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1

Tosh, F. Donald. "Adherence of Candida albicans to mucosal surfaces." Thesis, University of Glasgow, 1991. http://theses.gla.ac.uk/40982/.

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The research described in this thesis was aimed at the characterization of the Candida adhesin, and elucidation of the nature of the human epithelial cell receptor with which it combines. Previous data have shown that the fibrillar mannoprotein layer, produced when Candida albicans is grown in high concentrations of galactose, contains the proteinaceous adhesin. Different Candida species from leukoplakia patients were assayed for their ability to adhere to buccal cells. The results supported previous conclusions that there is a relationship between the ability of different Candida albicans strains to adhere to epithelial cells and their capacity for cell surface modification. Extracellular polymeric material (EPM) was isolated from culture supernates of C. albicans after growth in medium containing 500 mM galactose. When used to pretreat buccal epithelial cells, EPM inhibited adherence, which suggested that it contains an adhesin that binds to, and blocks epithelial cell receptors. Fractionation of EPM by affinity chromatography was performed. An index, the adhesion inhibition index (AII) was used to compare the various "lectin-like" components isolated from crude EPM. These studies indicated that use of different buccal cell donors gave different results, with the same C. albicans strain. Attempts to resolve EPM by SDS-polyacrylamide gel electrophonesis had previously proved unsuccessful. However here, success was achieved using the silver-stain technique. Chemical and enzymatic digestion of the EPM indicated that the protein portion , of the glycoprotein was more important than the carbohydrate at inhibiting adherence. N-Glycanase, papain, mild alkali treatment of EPM, followed by Synsorb-H-2 affinity adsorption chromatography, resulted in a purification of the yeast adhesin of more than 220 fold, relative to the crude EPM (on a protein weight basis). The nature of the epithelial cell receptor for C. albicans was investigated with potential receptor analogues such as sugars, lectins, monoclonal antibodies and saliva. The adhesion of C. albicans to the buccal cells of blood groups A and O, was found to be significant with respect to secretor status but not blood group. Caution should be shown in the interpretation of sugar inhibition tests. Nevertheless, N-acetyl-D- galactosamine was the most effective single sugar as an inhibitor of adhesion for buccal cell donors of blood group A; N-acetyl-D-galactosamine is the immunodominant blood group sugar for group A cells and the possibility exists that the blood group oligosaccharide on the buccal cell surface functions as the receptor for yeast adhesion. Further work would be needed to establish whether the purified adhesin had any therapeutic value in treating Candida infections.
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2

Frede, Annika. "Modulation of inflammatory responses at mucosal surfaces by nanoparticle-based siRNA delivery." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-inflammatory-responses-at-mucosal-surfaces-by-nanoparticlebased-sirna-delivery(188e5303-0b29-4d14-8635-7d1fcf448270).html.

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In this thesis nanoparticles consisting of a calcium phosphate core encapsulated by poly(lactic-co-glycolic) acid and polyethylenimine were developed for the delivery of siRNA in vivo. The nanoparticles were efficiently endocytosed by different cell types in vitro without exhibiting cytotoxic characteristics. Without possessing endogenous immune response activating properties, the nanoparticles had a highly preferable composition for the delivery of siRNA and subsequent gene knockdown. The delivery of siRNA with nanoparticles was tested in two different murine disease models: DSS-induced colitis as model for human IBD and a TH1-induced lung inflammation as model for COPD. In IBD and COPD chemokines and cytokines are predominant players in the progression of the inflammatory response. The local interference of cytokine signalling mediated by siRNA-loaded nanoparticles might therefore be a promising new therapeutic approach. In both murine models, the aim was to deliver siRNA directed against inflammation related cytokines by nanoparticles for the local treatment of mucosal inflammation. The local administration of nanoparticles loaded with siRNA to mice suffering from intestinal or lung inflammation led to significantly decreased target gene expression on mRNA as well as protein level in biopsies from the target tissues. Furthermore, reduced cytokine levels were accompanied by diminished inflammatory pathologies and augmented clinical signs of sickness. The results of this thesis indicate that a specific and local modulation of inflammatory responses by nanoparticle-based siRNA delivery is feasible and demonstrates a major therapeutic potential.
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3

O'Mahony, Rachel Mary. "Novel inhibitors of adhesin-receptor interactions involved in microbial infection at mucosal surfaces." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1446253/.

