mutations in the fukutin-related protein (FKRP) gene cause limb-girdle muscular dystrophy type 2I (LGMD2I) as well as other severe muscle disorders, including Walker-Warburg syndrome, muscle-eye-brain disease, and congenital muscular dystrophy type 1C. The FKRP gene encodes a putative glycosyltransferase, but its precise localization and functions have yet to be determined. In the present study, we demonstrated that normal FKRP is secreted into culture medium and mutations alter the pattern of secretion in CHO cells. L276I mutation associated with mild disease phenotype was shown to reduce the level of secretion whereas P448L and C318Y mutations associated with severe disease phenotype almost abolished the secretion. However, a truncated FKRP mutant protein lacking the entire C-terminal 185 amino acids due to the E310X nonsense mutation was able to secrete as efficiently as the normal FKRP. The N-terminal signal peptide sequence is apparently cleaved from the secreted FKRP proteins. Alteration of the secretion pathway by different mutations and spontaneous read-through of nonsense mutation may contribute to wide variations in phenotypes associated with FKRP-related diseases. PMID:19900540

  10. The effects of an anticipated challenge on diurnal cortisol secretion.

    PubMed

    Wetherell, Mark A; Lovell, Brian; Smith, Michael A

    2015-01-01

    In healthy, non-challenged individuals, the secretion of cortisol typically follows a diurnal profile characterized by a peak in the period following waking (cortisol awakening response) and a gradual decline throughout the day. In addition, cortisol secretion is increased in response to acutely stressful stimuli, particularly stressors involving social evaluation. The current study is the first to assess the impact of an anticipated acute laboratory stressor upon the typical diurnal pattern of HPA activation and relationship to acute cortisol secretion. A sample of 23 healthy young adults provided salivary cortisol samples at four time points (immediately upon awakening, 30-min post-awakening, 1200 h and before bed) on 2 consecutive days. On the second day, participants attended the laboratory and undertook an anticipated acute socially evaluative stressor immediately following provision of their 1200 h saliva sample. Heart rate, blood pressure and mood were recorded immediately before and after the stressor and at 10 and 20 min post-stressor along with additional salivary cortisol samples. Typical patterns of cortisol secretion were observed on both days and exposure to the laboratory stressor was associated with the expected increases in cortisol, heart rate, blood pressure and negative mood. However, significant differences in diurnal cortisol secretion were observed between the two days with greater secretion, in particular, during the period following awakening, evident on the day of the anticipated laboratory stressor. Furthermore, secretion of cortisol during the period following awakening was positively related to secretion during the acute reactivity periods. This is the first study to integrate a laboratory stressor into a typical day and assess its impact on indices of diurnal cortisol secretion in an ambulatory setting. The current findings support the notion that the cortisol awakening response is associated with anticipation of the upcoming day

  11. Regulation of lung surfactant secretion by intracellular pH.

    PubMed

    Chander, A

    1989-12-01

    We investigated secretion of lung surfactant phosphatidylcholine (PC) using isolated perfused rat lung preparation after labeling the lung lipids in vitro with [methyl-3H]choline. The perfusion medium was Krebs-Ringer bicarbonate buffer (pH 7.4) containing 10 mM glucose and 3% fatty acid-poor bovine serum albumin. After ventilation of lungs with air containing 5% CO2 (control) for 1 h, 0.91% +/- 0.04 (mean +/- SE, n = 6) of total lung lipid radioactivity (greater than 95% in PC) was recovered in the cell-free lavage fluid. The secretion of PC was increased with terbutaline (50 microM), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP, 100 microM), phorbol L2-myristate 13-acetate (30 ng/ml), and ATP (1 mM), in each case by approximately 150%. Secretion of PC was also increased by 160% if the lungs were ventilated with air containing 0% CO2. The low CO2-mediated PC secretion was time and concentration dependent. The dose-response curve for 0-10% CO2 was S-shaped. The low CO2-induced increase in PC secretion could be largely reversed with diffusible weak acids (25 mM, acetate or butyrate) in the perfusion medium. An increase (70%) in secretion was also induced with 10 mM NH4Cl, suggesting a role for intracellular alkalosis. These observations suggest that intracellular alkalosis stimulates lung surfactant secretion. Alkalosis-stimulated secretion of PC was additive with that with terbutaline (5 X 10(-7) to 5 X 10(-4) M) or 10(-4) M 8-BrcAMP, suggesting that alkalosis effect was not mediated through the beta-adrenergic pathway of surfactant secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2514603

  12. Restructuring of Pancreatic Islets and Insulin Secretion in a Postnatal Critical Window

    PubMed Central

    Aguayo-Mazzucato, Cristina; Sanchez-Soto, Carmen; Godinez-Puig, Victoria; Gutiérrez-Ospina, Gabriel; Hiriart, Marcia

    2006-01-01

    Function and structure of adult pancreatic islets are determined by early postnatal development, which in rats corresponds to the first month of life. We analyzed changes in blood glucose and hormones during this stage and their association with morphological and functional changes of alpha and beta cell populations during this period. At day 20 (d20), insulin and glucose plasma levels were two- and six-fold higher, respectively, as compared to d6. Interestingly, this period is characterized by physiological hyperglycemia and hyperinsulinemia, where peripheral insulin resistance and a high plasmatic concentration of glucagon are also observed. These functional changes were paralleled by reorganization of islet structure, cell mass and aggregate size of alpha and beta cells. Cultured beta cells from d20 secreted the same amount of insulin in 15.6 mM than in 5.6 mM glucose (basal conditions), and were characterized by a high basal insulin secretion. However, beta cells from d28 were already glucose sensitive. Understanding and establishing morphophysiological relationships in the developing endocrine pancreas may explain how events in early life are important in determining adult islet physiology and metabolism. PMID:17183663

  13. Por Secretion System-Dependent Secretion and Glycosylation of Porphyromonas gingivalis Hemin-Binding Protein 35

    PubMed Central

    Shoji, Mikio; Sato, Keiko; Yukitake, Hideharu; Kondo, Yoshio; Narita, Yuka; Kadowaki, Tomoko; Naito, Mariko; Nakayama, Koji

    2011-01-01

    The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis. We have recently found that P. gingivalis has a novel secretion system named the Por secretion system (PorSS), which is responsible for secretion of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain. These proteinases contain conserved C-terminal domains (CTDs) in their C-termini. Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of P. gingivalis and contributes to its haem utilization, also contains a CTD, suggesting that HBP35 is translocated to the cell surface via the PorSS. In this study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed that HBP35 is translocated to the cell surface via the PorSS and is glycosylated with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to be required for cell surface translocation and glycosylation. The GFP-CTD fusion study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD-region peptides were not found in samples of glycosylated HBP35 protein by peptide map fingerprinting analysis, and antibodies against CTD-regions peptides did not react with glycosylated HBP35 protein. These results suggest both that the CTD region functions as a recognition signal for the PorSS and that glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits were used for making antisera against bacterial proteins in this study. PMID:21731719

  14. Competitively coupled maps for hiding secret visual information

    NASA Astrophysics Data System (ADS)

    Vaidelys, M.; Ziaukas, P.; Ragulskis, M.

    2016-02-01

    A novel digital image hiding scheme based on competitively coupled maps is presented in this paper. Self-organizing patterns produced by an array of non-diffusively coupled nonlinear maps are exploited to conceal the secret. The secret image is represented in the form of a dot-skeleton representation and is embedded into a spatially homogeneous initial state far below the noise level. Self-organizing patterns leak the secret image at a predefined set of system parameters. Computational experiments are used to demonstrate the effectiveness and the security of the proposed image hiding scheme.

  15. Reversible Aptamer-Au Plasmon Rulers for Secreted Single Molecules

    SciTech Connect

    Lee, Somin Eunice; Chen, Qian; Bhat, Ramray; Petkiewicz, Shayne; Smith, Jessica M.; Ferry, Vivian E.; Correia, Ana Luisa; Alivisatos, A. Paul; Bissell, Mina J.

    2015-06-03

    Plasmon rulers, consisting of pairs of gold nanoparticles, allow single-molecule analysis without photobleaching or blinking; however, current plasmon rulers are irreversible, restricting detection to only single events. Here, we present a reversible plasmon ruler, comprised of coupled gold nanoparticles linked by a single aptamer, capable of binding individual secreted molecules with high specificity. We show that the binding of target secreted molecules to the reversible plasmon ruler is characterized by single-molecule sensitivity, high specificity, and reversibility. Lastly, such reversible plasmon rulers should enable dynamic and adaptive live-cell measurement of secreted single molecules in their local microenvironment.

  16. Calcium requirements for secretion in bovine chromaffin cells.

    PubMed Central

    Augustine, G J; Neher, E

    1992-01-01

    1. Measurements of membrane capacitance and intracellular Ca2+ concentration, [Ca2+]i, were used to examine the Ca2+ dependence of secretion in single adrenal chromaffin cells. 2. Intracellular dialysis of Ca2+, through a patch pipette, promoted secretion; the rate of secretion increased monotonically as [Ca2+]i was elevated, while the total amount of secretion reached a maximum at 1.5 microM-Ca2+ and declined at high [Ca2+]i. 3. Release of Ca2+ from internal stores, using bradykinin or ionomycin, transiently elevated [Ca2+]i and the rate of secretion. 4. Considering responses to both Ca2+ dialysis and release from internal stores, it appears that the rate of secretion increases over a range of [Ca2+]i levels above 0.2 microM and saturates at concentrations greater than 10 microM, if at all. Secretion appears to have a Hill coefficient for Ca2+ of about 2. At [Ca2+]i greater than 1-2 microM, prolonged elevation of [Ca2+]i, via dialysis, produced lower rates of secretion than transient elevation of [Ca2+]i caused by release from internal stores. This may have been caused by a depletion of readily releasable chromaffin granules during prolonged elevation of [Ca2+]i. 5. Brief depolarizing pulses produced transient rises in both [Ca2+]i and the rate of secretion. The ability of these pulses to evoke secretion 'washed out' during prolonged intracellular dialysis, due to both reduced Ca2+ influx and a diminished ability of the cell to secrete in response to a given Ca2+ load. 6. The kinetics of the secretory response depended upon the size of the depolarization-induced Ca2+ load; small rises in [Ca2+]i increased membrane capacitance only during the depolarization, while larger rises in [Ca2+]i produced increases both during and following the depolarization. The secretory responses that outlasted the depolarization appeared to be due to persistent elevation of [Ca2+]i. Secretory responses were sometimes followed by a slower decline in membrane capacitance, probably due to

  17. Continuous variable (2, 3) threshold quantum secret sharing schemes

    NASA Astrophysics Data System (ADS)

    Lance, Andrew M.; Symul, Thomas; Bowen, Warwick P.; Tyc, Tomás; Sanders, Barry C.; Lam, Ping Koy

    2003-01-01

    We present two schemes to perform continuous variable (2, 3) threshold quantum secret sharing (QSS) on the quadrature amplitudes of bright light beams. Both schemes require a pair of entangled light beams. The first scheme utilizes two phase sensitive optical amplifiers, whilst the second uses an electro-optic feedforward loop for the reconstruction of the secret. We examine the efficacy of QSS in terms of fidelity, as well as the signal transfer coefficients and the conditional variances of the reconstructed output state. We show that both schemes in the ideal case yield perfect secret reconstruction.

  18. Multiparty semiquantum secret sharing based on rearranging orders of qubits

    NASA Astrophysics Data System (ADS)

    Gao, Gan; Wang, Yue; Wang, Dong

    2016-04-01

    Based on the assumption of a perfect qubit, Boyer et al. proposed a novel semiquantum key distribution protocol [Phys. Rev. Lett. 99 (2007) 140501], in which quantum Alice shares a secret key with classical Bob. In this paper, we use Bell states to propose a multiparty semiquantum secret sharing (MSQSS) protocol, in which only the boss is quantum and all agents are classical. Classical agents are restricted to performing measurements in a computational basis and rearranging orders of qubits. Unless all classical agents collaborate, no subset of them can obtain the secret of the quantum boss. Also, we show that this proposed protocol is secure against eavesdropping.

  19. Prehepatic secretion and disposal of insulin in obese adolescents as estimated by three-hour, eight-sample oral glucose tolerance tests.

    PubMed

    Vogt, Josef A; Domzig, Christian; Wabitsch, Martin; Denzer, Christian

    2016-07-01

    The body compensates for early-stage insulin resistance by increasing insulin secretion. A reliable and easy-to-use mathematical assessment of insulin secretion and disposal could be a valuable tool for identifying patients at risk for the development of type 2 diabetes. Because the pathophysiology of insulin resistance is incompletely understood, assessing insulin metabolism with minimal assumptions regarding its metabolic regulation is a major challenge. To assess insulin secretion and indexes of insulin disposal, our marginalized and regularized absorption approach (MRA) was applied to a sparse sampling oral glucose tolerance test (OGTT) protocol measuring the insulin and C-peptide concentrations. Identifiability and potential bias of metabolic parameters were estimated from published data with dense sampling. The MRA was applied to OGTT data from 135 obese adolescents to demonstrate its clinical applicability. Individual prehepatic basal and dynamic insulin secretion and clearance levels were determined with a precision and accuracy greater than 10% of the nominal value. The intersubject variability in these parameters was approximately four times higher than the intrasubject variability, and there was a strong negative correlation between prehepatic secretion and plasma clearance of insulin. MRA-based analysis provides reliable estimates of insulin secretion and clearance, thereby enabling detailed glucose homeostasis characterization based on restricted datasets that are obtainable during routine patient care. PMID:27143555

  20. Argonaute 2 in Cell-Secreted Microvesicles Guides the Function of Secreted miRNAs in Recipient Cells

    PubMed Central

    Wang, Dong; Zhang, Chen-Yu; Zen, Ke; Li, Limin

    2014-01-01

    MicroRNAs (miRNAs) secreted by cells into microvesicles (MVs) form a novel class of signal molecules that mediate intercellular communication. However, several fundamental aspects of secreted miRNAs remain unknown, particularly the mechanism that governs the function or fate of exogenous miRNAs in recipient cells. In the present study, we provide evidence indicating that Argonaute 2 (Ago2) plays a role in stabilizing miRNAs and facilitating the packaging of secreted miRNAs into MVs. More importantly, Ago2 in origin cell-secreted MVs (but not in recipient cells) directs the function of secreted miRNAs. First, Ago2 overexpression clearly increased the level of miR-16 in cells transfected with a miR-16 mimic by protecting the miRNAs from degradation in lysosomes. Second, Ago2 overexpression increased the level of miR-16 in cell-secreted MVs, suggesting that Ago2 may facilitate the packaging of secreted miRNAs into MVs. Third, exogenous miR-16 delivered by MVs within the origin cells significantly reduced the Bcl2 protein level in recipient cells, and miR-16 and Bcl2 mRNA were physically associated with exogenous HA-tagged Ago2 (HA-Ago2). Finally, the effect of MV-delivered miR-16 on the production of the Bcl2 protein in recipient cells was not abolished by knocking down Ago2 in the recipient cells. PMID:25072345

  1. Structure of EspB, a secreted substrate of the ESX-1 secretion system of Mycobacterium tuberculosis

    PubMed Central

    Korotkova, Natalia; Piton, Jérémie; Wagner, Jonathan M.; Boy-Röttger, Stefanie; Japaridze, Aleksandre; Evans, Timothy J.; Cole, Stewart T.; Pojer, Florence; Korotkov, Konstantin V.

