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1
Gu, Shuang. "Secretin interactions in the type II secretion system." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/2482.
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The type II secretion system (T2SS) is the major terminal branch of the general secretory pathway. It is composed of 12-15 proteins, most in multiple copies, and spans the inner and outer membranes of Gram-negative bacteria. The T2SS secretin subunits form a large dodecameric torus-like structure in the outer membrane. The secretin is the only essential component in the outer membrane and secreted proteins and virulence factors pass through the pore in the toroidal secretin dodecamer and out into the environment. The interaction between the secretin and its partners plays a key role in regulation of the T2SS. The interaction between the so-called homology region of the innermembrane protein GspC (GspC-HR) and secretin provides the structural and functional integrity of the secretion machinery across the two cell membranes. The interaction between secretin and its pilotin translocates the secretin subunits to the outer membrane. In this Thesis, the interactions between secretin and its partners are studied at molecular level. The GspC-HR structure is solved using NMR spectroscopy. Its interaction with secretin (GspD) is elucidated using several biochemical and biophysical approaches and a model of the complex is proposed. Also, the interaction between secretin (GspD) and pilotin (GspS) is further charicterisied. An 18 residues secretin sequence is identified as responsible for interacting with pilotin. Upon binding to the pilotin, the unstructured secretin forms a helical structure.
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Woods, Birgitta A. "The effects of epinephrine, AVP, norepinephrine, and acetylcholine on lung liquid production in in vitro preparations of lungs from fetal guinea pigs (Cavia porcellus)." Thesis, University of British Columbia, 1991. http://hdl.handle.net/2429/29821.
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This study examined the effects of epinephrine, norepinephrine, AVP and ACh on fluid movement by the lungs of the late-term guinea pig fetus. Catecholamines and AVP are secreted in high amounts by the fetus during delivery, and could be important with respect to fetal lung fluid removal; this event is vital at the time of birth.
The lungs were supported in vitro for a duration of three hours, and production rates were measured using a dye-dilution technique. The average resting production rate in terms of ml/kg‧h declined with gestational age (54-67 days gestation; n=171). There was a lesser decline in the average resting production rate in terms of ml/h. The average production rate of untreated preparations in the first hour was 1.60 ± 0.26 ml/kg body weight per hour, and rates did not change significantly during the remaining two hours of experimentation (n=30). This rate is comparable to those reported from chronically catheterized fetal sheep.
Treatment was administered during the second hour of experimentation, following an ABA design. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of epinephrine: (a) 10‾⁵ M; (b) 10‾⁶ M; (c) 10‾⁷ M; (d) 5 x 10‾⁸ M; (e) 10‾⁸ M; and (f) 10‾⁹ M. With the exception of the top dose, epinephrine treatment caused an immediate reduction in fluid secretion, or fluid reabsorption. Sodium followed the movement of water in all cases. The effect of epinephrine at 10‾⁷ M was maximal, and the threshold dose for epinephrine was calculated at 1.78 x 10‾¹¹ M. Phentolamine and propranolol had no effect in control preparations. However, phentolamine completely blocked the effect of epinephrine, whereas propranolol was ineffective. Isoproterenol had no effect on pulmonary fluid production. Alpha-adrenergic receptors apparently mediate the effect of epinephrine on pulmonary fluid movement in the fetal guinea pig lung. This conclusion is different from that obtained in fetal sheep, in which beta-adrenergic receptors are utilized.
A possible synergism between epinephrine and AVP was examined. Lungs (n=12) were transferred to fresh Krebs-Henseleit saline containing either (a) 0.6 mU/ml AVP, or b) 0.6 mU/ml AVP combined with epinephrine at 10‾⁷ M. Treatment with AVP caused a slow, prolonged reduction in fluid production. Treatment with AVP together with epinephrine did not demonstrate synergism.
The effect of norepinephrine (NE) was examined. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of NE: (a) 1.24 x 10‾⁵ M; (b) 1.24 x 10‾⁶ M; (c) 1.24 x 10‾⁷ M; (d) 5.24 x 10‾⁸ M; (e) 1.24 x 10‾⁸ M; and (f) 1.24 x 10‾⁹ M. In all preparations, treatment with NE resulted in an immediate reduction in fluid production, and reabsorptions were observed at the higher doses. Sodium followed the movement of water in every case. The threshold dose was calculated at 3.16 x 10‾¹⁰ M. Phentolamine blocked the effect of NE, reinforcing the importance of pulmonary alpha-adrenergic receptors in the fetal guinea pig. There was no relationship between age and degree of response with treatment of either epinephrine or NE, but fetuses under 78.0 g did not respond to NE.
The effect of ACh was examined. Lungs (n=24) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of ACh: (a) 10‾⁴ M; (b) 10‾⁵ M; (c) 10‾⁶ M; and (d) 10‾⁸ M. At the three top doses, immediate and powerful reabsorptions of pulmonary fluid were observed in older fetuses (60 days gestation and above); significant falls were observed in the younger fetuses. This result was unexpected, as it was hypothesized that ACh would stimulate fluid production. The threshold dose for ACh was between 10‾⁶ M and 10‾⁸ M. Phentolamine blocked the effect of ACh. This result suggested that reabsorption is a result of an indirect effect of ACh acting through pulmonary alpha receptors.
The results in this study show that epinephrine, NE, AVP and ACh are all important promoters of fetal pulmonary fluid removal in the fetal guinea pig. Pulmonary alpha-adrenergic receptors
mediate the effects of epinephrine, NE and ACh (indirectly). The conclusions drawn from this study emphasize the importance of species' comparison in fetal research.
LIST OF ABBREVIATIONS
AVP Arginine Vasopressin
NE Norepinephrine
DOPA dihydroxyphenylalanine
PNMT Phenylethanolamine n-methyltransferase
ACh AcetylcholineScience, Faculty of
Zoology, Department of
Graduate
3
Lee, Pei-Chung. "Effector Secretion Control by the Pseudomonas aeruginosa Type III Secretion System." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301596980.
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Sani, Musa. "Weapons of mass secretion the type III secretion system of Shigella flexneri /." [S.l. : Groningen : s.n. ; University Library Groningen] [Host], 2007. http://irs.ub.rug.nl/ppn/304674354.
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Gabert, Vince Morllen. "Pancreatic secretion in pigs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/nq21570.pdf.
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Burquez-Montijo, Jose Alberto. "Studies on nectar secretion." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235811.
