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1.  Surrounding Sensitive Electronic Properties of Bi2Te3 Nanoplates—Potential Sensing Applications of Topological Insulators 
Scientific Reports  2014;4:4639.
Significant efforts have been paid to exploring the fundamental properties of topological insulators (TIs) in recent years. However, the investigation of TIs as functional materials for practical device applications is still quite limited. In this work, electronic sensors based on Bi2Te3 nanoplates were fabricated and the sensing performance was investigated. On exposure to different surrounding environments, significant changes in the conducting properties were observed by direct electrical measurements. These results suggest that nanostructured TIs hold great potential for sensing applications.
doi:10.1038/srep04639
PMCID: PMC3982166  PMID: 24717774
2.  Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism 
Scientific Reports  2014;4:4628.
The development of antitumor chemotherapy drugs remains a key goal for oncologists, and natural products provide a vast resource for anti-cancer drug discovery. In the current study, we found that the flavonoid dihydromyricetin (DHM) exhibited antitumor activity against liver cancer cells, including primary cells obtained from hepatocellular carcinoma (HCC) patients. In contrast, DHM was not cytotoxic to immortalized normal liver cells. Furthermore, DHM treatment resulted in the growth inhibition and remission of xenotransplanted tumors in nude mice. Our results further demonstrated that this antitumor activity was caused by the activation of the p53-dependent apoptosis pathway via p53 phosphorylation at serine (15Ser). Moreover, our results showed that DHM plays a dual role in the induction of cell death when administered in combination with cisplatin, a common clinical drug that kills primary hepatoma cells but not normal liver cells.
doi:10.1038/srep04628
PMCID: PMC3982169  PMID: 24717393
3.  Effect of an Eye Health Education Program on Older African Americans' Eye Care Utilization and Attitudes about Eye Care 
We examined the impact of an eye health education program for older African Americans on attitudes about eye care and utilization, using a randomized trial design in a community setting. Participants were older African Americans attending activities at senior centers. Ten centers were randomized to an eye health education (InCHARGE©) or social-contact control presentation. InCHARGE© addressed the importance of annual dilated comprehensive examination and strategies reducing barriers to care. The control presentation was on the importance of physical activity. Outcomes were attitudes about eye care through questionnaire 6 months post-event, and eye care utilization during 12 months post-event through medical record abstraction. At baseline > 80% participants in both arms said transportation and finding, communicating, and trusting a doctor were not problematic and agreed that yearly care was important. One-fourth said eye examination cost was problematic; one-half said spectacle cost was problematic. There were no group differences 6 months post-event. During 12 months pre-event, dilated exam rate was similar in the groups (38.3% InCHARGE©, 40.8% control), and unchanged during 12 months post-event. Results suggest less than half of older African Americans received annual dilated eye care. Group-administered eye health education did not increase this rate. Even before the program, they had positive attitudes about care, yet many cited examination and spectacle cost as problematic, which was not mitigated by health education. Evidence-based strategies in a community setting for increasing eye care utilization rate in older African Americans have yet to be identified. Policy changes may be more appropriate avenues for addressing cost.
PMCID: PMC3718503  PMID: 23862298
eye care utilization; eye health education; barriers to care
4.  Inhibition of Hepatitis C Virus Infection by DNA Aptamer against Envelope Protein 
Antimicrobial Agents and Chemotherapy  2013;57(10):4937-4944.
Hepatitis C virus (HCV) envelope protein (E1E2) is essential for virus binding to host cells. Aptamers have been demonstrated to have strong promising applications in drug development. In the current study, a cDNA fragment encoding the entire E1E2 gene of HCV was cloned. E1E2 protein was expressed and purified. Aptamers for E1E2 were selected by the method of selective evolution of ligands by exponential enrichment (SELEX), and the antiviral actions of the aptamers were examined. The mechanism of their antiviral activity was investigated. The data show that selected aptamers for E1E2 specifically recognize the recombinant E1E2 protein and E1E2 protein from HCV-infected cells. CD81 protein blocks the binding of aptamer E1E2-6 to E1E2 protein. Aptamers against E1E2 inhibit HCV infection in an infectious cell culture system although they have no effect on HCV replication in a replicon cell line. Beta interferon (IFN-β) and IFN-stimulated genes (ISGs) are not induced in virus-infected hepatocytes with aptamer treatment, suggesting that E1E2-specific aptamers do not induce innate immunity. E2 protein is essential for the inhibition of HCV infection by aptamer E1E2-6, and the aptamer binding sites are located in E2. Q412R within E1E2 is the major resistance substitution identified. The data indicate that an aptamer against E1E2 exerts its antiviral effects through inhibition of virus binding to host cells. Aptamers against E1E2 can be used with envelope protein to understand the mechanisms of HCV entry and fusion. The aptamers may hold promise for development as therapeutic drugs for hepatitis C patients.
doi:10.1128/AAC.00897-13
PMCID: PMC3811438  PMID: 23877701
5.  A Cucumber DELLA Homolog CsGAIP May Inhibit Staminate Development through Transcriptional Repression of B Class Floral Homeotic Genes 
PLoS ONE  2014;9(3):e91804.
In hermaphroditic Arabidopsis, the phytohormone gibberellin (GA) stimulates stamen development by opposing the DELLA repression of B and C classes of floral homeotic genes. GA can promote male flower formation in cucumber (Cucumis sativus L.), a typical monoecious vegetable with unisexual flowers, and the molecular mechanism remains unknown. Here we characterized a DELLA homolog CsGAIP in cucumber, and we found that CsGAIP is highly expressed in stem and male flower buds. In situ hybridization showed that CsGAIP is greatly enriched in the stamen primordia, especially during the hermaphrodite stage of flower development. Further, CsGAIP protein is located in nucleus. CsGAIP can partially rescue the plant height, stamen development and fertility phenotypes of Arabidopsis rga-24/gai-t6 mutant, and ectopic expression of CsGAIP in wide-type Arabidopsis results in reduced number of stamens and decreased transcription of B class floral homeotic genes APETALA3 (AP3) and PISTILLATA (PI). Our data suggest that monoecious CsGAIP may inhibit staminate development through transcriptional repression of B class floral homeotic genes in Arabidopsis.
doi:10.1371/journal.pone.0091804
PMCID: PMC3954735  PMID: 24632777
6.  MiR-132 Suppresses the Migration and Invasion of Lung Cancer Cells via Targeting the EMT Regulator ZEB2 
PLoS ONE  2014;9(3):e91827.
MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. Emerging evidence reveals that deregulation of miRNAs contributes to the human non-small cell lung cancer (NSCLC). In the present study, we demonstrated that the expression levels of miR-132 were dramatically decreased in examined NSCLC cell lines and clinical NSCLC tissue samples. Then, we found that introduction of miR-132 significantly suppressed the migration and invasion of lung cancer cells in vitro, suggesting that miR-132 may be a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor ZEB2 was one direct target genes of miR-132, evidenced by the direct binding of miR-132 with the 3′ untranslated region (3′ UTR) of ZEB2. Further, miR-132 could decrease the expression of ZEB2 at the levels of mRNA and protein. Notably, the EMT marker E-cadherin or vimentin, a downstream of ZEB2, was also down-regulated or up-regulated upon miR-132 treatment. Additionally, over-expressing or silencing ZEB2 was able to elevate or inhibit the migration and invasion of lung cancer cells, parallel to the effect of miR-132 on the lung cancer cells. Meanwhile, knockdown of ZEB2 reversed the enhanced migration and invasion mediated by anti-miR-132. These results indicate that miR-132 suppresses the migration and invasion of NSCLC cells through targeting ZEB2 involving the EMT process. Thus, our finding provides new insight into the mechanism of NSCLC progression. Therapeutically, miR-132 may serve as a potential target in the treatment of human lung cancer.
doi:10.1371/journal.pone.0091827
PMCID: PMC3953608  PMID: 24626466
7.  Encapsulation of MnO Nanocrystals in Electrospun Carbon Nanofibers as High-Performance Anode Materials for Lithium-Ion Batteries 
Scientific Reports  2014;4:4229.
A novel and controllable approach is developed for the synthesis of MnO nanocrystals embedded in carbon nanofibers (MnO/CNFs) through an electrospinning process. The as-formed MnO/CNFs have a porous structure with diameters of 100–200 nm and lengths up to several millimeters. When used as an anode material for lithium-ion batteries, the resulting MnO/CNFs exhibit superior electrochemical performances with high specific capacity, good cyclability, and excellent rate capability. The unique porous carbon nanofibers (PCNFs) can not only improve the contact area between the electrode and the electrolyte, but also alleviate the impact of the large volume effect of MnO during the electrochemical cycling. It is expected that the present synthetic strategy can be extended to synthesize other nanostructured oxides encapsulated in carbon nanofibers for extensive energy transfer and storage applications.
doi:10.1038/srep04229
PMCID: PMC3944319  PMID: 24598639
8.  Sequential Isolation in a Patient of Raoultella planticola and Escherichia coli Bearing a Novel ISCR1 Element Carrying blaNDM-1 
PLoS ONE  2014;9(3):e89893.
Background
The gene for New Delhi metallo-β-lactamase 1 (NDM-1) has been reported to be transmitted via plasmids which are easily transferable and capable of wide distribution. We report the isolation of two NDM-1 producing strains and possible in vivo transfer of blaNDM-1 in a patient.
