• Genomics & Informatics
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• 제3권1호
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• pp.8-14
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• 2005

Although much is known about the molecular biology of platelets, the megakaryocytes' (MKs) molecular biology was not understood so well because of their rareness. By the cloning and characterization of thrombopoietin (TPO), which is the principal regulator of the growth and development of the MKs, researches on the MKs have been growing rapidly. To understand megakaryocytopoiesis, we investigated the gene expression profile of the MKs using oligonucleotide microarray where 10,108 unique genes were spotted. Comparing the fluorescence intensities of which ratio is $\ge$ ${\mid}2{\mid}$, 372 genes were up-regulated and 541 genes were down-regulated in MKs. For confirmatory expression, RNase protection assay (RPA) establishing abundant apoptotic gene expression was carried out. In MKs, many of the known genes, including several platelet related genes, GATA binding protein were highly expressed. Particularly, TGF beta, clusterin (complement lysis inhibitor), and thymosin beta 4 (actin-sequestering molecules) were expressed highly in MKs. As MKs specific expressed genes may regulate normal and pathologic platelet (and/or MK) functions, the transcript profiling using microarray was useful on molecular understanding of MKs,

• 천문학회보
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• 제35권2호
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• pp.73.2-73.2
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• 2010

In order to understand internal dynamics of starless cores, molecular line emissions are usually observed. From profiles of the molecular lines, internal motions of starless cores have been deduced using a simple radiative transfer model such as the two-layer model (Myers et al.1996). This brings complexities arising from the chemical evolution. The motivation of this study is to follow the chemical evolution of a starless core that goes through gravitational contraction. For this purpose, we have performed hydrodynamical simulations with a marginally unstable Bonnor-Ebert sphere as an initial condition. We follow the chemical evolution of this core with changing conditions such as the chemical reaction rate at the dust surface and the strength of radiation field that penetrate into the core. At the core center, the molecules suffer from a higher degree of molecular depletion on the dust covered by ice rather than on the bare silicate dust. The stronger radiation field dissociates more molecules at the core envelope. From analysis on the line profile using the two-layer model, we found that the speed of inward motion deduced from the HCN F = 2-1 line adequately traces the true infall speed, when the dust is covered by ice and the core is exposed to the diffuse interstellar radiation field. Under different conditions, the two-layer model significantly underestimate the infall speed.

• Animal cells and systems
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• 제7권3호
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• pp.207-211
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• 2003

Caveolin-1 is a principal protein in the plasma membrane microdomains called caveolae. Caveolae play an important role in the transcytosis and pinocytosis. Therefore, caveolin-1 is most likely to work for the membrane dynamic events. In addition, caveolin-1 interacts with various signaling molecules. Although caveolin-1 possesses a variety of physiological functions, its structural properties were little construed. Here we analyzed the structural dynamics of the N-terminal caveolin-1 (residues 1-101), in order to better understand the structural properties in terms of its versatile functionality. We first analyzed its oligomeric form using GST-fused N-terminal domain, revealing that it equilibrates between a dimer and monomers in av concentration-dependent manner. The N-terminal domain of caveolin-1 was previously found to form a heptamer, so that our data suggest the dimeric form as an intermediate structure for the heptamer formation. Then, we obtained the folding profile, which indicated that $\DeltaG_{H2O}\;is\;about\;0.5\;\pm0.03$ kcal/mol. The stability of N-terminal domain is relatively low, indicating that N-terminal domain may not be crystalline. Conclusively, the dynamic and flexible structure of N-terminal domain appears more favorable to maintain the versatile functions of caveolin-1.

• Molecules and Cells
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• 제44권2호
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

• Journal of Microbiology and Biotechnology
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• 제32권1호
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• pp.126-140
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• 2022

Stem cells can be applied usefully in basic research and clinical field due to their differentiation and self-renewal capacity. The aim of this study was to establish an effective novel therapeutic cellular source and create its molecular expression profile map to elucidate the possible therapeutic mechanism and signaling pathway. We successfully obtained a mesenchymal stem cell population from human embryonic stem cells (hESCs) cultured on chemically defined feeder-free conditions and treated with connective tissue growth factor (CTGF) and performed the expressive proteomic approach to elucidate the molecular basis. We further selected 12 differentially expressed proteins in CTGF-induced hESC-derived mesenchymal stem cells (C-hESC-MSCs), which were found to be involved in the metabolic process, immune response, cell signaling, and cell proliferation, as compared to bone marrow derived-MSCs(BM-MSCs). Moreover, these up-regulated proteins were potentially related to the Wnt/β-catenin pathway. These results suggest that C-hESC-MSCs are a highly proliferative cell population, which can interact with the Wnt/β-catenin signaling pathway; thus, due to the upregulated cell survival ability or downregulated apoptosis effects of C-hESC-MSCs, these can be used as an unlimited cellular source in the cell therapy field for a higher therapeutic potential. Overall, the study provided valuable insights into the molecular functioning of hESC derivatives as a valuable cellular source.

