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
Abstract
Prais be to Allah the Lord of the Worlds and prayers and peace be upon our faithfull Prophet …. I wrote this Research entitled (The Imam Shams AL-din Abdulrahman Bin Qudamah AL-Maqdsi (died: 682 A.H) Slections in Slections in proving contract annulment choice (AL-tassriah)and its duration which Iclarrified the reason of choosing this title and my method in writing Morever, a brief Overriew of the life of Imam Shams AL-din Bin Qudamah and the meaning of (AL-tassriah)and whether it proves to the buyer to return it, beside the duration which (the tassriah) proven, and a conclusion in which I showed the results I reached and some recommendations that some researchers in the field of Jurispruden
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Objective: To enhance bonding strength between thermoplastic denture base and acrylic soft liner through ethyl acetate surface treatment. Materials and Methods: Modifications of thermoplastic acrylic denture base surface were investigated with SEM. FTIR was used to detect whether there was a chemical bond between thermoplastic acrylic and the organic solvent. A total of 80 samples were prepared and divided into 20 samples for the surface roughness test and 60 samples for the shear bond strength test. Failure type was assessed visually. Results: Shear bond strength and surface roughness values of un treated samples were lower in comparison to surface treated groups; the greatest post thermocycling bond strength value was recorded for the sam
... Show MoreThe study aims to examine the estimation of a sample of Palestinian University students in Gaza governorate to the contribution of teaching human sciences in their political education. It further aims to reveal whether there are statistically significant differences at a significance level (α≤ 0.05) between the averages of the sample. Such differences might be attributed to the following variables: sex, residential area, specialization. To achieve this, the researcher used the descriptive approach by applying a tool of (50) items on (618) randomly chosen male and female students from the largest Palestinian universities in the governorates of Gaza. Results have shown that: the overall degree of estimation to the contribution of teachi
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The world and the business environment are constantly witnessing many economic changes that have led to the expansion of the business' volume due to mergers and the increase in an investments volume and the complexity of business and the transformation of some systems, which was reflected on the size of the risk and uncertainty which led to necessity of a presence of transparent and objective accounting information In the way that reflects the financial performance of the economic units to be available to all users of that information, therefore, The need for the existence of indicators for transparency in the disclosure of accounting information that these units adhere to. Standards & Poor's indicators, which included items
... Show MorePost Modern Persian poetry that is rich with visions and creations has slowly but firmly regained its statues in modern Persian literature and poetry. Ali Baba Chahi is considered one of Iran’s most prominent postmodern and post-Nimaie writer and poet.
The present paper discusses the general style characteristics as well as the distinctive stylistic creations of Ali Baba Chahi as presented in his collected poems In Caves full of Daffodils.
In conclusion, the study crystallizes some of the stylistic characteristics of Ali Baba Chahi as a leading figure in postmodern poetry. The study, also, provides a comprehensive critical analysis of the collection of
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insulin-like Growth Factor 1 (IGF-1) gene has been described in several studies as a candidate gene for growth. The present study attempts to identify associations between body weight traits and polymorphisms at 279 position of 5'UTR flanking region of IGF-1 gene in broiler chickens. Three hundred broiler chickens from two breeds (Cobb 500 and Hubbard F-15) were used in this study. A single nucleotide polymorphism (SNP) at 279 position of 5'UTR region of the IGF-1 gene was identified in 20.6 and 60.3% of Cobb 500 and Hubbard F-15, respectively, using the PCR-RFLP technique. Allele frequencies were 83.87 and 42.80% for the T allele and 16.13 and 57.20% for the C allele in Cobb500 and Hubbard-15 breeds, respectively. Genotype frequencies were
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This study was included preparing acold aqueous extract of clove buds The study also comprised the isolation and studying the proteinous compound,which was seperated using gel filtration technique and determined approximately molecular weight of this isolated compound(6799) dalton . The aim of the study demonstrate effects of the crude aqueous, non proteinous extract, proteinous precipitate and proteinous compound on serum glucose, total cholesterol, triglyceride and high density lipoprotein-cholesterol levels, also glutathione and malondialdehyde levels in liver and kidney tissues in diabetic mice-induced alloxan.Extracts were administerated interaperitioneally. The results were indicated that the crude aqueous, non proteinous extr
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Abstract: The aim of this study is to assess the effectiveness of 940 nm diode laser in comparison to Endoactivator in elimination of smear layer in terms of radicular dentin permeability and ultra-structural changes of root canal walls by SEM evaluation. Twenty-eight single-rooted extracted lower premolars were instrumented up to size X4 (protaper Next, Dentsaply) and divided into two experimental groups according to the irrigation system, G1; activated by EndoActivator and G2; activated by Diode laser 940 nm, CW mode, 1.7 W. Afterward, the roots were made externally impermeable, filled with 2%methylene blue dye, divided horizontally into three segments representing the apical, middle, and coronal thirds then examined under stereo- micr
... Show MoreThe study is dealing with an application reengineering process clean solar cells in the Ministry of electricity, as aimed at the possibility of the applicability and impact of re-engineering to achieve the level of performance of the Ministry's operations, with the application of the cleaning process solar cells, developed, improved and found a correlation, statistically significant effect between variable re-engineering and performance as well as the application of process reengineering clean solar cells:1- Before the re-engineering process the total time for cleaning up and solar cell 20 minutes and number of columns performed per day 24 columns and total columns750 which were completed per month that re
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