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Microorganisms are becoming increasingly resistant to current antimicrobial agents and therefore new strategies and agents are being developed to combat infection. One strategy is to target and block the first step of microbial infection (adhesion of the microbe to the host tissue) by using molecules that mimic (or antibodies against) the microbial adhesin or its complementary host cell receptor. Plants have also been shown to provide natural sources of antimicrobial substances as well as inhibit microbial adhesion. One major problem in adhesion-inhibition studies has been the accurate quantification of adhesion. Most investigators have relied on manual counting while a few have used automated methods using image analysis software. The first aim of this study was therefore to compare the effectiveness of several current software packages, to develop the most accurate method of quantification and to use this method to test potential inhibitors of microbial adhesion. The organisms under investigation in this project were Candida albicans and Helicobacter pylori, both of which are becoming resistant to available antibiotic treatments. A new and accurate method of quantification was developed for assessing microbial adhesion using 'Metamorph' image analysis software. Aided by this system, several domain antibodies, carbohydrates and plant extracts were found to be successful inhibitors of C. albicans and H.pylori adhesion in vitro and therefore have the potential to form the basis of new and alternative therapies to treat infection caused by these microorganisms. Additionally, because it is not fully known why H. pylori preferentially colonises specific topographical regions of the human stomach, the second aim was to compare its adhesion to different topographical regions of the stomach, in an attempt to explain this phenomenon. No difference was found between the receptors present in the antrum or fundus of inflamed human stomachs. However, further investigations involving both inflamed and non-inflamed stomachs are warranted.
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4

Sid, Hicham [Verfasser]. "Host-pathogen interactions during mono- and multicausal infections of avian mucosal surfaces / Hicham Sid." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2016. http://d-nb.info/1123677514/34.

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5

Islam, Ayesha. "Interactions of human immunodeficiency virus type 1 with mucosal epithelial surfaces and Candida albicans." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/interactions-of-human-immunodeficiency-virus-type-1-with-mucosal-epithelial-surfaces-and-candida-albicans(c8f83c82-f3af-469e-9790-8626f4b96d0f).html.

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Despite the magnitude of the HIV pandemic, the events involved in the initial HIV-1 entry into the body are not yet fully understood. Although the principle mode of HIV-1 transmission is through mucosal surfaces, the oral epithelium appears to be less susceptible to HIV-1 infection than vaginal epithelium. In addition, infections with co-pathogens that elicit immune activation, such as Candida albicans, may also promote HIV-1 infection. The project objectives are to determine whether (i) HIV-1 is able to bind and integrate into oral and vaginal epithelial cell lines, (ii) epithelial cell lines are able to transfer viable virus from their surface to permissive cells, (iii) epithelial cells are responding to HIV-1 with changes in intracellular signalling or gene expression profiling, and (iv) Candida albicans can affect epithelial susceptibility to HIV-1 or whether it can bind and/or transfer HIV-1 to permissive cells. We demonstrate that oral, oro-pharyngeal and vaginal epithelial cell lines do not express canonical receptors for HIV-1 but they do express other receptors known to promote HIV-1 binding, including GalCer and syndecan-1. Oral and vaginal epithelial cell models can capture HIV-1, which subsequently does not appear to integrate into the epithelial genome. Therefore, viral replication is not supported. Notably, HIV-1 captured on the epithelial surface remains infectious and can be transferred to permissive cells. Furthermore, like epithelial cell lines, C. albicans can also directly bind and transfer HIV-1 to permissive cells. The carbohydrate moieties chitin and β-glucan appear to play a role in mediating viral binding. Notably, transfer of HIV-1 to permissive cells occurs from chitin but minimally from p-glucan. This indicates that fungal-viral interactions may occur at mucosal surfaces that potentially promote HIV-1 infection.
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6

Stange, Jörg. "Studies on host-pathogen interactions at mucosal barrier surfaces using the murine intestinal parasite Eimeria falciformis." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2013. http://dx.doi.org/10.18452/16716.

