• 대한미생물학회지
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• 제34권5호
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• pp.435-443
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• 1999

Orientia tsutsugamushi is obligate intracellular bacterium that grows within the cytoplasm of the eukaryotic host cells. Therefore capability of the attachment, entry into the host cell and intracellular survival should be critical process for oriential infection. In this study we investigated the cellular invasion mechanism of Orientia tsutsugamushi and the role of transmembrane heparan sulfate proteoglycan, which binds diverse components at the cellular microenvironment and is implicated as host cell receptors for a variety of microbial pathogens. First of all Orientia tsutsugamushi can invade a wide range of nonprofessional phagocytic cells including fibroblast, epithelial cells and endothelial cells of various host species, including Band T lymphocytes. Thus, it was postulated that the attachment of O. tsutsugamushi requires the recognition of ubiquitous surface structures of many kinds of host cells. Treatments with heparan sulfate and heparin inhibited the infection of Orientia tsutsugamushi in dose-dependent manner for L cell, mouse fibroblast, whereas other glycosaminoglycans such as chondroitin sulfate had no effect. Collectively, these findings provide strong evidence that initial interaction with heparan sulfate proteoglycan is required for the oriential invasion into host cells.

• Journal of Microbiology and Biotechnology
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• 제30권8호
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• pp.1261-1271
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• 2020

Cytochrome c_L (Cytc_L) is an essential protein in the process of methanol oxidation in methylotrophs. It receives an electron from the pyrroloquinoline quinone (PQQ) cofactor of methanol dehydrogenase (MDH) to produce formaldehyde. The direct electron transfer mechanism between Cytc_L and MDH remains unknown due to the lack of structural information. To help gain a better understanding of the mechanism, we determined the first crystal structure of heme c containing Cytc_L from the aquatic methylotrophic bacterium Methylophaga aminisulfidivorans MP^T at 2.13 Å resolution. The crystal structure of Ma-Cytc_L revealed its unique features compared to those of the terrestrial homologues. Apart from Fe in heme, three additional metal ion binding sites for Na⁺, Ca⁺, and Fe²⁺ were found, wherein the ions mostly formed coordination bonds with the amino acid residues on the loop (G93-Y111) that interacts with heme. Therefore, these ions seemed to enhance the stability of heme insertion by increasing the loop's steadiness. The basic N-terminal end, together with helix α4 and loop (G126 to Y136), contributed positive charge to the region. In contrast, the acidic C-terminal end provided a negatively charged surface, yielding several electrostatic contact points with partner proteins for electron transfer. These exceptional features of Ma-Cytc_L, along with the structural information of MDH, led us to hypothesize the need for an adapter protein bridging MDH to Cytc_L within appropriate proximity for electron transfer. With this knowledge in mind, the methanol oxidation complex reconstitution in vitro could be utilized to produce metabolic intermediates at the industry level.

• Molecules and Cells
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• 제22권1호
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• pp.97-103
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• 2006

Phosphoinositides are critical regulators of ion channel and transporter activity. There are multiple isomers of biologically active phosphoinositides in the plasma membrane and the different lipid species are non-randomly distributed. However, the mechanism by which cells impose selectivity and directionality on lipid movements and so generate a non-random lipid distribution remains unclear. In the present study we investigated which structural elements of phosphoinositides are responsible for their subcellular location and movement. We incubated phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) with short or long acyl chains in CHO and HEK cells. We show that phosphate number and acyl chain length determine cellular location and translocation movement. In CHO cells, $PI(4,5)P_2$ with a long acyl chain was released into the cytosol easily because of a low partition coefficient whereas long chain PI was released more slowly because of a high partition coefficient. In HEK cells, the cellular location and translocation movement of PI were similar to those of PI in CHO cells, whereas those of $PI(4,5)P_2$ were different; some mechanism restricted the translocation movement of $PI(4,5)P_2$, and this is in good agreement with the extremely low lateral diffusion of $PI(4,5)P_2$. In contrast to the dependence on the number of phosphates of the phospholipid head group of long acyl chain analogs, short acyl chain phospholipids easily undergo translocation movement regardless of cell type and number of phosphates in the lipid headgroup.

• Molecules and Cells
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• 제46권7호
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

• IMMUNE NETWORK
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• 제1권2호
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• pp.104-108
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• 2001

