Jungyeon Kim

PHO13 Deletion-Induced Transcriptional Activation Prevents Sedoheptulose Accumulation during Xylose Metabolism in Engineered Saccharomyces cerevisiae

The deletion of PHO13 (pho13Δ) in Saccharomyces cerevisiae, encoding a phosphatase enzyme of unknown specificity, results in the transcriptional activation of genes related to the pentose phosphate pathway (PPP) such as TAL1 encoding transaldolase. It has been also reported that the pho13Δ mutant of S. cerevisiae expressing a heterologous xylose pathway can metabolize xylose efficiently compared to its parental strain. However, the interaction between the pho13Δ-induced transcriptional changes and the phenotypes of xylose fermentation was not understood. Thus we investigated the global metabolic changes in response to pho13Δ when cells were exponentially growing on xylose. Among the 134 intracellular metabolites that we identified, the 98% reduction of sedoheptulose was found to be the most significant change in the pho13Δ mutant as compared to its parental strain. Because sedoheptulose-7-phosphate (S7P), a substrate of transaldolase, reduced significantly in the pho13Δ mutant as well, we hypothesized that limited transaldolase activity in the parental strain might cause dephosphorylation of S7P, leading to carbon loss and inefficient xylose metabolism. Mutants overexpressing TAL1 at different degrees were constructed, and their TAL1 expression levels and xylose consumption rates were positively correlated. Moreover, as TAL1 expression levels increased, intracellular sedoheptulose concentration dropped significantly. Therefore, we concluded that TAL1 upregulation, preventing the accumulation of sedoheptulose, is the most critical mechanism for the improved xylose metabolism by the pho13Δ mutant of engineered S. cerevisiae.

Food metabolomics: from farm to human

Metabolomics, one of the latest components in the suite of systems biology, has been used to understand the metabolism and physiology of living systems, including microorganisms, plants, animals and humans. Food metabolomics can be defined as the application of metabolomics in food systems, including food resources, food processing and diet for humans. The study of food metabolomics has increased gradually in the recent years, because food systems are directly related to nutrition and human health. This review describes the recent trends and applications of metabolomics to food systems, from farm to human, including food resource production, industrial food processing and food intake by humans.

Acute respiratory distress syndrome caused by miliary tuberculosis: a multicentre survey in South Korea.

BACKGROUND Miliary tuberculosis (TB) is an unusual cause of acute respiratory distress syndrome (ARDS). OBJECTIVE To evaluate the clinical characteristics and outcomes of patients with ARDS caused by miliary TB admitted to the intensive care unit (ICU). DESIGN A total of 67 patients were enrolled during the period 1999-2008. RESULTS The median age of the patients was 56 years (range 17-81), 19 (28.4%) were aged >71 years, and 38 (56.7%) were male. All-cause mortality in the ICU and hospital were respectively 58.2% and 61.2%. Of the total number of enrolled patients, 49 (73.1%) were prescribed anti-tuberculosis medication within 3 days of hospital admission. On the day of ARDS diagnosis (10.0 ± 3.7 vs. 7.4 ± 3.5, P = 0.005), non-survivors had a significantly higher Sequential Organ Failure Assessment (SOFA) score than survivors. Multivariate analysis showed that SOFA score on the day of ARDS diagnosis was a significant predictor of survival (OR 0.809, 95%CI 0.691-0.946, P = 0.008). It was difficult to determine the efficacy of systemic corticosteroids on patient survival. CONCLUSION ARDS caused by miliary TB was associated with a high in-hospital mortality rate, with SOFA score on the day of ARDS diagnosis being a valuable prognostic indicator.

Health care use and economic burden of patients with diagnosed chronic obstructive pulmonary disease in Korea.

BACKGROUND The prevalence and economic burden of chronic obstructive pulmonary disease (COPD) are increasing worldwide. However, little information is available concerning COPD-associated health care use and costs in Korea. OBJECTIVE To analyse 1) health care use, medical costs and medication use in 2009, and 2) changes in costs and medication use over 5 years (2006-2010). DESIGN Using the database of the Korean Health Insurance Review and Assessment Service, COPD patients were identified by searching on both ICD-10 codes and COPD medication. RESULTS A total of 192,496 COPD patients were identified in 2009. Total medical costs per person were US

Biomass, strain engineering, and fermentation processes for butanol production by solventogenic clostridia

2803 ± 3865; the average annual number of days of out-patient care and days of hospitalisation were respectively 40 ± 36 and 11 ± 33. Methylxanthine and systemic beta-agonists were the most frequently used drugs. However, the number of prescriptions for long-acting muscarinic antagonist increased rapidly. The total cost of COPD-related medications increased by 33.1% over 5 years. CONCLUSION The present study provides new insight into health care use and the economic burden of COPD in Korea. Changing patterns of COPD-related medication use could help inform COPD management policies.

Meta-analysis of associations between interleukin-10 polymorphisms and susceptibility to pre-eclampsia

Butanol is considered an attractive biofuel and a commercially important bulk chemical. However, economical production of butanol by solventogenic clostridia, e.g., via fermentative production of acetone-butanol-ethanol (ABE), is hampered by low fermentation performance, mainly as a result of toxicity of butanol to microorganisms and high substrate costs. Recently, sugars from marine macroalgae and syngas were recognized as potent carbon sources in biomass feedstocks that are abundant and do not compete for arable land with edible crops. With the aid of systems metabolic engineering, many researchers have developed clostridial strains with improved performance on fermentation of these substrates. Alternatively, fermentation strategies integrated with butanol recovery processes such as adsorption, gas stripping, liquid-liquid extraction, and pervaporation have been designed to increase the overall titer of butanol and volumetric productivity. Nevertheless, for economically feasible production of butanol, innovative strategies based on recent research should be implemented. This review describes and discusses recent advances in the development of biomass feedstocks, microbial strains, and fermentation processes for butanol production.