Methods
Clinical samples were collected for bacterial culture and antibiotic susceptibility testing from a patient during a 34-day hospitalization. The presence of blaNDM-1 was detected by PCR and sequencing. Plasmids of interest were sequenced. Medical records were reviewed for evidence of association between the administration of antibiotics and the acquisition of the NDM-1 resistance.
Results
A NDM-1 positive Raoultella planticola was isolated from blood on the ninth day of hospitalization without administration of any carbapenem antibiotics and a NDM-1 positive Escherichia coli was isolated from feces on the 29th day of hospitalization and eight days after imipenem administration. The blaNDM-1 was carried by a 280 kb plasmid pRpNDM1-1 in R. planticola and a 58 kb plasmid pEcNDM1-4 in E. coli. The two plasmids shared a 4812 bp NDM-1-ISCR1 element which was found to be excisable from the plasmid as a free form and transferrable in vitro to a NDM-1 negative plasmid from E. coli.
Conclusion
blaNDM-1 was embedded in an ISCR1 complex class 1 integron as a novel 4812 bp NDM-1-ISCR1 element. The element was found to be able to self excise to become a free form, which may provide a new vehicle for NDM-1 dissemination. This mechanism could greatly accelerate the spread of NDM-1 mediated broad spectrum β-lactam resistance.
doi:10.1371/journal.pone.0089893
PMCID: PMC3940617  PMID: 24594606
9.  Exposure to Diflubenzuron Results in an Up-Regulation of a Chitin Synthase 1 Gene in Citrus Red Mite, Panonychus citri (Acari: Tetranychidae) 
Chitin synthase synthesizes chitin, which is critical for the arthropod exoskeleton. In this study, we cloned the cDNA sequences of a chitin synthase 1 gene, PcCHS1, in the citrus red mite, Panonychus citri (McGregor), which is one of the most economically important pests of citrus worldwide. The full-length cDNA of PcCHS1 contains an open reading frame of 4605 bp of nucleotides, which encodes a protein of 1535 amino acid residues with a predicted molecular mass of 175.0 kDa. A phylogenetic analysis showed that PcCHS1 was most closely related to CHS1 from Tetranychus urticae. During P. citri development, PcCHS1 was constantly expressed in all stages but highly expressed in the egg stage (114.8-fold higher than in the adult). When larvae were exposed to diflubenzuron (DFB) for 6 h, the mite had a significantly high mortality rate, and the mRNA expression levels of PcCHS1 were significantly enhanced. These results indicate a promising use of DFB to control P. citri, by possibly acting as an inhibitor in chitin synthesis as indicated by the up-regulation of PcCHS1 after exposure to DFB.
doi:10.3390/ijms15033711
PMCID: PMC3975363  PMID: 24590130
Panonychus citri; chitin synthase 1; diflubenzuron; insect growth regulators; pest control
10.  PIAS1 Regulates Breast Tumorigenesis through Selective Epigenetic Gene Silencing 
PLoS ONE  2014;9(2):e89464.
Epigenetic gene silencing by histone modifications and DNA methylation is essential for cancer development. The molecular mechanism that promotes selective epigenetic changes during tumorigenesis is not understood. We report here that the PIAS1 SUMO ligase is involved in the progression of breast tumorigenesis. Elevated PIAS1 expression was observed in breast tumor samples. PIAS1 knockdown in breast cancer cells reduced the subpopulation of tumor-initiating cells, and inhibited breast tumor growth in vivo. PIAS1 acts by delineating histone modifications and DNA methylation to silence the expression of a subset of clinically relevant genes, including breast cancer DNA methylation signature genes such as cyclin D2 and estrogen receptor, and breast tumor suppressor WNT5A. Our studies identify a novel epigenetic mechanism that regulates breast tumorigenesis through selective gene silencing.
doi:10.1371/journal.pone.0089464
PMCID: PMC3933565  PMID: 24586797
11.  Mutation accumulation and fitness in mutator subpopulations of Escherichia coli 
Biology Letters  2013;9(1):20120961.
