Lack of Mitochondrial DNA Sequence Divergence between Two Subspecies of the Siberian Weasel from Korea: Mustela sibirica coreanus from the Korean Peninsula and M. s. quelpartis from Jeju Island

The objective of this study was to determine the degree of mitochondrial DNA (mtDNA) divergence between two subspecies of Mustela sibirica from Korea (M. s. coreanus on the Korean Peninsula and M. s. quelpartis on Jeju Island) and to examine the taxonomic status of M. s. quelpartis. Thus, we obtained complete sequences of mtDNA cytochrome b gene (1,140 bp) from the two subspecies, and these sequences were compared to a corresponding haplotype of M. s. coreanus, downloaded from GenBank. From this analysis, it was observed that the sequences from monogenic M. s. quelpartis on Jeju Island were identical to the sequences of four M. s. coreanus from four locations across the Korean Peninsula, and that the two subspecies formed a single clade; the average nucleotide distance between the two subspecies was 0.26% (range, 0.00 to 0.53%). We found that the subspecies quelpartis is not genetically distinct from the subspecies coreanus, and that this cytochrome b sequencing result does not support the current classification, distinguishing these two subspecies by pelage color. Further systematic analyses using morphometric characters and other DNA markers are necessary to confirm the taxonomic status of M. s. quelpartis

Interaction of testisin with maspin and its impact on invasion and cell death resistance of cervical cancer cells

AbstractPrevious studies have shown that testisin promotes malignant transformation in cancer cells. To define the mechanism of testisin-induced carcinogenesis, we performed yeast two-hybrid analysis and identified maspin, a tumor suppressor protein, as a testisin-interacting molecule. The direct interaction and cytoplasmic co-localization of testisin with maspin was confirmed by immunoprecipitation and confocal analysis, respectively. In cervical cancer cells, maspin modulated cell death and invasion; however, these effects were inhibited by testisin in parallel experiments. Of interest, the doxorubicin resistance was dramatically reduced by testisin knockdown (P=0.016). Moreover, testisin was found to be over-expressed in cervical cancer samples as compared to matched normal cervical tissues. Thus, we postulate that testisin may promote carcinogenesis by inhibiting tumor suppressor activity of maspin.Structured summaryMINT-7712215, MINT-7712176: Testisin (uniprotkb:Q9Y6M0) binds (MI:0407) to Maspin (uniprotkb:P36952) by pull down (MI:0096)MINT-7712188: Testisin (uniprotkb:Q9Y6M0) and Maspin (uniprotkb:P36952) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7712115: Testisin (uniprotkb:Q9Y6M0) physically interacts (MI:0915) with Maspin (uniprotkb:P36952) by two-hybrid (MI:0018)MINT-7712162, MINT-7712128: Maspin (uniprotkb:P36952) physically interacts (MI:0915) with Testisin (uniprotkb:Q9Y6M0) by anti bait co-immunoprecipitation (MI:0006)MINT-7712147: Testisin (uniprotkb:Q9Y6M0) physically interacts (MI:0915) with Maspin (uniprotkb:P36952) by anti tag co-immunoprecipitation (MI:0007

Efficacy and safety of ginsam, a vinegar extract from Panax ginseng, in type 2 diabetic patients: Results of a double‐blind, placebo‐controlled study

Abstract Aims/Introduction: The efficacy, dose–response relationship and safety of ginsam, a vinegar extract from Panax ginseng, were evaluated in an 8‐week, double‐blind, randomized, placebo‐controlled study in drug‐naïve patients with type 2 diabetes. Materials and Methods: A total of 72 diabetic patients were randomized to receive 1500, 2000 or 3000 mg of ginsam, or placebo daily for 8 weeks (n = 18 in each group). The primary end‐point was the changes from the baseline HbA1c level. The secondary end‐points were the changes of fasting and postprandial 2‐h glucose concentration, and the proportion of patients achieving a reduction in HbA1c >0.5%. Results: In the intention‐to‐treat analysis, ginsam treatment reduced HbA1c level significantly: −0.56 ± 0.25% in the 1500 mg group, −0.31 ± 0.12% in the 2000 mg group, and −0.29 ± 0.11% in the 3000 mg group (all P 0.5% differed significantly between the placebo group (11.1%) and the 1500 mg (27.8%) and 2000 mg (27.8%) groups. No severe adverse events were observed in any group. Conclusions: An 8‐week treatment with ginsam, a vinegar extract from P. ginseng, moderately improved HbA1c level and was well tolerated in type 2 diabetic patients with inadequate glycemic control. This trial was registered with ClinicalTrial.Gov (no. NCT01008163). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00185.x, 2011

