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Sample records for enhancing runx2 activity

  1. β-catenin enhances odontoblastic differentiation of dental pulp cells through activation of Runx2.

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    Nana Han

    Full Text Available An intense stimulus can cause death of odontoblasts and initiate odontoblastic differentiation of stem/progenitor cell populations of dental pulp cells (DPCs, which is followed by reparative dentin formation. However, the mechanism of odontoblastic differentiation during reparative dentin formation remains unclear. This study was to determine the role of β-catenin, a key player in tooth development, in reparative dentin formation, especially in odontoblastic differentiation. We found that β-catenin was expressed in odontoblast-like cells and DPCs beneath the perforation site during reparative dentin formation after direct pulp capping. The expression of β-catenin was also significantly upregulated during odontoblastic differentiation of in vitro cultured DPCs. The expression pattern of runt-related transcription factor 2 (Runx2 was similar to that of β-catenin. Immunofluorescence staining indicated that Runx2 was also expressed in β-catenin-positive odontoblast-like cells and DPCs during reparative dentin formation. Knockdown of β-catenin disrupted odontoblastic differentiation, which was accompanied by a reduction in β-catenin binding to the Runx2 promoter and diminished expression of Runx2. In contrast, lithium chloride (LiCl induced accumulation of β-catenin produced the opposite effect to that caused by β-catenin knockdown. In conclusion, it was reported in this study for the first time that β-catenin can enhance the odontoblastic differentiation of DPCs through activation of Runx2, which might be the mechanism involved in odontoblastic differentiation during reparative dentin formation.

  2. The correlated evolution of Runx2 tandem repeats, transcriptional activity, and facial length in carnivora.

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    Sears, K E; Goswami, A; Flynn, J J; Niswander, L A

    2007-01-01

    To assess the ability of protein-coding mutations to contribute to subtle, inter-specific morphologic evolution, here, we test the hypothesis that mutations within the protein-coding region of runt-related transcription factor 2 (Runx2) have played a role in facial evolution in 30 species from a naturally evolving group, the mammalian order Carnivora. Consistent with this hypothesis, we find significant correlations between changes in Runx2 glutamine-alanine tandem-repeat ratio, and both Runx2 transcriptional activity and carnivoran facial length. Furthermore, we identify a potential evolutionary mechanism for the correlation between Runx2 tandem repeat ratio and facial length. Specifically, our results are consistent with the Runx2 tandem repeat system providing a flexible genetic mechanism to rapidly change the timing of ossification. These heterochronic changes, in turn, potentially act on existing allometric variation in carnivoran facial length to generate the disparity in adult facial lengths observed among carnivoran species. Our results suggest that despite potentially great pleiotropic effects, changes to the protein-coding regions of genes such as Runx2 do occur and have the potential to affect subtle morphologic evolution across a diverse array of species in naturally evolving lineages.

  3. Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction.

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    Zhang, Xin; Ma, Yong; Fu, Xin; Liu, Qiang; Shao, Zhenxing; Dai, Linghui; Pi, Yanbin; Hu, Xiaoqing; Zhang, Jiying; Duan, Xiaoning; Chen, Wenqing; Chen, Ping; Zhou, Chunyan; Ao, Yingfang

    2016-01-08

    Runx2 is a powerful osteo-inductive factor and adipose-derived stem cells (ADSCs) are multipotent. However, it is unknown whether Runx2-overexpressing ADSCs (Runx2-ADSCs) could promote anterior cruciate ligament (ACL) reconstruction. We evaluated the effect of Runx2-ADSCs on ACL reconstruction in vitro and in vivo. mRNA expressions of osteocalcin (OCN), bone sialoprotein (BSP) and collagen I (COLI) increased over time in Runx2-ADSCs. Runx2 overexpression inhibited LPL and PPARγ mRNA expressions. Runx2 induced alkaline phosphatase activity markedly. In nude mice injected with Runx2-ADSCs, promoted bone formation was detected by X-rays 8 weeks after injection. The healing of tendon-to-bone in a rabbit model of ACL reconstruction treated with Runx2-ADSCs, fibrin glue only and an RNAi targeting Runx2, was evaluated with CT 3D reconstruction, histological analysis and biomechanical methods. CT showed a greater degree of new bone formation around the bone tunnel in the group treated with Runx2-ADSCs compared with the fibrin glue group and RNAi Runx2 group. Histology showed that treatment with Runx2-ADSCs led to a rapid and significant increase at the tendon-to-bone compared with the control groups. Biomechanical tests demonstrated higher tendon pullout strength in the Runx2-ADSCs group at early time points. The healing of the attachment in ACL reconstruction was enhanced by Runx2-ADSCs.

  4. ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGFβ Signaling Pathway.

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    Li, Xiao-Qing; Du, Xin; Li, Dong-Mei; Kong, Peng-Zhou; Sun, Yan; Liu, Pei-Fang; Wang, Qing-Shan; Feng, Yu-Mei

    2015-08-15

    Bone metastasis affects more than 70% of advanced breast cancer patients, but the molecular mechanisms of this process remain unclear. Here, we present clinical and experimental evidence to clarify the role of the integrin β-like 1 (ITGBL1) as a key contributor to bone metastasis of breast cancer. In an in vivo model system and in vitro experiments, ITGBL1 expression promoted formation of osteomimetic breast cancers, facilitating recruitment, residence, and growth of cancer cells in bone microenvironment along with osteoclast maturation there to form osteolytic lesions. Mechanistic investigations identified the TGFβ signaling pathway as a downstream effector of ITGBL1 and the transcription factor Runx2 as an upstream activator of ITGBL1 expression. In support of these findings, we also found that ITGBL1 was an essential mediator of Runx2-induced bone metastasis of breast cancer. Overall, our results illuminate how bone metastasis occurs in breast cancer, and they provide functional evidence for new candidate biomarkers and therapeutic targets to identify risk, to prevent, and to treat this dismal feature of advanced breast cancer. ©2015 American Association for Cancer Research.

  5. In vitro inhibitory effects of terpenoids from Chloranthus multistachys on epithelial-mesenchymal transition via down-regulation of Runx2 activation in human breast cancer.

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    Fu, Jianjiang; Wang, Shan; Lu, Hong; Ma, Junchao; Ke, Xiaoqin; Liu, Ting; Luo, Yongming

    2015-01-15

    From Chloranthus multistachys, three terpenoids - lupeol (1), henrilabdane B (2), and istanbulin A (3) were isolated. Structures of compounds were established by NMR and MS. We reported here that ISTA (3) suppressed cell invasion, but lupeol (1) and henrilabdane B (2) did not. Furthermore, ISTA significantly inhibited the ability of adhesion and migration in vitro. Next, mechanisms of ISTA-induced inhibitory effects on in vitro metastasis were investigated. Sequential treatment data revealed that ISTA dramatically inhibited EGF-induced EMT. Western blot indicated that ISTA also significantly suppressed expression of E-cadherin, vimentin, and slug. In addition, ISTA inhibited Runx2 activation and phosph-Runx2 expression. Collectively, ISTA exhibited significant inhibitory effects on in vitro metastatic potential via inducing EMT inhibition, which may be associated with inhibition of transcriptional activity of Runx2. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis

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    Gabet Yankel

    2010-09-01

    Full Text Available Abstract Background Prostate cancer (PCa cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2. Results We engineered a C4-2B PCa sub-line called C4-2B/Rx2dox, in which Doxycycline (Dox treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1, proteolytic enzymes (MMP9, CST7, cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A, intracellular signaling molecules (DUSP1, SPHK1, RASD1 and transcription factors (Sox9, SNAI2, SMAD3 functioning in epithelium to mesenchyme transition (EMT, tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal. Conclusions The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is

  7. Codonolactone, a sesquiterpene lactone isolated from Chloranthus henryi Hemsl, inhibits breast cancer cell invasion, migration and metastasis by downregulating the transcriptional activity of Runx2.

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    Wang, Wei; Chen, Bin; Zou, Ruolan; Tu, Xiuying; Tan, Songlin; Lu, Hong; Liu, Zhaojie; Fu, Jianjiang

    2014-11-01

    Metastasis is the most insidious aspect of breast cancer, but effective strategies to control this malignant process are still lacking. In previous studies, we screened over 200 extracts from plants of genus Chloranthaceae by bioactivity-guided fractionation, and found that Codonolactone (CLT) exhibited potential antimetastatic properties in breast cancer cells. This sesquiterpene lactone was isolated from Chloranthus henryi Hemsl, and is also found in other medical herbs, such as Codonopsis pilosula, Atractylodes macrocephala Koidz and others. Here, we report that CLT inhibited the ability of invasion and migration in metastatic breast cancer cells. Furthermore, CLT exhibited significant suppression on formation of lung metastatic foci of breast cancer in vivo. We next investigated the mechanism of CLT-induced metastasis inhibitory effects in breast cancer cells. A significant inhibition on activity and expression of MMP-9 and MMP-13 was observed. Moreover, data from western blotting, Runx2 transcription factor assay and chromatin immunoprecipitation assay showed that binding ability of Runx2 to sequences of the mmp-13 promoter was inhibited by CLT. Collectively, these findings suggested that the antimetastatic properties of CLT in breast cancer were due to the inhibition of MMPs, which might be associated with a downregulation of Runx2 transcriptional activity.

  8. The NAD-Dependent Deacetylase Sirtuin-1 Regulates the Expression of Osteogenic Transcriptional Activator Runt-Related Transcription Factor 2 (Runx2 and Production of Matrix Metalloproteinase (MMP-13 in Chondrocytes in Osteoarthritis

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    Koh Terauchi

    2016-06-01

    Full Text Available Aging is one of the major pathologic factors associated with osteoarthritis (OA. Recently, numerous reports have demonstrated the impact of sirtuin-1 (Sirt1, which is the NAD-dependent deacetylase, on human aging. It has been demonstrated that Sirt1 induces osteogenic and chondrogenic differentiation of mesenchymal stem cells. However, the role of Sirt1 in the OA chondrocytes still remains unknown. We postulated that Sirt1 regulates a hypertrophic chondrocyte lineage and degeneration of articular cartilage through the activation of osteogenic transcriptional activator Runx2 and matrix metalloproteinase (MMP-13 in OA chondrocytes. To verify whether sirtuin-1 (Sirt1 regulates chondrocyte activity in OA, we studied expressions of Sirt1, Runx2 and production of MMP-13, and their associations in human OA chondrocytes. The expression of Sirt1 was ubiquitously observed in osteoarthritic chondrocytes; in contrast, Runx2 expressed in the osteophyte region in patients with OA and OA model mice. OA relating catabolic factor IL-1βincreased the expression of Runx2 in OA chondrocytes. OA chondrocytes, which were pretreated with Sirt1 inhibitor, inhibited the IL-1β-induced expression of Runx2 compared to the control. Since the Runx2 is a promotor of MMP-13 expression, Sirt1 inactivation may inhibit the Runx2 expression and the resultant down-regulation of MMP-13 production in chondrocytes. Our findings suggest thatSirt1 may regulate the expression of Runx2, which is the osteogenic transcription factor, and the production of MMP-13 from chondrocytes in OA. Since Sirt1 activity is known to be affected by several stresses, including inflammation and oxidative stress, as well as aging, SIRT may be involved in the development of OA.

  9. Evolution of the interaction between Runx2 and VDR, two transcription factors involved in osteoblastogenesis

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    Barriga Elias H

    2010-03-01

    Full Text Available Abstract Background The mineralized skeleton is a major evolutionary novelty that has contributed to the impressive morphological diversifications of the vertebrates. Essential to bone biology is the solidified extracellular matrix secreted by highly specialized cells, the osteoblasts. We now have a rather complete view of the events underlying osteogenesis, from a cellular, molecular, genetic, and epigenetic perspective. Because this knowledge is still largely restricted to mammals, it is difficult, if not impossible, to deduce the evolutionary history of the regulatory network involved in osteoblasts specification and differentiation. In this study, we focused on the transcriptional regulators Runx2 and VDR (the Vitamin D Receptor that, in mammals, directly interact together and stabilize complexes of co-activators and chromatin remodellers, thereby allowing the transcriptional activation of target genes involved in extracellular matrix mineralization. Using a combination of functional, biochemical, and histological approaches, we have asked if the interaction observed between Runx2 and VDR represents a recent mammalian innovation, or if it results from more ancient changes that have occurred deep in the vertebrate lineage. Results Using immunohistochemistry and in situ hybridization in developing embryos of chick, frog and teleost fishes, we have revealed that the co-expression of Runx2 and VDR in skeletal elements has been particularly strengthened in the lineage leading to amniotes. We show that the teleost Runx2 orthologue as well as the three mammalian Runx1, Runx2 and Runx3 paralogues are able to co-immunoprecipitate with the VDR protein present in nuclear extracts of rat osteoblasts stimulated with 1α,25-dihydroxyvitamin D3. In addition, the teleost Runx2 can activate the transcription of the mammalian osteocalcin promoter in transfection experiments, and this response can be further enhanced by 1α,25-dihydroxyvitamin D3. Finally

  10. A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells.

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    Min Hwa Shin

    2016-02-01

    Full Text Available The inactivation of p53 creates a major challenge for inducing apoptosis in cancer cells. An attractive strategy is to identify and subsequently target the survival signals in p53 defective cancer cells. Here we uncover a RUNX2-mediated survival signal in p53 defective cancer cells. The inhibition of this signal induces apoptosis in cancer cells but not non-transformed cells. Using the CRISPR technology, we demonstrate that p53 loss enhances the apoptosis caused by RUNX2 knockdown. Mechanistically, RUNX2 provides the survival signal partially through inducing MYC transcription. Cancer cells have high levels of activating histone marks on the MYC locus and concomitant high MYC expression. RUNX2 knockdown decreases the levels of these histone modifications and the recruitment of the Menin/MLL1 (mixed lineage leukemia 1 complex to the MYC locus. Two inhibitors of the Menin/MLL1 complex induce apoptosis in p53 defective cancer cells. Together, we identify a RUNX2-mediated epigenetic mechanism of the survival of p53 defective cancer cells and provide a proof-of-principle that the inhibition of this epigenetic axis is a promising strategy to kill p53 defective cancer cells.

  11. SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2.

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    Kayvan Zainabadi

    Full Text Available Activation of SIRT1 has previously been shown to protect mice against osteoporosis through yet ill-defined mechanisms. In this study, we outline a role for SIRT1 as a positive regulator of the master osteoblast transcription factor, RUNX2. We find that ex vivo deletion of sirt1 leads to decreased expression of runx2 downstream targets, but not runx2 itself, along with reduced osteoblast differentiation. Reciprocally, treatment with a SIRT1 agonist promotes osteoblast differentiation, as well as the expression of runx2 downstream targets, in a SIRT1-dependent manner. Biochemical and luciferase reporter assays demonstrate that SIRT1 interacts with and promotes the transactivation potential of RUNX2. Intriguingly, mice treated with the SIRT1 agonist, resveratrol, show similar increases in the expression of RUNX2 targets in their calvaria (bone tissue, validating SIRT1 as a physiologically relevant regulator of RUNX2.

  12. Live cell imaging of the cancer-related transcription factor RUNX2 during mitotic progression.

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    Pockwinse, Shirwin M; Kota, Krishna P; Quaresma, Alexandre J C; Imbalzano, Anthony N; Lian, Jane B; van Wijnen, Andre J; Stein, Janet L; Stein, Gary S; Nickerson, Jeffrey A

    2011-05-01

    The nuclear matrix bound transcription factor RUNX2 is a lineage-specific developmental regulator that is linked to cancer. We have previously shown that RUNX2 controls transcription of both RNA polymerase II genes and RNA polymerase I-dependent ribosomal RNA genes. RUNX2 is epigenetically retained through mitosis on both classes of target genes in condensed chromosomes. We have used fluorescence recovery after photobleaching to measure the relative binding kinetics of enhanced green fluorescent protein (EGFP)-RUNX2 at transcription sites in the nucleus and nucleoli during interphase, as well as on mitotic chromosomes. RUNX2 becomes more strongly bound as cells go from interphase through prophase, with a doubling of the most tightly bound "immobile fraction." RUNX2 exchange then becomes much more facile during metaphase to telophase. During interphase the less tightly bound pool of RUNX2 exchanges more slowly at nucleoli than at subnuclear foci, and the non-exchanging immobile fraction is greater in nucleoli. These results are consistent with a model in which the molecular mechanism of RUNX2 binding is different at protein-coding and ribosomal RNA genes. The binding interactions of RUNX2 change as cells go through mitosis, with binding affinity increasing as chromosomes condense and then decreasing through subsequent mitotic phases. The increased binding affinity of RUNX2 at mitotic chromosomes may reflect its epigenetic function in "bookmarking" of target genes in cancer cells. Copyright © 2010 Wiley-Liss, Inc.

  13. Runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligament.

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    Makiko Iwasaki

    Full Text Available Ossification of the Posterior Longitudinal Ligament (OPLL is a disease that is characterized by the ectopic calcification of the ligament; however, the pathogenesis of OPLL remains to be investigated. We attempted to identify the in vivo role of Runx2, a master regulator of osteoblast differentiation and skeletal mineralization, in the pathogenesis of OPLL. The expression of Runx2 in the ligament was examined using in situ hybridization and immunohistochemistry and by monitoring the activity of a LacZ gene that was inserted into the Runx2 gene locus. To investigate the functional role of Runx2, we studied ENPP1(ttw/ttw mice, a mouse model of OPLL, that were crossed with heterozygous Runx2 mice to decrease the expression of Runx2, and we performed histological and quantitative radiological analyses using 3D-micro CT. Runx2 was expressed in the ligament of wild-type mice. The induction of Runx2 expression preceded the development of ectopic calcification in the OPLL-like region of the ENPP1(ttw/ttw mice. Runx2 haploinsufficiency ameliorated the development of ectopic calcification in the ENPP1(ttw/ttw mice. Collectively, this study demonstrated that Runx2 is expressed in an OPLL-like region, and its elevation is a prerequisite for developing the complete OPLL-like phenotype in a mouse model of OPLL.

  14. The role of Runx2 in facilitating autophagy in metastatic breast cancer cells.

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    Tandon, Manish; Othman, Ahmad H; Ashok, Vivek; Stein, Gary S; Pratap, Jitesh

    2018-01-01

    Breast cancer metastases cause significant patient mortality. During metastases, cancer cells use autophagy, a catabolic process to recycle nutrients via lysosomal degradation, to overcome nutritional stress for their survival. The Runt-related transcription factor, Runx2, promotes cell survival under metabolic stress, and regulates breast cancer progression and bone metastases. Here, we identify that Runx2 enhances autophagy in metastatic breast cancer cells. We defined Runx2 function in cellular autophagy by monitoring microtubule-associated protein light chain (LC3B-II) levels, an autophagy-specific marker. The electron and confocal microscopic analyses were utilized to identify alterations in autophagic vesicles. The Runx2 knockdown cells accumulate LC3B-II protein and autophagic vesicles due to reduced turnover. Interestingly, Runx2 promotes autophagy by enhancing trafficking of LC3B vesicles. Our mechanistic studies revealed that Runx2 promotes autophagy by increasing acetylation of α-tubulin sub-units of microtubules. Inhibiting autophagy decreased cell adhesion and survival of Runx2 knockdown cells. Furthermore, analysis of LC3B protein in clinical breast cancer specimens and tumor xenografts revealed significant association between high Runx2 and low LC3B protein levels. Our studies reveal a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. © 2017 Wiley Periodicals, Inc.

  15. Role of Runx2 phosphorylation in prostate cancer and association with metastatic disease.

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    Ge, C; Zhao, G; Li, Y; Li, H; Zhao, X; Pannone, G; Bufo, P; Santoro, A; Sanguedolce, F; Tortorella, S; Mattoni, M; Papagerakis, S; Keller, E T; Franceschi, R T

    2016-01-21

    The osteogenic transcription factor, Runx2, is abnormally expressed in prostate cancer (PCa) and associated with metastatic disease. During bone development, Runx2 is activated by signals known to be hyperactive in PCa including the RAS/MAP kinase pathway, which phosphorylates Runx2 on multiple serine residues including S301 and S319 (equivalent to S294 and S312 in human Runx2). This study examines the role of these phosphorylation sites in PCa. Runx2 was preferentially expressed in more invasive PCa cell lines (PC3>C4-2B>LNCaP). Furthermore, analysis using a P-S319-Runx2-specific antibody revealed that the ratio of P-S319-Runx2/total Runx2 as well as P-ERK/total ERK was highest in PC3 followed by C4-2B and LNCaP cells. These results were confirmed by immunofluorescence confocal microscopy, which showed a higher percentage of PC3 cells staining positive for P-S319-Runx2 relative to C4-2B and LNCaP cells. Phosphorylated Runx2 had an exclusively nuclear localization. When expressed in prostate cell lines, wild-type Runx2 increased metastasis-associated gene expression, in vitro migratory and invasive activity as well as in vivo growth of tumor cell xenografts. In contrast, S301A/S319A phosphorylation site mutations greatly attenuated these Runx2 responses. Analysis of tissue microarrays from 129 patients revealed strong nuclear staining with the P-S319-Runx2 antibody in primary PCas and metastases. P-S319-Runx2 staining was positively correlated with Gleason score and occurrence of lymph node metastases while little or no Runx2 phosphorylation was seen in normal prostate, benign prostate hyperplasia or prostatitis indicating that Runx2 S319 phosphorylation is closely associated with PCa induction and progression towards an aggressive phenotype. These studies establish the importance of Runx2 phosphorylation in prostate tumor growth and highlight its value as a potential diagnostic marker and therapeutic target.

  16. [Effect of overexpression of transcription factor Runx2 and Osterix on osteogenic differentiation of endothelial cells].

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    Yang, Guang-Zheng; Zhang, Wen-Jie; Ding, Xun; Zhang, Xiang-Kai; Jiang, Xin-Quan; Zhang, Zhi-Yuan

    2017-08-01

    To explore the effect of overexpression of Runx2 and Osterix (OSX) genes on osteogenic differentiation of human umbilical vein endothelial cells (HUVECs). Overexpressed Runx2 and OSX lentiviral vectors were transfected into HUVECs respectively. The osteogenic potential of transfected cells was identified by alkaline phosphatase (ALP) staining and ALP activity. Furthermore, real time-PCR, Western blot and immunofluorescence staining were performed to detect the expression of osteogenic genes and proteins in HUVECs. GraphPad Prism 6.01 software was used for statistical analysis. Overexpression of Runx2 gene was beneficial for osteogenic differentiation of HUVECs, while overexpression of osterix gene did not show osteogenic differential potential. Moreover, overexpression of Runx2 gene in HUVECs up-regulated the gene expression level of Runx2, OSX, ALP, bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN), and up-regulated protein level of OPN and OCN. Overexpression of Runx2 could promote osteogenic differentiation of HUVECs.

  17. The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial–Mesenchymal Transition

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    Zi Cao

    2017-02-01

    Full Text Available The transcription factor Runx2 has been reported to promote epithelial-mesenchymal transition (EMT in many tumors. Vasculogenic mimicry (VM is described as the mimicry of endothelial cells by tumor cells to form microvascular tubes in aggressive tumors. Galectin-3 has been reported to regulate cell invasion, migration, and VM formation; it could be regulated by Runx2. However, the relationship between Runx2, Galectin-3, EMT, and VM has not been studied in hepatocellular carcinoma (HCC. We examined Runx2 expression in 89 human HCC samples and found Runx2 expression was associated with VM. Clinical-pathological data analysis revealed that Runx2 expression was associated with a shorter survival period. Overexpression of Runx2 promoted EMT and enhanced cell migration, invasion, and VM formation in HepG2 cells. Conversely, the downregulation of Runx2 inhibited EMT and reduced cell invasion, migration, and VM formation in SMMC7721. Galectin-3 expression declined following the downregulation of Runx2 in HepG2 cells, and increased in SMMC7721 cells after Runx2 knockdown. We consistently demonstrated that the downregulation of LGALS3 in HepG2-Runx2 cells reduced cell migration; invasion and VM formation; while upregulation of LGALS3 in SMMC7721-shRunx2 cells enhanced cell migration, invasion, and VM formation. The results indicate that Runx2 could promote EMT and VM formation in HCC and Galectin-3 might have some function in this process.

  18. Glucocorticoids Antagonize RUNX2 During Osteoblast Differentiation in Cultures of ST2 Pluripotent Mesenchymal Cells

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    Koromila, Theodora; Baniwal, Sanjeev K.; Song, Yae S.; Martin, Anthony; Xiong, Jian; Frenkel, Baruch

    2018-01-01

    The efficacy of glucocorticoids (GCs) in treating a wide range of autoimmune and inflammatory conditions is blemished by severe side effects, including osteoporosis. The chief mechanism leading to GC-induced osteoporosis is inhibition of bone formation, but the role of RUNX2, a master regulator of osteoblast differentiation and bone formation, has not been well studied. We assessed effects of the synthetic GC dexamethasone (dex) on transcription of RUNX2-stimulated genes during the differentiation of mesenchymal pluripotent cells into osteoblasts. Dex inhibited a RUNX2 reporter gene and attenuated locus-dependently RUNX2-driven expression of several endogenous target genes. The anti-RUNX2 activity of dex was not attributable to decreased RUNX2 expression, but rather to physical interaction between RUNX2 and the GC receptor (GR), demonstrated by co-immunoprecipitation assays and co-immunofluorescence imaging. Investigation of the RUNX2/GR interaction may lead to the development of bone-sparing GC treatment modalities for the management of autoimmune and inflammatory diseases. PMID:23943595

  19. Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters.

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    Hasegawa, Sachi; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Matsushita, Masaki; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2016-02-05

    Endochondral ossification is an essential process for reparative phase of fracture healing, which starts with the differentiation of mesenchymal cells into chondrocytes followed by substitution of bone tissue. It is strictly controlled by the expression of crucial transcriptional factors: SOX9 in the early phase and RUNX2 in the late phase. Screening of FDA-approved compounds revealed that an anti-allergic drug, tranilast, that has been used for more than 30 years in clinical practice, enhanced the SOX9 promoter in chondrogenic cells and the RUNX2 promoter in osteoblastic cells. We observed that tranilast increased mRNA expression of both Sox9 and Runx2 in differentiating ATDC5 chondrogenic progenitor cells. Tranilast upregulated mRNA expression of chondrogenic marker genes (Col2a1, Acan, Col10a1, and Mmp13) in differentiating ATDC5 cells. Moreover, tranilast upregulated mRNA expression of essential signaling molecules involved in endochondral ossification (Pthrp, Ihh, and Axin2). In the later phase of differentiation of ATDC5 cells, tranilast increased synthesis of matrix proteoglycans, induced the alkaline phosphatase activity, and tended to accelerate mineralization. Tranilast is a potential agent that accelerates fracture repair by promoting the regulatory steps of endochondral ossification. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Synergistic Inhibition of Endochondral Bone Formation by Silencing Hif1α and Runx2 in Trauma-induced Heterotopic Ossification

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    Lin, Lin; Shen, Qi; Leng, Huijie; Duan, Xiaoning; Fu, Xin; Yu, Changlong

    2011-01-01

    Angiogenesis and osteogenesis are tightly coupled during bone development. We studied the effect of inhibition of Hif1α and Runt-related protein 2 (Runx2) on the formation of heterotopic ossification (HO). We constructed lentivirus vectors expressing Hif1α small interfering RNA (siRNA) and Runx2 siRNA. The inhibition of Hif1α function impaired osteoblast proliferation while osteoblasts differentiated normally. Osteoblasts lacking Runx2 proliferated normally while the differentiation was impaired. The osteoblast differentiation was significantly inhibited by co-Runx2 and Hif1α siRNA treatment. The formation of HO by inhibiting Runx2 and Hif1α in an animal model induced by Achilles tenotomy was investigated. The results showed that lacking of Runx2 and Hif1α could inhibit HO formation. Inhibition of Hif1α prevented HO formation only at the initial step and inhibition of Runx2 worked both at the initial step and after chondrogenesis. Angiogenesis and the expressions of osteogenic genes were downregulated in the Hif1α siRNA group. We found synergistic inhibition of endochondral bone formation by silencing Hif1α and Runx2. Our study provided new insight into the roles of Hif1α and Runx2 during the processes of endochondral bone formation, and had important implications for the new therapeutic methods to inhibit HO or to enhance bone formation. PMID:21629226

  1. The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells.

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    Choe, Moran; Brusgard, Jessica L; Chumsri, Saranya; Bhandary, Lekhana; Zhao, Xianfeng Frank; Lu, Song; Goloubeva, Olga G; Polster, Brian M; Fiskum, Gary M; Girnun, Geoffrey D; Kim, Myoung Sook; Passaniti, Antonino

    2015-10-01

    Activation of genes promoting aerobic glycolysis and suppression of mitochondrial oxidative phosphorylation is one of the hallmarks of cancer. The RUNX2 transcription factor mediates breast cancer (BC) metastasis to bone and is regulated by glucose availability. But, the mechanisms by which it regulates glucose metabolism and promotes an oncogenic phenotype are not known. RUNX2 expression in luminal BC cells correlated with lower estrogen receptor-α (ERα) levels, anchorage-independent growth, expression of glycolytic genes, increased glucose uptake, and sensitivity to glucose starvation, but not to inhibitors of oxidative phosphorylation. Conversely, RUNX2 knockdown in triple-negative BC cells inhibited mammosphere formation and glucose dependence. RUNX2 knockdown resulted in lower LDHA, HK2, and GLUT1 glycolytic gene expression, but upregulation of pyruvate dehydrogenase-A1 (PDHA1) mRNA and enzymatic activity, which was consistent with lower glycolytic potential. The NAD-dependent histone deacetylase, SIRT6, a known tumor suppressor, was a critical regulator of these RUNX2-mediated metabolic changes. RUNX2 expression resulted in elevated pAkt, HK2, and PDHK1 glycolytic protein levels that were reduced by ectopic expression of SIRT6. RUNX2 also repressed mitochondrial oxygen consumption rates (OCR), a measure of oxidative phosphorylation (respiration). Overexpression of SIRT6 increased respiration in RUNX2-positive cells, but knockdown of SIRT6 in cells expressing low RUNX2 decreased respiration. RUNX2 repressed SIRT6 expression at both the transcriptional and post-translational levels and endogenous SIRT6 expression was lower in malignant BC tissues or cell lines that expressed high levels of RUNX2. These results support a hypothesis whereby RUNX2-mediated repression of the SIRT6 tumor suppressor regulates metabolic pathways that promote BC progression. © 2015 Wiley Periodicals, Inc.

  2. RUNX2 regulates the effects of TNFalpha on proliferation and apoptosis in SaOs-2 cells.

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    Olfa, Ghali; Christophe, Chauveau; Philippe, Lencel; Romain, Salomez; Khaled, Hani; Pierre, Hardouin; Odile, Broux; Jean-Christophe, Devedjian

    2010-04-01

    The runt-related transcriptional factor RUNX2 is an essential mediator of the osteoblast phenotype and plays a pivotal role in the process of osteoblast differentiation. The involvement of RUNX2 includes the regulation of genes that are important in committing cells to the osteoblast lineage. Increasing evidences are consistent with a requirement of RUNX2 for stringent control of osteoblast proliferation and recent data even suggested that RUNX2 might act as a proapoptotic factor. Among the cytokines described as modulators of osteoblast functions, TNFalpha affects both apoptosis and the differentiation rate from mesenchymal precursor cells of osteoblast. Thus we evaluated on the human osteosarcoma cell line SaOs-2 stably transfected with a RUNX2 dominant negative construct (DeltaRUNX2) the effects of serum and TNFalpha on proliferation and apoptosis. In this study we showed that SaOs-2 clones expressing high levels of DeltaRUNX2 presented a higher proliferation rate than clones transfected with an empty vector. This increase in cell growth was accompanied by a rise in cyclins A1, B1 and E1 expression and a decrease in the cyclin inhibitor p21. Moreover we observed that the expression of the RUNX2 transgene protected the SaOs-2 cells from the antiproliferative and the apoptotic effects induced by TNFalpha. This was accompanied by the inhibition of Bax and activation of Bcl2 expression. Experiments done on SaOs-2 cells transiently transfected with siRNA confirmed that RUNX2 represents a critical link between cell fate, proliferation and growth control. This study also suggested that RUNX2 might control osteoblastic growth depending on the differentiation stage of the cells by regulating expression of elements involved in hormones and cytokines sensitivity. Copyright 2009 Elsevier Inc. All rights reserved.

  3. Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP-2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling Activation

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    Han Seok Yoo

    2017-05-01

    Full Text Available The present study evaluated the effects of a calcium (Ca supplement derived from Gallus gallus domesticus (GD on breaking force, microarchitecture, osteogenic differentiation and osteoclast differentiation factor expression in vivo in Ca-deficient ovariectomized (OVX rats. One percent of Ca supplement significantly improved Ca content and bone strength of the tibia. In micro-computed tomography analysis, 1% Ca supplement attenuated OVX- and low Ca-associated changes in bone mineral density, trabecular thickness, spacing and number. Moreover, 1% Ca-supplemented diet increased the expression of osteoblast differentiation marker genes, such as bone morphogenetic protein-2, Wnt3a, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin and collagenase-1, while it decreased the expression of osteoclast differentiation genes, such as thrombospondin-related anonymous protein, cathepsin K and receptor activator of nuclear factor kappa B. Furthermore, 1% Ca-supplemented diet increased the levels of phosphorylated extracellular signal-regulated kinase and c-Jun N-terminal kinase. The increased expression of osteoblast differentiation marker genes and activation of mitogen-activated protein kinase signaling were associated with significant increases in trabecular bone volume, which plays an important role in the overall skeletal strength. Our results demonstrated that 1% Ca supplement inhibited osteoclastogenesis, stimulated osteoblastogenesis and restored bone loss in OVX rats.

  4. Genetic analysis of Runx2 function during intramembranous ossification.

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    Takarada, Takeshi; Nakazato, Ryota; Tsuchikane, Azusa; Fujikawa, Koichi; Iezaki, Takashi; Yoneda, Yukio; Hinoi, Eiichi

    2016-01-15

    Runt-related transcription factor 2 (Runx2) is an essential transcriptional regulator of osteoblast differentiation and its haploinsufficiency leads to cleidocranial dysplasia because of a defect in osteoblast differentiation during bone formation through intramembranous ossification. The cellular origin and essential period for Runx2 function during osteoblast differentiation in intramembranous ossification remain poorly understood. Paired related homeobox 1 (Prx1) is expressed in craniofacial mesenchyme, and Runx2 deficiency in cells of the Prx1 lineage (in mice referred to here as Runx2prx1 (-/-)) resulted in defective intramembranous ossification. Runx2 was heterogeneously expressed in Prx1-GFP(+) cells located at the intrasutural mesenchyme in the calvaria of transgenic mice expressing GFP under the control of the Prx1 promoter. Double-positive cells for Prx1-GFP and stem cell antigen-1 (Sca1) (Prx1(+)Sca1(+) cells) in the calvaria expressed Runx2 at lower levels and were more homogeneous and primitive than Prx1(+)Sca1(-) cells. Osterix (Osx) is another transcriptional determinant of osteoblast lineages expressed by osteoblast precursors; Osx is highly expressed by Prx1(-)Runx2(+) cells at the osteogenic front and on the surface of mineralized bone in the calvaria. Runx2 deficiency in cells of the Osx lineage (in mice referred to here as Runx2osx (-/-)) resulted in severe defects in intramembranous ossification. These findings indicate that the essential period of Runx2 function in intramembranous ossification begins at the Prx1(+)Sca1(+) mesenchymal stem cell stage and ends at the Osx(+)Prx1(-)Sca1(-) osteoblast precursor stage. © 2016. Published by The Company of Biologists Ltd.

  5. Deletion of Osr2 Partially Rescues Tooth Development in Runx2 Mutant Mice.

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    Kwon, H J E; Park, E K; Jia, S; Liu, H; Lan, Y; Jiang, R

    2015-08-01

    Tooth organogenesis depends on genetically programmed sequential and reciprocal inductive interactions between the dental epithelium and neural crest-derived mesenchyme. Previous studies showed that the Msx1 and Runx2 transcription factors are required for activation of odontogenic signals, including Bmp4 and Fgf3, in the early tooth mesenchyme to drive tooth morphogenesis through the bud-to-cap transition and that Runx2 acts downstream of Msx1 to activate Fgf3 expression. Recent studies identified Osr2 as a repressor of tooth development and showed that inactivation of Osr2 rescued molar tooth morphogenesis in the Msx1(-/-) mutant mice as well as in mice with neural crest-specific inactivation of Bmp4. Here we show that Runx2 expression is expanded in the tooth bud mesenchyme in Osr2(-/-) mutant mouse embryos and is partially restored in the tooth mesenchyme in Msx1(-/-)Osr2(-/-) mutants in comparison with Msx1(-/-) and wild-type embryos. Whereas mandibular molar development arrested at the bud stage and maxillary molar development arrested at the bud-to-cap transition in Runx2(-/-) mutant mice, both mandibular and maxillary molar tooth germs progressed to the early bell stage, with rescued expression of Msx1 and Bmp4 in the dental papilla as well as expression of Bmp4, p21, and Shh in the primary enamel knot in the Osr2(-/-)Runx2(-/-) compound mutants. In contrast to the Msx1(-/-)Osr2(-/-) compound mutants, which exhibit nearly normal first molar morphogenesis, the Osr2(-/-)Runx2(-/-) compound mutant embryos failed to activate the expression of Fgf3 and Fgf10 in the dental papilla and exhibited significant deficit in cell proliferation in both the dental epithelium and mesenchyme in comparison with the control embryos. These data indicate that Runx2 synergizes with Msx1 to drive tooth morphogenesis through the bud-to-cap transition and that Runx2 controls continued tooth growth and morphogenesis beyond the cap stage through activation of Fgf3 and Fgf10 expression

  6. Runx2 expression is associated with pathologic new bone formation around radicular cysts: an immunohistochemical demonstration.