Bacterial populations in clinical and laboratory settings contain a significant proportion of mutants with elevated mutation rates (mutators). Mutators have a particular advantage when multiple beneficial mutations are needed for fitness, as in antibiotic resistance. Nevertheless, high mutation rates potentially lead to increasing numbers of deleterious mutations and subsequently to the decreased fitness of mutators. To test how fitness changed with mutation accumulation, genome sequencing and fitness assays of nine Escherichia coli mutY mutators were undertaken in an evolving chemostat population at three time points. Unexpectedly, the fitness in members of the mutator subpopulation became constant despite a growing number of mutations over time. To test if the accumulated mutations affected fitness, we replaced each of the known beneficial mutations with wild-type alleles in a mutator isolate. We found that the other 25 accumulated mutations were not deleterious. Our results suggest that isolates with deleterious mutations are eliminated by competition in a continuous culture, leaving mutators with mostly neutral mutations. Interestingly, the mutator–non-mutator balance in the population reversed after the fitness plateau of mutators was reached, suggesting that the mutator–non-mutator ratio in populations has more to do with competition between members of the population than the accumulation of deleterious mutations.
doi:10.1098/rsbl.2012.0961
PMCID: PMC3565518  PMID: 23221876
bacterial genomics; experimental evolution; mutators
12.  A novel molecular typing method of Mycobacteria based on DNA barcoding visualization 
Different subtypes of Mycobacterium tuberculosis (MTB) may induce diverse severe human infections, and some of their symptoms are similar to other pathogenes, e.g. Nontuberculosis mycobacteria (NTM). So determination of mycobacterium subtypes facilitates the effective control of MTB infection and proliferation. This study exploits a novel DNA barcoding visualization method for molecular typing of 17 mycobacteria genomes published in the NCBI prokaryotic genome database. Three mycobacterium genes (Rv0279c, Rv3508 and Rv3514) from the PE/PPE family of MT Band were detected to best represent the inter-strain pathogenetic variations. An accurate and fast MTB substrain typing method was proposed based on the combination of the aforementioned three biomarker genes and the 16S rRNA gene. The protocol of establishing a bacterial substrain typing system used in this study may also be applied to the other pathogenes.
doi:10.1186/2043-9113-4-4
PMCID: PMC3931916  PMID: 24555538
Mycobacterium; Molecular typing; Typing biomarker; Bioinformatics; Differential diagnosis of mycobacteria
13.  Different microbiological and clinical aspects of lower respiratory tract infections between China and European/American countries 
Journal of Thoracic Disease  2014;6(2):134-142.
Background
National treatment/diagnosis guidelines for lower respiratory tract infections (LRTIs) are generally based on local epidemiological data. Etiology and drug-resistance patterns could differ between China and European/American countries, and simply following their respective guidelines might cause problems in clinical practice. Therefore, we need to summarize the microbiology and clinical manifestations of LRTIs in China and develop our own guidelines.
Methods
Three major national multicenter epidemiology surveillance studies on LRTI were completed recently. The data were compared in detail with those from European/American studies.
Results
Clinical and microbiological differences were observed in community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and pulmonary mycosis between our country and European/American countries.
Conclusions
The microbiological and clinical characteristics of the major LRTIs in China differ in many respects from those in European/American countries. Patients should have personal treatment plans instead of simply following the guidelines from foreign countries
doi:10.3978/j.issn.2072-1439.2014.02.02
PMCID: PMC3944165  PMID: 24605227
Pathogens; epidemiology; antimicrobial resistance; lower respiratory tract infections (LRTIs)
14.  Differential expression of miRNA in rat myocardial tissues under psychological and physical stress 
In the current study, microRNA (miRNA) microarrays were used to detect differentially expressed miRNAs in the myocardial tissues of rat models under stress, to screen target miRNA candidates for miRNA therapy of stress-induced myocardial injury. Rats were bound and suspended in order to induce acute stress (AS) and chronic stress (CS) models. miRNA microarrays were used to detect differentially expressed miRNA in the myocardial tissues of the stressed and control groups. In comparison to the normal control, there were 68 differentially expressed miRNAs in the AS model, of which 32 were upregulated and 36 were downregulated. There were 55 differentially expressed miRNAs in the CS model, of which 20 were upregulated and 35 were downregulated. Of the 123 miRNAs, 15 miRNAs were differentially expressed between the AS and CS groups, of which four were significantly upregulated (rno-miR-296, rno-miR-141, rno-miR-382 and rno-miR-219-5p) and 11 were downregulated (significantly downregulated, rno-miR-135a and rno-miR-466b). The stress of being bound and suspended induces myocardial injury in the rats. Myocardial injury may cause the differential expression of certain miRNAs. Psychological stress may lead to the significant upregulation of rno-miR-296, rno-miR-141, rno-miR-382 and rno-miR-219-5p in addition to the significant downregulation of miR-135a and miR-466b.
doi:10.3892/etm.2014.1504
PMCID: PMC3961114  PMID: 24669248
stress; microRNAs; myocardium; rat; microarray
15.  Protein Kinase C Phosphomimetics Alter Thin Filament Ca2+ Binding Properties 
PLoS ONE  2014;9(1):e86279.
