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
Rhythm is considered one of the creative concepts in the recent architectural thought; it has emerged clearly as a mean of creating the highest levels of creativity in architecture, especially in contemporary architectural movements. The importance of rhythm has emerged, especially, when the architecture , its beginnings concentrated on the principle of the links with poetic structures. Many architectural studies deal with concept of rhythm in architecture with different ways various according to the trend of each study, this show the importance of studying the concept of rhythm in the architectural field in general. This study try to focus on the utilization of rhythm as creative system in architecture of heritage and contemporary
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Excessive intake of fluoride, mainly through drinking water is a serious health hazard affecting humans worldwide. In this study, the defluoridation capacities of locally available raw waste beef bones have been estimated. Several experimental parameters including contact time, pH, bone dose, fluoride initial concentration, bone grains size, agitation rate, and the effect of co-existence of anions in actual samples of wastewater were studied for fluoride removal from aqueous solutions. Results indicated excellent fluoride removal effeciency up to 99.7% at fluoride initial concentration of 10 mg F/L and 120 min contact time. Maximum fluoride uptake was obtained at neutral pH range 6-7. Fluoride removal kinetic was well described by the ps
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Shabak is one of minority related to Kurdish nation , speaking Bajalan variety especially Goran Dialect.
This study is a historic and diactological study about Kurdish Bajalan variety.The study is composed an introduction and tw0 chapters. The first chapter talks about Bajalan variety , and it has two axes . In the first axe , I talk about the geography of Bajalan variety and in the second axes the map of goran dialect . The second chapter is about Shabak variety and it is constituted of three axes : The first section is about Shabak variety , in the second section is allocated to the domicile of Shabak variety and in the third section , talks about the saint of shabak and in the end the
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Pulsed laser deposition (PLD) technique was applied to prepared Chromium oxide (Cr2O3) nanostructure doped with Titanium oxide (TiO2) thin films at different concentration ratios 3,5,7 and 9 wt % of TiO2. The effect of TiO2 dopant on the average size of crystallite of the synthesized nanostructures was examined by X-ray diffraction. The morphological properties were discussed using atomic force microscopy(AFM). Observed optical band gap value ranged from 2.68 eV to 2.55 eV by ultraviolet visible(UV-Vis.) absorption spectroscopy with longer wave length shifted in comparison with that of the bulk Cr2O3 ~3eV. This indicated that the synthesized samples a
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Background: The present study involved the following parts, the first part is evaluation of the levels of glycated hemoglobin(HbA1c), creatinine, uric acid(UA) and albumin in patients with diabetic nephropathy comparison with the group of healthy as a control group. The second part is the measurement and evaluation of oxidative stress represented in the malondihydehyde(MDA) as a biomarker of oxidative stress as well as the identification of vitamins C and E as an antioxidant in patients with diabetic nephropathy(DN) compared with the healthy group. Objective: The objective of this study is to estimate oxidative stress by calculate malondialdehyd as biomarker and evaluate some vitamins such as vit C and vit E as antioxidants in diabetic neph
... Show MoreA group of amine derivatives [4-aminobenzenesulfonamide derivatives, 2-aminopyridine and 2-aminothiazole] incorporated to α-carbon of diclofenac a well known non-steroidal anti-inflammatory drug (NSAID) to increase bulkiness were designed and synthesized for evaluation as a potential anti-inflammatory agents with expected COX-2 selectivity. In vivo acute anti-inflammatory activity of the selected final compounds (9, 12 and 13) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (3 mg/Kg) of diclofenac sodium. All tested compounds produced a significant reduction in paw edema with respect to the effect of propylene glycol 50
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Water pollution as a result of contamination with dye-contaminating effluents is a severe issue for water reservoirs, which instigated the study of biodegradation of Reactive Red 195 and Reactive Blue dyes by E. coli and Bacillus sp. The effects of occupation time, solution pH, initial dyes concentrations, biomass loading, and temperature were investigated via batch-system experiments by using the Design of Experiment (DOE) for 2 levels and 5 factors response surface methodology (RSM). The operational conditions used for these factors were optimized using quadratic techniques by reducing the number of experiments. The results revealed that the two types of bacteria had a powerful effect on biodegradable dyes. The regression analysis reveale
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A comparative study was done on the adsorption of methyl orange dye (MO) using non-activated and activated corn leaves with hydrochloric acid as an adsorbent material. Scanning electron microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR) were utilized to specify the properties of adsorbent material. The effect of several variables (pH, initial dye concentration, temperature, amount of adsorbent and contact time) on the removal efficiency was studied and the results indicated that the adsorption efficiency increases with the increase in the concentration of dye, adsorbent dosage and contact time, while inversely proportional to the increase in pH and temperature for both the treated and untreated corn leaves. The equi
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