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    Kusafuka, Kimihide; Sasaguri, Kenichi; Sato, Sadao; Takemura, Tamiko; Kameya, Toru

    2006-09-01

    Radicular cysts are the most common cysts in human jaw bones. These lesions induce bone remodeling of the surrounding alveolar bones, which was termed 'condensing osteitis', and was suggested to be related to cells of the osteoblastic lineage. The Runx2 (core-binding protein [cbfa]1/polyoma enhancer-binding protein [pebp]2alphaA) was shown to be a DNA-binding transcriptional molecule expressed in osteoprogenitor cells. We confirmed the specificity of anti-Runx2 antiserum, using Western blotting analysis. We investigated the expression and localization of Runx2 in 32 radicular cyst cases with bone tissue fragments, immunohistochemically. Signals for Runx2 were seen in 18 cases (56.3%) of radicular cysts with bone formation. These signals were immunolocalized in the nuclei of the spindle-shaped osteoprogenitor cells in the cyst walls, whereas only a few signals were seen in the cuboidal osteoblastic cells near the fibrous bones. Signals for type I collagen were immunolocalized in the dense collagen fibers in the cyst walls and in the matrix of the fibrous bone around the radicular cysts, whereas no signals were seen on the inner portions with inflammatory cell infiltration of the cyst walls. Very weak signals for transforming growth factor (TGF)-beta1 were infrequently seen in the osteoblasts of the fibrous bone, whereas signals for TGF-beta2 were observed in young osteocytes in the fibrous bones, in B-cell lymphocytes infiltrating into the inner portions, and on the cellular membranes of the lining epithelium. The nuclear expression of Runx2 in spindle-shaped cells in the outer portions may play an essential role in the induction of fibrous bone tissue around radicular cysts. TGF-beta2 may play a role in the production of type I collagen, which acts as a template for pathologic new bone formation, in radicular cysts.

  7. The odontogenic ameloblast-associated protein (ODAM) cooperates with RUNX2 and modulates enamel mineralization via regulation of MMP-20.

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    Lee, Hye-Kyung; Lee, Dong-Seol; Ryoo, Hyun-Mo; Park, Jong-Tae; Park, Su-Jin; Bae, Hyun-Sook; Cho, Moon-Il; Park, Joo-Cheol

    2010-10-15

    We have previously reported that the odontogenic ameloblast-associated protein (ODAM) plays important roles in enamel mineralization through the regulation of matrix metalloproteinase-20 (MMP-20). However, the precise function of ODAM in MMP-20 regulation remains largely unknown. The aim of the present study was to uncover the molecular mechanisms responsible for MMP-20 regulation. The subcellular localization of ODAM varies in a stage-specific fashion during ameloblast differentiation. During the secretory stage of amelogenesis ODAM was localized to both the nucleus and cytoplasm of ameloblasts. However, during the maturation stage of amelogenesis, ODAM was observed in the cytoplasm and at the interface between ameloblasts and the enamel layer, but not in the nucleus. Secreted ODAM was detected in the conditioned medium of ameloblast-lineage cell line (ALC) from days 14 to 21, which coincided with the maturation stage of amelogenesis. Interestingly, the expression of Runx2 and nuclear ODAM correlated with MMP-20 expression in ALC. We therefore examined whether ODAM cooperates with Runx2 to regulate MMP-20 and modulate enamel mineralization. Increased expression of ODAM and Runx2 augmented MMP-20 expression, and Runx2 expression enhanced expression of ODAM, although overexpression of ODAM did not influence Runx2 expression. Conversely, loss of Runx2 in ALC decreased ODAM expression, resulting in down-regulation of MMP-20 expression. Increased MMP-20 expression accelerated amelogenin processing during enamel mineralization. Our data suggest that Runx2 regulates the expression of ODAM and that nuclear ODAM serves an important regulatory function in the mineralization of enamel through the regulation of MMP-20 apart from a different, currently unidentified, function of extracellular ODAM. © 2010 Wiley-Liss, Inc.

  8. The Fam50a positively regulates ameloblast differentiation via interacting with Runx2.

    Science.gov (United States)

    Kim, Yuri; Hur, Sung-Woong; Jeong, Byung-Chul; Oh, Sin-Hye; Hwang, Yun-Chan; Kim, Sun-Hun; Koh, Jeong-Tae

    2017-06-02

    Differentiated ameloblasts secret enamel matrix proteins such as amelogenin, ameloblastin, and enamelin. Expression levels of these proteins are regulated by various factors. To find a new regulatory factor for ameloblast differentiation, we performed 2D-PAGE analysis using mouse ameloblast lineage cell line (mALCs) cultured with mineralizing medium. Of identified proteins, family with sequence similarity 50 member A (Fam50a) was significantly increased during differentiation of mALCs. Fam50a protein was also highly expressed in secretory ameloblasts of mouse tooth germs. In mALCs cultures, forced expression of Fam50a up-regulated the expression of enamel matrix protein genes such as amelogenin, ameloblastin, and enamelin. In addition, up-regulation of Fam50a also increased ALP activity and mineralized nodule formation in a dose-dependent manner. In contrast, knockdown of Fam50a decreased expression levels of enamel matrix protein genes, ALP activity, and mineralized nodule formation. By fluorescence microscopy, endogenous Fam50a protein was found to be localized to the nucleus of ameloblasts. In addition, Fam50a synergistically increased Ambn transactivation by Runx2. Moreover, Fam50a increased binding affinity of Runx2 to Ambn promoter by physically interacting with Runx2. Taken together, these results suggest Fam50a might be a new positive regulator of ameloblast differentiation. © 2017 Wiley Periodicals, Inc.

  9. Initial Characterization of Osteoblast Differentiation and Loss of RUNX2 Stability in the Newly Established SK11 Human Embryonic Stem Cell-Derived Cell Line

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    YU, JIA-LI; ADISETIYO, HELTY; LITTLE, GILLIAN H.; VANGSNESS, C. THOMAS; JIANG, JIANJIE; STERNBERG, HAL; WEST, MICHAEL D.; FRENKEL, BARUCH

    2018-01-01

    We describe a novel model for investigation of genetically normal human osteoblasts in culture. SK11 is a clonal progenitor cell line derived from human embryonic stem cells. Initially selected based on the expression of chondrogenic markers when differentiated in micromass culture, SK11 cells display typical mRNA expression patterns of bone phenotypic genes under osteogenic conditions. These include osterix, α1(I) collagen, alkaline phosphatase, osteonectin, osteopontin, and osteocalcin. Similar to well-characterized murine osteoblast cultures, the osteoblast master regulator RUNX2 was present during the first few days after plating, but the protein disappeared during the first week of culture. Loss of RUNX2 expression is considered an important regulatory feature for osteoblast maturation. Indeed, following ~2 weeks of differentiation, SK11 cultures exhibited robust calcium deposition, evidenced by alizarin red staining. We also introduced a lentiviral vector encoding doxycycline (dox)-inducible FLAG-tagged RUNX2 into SK11 cells. Dox-mediated enhancement of RUNX2 expression resulted in accelerated mineralization, which was further increased by co-treatment with BMP-2. Like the endogenous RUNX2, expression of the virally coded FLAG-RUNX2 was lost during the first week of culture despite persistent dox treatment. By following RUNX2 decay after dox withdrawal from day-5 versus day-3 cultures, we demonstrated a developmentally regulated decrease in RUNX2 stability. Availability of culture models for molecular investigation of genetically normal human osteoblasts is important because differences between murine and human osteoblasts, demonstrated here by the regulation of matrix Gla Protein, may have significant biomedical implications. PMID:25160731

  10. Identification of putative target genes of the transcription factor RUNX2.

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    Martin Kuhlwilm

    Full Text Available Comparisons of the genomes of Neandertals and Denisovans with present-day human genomes have suggested that the gene RUNX2, which encodes a transcription factor, may have been positively selected during early human evolution. Here, we overexpress RUNX2 in ten human cell lines and identify genes that are directly or indirectly affected by RUNX2 expression. We find a number of genes not previously known to be affected by RUNX2 expression, in particular BIRC3, genes encoded on the mitochondrial genome, and several genes involved in bone and tooth formation. These genes are likely to provide inroads into pathways affected by RUNX2 and potentially by the evolutionary changes that affected RUNX2 in modern humans.

  11. RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray, and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland

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    Laura McDonald

    2014-05-01

    Full Text Available RUNX2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. Upregulation of RUNX2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. However, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. Using a human tumour tissue microarray, we show that high RUNX2 expression is significantly associated with oestrogen receptor (ER/progesterone receptor (PR/HER2-negative breast cancers and that patients with high RUNX2 expression have a poorer survival rate than those with negative or low expression. We confirm RUNX2 as a gene that has a potentially important functional role in triple-negative breast cancer. To investigate the role of this gene in breast cancer, we made a transgenic model in which Runx2 is specifically expressed in murine mammary epithelium under the control of the mouse mammary tumour virus (MMTV promoter. We show that ectopic Runx2 perturbs normal development in pubertal and lactating animals, delaying ductal elongation and inhibiting lobular alveolar differentiation. We also show that the Runx2 transgene elicits age-related, pre-neoplastic changes in the mammary epithelium of older transgenic animals, suggesting that elevated RUNX2 expression renders such tissue more susceptible to oncogenic changes and providing further evidence that this gene might have an important, context-dependent role in breast cancer.

  12. Regulatory effects of bone morphogenetic protein-4 on tumour necrosis factor-α-suppressed Runx2 and osteoprotegerin expression in cementoblasts.

    Science.gov (United States)

    Wang, Yunlong; He, Hong; Cao, Zhengguo; Fang, Yi; Du, Mingyuan; Liu, Zhijian

    2017-08-01

    Root resorption is a common phenomenon presented in periodontitis and orthodontic treatment, both of which are accompanied by an elevated TNF-α expression level in the periodontal tissues. Previously, we proved that TNF-α showed an inhibitory effect on cementoblast differentiation, mineralization and proliferation. However, the effect of TNF-α on Runx2 and osteoprotegerin (OPG) expression remains undetermined. This study aimed to identify the influence of TNF-α on Runx2 and OPG expression in cementoblasts and to test whether BMP-2,-4,-6,-7 would affect TNF-α-regulated Runx2 and OPG. An immortalized murine cementoblast cell line OCCM-30 was used in this study. The expression of Runx2 and OPG were examined by qRT-PCR after stimulating cells with TNF-α. The role of signalling pathways, including MAPK, PI3K-Akt and NF-κB, were studied with the use of specific inhibitors. Cells were treated with TNF-α in combination with BMP-2,-4,-6 or -7, then the expression of Runx2 and OPG, the activity of MAPK and NF-κB pathways, and the proliferation ability were evaluated by qRT-PCR, Western blot and MTS assay respectively. TNF-α inhibited Runx2 and OPG mRNAs in OCCM-30 cells, and the inhibitory effects were further aggravated by blocking p38 MAPK or NF-κB pathway. TNF-α-inhibited Runx2 and OPG were up-regulated by BMP-4. The p38 MAPK and Erk1/2 pathways were further activated by the combined treatment of BMP-4 and TNF-α compared with TNF-α alone. Finally, the TNF-α-suppressed proliferation was not obviously affected by BMP-2,-4,-6 or -7. TNF-α inhibited Runx2 and OPG in cementoblasts, and the p38 MAPK and NF-κB pathways acted in a negative-feedback way to attenuate the inhibitory effects. TNF-α-inhibited Runx2 and OPG could be effectively up-regulated by BMP-4; however, further investigations are needed to fully elaborate the underlying mechanisms. © 2017 John Wiley & Sons Ltd.

  13. Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development.

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    Yumiko Togo

    Full Text Available Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1.

  14. Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development

    Science.gov (United States)

    Togo, Yumiko; Takahashi, Katsu; Saito, Kazuyuki; Kiso, Honoka; Tsukamoto, Hiroko; Huang, Boyen; Yanagita, Motoko; Sugai, Manabu; Harada, Hidemitsu; Komori, Toshihisa; Shimizu, Akira; MacDougall, Mary; Bessho, Kazuhisa

    2016-01-01

    Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP) and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1. PMID:27518316

  15. Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development.

    Science.gov (United States)

    Togo, Yumiko; Takahashi, Katsu; Saito, Kazuyuki; Kiso, Honoka; Tsukamoto, Hiroko; Huang, Boyen; Yanagita, Motoko; Sugai, Manabu; Harada, Hidemitsu; Komori, Toshihisa; Shimizu, Akira; MacDougall, Mary; Bessho, Kazuhisa

    2016-01-01

    Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP) and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1.

  16. Runx2-I isoform contributes to fetal bone formation even in the absence of specific N-terminal amino acids.

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    Hideaki Okura

    Full Text Available The Runt-related transcription factor 2 (Runx2 gene encodes the transcription factor Runx2, which is the master regulator of osteoblast development; insufficiency of this protein causes disorders of bone development such as cleidocranial dysplasia. Runx2 has two isoforms, Runx2-II and Runx2-I, and production of each isoform is controlled by a unique promoter: a distal promoter (P1 and a proximal promoter (P2, respectively. Although several studies have focused on differences and similarities between the two Runx2 isoforms, their individual roles in bone formation have not yet been determined conclusively, partly because a Runx2-I-targeted mouse model is not available. In this study, we established a novel Runx2-manipulated mouse model in which the first ATG of Runx2-I was replaced with TGA (a stop codon, and a neomycin-resistant gene (neo cassette was inserted at the first intron of Runx2-I. Homozygous Runx2-Ineo/neo mice showed severely reduced expression of Runx2-I, whereas Runx2-II expression was largely retained. Runx2-Ineo/neo mice showed neonatal lethality, and in these mice, intramembranous ossification was more severely defective than endochondral ossification, presumably because of the greater involvement of Runx2-I, compared with that of Runx2-II in intramembranous ossification. Interestingly, the depletion of neo rescued the above-described phenotypes, indicating that the isoform-specific N-terminal region of Runx2-I is not functionally essential for bone development. Taken together, our results provide a novel clue leading to a better understanding of the roles of Runx2 isoforms in osteoblast development.

  17. Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females.

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    Nigel A Morrison

    Full Text Available Runt related transcription factor 2 (RUNX2 is a key regulator of osteoblast differentiation. Several variations within the RUNX2 gene have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18 bp deletion within the polyalanine tract (17A>11A of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of distal radius and bones of intramembranous origin compared to bones of endochondral origin (p = 0.0001. In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p = 0.01, suggesting decreased bone turnover. The transactivation function of the 11A allele showed a minor quantitative decrease. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification.

  18. MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2.

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    Bai, Xiaoxue; Meng, Lin; Sun, Huijie; Li, Zhuo; Zhang, Xiufang; Hua, Shucheng

    2017-01-01

    Lung cancer is one of the most common causes of cancer related deaths worldwide. The role of several microRNAs (miRNAs) including miR-196b in different cancers has already been established. The study was aimed to explore the role of miR-196b in lung cancer and its possible underlying mechanism. Human lung cancer cell line A549 was transfected with miR-196b mimic, miR-196b inhibitor and corresponding controls. Then cell viability, migration, invasion, and apoptosis of A549 lung cancer cells either with overexpression or with suppression of miR-196b were estimated sequentially. Next, dual luciferase activity assay was performed to clarify whether Runx2 was a direct target of miR-196b. Finally, the expressions of main factors associated with epithelial mesenchymal transition (EMT), PI3K/AKT/GSK3β, Smad, and JNK pathways were detected by western blot. MiR-196b expression was significantly decreased in A549, H1650 and H1299 cell lines compared with in WI-38 and HEL-1 cell lines. Overexpression of miR-196b suppressed cell viability, migration, invasion, and induced apoptosis as well as inhibited TGF-β induced EMT process in A549 cells. In addition, Runx2 was a putative target of miR-196b, and Runx2 silence remarkably increased cell apoptosis and abolished the promotive effects of miR-196b suppression on cell viability, migration and invasion. Finally, miR-196b also mediated its action by inactivation of PI3K/AKT/GSK3β, Smad, and JNK pathways by down-regulation of Runx2. MiR-196b functions as a tumor suppressor that inhibited cell growth and metastasis of lung cancer cells by targeting Runx2. These findings provided further evidences for treatment of lung cancer. The Author(s). Published by S. Karger AG, Basel.

  19. Phosphorus overload and PTH induce aortic expression of Runx2 in experimental uraemia.

    Science.gov (United States)

    Graciolli, Fabiana G; Neves, Katia R; dos Reis, Luciene M; Graciolli, Rafael G; Noronha, Irene L; Moysés, Rosa M A; Jorgetti, Vanda

    2009-05-01

    Vascular calcification (VC) is commonly seen in patients with chronic kidney disease (CKD). Elevated levels of phosphate and parathormone (PTH) are considered nontraditional risk factors for VC. It has been shown that, in vitro, phosphate transforms vascular smooth muscle cells (VSMCs) into calcifying cells, evidenced by upregulated expression of runt-related transcription factor 2 (Runx2), whereas PTH is protective against VC. In addition, Runx2 has been detected in calcified arteries of CKD patients. However, the in vivo effect of phosphate and PTH on Runx2 expression remains unknown. Wistar rats were submitted to parathyroidectomy, 5/6 nephrectomy (Nx) and continuous infusion of 1-34 rat PTH (at physiological or supraphysiological rates) or were sham-operated. Diets varied only in phosphate content, which was low (0.2%) or high (1.2%). Biochemical, histological, immunohistochemistry and immunofluorescence analyses were performed. Nephrectomized animals receiving high-PTH infusion presented VC, regardless of the phosphate intake level. However, phosphate overload and normal PTH infusion induced phenotypic changes in VSMCs, as evidenced by upregulated aortic expression of Runx2. High-PTH infusion promoted histological changes in the expression of osteoprotegerin and type I collagen in calcified arteries. Phosphate, by itself is a potential pathogenic factor for VC. It is of note that phosphate overload, even without VC, was associated with overexpression of Runx2 in VSMCs. The mineral imbalance often seen in patients with CKD should be corrected.

  20. Bromopropane compounds inhibit osteogenesis by ERK-dependent Runx2 inhibition in C2C12 cells.

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    Jeong, Hyung Min; Choi, You Hee; Jeong, Hye Gwang; Jeong, Tae Cheon; Lee, Kwang Youl

    2014-02-01

    Bromopropane (BP) is a halogenated alkan compound used in various industries as chemical intermediates, extraction solvents, and degreasing compounds. Halogenated alkan compounds can damage the nervous system, immune system, and hematopoietic and reproductive functions in animals and humans. However, the effect of BPs on bone formation has not yet been examined. This study examined the effects of BPs on osteoblast differentiation and analyzed the mechanisms involved in C2C12, mesenchymal stem cells. BPs dose dependently reduced the alkaline phosphatase activity, expression levels and promoter activity of bone marker genes. Additionally, 1,2-dibromopropane (1,2-DBP) significantly reduced the levels and transcriptional activity of Runx2 and Osterix, major bone transcription factors, in BMP2 induced C2C12 cells. Furthermore, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were significantly inhibited by 1,2-DBP. These results demonstrate that BPs inhibit osteoblast differentiation by suppressing Runx2 and Osterix through the ERK/JNK pathway.

  1. Gene promoter polymorphism of RUNX2 and risk of osteoporosis in postmenopausal Indonesian women

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    Suryandari, Dwi A; Umami, Sri S; Kusdhany, Lindawati S; Siregar, Tut Wuri A; Rahardjo, Tri Budi W; Talbot, Christopher; Hogervorst, Eef

    2014-01-01

    Objectives: Osteoporosis is a metabolic bone disease of reduced bone mass density (BMD) and elevated risk of fracture due to an imbalance in bone formation and resorption. The risk and incidence of osteoporosis increase towards advanced age, particularly in postmenopausal women, and the risk is known to be affected by the variation in the expression of the associated regulatory genes. This work aimed to clarify the impact of variation in RUNX2 (runt domain transcription factor 2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding single-nucleotide polymorphism within RUNX2 promoter (P1) and risk of osteoporosis in postmenopausal Indonesian women. Methods: Using DNA sampling from blood, the variation at the single-nucleotide polymorphism (-330, G→T, rs59983488) at the RUNX2 P1 promoter was investigated using polymerase chain reaction–restriction fragment length polymorphism for 180 consenting postmenopausal Indonesian women. The subjects were examined for bone mass density and classification to normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Chi-square testing and logistic regression were mainly used for statistical assessment. Results: The results showed a general trend with increased risk of osteoporosis associated with the genotype TT (mutant type) and the corresponding T allele of the tested polymorphism of RUNX2 promoter P1. The trend was, however, not significant in multivariate testing adjusted for age and time after menopause. Conclusion: To confirm the potential risk with TT genotype would require testing of a much larger sample of subjects. As the tested single-nucleotide polymorphism only represents one of the relevant candidate locations of RUNX2, the results are taken nevertheless to suggest an impact by overall RUNX2 variation in the risk of osteoporosis in Indonesian postmenopausal women. PMID:26770724

  2. Gene promoter polymorphism of RUNX2 and risk of osteoporosis in postmenopausal Indonesian women

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    Elza I Auerkari

    2014-04-01

    Full Text Available Objectives: Osteoporosis is a metabolic bone disease of reduced bone mass density (BMD and elevated risk of fracture due to an imbalance in bone formation and resorption. The risk and incidence of osteoporosis increase towards advanced age, particularly in postmenopausal women, and the risk is known to be affected by the variation in the expression of the associated regulatory genes. This work aimed to clarify the impact of variation in RUNX2 (runt domain transcription factor 2, which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding single-nucleotide polymorphism within RUNX2 promoter (P1 and risk of osteoporosis in postmenopausal Indonesian women. Methods: Using DNA sampling from blood, the variation at the single-nucleotide polymorphism (-330, G→T, rs59983488 at the RUNX2 P1 promoter was investigated using polymerase chain reaction–restriction fragment length polymorphism for 180 consenting postmenopausal Indonesian women. The subjects were examined for bone mass density and classification to normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Chi-square testing and logistic regression were mainly used for statistical assessment. Results: The results showed a general trend with increased risk of osteoporosis associated with the genotype TT (mutant type and the corresponding T allele of the tested polymorphism of RUNX2 promoter P1. The trend was, however, not significant in multivariate testing adjusted for age and time after menopause. Conclusion: To confirm the potential risk with TT genotype would require testing of a much larger sample of subjects. As the tested single-nucleotide polymorphism only represents one of the relevant candidate locations of RUNX2, the results are taken nevertheless to suggest an impact by overall RUNX2 variation in the risk of osteoporosis in Indonesian postmenopausal women.

  3. Inhibition of the terminal differentiation of odontoblasts and their transdifferentiation into osteoblasts in Runx2 transgenic mice.

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    Miyazaki, Toshihiro; Kanatani, Naoko; Rokutanda, Satoshi; Yoshida, Carolina; Toyosawa, Satoru; Nakamura, Reiko; Takada, Shinji; Komori, Toshihisa

    2008-09-01

    Runx2 is an essential transcription factor for bone and tooth development whose function in odontoblast differentiation remains to be clarified. To pursue this issue, we examined tooth development in Runx2 transgenic mice under the control of Col1a1 promoter (Tg(Col1a1-Runx2) mice). Endogenous Runx2 protein was detected in the nuclei of preodontoblasts, immature odontoblasts, mesenchymal cells in the dental sac, and osteoblasts, while transgene expression was detected in odontoblasts and osteoblasts. Odontoblasts in Tg(Col1a1-Runx2) mice lost their columnar shape and dentin was deposited around the odontoblasts, which were cuboid or flat in shape. The dentin in Tg(Col1a1-Runx2) mice was thin and possessed lacunae that contained odontoblasts and bone canaliculi-like structures, while predentin and dentinal tubules were absent. We examined the expression of dentin matrix protein genes, Col1a1 and dentin sialophosphoprotein (DSPP), by in situ hybridization, and dentin matrix proteins, osteocalcin, osteopontin, and dentin matrix protein 1 (DMP1) as well as an intermediate filament, nestin, by immunohistochemistry to characterize odontoblasts in Tg(Col1a1-Runx2) mice. Results showed Col1a1 expression was down-regulated, DSPP expression was lost, and nestin expression was severely decreased in the odontoblasts of Tg(Col1a1-Runx2) mice. Further, the expressions of osteocalcin, osteopontin, and DMP1 were up-regulated in odontoblasts, although the up-regulation of osteocalcin expression was transient. These findings indicate that Runx2 inhibits the terminal differentiation of odontoblasts, and that Runx2 induces transdifferentiation of odontoblasts into osteoblasts forming a bone structure. Thus, Runx2 expression has to be down-regulated during odontoblast differentiation to acquire full odontoblast differentiation for dentinogenesis.

  4. FHL2 mediates tooth development and human dental pulp cell differentiation into odontoblasts, partially by interacting with Runx2.

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    Du, Jianxin; Wang, Qiang; Yang, Pishan; Wang, Xiaoying

    2016-04-01

    The differentiation of mesenchymal cells in tooth germ and dental pulp cells into odontoblasts is crucial for dentin formation, and the transcription factor runt-related transcription factor (Runx2) is necessary for odontoblast differentiation. Our previous study demonstrated that four and a half LIM domains 2 (FHL2) may play an important role in tooth development and human dental pulp cell differentiation. This study aimed to determine whether FHL2 mediated the mesenchymal cells in tooth development and human dental pulp cell differentiation into odontoblasts by interacting with Runx2. The expression patterns of FHL2 and Runx2 were examined at the early stages of mouse molar development using double immunofluorescence staining. Western blot analysis and co-immunoprecipitation (Co-IP) were conducted for the preliminary study of the relationship between FHL2 and Runx2 in human dental pulp cell differentiation into odontoblasts. Results of double immunofluorescence staining showed that FHL2 and Runx2 exhibited similar expression patterns at the early stages of tooth development. Western blot analysis indicated that the expression patterns of FHL2 and Runx2 were synchronized on day 7 of induction, whereas those on day 14 differed. Co-IP analysis revealed positive bands of protein complexes, revealing the interaction of FHL2 and Runx2 on days 0, 7 and 14 of induction. Our data suggested that FHL2 might interact with Runx2 to mediate mesenchymal cell differentiation at the early stages of tooth development and human dental pulp cell differentiation.

  5. RUNX2 tandem repeats and the evolution of facial length in placental mammals

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    Pointer Marie A

    2012-06-01

    Full Text Available Abstract Background When simple sequence repeats are integrated into functional genes, they can potentially act as evolutionary ‘tuning knobs’, supplying abundant genetic variation with minimal risk of pleiotropic deleterious effects. The genetic basis of variation in facial shape and length represents a possible example of this phenomenon. Runt-related transcription factor 2 (RUNX2, which is involved in osteoblast differentiation, contains a functionally-important tandem repeat of glutamine and alanine amino acids. The ratio of glutamines to alanines (the QA ratio in this protein seemingly influences the regulation of bone development. Notably, in domestic breeds of dog, and in carnivorans in general, the ratio of glutamines to alanines is strongly correlated with facial length. Results In this study we examine whether this correlation holds true across placental mammals, particularly those mammals for which facial length is highly variable and related to adaptive behavior and lifestyle (e.g., primates, afrotherians, xenarthrans. We obtained relative facial length measurements and RUNX2 sequences for 41 mammalian species representing 12 orders. Using both a phylogenetic generalized least squares model and a recently-developed Bayesian comparative method, we tested for a correlation between genetic and morphometric data while controlling for phylogeny, evolutionary rates, and divergence times. Non-carnivoran taxa generally had substantially lower glutamine-alanine ratios than carnivorans (primates and xenarthrans with means of 1.34 and 1.25, respectively, compared to a mean of 3.1 for carnivorans, and we found no correlation between RUNX2 sequence and face length across placental mammals. Conclusions Results of our diverse comparative phylogenetic analyses indicate that QA ratio does not consistently correlate with face length across the 41 mammalian taxa considered. Thus, although RUNX2 might function as a ‘tuning knob’ modifying face

  6. A variant of Runx2 that differs from the bone isoform in its splicing is expressed in spermatogenic cells

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    Satoru Kanto

    2016-04-01

    Full Text Available Background. Members of the Runx gene family encode transcription factors that bind to DNA in a sequence-specific manner. Among the three Runx proteins, Runx2 comprises 607 amino acid (aa residues, is expressed in bone, and plays crucial roles in osteoblast differentiation and bone development. We examined whether the Runx2 gene is also expressed in testes. Methods. Murine testes from 1-, 2-, 3-, 4-, and 10-week-old male mice of the C57BL/6J strain and W∕Wv strain were used throughout the study. Northern Blot Analyses were performed using extracts form the murine testes. Sequencing of cDNA clones and 5′-rapid amplification of cDNA ends were performed to determine the full length of the transcripts, which revealed that the testicular Runx2 comprises 106 aa residues coding novel protein. Generating an antiserum using the amino-terminal 15 aa of Runx2 (Met1 to Gly15 as an antigen, immunoblot analyses were performed to detect the predicted polypeptide of 106 aa residues with the initiating Met1. With the affinity-purified anti-Runx2 antibody, immunohistochemical analyses were performed to elucidate the localization of the protein. Furthermore, bioinformatic analyses were performed to predict the function of the protein. Results. A Runx2 transcript was detected in testes and was specifically expressed in germ cells. Determination of the transcript structure indicated that the testicular Runx2 is a splice isoform. The predicted testicular Runx2 polypeptide is composed of only 106 aa residues, lacks a Runt domain, and appears to be a basic protein with a predominantly alpha-helical conformation. Immunoblot analyses with an anti-Runx2 antibody revealed that Met1 in the deduced open reading frame of Runx2 is used as the initiation codon to express an 11 kDa protein. Furthermore, immunohistochemical analyses revealed that the Runx2 polypeptide was located in the nuclei, and was detected in spermatocytes at the stages of late pachytene, diplotene and

  7. Osteochondral tissue regeneration through polymeric delivery of DNA encoding for the SOX trio and RUNX2.

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    Needham, Clark J; Shah, Sarita R; Dahlin, Rebecca L; Kinard, Lucas A; Lam, Johnny; Watson, Brendan M; Lu, Steven; Kasper, F Kurtis; Mikos, Antonios G

    2014-10-01

    Native osteochondral repair is often inadequate owing to the inherent properties of the tissue, and current clinical repair strategies can result in healing with a limited lifespan and donor site morbidity. This work investigates the use of polymeric gene therapy to address this problem by delivering DNA encoding for transcription factors complexed with the branched poly(ethylenimine)-hyaluronic acid (bPEI-HA) delivery vector via a porous oligo[poly(ethylene glycol) fumarate] hydrogel scaffold. To evaluate the potential of this approach, a bilayered scaffold mimicking native osteochondral tissue organization was loaded with DNA/bPEI-HA complexes. Next, bilayered implants either unloaded or loaded in a spatial fashion with bPEI-HA and DNA encoding for either Runt-related transcription factor 2 (RUNX2) or SRY (sex determining region Y)-box 5, 6, and 9 (the SOX trio), to generate bone and cartilage tissues respectively, were fabricated and implanted in a rat osteochondral defect. At 6weeks post-implantation, micro-computed tomography analysis and histological scoring were performed on the explants to evaluate the quality and quantity of tissue repair in each group. The incorporation of DNA encoding for RUNX2 in the bone layer of these scaffolds significantly increased bone growth. Additionally, a spatially loaded combination of RUNX2 and SOX trio DNA loading significantly improved healing relative to empty hydrogels or either factor alone. Finally, the results of this study suggest that subchondral bone formation is necessary for correct cartilage healing. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Gut-derived serotonin induced by depression promotes breast cancer bone metastasis through the RUNX2/PTHrP/RANKL pathway in mice.

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    Zong, Jian-Chun; Wang, Xing; Zhou, Xiang; Wang, Chen; Chen, Liang; Yin, Liang-Jun; He, Bai-Cheng; Deng, Zhong-Liang

    2016-02-01

    Breast cancer metastasizes to the bone in a majority of patients with advanced disease resulting in bone destruction. The underlying mechanisms are complex, and both processes are controlled by an interaction between locally and systemically derived signals. Clinically, breast cancer patients with depression have a higher risk of bone metastasis, yet the etiology and mechanisms are yet to be elucidated. MDA‑MB‑231 breast cancer cells were used to establish a bone metastasis model by using intracardiac injection in nude mice. Chronic mild stress (CMS) was chosen as a model of depression in mice before and after inoculation of the cells. Knockdown of the RUNX‑2 gene was performed by transfection of the cells with shRNA silencing vectors against human RUNX‑2. A co‑culture system was used to test the effect of the MDA‑MB‑231 cells on osteoclasts and osteoblasts. RT‑PCR and western blotting were used to test gene and protein expression, respectively. We confirmed that depression induced bone metastasis by promoting osteoclast activity while inhibiting osteoblast differentiation. Free serotonin led to an increase in the expression of RUNX2 in breast cancer cells (MDA‑MB‑231), which directly inhibited osteoblast differentiation and stimulated osteoclast differentiation by the PTHrP/RANKL pathway, which caused bone destruction and formed osteolytic bone lesions. Additionally, the interaction between depression and breast cancer cells was interrupted by LP533401 or RUNX2 knockdown. In conclusion, depression promotes breast cancer bone metastasis partly through increasing levels of gut‑derived serotonin. Activation of RUNX2 in breast cancer cells by circulating serotonin appears to dissociate coupling between osteoblasts and osteoclasts, suggesting that the suppression of gut‑derived serotonin decreases the rate of breast cancer bone metastasis induced by depression.

  9. In vitro anti-angiogenic properties of LGD1069, a selective retinoid X-receptor agonist through down-regulating Runx2 expression on Human endothelial cells

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    Lu Hong

    2011-06-01

    Full Text Available Abstract Background LGD1069 (Targretin® is a selective retinoid X receptor (RXR ligand, which is used in patients for cutaneous T-cell lymphoma. Our published study reported that LGD1069 inhibited tumor-induced angiogenesis in non-small cell lung cancer. In present study, we found that LGD1069 suppressed the proliferation, adhesion, invasion and migration of endothelial cells directly, and affected the expression of vegf and some matrix genes. Methods Human umbilical vein endothelial cells (HUVECs were used for in vitro study. MTT assay and Sulforhodamine B assay were used for cell viability assay; the tube formation assay was used to investigate the effect of LGD1069 on angiogenesis in vitro. In vitro adhesion, migration and invasion of HUVEC cells were analyzed by Matrigel adhesion, migration and invasion assay. Gene expressions were measured by RT-PCR and Western blot analysis. Results Our data showed here that LGD1069 inhibited the activation of TGF-β/Smad pathway significantly. Furthermore, it was demonstrated that expression of Runx2 was suppressed pronouncedly during incubation with LGD1069. Runx2 is a DNA-binding transcription factor which plays a master role in tumor-induced angiogenesis and cancer cells metastasis by interaction with the TGF-β/Smad pathway of transcriptional modulators. Conclusions Our results suggested that LGD1069 may impair angiogenic and metastatic potential induced by tumor cells through suppressing expression of Runx2 directly on human endothelial cells, which may point out new pathway through which LGD1069 display anti-angiogenic properties, and provide new molecular evidence to support LGD1069 as a potent anti-metastatic agent in cancer therapy.

  10. Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells

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    Rama Garimella

    2017-03-01

    Full Text Available Osteosarcoma (OS is an aggressive malignancy of bone affecting children, adolescents and young adults. Understanding vitamin D metabolism and vitamin D regulated genes in OS is an important aspect of vitamin D/cancer paradigm, and in evaluating vitamin D as adjuvant therapy for human OS. Vitamin D treatment of 143B OS cells induced significant and novel changes in the expression of genes that regulate: (a inflammation and immunity; (b formation of reactive oxygen species, metabolism of cyclic nucleotides, sterols, vitamins and mineral (calcium, quantity of gap junctions and skeletogenesis; (c bone mineral density; and (d cell viability of skeletal cells, aggregation of bone cancer cells and exocytosis of secretory vesicles. Ingenuity pathway analysis revealed significant reduction in Runx2 target genes such as fibroblast growth factor -1, -12 (FGF1 and FGF12, bone morphogenetic factor-1 (BMP1, SWI/SNF related, matrix associated actin dependent regulator of chromatin subfamily a, member 4 (SMARCA4, Matrix extracellular phosphoglycoprotein (MEPE, Integrin, β4 (ITGBP4, Matrix Metalloproteinase -1, -28 (MMP1 and MMP28, and signal transducer and activator of transcription-4 (STAT4 in vitamin D treated 143B OS cells. These genes interact with the inflammation, oxidative stress and membrane vesicle biogenesis gene networks. Vitamin D not only inhibited the expression of Runx2 target genes MMP1, MMP28 and kallikrein related peptidase-7 (KLK7, but also migration and invasion of 143B OS cells. Vitamin D regulated Runx2 target genes or their products represent potential therapeutic targets and laboratory biomarkers for applications in translational oncology.

  11. The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification.

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    Lindsay E Laurie

    Full Text Available The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh, a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis.

  12. The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification.

    Science.gov (United States)

    Laurie, Lindsay E; Kokubo, Hiroki; Nakamura, Masataka; Saga, Yumiko; Funato, Noriko

    2016-01-01

    The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh), a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis.

  13. Lyophilized Platelet-Rich Fibrin (PRF Promotes Craniofacial Bone Regeneration through Runx2

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    Qi Li

    2014-05-01

    Full Text Available Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF. LPRF caused a 4.8-fold ± 0.4-fold elevation in Runt-related transcription factor 2 (Runx2 expression in alveolar bone cells, compared to a 3.6-fold ± 0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p < 0.001 when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

  14. The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis

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    Francis, W.R., E-mail: w.francis@swansea.ac.uk [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Owens, S.E.; Wilde, C. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Pallister, I. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Trauma and Orthopaedics, Morriston Hospital, Swansea (United Kingdom); Kanamarlapudi, V. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Zou, W., E-mail: weizou60@hotmail.com [College of Life Sciences, Liaoning Normal University, Dalian 116081 (China); Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, Dalian 116081 (China); Xia, Z. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom)

    2014-10-24

    Highlights: • ERα36 is the predominant ERα isoform involved in bone regulation in human BMSC. • ERα36 mRNA is significantly upregulated during the process of osteogenesis. • The pattern of ERα36 and runx2 mRNA expression is similar during osteogenesis. • ERα36 appears to be co-localised with runx2 during osteogenesis. - Abstract: During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments.

