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1.  Changes in HIV Incidence among People Who Inject Drugs in Taiwan following Introduction of a Harm Reduction Program: A Study of Two Cohorts 
PLoS Medicine  2014;11(4):e1001625.
Kenrad Nelson and colleagues report on the association between HIV incidence and exposure to a national harm-reduction program among people who inject drugs in Taiwan.
Please see later in the article for the Editors' Summary
Background
Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID.
Methods and Findings
The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6–12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06–0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates.
Conclusions
Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 35 million people worldwide are currently infected with HIV, the virus that causes AIDS, and about 2.3 million people become newly infected every year. HIV is mainly transmitted through unprotected sex with an infected partner. However, people who inject drugs (PWID) have a particularly high risk of HIV infection because blood transfer through needle and syringe sharing can transmit the virus. It is estimated that 5%–10% of all people living with HIV are PWID. Indeed, in some regions of the world the primary route of HIV transmission is through shared drug injection equipment and the prevalence (the proportion of a population that has a specific disease) of HIV infection among PWID is very high. In Asia, for example, more than a quarter of PWID are HIV positive. Because the high prevalence of HIV among PWID poses a global health challenge, bodies such as the Joint United Nations Programme on HIV/AIDS endorse harm reduction strategies to prevent risky injection behaviors among PWID. These strategies include the provision of clean needles and syringes, opioid substitution therapy such as methadone maintenance treatment, and antiretroviral treatment for HIV-positive PWID.
Why Was This Study Done?
Although harm reduction strategies for combating HIV epidemics among PWID have been implemented in several countries, few large-scale studies have examined the association between HIV incidence (the proportion of new cases of HIV in a population per year) and exposure to harm reduction programs among PWID. In this cohort study (an investigation that determines the characteristics of a group of people and then follows them over time), the researchers determine the association between harm reduction programs and HIV incidence among PWID in Taiwan. HIV infections used to be rare among the 60,000 PWID living in Taiwan, but after the introduction of a new HIV strain into the country in 2003, an HIV epidemic spread rapidly. In response, the Taiwanese government introduced a pilot program of harm reduction that included the provision of clean needles and syringes and health education in July 2005. The program was expanded to include methadone maintenance treatment in early 2006 and implemented nationwide in June 2006.
What Did the Researchers Do and Find?
The researchers enrolled two study populations. The first cohort comprised 3,851 PWID who were incarcerated for illicit drug use between 2004 and 2010 and who tested positive for HIV upon admission into prison. By using the BED assay, which indicates whether an HIV infection is recent, the researchers were able to determine the HIV incidence among the prisoners. In 2004, the estimated HIV incidence among prisoners with a history of drug injection was 6.44%. The incidence peaked in 2005 at 18.2%, but fell to 0.3% in 2010.
The second study population comprised 2,473 individuals who were HIV negative on January 1, 2006, and who had been incarcerated for drug use crimes but were released on July 16, 2007, during an amnesty. The researchers regularly interviewed these participants between their release and 2010 about their use of harm reduction interventions, and obtained other data about them (for example, diagnosis of HIV infection) from official databases. Analysis of all these data indicated that, in this cohort, attendance at methadone maintenance treatment clinics and frequent use of needle and syringe services were both associated with a significantly lower HIV incidence.
What Do These Findings Mean?
These findings suggest that the introduction of a comprehensive harm reduction program in Taiwan was associated with a significant reduction in the HIV incidence rate among PWID. These findings must be interpreted with caution, however. First, because the participants in the study were selected from PWID with histories of incarceration, the findings may not be representative of all PWID in Taiwan or of PWID in other countries. Second, PWID who chose to use needle and syringe services or methadone maintenance treatment clinics might have shared other unknown characteristics that affected their risk of HIV infection. Finally, some of the reduction in HIV incidence seen during the study is likely to be associated with the availability of free treatment, which has been offered to all HIV-positive individuals in Taiwan since 1997. Despite these limitations, these findings suggest that countries with a high prevalence and incidence of HIV among PWID should provide comprehensive harm reduction services to their populations to reduce risky drug injection behaviors.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001625.
Information is available from the US National Institute of Allergy and Infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on injecting drug users and HIV/AIDS and on harm reduction and HIV prevention (in English and Spanish)
The US National Institute on Drug Abuse also provides information about drug abuse and HIV/AIDS (in English and Spanish)
The 2013 UNAIDS World AIDS Day report provides up-to-date information about the AIDS epidemic and efforts to halt it
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001625
PMCID: PMC3979649  PMID: 24714449
2.  Transcriptome profiling and genome-wide DNA binding define the differential role of fenretinide and all-trans RA in regulating the death and survival of human hepatocellular carcinoma Huh7 cells 
Biochemical pharmacology  2013;85(7):10.1016/j.bcp.2013.01.023.
