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1.  Comparative genomics of grass EST libraries reveals previously uncharacterized splicing events in crop plants 
BMC Plant Biology  2015;15:39.
Crop plants such as rice, maize and sorghum play economically-important roles as main sources of food, fuel, and animal feed. However, current genome annotations of crop plants still suffer false-positive predictions; a more comprehensive registry of alternative splicing (AS) events is also in demand. Comparative genomics of crop plants is largely unexplored.
We performed a large-scale comparative analysis (ExonFinder) of the expressed sequence tag (EST) library from nine grass plants against three crop genomes (rice, maize, and sorghum) and identified 2,879 previously-unannotated exons (i.e., novel exons) in the three crops. We validated 81% of the tested exons by RT-PCR-sequencing, supporting the effectiveness of our in silico strategy. Evolutionary analysis reveals that the novel exons, comparing with their flanking annotated ones, are generally under weaker selection pressure at the protein level, but under stronger pressure at the RNA level, suggesting that most of the novel exons also represent novel alternatively spliced variants (ASVs). However, we also observed the consistency of evolutionary rates between certain novel exons and their flanking exons, which provided further evidence of their co-occurrence in the transcripts, suggesting that previously-annotated isoforms might be subject to erroneous predictions. Our validation showed that 54% of the tested genes expressed the newly-identified isoforms that contained the novel exons, rather than the previously-annotated isoforms that excluded them. The consistent results were steadily observed across cultivated (Oryza sativa and O. glaberrima) and wild (O. rufipogon and O. nivara) rice species, asserting the necessity of our curation of the crop genome annotations. Our comparative analyses also inferred the common ancestral transcriptome of grass plants and gain- and loss-of-ASV events.
We have reannotated the rice, maize, and sorghum genomes, and showed that evolutionary rates might serve as an indicator for determining whether the identified exons were alternatively spliced. This study not only presents an effective in silico strategy for the improvement of plant annotations, but also provides further insights into the role of AS events in the evolution and domestication of crop plants. ExonFinder and the novel exons/ASVs identified are publicly accessible at
Electronic supplementary material
The online version of this article (doi:10.1186/s12870-015-0431-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4323234  PMID: 25652661
Crop plants; Alternative splicing; Plant transcriptome evolution; Evolutionary rate; Comparative genomics; Bioinformatics
2.  Effects of Castration on Expression of Lipid Metabolism Genes in the Liver of Korean Cattle 
Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.
PMCID: PMC4283181  PMID: 25557684
Korean Cattle; Liver; Bulls; Steers; Gene Expression
3.  High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia 
BMC Neurology  2014;14(1):216.
Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs.
A total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed.
Mutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20 ± 18 years) compared with those with preservation of partial or total AAA cassette (32 ± 19 years, p = 0.041). For those with SPG4 mutations, disease severity was related to the patients’ current age, and the progression rate of disease was positively correlated with age at onset.
SPG4 accounts for most of the AD-HSP cases in Taiwanese, with a frequency significantly higher than in other populations. SPAST mutations which predict complete loss of the spastin AAA cassette were associated with an earlier onset of disease.
Electronic supplementary material
The online version of this article (doi:10.1186/s12883-014-0216-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4254010  PMID: 25421405
Hereditary spastic paraplegia; SPG4; SPAST; Spastin; AAA cassette
4.  Reliability Measure of a Clinical Test: Appreciation of Music in Cochlear Implantees (AMICI) 
The goals of this study were (1) to investigate the reliability of a clinical music perception test, Appreciation of Music in Cochlear Implantees (AMICI), and (2) examine associations between the perception of music and speech. AMICI was developed as a clinical instrument for assessing music perception in persons with cochlear implants (CIs). The test consists of four subtests: (1) music versus environmental noise discrimination, (2) musical instrument identification (closed-set), (3) musical style identification (closed-set), and (4) identification of musical pieces (open-set). To be clinically useful, it is crucial for AMICI to demonstrate high test-retest reliability, so that CI users can be assessed and retested after changes in maps or programming strategies.
Research Design
Thirteen CI subjects were tested with AMICI for the initial visit and retested again 10–14 days later. Two speech perception tests (consonant-nucleus-consonant [CNC] and Bamford-Kowal-Bench Speech-in-Noise [BKB-SIN]) were also administered.
Data Analysis
Test-retest reliability and equivalence of the test’s three forms were analyzed using paired t-tests and correlation coefficients, respectively. Correlation analysis was also conducted between results from the music and speech perception tests.
Results showed no significant difference between test and retest (p > 0.05) with adequate power (0.9) as well as high correlations between the three forms (Forms A and B, r = 0.91; Forms A and C, r = 0.91; Forms B and C, r = 0.95). Correlation analysis showed high correlation between AMICI and BKB-SIN (r = −0.71), and moderate correlation between AMICI and CNC (r = 0.4).
The study showed AMICI is highly reliable for assessing musical perception in CI users.
PMCID: PMC4219645  PMID: 24384082
Cochlear implants; music perception; test-retest reliability; speech perception
5.  Characterization of the anticancer effects of S115, a novel heteroaromatic thiosemicarbazone compound, in vitro and in vivo 
Acta Pharmacologica Sinica  2014;35(10):1302-1310.
To investigate the anticancer effects of S115, a novel heteroaromatic thiosemicarbazone compound in vitro and in vivo.
The anti-proliferative action of S115 was analyzed in 12 human and mouse cancer cell lines using MTT assay. Autograft and xenograft cancer models were made by subcutaneous inoculation of cancer cells into mice or nude mice. The mice were orally treated with S115 (2, 8, 32 mg·kg−1·d−1) for 7 d, and the tumor size was measured every 3 d. Cell apoptosis and cell cycle distribution were examined using flow cytometry, gene expression profile analyses, Western blots and RT-PCR.
The IC50 values of S115 against 12 human and mouse cancer cell lines ranged from 0.3 to 6.6 μmol/L. The tumor growth inhibition rate caused by oral administration of S115 (32 mg·kg−1·d−1) were 89.7%, 81.7%, 78.4% and 77.8%, respectively, in mouse model of B16 melanoma, mouse model of Colon26 colon cancer, nude mouse model of A549 lung cancer and nude mouse model of SK-OV-3 ovarian cancer. Furthermore, oral administration of S115 (7.5 mg·kg−1·d−1) synergistically enhanced the anticancer effects of cyclophosphamide, cisplatin, or 5-fluorouracil in mouse model of S180 sarcoma. Treatment of A549 human lung cancer cells with S115 (1.5 μmol/L) induced G0/G1 cell cycle arrest, and increased apoptosis. Furthermore, S115 downregulated the level of ubiquitin, and upregulated the level of Tob2 in A549 cells.
S115 exerts anticancer effects against a variety of cancer cells in vitro and in grafted cancer models by inducing apoptosis, downregulating ubiquitin and upregulating Tob2.
PMCID: PMC4186988  PMID: 25220642
anticancer drug; thiourea; thiosemicarbazone; melanoma; colon cancer; human lung cancer; ovarian cancer; cell cycle arrest; apoptosis; ubiquitin; Tob2
6.  Effect of Dominant Hand Paralysis on Quality of Life in Patients With Subacute Stroke 
Annals of Rehabilitation Medicine  2014;38(4):450-457.
To evaluate the degree to which the paralysis of a dominant hand affects quality of life (QOL) in patients with subacute stroke.
We recruited 75 patients with subacute hemiplegic stroke. Patients were divided into two groups according to the location of the lesion and the side of the dominant hand. Group 1 consisted of patients whose strokes affected the dominant hand (i.e., right hemiplegia and right dominant hand or left hemiplegia and left dominant hand). Group 2 consisted of patients whose strokes affected the non-dominant hand (i.e., left hemiplegia and right dominant hand or right hemiplegia and left dominant hand). The primary outcome measure was the Short-Form 36-Item Health Survey (SF-36), which was used to evaluate health-related QOL. Secondary outcomes were scores on the Modified Barthel Index (MBI) and Beck Depression Inventory (BDI).
We did not find any statistically significant differences between the groups in any SF-36 domain including the summaries of physical and mental component. Similarly, the MBI and BDI scores were not significantly different between the groups.
The effect of paralysis on the dominant hand and QOL in patients with subacute stroke was not significantly different from the effect of paralysis on the non-dominant hand.
PMCID: PMC4163584  PMID: 25229023
Dominance; Quality of life; Stroke
7.  Delayed Onset of Acute Limb Compartment Syndrome With Neuropathy After Venoarterial Extracorporeal Membrane Oxygenation Therapy 
Annals of Rehabilitation Medicine  2014;38(4):575-580.
Acute limb compartment syndrome (ALCS) is defined as compound symptoms resulting from poor oxygenation and decreased nutrition supply to muscles and nerves in a tightly confined compartment. The most common cause of ALCS is tibia fracture, followed by blunt trauma to soft tissue. However, non-traumatic causes are rare. We report an iatrogenic, non-traumatic ALCS case after venoarterial extracorporeal membrane oxygen (VA-ECMO) therapy. A 14-year-old male received VA-ECMO therapy due to cardiorespiratory failure after drowning. Although he had no symptoms during therapy, leg swelling appeared 10 hours after ECMO treatment. Two days after the leg swelling, the patient underwent a fasciotomy. Unfortunately, nerve conduction studies and electromyography showed multiple neuropathies in the lower leg. Despite 2 weeks of rehabilitation with electrical stimulation, an exercise program, and physical therapy, there was no definite change in muscle strength. To our knowledge, this is the first reported case of non-traumatic ALCS after VA-ECMO therapy in Korea.
PMCID: PMC4163600  PMID: 25229039
Anterior compartment syndrome; Extracorporeal membrane oxygenation
8.  GABAergic inhibition through synergistic astrocytic neuronal interaction transiently decreases vasopressin neuronal activity during hypoosmotic challenge 
The European journal of neuroscience  2013;37(8):1260-1269.
The neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurones using patch-clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased IPSC frequency and reduced firing rate of vasopressin neurones. Recovery occurred by 10 min exposure, even though the osmolality remained low. The GABAA receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l-aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β-alanine, an osmolyte of astrocytes and GABA transporter inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurones both showed positive staining of vesicular GABA transporters (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT-expressing neurones and increased co-localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored and astrocytic VGAT was relocated to ventral portion while decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neurone firing is only transiently suppressed under hypoosmotic conditions.
PMCID: PMC3627741  PMID: 23406012
glia; hypothalamo-neurohypophyseal system; in vitro brainstem slice; neuroendocrinology; transporters
9.  Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells 
BMC Nephrology  2014;15:35.
Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored.
To investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study.
Forty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro.
Dwelling time had a significant effect on the occurrence of EMT on MCs.
PMCID: PMC4015532  PMID: 24555732
Dwelling time; Epithelial-to-mesenchymal transition; Mesothelial cells; Peritoneal dialysis
10.  Haemolytic uremic syndrome following fire ant bites 
BMC Nephrology  2014;15:5.
Haemolytic-uremic syndrome (HUS) is a severe, life-threatening disease with symptoms such as haemolytic anaemia, renal failure, and a low platelet count. Possible aetiology includes bacterial infections, medication, post-hematopoietic cell transplantation, pregnancy, autoimmune disease, and acquired immunodeficiency syndrome.
Case presentation
We report the case of a 21-year-old healthy man who developed acute renal failure caused by HUS. Typical symptoms of HUS combined with severe uraemia developed following a large local reaction after suspected Solenopsis invicta (fire ant) bites. He was successfully treated with plasma exchange and achieved complete recovery of renal function.
This is the first case illustrating a serious systemic reaction of HUS to fire ant bites, and highlights this severe complication in patients who sustain fire ant bites.
PMCID: PMC3890644  PMID: 24400942
Fire ant; Haemolytic-uremic syndrome; Plasma exchange; Renal failure; Venomous insects
11.  Risk factors for endotracheal re-intubation following coronary artery bypass grafting 
Endotracheal re-intubation following coronary artery bypass grafting (CABG) is often associated with significant morbidity and mortality. However, few reports have focused on the independent risk factors for re-intubation following CABG. This study aimed to evaluate the independent risk factors for re-intubation following CABG.
The pre-, intra-, and post-operative materials in patients who had selective and isolated CABG performed on them from January 2004 to July 2012 in our hospital were analyzed retrospectively. Unvariate analysis and logistic regression were used to analyze the risk factor of postoperative re-intubation following CABG.
