Abstract Candida albicans is a commensal fungal pathogen that grows in yeast and hyphal forms in the human gut. C. albicans causes mucosal and cutaneous diseases that can result in significant mortality following systematic infections and it also exhibits drug resistance. Zebrafish have been an excellent model to investigate C. albicans infections because of their transparency and the availability of many transgenic lines. However, there is a limitation in using zebrafish as a model because the fish embryos cannot survive at 37°C therefore it is not suitable for studying Candida infections at physiological relevant human body temperature. In this thesis, the normal embryonic development of Arabian killifish (A. dispar) is investigated, revealing that embryogenesis was divided into 32 stages based on diagnostic patterns of development. A. dispar can also found to tolerate a wide range of temperatures and salinities. This suggests that A. dispar could be developed as a novel model to investigate host-pathogen interactions. The tolerance of A. dispar to high temperatures may in part be attributable to brown pigment cells with a highly fluorescent character that may have developed to allow the fish to adapt to live within extreme environmental conditions with strong sunlight and a wide range of temperatures (Chapter 3). In terms of Candida infections, this study examined A. dispar as a model to test C. albicans pathogenicity. The survival of A. dispar embryos following Candida infection showed a dose dependent relationship. We also found that A. dispar can survive longer than zebrafish after infection. Furthermore, C. albicans cells were observed to undergo a transition from yeast to hyphae at 37°C. An investigation of the ability of mutant strains of C. albicans with defects in cell wall mannosylation revealed a significant impact on virulence, host mortality, and the fishes’ immune response. The present study found that although the deletion of O- and N-mannan from the cell wall of C. albicans, affected fungal burden (attenuation), and the survival of the infected embryos per se was significantly decreased in the infections of the mutant strains compared to the WT. This data confirms the importance of the mannosylation state of the cell wall in triggering an immune recognition event (Chapter 4). A. dispar is also shown to be suitable for studying the effectiveness of 3 | P a g e antifungals. Fluconazole treatment of infected embryos and eggs promoted greater rates of survival at high doses, alongside a significant reduction of C. albicans CFUs (Chapter 4). When looking at the Candida-host interaction, we directly observed phagocytosed yeast cells within macrophages. Various detection methods were used to follow macrophages and neutrophils including Western blotting, immunostaining and histological staining (Sudan black and FITC-tyramide) allowing the monitoring of the time course of the immune cells. A biphasic response of macrophages was detected by L-plastin Western blotting, suggesting activation of two different type of macrophage: activated macrophage (M1) and alternative macrophage (M2). We also assayed reactive oxygen species (ROS) within infected embryos using a fluorescent probe (H2DCFDA), revealing the accumulation of the fluorescent probe at the sites of infection. Quantitative and qualitative analyses of the oxidative and immune response using the H2DCFDA and qPCR were also accomplished within A. dispar embryos after infection with both the WT and mutant strains of Candida albicans (WT, pmr1∆, mnt1-mnt2∆, and och1∆). The results confirmed that the mutant strains did not activate a host oxidative stress response nor immune cell accumulation when compared to WT, suggesting that the immune response is less activated against these mutants. Finally, a new transgenic line of A. dispar fish was developed using Betaactin-DsR-LoxP-GFP. The new transgenic A. dispar is suggested to be an ideal model for real time observation of host-pathogen interactions and for investigation of molecular functions of the immune response. Overall these results improve our understanding of the use of a new transparent fish model to study fungal pathogenesis and demonstrates the potential advantages of using this species in future studies of bacterial, fungal and viral pathogens at a physiologically relevant temperature for human infection. Such a model could lead us to investigate in more depth the key interactions between pathogens and their host and permit the screening and development of new antifungal therapies (that might target the pathogens directly or target the host immune system). View full metadata
This paper presents a fully computerized method to backup the router configuration file. The method consists of a friendly graphical interface programmed by Java programming language.
The proposed method is compared with the two existing methods, namely: TFTP server method and Copy/Paste method. The comparison reveals that the proposed method has many advantages over the existing ones. The proposed method has been implemented on Cisco routers (series 2500, 2600 and 2800).
In "historical" fiction, characters that never really existed, give expression to the impact of historical events on the people who really did live through them. The result is not history, as an accurate record of actual events, but fiction in which an earlier age is rendered through the personal joys and sufferings of characters. This paper
aims at investigating the historical realities presented in Dickens’s A Tale of Two Cities.
Judo has witnessed tremendous developments since its inception until the present day. It has been distinguished by its adaptation to the various challenges it has faced throughout the ages. Judo is one of the sports that have been affected by social, technological and cultural changes. These changes reflect its transformation from the traditional Japanese martial art to a global sport practiced. All over the world, therefore, studying the historical development of judo is important, as it provides valuable insights into the development of martial arts over a century, by studying the origins, principles and techniques of judo for the period (1880 - 1980), and also enables us to gain an understanding A deeper understanding of how the art form
... Show MorePerhaps the issue of media and the press, especially one of the most common topics that people deliberate and deal with permanently and continuously. An issue of such significance has pushed researchers to put the following question, “Is it possible to live without media?”, “Can people ignore the newspaper, radio, TV, or the other communication means?”
The answer is very simple. It is difficult for civilized society to overtake information, or dispense with circulation, at the individual or collective level. Yet, the question of how to make the media and how it determines its content still requires extensive media experience; and knowledge of the social structure and its relations; and ac
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Conflict is a common but complicated phenomenon. It has been extensively researched in many domains, including philosophy, sociology, psychology, and linguistics. Using the Critical Discourse Approach, this study examines the issue of self-society conflict in The Handmaid’s Tale. The significance of this work lies in the identification and explanation of the discursive strategies that force the ideological polarization of the positively portrayed self versus the negatively portrayed other. The purpose of this study is to answer two questions: what are the discursive strategies used in The Handmaid’s Tale to create a positive or negative representation, and how are these strategies implemented? Five extracts from The Handmaid’s
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In this paper, we characterize normal composition operators induced by holomorphic self-map , when and .Moreover, we study other related classes of operators, and then we generalize these results to polynomials of degree n.
The rising prevalence of obesity-related glomerulopathy (ORG) occurs in accordance with the rising prevalence of obesity worldwide. Clinically ORG is manifested by slowly progressing microalbuminuria that may develop to clinically evident proteinuria. Pathological characteristics of ORG include glomerular hypertrophy in the presence or absence of focal segmental glomerulosclerosis (FSGS). ORG can develop into clinically overt chronic renal insufficiency or even end-stage kidney disease. This article reviews the most important mechanisms for the development of ORG; that are abnormal renal hemodynamics, stimulation of renin-angiotensin-aldosterone system (RAAS), impairment of insulin sensetivity, ectopic lipid deposition, adipose tissue cy
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The photoconductivity and its dependence on light intensity have been investigated in a-Ge20Se80 thin films as a function of temperature between (293–323)K. The result showed that the photoconductivity and photosensitivity increase with increase of annealing temperature. This behavior is interpreted in terms of the dispersive diffusion –controlled recombination of localized electrons and holes.
In the last years, the self-balancing platform has become one of the most common candidates to use in many applications such as flight, biomedical fields, industry. This paper introduced the simulated model of a proposed self-balancing platform that described the self–balancing attitude in (X-axis, Y-axis, or both axis) under the influence of road disturbance. To simulate the self-balanced platform's performance during the tilt, an integration between Solidworks, Simscape, and Simulink toolboxes in MATLAB was used. The platform's dynamic model was drawn in SolidWorks and exported as a STEP file used in the Simscape Multibody environment. The system is controlled using the proportional-integral-deriva
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