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1.  Search for Information-Bearing Components in Neural Data 
PLoS ONE  2014;9(6):e99793.
Multivariate empirical mode decomposition (MEMD) is an important extension of EMD, suitable for processing multichannel data. It can adaptively decompose multivariate data into a set of intrinsic mode functions (IMFs) that are matched both in number and in frequency scale. This method is thus holds great potential for the analysis of multi- channel neural recordings as it is capable of ensuring all the intrinsic oscillatory modes are aligned not only across channels, but also across trials. Given a plethora of IMFs derived by MEMD, a question of significant interest is how to identify which IMFs contain information, and which IMFs are noise. Existing methods that exploit the dyadic filter bank structure of white noise decomposition are insufficient since the IMFs do not always adhere to the presumed dyadic relationship. Here we propose a statistical procedure to identify information-bearing IMFs, which is built upon MEMD that allows adding noise as separate channels to serve as a reference to facilitate IMF identification. In this procedure, Wasserstein distance is used to measure the similarity between the reference IMF and that from data. Simulations are performed to validate the method. Local field potentials from cortex of monkeys while performing visual tasks are used for demonstration.
PMCID: PMC4059688  PMID: 24932596
2.  Effects of Postmortem Interval on Mouse Ovary Oocyte Survival and Maturation 
PLoS ONE  2014;9(5):e98384.
To study the time- and temperature-dependent survival of ovarian oocytes collected from postmortem carcass, ICR mice were killed and placed for different periods (0, 1, 2, 4, 6, 8 and 10 h) at different temperatures (25°C, 4°C and 37°C). After preservation, oocyte morphology, germinal vesicle (GV) oocyte number, oocyte meiotic maturation percentage, mitochondrial distribution and intracellular glutathione (GSH) level were evaluated. The results showed no surviving oocytes could be collected by 2h, 6h, and 12 h after carcass preservation at 37°C, 25°C and 4°C, respectively. The number of collected GV oocytes in the ovary deceased as the preservation time lasted at the same temperature. Meanwhile at the same point in time, the ratio of germinal vesicle breakdown (GVBD) and the first polar body emission (PBE) gradually reduced as preservation temperature increased. In addition, the percentage of abnormal mitochondrial distribution in the preserved oocytes was obviously higher than that in the control oocytes, while GSH level was not altered in collected oocytes. Unexpectedly, neither chromosome arrangement nor spindle organization was affected as long as the oocytes from preserved carcasses could complete maturation. These data are helpful for proper use of ovary oocytes from postmortem carcass of valuable individuals.
PMCID: PMC4038583  PMID: 24874949
3.  Specific deletion of Cdc42 does not affect meiotic spindle organization/migration and homologous chromosome segregation but disrupts polarity establishment and cytokinesis in mouse oocytes 
Molecular Biology of the Cell  2013;24(24):3832-3841.
Oocyte-specific deletion of Cdc42 has little effect on meiotic spindle organization and migration to the cortex but inhibits polar body emission, although homologous chromosome segregation occurs. The failure of cytokinesis is due to loss of polarized Arp2/3 accumulation and actin cap formation, and thus the defective contract ring.
Mammalian oocyte maturation is distinguished by highly asymmetric meiotic divisions during which a haploid female gamete is produced and almost all the cytoplasm is maintained in the egg for embryo development. Actin-dependent meiosis I spindle positioning to the cortex induces the formation of a polarized actin cap and oocyte polarity, and it determines asymmetric divisions resulting in two polar bodies. Here we investigate the functions of Cdc42 in oocyte meiotic maturation by oocyte-specific deletion of Cdc42 through Cre-loxP conditional knockout technology. We find that Cdc42 deletion causes female infertility in mice. Cdc42 deletion has little effect on meiotic spindle organization and migration to the cortex but inhibits polar body emission, although homologous chromosome segregation occurs. The failure of cytokinesis is due to the loss of polarized Arp2/3 accumulation and actin cap formation; thus the defective contract ring. In addition, we correlate active Cdc42 dynamics with its function during polar body emission and find a relationship between Cdc42 and polarity, as well as polar body emission, in mouse oocytes.
