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
The research aims to clarify the response of the GDP to the M1 shock. It includes access to the results using standard methods, where the standard model was built according to quarterly data using the program STATA 17. According to the joint integration model ARDL, the research found a long-term equilibrium positive for the relationship between GDP and the money supply in Iraq, as the change in the money supply by a certain percentage will lead to a change in GDP by about 71% of that percentage. In the event of a shock in the Iraqi economy, the impact of the M1 will differ from what it was before the shock, as the shock will increase its effectiveness towards GDP by about 10% more than before the shock. At the same time, the relationship
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IFRS 17 aims to provide a unified basis for accounting for all types of insurance contracts, including reinsurance contracts, in a manner that benefits both investors and insurance companies and enhances the ability of the financial statements of insurance companies for comparison between companies listed in financial markets around the world. According to this standard, insurance contracts are accounted for on the basis of the Asset-Liability Approach and the use of fair values that the standard requires updating regularly in order to provide more useful information to the users of financial statements, as a result of the failure of reporting requirements for insurance contr
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The study aims to identify the degree of Tabuk University practices to raise the intellectual awareness of students through scientific research, as well as to identify the degree of Tabuk University practicing to raise the intellectual awareness through the educational process (faculty member – activities). The study also seeks to identify the degree of Tabuk University practicing to raise the intellectual awareness of students through community service and university media. The study is descriptive in nature that employed the questionnaire as a tool in collecting data. Total of (540) students were chosen randomly from different colleges at universities of Tabuk to form the study sample. The results showed that faculty member has pract
... Show MoreThe present analysis targets to recognize the influence of the separate teaching approach on the accomplishment of grammar for scholars of the College of Islamic Sciences. The target of attaining this target led the investigations developing the subsequent null theories: 1. No statistically substantial variance is happened at the consequence level of 0.05 between the mean scores of the scholars in the investigational category who learnt consistent with the separate learning approach and the mean scores of the scholars in the control category who learnt in the conventional method in the accomplishment test. 2. No statistically substantial variance has been observed at the consequence level of 0.05 in the mean differences between the
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Starting with a problem of the weakness of accounting disclosure in some companies administration when preparing and presenting the financial reports which are submitted to the Tax authority. This problem impacts on Tax authority performance (The effect on the quality of the performance of the tax authority), because of the lack of conviction for the information contained in those reports, and the failure to achieve accurate results in tax authority performance that leads to a negative impact on determining taxable income and affect tax revenue, as well as negative impact on determining taxable income and affect tax revenue, as well as negati
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The tax policy is an important tool of fiscal policy tools which is usedasits multiple tools the State seeks to achieve objectives, such as theachievement of economic development.The importance of the research comes from the importance ofeconomic development resulting from economic policies and prudent fiscaland appropriate to the economic situation of Iraq at the moment is the mostimportant tax policy that taxes one of the most important financial instruments.The research aims to clarify the role of tax policy in developing of theIraqi economy.In an effort to achieve the goals researchers tried to prove thehypothesis ((The tax policy and through multiple tools that seeks to contributeto the achievement of economic development in Iraq)).
... Show MoreThe emerge of capitalism beside appearing modern and contemporary political systems which had become hold out it is semi-domination on more vital space of human community life, it is through some vital apparatus, which the free market apparatus had make important one which depend on achieve the privileges of the capitalism elite whom standing on it, especially the finance elite. Thus the achievement of the profit had become the main podcasted of those elite which whom the really advancer of the Globalization system, this is which incarnated by the appears and extend of the (COVID-19) fatality pandemic in the end of last year, whereas reveals widespread of it in more than one states in the world, especially the developed coun
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The research aims to identify the relationship between spatial ability and the physical structure of concepts to the students of the Faculty of Education for Pure Sciences / Ibn al-Haitham، research involved students from the third class / morning study for the year 2011/2012 totaling (98) male and female students ،distributed into three groups which were selected randomly . The number of students (26 males and females) represented research sample after excluding repeaters and absentees، the research included two tests ; one test of spatial ability، which included (20) items and other test the physical structure of concepts، which included (12) items distributed into four domains ، the first (linking b
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Interested in many scholars and reseachers the subject of the media and means varied his roleinfluential in the definition of the public of issues and political, cultural, social and because of its spread wide and ability to address the people of all levels effect them in the formation consciousness of those issues and types of this awareness is an awareness of the tax, contribute to media formation consciousness tax through the definition of people what tax and importance of the role of its revenues to supplement the state budget by posting tax laws and regulations of applied and all what respect process account tax, to be in charge of the tax familiar enough about this, which avoid being cheated taxmisleading when rev
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