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This thesis explores the dynamic patterns in the secretion, reabsorption and concentration of nectar, and their relation with microclimate, flower visitors and the innervation of the nectaries. Case studies are presented, comprising Impatiens glandulifera, Brassica napus, Fritillaria imperialis and Borago officinalis. Nectar secretion rate and nectar solute concentration are affected by the environment, and probably by the genetic composition of the plants. Significant differences in nectar secretion rate and nectar concentration are found between plants, between times of the day and between days, but not among flowers on the same plant. Correlation matrices and correlograms help us to disentangle multiple interactions. In all the species studied, the environmental factor most likely to affect nectar secretion rate seems to be the temperature of the air. Other factors also contribute to explain the variation in nectar secretion rate, among them the stand age (probably acting through the relative sink strength of the flowers), and the number of flowers and fruits per module. The supply of assimilates to the nectary is explored by experimental defoliations and deprivation of light. In both cases an immediate response is elicited, but the degree of response varies between species. Brassica napus, for example, is much less sensitive to light deprivation or total defoliation than Fritillaria imperialis. Nectar solute concentration seems to depend mainly on the relative humidity of the air. However, some evidence suggests that plant water status might affect nectar concentration. These results, obtained from field experiments, were confirmed in controlled conditions in growth chambers. Other minor factors probably play a role, but their effects are obscured by complex physiological interactions. We conclude that in a given plant the nectar secretion rate will depend mainly on its physiological age, and on variations in air temperature, while the nectar solute concentration at a given moment will be mainly the product of the short-term plant-microclimate interaction. In this context, constraints on the evolution of nectar presentation systems are considered.
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Song, Soon Hoo. "Dynamics of insulin secretion." Thesis, University of Edinburgh, 2000. http://hdl.handle.net/1842/22645.
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I undertook four related projects that address the pattern of insulin secretion and the specific mechanisms by which b-cell positively influences these. Project one. Direct measurement of the pattern of insulin release in the portal vein (immediately downstream of the pancreas) in human subjects in the basal state and in response to glucose stimulation. Project two. Examination of the effects of acute inhibition of insulin secretion in humans with Type 2 diabetes mellitus by diazoxide on the pattern of insulin secretion. Project three. Development and validation of a method to quantify pulsatile insulin release by cultured human islets in an open loop perifusion system. Project four. Use of the system developed and validated in project 3 to test the hypothesis that transient b-cell rest in human islets induced by diazoxide (inhibiting insulin secretion by opening b cell potassium channels) prevents loss of the first phase insulin release and pulsatile insulin secretion caused by culture of the islets in glucose concentrations comparable to those seen in Type 2 diabetes mellitus. In these experiments, the following observations were made; (1) when insulin secretion was measured, in humans directly in the portal circulation, hyperglycaemia enhanced insulin secretion through the specific mechanism of amplification of the secretory burst mass while the insulin pulse frequency remained unchanged. (2) Acute partial inhibition of insulin secretion by diazoxide in patients with Type 2 diabetes mellitus did not effect the regularity of insulin secretion but did decrease the insulin clearance rate. (3) A deconvolution programme was established that was able to detect 90% of insulin pulses delivered by single human islets. (4). Using the novel islet perfusion system it was possible to show that human islets cultured at high glucose concentrations lost first phase insulin secretion and insulin pulse amplitude but these were restored in islets exposed to a transient period of b-cell rest. The overall conclusion of these studies is that the dynamics of insulin secretion are important as well as the absolute secretion rate and that the abnormalities in these dynamics may be related in part to b cell insulin stores that can be manipulated by transient b cell rest.
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Losada, Bohannon Liliana Cristina. "Identification and secretion of effectors from the Pseudomonas syringae type III secretion system." College Park, Md. : University of Maryland, 2004. http://hdl.handle.net/1903/1803.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2004.Thesis research directed by: Molecular and Cell Biology. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Bulahan, Rhobe Justine Artates. "Characterizing potential secretion components that increase secretion of recombinant proteins in Pichia Pastoris." Scholarly Commons, 2012. https://scholarlycommons.pacific.edu/uop_etds/812.
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The methylotropic yeast Pichia pastoris has been used for many applications, particularly for its ability to produce and readily secrete heterologous proteins. Nonetheless, there are obstacles in making this useful yeast into a more efficient secretion system that readily secretes problem proteins. In the Lin-Cereghino lab, mutant strains were developed by the method of restriction enzyme mediated integration. These mutants have the ability to secrete β-galactosidase at higher levels in comparison to the wild type. This study focused on characterizing the specific mutant ah2 for its ability to secrete HRP, SLPI, and CALB lipase proteins, as well as using transmission electron microscopy to observe the effect of the pREMI-Z mutation on the morphology. Analysis of the Ah2 protein resulted in a comparative β-galactosidase secretion study, as well as a growth rate study, between the original pREMI-Z ah2 mutant and ah2 mutant cells that were transformed with pKanB-AH2 rescue construct. Lastly, a cell localization experiment was done to examine where Ah2p localizes. By these analyses, we gain a bit more understanding of the P. pastoris secretion pathway, while also outlining a procedure by which to characterize the other pREMI-Z mutants.
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PEREZ, FRANCK. "Secretion regulee et secretion non conventionnelle : les homeoproteines comme outils et comme objets d'etudes." Paris 6, 1995. http://www.theses.fr/1995PA066693.
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Nous nous sommes d'abord attaches a developper un nouvel outil permettant l'etude, non invasive, de la secretion regulee. Nous avons tire parti des proprietes de l'homeodomaine d'antennapedia (antphd) qui a la capacite de traverser les membranes des cellules en culture par un mecanisme independant de l'endocytose classique. Nous avons fusionne a antphd les 33 acides amines carboxy-terminaux d'une petite proteine g, rab3a, impliquee dans l'exocytose regulee. Nous avons montre que la proteine de fusion ar3ac est internalisee sans degradation par des cellules en culture, validant ainsi antphd comme vecteur de peptides exogenes. Nous avons utilise ce vecteur pour etudier la fonction de rab3 dans le modele des cellules a prolactine. L'internalisation de la sequence carboxy-terminale de rab3a ainsi que celle de rab3b (et non celle de rab1 ou rab2) bloque efficacement l'exocytose regulee de ces cellules. Ceci montre que les proteines rab3 sont impliquees dans le controle de l'exocytose regulee et suggere que, malgre leur divergence, les sequences hypervariables des deux proteines rab3 interagissent avec un meme regulateur specifique. La mise en evidence de l'internalisation d'antphd a suggere un modele ou les proteines a homeodomaine pourraient, en plus de leur fonction en tant que facteurs de transcription, etre des facteurs nucleaires a action paracrine. Nous avons d'abord teste la capacite a traverser les membranes cytoplasmiques. Ajoutee dans le milieu extracellulaire, la proteine hoxa-5 est internalisee et s'accumule dans le noyau des cellules traitees. Les homeoproteines etant depourvues de peptide signal, leur eventuelle secretion ne pourrait se faire que par des voies non conventionnelles. Nos experiences de traduction in vitro et de surexpression dans des fibroblastes suggerent effectivement une interaction entre la proteine hoxa-5 et l'appareil de secretion, laissant ouverte la possibilite d'un role paracrine pour les proteines a homeodomaine
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Bruns, Caroline 1984. "GRh1-dependent unconventional protein secretion." Doctoral thesis, Universitat Pompeu Fabra, 2013. http://hdl.handle.net/10803/125070.