Adrenergic stimulation modulates cardiac function by altering the phosphorylation status of several cardiac proteins. The Troponin complex, which is the Ca2+ sensor for cardiac contraction, is a hot spot for adrenergic phosphorylation. While the effect of β-adrenergic related PKA phosphorylation of troponin I at Ser23/24 is well established, the effects of α-adrenergic induced PKC phosphorylation on multiple sites of TnI (Ser43/45, Thr144) and TnT (Thr194, Ser198, Thr203 and Thr284) are much less clear. By utilizing an IAANS labeled fluorescent troponin C, , we systematically examined the site specific effects of PKC phosphomimetic mutants of TnI and TnT on TnC’s Ca2+ binding properties in the Tn complex and reconstituted thin filament. The majority of the phosphomemetics had little effect on the Ca2+ binding properties of the isolated Tn complex. However, when incorporated into the thin filament, the phosphomimetics typically altered thin filament Ca2+ sensitivity in a way consistent with their respective effects on Ca2+ sensitivity of skinned muscle preparations. The altered Ca2+ sensitivity could be generally explained by a change in Ca2+ dissociation rates. Within TnI, phosphomimetic Asp and Glu did not always behave similar, nor were Ala mutations (used to mimic non-phosphorylatable states) benign to Ca2+ binding. Our results suggest that Troponin may act as a hub on the thin filament, sensing physiological stimuli to modulate the contractile performance of the heart.
doi:10.1371/journal.pone.0086279
PMCID: PMC3899258  PMID: 24466001
16.  Phylogenetic and Biological Significance of Evolutionary Elements from Metazoan Mitochondrial Genomes 
PLoS ONE  2014;9(1):e84330.
The evolutionary history of living species is usually inferred through the phylogenetic analysis of molecular and morphological information using various mathematical models. New challenges in phylogenetic analysis are centered mostly on the search for accurate and efficient methods to handle the huge amounts of sequence data generated from newer genome sequencing. The next major challenge is the determination of relationships between the evolution of structural elements and their functional implementation, which is largely ignored in previous analyses. Here, we described the discovery of structural elements in metazoan mitochondrial genomes, termed key K-strings, that can serve as a basis for phylogenetic tree construction. Although comprising only a small fraction (0.73%) of all K-strings, these key K-strings are pivotal to the tree construction because they allow for a significant reduction in the computational time required to construct phylogenetic trees, and more importantly, they make significant improvement to the results of phylogenetic inference. The trees constructed from the key K-strings were consistent overall to our current view of metazoan phylogeny and exhibited a more rational topology than the trees constructed by using other conventional methods. Surprisingly, the key K-strings tended to accumulate in the conserved regions of the original sequences, which were most likely due to strong selection pressure. Furthermore, the special structural features of the key K-strings should have some potential applications in the study of the structures and functions relationship of proteins and in the determination of evolutionary trajectory of species. The novelty and potential importance of key K-strings lead us to believe that they are essential evolutionary elements. As such, they may play important roles in the process of species evolution and their physical existence. Further studies could lead to discoveries regarding the relationship between evolution and processes of speciation.
doi:10.1371/journal.pone.0084330
PMCID: PMC3896360  PMID: 24465405
17.  Genome characteristics reveal the impact of lichenization on lichen-forming fungus Endocarpon pusillum Hedwig (Verrucariales, Ascomycota) 
BMC Genomics  2014;15:34.
Background
Lichen is a classic mutualistic organism and the lichenization is one of the fungal symbioses. The lichen-forming fungus Endocarpon pusillum is living in symbiosis with the green alga Diplosphaera chodatii Bialsuknia as a lichen in the arid regions.
Results
454 and Illumina technologies were used to sequence the genome of E. pusillum. A total of 9,285 genes were annotated in the 37.5 Mb genome of E. pusillum. Analyses of the genes provided direct molecular evidence for certain natural characteristics, such as homothallic reproduction and drought-tolerance. Comparative genomics analysis indicated that the expansion and contraction of some protein families in the E. pusillum genome reflect the specific relationship with its photosynthetic partner (D. chodatii). Co-culture experiments using the lichen-forming fungus E. pusillum and its algal partner allowed the functional identification of genes involved in the nitrogen and carbon transfer between both symbionts, and three lectins without signal peptide domains were found to be essential for the symbiotic recognition in the lichen; interestingly, the ratio of the biomass of both lichen-forming fungus and its photosynthetic partner and their contact time were found to be important for the interaction between these two symbionts.
