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 purpose behind building the linear regression model is to describe the real linear relation between any explanatory variable in the model and the dependent one, on the basis of the fact that the dependent variable is a linear function of the explanatory variables and one can use it for prediction and control. This purpose does not cometrue without getting significant, stable and reasonable estimatros for the parameters of the model, specifically regression-coefficients. The researcher found that "RUF" the criterian that he had suggested accurate and sufficient to accomplish that purpose when multicollinearity exists provided that the adequate model that satisfies the standard assumpitions of the error-term can be assigned. It
... Show MoreThe aim of this article is to study the dynamical behavior of an eco-epidemiological model. A prey-predator model comprising infectious disease in prey species and stage structure in predator species is suggested and studied. Presumed that the prey species growing logistically in the absence of predator and the ferocity process happened by Lotka-Volterra functional response. The existence, uniqueness, and boundedness of the solution of the model are investigated. The stability constraints of all equilibrium points are determined. The constraints of persistence of the model are established. The local bifurcation near every equilibrium point is analyzed. The global dynamics of the model are investigated numerically and confronted with the obt
... Show MoreThis paper discusses reliability R of the (2+1) Cascade model of inverse Weibull distribution. Reliability is to be found when strength-stress distributed is inverse Weibull random variables with unknown scale parameter and known shape parameter. Six estimation methods (Maximum likelihood, Moment, Least Square, Weighted Least Square, Regression and Percentile) are used to estimate reliability. There is a comparison between six different estimation methods by the simulation study by MATLAB 2016, using two statistical criteria Mean square error and Mean Absolute Percentage Error, where it is found that best estimator between the six estimators is Maximum likelihood estimation method.
Abstract
The study aimed to prepare a practical guide for procedures for auditing the strategies of municipal institutions in achieving sustainable development by adopting the idea of the audit matrix through which a classified report is prepared according to the dimensions of sustainable development, by preparing a specialized audit program for the purpose of auditing strategies for achieving sustainable development and emptying the results of the application of each of the paragraphs The program in the audit matrix that was prepared for the purpose of determining the impact of each observation and linkin
... Show MoreIn this paper, the problem of resource allocation at Al-Raji Company for soft drinks and juices was studied. The company produces several types of tasks to produce juices and soft drinks, which need machines to accomplish these tasks, as it has 6 machines that want to allocate to 4 different tasks to accomplish these tasks. The machines assigned to each task are subject to failure, as these machines are repaired to participate again in the production process. From past records of the company, the probability of failure machines at each task was calculated depending on company data information. Also, the time required for each machine to complete each task was recorded. The aim of this paper is to determine the minimum expected ti
... Show MoreIn this paper we estimate the coefficients and scale parameter in linear regression model depending on the residuals are of type 1 of extreme value distribution for the largest values . This can be regard as an improvement for the studies with the smallest values . We study two estimation methods ( OLS & MLE ) where we resort to Newton – Raphson (NR) and Fisher Scoring methods to get MLE estimate because the difficulty of using the usual approach with MLE . The relative efficiency criterion is considered beside to the statistical inference procedures for the extreme value regression model of type 1 for largest values . Confidence interval , hypothesis testing for both scale parameter and regression coefficients
... Show MoreThis study was conducted in the botanical garden, Department of biology, College of Science / Mustansiriyah University in spring season, where the starts from (15 February to 15 March, 2019). Under the natural environmental conditions in the greenhouse in order to evaluate the effectiveness of some plant extracts as a promoter for rooting the apical stem cutting of rosemary plants at different concentrations compared with the IBA growth regulator. Plant extracts are Parsley (Petroselinum crispum), Dill (Anethum graveolens) and date palm fruits (Phoenix dactylifera) were used with concentrations (0, 1.25, 2.5 g / l). The IBA concentration was (100 mg / L) with dipping time 24 hour for all treatments. The following measurements were taken aft
... Show MoreThis study evaluated yellow mealworm (Tenebrio molitor) larvae meal as an alternative animal-protein ingredient in diets for common carp (Cyprinus carpio) fingerlings. Two diets were compared for 60 days: a conventional fish-meal diet (T1; 32.09% crude protein) and a diet in which the animal-protein component was replaced weight-for-weight with T. molitor meal (T2; 23.88% crude protein). Each treatment was tested in duplicate tanks containing 28 fingerlings per tank, and growth was assessed over three consecutive 20-day phases. The initial mean body weight was 3.21 g. Weight gain differed significantly between treatments (p < 0.05), with the highest total value recorded in T2 (4.87 ± 0.47 g). The T2 diet produced a significantly higher fee
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