Fenretinide is significantly more effective in inducing apoptosis in cancer cells than all-trans retinoic acid (ATRA). The current study uses a genome-wide approach to understand the differential role fenretinide and ATRA have in inducing apoptosis in Huh7 cells. Fenretinide and ATRA-induced gene expressions and DNA bindings were profiled using microarray and chromatin immunoprecipitation with anti-RXRα antibody. The data showed that fenretinide was not a strong transcription regulator. Fenretinide only changed the expressions of 1 093 genes, approximately three times less than the number of genes regulated by ATRA (2 811). Biological function annotation demonstrated that both fenretinide and ATRA participated in pathways that determine cell fate and metabolic processes. However, fenretinide specifically induced Fas/TNFα-mediated apoptosis by increasing the expression of pro-apoptotic genes i.e., DEDD2, CASP8, CASP4, and HSPA1A/B; whereas, ATRA induced the expression of BIRC3 and TNFAIP3, which inhibit apoptosis by interacting with TRAF2. In addition, fenretinide inhibited the expression of the genes involved in RAS/RAF/ERK-mediated survival pathway. In contrast, ATRA increased the expression of SOSC2, BRAF, MEK, and ERK genes. Most genes regulated by fenretinide and ATRA were bound by RXRα, suggesting a direct effect. This study revealed that by regulating fewer genes, the effects of fenretinide become more specific and thus has fewer side effects than ATRA. The data also suggested that fenretinide induces apoptosis via death receptor effector and by inhibiting the RAS/RAF/ERK pathway. It provides insight on how retinoid efficacy can be improved and how side effects in cancer therapy can be reduced.
doi:10.1016/j.bcp.2013.01.023
PMCID: PMC3857153  PMID: 23396089
retinoic acid receptor; retinoid x receptor; nuclear receptor; hepatocellular carcinoma; ChIP-Seq
3.  Hypoxia-Inducible MiR-210 Is an Independent Prognostic Factor and Contributes to Metastasis in Colorectal Cancer 
PLoS ONE  2014;9(3):e90952.
MicroRNA-210 (miR-210), the master hypoxamir, plays pleiotropic roles in certain cancers; however, its role in the development of human colorectal cancer remains unclear. Herein, we report that miR-210 is frequently up-regulated in colorectal cancer tissues, with high miR-210 expression significantly correlating with large tumor size, lymph node metastasis, advanced clinical stage and poor prognosis. Functionally, miR-210 overexpression promotes the migration and invasion of colorectal cancer cells. Furthermore, miR-210 can be induced by hypoxia and mediates the hypoxia-induced metastasis of colorectal cancer cells. In addition, vacuole membrane protein 1 (VMP1) is identified as the direct and functional target of miR-210. Thus, miR-210 is a useful biomarker for hypoxic tumor cells and a prognostic factor that plays an essential role in colorectal cancer metastasis.
doi:10.1371/journal.pone.0090952
PMCID: PMC3954583  PMID: 24632577
4.  Complete Resequencing of 40 Genomes Reveals Domestication Events and Genes in Silkworm (Bombyx) 
Science (New York, N.Y.)  2009;326(5951):433-436.
A single–base pair resolution silkworm genetic variation map was constructed from 40 domesticated and wild silkworms, each sequenced to approximately threefold coverage, representing 99.88% of the genome. We identified ∼16 million single-nucleotide polymorphisms, many indels, and structural variations. We find that the domesticated silkworms are clearly genetically differentiated from the wild ones, but they have maintained large levels of genetic variability, suggesting a short domestication event involving a large number of individuals. We also identified signals of selection at 354 candidate genes that may have been important during domestication, some of which have enriched expression in the silk gland, midgut, and testis. These data add to our understanding of the domestication processes and may have applications in devising pest control strategies and advancing the use of silkworms as efficient bioreactors.
doi:10.1126/science.1176620
PMCID: PMC3951477  PMID: 19713493
5.  Spinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia 
PLoS ONE  2014;9(2):e89583.
Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP.
doi:10.1371/journal.pone.0089583
PMCID: PMC3933549  PMID: 24586889
6.  Cirrhosis Classification Based on Texture Classification of Random Features 
Accurate staging of hepatic cirrhosis is important in investigating the cause and slowing down the effects of cirrhosis. Computer-aided diagnosis (CAD) can provide doctors with an alternative second opinion and assist them to make a specific treatment with accurate cirrhosis stage. MRI has many advantages, including high resolution for soft tissue, no radiation, and multiparameters imaging modalities. So in this paper, multisequences MRIs, including T1-weighted, T2-weighted, arterial, portal venous, and equilibrium phase, are applied. However, CAD does not meet the clinical needs of cirrhosis and few researchers are concerned with it at present. Cirrhosis is characterized by the presence of widespread fibrosis and regenerative nodules in the hepatic, leading to different texture patterns of different stages. So, extracting texture feature is the primary task. Compared with typical gray level cooccurrence matrix (GLCM) features, texture classification from random features provides an effective way, and we adopt it and propose CCTCRF for triple classification (normal, early, and middle and advanced stage). CCTCRF does not need strong assumptions except the sparse character of image, contains sufficient texture information, includes concise and effective process, and makes case decision with high accuracy. Experimental results also illustrate the satisfying performance and they are also compared with typical NN with GLCM.
doi:10.1155/2014/536308
PMCID: PMC3953575
7.  Deep Vertebrate Roots for Mammalian Zinc Finger Transcription Factor Subfamilies 
Genome Biology and Evolution  2014;6(3):510-525.
While many vertebrate transcription factor (TF) families are conserved, the C2H2 zinc finger (ZNF) family stands out as a notable exception. In particular, novel ZNF gene types have arisen, duplicated, and diverged independently throughout evolution to yield many lineage-specific TF genes. This evolutionary dynamic not only raises many intriguing questions but also severely complicates identification of those ZNF genes that remain functionally conserved. To address this problem, we searched for vertebrate “DNA binding orthologs” by mining ZNF loci from eight sequenced genomes and then aligning the patterns of DNA-binding amino acids, or “fingerprints,” extracted from the encoded ZNF motifs. Using this approach, we found hundreds of lineage-specific genes in each species and also hundreds of orthologous groups. Most groups of orthologs displayed some degree of fingerprint divergence between species, but 174 groups showed fingerprint patterns that have been very rigidly conserved. Focusing on the dynamic KRAB-ZNF subfamily—including nearly 400 human genes thought to possess potent KRAB-mediated epigenetic silencing activities—we found only three genes conserved between mammals and nonmammalian groups. These three genes, members of an ancient familial cluster, encode an unusual KRAB domain that functions as a transcriptional activator. Evolutionary analysis confirms the ancient provenance of this activating KRAB and reveals the independent expansion of KRAB-ZNFs in every vertebrate lineage. Most human ZNF genes, from the most deeply conserved to the primate-specific genes, are highly expressed in immune and reproductive tissues, indicating that they have been enlisted to regulate evolutionarily divergent biological traits.
doi:10.1093/gbe/evu030
PMCID: PMC3971581  PMID: 24534434
zinc finger genes; transcription factor evolution; vertebrate gene families
8.  Microbial production of sabinene—a new terpene-based precursor of advanced biofuel 
Background
Sabinene, one kind of monoterpene, accumulated limitedly in natural organisms, is being explored as a potential component for the next generation of aircraft fuels. And demand for advanced fuels impels us to develop biosynthetic routes for the production of sabinene from renewable sugar.
Results
In this study, sabinene was significantly produced by assembling a biosynthetic pathway using the methylerythritol 4-phosphate (MEP) or heterologous mevalonate (MVA) pathway combining the GPP and sabinene synthase genes in an engineered Escherichia coli strain. Subsequently, the culture medium and process conditions were optimized to enhance sabinene production with a maximum titer of 82.18 mg/L. Finally, the fed-batch fermentation of sabinene was evaluated using the optimized culture medium and process conditions, which reached a maximum concentration of 2.65 g/L with an average productivity of 0.018 g h-1 g-1 dry cells, and the conversion efficiency of glycerol to sabinene (gram to gram) reached 3.49%.
Conclusions
This is the first report of microbial synthesis of sabinene using an engineered E. coli strain with the renewable carbon source as feedstock. Therefore, a green and sustainable production strategy has been established for sabinene.
doi:10.1186/1475-2859-13-20
PMCID: PMC3923588  PMID: 24512040
Sabinene; Geranyl diphosphate synthase; Sabinene synthase; Escherichia coli
9.  The centrosome regulates the Rab11-dependent recycling endosome pathway at appendages of the mother centriole 
Current biology : CB  2012;22(20):1944-1950.
