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
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Alice Walker's novel The Color Purple1983, whose events take place in the rural Georgia and addresses the most important issues in the early 20thcentury; like male dominant society and women submission to men, weaves a mosaic picture of male-female relationships. Black men like Alphonso, Albert and Harpo are portrayed as oppressors, cruel and they exercise power and violence over their wives and daughters. Through the negative portrayal of black male characters, Walker is accused to be a men hating writer because she ''Views oppression as an essentially masculine activity which springs from the male's aggressive need to dominate. In the novel, man is the premium mobile, the one by whom and t
... Show MoreThis study evaluated the structural changes of enamel treated by the Regenerate system and carbon dioxide (CO2) laser against acid challenge. Thirty human enamel slabs were prepared and assigned into three groups: Group I: untreated (control); Group II: treated with the Regenerate system; and Group III exposed to CO2 laser. All specimens were subjected to an acid challenge (pH 4.5–7.0) for 14 days. Specimens were evaluated and compared at 120 points using five Raman microspectroscopic peaks; the phosphate vibrations ν1, ν2, ν3, and ν4 at 960, 433, 1029, and 579 cm−1, respectively, and the carbonate at 1070 cm−1, followed by Vickers microhardness test. The ratio of carbonate to phosphate was correlated to the equivalent mic
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Poetry is regarded an interesting area of inquiry in linguistic studies due to its eccentric and aesthetic use of language. A lot of studies have been carried out so far for the analysis of poetry, yet few have dealt with pastoral poetry. The present research attempts to investigate the language of pastoral poetry in two different languages i.e. English and Arabic with the aim of finding similarities and differences. The data of the study consists of one English and one Arabic pastoral poems. Leech and Short's (2007) checklist is used as a model for analysis. The findings of the study reveal that there are more similarities than differences between English and Arabic pastoral poems as the poems rely on contrast
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Despite not being digested, trace elements and/or heavy metals are important for the activity of enzymes, physiological processes, and homeostasis. If certain trace elements are present in excess, they can have harmful effects and pose major health hazards. Objective: The aims to examine the connection between serum zinc, copper levels, and the Cu/Zn ratio, and several anthropometric parameters, including an index of body mass and the waist-hip ratio. In our study, we used atomic absorption spectrometry (AAS) to measure serum levels of copper (Cu) and zinc (Zn) in 60 individuals, 30 patients with kidney cancer and 30 healthy controls. We assessed serum uric acid, creatinine, and urea using the semi-auto analyzer BA-88A (Korea). The results
... Show MoreIn this study a polymeric composite material was prepared by hand
lay-up technique from epoxy resin as a matrix and magnesium oxide
(MgO) as a reinforcement with different weight fraction (5,10,15,
and 20)% to resin. Then the prepared samples were immersed under
normal condition in H2So4(1 M) solution, for periods ranging up to
10 weeks. The result revealed that the diffusion coefficient
decreasing as the concentration of MgO increase. Also we studied
Hardness for the prepared samples before and after immersion. The
result revealed that the hardness values increase as the concentration
of MgO increase, while the hardness for the samples after immersion
in H2SO4 dec
A research study in which a methodology for quality indicators that can be adopted to evaluate the educational process in educational institutions within a specific strategy helps individuals in charge of educational education to make appropriate decisions based on accurate and properly approved plans to achieve successful outcomes.
These indicators can be used to judge the quality of educational institutions in order to improve, improve and develop them. This study has concluded the necessity of putting quality into actual application in order to benefit from it in evaluating the future action of Iraqi educational institutions.
The external changes brought about by technology and family life have made the
... Show MoreThe basic objective of the research is to study the quality of the water flow service in the Directorate of Karbala sewage and how to improve it after identifying the deviations of the processes and the final product and then providing the possible solutions in addressing the causes of the deviations and the associated quality gaps. A number of quality tools were used and applied to all data Stations with areas and activities related to the drainage of rainwater, as the research community determines the stations of lifting rainwater in the Directorate of the streams of Karbala holy, and the station was chosen Western station to apply the non-random sampling method intended after meeting a number of. It is one of the largest and m
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Most reinforced concrete (RC) structures are constructed with square/rectangular columns. The cross-section size of these types of columns is much larger than the thickness of their partitions. Therefore, parts of these columns are protruded out of the partitions. The emergence of columns edges out of the walls has some disadvantages. This limitation is difficult to be overcome with square or rectangular columns. To solve this problem, new types of RC columns called specially shaped reinforced concrete (SSRC) columns have been used as hidden columns. Besides, the use of SSRC columns provides many structural and architectural advantages as compared with rectangular columns. Therefore, this study was conducted to explain the structura
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