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A part de la secreció convencional, en la qual les proteïnes són transportades a través del reticle endoplasmàtic (RE) i de l'aparell de Golgi, s'han descrit, per a diferents proteïnes i en organismes diversos, rutes de secreció no-convencional que circumval·len l'aparell de Golgi. No obstant, aquests mecanismes de secreció no estan ben entesos. Se sap que per a la secreció no-convencional de la proteïna d'unió a acil-CoA Acb1 a Saccharomyces cerevisiae són necessàries diverses proteïnes, com ara l'ortòleg de GRASP Grh1, proteïnes relacionades amb l'autofàgia, proteïnes involucra-des en la fusió de membranes amb els endosomes, membres de la maquinària ESCRT, i la t-SNARE de la membrana plasmàtica Sso1. La manera per la qual totes aquestes proteïnes cooperen per a dur a terme la secreció d'Acb1 és encara una incògnita.
Els resultats de les nostres investigacions indiquen que sota inani-ció de nutrients, condició que indueix la secreció no-convencional d'Acb1, Grh1 es concentra en estructures membranoses prop dels llocs de sortida del RE, de manera dependent de fosfatidilinositol-3-cinasa. Aquestes membranes, en forma de tassa, estan enriqui-des en PI(3)P i contenen la proteïna d'ESCRT-I Vps23 així com les proteïnes d'autofàgia Atg8 i Atg9, reunint així diverses proteïnes necessàries per a la secreció d'Acb1. Hem batejat aquestes estructures CUPS (per les sigles en anglès de compartiment per a la secreció no-convencional de proteïnes), basant-nos en la seva forma i el seu contingut. Proposem que els CUPS són l'estació de sortida per a la formació d'intermediaris vesiculars dedicats a la secreció no-convencionals que contenen Acb1.Besides conventional secretion, in which proteins are transported through the endoplasmic reticulum (ER) and the Golgi complex, unconventional secretion routes bypassing the Golgi complex have been described for different proteins in several organisms. How-ever, the mechanisms of their release remain poorly understood. It was reported that the unconventional secretion of the acyl-CoA binding protein Acb1 from Saccharomyces cerevisiae requires a diverse group of proteins including the GRASP ortholog Grh1, autophagy-related proteins, proteins involved in fusion of membranes with endosomes, members of the ESCRT-machinery, and the plasma membrane t-SNARE Sso1. How these proteins work together for Acb1 secretion remains elusive. Our findings indicate that upon nutrient starvation, the condition known to induce unconventional secretion of Acb1, Grh1 is concentrated in a phosphatidylinositol 3-kinase-dependent manner to unique membrane structures near the ER exit sites. These membranes –shaped like cups– are enriched in PI(3)P and contain the ESCRT-I protein Vps23 as well as the autophagy-related proteins Atg8 and Atg9 thereby bringing together different proteins required for Acb1 secretion. We have named these structures CUPS (Compartment for Unconventional Protein Secretion), based on their shape and content. CUPS, we propose, are the starting point for the formation of Acb1-containing vesicular intermediates dedicated for unconventional secretion.
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Oritseje, Florence Remi. "Sugar secretion by Ricinus nectaries." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46480.
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Matthews, Jaimie P. "Local control of milk secretion." Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.484928.
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Milk secretion is controlled locally, within the mammary, gland, by milk removal. This control is believed to be mediated through feedback inhibition by milk constituents. The aim of this study was to investigate the effects of milk-borne peptides, implicated in the local control ofmilk secretion, on protein secretion in bovine mammosphere culture. These peptides, tenned A, Band C, had previously been shown in mammary acini cultures to acutely inhibit the secretion of milk proteins. To this end, a bovine mammosphere culture system was developed whereby bovine mammary epithelial cells cultured on EHS matrix were stimulated to express milk protein genes and secrete the major milk proteins casein, (3-lactoglobulin and lactoferrin. Additionally, the recent claim that the phosphopeptide (3casein 1-28 (Silanikove et ai, 2000) was capable of controlling milk secretion was investigated in'mouse mammary acini and bovine mammosphere culture. The secretory perfonnance of the bovine mammosphere system was validated by western blot measurement ofcasein, (3-lactoglobulin and lactoferrin in conditioned culture medium, . and mammosphere fonnation was investigated by SEM and cryosectioning of cultured cell aggregates. Experiments investigating the effects ofthe peptides tested all three peptides in combination (triple peptide treatment), the peptide pair AC, peptide B and (3-casein 1-28. Peptide effects were assessed by measuring 3H-Ieucine incorporation into TCA precipitable protein following 2 and 4 days oftreatment. Additionally, the effect 'ofthe triple peptide on (3-casein and lactoferrin mRNA abundance, and on the secretion of the major bovine milk proteins casein, (3-lactoglobulin and lactoferrin, was measured by real time RT-PCR and western blotting respectively. (3-casein and lactoferrin mRNA abundance was significantly reduced in bovine mammosphere culture following triple peptide treatment for two days. At concentrations of 1 pM and 10 pM of all three test peptides, triple peptide treatment caused 35 % and 47 % reductions, respectively, in (3-casein mRNA levels, and 21 % and 35 % reductions respectively in lactoferrin mRNA levels. This was not reflected in changes in milk protein secretion, with no significant effect observed on total protein secretion or individual milk protein secretion after two days of treatment. This may be a consequence of the insensitivity ofthe blotting technique used, resulting in trends in the data for the three milk proteins being rendered insignificant due to large variations between replicates. On the other hand, triple peptide treatment for two days significantly increased mRNA levels of the purported housekeeping gene GAPDH, which rose by 75 % when treated with 10 JlM of the triple peptide. These effects may have been associat~d with aggregation of the three peptide~in culture: incubation of peptides A, Band C together at 37°C for 25 h resulted in the formation of apeptide multimer, which was detected by gel exclusion fast protein liquid chromatography. Although no definitive role for these peptides in the local control of milk secretion was established, the results suggest that the peptides may control milk secretion by reducing milk protein gene expression. Furthermore, GAPDH has recently been implicated in the control of ER - Golgi transport in the early secretory pathway in NRK cells. This role offers a potential explanation for the increase in GAPDH mRNA induced by peptide treatment, and suggests that these peptides may effect milk secretion by blocking GAPDH mediated retrograde vesicular transport. The data obtained in this study has extended information on factors which appear able to control mammary function locally, and together with our increasing understanding of the control of secretory pathways, has provided scope for further investigation of the mechanism by which milk-borne factors control milk secretion.
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Le, Thi Thu Hang. "Type VI secretion system effectors." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0044/document.