  15. MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation.

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    Ko, Jih-Yang; Chuang, Pei-Chin; Ke, Huei-Jin; Chen, Yu-Shan; Sun, Yi-Chih; Wang, Feng-Sheng

    2015-12-01

    Glucocorticoid treatment reportedly increases the morbidity of osteoporotic or osteonecrotic disorders. Exacerbated bone acquisition and escalated marrow adipogenesis are prominent pathological features of glucocorticoid-mediated skeletal disorders. MicroRNAs reportedly modulate tissue metabolism and remodeling. This study was undertaken to investigate the biological roles of microRNA-29a (miR-29a) in skeletal and fat metabolism in the pathogenesis of glucocorticoid-induced osteoporosis. Transgenic mice overexpressing miR-29a precursor or wild-type mice were given methylprednisolone. Bone mass, microarchitecture and histology were assessed by dual energy X-ray absorptiometry, μCT and histomorphometry. Differential gene expression and signaling components were delineated by quantitative RT-PCR and immunoblotting. Glucocorticoid treatment accelerated bone loss and marrow fat accumulation in association with decreased miR-29a expression. The miR-29a transgenic mice had high bone mineral density, trabecular microarchitecture and cortical thickness. miR-29a overexpression mitigated the glucocorticoid-induced impediment of bone mass, skeletal microstructure integrity and mineralization reaction and attenuated fatty marrow histopathology. Ex vivo, miR-29a increased osteogenic differentiation capacity and alleviated the glucocorticoid-induced promotion of adipocyte formation in primary bone-marrow mesenchymal progenitor cell cultures. Through inhibition of histone deacetylase 4 (HDAC4) expression, miR-29a restored acetylated Runx2 and β-catenin abundances and reduced RANKL, leptin and glucocorticoid receptor expression in glucocorticoid-mediated osteoporosis bone tissues. Taken together, glucocorticoid suppression of miR-29a signaling disturbed the balances between osteogenic and adipogenic activities, and thereby interrupted bone formation and skeletal homeostasis. miR-29a inhibition of HDAC4 stabilized the acetylation state of Runx2 and β-catenin that ameliorated the

  16. Metopic suture and RUNX2, a key transcription factor in osseous morphogenesis with possible important implications for human brain evolution.

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    Magherini, Stefano; Fiore, Maria Giulia; Chiarelli, Brunetto; Serrao, Antonio; Paternostro, Ferdinando; Morucci, Gabriele; Branca, Jacopo J V; Ruggiero, Marco; Pacini, Stefania

    2015-01-01

    Overall, the comparative data available on the timing of metopic suture closure in present-day and fossil members of human lineage, as well as great apes, seem to indicate that human brain evolution occurred within a complex network of fetopelvic constraints, which required modification of frontal neurocranial ossification patterns, involving delayed fusion of the metopic suture. It is very interesting that the recent sequencing of the Neanderthal genome has revealed signs of positive selection in the modern human variant of the RUNX2 gene, which is known to affect metopic suture fusion in addition to being essential for osteoblast development and proper bone formation. It is possible that an evolutionary change in RUNX2, affecting aspects of the morphology of the upper body and cranium, was of importance in the origin of modern humans. Thus, to contribute to a better understanding of the molecular evolution of this gene probably implicated in human evolution, we performed a comparative bioinformatic analysis of the coding sequences of RUNX2 in Homo sapiens and other non-human Primates. We found amino-acid sequence differences between RUNX2 protein isoforms of Homo sapiens and the other Primates examined, that might have important implications for the timing of metopic suture closure. Further studies are needed to clear the potential distinct developmental roles of different species-specific RUNX2 N-terminal isoforms. Meantime, our bioinformatic analysis, regarding expression of the RUNX2 gene in Homo sapiens and other non-human Primates, has provided a contribution to this important issue of human evolution.

  17. Transcriptional repression of RUNX2 is associated with aggressive clinicopathological outcomes, whereas nuclear location of the protein is related to metastasis in prostate cancer.

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    Yun, S J; Yoon, H-Y; Bae, S-C; Lee, O-J; Choi, Y-H; Moon, S-K; Kim, I Y; Kim, W-J

    2012-12-01

    Runt-related transcription factor 2 (RUNX2) is a transcription factor that is closely related to bone formation, and prostate cancer (CaP) is the most common cancer to metastasize to bone. The present study investigated the expression levels of RUNX2 in human prostate tissue, and the correlation between RUNX2 levels and the clinicopathological characteristics of CaP. A case-control study was conducted including 114 cases of newly diagnosed CaP and 114 age-matched BPH patients as controls. RUNX2 expression was estimated using real-time PCR and immunohistochemical staining. The mRNA expression of RUNX2 did not differ between CaP tissues and non-cancer BPH controls (P=0.825). However, RUNX2 expression was significantly decreased in patients with elevated PSA levels (≥20 ng ml(-1)), a Gleason score ≥8 and metastatic disease compared to those with low PSA, low Gleason score and non-metastatic disease (P=0.023, 0.005 and 0.014, respectively). Immunohistochemical analysis showed that 65.2% of the patients with positive RUNX2 nuclear staining had metastatic disease, which was present in only 25.9% of those with negative staining (P=0.010). RUNX2 mRNA expression was negatively correlated with CaP aggressiveness. Moreover, the nuclear location of RUNX2 may be a prognostic marker of metastasis in CaP.

  18. Expression of Runx2/Cbfa1/Pebp2alphaA during angiogenesis in postnatal rodent and fetal human orofacial tissues

    NARCIS (Netherlands)

    Bronckers, Antonius L. J. J.; Sasaguri, Kenichi; Cavender, Adriana C.; D'Souza, Rena N.; Engelse, Marten A.

    2005-01-01

    Transient expression of Runx2 is reported in endothelial cells and vascular smooth muscle cells during vessel formation in skin, stroma of forming bones and developing periodontal ligament, developing skeletal muscle cells, and fat tissue. The data suggest that Runx2 is expressed in a multipotential

  19. Losartan Inhibits Vascular Calcification by Suppressing the BMP2 and Runx2 Expression in Rats In Vivo.

    Science.gov (United States)

    Li, Mincai; Wu, Panfeng; Shao, Juan; Ke, Zhiqiang; Li, Dan; Wu, Jiliang

    2016-04-01

    The blockade of renin-angiotensin II system has been shown to reduce morbidity and mortality in hypertension, atherosclerosis, diabetes and chronic kidney disease. Since vascular calcification (VC) is commonly found in these diseases, the aim of this study was to examine whether or not losartan, a widely used angiotensin II receptor blockers, inhibits VC in rats in vivo. A rat model of VC was generated by treating rats with a combination of warfarin and vitamin K1. Two weeks after the treatments, the rats were treated with vehicle or without losartan (100 ng/kg/day) for 2 weeks. At the end of the experiments, aortic arteries were isolated for the examination of calcification morphology, mRNA and protein expression of BMP2 and Runx2, and osteoblast differentiation. Warfarin and vitamin K instigated vascular remodeling with calcified plaques in the aortic arteries in rats. Losartan significantly attenuated warfarin- and vitamin K-induced vascular injury and calcification. Consistently, losartan suppressed the levels of mRNA and protein expression of BMP2 and Runx2, two key factors for VC. Further, vascular calcified lesion areas expressed angiotensin II 1 receptor (AT1R). Finally, losartan treatment significantly inhibited apoptosis in vascular smooth muscle cell (VSMC) in rat arteries. We conclude that losartan suppresses VC by lowering the expression of AT1R, Runx2 and BMP2, and by inhibiting the apoptosis of VSMC in rat aortic arteries.

  20. Delivery of siRNA silencing Runx2 using a multifunctional polymer-lipid nanoparticle inhibits osteogenesis in a cell culture model of heterotopic ossification.

    Science.gov (United States)

    Mishra, Swati; Vaughn, Asa D; Devore, David I; Roth, Charles M

    2012-12-01

    Heterotopic ossification (HO) associated with traumatic neurological or musculoskeletal injuries remains a major clinical challenge. One approach to understanding better and potentially treating this condition is to silence one or more genes believed to be responsible for osteogenesis by small interfering RNA (siRNA) post-injury. Improved methods of delivering siRNA to myoprogenitor cells as well as relevant cell culture models of HO are needed to advance this approach. We utilize a model of HO featuring C2C12 myoprogenitor cells stimulated to the osteogenic phenotype by addition of BMP-2. For siRNA delivery, we utilize a nanocomposite consisting of DOTAP-based cationic liposomes coated with a graft copolymer of poly(propylacrylic acid) grafted with polyetheramine (Jeffamine), as this system has been shown previously to deliver antisense oligonucleotides safely into cells and out of endosomes for gene silencing in vitro and in vivo. Delivery of siRNA targeting Runx2, a transcription factor downstream of BMP-2, to stimulated C2C12 cells produced greater than 60% down-regulation of the Runx2 gene. This level of gene silencing was sufficient to inhibit alkaline phosphatase activity over the course of several days and calcium phosphate deposition over the course of 2 weeks. These results show the utility of the BMP-2/C2C12 model for capturing the cellular cell-fate decision in HO. Further, they suggest DOTAP/PPAA-g-Jeffamine as a promising delivery system for siRNA-based therapy for HO.

  1. Microtubule-associated protein tau (Mapt) is expressed in terminally differentiated odontoblasts and severely down-regulated in morphologically disturbed odontoblasts of Runx2 transgenic mice.

    Science.gov (United States)

    Miyazaki, Toshihiro; Baba, Tomomi T; Mori, Masako; Moriishi, Takeshi; Komori, Toshihisa

    2015-08-01

    Runx2 is an essential transcription factor for osteoblast and odontoblast differentiation and the terminal differentiation of chondrocytes. We have previously shown that the terminal differentiation of odontoblasts is inhibited in Runx2 transgenic {Tg(Col1a1-Runx2)} mice under the control of the 2.3-kb Col1a1 promoter, which directs the transgene expression to osteoblasts and odontoblasts. Odontoblasts show severe reductions in Dspp and nestin expression and lose their characteristic polarized morphology, including a long process extending to dentin, in Tg(Col1a1-Runx2) mice. We study the molecular mechanism of odontoblast morphogenesis by comparing gene expression in the molars of wild-type and Tg(Col1a1-Runx2) mice, focusing on cytoskeleton-related genes. Using microarray, we found that the gene expression of microtubule-associated protein tau (Mapt), a neuronal phosphoprotein with important roles in neuronal biology and microtubule dynamics and assembly, was high in wild-type molars but severely reduced in Tg(Col1a1-Runx2) molars. Immunohistochemical analysis revealed that Mapt was specifically expressed in terminally differentiated odontoblasts including their processes in wild-type molars but its expression was barely detectable in Tg(Col1a1-Runx2) molars. Double-staining of Mapt and Runx2 showed their reciprocal expression in odontoblasts. Mapt and tubulin co-localized in odontoblasts in wild-type molars. Immunoelectron microscopic analysis demonstrated Mapt lying around α-tubulin-positive filamentous structures in odontoblast processes. Thus, Mapt is a useful marker for terminally differentiated odontoblasts and might play an important role in odontoblast morphogenesis.

  2. HDAC4 Represses Vascular Endothelial Growth Factor Expression in Chondrosarcoma by Modulating RUNX2 Activity*

    OpenAIRE

    Sun, Xiaojuan; Wei, Lei; Chen, Qian; Terek, Richard M.

    2009-01-01

    Chondrosarcoma is a primary bone tumor with a dismal prognosis; most patients with this disease develop fatal pulmonary metastases, suggesting the need for a better systemic treatment. Anti-angiogenesis treatment may be useful, because angiogenesis is critical for both tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent pro-angiogenic factor and is regulated by pathways related to the normal physiologic response to hypoxia and genetic alterations related ...

  3. Effects of risedronate in Runx2 overexpressing mice, an animal model for evaluation of treatment effects on bone quality and fractures.

    Science.gov (United States)

    Geoffroy, Valerie; Paschalis, Eleftherios P; Libouban, Helene; Blouin, Stephane; Ostertag, Agnes; Chappard, Daniel; Cros, Magali; Phipps, Roger; de Vernejoul, Marie-Christine

    2011-06-01

    Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 μg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 μg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 μg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures.

  4. miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model

    Directory of Open Access Journals (Sweden)

    Krassimira Todorova

    2014-01-01

    Full Text Available Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660. We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB. The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development.

  5. RUNX-2, OPN and OCN expression induced by grey and white mineral trioxide aggregate in normal and hypertensive rats.

    Science.gov (United States)

    Martins, C M; de Azevedo Queiroz, I O; Ervolino, E; Cintra, L T A; Gomes-Filho, J E

    2017-11-16

    To investigate whether hypertension affects mineralization associated with white and grey mineral trioxide aggregate (MTA Angelus® ) implanted subcutaneously into rats by assaying osteoblastic biomarkers. Polyethylene tubes containing grey MTA Angelus® , white MTA Angelus® , intermediate restorative material (IRM; positive control) or an empty tube (negative control) were implanted into the dorsal connective tissue of spontaneous hypertensive (n = 12) and Wistar (normotensive; n = 10) rats. Half of the rats in each group were killed after 7 days, and the remaining after 30 days. Tubes with surrounding tissue were removed, and immunostaining was performed to detect RUNX-2, OPN and OCN proteins. The normality of data was analysed using the Shapiro-Wilk test. Comparison of two independent groups was performed using the Mann-Whitney U-test, to detect a significant difference. A post hoc test accounting for multiple comparisons was performed following Tukey's test (P MTA materials were associated with immunolabelling for RUNX-2 from low to moderate, which was less than that observed at normal blood pressure and the 7-day groups (P MTA conditions was considered low after both 7 and 30 days for the hypertensive condition, and was less than that in animals with normal blood pressure after 30 days (P MTA. Thus, hypertension can jeopardize the mineralization ability of MTA and may have a negative impact on endodontic treatment outcomes. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  6. Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Chieri [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi, E-mail: tsuyo-i@huhs.ac.jp [Division of Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We investigated the role of S1P signaling for osteoblast differentiation. Black-Right-Pointing-Pointer Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. Black-Right-Pointing-Pointer S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. Black-Right-Pointing-Pointer MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P

  7. microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells

    DEFF Research Database (Denmark)

    Hamam, D; Ali, D; Vishnubalaji, R

    2014-01-01

    MSC, and utilized bioinformatics as well as functional and biochemical assays, and identified several novel miRNAs differentially expressed during adipogenesis. Among these, miR-320 family (miR-320a, 320b, 320c, 320d and 320e) were ~2.2-3.0-fold upregulated. Overexpression of miR-320c in hMSC enhanced adipocytic......, MIB1 (mindbomb E3 ubiquitin protein ligase 1), PAX6 (paired box 6), YWHAH and ZWILCH. siRNA-mediated silencing of those genes enhanced adipocytic differentiation of hMSC, thus corroborating an important role for those genes in miR-320c-mediated adipogenesis. Concordant with that, lentiviral......The molecular mechanisms promoting lineage-specific commitment of human mesenchymal (skeletal or stromal) stem cells (hMSCs) into adipocytes (ADs) are not fully understood. Thus, we performed global microRNA (miRNA) and gene expression profiling during adipocytic differentiation of h...

  8. Morinda citrifolia Leaf Extract Enhances Osteogenic Differentiation Through Activation of Wnt/β-Catenin Signaling.

    Science.gov (United States)

    Gu, Hanna; Boonanantanasarn, Kanitsak; Kang, Moonkyu; Kim, Ikhwi; Woo, Kyung Mi; Ryoo, Hyun-Mo; Baek, Jeong-Hwa

    2017-10-05

    Morinda citrifolia (Noni) leaf is an herbal medicine with application in the domestic treatment of a broad range of conditions, including bone fracture and luxation. However, the basic mechanism underlying the stimulation of osteogenic differentiation by Noni leaf extract remains poorly understood. This study aimed to examine the effect of this extract on osteogenic differentiation and the mechanism by which Noni leaf extract enhances osteogenic differentiation. Aqueous extract of Noni leaves was prepared, and rutin and kaempferol-3-O-rutinoside were identified to be two of its major components. C2C12 and human periodontal ligament (hPDL) cells were used to study the effect of Noni. Noni did not show cytotoxicity at a concentration range of 0.015%-1.0% (w/v%) and significantly enhanced the activity of alkaline phosphatase (ALP) and expression levels of osteoblast differentiation markers, including Runx2, ALP, osterix, and osteocalcin, bone morphogenetic protein 2, Wnt3a, and β-catenin. In addition, Noni enhanced the matrix mineralization of hPDL cells. In the signaling pathways, Noni increased the phosphorylation levels of Akt and GSK3β and nuclear translocation and transcriptional activity of β-catenin, which were attenuated by the addition of Dkk-1, a Wnt inhibitor, or LY294002, a PI3K inhibitor. These results suggest that Noni leaf extract enhances osteogenic differentiation through the PI3K/Akt-dependent activation of Wnt/β-catenin signaling. Noni leaf extract might be a novel alternative medicine for bone and periodontal regeneration in patients with periodontal diseases.

  9. Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway.

    Science.gov (United States)

    Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

    2015-01-01

    Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

  10. Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

    Science.gov (United States)

    Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

    2015-01-01

    Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

  11. Naringin enhances osteogenic differentiation through the activation of ERK signaling in human bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Huichao Wang

    2017-04-01

    Full Text Available Objective(s: Naringin has been reported to regulate bone metabolism. However, its effect on osteogenesis remains unclear. The aim was to investigate the effect of naringin on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs through the activation of the ERK signaling pathway in osteogenic differentiation. Materials and Methods: Annexin V-FITC assay and MTT assay were used to measure the effect of naringin on cytotoxicity and proliferation of hBMSCs, respectively. Alkaline phosphatase activity analysis, Alizarin Red S staining, Western blotting, and real-time PCR assay were used to evaluate both the potential effect of naringin on osteogenic differentiation and the role of ERK signaling pathway in osteogenic differentiation. Results: Our results showed that naringin had no obvious toxicity on hBMSCs, and could significantly promote the proliferation of hBMSCs. Naringin also enhanced the osteogenic differentiation of hBMSCs and increased the protein and mRNA expression levels of osteogenic markers such as Runx-2, OXS, OCN, and Col1 in a dose-dependent manner. In addition, we found that the enhancing effect of naringin on osteogenic differentiation was related to the activation of phosphor-ERK, with an increase in duration of activity from 30 min to 120 min. More importantly, both the enhancing effect of naringin on osteogenic differentiation and the activity effect of naringin on ERK signaling pathway were reversed by U0126 addition. Conclusion: Our findings demonstrated that naringin promoted proliferation and osteogenesis of hBMSCs by activating the ERK signaling pathway and it might be a potential therapeutic agent for treating or preventing osteoporosis.

  12. Enhanced NIF neutron activation diagnostics.

    Science.gov (United States)

    Yeamans, C B; Bleuel, D L; Bernstein, L A

    2012-10-01

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  13. Dynamic regulation of Schwann cell enhancers after peripheral nerve injury.

    Science.gov (United States)

    Hung, Holly A; Sun, Guannan; Keles, Sunduz; Svaren, John

    2015-03-13

    Myelination of the peripheral nervous system is required for axonal function and long term stability. After peripheral nerve injury, Schwann cells transition from axon myelination to a demyelinated state that supports neuronal survival and ultimately remyelination of axons. Reprogramming of gene expression patterns during development and injury responses is shaped by the actions of distal regulatory elements that integrate the actions of multiple transcription factors. We used ChIP-seq to measure changes in histone H3K27 acetylation, a mark of active enhancers, to identify enhancers in myelinating rat peripheral nerve and their dynamics after demyelinating nerve injury. Analysis of injury-induced enhancers identified enriched motifs for c-Jun, a transcription factor required for Schwann cells to support nerve regeneration. We identify a c-Jun-bound enhancer in the gene for Runx2, a transcription factor induced after nerve injury, and we show that Runx2 is required for activation of other induced genes. In contrast, enhancers that lose H3K27ac after nerve injury are enriched for binding sites of the Sox10 and early growth response 2 (Egr2/Krox20) transcription factors, which are critical determinants of Schwann cell differentiation. Egr2 expression is lost after nerve injury, and many Egr2-binding sites lose H3K27ac after nerve injury. However, the majority of Egr2-bound enhancers retain H3K27ac, indicating that other transcription factors maintain active enhancer status after nerve injury. The global epigenomic changes in H3K27ac deposition pinpoint dynamic changes in enhancers that mediate the effects of transcription factors that control Schwann cell myelination and peripheral nervous system responses to nerve injury. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Enhancement of Bone Marrow-Derived Mesenchymal Stem Cell Osteogenesis and New Bone Formation in Rats by Obtusilactone A

    Directory of Open Access Journals (Sweden)

    Yi-Hsiung Lin

    2017-11-01

    Full Text Available The natural pure compound obtusilactone A (OA was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs. OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.

  15. Regulation of Calvarial Osteogenesis by Concomitant De-repression of GLI3 and Activation of IHH Targets

    Directory of Open Access Journals (Sweden)

    Lotta K. Veistinen

    2017-12-01

    , and as IHH may be regulated by RUNX2 these results raise the possibility of a regulatory feedback circuit to control calvarial osteogenesis and suture patency. Taken together, RUNX2-controlled osteoblastic cell fate is regulated by IHH through concomitant inhibition of GLI3-repressor formation and activation of downstream targets.

  16. Stabbing the Dragon with some enhanced activity

    Science.gov (United States)

    Johannink, Carl; Breukers, Martin

    2016-04-01

    The attempt to confirm the predicted activity for the minor shower 66 Draconid (541 SDD) was negative but instead a remarkable enhanced activity was observed from the same constellation: (336) DKD December kappa Draconids.

  17. Digital expression profiling identifies RUNX2, CDC5L, MDM2, RECQL4, and CDK4 as potential predictive biomarkers for neo-adjuvant chemotherapy response in paediatric osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Martin

    Full Text Available Osteosarcoma is the most common malignancy of bone, and occurs most frequently in children and adolescents. Currently, the most reliable technique for determining a patients' prognosis is measurement of histopathologic tumor necrosis following pre-operative neo-adjuvant chemotherapy. Unfavourable prognosis is indicated by less than 90% estimated necrosis of the tumor. Neither genetic testing nor molecular biomarkers for diagnosis and prognosis have been described for osteosarcomas. We used the novel nanoString mRNA digital expression analysis system to analyse gene expression in 32 patients with sporadic paediatric osteosarcoma. This system used specific molecular barcodes to quantify expression of a set of 17 genes associated with osteosarcoma tumorigenesis. Five genes, from this panel, which encoded the bone differentiation regulator RUNX2, the cell cycle regulator CDC5L, the TP53 transcriptional inactivator MDM2, the DNA helicase RECQL4, and the cyclin-dependent kinase gene CDK4, were differentially expressed in tumors that responded poorly to neo-adjuvant chemotherapy. Analysis of the signalling relationships of these genes, as well as other expression markers of osteosarcoma, indicated that gene networks linked to RB1, TP53, PI3K, PTEN/Akt, myc and RECQL4 are associated with osteosarcoma. The discovery of these networks provides a basis for further experimental studies of role of the five genes (RUNX2, CDC5L, MDM2, RECQL4, and CDK4 in differential response to chemotherapy.

  18. Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells by activating the APPL1-AMPK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Tong; Wu, Yu-wei; Lu, Hui; Guo, Yuan [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China); Tang, Zhi-hui, E-mail: tang_zhihui@live.cn [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China)

    2015-05-29

    Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with multi-lineage differentiation potential including osteogenesis and adipogenesis. While significant progress has been made in understanding the transcriptional control of hASC fate, little is known about how hASC differentiation is regulated by the autocrine loop. The most abundant adipocytokine secreted by adipocytes, adiponectin (APN) plays a pivotal role in glucose metabolism and energy homeostasis. Growing evidence suggests a positive association between APN and bone formation yet little is known regarding the direct effects of APN on hASC osteogenesis. Therefore, this study was designed to investigate the varied osteogenic effects and regulatory mechanisms of APN in the osteogenic commitment of hASCs. We found that APN enhanced the expression of osteoblast-related genes in hASCs, such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 (Runx2, also known as CBFa1), in a dose- and time-dependent manner. This was further confirmed by the higher expression levels of alkaline phosphatase and increased formation of mineralization nodules, along with the absence of inhibition of cell proliferation. Importantly, APN at 1 μg/ml was the optimal concentration, resulting in maximum deposition of calcium nodules, and was significant superior to bone morphogenetic protein 2. Mechanistically, we found for the first time that APN increased nuclear translocation of the leucine zipper motif (APPL)-1 as well as AMP-activated protein kinase (AMPK) phosphorylation, which were reversed by pretreatment with APPL1 siRNA. Our results indicate that APN promotes the osteogenic differentiation of hASCs by activating APPL1-AMPK signaling, suggesting that manipulation of APN is a novel therapeutic target for controlling hASC fate. - Highlights: • Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells. • The knock-down of APPL1 block the enhancement of

  19. Substance P Activates the Wnt Signal Transduction Pathway and Enhances the Differentiation of Mouse Preosteoblastic MC3T3-E1 Cells

    Directory of Open Access Journals (Sweden)

    Gang Mei

    2014-04-01

    Full Text Available Recent experiments have explored the impact of Wnt/β-catenin signaling and Substance P (SP on the regulation of osteogenesis. However, the molecular regulatory mechanisms of SP on the formation of osteoblasts is still unknown. In this study, we investigated the impact of SP on the differentiation of MC3T3-E1 cells. The osteogenic effect of SP was observed at different SP concentrations (ranging from 10−10 to 10−8 M. To unravel the underlying mechanism, the MC3T3-E1 cells were treated with SP after the pretreatment by neurokinin-1 (NK1 antagonists and Dickkopf-1 (DKK1 and gene expression levels of Wnt/β-catenin signaling pathway components, as well as osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin, and Runx2, were measured using quantitative polymerase chain reaction (PCR. Furthermore, protein levels of Wnt/β-catenin signaling pathway were detected using Western blotting and the effects of SP, NK1 antagonist, and DKK1 on β-catenin activation were investigated by immunofluorescence staining. Our data indicated that SP (10−9 to 10−8 M significantly up-regulated the expressions of osteoblastic genes. SP (10−8 M also elevated the mRNA level of c-myc, cyclin D1, and lymphocyte enhancer factor-1 (Lef1, as well as c-myc and β-catenin protein levels, but decreased the expression of Tcf7 mRNA. Moreover, SP (10−8 M promoted the transfer of β-catenin into nucleus. The effects of SP treatment were inhibited by the NK1 antagonist and DKK1. These findings suggest that SP may enhance differentiation of MC3T3-E1 cells via regulation of the Wnt/β-catenin signaling pathway.

  20. Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

    Science.gov (United States)

    John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

    2016-10-25

    A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacylethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings. The subject matter disclosed herein relates to enhancers of amidohydrolase activity.

  1. The Runx transcriptional co-activator, CBFβ, is essential for invasion of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lopez-Camacho Cesar

    2010-06-01

    Full Text Available Abstract Background The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFβ is a transcriptional co-activator that is recruited to promoters by Runx transcription factors and there is considerable evidence that CBFβ is essential for the function of Runx factors. However, overexpression of Runx1 can partially rescue the lethal phenotype in CBFβ-deficient mice, indicating that increased levels of Runx factors can, in some situations, overcome the requirement for CBFβ. Since Runx2 is overexpressed in metastatic breast cancer cells, and there are no reports of CBFβ expression in breast cells, we sought to determine whether Runx2 function in these cells was dependent on CBFβ. Such an interaction might represent a viable target for therapeutic intervention to inhibit bone metastasis. Results We show that CBFβ is expressed in the metastatic breast cancer cells, MDA-MB-231, and that it associates with Runx2. Matrigel invasion assays and RNA interference were used to demonstrate that CBFβ contributes to the invasive capacity of these cells. Subsequent analysis of Runx2 target genes in MDA-MB-231 cells revealed that CBFβ is essential for the expression of Osteopontin, Matrixmetalloproteinase-13, Matrixmetalloproteinase-9, and Osteocalcin but not for Galectin-3. Chromatin immunoprecipitation analysis showed that CBFβ is recruited to both the Osteopontin and the Galectin-3 promoters. Conclusions CBFβ is expressed in metastatic breast cancer cells and is essential for cell invasion. CBFβ is required for expression of several Runx2-target genes known to be involved in cell invasion. However, whilst CBFβ is essential for invasion, not all Runx2-target genes require CBFβ. We conclude that CBFβ is required for a subset of Runx2-target genes

  2. Platelet-rich concentrate in serum free medium enhances osteogenic differentiation of bone marrow-derived human mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Shani Samuel

    2016-09-01

    Full Text Available Previous studies have shown that platelet concentrates used in conjunction with appropriate growth media enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs. However, their potential in inducing osteogenesis of hMSCs when cultured in serum free medium has not been explored. Furthermore, the resulting osteogenic molecular signatures of the hMSCs have not been compared to standard osteogenic medium. We studied the effect of infrequent supplementation (8-day interval of 15% non-activated platelet-rich concentrate (PRC in serum free medium on hMSCs proliferation and differentiation throughout a course of 24 days, and compared the effect with those cultured in a standard osteogenic medium (OM. Cell proliferation was analyzed by alamar blue assay. Gene expression of osteogenic markers (Runx2, Collagen1, Alkaline Phosphatase, Bone morphogenetic protein 2, Osteopontin, Osteocalcin, Osteonectin were analyzed using Q-PCR. Immunocytochemical staining for osteocalcin, osteopontin and transcription factor Runx2 were done at 8, 16 and 24 days. Biochemical assays for the expression of ALP and osteocalcin were also performed at these time-points. Osteogenic differentiation was further confirmed qualitatively by Alizarin Red S staining that was quantified using cetylpyridinium chloride. Results showed that PRC supplemented in serum free medium enhanced hMSC proliferation, which peaked at day 16. The temporal pattern of gene expression of hMSCs under the influence of PRC was comparable to that of the osteogenic media, but at a greater extent at specific time points. Immunocytochemical staining revealed stronger staining for Runx2 in the PRC-treated group compared to OM, while the staining for Osteocalcin and Osteopontin were comparable in both groups. ALP activity and Osteocalcin/DNA level were higher in the PRC group. Cells in the PRC group had similar level of bone mineralization as those cultured in OM, as reflected by the intensity of

  3. Enhanced early osteogenic differentiation by silicon-substituted hydroxyapatite ceramics fabricated via ultrasonic spray pyrolysis route.

    Science.gov (United States)

    Honda, Michiyo; Kikushima, Koichi; Kawanobe, Yusuke; Konishi, Toshiisa; Mizumoto, Minori; Aizawa, Mamoru

    2012-12-01

    The influence of silicon-substituted hydroxyapatite (Si-HAp) on osteogenic differentiation was assessed by biological analysis. Si-HAp was prepared by ultrasonic spray pyrolysis (USSP) technique using various amounts of Si (0, 0.8, and 1.6 mass%). Chemical analysis revealed that Si was incorporated into the hydroxyapatite (HAp) lattice with no other crystalline phase and which caused the change of crystal structure. Biological analyses showed that the Si contents affected the cell proliferation and morphology, suggesting that there is an optimal Si content for cell culture. As for differentiation, alkaline phosphatase activity and osteocalcin production of Si-HAp were higher than those of HAp. Gene expression profiles also revealed that substitution of Si (0.8 mass%) up-regulated the expression levels of osteocalcin and especially Runx2, a master gene for osteoblast development. These results suggest that incorporating Si into the HAp lattice may enhance the bioactivity, particularly during early osteoblast development.

  4. Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

    2017-12-26

    A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacyl-ethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings.

  5. Portfolios Enhance Clinical Activity in Surgical Clerks.

    Science.gov (United States)

    Zundel, Sabine; Blumenstock, Gunnar; Zipfel, Stephan; Herrmann-Werner, Anne; Holderried, Friederike

    2015-01-01

    A change in German licensing legislation imposed a portfolio for surgical clerks. We aimed to analyze whether the implementation of the portfolio changed the amount of clinical exposure and activities during surgical clerkships. The study was conducted with a modified pre-post design at the University Hospital of Tuebingen, Germany. Before and after the implementation of the portfolio on April 1, 2013, final-year students (n = 557) who had just finished their surgical clerkship were interviewed with an online questionnaire. A total of 21 basic surgical skills were evaluated. Overall, 230 questionnaires were returned and analyzed; 51% were preintervention. Overall clinical activity for the whole study cohort varied for different activities between 98% and 32%. For 16 of 21 parameters, there was more clinical activity in the postintervention (portfolio) group. This difference was statistically significant for the following 7 activities: discharge, analgesia, local infiltration, patient positioning, drain in, blood transfusion, and emergency diagnostics. The implementation of the portfolio did enhance clinical activity for surgical clerks in the study cohort. Nevertheless, overall exposure is still unsatisfactory low for some activities. Additional changes and studies are necessary to further improve surgical education. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  6. Enhancing laboratory activities in nuclear medicine education.

    Science.gov (United States)

    Grantham, Vesper; Martin, Chris; Schmitz, Casey

    2009-12-01

    Hands-on or active learning is important in nuclear medicine education. As more curricula start to require greater standards and as distance education expands, the effective use of laboratories in nuclear medicine education remains important in physics, instrumentation, and imaging but is often overlooked or underutilized. Laboratory exercises are a unique opportunity for nuclear medicine educators to facilitate students' critical thinking and problem-solving skills in a manner that often cannot occur in lectures or during online education. Given the lack of current laboratory tools and publications, there exists a requirement for nuclear medicine educators to develop, enhance, and monitor educational tools for laboratory exercises. Expanding technologies, variations in imaging and measurement systems, and the need to ensure that the taught technology is relevant to nuclear medicine students are issues faced by nuclear medicine educators. This article, based on principles of instructional design, focuses on the components and development of effective and enhanced nuclear medicine laboratories in our current educational environment.

  7. Enhanced microglial activity in FAAH(-/-) animals.

    Science.gov (United States)

    Ativie, F; Albayram, O; Bach, K; Pradier, B; Zimmer, A; Bilkei-Gorzo, A

    2015-10-01

    Several lines of evidence suggest that the endocannabinoid system is involved in the regulation of glial activity. Enhanced levels of the endocannabinoid N-arachidonoyl ethanolamine (AEA, also referred to as anandamide) as well as non-cannabinoid lipids like palmitoylethanolamine (PEA) due to genetic deletion or pharmacologic blockade of its degrading enzyme fatty acid amide hydrolase (FAAH) reduced neuroinflammatory changes in models of neurodegeneration. Now we addressed the question if genetic deletion of FAAH also influences age-related neuroinflammation. To answer this question we compared the number and size of microglia in young and old wild-type and FAAH(-/-) mice and analysed the distribution of microglia sizes in the four groups. Additionally, we analysed IL-6 and IL-1β levels with ELISA and astrocyte activities as ratio of GFAP-positive areas in the hippocampus. Ageing was associated with an increased number and activity of microglia, elevated IL-6 and IL-1β levels and enhanced area covered by astrocytes in wild-type animals. Unexpectedly, in FAAH(-/-) animals the number of microglia and the ratio of activated microglia and IL-1β level were already higher in young animals than in age-matched wild-type controls. There was no further age-related increase in these inflammation markers in the knockout line. Our results suggest that AEA is involved in the regulation of microglia activity. Life-long elevation of AEA levels disturbs microglial regulation and leads to pro-inflammatory changes. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. How Soluble GARP Enhances TGFβ Activation.

    Directory of Open Access Journals (Sweden)

    Sven Fridrich

    Full Text Available GARP (glycoprotein A repetitions predominant is a cell surface receptor on regulatory T-lymphocytes, platelets, hepatic stellate cells and certain cancer cells. Its described function is the binding and accommodation of latent TGFβ (transforming growth factor, before the activation and release of the mature cytokine. For regulatory T cells it was shown that a knockdown of GARP or a treatment with blocking antibodies dramatically decreases their immune suppressive capacity. This confirms a fundamental role of GARP in the basic function of regulatory T cells. Prerequisites postulated for physiological GARP function include membrane anchorage of GARP, disulfide bridges between the propeptide of TGFβ and GARP and connection of this propeptide to αvβ6 or αvβ8 integrins of target cells during mechanical TGFβ release. Other studies indicate the existence of soluble GARP complexes and a functionality of soluble GARP alone. In order to clarify the underlying molecular mechanism, we expressed and purified recombinant TGFβ and a soluble variant of GARP. Surprisingly, soluble GARP and TGFβ formed stable non-covalent complexes in addition to disulfide-coupled complexes, depending on the redox conditions of the microenvironment. We also show that soluble GARP alone and the two variants of complexes mediate different levels of TGFβ activity. TGFβ activation is enhanced by the non-covalent GARP-TGFβ complex already at low (nanomolar concentrations, at which GARP alone does not show any effect. This supports the idea of soluble GARP acting as immune modulator in vivo.

  9. Enhanced osteoblastogenesis of adipose-derived stem cells on spermine delivery via β-catenin activation.

    Science.gov (United States)

    Guidotti, Serena; Facchini, Annalisa; Platano, Daniela; Olivotto, Eleonora; Minguzzi, Manuela; Trisolino, Giovanni; Filardo, Giuseppe; Cetrullo, Silvia; Tantini, Benedetta; Martucci, Ermanno; Facchini, Andrea; Flamigni, Flavio; Borzì, Rosa Maria

    2013-05-15

    The molecular mechanisms underlying spermine osteo-inductive activity on human adipose-derived stem cells (ASCs) grown in 3-dimensional (3D) cultures were investigated. Spermine belongs to the polyamine family, naturally occurring, positively charged polycations that are able to control several cellular processes. Spermine was used at a concentration close to that found in platelet-rich plasma (PRP), an autologous blood product containing growth and differentiation factors, which has recently become popular in in vitro and in vivo bone healing and engineering. Adipose tissue was surgically obtained from the hypodermis of patients undergoing hip arthroplasty. Patient age negatively affected both ASC yield and ASC ability to form 3D constructs. ASC 3D cultures were seeded in either non differentiating or chondrogenic conditions, with or without the addition of 5 μM spermine to evaluate its osteogenic potential across 1, 2, and 3 weeks of maturation. Osteogenic medium was used as a reference. The effects of the addition of spermine on molecular markers of osteogenesis, at both gene and protein level, and mineralization were evaluated. The effects of spermine were temporally defined and responsible for the progression from the early to the mature osteoblast differentiation phases. Spermine initially promoted gene and protein expression of Runx-2, an early marker of the osteoblast lineage; then, it increased β-catenin expression and activation, which led to the induction of Osterix gene expression, the mature osteoblast commitment factor. The finding that spermine induces ASC to differentiate toward mature osteoblasts supports the use of these easily accessible mesenchymal stem cells coupled with PRP for orthopedic applications.

  10. Mineral trioxide aggregate enhances the odonto/osteogenic capacity of stem cells from inflammatory dental pulps via NF-κB pathway.

