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1.  Cocrystallization and preliminary crystallographic analysis of an inactive MaoC-like hydratase mutant with the substrate crotonyl-CoA 
An inactive MaoC-like hydratase mutant from P. capsici was obtained and purified, and the purified mutant was cocrystallized in the presence of the substrate crotonyl-CoA.
MaoC-like hydratase (MaoC) is a recently identified enzyme involved in the biosynthetic pathway of polyhydroxyalkanoates (PHAs), which are completely biodegradable polymers used to produce green plastics. The inactive mutant D194N-MaoC was crystallized in the presence of the substrate crotonyl-CoA. Crystals were grown in a number of conditions, but only those produced using 20%(v/v) ethylene glycol were suitable for structural studies. Data were collected to 2.10 Å resolution using X-radiation and the crystal belonged to the orthorhombic space group P212121, with unit-cell parameters a = 81.40, b = 82.58, c = 123.99 Å.
doi:10.1107/S1744309112007671
PMCID: PMC3325826  PMID: 22505426
MaoC-like hydratase; crotonyl-CoA; Phytophthora capsici
2.  A Comparison of Growth and Development of Three Major Agricultural Insect Pests Infected with Heliothis virescens ascovirus 3h (HvAV-3h) 
PLoS ONE  2013;8(12):e85704.
Ascoviruses are double-stranded DNA viruses that are pathogenic to lepidopteran hosts, particularly noctuid larvae. Infection of a larva is characterized by retarded growth, reduced feeding and yellowish body color. In this paper, we reported the growth and development of three major agricultural noctuid insect pests, Helicoverpa armigera (Hübner), Spodoptera exigua (Hübner) and Spodoptera litura (Fabricius), infected with Heliothis virescens ascovirus 3h (HvAV-3h). Using 10-fold serial dilutions (0 to 7) of HvAV-3h-containing hemolymph to infect S. litura larvae, we found no significant difference in larval mortalities from 0 to 103-fold dilutions; however, significant differences were observed at 104-fold dilution and above. Using a 10-fold dilution of HvAV-3h-containing hemolymph to infect H. armigera, S. exigua and S. litura larvae, we found that the growth and development were significantly affected. All infected larvae could not pupate; the survival times of treated H. armigera, S. litura and S. exigua larvae were significantly longer than untreated control larvae. Body weight showed significant difference between treated and untreated control group from day 1 after inoculation in H. armigera and S. exigua, but day 2 in S. litura. Additionally, food intake also showed significant difference between treated and untreated control group from day 2 after inoculation in H. armigera and S. litura, but day 3 in S. exigua.
doi:10.1371/journal.pone.0085704
PMCID: PMC3875588  PMID: 24386488
3.  Chitosan Coupling Makes Microbial Biofilms Susceptible to Antibiotics 
Scientific Reports  2013;3:3364.
Microbial biofilms, prevalent in nature and inherently resistant to both antimicrobial agents and host defenses, can cause serious problems in the chemical, medical and pharmaceutical industries. Herein we demonstrated that conjugation of an aminoglycoside antibiotic (streptomycin) to chitosan could efficiently damage established biofilms and inhibit biofilm formation. This method was suitable to eradiate biofilms formed by Gram-positive organisms, and it appeared that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this anti-biofilm activity. Mechanistic insight demonstrated chitosan conjugation rendered streptomycin more accessible into biofilms, thereby available to interact with biofilm bacteria. Thus, this work represent an innovative strategy that antibiotic covalently linked to carbohydrate carriers can overcome antibiotic resistance of microbial biofilms, and might provide a comprehensive solution to combat biofilms in industrial and medical settings.
doi:10.1038/srep03364
PMCID: PMC3842539  PMID: 24284335
4.  Effects of N-Acetylcysteine in Ozone-Induced Chronic Obstructive Pulmonary Disease Model 
PLoS ONE  2013;8(11):e80782.
Introduction
Chronic exposure to high levels of ozone induces emphysema and chronic inflammation in mice. We determined the recovery from ozone-induced injury and whether an antioxidant, N-acetylcysteine (NAC), could prevent or reverse the lung damage.
