• Interdisciplinary Bio Central
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• 제3권1호
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• pp.5.1-5.5
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• 2011

Introduction: Many signal transduction pathways mediate cell's behavior by regulating expression level of involved genes. Abnormal behavior indicates loss of regulatory potential of pathways, and this can be attributed to loss of expression regulation of downstream genes. Therefore, function of pathways should be assessed by activity of a pathway itself and relative activity between a pathway and downstream genes, simultaneously. Results and Discussion: In this study, we suggested a new method to assess pathway's function by introducing concept of 'responsiveness'. The responsiveness was defined as a relative activity between a pathway itself and its downstream genes. The expression level of a downstream gene as a function of an upstream pathway activation characterizes disease status. In this aspect, by using the responsiveness we predicted potential progress in cancer development. We applied our method to predict primary and metastatic status of melanoma cancer. The result shows that the responsiveness-based approach achieves better performance than using gene or pathway information alone. The mean of ROC scores in the responsiveness-based approach was 0.90 for GSE7553 data set, increased more than 40% compared to a gene-based method. Moreover, identifying the abnormal regulatory patterns between pathway and its downstream genes provided more biologically interpretable information compared to gene or pathway based approaches.

• Genomics & Informatics
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• 제6권4호
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• pp.223-226
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• 2008

We introduce a computational approach for analysis of glycosylation in Post-PKS tailoring steps. It is a computational method to predict the deoxysugar biosynthesis unit pathway and the substrate specificity of glycosyltransferases involved in the glycosylation of polyketides. In this work, a directed and weighted graph is introduced to represent and predict the deoxysugar biosynthesis unit pathway. In addition, a homology based gene clustering method is used to predict the substrate specificity of glycosyltransferases. It is useful for the rational design of polyketide natural products, which leads to in silico drug discovery.

• Journal of Microbiology and Biotechnology
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• 제23권6호
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• pp.779-784
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• 2013

Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. The availability of ligand libraries has facilitated the search for novel drug targets using chemogenomics approaches, compared with the traditional method of drug discovery, which is time consuming and yields few leads with little intracellular information for guiding target selection. Recent subtractive genomics studies have revealed the putative drug targets in peptidoglycan biosynthesis pathways in Leptospira interrogans. Aligand library for the murD ligase enzyme in the peptidoglycan pathway has also been identified. Our approach in this research involves screening of the pre-existing ligand library of murD with related protein family members in the putative drug target assembly in the peptidoglycan biosynthesis pathway. A chemogenomics approach has been implemented here, which involves screening of known ligands of a protein family having analogous domain architecture for identification of leads for existing druggable protein family members. By means of this approach, one murC and one murF inhibitor were identified, providing a platform for developing an anti-leptospirosis drug targeting the peptidoglycan biosynthesis pathway. Given that the peptidoglycan biosynthesis pathway is exclusive to bacteria, the in silico identified mur ligase inhibitors are expected to be broad-spectrum Gram-negative inhibitors if synthesized and tested in in vitro and in vivo assays.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.367-378
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• 2016

Recently, it was reported that the role of mitochondria-reactive oxygen species (ROS) generating pathway in cisplatin-induced apoptosis is remarkable. Since a variety of molecules are involved in the pathway, a comprehensive approach to delineate the biological interactions of the molecules is required. However, quantitative modeling of the mitochondria-ROS generating pathway based on experiment and systemic analysis using the model have not been attempted so far. Thus, we conducted experiments to measure the concentration changes of critical molecules associated with mitochondrial apoptosis in both human mesothelioma H2052 and their ${\rho}^0$ cells lacking mitochondrial DNA (mtDNA). Based on the experiments, a novel mathematical model that can represent the essential dynamics of the mitochondrial apoptotic pathway induced by cisplatin was developed. The kinetic parameter values of the mathematical model were estimated from the experimental data. Then, we have investigated the dynamical properties of this model and predicted the apoptosis levels for various concentrations of cisplatin beyond the range of experiments. From parametric perturbation analysis, we further found that apoptosis will reach its saturation level beyond a certain critical cisplatin concentration.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1370-1375
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• 2023

In this study, we aimed to enhance the accumulation of chorismate (CHR) and anthranilate (ANT), key intermediates in the shikimate pathway, by modifying a shikimate over-producing recombinant strain of Corynebacterium glutamicum [19]. To achieve this, we utilized a CRISPR-driven genome engineering approach to compensate for the deletion of shikimate kinase (AroK) as well as ANT synthases (TrpEG) and ANT phosphoribosyltransferase (TrpD). In addition, we inhibited the CHR metabolic pathway to induce CHR accumulation. Further, to optimize the shikimate pathway, we overexpressed feedback inhibition-resistant Escherichia coli AroG and AroH genes, as well as C. glutamicum AroF and AroB genes. We also overexpressed QsuC and substituted shikimate dehydrogenase (AroE). In parallel, we optimized the carbon metabolism pathway by deleting the gntR family transcriptional regulator (IolR) and overexpressing polyphosphate/ATP-dependent glucokinase (PpgK) and glucose kinase (Glk). Moreover, acetate kinase (Ack) and phosphotransacetylase (Pta) were eliminated. Through our CRISPR-driven genome re-design approach, we successfully generated C. glutamicum cell factories capable of producing up to 0.48 g/l and 0.9 g/l of CHR and ANT in 1.3 ml miniature culture systems, respectively. These findings highlight the efficacy of our rational cell factory design strategy in C. glutamicum, which provides a robust platform technology for developing high-producing strains that synthesize valuable aromatic compounds, particularly those derived from the shikimate pathway metabolites.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.158-158
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• 1998

