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
There is a set of economic factors that affect the rationalization of decisions on unexploited resources within the economic unit and here determines the problem of the search for the question of what economic factors cause the emergence of asymmetric costs, and aims to identify these factors in the costs of adjustment to resources, change in The size of the activity of the economic unit, the general trend of sales change in the previous period, and the economic level of the country. Rh measure the impact of these factors on economic unity, and taking into consideration the impact when formulating decisions.
Inform the people of the Enlightenment including what was said in detail
In photography
For Mohammed Hashim bin Ahmed footy famous Balva Hashim (Tel: 1349 e)
The research aims to find out the effect of Cognitive Acceleration strategy and random excitement strategy in achievement of geography material and developing the reflective thinking for students of literary fifth class .
the researcher depended a partial control experimental design with the three groups(the competence groups of the pre & post tests), The sample is deliberately selected from first AL-Rusafah Directorate General of Education in Baghdad. AL.fardoos Interme
... Show MoreThe research aims to shed light on the obstacles that hinder the use of taxpayers' commercial books covered by provisions of the amended commercial book-keeping system No. 2 of 1985 and ways to address these obstacles. On this basis, the main null hypothesis was formulated that there is no statistically significant relationship between the obstacles to the adoption of the commercial books and taxable income.
The research data were collected on the base of three applied case studies of registered taxpayers in the General Commission of Taxes, GCT, together with the use of a questionnaire distributed to a sample of taxpayers ( companies ). The collected data were analyzed, the result were presented and the hypothesis was
... Show MoreThis study aims to investigate the degree of practicing the motivated classroom evaluation environment for learning and its relationship to different feedback patterns. To achieve the objectives of the study, the correlational descriptive research design was employed. A questionnaire was constructed consisting of two parts: the classroom evaluation environment (13) items, and feedback patterns (24) items on a five-point scale. The psychometric properties of the questionnaire were verified in terms of validity and reliability. The questionnaire was applied to a sample of (265) male and female teachers who work in the second cycle schools for grades (5-10) of basic education in all academic majors in the Governorate of Muscat in the Sultan
... Show MoreThe current research examines the employment of indicators of stereotypes and the dimensions of organizational clarification to achieve planned organizational behaviour on a sample of employees in a number of departments of the Faculties of Engineering, University of Kufa, for a sample of (122) teaching staff. This research proposes the use of positive indicators of stereotypes for both the organization and employees and their awareness of what they want to obtain and what should be done for both parties and the removal of organizational clarity represented by the functional dimension that explores to what degree the employee's understanding of the internal strategy of the organization and the strategic dimension that searches fo
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Background: Eucalyptus extracts and derivatives are natural substances with potent antimicrobial properties. This study investigated the in- vitro effects of non-nutritive sweeteners on the antifungal activity of alcoholic and aqueous Eucalyptus extracts against Candida albicans, a common oral pathogen. Materials and Method: Ten isolates of Candida albicans were isolated from dental students’ salivary samples. The alcoholic and aqueous extracts were prepared from fresh Eucalyptus leaves using maceration. The sensitivity of Candida albicans isolates to various concentrations of Eucalyptus extracts ranging from 50 to 250 (mg/mL) was evaluated via agar well diffusion method, while the agar streaking method was used to assess the minimum
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Resumen:
El horóscopo que es una predicción deducida de la posición de los astros del sistema solar y de los signos de Zodiaco, intenta no sólo predecir el futuro, sino también influir en el comportamiento del lector, orientándolo para que actúe adecuadamente y la invitación a actuar ante ese futuro que se aconseja mediante imperativos, perífrasis y otros recursos lingüísticos. Los horóscopos se caracterizan por su gran popularidad que existen en periódico o revista en columnas enteras dedicadas al tema, en donde se detallan la influencia que tendrá el día o el mes de cada uno de los signos correspondientes al zodíaco, siempre teniendo en cuenta la posici
... Show MoreWheat straw was modified with malonic acid in order to get low cost adsorbent have a good ability to remove copper and ferric ions from aqueous solutions, chemical modification temperature was 120°C and the time was 12 h. Parameters that affect the adsorption experiments were studied and found the optimum pH were 6 and 5 for copper and iron respectively and the time interval was 120 min and the adsorbent mass was 0.1 g. The values for adsorption isotherms parameters were determined according to Langmuir [qmax were 54.64 and 61.7 mg/g while b values were 0.234 and 0.22 mg/l] , Freundlich [Kf were 16.07 and 18.89 mg/g and n were 2.77 and 3.16], Temkin [B were 0.063 and 0.074 j/mol and At were 0.143 and 1.658 l/g] and for Dubinin-Radushkev
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