Methods
Mice were exposed to ozone (2.5 ppm, 3 hours/12 exposures, over 6 weeks) and studied 24 hours (24h) or 6 weeks (6W) later. Nac (100 mg/kg, intraperitoneally) was administered either before each exposure (preventive) or after completion of exposure (therapeutic) for 6 weeks.
Results
After ozone exposure, there was an increase in functional residual capacity, total lung volume, and lung compliance, and a reduction in the ratio of forced expiratory volume at 25 and 50 milliseconds to forced vital capacity (FEV25/FVC, FEV50/FVC). Mean linear intercept (Lm) and airway hyperresponsiveness (AHR) to acetylcholine increased, and remained unchanged at 6W after cessation of exposure. Preventive NAC reduced the number of BAL macrophages and airway smooth muscle (ASM) mass. Therapeutic NAC reversed AHR, and reduced ASM mass and apoptotic cells.
Conclusion
Emphysema and lung function changes were irreversible up to 6W after cessation of ozone exposure, and were not reversed by NAC. The beneficial effects of therapeutic NAC may be restricted to the ASM.
doi:10.1371/journal.pone.0080782
PMCID: PMC3832609  PMID: 24260479
5.  Structure Reveals Regulatory Mechanisms of a MaoC-Like Hydratase from Phytophthora capsici Involved in Biosynthesis of Polyhydroxyalkanoates (PHAs) 
PLoS ONE  2013;8(11):e80024.
Background
Polyhydroxyalkanoates (PHAs) have attracted increasing attention as “green plastic” due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC), which belongs to (R)-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R)-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic.
Methodology/Principal Findings
We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R)-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC.
Conclusions/Significance
The data in our study reveal the regulatory mechanism of an (R)-hydratase, providing information on enzyme engineering to produce low cost PHAs.
doi:10.1371/journal.pone.0080024
PMCID: PMC3823801  PMID: 24244597
6.  Fine mapping and epistatic interactions of the vernalization gene VRN-D4 in hexaploid wheat 
Wheat vernalization requirement is mainly controlled by the VRN1, VRN2, VRN3, and VRN4 genes. The first three have been cloned and have homoeologs in all three genomes. VRN4 has been found only in the D genome (VRN-D4) and has not been cloned. We constructed a high-density genetic map of the VRN-D4 region and mapped VRN-D4 within a 0.09 cM interval in the centromeric region of chromosome 5D. Using telocentric 5D chromosomes generated from the VRN-D4 donor Triple Dirk F, we determined that VRN-D4 is located on the short arm. The VRN-D4 candidate region is colinear with a 2.24 Mb region on Brachypodium distachyon chromosome 4, which includes 127 predicted genes. Ten of these genes have predicted roles in development but we detected no functional polymorphisms associated to VRN-D4. Two recombination events separated VRN-D4 from TaVIL-D1, the wheat homolog of Arabidopsis vernalization gene VIL1, confirming that this gene is not a candidate for VRN-D4. We detected significant interactions between VRN-D4 and other four genes controlling vernalization requirement (Vrn-A1, Vrn-B1, Vrn-D1, and Vrn-B3), which confirmed that VRN-D4 is part of the vernalization pathway and that it is either upstream or is part of the regulatory feedback loop involving VRN1, VRN2 and VRN3 genes. The precise mapping of VRN-D4 and the characterization of its interactions with other vernalization genes provide valuable information for the utilization of VRN-D4 in wheat improvement and for our current efforts to clone this vernalization gene.
Electronic supplementary material
The online version of this article (doi:10.1007/s00438-013-0788-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s00438-013-0788-y
PMCID: PMC3916708  PMID: 24213553
Wheat; Vernalization; VRN-D4; VRN1; Genetic mapping; VIL; Flowering
7.  Structural and biomechanical basis of mitochondrial movement in eukaryotic cells 
Mitochondria serve as energy-producing organelles in eukaryotic cells. In addition to providing the energy supply for cells, the mitochondria are also involved in other processes, such as proliferation, differentiation, information transfer, and apoptosis, and play an important role in regulation of cell growth and the cell cycle. In order to achieve these functions, the mitochondria need to move to the corresponding location. Therefore, mitochondrial movement has a crucial role in normal physiologic activity, and any mitochondrial movement disorder will cause irreparable damage to the organism. For example, recent studies have shown that abnormal movement of the mitochondria is likely to be the reason for Charcot–Marie–Tooth disease, amyotrophic lateral sclerosis, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and schizophrenia. So, in the cell, especially in the particular polarized cell, the appropriate distribution of mitochondria is crucial to the function and survival of the cell. Mitochondrial movement is mainly associated with the cytoskeleton and related proteins. However, those components play different roles according to cell type. In this paper, we summarize the structural basis of mitochondrial movement, including microtubules, actin filaments, motor proteins, and adaptin, and review studies of the biomechanical mechanisms of mitochondrial movement in different types of cells.