    2015-01-01

    Mycobacterium tuberculosis secretes multiple virulence factors during infection via the general Sec and Tat pathways, and via specialized ESX secretion systems, also referred to as type VII secretion systems. The ESX-1 secretion system is an important virulence determinant because deletion of ESX-1 leads to attenuation of M. tuberculosis. ESX-1 secreted protein B (EspB) contains putative PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains, and a C-terminal domain, which is processed by MycP1 protease during secretion. We determined the crystal structure of PE–PPE domains of EspB, which represents an all-helical, elongated molecule closely resembling the structure of the PE25–PPE41 heterodimer despite limited sequence similarity. Also, we determined the structure of full-length EspB, which does not have interpretable electron density for the C-terminal domain confirming that it is largely disordered. Comparative analysis of EspB in cell lysate and culture filtrates of M. tuberculosis revealed that mature secreted EspB forms oligomers. Electron microscopy analysis showed that the N-terminal fragment of EspB forms donut-shaped particles. These data provide a rationale for the future investigation of EspB's role in M. tuberculosis pathogenesis. PMID:26051906

  2. The secret life of the psychoanalyst.

    PubMed

    Chessick, R D

    2001-01-01

    conscious value systems, which in turn are based on the subdoxastic factors that make the analyst the person that he or she is. Some patients may even precipitate crises or other situations that test the analyst's value system and force the analyst to display his or her secret self in immediate decisions that cannot be avoided. This is especially true if the patient is frightened or terribly threatened by factors in the secret self of the analyst; in this situation the patient may behave like a child who knows his or her father or mother is really very angry under a seemingly calm exterior, and as a result the child deliberately precipitates a display of that parental anger to get it out on the surface, get it over with, and reduce the child's anxiety. I have called for a genealogical study of analysts' choices of theoretical orientation in various cultures, and herein I am calling for a study of the subdoxastic factors in each individual analyst's theoretical orientation. Every theoretical orientation is based on a value system and a set of desires that determine the goals the analyst consciously or unconsciously wishes for the patient to actualize in the treatment process in order for the analyst to feel that he or she has catalyzed a "successful" treatment. This is a preliminary formulation. Further work is needed to distinguish between countertransference in the sense that we ordinarily use that concept today, and these subdoxastic factors determining the analyst's theoretical orientation and value systems, as well as to increase our focus on a subclass of these factors, the cultural ambience and background practices that Heidegger, for example, has identified as being crucial in the formation of the analyst's self as well as that of the patient. PMID:11816355

  3. TRAPP Complexes in Secretion and Autophagy

    PubMed Central

    Kim, Jane J.; Lipatova, Zhanna; Segev, Nava

    2016-01-01

    TRAPP is a highly conserved modular multi-subunit protein complex. Originally identified as a “transport protein particle” with a role in endoplasmic reticulum-to-Golgi transport, its multiple subunits and their conservation from yeast to humans were characterized in the late 1990s. TRAPP attracted attention when it was shown to act as a Ypt/Rab GTPase nucleotide exchanger, GEF, in the 2000s. Currently, three TRAPP complexes are known in yeast, I, II, and III, and they regulate two different intracellular trafficking pathways: secretion and autophagy. Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1. Another small subunit, Trs20/Sedlin, is an adaptor required for the association of core TRAPP with larger subunits to form TRAPP II and TRAPP III. Whereas the molecular structure of the core TRAPP complex is resolved, the architecture of the larger TRAPP complexes, including their existence as dimers and multimers, is less clear. In addition to its Ypt/Rab GEF activity, and thereby an indirect role in vesicle tethering through Ypt/Rabs, a direct role for TRAPP as a vesicle tether has been suggested. This idea is based on TRAPP interactions with vesicle coat components. While much of the basic information about TRAPP complexes comes from yeast, mutations in TRAPP subunits were connected to human disease. In this review we will summarize new information about TRAPP complexes, highlight new insights about their function and discuss current controversies and future perspectives. PMID:27066478

  4. [Glutamate neurotransmission, stress and hormone secretion].

    PubMed

    Jezová, D; Juránková, E; Vigas, M

    1995-11-01

    Glutamate neurotransmission has been investigated in relation to several physiological processes (learning, memory) as well as to neurodegenerative and other disorders. Little attention has been paid to its involvement in neuroendocrine response during stress. Penetration of excitatory amino acids from blood to the brain is limited by the blood-brain barrier. As a consequence, several toxic effects but also bioavailability for therapeutic purposes are reduced. A free access to circulating glutamate is possible only in brain structures lacking the blood-brain barrier or under conditions of its increased permeability. Excitatory amino acids were shown to stimulate the pituitary hormone release, though the mechanism of their action is still not fully understood. Stress exposure in experimental animals induced specific changes in mRNA levels coding the glutamate receptor subunits in the hippocampus and hypothalamus. The results obtained with the use of glutamate receptor antagonists indicate that a number of specific receptor subtypes contribute to the stimulation of ACTH release during stress. The authors provided also data on the role of NMDA receptors in the control of catecholamine release, particularly in stress-induced secretion of epinephrine. These results were the first piece of evidence on the involvement of endogenous excitatory amino acids in neuroendocrine activation during stress. Neurotoxic effects of glutamate in animals are well described, especially after its administration in the neonatal period. In men, glutamate toxicity and its use as a food additive are a continuous subject of discussions. The authors found an increase in plasma cortisol and norepinephrine, but not epinephrine and prolactin, in response to the administration of a high dose of glutamate. It cannot be excluded that these effects might be induced even by lower doses in situations with increased vulnerability to glutamate action (age, individual variability). (Tab. 1, Fig. 6, Ref. 44

  5. A smallest 6 kda metalloprotease, mini-matrilysin, in living world: a revolutionary conserved zinc-dependent proteolytic domain- helix-loop-helix catalytic zinc binding domain (ZBD)

    PubMed Central

    2012-01-01

    Background The Aim of this study is to study the minimum zinc dependent metalloprotease catalytic folding motif, helix B Met loop-helix C, with proteolytic catalytic activities in metzincin super family. The metzincin super family share a catalytic domain consisting of a twisted five-stranded β sheet and three long α helices (A, B and C). The catalytic zinc is at the bottom of the cleft and is ligated by three His residues in the consensus sequence motif, HEXXHXXGXXH, which is located in helix B and part of the adjacent Met turn region. An interesting question is - what is the minimum portion of the enzyme that still possesses catalytic and inhibitor recognition?” Methods We have expressed a 60-residue truncated form of matrilysin which retains only the helix B-Met turn-helix C region and deletes helix A and the five-stranded β sheet which form the upper portion of the active cleft. This is only 1/4 of the full catalytic domain. The E. coli derived 6 kDa MMP-7 ZBD fragments were purified and refolded. The proteolytic activities were analyzed by Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 peptide assay and CM-transferrin zymography analysis. SC44463, BB94 and Phosphoramidon were computationally docked into the 3day structure of the human MMP7 ZBD and TAD and thermolysin using the docking program GOLD. Results This minimal 6 kDa matrilysin has been refolded and shown to have proteolytic activity in the Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 peptide assay. Triton X-100 and heparin are important factors in the refolding environment for this mini-enzyme matrilysin. This minienzyme has the proteolytic activity towards peptide substrate, but the hexamer and octamer of the mini MMP-7 complex demonstrates the CM-transferrin proteolytic activities in zymographic analysis. Peptide digestion is inhibited by SC44463, specific MMP7 inhibitors, but not phosphorimadon. Interestingly, the mini MMP-7 can be processed by autolysis and producing ~ 6 ~ 7 kDa fragments. Thus, many of the functions of the enzyme are retained indicating that the helix B-Met loop-helix C is the minimal functional “domain” found to date for the matrixin family. Conclusions The helix B-Met loop-helix C folding conserved in metalloprotease metzincin super family is able to facilitate proteolytic catalysis for specific substrate and inhibitor recognition. The autolysis processing and producing 6 kDa mini MMP-7 is the smallest metalloprotease in living world. PMID:22642296

  6. Analysis of the Proteins Secreted from the Oryza meyeriana Suspension-Cultured Cells Induced by Xanthomonas oryzae pv. oryzae.

    PubMed

    Chen, Xian; Dong, Yan; Yu, Chulang; Fang, XianPing; Deng, Zhiping; Yan, Chengqi; Chen, Jianping

    2016-01-01

    Oryza meyeriana, a wild species of rice from China, shows high resistance to Xanthomonas oryzae pv. oryzae (Xoo), the cause of rice bacterial blight, one of the most serious rice pathogens. To better understand the resistance mechanism, a proteomic study was conducted to identify changes in the proteins secreted in embryo cell suspension cultures in response to Xoo. After two-dimensional difference gel electrophoresis (2D-DIGE), 72 differentially expressed protein spots corresponding to 34 proteins were identified by Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry. Of the 34 proteins, 10 were up regulated and 24 down regulated. The secreted proteins identified were predicted to be involved in various biological processes, including signal transduction, defense, ROS and cell wall modification. 77% of the 34 proteins were predicted to have a signal peptide by Signal P. Quantitative Real-Time PCR showed that transcript levels of 14 secreted proteins were not well correlated with secreted protein levels. Peroxidase activity was up regulated in both O. meyriana and susceptible rice but was about three times higher in O. meyeriana. This suggests that peroxidases may play an important role in the early response to Xoo in O. meyeriana. These results not only provide a better understanding of the resistance mechanism of O. meyeriana, but have implications for studies of the interactions between other plants and their pathogens. PMID:27196123

  7. Analysis of the Proteins Secreted from the Oryza meyeriana Suspension-Cultured Cells Induced by Xanthomonas oryzae pv. oryzae

    PubMed Central

    Chen, Xian; Dong, Yan; Yu, Chulang; Fang, XianPing; Deng, Zhiping; Yan, Chengqi; Chen, Jianping

    2016-01-01

    Oryza meyeriana, a wild species of rice from China, shows high resistance to Xanthomonas oryzae pv. oryzae (Xoo), the cause of rice bacterial blight, one of the most serious rice pathogens. To better understand the resistance mechanism, a proteomic study was conducted to identify changes in the proteins secreted in embryo cell suspension cultures in response to Xoo. After two-dimensional difference gel electrophoresis (2D-DIGE), 72 differentially expressed protein spots corresponding to 34 proteins were identified by Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry. Of the 34 proteins, 10 were up regulated and 24 down regulated. The secreted proteins identified were predicted to be involved in various biological processes, including signal transduction, defense, ROS and cell wall modification. 77% of the 34 proteins were predicted to have a signal peptide by Signal P. Quantitative Real-Time PCR showed that transcript levels of 14 secreted proteins were not well correlated with secreted protein levels. Peroxidase activity was up regulated in both O. meyriana and susceptible rice but was about three times higher in O. meyeriana. This suggests that peroxidases may play an important role in the early response to Xoo in O. meyeriana. These results not only provide a better understanding of the resistance mechanism of O. meyeriana, but have implications for studies of the interactions between other plants and their pathogens. PMID:27196123

  8. Beyond the wall: Candida albicans secret(e)s to survive.

    PubMed

    Sorgo, Alice G; Heilmann, Clemens J; Brul, Stanley; de Koster, Chris G; Klis, Frans M

    2013-01-01

    The opportunistic fungal pathogen Candida albicans occupies various niches of the human body such as the skin and the mucosal surfaces of the gastrointestinal and urogenital tracts. It can also enter the blood stream and cause deadly, systemic infections, especially in immunocompromised patients, but also in immunocompetent individuals through inserted medical devices. To survive in these diverse host environments, C. albicans has developed specialized virulence attributes and rapidly adapts itself to local growth conditions and defense mechanisms. Candida albicans secretes a considerable number of proteins that are involved in biofilm formation, tissue invasion, immune evasion, and wall maintenance, as well as acquisition of nutrients including metal ions. The secretome of C. albicans is predicted to comprise 225 proteins. On a proteomic level, however, analysis of the secretome of C. albicans is incomplete as many secreted proteins are only produced under certain conditions. Interestingly, glycosylphosphatidylinositol proteins and known cytoplasmic proteins are also consistently detected in the growth medium. Importantly, a core set of seven wall polysaccharide-processing enzymes seems to be consistently present, including the diagnostic marker Mp65. Overall, we discuss the importance of the secretome for virulence and suggest potential targets for better and faster diagnostic methods. PMID:23170918

  9. Over-expression of secreted proteins from mammalian cell lines

    PubMed Central

    Dalton, Annamarie C; Barton, William A

    2014-01-01

    Secreted mammalian proteins require the development of robust protein over-expression systems for crystallographic and biophysical studies of protein function. Due to complex disulfide bonds and distinct glycosylation patterns preventing folding and expression in prokaryotic expression hosts, many secreted proteins necessitate production in more complex eukaryotic expression systems. Here, we elaborate on the methods used to obtain high yields of purified secreted proteins from transiently or stably transfected mammalian cell lines. Among the issues discussed are the selection of appropriate expression vectors, choice of signal sequences for protein secretion, availability of fusion tags for enhancing protein stability and purification, choice of cell line, and the large-scale growth of cells in a variety of formats. PMID:24510886

  10. Cephalo-traumatic secretion transfer in a hermaphrodite sea slug

    PubMed Central

    Lange, Rolanda; Werminghausen, Johanna; Anthes, Nils

    2014-01-01

    Mating rituals in the animal kingdom are often quite extraordinary, in particular when mating is traumatic. We here describe the exceptional traumatic mating behaviour of the currently undescribed sea slug, Siphopteron sp. 1. Similar to four congeners, Siphopteron sp. 1 routinely exhibits traumatic secretion transfer through a stylet-like penis appendage. Contrary to previous descriptions, however, prostate secretions are injected centrally into the partner's forehead, representing, to our knowledge, the first-known instance of ‘cephalo-traumatic secretion transfer’. We further provide a comparative quantification of within- and between-species variation in injection sites and derive a potential neurophysiological function of prostate secretions that are injected close to, or into, the central nervous system. PMID:24225459

  11. Cephalo-traumatic secretion transfer in a hermaphrodite sea slug.

    PubMed

    Lange, Rolanda; Werminghausen, Johanna; Anthes, Nils

    2014-01-01

    Mating rituals in the animal kingdom are often quite extraordinary, in particular when mating is traumatic. We here describe the exceptional traumatic mating behaviour of the currently undescribed sea slug, Siphopteron sp. 1. Similar to four congeners, Siphopteron sp. 1 routinely exhibits traumatic secretion transfer through a stylet-like penis appendage. Contrary to previous descriptions, however, prostate secretions are injected centrally into the partner's forehead, representing, to our knowledge, the first-known instance of 'cephalo-traumatic secretion transfer'. We further provide a comparative quantification of within- and between-species variation in injection sites and derive a potential neurophysiological function of prostate secretions that are injected close to, or into, the central nervous system. PMID:24225459

  12. A Generalized Information Theoretical Model for Quantum Secret Sharing

    NASA Astrophysics Data System (ADS)

    Bai, Chen-Ming; Li, Zhi-Hui; Xu, Ting-Ting; Li, Yong-Ming

    2016-07-01

    An information theoretical model for quantum secret sharing was introduced by H. Imai et al. (Quantum Inf. Comput. 5(1), 69-80 2005), which was analyzed by quantum information theory. In this paper, we analyze this information theoretical model using the properties of the quantum access structure. By the analysis we propose a generalized model definition for the quantum secret sharing schemes. In our model, there are more quantum access structures which can be realized by our generalized quantum secret sharing schemes than those of the previous one. In addition, we also analyse two kinds of important quantum access structures to illustrate the existence and rationality for the generalized quantum secret sharing schemes and consider the security of the scheme by simple examples.

  13. Quantum secret sharing between multiparty and multiparty without entanglement

    SciTech Connect

    Yan Fengli; Gao Ting

    2005-07-15

    We propose a quantum secret sharing protocol between multiparty (m members in group 1) and multiparty (n members in group 2) using a sequence of single photons. These single photons are used directly to encode classical information in a quantum secret sharing process. In this protocol, all members in group 1 directly encode their respective keys on the states of single photons via unitary operations; then, the last one (the mth member of group 1) sends 1/n of the resulting qubits to each of group 2. Thus the secret message shared by all members of group 1 is shared by all members of group 2 in such a way that no subset of each group is efficient to read the secret message, but the entire set (not only group 1 but also group 2) is. We also show that it is unconditionally secure. This protocol is feasible with present-day techniques.

  14. Microfluidic Devices for the Measurement of Cellular Secretion

    NASA Astrophysics Data System (ADS)

    Schrell, Adrian M.; Mukhitov, Nikita; Yi, Lian; Wang, Xue; Roper, Michael G.

    2016-06-01

    The release of chemical information from cells and tissues holds the key to understanding cellular behavior and dysfunction. The development of methodologies that can measure cellular secretion in a time-dependent fashion is therefore essential. Often these measurements are made difficult by the high-salt conditions of the cellular environment, the presence of numerous other secreted factors, and the small mass samples that are produced when frequent sampling is used to resolve secretory dynamics. In this review, the methods that we have developed for measuring hormone release from islets of Langerhans are dissected to illustrate the practical difficulties of studying cellular secretions. Other methods from the literature are presented that provide alternative approaches to particularly challenging areas of monitoring cellular secretion. The examples presented in this review serve as case studies and should be adaptable to other cell types and systems for unique applications.

