5 results on '"Sang, Yong"'
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2. Innate Immune Responses to Mucosal Infection are Regulated by RELMα
- Author
-
Kim, Sang Yong
- Subjects
- Immunology, CX3CR1, Granuloma, Heligmosomoides polygyrus, Influenza A virus, RELMα
- Abstract
Preclinical models of infection, such as murine infection models and transgenic mice, provide critical knowledge for the treatment and diagnosis of infections of significant public health concern. In particular, the mucosal barrier, such as the lung and intestine are susceptible to multiple infectious pathogens given their exposure to the external environment. The goal of this dissertation was to investigate the function of RELMα and CX3CR1 in mucosal infections with parasitic helminths and influenza virus, as these are pathogens of significant health concern worldwide. RELMα is a mouse protein, which has orthologs in humans such as resistin and RELMβ. First, we tested the function of RELMα and investigated factors that may regulate its expression in infection. RELMα accelerated resolution of inflammation and tissue repair in infection with mouse intestinal helminth Heligmosomoides polygyrus. We also discovered that choline kinase signaling was critical for optimal RELMα expression: when mice were infected with H. polygyrus and injected with choline kinase alpha inhibitor, RSM-932A, alternative activation of macrophages and RELMα expression was downregulated in RSM-932A-injected mice. Previous studies have reported RELMα expression in type 2 cytokine inflammation, however, the functional relevance of RELMα in other infectious contexts, such as viral infections, is unclear. RELMα was induced by IAV infection in the BALF and airway epithelial cells. RELMα induced influenza infections in mouse lung epithelial cells in vitro and in vivo, suggesting that RELMα expressed in lung epithelial cells promotes influenza infection of neighboring cells. In the last chapter of this thesis, we broadened our research scope to investigate the function of myeloid-derived cells in helminth infection by targeting CX3CR1, a critical chemokine receptor for monocyte recruitment from the blood vessel to the site of infection. CX3CR1 deficiency induced a more inflammatory response but lower parasite burden in the lung. CX3CR1-deficient monocytes were more cytotoxic and active than WT monocytes, demonstrating the regulatory function of CX3CR1 in monocytes. Collectively, these studies demonstrate diverse functions of RELMα and CX3CR1 in different infectious diseases and identify putative downstream targets by which RELMα and CX3CR1 modulate the immune response and tissue repair.
- Published
- 2022
3. Understanding mechanisms of zinc homeostasis in Schizosaccharomyces pombe
- Author
-
Choi, Sang Yong
- Subjects
- Nutrition
- Abstract
Zinc is essential for cell growth, but can be toxic when in excess. As a consequence, intracellular zinc levels are tightly controlled by complex mechanisms that maintain zinc homeostasis in all biological creatures. In eukaryotic cells, factors that affect zinc homeostasis include zinc transporters, zinc buffering molecules, and zinc-regulatory factors. The levels of these factors are precisely regulated to maintain optimal intracellular zinc levels. To extend the growing literature in the roles of genes involved in zinc homeostasis, this dissertation investigates the role of the above executants in maintaining cytosolic zinc levels in Schizosaccharomyces pombe. In S. pombe, Loz1 plays a specific role in repressing gene expression when zinc is in excess. In zinc-replete conditions, Loz1 down-regulates zrt1, a gene encoding a high affinity zinc uptake transporter, and indirectly up-regulates zym1 expression, a gene which encodes a zinc metallothionein. Deletion of Loz1, thus, causes constitutive zrt1 expression and low zym1 expression. In addition, cells lacking a functional loz1 gene hyperaccumulate zinc in zinc-rich medium. In chapters 2 and 3, I take advantage of the loz1 mutation, and other yeast mutants to determine the roles of specific zinc transporters and zinc buffering molecules in maintaining zinc levels in the cytosol. Specifically, I utilize genetically encoded zinc-responsive FRET-based sensors, which allow changes in the labile pool of cytosolic labile zinc to be measured. My results show that Zhf1, a zinc transporter in endoplasmic reticulum membrane, and Zrg17 and Cis4, which reside in Golgi membrane, play a role in maintaining the cytosolic labile zinc pools upon a zinc shock. In addition, my works describe how Loz1 controls zinc homeostasis in zinc-replete conditions and reveal that phytochelatins, small molecules that have a well-known role in the detoxification of toxic heavy metals, also have an important zinc buffering role.In chapters 4 and 5, I investigate the molecular mechanisms by which zinc-responsive transcription factors are regulated by zinc. Using chimeric proteins containing Loz1, this study examines the accessory domain adjacent to a double zinc finger, and shows that it is necessary for Loz1-mediated zinc-responsive changes in gene expression. This dissertation provides a platform for the understanding of zinc homeostasis mechanisms in fission yeast by examining the role that specific zinc transporters, zinc buffering molecules, and the zinc-regulated factor Loz1 play in regulating cellular zinc levels. The results suggest that specific zinc transporters and Loz1 control the labile zinc pool in cells. Also, the roles of phytochelatins are highlighted as zinc buffering molecules. This discovery extends the current knowledge of how zinc buffering molecules influence metal homeostasis. While a number of zinc transporters have been identified in various eukaryotic cells, the zinc buffering molecules that modify the labile zinc pool remain to be further investigated.