doi:10.2147/IJN.S52132
PMCID: PMC3810443  PMID: 24187495
mitochondrial movement; microtubules; actin filaments; motor proteins; adaptin
8.  Multicomponent Assembly of Highly Substituted Indoles via Coupled Palladium Catalyzed Coupling Reactions** 
A palladium-catalyzed reaction is presented for the synthesis of highly substituted indoles involving three independent components in a one-pot reaction. Two distinct palladium catalyzed coupling reactions occur using a single catalytic system: a Buchwald-Hartwig reaction and an arene-alkene coupling. Quantum chemical computations provide insight into the mechanism of the latter coupling step.
doi:10.1002/anie.201204633
PMCID: PMC3517165  PMID: 23001913
indole methodology; multicomponent; palladium catalysis
9.  Nuclear Factor κ-B Is Activated in the Pulmonary Vessels of Patients with End-Stage Idiopathic Pulmonary Arterial Hypertension 
PLoS ONE  2013;8(10):e75415.
Objectives
To assess activation of the inflammatory transcription factor NF-kappa B (NF-κB) in human idiopathic pulmonary arterial hypertension (PAH).
Background
Idiopathic PAH is a severe progressive disease characterized by pulmonary vascular remodeling and excessive proliferation of vascular cells. Increasing evidence indicates that inflammation is important in disease pathophysiology.
Methods
NF-κB-p65 and CD68, CD20 and CD45 were measured by immunohistochemistry and confocal microscopy on lung specimens from patients with idiopathic PAH (n = 12) and controls undergoing lung surgery (n = 14). Clinical data were recorded for all patients including invasive pulmonary hemodynamics for the PAH patients. Immunohistochemical images were analyzed by blinded observers to include standard pulmonary vascular morphometry; absolute macrophage counts/mm2 and p65-positivity (p65+) using composite images and image-analysis software; and cytoplasmic:nuclear p65+ of individual pulmonary arterial endothelial and smooth muscle cells (PASMC) in 10–20 pulmonary arteries or arterioles per subject. The expression of ET-1 and CCL5 (RANTES) in whole lung was determined by RT-qPCR.
Results
Macrophage numbers were increased in idiopathic PAH versus controls (49.0±4.5 vs. 7.95±1.9 macrophages/100 mm2, p<0.0001): these macrophages demonstrated more nuclear p65+ than in macrophages from controls (16.9±2.49 vs. 3.5±1.25%, p<0.001). An increase in p65+ was also seen in perivascular lymphocytes in patients with PAH. Furthermore, NF-κB activation was increased in pulmonary arterial endothelial cells (62.3±2.9 vs. 14.4±3.8, p<0.0001) and PASMC (22.6±2.3 vs. 11.2±2.0, p<0.001) in patients with PAH versus controls, with similar findings in arterioles. Gene expression of both ET-1 mRNA ((0.213±0.069 vs. 1.06±0.23, p<0.01) and CCL5 (RANTES) (0.16±0.045 vs. 0.26±0.039, p<0.05) was increased in whole lung homogenates from patients with PAH.
