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
Tourism is one of the most important sources of income of economic key countries in the world so are imports of tourism for some countries a source of income is not significant of the total revenues of States. Making those countries, and those countries a destination for visitors, and here should be interest in the Wealth and cultural heritage that distinguishes Islamic countries in general, and Iraq in particular, must be placed specialist studies in all areas for the development of this area of tourism, especially religious tourism to achieve a desired and desired of such research.It is the most important ways to develop tourism in general and religious tourism is of particular publications, advertising, and is important for us in this
... Show MoreThe problem of the search (how to employ own aesthetic values sculpture prominent decorations doors in the holy shrines) as research aims to detect these formulas employed in relief sculpture in accordance with the aesthetic values of the decorations that add structure in the form of doors shrines dimensions of functional and aesthetic and expressive By selecting the general system configurations spaces for doors and select the components of the structural configurations decorative prominent types (geometric and floral and linear and composite) as well as identify the techniques adopted in the executive configurations doors at the level of raw materials and processors show. Find and define the beauty of decorative formations prominent of
... Show MoreA condense study was done to compare between the ordinary estimators. In particular the maximum likelihood estimator and the robust estimator, to estimate the parameters of the mixed model of order one, namely ARMA(1,1) model.
Simulation study was done for a varieties the model. using: small, moderate and large sample sizes, were some new results were obtained. MAPE was used as a statistical criterion for comparison.
The process of stocks evaluating considered as a one of challenges for the financial analysis, since the evaluating focuses on define the current value for the cash flows which the shareholders expected to have. Due to the importance of this subject, the current research aims to choose Fama & French five factors Model to evaluate the common stocks to define the Model accuracy in Fama& French for 2014. It has been used factors of volume, book value to market value, Profitability and investment, in addition to Beta coefficient which used in capital assets pricing Model as a scale for Fama & French five factors Model. The research sample included 11 banks listed in Iraq stock market which have me
... Show MoreUnderstanding the effects of fear, quadratic fixed effort harvesting, and predator-dependent refuge are essential topics in ecology. Accordingly, a modified Leslie–Gower prey–predator model incorporating these biological factors is mathematically modeled using the Beddington–DeAngelis type of functional response to describe the predation processes. The model’s qualitative features are investigated, including local equilibria stability, permanence, and global stability. Bifurcation analysis is carried out on the temporal model to identify local bifurcations such as transcritical, saddle-node, and Hopf bifurcation. A comprehensive numerical inquiry is carried out using MATLAB to verify the obtained theoretical findings and und
... Show MoreThe Sunnah of the Prophet has a great impact in building human behavior, and the formation of Islamic thought, has worked to spread science in all of Egypt, as it carried to the people of the eternal prophecy of the love of science, it was a source of knowledge and civilization. It is a generous source, a rich source of the Islamic nation, always tender, and renewed benefit, which is not only a source of legislation and language but is a source of guidance for thought and guidance of behavior, and the Hadith The importance is obvious In the integration of Islam, and show aspects of human integration in the personality of Mustafa , and the Muslims are interested in talking - collected and codification -, and made the effort of the cent
... Show MoreThis study focusses on the effect of using ICA transform on the classification accuracy of satellite images using the maximum likelihood classifier. The study area represents an agricultural area north of the capital Baghdad - Iraq, as it was captured by the Landsat 8 satellite on 12 January 2021, where the bands of the OLI sensor were used. A field visit was made to a variety of classes that represent the landcover of the study area and the geographical location of these classes was recorded. Gaussian, Kurtosis, and LogCosh kernels were used to perform the ICA transform of the OLI Landsat 8 image. Different training sets were made for each of the ICA and Landsat 8 images separately that used in the classification phase, and used to calcula
... Show MoreThis study aimed at identifying the trend to applying the Joint Audit as an approach to improve the financial reports quality with all their characteristics (Relevance, Reliability, Comparability, Consistency), as well as enclose the difficulties that faced the auditors in the Gaza Strip in implementing the Joint Audit. In order to achieve the study aims, a measure was used to identify the trend to apply the Joint Audit and it was distributed to the study sample which is consisting of (119) individuals and retrieved thereof (99) valid for analysis, approximately (83.2%), (69) of them are Auditors, (30) financial managers and accountants. The researcher used the analytical descriptive method, and after analyzing the results, the s
... Show MoreCaptopril is an angiotensin converting enzyme inhibitor (ACEI) used to treat hypertension,
congestive heart failure, and myocardial infraction.
The only dosage form available for captopril is the plain tablet in strength of 12.5,25,50 and 100mg
tablet.
This investigation is concerned with factors affecting the formulation of captopril as a plain
tablet dosage form of 50mg. Many trials were made to prepare satisfactory tablets for the drug by
using wet – granulation methods with various additives. It was found that poly vinyl pyrrolidone
(P.V.P.) as binder gave the most satisfactory tablets. At the same time a shorter disintegrantion time
and slower dissolution rate were obtained with the addition of starch