    Science.gov (United States)

    Wang, Y; Yan, M; Fan, Z; Ma, L; Yu, Y; Yu, J

    2014-10-01

    This study was designed to investigate the effects of mineral trioxide aggregate (MTA) on the osteo/odontogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). inflammatory DPSCs were isolated from the inflammatory pulps of rat incisors and cocultured with MTA-conditioned medium. MTT assay and flow cytometry were performed to evaluate the proliferation of iDPSCs. Alkaline phosphatase (ALP) activity, alizarin red staining, real-time RT-PCR, and Western blot assay were used to investigate the differentiation capacity as well as the involvement of NF-κB pathway in iDPSCs. Mineral trioxide aggregate-treated iDPSCs demonstrated the higher ALP activity and formed more mineralized nodules than the untreated group. The odonto/osteoblastic markers (Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN, and Dspp/DSP, respectively) in MTA-treated iDPSCs were significantly upregulated as compared with untreated iDPSCs. Mechanistically, cytoplastic phos-P65 and nuclear P65 in MTA-treated iDPSCs were significantly increased in a time-dependent manner. Moreover, the inhibition of NF-κB pathway suppressed the MTA-induced odonto/osteoblastic differentiation of iDPSCs, as indicated by decreased ALP levels, weakened mineralization capacity and downregulated levels of odonto/osteoblastic genes (Osx, Ocn, and Dspp). Mineral trioxide aggregate enhances the odonto/osteogenic capacity of DPSCs from inflammatory sites via activating the NF-κB pathway. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation

    Directory of Open Access Journals (Sweden)

    Nagarajan Selvamurugan

    2017-01-01

    Full Text Available Pulsed electromagnetic fields (PEMFs have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs’ cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways. In the differentiation and mineralization stages, PEMF regulated preosteoblast gene expression and notably, the transforming growth factor-beta (TGF-β signaling pathway and microRNA 21 (miR21 were most highly regulated. PEMF stimulated activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and TGF-β signaling was essential for PEMF stimulation of alkaline phosphatase mRNA expression. Smad7, an antagonist of the TGF-β signaling pathway, was found to be miR21-5p’s putative target gene and PEMF caused a decrease in Smad7 expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating cells. Thus, PEMF could mediate its effects on bone metabolism by activation of the TGF-β signaling pathway and stimulation of expression of miR21-5p in hBMSCs.

  12. Ethanolic extract of Coelogyne cristata Lindley (Orchidaceae) and its compound coelogin promote osteoprotective activity in ovariectomized estrogen deficient mice.

    Science.gov (United States)

    Sharma, Chetan; Mansoori, Mohd Nizam; Dixit, Manisha; Shukla, Priyanka; Kumari, Tejaswita; Bhandari, S P S; Narender, T; Singh, Divya; Arya, K R

    2014-10-15

    Coelogyne cristata Lindley (CC) family Orchidaceae is an Indian medicinal plant used for the treatment of fractured bones in folk-tradition of Kumaon region, Uttarakhand, India. In continuation of our drug discovery program, feeding of ethanolic extract to ovariectomized estrogen deficient mice led to significant restoration of trabecular micro architecture in both femoral and tibial bones, better bone quality and also devoid of any uterine estrogenicity. Subsequently, coelogin, a pure compound was isolated from ethyl acetate fraction of C. cristata and evaluated in in vitro osteoblast cell cultures. Treatment of coelogin to osteoblasts led to enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen and RUNX-2. Based on these results, we propose that ethanolic extract of C. cristata and its pure compound coelogin have potential in the management of post menopausal osteoporosis. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Memory enhancing activity of Spondias mombin Anarcadiaceae ...

    African Journals Online (AJOL)

    Background: In traditional medical practices, several plants have been used to treat cognitive disorders associated with aging as well as neurodegenerative diseases such as Alzheimer's. Spondias mombin and Pycnanthus angolensis were found among recipes used ethnomedicine in Nigeria as memory enhancer.

  14. Enhancement of glutamine synthetase activity in Paenibacillus ...

    African Journals Online (AJOL)

    Accession No AB727983). High GS activity was recorded in the two strains, in presence of the divalent cations Mg+2 and Mn+2. Western blot analysis confirmed the presence of the GS at approximately ~60 kDa. GS activity was found to be affected by ...

  15. HIV Coinfection Enhances Complement Activation During Sepsis

    NARCIS (Netherlands)

    Huson, Michaëla A. M.; Wouters, Diana; van Mierlo, Gerard; Grobusch, Martin P.; Zeerleder, Sacha S.; van der Poll, Tom

    2015-01-01

    Human immunodeficiency virus (HIV)-induced complement activation may play a role in chronic immune activation in patients with HIV infection and influence the complement system during acute illness. We determined the impact of HIV infection on the complement system in patients with asymptomatic HIV

  16. Discovery of stimulation-responsive immune enhancers with CRISPR activation

    Science.gov (United States)

    Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

    2017-01-01

    The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues1–3. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption4–6, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa)7 to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs. PMID:28854172

  17. Discovery of stimulation-responsive immune enhancers with CRISPR activation

    Science.gov (United States)

    Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K.; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

    2017-09-01

    The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

  18. Enhancing Activity for the Oxygen Evolution Reaction

    DEFF Research Database (Denmark)

    Frydendal, Rasmus; Busch, Michael; Halck, Niels Bendtsen

    2014-01-01

    of all reaction intermediates cannot be optimized individually. However, experimental investigations have shown that drastic improvements can be realized for manganese and cobalt-based oxides if gold is added to the surface or used as substrate. We propose an explanation for these enhancements based...... on a hydrogen acceptor concept. This concept comprises a stabilization of an *-OOH intermediate, which effectively lowers the potential needed for breaking bonds to the surface. On this basis, we investigate the interactions between the oxides and gold by using DFT calculations. The results suggest...

  19. PAX 8 activates the enhancer of the human thyroperoxidase gene.

    OpenAIRE

    Esposito, C.; Miccadei, S; Saiardi, A.; Civitareale, D.

    1998-01-01

    In this study we report on a novel natural target of the paired domain transcription factor PAX 8 in the enhancer element of the human thyroperoxidase gene, one of the most important thyroid differentiation markers. It is the primary enzyme involved in thyroid hormone synthesis and PAX 8 has been previously identified as an activating factor of the rat thyroperoxidase gene promoter. In vitro, PAX 8 binds a cis element of the human enhancer and its exogenous expression induces the enhancer act...

  20. Activities enhance innovation: innovation strategy woodworking company

    Directory of Open Access Journals (Sweden)

    Denysenko Mykola Pavlovych

    2016-12-01

    Full Text Available A major factor in the development of economic systems in modern conditions is innovation, so the economy remains an important task − the development of internal processes based on innovation. The presence of innovative component in the production will increase the competitiveness of individual firms and the economy as a whole, as well as the volume of production and exports. New ideas and products, advanced technologies and organizational solutions increasingly determine the success of entrepreneurial activity, ensure the survival and financial stability of the enterprise. the necessity of implementation of innovation activities emerges as the main requirement. That is why the problems of innovative activity in economic systems nominated in the category of priorities in the structure of economic research. The article substantiates the position of innovative development of the woodworking industry.

  1. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  2. Is Enhanced Physical Activity Possible Using Active Videogames?

    OpenAIRE

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-01-01

    Our research indicated that 10–12-year-old children receiving two active Wii™ (Nintendo®; Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  3. Is Enhanced Physical Activity Possible Using Active Videogames?

    Science.gov (United States)

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii™ (Nintendo®; Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  4. Humorous Materials to Enhance Active Learning

    Science.gov (United States)

    Miller, J. L.; Wilson, K.; Miller, J.; Enomoto, K.

    2017-01-01

    The use of humour in teaching and learning can be contentious, with some authors suggesting that the efficacy of humorous materials is mediated by the culture of the student. Nevertheless, humour represents a potential vehicle for the introduction of active learning in a classroom setting, as judicious use of humour may lead to a more relaxed…

  5. Embedding Research Activities to Enhance Student Learning

    Science.gov (United States)

    Webster, Cynthia M.; Kenney, Jacqueline

    2011-01-01

    Purpose: The purpose of this paper's novel, research-oriented approach is to embed research-based activities in a core second-year course of a university business degree program to support and develop student research capabilities. Design/methodology/approach: The design draws on Boud and Prosser's work to foster participation in a…

  6. The Running Wheel Enhances Food Anticipatory Activity: An Exploratory Study.

    Science.gov (United States)

    Flôres, Danilo E F L; Bettilyon, Crystal N; Jia, Lori; Yamazaki, Shin

    2016-01-01

    Rodents anticipate rewarding stimuli such as daily meals, mates, and stimulant drugs. When a single meal is provided daily at a fixed time of day, an increase in activity, known as food anticipatory activity (FAA), occurs several hours before feeding time. The factors affecting the expression of FAA have not been well-studied. Understanding these factors may provide clues to the undiscovered anatomical substrates of food entrainment. In this study we determined whether wheel-running activity, which is also rewarding to rodents, modulated the robustness of FAA. We found that access to a freely rotating wheel enhanced the robustness of FAA. This enhancement was lost when the wheel was removed. In addition, while prior exposure to a running wheel alone did not enhance FAA, the presence of a locked wheel did enhance FAA as long as mice had previously run in the wheel. Together, these data suggest that FAA, like wheel-running activity, is influenced by reward signaling.

  7. Enhancing Resilience in Active Duty Military Personnel.

    Science.gov (United States)

    Crabtree-Nelson, Sonya; DeYoung, Lcdr Peter

    2017-02-01

    A systematic, evidence-based training program to support active duty military personnel through building unit-level resiliency in preparation for anticipated individual times of crisis is needed. Mental health nurses and social workers in the military possess critical training and expertise in identifying and supporting individual and community resilience factors. Their knowledge of the protective aspects of resilience can and should be used to educate all active duty military personnel, ensure military leaders are knowledgeable in how best to support their units, and provide research on the effectiveness of pre-combat resilience training. [Journal of Psychosocial Nursing and Mental Health Services, 55(2), 44-48.]. Copyright 2017, SLACK Incorporated.

  8. Active tails enhance arboreal acrobatics in geckos.

    Science.gov (United States)

    Jusufi, Ardian; Goldman, Daniel I; Revzen, Shai; Full, Robert J

    2008-03-18

    Geckos are nature's elite climbers. Their remarkable climbing feats have been attributed to specialized feet with hairy toes that uncurl and peel in milliseconds. Here, we report that the secret to the gecko's arboreal acrobatics includes an active tail. We examine the tail's role during rapid climbing, aerial descent, and gliding. We show that a gecko's tail functions as an emergency fifth leg to prevent falling during rapid climbing. A response initiated by slipping causes the tail tip to push against the vertical surface, thereby preventing pitch-back of the head and upper body. When pitch-back cannot be prevented, geckos avoid falling by placing their tail in a posture similar to a bicycle's kickstand. Should a gecko fall with its back to the ground, a swing of its tail induces the most rapid, zero-angular momentum air-righting response yet measured. Once righted to a sprawled gliding posture, circular tail movements control yaw and pitch as the gecko descends. Our results suggest that large, active tails can function as effective control appendages. These results have provided biological inspiration for the design of an active tail on a climbing robot, and we anticipate their use in small, unmanned gliding vehicles and multisegment spacecraft.

  9. Coordinated Neuronal Activity Enhances Corticocortical Communication.

    Science.gov (United States)

    Zandvakili, Amin; Kohn, Adam

    2015-08-19

    Relaying neural signals between cortical areas is central to cognition and sensory processing. The temporal coordination of activity in a source population has been suggested to determine corticocortical signaling efficacy, but others have argued that coordination is functionally irrelevant. We reasoned that if coordination significantly influenced signaling, spiking in downstream networks should be preceded by transiently elevated coordination in a source population. We developed a metric to quantify network coordination in brief epochs, and applied it to simultaneous recordings of neuronal populations in cortical areas V1 and V2 of the macaque monkey. Spiking in the input layers of V2 was preceded by brief epochs of elevated V1 coordination, but this was not the case in other layers of V2. Our results indicate that V1 coordination influences its signaling to direct downstream targets, but that coordinated V1 epochs do not propagate through multiple downstream networks as in some corticocortical signaling schemes. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Active Living by Design: Creating Activity-Enhancing Residential Settings

    OpenAIRE

    Zimring, Craig; Dalton, Ruth; Joseph, Anjali; Harris-Kojetin, Lauren; Kiefer, Kristen

    2005-01-01

    The focus of this study is to identify planning, programming and design factors in residential settings that encourage people over 50 to remain active, such as site selection, connection to the surrounding community, site design and walking paths, interior layout and circulation and provision of activity spaces, as well as more subtle factors such as overall wayfinding and ambience.

  11. Bioengineered nisin derivatives with enhanced activity in complex matrices

    Science.gov (United States)

    Rouse, Susan; Field, Des; Daly, Karen M.; O'Connor, Paula M.; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

    2012-01-01

    Summary Nisin A is the best known and most extensively characterized lantibiotic. As it is ribosomally synthesized, bioengineering‐based strategies can be used to generate variants. We have previously demonstrated that bioengineering of the hinge region of nisin A can result in the generation of variants with enhanced anti‐microbial activity against Gram‐positive pathogens. Here we created a larger bank of hinge variant producers and screened for producers that exhibit enhanced bioactivity as assessed by agar‐based assays against a selection of target strains. Further analysis of 12 ‘lead’ variants reveals that in many cases enhanced bioactivity is not attributable to enhanced specific activity but is instead as a consequence of an enhanced ability to diffuse through complex polymers. In the case of two variants, which contain the residues SVA and NAK, respectively, within the hinge region, we demonstrate that this enhanced trait enables the peptides to dramatically outperform nisin A with respect to controlling Listeria monocytogenes in commercially produced chocolate milk that contains carrageenan as a stabilizer. PMID:22260415

  12. The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis

    Science.gov (United States)

    Liu, Chia-Feng; Lefebvre, Véronique

    2015-01-01

    SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We use here genome-wide approaches to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. Using the RCS cell line as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes, we uncover that SOX6 and SOX9 bind thousands of genomic sites, frequently and most efficiently near each other. SOX9 recognizes pairs of inverted SOX motifs, whereas SOX6 favors pairs of tandem SOX motifs. The SOX proteins primarily target enhancers. While binding to a small fraction of typical enhancers, they bind multiple sites on almost all super-enhancers (SEs) present in RCS cells. These SEs are predominantly linked to cartilage-specific genes. The SOX proteins effectively work together to activate these SEs and are required for in vivo expression of their associated genes. These genes encode key regulatory factors, including the SOX trio proteins, and all essential cartilage extracellular matrix components. Chst11, Fgfr3, Runx2 and Runx3 are among many other newly identified SOX trio targets. SOX9 and SOX5/SOX6 thus cooperate genome-wide, primarily through SEs, to implement the growth plate chondrocyte differentiation program. PMID:26150426

  13. Women's Health-Enhancing Physical Activity and Eudaimonic Well Being

    Science.gov (United States)

    Ferguson, Leah J.; Kowalski, Kent C.; Mack, Diane E.; Wilson, Philip M.; Crocker, Peter R. E.

    2012-01-01

    In this study, we explored the role of health-enhancing physical activity (HEPA; Miilunpalo, 2001) in women's eudaimonic well being (i.e., psychological flourishing at one's maximal potential; Ryff, 1989). We used a quantitative approach (N = 349) to explore the relationship between HEPA and eudaimonic well being. While HEPA was not related to…

  14. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Schnorr, Kirk; Kramer, Randall

    2017-08-08

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  15. Enhancement of visible light irradiation photocatalytic activity of ...

    Indian Academy of Sciences (India)

    Mohamed Abdel Salam

    2017-09-25

    Sep 25, 2017 ... Yin D and Zhao F 2015 Visible-light-responsive sulfated vanadium-doped TS-1 with hollow structure: Enhanced photocatalytic activity in selective oxidation of cyclo- hexane J. Catal. 330 208. 11. Kim J, Ichikuni N, Hara T and Shimazu S 2016 Study on the selectivity of propane photo-oxidation reaction on.

  16. Activity enhancement of ligninolytic enzymes of Trametes versicolor ...

    African Journals Online (AJOL)

    Suspended cultures of white-rot fungus, Trametes versicolor, supplemented with bagasse powder showed a concentration dependent enhancement in the ligninolytic enzymes activity in liquid shake cultures. 2% (w/v) bagasse powder improved greater stability to the enzymes. The optimum pH is 3.5 and the optimum ...

  17. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2017-09-05

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  18. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Lan; Liu, Ye; Duan, Junxin; Wu, Wenping; Kramer, Randall

    2017-09-19

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  19. Enhanced food anticipatory activity associated with enhanced activation of extrahypothalamic neural pathways in serotonin2C receptor null mutant mice.

    Directory of Open Access Journals (Sweden)

    Jennifer L Hsu

    Full Text Available The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity. However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin(2C receptor (5-HT2CR null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.

  20. Active control for performance enhancement of electrically controlled rotor

    Directory of Open Access Journals (Sweden)

    Lu Yang

    2015-10-01

    Full Text Available Electrically controlled rotor (ECR system has the potential to enhance the rotor performance by applying higher harmonic flap inputs. In order to explore the feasibility and effectiveness for ECR performance enhancement using closed-loop control method, firstly, an ECR rotor performance analysis model based on helicopter flight dynamic model is established, which can reflect the performance characteristics of ECR helicopter at high advance ratio. Based on the simulation platform, an active control method named adaptive T-matrix algorithm is adopted to explore the feasibility and effectiveness for ECR performance enhancement. The simulation results verify the effectiveness of this closed-loop control method. For the sample ECR helicopter, about 3% rotor power reduction is obtained with the optimum 2/rev flap inputs at the advance ratio of 0.34. And through analyzing the distributions of attack of angle and drag in rotor disk, the underlying physical essence of ECR power reduction is cleared. Furthermore, the influence of the key control parameters, including convergence factor and weighting matrix, on the effectiveness of closed-loop control for ECR performance enhancement is explored. Some useful results are summarized, which can be used to direct the future active control law design of ECR performance enhancement.

  1. Enhancement of nitrate reductase activity by benzyladenine in Agrostemma githago

    Energy Technology Data Exchange (ETDEWEB)

    Kende, H.; Hahn, H.; Kays, S.E.

    1971-01-01

    Nitrate reductase activity in excised embryos of Agrostemma githago increases in response to both NO/sub 3//sup -/ and cytokinins. Discussed was whether cytokinins affected nitrate reductase activity directly or through NO/sub 3//sup -/, either by amplifying the effect of low endogenous NO/sub 3//sup -/ levels, or by making NO/sub 3//sup -/ available for induction from a metabolically inactive compartment. Nitrate reductase activity was enhanced on the average by 50% after 1 hour of benzyladenine treatment. In some experiments, the cytokinin response was detectable as early as 30 minutes after addition of benzyladenine. Nitrate reductase activity increased linearly for 4 hours and began to decay 13 hours after start of the hormone treatment. When embryos were incubated in solutions containing mixtures of NO/sub 3//sup -/ and benzyladenine, additive responses were obtained. The effects of NO/sub 3//sup -/ and benzyladenine were counteracted by abscisic acid. The increase in nitrate reductase activity was inhibited at lower abscisic acid concentrations in embryos which were induced with NO/sub 3//sup -/, as compared to embryos treated with benzyladenine. Casein hydrolysate inhibited the development of nitrate reductase activity. The response to NO/sub 3//sup -/ was more susceptible to inhibition by casein hydrolysate than the response to the hormone. When NO/sub 3//sup -/ and benzyladenine were withdrawn from the medium after maximal enhancement of nitrate reductase activity, the level of the enzyme decreased rapidly. Nitrate reductase activity increased again as a result of a second treatment with benzyladenine but not with NO/sub 3//sup -/. At the time of the second exposure to benzyladenine, no NO/sub 3//sup -/ was detectable in extracts of Agrostemma embryos. This is taken as evidence that cytokinins enhance nitrate reductase activity directly and not through induction by NO/sub 3//sup -/. 11 references, 5 figures, 3 tables.

  2. Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity.

    Science.gov (United States)

    Su, Yee-Fun; Yang, Tsunghan; Huang, Hoting; Liu, Leroy F; Hwang, Jaulang

    2012-01-01

    Increasing evidence has pointed to an important role of SUMOylation in cell cycle regulation, especially for M phase. In the current studies, we have obtained evidence through in vitro studies that the master M phase regulator CDK1/cyclin B kinase phosphorylates the SUMOylation machinery component Ubc9, leading to its enhanced SUMOylation activity. First, we show that CDK1/cyclin B, but not many other cell cycle kinases such as CDK2/cyclin E, ERK1, ERK2, PKA and JNK2/SAPK1, specifically enhances SUMOylation activity. Second, CDK1/cyclin B phosphorylates the SUMOylation machinery component Ubc9, but not SAE1/SAE2 or SUMO1. Third, CDK1/cyclin B-phosphorylated Ubc9 exhibits increased SUMOylation activity and elevated accumulation of the Ubc9-SUMO1 thioester conjugate. Fourth, CDK1/cyclin B enhances SUMOylation activity through phosphorylation of Ubc9 at serine 71. These studies demonstrate for the first time that the cell cycle-specific kinase CDK1/cyclin B phosphorylates a SUMOylation machinery component to increase its overall SUMOylation activity, suggesting that SUMOylation is part of the cell cycle program orchestrated by CDK1 through Ubc9.

  3. Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity.

    Directory of Open Access Journals (Sweden)

    Yee-Fun Su

    Full Text Available Increasing evidence has pointed to an important role of SUMOylation in cell cycle regulation, especially for M phase. In the current studies, we have obtained evidence through in vitro studies that the master M phase regulator CDK1/cyclin B kinase phosphorylates the SUMOylation machinery component Ubc9, leading to its enhanced SUMOylation activity. First, we show that CDK1/cyclin B, but not many other cell cycle kinases such as CDK2/cyclin E, ERK1, ERK2, PKA and JNK2/SAPK1, specifically enhances SUMOylation activity. Second, CDK1/cyclin B phosphorylates the SUMOylation machinery component Ubc9, but not SAE1/SAE2 or SUMO1. Third, CDK1/cyclin B-phosphorylated Ubc9 exhibits increased SUMOylation activity and elevated accumulation of the Ubc9-SUMO1 thioester conjugate. Fourth, CDK1/cyclin B enhances SUMOylation activity through phosphorylation of Ubc9 at serine 71. These studies demonstrate for the first time that the cell cycle-specific kinase CDK1/cyclin B phosphorylates a SUMOylation machinery component to increase its overall SUMOylation activity, suggesting that SUMOylation is part of the cell cycle program orchestrated by CDK1 through Ubc9.

  4. Semaphorin 4D Enhances Angiogenic Potential and Suppresses Osteo-/Odontogenic Differentiation of Human Dental Pulp Stem Cells.

    Science.gov (United States)

    Zou, Ting; Dissanayaka, Waruna Lakmal; Jiang, Shan; Wang, Shuai; Heng, Boon Chin; Huang, Xiaojing; Zhang, Chengfei

    2017-02-01

    To investigate the roles of semaphorin 4D (Sema4D)/plexin-B1 signaling on the angiogenic potential and osteo-/odontogenic differentiation of human dental pulp stem cells (DPSCs) and to uncover the corresponding molecular mechanisms. DPSCs were treated with Sema4D (10 μg/mL) for different time durations. Osteo-/odontogenic differentiation was assessed by quantifying alkaline phosphatase activity, mineralized nodule formation, and osteo-/odontogenic gene (ALP, Col1A1, BSP, RUNX2, and DSPP) and protein (Col1A1 and DSPP) expression. Involvement of the Sema4D/plexin-B1 signaling pathway was analyzed by Western blot analysis. Additionally, angiogenic gene and protein expression was assessed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. In vitro endothelial tube formation assay on Matrigel (BD Biosciences, San Jose, CA) was performed to evaluate the angiogenic inductive potential of the Sema4D-treated DPSCs conditioned medium. Results were analyzed using 1-way analysis of variance and the Student t test. Sema4D significantly inhibited ALP activity and mineralized nodule formation of DPSCs. Furthermore, Sema4D-treated DPSCs displayed marked down-regulation in the expression of osteo-/odontogenic genes (ALP, Col1A1, BSP, RUNX2, and DSPP) as well as proteins (Col1A1 and DSPP). Elevated levels of plexin-B1 and downstream RhoA protein expression together with phosphorylated plexin-B1 confirmed the involvement of Sema4D/plexin-B1 signaling. Protein expression of ErbB2 was up-regulated, and Met was slightly down-regulated. Furthermore, Sema4D-treated DPSCs exhibited enhanced expression of vascular endothelial growth factor at both the messenger RNA and protein level. Accordingly, the conditioned medium of Sema4D-treated DPSCs promoted the formation of vessel-like structures as shown by the Matrigel assay. Sema4D markedly enhances the angiogenic potential but suppresses osteo-/odontogenic differentiation of DPSCs. Sema4D

  5. Intermittent Administration of Parathyroid Hormone 1–34 Enhances Osteogenesis of Human Mesenchymal Stem Cells by Regulating Protein Kinase Cδ

    Directory of Open Access Journals (Sweden)

    Shu-Wen Kuo

    2017-10-01

    Full Text Available Human mesenchymal stem cells (hMSCs can differentiate into osteoblasts and are regulated by chemical cues. The recombinant N-terminal (1–34 amino acids fragment of the parathyroid hormone (PTH (1–34 is identified to promote osteogenesis. The osteoanabolic effects of intermittent PTH (1–34 treatment are linked to a complex consisting of signaling pathways; additionally, protein kinase C (PKC act as mediators of multifunctional signaling transduction pathways, but the role of PKC δ (PKCδ, a downstream target in regulating osteoblast differentiation during intermittent administration of PTH (1–34 is less studied and still remains elusive. The purpose of this study is to examine the role of PKCδ during intermittent and continuous PTH (1–34 administration using osteoblast-lineage-committed hMSCs. Relative gene expression of osteoblast-specific genes demonstrated significant upregulation of RUNX2, type I Collagen, ALP, and Osterix and increased alkaline phosphatase activity in the presence of PTH (1–34. Intermittent PTH (1–34 administration increased PKC activity at day 7 of osteogenic differentiation, whereas inhibition of PKC activity attenuated these effects. In addition, the specific isoform PKCδ was activated upon treatment. These findings demonstrate that intermittent PTH (1–34 treatment enhances the osteogenesis of hMSCs by upregulating osteoblast-specific genes via PKCδ activation.

  6. Energy intake during activity enhanced video game play.

    Science.gov (United States)

    Mellecker, Robin R; Lanningham-Foster, Lorraine; Levine, James A; McManus, Alison M

    2010-10-01

    The purpose of this study was to examine whether the addition of a motor component to video gaming alters energy consumption. To address this problem we used an experimental manipulation design with 9-13 year olds incorporating 'seated video game' and 'activity enhanced video game' conditions, whilst allowing snacks ad libitum. No difference in snacking between the two video gaming conditions was apparent. The children consumed 374 and 383kcalh(-1) during seated and activity enhanced video gaming, respectively. A secondary purpose was to examine consistency of energy intake during free choice video game play. We found no difference in energy intake between four 1h free choice video gaming sessions. Snacking energy intake whilst video gaming was 166% more than the calories required during resting conditions. This study has shown that the addition of a motor component to the video game environment does not alter snack energy intake. However, the high calorific consumption during both seated and activity enhanced video game play highlights the need for an active attempt to restrict snacking whilst playing video games.

  7. Enhancing learning in geosciences and water engineering via lab activities

    Science.gov (United States)

    Valyrakis, Manousos; Cheng, Ming

    2016-04-01

    This study focuses on the utilisation of lab based activities to enhance the learning experience of engineering students studying Water Engineering and Geosciences. In particular, the use of modern highly visual and tangible presentation techniques within an appropriate laboratory based space are used to introduce undergraduate students to advanced engineering concepts. A specific lab activity, namely "Flood-City", is presented as a case study to enhance the active engagement rate, improve the learning experience of the students and better achieve the intended learning objectives of the course within a broad context of the engineering and geosciences curriculum. Such activities, have been used over the last few years from the Water Engineering group @ Glasgow, with success for outreach purposes (e.g. Glasgow Science Festival and demos at the Glasgow Science Centre and Kelvingrove museum). The activity involves a specific setup of the demonstration flume in a sand-box configuration, with elements and activities designed so as to gamely the overall learning activity. Social media platforms can also be used effectively to the same goals, particularly in cases were the students already engage in these online media. To assess the effectiveness of this activity a purpose designed questionnaire is offered to the students. Specifically, the questionnaire covers several aspects that may affect student learning, performance and satisfaction, such as students' motivation, factors to effective learning (also assessed by follow-up quizzes), and methods of communication and assessment. The results, analysed to assess the effectiveness of the learning activity as the students perceive it, offer a promising potential for the use of such activities in outreach and learning.

  8. STAFF ACTIVE AND REFLECTIVE LEARNING (ARL) TO ENHANCE STUDENT MANAGEMENT

    OpenAIRE

    Tay Sing Leong; Lim See Yew

    2010-01-01

    The Staff Active Reflective Learning (ARL) is a new scheme designed to enhance student management though regular get-togethers of a group of teaching staff. It provides a platform for staff to share issues related to teaching, and seek solutions. This addresses current and future challenges faced in classroom management. The implementation of the Staff ARL is one of the recent initiatives taken under a new approach to shared learning within the School of Electronic and Info-Comm Technology. I...

  9. Modafinil enhances alerting-related brain activity in attention networks.

    Science.gov (United States)

    Ikeda, Yumiko; Funayama, Takuya; Tateno, Amane; Fukayama, Haruhisa; Okubo, Yoshiro; Suzuki, Hidenori

    2017-07-01

    Modafinil is a wake-promoting agent and has been reported to be effective in improving attention in patients with attentional disturbance. However, neural substrates underlying the modafinil effects on attention are not fully understood. We employed a functional magnetic resonance imaging (fMRI) study with the attention network test (ANT) task in healthy adults and examined which networks of attention are mainly affected by modafinil and which neural substrates are responsible for the drug effects. We used a randomized placebo-controlled within-subjects cross-over design. Twenty-three healthy adults participated in two series of an fMRI study, taking either a placebo or modafinil. The participants performed the ANT task, which is designed to measure three distinct attentional networks, alerting, orienting, and executive control, during the fMRI scanning. The effects of modafinil on behavioral performance and regional brain activity were analyzed. We found that modafinil enhanced alerting performance and showed greater alerting network activity in the left middle and inferior occipital gyri as compared with the placebo. The brain activations in the occipital regions were positively correlated with alerting performance. Modafinil enhanced alerting performance and increased activation in the occipital lobe in the alerting network possibly relevant to noradrenergic activity during the ANT task. The present study may provide a rationale for the treatment of patients with distinct symptoms of impaired attention.

  10. Enhanced antibacterial activities of leonuri herba extracts containing silver nanoparticles.

    Science.gov (United States)

    Im, A-Rang; Han, Lina; Kim, E Ray; Kim, Jinwoong; Kim, Yeong Shik; Park, Youmie

    2012-08-01

    We report an efficient and powerful green process to enhance the antibacterial activities of the Leonuri herba extract. Plant sources, especially leaves and herbs, are precious for the generation of gold and silver nanoparticles. Various kinds of polyphenols and hydroxyl groups are capable of processing a reduction reaction to generate metals from its corresponding salts. We have prepared gold and silver nanoparticles with 70% ethanol and water extracts. No other toxic chemicals were utilized and the extracts played dual roles as reducing and stabilizing agents. For the generation of nanoparticles, both oven incubation and autoclaving methods were applied and the reaction conditions were optimized. Surface plasmon resonance band indicated that the formation of nanoparticles was successful. Images of high-resolution transmission electron microscopy revealed mostly spherical nanoparticles ranging from 9.9 to 13.0 nm in size. A water extract containing silver nanoparticles exhibited remarkable (approximately 127-fold) enhancement in antibacterial activities against Pseudomonas aeruginosa, Escherichia coli and Enterobacter cloacae when compared with the water extract alone. In addition, antibacterial activity towards Gram-negative bacteria was greater than that against Gram-positive bacteria. The process reported here has the potential to be a new approach to improve the antibacterial activities of plant extracts. Copyright © 2011 John Wiley & Sons, Ltd.

  11. Vortical ciliary flows actively enhance mass transport in reef corals.

    Science.gov (United States)

    Shapiro, Orr H; Fernandez, Vicente I; Garren, Melissa; Guasto, Jeffrey S; Debaillon-Vesque, François P; Kramarsky-Winter, Esti; Vardi, Assaf; Stocker, Roman

    2014-09-16

    The exchange of nutrients and dissolved gasses between corals and their environment is a critical determinant of the growth of coral colonies and the productivity of coral reefs. To date, this exchange has been assumed to be limited by molecular diffusion through an unstirred boundary layer extending 1-2 mm from the coral surface, with corals relying solely on external flow to overcome this limitation. Here, we present direct microscopic evidence that, instead, corals can actively enhance mass transport through strong vortical flows driven by motile epidermal cilia covering their entire surface. Ciliary beating produces quasi-steady arrays of counterrotating vortices that vigorously stir a layer of water extending up to 2 mm from the coral surface. We show that, under low ambient flow velocities, these vortices, rather than molecular diffusion, control the exchange of nutrients and oxygen between the coral and its environment, enhancing mass transfer rates by up to 400%. This ability of corals to stir their boundary layer changes the way that we perceive the microenvironment of coral surfaces, revealing an active mechanism complementing the passive enhancement of transport by ambient flow. These findings extend our understanding of mass transport processes in reef corals and may shed new light on the evolutionary success of corals and coral reefs.

  12. Mushroom bodies enhance initial motor activity in Drosophila.

    Science.gov (United States)

    Serway, Christine N; Kaufman, Rebecca R; Strauss, Roland; de Belle, J Steven

    2009-01-01

    The central body (or central complex, CCX) and the mushroom bodies (MBs) are brain structures in most insect phyla that have been shown to influence aspects of locomotion. The CCX regulates motor coordination and enhances activity while MBs have, thus far, been shown to suppress motor activity levels measured over time intervals ranging from hours to weeks. In this report, we investigate MB involvement in motor behavior during the initial stages (15 minutes) of walking in Buridan's paradigm. We measured aspects of walking in flies that had MB lesions induced by mutations in six different genes and by chemical ablation. All tested flies were later examined histologically to assess MB neuroanatomy. Mutant strains with MB structural defects were generally less active in walking than wild-type flies. Most mutants in which MBs were also ablated with hydroxyurea (HU) showed additional activity decrements. Variation in measures of velocity and orientation to landmarks among wild-type and mutant flies was attributed to pleiotropy, rather than to MB lesions. We conclude that MBs upregulate activity during the initial stages of walking, but suppress activity thereafter. An MB influence on decision making has been shown in a wide range of complex behaviors. We suggest that MBs provide appropriate contextual information to motor output systems in the brain, indirectly fine tuning walking by modifying the quantity (i.e., activity) of behavior.

  13. Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2014-07-01

    Full Text Available Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in human mesenchymal stem cells (MSCs. Arginine potently induced the expression of type Iα1 collagen, osteocalcin, and ALP in a dose-dependent manner without causing cytotoxicity. Arginine significantly increased the mRNA expression of the osteogenic transcription factors runt-related transcription factor 2 (Runx2, DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by decreasing adipocyte formation and triglyceride (TG content in MSCs and inhibiting the mRNA expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ, CCAAT/enhancer-binding protein α (C/EBPα, and fatty acid binding protein 4 (Fabp4. This effect was associated with increased expression of Wnt5a, and nuclear factor of activated T-cells (NFATc, and was abrogated by antagonists of Wnt and NFATc, which indicated a role of Wnt and NFATc signaling in the switch from adipogenesis to osteoblastogenesis induced by arginine. In conclusion, this is the first report of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte formation through involving Wnt5a and NFATc signaling pathway.

  14. Enhanced antitumor activity of irofulven in combination with antimitotic agents.

    Science.gov (United States)

    Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Trani, Nicole A; Velasco, Tami R; Estes, Leita A; Suthipinijtham, Pharnuk

    2002-08-01

    The aim of this study was to determine the antitumor activity of irofulven when administered in combination with a variety of antimitotic agents. Irofulven in combination with either paclitaxel or docetaxel demonstrated synergistic activity in both the in vitro and in vivo studies. The majority of xenograft bearing animals that received suboptimal (irofulven and a taxane demonstrated complete cures. In contrast, in vitro studies produced either an additive or an antagonistic effect when irofulven was combined with other antimitotic agents such as vinca alkaloids, rhizoxin, s-trityl cysteine, or allocolchicine. Xenograft studies of irofulven and vinca alkaloids reflected in vitro results, as the tumor response in combination treated animals was less than the response in irofulven (monotherapy) treated animals. These results indicate that the therapeutic activity of irofulven is enhanced when combined with taxanes, and warrant further evaluation of these combinations.

  15. Mapping of functional regions of murine retrovirus long terminal repeat enhancers: Enhancer domains interact and are not independent in their contributions to enhancer activity

    Energy Technology Data Exchange (ETDEWEB)

    Hollon, T.; Yoshimura, F.K. (Univ. of Washington, Seattle (USA))

    1989-08-01

    The authors have used deletion and recombinant long terminal repeat (LTR) mutants to examine enhancer activity differences between LTRs of the nonpathogenic Akv and the thymus lymphomagenic MCF13 murine retroviruses. Deletion mutant analysis revealed that major control regions for MCF13 and Akv LTR enhancer activity were similar but not identical. For both LTRs, major control regions were distinctly different in a murine T-cell and a fibroblast cell line. Recombinant enhancer analysis showed that LTRs could be divided into three regions capable of altering the level of enhancer activity through cooperative or antagonistic interaction. The contribution of each region to enhancer activity was dependent on its context with respect to the other regions. LTR enhancer function in different cell types appears to be the result of the interaction of enhancer modular elements.

  16. Positive mood enhances reward-related neural activity.

    Science.gov (United States)

    Young, Christina B; Nusslock, Robin

    2016-06-01

    Although behavioral research has shown that positive mood leads to desired outcomes in nearly every major life domain, no studies have directly examined the effects of positive mood on the neural processes underlying reward-related affect and goal-directed behavior. To address this gap, participants in the present fMRI study experienced either a positive (n = 20) or neutral (n = 20) mood induction and subsequently completed a monetary incentive delay task that assessed reward and loss processing. Consistent with prediction, positive mood elevated activity specifically during reward anticipation in corticostriatal neural regions that have been implicated in reward processing and goal-directed behavior, including the nucleus accumbens, caudate, lateral orbitofrontal cortex and putamen, as well as related paralimbic regions, including the anterior insula and ventromedial prefrontal cortex. These effects were not observed during reward outcome, loss anticipation or loss outcome. Critically, this is the first study to report that positive mood enhances reward-related neural activity. Our findings have implications for uncovering the neural mechanisms by which positive mood enhances goal-directed behavior, understanding the malleability of reward-related neural activity, and developing targeted treatments for psychiatric disorders characterized by deficits in reward processing. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  17. Psychosocial Pain Management Moderation: The Limit, Activate, and Enhance Model.

