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
Praise be to Allah, The Lord of the worlds, and peace be upon
Muhammad the master of former and latter people, and peace be upon His
relatives, companions and those who followed Him to Judgment day.
After recognizing the prescription which is called (Al- Fadhaly's Thesis in
parsing of "There is no god but God") as it is related with the word of the
investigation of this issue attracted me, as being related with the idea of the
only one God that is mentioned in the prophetic speech, which is said by
Anas- God satisfies him- Who said, Said the Messenger Muhammad peace
be upon him " Goes out of the Hell who said: there is no god but God, and in
his heart a hair weight of charity, and goes out of the He
The insurance is considered as one of the sectors that is impact is vital to the national economy and development programs, Insurance companies as financial institutions have an effect an aspects of social, economic as well as the participation of enterprises in compensation for the risk potential losses and individuals, Insurance sector provides insurance service insurance which should be characterized by quality and satisfy needs and desires of the customer , so the raise insurance awareness in the community its members and institutions will help in maintaining the movement of production and service delivery standards, quality sought by the insured to obtain, as well as the development of promotional programs, and use
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Fresh water resources in terms of water quality is a crucial issue worldwide. In Egypt, the Nile River is the main source of fresh water in the country and monitoring its water quality is a major task on governments and research levels. In the present case study, the physical, chemical and algal distribution in Nile River was monitored over two seasons (winter and summer) in 2019. The aims of the study were to check the seasonal variation among the different water parameters and also to check the correlations between those parameters. Water samples were collected from the Nile in Cairo governorate in EGYPT. The different physiochemical and microbiological properties in water samples were assessed. The studied parameters were included: te
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Amaranthus viridis L. belongs to the Amaranthaceae family. It is a rich source of numerous phytochemicals and amino acids. The objective of this work was to optimize Ultrasound-Assisted Extraction (UAE) based on the extraction yield and Thin-Layer Chromatography (TLC) profile under different conditions, to compare the optimized UAE to the Soxhlet extraction method and evaluate the cytotoxic effects of the ethyl acetate fraction of the 80 % ethanolic extract on the SKGT-4 (human esophageal adenocarcinoma), AGS (human gastric adenocarcinoma) and A431 (human epidermoid carcinoma). A one-factor at a time experiment was carefully designed to assess the influence of the following factors on the extraction: time, frequency, solid-to-solven
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Background:SARS-CoV-2 infection has caused a global pandemic that continues to negatively impact human health. A large group of microbial domains including bacteria co-evolved and interacted in complex molecular pathogenesis along with SARS-CoV-2. Evidence suggests that periodontal disease bacteria are involved in COVID-19, and are associated with chronic inflammatory systemic diseases. This study was performed to investigate the association between bacterial loads of Porphyromonas gingivalis and pathogenesis of SARS-CoV-2 infection. Fifty patients with confirmed COVID-19 by reverse transcriptase-polymerase chain reaction, their age ranges between 20-76 years, and 35 healthy volunteers (matched accordingly with age and sex to th
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This study includes the preparation of the ferrite nanoparticles CuxCe0.3-XNi0.7Fe2O4 (where: x = 0, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3) using the sol-gel (auto combustion) method, and citric acid was used as a fuel for combustion. The results of the tests conducted by X-ray diffraction (XRD), emitting-field scanning electron microscopy (FE-SEM), energy-dispersive X-ray analyzer (EDX), and Vibration Sample Magnetic Device (VSM) showed that the compound has a face-centered cubic structure, and the lattice constant is increased with increasing Cu ion. On the other hand, the compound has apparent porosity and spherical particles, and t
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Objective : Sciatic nerve block (popliteal approach) and femoral N block is a new technique other than general anesthesia in below knee surgery because it provides adequate muscle relaxation, with good intraoperative and post-operative analgesia. Nefopam is non opioid, non-respiratory depressant and non-sedative was mixed with local anesthetics drug to study the effects. This study was done to compare the onset and duration of sensory and onset time and duration of action of motor block following administration of either bupivacaine alone with administration of bupivacaine and Nefopam in patients undergoing below knee lower limb surgeries under ultrasound guided regional anesthesia.
Methods: 100 patients with American society of anest
Cadmium has been known to be harmful to human healthy , manily Via contaminated drinking water , food supplies , tobacco and industrial pollutant . The aim of this study was to determine the toxicity of new Cadmium (II) complex ( Bis[ 5- ( P- nitrophenyl ) – ? 4 – Phenyl- 1,2,4- triazole -3- dithiocarbamatohydrazide] cadmium (II) Hydra ( 0.5) and compare it with anticancer drug cyclophosphamide ( CP) in female albino mice . This complex causes to several alterations in Enzymatic activity of Glutamate Pyruvate Transaminase (GPT) and Alkaline Phosphatase (ALP ) in three organs after the treatment of mice with different doses of a new cadmium (II) complex ( 0.09 / 0.25ml , 0.18/ 0.5ml and 0.25mg /0.7 ml /30 gm of mous
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The current study aims to identify the feeling of job alienation and organizational commitment among free lecturers in secondary schools, as well as to identify the significance of the differences in the feeling of job alienation according to the gender and the significance of the differences in organizational commitment according to the gender. It also aims to identify the correlation between the feeling of job alienation and organizational commitment. To achieve the objectives of the research, the researcher developed two scales: one consisted of (24) items to measure the vacancy in job alienation and the other consisted of (24) items to measure the organizational commitment. The two tools were applied to a sample of (200) male and fem
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