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
Social media is known as detectors platform that are used to measure the activities of the users in the real world. However, the huge and unfiltered feed of messages posted on social media trigger social warnings, particularly when these messages contain hate speech towards specific individual or community. The negative effect of these messages on individuals or the society at large is of great concern to governments and non-governmental organizations. Word clouds provide a simple and efficient means of visually transferring the most common words from text documents. This research aims to develop a word cloud model based on hateful words on online social media environment such as Google News. Several steps are involved including data acq
... Show More
(8)
(4)
(6)
(3)
The research problem focused through the researcher's experience in the gymnastics game and the lack of use of educational models that give the student an important role in the educational process, so it became necessary to identify the type of prevailing style for students, and the need for diversity in the use of educational models based on scientific theories, including the Daniel Document model. Based on three theories of learning, which are structural, behavioral, and meaningful learning. The research aimed to identify the effect of using the Daniel model for people with two types of brain control (left and right) to learn the skill of the Cartwheel in artistic gymnastics for students of the second stage. The researcher used the experi
... Show MoreNotwithstanding the importance of international cooperation as the other facet of international interactions, a strategy of conflict resolution, a maintainer of international peace and security, its provision in the United Nations conventions, as an objective of the United Nations after the international peace and security, however, the recognition of international cooperation has not been underlined by global, intellectual think tanks. While realism emphasized on the state's role in achieving international cooperation to ensure mutual and multilateral interests, liberalism focused on the role of international organizations in building such cooperation. Additionally, constructivist approaches developed other sub-variables to contribute to t
... Show More
Rapid and accurate identification of Methicillin Resistant Staphylococcus aureus is essential in limiting the spread of this bacterium. The aim of study is the detection of Methicillin Resistant Staphylococcus aureus (MRSA) and determining their susceptibility to some antimicrobial agent. A total of fifty clinical Staphylococcus aureus, isolated from the nose of health work staff in surgery unit of Kalar general hospital and from ear of patients attended to the same hospital. The susceptibilities of isolates were determined by the disc diffusion method with oxacillin (1 ?g) and cefoxitin (30 ?g), and by the mannitol salt agar supplemented with cefoxitin (MSA-CFOX), susceptibilities of isolates to other antimicrobial agent were determined b
... Show More
(1)
Background: The stethoscope is a tool that doctors use daily in the examination of patients and it can take part in the transmission of health care-associated infections. In a single day it may come in direct contact with multiple patients and the intra hospital environment may be contaminated by various type of bacteria and possibly transmit to others.
Objective:- The study was to know the attitude and knowledge about the stethoscope hygiene behavior among physicians and to determine the types of bacterial agents that can contaminate stethoscopes.
Type of the study: The study was a cross-sectional study
Metho
... Show More
The inhibitory effect of acetone, ethanol, and aqueous extracts of ten medicinal plants on β-lactamase from Staphylococcus sciuri and Klebsiella pneumoniae was investigated in vitro by starch-iodine agar plate method. The results revealed the success of starch-iodine method for the detection of the inhibition of β-lactamase activity by the various extracts of each individual plant. The acetone extracts of Catharanthus roseus, Eucalyptus camaldulensis, and Schinus terebinthifolius induced an inhibitory effect on β-lactamase from Staphylococcus sciuri. On the other hand, acetone extracts from only Eucalyptus camaldulensis, and Schinus
... Show More
(14)
(5)
The inhibitive action of Phenyl Thiourea (PTU) on the corrosion of mild steel in strong Hydrochloric acid, HCl, has been investigated by weight loss and potentiostatic polarization. The effect of PTU concentration, HCl concentration, and temperature on corrosion rate of mild steel were verified using 2 levels factorial design and surface response analysis through weight loss approach, while the electrochemical measurements were used to study the behavior of mild steel in 5-7N HCl at temperatures 30, 40 and 50 °C, in absence and presence of PTU. It was verified that all variables and their interaction were statistically significant. The adsorption of (PTU) is found to obey the Langmuir adsorption isotherm. The effect of temperature on th
... Show MoreIn this investigative endeavor, a novel concrete variety incorporating sulfur-2,4-dinitrophenylhydrazine modification was developed, and its diverse attributes were explored. This innovative concrete was produced using sulfur-2,4-dinitrophenylhydrazine modification and an array of components. The newly created sulfur-2,4-dinitrophenylhydrazine modifier was synthesized. The surface texture resulting from this modifier was examined using SEM and EDS techniques. The component ratios within concrete, chemical and physical traits derived from the sulfur-2,4-dinitrophenylhydrazine modifier, chemical and corrosion resistance of concrete, concrete stability against water absorption, concrete resilience against freezing, physical and mechanical p
... Show More
(7)
(1)