PMCID: PMC3861080  PMID: 24131996
4.  Local Anesthetics Induce Apoptosis in Human Thyroid Cancer Cells through the Mitogen-Activated Protein Kinase Pathway 
PLoS ONE  2014;9(2):e89563.
Local anesthetics are frequently used in fine-needle aspiration of thyroid lesions and locoregional control of persistent or recurrent thyroid cancer. Recent evidence suggests that local anesthetics have a broad spectrum of effects including inhibition of cell proliferation and induction of apoptosis in neuronal and other types of cells. In this study, we demonstrated that treatment with lidocaine and bupivacaine resulted in decreased cell viability and colony formation of both 8505C and K1 cells in a dose-dependent manner. Lidocaine and bupivacaine induced apoptosis, and necrosis in high concentrations, as determined by flow cytometry. Lidocaine and bupivacaine caused disruption of mitochondrial membrane potential and release of cytochrome c, accompanied by activation of caspase 3 and 7, PARP cleavage, and induction of a higher ratio of Bax/Bcl-2. Based on microarray and pathway analysis, apoptosis is the prominent transcriptional change common to lidocaine and bupivacaine treatment. Furthermore, lidocaine and bupivacaine attenuated extracellular signal-regulated kinase 1/2 (ERK1/2) activity and induced activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase. Pharmacological inhibitors of MAPK/ERK kinase and p38 MAPK suppressed caspase 3 activation and PARP cleavage. Taken together, our results for the first time demonstrate the cytotoxic effects of local anesthetics on thyroid cancer cells and implicate the MAPK pathways as an important mechanism. Our findings have potential clinical relevance in that the use of local anesthetics may confer previously unrecognized benefits in the management of patients with thyroid cancer.
PMCID: PMC3931808  PMID: 24586874
5.  Optimization of CDT-1 and XYL1 Expression for Balanced Co-Production of Ethanol and Xylitol from Cellobiose and Xylose by Engineered Saccharomyces cerevisiae 
PLoS ONE  2013;8(7):e68317.
Production of ethanol and xylitol from lignocellulosic hydrolysates is an alternative to the traditional production of ethanol in utilizing biomass. However, the conversion efficiency of xylose to xylitol is restricted by glucose repression, causing a low xylitol titer. To this end, we cloned genes CDT-1 (encoding a cellodextrin transporter) and gh1-1 (encoding an intracellular β-glucosidase) from Neurospora crassa and XYL1 (encoding a xylose reductase that converts xylose into xylitol) from Scheffersomyces stipitis into Saccharomyces cerevisiae, enabling simultaneous production of ethanol and xylitol from a mixture of cellobiose and xylose (main components of lignocellulosic hydrolysates). We further optimized the expression levels of CDT-1 and XYL1 by manipulating their promoters and copy-numbers, and constructed an engineered S. cerevisiae strain (carrying one copy of PGK1p-CDT1 and two copies of TDH3p-XYL1), which showed an 85.7% increase in xylitol production from the mixture of cellobiose and xylose than that from the mixture of glucose and xylose. Thus, we achieved a balanced co-fermentation of cellobiose (0.165 g/L/h) and xylose (0.162 g/L/h) at similar rates to co-produce ethanol (0.36 g/g) and xylitol (1.00 g/g).
PMCID: PMC3699558  PMID: 23844185
6.  Compressed carbon nanotubes: A family of new multifunctional carbon allotropes 
Scientific Reports  2013;3:1331.
The exploration of novel functional carbon polymorphs is an enduring topic of scientific investigations. In this paper, we present simulations demonstrating metastable carbon phases as the result of pressure induced carbon nanotube polymerization. The configuration, bonding, electronic, and mechanical characteristics of carbon polymers strongly depend on the imposed hydrostatic/non-hydrostatic pressure, as well as on the geometry of the raw carbon nanotubes including diameter, chirality, stacking manner, and wall number. Especially, transition processes under hydrostatic/non-hydrostatic pressure are investigated, revealing unexpectedly low transition barriers and demonstrating sp2→sp3 bonding changes as well as peculiar oscillations of electronic property (e.g., semiconducting→metallic→semiconducting transitions). These polymerized nanotubes show versatile and superior physical properties, such as superhardness, high tensile strength and ductility, and tunable electronic properties (semiconducting or metallic).