  15. Intracellular mediators of potassium-induced aldosterone secretion

    SciTech Connect

    Ganguly, A.; Chiou, S.; Davis, J.S. )

    1990-01-01

    We have investigated the intracellular messengers of potassium in eliciting aldosterone secretion in calf adrenal glomerulosa cells since there were unresolved issues relating to the role of phosphoinositides, cAMP and protein kinases. We observed no evidence of hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}) in {sup 3}H-inositol labeled alf adrenal cells or increase of cAMP in response to potassium. Addition of calcium channel blocker, nitrendipine after stimulating adrenal glomerulosa cells with potassium, markedly inhibited aldosterone secretion. A calmodulin inhibitor (W-7) produced greater reduction of aldosterone secretion than an inhibitor of protein kinase C (H-7). These results suggest that a rise in cytosolic free calcium concentration through voltage-dependent calcium channel and calmodulin are the critical determinants of aldosterone secretion stimulated by potassium.

  16. Secretion of a bacterial protein by mammalian cells.

    PubMed

    Clément, J M; Jehanno, M

    1995-12-15

    The MalE protein is a periplasmic maltooligosaccharide binding protein from Escherichia coli. This protein is widely used as a model for protein export in bacteria and as a vector for the export and one-step affinity purification of foreign polypeptides. Expression of MalE was studied in various animal cell lines. The protein was exported into the culture medium, following the classical pathway of eukaryotic protein secretion. This was shown by a combination of approaches including the use of inhibitors of the Golgi complex and immunocytological methods. The signal sequence of MalE is required for secretion and a specific signal can be added to MalE that targets it to the endoplasmic reticulum. This work opens the way to the study of the secretion of a bacterial protein and to its use as a vector for protein secretion and purification from mammalian cells. PMID:8590643

  17. PFIESTERIA SHUMWAYAE KILLS FISH BY MICROPREDATION NOT ECOTOXIN SECRETION

    EPA Science Inventory

    Massive fish kills in mid-Atlantic USA estuaries involving several million Atlantic menhaden, Brevoortia tyrannus,have been attributed to dinoflagellates of the toxic Pfiesteria complex (TPC). Potent ichthyotoxins secreted during Pfiesteria blooms are thought to be responsible fo...

  18. High-Yield Secretion of Multiple Client Proteins in Aspergillus

    SciTech Connect

    Segato, F.; Damasio, A. R. L.; Goncalves, T. A.; de Lucas, R. C.; Squina, F. M.; Decker, S. R.; Prade, R. A.

    2012-07-15

    Production of pure and high-yield client proteins is an important technology that addresses the need for industrial applications of enzymes as well as scientific experiments in protein chemistry and crystallization. Fungi are utilized in industrial protein production because of their ability to secrete large quantities of proteins. In this study, we engineered a high-expression-secretion vector, pEXPYR that directs proteins towards the extracellular medium in two Aspergillii host strains, examine the effect of maltose-induced over-expression and protein secretion as well as time and pH-dependent protein stability in the medium. We describe five client proteins representing a core set of hemicellulose degrading enzymes that accumulated up to 50-100 mg/L of protein. Using a recyclable genetic marker that allows serial insertion of multiple genes, simultaneous hyper-secretion of three client proteins in a single host strain was accomplished.

  19. Platelet secretion: From haemostasis to wound healing and beyond

    PubMed Central

    Golebiewska, Ewelina M.; Poole, Alastair W.

    2015-01-01

    Upon activation, platelets secrete more than 300 active substances from their intracellular granules. Platelet dense granule components, such as ADP and polyphosphates, contribute to haemostasis and coagulation, but also play a role in cancer metastasis. α-Granules contain multiple cytokines, mitogens, pro- and anti-inflammatory factors and other bioactive molecules that are essential regulators in the complex microenvironment of the growing thrombus but also contribute to a number of disease processes. Our understanding of the molecular mechanisms of secretion and the genetic regulation of granule biogenesis still remains incomplete. In this review we summarise our current understanding of the roles of platelet secretion in health and disease, and discuss some of the hypotheses that may explain how platelets may control the release of its many secreted components in a context-specific manner, to allow platelets to play multiple roles in health and disease. PMID:25468720

  20. Directional cell movement through tissues is controlled by exosome secretion

    PubMed Central

    Sung, Bong Hwan; Ketova, Tatiana; Hoshino, Daisuke; Zijlstra, Andries; Weaver, Alissa M.

    2015-01-01

    Directional cell movement through tissues is critical for multiple biological processes and requires maintenance of polarity in the face of complex environmental cues. Here we use intravital imaging to demonstrate that secretion of exosomes from late endosomes is required for directionally persistent and efficient in vivo movement of cancer cells. Inhibiting exosome secretion or biogenesis leads to defective tumour cell migration associated with increased formation of unstable protrusions and excessive directional switching. In vitro rescue experiments with purified exosomes and matrix coating identify adhesion assembly as a critical exosome function that promotes efficient cell motility. Live-cell imaging reveals that exosome secretion directly precedes and promotes adhesion assembly. Fibronectin is found to be a critical motility-promoting cargo whose sorting into exosomes depends on binding to integrins. We propose that autocrine secretion of exosomes powerfully promotes directionally persistent and effective cell motility by reinforcing otherwise transient polarization states and promoting adhesion assembly. PMID:25968605

  1. Eyes, ears, lips, fingertips, secrets: Dora, psychoanalysis, and the body.

    PubMed

    Balsam, Rosemary

    2015-02-01

    The topic of secrets will be expanded here to apply to complex secrets of the body, sex, and gender kept by both patients and analysts. Their detection is made harder by our field's current lack of interest in them compared to Freud's curiosity. We tend to ignore body narratives these days, with both men and women, keeping secret from ourselves daily challenges to theory that do indeed exist. Dora's case will be used to examine her own, her father's, and Freud's expectations of what constitutes a sexed and gendered portrait of grown-up males and females, and how they behave together. Contemporary embodied questions will emerge in discussion of Dora and her mother(s), the men in the story, and some male case vignettes. Ordinary secrets, hidden in broad daylight in both 1905 and in 2014, will be "revealed." PMID:25688679

  2. Melatonin in Epilepsy: A New Mathematical Model of Diurnal Secretion

    PubMed Central

    Kijonka, Marek; Pęcka, Marcin; Sokół, Maria

    2016-01-01

    Purpose. The main objective of the study was to create a mathematical model that describes the melatonin circadian secretion and, then the functionality of the model was tested by a comparison of the melatonin secretions in children with and without epilepsy. Material and Methods. The patients were divided into the epilepsy group (EG, n = 52) and the comparison group (CG, n = 30). The melatonin level was assessed by a radioimmunoassay method. The diurnal melatonin secretion was described using a nonlinear least squares method. Spearman's rank correlation coefficient was chosen to estimate the dependence of the acquired data. The model reproduces blood concentration profiles and its parameters were statistically analyzed using the Mann-Whitney-Wilcoxon test and logistic regression. Results. The correlation analysis performed for the EG and CG groups showed moderate correlations between age and the melatonin secretion model parameters. Patients with epilepsy are characterized by an increased phase shift of melatonin release. PMID:27478439

  3. Inhibition of intestinal chloride secretion by proanthocyanidins from Guazuma ulmifolia.

    PubMed

    Hör, M; Rimpler, H; Heinrich, M

    1995-06-01

    The antisecretory activity of Guazuma ulmifolia bark was examined in rabbit distal colon mounted in an Ussing chamber. Chloride secretion was stimulated by cholera toxin and prostaglandin E2 (PGE2). Guazuma ulmifolia extract (GUE) completely inhibited cholera toxin-induced secretion if the extract was added to the mucosal bath prior to the toxin. Adding the extract after administration of the toxin had no effect on secretion. GUE did not inhibit PGE2-induced chloride secretion. These results indicate an indirect antisecretory mechanism. SDS-PAGE analysis of cholera toxin treated with GUE confirmed this presumption. GUE specifically interacted with the A subunit of the toxin. Preliminary phytochemical examinations showed that the most active fraction contains procyanidins with a degree of polymerisation higher than 8. PMID:7617760

  4. Granular gland transcriptomes in stimulated amphibian skin secretions.

    PubMed Central

    Chen, Tianbao; Farragher, Susan; Bjourson, Anthony J; Orr, David F; Rao, Pingfan; Shaw, Chris

    2003-01-01

    Amphibian defensive skin secretions are complex, species-specific cocktails of biologically active molecules, including many uncharacterized peptides. The study of such secretions for novel peptide discovery is time-limited, as amphibians are in rapid global decline. While secretion proteome analysis is non-lethal, transcriptome analysis has until now required killing of specimens prior to skin dissection for cDNA library construction. Here we present the discovery that polyadenylated mRNAs encoding dermal granular gland peptides are present in defensive skin secretions, stabilized by endogenous nucleic acid-binding amphipathic peptides. Thus parallel secretory proteome and transcriptome analyses can be performed without killing the specimen in this model amphibian system--a finding that has important implications in conservation of biodiversity within this threatened vertebrate taxon and whose mechanistics may have broader implications in biomolecular science. PMID:12413397

  5. Microtubules Negatively Regulate Insulin Secretion in Pancreatic β Cells.

    PubMed

    Zhu, Xiaodong; Hu, Ruiying; Brissova, Marcela; Stein, Roland W; Powers, Alvin C; Gu, Guoqiang; Kaverina, Irina

    2015-09-28

    For glucose-stimulated insulin secretion (GSIS), insulin granules have to be localized close to the plasma membrane. The role of microtubule-dependent transport in granule positioning and GSIS has been debated. Here, we report that microtubules, counterintuitively, restrict granule availability for secretion. In β cells, microtubules originate at the Golgi and form a dense non-radial meshwork. Non-directional transport along these microtubules limits granule dwelling at the cell periphery, restricting granule availability for secretion. High glucose destabilizes microtubules, decreasing their density; such local microtubule depolymerization is necessary for GSIS, likely because granule withdrawal from the cell periphery becomes inefficient. Consistently, microtubule depolymerization by nocodazole blocks granule withdrawal, increases their concentration at exocytic sites, and dramatically enhances GSIS in vitro and in mice. Furthermore, glucose-driven MT destabilization is balanced by new microtubule formation, which likely prevents over-secretion. Importantly, microtubule density is greater in dysfunctional β cells of diabetic mice. PMID:26418295

  6. Effect of enteral nutrition on human pancreatic secretions.

    PubMed

    Grant, J P; Davey-McCrae, J; Snyder, P J

    1987-01-01

    The influence on pancreatic secretion of four enteral feeding products was evaluated in a unique patient with an isolated duodenal fistula for whom enteral feeding access was obtained via a gastrostomy with a small Silastic catheter passed through the gastrostomy and through a surgically created gastrojejunostomy. The patient was totally supported by intravenous nutrition during the study. Each enteral feeding solution was administered at full strength at 50 ml/hr for 2 days with a 24-hr collection of pancreatic secretions by the duodenal cutaneous fistula taken on the second day. Infusion of the enteral feeding solutions did not alter volume of fistula drainage. All solutions decreased bicarbonate and amylase secretion but increased lipase and total nitrogen excretion. From this study, it would appear reasonable to administer Vivonex HN and Criticare HN via the jejunum in patients with pancreatic disease, whereas Osmolite would appear less satisfactory, due to its much stronger stimulation of lipase secretion. PMID:3110448

  7. COPI selectively drives maturation of the early Golgi

    DOE PAGESBeta

    Papanikou, Effrosyni; Day, Kasey J.; Austin, Jotham; Glick, Benjamin S.

    2015-12-28

    COPI coated vesicles carry material between Golgi compartments, but the role of COPI in the secretory pathway has been ambiguous. Previous studies of thermosensitive yeast COPI mutants yielded the surprising conclusion that COPI was dispensable both for the secretion of certain proteins and for Golgi cisternal maturation. To revisit these issues, we optimized the anchor-away method, which allows peripheral membrane proteins such as COPI to be sequestered rapidly by adding rapamycin. Video fluorescence microscopy revealed that COPI inactivation causes an early Golgi protein to remain in place while late Golgi proteins undergo cycles of arrival and departure. These dynamics generatemore » partially functional hybrid Golgi structures that contain both early and late Golgi proteins, explaining how secretion can persist when COPI has been inactivated. Our findings suggest that cisternal maturation involves a COPI-dependent pathway that recycles early Golgi proteins, followed by multiple COPI-independent pathways that recycle late Golgi proteins.« less

  8. Cryptanalysis of quantum secret sharing with d -level single particles

    NASA Astrophysics Data System (ADS)

    Lin, Song; Guo, Gong-De; Xu, Yong-Zhen; Sun, Ying; Liu, Xiao-Fen

    2016-06-01

    In a recent paper [V. Karimipour and M. Asoudeh, Phys. Rev. A 92, 030301(R) (2015)], 10.1103/PhysRevA.92.030301, a multiparty quantum secret-sharing protocol based on d -level single particles was proposed. We discussed the security of this protocol and found that it is not secure for any one dishonest participant who can recover the secret without the aid of other participants.

  9. An intrinsic mechanism of secreted protein aging and turnover

    PubMed Central

    Yang, Won Ho; Aziz, Peter V.; Heithoff, Douglas M.; Mahan, Michael J.; Smith, Jeffrey W.; Marth, Jamey D.

    2015-01-01

    The composition and functions of the secreted proteome are controlled by the life spans of different proteins. However, unlike intracellular protein fate, intrinsic factors determining secreted protein aging and turnover have not been identified and characterized. Almost all secreted proteins are posttranslationally modified with the covalent attachment of N-glycans. We have discovered an intrinsic mechanism of secreted protein aging and turnover linked to the stepwise elimination of saccharides attached to the termini of N-glycans. Endogenous glycosidases, including neuraminidase 1 (Neu1), neuraminidase 3 (Neu3), beta-galactosidase 1 (Glb1), and hexosaminidase B (HexB), possess hydrolytic activities that temporally remodel N-glycan structures, progressively exposing different saccharides with increased protein age. Subsequently, endocytic lectins with distinct binding specificities, including the Ashwell–Morell receptor, integrin αM, and macrophage mannose receptor, are engaged in N-glycan ligand recognition and the turnover of secreted proteins. Glycosidase inhibition and lectin deficiencies increased protein life spans and abundance, and the basal rate of N-glycan remodeling varied among distinct proteins, accounting for differences in their life spans. This intrinsic multifactorial mechanism of secreted protein aging and turnover contributes to health and the outcomes of disease. PMID:26489654

  10. Cortactin promotes exosome secretion by controlling branched actin dynamics.

    PubMed

    Sinha, Seema; Hoshino, Daisuke; Hong, Nan Hyung; Kirkbride, Kellye C; Grega-Larson, Nathan E; Seiki, Motoharu; Tyska, Matthew J; Weaver, Alissa M

    2016-07-18

    Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms that regulate exosome secretion are poorly understood. Here, we show that the actin cytoskeletal regulatory protein cortactin promotes exosome secretion. Knockdown or overexpression of cortactin in cancer cells leads to a respective decrease or increase in exosome secretion, without altering exosome cargo content. Live-cell imaging revealed that cortactin controls both trafficking and plasma membrane docking of multivesicular late endosomes (MVEs). Regulation of exosome secretion by cortactin requires binding to the branched actin nucleating Arp2/3 complex and to actin filaments. Furthermore, cortactin, Rab27a, and coronin 1b coordinately control stability of cortical actin MVE docking sites and exosome secretion. Functionally, the addition of purified exosomes to cortactin-knockdown cells rescued defects of those cells in serum-independent growth and invasion. These data suggest a model in which cortactin promotes exosome secretion by stabilizing cortical actin-rich MVE docking sites. PMID:27402952

  11. Entanglement-secured single-qubit quantum secret sharing

    SciTech Connect

    Scherpelz, P.; Resch, R.; Berryrieser, D.; Lynn, T. W.

    2011-09-15

    In single-qubit quantum secret sharing, a secret is shared between N parties via manipulation and measurement of one qubit at a time. Each qubit is sent to all N parties in sequence; the secret is encoded in the first participant's preparation of the qubit state and the subsequent participants' choices of state rotation or measurement basis. We present a protocol for single-qubit quantum secret sharing using polarization entanglement of photon pairs produced in type-I spontaneous parametric downconversion. We investigate the protocol's security against eavesdropping attack under common experimental conditions: a lossy channel for photon transmission, and imperfect preparation of the initial qubit state. A protocol which exploits entanglement between photons, rather than simply polarization correlation, is more robustly secure. We implement the entanglement-based secret-sharing protocol with 87% secret-sharing fidelity, limited by the purity of the entangled state produced by our present apparatus. We demonstrate a photon-number splitting eavesdropping attack, which achieves no success against the entanglement-based protocol while showing the predicted rate of success against a correlation-based protocol.

