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 study of sex Structure and age characteristics of an important element of the
follow-up changes between different population groups, which are connected to a large degree
the demographic, social and economic characteristics, particularly since each population
group varying characteristics in terms of age, sex entail social, demographic, cultural and
economic implications, and from that the researcher has taken from Structure of sex and age
for population in the district of Tuz Khurmatu for (1997-2012 ) the subject of consideration
and maintain compared to see the contrast between them. Qualitative Research for installation
and the age of the urban and rural areas has touched the judiciary, as well as its respects
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Reservoir fluids properties are very important in reservoir engineering computations such as material balance calculations, well testing analyses, reserve estimates, and numerical reservoir simulations. Isothermal oil compressibility is required in fluid flow problems, extension of fluid properties from values at the bubble point pressure to higher pressures of interest and in material balance calculations (Ramey, Spivey, and McCain). Isothermal oil compressibility is a measure of the fractional change in volume as pressure is changed at constant temperature (McCain). The most accurate method for determining the Isothermal oil compressibility is a laboratory PVT analysis; however, the evaluation of exploratory wells often require an esti
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The present study aimed at identifying the effectiveness of Macaton method in improving some sensory and cognitive skills in autistic children. In order to achieve the aims of the study, the researcher used the experimental method. The present study sample was (10) children whose ages ranged between (7-10) years and were diagnosed medically with autism disorder. The researcher randomly selected the sample and divided it into two groups: the first group consisted of (5) children representing the experimental group, and (5) children representing the control group after extracting the equivalence between the two groups in terms of age, intelligence, economic and social level and the degree of communication. The program was implemented for t
... Show MoreThe digital communication of a product of communication and information revolution. It is characterized by accurate and comprehensive in its services and its effects, which brought changes in the structure of many communities and their organizational structures. They have significant impacts on the social systems and social relations, especially in the Arab societies, which are the focus of the globalized Western media, for many reasons: economical, political , cultural and social.
According to this perception, the Arab identity has become in an encounter with big challenges by the globalized media of trade and the media, which aims to achieve greater profits because of identity and its importance to the communities. This occurs par
Abstract:
Today, the financial and banking sector is witnessing a qualitative shift thanks to financial technology services, which provide their services to many individuals and companies in quick, easy and less expensive ways compared to traditional means. Financial technology is a new form of financial science that combines financial transactions and technological skills concerned with providing financial services and improving the work environment within Banking institutions, and financial technology provides many advantages such as lower transaction costs, instant payment, and saving more time and effort in conducting banking
... Show MoreThe administrative leadership relies on a variety of behavioral paths in the functional areas in which it operates, and thus indicates its ability and thus has the upper hand in the organizational events, and in such a way that it can draw lessons and evaluate the results so as to test the expectations within the framework of the changes.
Does the study sample leadership have the characteristics that enable it to contain both crises and environmental stresses?
The aim of the study was to determine the location of the administrative leaders in the system of the study sample from the issue of crises and environmental pressures. The study concluded with a number of conclusions, the m
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Abstract:
The research aims to identify the concept of trading securities in Iraq and to propose a new mechanism for the taxation of trading profits and the extent of its impact on tax revenues, as it was observed that there are professional investors in the trading market and some of them achieve huge annual profits. and this profit should be like other taxable profits. The General Commission of Taxes and in cooperation with the Iraq Stock Exchange should identifying those profits, subjecting them to income tax, and adding them to the tax base. The researcher relied on the use of the descriptive and analytical approach bas
... Show MoreThis paper is attempt to study the nonlinear second order delay multi-value problems. We want to say that the properties of such kind of problems are the same as the properties of those with out delay just more technically involved. Our results discuss several known properties, introduce some notations and definitions. We also give an approximate solution to the coined problems using the Galerkin's method.