Aging is a senescence and defined as a normal physiologic and structural alterations in almost all organ systems with age. As Leonard Hayflick, one of the first gerontologists to propose a theory of biologic aging, indicated that a theory of aging or longevity satisfies the changes of above conditions to be universal, progressive, intrinsic and deleterious. Although a number of theories have been proposed, it is now clear that cell aging (cell senescence) is multifactorial. No single mechanism can account for the many varied manifestations of biological aging. Many theories have been proposed in attempt to understand and explain the process of aging. Aging is effected in individual by genetic factors, diet, social conditions, and the occurrence of age-related diseases as diabetes, hypertension, and arthritis. It involves an endogenous molecular program of cellular senescence as well as continuous exposure throughout life to adverse exogenous influences, leading to progressive infringement on the cell's survivability so called wear and tear. So we could say the basic mechanism of aging depends on the irreversible and universal processes at cellular and molecular level. The immediate cause of these changes is probably an interference in the function of cell's macromolecules-DNA, RNA, and cell proteins-and in the flow of information between these macromolecules. The crucial questions, unanswered at present, concerns what causes these changes in truth. Common theories of aging are able to classify as followings for the easy comprehension. 1. Biological, 1) molecular theories - a. error theory, b. programmed aging theory, c. somatic mutation theory, d. transcription theory, e. run-out-of program theory, 2) cellular theories - a. wear and tear theory, b. cross-link theory, c. clinker theory, d. free radical theory, e. waste product theory, 3) system level theory-a. immunologic/autoimmune theory, 4) others - a. telomere theory, b. rate of living theory, c. stress theory, etc. Prevention of aging is theoretically depending on the cause or theory of aging. However no single theory is available and no definite method of delaying the aging process is possible by this moment. The most popular action is anti-oxidant therapy using vitamin E and C, melatonin and DHEA, etc. Another proposal for the reverse of life-span is TCP-17 and IL-16 administration from the mouse bone marrow B cell line study for the immunoglobulin VDJ rearrangement with RAG-1 and RAG-2. Recently conclusional suggestion for the extending of maximum life-span thought to be the calory restriction.

• BMB Reports
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• 제45권12호
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• pp.693-699
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• 2012

Together with protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs) serve as hallmarks in cellular signal transduction by controlling the reversible phosphorylation of their substrates. The human genome is estimated to encode more than 100 PTPs, which can be divided into eleven sub-groups according to their structural and functional characteristics. All the crystal structures of catalytic domains of sub-groups have been elucidated, enabling us to understand their precise catalytic mechanism and to compare their structures across all sub-groups. In this review, I describe the structure and mechanism of catalytic domains of PTPs in the structural context.

• Molecules and Cells
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• 제28권4호
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• pp.403-406
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• 2009

Rev is an essential regulatory protein for HIV-1 replication. Rev (11-20) is known as the significant region regarding the function of a nuclear entry inhibitory signal (NIS) of Rev. In this study, anticandidal effects and mechanism of action of Rev (11-20) were investigated. The result exhibited that Rev (11-20) contained candidacidal activities. To understand target site(s) of Rev (11-20), the intracellular localization of the peptide was investigated. The result showed that Rev (11-20) rapidly accumulated in the fungal cell surface. The cell wall regeneration test also indicated that Rev (11-20) exerted its anticandidal activity to fungal plasma membrane rather than cell wall. The fluorescent study using 1,6-diphenyl-1,3,5-hexatriene (DPH) further confirmed the membrane-disruption mechanism(s) of Rev (11-20). The present study suggests that Rev (11-20) possesses significant potential regarding therapeutic agents for treating fungal diseases caused by Candida species in humans.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2002년도 가을 학술발표논문집 Vol.29 No.2 (3)
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• pp.151-153
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• 2002

Mobile handhold devices such as PDA(Personal Digital Assistant) and Cellular Phone are more and more popular for personal web surfing. But today, most mobile handheld devices have relatively poor web browsing capability because of the small bandwidth of wireless connection, the small speed of CPU, the small capacity of RAM and Flash ROM, the small display size of LCD and the short lifecycle of battery. Users have to endure bigger communication latency than Desk PC's one because of these factors. In this paper, we propose an effective pre-refresh mechanism for handheld device's embedded web browser so as to make user's web surfing faster. The experiment was done using the simulator designed by ourselves and the experiment result demonstrates the proposed mechanism has a good performance to make web surfing faster.

• 미생물학회지
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• 제28권3호
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• pp.249-257
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• 1990

In the course of operating the accommodative and detoxifying mechanism against cadmium, its physio-biochemical changes were observed in Klebsiella aerogenes ATCC 10031. Changes of enzyme activity concerned phosphate metabolism, changes of phospholipid composition and in view of energy metabolism the changes of the nucleotide pool were examined. Activities of both alkaline and acid phosphatase were derepressed 4-10 folds under cadmium added cultures. Moreover, production of phospholipid such as lysophosphatidyl choline (LPC), phosphatidyl serine (PS) and phosphatidyl ethanolamone (PE) was increased and uridylate nucleotide pool was increased under Cd-surplus culture. These results i.e. overproduction of phosphatase catalyzing phosphate residue, increase of the production of PE and PS which have a close affinity with cadmium, and indrease of uridylate nucleotide pool used as a carrier of polysaccharide synthesis like bacterial capsule exhibited cellular responses for active defence against Cd-pressure. It was postulated that these phenomena should play another assistant roles in Cd-detoxifing mechanism.

• Journal of Microbiology and Biotechnology
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• 제24권3호
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• pp.354-358
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• 2014

A screening test showed that lycorine exhibited significant antifungal activity against 24 pathogenic crop fungi at concentrations of 500 ${\mu}g/ml$ and 100 ${\mu}g/ml$, respectively. Fusarium graminearum was selected for antifungal mechanism studies by observing its mycelial morphology and investigating the variations in its conductivity. In addition, the substance absorption and metabolism of F. graminearum were explored. The mechanism was revealed as being one by which lycorine destroyed the cellular membrane and further influenced substance absorption and cell metabolism.