  12. An unexpected knock on Corrigan’s secret door

    PubMed Central

    Woywodt, Alexander

    2010-01-01

    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. PMID:25984078

  13. Human Insulinomas Show Distinct Patterns of Insulin Secretion In Vitro.

    PubMed

    Henquin, Jean-Claude; Nenquin, Myriam; Guiot, Yves; Rahier, Jacques; Sempoux, Christine

    2015-10-01

    Insulinomas are β-cell tumors that cause hypoglycemia through inappropriate secretion of insulin. Characterization of the in vitro dynamics of insulin secretion by perifused fragments of 10 human insulinomas permitted their subdivision into three functional groups with similar insulin content. Group A (four patients with fasting and/or postprandial hypoglycemic episodes) showed qualitatively normal responses to glucose, leucine, diazoxide, tolbutamide, and extracellular CaCl2 omission or excess. The effect of glucose was concentration dependent, but, compared with normal islets, insulin secretion was excessive in both low- and high-glucose conditions. Group B (three patients with fasting hypoglycemic episodes) was mainly characterized by large insulin responses to 1 mmol/L glucose, resulting in very high basal secretion rates that were inhibited by diazoxide and restored by tolbutamide but were not further augmented by other agents except for high levels of CaCl2. Group C (three patients with fasting hypoglycemic episodes) displayed very low rates of insulin secretion and virtually no response to stimuli (including high CaCl2 concentration) and inhibitors (CaCl2 omission being paradoxically stimulatory). In group B, the presence of low-Km hexokinase-I in insulinoma β-cells (not in adjacent islets) was revealed by immunohistochemistry. Human insulinomas thus show distinct, though not completely heterogeneous, defects in insulin secretion that are attributed to the undue expression of hexokinase-I in 3 of 10 patients. PMID:26116696

  14. [Cytopathology of the breast. 1. Secretion and nipple cytology].

    PubMed

    Barten, M

    1991-01-01

    Cytological examinations of breast secretions, nipple smears and breast fine needle aspirates can establish important diagnostic findings provided that technical conditions and methodical advantages and disadvantages are taken into consideration. The first part of the paper is dealing with clinically relevant aspects of secretion and nipple cytology. These simple examinations are applicable by every gynaecologist. The source of cell material is the spontaneous exfoliation, which should be increased in nipple smears by additional procedures. Diagnostic findings of secretion cytology can be obtained in breast cancer, duct papilloma, cystic fibrosis, and inflammatory lesions. The value of secretion cytology for breast cancer detection is limited, because pathological secretion is only induced in a small number of patients. Cytological examinations of nipple lesions are useful especially in the presence of Paget's disease and other tumors of the nipple. Limitations are caused by difficulties in cell sampling. Easy practicability and little alteration of the patient are the major advantages of the secretion and nipple cytology, which stands opposite a limited sensitivity as disadvantage. PMID:1755254

  15. A molecular mechanism that stabilizes cooperative secretions in Pseudomonas aeruginosa

    PubMed Central

    Kim, Wook

    2010-01-01

    Summary Bacterial populations frequently act as a collective by secreting a wide range of compounds necessary for cell-cell communication, host colonization and virulence. However, how such behaviors avoid exploitation by spontaneous ‘cheater’ mutants that use but do not contribute to secretions remains unclear. We investigate this question using Pseudomonas aeruginosa swarming, a collective surface motility requiring massive secretions of rhamnolipid biosurfactants. We first show that swarming is immune to the evolution of rhlA− ‘cheaters’. We then demonstrate that P. aeruginosa resists cheating through metabolic prudence: wild-type cells secrete biosurfactants only when the cost of their production and impact on individual fitness is low, therefore preventing non-secreting strains from gaining an evolutionary advantage. Metabolic prudence works because the carbon-rich biosurfactants are only produced when growth is limited by another growth limiting nutrient, the nitrogen source. By genetically manipulating a strain to produce the biosurfactants constitutively we show that swarming becomes cheatable: a non-producing strain rapidly outcompetes and replaces this obligate cooperator. We argue that metabolic prudence, which may first evolve as a direct response to cheating or simply to optimize growth, can explain the maintenance of massive secretions in many bacteria. More generally, prudent regulation is a mechanism to stabilize cooperation. PMID:21166901

  16. Sibjotang Increases Atrial Natriuretic Peptide Secretion in Beating Rabbit Atria

    PubMed Central

    Kwon, Oh Jeong; Oh, Hyun Cheol; Lee, Yun Jung; Kim, Hye Yoom; Tan, Rui; Kang, Dae Gill; Lee, Ho Sub

    2015-01-01

    Sibjotang (Shizaotang), traditional herbal medicine formula, which was first documented in the Shanghanlun, has long been prescribed for the treatment of impairment of the body fluid homeostasis. The purpose of the present study was to identify the effects of Sibjotang on the secretion of a cardiac hormone, atrial natriuretic peptide (ANP), one of the main hormones involved in the regulation of the body fluid and blood pressure homeostasis. Water extract of Sibjotang increased ANP secretion concomitantly with an increase in atrial dynamics in a concentration-dependent manner. Sibjotang-induced increase in ANP secretion and positive inotropic effect were attenuated by GO6976 and LY333531, selective inhibitors of conventional protein kinase C, but not Rottlerin, an inhibitor of novel PKCδ. Similarly to the effect of Sibjotang, extracts of components of Sibjotang, Euphorbia kansui, and Daphne genkwa, but not Euphorbia pekinensis and Ziziphus jujuba, increased ANP secretion and atrial dynamics. Ingredients of Sibjotang, apigenin, rosmarinic acid, and salvianolic acid B decreased ANP secretion and atrial dynamics. These findings suggest that Sibjotang increases ANP secretion and atrial dynamics via activation of conventional protein kinase C signaling. This finding provides experimental evidence for the rationale in the use of Sibjotang in the treatment of impairment of the regulation of body fluid and blood pressure homeostasis. PMID:26495007

  17. Early Astronomy

    NASA Astrophysics Data System (ADS)

    Thurston, Hugh

    The earliest investigations that can be called scientific are concerned with the sky: they are the beginnings of astronomy. Many early civilizations produced astronomical texts, and several cultures that left no written records left monuments and artifacts-ranging from rock paintings to Stonehenge-that show a clear interest in astronomy. Civilizations in China, Mesopotamia, India and Greece had highly developed astronomies, and the astronomy of the Mayas was by no means negligible. Greek astronomy, as developed by the medieval Arab philosophers, evolved into the astronomy of Copernicus. This displaced the earth from the central stationary position that almost all earlier astronomies had assumed. Soon thereafter, in the first decades of the seventeenth century, Kepler found the true shape of the planetary orbits and Galileo introduced the telescope for astronomical observations.

  18. A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles.

    PubMed

    Walentek, Peter; Bogusch, Susanne; Thumberger, Thomas; Vick, Philipp; Dubaissi, Eamon; Beyer, Tina; Blum, Martin; Schweickert, Axel

    2014-04-01

    The embryonic skin of Xenopus tadpoles serves as an experimental model system for mucociliary epithelia (MCE) such as the human airway epithelium. MCEs are characterized by the presence of mucus-secreting goblet and multiciliated cells (MCCs). A third cell type, ion-secreting cells (ISCs), is present in the larval skin as well. Synchronized beating of MCC cilia is required for directional transport of mucus. Here we describe a novel cell type in the Xenopus laevis larval epidermis, characterized by serotonin synthesis and secretion. It is termed small secretory cell (SSC). SSCs are detectable at early tadpole stages, unlike MCCs and ISCs, which are specified at early neurulation. Subcellularly, serotonin was found in large, apically localized vesicle-like structures, which were entirely shed into the surrounding medium. Pharmacological inhibition of serotonin synthesis decreased the velocity of cilia-driven fluid flow across the skin epithelium. This effect was mediated by serotonin type 3 receptor (Htr3), which was expressed in ciliated cells. Knockdown of Htr3 compromised flow velocity by reducing the ciliary motility of MCCs. SSCs thus represent a distinct and novel entity of the frog tadpole MCE, required for ciliary beating and mucus transport across the larval skin. The identification and characterization of SSCs consolidates the value of the Xenopus embryonic skin as a model system for human MCEs, which have been known for serotonin-dependent regulation of ciliary beat frequency. PMID:24598162

  19. The secret: study of a perverse transference.

    PubMed

    Carignan, L

    1999-10-01

    This clinical communication describes the analysis of a perverse transference in an overtly bisexual man. An intricate interplay between heterosexual and homosexual relations enabled him to maintain some heterosexual functioning and to counteract or evacuate intolerable affects and vengeful impulses--originating from early traumas--through perverse acting out with sexual partners. Building on the notion that patients with sexual perversions recreate aspects of their perversion in the transference/countertransference relationship, where it must be analysed, the author illustrates through detailed clinical material how she was drawn into the fabric of her patient's perversion and how this was worked through. She offers an object-relational understanding of his perversion as a complex erotised defensive/reparative/vengeful manoeuvre permitting the disavowal and magical reversal into triumph and sexual pleasure of perceived threats to his personal or sexual identity. Engaging or changing in analysis evoked fears of losing his identity by surrendering to the analyst, rooted in the patient's early experience of serving as his mother's fetish-object. The author suggests that the patient needed to turn the analyst into a perverse partner (disavowing her other-ness) in order to reverse and triumph over this core trauma. She attributes the good treatment outcome to the detection and working through of the perverse transference and monitoring of her countertransference. PMID:10643571

  20. Xanthomonas campestris pv. vesicatoria Secretes Proteases and Xylanases via the Xps Type II Secretion System and Outer Membrane Vesicles

    PubMed Central

    Solé, Magali; Scheibner, Felix; Hoffmeister, Anne-Katrin; Hartmann, Nadine; Hause, Gerd; Rother, Annekatrin; Jordan, Michael; Lautier, Martine; Arlat, Matthieu

    2015-01-01

    ABSTRACT Many plant-pathogenic bacteria utilize type II secretion (T2S) systems to secrete degradative enzymes into the extracellular milieu. T2S substrates presumably mediate the degradation of plant cell wall components during the host-pathogen interaction and thus promote bacterial virulence. Previously, the Xps-T2S system from Xanthomonas campestris pv. vesicatoria was shown to contribute to extracellular protease activity and the secretion of a virulence-associated xylanase. The identities and functions of additional T2S substrates from X. campestris pv. vesicatoria, however, are still unknown. In the present study, the analysis of 25 candidate proteins from X. campestris pv. vesicatoria led to the identification of two type II secreted predicted xylanases, a putative protease and a lipase which was previously identified as a virulence factor of X. campestris pv. vesicatoria. Studies with mutant strains revealed that the identified xylanases and the protease contribute to virulence and in planta growth of X. campestris pv. vesicatoria. When analyzed in the related pathogen X. campestris pv. campestris, several T2S substrates from X. campestris pv. vesicatoria were secreted independently of the T2S systems, presumably because of differences in the T2S substrate specificities of the two pathogens. Furthermore, in X. campestris pv. vesicatoria T2S mutants, secretion of T2S substrates was not completely absent, suggesting the contribution of additional transport systems to protein secretion. In line with this hypothesis, T2S substrates were detected in outer membrane vesicles, which were frequently observed for X. campestris pv. vesicatoria. We, therefore, propose that extracellular virulence-associated enzymes from X. campestris pv. vesicatoria are targeted to the Xps-T2S system and to outer membrane vesicles. IMPORTANCE The virulence of plant-pathogenic bacteria often depends on TS2 systems, which secrete degradative enzymes into the extracellular milieu. T2S

  1. Secrets for Early Childhood Professionals--Working with Infants and Toddlers.

    ERIC Educational Resources Information Center

    Honig, Alice Sterling

    1997-01-01

    Examines the quality of infant and toddler care as a prerequisite for the emotional well-being of children. Offers suggestions on how day-care providers can work toward understanding and generously meeting infant needs: hold and mold; be a responsive reciprocal partner; enhance noticing skills; learn ages and stages; apply developmental theories;…

  2. ALE OF TWO CLUSTERS YIELDS SECRETS OF STAR BIRTH IN THE EARLY UNIVERSE

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This NASA Hubble Space Telescope (HST) image shows rich detail, previously only seen in neighboring star birth regions, in a pair of star clusters 166,000 light-years away in the Large Magellanic Cloud (LMC), in the southern constellation Doradus. The field of view is 130 light-years across and was taken with the Wide Field Planetary Camera 2. HST's unique capabilities -- ultraviolet sensitivity, ability to see faint stars, and high resolution -- have been utilized fully to identify three separate populations in this concentration of nearly 10,000 stars down to the 25th magnitude (more that twice as many as can be seen over the entire sky with the naked eye on a clear night on Earth). The field of view is only 130 light-years across. Previous observations with ground-based telescopes resolve less than 1,000 stars in the same region. About 60 percent of the stars belong to the dominant yellow cluster called NGC 1850, which is estimated to be 50 million years old. A scattering of white stars in the image are massive stars that are only about 4 million years old and represent about 20 percent of the stars in the image. (The remainder are field stars in the LMC.) Besides being much younger, the white stars are much more loosely distributed than the yellow cluster. The significant difference between the two cluster ages suggests these are two separate star groups that lie along the same line of sight. The younger, more open cluster probably lies 200 light-years beyond the older cluster. If it were in the foreground, then dust contained in the white cluster would obscure stars in the older yellow cluster. To observe two well-defined star populations separated by such a small gap of space is unusual. This juxtaposition suggests that supernova explosions in the older cluster might have triggered the birth of the younger cluster. This color composite image is assembled from exposures taken in ultraviolet, visible, and near-infrared light. Yellow stars correspond to Main Sequence stars (like our Sun) with average surface temperatures of 6000 Kelvin; red stars are cool giants and supergiants (3500 K); white stars are hot young stars (25,000 K or more) that are bright in ultraviolet. Credit: R. Gilmozzi, Space Telescope Science Institute/European Space Agency; Shawn Ewald, JPL; and NASA

  3. The proteins secreted by Trichomonas vaginalis and vaginal epithelial cell response to secreted and episomally expressed AP65

    PubMed Central

    Kucknoor, Ashwini S.; Mundodi, Vasanthakrishna; Alderete, John F.

    2007-01-01

    Summary We showed recently that contact of human vaginal epithelial cells (VECs) by Trichomonas vaginalis and incubation with trichomonad proteins in conditioned medium induced expression of VEC genes. We performed 2-D SDS-PAGE followed by MALDI-TOF to identify the major secreted proteins. Based on protein abundance and separation of spots in 2-D gels, 32 major secreted proteins were examined, which gave 19 proteins with accession numbers. These proteins included known secreted cysteine proteinases. In addition, other secreted proteins were enzymes of carbohydrate metabolism, adhesin protein AP65, heat shock proteins, thioredoxin reductase and coronins. We confirmed that the secreted trichomonad proteins induced expression of VEC genes, including interleukin 8 (IL-8), COX-2 and fibronectin. Purified AP65 added to VECs had a pronounced effect only on IL-8 gene expression, which was inhibited in the presence of 12G4 monoclonal antibody to AP65. Moreover, AP65 expressed episomally within epithelial cells was found to enhance the expression of IL-8 and COX-2. This may be the first report of analysis of the secreted proteins of T. vaginalis and of the host epithelial cell response to these proteins and to the prominent adhesin AP65. PMID:17590165

  4. Early Pregnancy Loss

    MedlinePlus

    ... is called early pregnancy loss , miscarriage , or spontaneous abortion . How common is early pregnancy loss? Early pregnancy ... testes that can fertilize a female egg. Spontaneous Abortion: The medical term for early pregnancy loss. Trimester: ...

  5. A Metalloprotease Secreted by the Type II Secretion System Links Vibrio cholerae with Collagen

    PubMed Central

    Park, Bo R.; Zielke, Ryszard A.; Wierzbicki, Igor H.; Mitchell, Kristie C.; Withey, Jeffrey H.

