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
Monetary policy occupies a prominent role in achieving monetary stability by adjusting the growth rates of the number of available means of payment in line with changes in the size of the gross domestic product in the country and expressed by the monetary stability coefficient agreed upon by the International Monetary Fund, a term that hides the fact that there is a rate of change in the volume of commodity or real production which expresses the levels of aggregate supply in the economy, which corresponds to the quantities of cash in circulation, which represent a net purchasing power and stimulate aggregate demand, which completes the picture of the existence of the market mechanism, expressed by the monetary or economic stability
... Show MoreThat internal control is particularly important in improvingperformance and tax reform، they play an important role in the regularity ofwork and development and the anti corruption and activating the decisionsand tax legislation، as contained in the organizational plan and the means،procedures and components designed from which to ensure a policy andimplementation plans The research aims to review the reality of the internalcontrol in the General Commission for Taxes and stand on the deficiencies init, with the strengthening of the role of internal control in the GeneralAuthority for taxes based on the laws and regulations and by using modernmeans to work as well as developing the performance of employees in thebody، including helpin
... Show MoreThis study aimed to reveal the degree possession of secondary teachers for effective teaching skills from the perspective of the teachers themselves in the Mafraq governorate .To achieve the objective of the study(45) teachers were chosen randomly, also a questionnaire composed of 17 was prepared spread over three skill areas (planning, implementation, evaluation).
After application of the tool on the sample results of the study showed that the degree of ownership ranged between medium and high.
The results showed no differences in the degree of ownership due to the variables of sex in favor of females and variable qualification for the benefit of people with qualified Master higher, while differences are attributed to the experien
The study aimed at ideutifying the impact of scieutific skills in strategy and liabits of mind amony stueuts in tenth grade . The study demanded to choose a sampie that coutaiun (42) student of the fourth grade of the secondary school who were dirided into tow groups , the first is experimental studied according to scieutific skill strategy , and the other controlling , studied according to the usualway . An achievement test has been taken that adopted staudard for mind skills as research tools that are applid after ascertaining sincerity proved at the end of the experiment .The study has reached to the conclusion that there are statistically significant differnces in farour of the experiment group in both
... Show MoreThe aim of this research is analysis the effect of the changes in (GDA, g, inflation) at average and standard economic curriculum in composition of the models, depending on SPSS program in analysis, and according to available date from central bank of Iraq and during the period from 2003 to 2018 and by using OLS and estimate of the equation and the results showed a statistical significance relation in incorporeal level 5% and the R2 value equal to 92.1 refer to the changes in independent variables explain 92% of changes of unemployment and the independent variables effect are very limit depend on estimated parameters in the model and respectively (0.986,0.229,-0.060), the research recommended necessity to active the inve
... Show MoreThis research aims at identifying the level of quality of University environment according to the viewpoint of female students taking the College of Sciences for Woman an example, as represented in the college units as registration unit and the unit of students' affairs, the curricula, instructors, study halls, the college library, scientific labs, computer access, stationary and photocopying services, health care center, the unit of artistic, cultural and sportive activity, the canteen, the college gardens, college buildings and equipment and bathrooms. To achieve the objectives of the research, the researcher prepared a questionnaire to identify the viewpoints of female students concerning the extent of the availability of the standards o
... Show MoreThe research aims at measuring the extent of the relationship and influence of the indicators of the Core competencies of the audit firms and offices in the Earning Quality of the private banks listed in the Iraq Stock Exchange under audit. The research community represents 38 banks. The sample of the research has been approved only 10 banks continue to issue their financial statements for the period (2007 – 2017), in addition to the audit offices assigned to audit these banks, which amounted to 14 companies and auditing offices. John's (1999) model revised by Kothari et al., (2005) was adopted to measure the Earning Quality by finding discretionary accruals and non-discretionary accruals, to measure the Core competencies indicators ,
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Many nations are seeing an increase in water pollution from dairy and cheese production due to the high organic and fat content in their waste products and the high temperature of their waste products, which elevates the water temperature and causes loss to ecosystem components. Reusing industrial wastewater that has been treated to guarantee no harm has been done to the environment is being hampered by a lack of water. This study compares the presence and absence of mixing in the anaerobic biological treatment of liquid waste for the cheese industry. To decrease heat exchange with the external environment, cube-shaped anaerobic reactors with dimensions of (30 x 30 x 30) cm and thick glass (10 mm) were utilized in this investigation
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RESRAD is a computer model designed to estimate risks and radiation doses from residual radioactive materials in soil. Thirty seven soil samples were collected from the area around the berms of Al-Tuwaitha site and two samples as background taken from an area about 3 km north of the site. The samples were measured by gamma-ray spectrometry system using high purity germanium (HPGe) detector. The results of samples measurements showed that three contaminated area with 238U and 235U found in the study area. Two scenarios were applied for each contaminated area to estimate the dose using RESRAD (onsite) version 7.0 code. The total dose of resident farmer scenario for area A, B and C are 0.854, 0.033 and 2.15×10-3 mSv.yr-1, respectively. Whi
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