Nuclear Factor Erythroid-Derived 2-Like 2-Induced Reductive Stress Favors Self-Renewal of Breast Cancer Stem-Like Cells via the FoxO3a-Bmi-1 Axis

Aims: A subpopulation of cancer cells, termed cancer stem cells (CSCs), has stemness properties, such as self-renewal and differentiation, which drive cancer recurrence and tumor resistance. CSCs possess enhanced protection capabilities to maintain reduced intracellular levels of reactive oxygen species (ROS) compared with nonstem-like cancer cells. This study investigated whether reductive stress could regulate self-renewal activity in breast CSCs. Results: We found that manifestation of stemness in breast cancer stem-like cells was associated with an elevated production of reduced glutathione (GSH) maintained by upregulation of glutamate cysteine ligase catalytic subunit (GCLC) and consequently, lowered ROS levels. This was accompanied by upregulation of phospho-AMP-activated protein kinase, FoxO3a, and Bmi-1. Notably, expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) protein was substantially increased in cells undergoing sphere formation. We noticed that expression of Bmi-1 was inhibited after introduction of Nrf2 short interfering RNA into MCF-7 mammosphere cells. Silencing of Nrf2 expression suppressed the xenograft growth of subcutaneously or orthotopically injected human breast cancer cells. Innovation: Association between Nrf2 and self-renewal signaling in CSCs has been reported, but the underlying molecular mechanism remains largely unresolved. This study demonstrates the Nrf2-mediated signaling pathway in maintenance of reductive stress in breast CSCs. Conclusion: Nrf2 overactivation in breast CSCs upregulates GCLC expression and consequently enhances GSH biosynthesis with concurrent reduction in intracellular ROS accumulation, thereby provoking the reductive stress. The consequent upregulation of nuclear FoxO3a and its binding to the promoter of the gene encoding Bmi-1 account for the self-renewal activity of breast cancer stem-like cells and their growth in a xenograft mouse model.

Dual quadratic differentials and entire minimal graphs in Heisenberg space

We define holomorphic quadratic differentials for spacelike surfaces with constant mean curvature in the Lorentzian homogeneous spaces $\mathbb{L}(\kappa,\tau)$ with isometry group of dimension 4, which are dual to the Abresch-Rosenberg differentials in the Riemannian counterparts $\mathbb{E}(\kappa,\tau)$, and obtain some consequences. On the one hand, we give a very short proof of the Bernstein problem in Heisenberg space, and provide a geometric description of the family of entire graphs sharing the same differential in terms of a 2-parameter conformal deformation. On the other hand, we prove that entire minimal graphs in Heisenberg space have negative Gauss curvature.Comment: 19 page

Retinoid production using metabolically engineered Escherichia coli with a two-phase culture system

<p>Abstract</p> <p>Background</p> <p>Retinoids are lipophilic isoprenoids composed of a cyclic group and a linear chain with a hydrophilic end group. These compounds include retinol, retinal, retinoic acid, retinyl esters, and various derivatives of these structures. Retinoids are used as cosmetic agents and effective pharmaceuticals for skin diseases. Retinal, an immediate precursor of retinoids, is derived by β-carotene 15,15'-mono(di)oxygenase (BCM(D)O) from β-carotene, which is synthesized from the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Retinoids are chemically unstable and biologically degraded via retinoic acid. Although extensive studies have been performed on the microbial production of carotenoids, retinoid production using microbial metabolic engineering has not been reported. Here, we report retinoid production using engineered <it>Escherichia coli </it>that express exogenous BCM(D)O and the mevalonate (MVA) pathway for the building blocks synthesis in combination with a two-phase culture system using a dodecane overlay.</p> <p>Results</p> <p>Among the BCM(D)O tested in <it>E. coli</it>, the synthetic retinoid synthesis protein (SR), based on bacteriorhodopsin-related protein-like homolog (Blh) of the uncultured marine bacteria 66A03, showed the highest β-carotene cleavage activity with no residual intracellular β-carotene. By introducing the exogenous MVA pathway, 8.7 mg/L of retinal was produced, which is 4-fold higher production than that of augmenting the MEP pathway (<it>dxs </it>overexpression). There was a large gap between retinal production and β-carotene consumption using the exogenous MVA pathway; therefore, the retinal derivatives were analyzed. The derivatives, except for retinoic acid, that formed were identified, and the levels of retinal, retinol, and retinyl acetate were measured. Amounts as high as 95 mg/L retinoids were obtained from engineered <it>E. coli </it>DH5α harboring the synthetic <it>SR </it>gene and the exogenous MVA pathway in addition to <it>dxs </it>overexpression, which were cultured at 29°C for 72 hours with 2YT medium containing 2.0% (w/v) glycerol as the main carbon source. However, a significant level of intracellular degradation of the retinoids was also observed in the culture. To prevent degradation of the intracellular retinoids through <it>in situ </it>extraction from the cells, a two-phase culture system with dodecane was used. The highest level of retinoid production (136 mg/L) was obtained after 72 hours with 5 mL of dodecane overlaid on a 5 mL culture.</p> <p>Conclusions</p> <p>In this study, we successfully produced 136 mg/L retinoids, which were composed of 67 mg/L retinal, 54 mg/L retinol, and 15 mg/L retinyl acetate, using a two-phase culture system with dodecane, which produced 68-fold more retinoids than the initial level of production (2.2 mg/L). Our results demonstrate the potential use of <it>E. coli </it>as a promising microbial cell factory for retinoid production.</p

