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
Coronary artery disease (CAD) is a major health concern and leading of death in individuals with type 2 diabetes mellitus (T2DM). Glutathione S – Transferase(GST) are known for their broad range of detoxification and in the metabolism of xenobiotics . The role of functional variants of these genes in the development of various disorder is proven. We investigated the possible role of these variants in the development of CAD in T2DM patients. In this case – control study a total of 60 patients (T2DM = 30 ; T2DM – CAD = 30) and 30 controls were included. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTT1/M1 (present / null) polymorphism, were performed for genotyping of study pa
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يهدف البحث إلى تقييم الكفاءة الوظيفية لمؤسسات التعليم الأهلي في أداء وظيفتها بمستوى عالٍ لتشبع حاجة سكان المدينة الذين فضّلوا التعليم الأهلي على التعليم داخل المؤسسات الحكومية مما أدى إلى انتشارها، وصولا إلى أهم الآثار المترتبة على ذلك الانتشار إذ نافست فيه مؤسسات التعليم الحكومي، بل وتنافست المؤسسات الأهلية فيما بينها لتقديم أفضل خدمة تعليمية للصراع من أجل البقاء، وتهدف أيضا إلى إظهار الوجه السلبي ا
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Praise be to Allaah.
My research has included the following: The field of application of semantics when fundamentalists are the book and the Sunnah. Imam Ibn Hajar agreed with the majority of fundamentalists that what is meant from the year (one word denotes one side on two things onwards), and agreed that the significance of the year specific to the rest of its members is not a definite and definite formulas of the public has the singular known as (the) Astragharism, and the plural known as ( The nationality stating that dumping, pluralism is defined as (add), and nakra, if it occurs in the context of the condition, denial and prohibition, the names of the condition, the connected names, and the word (all - all). And the year in whic
Abstract
The research aims to determine the role of the efficiency of Human Resources Information System in the effectiveness of Employees Performance Appraisal System in the Ministry of Higher Education and Scientific Research / Center for the ministry, it was touching the researchers need the ministry to devise methods that employ outputs Human Resources Information System in the organization surveyed for the development of methods and levels of process evaluate the performance of its employees, in order to identify the extent of the role played by human resources information system in the process of assessing the performance of employees, we raised the question of the President as follows:
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This study was conducted to detect the relationship between organic content in the sediment of Rivers Tigris and Diyala, at two locations south of Baghdad, with some environmental factors and the benthic invertebrates and values of diversity indices. Monthly samples collected from the area for the period November 2007 to October 2008. Results showed differences in the physical and chemical characteristics of the two sites, Where the annual average in Tigris and Diyala were respectively for: water temperature (19, 20) C°, pH (8, 8), dissolved oxygen (4, 8) mg / l , Biochemical oxygen Demand BOD5 (3,44 ) mg/l, TDS (632,1585) mg / l, TSS (42, 44) mg / l, turbidity (28,74) NTU, and total hardness as CaCO3 (485,823) mg / l ,Sulfat
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Background: The study aim was to evaluate thermocycling effect on microleakage of occlusal and cervical margins of MOD cavity filled with bulk filled composites in comparison to incrementally placed nanohybrid composite and to evaluate the difference in microleakage between enamel and dentin margins for the three materials groups. Materials and method: Forty eight maxillary first premolars were prepared with MOD cavities. Samples were divided into three groups of sixteen teeth according to material used: Grandio: Grandio. SDR: SDR +Grandio. X-tra: X-tra base + Grandio. Each group was subdivided into two according to be thermocycled or not. After 24 hrs immersion in 2% methylene blue, samples weresectioned and microleakage was estimated. Res
... Show MoreThe study has tackled three important variables on the strategic and organizational level, that are : (Administrative skill, strategic Entrepreneurship and organizational flexibility). Through the statistical analysis is, the research hers have sought to identify the relation among them. The study has been applied on a sample of (44) private banks in Iraq. A questionnaire, which has been designed according to a number of international standards, has been used. It's made of (29) items that cover the three variables to test their hypotheses. A number of statistical tools have been used A number of conclusion have been reached and recommendations have also been suggested.
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