Leukocyte cell-derived chemotaxin 2 (LECT2) is first isolated as a 16-kDa secreted protein from cultured fluid of phytohemagglutinin-activated human T-cell leukemia SKW-3 cells. Recently LECT2 has shown to be synthesized by human hepatocytes and stimulates the growth of chondrocytes. LECT2 is involved in chemotactic factor to neutrophils and may be associated with rheumatoid arthritis. Besides, LECT2 is evolutionarily conserved and acts as a repressor in the Wnt/£]-catenin signaling pathway. Wnt/£]-catenin signaling is implicated in liver carcinogenesis. However, the exact roles of LECT2 in liver carcinogenesis are not yet well characterized. This study is to investigate the extra roles of LECT2 in Wnt signaling. Our results showed that adenoviral administration of LECT2 over-expression suppress oncogenic processes such as migration, invasion, proliferation and colony formation, as well as alteration in cell cycle distributions. In animal model significantly suppress liver malignancies in orthotopic Novikoff hepatoma. In conclusion, we show that ad-LECT2 gene delivery attenuated cell carcinogenesis process via downregulated Wnt/£]-catenin signaling in vitro and suppressed tumor growth in vivo. Besides LECT2 over-expression represents a novel therapeutically factor for hepatocelluar carcinoma.

The key control step in E. coli chemotaxis is regulation of CheA kinase activity by a set of four transmembrane chemoreceptors. The receptor dimers can form trimeric complexes (trimers of dimers), and these trimers can be joined by a bridge thought to consist of a CheW monomer, a CheA dimer, and a second CheW monomer. It has been proposed that trimers of receptor dimers may be joined by CheW-CheA dimer-CheW links to form an extended hexagonal lattice that may be the structural basis of the chemoreceptor patches seen in E. coli. The receptor/CheA/CheW ternary complex is a membrane-spanning allosteric enzyme whose activity is regulated by protein interactions. The study presented in this dissertation investigated intermolecular and intramolecular interactions that affect the chemotactic signal processing. I have examined functional interactions between the serine receptor Tsr and the aspartate receptor Tar using a receptor coupled in vitro phosphorylation assay. The results reveal the emergent properties of mixed receptor populations and emphasize their importance in the integrated signal processing that underlies bacterial chemotaxis. A mutational analysis of the extreme C-terminus (last fifty residues) of Tar is also presented. The results implicate the receptor C-terminus in maintenance of baseline receptor activity and in attractant-induced transmembrane signaling. They also suggest how adaptive methylation might counteract the effects of attractant binding.

The hypothalamus is an integral part of the brain's regulation of mammalian physiology and behavior. Among many functions, this regulatory center activates the sympathetic nervous system, maintains appropriate body temperature, controls food intake, and controls release of hormones from the pituitary gland. Deep within the hypothalamus lie a paired cluster of cells, the suprachiasmatic nuclei (SCN), which function as the chief circadian pacemaker. The goal of the present thesis research was to study rhythmically controlled ATP gliotransmission. I used an immortalized SCN2.2 hypothalamic cell line to determine the mechanism by which ATP signaling is regulated in this context. Additionally, this research aimed to elucidate if clock-controlled ATP gliotransmission is fundamentally distinct from stimulus-evoked calcium-dependent mechanisms that regulate intercellular ATP signaling among astrocytes. In this thesis, I show that there are multiple ATP signaling mechanisms present among SCN2.2 cells. cAMP-dependent signaling mediates clock-controlled ATP accumulation but not stimulus-evoked ATP signaling. In addition, pharmacological studies suggest that disparate purinergic receptor-mediated mechanisms are involved in the regulation of clock-controlled versus stimulus-evoked ATP signaling. Rhythmic accumulation of ATP in SCN2.2 cultures is modulated by calcium-dependent processes. Peaks in ATP accumulation coincide with elevated mitochondrial calcium levels, while troughs in ATP accumulation coincide with periods of high cytosolic calcium levels, suggesting a possible mechanistic link between circadian shifts in intracellular calcium handling and ATP handling in SCN2.2 cells. Clock-controlled ATP accumulation in SCN2.2 cells is not a by-product of rhythmic cell cycle or rhythmic cell death. Overall, my research suggests that the ATP accumulation rhythm in SCN2.2 cells is likely an output of the biological clock, mediated by astrocytic calcium signaling processes, and not an output of cell division or cell death. Estimation of ATP accumulation in SCN2.2 cultures at peak time points suggests that clock-controlled ATP release is critical to the function of astrocytes in the mammalian brain, perhaps in the regulation of brain metabolism, the regulation of sleep/wake physiology, or the integration of both.