Copy number variations (CNVs) identified in Korean individuals

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) are deletions, insertions, duplications, and more complex variations ranging from 1 kb to sub-microscopic sizes. Recent advances in array technologies have enabled researchers to identify a number of CNVs from normal individuals. However, the identification of new CNVs has not yet reached saturation, and more CNVs from diverse populations remain to be discovered.</p> <p>Results</p> <p>We identified 65 copy number variation regions (CNVRs) in 116 normal Korean individuals by analyzing Affymetrix 250 K Nsp whole-genome SNP data. Ten of these CNVRs were novel and not present in the Database of Genomic Variants (DGV). To increase the specificity of CNV detection, three algorithms, CNAG, dChip and GEMCA, were applied to the data set, and only those regions recognized at least by two algorithms were identified as CNVs. Most CNVRs identified in the Korean population were rare (<1%), occurring just once among the 116 individuals. When CNVs from the Korean population were compared with CNVs from the three HapMap ethnic groups, African, European, and Asian; our Korean population showed the highest degree of overlap with the Asian population, as expected. However, the overlap was less than 40%, implying that more CNVs remain to be discovered from the Asian population as well as from other populations. Genes in the novel CNVRs from the Korean population were enriched for genes involved in regulation and development processes.</p> <p>Conclusion</p> <p>CNVs are recently-recognized structural variations among individuals, and more CNVs need to be identified from diverse populations. Until now, CNVs from Asian populations have been studied less than those from European or American populations. In this regard, our study of CNVs from the Korean population will contribute to the full cataloguing of structural variation among diverse human populations.</p

Efficient Photoelectrochemical Water Oxidation by Metal-Doped Bismuth Vanadate Photoanode with Iron Oxyhydroxide Electrocatalyst

Intensive attention has been currently focused on the discovery of semiconductor and proficient cocatalysts for eventual applications to the photoelectrochemical water splitting system. A W-Mo-doped BiVO4 semiconductor was prepared by the surfactant-assisted thermal decomposition method on a fluorine-doped tin oxide conductive film. The W-Mo-doped BiVO4 films showed a porous morphology with the grain sizes of about 270 nm. Because the hole diffusion length of BiVO4 is about 100 nm, the W-Mo-doped BiVO4 film in this study is an ideal candidate for the photoelectrochemical water oxidation. Iron oxyhydroxide (FeOOH) electrocatalyst was chemically deposited on the W-Mo-doped BiVO4 to investigate the effect of the electrocatalyst on the semiconductor. The W-Mo-doped BiVO4/FeOOH composite electrode showed enhanced activity compared to the pristine W-Mo-doped BiVO4 electrode for water oxidation reaction. The chemical deposition is a promising method for the deposition of FeOOH on semiconductor

Android Fat Depot Is More Closely Associated with Metabolic Syndrome than Abdominal Visceral Fat in Elderly People

BACKGROUND: Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. METHODS AND FINDINGS: As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm(2) and 126.9±55.2 cm(2) in men (P = 0.045) and 120.0±46.7 cm(2) and 211.8±65.9 cm(2) in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. CONCLUSIONS: Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution