Hyun-Jin Kim

Metabolomic Analysis of Livers and Serum from High-Fat Diet Induced Obese Mice

Liver and serum metabolites of obese and lean mice fed on high fat or normal diets were analyzed using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry, gas chromatography-mass spectrometry, and partial least-squares-discriminant analysis (PLS-DA). Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids, phosphatidylcholines (PCs), and lysophosphatidylcholines (lysoPCs)), lipid metabolism intermediates (betaine, carnitine, and acylcarnitines), amino acids, acidic compounds, monosaccharides, and serotonin. A high-fat diet increased lipid metabolites but decreased lipid metabolism intermediates and the NAD/NADH ratio, indicating that abnormal lipid and energy metabolism induced by a high-fat diet resulted in fat accumulation via decreased β-oxidation. In addition, this study revealed that the levels of many metabolites, including serotonin, betaine, pipecolic acid, and uric acid, were positively or negatively related to obesity-associated diseases. On the basis of these metabolites, we proposed a metabolic pathway related to high-fat diet-induced obesity. These metabolites can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.

Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR‐γ signal pathways

Ginsenosides, the active component of ginseng, exerts antidiabetic and anticancer effects. This study investigated the molecular basis of ginsenoside Rg3, a red ginseng rich constituent, focusing on its ability to inhibit adipocyte differentiation in 3T3‐L1 cells. The data show that ginsenoside Rg3 was effective in the inhibition of adipocyte differentiation. This inhibitory effect of ginsenoside Rg3 on adipocyte differentiation was accompanied by PPAR‐γ inhibition in rosiglitazone‐treated cells. The study also tested whether AMP‐activated protein kinase (AMPK) activation was involved in the inhibitory effects of ginsenoside Rg3. AMPK plays a role in maintaining health in the context of diseases such as type 2 diabetes, obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time‐dependently activated AMPK. Taken together, these results suggest that the antiobesity effect of red ginseng rich constituent, ginsenoside Rg3, involves the AMPK signaling pathway and PPAR‐γ inhibition. Copyright

Genistein protects the kidney from cisplatin-induced injury.

Oxidative stress and inflammation contribute to the pathogenesis of cisplatin-induced nephrotoxicity. We found that genistein, a tyrosine kinase inhibitor with broad specificities, and which also has estrogen-like activity, had protective effects on cisplatin-induced renal injury in mice. Genistein significantly decreased reactive oxygen species production, the expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 proteins, as well as the translocation of the p65 subunit of nuclear factor-kappaB into the nucleus and the infiltration of macrophages, all of which were increased in the kidney by cisplatin treatment. Genistein also decreased cisplatin-induced apoptosis by regulating p53 induction in kidney. Genistein significantly reduced reactive oxygen species production in cisplatin-treated normal human kidney HK-2 cells. These studies show that genistein or similar compounds might be useful in prevention of cisplatin-induced renal injury.

Association of the CD14 gene –159C polymorphism with progression of IgA nephropathy

The risk factors associated with the progression of IgA nephropathy (IgAN), the most common form of glomerulonephritis, are unclear. It has been suggested that CD14 signalling in response to various microbes affects the natural history of chronic inflammatory conditions. It has been hypothesised that variants in the promoter region of the CD14 gene might alter the expression of CD14, and this in turn could influence the progressive nature of IgAN. PCR-RFLP was used to determine the polymorphism at the −159 site (T to C). The distribution of the CD14/−159 polymorphism was no different in patients with IgAN (n=216) compared to 171 healthy controls. After follow up for 86 months, it was found that an excess of the C genotype occurred in patients with progressive disease (p=0.03) and the risk of disease progression increased as the number of C alleles increased (p for trend = 0.002). The hazard ratio for progression in the patients with the CC genotype was 3.2 (p=0.025) compared with the patients possessing the TT genotype. After LPS stimulation, sCD14 was released more abundantly from the PBMCs of the TT subjects than from that of the CC subjects (p=0.006), even though mCD14 expression level was no different. In addition, the TT subjects released less IL-6 than the CC subjects after stimulation (p=0.0003). These results suggest that the CD14/−159 polymorphism is an important marker for the progression of IgAN and may modulate the level of the inflammatory responses.

Potassium Mediates Escherichia coli Enzyme IIA Ntr -dependent Regulation of Sigma Factor Selectivity

An Escherichia coli mutant devoid of enzyme IIANtr (EIIANtr) of the nitrogen PTS is extremely sensitive to leucine‐containing peptides due to decreased expression of acetohydroxy acid synthase. This decreased expression is due to defective potassium homeostasis. We further elucidate here the mechanism for regulation of gene expression by the intracellular level of K+. The leucine hypersensitivity of a ptsN (encoding EIIANtr) mutant was suppressed by deleting rpoS, encoding the stationary phase σ factor. Despite intracellular levels of sigma factors comparable to the wild‐type strain, most of the genes downregulated in a ptsN mutant are controlled by σ70, while all the upregulated genes are controlled by σS, implying that the balance of sigma activities is modified by ptsN deletion. This change of sigma factor activities in the deletion mutant was found to be due to increased levels of K+. In vitro transcription assays demonstrated that a σ70 controlled gene and a σS controlled gene were differentially affected by potassium concentration. Biochemical studies revealed that K+ is responsible for sigma factor competition by differentially influencing the binding of σ70 and σS to core RNA polymerase. Taken together, the data suggest that EIIANtr controls sigma factor selectivity by regulating the intracellular K+ level.

Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population

Background Musical abilities such as recognising music and singing performance serve as means for communication and are instruments in sexual selection. Specific regions of the brain have been found to be activated by musical stimuli, but these have rarely been extended to the discovery of genes and molecules associated with musical ability. Methods A total of 1008 individuals from 73 families were enrolled and a pitch-production accuracy test was applied to determine musical ability. To identify genetic loci and variants that contribute to musical ability, we conducted family-based linkage and association analyses, and incorporated the results with data from exome sequencing and array comparative genomic hybridisation analyses. Results We found significant evidence of linkage at 4q23 with the nearest marker D4S2986 (LOD=3.1), whose supporting interval overlaps a previous study in Finnish families, and identified an intergenic single nucleotide polymorphism (SNP) (rs1251078, p=8.4×10−17) near UGT8, a gene highly expressed in the central nervous system and known to act in brain organisation. In addition, a non-synonymous SNP in UGT8 was revealed to be highly associated with musical ability (rs4148254, p=8.0×10−17), and a 6.2u2005kb copy number loss near UGT8 showed a plausible association with musical ability (p=2.9×10−6). Conclusions This study provides new insight into the genetics of musical ability, exemplifying a methodology to assign functional significance to synonymous and non-coding alleles by integrating multiple experimental methods.

Dephosphorylated NPr of the nitrogen PTS regulates lipid A biosynthesis by direct interaction with LpxD.

Bacterial phosphoenolpyruvate-dependent phosphotransferase systems (PTS) play multiple roles in addition to sugar transport. Recent studies revealed that enzyme IIA(Ntr) of the nitrogen PTS regulates the intracellular concentration of K(+) by direct interaction with TrkA and KdpD. In this study, we show that dephosphorylated NPr of the nitrogen PTS interacts with Escherichia coli LpxD which catalyzes biosynthesis of lipid A of the lipopolysaccharide (LPS) layer. Mutations in lipid A biosynthetic genes such as lpxD are known to confer hypersensitivity to hydrophobic antibiotics such as rifampin; a ptsO (encoding NPr) deletion mutant showed increased resistance to rifampin and increased LPS biosynthesis. Taken together, our data suggest that unphosphorylated NPr decreases lipid A biosynthesis by inhibiting LpxD activity.

All solid state flexible supercapacitors operating at 4 V with a cross-linked polymer–ionic liquid electrolyte

4 V-operated all solid symmetrical supercapacitors that employ mixtures of various weight compositions with cross-linked poly-4-vinylphenol (c-P4VPh) and 1-ethyl-3-methyl imidazolium bis(trifluoromethylsulfonyl)imide (EMITFSI) electrolytes have been demonstrated and characterized. The values at 1:3, 3.5, 4 and 4.5 (c-P4VPh:EMITFSI) offer free-standing membranes with high ionic conductivity. In the case of 1:3.5, the best specific capacitance (172.44 F g−1 in a single-electrode) and energy density (72.23 W h kg−1) were obtained at symmetrical cells based on porous carbon electrodes. Every prepared SC was reliable over 1000 cycles in the range of 0–4 V. They also have excellent flexibility and maintain capacitance after completing the bending test a thousand times.

Increased [PSI+] Appearance by Fusion of Rnq1 with the Prion Domain of Sup35 in Saccharomyces cerevisiae

ABSTRACT During propagation, yeast prions show a strict sequence preference that confers the specificity of prion assembly. Although propagations of [PSI+] and [RNQ+] are independent of each other, the appearance of [PSI+] is facilitated by the presence of [RNQ+]. To explain the [RNQ+] effect on the appearance of [PSI+], the cross-seeding model was suggested, in which Rnq1 aggregates act as imperfect templates for Sup35 aggregation. If cross-seeding events take place in the cytoplasm of yeast cells, the collision frequency between Rnq1 aggregates and Sup35 will affect the appearance of [PSI+]. In this study, to address whether cross-seeding occurs in vivo, a new [PSI+] induction method was developed that exploits a protein fusion between the prion domain of Sup35 (NM) and Rnq1. This fusion protein successfully joins preexisting Rnq1 aggregates, which should result in the localization of NM around the Rnq1 aggregates and hence in an increased collision frequency between NM and Rnq1 aggregates. The appearance of [PSI+] could be induced very efficiently, even with a low expression level of the fusion protein. This study supports the occurrence of in vivo cross-seeding between Sup35 and Rnq1 and provides a new tool that can be used to dissect the mechanism of the de novo appearance of prions.

Impact of acute exercise on brachial artery flow-mediated dilatation in young healthy people

BackgroundAlthough chronic effects of exercise on endothelial function are established, the impact of acute exercise on flow-mediated dilatation (FMD) of brachial artery has not been elucidated yet.MethodsEighty-six young healthy volunteers were prospectively enrolled from January 2011 to December 2011. The subjects completed FMD tests at rest and immediately after treadmill exercise test. Primary outcome was the impact of acute exercise on FMD, measured by the difference of FMD before and after exercise. Secondary outcomes were the relationship of gender and exercise habit with FMD.ResultsSeventy-four subjects who met the eligibility criteria were included for analysis. Thirty-five (47.3%) were male, and the mean age was 22.7±2.7 years. FMD was reduced after exercise (8.98±4.69 to 7.51±4.03%; P=0.017) and the reduction was found in female group (10.36±5.26 to 7.62±3.71%; P=0.002) but not in male group. Post-exercise FMD was significantly impaired in subjects who did not exercise regularly (6.92±3.13% versus 8.95±5.33%; P=0.003). The decrease of FMD after exercise was greater in female group (−2.75±5.28% versus 0.27±3.24%; P=0.003) and was associated with exercise habit (β=2.532; P=0.027).ConclusionsIn healthy young subjects, FMD was reduced after a bout of acute exercise. The impact of acute exercise showed significant differences according to gender and exercise habit. FMD impairment after acute exercise was observed in females and subjects without regular exercise.