Aldose reductase inhibitory compounds from extracts of Dipsacus asper

Amethanolic extract of Dipsacus asper, having anti-diabetic activity, was examined as a possible aldose reductase (ALR2) inhibitor, a key enzyme involved in diabetic complications. Bioactivity guided fractionation led to the isolation of ten compounds, ursolic acid (1), oleanolic acid-3-O-α-L-arabinopyranoside (2), daucosterol (3), hederagenin-3-O-α-L-arabinopyranoside (4), sweroside(5), caffeic acid (6), esculetin (7), protocatechualdehyde (8), loganin (9), and vanilic acid (10) from the ethyl acetate fraction of D. asper methanol extract. Among them, compounds 4, 6, 7, and 8 exhibited inhibitory effects on aldose reductase, with IC₅₀ values of 23.70, 16.71, 34.36, and 21.81 μM, respectively. This is the first report on the isolation of these compounds from D. asper, and the ALR2 inhibitory activity of hederagenin-3-O-α-L-arabinopyranoside. These results suggest the successful use of the extract of D. asper for ameliorating diabetic complications.     

A frequency monitoring system development for wide-area power grid protection

There have been recent research activities on GPS-based FNET to prevent wide-area blackouts by monitoring frequency deviation. This paper introduces a system for monitoring regional frequencies in power grid developed as an advanced research project for intelligent wide-area protective relaying in South Korea. The system is implemented by modeling an actual 345 kV transmission system of South Korea using EMTP-RV and by measuring voltages and currents at five regions. The frequencies are estimated using our previous proposed method, a frequency estimation algorithm with gain compensation. The monitoring system implemented is used to examine frequency propagation effects and various fault conditions. Simulation results showed that the proposed system could achieve good performance regarding the frequency monitoring under both steady states and dynamic fault conditions.     

Generation and analysis of expressed sequence tags for microsatellite marker development in Calamus simplicifolius C. F. Wei

Rattans serve as an important source of raw non-wood materials for furniture and handicraft industries worldwide. However, their genomic sequence information in public databases is very limited. In this study, a set of 2,528 good-quality expressed sequence tags (ESTs) were generated from a full-length cDNA library constructed previously with root, stem and male inflorescence tissues of Calamus simplicifolius C. F. Wei, a rattan species native to Hainan Island, China. The ESTs were assembled into 1,588 unigenes, including 1,221 singletons and 367 contigs. BlastX searches against the GenBank non-redundant protein database revealed that 1,248 (78.6 %) unigenes had at least one significant match (E ≤ 10^?5). The gene ontology functional classification assigned 991, 669 and 977 of the unigenes to the cellular component, molecular function and biological process categories, respectively. A total of 71 simple sequence repeat (SSR) loci were developed among these ESTs, including 65 polymorphic across 19 rattan species representing three genera. High levels of cross-species/genus transferability were observed for the EST-SSRs. For the polymorphic EST-SSR markers, the number of alleles per locus and polymorphic information content ranged from 2 to 25 (mean 11.1) and from 0.135 to 0.949 (mean 0.695), respectively. The EST sequences and the EST-SSR primers have been deposited in GenBank databases of EST (IDs JK838364–40891) and Probe (IDs Pr16718978–9048, to be assigned).     

Subtype Identification in Acutely Dissociated Rat Nodose Ganglion Neurons Based on Morphologic Parameters

Nodose ganglia are composed of A-, Ah- and C-type neurons. Despite their important roles in regulating visceral afferent function, including cardiovascular, pulmonary, and gastrointestinal homeostasis, information about subtype-specific expression, molecular identity, and function of individual ion transporting proteins is scarce. Although experiments utilizing the sliced ganglion preparation have provided valuable insights into the electrophysiological properties of nodose ganglion neuron subtypes, detailed characterization of their electrical phenotypes will require measurements in isolated cells. One major unresolved problem, however, is the difficulty to unambiguously identify the subtype of isolated nodose ganglion neurons without current-clamp recording, because the magnitude of conduction velocity in the corresponding afferent fiber, a reliable marker to discriminate subtypes in situ, can no longer be determined. Here, we present data supporting the notion that application of an algorithm regarding to microscopic structural characteristics, such as neuron shape evaluated by the ratio between shortest and longest axis, neuron surface characteristics, like membrane roughness, and axon attachment, enables specific and sensitive subtype identification of acutely dissociated rat nodose ganglion neurons, by which the accuracy of identification is further validated by electrophysiological markers and overall positive predictive rates is 89.26% (90.04%, 76.47%, and 98.21% for A-, Ah, and C-type, respectively). This approach should aid in gaining insight into the molecular correlates underlying phenotypic heterogeneity of nodose ganglia. Additionally, several critical points that help for neuron identification and afferent conduction calibration are also discussed.     

