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 explain the References of receiving the explicit and implicit knowledge mentioned in the Noble Qur'an. The two researchers adopted the documentary and inductive approach to study the topic. Among the conclusions of the research: The Noble Qur'an dealt with many terms and concepts that refer to the References of making explicit knowledge available, including books, which were represented by the divine books (the Qur'an, the Torah, the Zabur and the Gospel) and their concepts (the book, the Qur'an, the guidance, the remembrance, the revelation, the light, the newspapers, the plates). He dealt with many concepts that refer to the References of providing tacit knowledge, which was represented by the communication between tw
... Show MoreThe cinematographer mediates through the means of cinema and television a set of elements complementing each other in the light of developments in various sciences, culture and arts for the purpose of conveying the meaning to the recipient and achieve aesthetic taste. Despite the diversity of cinematographic media with its multiple forms, The researcher started from the principle of definition and knowledge of a technical phenomenon that emerged in the cinematographic medium through the treatment of dramatic events through the solutions of the exit line depends on the narrative of events in one place contributes to attract Mam spectator since this interesting phenomenon in the mediator, there .van question arises the adoption of that vis
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Suggestion Plan for the Reclassification of U.N Publications in Central Library
Gypseous soil is considered as a problematic soil for embankment construction, however, implementation of emulsified asphalt as a stabilization agent could be a proper solution for enhancing its properties as a subgrade soil. In this work, the sustainability of asphalt stabilized soil has been assessed in terms of its resistance to cyclic (freezing-thawing) and (heating-cooling) processes. Specimens have been prepared at optimum fluid content (moisture and emulsion) and tested under direct shear stresses while subjected to 30 cycles of (freezing-thawing) and (heating-cooling). Both of dry and soaked testing conditions have been implemented. Data have been observed after each 10 cycles, and compared with that of reference mix. It was conclud
... Show MoreA novel mixed natural coagulant has been developed to remove sewage pollutants and heavy metals from Qanat- al- Jayesh by using low cost adsorbent natural materials. In these materials, significant interaction contains Arabic gum mixed with extracted silica from rice husk ash (natural coagulants) by the Batch device approach, using two variables, pH values ranging from 5-8 and contact times between 0.25-5 hrs. All wastewater samples were collected after treatment by adsorbents and examined for determination of residual heavy metal concentrations: Pb, Ni, Zn and Cu by atomic absorption spectroscopy (AAS), turbidity, pH, total dissolved salts (TDS), electrical conductivity (EC) and total salinity (TS). The results obtained indicate Th
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The current research aims to reveal the strength of education and the direction of the relationship between the formal thinking and learning methods of Kindergarten department students. To achieve this objective, the researcher developed a scale of formal thinking according to the theory of (Inhelder & Piaget 1958) consisting of (25) items in the form of declarative phrases derived from the analysis of formal thinking skills based on a professional situation that students are expected to interact with in a professional way. The research sample consisted of (100) female students selected randomly who were divided into four groups based on the academic stages, the results revealed that The level of formal thinking of the main sample is
... Show MoreThe study aimed at the following:
Identify the differences in average scores core thinking skills kindergarten children by variable sex (male - female), and by variable age (5.6 - 5.11).
To achieve this researcher adopted a standardized test of core thinking skills for the kindergarten children, which was built and standardization by the researcher Meyada Asaad Mussa 2012 . applied test on a sample of (814) ) boys and girls who were randomly chosen form, from directorates of Baghdad Education Adoption of the proportional distribution.
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The present study was conducted with a view to determine whether focal laser therapy result in visual recovery and regression of macular edema in patients with non proliferative diabetic retinopathy and maculopathy ,and whether combined focal and scatter laser therapy in patients with proliferative diabetic retinopathy and maculopathy results in visual recovery ,regression of macular edema and regression of the risk factors. In the present work, a frequency doubled Nd: YAG laser was used for the treatment of diabetic retinopathy. The study evaluates 41 eyes of 33 diabetic patients both with Insulin Dependent Diabetes Mellitus IDDM, (n=16) and Non Insulin Dependent Diabetes Mellitus NIDDM, (n=17) with diabetic retinopathy divided into two
... Show MoreThis study Ajert to modify the chemical composition of milk fat cows and make it similar to the installation of milk fat mother through the addition of protein and soybean oil to be given Alkhltatnsp sensory protein that the best plan is the ratio of 1:1
The diabetic foot is considered one of the long term diabetes complications caused by a defect in blood vessel and nerve system. This requires dealing with diabetic foot with professional medical care, so as to prevent its development in advanced stages which could end to gangrene and amputation of the foot. This study has been initiated through follow-up of twelve patients with diabetes and the presence various occlusions in lower limb artery. One patient from them was chosen for investigation, this patient has stenosis in popliteal artery and presence multiple stenosis in superficial femoral artery. This study based on analysis present case of patient and prediction for progress stenosis in superficial femoral artery till arrive semi t
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