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
There is no doubt that Jane Austen is one of the most studied authors of the late 18th and early 19th centuries. Her female characters have been extensively studied and they seem to have aroused much interest as manifestations of the conduct of their time. Her heroines have realized that there were many mistakes in the rules of conduct that controlled and restricted their behaviors. Thus, they have found no fault in correcting these mistakes, by behaving naturally without acting. Elizabeth Bennet the heroine of Pride and Prejudice and Marianne Dashwood of Sense and Sensibility are the chosen examples of that kind of women.
The problem of the research lies in the lack of standard levels for modern administration as a guide for evaluating weaknesses and strengths as well as finding solutions. The aim of the research lies in identifying standard levels for modern administration in Iraqi central Olympic committee and international federations. The subjects were (24) Olympic committee' federations. All procedures were standardized to fit our modern administration work. The data was collected and treated using proper statistical operations. The researcher concluded standard levels for modern administration in international federation of the Iraqi Olympic committee, in addition to that he concluded that most administrations levels ranged within four levels (good, fa
... Show MoreThe radial wave function R(r) and the radial distribution function P(r) as a function of (r), for the Hydrogen atom was calculated for several atomic state (1s,2s,2p,3s,3p,3d) The results were compared with Hydrogen like atom(He+,Li+2,Be+3).
The Local manufacturing scanning gamma system designed in Tuwaitha site for nondestructive assay method of radioactive waste drums, where it consist of two main parts with their belongings for controlling the of detector and drum movements up-down and rotation respectively. The volume of the used drum is 220 L with 85 cm height. The drum filled with Portland cement. Six cylindrical holes were made within cement drum and distributed in radial arrangement.The152Eu source inserted in these holes individually, to measure the average angular count rate of gamma radiation. The full energy efficiency value for geometry of drum and detector is computed for thirteen photo peaks. The average efficiency represented by the curve of these peaks indic
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A spectrophotometric determination of azithromycin was optimized using the simplex model. The approach has been proven to be accurate and sensitive. The analyte has been reacted with bromothymol blue (BTB) to form a colored ion pair which has been extracted in chloroform in a buffer medium of pH=4 of potassium phthalate. The extracted colored product was assayed at 415 nm and exhibited a linear quantification range over (1 - 20) g/ml. The excipients did not exhibit any interferences with the proposed approach for assaying azithromycin in pharmaceutical formulations.
The research aimed at designing teaching program using jigsaw in learning spiking in volleyball as well as identifying the effect of these exercises on learning spring in volleyball. The researchers used the experimental method on (25) students as experimental group and (27) students as controlling group and (15) students as pilot study group. The researchers conducted spiking tests then the data was collected and treated using proper statistical operations to conclude that the strategy have a positive effect in experimental group. Finally, the researchers recommended using the strategy in making similar studies on other subjects and skills.
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Mobile Wireless sensor networks have acquired a great interest recently due to their capability to provide good solutions and low-priced in multiple fields. Internet of Things (IoT) connects different technologies such as sensing, communication, networking, and cloud computing. It can be used in monitoring, health care and smart cities. The most suitable infrastructure for IoT application is wireless sensor networks. One of the main defiance of WSNs is the power limitation of the sensor node. Clustering model is an actual way to eliminate the inspired power during the transmission of the sensed data to a central point called a Base Station (BS). In this paper, efficient clustering protocols are offered to prolong network lifetime. A kern
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Integrated project delivery is collaboratively applying the skills and knowledge of all participants to optimize the project's results, increase owner value, decrease waste, and maximize efficiency during the design, fabrication, and construction processes. This study aims to determine IPD criteria positively impacting value engineering. To do this, the study has considered 9 main criteria according to PMP classification that already covers all project phases and 183 sub-criteria obtained from theoretical study and expert interviews (fieldwork). In this study, the SPSS (V26) program was used to analyze the main criteria and sub-criteria priorities from top to bottom according to their values of the Relative Importance In
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A total of 589 fishes, belonging to 23 species were collected from eight different localities
in north and mid Iraq during 1993. The parasitological inspection of such fishes revealed the
presence of 59 parasite species and two fungi. Among such parasites, five monogenetic
trematodes were recorded on the gills of some fishes for the first time in Iraq. These
included:- Ancyrocephalus vanbenedenii on Liza abu from Tigris river at Al-Zaafaraniya,
south of Baghdad; Dactylogyrus anchoratus on Cyprinus carpio from Tigris river at Al –
Zaafaranya D. minutus on C. carpio from both Tigris river at Al-Zaafaraniya and Euphrates
river at Al-Qadisiya dam lake; Discocotyle sagittata on L. abu from both the drainage system
at