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Mon travail a porté sur la caractérisation des effecteurs toxiques et protéines d’immunité du T6SS Sci-1 d’Escherichia coli Entero-agrégatif, éléments de la lutte inter-bactérienne. Nous avons identifié en outre Tle1, un effecteur de toxine codé par ce groupe et montré que Tle1 possède des activités de phospholipase A1 et A2 requises pour détruire la cellule proie dans la compétition interbactérienne. L'auto-protection de la cellule attaquante est assurée par une lipoprotéine de membrane externe, Tli1, qui lie Tle1 dans un rapport stoechiométrique 1: 1 avec une affinité nanomolaire et inhibe son activité phospholipase. Il a été prédit que la protéine 435 provenant à partir d'un groupe de gènes T6SS1 de l'agent pathogène AIEC LF82 est une phospholipase de la famille d'effecteurs Tle3 avec une activité PLA1. Sa toxicité peut être neutralisée par la protéine d'immunité cognate 434 qui est un Tli3 putatif, en formant le complexe de protéine Tle3 - Tli3. Les deux protéines séparées et leur complexe ont ensuite été appelées protéines complexes Tle3AIEC, Tli3AIEC et Tle3AIEC - Tli3AIEC, respectivement. Afin d'étudier plus en détail le mécanisme de Tle3-AIEC et de Tli3-AIEC, nous avons réalisé l'expression, la purification, la caractérisation, la cristallisation des deux protéines et des études cristallographiques de rayons X préliminaires du complexe Tle3-AIEC/Tli3-AIEC afin de comprendre comment la protéine Tle3-AIEC reconnaît et se lie à son effecteur apparenté Tli3-AIEC et inhibe son activité. Les données préliminaires de diffraction des rayons X ont été recueillies à partir de cristaux Tle3AIEC-SeMet/Tli3AIEC à une résolution de 3,8 ÅHere, we analyzed the Entero-aggregative Escherichia coli Sci-1 T6SS toxin effectors. We identified Tle1, a toxin effector encoded by this cluster and show that Tle1 possesses phospholipase A1 and A2 activities required for the inter-bacterial competition. Self-protection of the attacker cell is secured by an outer membrane lipoprotein, Tli1, which binds Tle1 in a 1:1 stoichiometric ratio with nanomolar affinity, and inhibits its phospholipase activity.The protein 435 from the pathogen AIEC LF82 has been predicted to be a phospholipase of the Tle3 effector family with PLA1 activity from a T6SS1 gene cluster. Its toxicity can be neutralized by the cognate immunity protein 434 that is a putative Tli3, by forming Tle3 - Tli3 protein complex. The two separated proteins and their complex were then called Tle3AIEC, Tli3AIEC and Tle3AIEC - Tli3AIEC complex proteins, respectively. In order to further investigate the related mechanism of Tle3AIEC and Tli3AIEC, we performed expression, purification, characterization, crystallization of the two proteins and preliminary X-ray crystallographic studies of the Tle3AIEC - Tli3AIEC complex in order to understand how Tle3AIEC protein recognizes and binds to its cognate Tli3AIEC effector and inhibits its activity. X-ray diffraction data were collected from selenomethionine-derivatize Tle3AIEC SeMet - Tli3AIEC crystals to a resolution of 3.8 Å
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Vieira, Elaine. "Signal Transduction of Glucagon Secretion." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6319.
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Eliasson, Lars. "On minor salivary gland secretion /." Göteborg : Department of Cariology, Institute of Odontology, Sahlgrenska Academy at Göteborg University, 2006. http://hdl.handle.net/2077/712.
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Lertkowit, Nantaporn. "Therapeutic modulation of gastric secretion." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569665.
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The pyloric antral hormone gastrin stimulates acid secretion and regulates proliferation, migration and differentiation of cells in the gastric epithelium. Hypergastrinaemia is associated with enterochromaffin-like (ECL) cell neuroendocrine tumours and may contribute to the progression of other tumours. Multiple active peptides may be derived from the gastrin precursor that are thought to act on different receptors. Therapy directed at suppressing the release of all forms of gastrin through the use of botulinum toxins (BoNTs) that specifically target secretion of G-cells, is therefore attractive. The aim of this study was to assess the feasibility of using retargeted BoNTs to inhibit gastrin release from human G-cells. Cultures of human antral gastric glands were shown by immunocytochemistry to express both t- and v-SNAREs (the proteins essential for regulated exocytosis which are cellular targets of BoNTs) in G-cells. In addition, G-cells in cultured glands were shown to secrete gastrin, basally and 'dose-dependently in response to gastrin releasing peptide (GRP). Acute treatment of glands with GRP-liganded BoNTs enhanced gastrin release, but two GRP receptor (GRPR) antagonists that attenuated the effect of GRP did not significantly inhibit gastrin secretion induced by GRP-liganded BoNTs. The prolonged treatment with GRP-liganded BoNTs, as well as other BoNT fusion proteins, did not suppress gastrin secretion. In further experiments, transfection of plasmids encoding active BoNT proteases and siRNA-mediated knockdown of SNAREs were employed. However, both methods failed to demonstrate the effect of disruption of SNARE complex formation on gastrin secretion, partly due to the low transfection efficiency attained. Treatment with either GRP or epidermal growth factor (EGF) stimulated proliferation of antral epithelial cells as indicated by EdU incorporation. However, no effect was observed with GRP-liganded BoNTs treatments. Taken together with the effect of GRPR antagonists the data suggest that these fusion proteins do not act on GRPR. Sub-epithelial cells such as myofibroblasts are known to release growth factors and other chemical mediators that regulate epithelial cell function. In pernicious anaemia patients there is hypergastrinaemia and it was considered possible that in this condition there was enhanced release of sub-epithelial gastrin secretagogues that could provide novel targets to direct BoNTs to G-cells. Microarray analysis of myofibroblasts from normal and pernicious anaemia subjects was performed and transcript profiles characterised to define putative novel paracrine stimulants of G-cells. The results indicated a possible role of keratinocyte growth factor (KGF) in controlling gastrin secretion, at least in the inflammatory condition. The expression of SNAREs in G-cells suggests selective targeting of BoNTs to these cells might be therapeutically useful. Further work is required to determine the feasibility of using GRP-retargeted BoNTs which appear to act on G-cells, though not via the GRPR. This work has also identified other possible retargeting strategies notably the use ofKGF-liganded BoNT fusion proteins.
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Finnie, Christine. "Protein secretion by Rhizobium leguminosarum." Thesis, University of East Anglia, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361420.
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Payne, Thomas. "Protein secretion in Saccharomyces cerevisiae." Thesis, University of Nottingham, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438772.
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Clarke, Mairi. "Secretion in 3T3-L1 adipocytes." Thesis, University of Glasgow, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439152.
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Cavet, Megan Elizabeth. "Intestinal secretion of organic solutes." Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318538.
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McNally, Oonagh Rose. "Monokine secretion by tumouricidal macrophages." Thesis, University of Ulster, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359349.
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Van, den Bosch Marion T. J. "Signalling mechanisms regulating platelet secretion." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.685919.
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Platelets are vital in haemostasis to prevent bleeding after injury. Uncontrolled platelet activation, however, leads to thrombosis. Platelet granule secretion is critical in thrombus formation and, due to the wide variety of granule contents released, also plays a role in many other physiological and pathological processes. The signalling molecule PKC is key in secretion of both dense and a-granules, but the downstream pathways that link it to secretion still need to be defined. A regulator of a-granule release, specifically, is ADP, which acts on the P2Y12 receptor after being secreted by dense granules. How it may control the release of functionally different cargoes is poorly understood. I first identified an extensive range of candidate platelet PKC substrates through proteomics screening using an anti-phosphopeptide antibody-based approach. Among these, I validated cytohesin-2, an Arf-GEF not previously characterised in platelets. This study demonstrated that, upon platelet activation, PKC phosphorylation of cytohesin-2 relieves the basal suppression of dense granule release, shedding new light on how PKC regulates secretion. I next examined the role of ADP in a-granule secretion with a specific focus on whether P2Y12 can induce differential cargo release, considering the implications for the clinical use of the P2Y12 blocker, clopidogrel. I investigated this using a P2Y12 antagonist and the Munc13-4-1 - mouse model where dense granule secretion is ablated and therefore autocrine ADP is not released. Results revealed that the secretion of certain a-granule contents is more dependent on ADP than others and that, in the absence of ADP signalling, granules may release contents without complete fusion with the plasma membrane. Taken together, this thesis provides new findings on the regulation of dense and a-granule secretion, which can be used in the design of improved therapies for thrombosis and other disorders where platelet granule contents play a role.
