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
The problem of the paper focused on the role of the learning organization in the crisis management strategy, and the extent of the actual interest in both the learning organization and the crisis management and aimed at diagnosing and analyzing that and surrounding questions. The Statistical Package for the Social Sciences (SPSS) program was used to calculate the results and the correlation coefficient between the two main variables. The methodology was descriptive and analytical. The case study was followed by a questionnaire that was distributed to a sample of 31 teachers. The paper adopted a seven-dimensional model of systemic thinking that encourages questioning, empowerment, provision of advanced technologies, and strategic lea
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The paper discusses the lack of a uniform definition of politeness due to the constant tension between its universality and language specificity, and argues that some of the theoretical debate could be resolved if the distinction between politeness as a commonsense notion and politeness as a theoretical construct were clearly addressed and acknowledged in the research.
Coronavirus: (COVID-19) is a recently discovered viral disease caused by a new strain of coronavirus.
The majority of patients with corona-virus infections will have a mild-moderate respiratory disease that recovers without special care. Most often, the elderly, and others with chronic medical conditions such as asthma, coronary disease, respiratory illness, and malignancy are seriously ill.
COVID-19 is spread mostly by salivary droplets or nasal secretions when an infected person coughs or sneezes.
COVID-19 causes severe acute respiratory illness (SARS-COV-2). The first incidence was recorded in Wuhan, China, in 2019. Since then it spreads leading to a pandemic.
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Allah legislated marriage and made it dwelling, fellowship and mercy between
the two couples, Prophet Moh'd (peace of Allah and blessing be upon him) ordered a
husband to look after his wife, treat her with full charity and make love with here
every kindly. On the other hand, he ordered a wife to obey her husband and respect
him deeply, nevertheless, some obstacles may sometimes be appeared within the life
of their marriage, this may be caused by either a husband or a wife. This problem is
called lifely disobedience (AL-Noshooz).
In the other words, this means that a wife begins to hate her husband, refuse his orders
and not obey him.
In brief, they hate each other which leads to some marks appear in their
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Renewable energy resources have become a promissory alternative to overcome the problems related to atmospheric pollution and limited sources of fossil fuel energy. The technologies in the field of renewable energy are used also to improve the ventilation and cooling in buildings by using the solar chimney and heat exchanger. This study addresses the design, construction and testing of a cooling system by using the above two techniques. The aim was to study the effects of weather conditions on the efficiency of this system which was installed in Baghdad for April and May 2020. The common weather in these months is hot in Baghdad. The test room of the design which has a size of 1 m3 was situated to face the geographical south. The te
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The present study aimed at examining the factors that affect the choice of A major among a sample of BA fe(male) students at the levels 3-8 in King Abdulaziz University (KAU), in Jeddah, Saudi Arabia. To meet this objective, a descriptive survey method was used together with a questionnaire that consisted of 4 axes to answer the central question: What are the factors affecting the choice of a major at the university? Results have shown that the item that measured the students’ ability to choose the major ranked (First); it was concerned with the effect on the students' choice of his/her major in the university. On the last position and with respect to this effect came the professional tendencies and desires. Results have also shown tha
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This Study Sought to Determine The Relationship and Impact Between The Tax Core Capabilities and Tax Settlement The Study Took Place in The Tax Administration, and Based The Problem Was to Two Hypotheses As Solutions Initial Mocked Content to Explain The Relationship Between The Phenomena, and to Test The Validity of Assumptions And Due To The Fact That The General Authority for Taxes is The Body for The Advancement of The Collection Tax In Iraq Random Sample Was Selected to Represent The Population of The Study, Since The Sample Included 22 Individuals Representing 70% of The Total Community to Study, Represented by The Director General, Agents and Directors of Departments and Branch Managers Managers Working in The General Authority fo
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الخلاصة
تعد الانتخابات بمثابة الطريق المؤدي إلى الديمقراطية كونها النمط الأكثر شيوعاً لمشاركة المواطنين في الحياة السياسية للبلدان واختيار ممثليهم في المجالس التشريعية، حيث أن مطلب إجراء انتخابات حرة ونزيهة لم يعد مطلباً داخلياً فحسب بل مطلباً دولياً يصرّ المجتمع الدولي على الوفاء به وهذا يلقي على عاتق كل دولة أن تضع من الضمانات ما يكفل ممارسة هذه الانتخابات ب
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