PMCID: PMC3580323  PMID: 23435585
7.  Specific Disruption of Tsc1 in Ovarian Granulosa Cells Promotes Ovulation and Causes Progressive Accumulation of Corpora Lutea 
PLoS ONE  2013;8(1):e54052.
Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor negatively regulating mammalian target of rapamycin complex 1 (mTORC1). It is reported that mice lacking Tsc1 gene in oocytes show depletion of primordial follicles, resulting in premature ovarian failure and subsequent infertility. A recent study indicated that deletion of Tsc1 in somatic cells of the reproductive tract caused infertility of female mice. However, it is not known whether specific disruption of Tsc1 in granulosa cells influences the reproductive activity of female mice. To clarify this problem, we mated Tsc1flox/flox mice with transgenic mice strain expressing cyp19-cre which exclusively expresses in granulosa cells of the ovary. Our results demonstrated that Tsc1flox/flox; cyp19-cre mutant mice were fertile, ovulating more oocytes and giving birth to more pups than control Tsc1flox/flox mice. Progressive accumulation of corpora lutea occurred in the Tsc1flox/flox; cyp19-cre mutant mice with advanced age. These phenotypes could be explained by the elevated activity of mTORC1, as indicated by increased phosphorylation of rpS6, a substrate of S6 in the Tsc1flox/flox; cyp19-cre mutant granulosa cells. In addition, rapamycin, a specific mTORC1 inhibitor, effectively rescued the phenotype caused by increased mTORC1 activity in the Tsc1cko ovaries. Our data suggest that conditional knockout of Tsc1 in granulosa cells promotes reproductive activity in mice.
PMCID: PMC3545997  PMID: 23335988
8.  Tetrahymena: An Alternative Model Host for Evaluating Virulence of Aeromonas Strains 
PLoS ONE  2012;7(11):e48922.
An easier assessment model would be helpful for high-throughput screening of Aeromonas virulence. The previous study indicated the potential of Tetrahymena as a permissive model to examine virulence of Aeromonas hydrophila. Here our aim was to assess virulence of Aeromonas spp. using two model hosts, a zebrafish assay and Tetrahymena-Aeromonas co-culture, and to examine whether data from the Tetrahymena thermophila model reflects infections in the well-established animal model. First, virulence of 39 Aeromonas strains was assessed by determining the 50% lethal dose (LD50) in zebrafish. LD50 values ranging from 1.3×102 to 3.0×107 indicated that these strains represent a high to moderate degree of virulence and could be useful to assess virulence in the Tetrahymena model. In Tetrahymena-Aeromonas co-culture, we evaluated the virulence of Aeromonas by detecting relative survival of Aeromonas and Tetrahymena. An Aeromonas isolate was considered virulent when its relative survival was greater than 60%, while the Aeromonas isolate was considered avirulent if its relative survival was below 40%. When relative survival of T. thermophila was lower than 40% after co-culture with an Aeromonas isolate, the bacterial strain was regarded as virulent. In contrast, the strain was classified as avirulent if relative survival of T. thermophila was greater than 50%. Encouragingly, data from the 39 Aeromonas strains showed good correlation in zebrafish and Tetrahymena-Aeromonas co-culture models. The results provide sufficient data to demonstrate that Tetrahymena can be a comparable alternative to zebrafish for determining the virulence of Aeromonas isolates.
PMCID: PMC3493589  PMID: 23145022
9.  Frequent Gain and Loss of Introns in Fungal Cytochrome b Genes 
PLoS ONE  2012;7(11):e49096.