Conclusions
The present study lays a genomic analysis of the lichen-forming fungus E. pusillum for demonstrating its general biological features and the traits of the interaction between this fungus and its photosynthetic partner D. chodatii, and will provide research basis for investigating the nature of its drought resistance and symbiosis.
doi:10.1186/1471-2164-15-34
PMCID: PMC3897900  PMID: 24438332
Mycobiont; Phycobiont; Lichenization; Symbiosis; Symbiosis-related gene; Photosynthetic products
18.  Fully Automated Detection of Corticospinal Tract Damage in Chronic Stroke Patients 
Structural integrity of the corticospinal tract (CST) after stroke is closely linked to the degree of motor impairment. However, current methods for measurement of fractional atrophy (FA) of CST based on region of interest (ROI) are time-consuming and open to bias. Here, we used tract-based spatial statistics (TBSS) together with a CST template with healthy volunteers to quantify structural integrity of CST automatically. Two groups of patients after ischemic stroke were enrolled, group 1 (10 patients, 7 men, and Fugl-Meyer assessment (FMA) scores ⩽ 50) and group 2 (12 patients, 12 men, and FMA scores = 100). CST of FAipsi, FAcontra, and FAratio was compared between the two groups. Relative to group 2, FA was decreased in group 1 in the ipsilesional CST (P < 0.01), as well as the FAratio (P < 0.01). There was no significant difference between the two subgroups in the contralesional CST (P = 0.23). Compared with contralesional CST, FA of ipsilesional CST decreased in group 1 (P < 0.01). These results suggest that the automated method used in our study could detect a surrogate biomarker to quantify the CST after stroke, which would facilitate implementation of clinical practice.
doi:10.1155/2014/370849
PMCID: PMC3914349  PMID: 24527059
19.  Sequential Bearings-Only-Tracking Initiation with Particle Filtering Method 
The Scientific World Journal  2013;2013:489121.
The tracking initiation problem is examined in the context of autonomous bearings-only-tracking (BOT) of a single appearing/disappearing target in the presence of clutter measurements. In general, this problem suffers from a combinatorial explosion in the number of potential tracks resulted from the uncertainty in the linkage between the target and the measurement (a.k.a the data association problem). In addition, the nonlinear measurements lead to a non-Gaussian posterior probability density function (pdf) in the optimal Bayesian sequential estimation framework. The consequence of this nonlinear/non-Gaussian context is the absence of a closed-form solution. This paper models the linkage uncertainty and the nonlinear/non-Gaussian estimation problem jointly with solid Bayesian formalism. A particle filtering (PF) algorithm is derived for estimating the model's parameters in a sequential manner. Numerical results show that the proposed solution provides a significant benefit over the most commonly used methods, IPDA and IMMPDA. The posterior Cramér-Rao bounds are also involved for performance evaluation.
doi:10.1155/2013/489121
PMCID: PMC3886398  PMID: 24453865
20.  Chemokines in Chronic Liver Allograft Dysfunction Pathogenesis and Potential Therapeutic Targets 
Despite advances in immunosuppressive drugs, long-term success of liver transplantation is still limited by the development of chronic liver allograft dysfunction. Although the exact pathogenesis of chronic liver allograft dysfunction remains to be established, there is strong evidence that chemokines are involved in organ damage induced by inflammatory and immune responses after liver surgery. Chemokines are a group of low-molecular-weight molecules whose function includes angiogenesis, haematopoiesis, mitogenesis, organ fibrogenesis, tumour growth and metastasis, and participating in the development of the immune system and in inflammatory and immune responses. The purpose of this review is to collect all the research that has been done so far concerning chemokines and the pathogenesis of chronic liver allograft dysfunction and helpfully, to pave the way for designing therapeutic strategies and pharmaceutical agents to ameliorate chronic allograft dysfunction after liver transplantation.
doi:10.1155/2013/325318
PMCID: PMC3870628  PMID: 24382971
21.  Development of a DNA Microarray for Molecular Identification of All 46 Salmonella O Serogroups 
Applied and Environmental Microbiology  2013;79(11):3392-3399.
Salmonella is a major cause of food-borne disease in many countries. Serotype determination of Salmonella is important for disease assessment, infection control, and epidemiological surveillance. In this study, a microarray system that targets the O antigen-specific genes was developed for simultaneously detecting and identifying all 46 Salmonella O serogroups. Of these, 40 serogroups can be confidently identified, and the remaining 6, in three pairs (serogroups O67 and B, E1 and E4, and A and D1), need to be further distinguished from each other using PCR methods or conventional serotyping methods. The microarray was shown to be highly specific when evaluated against 293 Salmonella strains, 186 Shigella strains, representative Escherichia coli strains, and 10 strains of other bacterial species. The assay correctly identified 288 (98%) of the Salmonella strains. The detection sensitivity was determined to be 50 ng genomic DNA per sample. By testing simulated samples in a tomato background, 2 to 8 CFU per gram inoculated could be detected after enrichment. This newly developed microarray assay is the first molecular protocol that can be used for the comprehensive detection and identification of all 46 Salmonella O serogroups. Compared to the traditional serogrouping method, the microarray provides a reliable, high-throughput, and sensitive approach that can be used for rapid identification of multiple Salmonella O serogroups simultaneously.
