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
Stereo lithography (SLA) three-dimensional (3D) printing process is a type of additive manufacturing techniques that uses digital models from computer-aided design to automatically produce customized 3D objects. Around 30 years, it has been widely utilized in the manufacturing, design, engineering, industrial sectors and its applications in dentistry for manufacturing prosthodontics are very important. The stereo lithography technology is highly regarded because it can produce items with excellent precision especially when selecting the best process parameters. This review article offers a useful and scientific summary of SLA three-dimensional printing technology and its brief history. The specific type of 3D printers which is SLA t
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The moral aspect is an important one in the structure of personality , and the lack of moral aspect is responsible for what we suffering today from problems . there is no exaggeration to say that many of our current problems are moral problems , and reflects the lack of moral growth.
The goal of research is to build scale in order to detect the level of moral reasoning among junior high school students in Baghdad , The researcher followed the procedures in the construction of scientific standards in order to measur
... Show MoreThe present paper applies Fanon Psychological reading of the problem of the Black introduced in his book Black Skin White Mask to Crooks, The black Character in John Steinbeck’s Of Mice and Men. The analysis of this character infers three essential points regarding the artistic achievement of the author. First, he uses a fictional character that offers a psychological interpretation of the black problem of alienation and loneliness in a way that does not disgrace the black. Second, he applies Fanon’s way of showing the various attitudes that the black adopts in contact with the white society. Third, he affirms that the black inferiority complex comes as a result of double proc
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Abstract
Due to the momentum of winning in the streets of the city of Baghdad as a result of the large number of checkpoints so felt researcher to conduct a field visit to find out the main reasons that led to this congestion and to find practical solutions to mitigate wastage winning the arrival time citizen to where you want the least possible time.
This research aims to overcome the difficulties experienced by citizens to reach their places of work and reduce waste at the time of service and waiting time as well as reduce the cost of waiting.
Has emerged study a set of conclusions, including the use of model queue (G / G / C) and the mome
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This study unveils the ideologies of women empowerment encoded in the Mona Lisa Smile movie (2003). It reveals how the stereotypical image of women born only to be wives and do the duties of upbringing and housework is challenged. Katherine Ann Watson (Julia Roberts), the main character in the movie, wants to make a difference in the next generation of women. She rejects the imposed traditional ideologies. Linguistically, she opposes conventional thinking and seeks to persuade her students that life is about more than getting married. The primary focus of this study is to examine and clarify how the characters’ linguistic choices convey their ideologies concerning the notion of women empowerment. To do this, the researchers apply
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This study presented an endeavour to integrate the value chain activities with the Balanced Scorecard for a comprehensive evaluation of an organization’s strategic performance. It also demonstrated the connection and the integration of the activities of the value chain with the Balanced Scorecard. The financial measurement was linked with non-financial measurement by integrating these techniques to achieve an appropriate performance that supports all aspects of the organizational performance. Consequently, the research problem in this study emerged, which is due to the concentration of many organizations on the measurement of financial performance. Notably, the latter caused the decline of some organizations from the competitive market. T
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Objectives: The study aims to evaluate patients’ performance toward insulin injection after training program to
identify the variation in skill of patients in insulin injection technique with regard to some variable (i.e.
educational level and duration of insulin injection.
Methodology: A quasi experimental study has been conducted on diabetic patients.
An observational checklist had been prepared which consisted of 4 main areas with 37 sub-items, which are
syringe preparation for injection, insulin drawing; skin preparation for injection and insulin injection. Each of the
sub-items has 2 options yes or no. One score for positive answer and zero for no.
The sample of the study consisted of (n =30) males and females
In most recent studies, long-term retention after orthodontic treatment has been hypothesized that may be necessary to maintain the stability of the dentition and avoid post-treatment changes. The bonded fixed retainer is characterized by its clinical effectiveness, patient acceptance, and lack of patient complaints as compared with a removable retainer. An electronic database (such as PubMed, PubMed Central, Web of Science, Science Direct, Cochrane Library, Scopus, and ResearchGate) has been collected using specific keywords. Of the 152 articles, only randomized clinical trials that investigated different types of fixed retainers or compared fixed with removable retainers were illustrated in tables and included in this review. The
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Summed up the idea of this research in an attempt to find the establishment of the knowledge convergence to show the features of verbal acts that occurred a prime location in the lesson deliberative theory book unique contract ( IbnAbdRabbaAndalusian ) to prove that Arabic was the old literary studies included many of the features of this theory in both theoretical and practical