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Hu, Hong-Zhen. "Purinergic neurogenic intestinal mucosal secretion." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1100028634.
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Thesis (Ph. D.)--Ohio State University, 2004.Document formatted into pages; contains 171 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 Nov. 10.
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Zisakis, Athanasios. "Cytokine secretion in glioblastoma patients." Thesis, University of Central Lancashire, 2008. http://clok.uclan.ac.uk/19220/.
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Gliomas are the most common primary tumours of the central nervous system with a lethality rate approaching 80% in the first year of glioblastoma diagnosis. Their highly invasive nature renders local therapies such as surgery and radiation ineffective; whereas novel approaches such as immunotherapy are being actively studied as possible adjuncts in the treatment of patients with malignant gliomas. A number of factors have been proposed to play a role in glioma immune escape, including their poor immunogenicity since they do not express specific glioma antigens; their location within the CNS, which is considered to be an immune-privileged organ and some indications that glioma cells are capable of releasing various immunosuppressive cytokines, which inhibit the cytotoxic function of T cells. Cytokines are multifunctional pleiotropic proteins, which are involved in intercellular communication and cellular activation, and they may exert their effects in the CNS both directly and indirectly. Since they may originate either from peripheral immune organs, and cross the blood-brain barrier or they may be produced by the neuronal cells within the CNS, their properties are both immunoregulatory and neuromodulatory. This thesis investigated gliomas for the expression of cytokines and implicated their expression in the malignancy and the angiogenesis of the tumours. Cytokine secretion was evaluated from isolated peripheral blood mononuclear cells (PBMCs) of 33 patients with malignant gliomas (grade IV) immediately before surgery, in parallel with a control group of 23 age-matched individuals, and in 5 primary glioma cell cultures using the sensitive ELISPOT methodology. Thi cytokines tumour necrosis factor (TNF-a) and interferon (IFN7) were markedly reduced compared to control levels (P=0.01 and P < 0.001, respectively). In contrast, Th2 interleukins IL-(4) and IL-(10) were strongly expressed in both peripheral lymphocytes and glioma cell cultures (P < 0.05 and P < 0.001 respectively). Immunohistochemical localisation of IL-6, IL-8, COX, IL-lO, VEGF (vascular endothelial growth factor) and CD34 expression levels was performed in formalin-fixed paraffin-embedded tissue sections taken from 23 patients. Microvessels highlighted by means of anti-CD34 irnmunohistochemistry were enumerated with computer assisted image analysis. IL-6 was identified immunohistochemically in all specimens and showed an elevation in expression as necrosis grade increased (p=O.00S). IL-6 was also increased as the histological grade of the tumour increased (p0.020). IL-S expression was detected in all cases of gliomas with a mean of 19.5% of the cells. Expression was not related to either necrosis grade or increase in tumour grade. COX immunoreactivity was detected in all cases with an average of 29.1% positive cells. However, COX immunoreactivity was not significantly correlated with either necrosis or tumour grade. VEGF immunoreactivity occurred in 58.3% of cells and demonstrated a positive correlation with tumour grade (pzr0.035). The expression level of IL-10 was low both in terms of staining intensity and percentage of positive cells, and did not correlate with either necrosis or histological grade. CD34 immunoreactivity indicated that vascular volumetric parameters were not affected by either tumour or by necrosis grade. The expression of soluble CD95 as measured using a specific ELISA was not significantly (p > 0.05) reduced in the serum of 43 glioma patients compared to normal levels. In conclusion, these results indicate that patients harbouring malignant gliomas exhibit a broad suppression of cell-mediated immunity possibly due to the marked dysregulation in their cytokinetic profile. Glial tumours seem to induce a Thi (stimulatory) to Th2-type (inhibitory) cytokine shift which further supports humoral immunity at the expense of cell-mediated immune responses, contributing to the inefficient anti-tumour responses generated in these patients.
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LANGLOIS, ANNIK. "Contribution a l'etude de la regulation hormonale des secretions digestives chez le porc : effets du polypeptide pancreatique sur la secretion pancreatique exocrine et la secretion biliaire chez l'animal conscient." Paris 7, 1989. http://www.theses.fr/1989PA077080.
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Palomäki, Tiina. "Identification of a secretion signal for the type II protein secretion pathway in Erwinia carotovora." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/palomaki/.
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Odes, Harold Selwyn. "Regulation of duodenal mucosal bicarbonate secretion." Thesis, University of Cape Town, 1993. http://hdl.handle.net/11427/25542.
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The present research studied the regulation of duodenal bicarbonate secretion in the anaesthetized guinea-pig, using a model that permitted the study of active transport of bicarbonate. It was determined that dibutyryl 3' ,5'-cyclic adenosine monophosphate, vasoactive intestinal polypeptide, prostaglandin E2, carbachol and theophylline are the chief agonists of duodenal bicarbonate secretion. Vasoactive intestinal polypeptide and prostaglandin E2 act directly via distinct receptors on the duodenal enterocytes, activating adenylate cyclase and protein kinase A in sequence to initiate bicarbonate secretion. In addition, there is good evidence that the inositol phospholipid and protein kinase C cascade is also involved, possibly to a lesser extent, since tetradecanoyl-phorbolacetate and prostaglandin F2a were agonists of bicarbonate secretion. Carbachol, using a m-cholinoceptor pathway, stimulates duodenal bicarbonate secretion by releasing vasoactive intestinal polypeptide. Consistent with this finding is the observation that carbachol has no receptors on duodenal enterocytes. The role of the nicotinic pathway in bicarbonate secretion, however, remains uncertain. Duodenal bicarbonate secretion can be inhibited by somatostatin and acetazolamide. Somatostatin selectively suppresses carbachol-stimulated and VIP-stimulated duodenal bicarbonate secretion, but not PGE2-stimulated bicarbonate secretion. Receptors for somatostatin coupled to adenylate cyclase could not be detected on isolated duodenal enterocytes, which strengthens the hypothesis that carbachol does not act directly on these epithelial cells, but via a second transmitter, vasoactive intestinal polypeptide. Carbonic anhydrase activity is necessary for secretion of bicarbonate, since acetazolamide-inhibition of this enzyme decreased bicarbonate secretion, both basal and stimulated by many different agonists. Carbonic anhydrase serves as a common final step in the generation of bicarbonate in duodenal enterocytes. This enzyme was located in the cytoplasm of cells in the villus as well as the crypt cells, implying that bicarbonate secretion occurs along the length of the villus and crypt. In summary, the present research has shown direct stimulation of duodenal bicarbonate secretion by vasoactive intestinal polypeptide, which participates also in themcholinergic pathway, and by prostaglandin E2. Adenylate cyclase and protein kinase A appear to be the intracellular messengers with the primary function of initiating duodenal bicarbonate secretion. However, there is convincing evidence that the inositol phospholipid and protein kinase C cascade also activates this secretion. Somatostatin selectively stops duodenal bicarbonate secretion. Carbonic anhydrase activity in the crypt and villus is required as the final common step in bicarbonate production.