Morphology and kinetics studies on cephalosporin C production by Cephalosporium acremonium M25 in a 30-l bioreactor using a mixture of inocula

OBJECTIVE To investigate whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to pre-eclampsia. METHODS A meta-analysis was conducted on the associations between IL-10-1082 G/A, -819 C/T and -592 C/A polymorphisms and pre-eclampsia using allele contrast, a recessive model, a dominant model and an additive model. RESULTS Thirteen groups from 11 papers involving 1534 patients with pre-eclampsia and 2271 controls were considered in the meta-analysis. Meta-analysis of the IL-10-1082 G/A polymorphism in 3500 study subjects revealed no association between pre-eclampsia and the IL-10-1082 G allele [odds ratio (OR) 0.890, 95% confidence interval (CI) 0.729-1.087; p=0.254]. Stratification by ethnicity indicated an association between the IL-10-1082 G allele and pre-eclampsia in the Iranian groups (OR 1.408, 95% CI 1.097-1.807; p=0.007), but not in the European groups (OR 0.759, 95% CI 0.506-1.136; p=0.180). Meta-analysis revealed an association between pre-eclampsia and the IL-10-819 C allele in all study subjects (OR 1.296, 95% CI 1.012-1.661; p=0.040), particularly among the Iranian groups (OR 1.390, 95% CI 1.067-1.811; p=0.015). Meta-analysis showed no association between pre-eclampsia and the IL-10-592 C allele (OR 1.215, 95% CI 0.967-1.527; p=0.094) in any groups, except for the Iranian groups (OR 1.380, 95% CI 1.056-1.805; p=0.018). However, the associations found in the meta-analysis became non-significant after exclusion of the studies in which the controls showed deviation from Hardy-Weinberg equilibrium. CONCLUSIONS This meta-analysis suggests that IL-10-1082 G/A, -819 C/T and -592 C/A polymorphisms are unlikely to be important in susceptibility to pre-eclampsia.

A Comparative Metabolomic Evaluation of Behcet’s Disease with Arthritis and Seronegative Arthritis Using Synovial Fluid

Aims:  In this study, the relationship between morphology and cephalosporin C (CPC) production in a 30‐l bioreactor culture of Cephalosporium acremonium M25 using a 3 : 7 seed mixture was investigated. In addition, the kinetic model was established and applied.

Metabolite profiles of synovial fluid change with the radiographic severity of knee osteoarthritis

Behcet’s disease (BD) with arthritis is often confused with seronegative arthritis (SNA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. To investigate possible metabolic patterns and potential biomarkers of BD with arthritis, metabolomic profiling of synovial fluid (SF) from 6 patients with BD with arthritis and 18 patients with SNA was performed using gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between BD with arthritis and SNA. A set of 11 metabolites were identified as potential biomarkers for BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, BD with arthritis exhibited relatively high levels of glutamate, valine, citramalate, leucine, methionine sulfoxide, glycerate, phosphate, lysine, isoleucine, urea, and citrulline. There were two markers identified, elevated methionine sulfoxide and citrulline, that were associated with increased oxidative stress, providing a potential link to BD-associated neutrophil hyperactivity. Glutamate, citramalate, and valine were selected and validated as putative biomarkers for BD with arthritis (sensitivity, 100%; specificity, 61.1%). This is the first report to present potential biomarkers from SF for discriminating BD with arthritis from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of BD with arthritis.

Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

OBJECTIVES To investigate potential pathogenic pathways in the synovial fluid of osteoarthritis (OA) patients at different disease stages [early vs. late, determined based on the Kellgren-Lawrence (KL) grading scale], through metabolite profiles that were performed by using gas-chromatography/time-of-flight mass spectrometry (GC/TOF MS). METHODS Synovial fluid samples were obtained from 15 patients with knee OA, divided into early- (KL grade: 1 and 2) and late-stage OA (KL grade: 3 and 4). Metabolite profiles of OA based on KL grading scale were performed using GC/TOF MS, with multivariate statistical analyses conducted by orthogonal partial least squares discriminant analysis (OPLS-DA) and hierarchical clustering analysis (HCA). RESULTS A total of 114 metabolites were identified and classified into various classes, such as amino acids, sugars and sugar alcohols, fatty acids, and organic acids. Significant discrimination of metabolite profiles between the early- and late-stage OA groups was shown by OPLS-DA and HCA. Twenty-eight metabolites, including malate, ethanolamine, squalene, glycerol, myristic acid, oleic acid, lanosterol, heptadecanoic acid, and capric acid, were identified as critical metabolites for discriminating between the early- and late-OA groups by using Students t-test, as they showed significant differences in abundance between the two OA groups. These metabolites were related to fatty acid metabolism, glycerolipid metabolism, and the tricarboxylic acid cycle. CONCLUSIONS These results revealed that metabolite profiles are robustly altered along the radiographic stage of knee OA. Metabolomic approaches based on GC/TOF MS could provide valuable information on the underlying pathogenic mechanisms of OA progression.