Among the 1,244 patients investigated, 97 cases suffered from postoperative re-intubation, and the incidence rate of postoperative re-intubation was 7.8%. The in-hospital mortality in the re-intubation group was significantly higher than that in the non-re-intubation group (9.3% versus 1.4%, P = 0.004). Re-intubation also correlated with many negative outcomes such as pneumonia, tracheotomy, acute renal failure, infection of incision, prolonged mechanical ventilation time, prolonged intensive care unit (ICU) stay and prolonged hospital stay. The most commonly cause of re-intubation after CABG was hypoxemia due to cardiogenic and noncardiogenic disease, which accounted for 72.2%. The relative factors of postoperative re-intubation were tested through unvariate analysis and logistic regression, and the associated factors were obtained. The associated factors for re-intubation following CABG included preoperative chronic obstructive pulmonary disease (COPD) (OR = 2.134, 95% CI = 1.472-2.967), preoperative congestive heart failure (CHF) (OR = 2.325, 95% CI = 1.512-3.121), postoperative relative hypoxemia (OR = 2.743, 95% CI = 1.657-3.326), postoperative acute kidney injury (AKI) (OR = 2.976, 95% CI = 2.127-4.023), postoperative total mechanical ventilation time (OR = 1.976, 95% CI = 1.347-2.645).
Preoperative COPD, preoperative CHF, postoperative relative hypoxemia, postoperative AKI and postoperative total mechanical ventilation time were five independent risk factors for re-intubation following CABG.
PMCID: PMC3842842  PMID: 24209453
Coronary artery bypass grafting; Risk factors; Complication
12.  A Bayesian Approach to Dose-Response Assessment and Synergy and Its Application to In Vitro Dose-Response Studies 
Biometrics  2010;66(4):1275-1283.
In this article, we propose a Bayesian approach to dose-response assessment and the assessment of synergy between two combined agents. We consider the case of an in vitro ovarian cancer research study aimed at investigating the antiproliferative activities of four agents, alone and paired, in two human ovarian cancer cell lines. In this study, independent dose-response experiments were repeated three times. Each experiment included replicates at investigated dose levels including control (no drug). We have developed a Bayesian hierarchical nonlinear regression model that accounts for variability between-experiments, variability within experiments (i.e., replicates), and variability in the observed responses of the controls. We use Markov chain Monte Carlo (MCMC) to fit the model to the data and carry out posterior inference on quantites of interest (e.g., median inhibitory concentration IC50). In addition, we have developed a method, based on Loewe additivity, that allows one to assess the presence of synergy with honest accounting of uncertainty. Extensive simulation studies show that our proposed approach is more reliable in declaring synergy compared to current standard analyses such as the Median-Effect Principle/Combination Index method (Chou and Talalay, 1984), that ignore important sources of variability and uncertainty.
PMCID: PMC3773943  PMID: 20337630
Combination Index method; Drug interaction; Emax model; Interaction index; Median-effect principle; Loewe additivity model
13.  Green tea extract protects against nonalcoholic steatohepatitis in ob/ob mice by decreasing oxidative and nitrative stress responses induced by proinflammatory enzymes☆ 
Oxidative and nitrative stress responses resulting from inflammation exacerbate liver injury associated with nonalcoholic steatohepatitis (NASH) by inducing lipid peroxidation and protein nitration. The objective of this study was to investigate whether the anti-inflammatory properties of green tea extract (GTE) would protect against NASH by suppressing oxidative and nitrative damage mediated by proinflammatory enzymes. Obese mice (ob/ob) and their 5-week-old C57BL6 lean littermates were fed 0%, 0.5% or 1% GTE for 6 weeks (n=12–13 mice/group). In obese mice, hepatic lipid accumulation, inflammatory infiltrates and serum alanine aminotransferase activity were markedly increased, whereas these markers of hepatic steatosis, inflammation and injury were significantly reduced among obese mice fed GTE. GTE also normalized hepatic 4-hydroxynonenal and 3-nitro-tyrosine (N-Tyr) concentrations to those observed in lean controls. These oxidative and nitrative damage markers were correlated with alanine aminotransferase (P<.05; r=0.410–0.471). Improvements in oxidative and nitrative damage by GTE were also associated with lower hepatic nicotinamide adenine dinucleotide phosphate oxidase activity. Likewise, GTE reduced protein expression levels of hepatic myeloperoxidase and inducible nitric oxide synthase and decreased the concentrations of nitric oxide metabolites. Correlative relationships between nicotinamide adenine dinucleotide phosphate oxidase and hepatic 4-hydroxynonenal (r=0.364) as well as nitric oxide metabolites and N-Tyr (r=0.598) suggest that GTE mitigates lipid peroxidation and protein nitration by suppressing the generation of reactive oxygen and nitrogen species. Further study is warranted to determine whether GTE can be recommended as an effective dietary strategy to reduce the risk of obesity-triggered NASH.
