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
My study here is about the (possible for itself) features especially in the (Alashaira) opinion, also I touch to the other logicians opinions, I clarified these features concisely in the preface to be clear in front of the reader, I made it in two studies and five subjects.I talked about the meaning of the existence in the ((possible for itself) theme, and I clarified its types in the logicians and the philosophers' opinions, through which the existence and the nonexistence are equal in it, as it cannot be existed nor be nonsexist unless with a separated reason, and there is no necessity to oblige its existence, or its nonexistence is impossible.Then I talked about the outweighing of the (possible for itself) as one side of the exi
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Suggestion Plan for the Reclassification of U.N Publications in Central Library
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The aim of this paper is to approximate multidimensional functions f∈C(R^s) by developing a new type of Feedforward neural networks (FFNS) which we called it Greedy ridge function neural networks (GRGFNNS). Also, we introduce a modification to the greedy algorithm which is used to train the greedy ridge function neural networks. An error bound are introduced in Sobolov space. Finally, a comparison was made between the three algorithms (modified greedy algorithm, Backpropagation algorithm and the result in [1]).
Obiovisly that the holy thresholds are directly related to Islam and Muslims and related to the general culture of the Islamic peoples. In terms of architecture, it is considered a distinctive architectural scene that reviews the history of this origin and its architectural styles. Recently, with the increase in the number of pilgrims and visitors to the holy shrines, there is a need to develop and expand the buildings and provide them with services and introduce modern technology. The building of the holy thresholds consists of a number of functional design indicators: The general problem of research is that there is no clear theoretical framework for the design indicators for the development of the holy shrines according to the functio
... Show MoreCoaxial (wire-cylinder) electrodes arrangements are widely used for electrostatic deposition of dust particles in flue gases, when a high voltage is applied to electrodes immersed in air and provide a strongly non-uniform electric field. The efficiency of electrostatic filters mainly depends on the value of the applied voltage and the distribution of the electric field. In this work, a two-dimensional computer simulation was constructed to study the effect of different applied voltages (20, 22, 25, 26, 28, 30 kV) on the inner electrode and their effect on the efficiency of the electrostatic precipitator. Finite Element Method (FEM) and COMSOL Multiphysics software were used to simulate the cross section of a wire cylinder. The results sh
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The research aimed to identify the causal relationship between forgiveness and psychological hardness for university students, by answering the following questions: Does forgiveness cause psychological hardiness? Does psychological hardiness cause forgiveness? Is the relationship between the two variables a reciprocal relationship? The research sample consisted of (300) male and female students from the universities of Baghdad and Al-Mustansiriya University. To extract the psychometric properties of the two scales: forgiveness and psychological hardiness, a sample of (50) male and female students employed to repeat the test, making the six connections between the two research variables. To determine the causal relationship, The Pearson c
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