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
True random number generators are essential components for communications to be conconfidentially secured. In this paper a new method is proposed to generate random sequences of numbers based on the difference of the arrival times of photons detected in a coincidence window between two single-photon counting modules
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Media studies have focused mostly on the issue of the mental image because the image that is formed in the mind has become not only a photo of a human being and having kept for himself. This image has an outside influence which may sometimes up to the formation of the fate of others and it sometimes includes individuals and groups together.
This study comes in the context of identifying the image of Iraqi political parties among Iraqi university students and the nature of the view that students have in their minds about these parties.
Chapter one includes the problem of the research, the importance of the study, the goals and method used. Chapter two is divided into two sections: section one deals with the concept of the mental i
Various visual media are becoming an increasingly important and active instrument of communication. This fact has led some political parties and leading personalities in Iraq to make use of them as an accepted forum for the discussion of public affairs usually in a manner that conforms to their declared policy. They have to draw as much popular support as they could for the causes which they fight for. As a result, a state of great confusion has been created from the contradictory statements made by the contending parties and gave left grave consequences on all types of the audience receiving them. The problem of the study can be summarized in one major question: What is the opinions of the audience as regards the statements made by the
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The research seeks to identify the contemporary events that face the use of electronic payment methods to localize the salaries of state employees and its impact in enhancing the mental image of customers, and to achieve this purpose from the fact that a questionnaire was designed and distributed to an optional sample of (31) individual customers (employees) dealing With the researched private banks, it has been analyzed and reached a number of conclusions and recommendations, the most prominent of which is the lack of modernity of electronic payment methods by customers, which is reflected in the mental image of customers and the achievement of their satisfaction, in the Emiratization project for salaries needs an advanced leade
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Praise be to God, Lord of the Worlds, and prayers and peace be upon the Master of the Messengers, his family and all his companions, then after:
This is a brief research that contained its two rudders the command and its Style in Surat Al-Ma’idah a fundamental rhetorical study, and the study clarified the meaning of imperative in both; the Arabic language and in the terminology of the fundamentalists and rhetoricians in a concise manner, and then indicated the imperative of the command , the true meaning, and the meanings interpretated as an imperative form. I have mentioned some verses of Surat Al-Ma’idah, so what I have quot
... Show MoreThe treasury bills one internal government debt instruments in iraq that were used to finance temporary deficits in the government budget, There fore the government resorted to issuing for the purpose of providing liquidity, As well as to invest in productive progects, After that it was financing the budget deficit by the monetary authovity of the central baalpennek [the new cash velease] which led to negative effects on the Iraqi econome, Thus we find that the treasury transfers have formed alarge proportion of the gross domestic government debt to finance the deficit ayear ago 2003. &nbs
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Abstract
Abstract has many advantages as has historically been one of the regions leading cultural centers . for centuries , it has been a center of commertial and financial operations in Iraq. it is also rich in archeological sites and natural resources, but because of its wars and implementation of urban development strategies are effective and sustainable , so contracted the secretariat of Baghdad with the company (khatib and scirntiffic) for the preparation of the comprehensive development plan for the city of Baghdad in 2030 and funded by the world bank and the fact that the plan was approved ( three stages of it ) and only one phase remains the fourth stage, which is under discussion the aim of the
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