• Molecules and Cells
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• 제45권5호
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• pp.343-352
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• 2022

The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the gene-regulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

• International Journal of Oral Biology
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• 제49권3호
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• pp.53-60
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• 2024

Nicotinamide (NAM), a water-soluble derivative of vitamin B3, has emerged as a potential therapeutic agent for bone-related disorders. In particular, it promotes bone metabolism and alleviates delayed tooth eruptions associated with cleidocranial dysplasia (CCD). NAM serves as a precursor for nicotinamide adenine dinucleotide, a key coenzyme involved in cellular metabolism that plays an essential role in oxidative phosphorylation and mitochondrial function. Recent research has highlighted the capacity of NAM to enhance osteogenic differentiation and regulate the interaction between osteoblasts and osteoclasts, which is critical for maintaining bone homeostasis. Moreover, the effect of NAM in preventing delayed tooth eruptions in CCD models underscores its potential as a noninvasive therapeutic option. Considering its safety profile and therapeutic potential, NAM is a promising candidate for long-term treatment of bone diseases and prevention of age-related bone disorders.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.198-207
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• 2007

[ $^{18}F$ ]-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of glial tumors were evaluated to determine whether glial tumors with high $^{18}F$-FDG uptake have more aggressive biological potential than with low uptake. Surgical specimens were obtained from the 12 patients with glial tumors (4 males and 8 females, age range 42-68 years). The tumor samples were divided into two groups based on the $^{18}F$-FDG uptake PET scan findings: high $^{18}F$-FDG uptake (n=4) and low $^{18}F$-FDG uptake (n=8). The pathological tumor grade was closely correlated with the $^{18}F$-FDG uptake pattern: Glial tumors with high $^{18}F$-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were grade II. The total RNA was extracted from the frozen tissues of all glial tumors (n=12), and adjacent non-cancerous tissue (n=3). The gene expression profiles were evaluated using cDNA microarray. The glial tumors with high $^{18}F$-FDG uptake showed increase expression of 15 genes compared to those with low uptake (P<0.005). Nine genes were down-regulated. Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, glial tumors with high $^{18}F$-FDG uptake appear to have more aggressive biological properties than those with low uptake.

• Bulletin of the Korean Chemical Society
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• 제33권3호
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• pp.911-916
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• 2012

Ion selectivity in a simple cyclic peptide nanotube, composed of four cyclo[-(D-Ala-Glu-D-Ala-Gln)$_2-$] units, is investigated by calculating the PMF profiles of $Na^+$, $K^+$, and $Cl^-$ ions permeating through the peptide nanotube in water. The final PMF profiles of the ions obtained from the umbrella sampling (US) method show an excellent agreement with those from the thermodynamic integration (TI) method. The PMF profiles of $Na^+$ and $K^+$ display free energy wells while the PMF curve of $Cl^-$ features free energy barriers, indicating the selectivity of the cyclic peptide nanotube to cations. Decomposition of the total mean force into the contribution from each component in the system is also accomplished by using the TI method. The mean force decomposition profiles of $Na^+$ and $K^+$ demonstrate that the dehydration free energy barriers by water molecules near the channel entrance and inside the channel are completely compensated for by attractive electrostatic interactions between the cations and carbonyl oxygens in the nanotube. In the case of $Cl^-$, the dehydration free energy barriers are not eliminated by an interaction between the anion and the peptide nanotube, leading to the high free energy barriers in the PMF profile. Calculations of the coordination numbers of the ions with oxygen atoms pertaining to either water molecules or carbonyl groups in the peptide nanotube reveal that the stabilization of the cations in the midplane regions of the nanotube arises from the favorable interaction of the cations with the negatively charged carbonyl oxygens.

• Molecular & Cellular Toxicology
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• 제4권2호
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• pp.164-169
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• 2008

Methylmercury (MeHg) is known to have devastating effects on the mammalian nervous system. In order to characterize the mechanism of MeHg-induced neurotoxicity, we investigated the analysis of transcriptional profiles on human 8k cDNA microarray by treatment of $1.4{\mu}M$ MeHg at 3, 12, 24 and 48h in human neuroblastoma SH-SY5Y cell line. Some of the identified genes by MeHg treatment were significant at early time points (3h), while that of others was at late time points (48h). The early response genes that may represent those involved directly in the MeHg response included pantothenate kinase 3, a kinase (PRKA) anchor protein (yotiao) 9, neurotrophic tyrosine kinase, receptor, type 2 gene, associated with NMDA receptor activity regulation or perturbations of central nervous system homeostasis. Also, when SH-SY5Y cells were subjected to a longer exposure (48h), a relative increase was noted in a gene, glutamine-fructose-6-phosphate transaminase 1, reported that overexpression of this gene may lead to the increased resistance to MeHg. To confirm the alteration of these genes in cultured neurons, we then applied real time-RT PCR with SYBR green. Thus, this result suggests that a neurotoxic effect of the MeHg might be ascribed that MeHg alters neuronal receptor regulation or homeostasis of neuronal cells in the early phase. However, in the late phase, it protects cells from neurotoxic effects of MeHg.