    2015-01-01

    Vibrio cholerae is autochthonous to various aquatic niches and is the etiological agent of the life-threatening diarrheal disease cholera. The persistence of V. cholerae in natural habitats is a crucial factor in the epidemiology of cholera. In contrast to the well-studied V. cholerae-chitin connection, scarce information is available about the factors employed by the bacteria for the interaction with collagens. Collagens might serve as biologically relevant substrates, because they are the most abundant protein constituents of metazoan tissues and V. cholerae has been identified in association with invertebrate and vertebrate marine animals, as well as in a benthic zone of the ocean where organic matter, including collagens, accumulates. Here, we describe the characterization of the V. cholerae putative collagenase, VchC, encoded by open reading frame VC1650 and belonging to the subfamily M9A peptidases. Our studies demonstrate that VchC is an extracellular collagenase degrading native type I collagen of fish and mammalian origin. Alteration of the predicted catalytic residues coordinating zinc ions completely abolished the protein enzymatic activity but did not affect the translocation of the protease by the type II secretion pathway into the extracellular milieu. We also show that the protease undergoes a maturation process with the aid of a secreted factor(s). Finally, we propose that V. cholerae is a collagenovorous bacterium, as it is able to utilize collagen as a sole nutrient source. This study initiates new lines of investigations aiming to uncover the structural and functional components of the V. cholerae collagen utilization program. PMID:25561716

  6. A metalloprotease secreted by the type II secretion system links Vibrio cholerae with collagen.

    PubMed

    Park, Bo R; Zielke, Ryszard A; Wierzbicki, Igor H; Mitchell, Kristie C; Withey, Jeffrey H; Sikora, Aleksandra E

    2015-03-01

    Vibrio cholerae is autochthonous to various aquatic niches and is the etiological agent of the life-threatening diarrheal disease cholera. The persistence of V. cholerae in natural habitats is a crucial factor in the epidemiology of cholera. In contrast to the well-studied V. cholerae-chitin connection, scarce information is available about the factors employed by the bacteria for the interaction with collagens. Collagens might serve as biologically relevant substrates, because they are the most abundant protein constituents of metazoan tissues and V. cholerae has been identified in association with invertebrate and vertebrate marine animals, as well as in a benthic zone of the ocean where organic matter, including collagens, accumulates. Here, we describe the characterization of the V. cholerae putative collagenase, VchC, encoded by open reading frame VC1650 and belonging to the subfamily M9A peptidases. Our studies demonstrate that VchC is an extracellular collagenase degrading native type I collagen of fish and mammalian origin. Alteration of the predicted catalytic residues coordinating zinc ions completely abolished the protein enzymatic activity but did not affect the translocation of the protease by the type II secretion pathway into the extracellular milieu. We also show that the protease undergoes a maturation process with the aid of a secreted factor(s). Finally, we propose that V. cholerae is a collagenovorous bacterium, as it is able to utilize collagen as a sole nutrient source. This study initiates new lines of investigations aiming to uncover the structural and functional components of the V. cholerae collagen utilization program. PMID:25561716

  7. 31 CFR 401.1 - Secret Service agents authorized to make seizures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in...

  8. 31 CFR 401.1 - Secret Service agents authorized to make seizures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in...

  9. 31 CFR 401.1 - Secret Service agents authorized to make seizures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in...

  10. 31 CFR 401.1 - Secret Service agents authorized to make seizures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in...

  11. 31 CFR 401.1 - Secret Service agents authorized to make seizures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in...

  12. Secret Science: Exploring Cold War Greenland

    NASA Astrophysics Data System (ADS)

    Harper, K.

    2013-12-01

    During the early Cold War - from the immediate postwar period through the 1960s - the United States military carried out extensive scientific studies and pursued technological developments in Greenland. With few exceptions, most of these were classified - sometimes because new scientific knowledge was born classified, but mostly because the reasons behind the scientific explorations were. Meteorological and climatological, ionospheric, glaciological, seismological, and geological studies were among the geophysical undertakings carried out by military and civilian scientists--some in collaboration with the Danish government, and some carried out without their knowledge. This poster will present some of the results of the Exploring Greenland Project that is coming to a conclusion at Denmark's Aarhus University.

  13. Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα

    PubMed Central

    Wunderle, Lina; Knopf, Julia D.; Kühnle, Nathalie; Morlé, Aymeric; Hehn, Beate; Adrain, Colin; Strisovsky, Kvido; Freeman, Matthew; Lemberg, Marius K.

    2016-01-01

    Rhomboid intramembrane proteases are the enzymes that release active epidermal growth factor receptor (EGFR) ligands in Drosophila and C. elegans, but little is known about their functions in mammals. Here we show that the mammalian rhomboid protease RHBDL4 (also known as Rhbdd1) promotes trafficking of several membrane proteins, including the EGFR ligand TGFα, from the endoplasmic reticulum (ER) to the Golgi apparatus, thereby triggering their secretion by extracellular microvesicles. Our data also demonstrate that RHBDL4-dependent trafficking control is regulated by G-protein coupled receptors, suggesting a role for this rhomboid protease in pathological conditions, including EGFR signaling. We propose that RHBDL4 reorganizes trafficking events within the early secretory pathway in response to GPCR signaling. Our work identifies RHBDL4 as a rheostat that tunes secretion dynamics and abundance of specific membrane protein cargoes. PMID:27264103

  14. Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα.

    PubMed

    Wunderle, Lina; Knopf, Julia D; Kühnle, Nathalie; Morlé, Aymeric; Hehn, Beate; Adrain, Colin; Strisovsky, Kvido; Freeman, Matthew; Lemberg, Marius K

    2016-01-01

    Rhomboid intramembrane proteases are the enzymes that release active epidermal growth factor receptor (EGFR) ligands in Drosophila and C. elegans, but little is known about their functions in mammals. Here we show that the mammalian rhomboid protease RHBDL4 (also known as Rhbdd1) promotes trafficking of several membrane proteins, including the EGFR ligand TGFα, from the endoplasmic reticulum (ER) to the Golgi apparatus, thereby triggering their secretion by extracellular microvesicles. Our data also demonstrate that RHBDL4-dependent trafficking control is regulated by G-protein coupled receptors, suggesting a role for this rhomboid protease in pathological conditions, including EGFR signaling. We propose that RHBDL4 reorganizes trafficking events within the early secretory pathway in response to GPCR signaling. Our work identifies RHBDL4 as a rheostat that tunes secretion dynamics and abundance of specific membrane protein cargoes. PMID:27264103

  15. Model for Glucagon Secretion by Pancreatic α-Cells

    PubMed Central

    González-Vélez, Virginia; Dupont, Geneviève; Gil, Amparo; González, Alejandro; Quesada, Iván

    2012-01-01

    Glucagon hormone is synthesized and released by pancreatic α-cells, one of the islet-cell types. This hormone, along with insulin, maintains blood glucose levels within the physiological range. Glucose stimulates glucagon release at low concentrations (hypoglycemia). However, the mechanisms involved in this secretion are still not completely clear. Here, using experimental calcium time series obtained in mouse pancreatic islets at low and high glucose conditions, we propose a glucagon secretion model for α-cells. Our model takes into account that the resupply of releasable granules is not only controlled by cytoplasmic , as in other neuroendocrine and endocrine cells, but also by the level of extracellular glucose. We found that, although calcium oscillations are highly variable, the average secretion rates predicted by the model fall into the range of values reported in the literature, for both stimulated and non-stimulated conditions. For low glucose levels, the model predicts that there would be a well-controlled number of releasable granules refilled slowly from a large reserve pool, probably to ensure a secretion rate that could last for several minutes. Studying the α-cell response to the addition of insulin at low glucose, we observe that the presence of insulin reduces glucagon release by decreasing the islet level. This observation is in line with previous work reporting that dynamics, mainly frequency, is altered by insulin [1]. Thus, the present results emphasize the main role played by and glucose in the control of glucagon secretion by α-cells. Our modeling approach also shows that calcium oscillations potentiate glucagon secretion as compared to constant levels of this cellular messenger. Altogether, the model sheds new light on the subcellular mechanisms involved in α-cell exocytosis, and provides a quantitative predictive tool for studying glucagon secretion modulators in physiological and pathological conditions. PMID:22412861

  16. Vesicular Nucleotide Transporter-Mediated ATP Release Regulates Insulin Secretion

    PubMed Central

    Geisler, Jessica C.; Corbin, Kathryn L.; Li, Qin; Feranchak, Andrew P.; Nunemaker, Craig S.

    2013-01-01

    Extracellular ATP plays a critical role in regulating insulin secretion in pancreatic β cells. The ATP released from insulin secretory vesicles has been proposed to be a major source of extracellular ATP. Currently, the mechanism by which ATP accumulates into insulin secretory granules remains elusive. In this study, the authors identified the expression of a vesicular nucleotide transporter (VNUT) in mouse pancreas, isolated mouse islets, and MIN6 cells, a mouse β cell line. Immunohistochemistry and immunofluorescence revealed that VNUT colocalized extensively with insulin secretory granules. Functional studies showed that suppressing endogenous VNUT expression in β cells by small hairpin RNA knockdown greatly reduced basal- and glucose-induced ATP release. Importantly, knocking down VNUT expression by VNUT small hairpin RNA in MIN6 cells and isolated mouse islets dramatically suppressed basal insulin release and glucose-stimulated insulin secretion (GSIS). Moreover, acute pharmacologic blockade of VNUT with Evans blue, a VNUT antagonist, greatly attenuated GSIS in a dose-dependent manner. Exogenous ATP treatment effectively reversed the insulin secretion defect induced by both VNUT knockdown and functional inhibition, indicating that VNUT-mediated ATP release is essential for maintaining normal insulin secretion. In contrast to VNUT knockdown, overexpression of VNUT in β cells resulted in excessive ATP release and enhanced basal insulin secretion and GSIS. Elevated insulin secretion induced by VNUT overexpression was reversed by pharmacologic inhibition of P2X but not P2Y purinergic receptors. This study reveals VNUT is expressed in pancreatic β cells and plays an essential and novel role in regulating insulin secretion through vesicular ATP release and extracellular purinergic signaling. PMID:23254199

  17. Nonlinear analysis and prediction of pulsatile hormone secretion

    SciTech Connect

    Prank, K. |; Kloppstech, M.; Nowlan, S.J.; Harms, H.M.; Brabant, G.; Hesch, R.; Sejnowski, T.J.

    1996-06-01

    Pulsatile hormone secretion is observed in almost every hormonal system. The frequency of episodic hormone release ranges from approximately 10 to 100 pulses in 24 hours. This temporal mode of secretion is an important feature of intercellular information transfer in addition to a dose-response dependent regulation. It has been demonstrated in a number of experiments that changes in the temporal pattern of pulsatile hormone secretion specifically regulate cellular and organ function and structure. Recent evidence links osteoporosis, a disease characterized by loss of bone mass and structure, to changes in the dynamics of pulsatile parathyroid hormone (PTH) secretion. In our study we applied nonlinear and linear time series prediction to characterize the secretory dynamics of PTH in both healthy human subjects and patients with osteoporosis. Osteoporotic patients appear to lack periods of high predictability found in normal humans. In contrast to patients with osteoporosis patients with hyperparathyroidism, a condition which despite sometimes reduced bone mass has a preserved bone architecture, show periods of high predictability of PTH secretion. Using stochastic surrogate data sets which match certain statistical properties of the original time series significant nonlinear determinism could be found for the PTH time series of a group of healthy subjects. Using classical nonlinear analytical techniques we could demonstrate that the irregular pattern of pulsatile PTH secretion in healthy men exhibits characteristics of deterministic chaos. Pulsatile secretion of PTH in healthy subjects seems to be a first example of nonlinear determinism in an apparently irregular hormonal rhythm in human physiology. {copyright} {ital 1996 American Institute of Physics.}

  18. Adrenergic Modulation of Pancreatic Glucagon Secretion in Man

    PubMed Central

    Gerich, John E.; Langlois, Maurice; Noacco, Claudio; Schneider, Victor; Forsham, Peter H.

    1974-01-01

    In order to characterize the influence of the adrenergic system on pancreatic glucagon secretion in man, changes in basal glucagon secretion during infusions of pure alpha and beta adrenergic agonists and their specific antagonists were studied. During infusion of isoproterenol (3 μg/min), a beta adrenergic agonist, plasma glucagon rose from a mean (±SE) basal level of 104±10 to 171±15 pg/ml, P < 0.0002. Concomitant infusion of propranolol (80 μg/min), a beta adrenergic antagonist, prevented the effects of isoproterenol, although propranolol itself had no effect on basal glucagon secretion. During infusion of methoxamine (0.5 mg/min), an alpha adrenergic agonist, plasma glucagon declined from a mean basal level of 122±15 to 75±17 pg/ml, P < 0.001. Infusion of phentolamine (0.5 mg/min), an alpha adrenergic antagonist, caused a rise in plasma glucagon from a mean basal level of 118±16 to 175±21 pg/ml, P < 0.0001. Concomitant infusion of methoxamine with phentolamine caused a reversal of the effects of phentolamine. The present studies thus confirm that catecholamines affect glucagon secretion in man and demonstrate that the pancreatic alpha cell possesses both alpha and beta adrenergic receptors. Beta adrenergic stimulation augments basal glucagon secretion, while alpha adrenergic stimulation diminishes basal glucagon secretion. Furthermore, since infusion of phentolamine, an alpha adrenergic antagonist, resulted in an elevation of basal plasma glucagon levels, there appears to be an inhibitory alpha adrenergic tone governing basal glucagon secretion. The above findings suggest that catecholamines may influence glucose homeostasis in man through their effects on both pancreatic alpha and beta cell function. Images PMID:4825234

  19. Potentiation of stimulus-induced insulin secretion in protein kinase C-deficient RINm5F cells.

    PubMed Central

    Li, G D; Regazzi, R; Ullrich, S; Pralong, W F; Wollheim, C B

    1990-01-01

    The role of protein kinase C (PKC) in stimulus recognition and insulin secretion was investigated after long-term (24 h) treatment of RINm5F cells with phorbol 12-myristate 13-acetate (PMA). Three methods revealed that PKC was no longer detectable, and PMA-induced insulin secretion was abolished. Such PKC-deficient cells displayed enhanced insulin secretion (2-6-fold) in response to vasopressin and carbachol (activating phospholipase C) as well as to D-glyceraldehyde and alanine (promoting membrane depolarization and voltage-gated Ca2+ influx). Insulin release stimulated by 1-oleoyl-2-acetylglycerol (OAG) was also greater in PKC-deficient cells. OAG caused membrane depolarization and raised the cytosolic Ca2+ concentration ([Ca2+]i), both of which were unaffected by PKC down-regulation. Except for that caused by vasopressin, the secretagogue-induced [Ca2+]i elevations were similar in control and PKC-depleted cells. The [Ca2+]i rise evoked by vasopressin was enhanced during the early phase (observed both in cell suspensions and at the single cell level) and the stimulation of diacylglycerol production was also augmented. These findings suggest more efficient activation of phospholipase C by vasopressin after PKC depletion. Electrically permeabilized cells were used to test whether the release process is facilitated after long-term PMA treatment. PKC deficiency was associated with only slightly increased responsiveness to half-maximally (2 microM) but not to maximally stimulatory Ca2+ concentrations. At 2 microM-Ca2+ vasopressin caused secretion, which was also augmented by PMA pretreatment. The difference between intact and permeabilized cells could indicate the loss in the latter of soluble factors which mediate the enhanced secretory responses. However, changes in cyclic AMP production could not explain the difference. These results demonstrate that PKC not only exerts inhibitory influences on the coupling of receptors to phospholipase C but also interferes with

  20. Effect of environmental pollutants on oxytocin synthesis and secretion from corpus luteum and on contractions of uterus from pregnant cows

    SciTech Connect

    Mlynarczuk, Jaroslaw; Wrobel, Michal H.; Kotwica, Jan

    2010-09-15

    Chloro-organic compounds are persistent environmental pollutants and affect many reproductive processes. Oxytocin (OT) synthesized in luteal cells is a local regulator of ovarian activity and uterine contractions. Therefore the effect of xenobiotics on the OT prohormone synthesis, secretion of OT and progesterone (P4) from luteal cells and on myometrial contractions during early pregnancy in cows was investigated. Luteal cells and myometrial strips from a cow at early pregnancy were treated with polychlorinated biphenyl 77 (PCB 77), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE) and hexachlorocyclohexane (HCH) (1 or 10 ng/ml). The mRNA expression of neurophysin-I/oxytocin (NP-I/OT) and peptidyl-glycine-{alpha}-amidating mono-oxygenase (PGA) and concentration of OT and P4 were determined by RT-PCR and EIA, respectively. Moreover, the effect of xenobiotics given with P4 (12 ng/ml) on the basal and OT (10{sup -7} M) stimulated contractions of myometrial strips was studied. Xenobiotics increased (P < 0.05) OT secretion but DDE only stimulated P4 secretion. The ratio of P4 to OT in culture medium was decreased by all xenobiotics during 9-12 weeks of pregnancy. All xenobiotics, except HCH, increased (P < 0.05) mRNA expression of NP-I/OT during all stages of pregnancy and all treatments decreased (P < 0.05) expression of mRNA for PGA during 9-12 weeks of pregnancy. Myometrial strips were relaxed (P < 0.01) after pre-incubation with P4, while each of the xenobiotics jointly with P4 increased (P < 0.01) myometrial contractions. In conclusion, the xenobiotics used increased both expression of mRNA for genes involved in OT synthesis and secretion of OT from luteal cells. This decreases the ratio of P4 to OT and presumably, in this manner, the chloro-organic compounds can influence uterine contractions and enhance risk of abortions in pregnant females.

