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
Background: Periodontitis (PD) is well-known chronic disease affecting the periodontal ligament and alveolar bone, Osteoarthritis (OA) is a chronic joint disease with compound reasons characterized by synovial inflammation, subchondral bone remodeling, also the formation of osteophytes, that cause cartilage degradation. Chronic periodontitis and osteoarthritis are considered widely prevalent diseases and related to tissue destruction due to chronic inflammation in general health and oral health. The aim of this study is todetermine the association of chronic periodontitis and osteoarthritits in patients by analysing tumor necrosis factor alpha TNFα and high sensitive c-reactive protein (hsCRP) in the serum. Materials and Method: A tot
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COVID-19 is a pandemic disease that has a wide spectrum of symptoms from asymptomatic to severe fatal cases due to hyperactivation of the immune system and secretion of pro-inflammatory cytokines. This study aimed to assess the level and impact of interleukin (IL)-13, IL-33, and tumor necrosis factor (TNF)-α cytokines on immune responses in mild and moderate COVID-19-infected Iraqi patients. A prospective case-control study was conducted from January 2023 to January 2024; it included 80 patients infected with moderate COVID-19 infection who consulted in different private clinics and 40 healthy controls. The serum of both groups was tested for quantification of serum IL-13, IL-33, and TNF-α using the human enzyme-linked immunosorbe
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The δ-mixing of γ-transitions in 70As populated in the 32 70 70 33 Ge p n As (, ) γ reaction is calculated in the present work by using the a2-ratio methods. In one work we applied this method for two cases, the first one is for pure transition and the sacend one is for non pure transition, We take into account the experimental a2-coefficient for previous works and δ -values for one transition only.The results obtained are, in general, in a good agreement within associated errors, with those reported previously , the discrepancies that occur are due to inaccuracies existing in the experimental data of the previous works.
The study of the " Speech act " in grammatical codes reveals great efforts in the study of the elements of linguistic communication contained in their efforts, and is part of the study of the linguistics of heritage, and the research has been designed to identify the verbal act in the blog of Ibn al-Khabaz (guiding the shine) by studying its sections comprehensively; To the spirit of grammatical discourse as well as the combination of the concept of the semantic act already verbal according to Searle, and its response in the form of indirect verbal acts more than direct acts, as well as the pure formulas of the opinions of the violators in the speech of Ibn al-Khabaz other than the proven verbal formulas Approval and approval, the class
... Show MoreAbstract: The aim of the research identify the effect of using the five-finger strategy in learning a movement chain on the balance beam apparatus for students in the third stage in the College of Physical Education and Sports Science, as well as to identify which groups (experimental and controlling) are better in learning the kinematic chain on the balance beam device, has been used The experimental approach is to design the experimental and control groups with pre-and post-test. The research sample was represented by third-graders, as the third division (j) was chosen by lot to represent the experimental group, and a division Third (i) to represent the control group, after which (10) students from each division were tested by lot to repr
... Show MoreThere are many harmful acts that occur from drunkards in this case, especially those resulting from car accidents. The world is witnessing dozens or even hundreds of car accidents due to alcohol consumption. These accidents often result in serious injuries that could lead to the death of the drunk driver and those in the car As well as other persons present in the other vehicles with which the incident occurred or pedestrians on the street, as well as damage to private or public property, and if the order of return of the affected persons on the pretext of civil liability (tort) is made as a direct cause of the harmful act, Is entitled Do they like this refer to the liquor seller or their provider as the culprit? Or are they not related to
... Show MoreThe subject of the evolution of fire insurance of the hottest topics accidents, because it falls within the commercial insurance, as its importance is reflected for being a security source and contentment of the insured person and so it is worth pointing out the importance of fire insurance in enterprises and organizations of all kinds, because of the guarantee of its assets from meridian as well as protection from the effects of the fire therefore ensure continuity in the performance of their activities
The research aims to shed light on the impact of the application of the electronic services system on electronic banking activities in a sample of Iraqi banks, as investment in technology is the most important factor for the success and future growth of administrative companies in general, and banking in particular, as global economic developments in the field of Technology has led the majority of banking sectors in the world to undergo deep reforms and radical changes in the entity of their systems and mechanisms to confront competition and keep pace with economic changes, as the concept of banking services and its diversity changed with it, especially since persistence in the traditional approach no longer gi
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