The non-mevalonate pathway is a newly discovered isoprenoid biosynthetic pathway in some bacteria, cyanobacteria, algae and plants. Because isoprenoid metabolites (ubiquinone, menaquinone, undecaprenol) are essential for bacterial growth, this pathway may represent a novel target for antibacterial agents. Antibiotics with a unique mechanism of action are needed to combat the risk of antibiotic resistance that is a current worldwide problem. In order to study this pathway as viable target, it was necessary to verify use of the pathway in our model system, the bacterium Bacillus subtilis. Incubation experiments with [6,6-$^2$H$_2$]-D-glucose and [l-$^2$H$_3$]-deoxy-D-xylulose were conducted to provide labeled menaquinone-7 (MK -7), the most abundant isoprenoid in B. subtilis. $^2$H-NMR analysis of the MK-7 revealed labeling patterns that strongly support utilization of the non-mevalonate pathway. Another approach to study the pathway is by structure activity relationships of proposed inhibitors of the pathway. Fosmidomycin is a phosphonic acid with antibacterial activity known to inhibit isoprenoid biosynthesis in susceptible bacteria and may act by inhibiting the non-mevalonate pathway. Fosmidomycin and an N-methyl analog were synthesized and tested for antibacterial activity. Fosmidomycin was active against Escherichia coli and B. subtilis, while N-formyl-N-methyl-3-amino-propylphosphonic acid was inactive.

• The Korean Journal of Pain
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• 제26권4호
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• pp.396-400
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• 2013

Conventional transcrural CPB via the "walking off" the vertebra technique may injure vital organs while attempting to proximally spread injectate around the celiac plexus. Therefore, we attempted the CT-simulated fluoroscopy-guided transdiscal approach to carry out transcrural CPB in a safer manner, spreading the injectate more completely and closely within the celiac plexus area. A 54-year-old male patient with pancreatic cancer suffered from severe epigastric pain. The conventional transcrural approach was simulated, but the needle pathway was impeded by the kidney on the right side and by the aorta on the left side. After simulating the transdiscal pathway through the T11-12 intervertebral disc, we predetermined the optimal insertion point (3.6 cm from the midline), insertion angle (18 degrees), and advancement plane, as well as the proper depth. With the transdiscal approach, we successfully performed transcrural CPB within a narrow angle, and the bilateral approach was not necessary as we were able to achieve the bilateral spread of the injectate with the single approach.

• 미생물과산업
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• 제12권1호
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• pp.9-14
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• 1986

We have adopted a genetic approach to identifying those residues and local sequences in a polypeptide chain which play an important role on the folding pathway. Our approach has been to isolate and characterize mutants which specifically alter the folding and subunit association pathway of a polypeptide chain, without altering the native protein. Such mutants distinguish residues involved in the kinetic control of conformation from residues involved in the stability and activity of the native protein. This approach is complementary to the efforts to characterize mutations which alter the stability of the mature protein(6,7,8). It is likely that many residues will have roles in both aspects of the functioning of the polypeptide chain. We thought it likely, however, that at least with large proteins, these aspects might be segregated in different local sequences.

• 가정과삶의질연구
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• 제27권1호
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• pp.45-60
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• 2009

This study was designed to examine the meaning of housing in modern Korea, and to draw the interrelationship of people and housing. In-depth interviews were conducted, and the qualitative research investigated various aspects of housing history among four individuals during the different phases of social and economic transitions. Each narratives showed the unique characteristics of life history, and the conceptual frameworks for interpretation were microsociological approach by Morris and Winter(1978) and pathway approach by Clapham(2005). One narrater named "K" had gone through various housing experiences since her birth in 1933 at a traditional Korean housing, and she moved to a traditional rural community. Another narrater called "S" was born in housing built during the Japanese colonization, gained wealth through the housing boom of the industrialization, and has lived in a suburban condominium. "G" spent her entire life in an urban area, had never owned a house, and lived in a house with poor quality. The other narrater named "L" had lived in a single-family home with a large yard since her childhood, and she has resided in multi-family housing by herself after having a lot of experiences of building houses. The results revealed that housing could play as a simple role as a shelter, be transformed over family life cycle, become prestige of extended family, social and family status, investment. Meaning of housing from the pathway approach were closely related to hometown, the relation to birth family at postmarriage, economic status, and housing experiences according to the social change. As a conclusion, the meaning of housing is vary, and housing conveys numerous implications including psychological, social and economic aspects.

• Archives of Plastic Surgery
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• 제34권6호
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• pp.713-718
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• 2007

Purpose: The aim of this study is to develop and apply the critical pathway to the orbital wall fracture patients and to elucidate its effect. Methods: Critical pathway(CP) sheet and questionnaire were developed by a team approach. Critical pathway was applied to 7 orbital wall fracture patients (CP group) from April 2006 to September 2006. Length of hospitalization and cost for hospitalization of CP group were compared to those of the 10 patients who had same disease entities and treated by conventional regimen(control group). Results: Length of hospitalization in the CP group (7.20 day) were insignificantly shorter than that of control group(8.71 day). Mean cost for hospitalization of the CP group(776,398 won) were insignificantly lower than that of control group(1,028,531 won). The patients satisfaction for the explanation regarding operation procedure, therapeutic operation fee, length of hospitalization and medical personnel were all affirmative. Conclusion: Critical pathway that we developed for orbital wall fracture definitely improved the quality of treatment. Furthermore, other critical pathways should be developed for another facial trauma patients.