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Wir nutzten in dieser Studie den apikomplexen Parasiten Eimeria falciformis als Modell. Unsere Ergebnisse zeigen, dass das in infizierten Wildtypmäusen dominierende Zytokin IFN-γ für Immunschutz und für die Entwicklung der Darmpathologie entbehrlich war. E. falciformis-infizierte IFN-γR-/- and IFN-γ-/- Mäuse zeigten extremen Körpergewichtsverlust und starke Pathologie im Darm. Die Entwicklung des Parasiten in diesen Mäusen war überraschenderweise reduziert. Diese Beobachtungen gingen mit einer drastisch erhöhten Produktion von parasiten-spezifischem IL-17A und IL-22 durch CD4+ T Zellen einher. Gleichzeitige Neutralisierung von IL-17A und IL-22 in E. falciformis-infizierten IFN-γR-/- Mäusen verringerte den Körpergewichtsverlust und die Darmpathologie, und führte zu einer erhöhten Ausscheidung von Parasiten. Die Behandlung einer E. falciformis-infizierten intestinalen Epithelzelllinie mit IL-17A oder IL-22 führte zu einer signifikant reduzierten Entwicklung von E. falciformis in vitro. Diese Daten demonstrieren erstmalig einen anti-parasitären Effekt von IL-22 im Darm und deuten auf redundante Rollen von IL-17A und IL-22 im Hinblick auf die Förderung von Darmpathologie in Abwesenheit von IFN-γ hin. Um E. falciformis als Modellsystem weiter zu entwickeln, haben wir die Transfektion von E. falciformis Sporozoiten mit verschiedenen Plasmiden die den Reporter YFP und den Resistenzmarker DHTS enthalten etabliert. Rektal in Mäuse injizierte Sporozoiten entwickelten sich erfolgreich zu Oocysten, wenn auch mit geringerer Effizienz im Vergleich zur oralen Infektion mit Oozysten. Wiederholte in vivo Selektion YFP-exprimierender Oozysten führte zu Populationen mit maximal 34 % YFP-exprimierenden Parasiten. Wir demonstrieren in dieser Arbeit zum ersten Mal die Transfektion von E. falciformis und zeigen Perspektiven im Hinblick auf die Etablierung einer stabil transgenen Parasitenlinie auf.
The roles of Th1 and Th17 responses as mediators of host protection and pathology in the intestine are the subjects of intense research. Here we investigated a model of intestinal inflammation driven by the intracellular apicomplexan parasite Eimeria falciformis. Although IFN-γ was the predominant cytokine during E. falciformis infection in wild type mice, it was found to be dispensable for host defence and the development of infection-driven intestinal inflammation. E. falciformis-infected IFN-γR-/- and IFN-γ-/- mice developed dramatically exacerbated body weight loss and intestinal pathology, but surprisingly harboured fewer parasites. This was associated with a striking increase in parasite-specific IL-17A and IL-22 production in the mesenteric lymph nodes and at the site of infection. Concurrent neutralisation of IL-17A and IL-22 in E. falciformis infected IFN-γR-/- mice resulted in a reduction in infection induced body weight loss and inflammation and significantly increased parasite shedding. Taken together these data demonstrate for the first time an anti-parasitic effect of IL-22 during an intestinal infection and suggest that IL-17A and IL-22 have redundant roles in driving intestinal pathology in the absence of IFN-γ signalling. To further develop E. falciformis as a model system, we established transfection of E. falciformis sporozoites using various plasmids that contain the fluorescent reporter YFP and the resistance marker DHTS. Sporozoites applied rectally to mice were shown to complete their life cycle, albeit with a lower efficiency in comparison to oral infection with oocysts. Repeated in vivo selection using pyrimethamine and/or FACS and manual sorting led to a maximum percentage of 34 % YFP-expressing oocysts. Taken together, we demonstrate for the first time transfection of E. falciformis and provide perspectives for further work on the establishment of a stable transgenic parasite line.
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7

Shawky, Samia Ali. "Maternally acquired immunoglobulin G in turkey poults : distribution on mucosal surfaces and protective role in the gut /." The Ohio State University, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487842372894338.

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8

Clarke, Christopher John. "Antigen presentation to mucosal surfaces : the influence of liposome entrapment and cholera toxin on the immune response to fed protein antigens." Thesis, University of Bristol, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330040.

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9

Stange, Jörg [Verfasser], Richard [Akademischer Betreuer] Lucius, Kai [Akademischer Betreuer] Matuschewski, and Alf [Akademischer Betreuer] Hamann. "Studies on host-pathogen interactions at mucosal barrier surfaces using the murine intestinal parasite Eimeria falciformis / Jörg Stange. Gutachter: Richard Lucius ; Kai Matuschewski ; Alf Hamann." Berlin : Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2013. http://d-nb.info/1033837199/34.

