For glutamate and the developing optic pathway, glutamate and its ionotropic receptor subunits are expressed widely in retina and ventral diencephalon, and in cells that are related to the chiasm formation. These studies indicate that glutamate may act as a communicator or attractor to coordinate with other factors to affect the retinal axon pathfinding in the prenatal optic pathway. / Furthermore, for the function of glutamate, AMPARs and KARs in the optic chiasm formation, we did retinal explant culture experiment at E14 in vitro, with application of different concentration of L-glutamate (500muM -1mM), AMPAR antagonists: CP465022 hydrochloride (2-20muM) and GYK15466 dihydrochloride (25-150muM), and KAR antagonists: CNQX (50-500muM) and UBP301 (5-25muM). The results show that L-glutamate promotes retinal axon outgrowth; AMPA receptor antagonists inhibit that; and KAR antagonists have no effect on that. In the presence of different combinations of ionotropic receptor antagonists (including NMDAR antagonist), they suggest that the blockage of glutamate iontroptic receptors displays an obvious effect of inhibiting neurite outgrowth in E14 retinal explants. However, inhibiting kainate receptors show little effect on retinal neurite outgrowth which is different from that of blocking AMPARs. We also did E13 and E15 brain slice culture experiments, and found that blocking of glutamate ionotropic receptors affects crossed axon projection in the midline at early stage, but has no effect to the uncrossed one. / Glutamate is the dominant amino acid neurotransmitter in the central nervous system naturally occurring in the L-form. Glutamate ionotropic receptors can be further a-amino-3-hydroxy-5-methy1-4-isoxazole-propionate divided into three types by their ligand (AMPA, specificities: GluR1-4), N-methyl-D-aspartate (NMDA, NR1-3) and kainate (KA, GluR5-7 and KA1-2) receptors, which function as ligand-gated ion channels. In this study, we focus on the AMPARs and KARs which are expressed in the developing brain. / Here, we used semi-quantitative RT-PCR to analyze mRNA expression levels of AMPAR and KAR subunits in the mouse retina and ventral diencephalons at different developmental stages, and in adult retina. The results show that both AMPAR and KAR subunits can be detected in retina and ventral diencephalon at as early as E13. We also used specific antibodies to investigate glutamate, AMPAR and KAR subunit expression in the mouse retinofugal pathway. We found that: 1) Glutamate is expressed at as early as E13. In retina, it tends to localize in retinal ganglion cells (RGCs) and their axons; in ventral diencephalon, it is most intense in optic stalk, optic chiasm and optic tract. It is also localized with chiasmatic neurons, which are related to the formation of optic chiasm. 2) For the individual AMPAR and KAR subunits, all of them are expressed at as early as E13. The immunoreactive GluRl and GluR5/6/7 are distributed preferentially in the RGCs and their axons; the staining of GluR2/3 and GluR4 are largely found in RGCs and the supporting cells around the pathway, but for GluR4, its staining is weakly detected in optic fibers and strongly in the midline of chiasm. Although the staining patterns of these specific subunits are different, they are all localized in chiasmatic neurons in diencephalon. / Cheng, Xiaojing. / "November 2010." / Adviser: Sun On Chan. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 137-152). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

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The prediction of detonation properties of the new generation of high-nitrogen energetic materials (HNEM) is based on knowledge of their heats of formation, which are sum of values of particular nitrogen heterocyclic fragments. The diploma thesis describes theoretical calculations of heats of formation in gas phase ?f H°(298,g) for series of azines (number of N atoms 2-6) and azoles (number of N atoms 2-5) by means of quantum chemical methods. The semiempirical methods as PM3, DFT methods utilizing isodesmic approach and finally thermochemical G-recipes were used. All calculated values of heats of formation were scrutinized and for future application to HNEM materials the DFT B3LYP/cc-pVTZ method and thermochemical recipe T1 were recommended.

<p>  </p> <p>Fungal pathogens are an increasing threat to humans, plants, and animals worldwide. Death and disease caused by fungal pathogens results in the loss of over 1.5 million lives, 12 million tons of crops, and even entire species every year. <em>Candida </em>species are the leading cause of invasive fungal species lead by <em>Candida albicans, </em>and <em>Candida glabrata </em>in second. <em>Candida glabrata </em>intrinsically has a low susceptibility to azole treatment, and multidrug resistant isolates are becoming more common. Additionally, new emerging <em>Candida </em>species have been found, and most clinical isolates are resistant to one or more drugs. There is a critical need to better understand drug resistance and pathogenesis to generate new therapies. </p> <p>Drug resistance can be caused by several different genetic factors, but until recently epigenetic factors have been frequently overlooked. Epigenetic research has revolutionized the treatment and detection of many cancers. And now, early research has shown epigenetic mechanisms play a role in drug resistance and pathogenesis in fungal species. Limited resources exist to combat fungal infections and understanding the epigenetic mechanisms that contribute to drug resistance and pathogenicity will provide new drug targets for future treatment.</p> <p>Previous publications from the Briggs’ lab showed Set1-mediated histone H3K4 methylation was necessary for proper ergosterol homeostasis and Brefeldin A resistance. One of the three classes of antifungals, azoles, target the ergosterol pathway. The ergosterol connection resulted into this thesis project, investigating the role of Set1-mediated histone H3K4 methylation in drug resistance and pathogenicity in <em>Saccharomyces cerevisiae, Candida glabrata, Candida albicans, </em>and <em>Candida auris. </em>This research was the first to characterize the Set1 complex in <em>C. glabrata </em>and show it is the sole histone H3K4 methyltransferase in <em>C. glabrata </em>and <em>C. auris. </em>Additionally, it shows loss of <em>SET1 </em>in <em>C. glabrata </em>and <em>C. auris </em>reduces pathogenicity and alters drug efficacy. Interestingly, although the loss of <em>SET1</em> seems to cause a similar pathogenic defect in all three <em>Candida </em>species, the role Set1 plays in drug efficacy including which drug and severity varies amongst species and isolates. Altogether, this research project provides new possible drug targets for fungal treatment and knowledge added to the scientific community on the role of epigenetics in fungal pathogens. </p>