doi:10.1128/AEM.00225-13
PMCID: PMC3648052  PMID: 23524674
22.  Community-wide assessment of protein-interface modeling suggests improvements to design methodology 
Fleishman, Sarel J | Whitehead, Timothy A | Strauch, Eva-Maria | Corn, Jacob E | Qin, Sanbo | Zhou, Huan-Xiang | Mitchell, Julie C. | Demerdash, Omar N.A | Takeda-Shitaka, Mayuko | Terashi, Genki | Moal, Iain H. | Li, Xiaofan | Bates, Paul A. | Zacharias, Martin | Park, Hahnbeom | Ko, Jun-su | Lee, Hasup | Seok, Chaok | Bourquard, Thomas | Bernauer, Julie | Poupon, Anne | Azé, Jérôme | Soner, Seren | Ovali, Şefik Kerem | Ozbek, Pemra | Ben Tal, Nir | Haliloglu, Türkan | Hwang, Howook | Vreven, Thom | Pierce, Brian G. | Weng, Zhiping | Pérez-Cano, Laura | Pons, Carles | Fernández-Recio, Juan | Jiang, Fan | Yang, Feng | Gong, Xinqi | Cao, Libin | Xu, Xianjin | Liu, Bin | Wang, Panwen | Li, Chunhua | Wang, Cunxin | Robert, Charles H. | Guharoy, Mainak | Liu, Shiyong | Huang, Yangyu | Li, Lin | Guo, Dachuan | Chen, Ying | Xiao, Yi | London, Nir | Itzhaki, Zohar | Schueler-Furman, Ora | Inbar, Yuval | Patapov, Vladimir | Cohen, Mati | Schreiber, Gideon | Tsuchiya, Yuko | Kanamori, Eiji | Standley, Daron M. | Nakamura, Haruki | Kinoshita, Kengo | Driggers, Camden M. | Hall, Robert G. | Morgan, Jessica L. | Hsu, Victor L. | Zhan, Jian | Yang, Yuedong | Zhou, Yaoqi | Kastritis, Panagiotis L. | Bonvin, Alexandre M.J.J. | Zhang, Weiyi | Camacho, Carlos J. | Kilambi, Krishna P. | Sircar, Aroop | Gray, Jeffrey J. | Ohue, Masahito | Uchikoga, Nobuyuki | Matsuzaki, Yuri | Ishida, Takashi | Akiyama, Yutaka | Khashan, Raed | Bush, Stephen | Fouches, Denis | Tropsha, Alexander | Esquivel-Rodríguez, Juan | Kihara, Daisuke | Stranges, P Benjamin | Jacak, Ron | Kuhlman, Brian | Huang, Sheng-You | Zou, Xiaoqin | Wodak, Shoshana J | Janin, Joel | Baker, David
Journal of molecular biology  2011;414(2):10.1016/j.jmb.2011.09.031.
The CAPRI and CASP prediction experiments have demonstrated the power of community wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting there may be important physical chemistry missing in the energy calculations. 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the non-polar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were on average structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a non-binder.
doi:10.1016/j.jmb.2011.09.031
PMCID: PMC3839241  PMID: 22001016
23.  Nonlocal quantum macroscopic superposition in a high-thermal low-purity state 
Physical review. A  2008;78(6):10.1103/PhysRevA.78.063824.