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10

Burden, Matthew. "An investigation into making a bispecific scFv antibody that recognises both pIgR. and IgG Fc by phage display technology in order to transport IgG to mucosal surfaces." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486114.

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The polymeric immunoglobulin receptor (pIgR) transports polymeric immunoglobulins across the epithelial cell layer into mucosal secretions. It was hoped that pIgR could be exploited to actively transport IgG by constructing a bispecific· molecule capable of simultaneously binding IgG and pIgR. Increasing the IgG' delivered to mucosal secretions may benefit patients undergoing intravenous immunoglobulin therapy by increasing the mucosal defence against invading pathogens. Phage display, using synthetic phagemid libraries (I and J), was used to generate scFv to secretory component (SC), the extracellular portion of pIgR. Phage raised against peptides of pIgR yielded no SC binding clones. Subsequent selections against SC were successful. An in vitro transport assay was used to measure transport of anti-SC clones. No transport could be detected in the initial assay, so it was optimised to increase sensitivity. Subsequent selections using this assay suggested that the dominant epitope recognised by the J library in SC was distinct from those that bound on pIgR that led to the highest level of transport. The dominant epitope recognised by the I library was present on both pIgR and SC. The clones were of weak binding possibly because of the restrictive design ofthe library and apparent bias seen in the sequences ofthe unselected clones. Affinity maturation was applied to the VL CDR3 in an attempt to improve the level of transcytosis of an anti-SC clone in the transport assay. A small improvement of transport was observed. Recombinant techniques used to create a bispecific scFv tandem were unsuocessful, in that its construction led to loss of binding specificities of both scFvs. Investigations in vivo were carried out as the first step of establishing an assay to test the final bispecific reagent. Study of the transport of an anti-pIgR phage suggested it was enriched compared to control phage in the faeces of mice injected intravenously.
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11

Howard, Sean Ryan. "Mucosal surface molecules of the urinary bladder." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ38592.pdf.

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12

Bäckhed, Fredrik. "Role of toll-like receptors in host responses to mucosal bacterial infections /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-367-8/.

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13

Chen, Nan. "Size and surface properties determining nanoparticle uptake and transport in the nasal mucosa." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/1562.

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14

Pountney, David James. "Studies of the mechanism and regulation of intestinal iron absorption with special reference to a mucosal surface reducing activity." Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339140.

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15

Juel, Ingebjørg S. "Intestinal injury and recovery after ishemia - An experimental study on restitution of the surface epithelium, intestinal permeability, and release of biomarkers from the mucosa." Doctoral thesis, Norwegian University of Science and Technology, Department of Cancer Research and Molecular Medicine, 2007. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-1817.

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16

Nielson, Joseph R. "Three Dimensional Characterization of Vocal Fold Fluid Structure Interactions." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3662.

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Voice quality is strongly linked to quality of life; those who suffer from voice disorders are adversely affected in their social, family, and professional relationships. An effort has been made to more fully understand the physics behind how the voice is created, specifically the fluid structure interactions that occur during vocal fold vibration. Many techniques have been developed and implemented to study both the motion of the vocal folds and the airflow that creates the motion. Until recently these techniques have sought to understand a highly three-dimensional phenomenon with 1D or 2D perspectives.This research focuses on the development and implementation of an experimental technique to obtain three-dimensional characterizations of vocal fold motion and fluid flow. Experiments were performed on excised human vocal fold models at the University Hospital Erlangen Medical School in Erlangen, Germany. A novel technique for tracking the motion of the vocal folds using multiple camera viewpoints and limited user interaction was developed. Four high-speed cameras (2000 fps) recorded an excised vocal fold model vibrating at 250 Hz. Based on the images from these four cameras a fully 3D reconstruction of the superior surface of the vocal folds was achieved. The 3D reconstruction of 70 consecutive time steps was assembled to characterize the motion of the vocal folds over eight cycles. The 3D reconstruction accurately modeled the observed behavior of vocal fold vibration with a clearly visible mucosal wave. The average reprojection error for this technique was on par with other contemporary techniques (~20 micrometers). A whole field, time resolved, three-dimensional reconstruction of the vocal fold fluid flow was obtained using synthetic aperture particle image velocimetry. Simultaneous 3D flow fields, subglottal pressure waves, and superior surface motion were presented for 2 consecutive cycles of oscillation. The vocal fold fluid flow and motion measurements correlated with behavior observed in previous three-dimensional studies. A higher resolution view of one full cycle of oscillation was compiled from 16 time resolved data sets via pressure data. The result was a full three-dimensional characterization of the evolution and disintegration of the glottal jet.
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17

VanCott, John Louis. "Protective immunity against transmissible gastroenteritis virus (TGEW) : enumeration of antibody-secreting cells and identification of mononuclear cell surface markers in systemic and mucosal lymphoid tissues of young pigs exposed to TGEV... /." The Ohio State University, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487842372895095.