Summary
The recycling endosome localizes to a pericentrosomal region via microtubule-dependent transport. We previously showed that Sec15, an effector of the recycling endosome component, Rab11-GTPase, interacts with the mother centriole appendage protein, centriolin, suggesting an interaction between endosomes and centrosomes (1, 2). Here we show that the recycling endosome associates with the appendages of the mother (older) centriole. We show that the mother centriole appendage proteins, centriolin and cenexin/ODF2, regulate association of the endosome components Rab11, the Rab11 GTP-activating protein Evi5, and the exocyst at the mother centriole. Development of an in vitro method for reconstituting endosome protein complexes onto isolated membrane-free centrosomes demonstrates that purified GTP-Rab11 but not GDP-Rab11 binds to mother centriole appendages in the absence of membranes. Moreover, centriolin depletion displaces the centrosomal Rab11 GAP, Evi5, and increases mother-centriole-associated Rab11; depletion of Evi5 also increases centrosomal Rab11. This indicates that centriolin localizes Evi5 to centriolar appendages to turn off centrosomal Rab11 activity. Finally, centriolin depletion disrupts recycling endosome organization and function suggesting a role for mother centriole proteins in the regulation of Rab11 localization and activity at the mother centriole.
doi:10.1016/j.cub.2012.08.022
PMCID: PMC3917512  PMID: 22981775
10.  A Longitudinal Study of Posttraumatic Stress Disorder Symptoms and Its Relationship with Coping Skill and Locus of Control in Adolescents after an Earthquake in China 
PLoS ONE  2014;9(2):e88263.
Background/Objectives
Post-traumatic stress disorder is a common psychological maladaptation among adolescents after undergoing an earthquake. Knowledge about the prevalence and maintenance of post-traumatic stress disorder symptoms and the changes of its predictors over time can help medical providers assist adolescent survivors with mitigating long-term impacts. This study examined the changes in posttraumatic stress disorder symptoms and its relationship with coping skill and locus of control among adolescent earthquake survivors in China.
Methodology/Findings
The study used an observational longitudinal design. A total of 1420 adolescents were evaluated twice after the earthquake by using the Post-traumatic stress disorder Checklist-Civilian Version, The Internality, Powerful others and Chance scale and the Coping Styles Scale. The results indicated that the mean scores of posttraumatic stress disorder symptoms were decreased significantly and the positive rates of posttraumatic stress disorder symptoms also declined remarkably at 17 months compared to the 3 months post-earthquake. Internality locus of control and problem solving coping skill were effective resilient factors for the development and maintenance of posttraumatic stress disorder symptoms, while chance locus of control was a powerful risk factor of posttraumatic stress disorder symptoms as well as being female, being injured and property loss.
Conclusions/Significance
Continuous screening is recommended to identify adolescent earthquake survivors with posttraumatic stress disorder symptoms. More attention should be paid to adolescent survivors who are prone to adopt passive coping strategies responding to trauma events and who own external causal attribution.
doi:10.1371/journal.pone.0088263
PMCID: PMC3917873  PMID: 24516622
11.  An evaluation of genotyping by sequencing (GBS) to map the Breviaristatum-e (ari-e) locus in cultivated barley 
BMC Genomics  2014;15:104.
Abstract
We explored the use of genotyping by sequencing (GBS) on a recombinant inbred line population (GPMx) derived from a cross between the two-rowed barley cultivar ‘Golden Promise’ (ari-e.GP/Vrs1) and the six-rowed cultivar ‘Morex’ (Ari-e/vrs1) to map plant height. We identified three Quantitative Trait Loci (QTL), the first in a region encompassing the spike architecture gene Vrs1 on chromosome 2H, the second in an uncharacterised centromeric region on chromosome 3H, and the third in a region of chromosome 5H coinciding with the previously described dwarfing gene Breviaristatum-e (Ari-e).
Background
Barley cultivars in North-western Europe largely contain either of two dwarfing genes; Denso on chromosome 3H, a presumed ortholog of the rice green revolution gene OsSd1, or Breviaristatum-e (ari-e) on chromosome 5H. A recessive mutant allele of the latter gene, ari-e.GP, was introduced into cultivation via the cv. ‘Golden Promise’ that was a favourite of the Scottish malt whisky industry for many years and is still used in agriculture today.