In this study, all available cytochrome b (Cyt b) genes from the GOBASE database were compiled and the evolutionary dynamics of the Cyt b gene introns was assessed. Cyt b gene introns were frequently present in the fungal kingdom and some lower plants, but generally absent or rare in Chromista, Protozoa, and Animalia. Fungal Cyt b introns were found at 35 positions in Cyt b genes and the number of introns varied at individual positions from a single representative to 32 different introns at position 131, showing a wide and patchy distribution. Many homologous introns were present at the same position in distantly related species but absent in closely related species, suggesting that introns of the Cyt b genes were frequently lost. On the other hand, highly similar intron sequences were observed in some distantly related species rather than in closely related species, suggesting that these introns were gained independently, likely through lateral transfers. The intron loss-and-gain events could be mediated by transpositions that might have occurred between nuclear and mitochondria. Southern hybridization analysis confirmed that some introns contained repetitive sequences and might be transposable elements. An intron gain in Botryotinia fuckeliana prevented the development of QoI fungicide resistance, suggesting that intron loss-and-gain events were not necessarily beneficial to their host organisms.
PMCID: PMC3492308  PMID: 23145081
10.  Balance of XYL1 and XYL2 expression in different yeast chassis for improved xylose fermentation 
Reducing xylitol formation is necessary in engineering xylose utilization in recombinant Saccharomyces cerevisiae for ethanol production through xylose reductase/xylitol dehydrogenase pathway. To balance the expression of XYL1 and mutant XYL2 encoding xylose reductase (XR) and NADP+-dependent xylitol dehydrogenase (XDH), respectively, we utilized a strategy combining chassis selection and direct fine-tuning of XYL1 and XYL2 expression in this study. A XYL1 gene under the control of various promoters of ADH1, truncated ADH1 and PGK1, and a mutated XYL2 with different copy numbers were constructed into different xylose-utilizing modules, which were then expressed in two yeast chassises W303a and L2612. The strategy enabled an improved L2612-derived recombinant strain with XYL1 controlled by promoter PGK1 and with two copies of XYL2. The strain exhibited a 21.3% lower xylitol yield and a 40.0% higher ethanol yield. The results demonstrate the feasibility of the combinatorial strategy for construction of an efficient xylose-fermenting S. cerevisiae.
PMCID: PMC3464680  PMID: 23060871
pathway balance; chassis; xylose reductase; xylitol dehydrogenase; xylose; ethanol
11.  Hepatoprotective activities of a sesquiterpene-rich fraction from the aerial part of Cichorium glandulosum 
Chinese Medicine  2012;7:21.
Cichorium glandulosum Boiss. et Huet is used for treatment of liver disorders, and its effects are attributed to sesquiterpenes. This study aims to investigate the hepatoprotective effects of a sesquiterpene-rich fraction (SRF) from the aerial part of C. glandulosum on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in mice, and on priming with Bacillus Calmette–Guerin (BCG) followed by lipopolysaccharide (LPS)-induced immunological liver injury in mice.
SRF was suspended in water and administered to mice at 0.05, 0.10 and 0.20 g/kg body weight for 7 consecutive days. An active control drug (bifendate pills) was suspended in distilled water and administered to mice at 0.40 g/kg body weight for 7 consecutive days. Hepatotoxicity was induced by intraperitoneal injection of 0.1% CCl4 (0.2 mL/mouse) at 13 h before the last drug administration, or by tail intravenous injection of BCG (0.2 mL/mouse) before the first drug administration and LPS (0.2 mL/mouse; 8 μg) at 15 h before the last drug administration. Blood samples and the livers were collected for evaluation of the biochemical parameters of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBIL).
SRF significantly reduced the impact of CCl4 toxicity. The highest dose of SRF (0.20 g/kg) was the most effective, reflected by significant reductions in the levels of AST (P = 0.001), ALT (P = 0.000) and TBIL (P = 0.009). The serum enzymatic levels induced by BCG and subsequent LPS injection were significantly and dose-dependently restored by SRF, reflected by significant reductions in the levels of AST (P = 0.003), ALT (P = 0.003) and TBIL (P = 0.007) for the highest dose of SRF (0.20 g/kg).
SRF is hepatoprotective in animal models of chemical and immunological acute liver injury.
PMCID: PMC3507663  PMID: 23021236
12.  Intrinsic mode entropy based on multivariate empirical mode decomposition and its application to neural data analysis 
Cognitive Neurodynamics  2011;5(3):277-284.