  1. Synthesis and secretion of Muc4/sialomucin complex: implication of intracellular proteolysis.

    PubMed Central

    Komatsu, Masanobu; Arango, Maria E; Carraway, Kermit L

    2002-01-01

    Muc4/sialomucin complex (SMC) is a heterodimeric glycoprotein complex implicated in epithelial protection and overexpressed in some tumours. It is encoded by a single gene, and the two subunits are produced by proteolytic cleavage at a time before substantial O-glycosylation, near the time of transit from the endoplasmic reticulum to the Golgi. Although Muc4/SMC is translated as a membrane protein, it is produced as a soluble form in many epithelia. Transfection experiments using Cos-7, HBL-100 human epithelial, MCF-7 human breast tumour and HC11 mouse mammary cell lines showed that soluble rat Muc4/SMC is produced by a proteolytic cleavage mechanism and released by secretion from multiple cell lines, including both human and mouse normal epithelial cells and tumour cells. Similar transfection experiments demonstrated the same mechanism for the human analogue MUC4. Gel electrophoresis analyses of deglycosylated membrane and soluble transmembrane subunits and of the membrane-associated cleavage fragment indicated a released cleavage product of 25 kDa, resulting from cleavage between two epidermal growth factor-like domains. Further evidence for this site was obtained from deletion mutants removing this region of the protein, which blocked secretion. Finally, pulse-chase analyses of Muc4/SMC biosynthesis indicated no kinetic difference between the timing of the cleavage to release the soluble form and that to produce the two subunits, indicating that the soluble form is created early in transit to the cell surface. These studies provide the first clear evidence that membrane mucins can be released from cells by an intracellular proteolytic mechanism that leads to secretion of the soluble form of the mucin. PMID:12186632

  2. The Xylella fastidiosa PD1063 protein is secreted in association with outer membrane vesicles.

    PubMed

    Pierce, Brittany K; Voegel, Tanja; Kirkpatrick, Bruce C

    2014-01-01

    Xylella fastidiosa is a gram-negative, xylem-limited plant pathogenic bacterium that causes disease in a variety of economically important agricultural crops including Pierce's disease of grapevines. Xylella fastidiosa biofilms formed in the xylem vessels of plants play a key role in early colonization and pathogenicity by providing a protected niche and enhanced cell survival. Here we investigate the role of Xylella fastidiosa PD1063, the predicted ortholog of Xanthomonas oryzae pv. oryzae PXO_03968, which encodes an outer membrane protein. To assess the function of the Xylella fastidiosa ortholog, we created Xylella fastidiosa mutants deleted for PD1063 and then assessed biofilm formation, cell-cell aggregation and cell growth in vitro. We also assessed disease severity and pathogen titers in grapevines mechanically inoculated with the Xylella fastidiosa PD1063 mutant. We found a significant decrease in cell-cell aggregation among PD1063 mutants but no differences in cell growth, biofilm formation, disease severity or titers in planta. Based on the demonstration that Xanthomonas oryzae pv. oryzae PXO_03968 encodes an outer membrane protein, secreted in association with outer membrane vesicles, we predicted that PD1063 would also be secreted in a similar manner. Using anti-PD1063 antibodies, we found PD1063 in the supernatant and secreted in association with outer membrane vesicles. PD1063 purified from the supernatant, outer membrane fractions and outer membrane vesicles was 19.2 kD, corresponding to the predicted size of the processed protein. Our findings suggest Xylella fastidiosa PD1063 is not essential for development of Pierce's disease in Vitis vinifera grapevines although further research is required to determine the function of the PD1063 outer membrane protein in Xylella fastidiosa. PMID:25426629

  3. The Xylella fastidiosa PD1063 Protein Is Secreted in Association with Outer Membrane Vesicles

    PubMed Central

    Pierce, Brittany K.; Voegel, Tanja; Kirkpatrick, Bruce C.

    2014-01-01

    Xylella fastidiosa is a gram-negative, xylem-limited plant pathogenic bacterium that causes disease in a variety of economically important agricultural crops including Pierce's disease of grapevines. Xylella fastidiosa biofilms formed in the xylem vessels of plants play a key role in early colonization and pathogenicity by providing a protected niche and enhanced cell survival. Here we investigate the role of Xylella fastidiosa PD1063, the predicted ortholog of Xanthomonas oryzae pv. oryzae PXO_03968, which encodes an outer membrane protein. To assess the function of the Xylella fastidiosa ortholog, we created Xylella fastidiosa mutants deleted for PD1063 and then assessed biofilm formation, cell-cell aggregation and cell growth in vitro. We also assessed disease severity and pathogen titers in grapevines mechanically inoculated with the Xylella fastidiosa PD1063 mutant. We found a significant decrease in cell-cell aggregation among PD1063 mutants but no differences in cell growth, biofilm formation, disease severity or titers in planta. Based on the demonstration that Xanthomonas oryzae pv. oryzae PXO_03968 encodes an outer membrane protein, secreted in association with outer membrane vesicles, we predicted that PD1063 would also be secreted in a similar manner. Using anti-PD1063 antibodies, we found PD1063 in the supernatant and secreted in association with outer membrane vesicles. PD1063 purified from the supernatant, outer membrane fractions and outer membrane vesicles was 19.2 kD, corresponding to the predicted size of the processed protein. Our findings suggest Xylella fastidiosa PD1063 is not essential for development of Pierce's disease in Vitis vinifera grapevines although further research is required to determine the function of the PD1063 outer membrane protein in Xylella fastidiosa. PMID:25426629

  4. Secretion of alpha-immunoreactive inhibin by human pre-embryos cultured in vitro.

    PubMed

    Phocas, I; Sarandakou, A; Rizos, D; Dimitriadou, F; Mantzavinos, T; Zourlas, P A

    1992-04-01

    alpha-Immunoreactive inhibin was measured using an enzyme immunoassay kit in the culture medium (Ham's F-10 medium supplemented with 14% heat-inactivated human serum) from day 3 or 4 to day 14 post-fertilization of 31 surplus pre-embryos from eight women participating in an in-vitro fertilization programme. Inhibition secretion was demonstrated in all of them from the fourth day after fertilization (mean +/- SEM: 3.0 +/- 0.7 U) and was independent of the morphological development of pre-embryos (2-4 cells, n = 4; 6-8 cells, n = 4; 8-10 cells, n = 9; 10-12 cells, n = 4; morulae, n = 5 and blastocysts, n = 4). On days 7, 10, 13 and 14 post-fertilization, mean inhibin values +/- SEM for non-disintegrated pre-embryos were respectively: 6.5 +/- 0.9 U, 12.3 +/- 2.0 U, 16.8 +/- 3.2 U and 20.2 +/- 3.7 U; however, when disintegration was noted on days 10 and 13 after fertilization, inhibin mean values were 9.0 +/- 1.4 U and 8.4 +/- 1.7 U respectively. Inhibin levels were significantly correlated with human chorionic gonadotrophin levels in the same culture media only on day 13, while correlation with pregnancy specific beta 1-glycoprotein occurred on day 7 post-fertilization. In conclusion, early human pre-embryos secrete alpha-immunoreactive inhibin before the cytotrophoblast is formed. This secretion increases significantly with time when development is continued, while disintegration is followed by a net decline in the rate of inhibin release. PMID:1522200

  5. Circannual changes in progesterone secretion in intact ewes, luteinizing hormone secretion in ovariectomized estradiol-implanted ewes, and prolactin secretion in three sheep breeds anticipated to differ in seasonality of reproduction.

    PubMed

    Goff, Katherine J; Knight, James W; Pelzer, Kevin D; Akers, R Michael; Notter, David R

    2013-05-01

    Changes in progesterone secretion in intact ewes (7 or 9 per breed) and luteinizing hormone secretion in ovariectomized, estradiol-implanted ewes (9 or 10 per breed) were monitored for 12 mo in Suffolk, tropically adapted St. Croix, and OOS ewes. The OOS line is a composite population of 50% Dorset, 25% Rambouillet, and 25% Finnish Landrace breeding that was selected for 10 yr for ability to lamb in October and early November. Ewes were isolated from rams, and blood samples were collected twice weekly. Circulating prolactin concentrations were also determined from blood samples collected near the summer and winter solstice and vernal and autumnal equinox. Intact OOS ewes entered anestrus later, began the subsequent breeding season sooner, and had a shorter seasonal anestrus than Suffolk and St. Croix ewes (P ≤ 0.005). St. Croix ewes did not differ from Suffolk ewes in date of onset or cessation of breeding or duration of anestrus (P ≥ 0.06). Breed differences in duration of luteinizing hormone inhibition in ovariectomized ewes were essentially identical to those observed for duration of anestrous. Prolactin concentrations varied during the year: annual changes were larger in relatively seasonal Suffolk ewes than in tropically-derived St. Croix ewes (P<0.01), and OOS ewes were intermediate to, and tended to differ from (P<0.10), the other two breeds. We conclude that OOS ewes developed by selection for fertility in spring matings had an abbreviated seasonal anestrus that is one of the shortest ever reported for temperate breeds, and that tropical St. Croix sheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. PMID:23528712

  6. Effects of aldosterone on insulin sensitivity and secretion

    PubMed Central

    Luther, James M.

    2014-01-01

    Dr. Conn originally reported an increased risk of diabetes in patients with hyperaldosteronism in the 1950’s, although the mechanism remains unclear. Aldosterone-induced hypokalemia was initially described to impair glucose tolerance by impairing insulin secretion. Correction of hypokalemia by potassium supplementation only partially restored insulin secretion and glucose tolerance, however. Aldosterone also impairs glucose-stimulated insulin secretion in isolated pancreatic islets via reactive oxygen species in a mineralocorticoid receptor-independent manner. Aldosterone-induced mineralocorticoid receptor activation also impairs insulin sensitivity in adipocytes and skeletal muscle. Aldosterone may produce insulin resistance secondarily by altering potassium, increasing inflammatory cytokines, and reducing beneficial adipokines such as adiponectin. Renin-angiotensin system antagonists reduce circulating aldosterone concentrations and also the risk of type 2 diabetes in clinical trials. These data suggest that primary and secondary hyperaldosteronism may contribute to worsening glucose tolerance by impairing insulin sensitivity or insulin secretion in humans. Future studies should define the effects of MR antagonists and aldosterone on insulin secretion and sensitivity in humans. PMID:25194457

  7. Targeting bacterial secretion systems: benefits of disarmament in the microcosm.

    PubMed

    Baron, Christian; Coombes, Brian

    2007-03-01

    Secretion systems are used by many bacterial pathogens for the delivery of virulence factors to the extracellular space or directly into host cells. They are attractive targets for the development of novel anti-virulence drugs as their inactivation would lead to pathogen attenuation or avirulence, followed by clearance of the bacteria by the immune system. This review will present the state of knowledge on the assembly and function of type II, type III and type IV secretion systems in Gram-negative bacteria focusing on insights provided by structural analyses of several key components. The suitability of transcription factors regulating the expression of secretion system components and of ATPases, lytic transglycosylases and protein assembly factors as drug targets will be discussed. Recent progress using innovative in vivo as well as in vitro screening strategies led to a first set of secretion system inhibitors with potential for further development as anti-infectives. The discovery of such inhibitors offers exciting and innovative opportunities to further develop these anti-virulence drugs into monotherapy or in combination with classical antibiotics. Bacterial growth per se would not be inhibited by such drugs so that the selection for mutations causing resistance could be reduced. Secretion system inhibitors may therefore avoid many of the problems associated with classical antibiotics and may constitute a valuable addition to our arsenal for the treatment of bacterial infections. PMID:17346208

  8. Acetylation modification regulates GRP78 secretion in colon cancer cells

    PubMed Central

    Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu

    2016-01-01

    High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors. PMID:27460191

  9. Acetylation modification regulates GRP78 secretion in colon cancer cells.

    PubMed

    Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu

    2016-01-01

    High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors. PMID:27460191

  10. Traffic Noise Exposure Increases Gastric Pepsin Secretion in Rat.

    PubMed

    Moslehi, Azam; Nabavizadeh, Fatemeh; Keshavarz, Mansoor; Rouhbakhsh, Nematollah; Sotudeh, Masoud; Salimi, Ehsan; Barzegar Behrooz, Amir

    2016-03-01

    Noise is considered as one of the most severe sources of environmental and workplace constraints. Many noise effects are well known on immune function, hormonal levels, cardiovascular and respiratory systems. In this study, our aim is to evaluate the effects of traffic noise exposure on basal and stimulated gastric pepsin secretion. 48 male rats were exposed to traffic noise (86 dB) for a short term of (8h/day for 1 day) and a long term of (8h/day for 7, 14, 21 and 28 days) as well as a control group. The gastric contents were collected by the wash-out technique. Pepsin secretion was measured by employing the Anson method. Histological studies were carried out on the epithelial layer. The corticosteroid hormone was measured in the serum for the stress augmentation. The present finding indicated no changes in pepsin secretion content in the short term, but in the 14 and 21 days traffic noise exposure, basal gastric pepsin secretion increased markedly compared to the control group. Histological results showed that the number of oxyntic glands and cell nuclei decreased in comparison with the control group while the thickness of the epithelial layer increases. In addition, the corticosterone levels increase in all groups in comparison with the control. It seems that the increase of gastric pepsin secretion is due to the description and translation processes in the peptic cells and needs enough time for completion. PMID:27107524

  11. Effect of free dietary glutamate on gastric secretion in dogs.

    PubMed

    Zolotarev, Vasiliy; Khropycheva, Raisa; Uneyama, Hisayuki; Torii, Kunio

    2009-07-01

    The amino acid, L-glutamate, which is abundant in many foodstuffs, is a potent stimulator of gastric vagal afferents. The aim of the study was to evaluate a role of dietary glutamate in neuroendocrine control of gastric secretion of acid, pepsinogen, and fluid. In mongrel dogs with small gastric pouches surgically prepared according to Pavlov (vagally innervated) or Heidenhain (vagally decentralized), secretion in a pouch was induced by infusion into the main stomach of an amino acid-rich diet lacking glutamate (Elental) or the same diet supplemented with monosodium glutamate (MSG). Having no effect alone, MSG (100 mM) potentiated secretion induced by Elental both in Pavlov and Heidenhain models. In the Pavlov pouch, the effect of MSG was markedly reduced after i.v. injection of granisetron, an antagonist of 5-HT(3) receptors. In the Heidenhain model, MSG enhanced the stimulatory effect of pentagastrin (1 microg/kg, s.c.). In conclusion, dietary glutamate at doses not exceeding its common concentrations in foods substantially potentiates gastric phase secretion induced by stimulation of gastric mucosa with an amino acid-rich diet or by administration of pentagastrin. The effect of glutamate is partially mediated via serotonin secretion and stimulation of 5-HT(3) receptors. PMID:19686114

  12. Constitutive secretion of chemokines by cultured human trabecular meshwork cells.

    PubMed

    Shifera, Amde Selassie; Trivedi, Sheetal; Chau, Phuonglan; Bonnemaison, Lucia H; Iguchi, Rumiko; Alvarado, Jorge A

    2010-07-01

    Trabecular meshwork endothelial (TME) cells secrete a number of factors, such as enzymes and cytokines, which modulate the functions of the cells and the extracellular matrix of the conventional aqueous outflow pathway. TME cells usually secrete these factors in response to stimuli such as mechanical stretching, laser irradiation and pro-inflammatory cytokines. Here, we report that cultured human TME cells isolated from two non-glaucomatous individuals secrete significant quantities of the chemotactic cytokines IL8, CXCL6 and MCP1 in the absence of any stimulation. The secretion of these chemokines was augmented by treatment with the pro-inflammatory cytokines TNFalpha and IL1beta. By way of comparison, there was little or very low production of the three chemokines by human non-pigmented ciliary epithelial cells in the absence of stimulation. Our findings provide support to our recent observations that monocytes, presumably under the influence of chemotactic signals, circulate through the trabecular meshwork in the normal state and also that cytokines regulate the permeability of Schlemm's canal endothelial cells. In addition, the fact that normal TME cells constitutively secrete chemotactic cytokines strengthens the notion that cytokines play a key role in the homeostasis of the outflow of the aqueous humor and, possibly, in the pathogenesis of glaucoma. PMID:20403352

  13. Secretion of macrophage urokinase plasminogen activator is dependent on proteoglycans.

    PubMed

    Pejler, Gunnar; Winberg, Jan-Olof; Vuong, Tram T; Henningsson, Frida; Uhlin-Hansen, Lars; Kimata, Koji; Kolset, Svein O

    2003-10-01

    The importance of proteoglycans for secretion of proteolytic enzymes was studied in the murine macrophage cell line J774. Untreated or 4beta-phorbol 12-myristate 13-acetate (PMA)-stimulated macrophages were treated with hexyl-beta-d-thioxyloside to interfere with the attachment of glycosaminoglycan chains to their respective protein cores. Activation of the J774 macrophages with PMA resulted in increased secretion of trypsin-like serine proteinase activity. This activity was completely inhibited by plasminogen activator inhibitor 1 and by amiloride, identifying the activity as urokinase plasminogen activator (uPA). Treatment of both the unstimulated or PMA-stimulated macrophages with xyloside resulted in decreased uPA activity and Western blotting analysis revealed an almost complete absence of secreted uPA protein after xyloside treatment of either control- or PMA-treated cells. Zymography analyses with gels containing both gelatin and plasminogen confirmed these findings. The xyloside treatment did not reduce the mRNA levels for uPA, indicating that the effect was at the post-translational level. Treatment of the macrophages with xylosides did also reduce the levels of secreted matrix metalloproteinase 9. Taken together, these findings indicate a role for proteoglycans in the secretion of uPA and MMP-9. PMID:14511379

  14. Protein secretion and surface display in Gram-positive bacteria

    PubMed Central

    Schneewind, Olaf; Missiakas, Dominique M.