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18

Murray, Preston Roylance. "Flow-induced Responses of Normal, Bowed, and Augmented Synthetic Vocal Fold Models." BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/2873.

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The voice is the primary mode of communication for humans. Because the voice is so important, voice disorders tend to severely diminish quality of life. A better understanding of the physics of voice production can help to improve treatment of voice disorders. For this thesis research a self-oscillating synthetic vocal fold model was developed, compared with previous synthetic vocal fold models, and used to explore the physical effects of augmentation injections on vibration dynamics. The research was conducted in two stages. First, four vocal fold models were evaluated by quantifying onset pressure, frequency, maximum glottal gap, flow rate, and medial surface motion. The newly developed model, differentiated from the other models by the inclusion of more layers, adjusted geometry, and an extremely soft superficial lamina propria layer, was included in this study. One of the models, created using MRI-derived geometry, had the most defined mucosal wave. The newly-developed model had the lowest onset pressure, flow rate, and smallest maximum glottal width, and the model motion compared very well with published excised human larynx data. Second, the new model was altered to simulate bowing by decreasing the volume of the body layer relative to that of a normal, unbowed model. Two models with varying degrees of bowing were created and tested while paired with normal models. Pre- and post-injection data (onset pressure, vibration frequency, glottal flow rate, open quotient, and high-speed image sequences) were recorded and compared. General pre- to post-injection trends included decreased onset pressure, glottal flow rate, and open quotient, and increased vibration frequency. Additionally, there was a decrease in mucosal wave velocity and an increase in phase angle. The thesis results are anticipated to aid in better understanding the physical effects of augmentation injections, with the ultimate goal of obtaining more consistent surgical outcomes, and also to contribute to the advancement of voice research through the development of the new synthetic model.
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19

Legrand, Thibault Philippe Raymond Albert. "The functional role of the fish microbiome." Thesis, 2021. https://hdl.handle.net/2440/135964.

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Aquaculture is the fastest growing sector of agriculture, currently producing more than half of all seafood. Within Australia, yellowtail kingfish (Seriola lalandi) is an emerging fish species farmed in temperate waters. While the production of this species is in constant growth, the development of this industry is not without hurdles. For instance, diseases associated with the mucosal surfaces of the fish (e.g. gut enteritis - an inflammation of the gastrointestinal tract) are a recurrent issue in the production of this species. However, the underlying mechanisms inducing this gut inflammation remain poorly understood. New research has elucidated the importance of microbial communities in mucosal surfaces (microbiota) that may play a key role in this disease. These mucosal surfaces (comprising the gut, skin, gill and olfactory organs) support important functions for the host including digestion and nutrient uptake, osmoregulation and recycling waste products, provide the first line of defence against potential pathogens, and form a barrier – along with the host microbiota. Most fish mucosal diseases are linked to the disruption of these microbial communities, which no longer supports the wellfunctioning of these mucosal surfaces and therefore influence fish health. Within this thesis, I synthesise our current understanding of the fish microbiota, in particular in a health and disease context (Chapter I). I also explain how this wealth of information can be of particular value for the aquaculture industry by proposing new prospects to improve the fish resilience to disease. Using the yellowtail kingfish as species model, I explore both changes in the fish microbiota across the gut and skin mucosal surfaces and the evolution of the fish immune response during gut enteritis (Chapter II). By doing so, I also investigate important host-microbiota interactions to further understand the interplay between the fish immune system and its microbiota during disease. Of particular note, I found significant gene expression changes (e.g. upregulation of cytokines related genes) and microbiota perturbations (e.g. loss of diversity) in the skin of fish at the early state of the disease, revealing the sensitivity of this mucosal tissue in response to a gut disease. In Chapter III, I explored the impacts of novel treatment options by modulating the fish microbiota using faecal microbiota transplantation (FMT) in conjunction or in replacement of antibiotic treatment to re-establish a more balanced and healthy fish gut microbiota. This also shed light on the process of microbial repopulation following antibiotic exposure, a feature well under studied though paramount for the successful recovery of the host. In this study, antibiotics greatly influenced the fish gut microbiota and was marked by a significant decrease in diversity, accompanied by an increase in the relative abundance of an uncultured Mycoplasmataceae sp. in the antibiotic treated fish. The effect of the FMT treatment appeared to vary substantially between individuals, and was associated with stark differences in bacterial diversity, suggesting that modulation of the gut microbiota can only be induced in some individuals and for a short time period. In the final Chapter, I develop a new laboratory protocol using PMA to assess microbial viability in the fish gut microbiota. Such information is particularly relevant when investigating the influence of the microbiota in health and disease to better characterise the activity and likely role of these microbial communities, a feature currently overlooked with the gold standard 16S metabarcoding approach. Using this approach, I found that PMA treatment reduced the microbial diversity and richness from both digesta and mucosal gut samples, as well as induced a loss of important bacterial members considered as beneficial (e.g. lactic acid bacteria). In essence, my research aimed to explore the involvement of the fish microbiota in the health and fitness of the host and improve our understanding of host-microbiota interactions. Such knowledge would ultimately allow us to better modulate the fish microbiota and develop new treatment options. Overall, my thesis contributes to fish health research by providing context and perspective of the fish microbiota. Even though much more effort is needed, I aimed at producing translational research by demonstrating the importance of such studies for the aquaculture industry to potentially enhance fish resilience to infection/disease and ultimately improve current production systems.
Thesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 2021
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20

