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 nature of the dark sector of the Universe remains one of the outstanding problems in modern cosmology, with the search for new observational probes guiding the development of the next generation of observational facilities. Clues come from tension between the predictions from Λ cold dark matter (ΛCDM) and observations of gravitationally lensed galaxies. Previous studies showed that galaxy clusters in the ΛCDM are not strong enough to reproduce the observed number of lensed arcs. This work aims to constrain the warm dark matter (WDM) cosmologies by means of the lensing efficiency of galaxy clusters drawn from these alternative models. The lensing characteristics of two samples of simulated clusters in the Λ warm dark matter and ΛCDM
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The development of a meaningful dissolution procedure for drug products with limited water solubility has been a challenge to both the pharmaceutical industry and the agencies that regulate them. Natural surfactants aid in the dissolution and subsequent absorption of drugs with limited aqueous solubility. In vitro, various techniques have been used to achieve adequate dissolution of the sparingly water – soluble or water insoluble drug products such as the use of mechanical methods (i.e., increased agitation and the disintegration method) or hydro alcoholic medium or large volumes of medium. The necessity of assuring the quality of drugs , especially those with low aqueous solubility and in vivo absorption , has led to the development and
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This paper was aimed to study the efficiency of forward osmosis (FO) process as a new application for the treatment of wastewater from textile effluent and the factors affecting the performance of forward osmosis process.
The draw solutions used were magnesium chloride (MgCl2), and aluminum sulphate (Al2 ( SO4)3 .18 H2O), and the feed solutions used were reactive red, and disperse blue dyes.
Experimental work were includes operating the forward osmosis process using thin film composite (TFC) membrane as flat sheet for different draw solutions and feed solutions. The operating parameters studied were : draw solutions concentration (10 – 90 g/l), feed solutions concentration (5 – 30 mg/l), draw solutions flow rate (10 – 50 l/hr
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The current research aims to reveal the strength of education and the direction of the relationship between the formal thinking and learning methods of Kindergarten department students. To achieve this objective, the researcher developed a scale of formal thinking according to the theory of (Inhelder & Piaget 1958) consisting of (25) items in the form of declarative phrases derived from the analysis of formal thinking skills based on a professional situation that students are expected to interact with in a professional way. The research sample consisted of (100) female students selected randomly who were divided into four groups based on the academic stages, the results revealed that The level of formal thinking of the main sample is
... Show MoreThe aim of this work is to evaluate the onc-electron expectation values < r > from the radial electronic density funetion D(r) for different wave ?'unctions for the 2s state of Li atom. The wave functions used were published in 1963,174? and 1993 , respectavily. Using " " ' wave function as a Slater determinant has used the positioning technique for the analysis open shell system of Li (Is2 2s) State.
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Shehadt 683 fish of different fish present in the tank Haditha Dam during the period of February 1993 and the end Maes 1994 to identify the nutritional content of the digestive tract or the stomach for these fish and their impact on the environment of the tank and found that Fish fine linen and Alhalg animal feeding predators feed on small fish, mainly the fish brown plantnutrition
The study aimed at the following:
Identify the differences in average scores core thinking skills kindergarten children by variable sex (male - female), and by variable age (5.6 - 5.11).
To achieve this researcher adopted a standardized test of core thinking skills for the kindergarten children, which was built and standardization by the researcher Meyada Asaad Mussa 2012 . applied test on a sample of (814) ) boys and girls who were randomly chosen form, from directorates of Baghdad Education Adoption of the proportional distribution.
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The main objective of present work is to describe the feasibility of friction stir welding (FSW) for
joining of low carbon steel with dimensions (3 mm X 80 mm X 150 mm). A matrix (3×3) of welding
parameters (welding speed and tool rotational speed) was used to see influence of each parameter on
properties of welded joint .Series of (FSW) experiments were conducted using CNC milling machine
utilizing the wide range of rotational speed and transverse speed of the machine. Effect of welding
parameters on mechanical properties of weld joints were investigated using different mechanical tests
including (tensile and microhardness tests ). Micro structural change during (FSW) process was
studied and different welding zones