Entropy, a measure of the regularity of a time series, has long been used to quantify the complexity of brain dynamics. Given the multiple spatiotemporal scales inherent in the brain, traditional entropy analysis based on a single scale is not adequate to accurately describe the underlying nonlinear dynamics. Intrinsic mode entropy (IMEn) is a recent development with appealing properties to estimate entropy over multiple time scales. It is a multiscale entropy measure that computes sample entropy (SampEn) over different scales of intrinsic mode functions extracted by empirical mode decomposition (EMD) method. However, it suffers from both mode-misalignment and mode-mixing problems when applied to multivariate time series data. In this paper, we address these two problems by employing the recently introduced multivariate empirical mode decomposition (MEMD). First, we extend the MEMD to multi-channel multi-trial neural data to ensure the IMEn matched at different scales. Second, for the discriminant analysis of IMEn, we propose to improve the discriminative ability by including variance that has not been used before in entropy analysis. Finally, we apply the proposed approach to the multi-electrode local field potentials (LFPs) simultaneously collected from visual cortical areas of macaque monkeys while performing a generalized flash suppression task. The results have shown that the entropy of LFP is indeed scale-dependent and is closely related to the perceptual conditions. The discriminative results of the perceptual conditions, revealed by support vector machine, show that the accuracy based on IMEn and variance reaches 83.05%, higher than that only by IMEn (76.27%). These results suggest that our approach is sensitive to capture the complex dynamics of neural data.
PMCID: PMC3179544  PMID: 22942916
Entropy; Multivariate empirical mode decomposition; Neural signal analysis
13.  Noise-Assisted Instantaneous Coherence Analysis of Brain Connectivity 
Characterizing brain connectivity between neural signals is key to understanding brain function. Current measures such as coherence heavily rely on Fourier or wavelet transform, which inevitably assume the signal stationarity and place severe limits on its time-frequency resolution. Here we addressed these issues by introducing a noise-assisted instantaneous coherence (NAIC) measure based on multivariate mode empirical decomposition (MEMD) coupled with Hilbert transform to achieve high-resolution time frequency representation of neural coherence. In our method, fully data-driven MEMD, together with Hilbert transform, is first employed to provide time-frequency power spectra for neural data. Such power spectra are typically sparse and of high resolution, that is, there usually exist many zero values, which result in numerical problems for directly computing coherence. Hence, we propose to add random noise onto the spectra, making coherence calculation feasible. Furthermore, a statistical randomization procedure is designed to cancel out the effect of the added noise. Computer simulations are first performed to verify the effectiveness of NAIC. Local field potentials collected from visual cortex of macaque monkey while performing a generalized flash suppression task are then used to demonstrate the usefulness of our NAIC method to provide highresolution time-frequency coherence measure for connectivity analysis of neural data.
PMCID: PMC3368308  PMID: 22690209
14.  Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination 
Biochimica et biophysica acta  2010;1812(4):565-571.
Recent studies recognize that Hypocretin system (also known as Orexin) plays a critical role in sleep/wake disorders and feeding behaviors. However, little is known about the regulation of the Hypocretin system. It is also known that tumor necrosis factor alpha (TNF-α) is involved in regulation of sleep/wake cycle. Here, we test our hypothesis that the Hypocretin system is regulated by TNF-α. Prepro-Hypocretin and Hypocretin receptor 2 (HcrtR2) can be detected at a very low level in rat B35 neuroblastoma cells. In response to TNF-α, Prepro-Hypocretin mRNA and protein levels are down-regulated, and also HcrtR2 protein level is down-regulated in B35 cells. To investigate the mechanism, exogenous rat Prepro-Hypocretin and rat HcrtR2 were overexpressed in B35 cells. In response to TNF-α, protein and mRNA of Prepro-Hypocretin are significantly decreased (by 93% and 94%, respectively), and the half-life of Prepro-Hypocretin mRNA is decreased in a time- and dose-dependent manner. The level of HcrtR2 mRNA level is not affected by TNF-α treatment; however, HcrtR2 protein level is significantly decreased (by 86%) through ubiquitination in B35 cells treated with TNF-α. Downregulation of cellular inhibitor of apoptosis protein-1 and -2 (cIAP-1 and -2) abrogates the HcrtR2 ubiquitination induced by TNF-α. The control green fluorescent protein (GFP) expression is not affected by TNF-α treatment. These studies demonstrate that TNF-α can impair the function of the Hypocretin system by reducing the levels of both Prepro-Hypocretin and HcrtR2.