    Science.gov (United States)

    Day, Melissa A; Ehde, Dawn M; Jensen, Mark P

    2015-10-01

    There is a growing emphasis in the pain literature on understanding the following second-order research questions: Why do psychosocial pain treatments work? For whom do various treatments work? This critical review summarizes research that addresses the latter question and proposes a moderation model to help guide future research. A theoretical moderation framework for matching individuals to specific psychosocial pain interventions has been lacking. However, several such frameworks have been proposed in the broad psychotherapy and implementation science literature. Drawing on these theories and adapting them specifically for psychosocial pain treatment, here we propose a Limit, Activate, and Enhance model of pain treatment moderation. This model is unique in that it includes algorithms not only for matching treatments on the basis of patient weaknesses but also for directing patients to interventions that build on their strengths. Critically, this model provides a basis for specific a priori hypothesis generation, and a selection of the possible hypotheses drawn from the model are proposed and discussed. Future research considerations are presented that could refine and expand the model based on theoretically driven empirical evidence. The Limit, Activate, and Enhance model presented here is a theoretically derived framework that provides an a priori basis for hypothesis generation regarding psychosocial pain treatment moderators. The model will advance moderation research via its unique focus on matching patients to specific treatments that (1) limit maladaptive responses, (2) activate adaptive responses, and (3) enhance treatment outcomes based on patient strengths and resources. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Contrast-enhanced ultrasonography revealed active thoracic bleeding.

    Science.gov (United States)

    Sugihara, Takaaki; Koda, Masahiko; Tokunaga, Shiho; Matono, Tomomitsu; Nagahara, Takakazu; Ueki, Masaru; Murawaki, Yoshikazu; Kaminou, Toshio

    2010-07-01

    A 61-year-old woman with a hepatocellular carcinoma located in the subphrenic region was treated by radiofrequency ablation (RFA) under artificial pleural effusion. During RFA, B-mode ultrasonography showed a swirling high echoic lesion in the artificial pleural effusion. A real-time scan performed using contrast-enhanced ultrasonography (CEUS) revealed a jet-like extravasation of contrast medium and pooling of microbubbles in the pleural cavity, which were confirmed by angiography. CEUS successfully identified the site of bleeding and can be regarded an effective tool for detecting active bleeding in an emergency.

  19. Intelligent Architecture for Enhanced Observability for Active Distribution System

    DEFF Research Database (Denmark)

    Pokhrel, Basanta Raj; Nainar, Karthikeyan; Bak-Jensen, Birgitte

    2017-01-01

    to utilize advanced solutions by observing the system state in real time. Existing distribution automation and control system have to be upgraded to meet this technological challenge. This necessitates the use of real time system states of the grid which is a crucial factor for system operation in higher...... for active distribution network which satisfies the need for higher observability reach with less field observation. Improved state estimation with composite load forecasting model is aimed for enhanced observability. This paper also summarizes the application of intelligent architecture in the operation...

  20. Gene activation regresses atherosclerosis, promotes health, and enhances longevity

    Directory of Open Access Journals (Sweden)

    Luoma Pauli V

    2010-07-01

    Full Text Available Abstract Background Lifestyle factors and pharmacological compounds activate genetic mechanisms that influence the development of atherosclerotic and other diseases. This article reviews studies on natural and pharmacological gene activation that promotes health and enhances longevity. Results Living habits including healthy diet and regular physical activity, and pharmacotherapy, upregulate genes encoding enzymes and apolipoprotein and ATP-binding cassette transporters, acting in metabolic processes that promote health and increase survival. Cytochrome P450-enzymes, physiological factors in maintaining cholesterol homeostasis, generate oxysterols for the elimination of surplus cholesterol. Hepatic CTP:phosphocholine cytidylyltransferase-α is an important regulator of plasma HDL-C level. Gene-activators produce plasma lipoprotein profile, high HDL-C, HDL2-C and HDL-C/cholesterol ratio, which is typical of low risk of atherosclerotic disease, and also of exceptional longevity together with reduced prevalence of cardiovascular, metabolic and other diseases. High HDL contributes to protection against inflammation, oxidation and thrombosis, and associates with good cognitive function in very old people. Avoiding unhealthy stress and managing it properly promotes health and increases life expectancy. Conclusions Healthy living habits and gene-activating xenobiotics upregulate mechanisms that produce lipoprotein pattern typical of very old people and enhance longevity. Lipoprotein metabolism and large HDL2 associate with the process of living a very long life. Major future goals for health promotion are the improving of commitment to both wise lifestyle choices and drug therapy, and further the developing of new and more effective and well tolerated drugs and treatments.

  1. Active medulloblastoma enhancers reveal subgroup-specific cellular origins

    Science.gov (United States)

    Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

    2016-01-01

    Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

  2. Psychopaths show enhanced amygdala activation during fear conditioning

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    Douglas eSchultz

    2016-03-01

    Full Text Available Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into primary and secondary psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional fearlessness, while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  3. Enhanced biological activity of carotenoids stabilized by phenyl groups.

    Science.gov (United States)

    You, Ji Suk; Jeon, Sunhwa; Byun, Youn Jung; Koo, Sangho; Choi, Shin Sik

    2015-06-15

    Carotenoids are lipid soluble food ingredients with multifunction including antioxidant and anticancer activities. However, carotenoids are destructively oxidized upon reaction with radicals resulting in toxic effects on biological systems. Two synthetic carotenoids (BAS and BTS) containing the aromatic phenyl groups with a para-substituent (OMe and Me, respectively) at C-13 and C-13' position were prepared in order to overcome a structural instability of carotenoid. Both BAS and BTS exerted stronger radical scavenging activity than β-carotene in DPPH and ABTS assays. In particular, BTS significantly reduced in vivo ROS (reactive oxygen species) levels and improved body growth and reproduction of Caenorhabditiselegans. BTS has a great potential for the advanced and modified carotenoid material with stability leading to enhanced bioavailability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Hyperbaric Oxygen Environment Can Enhance Brain Activity and Multitasking Performance.

    Science.gov (United States)

    Vadas, Dor; Kalichman, Leonid; Hadanny, Amir; Efrati, Shai

    2017-01-01

    Background: The Brain uses 20% of the total oxygen supply consumed by the entire body. Even though, multitasking), the oxygen supply is shifted from one brain region to another, via blood perfusion modulation. The aim of the present study was to evaluate whether a hyperbaric oxygen (HBO) environment, with increased oxygen supply to the brain, will enhance the performance of complex and/or multiple activities. Methods: A prospective, double-blind randomized control, crossover trial including 22 healthy volunteers. Participants were asked to perform a cognitive task, a motor task and a simultaneous cognitive-motor task (multitasking). Participants were randomized to perform the tasks in two environments: (a) normobaric air (1 ATA 21% oxygen) (b) HBO (2 ATA 100% oxygen). Two weeks later participants were crossed to the alternative environment. Blinding of the normobaric environment was achieved in the same chamber with masks on while hyperbaric sensation was simulated by increasing pressure in the first minute and gradually decreasing to normobaric environment prior to tasks performance. Results: Compared to the performance at normobaric conditions, both cognitive and motor single tasks scores were significantly enhanced by HBO environment (p Multitasking performance was also significantly enhanced in HBO environment (p = 0.006 for the cognitive part and p = 0.02 for the motor part). Conclusions: The improvement in performance of both single and multi-tasking while in an HBO environment supports the hypothesis which according to, oxygen is indeed a rate limiting factor for brain activity. Hyperbaric oxygenation can serve as an environment for brain performance. Further studies are needed to evaluate the optimal oxygen levels for maximal brain performance.

  5. Silver enhances antibiotic activity against gram-negative bacteria.

    Science.gov (United States)

    Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

    2013-06-19

    A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

  6. Gene Regulatory Enhancers with Evolutionarily Conserved Activity Are More Pleiotropic than Those with Species-Specific Activity.

    Science.gov (United States)

    Fish, Alexandra; Chen, Ling; Capra, John A

    2017-10-01

    Studies of regulatory activity and gene expression have revealed an intriguing dichotomy: There is substantial turnover in the regulatory activity of orthologous sequences between species; however, the expression level of orthologous genes is largely conserved. Understanding how distal regulatory elements, for example, enhancers, evolve and function is critical, as alterations in gene expression levels can drive the development of both complex disease and functional divergence between species. In this study, we investigated determinants of the conservation of regulatory enhancer activity for orthologous sequences across mammalian evolution. Using liver enhancers identified from genome-wide histone modification profiles in ten diverse mammalian species, we compared orthologous sequences that exhibited regulatory activity in all species (conserved-activity enhancers) to shared sequences active only in a single species (species-specific-activity enhancers). Conserved-activity enhancers have greater regulatory potential than species-specific-activity enhancers, as quantified by both the density and diversity of transcription factor binding motifs. Consistent with their greater regulatory potential, conserved-activity enhancers have greater regulatory activity in humans than species-specific-activity enhancers: They are active across more cellular contexts, and they regulate more genes than species-specific-activity enhancers. Furthermore, the genes regulated by conserved-activity enhancers are expressed in more tissues and are less tolerant of loss-of-function mutations than those targeted by species-specific-activity enhancers. These consistent results across various stages of gene regulation demonstrate that conserved-activity enhancers are more pleiotropic than their species-specific-activity counterparts. This suggests that pleiotropy is associated with the conservation of regulatory across mammalian evolution. © The Author 2017. Published by Oxford University

  7. Sports activities enhance the prevalence of rhinitis symptoms in schoolchildren.

    Science.gov (United States)

    Kusunoki, Takashi; Takeuchi, Jiro; Morimoto, Takeshi; Sakuma, Mio; Mukaida, Kumiko; Yasumi, Takahiro; Nishikomori, Ryuta; Heike, Toshio

    2016-03-01

    To evaluate the association between sports activities and allergic symptoms, especially rhinitis, among schoolchildren. This longitudinal survey of schoolchildren collected data from questionnaires regarding allergic symptoms based on the International Study of Asthma and Allergies in Childhood (ISAAC) program and sports participation that were distributed to the parents of children at all 12 public primary schools in Ohmi-Hachiman City, Shiga Prefecture, Japan. Data were collected annually from 2011 until 2014, when the children reached 10 years of age. Blood samples were obtained in 2014, and the levels of immunoglobulin (Ig)E specific to four inhalant allergens were measured. Data from 558 children were analyzed. At 10 years of age, prevalence of asthma and eczema did not differ significantly, while rhinitis was significantly higher (p = 0.009) among children who participated in sports. Prevalence of rhinitis increased as the frequency or duration of sports participation increased (p sports (p = 0.03). Among those who participated in continuous sports activities, the prevalence of rhinitis was significantly higher with prolonged eczema (p = 0.006). Sports activities did not increase sensitization to inhalant allergens. Sports activities enhance the prevalence of rhinitis in schoolchildren. Prolonged eczema, together with sports participation, further promotes the symptoms. The mechanisms of these novel findings warrant further investigation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

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    Hongyu Zhang

    2015-09-01

    Full Text Available Background/Aims: BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. Methods: Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB, we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. Results: We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP activity in MSCs as well as late osteogenic markers osteopontin (OPN, osteocalcin (OCN and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. Conclusion: Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhibition of PKA/CREB signaling may impair BMP9-induced osteogenic differentiation of MSCs, implying that activation of PKA/CREB signaling is required for BMP9 osteoinductive activity.

  9. Regulating effect of borosilicate bioglass extract on the osteoblast proliferation activity and osteogenesis signaling pathway function

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    Xiao-Hui He

    2017-11-01

    Full Text Available Objective: To study the regulating effect of borosilicate bioglass extract on the osteoblast proliferation activity and osteogenesis signaling pathway function. Methods: Osteoblasts MG-63 were cultured and divided into borosilicate group and control group that were treated with the culture medium containing borosilicate bioglass extract and the culture medium without extract respectively. After 24 h of treatment, the cell proliferation activity as well as the expression of proliferation activity markers, Wnt signaling pathway molecules and PI3K/ AKT signaling pathway molecules was measured. Results: After 24 h of treatment, MTT cell viability of borosilicate group was significantly higher than that of control group, and ALP, OC, OPN, COL-I, Runx2, Wnt1, Wnt3a, β-catenin, LRP5, LRP6, p-PI3K, p-AKT, Bcl-2 and BMP protein expression in cells were significantly higher than those of control group. Conclusion: Borosilicate bioglass extract can enhance the proliferation activity of osteoblasts by activating Wnt pathway and PI3K/AKT pathway.

  10. Aged refuse enhances anaerobic digestion of waste activated sludge.

    Science.gov (United States)

    Zhao, Jianwei; Gui, Lin; Wang, Qilin; Liu, Yiwen; Wang, Dongbo; Ni, Bing-Jie; Li, Xiaoming; Xu, Rui; Zeng, Guangming; Yang, Qi

    2017-10-15

    In this work, a low-cost alternative approach (i.e., adding aged refuse (AR) into waste activated sludge) to significantly enhance anaerobic digestion of sludge was reported. Experimental results showed that with the addition dosage of AR increasing from 0 to 400 mg/g dry sludge soluble chemical oxygen demand (COD) increased from 1150 to 5240 mg/L at the digestion time of 5 d, while the maximal production of volatile fatty acids (VFA) increased from 82.6 to 183.9 mg COD/g volatile suspended solids. Although further increase of AR addition decreased the concentrations of both soluble COD and VFA, their contents in these systems with AR addition at any concentration investigated were still higher than those in the blank, which resulted in higher methane yields in these systems. Mechanism studies revealed that pertinent addition of AR promoted solubilization, hydrolysis, and acidogenesis processes and did not affect methanogenesis significantly. It was found that varieties of enzymes and anaerobes in AR were primary reason for the enhancement of anaerobic digestion. Humic substances in AR benefited hydrolysis and acidogenesis but inhibited methanogenesis. The effect of heavy metals in AR on sludge anaerobic digestion was dosage dependent. Sludge anaerobic digestion was enhanced by appropriate amounts of heavy metals but inhibited by excessive amounts of heavy metals. The relative abundances of microorganisms responsible for sludge hydrolysis and acidogenesis were also observed to be improved in the system with AR addition, which was consistent with the performance of anaerobic digestion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Resonant enhancement of relativistic electron fluxes during geomagnetically active periods

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    I. Roth

    Full Text Available The strong increase in the flux of relativistic electrons during the recovery phase of magnetic storms and during other active periods is investigated with the help of Hamiltonian formalism and simulations of test electrons which interact with whistler waves. The intensity of the whistler waves is enhanced significantly due to injection of 10-100 keV electrons during the substorm. Electrons which drift in the gradient and curvature of the magnetic field generate the rising tones of VLF whistler chorus. The seed population of relativistic electrons which bounce along the inhomogeneous magnetic field, interacts resonantly with the whistler waves. Whistler wave propagating obliquely to the magnetic field can interact with energetic electrons through Landau, cyclotron, and higher harmonic resonant interactions when the Doppler-shifted wave frequency equals any (positive or negative integer multiple of the local relativistic gyrofrequency. Because the gyroradius of a relativistic electron may be the order of or greater than the perpendicular wavelength, numerous cyclotron, harmonics can contribute to the resonant interaction which breaks down the adiabatic invariant. A similar process diffuses the pitch angle leading to electron precipitation. The irreversible changes in the adiabatic invariant depend on the relative phase between the wave and the electron, and successive resonant interactions result in electrons undergoing a random walk in energy and pitch angle. This resonant process may contribute to the 10-100 fold increase of the relativistic electron flux in the outer radiation belt, and constitute an interesting relation between substorm-generated waves and enhancements in fluxes of relativistic electrons during geomagnetic storms and other active periods.

    Key words. Magnetospheric physics (energetic particles · trapped; plasma waves and instabilities; storms and substorms

  12. Enhanced capacitive properties of commercial activated carbon by re-activation in molten carbonates

    Science.gov (United States)

    Lu, Beihu; Xiao, Zuoan; Zhu, Hua; Xiao, Wei; Wu, Wenlong; Wang, Dihua

    2015-12-01

    Simple, affordable and green methods to improve capacitive properties of commercial activated carbon (AC) are intriguing since ACs possess a predominant role in the commercial supercapacitor market. Herein, we report a green reactivation of commercial ACs by soaking ACs in molten Na2CO3-K2CO3 (equal in mass ratios) at 850 °C combining the merits of both physical and chemical activation strategies. The mechanism of molten carbonate treatment and structure-capacitive activity correlations of the ACs are rationalized. Characterizations show that the molten carbonate treatment increases the electrical conductivity of AC without compromising its porosity and wettability of electrolytes. Electrochemical tests show the treated AC exhibited higher specific capacitance, enhanced high-rate capability and excellent cycle performance, promising its practical application in supercapacitors. The present study confirms that the molten carbonate reactivation is a green and effective method to enhance capacitive properties of ACs.

  13. Enhancing anaerobic digestion of poultry blood using activated carbon

    Directory of Open Access Journals (Sweden)

    Maria José Cuetos

    2017-05-01

    Full Text Available The potential of using anaerobic digestion for the treatment of poultry blood has been evaluated in batch assays at the laboratory scale and in a mesophilic semi-continuous reactor. The biodegradability test performed on residual poultry blood was carried out in spite of high inhibitory levels of acid intermediaries. The use of activated carbon as a way to prevent inhibitory conditions demonstrated the feasibility of attaining anaerobic digestion under extreme ammonium and acid conditions. Batch assays with higher carbon content presented higher methane production rates, although the difference in the final cumulative biogas production was not as sharp. The digestion of residual blood was also studied under semi-continuous operation using granular and powdered activated carbon. The average specific methane production was 216 ± 12 mL CH4/g VS. This result was obtained in spite of a strong volatile fatty acid (VFA accumulation, reaching values around 6 g/L, along with high ammonium concentrations (in the range of 6–8 g/L. The use of powdered activated carbon resulted in a better assimilation of C3-C5 acid forms, indicating that an enhancement in syntrophic metabolism may have taken place. Thermal analysis and scanning electron microscopy (SEM were applied as analytical tools for measuring the presence of organic material in the final digestate and evidencing modifications on the carbon surface. The addition of activated carbon for the digestion of residual blood highly improved the digestion process. The adsorption capacity of ammonium, the protection this carrier may offer by limiting mass transfer of toxic compounds, and its capacity to act as a conductive material may explain the successful digestion of residual blood as the sole substrate.

  14. Dental pulp stem cells from traumatically exposed pulps exhibited an enhanced osteogenic potential and weakened odontogenic capacity.

    Science.gov (United States)

    Wang, Yanping; Yan, Ming; Wang, Zhanwei; Wu, Jintao; Wang, Zilu; Zheng, Yangyu; Yu, Jinhua

    2013-11-01

    Traumatic pulp exposure can bring about some permanent damages to tooth tissues including dental pulps. This study was designed to evaluate the effects of traumatic pulp exposure on the osteo/odontogenic capacity of dental pulp stem cells (DPSCs). Rat incisors were artificially fractured and dental pulps were exposed to the oral environment for 48 h. Then, multi-colony-derived DPSCs from the injured pulps (iDPSCs) were isolated. Their osteo/odontogenic differentiation and the involvement of NF-κB pathway were subsequently investigated. iDPSCs presented a lower proliferative capacity than normal DPSCs (nDPSCs), as indicated by MTT and FCM assay. ALP levels in iDPSCs were significantly higher (Ppulp complex while all iDPSCs pellets formed the osteodentin-like tissues which were immunopositive for OCN. Mechanistically, iDPSCs expressed the higher levels of cytoplasmic phosphorylated IκBα/P65 and nuclear P65 than nDPSCs, indicating an active cellular NF-κB pathway in iDPSCs. After the inhibition of NF-κB pathway, the osteogenic potential in iDPSCs was significantly down-regulated while odontogenic differentiation was up-regulated, as indicated by the decreased Alp/Runx2/Ocn and uprised Dspp expression. Pulp exposure for 48 h decreased the odontogenic capacity and enhanced the osteogenic potential of DPSCs via the NF-κB signalling pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Resveratrol enhances antitumor activity of TRAIL in prostate cancer xenografts through activation of FOXO transcription factor.

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    Suthakar Ganapathy

    Full Text Available BACKGROUND: Resveratrol (3, 4', 5 tri-hydroxystilbene, a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining and inducing apoptosis (TUNEL staining. The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27(/KIP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells and markers of metastasis (MMP-2 and MMP-9. The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity. CONCLUSIONS/SIGNIFICANCE: These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.

  16. Active Transport Can Greatly Enhance Cdc20:Mad2 Formation

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    Bashar Ibrahim

    2014-10-01

    Full Text Available To guarantee genomic integrity and viability, the cell must ensure proper distribution of the replicated chromosomes among the two daughter cells in mitosis. The mitotic spindle assembly checkpoint (SAC is a central regulatory mechanism to achieve this goal. A dysfunction of this checkpoint may lead to aneuploidy and likely contributes to the development of cancer. Kinetochores of unattached or misaligned chromosomes are thought to generate a diffusible “wait-anaphase” signal, which is the basis for downstream events to inhibit the anaphase promoting complex/cyclosome (APC/C. The rate of Cdc20:C-Mad2 complex formation at the kinetochore is a key regulatory factor in the context of APC/C inhibition. Computer simulations of a quantitative SAC model show that the formation of Cdc20:C-Mad2 is too slow for checkpoint maintenance when cytosolic O-Mad2 has to encounter kinetochores by diffusion alone. Here, we show that an active transport of O-Mad2 towards the spindle mid-zone increases the efficiency of Mad2-activation. Our in-silico data indicate that this mechanism can greatly enhance the formation of Cdc20:Mad2 and furthermore gives an explanation on how the “wait-anaphase” signal can dissolve abruptly within a short time. Our results help to understand parts of the SAC mechanism that remain unclear.

  17. Uncoupling evolutionary changes in DNA sequence, transcription factor occupancy and enhancer activity.

    Science.gov (United States)

    Khoueiry, Pierre; Girardot, Charles; Ciglar, Lucia; Peng, Pei-Chen; Gustafson, E Hilary; Sinha, Saurabh; Furlong, Eileen Em

    2017-08-09

    Sequence variation within enhancers plays a major role in both evolution and disease, yet its functional impact on transcription factor (TF) occupancy and enhancer activity remains poorly understood. Here, we assayed the binding of five essential TFs over multiple stages of embryogenesis in two distant Drosophila species (with 1.4 substitutions per neutral site), identifying thousands of orthologous enhancers with conserved or diverged combinatorial occupancy. We used these binding signatures to dissect two properties of developmental enhancers: (1) potential TF cooperativity, using signatures of co-associations and co-divergence in TF occupancy. This revealed conserved combinatorial binding despite sequence divergence, suggesting protein-protein interactions sustain conserved collective occupancy. (2) Enhancer in-vivo activity, revealing orthologous enhancers with conserved activity despite divergence in TF occupancy. Taken together, we identify enhancers with diverged motifs yet conserved occupancy and others with diverged occupancy yet conserved activity, emphasising the need to functionally measure the effect of divergence on enhancer activity.

  18. Polyphosphate Kinase from Activated Sludge Performing Enhanced Biological Phosphorus Removal†

    Science.gov (United States)

    McMahon, Katherine D.; Dojka, Michael A.; Pace, Norman R.; Jenkins, David; Keasling, Jay D.

    2002-01-01

    A novel polyphosphate kinase (PPK) was retrieved from an uncultivated organism in activated sludge carrying out enhanced biological phosphorus removal (EBPR). Acetate-fed laboratory-scale sequencing batch reactors were used to maintain sludge with a high phosphorus content (approximately 11% of the biomass). PCR-based clone libraries of small subunit rRNA genes and fluorescent in situ hybridization (FISH) were used to verify that the sludge was enriched in Rhodocyclus-like β-Proteobacteria known to be associated with sludges carrying out EBPR. These organisms comprised approximately 80% of total bacteria in the sludge, as assessed by FISH. Degenerate PCR primers were designed to retrieve fragments of putative ppk genes from a pure culture of Rhodocyclus tenuis and from organisms in the sludge. Four novel ppk homologs were found in the sludge, and two of these (types I and II) shared a high degree of amino acid similarity with R. tenuis PPK (86 and 87% similarity, respectively). Dot blot analysis of total RNA extracted from sludge demonstrated that the Type I ppk mRNA was present, indicating that this gene is expressed during EBPR. Inverse PCR was used to obtain the full Type I sequence from sludge DNA, and a full-length PPK was cloned, overexpressed, and purified to near homogeneity. The purified PPK has a specific activity comparable to that of other PPKs, has a requirement for Mg2+, and does not appear to operate in reverse. PPK activity was found mainly in the particulate fraction of lysed sludge microorganisms. PMID:12324346

  19. Survivin S81A Enhanced TRAIL's Activity in Inducing Apoptosis

    Directory of Open Access Journals (Sweden)

    Ferry Sandra

    2010-12-01

    Full Text Available BACKGROUND: Survivin is rarely expressed in normal healthy adult tissues, however, it is upregulated in the majority of cancers. Survivin, which belongs to IAPs family, has been widely reported to protect cells from apoptosis by inhibiting caspases pathway. Survivin’s mitotic activity is modulated by many kinases, and its phosphor status can also influence its ability to inhibit apoptosis. There are several important survivin’s phosphorylation sites, such as S20 and T34. We have continued our investigation on other potential survivin’s phosphorylation sites that could be important site for regulating survivin’s cyto-protection. METHODS: By assuming that S81 could be a potential target to modify activity of survivin, wild-type survivin (Survivin, antisense survivin (Survivin-AS, mutated-survivin Thr34Ala (Survivin-T34A and mutated-survivin Ser81Ala (Survivin-S81A were constructed and inserted into pMSCV-IRES-GFP vector with cytomegalovirus (CMV promoter. Each retroviral product was produced in BOSC23 cells. LY294002 pretreatment and TRAIL treatment along with infection of retroviral products were performed in murine fibrosarcoma L929 cells. For analysis, flow cytometric apoptosis assay and western blot were performed. RESULTS: In our present study, survivin for providing cytoprotection was regulated by PI3K. The results showed that LY294002, an inhibitor of PI3K, effectively suppressed survivin-modulated cytoprotection in a TRAIL-induced apoptotic model. In addition, mutated survivin S81A showed marked suppression on survivin’s cytoprotection. Along with that, TRAIL’s apoptotic activity was enhanced for inducing apoptosis. CONCLUSIONS: We suggested that survivin could inhibit apoptosis through PI3K and S81A could be another potential target in order to inhibit Survivin-modulated cytoprotection as well as to sensitize efficacy of TRAIL or other related apoptotic inducers. KEYWORDS: apoptosis, survivin, TRAIL, S81A, L929, LY294002.

  20. Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

    National Research Council Canada - National Science Library

    Chen-Lin Hsieh; Teng Fei; Yiwen Chen; Tiantian Li; Yanfei Gao; Xiaodong Wang; Tong Sun; Christopher J. Sweeney; Gwo-Shu Mary Lee; Shaoyong Chen; Steven P. Balk; Xiaole Shirley Liu; Myles Brown; Philip W. Kantoff

    2014-01-01

    .... Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e...

  1. Health-enhancing physical activity among Saudi adults using the International Physical Activity Questionnaire (IPAQ).

    Science.gov (United States)

    Al-Hazzaa, Hazzaa M

    2007-01-01

    To describe the physical activity profile of Saudi adults living in Riyadh, using the International Physical Activity Questionnaire (IPAQ) short-version telephone format. Physical activity was assessed using the official Arabic short form of IPAQ, intended for use in telephone interview. The instrument asks for times spent in walking, moderate- and vigorous-intensity physical activity of at least 10 min duration. The sample consisted of 1616 Saudis, between 15 and 78 years of age, living in Riyadh. Participants were drawn from a list of names in the telephone book using a simple random method. Telephone interviews were administered during the spring of 2003 by trained male interviewers. The final sample size was 1064 Saudi males and females (response rate of 66%), with males comprising about 66% of the respondents. Over 43% of Saudis did not participate in any type of moderate-intensity physical activity lasting for at least 10 min. More than 72% of the sample did not engage in any type of vigorous-intensity physical activity lasting for at least 10 min. The proportion of Saudis who walked for 150 min or more per week was 33.3%. Females were engaged more in moderate physical activity than males, whereas males participated more in vigorous activity compared with females. Activity levels did not show significant relationships with education level or job hours per week. Based on the three activity categories established by IPAQ, 40.6% of Saudis were inactive, 34.3% were minimally active and 25.1% were physically active. Physical inactivity increased with advancing age. The data suggest that the prevalence of physical inactivity among Saudis adults is relatively high. Efforts are needed to encourage Saudis to be more physically active, with the goal of increasing the proportion of Saudis engaging in health-enhancing physical activity.

  2. Enhanced biological activities of gamma-irradiated persimmon leaf extract.

    Science.gov (United States)

    Cho, Byoung-Ok; Nchang Che, Denis; Yin, Hong-Hua; Jang, Seon-Il

    2017-05-16

    The aim of this study was to compare the anti-oxidative and anti-inflammatory activities of gamma-irradiated persimmon leaf extract (GPLE) with those of non-irradiated persimmon leaf extract (PLE). Ethanolic extract of persimmon leaf was exposed to gamma irradiation at a dose of 10 kGy. After gamma irradiation, the color of the extract changed from dark brown to light brown. The anti-oxidative and anti-inflammatory activities of GPLE and PLE were assessed from: total polyphenol and total flavonoid contents; 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay; 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and levels of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). The total polyphenol contents of GPLE and PLE were determined to be 224.44 ± 1.54 and 197.33 ± 5.81 mg gallic acid equivalents (GAE)/g, respectively, and the total flavonoid contents of GPLE and PLE were 206.27 ± 1.15 and 167.60 ± 2.00 mg quercetin equivalents (QUE)/g, respectively. The anti-oxidant activities of GPLE and PLE as measured by DPPH assays were 338.33 ± 30.19 μg/ml (IC50) and 388.68 ± 8.45 μg/ml (IC50), respectively, and those measured by ABTS assays were 510.49 ± 15.12 μg/ml (IC50) and 731.30 ± 10.63 μg/ml (IC50), respectively. IC50 is the inhibitor concentration that reduces the response by 50%. GPLE strongly inhibited the production of NO, PGE2 and IL-6 compared with PLE in lipopolysaccharide-stimulated RAW264.7 macrophages. Furthermore, GPLE significantly inhibited the production of TNF-α and IL-6 cytokines compared with PLE in phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated HMC-1 human mast cells. These results indicate that gamma irradiation of PLE can enhance its anti-oxidative and anti-inflammatory activities through elevation of the phenolic contents. Therefore, gamma-irradiated PLE has potential for use in the food and cosmetic

  3. Electroporation Enhances the Metabolic Activity of Lactobacillus plantarum 564

    Directory of Open Access Journals (Sweden)

    Branko Bugarski

    2013-01-01

    Full Text Available The exposure of bacterial cells to pulsed electric fields (PEF leads to the reversible formation of pores in the cell membrane if an applied energy is below the critical level. Therefore, the effect of electric field pulses with amplitudes below 14 kV/cm and the applied energy up to 12.2 J/cm3 on the growth of Lactobacillus plantarum 564 cells was investigated. After PEF treatments, the growth of lactobacilli in De Man-Rogosa-Sharpe broth at 37 °C was monitored by isothermal calorimetry, absorbance and plate counts. All the applied treatments resulted in a higher growth rate of PEF-treated cells during early and mid-log phase, especially bacterial samples treated with lower field intensities (1.3–5.5 J/cm3. The transport of ions and molecules through the cell membrane (which facilitates the growth of electroporated lactobacilli was particularly evident in the mid-exponential growth phase, where the doubling time was reduced more than 3 times after the exposure to electric pulses of 5.5 J/cm3. The heat production rate during the growth of electroporated cells was also higher, indicating the enhanced metabolic activity of PEF-treated cells. Moreover, the electroporated cells had a better acidification ability than the untreated ones. It can be summarized that the applied PEF treatments with an energy input of below 12 J/cm3 potentially induce reversible electroporation of the cell membrane, which has a positive impact on the growth and metabolic activity of the cells of lactobacilli.

  4. Reduction of Streptolysin O (SLO Pore-Forming Activity Enhances Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Peter A. Keyel

    2013-06-01

    Full Text Available Pore-forming toxins are utilized by bacterial and mammalian cells to exert pathogenic effects and induce cell lysis. In addition to rapid plasma membrane repair, macrophages respond to pore-forming toxins through activation of the NLRP3 inflammasome, leading to IL-1β secretion and pyroptosis. The structural determinants of pore-forming toxins required for NLRP3 activation remain unknown. Here, we demonstrate using streptolysin O (SLO that pore-formation controls IL-1β secretion and direct toxicity. An SLO mutant incapable of pore-formation did not promote direct killing, pyroptosis or IL-1β production. This indicated that pore formation is necessary for inflammasome activation. However, a partially active mutant (SLO N402C that was less toxic to macrophages than wild-type SLO, even at concentrations that directly lysed an equivalent number of red blood cells, enhanced IL-1β production but did not alter pyroptosis. This suggests that direct lysis may attenuate immune responses by preventing macrophages from successfully repairing their plasma membrane and elaborating more robust cytokine production. We suggest that mutagenesis of pore-forming toxins represents a strategy to enhance adjuvant activity.

  5. Enhanced activity of the Southern Taurids in 2005 and 2015

    Science.gov (United States)

    Olech, A.; Żołądek, P.; Wiśniewski, M.; Tymiński, Z.; Stolarz, M.; Bęben, M.; Dorosz, D.; Fajfer, T.; Fietkiewicz, K.; Gawroński, M.; Gozdalski, M.; Kałużny, M.; Krasnowski, M.; Krygiel, H.; Krzyżanowski, T.; Kwinta, M.; Łojek, T.; Maciejewski, M.; Miernicki, S.; Myszkiewicz, M.; Nowak, P.; Polak, K.; Polakowski, K.; Laskowski, J.; Szlagor, M.; Tissler, G.; Suchodolski, T.; Węgrzyk, W.; Woźniak, P.; Zaręba, P.

    2017-08-01

    In this paper, we present an analysis of Polish Fireball Network (PFN) observations of enhanced activity of the Southern Taurid meteor shower in 2005 and 2015. In 2005, between October 20 and November 10, seven stations of the PFN determined 107 accurate orbits, with 37 of them belonging to the Southern Taurid shower. In the same period of 2015, 25 stations of the PFN recorded 719 accurate orbits with 215 orbits of the Southern Taurids. Both maxima were rich in fireballs, which accounted for 17 per cent of all observed Taurids. The whole sample of Taurid fireballs is uniform in the sense of starting and terminal heights of the trajectory. However, a clear decreasing trend in geocentric velocity with increasing solar longitude was observed. The orbital parameters of observed Southern Taurids were compared to orbital elements of near-Earth objects (NEOs) from the NEODyS-2 data base. Using the Drummond criterion D΄ with a threshold as low as 0.06, we found over 100 fireballs strikingly similar to the orbit of asteroid 2015 TX24. Several dozens of Southern Taurids have orbits similar to three other asteroids: 2005 TF50, 2005 UR and 2010 TU149. All mentioned NEOs have orbital periods very close to the 7 : 2 resonance with Jupiter's orbit. This confirms the theory of a resonant meteoroid swarm within the Taurid complex, which predicts that, in specific years, the Earth is hit by a greater number of meteoroids capable of producing fireballs.

  6. Eugenol nanocapsule for enhanced therapeutic activity against periodontal infections.

    Science.gov (United States)

    Pramod, Kannissery; Aji Alex, M R; Singh, Manisha; Dang, Shweta; Ansari, Shahid H; Ali, Javed

    2016-01-01

    Eugenol is a godsend to dental care due to its analgesic, local anesthetic, and anti-inflammatory and antibacterial effects. The aim of the present research work was to prepare, characterize and evaluate eugenol-loaded nanocapsules (NCs) against periodontal infections. Eugenol-loaded polycaprolactone (PCL) NCs were prepared by solvent displacement method. The nanometric size of the prepared NCs was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The in vitro drug release was found to follow a biphasic pattern and followed Michaelis-Menten like model. The percentage cell viability values near to 100 in the cell viability assay indicated that the NCs are not cytotoxic. In the in vivo studies, the eugenol NC group displayed significant difference in the continuity of epithelium of the interdental papilla in comparison to the untreated, pure eugenol and placebo groups. The in vivo performance of the eugenol-loaded NCs using ligature-induced periodontitis model in rats indicated that eugenol-loaded NCs could prevent septal bone resorption in periodontitis. On the basis of our research findings it could be concluded that eugenol-loaded PCL NCs could serve as a novel colloidal drug delivery system for enhanced therapeutic activity of eugenol in the treatment of periodontal infections.

  7. Penetrating cations enhance uncoupling activity of anionic protonophores in mitochondria.

    Directory of Open Access Journals (Sweden)

    Yuri N Antonenko

    Full Text Available Protonophorous uncouplers causing a partial decrease in mitochondrial membrane potential are promising candidates for therapeutic applications. Here we showed that hydrophobic penetrating cations specifically targeted to mitochondria in a membrane potential-driven fashion increased proton-translocating activity of the anionic uncouplers 2,4-dinitrophenol (DNP and carbonylcyanide-p-trifluorophenylhydrazone (FCCP. In planar bilayer lipid membranes (BLM separating two compartments with different pH values, DNP-mediated diffusion potential of H(+ ions was enhanced in the presence of dodecyltriphenylphosphonium cation (C12TPP. The mitochondria-targeted penetrating cations strongly increased DNP- and carbonylcyanide m-chlorophenylhydrazone (CCCP-mediated steady-state current through BLM when a transmembrane electrical potential difference was applied. Carboxyfluorescein efflux from liposomes initiated by the plastoquinone-containing penetrating cation SkQ1 was inhibited by both DNP and FCCP. Formation of complexes between the cation and CCCP was observed spectophotometrically. In contrast to the less hydrophobic tetraphenylphosphonium cation (TPP, SkQ1 and C12TPP promoted the uncoupling action of DNP and FCCP on isolated mitochondria. C12TPP and FCCP exhibited a synergistic effect decreasing the membrane potential of mitochondria in yeast cells. The stimulating action of penetrating cations on the protonophore-mediated uncoupling is assumed to be useful for medical applications of low (non-toxic concentrations of protonophores.