Quantum state exchange between light and matter is an important ingredient for future quantum information networks as well as other applications. Photons are the fastest and simplest carriers of information for transmission but in general, it is difficult to localize and store photons, so usually one prefers choosing matter as quantum memory elements. Macroscopic superposition and nonlocal quantum interactions have received considerable interest for this purpose over recent years in fields ranging from quantum computers to cryptography, in addition to providing major insights into physical laws. However, these experiments are generally performed either with equipment or under conditions that are unrealistic for practical applications. Ideally, the two can be combined using conventional equipment and conditions to generate a “quantum teleportation”-like state, particularly with a very small amount of purity existing in an overall highly mixed thermal state (relatively low decoherence at high temperatures). In this study we used an experimental design to demonstrate these principles. We performed optical coherence tomography (OCT) using a thermal source at room temperatures of a specifically designed target in the sample arm. Here, position uncertainty (i.e., dispersion) was induced in the reference arm. In the sample arm (target) we placed two glass plates separated by a different medium while altering position uncertainty in the reference arm. This resulted in a chirped signal between the glass plate reflective surfaces in the combined interferogram. The chirping frequency, as measured by the fast Fourier transform (FFT), varies with the medium between the plates, which is a nonclassical phenomenon. These results are statistically significant and occur from a superposition between the glass surface and the medium with increasing position uncertainty, a true quantum-mechanical phenomenon produced by photon pressure from two-photon interference. The differences in chirping frequency with medium disappears when second-order correlations are removed by dual balanced detection, confirming the proposed mechanism. We demonstrated that increasing position uncertainty at one site leads to position uncertainty (quantum position probability amplitude) nonlocally via second-order correlations (two-photon probability amplitude) from a low coherence thermal source (low purity, high local entropy). The implications, first, are that the phenomenon cannot be explained through classical mechanisms but can be explained within the context of quantum mechanics, particularly relevant to the second-order correlations where controversy exists. More specifically, we provide the theoretical framework that these results indicate a nonlocal macroscopic superposition is occurring through a two-photon probability amplitude-induced increase in the target position probability amplitude uncertainty. In addition, as the experiments were performed with a classical source at room temperature, it supports both the quantum-mechanical properties of second-order correlations and that macroscopic superposition is obtainable in a target not in a single coherent state (mixed state). Future work will focus on generalizing the observations outside the current experimental design and creating embodiments that allow practical application of the phenomenon.
doi:10.1103/PhysRevA.78.063824
PMCID: PMC3818030  PMID: 24204102
24.  Dihydromyricetin Reduced Bcl-2 Expression via p53 in Human Hepatoma HepG2 Cells 
PLoS ONE  2013;8(11):e76886.
Dihydromyricetin (DHM) is a major active ingredient of flavonoids compounds. It exhibited anticancer activity and induced apoptosis in human hepatocellular carcinoma HepG2 cells according to our previous data. In this study, we investigated whether p53 is involved in DHM-triggered viability inhibition and apoptosis induction in cancer cells. MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay was employed to evaluate the viability of HepG2 cells after DHM treatment. Meanwhile, p53 small interfering RNA (siRNA) was adopted to silence p53 expression. Protein level of p53 and Bax/Bcl-2 were evaluated by western blot analysis. Cell counting assay showed that DHM inhibited HepG2 cell growth effectively in a time- and dose-dependent manner. P53 expression was significantly increased after DHM treatment, whereas Bcl-2 was reduced potently. Furthermore, after co-treatment with Pifithrin-α (PFT-α, p53 inhibitor), Bcl-2 expression was reversed. The expression of Bax was no significant change, which was also observed after p53 silence. These findings defined and supported a novel function that DHM could induce human hepatocellular carcinoma HepG2 cells apoptosis by up-regulating Bax/Bcl-2 expression via p53 signal pathway.
doi:10.1371/journal.pone.0076886
PMCID: PMC3817187  PMID: 24223706
25.  Sphingosine-1–Phosphate Receptor–3 Is a Novel Biomarker in Acute Lung Injury 
The inflamed lung exhibits oxidative and nitrative modifications of multiple target proteins, potentially reflecting disease severity and progression. We identified sphingosine-1–phosphate receptor–3 (S1PR3), a critical signaling molecule mediating cell proliferation and vascular permeability, as a nitrated plasma protein in mice with acute lung injury (ALI). We explored S1PR3 as a potential biomarker in murine and human ALI. In vivo nitrated and total S1PR3 concentrations were determined by immunoprecipitation and microarray studies in mice, and by ELISA in human plasma. In vitro nitrated S1PR3 concentrations were evaluated in human lung vascular endothelial cells (ECs) or within microparticles shed from ECs after exposure to barrier-disrupting agonists (LPS, low-molecular-weight hyaluronan, and thrombin). The effects of S1PR3-containing microparticles on EC barrier function were assessed by transendothelial electrical resistance (TER). Nitrated S1PR3 was identified in the plasma of murine ALI and in humans with severe sepsis-induced ALI. Elevated total S1PR3 plasma concentrations (> 251 pg/ml) were linked to sepsis and ALI mortality. In vitro EC exposure to barrier-disrupting agents induced S1PR3 nitration and the shedding of S1PR3-containing microparticles, which significantly reduced TER, consistent with increased permeability. These changes were attenuated by reduced S1PR3 expression (small interfering RNAs). These results suggest that microparticles containing nitrated S1PR3 shed into the circulation during inflammatory lung states, and represent a novel ALI biomarker linked to disease severity and outcome.
doi:10.1165/rcmb.2012-0048OC
PMCID: PMC3547106  PMID: 22771388
acute lung injury; sphingosine-1–phosphate receptor–3; microparticles; nitration; biomarker

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