Tsai, Jeng-Shiang, and 蔡政翔. "Surface assembly of Poly (I:C) on Polyethyleneimine modified Gelatin Nanoparticles as Immunostimulatory Carriers of Antigen for Mucosal Delivery." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/47917116109783463654.

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碩士
國立臺灣大學
醫學工程學研究所
104
In the past, the vaccine has been research to attack the disease. This disease is including about the infectious disease. However, up to now the vaccine administrations are used to inject the vaccine in body. The injection owing to cause the pain, many people don’t want to accept the vaccine injection. Because of this reason, we want to use the mucosal delivery to change the disadvantage of the injection. The history of making vaccine has been used to achieve the goals which are better effective result and the safe. However, Live/attenuated vaccines have the good result but they are not safe for the patient. And the inactivated vaccine has decreased the dosage for the patient safe but it was not effective for curing the disease. We need to find the method which can decrease the dosage and have the better treatment effect. So we can use the delivery system to overcome this aim. The successful vaccine needs three important things including with antigen, delivery system and immune-stimulator. In this study, the Ovalbumin (OVA) was used to be the antigen model. The positive gelatin nanoparticles were used to be the material of delivery system. And the Poly (I: C) was used to be the immune-stimulator. Poly (I: C) and OVA were exposed on the outer surface of positive gelatin nanoparticles. The particle sizes of each positive gelatin nanoparticle with OVA and Poly (I: C) were controlled to smaller than 500nm. And the absorption of OVA at this particle has up to 95%. We demonstrated the Poly (I:C) and OVA incorporated positive gelatin nanoparticles effectively facilitated antigen uptake by mouse bone-marrow derived dendritic cells (BMDCs) and macrophage in vitro, led to higher expression of maturation markers, including CD80&86, and induced higher production of pro-inflammatory cytokine. In vivo use the C57BL/6 mice and the immunization procedure was repeated 2times at 2 weeks interval. C57BL/6 mice immunized by intranasal with the Poly (I: C) and OVA incorporated positive gelatin nanoparticles produced high levels of OVA-specific IgG antibodies in their serum and secretory-IgA (s-IgA) in nasal wash fluid. Spleen cells from mice receiving the Poly (I: C) and OVA incorporated positive gelatin nanoparticles were re-stimulated with OVA and showed significantly augmented levels of IFN-γ. In addition, intranasal administration of the Poly (I: C) and OVA incorporated positive gelatin nanoparticles resulted in complete protection against EG7 tumor challenge in C57BL/6 mice. Taken together, these results indicate that nasal administration of the Poly (I: C) and OVA incorporated positive gelatin nanoparticles mediates the development of an effective immunity against tumors and might be useful for further clinical anti-tumor application.
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