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
This paper generalizes and improves the results of Margenstren, by proving that the number of -practical numbers which is defined by has a lower bound in terms of . This bound is more sharper than Mangenstern bound when Further general results are given for the existence of -practical numbers, by proving that the interval contains a -practical for all
(1)
(6)
(4)
(28)
(24)
Large amounts of plasma, the universe’s fourth most common kind of stuff, may be found across our galaxy and other galaxies. There are four types of matter in the cosmos, and plasma is the most common. By heating the compressed air or inert gases to create negatively and positively charged particles known as ions, electrically neutral particles in their natural state are formed. Many scientists are currently focusing their efforts on the development of artificial plasma and the possible advantages it may have for humankind in the near future. In the literature, there is a scarcity of information regarding plasma applications. It’s the goal of this page to describe particular methods for creating and using plasma, which may be us
... Show More
(21)
(15)
In this paper, various aspects of smart grids are described. These aspects include the components of smart grids, the detailed functions of the smart energy meters within the smart grids and their effects on increasing the awareness, the advantages and disadvantages of smart grids, and the requirements of utilizing smart grids. To put some light on the difference between smart grids and traditional utility grids, some aspects of the traditional utility grids are covered in this paper as well.
The No Mobile Phone Phobia or Nomophobia notion is referred to the psychological condition once humans have a fear of being disconnected from mobile phone connectivity. Hence, it is considered as a recent age phobia that emerged nowadays as a consequence of high engagement between people, mobile data, and communication inventions, especially the smart phones. This review is based on earlier observations and current debate such as commonly used techniques that modeling and analyzing this phenomenon like statistical studies. All that in order to possess preferable comprehension concerning human reactions to the speedy technological ubiquitous. Accordingly, humans ought to restrict their utilization of mobile phones instead of prohibit
... Show More
(3)
Labor movement is considered important in Britain because it is an international phenomenon of the feudal system and one of the flowerings of the era of the capitalist machine. At the beginning of the 18th century, the world witnessed a change and progress in many aspects of the industrial fields such as the different means of production .this era is called the industrial revolution which especially appeared in Britain and extended to other areas of the world .it leads to many changes in Europe and participated in different economic, political and cultural and social fields. and it has a very important role in progress and development but its disadvantage is that it is exploited by the capitalists to achieve their special rights .in othe
... Show MoreEndoscopy is a rapidly growing field of Neurosurgery, it is defined as the applying of endoscope to treat different conditions of brain pathology within cerebral ventricular system and beyond it, endoscopic procedures performed by using different equipment and recording system to make a better visualization enhancing the surgeon's view by increasing illumination and magnification to look around corner and to capture image on video or digital format for later studies.
(1)
This research which is entitled (Devine Beauty), aims at studying the philosophical and literary extensive visions of Andalusian poets in search of pleasure in the beauty of divine self and its impact on the formation of a philosophical frame of mind. It also attempts to investigate the aesthetic aspects that highlight the prestige and greatness and majesty of that absolute beauty.
The most important conclusion of the reach is the Bany Ahmar poets use the beauty of women and the pleasure of wine as cods to reach divine beauty and get the happiness desired with the reflection of absolute beauty in a clear philosophy and thinking of the kingdom of God Almighty.
This study had succeeded in producing a new graphical representation of James abacus called nested chain abacus. Nested chain abacus provides a unique mathematical expression to encode each tile (image) using a partition theory where each form or shape of tile will be associated with exactly one partition.Furthermore, an algorithm of nested chain abacus movement will be constructed, which can be applied in tiling theory.