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
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The current research included " Diagnosis of the reality of the gap for the requirements of Business Continuity Management System According to International Standard (ISO 22301: 2012) in Midland Refineries Company (Daura Refinery) " , for development of an administrative system for Business Continuity is considered a priority in the present day, and in the light of the organizations dependence on computers and information technology in work and communication with others . the international legitimacy (represented by the international organization for standardization (ISO)) remains the basis for matching and commitment , and the importance of the application of Business Continuity Management Syst
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During the course of fixed orthodontic therapy, patients should be instructed to eat specific food stuffs and beverages in order to maintain good health for the dentition and supporting structures and prevent frequent attachment debonding that prolong the treatment duration. After searching and collecting articles from 1930 till July 2021, the current review was prepared to emphasize various types of foods that should be taken during the course of fixed orthodontic therapy and to explain the effect of various food stuffs and beverages on the growth and development of craniofacial structures, tooth surfaces, root resorption, tooth movement, retention and stability after orthodontic treatment and the effect on the components of fixed ortho
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In this review paper, several research studies were surveyed to assist future researchers to identify available techniques in the field of infectious disease modeling across complex networks. Infectious disease modelling is becoming increasingly important because of the microbes and viruses that threaten people’s lives and societies in all respects. It has long been a focus of research in many domains, including mathematical biology, physics, computer science, engineering, economics, and the social sciences, to properly represent and analyze spreading processes. This survey first presents a brief overview of previous literature and some graphs and equations to clarify the modeling in complex networks, the detection of soc
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Objectives: Although the Frankfort Horizontal (FH) and sella-nasion were routinely used as craniofacial reference planes, the inter-individual orientations were changeable when related to true horizontal (HOR). Natural head position (NHP) is a reproducible, standardized position, with the head in an upright posture and eyes focused on a point in the distance at eye level so that the visual axis is horizontal. The natural head position has importance in anthropological as well as in orthodontic fields, as this position has a relatively fixed relationship to the true horizontal and vertical planes. However, NHP is clinically not simple and it takes long time to be recorded, in addition to a deficiency in the tools utilized in the NHP and l
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In this review paper, several research studies were surveyed to assist future researchers to identify available techniques in the field of infectious disease modeling across complex networks. Infectious disease modelling is becoming increasingly important because of the microbes and viruses that threaten people’s lives and societies in all respects. It has long been a focus of research in many domains, including mathematical biology, physics, computer science, engineering, economics, and the social sciences, to properly represent and analyze spreading processes. This survey first presents a brief overview of previous literature and some graphs and equations to clarify the modeling in complex networks, the detection of soc
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Optimization of gas lift plays a substantial role in production and maximizing the net present value of the investment of oil field projects. However, the application of the optimization techniques in gas lift project is so complex because many decision variables, objective functions and constraints are involved in the gas lift optimization problem. In addition, many computational ways; traditional and modern, have been employed to optimize gas lift processes. This research aims to present the developing of the optimization techniques applied in the gas lift. Accordingly, the research classifies the applied optimization techniques, and it presents the limitations and the range of applications of each one to get an acceptable level of accura
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Taurodontism is a rare developmental dental anomaly marked by apical displacement of the pulpal floor, enlarged pulp chambers, and root bifurcation or trifurcation near the apex. Its etiology involves genetic mutations, syndromic associations, or developmental disturbances of Hertwig’s epithelial root sheath. Diagnosis relies mainly on radiographic assessment, with CBCT offering superior accuracy, and indices such as Shaw’s and Shifman’s aiding classification. Clinically, taurodontism complicates endodontic, surgical, orthodontic, and restorative procedures and may indicate underlying systemic disorders. Early recognition and interdisciplinary planning are crucial to optimizing patient outcomes. DOI: ht
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