  8. Doxycycline exerted neuroprotective activity by enhancing the activation of neuropeptide GPCR PAC1.

    Science.gov (United States)

    Yu, Rongjie; Zheng, Lijun; Cui, Yue; Zhang, Huahua; Ye, Heng

    2016-04-01

    Doxycycline has significant neuroprotective effect with anti-inflammatory and anti-apoptotic activity. We found for the first time that doxycycline specially promoted the proliferation of Chinese hamster ovary (CHO) cells with high expression of neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) preferring G protein-coupled receptor (GPCR), PACAP receptor 1(PAC1) and induced the internalization of PAC1 tagged with yellow fluorescent protein (YFP) indicating doxycycline interacted with PAC1. The homology modeling of PAC1 and molecular docking of doxycycline with PAC1 showed the theoretical binding of doxycycline to PAC1 at the site where PACAP(30-37) recognized. The competition binding assay and PAC1 site-specific mutation of Asp116, which formed two hydrogen bonds with Dox, confirmed the binding of doxycycline to PAC1 imitating PACAP(30-37). Doxycycline (100 ng/mL) significantly promoted the proliferative activities of vasoactive intestinal polypeptide (VIP) and oligopeptide HSDGIF responsible for the activation of PAC1 in PAC1-CHO cells, indicating that doxycycline facilitated the binding and the activation of PAC1 imitating PACAP(28-38). In Neuro2a cells with endogenous expression of PAC1 and its ligands, doxycycline not only promoted the proliferation of Neuro2a cells but also protected the cells from scopolamine induced apoptosis, which was inhibited by cAMP-PKA signal pathway inhibitor H-89, PAC1 shRNA or PACAP antagonist PACAP(6-38). The in vivo study showed long-term treatment with doxycycline (100ug/kg) had significant effect against scopolamine induced amnesia, and the synergetic anti-apoptotic, anti-oxidative and neuroprotective effect of doxycycline with VIP was more efficient than doxycycline alone or VIP alone, indicating doxycycline enhanced the activation of PAC1 in vivo effectively. Furthermore, doxycycline analogue minocycline also had similar theoretically binding site on PAC1 to doxycycline and displayed corresponding

  9. Design of New Antibacterial Enhancers Based on AcrB’s Structure and the Evaluation of Their Antibacterial Enhancement Activity

    Directory of Open Access Journals (Sweden)

    Yi Song

    2016-11-01

    Full Text Available Previously, artesunate (AS and dihydroartemisinine 7 (DHA7 were found to have antibacterial enhancement activity against Escherichia coli via inhibition of the efflux pump AcrB. However, they were only effective against E. coli standard strains. This study aimed to develop effective antibacterial enhancers based on the previous work. Our results demonstrate that 86 new antibacterial enhancers were designed via 3D-SAR and molecular docking. Among them, DHA27 had the best antibacterial enhancement activity. It could potentiate the antibacterial effects of ampicillin against not only E. coli standard strain but also clinical strains, and of β-lactam antibiotics, not non-β-lactamantibiotics. DHA27 could increase the accumulation of daunomycin and nile red within E. coli ATCC 35218, but did not increase the bacterial membrane permeability. DHA27 reduced acrB’s mRNA expression of E. coli ATCC 35218 in a dose-dependent manner, and its antibacterial enhancement activity is related to the degree of acrB mRNA expression in E. coli clinical strains. The polypeptides from AcrB were obtained via molecular docking assay; the pre-incubated polypeptides could inhibit the activity of DHA27. Importantly, DHA27 had no cytotoxicity on cell proliferation. In conclusion, among newly designed antibacterial enhancers, DHA27 had favorable physical and pharmacological properties with no significant cytotoxicity at effective concentrations, and might serve as a potential efflux pump inhibitor in the future.

  10. Design of New Antibacterial Enhancers Based on AcrB's Structure and the Evaluation of Their Antibacterial Enhancement Activity.

    Science.gov (United States)

    Song, Yi; Qin, Rongxin; Pan, Xichun; Ouyang, Qin; Liu, Tianyu; Zhai, Zhaoxia; Chen, Yingchun; Li, Bin; Zhou, Hong

    2016-11-18

    Previously, artesunate (AS) and dihydroartemisinine 7 (DHA7) were found to have antibacterial enhancement activity against Escherichia coli via inhibition of the efflux pump AcrB. However, they were only effective against E. coli standard strains. This study aimed to develop effective antibacterial enhancers based on the previous work. Our results demonstrate that 86 new antibacterial enhancers were designed via 3D-SAR and molecular docking. Among them, DHA27 had the best antibacterial enhancement activity. It could potentiate the antibacterial effects of ampicillin against not only E. coli standard strain but also clinical strains, and of β-lactam antibiotics, not non-β-lactamantibiotics. DHA27 could increase the accumulation of daunomycin and nile red within E. coli ATCC 35218, but did not increase the bacterial membrane permeability. DHA27 reduced acrB's mRNA expression of E. coli ATCC 35218 in a dose-dependent manner, and its antibacterial enhancement activity is related to the degree of acrB mRNA expression in E. coli clinical strains. The polypeptides from AcrB were obtained via molecular docking assay; the pre-incubated polypeptides could inhibit the activity of DHA27. Importantly, DHA27 had no cytotoxicity on cell proliferation. In conclusion, among newly designed antibacterial enhancers, DHA27 had favorable physical and pharmacological properties with no significant cytotoxicity at effective concentrations, and might serve as a potential efflux pump inhibitor in the future.

  11. Osteogenic activity and antibacterial effect of zinc oxide/carboxylated graphene oxide nanocomposites: Preparation and in vitro evaluation.

    Science.gov (United States)

    Chen, Junyu; Zhang, Xin; Cai, He; Chen, Zhiqiang; Wang, Tong; Jia, Lingling; Wang, Jian; Wan, Qianbing; Pei, Xibo

    2016-11-01

    The aim of this study was to prepare nanocomposites of carboxylated graphene oxide (GO-COOH) sheets decorated with zinc oxide (ZnO) nanoparticles (NPs) and investigate their advantages in the field of bone tissue engineering. First, ZnO/GO-COOH nanocomposites were synthesized by facile reactions, including the carboxylation of graphene oxide (GO) and the nucleation of ZnO on GO-COOH sheets. The synthesized ZnO/GO-COOH nanocomposites were then characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectra, and transmission electron microscopy (TEM). The biocompatibility, osteogenic activity and antibacterial effect of ZnO/GO-COOH nanocomposites were further investigated. In the nanocomposites, ZnO nanoparticles with a size of approximately 12nm were uniformly decorated on GO-COOH sheets. Compared with GO-COOH and the control group, ZnO/GO-COOH nanocomposites significantly enhanced ALP activity, osteocalcin production and extracellular matrix mineralization as well as up-regulated osteogenic-related genes (ALP, OCN, and Runx2) in MG63 osteoblast-like cells. Moreover, ZnO/GO-COOH nanocomposites had an antibacterial effect against Streptococcus mutans. These results indicated that ZnO/GO-COOH nanocomposites exhibited both osteogenic activity and antibacterial effect and had great potential for designing new biomaterials in the field of bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Compositions comprising a polypeptide having cellulolytic enhancing activity and an organic compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew; Johansen, Katja Salomon

    2017-05-30

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and an organic compound. The present invention also relates to methods of using the compositions.

  13. Compositions comprising a polypeptide having cellulolytic enhancing activity and a quinone compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2017-09-05

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a quinone compound. The present invention also relates to methods of using the compositions.

  14. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicyclic compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-10-04

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

  15. Compositions comprising a polypeptide having cellulolytic enhancing activity and a dioxy compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Matthew; Xu, Feng; Quinlan, Jason

    2016-07-19

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a dioxy compound. The present invention also relates to methods of using the compositions.

  16. Compositions comprising a polypeptide having cellulolytic enhancing activity and a quinone compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-03-01

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a quinone compound. The present invention also relates to methods of using the compositions.

  17. Compositions comprising a polypeptide having cellulolytic enhancing activity and a heterocyclic compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2016-08-02

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a heterocyclic compound. The present invention also relates to methods of using the compositions.

  18. Enhancing Physical Education with a Supplemental Physical Activity Program

    Science.gov (United States)

    Adkins, Megan; Bice, Matthew R.; Heelan, Kate; Ball, James

    2017-01-01

    For decades, schools have played a pivotal role in providing physical activity opportunities to children. For many students, school-time physical activity serves as the primary source of activity, via activity clubs, classroom physical activity breaks, and family health awareness nights. The purpose of this article is to describe how three schools…

  19. An overview of skin penetration enhancers: penetration enhancing activity, skin irritation potential and mechanism of action

    Directory of Open Access Journals (Sweden)

    Sarunyoo Songkro

    2009-08-01

    Full Text Available Transdermal drug delivery has attracted considerable attention over the past 2-3 decades in regard of its many potentialadvantages. However, the role of the skin as a protective barrier renders skin absorption of most drugs problematic. Therefore,skin penetration enhancers are frequently used in the field of transdermal drug delivery in order to reversibly reduce thebarrier function of the stratum corneum, the outermost layer of the skin. To date, a wide range of chemical compounds havebeen shown to enhance the skin penetration of therapeutic drugs. This review presents a critical account of the most commonlyused chemical penetration enhancers (fatty acids and surfactants, and some newer classes of chemical enhancers (terpenes,polymers, monoolein, oxazolidinones, with emphasis on their efficacy, mechanism of action, and skin irritation potential. Thisreview also discusses the traditional and more recently developed methods for the screening and evaluation of chemical penetration enhancers, and addresses the continuing problems in the rational selection of a chemical penetration enhancer for a specific drug to be delivered via the transdermal route.

  20. Enhancement of human natural cytotoxicity by Plasmodium falciparum antigen activated lymphocytes

    DEFF Research Database (Denmark)

    Theander, T G; Pedersen, B K; Bygbjerg, I C

    1987-01-01

    stimulation enhanced the cytotoxic activity and induced strong proliferative responses in all MNC preparations. The role of NK cells in the protection against malaria is unknown, but they play a role in the protection against virus infection and in the immune surveillance against cancer. Our findings indicate...... cell (NK cell) sensitive cell line, K562, were measured. It was found that SPag stimulation enhanced cytotoxic activity of MNC from donors whose lymphocytes exhibited a strong proliferative response to the antigen. MNC with low proliferative responsiveness showed increased cytotoxic activity if the MNC...... that malaria antigens either directly or through the activation of immunoregulatory cells enhance the NK cell activity....

  1. Electrochemical synthesis of three-dimensional porous reduced graphene oxide film: Preparation and in vitro osteogenic activity evaluation.

    Science.gov (United States)

    Tian, Zizhu; Huang, Lixun; Pei, Xibo; Chen, Junyu; Wang, Tong; Yang, Tao; Qin, Han; Sui, Lei; Wang, Jian

    2017-07-01

    In this study, three-dimensional reduced graphene oxide (3D-rGO) porous films were fabricated using a two-step electrochemical method, including an electrochemical deposition process for the self-assembly of GO and an electrochemical bubbling-based transfer. The morphology, physical properties, and phase composition of the 3D-rGO films were characterized, and the cellular bioactivities were evaluated using pre-osteoblasts (MC3T3-E1 cells). The attachment, proliferation and differentiation of the MC3T3-E1 cells on the 3D-rGO films was analyzed by scanning electron microscopy (SEM), Cell Counting Kit-8 (CCK-8) assays and live/dead cell staining, and alkaline phosphatase (ALP) activity assays, respectively. The expression of osteogenic-related genes in MC3T3-E1 cells was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the 3D-rGO films supported cell viability and proliferation, as well as significantly enhanced ALP activity and osteogenic-related genes (ALP, OPN, Runx2) expressions. Our findings indicate the promising potential of the 3D-rGO porous films for bone tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Educating Students for a Lifetime of Physical Activity: Enhancing Mindfulness, Motivation, and Meaning

    Science.gov (United States)

    Ennis, Catherine D.

    2017-01-01

    For many years, pedagogical scholars and physical education (PE) teachers have worked to enhance effective teaching and learning environments. Yet for some children, youth, and young adults, many of the benefits associated with a physically active lifestyle remain elusive. Enhancing programming and performance to meet physical activity goals may…

  3. Osteogenic activity and antibacterial effect of porous titanium modified with metal-organic framework films.

    Science.gov (United States)

    Chen, Junyu; Zhang, Xin; Huang, Chao; Cai, He; Hu, Shanshan; Wan, Qianbing; Pei, Xibo; Wang, Jian

    2017-03-01

    As a new class of crystalline nanoporous materials, metal-organic frameworks (MOFs) have recently been used for biomedical applications due to their large surface area, high porosity, and theoretically infinite structures. To improve the biological performance of titanium, MOF films were applied to surface modification of titanium. Zn-based MOF films composed of zeolitic imidazolate framework-8 (ZIF-8) crystals with nanoscale and microscale sizes (nanoZIF-8 and microZIF-8) were prepared on porous titanium surfaces by hydrothermal and solvothermal methods, respectively. The ZIF-8 films were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The nanoZIF-8 film exhibited good biocompatibility, whereas the microZIF-8 film showed obvious cytotoxicity to MG63 cells. Compared to pure titanium and alkali- and heat-treated porous titanium, the nanoZIF-8 film not only enhanced alkaline phosphatase (ALP) activity, extracellular matrix mineralization, and expression of osteogenic genes (ALP, Runx2) in MG63 cells but also inhibited the growth of Streptococcus mutans. These results indicate that MOF films or coatings may be promising candidates for bone tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 834-846, 2017. © 2016 Wiley Periodicals, Inc.

  4. Food constituents enhance urease activity in Healicobacter pylori.

    OpenAIRE

    Mizote, Tomoko; Inatsu, Sakiko; Ehara, Keiko

    2005-01-01

    Urease activity of Helicobacter pylori recovered from the stomach of H. pylori-infected Mongolian gerbils was affected by the diet used after infection. The effect of dietary components on urease activity was investigated by growth of H. pylori in…

  5. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Charlotte Proudhon

    2016-06-01

    Full Text Available V(DJ recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control.

  6. Enhanced activation of periodate by iodine-doped granular activated carbon for organic contaminant degradation.

    Science.gov (United States)

    Li, Xiaowan; Liu, Xitao; Lin, Chunye; Qi, Chengdu; Zhang, Huijuan; Ma, Jun

    2017-08-01

    In this study, iodine-doped granular activated carbon (I-GAC) was prepared and subsequently applied to activate periodate (IO4(-)) to degrade organic contaminants at ambient temperature. The physicochemical properties of GAC and I-GAC were examined using scanning electron microscopy, N2 adsorption/desorption, Raman spectroscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. No significant difference was observed between the two except for the existence of triiodide (I3(-)) and pentaiodide (I5(-)) on I-GAC. The catalytic activity of I-GAC towards IO4(-) was evaluated by the degradation of acid orange 7 (AO7), and superior catalytic performance was achieved compared with GAC. The effects of some influential parameters (preparation conditions, initial solution pH, and coexisting anions) on the catalytic ability were also investigated. Based on radical scavenging experiments, it appeared that IO3 was the predominant reactive species in the I-GAC/IO4(-) system. The mechanism underlying the enhanced catalytic performance of I-GAC could be explained by the introduction of negatively charged I3(-) and I5(-) into I-GAC, which induced positive charge density on the surface of I-GAC. This accelerated the interaction between I-GAC and IO4(-), and subsequently mediated the increasing generation of iodyl radicals (IO3). Furthermore, a possible degradation pathway of AO7 was proposed according to the intermediate products identified by gas chromatography-mass spectrometry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. An atlas of active enhancers across human cell types and tissues

    DEFF Research Database (Denmark)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene

    2014-01-01

    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples......, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which...... is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility...

  8. Resonance surface enhanced Raman optical activity of myoglobin as a result of optimized resonance surface enhanced Raman scattering conditions

    DEFF Research Database (Denmark)

    Abdali, Salim; Johannessen, Christian; Nygaard, Jesper

    2007-01-01

    Using Surface enhanced ROA (SEROA), novel results are achieved by combining Raman Optical Activity (ROA) and resonance Surface Enhanced Raman Scattering (SERRS), applied on myoglobin. The novelty of this work is ascribed the first time reporting on chiral results of a study performed on a protein...... has shown that the SERS effect behaves consequently, depending on the concentration ratio of each component, i.e., myoglobin, Ag colloids and NaCl. Accordingly, it is shown here that SERS intensity has its maximum at certain concentration of these components, whereas below or above this value...

  9. Variation of antioxidative activity and growth enhancement of Brassicaceae induced by low-pressure oxygen plasma

    Science.gov (United States)

    Ono, Reoto; Hayashi, Nobuya

    2015-06-01

    The mechanism of growth enhancement induced by active oxygen species generated in an oxygen plasma is investigated. The plant growth enhancement induced by the active oxygen species would relate to an antioxidative activity, which is one of the biological responses. The amount of generated active oxygen species is varied by the oxygen gas pressure in a low-pressure RF glow discharge plasma. The antioxidative activity of sprouts of Brassicaceae induced by the oxygen plasma is maximized at pressures between 30 and 40 Pa, whereas the antioxidative activity becomes small at around 60 and 80 Pa. The pressure dependence of the antioxidative activity of sprout stems is opposite to that of the stem length of the sprouts. The growth enhancement would be induced by the increase in the concentration of active oxygen species in plants owing to the decrease in the amount of antioxidative substances.

  10. Short Communication : Enhancing the Quality and Activity of ...

    African Journals Online (AJOL)

    Effects of application of benzoic acid, sodium benzoate and sodium metabisulfite, prior to sun drying of papaya latex, on enzymic activity, colour appearance and smell of the crude papain produced were investigated. The preservatives improved appearance/colour, smell and enzymic activity with respect to control sample ...

  11. Story Based Activities Enhance Literacy Skills in Preschool Children

    Science.gov (United States)

    Yazici, Elçin; Bolay, Hayrunnisa

    2017-01-01

    We investigated the impact of story-based activities on literacy skills in pre-school children. The efficacy of story-based activities program were tested by literacy skills survey test. Results showed that, the scores of overall literacy skills and all subsets skills in the study group (n = 45) were statistically significantly higher than the…

  12. Intense synaptic activity enhances temporal resolution in spinal motoneurons

    DEFF Research Database (Denmark)

    Berg, Rune W; Ditlevsen, Susanne; Hounsgaard, Jørn Dybkjær

    2008-01-01

    , agility in motor systems has received little attention. Here we analyze how intense synaptic activity affects integration time in spinal motoneurons during functional motor activity and report a 10-fold decrease. As a result, action potentials can only be predicted from the membrane potential within 10 ms...

  13. Low dose radiation enhances the Locomotor activity of D. melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Ki Moon; Lee, Buyng Sub; Nam Seon Young; Kim, Ji Young; Yang, Kwang Hee; Choi, Tae In; Kim, Cha Soon [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Gyeongju (Korea, Republic of)

    2013-04-15

    Mild stresses at low level including radiation can induce the beneficial effects in many vertebrate and invertebrate species. However, a large amount of studies in radiation biology have focused on the detrimental effects of high dose radiation (HDR) such as the increased incidence of cancers and developmental diseases. Low dose radiation (LDR) induces biologically favorable effects in diverse fields, for example, cancer development, genomic instability, immune response, and longevity. Our previous data indicated that LDR promotes cells proliferation of which degree is not much but significant, and microarray data explained that LDR irradiated fruit flies showing the augmented immunity significantly changed the program for gene expression of many genes in Gene Ontology (GO) categories related to metabolic process. Metabolic process in development one of major contributors in organism growth, interbreeding, motility, and aging. Therefore, it is valuable to examine whether LDR change the physiological parameters related to metabolism, and how LDR regulates the metabolism in D. melanogaster. In this study, to investigate that LDR influences change of the metabolism, a representative parameter, locomotor activity. In addition, the activation of several cellular signal molecules was determined to investigate the specific molecular mechanism of LDR effects on the metabolism. We explored whether ionizing radiation affects the motility activity. We performed the RING assays to evaluate the locomotor activity, a representative parameter presenting motility of fruit flies. HDR dramatically decreased the motor activity of irradiated flies. Surprisingly, the irradiated flies at low dose radiation in both acute and chronic showed the significantly increased locomotor activity, compared to non-irradiated flies. Irradiation would induce change of the several signal pathways for flies to respond to it. The activation of some proteins involved in the cells proliferation and stress

  14. Sustainable Regeneration of Nanoparticle Enhanced Activated Carbon in Water

    Science.gov (United States)

    The regeneration and reuse of exhausted granular activated carbon (GAC) is an appropriate method for lowering operational and environmental costs. Advanced oxidation is a promising environmental friendly technique for GAC regeneration. The main objective of this research was to ...

  15. Enhanced biocidal activity and optical properties of zinc oxide nanoneedles

    Science.gov (United States)

    Ramani, Meghana; Ponnusamy, S.; Muthamizhchelvan, C.

    2012-06-01

    Zinc oxide nanoneedles were successfully synthesized by simple wet chemical method. X-ray diffraction studies reveal the formation of wurtzite-type of ZnO. Optical studies indicate the presence of defects in the form of oxygen vacancies and zinc interstitials. As an application study, this sample was tested for its antibacterial activity. These nanoneedles were found to exhibit excellent biocidal activity against both gram positive and gram negative bacteria.

  16. Enhanced Photocatalytic Activity of Vacuum activated TiO2 Induced by Oxygen Vacancies.

    Science.gov (United States)

    Dong, Guoyan; Wang, Xin; Chen, Zhiwu; Lu, Zhenya

    2017-12-18

    TiO2 (Degussa P25) photocatalysts harboring an abundant oxygen vacancies (vacuum P25) were manufactured using a simple and economic vacuum deoxidation process. Control experiments showed that temperature and time of vacuum deoxidation had a significant effect on vacuum P25 photocatalytic activity. After 240 min of visible light illumination, the optimal vacuum P25 photocatalysts (vacuum deoxidation treated at 330°C for 3h) reaches as high as 94% and 88% of photodegradation efficiency for Rhodamine B (RhB) and tetracycline respectively, which are around 4.5 and 4.9 times as that of pristine P25. The XPS, PL and EPR analyses indicated that the oxygen vacancies were produced in the vacuum P25 during the vacuum deoxidation process. The oxygen vacancies states can produce vacancy energy level located below the conduction band minimum, which resulting in the band gap narrowing, thus extending the photoresponse wavelength range of vacuum P25. The positron annihilation analysis indicated that the concentrations ratio of bulk and surface oxygen vacancies could be adjusted by changing the vacuum deoxidation temperature and time. Decreasing the ratio of bulk and surface oxygen vacancies was shown to improve photo-generated electron-hole pairs separation efficiency, which leads to an obvious enhancement of the visible photocatalytic activities of vacuum P25. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Pyrrolidone Modifying Gold Nanocatalysts for Enhanced Catalytic Activities in Aerobic Oxidation of Alcohols and Carbon Monoxide

    Directory of Open Access Journals (Sweden)

    Yingji Song

    2017-01-01

    Full Text Available Enhancing the catalytic activity of supported metal nanoparticle is a great demand but extremely challenging to make. We reported a simple strategy for enhancing the activities by employing the polyvinylpyrrolidone (PVP additive, where a series of supported Au nanoparticle catalysts including Au/C, Au/BN, Au/TiO2, and Au/SBA-15 exhibited significantly higher activities in the oxidation of various alcohols and carbon monoxide by molecular oxygen after adding PVP to the reaction system. The XPS study indicates that PVP could electronically interact with Au to form high active Au sites for molecular oxygen, thus causing improved activities for the various oxidation reactions.

  18. The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Onuma, Hirohisa; Inukai, Kouichi, E-mail: kinukai@ks.kyorin-u.ac.jp; Kitahara, Atsuko; Moriya, Rie; Nishida, Susumu; Tanaka, Toshiaki; Katsuta, Hidenori; Takahashi, Kazuto; Sumitani, Yoshikazu; Hosaka, Toshio; Ishida, Hitoshi

    2014-08-22

    Highlights: • PPARγ activation was involved in the GLP-1-mediated anti-inflammatory action. • Exendin-4 enhanced endogenous PPARγ transcriptional activity in HUVECs. • H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement. • The anti-inflammatory effects of GLP-1 may be explained by PPARγ activation. - Abstract: Recent studies have suggested glucagon-like peptide-1 (GLP-1) signaling to exert anti-inflammatory effects on endothelial cells, although the precise underlying mechanism remains to be elucidated. In the present study, we investigated whether PPARγ activation is involved in the GLP-1-mediated anti-inflammatory action on endothelial cells. When we treated HUVEC cells with 0.2 ng/ml exendin-4, a GLP-1 receptor agonist, endogenous PPARγ transcriptional activity was significantly elevated, by approximately 20%, as compared with control cells. The maximum PPARγ activity enhancing effect of exendin-4 was observed 12 h after the initiation of incubation with exendin-4. As H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement, the signaling downstream from GLP-1 cross-talk must have been involved in PPARγ activation. In conclusion, our results suggest that GLP-1 has the potential to induce PPARγ activity, partially explaining the anti-inflammatory effects of GLP-1 on endothelial cells. Cross-talk between GLP-1 signaling and PPARγ activation would have major impacts on treatments for patients at high risk for cardiovascular disease.

  19. Enhanced activities of organically bound tritium in biota samples.

    Science.gov (United States)

    Svetlik, I; Fejgl, M; Malátová, I; Tomaskova, L

    2014-11-01

    A pilot study aimed on possible occurrence of elevated activity of non-exchangable organically bound tritium (NE-OBT) in biota was performed. The first results showed a significant surplus of NE-OBT activity in biota of the valley of Mohelno reservoir and Jihlava river. The liquid releases of HTO from the nuclear power plant Dukovany is the source of tritium in this area. This area can be a source of various types of natural samples for future studies of tritium pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Glycerol enhances fungal germination at the water-activity limit for life

    NARCIS (Netherlands)

    Stevenson, Andrew; Hamill, Philip G; Medina, Ángel; Kminek, Gerhard; Rummel, John D; Dijksterhuis, Jan; Timson, David J; Magan, Naresh; Leong, Su-Lin L; Hallsworth, John E

    2016-01-01

    For the most-extreme fungal xerophiles, metabolic activity and cell division typically halts between 0.700 and 0.640 water activity (approximately 70.0-64.0% relative humidity). Here, we investigate whether glycerol can enhance xerophile germination under acute water-activity regimes, using an

  1. Glycerol enhances fungal germination at the water-activity limit for life

    NARCIS (Netherlands)

    Stevenson, Andrew; Hamill, Philip G; Medina, Ángel; Kminek, Gerhard; Rummel, John D; Dijksterhuis, Jan; Timson, David J; Magan, Naresh; Leong, Su-Lin L; Hallsworth, John E

    2017-01-01

    For the most-extreme fungal xerophiles, metabolic activity and cell division typically halts between 0.700 and 0.640 water activity (approximately 70.0-64.0% relative humidity). Here, we investigate whether glycerol can enhance xerophile germination under acute water-activity regimes, using an

  2. THE ENHANCEMENT OF THE PHYSICAL ABSORPTION OF GASES IN AQUEOUS ACTIVATED CARBON SLURRIES

    NARCIS (Netherlands)

    TINGE, JT; DRINKENBURG, AAH

    The enhancement of the gas-liquid mass transfer rates in aqueous slurries containing small activated carbon particles was studied in a semi-batchwise operated stirred cell absorber with a plane interface. The maximum observed enhancement factors for absorption of propane, ethene and hydrogen in the

  3. Slow-light enhancement of spontaneous emission in active photonic crystal waveguides

    DEFF Research Database (Denmark)

    Ek, Sara; Chen, Yaohui; Semenova, Elizaveta

    2012-01-01

    Photonic crystal defect waveguides with embedded active layers containing single or multiple quantum wells or quantum dots have been fabricated. Spontaneous emission spectra are enhanced close to the bandedge, consistently with the enhancement of gain by slow light effects. These are promising re...... results for future compact devices for terabit/s communication, such as miniaturised semiconductor optical amplifiers and mode-locked lasers....

  4. Orphan CpG islands define a novel class of highly active enhancers.

    Science.gov (United States)

    Bell, Joshua S K; Vertino, Paula M

    2017-06-03

    CpG islands (CGI) are critical genomic regulatory elements that support transcriptional initiation and are associated with the promoters of most human genes. CGI are distinguished from the bulk genome by their high CpG density, lack of DNA methylation, and euchromatic features. While CGI are canonically known as strong promoters, thousands of 'orphan' CGI lie far from any known transcript, leaving their function an open question. We undertook a comprehensive analysis of the epigenetic state of orphan CGI across over 100 cell types. Here we show that most orphan CGI display the chromatin features of active enhancers (H3K4me1, H3K27Ac) in at least one cell type. Relative to classical enhancers, these enhancer CGI (ECGI) are stronger, as gauged by chromatin state and in functional assays, are more broadly expressed, and are more highly conserved. Likewise, ECGI engage in more genomic contacts and are enriched for transcription factor binding relative to classical enhancers. In human cancers, these epigenetic differences between ECGI vs. classical enhancers manifest in distinct alterations in DNA methylation. Thus, ECGI define a class of highly active enhancers, strengthened by the broad transcriptional activity, CpG density, hypomethylation, and chromatin features they share with promoter CGI. In addition to indicating a role for thousands of orphan CGI, these findings suggests that enhancer activity may be an intrinsic function of CGI in general and provides new insights into the evolution of enhancers and their epigenetic regulation during development and tumorigenesis.

  5. 78 FR 47676 - Agency Information Collection Activities; Comment Request; Credit Enhancement for Charter School...

    Science.gov (United States)

    2013-08-06

    ... Agency Information Collection Activities; Comment Request; Credit Enhancement for Charter School... in response to this notice will be considered public records. Title of Collection: Credit Enhancement.... chapter 3501 et seq.), ED is proposing an extension of an existing information collection. DATES...

  6. Brains and Brawn: Complex Motor Activities to Maximize Cognitive Enhancement

    Science.gov (United States)

    Moreau, David

    2015-01-01

    The target articles in this special issue address the timely question of embodied cognition in the classroom, and in particular the potential of this approach to facilitate learning in children. The interest for motor activities within settings that typically give little space to nontraditional content is proof of a shift from a Cartesian…

  7. Tutorials as a way of enhancing active participation in university ...

    African Journals Online (AJOL)

    This article explored the need for tertiary level students, studying through a medium (English) that is not their primary language, to develop their ability to participate actively in tutorials so as to improve both understanding of their subject areas and spoken discourse competence in English. This problem was, however, dealt ...

  8. Jungle Honey Enhances Immune Function and Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Miki Fukuda

    2011-01-01

    Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.

  9. Microbial enrichment to enhance the disease suppressive activity of compost

    NARCIS (Netherlands)

    Postma, J.; Montenari, M.; Boogert, van den P.H.J.F.

    2003-01-01

    Compost amended soil has been found to be suppressive against plant diseases in various cropping systems. The level and reproducibility of disease suppressive properties of compost might be increased by the addition of antagonists. In the present study, the establishment and suppressive activity of

  10. Prior-to-Exam: What Activities Enhance Performance?

    Science.gov (United States)

    Rhoads, C. J.; Healy, Therese

    2013-01-01

    Can instructors impact their student performance by recommending an activity just prior to taking an exam? In this study, college students were randomly assigned to one of three treatment groups (study, exercise, or meditation) or a control group. Each group was given two different types of tests; a traditional concept exam, and a non-traditional…

  11. Enhanced Memory as a Common Effect of Active Learning

    Science.gov (United States)

    Markant, Douglas B.; Ruggeri, Azzurra; Gureckis, Todd M.; Xu, Fei

    2016-01-01

    Despite widespread consensus among educators that "active learning" leads to better outcomes than comparatively passive forms of instruction, it is often unclear why these benefits arise. In this article, we review research showing that the opportunity to control the information experienced while learning leads to improved memory…

  12. Enhanced 3D face processing using an active vision system

    DEFF Research Database (Denmark)

    Lidegaard, Morten; Larsen, Rasmus; Kraft, Dirk

    2014-01-01

    We present an active face processing system based on 3D shape information extracted by means of stereo information. We use two sets of stereo cameras with different field of views (FOV): One with a wide FOV is used for face tracking, while the other with a narrow FOV is used for face identification...

  13. Soluble ICAM-1 activates lung macrophages and enhances lung injury

    DEFF Research Database (Denmark)

    Schmal, H; Czermak, B J; Lentsch, A B

    1998-01-01

    Because of the important role of rat ICAM-1 in the development of lung inflammatory injury, soluble recombinant rat ICAM-1 (sICAM-1) was expressed in bacteria, and its biologic activities were evaluated. Purified sICAM-1 did bind to rat alveolar macrophages in a dose-dependent manner and induced...

  14. Palladium-platinum core-shell icosahedra with substantially enhanced activity and durability towards oxygen reduction

    National Research Council Canada - National Science Library

    Wang, Xue; Choi, Sang-Il; Roling, Luke T; Luo, Ming; Ma, Cheng; Zhang, Lei; Chi, Miaofang; Liu, Jingyue; Xie, Zhaoxiong; Herron, Jeffrey A; Mavrikakis, Manos; Xia, Younan

    2015-01-01

    .... For the core-shell nanocrystals with an average of 2.7 platinum overlayers, their specific and platinum mass activities towards oxygen reduction are enhanced by eight- and sevenfold, respectively, relative to a commercial catalyst...

  15. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    Science.gov (United States)

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-02-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

  16. Variants of polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Matt; Wogulis, Mark

    2017-11-14

    The present invention relates to polypeptide having cellulolytic enhancing activity variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

  17. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    Science.gov (United States)

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-01-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology. PMID:26861509

  18. PECASE: Resonantly-Enhanced Lanthanide Emitters for Subwavelength-Scale, Active Photonics

    Science.gov (United States)

    2015-03-19

    AFRL-AFOSR-VA-TR-2016-0052 PECASE- RESONATLY-ENHANCHED LANTHANIDE EMITTERS FOR SUBWAVELENGTH-SCALE, ACTIVE Photonics Rashid Zia BROWN UNIVERSITY IN...From - To) 15 Dec. 2009 – 14 Dec. 2014 4. TITLE AND SUBTITLE i i i 5a. CONTRACT NUMBER PECASE: Resonantly-Enhanced Lanthanide Emitters for...PECASE: Resonantly-Enhanced Lanthanide Emitters for Subwavelength-Scale, Active Photonics Contract/Grant #: FA9550-10-1-0026 Reporting Period: 15

  19. Enhanced Osteogenic and Vasculogenic Differentiation Potential of Human Adipose Stem Cells on Biphasic Calcium Phosphate Scaffolds in Fibrin Gels

    Directory of Open Access Journals (Sweden)

    Fransisca A. S. van Esterik

    2016-01-01

    Full Text Available For bone tissue engineering synthetic biphasic calcium phosphate (BCP with a hydroxyapatite/β-tricalcium phosphate (HA/β-TCP ratio of 60/40 (BCP60/40 is successfully clinically applied, but the high percentage of HA may hamper efficient scaffold remodelling. Whether BCP with a lower HA/β-TCP ratio (BCP20/80 is more desirable is still unclear. Vascular development is needed before osteogenesis can occur. We aimed to test the osteogenic and/or vasculogenic differentiation potential as well as degradation of composites consisting of human adipose stem cells (ASCs seeded on BCP60/40 or BCP20/80 incorporated in fibrin gels that trigger neovascularization for bone regeneration. ASC attachment to BCP60/40 and BCP20/80 within 30 min was similar (>93%. After 11 days of culture BCP20/80-based composites showed increased alkaline phosphatase activity and DMP1 gene expression, but not RUNX2 and osteonectin expression, compared to BCP60/40-based composites. BCP20/80-based composites also showed enhanced expression of the vasculogenic markers CD31 and VEGF189, but not VEGF165 and endothelin-1. Collagen-1 and collagen-3 expression was similar in both composites. Fibrin degradation was increased in BCP20/80-based composites at day 7. In conclusion, BCP20/80-based composites showed enhanced osteogenic and vasculogenic differentiation potential compared to BCP60/40-based composites in vitro, suggesting that BCP20/80-based composites might be more promising for in vivo bone augmentation than BCP60/40-based composites.

  20. In vitro vitamin K(2) and 1α,25-dihydroxyvitamin D(3) combination enhances osteoblasts anabolism of diabetic mice.

    Science.gov (United States)

    Poon, Christina C W; Li, Rachel W S; Seto, Sai Wang; Kong, Siu Kai; Ho, Ho Pui; Hoi, Maggie P M; Lee, Simon M Y; Ngai, Sai Ming; Chan, Shun Wan; Leung, George P H; Kwan, Yiu Wa

    2015-11-15

    In this study, we evaluated the anabolic effect and the underlying cellular mechanisms involved of vitamin K2 (10 nM) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) (10 nM), alone and in combination, on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (+/+) and obese/diabetic (db/db) mice. A lower alkaline phosphatase (ALP) activity plus a reduced expression of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4 and OSX) were consistently detected in osteoblasts of db/db mice compared to lean mice. A significantly higher calcium deposits formation in osteoblasts was observed in lean mice when compared to db/db mice. Co-administration of vitamin K2 (10 nM) and 1,25(OH)2D3 (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K2 and 1,25(OH)2D3 co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and bone formation transcription factors, with a greater magnitude of increase observed in osteoblasts of db/db mice. Combined vitamins K2 plus 1,25(OH)2D3 treatment significantly enhanced migration and the re-appearance of surface microvilli and ruffles of osteoblasts of db/db mice. Thus, our results illustrate that vitamins K2 plus D3 combination could be a novel therapeutic strategy in treating diabetes-associated osteoporosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Silver-enhanced block copolymer membranes with biocidal activity

    KAUST Repository

    Madhavan, Poornima

    2014-11-12

    Silver nanoparticles were deposited on the surface and pore walls of block copolymer membranes with highly ordered pore structure. Pyridine blocks constitute the pore surfaces, complexing silver ions and promoting a homogeneous distribution. Nanoparticles were then formed by reduction with sodium borohydride. The morphology varied with the preparation conditions (pH and silver ion concentration), as confirmed by field emission scanning and transmission electron microscopy. Silver has a strong biocide activity, which for membranes can bring the advantage of minimizing the growth of bacteria and formation of biofilm. The membranes with nanoparticles prepared under different pH values and ion concentrations were incubated with Pseudomonas aeruginosa and compared with the control. The strongest biocidal activity was achieved with membranes containing membranes prepared under pH 9. Under these conditions, the best distribution with small particle size was observed by microscopy.

