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 optical absorption data of Hydrogenated Amorphous Silicon was analyzed using a Dunstan model of optical absorption in amorphous semiconductors. This model introduces disorder into the band-band absorption through a linear exponential distribution of local energy gaps, and it accounts for both the Urbach and Tauc regions of the optical absorption edge.Compared to other models of similar bases, such as the O’Leary and Guerra models, it is simpler to understand mathematically and has a physical meaning. The optical absorption data of Jackson et al and Maurer et al were successfully interpreted using Dunstan’s model. Useful physical parameters are extracted especially the band to the band energy gap , which is the energy gap in the a
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Acquisition provisions in Islamic jurisprudence
It is well known that the spread of cancer or tumor growth increases in polluted environments. In this paper, the dynamic behavior of the cancer model in the polluted environment is studied taking into consideration the delay in clearance of the environment from their contamination. The set of differential equations that simulates this epidemic model is formulated. The existence, uniqueness, and the bound of the solution are discussed. The local and global stability conditions of disease-free and endemic equilibrium points are investigated. The occurrence of the Hopf bifurcation around the endemic equilibrium point is proved. The stability and direction of the periodic dynamics are studied. Finally, the paper is ended with a numerical simul
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This study has contributed to understanding a delayed prey-predator system involving cannibalism. The system is assumed to use the Holling type II functional response to describe the consuming process and incorporates the predator’s refuge against the cannibalism process. The characteristics of the solution are discussed. All potential equilibrium points have been identified. All equilibrium points’ local stability analyses for all time delay values are investigated. The system exhibits a Hopf bifurcation at the coexistence equilibrium, which is further demonstrated. The center manifold and normal form theorems for functional differential equations are then used to establish the direction of Hopf bifurcation and the stability of the per
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Naber and toning in the modern Arab poetry Mahmoud Darwish, a model
When we talk about the foresight in films, it is necessary to talk about dreams because foresight represents one of its distinct types. The Precognitive vision has become a possible material in dealing with as subjects in the film industry that adopt these ideas with their philosophical and scientific orientations, because they represent the imagination that predictors are specialized with. It can be invested through the introduction of a vision of another kind to achieve its goals and ambitions in the film industry and in particular the huge institutions of production as in Hollywood. The cinema works in the light of those concepts of production which found the prognostic dream (the foresight) as a distinctive genre in its films,
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Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of central nervous system with complex etiopathogenesis that impacts young adults (Lee et al., 2015), and MS impacts younger and middle aged character and leads to a range of disabilities that can alter their daily routines (Yara et al, 2010). Although, the exact cause of MS is still undetermined, the disease is mediated by adaptive immunity through the infiltration of T cells into the central nervous system (Bjelobaba et al, 2017). MS causes the Focal neurological symptomsand biochemical changes in the molecular level and the variation of neural cells such as loss or alteration of sensation, motor function, visible signs such as blurred vision or transient blindness,
... Show MoreIn the present study, magnet silica-coated Ag2WO4/Ag2S nanocomposites (FOSOAWAS) were fabricated via a multistep method to address the drawbacks related to single photocatalysts (pure Ag2WO4 and pure Ag2S) and to clarify the significant influence of semiconductor heterojunction on the enhancement of visible-light-driven organic degradation. Different techniques were performed to investigate the elemental composition, morphology, magnetic and photoelectrochemical properties of the fabricated FOSOAWAS photocatalyst. The FOSOAWAS photocatalyst (1 g/L) exhibited excellent photodegradation efficiency (99.5%) against Congo red dye (CR = 20 ppm) after 140 min of visible-light illumination. This result confirmed the ability of the heterojunction be
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