Conclusions
NF-κB is activated in pulmonary macrophages, lymphocytes, endothelial and PASMC in patients with end-stage idiopathic PAH. Future research should determine whether NF-κB activation is a driver or bystander of pulmonary vascular inflammation and if the former, its potential role as a therapeutic target.
doi:10.1371/journal.pone.0075415
PMCID: PMC3790752  PMID: 24124488
10.  Evidence of an anti-apoptotic effect of qinghuobaiduyin on intestinal mucosa following burn injury 
Burn injuries are common in wartime and in times of peace. The prevention and therapy of ischemia-reperfusion injury to the organs, in particular the intestine, during the burn shock and recovery process has become a popular yet challenging area of research. Studies concerning the apoptosis of the cells of the burned intestinal mucosa have gained considerable attention. Qinghuobaiduyin (QHBDY) is a traditional Chinese medicine that has been used as a clinical prescription since 1995 to treat burn patients due to its opsonization function in the immune system and favorable clinical therapeutic effect. The aim of this study was to investigate the effect of QHBDY on the apoptosis of intestinal mucosa following burn injury. An animal model was constructed comprising severely burned rats that were treated with various dosages of QHBDY. Tissues from the small intestine were collected to investigate the apoptosis rate by TUNEL assay and the protein expression levels of heat shock protein 70 (Hsp70) and caspase-3 by immunohistochemistry. In addition, IEC-18 cells treated with QHBDY and burn serum were investigated. The cell apoptosis rate was analyzed by flow cytometry (FCM), the protein expression levels of Hsp70 were measured by western blot analysis and caspase-3 activity was analyzed by a colorimetric assay. The results showed that in animal experiments, compared with the burned group, the apoptosis rates in the treatment group was decreased, the protein expression level of Hsp70 was increased while Caspase-3 was decreased. In cell experiments, after treatment with QHBDY, the cell apoptosis rate was lower than that of the burn serum group. In addition, Hsp70 protein expression was upregulated and caspase-3 activity was decreased. QHBDY may play an important role in the prevention of apoptosis at the whole animal and cellular levels.
doi:10.3892/etm.2013.1314
PMCID: PMC3829758  PMID: 24255668
qinghuobaiduyin; burn injury; apoptosis; intestinal mucosa
11.  Smad3 Inactivation and MiR-29b Upregulation Mediate the Effect of Carvedilol on Attenuating the Acute Myocardium Infarction-Induced Myocardial Fibrosis in Rat 
PLoS ONE  2013;8(9):e75557.
Carvedilol, a nonselective β-adrenoreceptor antagonist, protects against myocardial injury induced by acute myocardium infarction (AMI). The mechanisms underlying the anti-fibrotic effects of carvedilol are unknown. Recent studies have revealed the critical role of microRNAs (miRNAs) in a variety of cardiovascular diseases. This study investigated whether miR-29b is involved in the cardioprotective effect of carvedilol against AMI-induced myocardial fibrosis. Male SD rats were randomized into several groups: the sham surgery control, left anterior descending (LAD) surgery-AMI model, AMI plus low-dose carvedilol treatment (1 mg/kg per day, CAR-L), AMI plus medium-dose carvedilol treatment (5 mg/kg per day, CAR-M) and AMI plus high-dose carvedilol treatment (10 mg/kg per day, CAR-H). Cardiac remodeling and impaired heart function were observed 4 weeks after LAD surgery treatment; the observed cardiac remodeling, decreased ejection fraction, and fractional shortening were rescued in the CAR-M and CAR-H groups. The upregulated expression of Col1a1, Col3a1, and α-SMA mRNA was significantly reduced in the CAR-M and CAR-H groups. Moreover, the downregulated miR-29b was elevated in the CAR-M and CAR-H groups. The in vitro study showed that Col1a1, Col3a1, and α-SMA were downregulated and miR-29b was upregulated by carvedilol in a dose-dependent manner in rat cardiac fibroblasts. Inhibition of ROS-induced Smad3 activation by carvedilol resulted in downregulation of Col1a1, Col3a1, and α-SMA and upregulation of miR-29b derived from the miR-29b-2 precursor. Enforced expression of miR-29b significantly suppressed Col1a1, Col3a1, and α-SMA expression. Taken together, we found that smad3 inactivation and miR-29b upregulation contributed to the cardioprotective activity of carvedilol against AMI-induced myocardial fibrosis.
doi:10.1371/journal.pone.0075557
PMCID: PMC3783413  PMID: 24086569
12.  C4-Alkoxy-HPD: a Potent Class of Synthetic Modulators Surpassing Nature in AI-2 Quorum Sensing 
Journal of the American Chemical Society  2012;134(33):13562-13564.