The overall goal of this research was to understand the role of inter-kingdom signaling in enterohemorrhagic Escherichia coli (EHEC) infections of the human gastro-intestinal (GI) tract from the perspective of both the invading pathogen and the human intestinal epithelial cells, which they colonize. Differential gene expression of EHEC was studied upon exposure to the human neuroendocrine hormones epinephrine and norepinephrine. We determined that these hormones increase EHEC chemotaxis, motility, biofilm formation, colonization of host cells, and virulence gene expression. We also studied the EHEC response to the GI tract commensal bacterial signaling molecules indole and autoinducer-2 (AI-2). We observed that indole decreases all the EHEC phenotypes that are increased by the human hormones and represses EHEC virulence. However, the effect of AI-2 was similar to that observed with hormones and opposite to that observed with indole, i.e. AI-2 increases EHEC virulence phenotypes. We studied changes in host cell transcriptome in the presence of the commensal bacterial signal indole. Indole increases expression of genes involved in tight junction and gap junction formation, and production of mucins and actin cytoskeleton genes. Indole also down-regulates genes encoding for pro-inflammatory cytokines, chemokines, and Toll-like receptors. The gene expression results were confirmed with phenotypic assays where we observed an increase in trans-epithelial resistance, increase in the anti-inflammatory cytokine IL-10, decrease in the pro-inflammatory cytokine IL-8, decrease in the activity of the pro-inflammatory transcription factor NF-κB, and decrease in colonization by EHEC of the indole-pre-treated HCT-8 cells. We established that factors secreted by epithelial cells are important determinants of EHEC virulence. Gene expression studies showed that 34 out of 41 LEE virulence genes were induced when EHEC was cultured in conditioned medium. In addition, the data showed increased expression of the shiga toxin-2 prophage 933W. These changes in gene expression were corroborated by a 5-fold increase in HCT-8 cell colonization and increased intracellular Stx2 phage titers. We determined that the HCT-8-secreted factor(s) was protein-based and that it was greater than 3 kDa in size. In conclusion, we have characterized the pathogen response to various eukaryotic and prokaryotic GI tract signals. We have established, for the first time, that the commensal bacterial signal indole is an inter-kingdom signal for the host epithelial cells. Overall, our studies provide a greater understanding of host-pathogen interactions.

We previously described BT2, a BTB/POZ domain containing protein, as an activator of telomerase in Arabidopsis thaliana. In the current study, I present evidence of its interesting roles in mediating multiple hormone, stress and metabolic responses in plants. Steady-state expression of BT2 mRNA was regulated diurnally and was under the control of circadian clock, with a maximum expression in the dark. BT2 mRNA was responsive to nutrient status and to multiple biotic and abiotic stress signals. Using bt2 loss-of-function and BT2 over-expressing lines, I show that BT2 suppresses sugar and ABA-mediated responses during germination. BT2 is also essential for transcriptional gene activation mediated by CaMV 35S enhancers in Arabidopsis. Loss of BT2 in several well-characterized 35S enhancer activation-tagged lines such as yucca1d, pap1d, jaw1d etc., resulted in suppression of the activation phenotypes. The suppression of the phenotypes was due to decreased transcription of the activation-tagged genes. I further demonstrate that BT2 genetically interacts with CULLIN3. I propose that BT2 and CULLIN3 are components of a ubiquitin ligase complex. Together with associated proteins BET9 and BET10, the BT2 complex is required for CaMV 35S enhancer-mediated activation of gene expression and may regulate expression of target genes involved in multiple responses to fluctuating biotic and abiotic conditions. I also found that BT2 protein levels are tightly regulated in plants. BT2 protein was primarily localized in the nucleus and was developmentally regulated. BT2 turn-over was regulated in part by the 26S-proteosome, and rare codons present in its open reading frame affected BT2 protein accumulation. In addition to BT2, its orthologs, BT1, BT3, BT4 and BT5, also responded to light, clock and nutrients, with some differences. Moreover, BT1, BT3 and BT4 were also required for 35S enhancer-mediated activation of gene expression. I propose that BT family proteins assemble into multi-protein complexes to mediate multiple responses to changing environmental and nutritional conditions.

The purpose of the article is to analyze the relationship among dividend policy,future earnings and growth opportunities.And the results are below: 1.Total dividend and cash dividend can predict future earnings,but stock dividend can only reflect current earnings 2.total dividend and stock dividend are signaling effect,but I have a diffent result in cash dividend. Using MBA,MBE and E/P as substitute variables,it is contracting effect.But using R&D as a substitute variable,it is signaling effect.

Competitive reaction to entry is an important issue in the marketing and economics areas. The monopolistic incumbent of a market often faces competitive entry if the market is profitable. This is a common issue that often occurs in the market transition from monopoly to competition. The entrant not only enters the market, but also wants to signal to tell consumers his quality level. The incumbent's reaction is also a signal to the consumers. Thus, how should the incumbent do? The paper "Response to Competitive Entry: A Rationale for Delayed Defensive Reaction" which is written by Ajay Kalra, Surendra Rajiv and Kannan Srinivasan (1998) and published in Marketing Science provides a completed and clear explanation of this issue. They claim that the incumbent would delay the defensive reaction to the competitive entry under information asymmetry. But it is still incorrect. Hence, we want to provide a revision to support that delayed defensive reaction is really a rational response to competitive entry, and explain this issue correctly and logically. We analyze the strategic interactions of the incumbent and the entrants which were omitted previously. Finally, we would obtain the conclusion that is also supporting this point of view¡G delayed defensive reaction is really a rational response to competitive. And it is really a Nash equilibrium, no firms would deviate.

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This paper examines how various monetary policy signals such as official discount rate changes¡Bspeeches and monetary aggregate M2 annual growth rate affect the structure of interest rates in Taiwan. The model of the thesis is based on the Svensson model (1994) which is the extension of the parsimonious model defined by Nelson and Siegel (1987). It is being shown, that the term of interest rates, estimated based on Svensson model result in a fault value for Taiwan, due to a unsound bond market especially in the short term and one-year interest rates. There is no proof that unexpected movements in the short end of the yield curve are mainly driven by unexpected changes in the official discount rate. Speeches are found to be a more important determinant for the longer end of the term structure. The conclusion is that central bank communication is an essential part of the conduct of monetary policy.

Thesis (Ph. D.)--Case Western Reserve University, 2004. / [School of Medicine] Department of Physiology and Biophysics. Includes bibliographical references. Available online via OhioLINK's ETD Center.