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Joseph, Sabrina S. "Functional Analysis of the YopN/SycN/YscB/TyeA Complex of Yersinia pestis." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/312.
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A plasmid-encoded Type III Secretion System (T3SS) is employed by human pathogenic yersiniae to inject effector proteins, termed Yops, directly into host cells. The secretion of Yops is tightly regulated, and occurs only upon contact with a eukaryotic cell in vivo or in media devoid of calcium in vitro. A complex containing the secreted protein YopN, its heterodimeric chaperone SycN/YscB, and TyeA is required to prevent secretion of effector Yops until the appropriate secretion-triggering signals are encountered. The mechanism by which these proteins regulate the T3S process is unknown. A mutational analysis of YopN and TyeA was performed to identify regions and residues of these proteins that are required to regulate Yop secretion. Amino-acid residues of TyeA were identified that were specifically required for the interaction of TyeA with YopN, confirming that the YopN/TyeA interaction is essential for the regulation of Yop secretion. Furthermore, analysis of TyeA mutants identified a surface-exposed region that was critical for the regulation of Yop secretion, but not required for interaction with YopN. YopN residues critical for the regulation of secretion clustered within the N- and C-terminal regions of YopN that were required to interact with the SycN/YscB chaperone and TyeA, respectively. No residues critical for the regulation of secretion were identified in the central region of YopN, suggesting that this region acts primarily to maintain proper positioning of the functional N- and C-terminal regions of this complex. A novel role for the chaperone binding domain (CBD) of YopN in the regulation of Yop secretion was identified. This role was separate from its role in binding the SycN/YscB chaperone and targeting YopN for secretion. Finally, it was demonstrated that the SycN/YscB chaperone is dispensable for the regulation of secretion if the expression of both YopN and TyeA is increased, indicating that these chaperones have no direct role in the regulation of Yop secretion. These results indicate that the YopN secretion signal and SycN/YscB chaperone function to efficiently target the YopN/TyeA complex to the T3S apparatus, whereas the YopN CBD and C-terminal region of YopN complexed with TyeA mediate the block in Yop secretion.
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Colombo, Marina. "Mechanisms of exosome biogenesis and secretion." Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T027/document.
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Les exosomes sont des vésicules membranaires de 30 à 100 nm de diamètre, formées dans les endosomes multivésiculaires et sécrétées par la plupart des cellules. Les propriétés biophysiques et biochimiques des exosomes ainsi que les mécanismes permettant leur biogénèse et sécrétion ont fait l’objet de nombreuses études. Cependant, ces derniers sont encore méconnus, limitant l'analyse des fonctions des exosomes in vivo. Au moins deux mécanismes ont été proposés pour la biogénèse des exosomes : un mécanisme nécessiterait l’action de protéines impliquées dans le tri endosomal, les ESCRT (« endosomalsorting complex required for transport »). Un autre mécanisme serait indépendant de leur fonction. La sécrétion des exosomes, une fois générés dans les endosomes, requiert la petite GTPase, Rab27a, comme montré dans un modèle cellulaire humain. Mes travaux de thèse ont porté sur l’étude des mécanismes moléculaires impliqués dans la biogénèse et la sécrétion des exosomes. Une première étude visant à analyser la fonction de Rab27a dans des cellules murines, m’a permis de mettre en évidence l’existence de différentes populations d’exosomes, dont la sécrétion dépend ou non de Rab27a. Une deuxième étude a eu pour objectif d’analyser l’implication des ESCRT dans la biogénèse des exosomes dans des cellules HeLa CIITA. Le criblage d’une librairie d’ARN d’interférence dirigés contre les différentes protéines ESCRT, a permis l’identification de 7 molécules potentiellement impliquées dans cette voie : HRS, STAM1, TSG101, leur inactivation induisant la diminution de la sécrétion des exosomes. L’inactivation de CHMP4C, VPS4B,VTA1 et ALIX, au contraire, l’augmente. L’inhibition de l’expression de ces candidats suivie de l’analyse des exosomes sécrétés a démontré l’hétérogénéité des vésicules sécrétées, et une modification de leur taille et de leur composition protéique par rapport aux cellules contrôle. Plus particulièrement, l’inactivation d’ALIX induit une augmentation de lasécrétion d‘exosomes de plus grande taille, et l’enrichissement sélectif en molécules de CMH de classe II. En accord, j’ai montré que les cellules inactivées pour ALIX, aussi bien des cellules HeLa que des cellules dendritiques humaines ont une plus forte expression de CMH de classe II à la surface et dans des compartiments intracellulaires. Ces résultats suggèrent l’implication de certains membres de la famille ESCRT dans la voie de biogenèse et sécrétion des exosomes, ainsi qu’un rôle potentiel d’Alix dans le trafic des molécules CMH de classe II, et dans la modulation de la composition protéique des exosomesExosomes are small membrane vesicles with sizes ranging from 30 to 100 nm in diameter, which are formed in multivesicular endosomes and secreted by most cell types. Numerous studies have focused on the biophysical and biochemical properties of exosomes, as well as the mechanisms of biogenesis and secretion of these vesicles. However, these aspects are not fully understood, which limits the analysis of the functions of exosomes in vivo. At least two mechanisms have been proposed for the biogenesis of exosomes : one would rely on the function of proteins involved in endosomal sorting, the ESCRT family (for “endosomal sorting complex required for transport”). Another mechanism would be independent of their activity. Once exosomes are formed in endosomes, their secretion requires the small GTPase RAB27A, as shown in a human cell line. The objective of my PhD project was to gain insights into the molecular mechanisms that drive exosome biogenesis and secretion. A first study performed to analyze the function of Rab27a in murine cells allowed me to show the existence of different populations of exosomes, dependent or not on Rab27a for their secretion. A second study was aimed at analyzing the involvement of ESCRT proteins in exosome biogenesis in HeLa-CIITA cells. Seven molecules potentially involved in this process were identified on the basis of the screening of an RNA interference library directed against the different ESCRT proteins: the inactivation of HRS, STAM1 and TSG101 induced a decrease in exosome secretion, whereas the down regulation of CHMP4C, VPS4B, VTA1 and ALIX increased it. Gene expression of the different candidate proteins was inhibited and exosomes secreted by these cells were analyzed: we showed the heterogeneity of the secreted vesicles, as well as an alteration of their size and protein composition, as compared to control cells. In particular, the inactivation of ALIX induced an increase in the secretion of larger vesicles, and the selective enrichment of these vesicles in MHC class II molecules. Accordingly, I showed that both HeLa-CIITA and human primary dendritic cells inactivated for ALIX possess a higher expression of MHC class II molecules at the cell surface and in intracellular compartments. These results suggest that some members of the ESCRT family are involved in the exosome biogenesis and secretion pathway, and propose a potential role of ALIX in the trafficking of MHC class II molecules and in the modulation of the protein composition of exosomes
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Beck, Caroline. "Assembly and secretion of atherogenic lipoproteins /." Göteborg : The Wallenberg Laboratory for Cardiovascular Research, Dept. of Molecular and Clinical Medicine, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, 2008. http://hdl.handle.net/2077/9855.
