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
In this research, we highlight the most important research related to the mixed ligand complexes of the drug trimethoprim (TMP), and for the past 7 years where this drug has been used as a chelating ligand and gives stability to the complexes with ions of metal elements where these complexes, prepared and diagnosed, and for some research the bacterial activity was studied against different types of bacteria
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The aim of this paper is to translate the basic properties of the classical complete normed algebra to the complete fuzzy normed algebra at this end a proof of multiplication fuzzy continuous is given. Also a proof of every fuzzy normed algebra without identity can be embedded into fuzzy normed algebra with identity and is an ideal in is given. Moreover the proof of the resolvent set of a non zero element in complete fuzzy normed space is equal to the set of complex numbers is given. Finally basic properties of the resolvent space of a complete fuzzy normed algebra is given.
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This paper aims at presenting a comparison between objective and subjective tests . This paper attemptsto shed light on these two aspects of tests and make do a compression by using suitable techniques for objective and subjective tests .
The paper compares between the two techniques used by the objective and subjective tests respectively, the time and efforts required by each type, the extent to which each type can be reliable, and the skills each type is suitable to measure.
The paper shows that objective tests, on the contrary of the subjective ones, encourages guess> Objective tests are used to test specific areas of langua
... Show MoreIn this paper, some commonly used hierarchical cluster techniques have been compared. A comparison was made between the agglomerative hierarchical clustering technique and the k-means technique, which includes the k-mean technique, the variant K-means technique, and the bisecting K-means, although the hierarchical cluster technique is considered to be one of the best clustering methods. It has a limited usage due to the time complexity. The results, which are calculated based on the analysis of the characteristics of the cluster algorithms and the nature of the data, showed that the bisecting K-means technique is the best compared to the rest of the other methods used.
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In this research, we highlight the most important research related to the mixed ligand complexes of the drug trimethoprim (TMP), and for the past 7 years where this drug has been used as a chelating ligand and gives stability to the complexes with ions of metal elements where these complexes, prepared and diagnosed, and for some research the bacterial activity was studied against different types of bacteria.
Maxillofacial trauma in females is not widely reported. This study aimed to analyze the clinical characteristics and the patterns of maxillofacial injuries in females and to determine the differences in these patterns among different causes. This retrospective study analyzed several variables, including demographic, social, injury-related, and treatment-related variables, and compared these variables in relation to the main etiologies of maxillofacial trauma. The main etiologies of maxillofacial injuries involving females were assault, followed by road traffic accidents, and falls. There were significant differences in relation to the 3 etiologies in age groups (
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Drilling well design optimization reduces total Authorization for Expenditures (AFE) by decreasing well constructing time and expense. Well design is not a constant pattern during the life cycle of the field. It should be optimized by continuous improvements for all aspects of redesigning the well depending on the actual field conditions and problems. The core objective of this study is to deliver a general review of the well design optimization processes and the available studies and applications to employ the well design optimization to solve problems encountered with well design so that cost effectiveness and perfect drilling well performance are achievable. Well design optimization processes include unconventional design(slimhole) co
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It is axiomatic that languages mirror the world view of their users. Manipulating honorific forms among people inevitably reflects this truth . Honorifics are conventionalized forms or expressions manifested in all the world's languages and are used to express the social status of the participants in the verbal interaction and to convey indications like politeness and respect . English is no exception. However the question is what exactly creates these forms and their meanings. Although honorifics have been extensively researched from a grammatical and semantic angle , yet they haven’t received that significant attention i
... Show MoreFor the graph , the behavior associated with to the majority of the graphical properties of this graph is covered in this article. The reflection of the capabilities of on the Ly constructions is one of the key ideas addressed throughout this paper. For instance, by this technique we can comprehend the mechanism via which groups of relatively tiny structure are exist within Ly.