  2. Observational evidence for enhanced magnetic activity of superflare stars.

    Science.gov (United States)

    Karoff, Christoffer; Knudsen, Mads Faurschou; De Cat, Peter; Bonanno, Alfio; Fogtmann-Schulz, Alexandra; Fu, Jianning; Frasca, Antonio; Inceoglu, Fadil; Olsen, Jesper; Zhang, Yong; Hou, Yonghui; Wang, Yuefei; Shi, Jianrong; Zhang, Wei

    2016-03-24

    Superflares are large explosive events on stellar surfaces one to six orders-of-magnitude larger than the largest flares observed on the Sun throughout the space age. Due to the huge amount of energy released in these superflares, it has been speculated if the underlying mechanism is the same as for solar flares, which are caused by magnetic reconnection in the solar corona. Here, we analyse observations made with the LAMOST telescope of 5,648 solar-like stars, including 48 superflare stars. These observations show that superflare stars are generally characterized by larger chromospheric emissions than other stars, including the Sun. However, superflare stars with activity levels lower than, or comparable to, the Sun do exist, suggesting that solar flares and superflares most likely share the same origin. The very large ensemble of solar-like stars included in this study enables detailed and robust estimates of the relation between chromospheric activity and the occurrence of superflares.

  3. Modification of polymer surfaces to enhance enzyme activity and stability

    DEFF Research Database (Denmark)

    Hoffmann, Christian

    already been developed, combining the same goal to improve enzyme activity, stability and selectivity. Polymer materials have shown, due to their easy processibility and versatile properties, high potential as enzyme support. However, in order to achieve improved enzyme performance, the combination...... of different factors, such as the nature of the enzyme, the properties of the support, the type of immobilization and the interaction between enzyme and support, has to be taken into consideration. In this thesis, these factors are pursued and addressed by exploiting various types of polymers with focus...... of immobilized enzymes. Micro-environmental changes were generated through the introduction of tailored surface functionalities via thiol-ene chemistry (TEC) and surface chain transfer free radical polymerization (SCT-FRP), which demonstrated a significant influence on the activity of immobilized horseradish...

  4. Enhanced ULF electromagnetic activity detected by DEMETER above seismogenic regions

    CERN Document Server

    Athanasiou, M; David, C; Anagnostopoulos, G

    2013-01-01

    In this paper we present results of a comparison between ultra low frequency (ULF) electromagnetic (EM) radiation, recorded by an electric field instrument (ICE) onboard the satellite DEMETER in the topside ionosphere, and the seismicity of regions with high and lower seiismic activity. In particular we evaluated the energy variations of the ULF Ez-electric field component during a period of four years (2006-2009), in order to examine check the possible relation of ULF EM radiation with seismogenic regions located in central America, Indonesia, Eastern Mediterranean Basin and Greece. As a tool of evaluating the ULF Ez energy variations we used Singular Spectrum Analysis (SSA) techniques. The results of our analysis clearly show a significant increase of the ULF EM energy emmited from regions of highest seismic activity at the tectonic plates boundaries. We interpret these results as suggesting that the highest ULF EM energy detected in the topside ionosphere is originated from seismic processes within Earth's...

  5. Silver-enhanced block copolymer membranes with biocidal activity.

    Science.gov (United States)

    Madhavan, Poornima; Hong, Pei-Ying; Sougrat, Rachid; Nunes, Suzana P

    2014-01-01

    Silver nanoparticles were deposited on the surface and pore walls of block copolymer membranes with highly ordered pore structure. Pyridine blocks constitute the pore surfaces, complexing silver ions and promoting a homogeneous distribution. Nanoparticles were then formed by reduction with sodium borohydride. The morphology varied with the preparation conditions (pH and silver ion concentration), as confirmed by field emission scanning and transmission electron microscopy. Silver has a strong biocide activity, which for membranes can bring the advantage of minimizing the growth of bacteria and formation of biofilm. The membranes with nanoparticles prepared under different pH values and ion concentrations were incubated with Pseudomonas aeruginosa and compared with the control. The strongest biocidal activity was achieved with membranes containing membranes prepared under pH 9. Under these conditions, the best distribution with small particle size was observed by microscopy.

  6. The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65

    Directory of Open Access Journals (Sweden)

    Liane Jurida

    2015-02-01

    Full Text Available The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-κB subunit p65 in relation to active enhancers and promoters of transcribed genes by chromatin immunoprecipitation sequencing (ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin 1 (IL-1-induced H3K27ac and p65 binding. Inhibition of TAK1 or IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-κB p50, and of AP-1 transcription factors to both promoters and enhancers. This study provides a high-resolution view of epigenetic changes occurring during the IL-1 response and allows the genome-wide identification of a distinct class of inducible p65 NF-κB-dependent enhancers in epithelial cells.

  7. Assessing attitude: the case of health-enhancing physical activity.

    Science.gov (United States)

    Marttila, Jukka; Nupponen, Ritva

    2006-01-01

    The basic phases of constructing compact questionnaire scales for health-promotion interventions are demonstrated in the case of attitudes towards two modes of physical activity, outdoor aerobic exercise (OAE) and everyday commuting activity (ECA). The scales were to show good psychometric properties and to provide adequate indicators of attitude. Behaviours and criteria were specified for both OAE and ECA. The items describing the emotional (affect) and cognitive (outcome-expectations) aspects of attitude towards OAE and ECA behaviours were selected on the basis of a pilot study. The scales under development were used in a Finnish population survey on health, personal resources and physical activity (n = 1,516). Item analyses were completed for purposes of refining the scale; principal component analyses and factor analyses were used to establish the dimensional structure of the scales. Evidence of discriminatory validity was provided by comparing the scale scores of the different groups of respondents with regular, with sub-criterion, and without any OAE and ECA behaviours, respectively. The purported psychometric properties were met in the case of the affective and, less obviously, the positive outcome-expectation scales. The negative expectation scales need to be reconstructed with additional items. The psychometric properties of the affective scales and the positive expectation scales allow conclusions to be drawn regarding group differences in attitudes towards OAE or ECA behaviours. These scales are ready to be cross-validated in a new sample. Test-retest reliability should also be established.

  8. Music training enhances rapid plasticity of N1 and P2 source activation for unattended sounds

    Directory of Open Access Journals (Sweden)

    Miia eSeppänen

    2012-03-01

    Full Text Available Neurocognitive studies demonstrate that long-term musical training enhances the processing of unattended sounds. It is not clear, however, whether musical training modulates also rapid (within tens of minutes neural plasticity for sound encoding. To study this, we examined whether adult musicians display enhanced rapid neural plasticity when compared to nonmusicians. More specifically, we examined the modulation of P1, N1, and P2 responses to regular standard sounds in an oddball paradigm between unattended passive blocks which were separated by an active task. Source analysis for event-related potentials showed that N1 and P2 source activation decreased selectively in musicians already after fifteen minutes of passive exposure to sounds and that P2 source activation re-enhanced after the active task in musicians. Additionally, event-related potential (ERP analysis revealed that in both musicians and nonmusicians, P2 ERP amplitude enhanced after fifteen minutes of passive exposure but only at frontal electrodes. Furthermore, in musicians, N1 ERP enhanced after the active discrimination task but only at parietal electrodes. Musical training modulates the rapid plasticity reflected in N1 and P2 source activation for unattended regular standard sounds. Enhanced rapid plasticity of N1 and P2 might reflect the faster auditory perceptual learning in musicians when compared to nonmusicians.

  9. A model for microcapsule drug release with ultrasound activated enhancement.

    Science.gov (United States)

    Hall, Elizabeth Anne Howlett; Tsao, Nadia

    2017-10-26

    Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been filled with a fluorescent acridium salt (lucigenin) as a model for a drug loaded delivery vehicle. The uptake and delivery was studied and compared with similar microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively charged lucigenin was encapsulated through an electrostatic mechanism, following a Type I Langmuir isotherm as expected, but with additional multilayer uptake that leads to much higher loading for the SiPCL system (~280 µg/2.4 × 109 microcapsules compared with ~135 µg/2.4 × 109 microcapsules for S/M/S). Whereas lucigenin release from the S/M/S bubbles and capsules loaded below the solubility limit is consistent with diffusion from a monolithic structure, the SiPCL structures show distinct release patterns; the Weibull function predicts a general trend for diffusion from normal Euclidean space at short times tending towards diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (Td) increases from 1 - 2 days for the S/M/S and the low concentration loaded SiPCl vehicles to ~10 days for the high loaded microcapsule. However, the Td can be reduced on insonation to 2 days, indicating the potential to gain control over local enhanced release with ultrasound. This was tested for a docetaxel model and its effect of C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC50 in solution.

  10. Enhancing mHealth Technology in the PCMH Environment to Activate Chronic Care Patients

    Science.gov (United States)

    2017-09-01

    Award Number: W81XWH-15-C-0070 TITLE: Enhancing mHealth Technology in the PCMH Environment to Activate Chronic Care Patients PRINCIPAL...Enhancing mHealth Technology in the PCMH Environment to Activate Chronic Care Patients 5a. CONTRACT NUMBER W81XWH-15-C-0070 5b. GRANT NUMBER 5c...Continuing Education Meeting - Poster #2 – presented 11/29/16, National Harbor, Maryland – “Enhancing mHealth Technology in the DoD’s PCMH Environment to

  11. Molecular dynamics study of enhanced Man5B enzymatic activity.

    Science.gov (United States)

    Bernardi, Rafael C; Cann, Isaac; Schulten, Klaus

    2014-01-01

    Biofuels are a well-known alternative to the largely used fossil-derived fuels, however the competition with food production is an ethical dilemma. Fortunately a solution is offered by second-generation biofuels which can be produced from agricultural waste or, more specifically, from plant cell wall polysaccharides. The conversion process involves typically enzymatic hydrolysis of lignocellulosic biomass and then separation of its constituent sugars that are further fermented to produce ethanol. Over the years several technologies have been developed that allow this conversion process to occur and the objective is now to make this process cost-competitive in today's markets. We observe that reduction of enzymatic efficiency in the presence of gluco-oligosaccharides is associated with a loss of the enzyme's flexibility, the latter being required to bind new substrate, while the presence of manno-oligosaccharides does not pose this problem. Molecular dynamics simulations identify key contacts between substrates and the enzyme catalytic pocket that might be modified through site-directed mutagenesis to prevent loss of enzymatic efficiency. Based on previous experimental studies and the new molecular dynamics data, we suggest that cellohexaose in the active site pocket slows down or even inhibits Man5B enzymatic activity. The assumption of such a mechanism is reasonable since when the gluco-oligosaccharide substrate is attached to the catalytic pocket it takes much longer to leave the pocket and thus prevents other substrates from reaching the active site. The insight is of crucial importance since the inhibition of enzymes by the enzymatic product or by an unsuitable substrate is a major technological problem in reducing the competitiveness of second-generation biofuel production.

  12. Carbohydrate Electrolyte Solutions Enhance Endurance Capacity in Active Females

    Directory of Open Access Journals (Sweden)

    Feng-Hua Sun

    2015-05-01

    Full Text Available The purpose of the present study was to investigate the effects of supplementation with a carbohydrate-electrolyte solution (CES in active females during a prolonged session of submaximal running to exhaustion. Eight healthy active females volunteered to perform a session of open-ended running to exhaustion at 70% of their maximal oxygen consumption on a treadmill during the follicular phase of their menstrual cycle on two occasions. During each run, the subjects consumed either 3mL·kg−1 body mass of a 6% CES or a placebo drink (PL every 20 min during exercise. The trials were administered in a randomized double-blind, cross-over design. During the run, the subjects ingested similar volumes of fluid in two trials (CES: 644 ± 75 mL vs. PL: 593 ± 66 mL, p > 0.05. The time to exhaustion was 16% longer during the CES trial (106.2 ± 9.4 min than during the PL trial (91.6 ± 5.9 min (p < 0.05. At 45 min during exercise, the plasma glucose concentration in the CES trial was higher than that in PL trial. No differences were observed in the plasma lactate level, respiratory exchange ratio, heart rate, perceived rate of exertion, sensation of thirst, or abdominal discomfort between the two trials (p > 0.05. The results of the present study confirm that CES supplementation improves the moderate intensity endurance capacity of active females during the follicular phases of the menstrual cycle. However, the exogenous oxidation of carbohydrate does not seem to explain the improved capacity after CES supplementation.

  13. Activity enhances dopaminergic long-duration response in Parkinson disease

    Science.gov (United States)

    Auinger, Peggy; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Mendis, Tilak

    2012-01-01

    Objective: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. Methods: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks. Results: The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands. Conclusions: Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during “off” medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects. PMID:22459675

  14. Integration of Bass Enhancement and Active Noise Control System in Automobile Cabin

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2008-01-01

    Full Text Available With the advancement of digital signal processing technologies, consumers are more concerned with the quality of multimedia entertainment in automobiles. In order to meet this demand, an audio enhancement system is needed to improve bass reproduction and cancel engine noise in the cabins. This paper presents an integrated active noise control system that is based on frequency-sampling filters to track and extract the bass information from the audio signal, and a multifrequency active noise equalizer to tune the low-frequency engine harmonics to enhance the bass reproduction. In the noise cancellation mode, a maximum of 3 dB bass enhancement can be achieved with significant noise suppression, while higher bass enhancement can be achieved in the bass enhance mode. The results show that the proposed system is effective for solving both the bass audio reproduction and the noise control problems in automobile cabins.

  15. Intelligent Architecture for Enhanced Observability for Active Distribution System

    DEFF Research Database (Denmark)

    Pokhrel, Basanta Raj; Nainar, Karthikeyan; Bak-Jensen, Birgitte

    2017-01-01

    to utilize advanced solutions by observing the system state in real time. Existing distribution automation and control system have to be upgraded to meet this technological challenge. This necessitates the use of real time system states of the grid which is a crucial factor for system operation in higher...... accuracy. Therefore, in this paper observability scope and evaluation methodology for the future active distribution network with high penetration of renewable resources and flexible loads are analyzed and reviewed. Based on the state of the art a high level architecture has been formulated and presented...

  16. Experimental human endotoxemia enhances brain activity during social cognition.

    Science.gov (United States)

    Kullmann, Jennifer S; Grigoleit, Jan-Sebastian; Wolf, Oliver T; Engler, Harald; Oberbeck, Reiner; Elsenbruch, Sigrid; Forsting, Michael; Schedlowski, Manfred; Gizewski, Elke R

    2014-06-01

    Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms. However, possible effects of increased immune responses on social cognition remain unknown. Therefore, this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind (ToM) ability. In this double-blind randomized crossover functional magnetic resonance imaging study, 18 healthy right-handed male volunteers received an injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline, respectively. Plasma levels of pro- and anti-inflammatory cytokines as well as mood ratings were analyzed together with brain activation during a validated ToM task (i.e. Reading the Mind in the Eyes Test). LPS administration induced pronounced transient increases in pro- (IL-6, TNF-α) and anti-inflammatory (IL-10, IL-1ra) cytokines as well as decreases in mood. Social cognition performance was not affected by acute inflammation. However, altered neural activity was observed during the ToM task after LPS administration, reflected by increased responses in the fusiform gyrus, temporo-parietal junction, superior temporal gyrus and precuneus. The increased task-related neural responses in the LPS condition may reflect a compensatory strategy or a greater social cognitive processing as a function of sickness. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  17. [Flipped classroom as a strategy to enhance active learning].

    Science.gov (United States)

    Wakabayashi, Noriyuki

    2015-03-01

    This paper reviews the introduction of a flipped class for fourth grade dentistry students, and analyzes the characteristics of the learning method. In fiscal 2013 and 2014, a series of ten three-hour units for removable partial prosthodontics were completed with the flipped class method; a lecture video of approximately 60 minutes was made by the teacher (author) and uploaded to the university's e-learning website one week before each class. Students were instructed to prepare for the class by watching the streaming video on their PC, tablet, or smartphone. In the flipped class, students were not given a lecture, but were asked to solve short questions displayed on screen, to make a short presentation about a part of the video lecture, and to discuss a critical question related to the main subject of the day. An additional team-based learning (TBL) session with individual and group answers was implemented. The average individual scores were considerably higher in the last two years, when the flipped method was implemented, than in the three previous years when conventional lectures were used. The following learning concepts were discussed: the role of the flipped method as an active learning strategy, the efficacy of lecture videos and short questions, students' participation in the class discussion, present-day value of the method, cooperation with TBL, the significance of active learning in relation with the students' learning ability, and the potential increase in the preparation time and workload for students.

  18. Enhancing Hebbian Learning to Control Brain Oscillatory Activity.

    Science.gov (United States)

    Soekadar, Surjo R; Witkowski, Matthias; Birbaumer, Niels; Cohen, Leonardo G

    2015-09-01

    Sensorimotor rhythms (SMR, 8-15 Hz) are brain oscillations associated with successful motor performance, imagery, and imitation. Voluntary modulation of SMR can be used to control brain-machine interfaces (BMI) in the absence of any physical movements. The mechanisms underlying acquisition of such skill are unknown. Here, we provide evidence for a causal link between function of the primary motor cortex (M1), active during motor skill learning and retention, and successful acquisition of abstract skills such as control over SMR. Thirty healthy participants were trained on 5 consecutive days to control SMR oscillations. Each participant was randomly assigned to one of 3 groups that received either 20 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) over M1. Learning SMR control across training days was superior in the anodal tDCS group relative to the other 2. Cathodal tDCS blocked the beneficial effects of training, as evidenced with sham tDCS. One month later, the newly acquired skill remained superior in the anodal tDCS group. Thus, application of weak electric currents of opposite polarities over M1 differentially modulates learning SMR control, pointing to this primary cortical region as a common substrate for acquisition of physical motor skills and learning to control brain oscillatory activity. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  19. Enhancing physical activity and brain reorganization after stroke.

    Science.gov (United States)

    Carr, Janet H; Shepherd, Roberta B

    2011-01-01

    It is becoming increasingly clear that, if reorganization of brain function is to be optimal after stroke, there needs to be a reorganisation of the methods used in physical rehabilitation and the time spent in specific task practice, strength and endurance training, and aerobic exercise. Frequency and intensity of rehabilitation need to be increased so that patients can gain the energy levels and vigour necessary for participation in physical activity both during rehabilitation and after discharge. It is evident that many patients are discharged from inpatient rehabilitation severely deconditioned, meaning that their energy levels are too low for active participation in daily life. Physicians, therapists, and nursing staff responsible for rehabilitation practice should address this issue not only during inpatient rehabilitation but also after discharge by promoting and supporting community-based exercise opportunities. During inpatient rehabilitation, group sessions should be frequent and need to include specific aerobic training. Physiotherapy must take advantage of the training aids available, including exercise equipment such as treadmills, and of new developments in computerised feedback systems, robotics, and electromechanical trainers. For illustrative purposes, this paper focuses on the role of physiotherapists, but the necessary changes in practice and in attitude will require cooperation from many others.

  20. Enhancing Physical Activity and Brain Reorganization after Stroke

    Directory of Open Access Journals (Sweden)

    Janet H. Carr

    2011-01-01

    Full Text Available It is becoming increasingly clear that, if reorganization of brain function is to be optimal after stroke, there needs to be a reorganisation of the methods used in physical rehabilitation and the time spent in specific task practice, strength and endurance training, and aerobic exercise. Frequency and intensity of rehabilitation need to be increased so that patients can gain the energy levels and vigour necessary for participation in physical activity both during rehabilitation and after discharge. It is evident that many patients are discharged from inpatient rehabilitation severely deconditioned, meaning that their energy levels are too low for active participation in daily life. Physicians, therapists, and nursing staff responsible for rehabilitation practice should address this issue not only during inpatient rehabilitation but also after discharge by promoting and supporting community-based exercise opportunities. During inpatient rehabilitation, group sessions should be frequent and need to include specific aerobic training. Physiotherapy must take advantage of the training aids available, including exercise equipment such as treadmills, and of new developments in computerised feedback systems, robotics, and electromechanical trainers. For illustrative purposes, this paper focuses on the role of physiotherapists, but the necessary changes in practice and in attitude will require cooperation from many others.

  1. Capacitance enhancement of polyaniline coated curved-graphene supercapacitors in a redox-active electrolyte

    KAUST Repository

    Chen, Wei

    2013-01-01

    We show, for the first time, a redox-active electrolyte in combination with a polyaniline-coated curved graphene active material to achieve significant enhancement in the capacitance (36-92% increase) compared to supercapacitors that lack the redox-active contribution from the electrolyte. The supercapacitors based on the redox-active electrolyte also exhibit excellent rate capability and very long cycling performance (>50 000 cycles). This journal is © The Royal Society of Chemistry.

  2. Defying the activity-stability trade-off in enzymes: taking advantage of entropy to enhance activity and thermostability.

    Science.gov (United States)

    Siddiqui, Khawar Sohail

    2017-05-01

    The biotechnological applications of enzymes are limited due to the activity-stability trade-off, which implies that an increase in activity is accompanied by a concomitant decrease in protein stability. This premise is based on thermally adapted homologous enzymes where cold-adapted enzymes show high intrinsic activity linked to enhanced thermolability. In contrast, thermophilic enzymes show low activity around ambient temperatures. Nevertheless, genetically and chemically modified enzymes are beginning to show that the activity-stability trade-off can be overcome. In this review, the origin of the activity-stability trade-off, the thermodynamic basis for enhanced activity and stability, and various approaches for escaping the activity-stability trade-off are discussed. The role of entropy in enhancing both the activity and the stability of enzymes is highlighted with a special emphasis placed on the involvement of solvent water molecules. This review is concluded with suggestions for further research, which underscores the implications of these findings in the context of productivity curves, the Daniel-Danson equilibrium model, catalytic antibodies, and life on cold planets.

  3. Functional assessment of human enhancer activities using whole-genome STARR-sequencing.

    Science.gov (United States)

    Liu, Yuwen; Yu, Shan; Dhiman, Vineet K; Brunetti, Tonya; Eckart, Heather; White, Kevin P

    2017-11-20

    Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome.  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity. This approach builds upon previously developed STARR-seq in the fly genome and CapSTARR-seq techniques in targeted human genomic regions. With an improved library preparation strategy, our approach greatly increases the library complexity per unit of starting material, which makes it feasible and cost-effective to explore the landscape of regulatory activity in the much larger human genome. In addition to our ability to identify active, accessible enhancers located in open chromatin regions, we can also detect sequences with the potential for enhancer activity that are located in inaccessible, closed chromatin regions. When treated with the histone deacetylase inhibitor, Trichostatin A, genes nearby this latter class of enhancers are up-regulated, demonstrating the potential for endogenous functionality of these regulatory elements. WHG-STARR-seq provides an improved approach to current pipelines for analysis of high complexity genomes to gain a better understanding of the intricacies of transcriptional regulation.

  4. Enhancement of human natural cytotoxicity by Plasmodium falciparum antigen activated lymphocytes.

    Science.gov (United States)

    Theander, T G; Pedersen, B K; Bygbjerg, I C; Jepsen, S; Larsen, P B; Kharazmi, A

    1987-12-01

    Mononuclear cells (MNC) isolated from malaria immune donors and from donors never exposed to malaria were stimulated in vitro with soluble purified Plasmodium falciparum antigens (SPag) or PPD. After 7 days of culture the proliferative response and the cytotoxic activity against the natural killer cell (NK cell) sensitive cell line, K562, were measured. It was found that SPag stimulation enhanced cytotoxic activity of MNC from donors whose lymphocytes exhibited a strong proliferative response to the antigen. MNC with low proliferative responsiveness showed increased cytotoxic activity if the MNC were preincubated with interleukin 2 (IL-2) for one hour before the start of the cytotoxic assay. SPag activation did not enhance the cytotoxic activity of MNC which did not respond to the antigen in the proliferation assay, and preincubation of these cells with IL-2 did not increase the activity. PPD stimulation enhanced the cytotoxic activity and induced strong proliferative responses in all MNC preparations. The role of NK cells in the protection against malaria is unknown, but they play a role in the protection against virus infection and in the immune surveillance against cancer. Our findings indicate that malaria antigens either directly or through the activation of immunoregulatory cells enhance the NK cell activity.

  5. Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity

    Directory of Open Access Journals (Sweden)

    Sarah J. Annesley

    2016-11-01

    Full Text Available In combination with studies of post-mortem Parkinson's disease (PD brains, pharmacological and genetic models of PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis and mitochondrial respiration. We have re-examined the role of mitochondrial dysfunction in lymphoblasts isolated from individuals with idiopathic PD and an age-matched control group. As previously reported for various PD cell types, the production of reactive oxygen species (ROS by PD lymphoblasts was significantly elevated. However, this was not due to an impairment of mitochondrial respiration, as is often assumed. Instead, basal mitochondrial respiration and ATP synthesis are dramatically elevated in PD lymphoblasts. The mitochondrial mass, genome copy number and membrane potential were unaltered, but the expression of indicative respiratory complex proteins was also elevated. This explains the increased oxygen consumption rates by each of the respiratory complexes in experimentally uncoupled mitochondria of iPD cells. However, it was not attributable to increased activity of the stress- and energy-sensing protein kinase AMPK, a regulator of mitochondrial biogenesis and activity. The respiratory differences between iPD and control cells were sufficiently dramatic as to provide a potentially sensitive and reliable biomarker of the disease state, unaffected by disease duration (time since diagnosis or clinical severity. Lymphoblasts from control and PD individuals thus occupy two distinct, quasi-stable steady states; a ‘normal’ and a ‘hyperactive’ state characterized by two different metabolic rates. The apparent stability of the ‘hyperactive’ state in patient-derived lymphoblasts in the face of patient ageing, ongoing disease and mounting disease severity suggests an early, permanent switch to an alternative metabolic steady state. With its associated, elevated ROS production, the ‘hyperactive’ state might not cause

  6. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    Science.gov (United States)

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  7. Milling solid proteins to enhance activity after melt-encapsulation.

    Science.gov (United States)

    Lee, Parker W; Maia, João; Pokorski, Jonathan K

    2017-11-25

    Polymeric systems for the immobilization and delivery of proteins have been extensively used for therapeutic and catalytic applications. While most devices have been created via solution based methods, hot melt extrusion (HME) has emerged as an alternative due to the high encapsulation efficiencies and solvent-free nature of the process. HME requires high temperatures and mechanical stresses that can result in protein aggregation and denaturation, but additives and chemical modifications have been explored to mitigate these effects. This study explores the use of solid-state ball milling to decrease protein particle size before encapsulation within poly(lactic-co-glycolic acid) (PLGA) via HME. The impact of milling on particle dispersion, retained enzymatic activity, secondary structure stability, and release was explored for lysozyme, glucose oxidase, and the virus-like particle derived from Qβ to fully understand the impact of milling on protein systems with different sizes and complexities. The results of this study describe the utility of milling to further increase the stability of protein/polymer systems prepared via HME. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma.

    Science.gov (United States)

    Koto, Karen S; Lescault, Pamela; Brard, Laurent; Kim, Kyukwang; Singh, Rakesh K; Bond, Jeff; Illenye, Sharon; Slavik, Marni A; Ashikaga, Takamaru; Saulnier Sholler, Giselle L

    2011-05-01

    Medulloblastoma, a neuroectodermal tumor arising in the cerebellum, is the most common brain tumor found in children. We recently showed that nifurtimox induces production of reactive oxygen species (ROS) and subsequent apoptosis in neuroblastoma cells both in vitro and in vivo. Tetrathiomolybdate (TM) has been shown to decrease cell proliferation by inhibition of superoxide dismutase-1 (SOD1). Since both nifurtimox and TM increase ROS levels in cells, we investigated whether the combination of nifurtimox and TM would act synergistically in medulloblastoma cell lines (D283, DAOY). Genome-wide transcriptional analysis, by hybridizing RNA isolated from nifurtimox and TM alone or in combination treated and control cells (D283) on Affymetrix exon array gene chips was carried out to further confirm synergy. We show that nifurtimox and TM alone and in combination decreased cell viability and increased ROS levels synergistically. Examination of cell morphology following drug treatment (nifurtimox + TM) and detection of caspase-3 activation via Western blotting indicated that cell death was primarily due to apoptosis. Microarray data from cells treated with nifurtimox and TM validated the induction of oxidative stress, as many Nrf2 target genes (HMOX1, GCLM, SLC7A11 and SRXN1) (pnifurtimox + TM. Taken together, our results suggest nifurtimox and TM act synergistically in medulloblastoma cells in vitro, and that this combination warrants further studies as a new treatment for medulloblastoma.

  9. The enhancement of immunological activity by mild hypothermia

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawal, Takeo; Gu, Yeun Hwa; Miyata, Katuyuki [Graduate School of Suzuka Univ. of Med Sci. Master, Suzuka (Japan)] (and others)

    2004-11-15

    In general, the term hypothermia is applied for the therapeutic method for the treatment of cancer using micro wave, RF wave thermal system or intra-tissue thermal device. It was found to be a tumor necrosis factor (TNF), which is one of cytokines secreted by macrophages 'P'j. With remarkable progress in the instruments and technique in recent years, fundamental and clinical research showed extensive development 'Q'j. At present, hypothermia is clinically very important as inter- disciplinary therapeutic method, and studies are being performed on combined effects with surgical treatment, radiotherapy, chemotherapy and gene therapy for the treatment of malignant tumor 'R'j. Also, hypothermia is characterized by its selective thermal effect on tumor 'S'j. In this sense, it is called mild hypothermia. There have been not many reports, which described mild hypothermia for the purpose of treating the cases with cancer. This suggests the possibility of immunological response by heating relatively mild temperature (39-42). In this respect, by experiments using mouse as model, we evaluated the effects of hypothermia under temperature of 42.5 and lower and demonstrated that the activation of immunological response is increased and anti-tumor effect can be obtained.

  10. Garden-like perovskite superstructures with enhanced photocatalytic activity.

    Science.gov (United States)

    Ye, Meidan; Wang, Mengye; Zheng, Dajiang; Zhang, Nan; Lin, Changjian; Lin, Zhiqun

    2014-04-07

    By subjecting amorphous flower-like TiO2 to a facile hydrothermal synthesis in the presence of Sr(2+), garden-like perovskite SrTiO3 superstructures were achieved. The amorphous TiO2 was preformed using ZnO flowers as templates. Different three-dimensional SrTiO3 architectures were coexisted in the garden, including SrTiO3 flowers composed of several hollow sword-shaped petals, many sheet-shaped petals or numerous flake-shaped petals, and SrTiO3 grass consisting of a number of long blades. These SrTiO3 superstructures were simultaneously grown on fluorine-doped tin oxide (FTO) substrates. On the basis of a comprehensive study on the effects of growth time, temperature, initial concentrations of precursor, and pH, the formation of these various hierarchical architectures was attributed primarily to the dissolution of amorphous TiO2 and precipitation of perovskite crystals, followed by the Ostwald ripening process of perovskite nanocrystals and self-organization of perovskite building blocks. Interestingly, this approach can be readily extended to create other perovskite structures, including dendritic BaTiO3 and nest-like CaTiO3, as well as PbTiO3 transformed from plate-like pyrochlore Pb2Ti2O6 after post-thermal treatment. Garden-like SrTiO3 superstructures showed a superior photocatalytic performance when compared to other as-prepared semiconductors and perovskite materials (i.e., ZnO, TiO2, BaTiO3, CaTiO3 and PbTiO3), probably due to their intrinsic photocatalytic activity and special garden-like features with a coexistence of various structures that significantly facilitated the adsorption and diffusion of methyl blue (MB) molecules and oxygen species in the photochemical reaction of MB degradation.

  11. Titin force enhancement following active stretch of skinned skeletal muscle fibres.

    Science.gov (United States)

    Powers, Krysta; Joumaa, Venus; Jinha, Azim; Moo, Eng Kuan; Smith, Ian Curtis; Nishikawa, Kiisa; Herzog, Walter

    2017-09-01

    In actively stretched skeletal muscle sarcomeres, titin-based force is enhanced, increasing the stiffness of active sarcomeres. Titin force enhancement in sarcomeres is vastly reduced in mdm, a genetic mutation with a deletion in titin. Whether loss of titin force enhancement is associated with compensatory mechanisms at higher structural levels of organization, such as single fibres or entire muscles, is unclear. The aim of this study was to determine whether mechanical deficiencies in titin force enhancement are also observed at the fibre level, and whether mechanisms compensate for the loss of titin force enhancement. Single skinned fibres from control and mutant mice were stretched actively and passively beyond filament overlap to observe titin-based force. Mutant fibres generated lower contractile stress (force divided by cross-sectional area) than control fibres. Titin force enhancement was observed in control fibres stretched beyond filament overlap, but was overshadowed in mutant fibres by an abundance of collagen and high variability in mechanics. However, titin force enhancement could be measured in all control fibres and most mutant fibres following short stretches, accounting for ∼25% of the total stress following active stretch. Our results show that the partial loss of titin force enhancement in myofibrils is not preserved in all mutant fibres and this mutation likely affects fibres differentially within a muscle. An increase in collagen helps to reestablish total force at long sarcomere lengths with the loss in titin force enhancement in some mutant fibres, increasing the overall strength of mutant fibres. © 2017. Published by The Company of Biologists Ltd.

  12. The influence of adsorption capacity on enhanced gas absorption in activated carbon slurries

    NARCIS (Netherlands)

    Holstvoogd, R.D.; van Swaaij, Willibrordus Petrus Maria

    1990-01-01

    The enhanced absorption of gases in aqueous activated carbbon slurries of fine particles is studied with a non-steady-state absorption model, taking into account the finite adsorption capacity of the carbon particles. It has been found that, for the different gas/activated carbon slurry systems

  13. Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Olsen, Ole H; Fodje, Michel

    2008-01-01

    The intrinsic activity of coagulation factor VIIa (FVIIa) is dependent on Ca(2+) binding to a loop (residues 210-220) in the protease domain. Structural analysis revealed that Ca(2+) may enhance the activity by attenuating electrostatic repulsion of Glu(296) and/or by facilitating interactions...... by a combination of charge neutralization and loop stabilization....

  14. Earth-Heart Astronomy: Astronomy-Related Activities to Enhance Education for Sustainable Development

    Science.gov (United States)

    Townsend, Christopher

    2010-01-01

    This article outlines a range of engaging outdoor daytime activities to enhance astronomical understanding and our place in the universe. They are practical activities with "soul" which engender environmental and social responsibility on a local (yet planetary) scale. They link astronomical and global considerations with a notion of…

  15. Enhanced Multisensory Integration and Motor Reactivation after Active Motor Learning of Audiovisual Associations

    Science.gov (United States)

    Butler, Andrew J.; James, Thomas W.; James, Karin Harman

    2011-01-01

    Everyday experience affords us many opportunities to learn about objects through multiple senses using physical interaction. Previous work has shown that active motor learning of unisensory items enhances memory and leads to the involvement of motor systems during subsequent perception. However, the impact of active motor learning on subsequent…

  16. An atlas of active enhancers across human cell types and tissues

    NARCIS (Netherlands)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene; Hoof, Ilka; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Zhao, Xiaobei; Schmidl, Christian; Suzuki, Takahiro; Ntini, Evgenia; Arner, Erik; Valen, Eivind; Li, Kang; Schwarzfischer, Lucia; Glatz, Dagmar; Raithel, Johanna; Lilje, Berit; Rapin, Nicolas; Bagger, Frederik Otzen; Jørgensen, Mette; Andersen, Peter Refsing; Bertin, Nicolas; Rackham, Owen; Burroughs, A. Maxwell; Baillie, J. Kenneth; Ishizu, Yuri; Shimizu, Yuri; Furuhata, Erina; Maeda, Shiori; Negishi, Yutaka; Mungall, Christopher J.; Meehan, Terrence F.; Lassmann, Timo; Itoh, Masayoshi; Kawaji, Hideya; Kondo, Naoto; Kawai, Jun; Lennartsson, Andreas; Daub, Carsten O.; Heutink, Peter; Hume, David A.; Jensen, Torben Heick; Suzuki, Harukazu; Hayashizaki, Yoshihide; Müller, Ferenc; Forrest, Alistair R. R.; Carninci, Piero; Rehli, Michael; Sandelin, Albin; de Hoon, Michiel J. L.; Haberle, Vanja; Kulakovskiy, Ivan V.; Lizio, Marina; Mungall, Christoher J.; Schmeier, Sebastian; Dimont, Emmanuel; Schmid, Christian; Schaefer, Ulf; Medvedeva, Yulia A.; Plessy, Charles; Vitezic, Morana; Severin, James; Semple, Colin A.; Young, Robert S.; Francescatto, Margherita; Alam, Intikhab; Albanese, Davide; Altschuler, Gabriel M.; Arakawa, Takahiro; Archer, John A. C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Califano, Andrea; Cannistracti, Carlo V.; Carbajo, Daniel; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie A.; Detmar, Michael; Diehl, Alexander D.; Dohi, Taeko; Drabløs, Finn; Edge, Albert S. B.; Edinger, Matthias; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey; Fang, Hai; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Jun-ichi; Geijtenbeek, Teunis B.; Gibson, Andrew P.; Gingeras, Thomas; Goldowitz, Daniel; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J.; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard; Hitchens, Kelly J.; Ho Sui, Shannan J.; Hofman, Oliver M.; Hori, Fumi; Huminiecki, Lukasz; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha; Jurman, Giuseppe; Kaczkowski, Bogumil; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, S. Peter; Knox, Alan J.; Kojima, Miki; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F. J.; Lee, Weonju; Lipovich, Leonard; Mackay-sim, Alan; Manabe, Ri-ichiroh; Mar, Jessica C.; Marchand, Benoit; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison; Mizuno, Yosuke; de Lima Morais, David A.; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohmiya, Hiroko; Ohno, Hiroshi; Onshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerie; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert; Patrikakis, Margaret; Persson, Helena; Piazza, Silvano; Prendergast, James G. D.; Rackham, Owen J. L.; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Rye, Morten B.; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schneider, Claudio; Schultes, Erik A.; Schultz-Tanzil, Gudula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Christophe; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter A. C.; Tagami, Michihira; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyodo, Tetsuro; van de Wetering, Marc; van den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter G.; Zucchelli, Silvia; Summers, Kim M.; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Allbin

    2014-01-01

    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples,

  17. Networking in Sport Management: Ideas and Activities to Enhance Student Engagement and Career Development

    Directory of Open Access Journals (Sweden)

    Alan S. Kornspan

    2013-01-01

    Full Text Available The primary purpose of this paper is to present information regarding the development of networking skills to enhance the career development of sport management students. Specifically, literature is reviewed which supports the importance of networking in the attainment of employment and career advancement in the sport industry. This is followed by an overview of emerging networking activities that allow opportunities for sport management students to expand their network. Sport industry career fairs and career conferences that students can attend are discussed. Additionally, sport industry professional associations that students can become involved with are presented. This is then followed with information related to the development of sport management clubs and various events that can be promoted to enhance the networking process. Specifically, activities provided by university faculty to enhance the educational experience of sport management students are detailed. Finally, a sample schedule of semester activities focused on student engagement and networking activities is provided.