PMCID: PMC3042489  PMID: 21094253
Prepro-Hypocretin; Hypocretin; Orexin; Tumor necrosis factor; narcolepsy; sleep disorder; Hypocretin receptor; Orexin receptor; Prepro-Orexin
15.  Template Free Synthesis of Hollow Ball-Like Nano-Fe2O3 and Its Application to the Detection of Dimethyl Methylphosphonate at Room Temperature 
Sensors (Basel, Switzerland)  2012;12(4):4594-4604.
This paper is focused on the template-free synthesis of nanosized ferric oxide (nano-Fe2O3) and its application in quartz crystal microbalance (QCM) resonators to detect dimethyl methylphosphonate (DMMP), a simulant of Sarin. The X-ray diffraction (XRD) patterns confirm that the synthesized samples are made of Fe2O3 and the scanning electron microscopy (SEM) pictures show that the samples have ball-like shapes. The DMMP sensors with a sensing film of hollow ball-like and solid ball-like Fe2O3 are fabricated and their sensing characteristics are compared. The sensitivity of the hollow ball-like Fe2O3 sensor is more than 500% higher than the one of the solid ball-like Fe2O3 sensor. The hollow ball-like nano-Fe2O3 can be synthesized by a novel low temperature hydrothermal method. The sensors with the hollow ball-like Fe2O3 film perform well in a range of 1 to 6 ppm, with a sensitivity of 29 Hz/ppm at room temperature, while the appropriate recoverability and selectivity are maintained. In addition, the performance of different thicknesses of the sensing film of the hollow ball-like nano-Fe2O3 is investigated and the optimized relative film thickness of the hollow ball-like nano-Fe2O3 is found to be 20 μg/mm2.
PMCID: PMC3355429  PMID: 22666047
nano-Fe2O3; quartz crystal microbalance (QCM); dimethyl methylphosphonate (DMMP); gas sensor
16.  {2-[(3,5-Dimethyl-2H-pyrrol-2-yl­idene-κN)(4-nitro­phen­yl)meth­yl]-3,5-dimethyl-1H-pyrrol-1-ido-κN}difluoridoboron 
In an effort to discover novel and potential boron–dipyrromethene (BODIPY) dyes, the title compound, C19H18BF2N3O2, was prepared from 2,4-dimethyl­pyrrole, 4-nitro­benzaldehyde and BF3·Et2O in a one-pot reaction. There are two independent mol­ecules, A and B, in the asymmetric unit in which the dihedral angles between the benzene ring and boron–dipyrromethene mean plane have significantly different values [82.71 (8)° for mol­ecule A and 73.16 (8)° for mol­ecule B]. Inter­molecular C—H⋯π inter­actions help to stabilize the crystal structure.
PMCID: PMC3254419  PMID: 22259564
17.  Monilinia Species Causing Brown Rot of Peach in China 
PLoS ONE  2011;6(9):e24990.
In this study, 145 peaches and nectarines displaying typical brown rot symptoms were collected from multiple provinces in China. A subsample of 26 single-spore isolates were characterized phylogenetically and morphologically to ascertain species. Phylogenetic analysis of internal transcribed spacer (ITS) regions 1 and 2, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), β-tubulin (TUB2) revealed the presence of three distinct Monilinia species. These species included Monilinia fructicola, Monilia mumecola, and a previously undescribed species designated Monilia yunnanensis sp. nov. While M. fructicola is a well-documented pathogen of Prunus persica in China, M. mumecola had primarily only been isolated from mume fruit in Japan. Koch's postulates for M. mumecola and M. yunnanensis were fulfilled confirming pathogenicity of the two species on peach. Phylogenetic analysis of ITS, G3PDH, and TUB2 sequences indicated that M. yunnanensis is most closely related to M. fructigena, a species widely prevalent in Europe. Interestingly, there were considerable differences in the exon/intron structure of the cytochrome b (Cyt b) gene between the two species. Morphological characteristics, including spore size, colony morphology, lesion growth rate, and sporulation, support the phylogenetic evidence suggesting the designation of M. yunnanensis as a new species. A new multiplex PCR method was developed to facilitate the detection of M. yunnanensis and differentiation of Monilinia spp. causing brown rot of peach in China.