PMCID: PMC3704146  PMID: 21543212
Green tea; NADPH oxidase; Myeloperoxidase; Lipid peroxidation; Protein nitration; Nonalcoholic steatohepatitis
14.  Coupling visualization and data analysis for knowledge discovery from multi-dimensional scientific data 
Procedia computer science  2010;1(1):1757-1764.
Knowledge discovery from large and complex scientific data is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the growing number of data dimensions and data objects presents tremendous challenges for effective data analysis and data exploration methods and tools. The combination and close integration of methods from scientific visualization, information visualization, automated data analysis, and other enabling technologies —such as efficient data management— supports knowledge discovery from multi-dimensional scientific data. This paper surveys two distinct applications in developmental biology and accelerator physics, illustrating the effectiveness of the described approach.
PMCID: PMC3677775  PMID: 23762211
scientific visualization; information visualization; data analysis; multi-dimensional data; laser wakefield particle acceleration; 3D gene expression
15.  Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development 
Cancer is one of the leading causes of death worldwide. Commonly used cancer treatments, including chemotherapy and radiation therapy, often have side effects and a complete cure is sometimes impossible. Therefore, prevention, suppression, and/or delaying the onset of the disease are important. The onset of gastroenterological cancers is closely associated with an individual’s lifestyle. Thus, changing lifestyle, specifically the consumption of fruits and vegetables, can help to protect against the development of gastroenterological cancers. In particular, naturally occurring bioactive compounds, including curcumin, resveratrol, isothiocyanates, (-)-epigallocatechin gallate and sulforaphane, are regarded as promising chemopreventive agents. Hence, regular consumption of these natural bioactive compounds found in foods can contribute to prevention, suppression, and/or delay of gastroenterological cancer development. In this review, we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities, which are exerted by regulating or targeting specific molecules against gastroenterological cancers, including esophageal, gastric and colon cancers.
PMCID: PMC3582010  PMID: 23467658
Curcumin; Resveratrol; (-)-Epigallocatechin gallate; Isothiocyanates; Sulforaphane; Gastroenterological cancers; Molecular target
16.  Identification of Chromosomal HP0892-HP0893 Toxin-Antitoxin Proteins in Helicobacter pylori and Structural Elucidation of Their Protein-Protein Interaction* 
The Journal of Biological Chemistry  2013;288(8):6004-6013.
Background: HP0892 of H. pylori shares high structural similarity with other toxin-antitoxin (TA) system toxins.
Results: RNase activity and cell toxicity of HP0892 is inhibited by HP0893 via strong protein-protein interaction.
Conclusion: HP0892-HP0893 pair is a TA system with a protein-protein interaction mode similar to other TA pairs.
Significance: It is highly probable that HP0892-HP0893 TA pair is involved in H. pylori virulence.
Bacterial chromosomal toxin-antitoxin (TA) systems have been proposed not only to play an important role in the stress response, but also to be associated with antibiotic resistance. Here, we identified the chromosomal HP0892-HP0893 TA proteins in the gastric pathogen, Helicobacter pylori, and structurally characterized their protein-protein interaction. Previously, HP0892 protein was suggested to be a putative TA toxin based on its structural similarity to other RelE family TA toxins. In this study, we demonstrated that HP0892 binds to HP0893 strongly with a stoichiometry of 1:1, and HP0892-HP0893 interaction occurs mainly between the N-terminal secondary structure elements of HP0892 and the C-terminal region of HP0893. HP0892 cleaved mRNA in vitro, preferentially at the 5′ end of A or G, and the RNase activity of HP0892 was inhibited by HP0893. In addition, heterologous expression of HP0892 in Escherichia coli cells led to cell growth arrest, and the cell toxicity of HP0892 was neutralized by co-expression with HP0893. From these results and a structural comparison with other TA toxins, it is concluded that HP0892 is a toxin with intrinsic RNase activity and HP0893 is an antitoxin against HP0892 from a TA system of H. pylori. It has been known that hp0893 gene and another TA antitoxin gene, hp0895, of H. pylori, are both genomic open reading frames that correspond to genes that are potentially expressed in response to interactions with the human gastric mucosa. Therefore, it is highly probable that TA systems of H. pylori are involved in virulence of H. pylori.
