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
Rapid and continuous developments and changes in the modern business environment in all areas of economic, environmental, social, technology and communications push economic units to search for modern methods and methodologies to produce products at low cost as well as produce products that meet the wishes of customers in terms of quality and environment to maintain their market position, and accounting for the costs of the flow of materials is one of the most prominent environmental management accounting techniques capable of providing information to help produce
Training has an effect on employees’ performances. Accordingly, the person who is responsible for employees’ development must figure out the most effective way to train and develop employees. Central Michigan University (CMU) has recognized the importance of providing appropriate training for employees who have a duty in advising students. The reason is that these employees have a significant impact on students’ educational performances. Thus, special attention to this category of employees is needed to improve advising quality. This research attempted to explore the impact of training on academic advising at CMU. Face-to-face interviews and online surveys were used as data collection tools for this study. The study scope c
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Pyrolysis of high density polyethylene (HDPE) was carried out in a 750 cm3 stainless steel autoclave reactor, with temperature ranging from 470 to 495° C and reaction times up to 90 minute. The influence of the operating conditions on the component yields was studied. It was found that the optimum cracking condition for HDPE that maximized the oil yield to 70 wt. % was 480°C and 20 minutes. The results show that for higher cracking temperature, and longer reaction times there was higher production of gas and coke. Furthermore, higher temperature increases the aromatics and produce lighter oil with lower viscosity.
This paper present a simple and sensitive method for the determination of DL-Histidine using FIA-Chemiluminometric measurement resulted from oxidation of luminol molecule by hydrogen peroxide in alkaline medium in the presence of DL-Histidine. Using 70?l. sample linear plot with a coefficient of determination 95.79% for (5-60) mmol.L-1 while for a quadratic relation C.O.D = 96.44% for (5-80) mmol.L-1 and found that guadratic plot in more representative. Limit of detection was 31.93 ?g DL-Histidine (S/N = 3), repeatability of measurement was less that 5% (n=6). Positive and negative ion interferances was removed by using minicolume containing ion exchange resin located after injection valve position.
Based on the systematic scientific investigation of artistic achievement, researchers (critics) adhere to mechanisms based on epistemology, through which it is envisaged to reveal the meaning of the achievement as the product of three actors: the effectiveness of an artistic sense, the effectiveness of an idea, and the arousal of taste according to systematic criticism procedures that investigate the new artistic achievement. Or, in a specific way, the possibility of meaning in all the accomplished from the aesthetics of artistic presentation and the character of the self-accomplished by the "artist" and the critic invokes his critical tools with certain cognitive foundations. In defining its nature from the rest of the other cultural ac
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The research aims to build a list of digital citizenship axes and standards and indicators emanating from them, which should be included in the content of the computer textbook scheduled for second grade intermediate students in Iraq, and the analysis of the above mentioned book according to the same list using the descriptive analytical method ((method of content analysis)). The research community and its sample consisted of the content of the computer textbook scheduled for the second year intermediate students for the academic year 2018-2019, and the research tool was built in its initial form after reference to a set of specialized literature and previous studies that dealt with topics related to digital citizenship, and the authenticit
... Show MoreThe study showed that there are (28) plant families present in Al-Razzaza Lake. The families are (Amaranthaceae, Amaryllidaceae, Aizoaceae, Apiaceae, Apocynaceae, Asteraceae, Brassicaceae, Boraginaceae, Capparaceae, Caryophyllaceae, Cistaceae, Colchicaceae, Convolvulaceae, Cynomoriaceae, Fabaceae, Frankeniaceae, Lamiaceae, Liliaceae, Malvaceae, Orobanchaceae, Plantaginaceae, Poaceae, Polygonaceae, Ranunculaceae, Solanaceae, Tamaricaceae,Typhaceae, Zygophyllaceae). Asteraceae family is the largest number of species found in abundance in this lake, followed by the Fabaceae family.
Solar energy is the most abundant renewable energy source. This energy can be converted directly into electricity using solar panels. The fixed tilt solar panels are the most practical and the most widely installed throughout the world. Optimum tilt angle calculation has the advantage that it does not use expensive solar trackers. This research calculates the seasonal optimum tilt angle of solar panels for 17 cities in Iraq and 83 cities in 83 countries distributed around the world. Solar Panel Angle Calculator program was used in calculating the optimum tilt angles from vertical. The optimum tilt angle varies between 6° and 112° throughout the year. This angle for winter, spring/ autumn and summer seasons are found to be between
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