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
Competitive advantage is a substantial strategic objective for organizations. It requires high levels in the quality of products and services provided to customers, continuous improvement of costing , care for creativity and innovative employees, and speed unique to the marketing and financial engineering, and business re-engineering processes. The situation in this area, requires actors to attract and develop human resources, including help in proper implementation of the strategic tasks that targeted by those institutions. According to the opinions and viewpoints of management scholars, the competitive advantage resource is the most important issue for organizations in the third millennium, which can be a
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The topic of context is one of the important topics, which was mentioned as a concept in several fields and different fields, and there were many points of view that defined that concept.
He specified the title of the research (design contexts in the design of the interior space), as the research sought to identify the concept of context in the interior design of the spaces of sewing workshops. The research was divided into four chapters:
The first chapter, which consists of the methodological framework, the problem of research and the need for it, the importance of research, the goal and limits of research for sewing workshops for vocational schools from (2020-2021).
The second chapter: consists of previous studies and the theo
Despite the principle of separation of powers brought by the French Revolution, which entrusted the task of drafting legislation and its amendment to the legislative authority and the task of settling disputes and settling them in the judiciary. However, since that date, the French judiciary has played a major role in the development of French civil law (In spite of all the economic and social developments that have taken place in French society throughout these years) since its promulgation until February of 2016, the date of the Legislative Decree No. 131 of the year 2016 A modification is the largest in the history of the French Civil Code (which was the judicial precedents in which a significant impact), was assisted by the French judic
... Show MoreLawful protection of the human gene conceded a moral concern regarding the future of existence human. After the discovery of the human genetic map, scientific experiments and research related to the human gene increased, negative applications of genetic engineering in particular that violate essential human rights, the right to human dignity to be specific. These practices represent actual challenges to the existence and diversity of current and future generations. Therefore, the presence of legal rules at the domestic and global levels is an absolute necessity to prohibit these threats and determine civil and criminal accountability for those who infringe any laws related to this issue.
The fact of having Journalism being open to people from different orientations professions, working as journalists requiring protection just to spread corruption, is one of the biggest threats faced by journalism.
Journalists noticed the spread of unprincipled journalists with no journalistic ethics amongst them, they tried to protect their profession from these corrupt outsiders who might annihilate the mighty of journalism. The principles of the journalism profession known as journalistic ethics, are one the most important formulations of the law concluded by the journalists and those concerned by the the profession, they were then published in public in order to prove their professionalism, especially for those who don’t und
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The research deals with Iraq's position of the Lebanese civil war and the Efforts made by Iraq in order to stop the bleeding of this war, the research also deals with the nature of regime in Lebanon and the developments that preceded the war and the positions of the internal and external competing forces, as weu as handling the Iraqi Syrian disagreement and it's impaet on the situation of Lebanon and the war developments.
The research focused on the Iraq's position towards the externd proposed solutions to solve the Lebanese civil war.
Brain Fingerprinting (BF) is one of the modern technologies that rely on artificial intelligence in the field of criminal evidence law. Brain information can be obtained accurately and reliably in criminal procedures without resorting to complex and multiple procedures or questions. It is not embarrassing for a person or even violates his human dignity, as well as gives immediate and accurate results. BF is considered one of the advanced techniques related to neuroscientific evidence that relies heavily on artificial intelligence, through which it is possible to recognize whether the suspect or criminal has information about the crime or not. This is done through Magnetic Resonance Imaging (EEG) of the brain and examining
... Show MoreThe study of services in villages is one of the imperative matters that must be focused on, because it leads to increased attention, which reduces the differences between the countryside and the urban. The extent of its.
It is well known that community services need to be reached by a person, unlike the anchor services that reach people, here the population distribution plays an important and prominent role in signing these services, so the dispersed distribution pattern and the gathering pattern appeared in the distribution, thus an effect on the time and distance that the person walked to obtain The services are community-based. Therefore
... Show MoreDepartments and offices of public relations and media in any institution or company is the most important departments that reflect the results of their work negatively or positively on their reputation. This goes beyond the trust and credibility that its internal and external audiences will give it. Where such matter requires the staff, working in these departments and offices, to have communication skills that qualify them to do the role of marketing the communication message. Yet, the communication skills of public relations and media staff vary from person to person depending on the communication position. This skill has two criteria: Achieving the communication goal and the speed in achieving it as a number of skills
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