PMCID: PMC3581365  PMID: 23297406
Helicobacter pylori; Nuclear Magnetic Resonance; Protein Structure; Protein-Protein Interactions; Ribonuclease; HP0892; HP0893; YafQ; Toxin-Antitoxin System; Virulence
17.  Risk factor analysis of coexisting endometrial carcinoma in patients with endometrial hyperplasia: a retrospective observational study of Taiwanese Gynecologic Oncology Group 
To evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissue-diagnosed endometrial hyperplasia.
Between January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated.
Age ≥53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14 to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index ≥27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors.
Coexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.
PMCID: PMC3549502  PMID: 23346309
Coexisting endometrial carcinoma; Endometrial hyperplasia; Hysterectomy; Risk factors
18.  Health-Related Quality of Life in Breast Cancer Patients with Lymphedema Who Survived More than One Year after Surgery 
Journal of Breast Cancer  2012;15(4):449-453.
To identify the influence of lymphedema on health-related quality of life (HRQOL) more than 1 year after breast cancer surgery.
Ninety-six breast cancer patients who survived more than 1 year after surgery and 104 members of the general population were recruited. Patients were divided into 2 groups according to the presence of lymphedema. HRQOL was evaluated with the Short-Form 36-Item Health Survey.
There were no statistically significant differences in any scales between groups: groups of breast cancer survivors with and without lymphedema. Compared with the general population, breast cancer survivors had lower quality of life scores in all scales, although the vitality and mental health scales did not differ from chance variation at the 5% level.
In this study, the presence of lymphedema in breast cancer patients who survived over 1 year after surgery might not affect the quality of life. However quality of life of breast cancer survivors is lower than in general population except for some mental health components.
PMCID: PMC3542854  PMID: 23346175
Breast neoplasms; Lymphedema; Quality of life
19.  Bidirectional Scaling of Astrocytic Metabotropic Glutamate Receptor Signaling following Long-Term Changes in Neuronal Firing Rates 
PLoS ONE  2012;7(11):e49637.
Very little is known about the ability of astrocytic receptors to exhibit plasticity as a result of changes in neuronal activity. Here we provide evidence for bidirectional scaling of astrocytic group I metabotropic glutamate receptor signaling in acute mouse hippocampal slices following long-term changes in neuronal firing rates. Plasticity of astrocytic mGluRs was measured by recording spontaneous and evoked Ca2+ elevations in both astrocytic somata and processes. An exogenous astrocytic Gq G protein-coupled receptor was resistant to scaling, suggesting that the alterations in astrocyte Ca2+ signaling result from changes in activity of the surface mGluRs rather than a change in intracellular G protein signaling molecules. These findings suggest that astrocytes actively detect shifts in neuronal firing rates and adjust their receptor signaling accordingly. This type of long-term plasticity in astrocytes resembles neuronal homeostatic plasticity and might be important to ensure an optimal or expected level of input from neurons.