Results
Using GBS mapping data and phenotypic measurements we show that ari-e.GP maps to a small genetic interval on chromosome 5H and that alternative alleles at a region encompassing Vrs1 on 2H along with a region on chromosome 3H also influence plant height. The location of Ari-e is supported by analysis of near-isogenic lines containing different ari-e alleles. We explored use of the GBS to populate the region with sequence contigs from the recently released physically and genetically integrated barley genome sequence assembly as a step towards Ari-e gene identification.
Conclusions
GBS was an effective and relatively low-cost approach to rapidly construct a genetic map of the GPMx population that was suitable for genetic analysis of row type and height traits, allowing us to precisely position ari-e.GP on chromosome 5H. Mapping resolution was lower than we anticipated. We found the GBS data more complex to analyse than other data types but it did directly provide linked SNP markers for subsequent higher resolution genetic analysis.
doi:10.1186/1471-2164-15-104
PMCID: PMC3922333  PMID: 24498911
Barley; Dwarfing gene; Genotyping by sequencing; Physical map
12.  Stellated Ag-Pt bimetallic nanoparticles: An effective platform for catalytic activity tuning 
Scientific Reports  2014;4:3969.
The usefulness of Pt-based nanomaterials for catalysis can be greatly enhanced by coupling morphology engineering to the strategic presence of a second or even third metal. Here we demonstrate the design and preparation of stellated Ag-Pt bimetallic nanoparticles where significant activity difference between the methanol oxidation reaction (MOR) and the oxygen reduction reaction (ORR) may be realized by relegating Ag to the core or by hollowing out the core. In particular the stellated Pt surface, with an abundance of steps, edges, corner atoms, and {111} facets, is highly effective for the ORR but is ineffective for MOR. MOR activity is only observed in the presence of a Ag core through electronic coupling to the stellated Pt shell. The bimetallic Ag-Pt stellates therefore demonstrate the feasibility of tuning a Pt surface for two very different structure sensitive catalytic reactions. Stellated bimetallics may therefore be an effective platform for highly tunable catalyst designs.
doi:10.1038/srep03969
PMCID: PMC3913913  PMID: 24495979
13.  Decadal Changes in Zooplankton of the Northeast U.S. Continental Shelf 
PLoS ONE  2014;9(1):e87720.
The abundance of the subarctic copepod, Calanus finmarchicus, and temperate, shelf copepod, Centropages typicus, was estimated from samples collected bi-monthly over the Northeast U.S. continental shelf (NEUS) from 1977–2010. Latitudinal variation in long term trends and seasonal patterns for the two copepod species were examined for four sub-regions: the Gulf of Maine (GOM), Georges Bank (GB), Southern New England (SNE), and Mid-Atlantic Bight (MAB). Results suggested that there was significant difference in long term variation between northern region (GOM and GB), and the MAB for both species. C. finmarchicus generally peaked in May – June throughout the entire study region and Cen. typicus had a more complex seasonal pattern. Time series analysis revealed that the peak time for Cen. typicus switched from November – December to January - March after 1985 in the MAB. The long term abundance of C. finmarchicus showed more fluctuation in the MAB than the GOM and GB, whereas the long term abundance of Cen. typicus was more variable in the GB than other sub-regions. Alongshore transport was significantly correlated with the abundance of C. finmarchicus, i.e., more water from north, higher abundance for C. finmarchicus. The abundance of Cen. typicus showed positive relationship with the Gulf Stream north wall index (GSNWI) in the GOM and GB, but the GSNWI only explained 12–15% of variation in Cen. typicus abundance. In general, the alongshore current was negatively correlated with the GSNWI, suggesting that Cen. typicus is more abundant when advection from the north is less. However, the relationship between Cen. typicus and alongshore transport was not significant. The present study highlights the importance of spatial scales in the study of marine populations: observed long term changes in the northern region were different from the south for both species.
doi:10.1371/journal.pone.0087720
PMCID: PMC3909209  PMID: 24498177
14.  The Relationship between Diaspore Characteristics with Phylogeny, Life History Traits, and Their Ecological Adaptation of 150 Species from the Cold Desert of Northwest China 
The Scientific World Journal  2014;2014:510343.
