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
A large number of researchers had attempted to identify the pattern of the functional relationship between fertility from a side and economic and social characteristics of the population from another, with the strength of effect of each. So, this research aims to monitor and analyze changes in the level of fertility temporally and spatially in recent decades, in addition to estimating fertility levels in Iraq for the period (1977-2011) and then make forecasting to the level of fertility in Iraq at the national level (except for the Kurdistan region), and for the period of (2012-2031). To achieve this goal has been the use of the Lee-Carter model to estimate fertility rates and predictable as well. As this is the form often has been familiar
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The researcher studies and explains the content of some pictures that are published in al-Mada newspaper. The research is important as it deals with a topic that has a relation with visual culture and its role to transfer the press letter to the audience. The researcher finds that cartoonist exposed the security services through important people who have a major role in state policy and reveals the level of corruption and the weak treatments for this phenomenon and its reflection on the whole society and individuals. In addition to that, cartoonists try to encourage the public for going on the peaceful demonstrations since it is a good tool to make pressure on the government to punish the corrupts.
Teen-Computer Interaction (TeenCI) stands in an infant phase and emerging in positive path. Compared to Human-Computer Interaction (generally dedicated to adult) and Child-Computer Interaction, TeenCI gets less interest in terms of research efforts and publications. This has revealed extensive prospects for researchers to explore and contribute in the region of computer design and evaluation for teen, in specific. As a subclass of HCI and a complementary for CCI, TeenCI that tolerates teen group, should be taken significant concern in the sense of its context, nature, development, characteristics and architecture. This paper tends to discover teen’s emotion contribution as the first attempt towards building a conceptual model for TeenC
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The cyanobacterial neurotoxin
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The purchase of a home and access to housing is one of the most important requirements for the life of the individual and the stability of living and the development of the prices of houses in general and in Baghdad in particular affected by several factors, including the basic area of the house, the age of the house, the neighborhood in which the housing is available and the basic services, Where the statistical model SSM model was used to model house prices over a period of time from 2000 to 2018 and forecast until 2025 The research is concerned with enhancing the importance of this model and describing it as a standard and important compared to the models used in the analysis of time series after obtaining the
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Objective: To conduct a standardized method for cavity preparation on the palatal surface of rat maxillary molars and to introduce a standardized method for tooth correct alignment within the specimen during the wax embedding procedure to better detect cavity position within the examined slides. Materials and methods: Six male Wistar rats, aged 4-6 weeks, were used. The maxillary molars of three animals were sectioned in the frontal plane to identify the thickness of hard tissue on the palatal surface of the first molar which was (250-300µm). The end-cutting bur (with a cutting head diameter of 0.2mm) was suitable for preparing a dentinal cavity (70-80µm) depth. Cavity preparation was then performed using the same bur on the tooth surf
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Objective: To conduct a standardized method for cavity preparation on the palatal surface of rat maxillary molars and to introduce a standardized method for tooth correct alignment within the specimen during the wax embedding procedure to better detect cavity position within the examined slides. Materials and methods: Six male Wistar rats, aged 4-6 weeks, were used. The maxillary molars of three animals were sectioned in the frontal plane to identify the thickness of hard tissue on the palatal surface of the first molar which was (250-300µm). The end-cutting bur (with a cutting head diameter of 0.2mm) was suitable for preparing a dentinal cavity (70-80µm) depth. Cavity preparation was then performed using the same bur on the tooth
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