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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Background: Malignant lymphoma is a term that describes primary tumors of the lymphoreticular system, almost all of which arise from lymphocytes.MMP-1 is the most ubiquitously expressed interstitial collagenase, a subfamily of MMPs that cleaves stromal collagens. It is also called collagenase-1.TIMPs which inhibits MMP activity and thereby restrict extracellular matrix breakdown, TIMP-1 is a stromal factor that has a wide spectrum of functions in different tissues. Material and Methods: This study was performed on (68) formalin-fixed, paraffin-embedded blocks, histopathologically diagnosed as lymphoma (head and neck lesions). Immunohistochemical staining of MMP1and TIMP1 was performed on each case of the study sample. Results: The expressio
... Show MoreStrives Total Productive Maintenance to increase the overall effectiveness of the equipment through the early involvement in the design and manufacture of equipment productivity. It also operates in an environment of simultaneous engineering work on the synchronization of activities to take advantage of early information by maintenance engineers, design, operation, and that helps to reduce the faults and facilitate future maintenance tasks.
Has adopted a search in the theoretical concept of the total maintenance productivity and concurrent engineering activities carried out during which the conjunction a
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We propose a novel strategy to optimize the test suite required for testing both hardware and software in a production line. Here, the strategy is based on two processes: Quality Signing Process and Quality Verification Process, respectively. Unlike earlier work, the proposed strategy is based on integration of black box and white box techniques in order to derive an optimum test suite during the Quality Signing Process. In this case, the generated optimal test suite significantly improves the Quality Verification Process. Considering both processes, the novelty of the proposed strategy is the fact that the optimization and reduction of test suite is performed by selecting only mutant killing test cases from cumulating t-way test ca
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New speaker identification test’s feature, extracted from the differentiated form of the wave file, is presented. Differentiation operation is performed by an operator similar to the Laplacian operator. From the differentiated record’s, two parametric measures have been extracted and used as identifiers for the speaker; i.e. mean-value and number of zero-crossing points.
The article is devoted to the Russian-Arabic translation, a particular theory of which has not been developed in domestic translation studies to the extent that the mechanisms of translation from and into European languages are described. In this regard, as well as with the growing volumes of Russian-Arabic translation, the issues of this private theory of translation require significant additions and new approaches. The authors set the task of determining the means of translation (cognitive and mental operations and language transformations) that contribute to the achievement of the most equivalent correspondences of such typologically different languages as Russian and Arabic. The work summarizes and analyzes the accumulated exper
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The Current research aims to identify ( the effect of Carin model in the achievement of the first intermediate Grade Students and their Reflective Thinking in physics Subject ) the researcher selected the experimental design with a partial adjust , The research sample consisted of ( 47 ) Students with ( 23 ) Students in the experimental group and ( 24 ) Students in the control group , The two groups rewarded in the variables chronological age in months , Reflective Thinking and the degrees in physics in the first course. The researcher coined the purposes of behavioral which belong to chapter fifth, sixth, and seventh of physics books scheduled of the school year ( 2015-2016 ) and prepared appropriate lesson plans for the two experimenta
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The current research aims to identify the effect of using a model of generative learning in the achievement of first-middle students of chemical concepts in science. The researcher adopted the null hypothesis, which is there is no statistically significant difference at the level (0.05) between the mean scores of the experimental group who study using the generative learning model and the average scores of the control group who study using the traditional method in the chemical concepts achievement test. The research consisted of (200) students of the first intermediate at Al-Farqadin Intermediate School for Boys affiliated with the Directorate of General Education in Baghdad Governorate / Al-Karkh 3 wit
... Show MoreAutorías: Muayad Kadhim Raheem, Lina Fouad Jawad. Localización: Opción: Revista de Ciencias Humanas y Sociales. Nº. 21, 2019. Artículo de Revista en Dialnet.