- Published
- 2015
4. Electric Modulation of Conduction and Optical Characteristics in Ca-doped BiFeO3 Films for Memory Device Applications
- Author
-
Kim, Sang-Yong
- Subjects
- Materials Science, BiFeO3, Ca, doping, memory
- Abstract
This dissertation details the synthesis and properties of Ca-doped BiFeO3 thin films. The phase diagram was established as a function of the Ca doping concentration and temperature through structural analysis to study the effect of divalent-ion-calcium doping on BiFeO3 films. A ferroelectric-paraelectric boundary exists around at 10% Ca doping ratio. For this doping concentration, the largest transition of conduction states was observed. The mechanisms for the observed effects are discussed on the basis of the interplay of ionic and electronic conduction through the redistribution of oxygen vacancies by application of electric fields. Application of electric fields enables to control and manipulate this electronic transition to the extent that a p-n junction can be created, erased and inverted in this material. Beside this conduction transition, the visible shading effect was observed with application of electric fields. Based on these reversible transitions of the electrical and optical characteristics of Ca-doped BiFeO3, electrical and optical memory devices are proposed in this dissertation. The memory device built with a hetero-junction presented a nonvolatile conduction modulation with a rectified current behavior, which is essential for realizing random access memory devices. The switching mechanism is elucidated by junction property modification ascribed to the change of local oxygen vacancy concentration. In addition, the optical characteristics of Ca-doped BiFeO3 films for potential electro-optic memory devices were measured and evaluated. Detailed discussion about the origin of the shading effect is given based on the change of a polar order parameter and an oxygen vacancy ordered state.
- Published
- 2011
5. The glutamate transport system in the synaptic vesicle: Mechanism and regulation.
- Author
-
Lee, Francis Sang Yong
- Subjects
- Biology, Neuroscience
- Abstract
Transport of glutamate, the major excitatory neurotransmitter in the mammalian central nervous system (CNS), into synaptic vesicles may represent the first critical step in the neurotransmitter pathway for glutamate. This thesis describes biochemical and bioenergetic analyses of vesicular glutamate transport. In the first section of the thesis, steady-state transport experiments demonstrated that under physiological conditions, $\Delta\Psi$ and $\Delta$pH both contribute to the driving force of glutamate transport and that $\Delta\mu$-driven glutamate uptake relies upon counter-transport of H$\sp+$ and Cl$\sp-$. Kinetic studies demonstrated that in the absence of $\Delta\mu$, the neutral form of glutamate is capable of being transported with a K$\sb{\rm m}$ of 5.47 mM and a V$\sb{\rm max}$ of 2.76 nmol/min/mg. The presence of $\Delta\Psi$ led to an 8.2-fold decrease in K$\sb{\rm m}$ for anionic glutamate with a 2.3-fold decrease in V$\sb{\rm max}$. Conversely, the imposition of $\Delta$pH (in the presence of $\Delta\Psi$) increased V$\sb{\rm max}$ up to 2.9-fold with little change in K$\sb{\rm m}$. These studies suggest that anionic glutamate uptake requires not only a transporter with the proper affinity, which is set by $\Delta\Psi,$ but also a translocation process, whose maximal rate depends on a proton gradient. In the second section, studies demonstrated the partial purification (230-fold enrichment) of a proteinaceous factor that modulates vesicular glutamate levels. This factor has an approximate molecular weight of 180 kDa and is temperature and protease sensitive. In addition, the factor itself appears to require activation that involves the presence of synaptic vesicles and ATP hydrolysis. The factor is postulated to be a component of a regulatory system that modulates presynaptic glutamate levels. In the third section, the vesicular glutamate uptake system in epileptic (EL) mice, an animal model of temporal lobe epilepsy, was investigated. The total and specific activities of vesicular glutamate uptake were significantly higher in the hippocampus of stimulated EL mice than of stimulated B6 mice (704% and 207%, respectively). This enhancement was not only specific to one brain region but also dependent on age and seizure history. The results suggest that elevated vesicular glutamate levels in the hippocampus may be involved in seizure manifestation in these animals.
- Published
- 1996
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