Loss of VHL promotes progerin expression,leading to impaired p14/ARF function and suppression of p53 activity

Renal cell carcinomas (RCCs) are frequently occurring genitourinary malignancies in the aged population. A morphological characteristic of RCCs is an irregular nuclear shape, which is used to index cancer grades. Other features of RCCs include the genetic inactivation of the von Hippel-Lindau gene, VHL, and p53 genetic-independent inactivation. An aberrant nuclear shape or p53 suppression has not yet been demonstrated. We examined the effect of progerin (an altered splicing product of the LMNA gene linked to Hutchinson Gilford progeria syndrome; HGPS) on the nuclear deformation of RCCs in comparison to that of HGPS cells. In this study, we showed that progerin was suppressed by pVHL and was responsible for nuclear irregularities as well as p53 inactivation. Thus, progerin suppression can ameliorate nuclear abnormalities and reactivate p53 in response to genotoxic addition. Furthermore, we found that progerin was a target of pVHL E3 ligase and suppressed p53 activity by p14/ARF inhibition. Our findings indicate that the elevated expression of progerin in RCCs results from the loss of pVHL and leads to p53 inactivation through p14/ARF suppression. Interestingly, we showed that progerin was expressed in human leukemia and primary cell lines, raising the possibility that the expression of this LMNA variant may be a common event in age-related cancer progression.     

Does Serum 25-Hydroxyvitamin D Influence Muscle Development during Puberty in Girls? - A 7-Year Longitudinal Study

Vitamin D is well known for its regulatory role in calcium and phosphate homeostasis, but its role in muscle mass and strength during growth remains inconclusive. We explored the association of serum 25-hydroxyvitamin D (25(OH)D) with muscle development in girls from 11 to 18-years old. Whole body lean tissue mass (LM_WB), appendicular lean mass (aLM), muscle cross-sectional area at the lower leg (mCSA), maximal voluntary contraction of elbow flexors (MVC_elbow) and knee extensors (MVC_knee) were assessed in 217 girls aged 10–13 years (at baseline), 215 in 2-year and 226 in 7.5-year follow-up. Serum concentration of 25(OH)D and intact parathyroid hormone (PTH) were analyzed retrospectively and girls were categorized according to their 25(OH)D levels (consistently insufficient 25(OH)D G_LL <50 nmol/l and consistently sufficient G_HH >50 nmol/l from baseline to 7-year follow-up). We found that 25(OH)D level declined until menarche (p<0.05) while LM_WB, aLM, mCSA, MVC_elbow and MVC_knee continued to increase (p<0.001 for all) post menarche. At pre-menarche, the G_LL (n = 34) had higher LM_WB and aLM than the G_HH (n = 21, p<0.05), while post-menarche the G_HH (n = 15) had a greater catch-up gain in LM_WB (p = 0.004), aLM (p = 0.001) and mCSA (p = 0.027) compared to the G_LL (n = 65) over the first 2-year period. At the age of 18, no differences in muscle mass/strength between the low (n = 151) and high (n = 77) levels of 25(OH)D groups were found. This finding was independent of vitamin D receptor genotype and other confounders. In conclusion, our results showed that levels of 25(OH)D have no significant negative influence on the development of muscle mass and strength during pubertal growth both with longitudinal and cross-sectional comparison. On the contrary, our results suggest that the temporary negative association between 25(OH)D and muscle mass arises as a consequence of fast growth prior to menarche, and this negative association is diminished through catch-up growth after menarche.     

Molecular Mechanisms of Regulation and Action of microRNA-199a in Testicular Germ Cell Tumor and Glioblastomas

MicroRNA-199a (miRNA-199a) has been shown to have comprehensive functions and behave differently in different systems and diseases. It is encoded by two loci in the human genome, miR-199a-1 in chromosome 19 and miR-199a-2 in chromosome 1. Both loci give rise to the same miRNAs (miR-199a-5p and miR-199a-3p). The cause of the diverse action of the miRNA in different systems is not clear. However, it is likely due to different regulation of the two genomic loci and variable targets of the miRNA in different cells and tissues. Here we studied promoter methylation of miR-199a in testicular germ cell tumors (TGCTs) and glioblastomas (gliomas) and discovered that hypermethylation in TGCTs of both miR-199a-1 and -2 resulted in its reduced expression, while hypomethylation of miR-199a-2 but not -1 in gliomas may be related to its elevated expression. We also identified a common regulator, REST, which preferentially bound to the methylated promoters of both miR-199a-1 and miR-199a-2. The action of miR-199a is dependent on its downstream targets. We identified MAFB as a putative target of miRNA-199a-5p in TGCTs and confirmed that the tumor suppression activity of the microRNA is mediated by its target MAFB. By studying the mechanisms that control the expressions of miR-199a and its various downstream targets, we hope to use miR-199a as a model to understand the complexity of miRNA biology.