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 parliamentary election is one of the features of democratic systems that give individuals the right to participate in government and political election-making. Typically, the process of parliamentary elections received wide attention from media, as well as attention from large segments of the public because they understand the vast importance to assume political positions and associated fates of people and their destinies. Its importance comes from the fact that it allows citizens the right to participate in managing the public affairs by granting their confidence and voices to the elected president or his representatives in the parliamentary.
Media task is to emerge democratic societies, in particular, in the mission of urging p
بسبب محدودية الموارد الطبيعية، فأن سكان الخليج ومنذ القدم وجهوا جلّ نشاطاتهم توجهاً بحرياً: صيد الاسماك وصناعة اللؤلؤ العنصر الرئيس في حجم التشغيل، وتكوين الفائض الاقتصادي في المنطقة آنذاك.
لقد تزايدت أهمية هذا النشاط بخاصة بعد النصف الثاني من القرن التاسع عشر، لرواج تجارة اللؤلؤ عالمياً، وأنفتاح الخليج على الدول الاوروبية التي شهدت نهضة صناعية متسارعة، وحيث وصلت الخليج العديد من بضائع
... Show More
This study includes synthesis of some nitrogenous heterocyclic compounds linked to amino acid esters or heterocyclic amines that may have a potential activity as antimicrobial and/or cytotoxic. Quinolines are an important group of organic compounds that possess useful biological activity as antibacterial, antifungal and antitumor .8-Hydroxyquinoline (8-HQ) and numerous of its derivatives exhibit potent activities against fungi and bacteria which make them good candidates for the treatment of many parasitic and microbial infection diseases.
These pharmacological properties of quinolones aroused our interest in synthesizing several new compounds featuring heterocyclic rings of the quinoline derivatives linke
... Show More
(3)
The study aims to use the European Excellence Model (EFQM) in assessing the institutional performance of the National Center for Administrative Development and Information Technology in order to determine the gap between the actual reality of the performance of the Center and the standards adopted in the model, in order to know the extent to which the Center seeks to achieve excellence in performance to improve the level of services provided and the adoption of methods Modern and contemporary management in the evaluation of its institutional performance.
The problem of the study was the absence of an institutional performance evaluation system at the centre whereby weaknesses (areas of improvement) and st
... Show More
The purpose of this paper is to statistically classify and categorize Building Information Modelling (BIM)-Facility Management (FM) publications in order to extract useful information related to the adoption and use of BIM in FM.
This study employs a quantitative approach using science mapping techniques to examine BIM-FM publications using Web of Science (WOS) database for the period between 2000 and April 2018.
The findi
(38)
(35)
In the present study, activated carbon supported metal oxides was prepared for thiophene removal from model fuel (Thiophene in n-hexane) using adsorptive desulfurization technique. Commercial activated carbon was loaded individually with copper oxide in the form of Cu2O/AC. A comparison of the kinetic and isotherm models of the sorption of thiophene from model fuel was made at different operating conditions including adsorbent dose, initial thiophene concentration and contact time. Various adsorption rate constants and isotherm parameters were calculated. Results indicated that the desulfurization was enhanced when copper was loaded onto activated carbon surface. The highest desulfurization percent for Cu2O/AC and o
... Show MoreIn this review of literature, the light will be concentrated on the role of stem cells as an approach in periodontal regeneration.
1,3,4-oxadizole and pyrazole derivatives are very important scaffolds for medicinal chemistry. A literature survey revealed that they possess a wide spectrum of biological activities including anti-inflammatory and antitumor effects.
To describe the synthesis and evaluation of two classes of new niflumic acid (NF) derivatives, the 1,3,4-oxadizole derivatives (compounds 3 and (4A-E) and pyrazole derivatives (compounds 5 and 6), as EGFR tyrosine kinase inhibitors in silico and in vitro.
The designed compounds were synthesized using convent
(11)
(9)
Social media has become an essential educational tool nowadays. Most existing research on digital learning in EFL contexts has primarily focused on traditional classroom-based instruction and less attention has been paid to social media platforms. The present study aims to fill the gap by using social semiotics to analyze four Instagram posts: two from BBC Learning English (@bbclearningenglish) and the other two from Learn English with Emma (@englishwithemma). Instagram posts are classified as multimodal texts with participatory and representational elements. The study adopts Kress and van Leeuwen’s (2005) Social Semiotic Multimodal Framework to analyze four purposely selected posters by answering the following research questions
... Show More