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
This research aims to examine the effectiveness of a teaching strategy based on the cognitive model of Daniel in the development of achievement and the motivation of learning the school mathematics among the third intermediate grade students in the light of their study of "Systems of Linear Equations”. The research was conducted in the first semester (1439/1440AH), at Saeed Ibn Almosaieb Intermediate School, in Arar, Saudi Arabia. A quasi-experimental design has been used. In addition, a (pre & post) achievement test (20 Questions) and a (pre & post) scale of learning motivation to the school mathematics (25 Items) have been applied on two groups: a control group (31Students), and an experimental group (29 Students). The resear
... Show More
Objectives To tailor composites of polyethylene–hydroxyapatite to function as a new intracanal post for the restoration of endodontically treated teeth (ETT). Methods Silanated hydroxyapatite (HA) and zirconium dioxide (ZrO2) filled low-density polyethylene (LDPE) composites were fabricated by a melt extrusion process and characterised using infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The flexural strength and modulus were determined in dry state and post ageing in simulated body fluid and fractured surfaces analysed by SEM. The water uptake and radiographic appearance of the experimental composites were also measured and compared with a commercially known endodontic fibre
... Show More
(3)
(27)
Computations of the relative permeability curves were made through their representation by two functions for wetting and nonwetting phases. Each function contains one parameter that controls the shape of the relative permeability curves. The values of these parameters are chosen to minimize an objective function, that is represented as a weighted sum of the squared differences between experimentally measured data and the corresponding data calculated by a mathematical model simulating the experiment. These data comprise the pressure drop across core samples and the recovery response of the displacing phase. Two mathematical models are constructed in this study to simulate incompressible, one-dimensional, two-phase flow. The first model d
... Show More
(1)
يؤدي عرض معلومات مضللة او محرفة ضمن القوائم المالية والتي تعد أهم مصادر المعلومات الموثوقة التي يُعول عليها لاتخاذ القرارات السليمة الى عدم قدرتها على عكس نتيجة النشاط والمركز المالي لها او اعمال الوحدة الاقتصادية لتلك الفترات الزمنية بصورة صادقة وعادلة نتيجة لنوعية المعلومات المفصح عنها في القوائم المالية لذلك زاد الاهتمام بتطوير الممارسات المحاسبية لتتضمن افصاحات كافية بغرض اعطائهم صورة صادقة وعادلة
... Show MoreA novel azo dye ligand namely (2-(pyridin-3-yldiazenyl)naphthalen-1-ol (HPYNA), was synthesized by the coupling reaction of diazonium salt of 3-aminopyridine with naphthol. The palladium(II) complex for HPYNA ligand was prepared by reacting palladium(II) ions with the HPYNA ligand. These synthesized compounds were characterized using different techniques, including mass, 1H-NMR, infrared, and UV-Vis spectroscopy. The infrared results show that the azo ligand reacts as a bidentate via the oxygen atom of phenol and nitrogen atom of the azo group. The palladium(II) complex is square-planer with diamagnetic properties depending on the results of electronic transitions and magnetic sensitivity. The HPYNA ligand and palladium complex show
... Show More
(5)
(2)
This study is about the role of the Internet in spreading rumors, especially through social networking sites "Facebook" model as the effectiveness of social networks lies in the speed of transmission of events; these two characteristics are important to the public, making the Internet a strong contender for television and its relationship with the public. That's why we find that the Internet today has become a fertile environment for the growth and spread of rumors. The more limited the platforms and places of publication, the greater the responsibility in the search for the original source in spreading this or that rumor, as the Internet is considered an easy means in the production, spreading and re-spreading of
... Show More
abstract:
Objectives: The study aims to reveal the approach of Imam Al-Salmi in the weighting between the apparently conflicting texts, and to show the extent of his agreement and disagreement with the rest of the fundamentalists, and does he have vocabulary that can be used to elicit legal rulings in modern contemporary issues?
Method: The method of induction and analysis is one of the main tools to reach the research results. The study resorted to following the sayings of Imam Al-Salmi in various sources and fatwas and standing on them, then analyzing and applying them to the various branches of jurisprudence in the various jurisprudential chapters.
... Show More