Bacteria have developed cell-to-cell communication mechanisms, termed quorum sensing (QS), which regulate bacterial gene expression in a cell population-dependent manner. Autoinducer-2 (AI-2), a class of QS signaling molecules derived from (4S)-4,5-dihydroxy-2,3-pentanedione (DPD), has been identified in both Gram-negative and Gram-positive bacteria. Despite considerable interest in the AI-2 QS system, the biomolecular communication used by distinct bacterial species still remains shrouded. Herein we report the synthesis and evaluation of a new class of DPD analogs, C4-alkoxy-5-hydroxy-2,3-pentanediones, termed C4-alkoxy-HPDs. Remarkably, two of the analogs were more potent QS agonists than the natural ligand, DPD, in Vibrio harveyi. The findings presented extend insights into ligand-receptor recognition/signaling in the AI-2 mediated QS system.
doi:10.1021/ja305532y
PMCID: PMC3438919  PMID: 22866957
13.  Accurate Quantification of microRNA via Single Strand Displacement Reaction on DNA Origami Motif 
PLoS ONE  2013;8(8):e69856.
DNA origami is an emerging technology that assembles hundreds of staple strands and one single-strand DNA into certain nanopattern. It has been widely used in various fields including detection of biological molecules such as DNA, RNA and proteins. MicroRNAs (miRNAs) play important roles in post-transcriptional gene repression as well as many other biological processes such as cell growth and differentiation. Alterations of miRNAs' expression contribute to many human diseases. However, it is still a challenge to quantitatively detect miRNAs by origami technology. In this study, we developed a novel approach based on streptavidin and quantum dots binding complex (STV-QDs) labeled single strand displacement reaction on DNA origami to quantitatively detect the concentration of miRNAs. We illustrated a linear relationship between the concentration of an exemplary miRNA as miRNA-133 and the STV-QDs hybridization efficiency; the results demonstrated that it is an accurate nano-scale miRNA quantifier motif. In addition, both symmetrical rectangular motif and asymmetrical China-map motif were tested. With significant linearity in both motifs, our experiments suggested that DNA Origami motif with arbitrary shape can be utilized in this method. Since this DNA origami-based method we developed owns the unique advantages of simple, time-and-material-saving, potentially multi-targets testing in one motif and relatively accurate for certain impurity samples as counted directly by atomic force microscopy rather than fluorescence signal detection, it may be widely used in quantification of miRNAs.
doi:10.1371/journal.pone.0069856
PMCID: PMC3749204  PMID: 23990889
14.  Comparison of Toxicity of Benzene Metabolite Hydroquinone in Hematopoietic Stem Cells Derived from Murine Embryonic Yolk Sac and Adult Bone Marrow 
PLoS ONE  2013;8(8):e71153.
Benzene is an occupational toxicant and an environmental pollutant that potentially causes hematotoxicity and leukemia in exposed populations. Epidemiological studies suggest an association between an increased incidence of childhood leukemia and benzene exposure during the early stages of pregnancy. However, experimental evidence supporting the association is lacking at the present time. It is believed that benzene and its metabolites target hematopoietic stem cells (HSCs) to cause toxicity and cancer in the hematopoietic system. In the current study, we compared the effects of hydroquinone (HQ), a major metabolite of benzene in humans and animals, on mouse embryonic yolk sac hematopoietic stem cells (YS-HSCs) and adult bone marrow hematopoietic stem cells (BM-HSCs). YS-HSCs and BM-HSCs were isolated and enriched, and were exposed to HQ at increasing concentrations. HQ reduced the proliferation and the differentiation and colony formation, but increased the apoptosis of both YS-HSCs and BM-HSCs. However, the cytotoxic and apoptotic effects of HQ were more apparent and reduction of colony formation by HQ was more severe in YS-HSCs than in BM-HSCs. Differences in gene expression profiles were observed in HQ-treated YS-HSCs and BM-HSCs. Cyp4f18 was induced by HQ both in YS-HSCs and BM-HSCs, whereas DNA-PKcs was induced in BM-HSCs only. The results revealed differential effects of benzene metabolites on embryonic and adult HSCs. The study established an experimental system for comparison of the hematopoietic toxicity and leukemogenicity of benzene and metabolites during mouse embryonic development and adulthood.
doi:10.1371/journal.pone.0071153
PMCID: PMC3734044  PMID: 23940708
15.  mGluR5 Ablation in Cortical Glutamatergic Neurons Increases Novelty-Induced Locomotion 
PLoS ONE  2013;8(8):e70415.
