• Genomics & Informatics
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• v.4 no.4
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• pp.182-187
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• 2006

6-Phosphogluconolactonase (6PGL) is one of the key enzymes in the ubiquitous pathways of central carbon metabolism, but bacterial 6PGL had been long known as a missing enzyme even after complete bacterial genome sequence information became available. Although recent experimental characterization suggests that there are two types of 6PGLs (DevB and YbhE), their phylogenetic distribution is severely biased. Here we present that proteins in COG group previously described as 3-oarboxymuconate cyclase (COG2706) are actually the YbhE-type 6PGLs, which are widely distributed in Proteobacteria and Fimicutes. This case exemplifies how erroneous functional description of a member in the reference database commonly used in transitive genome annotation cause systematic problem in the prediction of genes even with universal cellular functions.

• BMB Reports
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• v.44 no.5
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• pp.291-297
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• 2011

Aging is one of the most complicated biological processes in all species. A number of different model organisms from yeast to monkeys have been studied to understand the aging process. Until recently, many different age-related genes and age-regulating cellular pathways, such as insulin/IGF-1-like signal, mitochondrial dysfunction, Sir2 pathway, have been identified through classical genetic studies. Parallel to genetic approaches, genome-wide approaches have provided valuable insights for the understanding of molecular mechanisms occurring during aging. Gene expression profiling analysis can measure the transcriptional alteration of multiple genes in a genome simultaneously and is widely used to elucidate the mechanisms of complex biological pathways. Here, current global gene expression profiling studies on normal aging and age-related genetic/environmental interventions in widely-used model organisms are briefly reviewed.

• CELLMED
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• v.3 no.1
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• pp.1.1-1.7
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• 2013

The present review investigates the role of the cytoprotective enzyme heme oxygenase-1 (HO-1) in human diseases and explores strategies for its clinical use. In recent years, there has been a growing evidence, for the beneficial effects of some phytoconstituents via induction of HO-1 expression, contained in commonly used spices, fruits, and herbs, in preventing various pathologic conditions, including cancer, diabetes, and cardiovascular diseases. HO-1 catalyzes the rate-limiting step in heme catabolism to generate ferrous iron, carbon monoxide, and biliverdin. HO-1 is reported to play crucial roles in cellular protection, such as anti-inflammatory, anti-proliferative and anti-apoptotic effects. These evidences indicate that HO-1 may functions as a potential therapeutic target in various human diseases. The article highlights the current status of the development of the HO-1 modulation pathway using dietary phytoconstituents.

• Korean Journal of Biological Psychiatry
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• v.18 no.4
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• pp.189-196
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• 2011

Major depressive disorder is characterized by cellular and molecular alterations resulting in the depressive behavioral phenotypes. Preclinical and clinical studies have demonstrated the deficits, including cell atrophy and loss, in limbic and cortical regions of patients with depression, which is restored with antidepressants by reestablishing proper molecular changes. These findings have implicated the involvement of relevant intracellular signaling pathways in the pathogenetic and therapeutic mechanisms of depressive disorders. This review summarizes the current knowledge of the signal transduction mechanisms related to depressive disorders, including cyclic-AMP, mitogen-activated protein kinase, Akt, and protein translation initiation signaling cascades. Understanding molecular components of signaling pathways regulating neurobiology of depressive disorders may provide the novel targets for the development of more efficacious treatment modalities.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.311-317
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• 2008

Zebrafish were exposed to commercial silver nanoparticles (${\sim}$10-20 nm) at 0.4 and 4 ppm during cadual fin regeneration. The silver was in the $Ag^+$ ionic form. Fin regeneration was slow in the group exposed to the lower concentration. The cadual fin, gill, and muscle were assayed after 48 hours and subjected to histological analysis. In all tissues sampled, fish exposed to nanoparticles exhibited infiltration, large mitochondria with empty matrices, and accumulation of nano-sized silver in blood vessels. The results suggested mitochondrial damage and induction of inflammation. Microarray analysis of RNA from young zebrafish (52 hours post-fertilization) that were exposed to nanometer-sized silver particles, showed alteration in expression of the p53 gene pathway related to apoptosis. Gene expression changes in the nanoparticle-treated zebrafish led to phenotypic changes, reflecting increased apoptosis.