Diaspore characteristics of 22 families, including 102 genera and 150 species (55 represented by seeds and 95 by fruits) from the Gurbantunggut Desert were analyzed for diaspore biological characteristics (mass, shape, color, and appendage type). The diaspore mass and shape were significantly different in phylogeny group (APG) and dispersal syndromes; vegetative periods significantly affected diaspore mass, but not diaspore shape; and ecotypes did not significantly affect diaspore mass and shape, but xerophyte species had larger diaspore mass than mesophyte species. Unique stepwise ANOVA results showed that variance in diaspore mass and shape among these 150 species was largely dependent upon phylogeny and dispersal syndromes. Therefore, it was suggested that phylogeny may constrain diaspore mass, and as dispersal syndromes may be related to phylogeny, they also constrained diaspore mass and shape. Diaspores of 85 species (56.67%) had appendages, including 26 with wings/bracts, 18 with pappus/hair, 14 with hooks/spines, 10 with awns, and 17 with other types of appendages. Different traits (mass, shape, color, appendage, and dispersal syndromes) of diaspore decided plants forming different adapted strategies in the desert. In summary, the diaspore characteristics were closely related with phylogeny, vegetative periods, dispersal syndromes, and ecotype, and these characteristics allowed the plants to adapt to extreme desert environments.
doi:10.1155/2014/510343
PMCID: PMC3925582  PMID: 24605054
15.  Application of Butterfly Clos-Network in Network-on-Chip 
The Scientific World Journal  2014;2014:102651.
This paper studied the topology of NoC (Network-on-Chip). By combining the characteristics of the Clos network and butterfly network, a new topology named BFC (Butterfly Clos-network) network was proposed. This topology integrates several modules, which belongs to the same layer but different dimensions, into a new module. In the BFC network, a bidirectional link is used to complete information exchange, instead of information exchange between different layers in the original network. During the routing period, other nondestination nodes can be used as middle stages to transfer data packets to complete the routing mission. Therefore, this topology has the characteristic of multistage. Simulation analyses show that BFC inherits the rich path diversity of Clos network, and it has a better performance than butterfly network in throughput and delay in a quite congested traffic pattern.
doi:10.1155/2014/102651
PMCID: PMC3926393
16.  Selective electrocatalysts toward a prototype of the membraneless direct methanol fuel cell 
Scientific Reports  2014;4:3813.
Mastery over the structure of nanomaterials enables control of their properties to enhance their performance for a given application. Herein we demonstrate the design and fabrication of Pt-based nanomaterials with enhanced catalytic activity and superior selectivity toward the reactions in direct methanol fuel cells (DMFCs) upon the deep understanding of the mechanisms of these electrochemical reactions. In particular, the ternary Au@Ag2S-Pt nanocomposites display superior methanol oxidation reaction (MOR) selectivity due to the electronic coupling effect among different domains of the nanocomposites, while the cage-bell structured Pt-Ru nanoparticles exhibit excellent methanol tolerance for oxygen reduction reaction (ORR) at the cathode because of the differential diffusion of methanol and oxygen in the porous Ru shell of the cage-bell nanoparticles. The good catalytic selectivity of these Pt-based nanomaterials via structural construction enables a DMFC to be built without a proton exchange membrane between the fuel electrode and the oxygen electrode.
doi:10.1038/srep03813
PMCID: PMC3897953  PMID: 24448514
17.  NURBS: a database of experimental and predicted nuclear receptor binding sites of mouse 
Bioinformatics  2012;29(2):295-297.
Summary: Nuclear receptors (NRs) are a class of transcription factors playing important roles in various biological processes. An NR often impacts numerous genes and different NRs share overlapped target networks. To fulfil the need for a database incorporating binding sites of different NRs at various conditions for easy comparison and visualization to improve our understanding of NR binding mechanisms, we have developed NURBS, a database for experimental and predicted nuclear receptor binding sites of mouse (NURBS). NURBS currently contains binding sites across the whole-mouse genome of 8 NRs identified in 40 chromatin immunoprecipitation with massively parallel DNA sequencing experiments. All datasets are processed using a widely used procedure and same statistical criteria to ensure the binding sites derived from different datasets are comparable. NURBS also provides predicted binding sites using NR-HMM, a Hidden Markov Model (HMM) model.
Availability: The GBrowse-based user interface of NURBS is freely accessible at http://shark.abl.ku.edu/nurbs/. NR-HMM and all results can be downloaded for free at the website.
Contact: jwfang@ku.edu
doi:10.1093/bioinformatics/bts693
PMCID: PMC3546791  PMID: 23196988
18.  An Automatic Image Inpainting Algorithm Based on FCM 
The Scientific World Journal  2014;2014:201704.