The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R) dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.
doi:10.1371/journal.pone.0070415
PMCID: PMC3734292  PMID: 23940572
16.  An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation 
PLoS Pathogens  2013;9(8):e1003520.
Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo.
Author Summary
Viruses exploit receptors on the host cell to cause infection. Therapies aimed at blocking virus-receptor interactions have the potential to prevent viral disease. Cellular receptors are also important for normal host cell function. Therefore, new therapies targeting these receptors to block viral infection may also inadvertently alter the physiology of the host cell. Viral pathogens, such as the cold virus (rhinovirus), are believed to be the major cause of asthma attacks and exacerbations in chronic obstructive pulmonary disease (COPD). In this study, we show that it is possible to identify novel therapeutic antibodies that block infection with rhinovirus without impairing the receptors' main function of cell adhesion. We then use animal models that show that an antibody can inhibit virus-induced lung inflammation and disease. Moreover, we show that this antibody can also inhibit a virally induced asthma exacerbation. This work is relevant in that it shows that antibodies can be tailored to distinct regions of viral receptors to block infection without inhibiting the receptors' normal cellular function. This is important for the development of new treatments that will prevent diseases caused by infection with rhinovirus, such as exacerbations of asthma and COPD.
doi:10.1371/journal.ppat.1003520
PMCID: PMC3731244  PMID: 23935498
17.  Triple versus dual antiplatelet therapy for coronary heart disease patients undergoing percutaneous coronary intervention: A meta-analysis 
Coronary heart disease (CHD) is the leading cause of mortality worldwide. Previous studies have suggested that cilostazol-based triple antiplatelet therapy (TAT) may be more effective than conventional dual antiplatelet therapy (DAT) at improving the clinical outcomes of patients with CHD undergoing percutaneous coronary intervention (PCI). However, individually published results are inconclusive. The present meta-analysis evaluated controlled clinical studies to compare the clinical outcomes between TAT and DAT in patients with CHD undergoing PCI. Ten controlled clinical studies were included, with a total of 7,670 patients with CHD undergoing PCI. The total number included 3,925 patients treated with DAT (aspirin and clopidogrel) and 3745 patients treated with TAT (addition of cilostazol to DAT). The crude odds ratio (OR) with a 95% confidence interval (CI) was calculated with either the fixed or random effects model. The meta-analysis results indicated that patients in the TAT group had a significantly lower rate of restenosis compared with that of the DAT group (OR=0.59, 95% CI: 0.45–0.77; P<0.001). The rate of major adverse cardiac events (MACE) and target lesion revascularization (TLR) in the TAT group were significantly lower compared with those in the DAT group (MACE: OR=0.69, 95% CI: 0.56–0.85, P<0.001; TLR: OR=0.61, 95% CI: 0.43–0.88, P=0.008). However, no significant differences between the TAT and DAT groups in terms of mortality rate, myocardial infarction, target vessel revascularization and stent thrombosis were observed. In conclusion, the results of the present meta-analysis indicated that the efficacy and safety of cilostazol-based TAT therapy is greater than that of conventional DAT therapy for patients with CHD undergoing PCI.
doi:10.3892/etm.2013.1238
PMCID: PMC3797250  PMID: 24137311
cilostazol; antiplatelet therapy; percutaneous coronary intervention; coronary heart disease; meta-analysis
18.  Are Onconeural Antibodies a Clinical Phenomenology in Paraneoplastic Limbic Encephalitis? 
Mediators of Inflammation  2013;2013:172986.