    2012-01-01

    The cell wall peptidoglycan of Gram-positive bacteria functions as a surface organelle for the transport and assembly of proteins that interact with the environment, in particular, the tissues of an infected host. Signal peptide-bearing precursor proteins are secreted across the plasma membrane of Gram-positive bacteria. Some precursors carry C-terminal sorting signals with unique sequence motifs that are cleaved by sortase enzymes and linked to the cell wall peptidoglycan of vegetative forms or spores. The sorting signals of pilin precursors are cleaved by pilus-specific sortases, which generate covalent bonds between proteins leading to the assembly of fimbrial structures. Other precursors harbour surface (S)-layer homology domains (SLH), which fold into a three-pronged spindle structure and bind secondary cell wall polysaccharides, thereby associating with the surface of specific Gram-positive microbes. Type VII secretion is a non-canonical secretion pathway for WXG100 family proteins in mycobacteria. Gram-positive bacteria also secrete WXG100 proteins and carry unique genes that either contribute to discrete steps in secretion or represent distinctive substrates for protein transport reactions. PMID:22411983

  15. Secretion of monocyte chemotactic activity by alveolar macrophages.

    PubMed Central

    Denholm, E. M.; Wolber, F. M.; Phan, S. H.

    1989-01-01

    The purpose of this study was to determine if alveolar macrophages (AMs) are a source of monocyte chemoattractants and the role bleomycin interaction with AMs may play in the recruitment of monocytes to the lung in a rodent model of bleomycin-induced pulmonary fibrosis. AMs isolated from rats with bleomycin-induced fibrosis secreted significantly greater amounts of monocyte chemoattractants than those isolated from normal rats. When AMs from normal rats were stimulated with bleomycin in vitro, monocyte chemotactic activity was secreted into the medium. Chemotactic activity secretion by AM stimulated with 0.01 to 0.1 micrograms/ml bleomycin was significantly higher than that of cells incubated in medium alone. This activity was truly chemotactic for monocytes, but caused only minimal migration of normal AMs. Bleomycin itself at concentrations of 1 pg/ml to 10 micrograms/ml had no monocyte chemoattractant activity. Characterization of the chemotactic activity in conditioned media (CM) from bleomycin-stimulated AM demonstrated that the major portion of the activity bound to gelatin, was heterogeneous, with estimated molecular weights of 20 to 60 kd, and was inactivated by specific antifibronectin antibody. These findings suggest that fibronectin fragments are primarily responsible for the monocyte chemotactic activity secreted by AMs. Through increased secretion of such chemotactic substances, AMs could play a key role in the recruitment of peripheral blood monocytes into the lung in inflammatory lung disease and fibrosis. PMID:2476935

  16. Peroxicretion: a novel secretion pathway in the eukaryotic cell

    PubMed Central

    Sagt, Cees MJ; ten Haaft, Peter J; Minneboo, Ingeborg M; Hartog, Miranda P; Damveld, Robbert A; Metske van der Laan, Jan; Akeroyd, Michiel; Wenzel, Thibaut J; Luesken, Francisca A; Veenhuis, Marten; van der Klei, Ida; de Winde, Johannes H

    2009-01-01

    Background Enzyme production in microbial cells has been limited to secreted enzymes or intracellular enzymes followed by expensive down stream processing. Extracellular enzymes consists mainly of hydrolases while intracellular enzymes exhibit a much broader diversity. If these intracellular enzymes could be secreted by the cell the potential of industrial applications of enzymes would be enlarged. Therefore a novel secretion pathway for intracellular proteins was developed, using peroxisomes as secretion vesicles. Results Peroxisomes were decorated with a Golgi derived v-SNARE using a peroxisomal membrane protein as an anchor. This allowed the peroxisomes to fuse with the plasma membrane. Intracellular proteins were transported into the peroxisomes by adding a peroxisomal import signal (SKL tag). The proteins which were imported in the peroxisomes, were released into the extra-cellular space through this artificial secretion pathway which was designated peroxicretion. This concept was supported by electron microscopy studies. Conclusion Our results demonstrate that it is possible to reroute the intracellular trafficking of vesicles by changing the localisation of SNARE molecules, this approach can be used in in vivo biological studies to clarify the different control mechanisms regulating intracellular membrane trafficking. In addition we demonstrate peroxicretion of a diverse set of intracellular proteins. Therefore, we anticipate that the concept of peroxicretion may revolutionize the production of intracellular proteins from fungi and other microbial cells, as well as from mammalian cells. PMID:19457257

  17. Green tea polyphenols modulate insulin secretion by inhibiting glutamate dehydrogenase.

    PubMed

    Li, Changhong; Allen, Aron; Kwagh, Jae; Doliba, Nicolai M; Qin, Wei; Najafi, Habiba; Collins, Heather W; Matschinsky, Franz M; Stanley, Charles A; Smith, Thomas J

    2006-04-14

    Insulin secretion by pancreatic beta-cells is stimulated by glucose, amino acids, and other metabolic fuels. Glutamate dehydrogenase (GDH) has been shown to play a regulatory role in this process. The importance of GDH was underscored by features of hyperinsulinemia/hyperammonemia syndrome, where a dominant mutation causes the loss of inhibition by GTP and ATP. Here we report the effects of green tea polyphenols on GDH and insulin secretion. Of the four compounds tested, epigallocatechin gallate (EGCG) and epicatechin gallate were found to inhibit GDH with nanomolar ED(50) values and were therefore found to be as potent as the physiologically important inhibitor GTP. Furthermore, we have demonstrated that EGCG inhibits BCH-stimulated insulin secretion, a process that is mediated by GDH, under conditions where GDH is no longer inhibited by high energy metabolites. EGCG does not affect glucose-stimulated insulin secretion under high energy conditions where GDH is probably fully inhibited. We have further shown that these compounds act in an allosteric manner independent of their antioxidant activity and that the beta-cell stimulatory effects are directly correlated with glutamine oxidation. These results demonstrate that EGCG, much like the activator of GDH (BCH), can facilitate dissecting the complex regulation of insulin secretion by pharmacologically modulating the effects of GDH. PMID:16476731

  18. The dynamics of secretion during sea urchin embryonic skeleton formation

    SciTech Connect

    Wilt, Fred H.

    2008-05-01

    Skeleton formation involves secretion of massive amounts of mineral precursor, usually a calcium salt, and matrix proteins, many of which are deposited on, or even occluded within, the mineral. The cell biological underpinnings of this secretion and subsequent assembly of the biomineralized skeletal element is not well understood. We ask here what is the relationship of the trafficking and secretion of the mineral and matrix within the primary mesenchyme cells of the sea urchin embryo, cells that deposit the endoskeletal spicule. Fluorescent labeling of intracellular calcium deposits show mineral precursors are present in granules visible by light microscopy, from whence they are deposited in the endoskeletal spicule, especially at its tip. In contrast, two different matrix proteins tagged with GFP are present in smaller post-Golgi vesicles only seen by electron microscopy, and the secreted protein are only incorporated into the spicule in the vicinity of the cell of origin. The matrix protein, SpSM30B, is post-translationally modified during secretion, and this processing continues after its incorporation into the spicule. Our findings also indicate that the mineral precursor and two well characterized matrix proteins are trafficked by different cellular routes.

  19. Type VI Secretion System Toxins Horizontally Shared between Marine Bacteria

    PubMed Central

    Salomon, Dor; Klimko, John A.; Trudgian, David C.; Kinch, Lisa N.; Grishin, Nick V.; Mirzaei, Hamid; Orth, Kim

    2015-01-01

    The type VI secretion system (T6SS) is a widespread protein secretion apparatus used by Gram-negative bacteria to deliver toxic effector proteins into adjacent bacterial or host cells. Here, we uncovered a role in interbacterial competition for the two T6SSs encoded by the marine pathogen Vibrio alginolyticus. Using comparative proteomics and genetics, we identified their effector repertoires. In addition to the previously described effector V12G01_02265, we identified three new effectors secreted by T6SS1, indicating that the T6SS1 secretes at least four antibacterial effectors, of which three are members of the MIX-effector class. We also showed that the T6SS2 secretes at least three antibacterial effectors. Our findings revealed that many MIX-effectors belonging to clan V are “orphan” effectors that neighbor mobile elements and are shared between marine bacteria via horizontal gene transfer. We demonstrated that a MIX V-effector from V. alginolyticus is a functional T6SS effector when ectopically expressed in another Vibrio species. We propose that mobile MIX V-effectors serve as an environmental reservoir of T6SS effectors that are shared and used to diversify antibacterial toxin repertoires in marine bacteria, resulting in enhanced competitive fitness. PMID:26305100

  20. Quantum secret sharing with continuous-variable cluster states

    NASA Astrophysics Data System (ADS)

    Lau, Hoi-Kwan; Weedbrook, Christian

    2013-10-01

    We extend the formalism of cluster-state quantum secret sharing, as presented by Markham and Sanders [Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.78.042309 78, 042309 (2008)] and Keet [Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.82.062315 82, 062315 (2010)], to the continuous-variable regime. We show that both classical and quantum information can be shared by distributing continuous-variable cluster states through either public or private channels. We find that the adversary structure is completely denied from the secret if the cluster state is infinitely squeezed, but some secret information would be leaked if a realistic finitely squeezed state is employed. We suggest benchmarks to evaluate the security in the finitely squeezed cases. For the sharing of classical secrets, we borrow techniques from the continuous-variable quantum key distribution to compute the secret-sharing rate. For the sharing of quantum states, we estimate the amount of entanglement distilled for teleportation from each cluster state.

  1. Maturation processes and structures of small secreted peptides in plants

    PubMed Central

    Tabata, Ryo; Sawa, Shinichiro

    2014-01-01

    In the past decade, small secreted peptides have proven to be essential for various aspects of plant growth and development, including the maintenance of certain stem cell populations. Most small secreted peptides identified in plants to date are recognized by membrane-localized receptor kinases, the largest family of receptor proteins in the plant genome. This peptide-receptor interaction is essential for initiating intracellular signaling cascades. Small secreted peptides often undergo post-translational modifications and proteolytic processing to generate the mature peptides. Recent studies suggest that, in contrast to the situation in mammals, the proteolytic processing of plant peptides involves a number of complex steps. Furthermore, NMR-based structural analysis demonstrated that post-translational modifications induce the conformational changes needed for full activity. In this mini review, we summarize recent advances in our understanding of how small secreted peptides are modified and processed into biologically active peptides and describe the mature structures of small secreted peptides in plants. PMID:25071794

  2. Bayesian analysis of the kinetics of quantal transmitter secretion at the neuromuscular junction.

    PubMed

    Saveliev, Anatoly; Khuzakhmetova, Venera; Samigullin, Dmitry; Skorinkin, Andrey; Kovyazina, Irina; Nikolsky, Eugeny; Bukharaeva, Ellya

    2015-10-01

    The timing of transmitter release from nerve endings is considered nowadays as one of the factors determining the plasticity and efficacy of synaptic transmission. In the neuromuscular junction, the moments of release of individual acetylcholine quanta are related to the synaptic delays of uniquantal endplate currents recorded under conditions of lowered extracellular calcium. Using Bayesian modelling, we performed a statistical analysis of synaptic delays in mouse neuromuscular junction with different patterns of rhythmic nerve stimulation and when the entry of calcium ions into the nerve terminal was modified. We have obtained a statistical model of the release timing which is represented as the summation of two independent statistical distributions. The first of these is the exponentially modified Gaussian distribution. The mixture of normal and exponential components in this distribution can be interpreted as a two-stage mechanism of early and late periods of phasic synchronous secretion. The parameters of this distribution depend on both the stimulation frequency of the motor nerve and the calcium ions' entry conditions. The second distribution was modelled as quasi-uniform, with parameters independent of nerve stimulation frequency and calcium entry. Two different probability density functions for the distribution of synaptic delays suggest at least two independent processes controlling the time course of secretion, one of them potentially involving two stages. The relative contribution of these processes to the total number of mediator quanta released depends differently on the motor nerve stimulation pattern and on calcium ion entry into nerve endings. PMID:26129670

  3. Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells

    PubMed Central

    Phang, Wai-Mei; Tan, Aik-Aun; Gopinath, Subash C.B.; Hashim, Onn H.; Kiew, Lik Voon; Chen, Yeng

    2016-01-01

    Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. PMID:27226773

  4. Preimplantation embryo-secreted factors modulate maternal gene expression in rat uterus.

    PubMed

    Yamagami, Kazuki; Islam, M Rashedul; Yoshii, Yuka; Mori, Kazuki; Tashiro, Kosuke; Yamauchi, Nobuhiko

    2016-05-01

    In mammalian reproduction, embryo implantation into the uterus is spatiotemporally regulated by a complex process triggered by a number of factors. Although previous studies have suggested that uterine receptivity is mediated by blastocyst-derived factors, specific functions of embryos remain to be defined during preimplantation. Therefore, the present study was conducted to identify the maternal genes regulated by embryo-secreted factors in the rat uterus. RNA-sequencing (RNA-seq) data revealed that 10 genes are up-regulated in the delayed implantation uterus compared with the pseudopregnancy uterus. The RNA-seq results were further verified by real-time quantitative polymerase chain reaction. Sulf1 expression is significantly (P < 0.05) induced in the delayed implantation uterus, although Areg, Calca, Fxyd4 and Lamc3 show a definite but non-statistically significant increase in their expression levels. During early pregnancy, the levels of Areg, Calca, Fxyd4, Lamc3 and Sulf1 expression at 3.5 days post coitus (dpc) are significantly (P < 0.05) higher than those at 1.5 dpc. Treatment with embryo-conditioned media revealed that Lamc3 and Sulf1 are up-regulated compared with the other genes studied. Thus, embryo-derived factors regulate maternal gene expression, with Lamc3 and Sulf1 possibly being suitable markers for a response study of embryo-secreted factors to improve our understanding of embryo-maternal communication. PMID:26685865

  5. Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells.