There are many existing image inpainting algorithms in which the repaired area should be manually determined by users. Aiming at this drawback of the traditional image inpainting algorithms, this paper proposes an automatic image inpainting algorithm which automatically identifies the repaired area by fuzzy C-mean (FCM) algorithm. FCM algorithm classifies the image pixels into a number of categories according to the similarity principle, making the similar pixels clustering into the same category as possible. According to the provided gray value of the pixels to be inpainted, we calculate the category whose distance is the nearest to the inpainting area and this category is to be inpainting area, and then the inpainting area is restored by the TV model to realize image automatic inpainting.
doi:10.1155/2014/201704
PMCID: PMC3910136  PMID: 24516358
19.  Natural orifice surgery in thoracic surgery 
Journal of Thoracic Disease  2014;6(1):61-63.
doi:10.3978/j.issn.2072-1439.2014.01.02
PMCID: PMC3895588  PMID: 24455178
20.  Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis 
Nature  2013;498(7455):10.1038/nature12199.
Through their functional diversification, distinct lineages of CD4+ T cells play key roles in either driving or constraining immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment1. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma2, Crohn’s disease3–4, coeliac disease5, vitiligo6, multiple sclerosis7 and type 1 diabetes8. While these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for Bach2 in the maintenance of immune homeostasis has not been established. Here, we define Bach2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programmes of multiple effector lineages in CD4+ T cells. Bach2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg cell dependent. Assessment of the genome-wide function of Bach2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, Bach2 constrained full effector differentiation within Th1, Th2 and Th17 cell lineages. These findings identify Bach2 as a key regulator of CD4+ T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity.
doi:10.1038/nature12199
PMCID: PMC3710737  PMID: 23728300
21.  Pulmonary gangliocytic paraganglioma: a case report and review of the literature 
Gangliocytic paraganglioma (GP) is a rare histologic type of neuroendocrine tumors. We report a case of pulmonary GP in a 29-year-old male presenting with an asymptomatic endobronchial nodule. Grossly, the tumor showed a 4.0x3.8x3.5 cm well-defined nodule with yellowish cut surface. Microscopically, the tumor was composed of three distinct cellular types: epithelioid cells, ganglion-like cells and spindle cells. Meanwhile, transitional cells, having morphologic features between ganglion-like and epithelioid cells, were also presented. The epithelioid cells arranged in various morphologic architectures, including Zellballen, papillary, cystic and microcystic pattern. The epithelioid cells were positive for AE1/AE3, CAM 5.2, chromogranin A and synaptophysin. Ganglion-like cells showed immunoreactivity for chromogranin A and synaptophysin. A few ganglion-like cells were also positive for AE1/AE3 and/or CAM 5.2. The spindle cells were positive for S-100 protein and neurofilament. The transitional cells showed a similar immunohistochemical profile to the epithelioid cells. The authors believe stem cell theory is a reasonable explanation for the origin of GP. GP probably originate from some kind of mucosa associated stem cell which can differentiate into diverse cellular lineages.
PMCID: PMC3885502  PMID: 24427368
Gangliocytic paraganglioma; bronchial; histomorphology; immunohistochemistry; histogenesis
22.  PI3K/Akt Signal Pathway Involved in the Cognitive Impairment Caused by Chronic Cerebral Hypoperfusion in Rats 
PLoS ONE  2013;8(12):e81901.
Chronic cerebral hypoperfusion (CCH) is a common pathophysiological state that usually occurs in conditions such as vascular dementia and Alzheimer's disease, both of which are characterized by cognitive impairment. In previous studies we found that learning capacity and memory were gradually impaired with CCH, which altered the expression of synaptophysin, microtubule associated protein-2, growth associated protein-43, brain-derived neurotrophic factor, nerve growth factor, N-methyl-D-aspartate receptor subunit 1, cAMP response element-binding protein and tau hyperphosphorylation in the hippocampus. However, the molecular basis of cognitive impairment in CCH remains obscure. Here we explore the hypothesis that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway is involved in this type of cognitive impairment. In order to determine if the expression of PI3K, Akt and phosphorylated Akt (p-Akt) proteins are altered at different stages of CCH with differing levels of cognitive impairment. we performed permanent, bilateral occlusion of the common carotid arteries (2-VO) to induce CCH. Adult male SD rats were randomly divided into sham-operated group, 2-VO 1 week group, 2-VO 4 weeks group and 2-VO 8 weeks group. Behavior tests were utilized to assess cognitive abilities, while western blots were utilized to evaluate protein expression. Rats in the 2-VO groups spent less time exploring novel objects than those in the sham-operated group, and the discrimination ratio of the 2-VO 8 weeks group and the sham-operated group were higher than chance (0.50). Escape latencies in the Morris water maze task in the 2-VO 1 week group were longer than those in the sham-operated group on day 4 and day 5, while escape latencies in the 2-VO 4 weeks group were longer than those in the sham-operated group from day 3 to day 5. Escape latencies in 2-VO 8 weeks group were longer than those in the sham-operated group from day 2 to day 5. NE (northeast) square swimming times in the 2-VO 1 week group, 2-VO 4 weeks group and 2-VO 8 weeks group were shorter than that in the sham-operated group. Western blotting showed that the PI3K expression in the 2-VO 1 week group was lower than that in sham-operated group, while p-Akt expression in the 2-VO 8 weeks group was higher than that in the sham-operated group. There was a linear relationship between the PI3K expression and the discrimination ratio, as well as a linear relationship between the PI3K and NE square swimming time. Thus, we propose that the PI3K/Akt signal pathway is an important cell pathway that is associated with the cognitive impairment following CCH.
