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
Research summary
Backbiting pronouns have gained great importance in contemporary textual linguistic studies, as they play a coordinating function in the text and link its parts.
Interpreters did not overlook the role of backbiting pronouns in achieving the function of consistency and coherence in the Qur’anic text, as they referred to this, including Ibn Ashour, who had many analytical practices related to referral issues and their complexities. The Qur'anic reference to the pronouns of backbiting, so the researcher traced these phenomena and their evidence in the Holy Qur'an, aiming to clarify their role in enriching the significance and in the coherence and harmony
... Show MoreThe novel has recently received great attention from readers and before them writers, due to the role it is playing, and this indicates an important rule, which is whenever there is art or creativity, there must be a criticism of its own, and this criticism is certainly no less important than its owner, so we find There are critics who have their distinguished literary position in following up the narrative development, and trying to describe the transformation of its elements, including Professor Fadel Thamer, and whoever wants to approach an element of the novel as an explorer, he must stand on the visions of this critic about it, and this is what made us take the element (personality) Tracking the most important opinions of the critic
... Show MoreThe report includes a group of symbols that are employed within a framework that gives a language of greater impact. This research discusses the problem of the semiotic employment of religious symbols in press reports published in the electronic press across two levels: Reading to perceive the visual message in its abstract form, and the second for re-understanding and interpretation, as this level gives semantics to reveal the implicit level of media messages through a set of semiotic criteria on which it was based to cut texts to reach the process of understanding and interpretation.
The report includes a group of symbols that are employed within a framework that gives a language of greater impact. This research discusses the p
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The Gulf Cooperation Council (GCC) is the only one in the Arab system, which has been able to formulate a strategic vision with its dimensions and objectives, and that for its great achievements have contributed significantly to the development of the external and internal economic relations of the Gulf Cooperation Council six through the consolidation of economic policies, projects and joint institutions . There is no doubt that the establishment of the Cooperation Council for the Arab Gulf States six, has made security expensive as long as the aspiration to them the leaders and peoples of the region is the adoption of the GCC countries on itself in order to build a self strength ensures cut off the road to all interference in the affai
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This paper aims at discovering the real implication of deduction in the Arabic culture
with concentration on its applications in Arabic grammar, logic, and fundamentals of Islamic
legislations. Some light has been shed on deduction in the Arabic culture but most of recent
works did not analyze deduction according to the pragmatic analysis. This paper will answer
the following questions:
to what extent deduction in Arabic grammar could comprehend with deduction l logic and
fundamentals of thinking in Islamic thought?
how can we find the deduction thinking in the Qur’anic surah if Ghafir?
Can we find parts of deduction in the surah?
The methodology in this paper is descriptive analytical. This metho
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يشهد المسرح الدولي قضايا مستجدة ومستحدثة مثل تعدد الفاعلين من الدول ومن غير الدول وتزايد مساحات نفوذهم وتأثيرهم ،ومن جانب اخر أثرت جائحة كورونا على البيئة والمناخ بشكل ملموس على جوانب عدة. فضلا عن ذلك تأثرت جميع المجتمعات البشرية بالإرهاب والهجمات الالكترونية وغيرها ومن بينها دول والمجتمع الدولي بإفراده مؤسسات وكيان اقتصادي وسياسي وقانوني وأمني وامتداد اثاره واسبابه الكثيرة والمتداخلة وما يثيره من خلق حا
... Show MoreThis study came to discuss the subject of industries dependent on petrochemical industries in Iraq (plastic as a model) during the period 2005–2020, and the study concluded that the plastic industries contribute to areas of advancement and progress and opportunities to deal efficiently with the challenges posed by the new variables, the most important of which is the information revolution. communications and trade liberalization, and this is what contributes to the competitiveness of these industries. And because the petrochemical industry in Iraq has an active role in establishing plastic industrial clusters and clusters of micro, small, and medium industries by providing the necessary feedstock for these industries in various fields
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It is very necessary for the political theater to be within the space of every theatrical performance, so that the theater carries the diverse and enlightened values and cultures of this world. political theatre. In the first chapter, the researcher dealt with (the methodological framework), which includes the research problem identified by the researcher with the following question (the functional diversity of the directorial vision in the political theater)
Importance, purpose, limits and seal by defining terminology.
In the second chapter, the researcher dealt with the theoretical framework on two topics, the first (transformations of directorial vision in theatrical performance) and the second topic (aesthetic experiences i
Discretionary Punishment, Public Regulation, Interest