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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The research aims to achieve the basis of tax justice by making a comparison between the tax accounting process according to the application of the International Financial Reporting Standard IFRS15 and the tax accounting procedures currently used in the General Authority for Taxes to determine the annual and total tax differences, to give credibility and enhance transparency in the reports and financial statements of companies Long-term contracts when prepared in accordance with the requirements of applying the international standard IFRS15 “Revenue from Contracts with Customers”, which increases the possibility of relying on them when calculating taxes. Thus, the resea
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Problem of current research can determine the dimensions to answer the following question: The effect of teaching using the six thinking hats on academic achievement for students in the second grade average in the subject of Family Education. The importance of research: research is gaining importance in terms of:
1. That this research is the first of its kind in the researcher's knowledge _ which deals with the teaching of Family Education by using the six hats, the researcher hopes to fill a gap in the educational field and serve in other studies serve the materials home economics. 2. Keep pace with the new field of modern education and strategies. 3. Highlight on the educational strategy in the field of creative
Some auditors may think that the audit process ends with discovering misstatements and informing management about them, while the discovery of misstatements may be classified by some as the first step in the phase of separating these distortions, as the auditor should collect these misstatements, evaluate them and detail them into misstatements involving errors or misstatements involving fraud Then evaluating it to material or immaterial according to what was stated in the international auditing standards and directing management to amend the essential ones. The importance of this research lies in identifying the concept of distortions and their types, identifying the method of evaluating distortions into substantial and non-essent
... Show MoreThe aim of the present study is to provide the adequate knowledge about the role of time management in facilitate the work requirements for employees of the administrative department at the Ministry of Higher Education and Scientific Research. The research depend on studying four important dimensions which are (time planning, time organization, time direction and time observation). In addition to study other five dimensions which are (new procedures, clear procedures, short procedures, the available information and the simplicity of the methods
used).Questionnaire sheets consist of (38 questions) distributed to (170) employees and (146) sheets only were considered in the study. SPSS program was used
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The research aims to analyze the impact of exchange rate fluctuations (EXM and EXN) and inflation (INF) on the gross domestic product (GDP) in Iraq for the period 1988-2020. The research is important by analyzing the magnitude of the macroeconomic and especially GDP effects of these variables, as well as the economic effects of exchange rates on economic activity. The results of the standard analysis using the ARDL model showed a long-term equilibrium relationship, according to the Bound Test methodology, from explanatory (independent) variables to the internal (dependent) variable, while the value of the error correction vector factor was negative and moral at a level less than (1%). The relationship bet
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يعد العلاج الحركي من الوسائل العلاجية التأهيلية من الوسائل المهمة الامنة لأنها تؤمن على حياة الانسان بكافة شؤونه وتعد التمرينات التأهيلية اسلوبا فعالاً وطبيعياً لا تعرض المريض الى مضاعفات على وظائف الجسم الاخرى لأنها خالية من اي دواء كيمياوي ضار ، كما استخدمت تقنيات حديثة في العلاج الطبيعي بشكل واسع معد حسب اسس علمية منها تمرينات (Core) التي تساعد في تخفيف الالام بالانزلاق الغضروفي للفقرة الرابعة والخا
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This research aims to demonstrate the impact of the going concern assumption in different accounting applications to provide a realistic look and more accurate result of activity and financial situation, as well as determining the responsibility of the Company's administration in compliance with the going concern assumption during the preparation for their financial statements, and to clarify the concept of integration between internal audit and external audit about going concern assumption, besides its importance and usefulness on the work of both of the internal auditor and the external auditor, as well as on the company under auditing process.This research purports preparing an internal audit program, including a set of auditing actio
... Show MoreThe importance of the research lies in knowing the effect of the exercises of the reciprocal method in developing some physical abilities in learning the performance of the players for the effectiveness of the long jump in an economical manner in terms of time and effort and knowing their positive impact and the extent of their impact in creating the required learning for students, and the research aims to prepare reciprocal style exercises in developing some abilities The researchers used the experimental method in the pre and post test for the experimental and control groups to suit the nature of the research, and the research community was identified for the long jump players, the Specialized School for Talent Care in the 2022 sports sea
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