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
Pinter's play One for the Road (1984) is considered one of his important plays because
it focuses on political issues, which he has not presented overtly before. Generally speaking,
Pinter's early plays describe man's existential fear of an unnamed danger which might be
represented by an intruder who invades the characters' solitude , threatens their peace, and
brings their hidden fears to the surface. Pinter began to write political plays as a result of his
political attitudes and his involvement in political activities over the last three decades.
Pinter's One for the Road deals with the oppressive and authoritarian operations of
state power. This play and Pinter's political plays which followed it, like Mountain
Objective conditions for the possibility of punishment are legal or material facts –positive or negative that depart from the activity of the offender. The legislator comments on their subsequent verification on the formation of some crimes the possibility of.The application of punishment to the offender , but although they are facts of an object nature that approach and overlap with many systems and cases , they are distinguished by a certain subjectivity that differentiates them from each case that may seem similar or approach them. To clarify the ambiguity that may surround these conditions , Which may lead to confusion between them and what be similar to other cases due to the common effect that they have in common , which is the f
... Show MoreThe GPS navigation measurements become more widely used in many civilian and scientific application. All GPS navigation data holds many errors, the main error sources arise from the geodetic Datum variation when user apply the GPS measurements with the map. Geodetic datums define the size and shape of the earth and the origin and orientation of the coordinate systems used to map the earth surface. In this paper, the Datum transformation was evaluated in two mathematical methods to overcome the errors due to the difference between the WGS-84 and our country Datum Clarck-1880. The results was evaluated and investigated using Carmin GPS device for GCPs comparison, topographic map for Hilla city, mid Iraq 1:100000 scale, and two georefrencing
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This study aimed at analyzing and studying the strategic and geopolitical importance of the Sahel region, which increased the regional competition for the resources of the region, especially the energy resources that have been and continue to be one of the axes of conflict and competition between these forces.
The researcher tried to review the competition between the international force, France, the United States of America, China, Algeria and Libya, and the African coast. We note that there is a positive correlation between the severity of the conflict and the intensity of the competition of the major powers to control the countries of the region and the extent of political and economic stability These countries are directly affecte
Huge yearly investments were made by organizations for the development and maintenance. However, it has been reported that most of the IT projects fails as it is delayed, over budget and discontinued quality. A systematic literature review (SLR) was conducted to identify the critical success factors (CSFs) for the IT projects. Nine (9) CSFs was identified from the SLR. An online survey was conducted among 103 respondents from developers and IT managers. The data was analyzed using the Statistical Package for Social Science (SPSS 22). The findings showed that the highest CSFs of IT projects is commitment and motivation. Project monitoring was found the lowest score ranked by respondents.
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Abstract:
The great importance that distinguish these factorial experiments made them subject a desirable for use and application in many fields, particularly in the field of agriculture, which is considered the broad area for experimental designs applications.
And the second case for the factorial experiment, which faces researchers have great difficulty in dealing with the case unbalance we mean that frequencies treatments factorial are not equal meaning (that is allocated a number unequal of blocks or units experimental per tre
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A study of the emission spectra of isotopic for electronic states has been carried out. The energies of the vibration levels ( =0,1,..25) and the values of spectral lines R(J) and P(J) versus rotational quantum number (J=0,1..25). It was found that were an increase of the value of R(J) with the increase of the values of J was found while the value of P(J) decreases with decreasing of the values of J . It was found that corresponding to R(J) and P(J) the spectral line R(J) increases when the values of m increased.
Objectives To quantify the reproducibility of the drill calibration process in dynamic navigation guided placement of dental implants and to identify the human factors that could affect the precision of this process in order to improve the overall implant placement accuracy. Methods A set of six drills and four implants were calibrated by three operators following the standard calibration process of NaviDent® (ClaroNav Inc.). The reproducibility of the position of each tip of a drill or implant was calculated in relation to the pre-planned implants’ entry and apex positions. Intra- and inter-operator reliabilities were reported. The effects of the drill length and shape on the reproducibility of the calibration process were also investig
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