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Dickson, Suzanne Lee. "Neural control of growth hormone secretion." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283947.
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Turner, A. F. "The role of calmodulin in secretion." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375308.
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Lam, S. K. "The avian thyroid : Regulation and secretion." Thesis, University of Hull, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381877.
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Durie, Ruth Frances. "A population model of vasopressin secretion." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/2220.
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Computer modelling is a powerful tool for clarifying and testing theory. In neuroscience, this often means replicating firing patterns. Models need evaluation functions to quantify the significance of features in the firing patterns, but usually the effect of firing is insufficiently understood. The magnocellular vasopressin neurons of the hypothalamus do have an output that is both well understood and quantifiable: they secrete a hormone into the bloodstream in proportion to blood osmolarity and volume, regulating these properties within a narrow physiologically acceptable range. This response of vasopressin secretion to osmotic pressure must be maintained to defend blood pressure. The neurons display a distinctive phasic firing pattern, which a model was developed to mimic. A further, unique step was then taken of extending this model by developing a model for the effect of firing, a stimulus-secretion model. The firing pattern model and stimulus secretion model were then linked and then noisily duplicated to produce a population. This population had a measurable performance - secretion - allowing evaluation of the model in a novel fashion. The population could replicate the secretory response to osmotic pressure observed in vivo. It is possible to test the effect of features by incorporating them into the model and observing the response. A demonstration of this was conducted by changing the mix of excitatory and inhibitory PSPs, showing that inhibition was necessary for an efficient response. Effective techniques may well be reused elsewhere in the brain, so exploring their significance in a simple system may allow understanding of more complex ones. This project has constructed a model from firing to effect, offering novel possibilities for quantification and therefore evaluation. The main outcomes from this work are construction of a simple model system in which features can be benchmarked; that a integrate and fire model modified to include bistability can explain the firing of vasopressin neurons; that secretion could well also be controlled by a pool structure, similar to other secretory systems and that a population of these cells can produce a linear output. It has also confirmed that balanced excitatory and inhibitory input is necessary for the most efficient response. It shows that population performance is a trade-off between maximising efficiency, maintaining the secretory response over a wide dynamic range and maximising the maximum achievable secretion rate.
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Gandasi, Nikhil R. "Molecular mechanisms of biphasic insulin secretion." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-259071.
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Pancreatic beta-cells secrete insulin in response to increase in blood glucose concentration with a rapid first phase and slower, sustained second phase. This secretion pattern is similar in entire pancreas, isolated islets of Langerhans and single beta-cells and it is disrupted in type 2-diabetes. Insulin stored in secretory vesicles has to undergo preparatory steps upon translocation to the plasma membrane which include docking and priming before being released by exocytosis. A better understanding of the molecules involved in these steps is required to determine the rate limiting factors for sustained secretion. Here these processes were studied in real time using total internal reflection fluorescence microscopy, which enables observation of insulin granules localized at the plasma membrane. A pool of granules morphologically docked at the plasma membrane was found to be depleted upon repeated stimulations. Recovery of the docked pool of granules took tens of minutes and became rate limiting for sustained secretion. Shorter depolarization stimuli did not deplete the docked pool and allowed rapid recovery of releasable granules. When a new granule arrived at the plasma membrane, docking was initiated by de novo formation of syntaxin/munc18 clusters at the docking site. Two-thirds of the granules which arrived at the plasma membrane failed to recruit these proteins and hence failed to dock. Priming involved recruitment of several other proteins including munc13, SNAP25 and Cav1.2 channels. Exocytosing granules were in close proximity to Ca2+ influx sites with high degree of association with Cav1.2 channels. This is because of the association of these channels to exocytosis site through syntaxin and SNAP25. During exocytosis the assembled release machinery disintegrated and the proteins at the release site dispersed. Syntaxin dispersal was initiated already during fusion pore formation rather than after release during exocytosis. This was studied using a newly developed red fluorescent probe - NPY-tdmOrange2 which was the most reliable pH sensitive red granule marker to label insulin granules. Overall these data give new insights into the molecular mechanisms involved in biphasic insulin secretion. Disturbances in the secretion at the level of granule docking and fusion may contribute to the early manifestations of type-2 diabetes.
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Baxter, Debbie Jane. "Molecular mechanisms of biliary lipid secretion." Thesis, Liverpool John Moores University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298908.
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Pratignyo, Sigit Edi. "Invertase secretion by immobilised aspergillus spores." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357102.
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Graham, A. "The synthesis and secretion of glycerolipids." Thesis, University of Nottingham, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254976.
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Gage, Matthew Charles. "The proteomics of mast cell secretion." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434752.
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Barker, Adam Ian. "The epidemiology of early insulin secretion." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608170.
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Hine, Donna Louise. "Mitochondrial DNA depletion and insulin secretion." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/1906.
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Type 2 diabetes is an age-related condition and is characterised by a progressive decline in insulin secretion. Mitochondria play a key role in energy generation for insulin secretion. We previously reported an age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. TFAM, mtDNA Transcription Factor A, regulates mtDNA transcription and mtDNA copy number. Aims: We aimed to replicate the percentage decrease in mtDNA copy number that we observed with ageing in human islets, and to explore whether this affected mitochondrial function and insulin secretion. Methods: Two independent models of mtDNA depletion were created. The first model knocked down TFAM gene expression using siRNA technology. The second model subjected cells to didanosine, a nucleoside analogue of adenosine with a high affinity to POLG, a mtDNA polymerase. Results: Both models produced comparable levels of mtDNA depletion. Upon investigating the effects of partial mtDNA depletion on mitochondrial function, we found that both mtDNA depletion models displayed reduced mtDNA gene transcription and translation. However, neither model of mtDNA depletion affected ATP content or mitochondrial membrane potential. Glucose-stimulated insulin secretion was decreased following mtDNA depletion in the TFAM knock down cells which was rescued following treatment with the insulin secretagogue glibenclamide. Conversely, didanosine-induced mtDNA depleted cells showed increased insulin secretion. Conclusions: Both models generated a similar degree of mtDNA depletion, which was comparable to the percentage decrease seen in human islets with ageing. Both models were seen to impair mitochondrial function, but with opposing effects on insulin secretion. The TFAM model findings are in line with previous studies of severe mtDNA depletion, suggesting that the increase in insulin secretion seen with didanosine is due to drug off target effects. Strategies to slow islet mtDNA depletion in man could help to preserve insulin secretion and delay the development of Type 2 diabetes.