doi:10.1371/journal.pone.0081901
PMCID: PMC3858283  PMID: 24339978
23.  Protective Effect of Ginsenoside Rb1 against Intestinal Ischemia-Reperfusion Induced Acute Renal Injury in Mice 
PLoS ONE  2013;8(12):e80859.
Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway.
doi:10.1371/journal.pone.0080859
PMCID: PMC3851764  PMID: 24324637
24.  Cloning and functional analysis of a novel ascorbate peroxidase (APX) gene from Anthurium andraeanum *  
An 888-bp full-length ascorbate peroxidase (APX) complementary DNA (cDNA) gene was cloned from Anthurium andraeanum, and designated as AnAPX. It contains a 110-bp 5′-noncoding region, a 28-bp 3′-noncoding region, and a 750-bp open reading frame (ORF). This protein is hydrophilic with an aliphatic index of 81.64 and its structure consisting of α-helixes, β-turns, and random coils. The AnAPX protein showed 93%, 87%, 87%, 87%, and 86% similarities to the APX homologs from Zantedeschia aethiopica, Vitis pseudoreticulata, Gossypium hirsutum, Elaeis guineensis, and Zea mays, respectively. AnAPX gene transcript was measured non-significantly in roots, stems, leaves, spathes, and spadices by real-time polymerase chain reaction (RT-PCR) analysis. Interestingly, this gene expression was remarkably up-regulated in response to a cold stress under 6 °C, implying that AnAPX might play an important role in A. andraeanum tolerance to cold stress. To confirm this function we overexpressed AnAPX in tobacco plants by transformation with an AnAPX expression construct driven by CaMV 35S promoter. The transformed tobacco seedlings under 4 °C showed less electrolyte leakage (EL) and malondialdehyde (MDA) content than the control. The content of MDA was correlated with chilling tolerance in these transgenic plants. These results show that AnAPX can prevent the chilling challenged plant from cell membrane damage and ultimately enhance the plant cold tolerance.
doi:10.1631/jzus.B1300105
PMCID: PMC3863369  PMID: 24302711
AnAPX; Gene expression; Cold stress; Anthurium andraeanum
25.  Effect of Exogenous Factors on Bacteriocin Production from Lactobacillus paracasei J23 by Using a Resting Cell System 
A resting cell system was developed for bacteriocin Lac-B23 production from Lactobacillus paracasei J23. The resting cell medium contained (g/L): Glucose 20, Sodium acetate 5.0, MnSO4 0.25 MgSO4 0.5, Ammoniumhydrogencitrate 1.0, KH2PO4 1.0. The resting cell incubation time and temperature were 20 h and 37 °C and the effects of exogenous factors, including amino acids, glycerol, pyruvic acid, and α-ketoglutaric acid were investigated. Cys and Gly could stimulate the production of bacteriocin, while no stimulus effect was observed for Glu, Tyr and Ala. Glycerol and pyruvic acid increased bacteriocin production and the optimum concentrations were 1% and 30 g/L, respectively. Bacteriocin could act as an inducer of its own biosynthesis. These findings are of importance for the further study of bacteriocin biosynthesis regulation and for the improvement of bacteriocin production yields.
doi:10.3390/ijms141224355
PMCID: PMC3876115  PMID: 24351821
lactic acid bacteria; bacteriocin; Lactobacillus paracasei; resting cell; system; exogenous factors

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