PMCID: PMC3499417  PMID: 23166735
20.  Effects of Synchronization of Carbohydrate and Protein Supply in Total Mixed Ration with Korean Rice Wine Residue on Ruminal Fermentation, Nitrogen Metabolism and Microbial Protein Synthesis in Holstein Steers 
Three Holstein steers in the growing phase, each with a ruminal cannula, were used to test the hypothesis that the synchronization of the hourly rate of carbohydrate and nitrogen (N) released in the rumen would increase the amount of retained nitrogen for growth and thus improve the efficiency of microbial protein synthesis (EMPS). In Experiment 1, in situ degradability coefficients of carbohydrate and N in feeds including Korean rice wine residue (RWR) were determined. In Experiment 2, three total mixed ration (TMR) diets having different rates of carbohydrate and N release in the rumen were formulated using the in situ degradability of the feeds. All diets were made to contain similar contents of crude protein (CP) and neutral detergent fiber (NDF) but varied in their hourly pattern of nutrient release. The synchrony index of the three TMRs was 0.51 (LS), 0.77 (MS) and 0.95 (HS), respectively. The diets were fed at a restricted level (2% of the animal’s body weight) in a 3×3 Latin-square design. Synchronizing the hourly supply of energy and N in the rumen did not significantly alter the digestibility of dry matter, organic matter, crude protein, NDF or acid detergent fiber (ADF) (p>0.05). The ruminal NH3-N content of the LS group at three hours after feeding was significantly higher (p<0.05) than that of the other groups; however, the mean values of ruminal NH3-N, pH and VFA concentration among the three groups were not significantly different (p>0.05). In addition, the purine derivative (PD) excretion in urine and microbial-N production (MN) among the three groups were not significantly different (p>0.05). In conclusion, synchronizing dietary energy and N supply to the rumen did not have a major effect on nutrient digestion or microbial protein synthesis (MPS) in Holstein steers.
PMCID: PMC4093039  PMID: 25049518
By-product; Dairy Steer; Microbial Protein Synthesis; Purine Derivative; Rice Wine Residue; Synchronization)
21.  Effectiveness of sensory processing strategies on activity level in inclusive preschool classrooms 
The purpose of this study was to investigate the effectiveness of sensory processing strategies in improving the activity level of children with sensory integration dysfunction.
The study used a matching-only pretest–posttest control group design, which requires random matching of sensory integration dysfunction to the corresponding intervention group (n = 18) and control group (n = 18). The intervention group comprised 3–6-year-old children who received an 8-week school-day intervention during implementation of the theme curriculum.
The 8-week treatment significantly reduced the activity level and foot-swinging episodes in children with sensory integration dysfunction, and obtained a medium-effect size. However, the level of improvement in the control group did not show any statistically significant change.
Sensory processing strategies could improve activity levels in children with sensory integration dysfunction. However, this study was unable to exclude a developmental effect. The social validity results show that sensory processing strategies can be integrated into the theme curriculum and improve activity levels in children.
PMCID: PMC3484897  PMID: 23118541
activity level; preschool inclusive classroom; sensory integration dysfunction; sensory processing strategy
22.  Cyclin B1 Vaccine Delays Spontaneous Tumors 
We previously identified cyclin B1-specific T cells and antibodies in cancer patients with cyclin B1+ tumors and also in some healthy individuals. We also demonstrated that these responses may be important in cancer immunosurveillance by showing that vaccination against cyclin B1 prevents growth of transplantable cyclin B1+ tumors in mice. Constitutive overexpression of cyclin B1 was determined to correlate with the lack of p53 function. This allowed us to use p53−/− mice as a model that better approximates human disease. p53−/− mice spontaneously develop cyclin B1+ tumors. At 5–6 weeks of age, when the mice were still healthy with no evidence of tumor, they received the cyclin B1 vaccine and were then observed for tumor growth. We demonstrate that cyclin B1 vaccination can delay spontaneous cyclin B1+ tumor growth and increases median survival of tumor bearing p53−/− mice.
PMCID: PMC3472441  PMID: 19769738
cancer vaccines; immunosurveillance; mouse model
23.  Decitabine and suberoylanilide hydroxamic acid (SAHA) inhibit growth of ovarian cancer cell lines and xenografts while inducing expression of imprinted tumor suppressor genes, apoptosis, G2/M arrest and autophagy 
Cancer  2011;117(19):4424-4438.
Epigenetic therapy has had a significant impact on the management of hematologic malignancies, but its role in the treatment of ovarian cancer remains to be defined. We have shown earlier that treatment of ovarian and breast cancer cells with DNA methyltransferase and HDAC inhibitors can upregulate expression of imprinted tumor suppressors. In this study, demethylating agents and HDAC inhibitors were tested for their ability to induce re-expression of tumor suppressor genes, inhibiting growth of ovarian cancer cells in culture and in xenografts.