Paraneoplastic neurological syndromes (PNSs) occur in patients with cancer and can cause clinical symptoms and signs of dysfunction of the nervous system that are not due to a local effect of the tumor or its metastases. Most of these clinical syndromes in adults are associated with lung cancer, especially small cell lung cancer (SCLC), lymphoma, and gynecological tumors. The finding of highly specific antibodies directed against onconeural antigens has revolutionized the diagnosis and promoted the understanding of these syndromes and led to the current hypothesis of an autoimmune pathophysiology. Accumulating data strongly suggested direct pathogenicity of these antibodies. The field of PNS has expanded rapidly in the past few years with the discovery of limbic encephalitis associated with glutamic acid decarboxylase (GAD) 65, the voltage (VGKC-gated potassium channel) complex, the methyl (N-NMDA-D-aspartate), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and gamma aminobutyric acid (GABA) (B) receptors, and so forth. Despite this, the clinical spectrum of these diseases has not yet been fully investigated. The clinical importance of these conditions lies in their frequent response to immunotherapies and, less commonly, their association with distinctive tumors. This review provides an overview on the pathogenesis and diagnosis of PNS, with emphasis on the role of antibodies in limbic encephalitis.
doi:10.1155/2013/172986
PMCID: PMC3745958  PMID: 23983403
19.  Isolation and characterization of LHT-type plant amino acid transporter gene from Panax ginseng Meyer 
Journal of Ginseng Research  2013;37(3):361-370.
A lysine histidine transporter (LHT) cDNA was isolated and characterized from the roots of Panax ginseng, designated PgLHT. The cDNA is 1,865 bp with an open reading frame that codes for a protein with 449 amino acids and a calculated molecular mass of 50.6 kDa with a predicted isoelectric point of 8.87. Hydropathy analysis shows that PgLHT is an integral membrane protein with 9 putative membrane-spanning domains. Multiple sequence alignments show that PgLHT shares a high homology with other plant LHTs. The expression profile of the gene was investigated by real-time quantitative polymerase chain reaction during various chemical treatments. PgLHT was up-regulated in the presence of abscisic acid, salicylic acid, methyl jasmonate, NaCl, and amino acids. To further explore the function of PgLHT gene, full-length cDNA of PgLHT was introduced into P. ginseng by Agrobacterium rhizogenes A4. The overexpression of PgLHT in the hairy roots led to an obviously increase of biomass compared to the controls, and after addition of the amino acids, the overexpressed-PgLHT hairy roots grew more rapidly than untreated controls during early stage of the culture cycle. The results suggested that the PgLHT isolated from ginseng might have role in the environmental stresses and growth response.
doi:10.5142/jgr.2013.37.361
PMCID: PMC3818964  PMID: 24198663
Panax ginseng; LHT gene; Abiotic stresses; Real-time quantitative polymerase chain reaction
20.  Performance of breast cancer screening methods and modality among Chinese women: a report from a society-based breast screening program (SBSP) in Shanghai 
SpringerPlus  2013;2:276.
To evaluate the screening performance of individual and combined use of clinical breast examination, ultrasonography and mammography in Chinese women, we conducted a biennial breast cancer screening program among 14,464 women aged 35 to 74 years old who lived in Qibao County, Minhang district of Shanghai, China, between May 2008 and Sept 2012. All participants were submitted to clinical breast examination, and then women with positive results and all women at age of 45-69 years old were preformed breast ultrasonography and mammography. The examination results were compared against pathological findings as the gold standard of reference. A total of 66 women were diagnosed with breast cancer in the two rounds of the screening, yielding an incident rate of 194 per 100,000 person-years. The sensitivity of clinical breast examination, ultrasonography and mammography alone were 61.4%, 53.7% and 67.3%, respectively. While mammography performed better in elder age groups and hormone receptor positive disease groups, ultrasonography had a higher sensitivity in younger age group and did not differ in sensitivity by estrogen receptor or progesterone receptor status. Combined use of the two imaging examinations increased the sensitivity in almost all age groups, but had a higher sensitivity in hormone receptor positive cancers than in those negative. Our results suggest that the Qibao modality is an effective strategy for breast cancer screening among Chinese women, especially for early detection of elder and hormone receptor positive breast cancer.
doi:10.1186/2193-1801-2-276
PMCID: PMC3724976  PMID: 23961381
Breast cancer screening; Clinical breast examination; Mammography; Breast ultrasonography; Sensitivity; Specificity
21.  Retraction: Stereochemical Insignificance Discovered in Acinetobacter baumannii Quorum Sensing 
PLoS ONE  2013;8(5):10.1371/annotation/1345f9b0-016e-4123-9e72-6ccc4fa17ba2.
doi:10.1371/annotation/1345f9b0-016e-4123-9e72-6ccc4fa17ba2
PMCID: PMC3655197  PMID: 23690906
22.  Acoustic rainbow trapping 
Scientific Reports  2013;3:1728.
