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: The synthesis and characterization of novel liquid crystalline compounds have garnered signi|cant attention due to their potential applications in biomedical sciences, including drug delivery systems, biosensing, and diagnostic tools. This study focuses on synthesizing and characterizing new thiazolothiadiazole-based liquid crystals and evaluating their mesophase properties. Methods: A series of novel compounds containing 5H-thiazolo[4,3−b][1,3,4] thiadiazole units were synthesized via multi-step chemical reactions. The synthesis involved the reaction of chloroethyl acetate with 4−hydroxybenzaldehyde to yield an aldehyde intermediate, followed by subsequent transformations using hydrazine hydrate, ethylacetoacetate, and 1,2
... Show MoreThe compound 3-[4Ì„-(4Ë-methoxy benzoyloxy) benzylideneamino]-2-thioxo-imidazolidine-4-one [III] was prepared from the cyclization of thiosemicarbazone [II] with
ethyl α -chloroacetate in the presence of fused sodium acetate. Treatment the later compound
with acetic anhydride yielded the corresponding 1-Acetyl-3-[ 4Ì„- (4Ë- methoxy benzoyloxy)
benzylideneamino] – 2 – thioxo -imidazolidine-4-one [IV]. 1,3-Oxazepine derivatives [V]a-d
and [VI]a-d are obtained from the reaction of compounds[III] and [IV] with different acid
anhydrides, in dry benzene. The FTIR and
1
HNMR spectroscopy are indicated a good
evidence for the formation of the synthesized compounds. Some of the synthesized
This work involves synthesis of novel Schiff bases derivatives contining isoxazoline or pyrazoline units starting with chalcons . 4-Aminoacetophenone was react with pnitrobenzaldehyde or p-chlorobenzaldehyde in basic medium giving chalcones [I]a,b by claisenschemidt reactions. The chalcones [I]a,b were reacted with hydroxylamine hydrochloride giving isoxazolines [II]a,b in basic medium. The chalcone [I]a could also reacted with hydrazine hydrate to give pyrazolines [III]a . The novel Schiff bases with structural formula [VIII]n , [IX]n , [X]m and [XI]m were prepared by the reaction of amino compounds ; isoxazoline [II]a,b and pyrazolines [III]a with monoaldehydes [VI]n and dialdehydes [VII]m , respectively in dry benze
... Show MoreBackground: Pseudomonas aeruginosa is a devious pathogen with the tendency to prompt many acute and serious chronic diseases. This study aims to detect novel genes (Toxins-Antitoxins II system), especially; higB and higA encoded from P. aeruginosa by PCR technique and the relation between these genes and antibiotic resistance of P. aeruginosa. Methods: This study detected 50 isolates of P. aeruginosa from distinct clinical sources. The most common origin of isolates was (44%) burn swabs, (22%) urine culture, (12%) wound swabs, (14%) sputum, and (8%) ear swabs. The bacteria were isolated using implantation MacConkey agar and blood agar, as well as biochemical tests including oxidase test, catalase test then VITEK-2 System of P. aerug
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The synthesis, characterization and liquid crystalline properties of N4,N40-bis((1 H-benzo[d]imidazol-2- yl)methyl)-3,30-dimethyl-[1,10-biphenyl]-4,40-diamine and of their corresponding Mn(II), Fe(II), Ni (II), Cu(II), and Zn(II) complexes are described. The ligand and complexes have been characterized by elemental analysis, magnetic susceptibility measurements (meff), conductometric measurements and Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (1H NMR), (13C-NMR) and UV–Vis spectroscopy. Spectral investigations suggested octahedral coordination geometrical arrangement for M(II) complexes. The phase transition temperatures were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed by op
... Show MoreThe synthesis, characterization and liquid crystalline properties of N4,N40-bis((1 H-benzo[d]imidazol-2- yl)methyl)-3,30-dimethyl-[1,10-biphenyl]-4,40-diamine and of their corresponding Mn(II), Fe(II), Ni (II), Cu(II), and Zn(II) complexes are described. The ligand and complexes have been characterized by elemental analysis, magnetic susceptibility measurements (meff), conductometric measurements and Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (1H NMR), (13C-NMR) and UV–Vis spectroscopy. Spectral investigations suggested octahedral coordination geometrical arrangement for M(II) complexes. The phase transition temperatures were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed by op
... Show MoreThe synthesis, characterization and liquid crystalline properties of N4,N40 -bis((1 H-benzo[d]imidazol-2- yl)methyl)-3,30 -dimethyl-[1,10 -biphenyl]-4,40 -diamine and of their corresponding Mn(II), Fe(II), Ni (II), Cu(II), and Zn(II) complexes are described. The ligand and complexes have been characterized by elemental analysis, magnetic susceptibility measurements (meff), conductometric measurements and Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (1 H NMR), (13C-NMR) and UV–Vis spectroscopy. Spectral investigations suggested octahedral coordination geometrical arrangement for M(II) complexes. The phase transition temperatures were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed
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The differential cross section for the Rhodium and Tantalum has been calculated by using the Cross Section Calculations (CSC) in range of energy(1keV-1MeV) . This calculations based on the programming of the Klein-Nashina and Rayleigh Equations. Atomic form factors as well as the coherent functions in Fortran90 language Machine proved very fast an accurate results and the possibility of application of such model to obtain the total coefficient for any elements or compounds.
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Chemical pollution is a very important issue that people suffer from and it often affects the nature of health of society and the future of the health of future generations. Consequently, it must be considered in order to discover suitable models and find descriptions to predict the performance of it in the forthcoming years. Chemical pollution data in Iraq take a great scope and manifold sources and kinds, which brands it as Big Data that need to be studied using novel statistical methods. The research object on using Proposed Nonparametric Procedure NP Method to develop an (OCMT) test procedure to estimate parameters of linear regression model with large size of data (Big Data) which comprises many indicators associated with chemi
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Mixture experiments are response variables based on the proportions of component for this mixture. In our research we will compare the scheffʼe model with the kronecker model for the mixture experiments, especially when the experimental area is restricted.
Because of the experience of the mixture of high correlation problem and the problem of multicollinearity between the explanatory variables, which has an effect on the calculation of the Fisher information matrix of the regression model.
to estimate the parameters of the mixture model, we used the (generalized inverse ) And the Stepwise Regression procedure
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