Ovarian cancer cells (Hey and SKOv3) were treated with demethylating agents [decitabine (DAC), azacytidine (AZA)] or HDAC inhibitors [(suberoylanilide hydroxamic acid (SAHA), trichosporin A (TSA)] to determine their impact on cellular proliferation, cell cycle regulation, apoptosis, autophagy and re-expression of ARHI and PEG3, two growth inhibitory imprinted tumor suppressor genes. The in vivo activity of DAC and SAHA was assessed in a Hey xenograft model.
A combination of DAC and SAHA produced synergistic inhibition of Hey and SKOv3 growth, by apoptosis and cell cycle arrest. DAC induced autophagy in Hey cells that could be enhanced by SAHA. Treatment with both agents induced re-expression of ARHI and PEG3 in cultured cells and in xenografts, correlating with growth inhibition. Knockdown of ARHI decreased DAC-induced autophagy. DAC and SAHA inhibited growth of Hey xenografts and induced autophagy in vivo.
A combination of DAC and SAHA inhibited ovarian cancer growth while inducing apoptosis, G2/M arrest, autophagy and re-expression of imprinted tumor suppressor genes.
PMCID: PMC3137708  PMID: 21491416
ovarian cancer; autophagy; decitabine (DAC); suberoylanilide hydroxamic acid (SAHA); imprinted tumor suppressor genes; ARHI; PEG3
24.  Calcium Signaling and Gliotransmission in Normal vs. Reactive Astrocytes 
A prominent area of neuroscience research over the past 20 years has been the acute modulation of neuronal synaptic activity by Ca2+-dependent release of the transmitters ATP, D-serine, and glutamate (called gliotransmitters) by astrocytes. Although the physiological relevance of this mechanism is under debate, emerging evidence suggests that there are critical factors in addition to Ca2+ that are required for gliotransmitters to be released from astrocytes. Interestingly, these factors include activated microglia and the proinflammatory cytokine Tumor Necrosis Factor α (TNFα), chemotactic cytokine Stromal cell-Derived Factor-1α (SDF-1α), and inflammatory mediator prostaglandin E2 (PGE2). Of note, microglial activation and release of inflammatory molecules from activated microglia and reactive astrocytes can occur within minutes of a triggering stimulus. Therefore, activation of astrocytes by inflammatory molecules combined with Ca2+ elevations may lead to gliotransmitter release, and be an important step in the early sequence of events contributing to hyperexcitability, excitotoxicity, and neurodegeneration in the damaged or diseased brain. In this review, we will first examine evidence questioning Ca2+-dependent gliotransmitter release from astrocytes in healthy brain tissue, followed by a close examination of recent work suggesting that Ca2+-dependent gliotransmitter release occurs as an early event in the development of neurological disorders and neuroinflammatory and neurodegenerative diseases.
PMCID: PMC3395812  PMID: 22811669
glia; IP3R; microglia; neurological disorder; neurodegenerative disease; TNFα; Gq GPCR; inflammation
25.  Overview of the Shenzhen Emergency Medical Service Call Pattern 
In Shenzhen, the Emergency Medical Service (EMS) system has been in service since 1997. This study aims to examine the operation of Shenzhen 120 EMS center and to identify the reasons of calling EMS.
In this retrospective quantitative descriptive study, the data from the Shenzhen 120 EMS registry in 2011 were analyzed.
Shenzhen 120 EMS center is a communication command center. When the number of 120 are dialed, it is forwarded to the closest appropriate hospital for ambulance dispatch. In 2011, the Shenzhen 120 EMS center received 153 160 ambulance calls, with an average of 420 calls per day. Calling emergency services was mainly due to traffic accidents. Trauma and other acute diseases constituted a majority of ambulance transports. The adult patients aged 15–60 years are the principal users of EMS. There are no recognized ‘paramedic’ doctors and nurses. The pre-hospital emergency service is under the operation of emergency departments of hospitals. Shenzhen at present does not have specialized pre-hospital training for doctors and nurses in post-trauma management. Moreover, specialized pre-hospital training, financial support, and public health education on proper use of EMS should be emphasized.
The Shenzhen 120 EMS center has its own epidemiology characteristics. Traumatic injury and traffic accident are the main reasons for calling ambulance service. In-depth study emphasizing the distribution and characteristics of trauma patients is crucial to the future development of EMS.
PMCID: PMC4129808  PMID: 25215072
Emergency Medical Service System; Shenzhen; Pre-hospital emergency care

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