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
In this study, a bioadhesive dosage form of eoconazole nitrate for vaginal delivery was designed using a combination of bioadhesive polymers: Carbopol 941 p and sodium carboxymethylcellulose or methylcellulose in different ratios. The bioadhesive strength was evaluated by measuring the force required to detach the tablet from sheep vaginal mucosal membrane. It was found that the bioadhesive force was directly proportional to Carbopol 941 p content in the different formulae. The formulae were tested for their swelling behavior using agar gel plate method. The results showed that formulae containing a combination of Carbopol 941 p and sodium carboxymethylcellulose had greater swelling index
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The present study investigates the relation between the biliteral and triliteral roots which is the introduction to comprehend the nature of the Semitic roots during its early stage of development being unconfirmed to a single pattern. The present research is not meant to decide on the question of the biliteral roots in the Semitic languages, rather it is meant to confirm the predominance of the triliteral roots on these languages which refers, partially, to analogy adopted by the majority of linguists. This tendency is frequently seen in the languages which incline to over generalize the triliteral phenomenon, i. e., to transfer the biliteral roots to the triliteral room, that is, to subject it to the predominant pattern regarding the r
... Show MoreThe semiotic trend of recent monetary trends task that took a wide range of attention of critics and readers alike, especially after the deployment, which accompanied him after widespread acts critic Grimas and powers applicable to the literary texts and is thus expanded its care circle, hence the choice of the novel (absent) woman Iraqi novelist (Mahdi ‘Issa falcon) model to be applied to the study chose to be a semiotic approach through the use of procedural mechanisms for its critical tool (Paris School of semiotics), cash and views of its founder critic Grimas.The research in the introduction and pave came we made it a vision for literary semiotic and its impact trend in cash and cash is and what it desire to clarify some poked suc
... Show MoreThe operative system of theatrical performance depends on the construction of the scenographic space, as it constitutes the most aesthetic effect of the recipient, and the body of the theatrical discourse that contains the signs of the show, and it comes as an embodiment of the directing vision of the show director, so most of the world directors resorted to attention to the output treatment to establish the scenographic space, and thus it possesses a contrast in The embodiment of the directing vision according to the stylistic and hermeneutical dimension of the director, so the two researchers found the importance of studying the topic, and the study came under the title (Directing Treatments of the Scenographic Space in the Iraqi Theat
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This research dealt with the subject of negotiation skills of employees in public relations departments which is one of many skills supposed to be available to these employees. These skills combined help in the success of the job of public relations departments; and give them an important and vital role within the roles distributed in the departments of any government institution wither is governmental or non-governmental.
Negotiation is a skill that requires intelligence, tact, culture, information, intuition, and knowing to use the means of communication to access the information that is useful in reaching satisfactory results
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The goal of the research is to develop a sustainable rating system for roadway projects in Iraq for all of the life cycle stages of the projects which are (planning, design, construction and operation and maintenance). This paper investigates the criteria and its weightings of the suggested roadway rating system depending on sustainable planning activities. The methodology started in suggesting a group of sustainable criteria for planning stage and then suggesting weights from (1-5) points for each one of it. After that data were collected by using a closed questionnaire directed to the roadway experts group in order to verify the criteria weightings based on the relative importance of the roadway related impacts
... Show MoreIn the present article, we implement the new iterative method proposed by Daftardar-Gejji and Jafari (NIM) [V. Daftardar-Gejji, H. Jafari, An iterative method for solving nonlinear functional equations, J. Math. Anal. Appl. 316 (2006) 753-763] to solve two problems; the first one is the problem of spread of a non-fatal disease in a population which is assumed to have constant size over the period of the epidemic, and the other one is the problem of the prey and predator. The results demonstrate that the method has many merits such as being derivative-free, overcome the difficulty arising in calculating Adomian polynomials to handle the nonlinear terms in Adomian Decomposition Method (ADM), does not require to calculate Lagrange multiplier a
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Objective: The evaluation of serum osteocalcin (OSN) for Iraqi infertile patients to see the effect of osteocalcin insufficiency, which may lead to a decreased level of testosterone production in males that may cause infertility. Methods: Forty two newly diagnosed infertile males age range (24–47) years and thirty two apparently healthy males as controls age range (25–58) years. Serum levels of testosterone (TEST), stimulating follicle hormone (FSH) and luteinizing hormone (LH), prolactin (PROL), osteocalcin OSN, and fasting blood sugar (FBS) were performed in both patients and controls. Estimation of serum OSN by Immulite1000 auto-analyzer, TEST, FSH, LH, PROL, and FBS by Immulite2000 auto-analyzer. Results: Infertile patients
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The aim of this essay is to use a single-index model in developing and adjusting Fama-MacBeth. Penalized smoothing spline regression technique (SIMPLS) foresaw this adjustment. Two generalized cross-validation techniques, Generalized Cross Validation Grid (GGCV) and Generalized Cross Validation Fast (FGCV), anticipated the regular value of smoothing covered under this technique. Due to the two-steps nature of the Fama-MacBeth model, this estimation generated four estimates: SIMPLS(FGCV) - SIMPLS(FGCV), SIMPLS(FGCV) - SIM PLS(GGCV), SIMPLS(GGCV) - SIMPLS(FGCV), SIM PLS(GGCV) - SIM PLS(GGCV). Three-factor Fama-French model—market risk premium, size factor, value factor, and their implication for excess stock returns and portfolio return
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