• Molecules and Cells
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• v.22 no.2
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• pp.228-232
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• 2006

The Drosophila protein, Rbp9, is homologous to human Hu, which is reported to be involved in small cell lung cancer. Rbp9 functions in cystocyte differentiation, and mutations in Rbp9 cause ovarian tumors. Here we show that the antimicrobial peptide, Attacin, is upregulated in Rbp9 mutants, especially in ovaries where tumors form. Upregulation seems to result from activation of the NF-${\kappa}B$ pathway since we detected nuclear localization of Relish in Rbp9 mutant ovaries but not in wild type ovaries. Inactivation of NF-${\kappa}B$ in the Rbp9 mutant allows prolonged survival of malformed egg chambers. We conclude that Drosophila initiates an anti-tumor defense response via activation of NF-${\kappa}B$.

• Molecules and Cells
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• v.25 no.3
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• pp.397-406
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• 2008

Computational modeling of signal transduction is currently attracting much attention as it can promote the understanding of complex signal transduction mechanisms. Although several mathematical models have been used to examine signaling pathways, little attention has been given to crosstalk mechanisms. In this study, an attempt was made to develop a computational model for the pathways involving growth-factor-mediated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt). In addition, the dynamics of the protein activities were analyzed based on a set of kinetic data. The simulation approach integrates the information on several levels and predicts systems behavior. The in-silico analysis conducted revealed that the Raf and Akt pathways act independently.

• Molecules and Cells
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• v.38 no.4
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• pp.297-303
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• 2015

Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understand insulin signaling and glucose metabolism. While recent large-scale "omics" studies have revealed the acetylome to be comparable in size to the phosphorylome, the acetylation of insulin signaling proteins and its functional relevance to insulin-stimulated glucose transport and glucose metabolism is not fully understood. In this Mini Review we discuss the acetylation status of proteins involved in the insulin signaling pathway and review their potential effect on, and relevance to, insulin action in skeletal muscle.

• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.923-931
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• 2013

Rapamycin, known as an inhibitor of Target of Rapamycin (TOR), is an immunosuppressant drug used to prevent rejection in organ transplantation. Despite the close association of the TOR signaling cascade with various scopes of metabolism, it has not yet been thoroughly investigated at the metabolome level. In our current study, we applied mass spectrometric analysis for profiling primary metabolism in order to capture the responsive dynamics of the Chlamydomonas metabolome to the inhibition of TOR by rapamycin. Accordingly, we identified the impact of the rapamycin treatment at the level of metabolomic phenotypes that were clearly distinguished by multivariate statistical analysis. Pathway analysis pinpointed that inactivation of the TCA cycle was accompanied by the inhibition of cellular growth. Relative to the constant suppression of the TCA cycle, most amino acids were significantly increased in a time-dependent manner by longer exposure to rapamycin treatment, after an initial down-regulation at the early stage of exposure. Finally, we explored the isolation of the responsive metabolic factors into the rapamycin treatment and the culture duration, respectively.

• Journal of Integrative Natural Science
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• v.7 no.4
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• pp.227-233
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• 2014

Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Activation of caspases-3 stimulates a signaling pathway that ultimately leads to the death of the cell. Hence, caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage. In this work, comparative molecular similarity indices analysis (CoMSIA) was performed on a series of 3,4-dihydropyrimidoindolones derivatives which are inhibitors of caspase-3. The best predictions were obtained for CoMSIA model ($q^2$ = 0.586, $r^2$ = 0.955). The predictive ability of test set ($r^2_{pred}$) was 0.723. Statistical parameters from the generated QSAR models indicated the data is well fitted and have high predictive ability. Our theoretical results could be useful to design novel and more potent caspase-3 derivatives.