Spatial modulation of sound velocity below the wavelength scale can introduce strong frequency-dependent acoustic responses in tailored composite materials, regardless the fact that most natural bulk materials have negligible acoustic dispersions. Here, for the first time, we experimentally demonstrate a metamaterial that traps broadband acoustic waves and spatially separates different frequency components, as the result of dispersion and wave velocity control by designed gradient subwavelength structures. The trapping positions can be predicted by the microscopic picture of balanced interplay between the acoustic resonance inside individual apertures and the mutual coupling among them. With the enhanced wave-structure interactions and the tailored frequency responses, such metamaterial allows precise spatial-spectral control of acoustic waves and opens new venue for high performance acoustic wave sensing, filtering, and nondestructive metrology.
doi:10.1038/srep01728
PMCID: PMC3635056
23.  Retraction: Stereochemical Insignificance Discovered in Acinetobacter baumannii Quorum Sensing 
PLoS ONE  2013;8(4):10.1371/annotation/8f2ddf91-3499-4627-9a91-449b78465f9d.
doi:10.1371/annotation/8f2ddf91-3499-4627-9a91-449b78465f9d
PMCID: PMC3634625  PMID: 23853689
24.  Genome Sequence of a Novel Reassortant H3N2 Avian Influenza Virus from Domestic Mallard Ducks in Eastern China 
Genome Announcements  2013;1(2):e00221-12.
The H3 subtype avian influenza virus (AIV) can provide genes for human influenza virus through gene reassortment, which raises great concerns in terms of its potential threat to human health. Here, we report the complete genome sequence of a novel H3N2 AIV isolated from domestic ducks in the Jiangsu province of eastern China in 2004, which is a natural recombinant virus whose genes are derived from H3N8, H5N1, H5N2, H11N2, H4N6, and H1N1 AIVs. This genome will help to understand the epidemiology and molecular characteristics of H3N2 influenza virus in eastern China.
doi:10.1128/genomeA.00221-12
PMCID: PMC3624687  PMID: 23580713
25.  Prioritization of candidate disease genes by topological similarity between disease and protein diffusion profiles 
BMC Bioinformatics  2013;14(Suppl 5):S5.
Background
Identification of gene-phenotype relationships is a fundamental challenge in human health clinic. Based on the observation that genes causing the same or similar phenotypes tend to correlate with each other in the protein-protein interaction network, a lot of network-based approaches were proposed based on different underlying models. A recent comparative study showed that diffusion-based methods achieve the state-of-the-art predictive performance.
Results
In this paper, a new diffusion-based method was proposed to prioritize candidate disease genes. Diffusion profile of a disease was defined as the stationary distribution of candidate genes given a random walk with restart where similarities between phenotypes are incorporated. Then, candidate disease genes are prioritized by comparing their diffusion profiles with that of the disease. Finally, the effectiveness of our method was demonstrated through the leave-one-out cross-validation against control genes from artificial linkage intervals and randomly chosen genes. Comparative study showed that our method achieves improved performance compared to some classical diffusion-based methods. To further illustrate our method, we used our algorithm to predict new causing genes of 16 multifactorial diseases including Prostate cancer and Alzheimer's disease, and the top predictions were in good consistent with literature reports.
Conclusions
Our study indicates that integration of multiple information sources, especially the phenotype similarity profile data, and introduction of global similarity measure between disease and gene diffusion profiles are helpful for prioritizing candidate disease genes.
Availability
Programs and data are available upon request.
doi:10.1186/1471-2105-14-S5-S5
PMCID: PMC3622672  PMID: 23734762

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