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 effects of T-shaped fins on the improvement of phase change materials (PCM) melting are numerically investigated in vertical triple-tube storage containment. The PCM is held in the middle pipe of a triple-pipe heat exchanger while the heat transfer fluid flows through the internal and external pipes. The dimension effects of the T-shaped fins on the melting process of the PCM are investigated to determine the optimum case. Results indicate that while using T-shaped fins improves the melting performance of the PCM, the improvement potential is mainly governed by the fin’s body rather than the head. Hence, the proposed T-shaped fin did not noticeably improve melting at the bottom of the PCM domain; additionally, a flat fin is ad
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Praise be to God, Lord of the Worlds, and prayers and peace be upon the most honorable of creation, Muhammad, whom God sent as a mercy to the worlds, and his pure God and his faithful companions. The Islamic heritage was replete with texts issued from among the pure infallibility, which constituted a prominent teacher that takes the student to stop there in search of its goals, purposes and beauty. The choice was made from those texts that were issued by the imams of Muslims in the Abbasid era, namely Imam Muhammad al-Jawad, his son Imam Ali al-Hadi and his grandson Imam Hassan Zaki al-Askari. (Peace be upon them), and scholars have called them (sons of satisfaction), and researchers have shed light on these texts from rhetorical, artistic
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The aim: to evaluate combined microscopy techniques for determining the morphological and optical properties of methadone hydrochloride (MDN) crystals. Materials and methods: MDN crystal formation was optimized using a closed container method and crystals were characterized using polarized light microscope (PLM), scanning electron microscopy (SEM) and confocal microscopy (CM). SEM and CM were used to determine MDN crystal thickness and study its relationship with crystal retardation colours using the Michel-Levy Birefringence approach. Results: Dimensions (mean±SD) of diamond shaped MDN crystals were confirmed using SEM and CM. Crystals were 46.4±15.2 Vs 32.0±8.3 µm long, 28.03±8.2 Vs 20.85±5.5 µm wide, and 6.62±
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Purpose – The main purpose of this research is to highlight the main role of strategic leadership skills for top managements in accessing to effective management in accordance with the (VUCA Prime) methodology in (VUCA) environment as Miniature virtual environment, which refers to (Volatility), (Uncertainty), (Complexity), and (Ambiguity).
methodology – To achieve the research objective, this study selected the quantitative approach in research design, Questionnaire was used as the main instrument for data collection, the sample comprised the opinion poll (106) individual who functions as a head department. (Structural equation modelling by (Smart Pls3)
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Whatever the designers of the advertisement in choosing the text and spoken phrases, those phrases cannot give or convey the full meaning to the recipient only if this spoken and written language is reinforced with another language based on the signals, movements, and symbols that are displayed using the body or other artistic elements of the advertisement such as pictures, colors, music, effects, and other elements used in the artistic construction of television advertising. All these artistic elements contribute to the completion of the advertising idea and make it ready to be displayed to the public.
Scientists and researchers, in the field of psychology, have relied a lot on this language (body language). And some of them put
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Today, the five Caspian riparian states on the shores of the Caspian Sea (Kazakhstan, Turkmenistan, Azerbaijan, Russia, and Iran) have become a front for ambitions and international and regional competition, especially in light of the features and characteristics that natural geography has endowed them with and their enjoyment of a group of economic and mineral wealth that are not optimally exploited so far which made it a strategic attraction area for international trends and interventions, especially Western ones. It is a battleground for major international companies aiming to monopolize promising industrial investments in order to impose control and influence on the region’s resources and economic wealth and thus impose their forei
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Takbiratul Ehram "The First Takbeer to Start Prayer" means: the words that the worshiper says to start his prayers, and refrain from anything invalidates it. the findings revealed that the four school jurists agreed that the prayer is not valid without Takbiratul Ehram "The First Takbeer to Start Prayer", and they disagreed on its description, so the majority of jurists said that it is a pillar, and some of them called it an obligatory, but Hanafi made it a condition. Likewise, the four jurists agreed that the one who articulates Takbiratul Ehram "The First Takbeer to Start Prayer" with the word: “Allahu Akbar,”; his Takbeer is correct, and they disagreed about the one who adds a word, or replaced it with another, where the m
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