PMCID: PMC3181254  PMID: 21980371
18.  The Role of the p38 MAPK Signaling Pathway in High Glucose-Induced Epithelial-Mesenchymal Transition of Cultured Human Renal Tubular Epithelial Cells 
PLoS ONE  2011;6(7):e22806.
Epithelial-mesenchymal transition of tubular epithelial cells, which is characterized by a loss of epithelial cell characteristics and a gain of ECM-producing myofibroblast characteristics, is an essential mechanism that is involved in tubulointerstitial fibrosis, an important component of the renal injury that is associated with diabetic nephropathy. Under diabetic conditions, p38 MAPK activation has been reported in glomeruli and mesangial cells; however, studies on p38 MAPK in TECs are lacking. In this study, the role of p38 MAPK in AP-1 activation and in the EMT in the human proximal tubular epithelial cell line (HK-2) under high glucose concentration conditions is investigated.
Methodology/Principal Findings
A vector for small interfering RNA that targets p38 MAPK was constructed; the cells were then either transfected with p38 siRNA or pretreated with a chemical inhibitor of AP-1 and incubated with low glucose plus TGF-β1 or high glucose for 48 h. Cells that were not transfected or pretreated and were exposed to low glucose with or without TGF-β1 or high glucose for 48 h were considered to be the controls. We found that high glucose induced an increase in TGF-β1. And high glucose-induced p38 MAPK activation was inhibited by p38 siRNA (P<0.05). A significant decline in E-cadherin and CK expression and a notable increase in vimentin and α-SMA were detected when exposed to low glucose with TGF-β1 or high glucose, and a significant raise of secreted fibronectin were detected when exposed to high glucose; whereas these changes were reversed when the cells were treated with p38 siRNA or AP-1 inhibitor (P<0.05). AP-1 activity levels and Snail expression were up-regulated under high glucose conditions but were markedly down-regulated through knockdown of p38 MAPK with p38 siRNA or pretreatment with AP-1 inhibitor (P<0.05).
This study suggests that p38 MAPK may play an important role in the high glucose-induced EMT by activating AP-1 in tubular epithelial cells.
PMCID: PMC3146517  PMID: 21829520
19.  A gene pattern mining algorithm using interchangeable gene sets for prokaryotes 
BMC Bioinformatics  2008;9:124.
Mining gene patterns that are common to multiple genomes is an important biological problem, which can lead us to novel biological insights. When family classification of genes is available, this problem is similar to the pattern mining problem in the data mining community. However, when family classification information is not available, mining gene patterns is a challenging problem. There are several well developed algorithms for predicting gene patterns in a pair of genomes, such as FISH and DAGchainer. These algorithms use the optimization problem formulation which is solved using the dynamic programming technique. Unfortunately, extending these algorithms to multiple genome cases is not trivial due to the rapid increase in time and space complexity.
In this paper, we propose a novel algorithm for mining gene patterns in more than two prokaryote genomes using interchangeable sets. The basic idea is to extend the pattern mining technique from the data mining community to handle the situation where family classification information is not available using interchangeable sets. In an experiment with four newly sequenced genomes (where the gene annotation is unavailable), we show that the gene pattern can capture important biological information. To examine the effectiveness of gene patterns further, we propose an ortholog prediction method based on our gene pattern mining algorithm and compare our method to the bi-directional best hit (BBH) technique in terms of COG orthologous gene classification information. The experiment show that our algorithm achieves a 3% increase in recall compared to BBH without sacrificing the precision of ortholog detection.
The discovered gene patterns can be used for the detecting of ortholog and genes that collaborate for a common biological function.
PMCID: PMC2279103  PMID: 18302784

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