    PubMed

    Phang, Wai-Mei; Tan, Aik-Aun; Gopinath, Subash C B; Hashim, Onn H; Kiew, Lik Voon; Chen, Yeng

    2016-01-01

    Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. PMID:27226773

  6. Melatonin modulates secretion of growth hormone and prolactin by trout pituitary glands and cells in culture.

    PubMed

    Falcón, J; Besseau, L; Fazzari, D; Attia, J; Gaildrat, P; Beauchaud, M; Boeuf, G

    2003-10-01

    In Teleost fish, development, growth, and reproduction are influenced by the daily and seasonal variations of photoperiod and temperature. Early in vivo studies indicated the pineal gland mediates the effects of these external factors, most probably through the rhythmic production of melatonin. The present investigation was aimed at determining whether melatonin acts directly on the pituitary to control GH and prolactin (PRL) secretion in rainbow trout. We show that 2-[125I]-iodomelatonin, a melatonin analog, binds selectively to membrane preparations and tissue sections from trout pituitaries. The affinity was within the range of that found for the binding to brain microsomal preparations, but the number of binding sites was 20-fold less than in the brain. In culture, melatonin inhibited pituitary cAMP accumulation induced by forskolin, the adenyl cyclase stimulator. Forskolin also induced an increase in GH release, which was reduced in the presence of picomolar concentrations of melatonin. At higher concentrations, the effects of melatonin became stimulatory. In the absence of forskolin, melatonin induced a dose-dependent increase in GH release, and a dose-dependent decrease in PRL release. Melatonin effects were abolished upon addition of luzindole, a melatonin antagonist. Our results provide the first evidence that melatonin modulates GH and PRL secretion in Teleost fish pituitary. Melatonin effects on GH have never been reported in any vertebrate before. The effects result from a direct action of melatonin on pituitary cells. The complexity of the observed responses suggests several types of melatonin receptors might be involved. PMID:12960030

  7. Recombinant LPG3 Stimulates IFN-Γ and TNF-A Secretion by Human NK Cells

    PubMed Central

    RASOLZADEH, Sanaz; HAJI FATAHALIHA, Mostafa; HOSSEINI, Maryam; JAFARI, Reza; MIAHIPOUR, Abolfazl; MOVASSAGHPOUR, Ali Akbar; BABALO, Zohreh; RAFATI, Sima; YOUSEFI, Mehdi

    2015-01-01

    Background: Natural killer (NK) cells play an important role in early stages of innate immune responses against viral and tumoral attacks. Activation of NK cells by leishmaniasis results in secretion of cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, which enhances the phagocytosis and clearance of parasite. Lipophosphoglycan 3 (LPG3), the Leishmania homologous with GRP94 (glucose regulated protein 94), a member of HSP90 family, contributes to LPG assembly as the most abundant macromolecule on the surface of Leishmania promastigotes. Methods: We purified NK cells from healthy individuals (n=10) using magnetic-activated cell sorting (MACS) technology. Purified NK cells were co-incubated with different concentrations of recombinant LPG3 (rLPG3), and its N-terminal (NT) and C-terminal (CT) fragments. Finally, the production of IFN-γ and TNF-α by NK cells were measured by ELISA. Results: Recombinant LPG3 but not its fragments (CT and NT), can significantly enhance the production of TNF-α by NK cells (P<0.05). Moreover, rLPG3, CT, and NT fragments were markedly stimulated the secretion of IFN-γ by NK cells (P<0.001). Conclusion: The Leishmania LPG3 antigen can effectively activate NK cells, in vitro. Leishmania LPG3 participates in the innate immunity against leishmaniasis and thereby improves the effective parasite destruction. However, its efficiency should be tested in vivo. PMID:26811721

  8. Recombinant LPG3 Stimulates IFN-Γ and TNF-Α Secretion by Human NK Cells

    PubMed Central

    RASOLZADEH, Sanaz; HAJI FATAHALIHA, Mostafa; HOSSEINI, Maryam; JAFARI, Reza; MIAHIPOUR, Abolfazl; SADREDDINI, Sevil; BABALO, Zohreh; SAMADI KAFIL, Hossein; YOUSEFI, Mehdi

    2015-01-01

    Background: Natural killer (NK) cells play an important role in early stages of innate immune responses against viral and tumoral attacks. Activation of NK cells by leishmaniasis results in secretion of cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, which enhance the phagocytosis and clearance of parasite. Lipophosphoglycan 3 (LPG3), the Leishmania homologous with GRP94 (glucose regulated protein 94), a member of HSP90 family, contributes to LPG assembly as the most abundant macromolecule on the surface of Leishmania promastigotes. Methods: We purified NK cells from healthy individuals (n=10) using magnetic-activated cell sorting (MACS) technology. Purified NK cells were co-incubated with different concentrations of recombinant LPG3 (rLPG3), and its N-terminal (NT) and C-terminal (CT) fragments. Finally, the production of IFN-γ and TNF-α by NK cells were measured by ELISA. Results: Recombinant LPG3 but not its fragments (CT and NT), could significantly enhance the production of TNF-α by NK cells (P<0.05). Moreover, rLPG3, CT, and NT fragments were markedly stimulated the secretion of IFN-γ by NK cells (P<0.001). Conclusion: The Leishmania LPG3 antigen could effectively activate NK cells, in vitro. Leishmania LPG3 participates in the innate immunity against leishmaniasis and thereby improves the effective parasite destruction. However, its efficiency should be tested in vivo. PMID:26622301

  9. Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion

    PubMed Central

    Chen, Gang; Park, Chul-Kyu; Xie, Rou-Gang; Ji, Ru-Rong

    2015-01-01

    Neuropathic pain remains a pressing clinical problem. Here, we demonstrate that a local, intrathecal (i.t.) injection of bone marrow stromal cells (BMSCs) following lumbar puncture alleviates early- and late-phase neuropathic pain symptoms, such as allodynia and hyperalgesia, for several weeks in murine chronic constriction injury (CCI) and spared nerve injury models. Moreover, i.t. BMSCs reduced CCI-induced spontaneous pain and axonal injury of dorsal root ganglion (DRG) neurons and inhibited CCI-evoked neuroinflammation in DRGs and spinal cord tissues. BMSCs secreted TGF-β1 into the cerebrospinal fluid, and neutralization of TGF-β1, but not IL-10, reversed the analgesic effect of BMSCs. Conversely, i.t. administration of TGF-β1 potently inhibited neuropathic pain. TGF-β1 acted as a powerful neuromodulator and rapidly (within minutes) suppressed CCI-evoked spinal synaptic plasticity and DRG neuronal hyperexcitability via TGF-β receptor 1–mediated noncanonical signaling. Finally, nerve injury upregulated CXCL12 in lumbar L4–L6 DRGs, and this upregulation caused migration of i.t.-injected BMSCs to DRGs through the CXCL12 receptor CXCR4, which was expressed on BMSCs. BMSCs that migrated from the injection site survived at the border of DRGs for more than 2 months. Our findings support a paracrine mechanism by which i.t. BMSCs target CXCL12-producing DRGs to elicit neuroprotection and sustained neuropathic pain relief via TGF-β1 secretion. PMID:26168219

  10. Contrasted evolutionary constraints on secreted and non-secreted proteomes of selected Actinobacteria

    PubMed Central

    2013-01-01

    Background Actinobacteria have adapted to contrasted ecological niches such as the soil, and among others to plants or animals as pathogens or symbionts. Mycobacterium genus contains mostly pathogens that cause a variety of mammalian diseases, among which the well-known leprosy and tuberculosis, it also has saprophytic relatives. Streptomyces genus is mostly a soil microbe known for its secondary metabolites, it contains also plant pathogens, animal pathogens and symbionts. Frankia, a nitrogen-fixing actinobacterium establishes a root symbiosis with dicotyledonous pionneer plants. Pathogens and symbionts live inside eukaryotic cells and tissues and interact with their cellular environment through secreted proteins and effectors transported through transmembrane systems; nevertheless they also need to avoid triggering host defense reactions. A comparative genome analysis of the secretomes of symbionts and pathogens allows a thorough investigation of selective pressures shaping their evolution. In the present study, the rates of silent mutations to non-silent mutations in secretory proteins were assessed in different strains of Frankia, Streptomyces and Mycobacterium, of which several genomes have recently become publicly available. Results It was found that secreted proteins as a whole have a stronger purifying evolutionary rate (non-synonymous to synonymous substitutions or Ka/Ks ratio) than the non-secretory proteins in most of the studied genomes. This difference becomes statistically significant in cases involving obligate symbionts and pathogens. Amongst the Frankia, secretomes of symbiotic strains were found to have undergone evolutionary trends different from those of the mainly saprophytic strains. Even within the secretory proteins, the signal peptide part has a higher Ka/Ks ratio than the mature part. Two contrasting trends were noticed amongst the Frankia genomes regarding the relation between selection strength (i.e. Ka/Ks ratio) and the codon adaptation

  11. HCO3(-) secretion by murine nasal submucosal gland serous acinar cells during Ca2+-stimulated fluid secretion.

    PubMed

    Lee, Robert J; Harlow, Janice M; Limberis, Maria P; Wilson, James M; Foskett, J Kevin

    2008-07-01

    Airway submucosal glands contribute to airway surface liquid (ASL) composition and volume, both important for lung mucociliary clearance. Serous acini generate most of the fluid secreted by glands, but the molecular mechanisms remain poorly characterized. We previously described cholinergic-regulated fluid secretion driven by Ca(2+)-activated Cl(-) secretion in primary murine serous acinar cells revealed by simultaneous differential interference contrast (DIC) and fluorescence microscopy. Here, we evaluated whether Ca(2+)-activated Cl(-) secretion was accompanied by secretion of HCO(3)(-), possibly a critical ASL component, by simultaneous measurements of intracellular pH (pH(i)) and cell volume. Resting pH(i) was 7.17 +/- 0.01 in physiological medium (5% CO(2)-25 mM HCO(3)(-)). During carbachol (CCh) stimulation, pH(i) fell transiently by 0.08 +/- 0.01 U concomitantly with a fall in Cl(-) content revealed by cell shrinkage, reflecting Cl(-) secretion. A subsequent alkalinization elevated pH(i) to above resting levels until agonist removal, whereupon it returned to prestimulation values. In nominally CO(2)-HCO(3)(-)-free media, the CCh-induced acidification was reduced, whereas the alkalinization remained intact. Elimination of driving forces for conductive HCO(3)(-) efflux by ion substitution or exposure to the Cl(-) channel inhibitor niflumic acid (100 microM) strongly inhibited agonist-induced acidification by >80% and >70%, respectively. The Na(+)/H(+) exchanger (NHE) inhibitor dimethylamiloride (DMA) increased the magnitude (greater than twofold) and duration of the CCh-induced acidification. Gene expression profiling suggested that serous cells express NHE isoforms 1-4 and 6-9, but pharmacological sensitivities demonstrated that alkalinization observed during both CCh stimulation and pH(i) recovery from agonist-induced acidification was primarily due to NHE1, localized to the basolateral membrane. These results suggest that serous acinar cells secrete HCO(3

  12. Regulation of surfactant secretion in alveolar type II cells.

    PubMed

    Andreeva, Alexandra V; Kutuzov, Mikhail A; Voyno-Yasenetskaya, Tatyana A

    2007-08-01

    Molecular mechanisms of surfactant delivery to the air/liquid interface in the lung, which is crucial to lower the surface tension, have been studied for more than two decades. Lung surfactant is synthesized in the alveolar type II cells. Its delivery to the cell surface is preceded by surfactant component synthesis, packaging into specialized organelles termed lamellar bodies, delivery to the apical plasma membrane and fusion. Secreted surfactant undergoes reuptake, intracellular processing, and finally resecretion of recycled material. This review focuses on the mechanisms of delivery of surfactant components to and their secretion from lamellar bodies. Lamellar bodies-independent secretion is also considered. Signal transduction pathways involved in regulation of these processes are discussed as well as disorders associated with their malfunction. PMID:17496061

  13. Comparative Study of the Labial Gland Secretion in Termites (Isoptera)

    PubMed Central

    Sillam-Dussès, David; Krasulová, Jana; Vrkoslav, Vladimír; Pytelková, Jana; Cvačka, Josef; Kutalová, Kateřina; Bourguignon, Thomas; Miura, Toru; Šobotník, Jan

    2012-01-01

    Labial glands are present in all castes and developmental stages of all termite species. In workers, their secretion contains a food-marking pheromone and digestive enzymes, while soldier secretion plays a defensive role. However, these functions were studied only in a limited set of species, and do not allow drawing general conclusions. Hence, we have investigated the chemical composition of the labial gland extracts from soldiers and workers in 15 termite species belonging to 6 families using an integrative approach based on proteomic and small-molecule profiling. We confirmed the presence of hydroquinone and cellulase in the labial glands of workers, and we identified new toxic compounds in soldiers and workers of several species. Our results highlight the dual role of labial gland secretion, i.e. the defensive role in soldiers and workers of several termite species, and the digestive function in workers. PMID:23071569

  14. Protein secretion in Pichia pastoris and advances in protein production.

    PubMed

    Damasceno, Leonardo M; Huang, Chung-Jr; Batt, Carl A

    2012-01-01

    Yeast expression systems have been successfully used for over 20 years for the production of recombinant proteins. With the growing interest in recombinant protein expression for various uses, yeast expression systems, such as the popular Pichia pastoris, are becoming increasingly important. Although P. pastoris has been successfully used in the production of many secreted and intracellular recombinant proteins, there is still room for improvement of this expression system. In particular, secretion of recombinant proteins is still one of the main reasons for using P. pastoris. Therefore, endoplasmic reticulum protein folding, correct glycosylation, vesicular transport to the plasma membrane, gene dosage, secretion signal sequences, and secretome studies are important considerations for improved recombinant protein production. PMID:22057543

  15. Secret sharing with a single d -level quantum system

    NASA Astrophysics Data System (ADS)

    Tavakoli, Armin; Herbauts, Isabelle; Żukowski, Marek; Bourennane, Mohamed

    2015-09-01

    We give an example of a wide class of problems for which quantum-information protocols based on multisystem entanglement can be mapped into much simpler ones involving one system. Secret sharing is a cryptographic primitive which plays a central role in various secure multiparty computation tasks and management of keys in cryptography. In secret sharing protocols, a classical message is divided into shares given to recipient parties in such a way that some number of parties need to collaborate in order to reconstruct the message. Quantum protocols for the task commonly rely on multipartite GHZ entanglement. We present a multiparty secret sharing protocol which requires only sequential communication of a single quantum d -level system (for any prime d ). It has huge advantages in scalability and can be realized with state-of-the-art technology.

  16. Identification and characterization of secreted proteins in Eimeria tenella

    NASA Astrophysics Data System (ADS)

    Ramlee, Intan Azlinda; Firdaus-Raih, Mohd; Wan, Kiew-Lian

    2015-09-01

    Eimeria tenella is a protozoan parasite that causes coccidiosis, an economically important disease in the poultry industry. The characterization of proteins that are secreted by parasites have been shown to play important roles in parasite invasion and are considered to be potential control agents. In this study, 775 proteins potentially secreted by E. tenella were identified. These proteins were further filtered to remove mitochondrial proteins. Out of 763 putative secreted proteins, 259 proteins possess transmembrane domains while another 150 proteins have GPI (Glycosylphosphatidylinositol) anchors. Homology search revealed that 315 and 448 proteins have matches with known and hypothetical proteins in the database, respectively. Within this data set, previously characterized secretory proteins such as micronemes, rhoptry kinases and dense granules were detected.

  17. Effects of smoking on ACTH and cortisol secretion

    SciTech Connect

    Seyler, L.E. Jr.; Fertig, J.; Pomerleau, O.; Hunt, D.; Parker, K.

    1984-01-02

    The relationships among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarattes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. This data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism.

  18. Cooperative secretions facilitate host range expansion in bacteria

    PubMed Central

    McNally, Luke; Viana, Mafalda; Brown, Sam P.

    2014-01-01

    The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses. PMID:25091146

  19. Cardiopulmonary exercise: a recently discovered secret of tai chi.

    PubMed

    Ng, R K

    1992-08-01

    Every piece of literature or book about tai chi claims it to be the supreme martial art (soft style) and a therapeutic exercise. Nevertheless, none of the authors can describe scientifically how and why it works. Many people did not gain any health benefit in practicing tai chi and only very few people were able to apply its legendary secret power. During the last 10 years, the author thought he had discovered the secret in Hong Kong and brought it to Los Angeles. The secret lies in the fundamental movements of the body, called tai chi basic exercise routines. The entry level of the exercise has many similarities with medical treatments for respiratory illness and with walking exercise--the most recommended aerobic exercise for coronary artery disease. PMID:1399544

  20. [Intrasellar small TSH secreting pituitary adenomas, 2 case reports].

    PubMed

    Ogawa, Yoshikazu; Tominaga, Teiji; Ikeda, Hidetoshi

    2007-07-01

    Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma accounts for 1% of pituitary adenoma and often manifests as invasive macroadenoma. If the TSH value is not high enough to cause clinical symptoms presenting as inappropriate secretion of TSH, the tumor may be missed or misdiagnosed as Graves disease. Some of these patients receive inadequate treatment with the antithyroid agent, radioiodine treatment, and thyroidectomy. This tumor is also known as a tough and firm tumor because of the significant interstitial fibrosis. We report two cases of TSH-secreting pituitary adenomas which were comparatively small. Although a tough and difficult operation was expected, actual tumor dissection was easy and gross total removal was achieved within less than 3 hours. We discuss the relationship between the intraoperative findings and histopathology, as well as the ultrastructure and endocrinology. PMID:17633511