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De, Obeso Fernandez Del Valle Alvaro. "Protein secretion and encystation in Acanthamoeba." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31483.
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Free-living amoebae (FLA) are protists of ubiquitous distribution characterised by their changing morphology and their crawling movements. They have no common phylogenetic origin but can be found in most protist evolutionary branches. Acanthamoeba is a common FLA that can be found worldwide and is capable of infecting humans. The main disease is a life altering infection of the cornea named Acanthamoeba keratitis. Additionally, Acanthamoeba has a close relationship to bacteria. Acanthamoeba feeds on bacteria. At the same time, some bacteria have adapted to survive inside Acanthamoeba and use it as transport or protection to increase survival. When conditions are adverse, Acanthamoeba is capable of differentiating into a protective cyst. This study had three objectives. First, isolate and identify new FLA and Acanthamoeba strains. Second, identify encystation factors of Acanthamoeba. Third, identify and characterise new potential antimicrobial proteins produced by Acanthamoeba. The isolation of environmental amoebae was performed, and several strains of Acanthamoeba were identified from previously known genotypes. Also, two new species of FLA were identified: Allovahlkampfia minuta and Leptomyxa valladaresi. The dynamics of encystment were studied in different strains of Acanthamoeba. RNAseq was used to study gene expression during differentiation and identify differentially expressed genes. We identified different encystment factors including at least two encystment related proteases. A new antimicrobial zymogram was developed that identified antimicrobial proteins being secreted by Acanthamoeba. A 33 kDa protease was found to be able to lyse bacteria. We created DNA constructs encoding the protease and a lysozyme from Acanthamoeba for heterologous expression. The genes were successfully cloned. However, bacteria were not able to produce the proteins most probably due to their antimicrobial characteristics. Further studies are required regarding encystment and antimicrobial factors identified. Such experiments should help elucidate critical factors of Acanthamoeba's biology that could help treat several infections.
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Modlin, Irvin M. "Control mechanisms of mammalian pepsinogen secretion." Doctoral thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/27173.
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The objective of this thesis was to delineate aspects of the control mechanisms of mammalian pepsinogen secretion. In order to accomplish this goal, a comprehensive study was undertaken which would establish an historical perspective of the subject, validate appropriate methodology and then seek to answer specific questions regarding the physiology and pathophysiology of pepsinogen secretion. More specifically, the objectives of this thesis were: 1. To review the historical background of the subject of pepsinogen in the context of the physiology of digestion with specific emphasis on the work and lives of the two major initial proponents of pepsinogen research (Schwann and Langley). 2. To provide a contemporary overview and evaluation of the current status of pepsinogen pathophysiology. 3. To modify and adapt experimental models necessary for the study of pepsinogen and acid secretion in mammalian gastric mucosa and cells. 4. To establish and validate a pepsinogen assay sensitive and reproducible enough for use in mammalian mucosa! and cellular secretory systems. 5. To delineate the fundamental (second messenger) control mechanisms (cyclic AMP and calcium calmodulin) of pepsinogen secretion in the isolated gastric gland model. 6. To define whether the process of pepsinogen secretion is independent of acid secretion in intact mucosa! preparations. 7. To identify different classes of pharmacological agents which would inhibit pepsinogen secretion and/or release. 8. To identify whether conditions present in critically ill patients liable to mucosal "stress ulceration" might influence the release of pepsinogen.
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Almutairi, Mohammed Mashari. "Role of Bumetanide on Insulin Secretion." Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1408377608.
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Hill, Eric J. "Polarised secretion of leukaemia inhibitory factor." Thesis, Aston University, 2004. http://publications.aston.ac.uk/11019/.
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Leukaemia inhibitory factor (LIF) is a cytokine that is active on a wide variety of cells. Multiple LIF transcripts have been described. The transcripts LIF-D and LIF-M encode different signal peptides, which in mouse have been associated with differential localisation of the mature protein. LIF-D is associated with a freely diffusible protein, whereas the LIF-M is associated with the extracellular matrix. The polarity of LIF secretion has yet to be described and could illuminate the mechanisms of LIF localisation. Here the polarised endogenous secretion of human LIF and IL-6 in Caco-2 cells was characterised under normal culture conditions and following induction with IL-1b. Whether the apical or basolateral membrane was stimulated influenced the pattern of secretion (LIF: Unstimulated, 59% basolateral. Dual stimulation, 68% basolateral. Basolateral stimulation, 79% basolateral. Apical stimulation, 53% basolateral). IL-6 displayed a similar dependence on the site of stimulation but was predominantly secreted at the membrane that was stimulated. To determine the effect of the alternate signal peptides on the polarity of LIF secretion, LIF was epitope tagged with FLAG. Epitope-tagging with FLAG was used to separate endogenous from exogenous protein expression. However, despite the normal biological activity of LIF-FLAG and detection of the FLAG in a western blot, detection of the LIF-FLAG under non-reducing conditions was not observed, and therefore it was unsuitable for secretion studies. Untagged LIF was expressed exogenously in Madin-Darby canine kidney (MDCK) cells under the control of a tetracycline response promoter that allowed a variety of LIF expression levels to be tested. Exogenous murine LIF was secreted predominantly from the apical (60%) membrane of MDCK cells irrespective of the signal peptide expressed.
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Garrison, Jennifer L. "Small molecule modulation of protein secretion." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3261264.
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Ravindran, Sandeep. "Effector protein secretion by toxoplasma gondii /." May be available electronically:, 2009. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
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Holland, Alexandria. "Optimisation of feedstock utilisation by Geobacillus thermoglucosidasius." Thesis, University of Bath, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.723323.
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Geobacillus thermoglucosidasius (GT) is a thermophilic, ethanol-producing bacterium capable of utilising both hexose and pentose sugars for fermentation. One strategy to improve fermentation yields would be to engineer GT strains to secrete hydrolases to increase the amount of available sugars from various feedstocks. Therefore, optimised protein secretion would be vital to improve feedstock utilisation. Secretion in the related mesophile Bacillus subtilis (BS) has been well studied, and several strategies have been developed to improve secretion of heterologous proteins in BS, one such strategy being the manipulation or changing of the signal peptide. One aim is to identify any differences in the secretion machinery and signal sequences between GT and BS. Another aim is to analyse any effects of overproduction of hydrolases and to identify any bottlenecks in protein secretion in GT. Using bio-informatics tools we find that although GT is a thermophile, the signal peptides in this organism do not differ significantly from those in BS. From a shotgun mass spectrometry approach it was also observed that unlike BS, GT undergoes significant cell lysis during growth releasing cytoplasmic proteins into the extracellular milieu, which could have implications on the levels of secreted hydrolases. A model enzyme was selected and over-produced at high levels in order to stress the secretion system in GT so as to identify any bottlenecks in secretion. The results thus far indicate that the rate limiting step in secretion could be post-translocation where the enzyme is degraded by proteases in the cell wall and extracellular milieu. The addition of protease inhibitor to growth media, increases the activity and abundance of the enzyme, suggesting that proteolysis may be a major factor when over-producing secreted enzymes at high levels.
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