  18. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Wang

    2016-01-01

    Full Text Available Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

  19. Anticancer and enhanced antimicrobial activity of biosynthesizd silver nanoparticles against clinical pathogens

    Science.gov (United States)

    Rajeshkumar, Shanmugam; Malarkodi, Chelladurai; Vanaja, Mahendran; Annadurai, Gurusamy

    2016-07-01

    The present investigation shows the biosynthesis of eco-friendly silver nanoparticles using culture supernatant of Enterococcus sp. and study the effect of enhanced antimicrobial activity, anticancer activity against pathogenic bacteria, fungi and cancer cell lines. Silver nanoparticles was synthesized by adding 1 mM silver nitrate into the 100 ml of 24 h freshly prepared culture supernatant of Enterococcus sp. and were characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Selected Area Diffraction X-Ray (SAED), Energy Dispersive X Ray (EDX) and Fourier Transform Infra red Spectroscopy (FT-IR). The synthesized silver nanoparticles were impregnated with commercial antibiotics for evaluation of enhanced antimicrobial activity. Further these synthesized silver nanoparticles were assessed for its anticancer activity against cancer cell lines. In this study crystalline structured nanoparticles with spherical in the size ranges from 10 to 80 nm and it shows excellent enhanced antimicrobial activity than the commercial antibiotics. The in vitro assay of silver nanoparticles on anticancer have great potential to inhibit the cell viability. Amide linkages and carboxylate groups of proteins from Enterococcus sp. may bind with silver ions and convert into nanoparticles. The activities of commercial antibiotics were enhanced by coating silver nanoparticles shows significant improved antimicrobial activity. Silver nanoparticles have the great potential to inhibit the cell viability of liver cancer cells lines (HepG2) and lung cancer cell lines (A549).

  20. Glycerol enhances fungal germination at the water-activity limit for life

    OpenAIRE

    Stevenson, Andrew; Hamill, Philip G.; Medina, Ángel; Kminek, Gerhard; Rummel, John D.; Dijksterhuis, Jan; Timson, David J.; Magan, Naresh; Leong, Su-lin L.; Hallsworth, John E.

    2016-01-01

    For the most-extreme fungal xerophiles, metabolic activity and cell division typically halts between 0.700 and 0.640 water activity (approximately 70.0-64.0% relative humidity). Here, we investigate whether glycerol can enhance xerophile germination under acute water-activity regimes, using an experimental system which represents the biophysical limit of Earth's biosphere. Spores of a variety of species including Aspergillus penicillioides, Eurotium halophilicum, Xerochrysium xerophilium (for...

  1. Surface enhanced Raman optical activity of molecules on orientationally averaged substrates: theory of electromagnetic effects.

    Science.gov (United States)

    Janesko, Benjamin G; Scuseria, Gustavo E

    2006-09-28

    We present a model for electromagnetic enhancements in surface enhanced Raman optical activity (SEROA) spectroscopy. The model extends previous treatments of SEROA to substrates, such as metal nanoparticles in solution, that are orientationally averaged with respect to the laboratory frame. Our theoretical treatment combines analytical expressions for unenhanced Raman optical activity with molecular polarizability tensors that are dressed by the substrate's electromagnetic enhancements. We evaluate enhancements from model substrates to determine preliminary scaling laws and selection rules for SEROA. We find that dipolar substrates enhance Raman optical activity (ROA) scattering less than Raman scattering. Evanescent gradient contributions to orientationally averaged ROA scale to first or higher orders in the gradient of the incident plane-wave field. These evanescent gradient contributions may be large for substrates with quadrupolar responses to the plane-wave field gradient. Some substrates may also show a ROA contribution that depends only on the molecular electric dipole-electric dipole polarizability. These conclusions are illustrated via numerical calculations of surface enhanced Raman and ROA spectra from (R)-(-)-bromochlorofluoromethane on various model substrates.

  2. Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis.

    Science.gov (United States)

    Lee, Ji-Eun; Park, Young-Kwon; Park, Sarah; Jang, Younghoon; Waring, Nicholas; Dey, Anup; Ozato, Keiko; Lai, Binbin; Peng, Weiqun; Ge, Kai

    2017-12-20

    The epigenomic reader Brd4 is an important drug target for cancers. However, its role in cell differentiation and animal development remains largely unclear. Using two conditional knockout mouse strains and derived cells, we demonstrate that Brd4 controls cell identity gene induction and is essential for adipogenesis and myogenesis. Brd4 co-localizes with lineage-determining transcription factors (LDTFs) on active enhancers during differentiation. LDTFs coordinate with H3K4 mono-methyltransferases MLL3/MLL4 (KMT2C/KMT2D) and H3K27 acetyltransferases CBP/p300 to recruit Brd4 to enhancers activated during differentiation. Brd4 deletion prevents the enrichment of Mediator and RNA polymerase II transcription machinery, but not that of LDTFs, MLL3/MLL4-mediated H3K4me1, and CBP/p300-mediated H3K27ac, on enhancers. Consequently, Brd4 deletion prevents enhancer RNA production, cell identity gene induction and cell differentiation. Interestingly, Brd4 is dispensable for maintaining cell identity genes in differentiated cells. These findings identify Brd4 as an enhancer epigenomic reader that links active enhancers with cell identity gene induction in differentiation.

  3. ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Blow, Matthew J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Ren, Bing; Rubin, Edward M.; Pennacchio, Len A.

    2009-02-01

    A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover since they are scattered amongst the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here, we performed chromatin immunoprecipitation with the enhancer-associated protein p300, followed by massively-parallel sequencing, to map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases revealed reproducible enhancer activity in those tissues predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities and suggest that such datasets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

  4. ChIP-seq Mapping of Distant-Acting Enhancers and Their In Vivo Activities

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Pennacchio, Len A.

    2011-06-01

    The genomic location and function of most distant-acting transcriptional enhancers in the human genome remains unknown We performed ChIP-seq for various transcriptional coactivator proteins (such as p300) directly from different embryonic mouse tissues, identifying thousands of binding sitesTransgenic mouse experiments show that p300 and other co-activator peaks are highly predictive of genomic location AND tissue-specific activity patterns of distant-acting enhancersMost enhancers are active only in one or very few tissues Genomic location of tissue-specific p300 peaks correlates with tissue-specific expression of nearby genes Most binding sites are conserved, but the global degree of conservation varies between tissues

  5. Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer′s disease mice

    Directory of Open Access Journals (Sweden)

    Gao-shang Chai

    2016-01-01

    Full Text Available Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer′s disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer′s disease. Recent studies have demonstrated that environmental novelty activates β2 -adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2 -adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer′s disease. To test this hypothesis, we investigated the effects and mechanisms of action of β2 -adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 (APP/PS1 mice using the agonist clenbuterol (intraperitoneal injection, 2 mg/kg. We found that β2 -adrenoceptor activation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines. These effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2 -adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2 -adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS1 mice.

  6. Immobilization of enzymes to silver island films for enhanced enzymatic activity.

    Science.gov (United States)

    Abel, Biebele; Aslan, Kadir

    2014-02-01

    The performance of the enzyme-based biosensors depends on the enzymatic activity and the use of an appropriate technique for immobilization of enzymes. The incorporation of silver island films (SIFs) into the enzyme-based biosensors is expected to enhance the enzymatic activity and to increase the detectability of analytes of interest. Two enzymes, β-galactosidase (β-Gal) and alkaline phosphatase (AP) were immobilized onto SIFs using the interactions of avidin-modified enzymes with (i) a monolayer of biotinylated bovine serum albumin (b-BSA) and/or (ii) a monolayer of biotinylated poly(ethylene-glycol)-amine (BEA molecular weight: 550-10,000Da). To confirm the effect of SIFs on enzymatic activity, two control surfaces (no silver) were also employed. No enhancement in enzymatic activity for β-Gal on all SIFs was observed, which was attributed to the inhibition of β-Gal activity due to direct interactions of β-Gal with SIFs. The AP activity on SIFs with BEA was significantly larger than that observed on SIFs with b-BSA, where a 300% increase in AP activity was observed as compared to control surfaces. These observations suggest that SIFs can significantly enhance AP activity, which could help improve the detection limits of ELISAs and immunoassays that employ AP. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis.

    Science.gov (United States)

    Starita, Lea M; Pruneda, Jonathan N; Lo, Russell S; Fowler, Douglas M; Kim, Helen J; Hiatt, Joseph B; Shendure, Jay; Brzovic, Peter S; Fields, Stanley; Klevit, Rachel E

    2013-04-02

    Although ubiquitination plays a critical role in virtually all cellular processes, mechanistic details of ubiquitin (Ub) transfer are still being defined. To identify the molecular determinants within E3 ligases that modulate activity, we scored each member of a library of nearly 100,000 protein variants of the murine ubiquitination factor E4B (Ube4b) U-box domain for auto-ubiquitination activity in the presence of the E2 UbcH5c. This assay identified mutations that enhance activity both in vitro and in cellular p53 degradation assays. The activity-enhancing mutations fall into two distinct mechanistic classes: One increases the U-box:E2-binding affinity, and the other allosterically stimulates the formation of catalytically active conformations of the E2∼Ub conjugate. The same mutations enhance E3 activity in the presence of another E2, Ube2w, implying a common allosteric mechanism, and therefore the general applicability of our observations to other E3s. A comparison of the E3 activity with the two different E2s identified an additional variant that exhibits E3:E2 specificity. Our results highlight the general utility of high-throughput mutagenesis in delineating the molecular basis of enzyme activity.

  8. Enhanced repair effect of toll-like receptor 4 activation on neurotmesis: assessment using MR neurography.

    Science.gov (United States)

    Li, H J; Zhang, X; Zhang, F; Wen, X H; Lu, L J; Shen, J

    2014-08-01

    Alternative use of molecular approaches is promising for improving nerve regeneration in surgical repair of neurotmesis. The purpose of this study was to determine the role of MR imaging in assessment of the enhanced nerve regeneration with toll-like receptor 4 signaling activation in surgical repair of neurotmesis. Forty-eight healthy rats in which the sciatic nerve was surgically transected followed by immediate surgical coaptation received intraperitoneal injection of toll-like receptor 4 agonist lipopolysaccharide (n = 24, study group) or phosphate buffered saline (n = 24, control group) until postoperative day 7. Sequential T2 measurements and gadofluorine M-enhanced MR imaging and sciatic functional index were obtained over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and gadofluorine enhancement of the distal nerve stumps were measured and compared between nerves treated with lipopolysaccharide and those treated with phosphate buffered saline. Nerves treated with lipopolysaccharide injection achieved better functional recovery and showed more prominent gadofluorine enhancement and prolonged T2 values during the degenerative phase compared with nerves treated with phosphate buffered saline. T2 values in nerves treated with lipopolysaccharide showed a more rapid return to baseline level than did gadofluorine enhancement. Histology exhibited more macrophage recruitment, faster myelin debris clearance, and more pronounced nerve regeneration in nerves treated with toll-like receptor 4 activation. The enhanced nerve repair with toll-like receptor 4 activation in surgical repair of neurotmesis can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting such improved nerve regeneration. © 2014 by American Journal of Neuroradiology.

  9. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  10. SUMF1 enhances sulfatase activities in vivo in five sulfatase deficiencies.

    Science.gov (United States)

    Fraldi, Alessandro; Biffi, Alessandra; Lombardi, Alessia; Visigalli, Ilaria; Pepe, Stefano; Settembre, Carmine; Nusco, Edoardo; Auricchio, Alberto; Naldini, Luigi; Ballabio, Andrea; Cosma, Maria Pia

    2007-04-15

    Sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. Deficiency of lysosomal sulfatases leads to human diseases characterized by the accumulation of either GAGs (glycosaminoglycans) or sulfolipids. The catalytic activity of sulfatases resides in a unique formylglycine residue in their active site generated by the post-translational modification of a highly conserved cysteine residue. This modification is performed by SUMF1 (sulfatase-modifying factor 1), which is an essential factor for sulfatase activities. Mutations in the SUMF1 gene cause MSD (multiple sulfatase deficiency), an autosomal recessive disease in which the activities of all sulfatases are profoundly reduced. In previous studies, we have shown that SUMF1 has an enhancing effect on sulfatase activity when co-expressed with sulfatase genes in COS-7 cells. In the present study, we demonstrate that SUMF1 displays an enhancing effect on sulfatases activity when co-delivered with a sulfatase cDNA via AAV (adeno-associated virus) and LV (lentivirus) vectors in cells from individuals affected by five different diseases owing to sulfatase deficiencies or from murine models of the same diseases [i.e. MLD (metachromatic leukodystrophy), CDPX (X-linked dominant chondrodysplasia punctata) and MPS (mucopolysaccharidosis) II, IIIA and VI]. The SUMF1-enhancing effect on sulfatase activity resulted in an improved clearance of the intracellular GAG or sulfolipid accumulation. Moreover, we demonstrate that the SUMF1-enhancing effect is also present in vivo after AAV-mediated delivery of the sulfamidase gene to the muscle of MPSIIIA mice, resulting in a more efficient rescue of the phenotype. These results indicate that co-delivery of SUMF1 may enhance the efficacy of gene therapy in several sulfatase deficiencies.

  11. Origin of Activity and Stability Enhancement for Ag3PO4 Photocatalyst after Calcination

    Directory of Open Access Journals (Sweden)

    Pengyu Dong

    2016-11-01

    Full Text Available Pristine Ag3PO4 microspheres were synthesized by a co-precipitation method, followed by being calcined at different temperatures to obtain a series of calcined Ag3PO4 photocatalysts. This work aims to investigate the origin of activity and stability enhancement for Ag3PO4 photocatalyst after calcination based on the systematical analyses of the structures, morphologies, chemical states of elements, oxygen defects, optical absorption properties, separation and transfer of photogenerated electron-hole pairs, and active species. The results indicate that oxygen vacancies (VO˙˙ are created and metallic silver nanoparticles (Ag NPs are formed by the reaction of partial Ag+ in Ag3PO4 semiconductor with the thermally excited electrons from Ag3PO4 and then deposited on the surface of Ag3PO4 microspheres during the calcination process. Among the calcined Ag3PO4 samples, the Ag3PO4-200 sample exhibits the best photocatalytic activity and greatly enhanced photocatalytic stability for photodegradation of methylene blue (MB solution under visible light irradiation. Oxygen vacancies play a significantly positive role in the enhancement of photocatalytic activity, while metallic Ag has a very important effect on improving the photocatalytic stability. Overall, the present work provides some powerful evidences and a deep understanding on the origin of activity and stability enhancement for the Ag3PO4 photocatalyst after calcination.

  12. Magnetic field-induced T cell receptor clustering by nanoparticles enhances T cell activation and stimulates antitumor activity.

    Science.gov (United States)

    Perica, Karlo; Tu, Ang; Richter, Anne; Bieler, Joan Glick; Edidin, Michael; Schneck, Jonathan P

    2014-03-25

    Iron-dextran nanoparticles functionalized with T cell activating proteins have been used to study T cell receptor (TCR) signaling. However, nanoparticle triggering of membrane receptors is poorly understood and may be sensitive to physiologically regulated changes in TCR clustering that occur after T cell activation. Nano-aAPC bound 2-fold more TCR on activated T cells, which have clustered TCR, than on naive T cells, resulting in a lower threshold for activation. To enhance T cell activation, a magnetic field was used to drive aggregation of paramagnetic nano-aAPC, resulting in a doubling of TCR cluster size and increased T cell expansion in vitro and after adoptive transfer in vivo. T cells activated by nano-aAPC in a magnetic field inhibited growth of B16 melanoma, showing that this novel approach, using magnetic field-enhanced nano-aAPC stimulation, can generate large numbers of activated antigen-specific T cells and has clinically relevant applications for adoptive immunotherapy.

  13. Enhancement of the antifungal activity of antimicrobial drugs by Eugenia uniflora L.

    Science.gov (United States)

    Santos, Karla K A; Matias, Edinardo F F; Tintino, Saulo R; Souza, Celestina E S; Braga, Maria F B M; Guedes, Gláucia M M; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique Douglas Melo

    2013-07-01

    Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity.

  14. Bimetallic alloy Pt/Ag nanoparticles with enhanced catalytic activity for formic acid oxidation

    Science.gov (United States)

    Guo, Chunmei; Hu, Jingbo

    2014-05-01

    Here, we report the synthesis of Pt/Ag bimetallic alloy catalyst through combining the ion implantation and electrodeposition method. Ag nanoparticles are employed as the seeds for the growth of Pt nanoparticles. Pt/Ag alloy catalyst demonstrates much higher catalytic activity than pure Pt catalyst, which is about three times more active on the basis of equivalent Pt electrochemically active surface area than that of the pure Pt catalyst. The ion implantation of Ag efficiently enhances the catalytic activity of Pt catalyst for formic acid oxidation.

  15. Low-power laser irradiation enhance macrophage phagocytic capacity through Src activation

    Science.gov (United States)

    Wu, Shengnan; Zhou, Feifan; Xing, Da

    2012-03-01

    Phagocytosis and subsequent degradation of pathogens by macrophages play a pivotal role in host innate immunity in mammals. Laser irradiation has been found to produce photobiological effects with evidence of interference with organic functions. In this study, we focused our attention on the effects of He-Ne laser on the phagocytic activity of macrophages, the regulation mechanism of phagocytosis was also discussed. Our results indicated that Low-power laser irradiation can enhance the phagocytosis of macrophage through activation of Src.

  16. Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Lorenzen, I; Henriksen, O

    1994-01-01

    Dynamic T1-weighted FLASH MR imaging, obtained just after i.v. gadopentetate dimeglumine injection, and pre- and postcontrast T1-weighted spin-echo (T1-SE) MR imaging were performed to compare their information value with respect to inflammatory activity in immunoinflammatory gonarthritis. We exa...... of synovium could differentiate between healthy and arthritic knees. Gadolinium-enhanced dynamic FLASH imaging may provide clinically useful information about the actual inflammatory activity of arthritic joints....

  17. [The optimizing influence of melatonin on the behavioral activity of cognitive enhancers].

    Science.gov (United States)

    Beĭer, É V; Khazhbiev, A A; Arushanian, É B

    2013-01-01

    The pineal hormone melatonin (0.1 mg/kg) differently changed the behavioral shifts induced by piracetam, bilobil, and ginseng in the open-field and elevated plus-maze tests in rats. Melatonin more effectively optimized memory in the model of passive avoidance conditioned reflex. It is suggested that the observed enhancement of the specific activity of nootropic drugs is related to the melatonin-induced changes in the hippocampal activity.

  18. Enhancer of Acetyltransferase Chameau (EAChm) Is a Novel Transcriptional Co-Activator

    OpenAIRE

    Takeya Nakagawa; Tsuyoshi Ikehara; Masamichi Doiguchi; Yuko Imamura; Miki Higashi; Mitsuhiro Yoneda; Takashi Ito

    2015-01-01

    Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT) plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm) famil...

  19. Integration of Bass Enhancement and Active Noise Control System in Automobile Cabin

    OpenAIRE

    Wang, Liang; Gan, Woon Seng; Kuo, Sen M.

    2008-01-01

    With the advancement of digital signal processing technologies, consumers are more concerned with the quality of multimedia entertainment in automobiles. In order to meet this demand, an audio enhancement system is needed to improve bass reproduction and cancel engine noise in the cabins. This paper presents an integrated active noise control system that is based on frequency-sampling filters to track and extract the bass information from the audio signal, and a multifrequency active noise eq...

  20. Synthesis of hierarchical anatase TiO 2 nanostructures with tunable morphology and enhanced photocatalytic activity

    KAUST Repository

    Rahal, Raed

    2012-01-01

    A facile one-pot method to prepare three-dimensional hierarchical nanostructures of titania with good control over their morphologies without the use of hydrofluoric acid is developed. The reaction is performed under microwave irradiation conditions in pure water, and enables enhanced photocatalytic activity. This study indicates that photocatalytic activity depends not only on the surface area but also on the morphology of the titania. © 2012 The Royal Society of Chemistry.

  1. Alendronate promotes osteoblast differentiation and bone formation in ovariectomy-induced osteoporosis through interferon-β/signal transducer and activator of transcription 1 pathway

    Science.gov (United States)

    Ma, Xiaoqing; Xu, Zhongyang; Ding, Shaofeng; Yi, Guangkun; Wang, Qian

    2018-01-01

    Alendronate is commonly used for the treatment of postmenopausal osteoporosis; however, the underlying pathological molecular mechanisms of its action remain unclear. In the present study, the alendronate-treated signaling pathway in bone metabolism in rats with ovariectomy induced by osteoporosis was investigated. Rats with osteoporosis were orally administered alendronate or phosphate-buffered saline (control). In addition, the interferon-β (IFN-β)/signal transducer and activator of transcription 1 (STAT1) signaling pathway was investigated in osteoblasts following treatment with alendronate in vitro and in vivo. During the differentiation period, IFN-β (100 ng/ml) was used to treat the osteoblast cells, and the activity, viability and bone metabolism-associated gene expression levels (STAT1, p-STAT1, Fra1, TRAF6 and SOCS1) were analyzed in osteoblast cells. Histopathological changes were used to evaluate osteoblasts, osteoclasts, inflammatory phase of bone healing and osteonecrotic areas. The results demonstrated that alendronate significantly inhibited the activity of osteoporotic osteoclasts by stimulating expression of IFN-β, as well as markedly improved the viability and activity of osteoblasts compared with the control group. In addition, alendronate increased the expression and phosphorylation levels of STAT1 in osteoclasts, enhanced osteoblast differentiation, upregulated the expression levels of alkaline phosphatase and osteocalcin, and increased the expression of osteoblast differentiation-associated genes (osteocalcin, osterix and Runx2). Inhibition of IFN-β expression canceled the benefits of alendronate-mediated osteoblast differentiation. Notably, alendronate enhanced bone formation in rats with osteoporosis induced by ovariectomy. In conclusion, these findings suggest that alendronate can regulate osteoblast differentiation and bone formation in rats with osteoporosis induced by ovariectomy through upregulation of IFN-β/STAT1 signaling

  2. Bicarbonate enhances the in vitro antibiotic activity of kanamycin in Escherichia coli.

    Science.gov (United States)

    Gutiérrez-Huante, M; Martínez, H; Bustamante, V H; Puente, J L; Sánchez, J

    2015-05-01

    Growth of enteropathogenic Escherichia coli E2348/69 was inhibited by bicarbonate in a dose-dependent manner, showing approximately 5% growth reduction at 5 mmol l(-1) while kanamycin at 3·12 μg ml(-1) inhibited growth by 15%, yet when kanamycin and bicarbonate were combined at these concentrations, inhibition increased to 80%. Unexpectedly, at bicarbonate concentrations >20 mmol l(-1) enhancement of the antibiotic activity virtually disappeared, i.e. there was a paradoxical Eagle-like effect. How bicarbonate acts is unclear, but neutral or alkaline pH also enhanced the activity of kanamycin. However, several differences indicated a separate effect of bicarbonate. First, bicarbonate inhibited growth more than the corresponding increments in pH. Second, at low concentration, the antibiotic enhancing effect of bicarbonate was stronger than the effect of pH alone. Third, 5 mmol l(-1) bicarbonate significantly enhanced the activity of kanamycin while the corresponding pH had no effect. Fourth, the Eagle-like effect was exclusive of bicarbonate because changes in pH did not induce an analogous behaviour. Notwithstanding the mechanism, the enhancing effect of bicarbonate was indubitable. Consequently, it seems worthwhile to explore further its potential to improve the efficacy of aminoglycosides and maybe even other antibiotics. Bicarbonate at a low concentration enhanced the in vitro antibiotic activity of kanamycin and gentamicin. Even though the action mechanism of bicarbonate is hitherto unknown, it seems worthwhile to explore further its capacity to improve the efficacy of aminoglycosides. Clearly, the well-known harmful side-effects of aminoglycosides are a concern. However, it has recently been shown in a fish model that bicarbonate may protect ciliary cells against the damage caused by aminoglycosides. So, it seems possible that bicarbonate could help reduce aminoglycoside dosage at the same time that it might help lessen the damage to auditory ciliary cells in

  3. The absorption of gases in aqueous activated carbon slurries enhanced by adsorbing or catalytic particles

    NARCIS (Netherlands)

    Holstvoogd, R.D.; van Swaaij, Willibrordus Petrus Maria; van Dierendonck, L.L.

    1988-01-01

    The enhanced absorption of gases in aqueous activated carbon slurries of fine particles is studied with an instationary absorption model taking into account the finite adsorption capacity of the carbon particles, and with a stationary geometrical model, which describes the absorption into a highly

  4. Single crystalline tantalum oxychloride microcubes: controllable synthesis, formation mechanism and enhanced photocatalytic hydrogen production activity.

    Science.gov (United States)

    Tu, Hao; Xu, Leilei; Mou, Fangzhi; Guan, Jianguo

    2015-08-11

    Single crystalline microcubes of a new tantalum compound, tantalum oxychloride (TaO2.18Cl0.64), have been fabricated hydrothermally in a concentrated aqueous solution of hydrochloric acid and acetic acid. They contain a superstructure and exhibit remarkably enhanced photocatalytic activities for hydrogen production due to the improved light harvest and facilitated charge transport.

  5. Reproducibility and relative validity of the Short Questionnaire to Assess Health-enhancing physical activity

    NARCIS (Netherlands)

    Wendel-Vos, G.C.W.; Schuit, A.J.; Saris, W.H.M.; Kromhout, D.

    2003-01-01

    Objective: The purpose of this study is to determine reproducibility and relative validity of the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH). Methods: Participants (36 men and 14 women, aged 27-58) were asked to complete the SQUASH twice with an inbetween period of

  6. Cross-sector cooperation in health-enhancing physical activity policymaking

    DEFF Research Database (Denmark)

    Hämäläinen, Riitta-Maija; Aro, Arja R.; Juel Lau, Cathrine

    2016-01-01

    in health-enhancing physical activity (HEPA) policies in six European Union (EU) member states. METHODS: Qualitative content analysis of HEPA policies and semi-structured interviews with key policymakers in six European countries. RESULTS: Cross-sector cooperation varied between EU member states within HEPA...

  7. Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

    Directory of Open Access Journals (Sweden)

    Soo-Yeon Lee

    2018-01-01

    Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

  8. Bioengineered Nisin A Derivatives with Enhanced Activity against Both Gram Positive and Gram Negative Pathogens

    Science.gov (United States)

    Field, Des; Begley, Maire; O’Connor, Paula M.; Daly, Karen M.; Hugenholtz, Floor; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

    2012-01-01

    Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G), with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E) with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria. PMID:23056510

  9. Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens.

    Directory of Open Access Journals (Sweden)

    Des Field

    Full Text Available Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G, with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria.

  10. Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease

    OpenAIRE

    Rombouts, S.; Barkhof, F; van Meel, C S; Scheltens, P

    2002-01-01

    Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition.

  11. The Creative Brain: Corepresenting Schema Violations Enhances TPJ Activity and Boosts Cognitive Flexibility

    Science.gov (United States)

    Ritter, Simone M.; Kühn, Simone; Müller, Barbara C. N.; van Baaren, Rick B.; Brass, Marcel; Dijksterhuis, Ap

    2014-01-01

    Cognitive flexibility is one of the essential mental abilities underlying creative thinking. Previous findings have shown that cognitive flexibility can be enhanced by schema violations, and it has been suggested that active involvement is needed for schema violations to facilitate cognitive flexibility. The possibility that identification with an…

  12. Chronic Enhancement of CREB Activity in the Hippocampus Interferes with the Retrieval of Spatial Information

    Science.gov (United States)

    Viosca, Jose; Malleret, Gael; Bourtchouladze, Rusiko; Benito, Eva; Vronskava, Svetlana; Kandel, Eric R.; Barco, Angel

    2009-01-01

    The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a…

  13. Participation in Sports-Related Extracurricular Activities: A Strategy That Enhances School Engagement

    Science.gov (United States)

    St-Amand, Jerome; Girard, Stéphanie; Hiroux, Marie-Hélène; Smith, Jonathan

    2017-01-01

    This article outlines a strategy that we, as high school teachers, used in the academic year 2012-2013 to improve a student's school engagement. Extracurricular activities such as sports have proven useful (among other strategies) to counter school disengagement, specifically in enhancing positive social relations among the teachers and students…

  14. Effects of Active Learning on Enhancing Student Critical Thinking in an Undergraduate General Science Course

    Science.gov (United States)

    Kim, Kyoungna; Sharma, Priya; Land, Susan M.; Furlong, Kevin P.

    2013-01-01

    To enhance students' critical thinking in an undergraduate general science course, we designed and implemented active learning modules by incorporating group-based learning with authentic tasks, scaffolding, and individual reports. This study examined the levels of critical thinking students exhibited in individual reports and the students'…

  15. Adalimumab treatment may replace or enhance the activity of steroids in steroid-refractory tuberculous meningitis.

    Science.gov (United States)

    Lee, Ho-Su; Lee, Yumi; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

    2012-08-01

    We describe a paradoxical response involving the central nervous system in a patient with steroid-refractory tuberculous meningitis that was unresponsive to systemic corticosteroids but was improved with adalimumab. The immunomodulatory effect of tumor necrosis factor inhibitors may have a role in replacing or enhancing the activity of steroids in the management of steroid-refractory tuberculous meningitis.

  16. A non-toxic herbal remedy which enhance lymphocyte activity and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-11-19

    Nov 19, 2008 ... A non-toxic herbal remedy which enhance lymphocyte activity and cytokine secretion: Ganoderma lucidum. Hao Liang1, Wings TY Loo2, Barry H.S. Yeung3, Mary NB Cheung2, Min Wang1, JP Chen4*. 1State Key Laboratory for Oral Diseases and Department of Prosthodontics, West China Hospital of ...

  17. Virtual nature environment with nature sound exposure induce stress recovery by enhanced parasympathetic activity

    DEFF Research Database (Denmark)

    Annerstedt, Matilda; Jönsson, Peter; Wallergård, Mattias

    2013-01-01

    of nature) and in one control condition. Cardiovascular data and saliva cortisol were collected. Repeated ANOVA measurements indicated parasympathetic activation in the group subjected to sounds of nature in a virtual natural environment, suggesting enhanced stress recovery may occur in such surroundings...

  18. Does the Room Matter? Active Learning in Traditional and Enhanced Lecture Spaces

    Science.gov (United States)

    Stoltzfus, Jon R.; Libarkin, Julie

    2016-01-01

    SCALE-UP–type classrooms, originating with the Student-Centered Active Learning Environment with Upside-down Pedagogies project, are designed to facilitate active learning by maximizing opportunities for interactions between students and embedding technology in the classroom. Positive impacts when active learning replaces lecture are well documented, both in traditional lecture halls and SCALE-UP–type classrooms. However, few studies have carefully analyzed student outcomes when comparable active learning–based instruction takes place in a traditional lecture hall and a SCALE-UP–type classroom. Using a quasi-experimental design, we compared student perceptions and performance between sections of a nonmajors biology course, one taught in a traditional lecture hall and one taught in a SCALE-UP–type classroom. Instruction in both sections followed a flipped model that relied heavily on cooperative learning and was as identical as possible given the infrastructure differences between classrooms. Results showed that students in both sections thought that SCALE-UP infrastructure would enhance performance. However, measures of actual student performance showed no difference between the two sections. We conclude that, while SCALE-UP–type classrooms may facilitate implementation of active learning, it is the active learning and not the SCALE-UP infrastructure that enhances student performance. As a consequence, we suggest that institutions can modify existing classrooms to enhance student engagement without incorporating expensive technology. PMID:27909018

  19. Developing design-based STEM education learning activities to enhance students' creative thinking

    Science.gov (United States)

    Pinasa, Siwa; Siripun, Kulpatsorn; Yuenyong, Chokchai

    2018-01-01

    Creative thinking on applying science and mathematics knowledge is required by the future STEM career. The STEM education should be provided for the required skills of future STEM career. This paper aimed to clarify the developing STEM education learning activities to enhance students' creative thinking. The learning activities were developed for Grade 10 students who will study in the subject of independent study (IS) of Khon Kaen Wittayayon School, Khon Kaen, Thailand. The developing STEM education learning activities for enhancing students' creative thinking was developed regarding on 6 steps including (1) providing of understanding of fundamental STEM education concept, (2) generating creative thinking from prototype, (4) revised ideas, (5) engineering ability, and (6) presentation and discussion. The paper will clarify the 18 weeks activities that will be provided based these 6 steps of developing learning activities. Then, these STEM learning activities will be discussed to provide the chance of enhancing students' creative thinking. The paper may have implication for STEM education in school setting.

  20. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Manpreet S. Chahal

    2010-07-01

    Full Text Available Phospholipase D2 (PLD2 generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  1. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.

    Science.gov (United States)

    Chahal, Manpreet S; Brauner, Daniel J; Meier, Kathryn E

    2010-07-02

    Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  2. Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity.

    Science.gov (United States)

    De Franco, Antonio; Di Veronica, Alessandra; Armuzzi, Alessandro; Roberto, Italia; Marzo, Manuela; De Pascalis, Barbara; De Vitis, Italo; Papa, Alfredo; Bock, Enrico; Danza, Francesco M; Bonomo, Lorenzo; Guidi, Luisa

    2012-02-01

    To quantitatively assess microvascular activation in the thickened ileal walls of patients with Crohn disease (CD) by using contrast-enhanced ultrasonography (US) and evaluate its correlation with widely used indexes of CD activity. This prospective study was approved by the ethics committee, and written informed consent was obtained from all patients. The authors examined 54 consecutively enrolled patients (mean age, 35.29 years; age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the terminal ileum. Ileal wall segments thicker than 3 mm were examined with low-mechanical-index contrast-enhanced US and a second-generation US contrast agent. The authors analyzed software-plotted time-enhancement intensity curves to determine the maximum peak intensity (MPI) and wash-in slope coefficient (β) and evaluated their correlation with (a) the composite index of CD activity (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum. Statistical analysis was performed with the Mann-Whitney test, Spearman rank test, and receiver operating characteristic (ROC) analysis. MPI and β coefficients were significantly increased in the 36 patients with a CICDA indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES-CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed accurate identification (compared with CICDA) of active CD with an MPI threshold of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a β coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). Contrast-enhanced US of the ileal wall is a promising method for objective, reproducible assessment of disease activity in patients with ileal CD. © RSNA, 2011

  3. Nitro-Substituted Hoveyda-Grubbs Ruthenium Carbenes : Enhancement of Catalyst Activity through Electronic Activation

    NARCIS (Netherlands)

    Michrowska, Anna; Bujok, Robert; Harutyunyan, Syuzanna; Sashuk, Volodymyr; Dolgonos, Grigory; Grela, Karol

    2004-01-01

    The design, synthesis, stability, and catalytic activity of nitro-substituted Hoveyda-Grubbs metathesis catalysts are described. The highly active and stable meta- and para-substituted complexes are attractive from a practical point of view. These catalysts operate in very mild conditions and can be

  4. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  5. Educating Students for a Lifetime of Physical Activity: Enhancing Mindfulness, Motivation, and Meaning.

    Science.gov (United States)

    Ennis, Catherine D

    2017-09-01

    For many years, pedagogical scholars and physical education (PE) teachers have worked to enhance effective teaching and learning environments. Yet for some children, youth, and young adults, many of the benefits associated with a physically active lifestyle remain elusive. Enhancing programming and performance to meet physical activity goals may require moving programs beyond "effective." It will require teachers and program leaders to focus programmatic attention on strategies to actually increase students' out-of-class physical activity behavior. Transformative PE provides physical activity content within a nurturing and motivating environment that can change students' lives. It focuses on PE students' role in cognitive decision making, self-motivation, and their search for personal meaning that can add connection and relevance to physical activities. In this SHAPE America - Society of Health and Physical Educators Research Quarterly for Exercise and Sport Lecture, I have synthesized the research on these topics to emphasize useful findings applicable to teachers' everyday planning and teaching. Using sport, physical activity, dance, and adventure activities as the means to an end for personal and social growth, we can meet our commitment to effective standards-based education while preparing students for a lifetime of physical activity.

  6. Impairment of GABA transporter GAT-1 terminates cortical recurrent network activity via enhanced phasic inhibition

    Directory of Open Access Journals (Sweden)

    Daniel Simon Razik

    2013-09-01

    Full Text Available In the central nervous system, GABA transporters (GATs very efficiently clear synaptically released GABA from the extracellular space, and thus exert a tight control on GABAergic inhibition. In neocortex, GABAergic inhibition is heavily recruited during recurrent phases of spontaneous action potential activity which alternate with neuronally quiet periods. Therefore, such activity should be quite sensitive to minute alterations of GAT function. Here, we explored the effects of a gradual impairment of GAT-1 and GAT-2/3 on spontaneous recurrent network activity – termed network bursts and silent periods – in organotypic slice cultures of rat neocortex. The GAT-1 specific antagonist NO-711 depressed activity already at nanomolar concentrations (IC50 for depression of spontaneous multiunit firing rate of 42 nM, reaching a level of 80% at 500-1000 nM. By contrast, the GAT-2/3 preferring antagonist SNAP-5114 had weaker and less consistent effects. Several lines of evidence pointed towards an enhancement of phasic GABAergic inhibition as the dominant activity-depressing mechanism: network bursts were drastically shortened, phasic GABAergic currents decayed slower, and neuronal excitability during ongoing activity was diminished. In silent periods, NO-711 had little effect on neuronal excitability or membrane resistance, quite in contrast to the effects of muscimol, a GABA mimetic which activates GABAA receptors tonically. Our results suggest that an enhancement of phasic GABAergic inhibition efficiently curtails cortical recurrent activity and may mediate antiepileptic effects of therapeutically relevant concentrations of GAT-1 antagonists.

  7. Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities.

    Science.gov (United States)

    Cho, Namki; Lee, Ki Yong; Huh, Jungmoo; Choi, Ji Hoon; Yang, Heejung; Jeong, Eun Ju; Kim, Hong Pyo; Sung, Sang Hyun

    2013-08-01

    The neuroprotective potential of flavonoids within the brain comprises anti-apoptosis of neuronal cells, anti-neuroinflammation and enhancement of cognitive function. We reported that Rhus vernciflua inhibits glutamate-induced neurotoxicity in primary cultured rat cortical cells. Here we narrowed it down to get neuroprotective fractions from the plant yielding flavonoid-rich ethyl acetate fraction (PREF). Among its active flavonoids, fisetin exhibited not only inhibitory effect against lipopolysaccharide (LPS)-induced neuroinflammation by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also memory enhancing effects via reactivation of cAMP responsive element binding protein (CREB)-brain derived neurotrophic factor (BDNF) pathway in memory-impaired mice by scopolamine. Butein also showed a similar activity to fisetin even though to a lesser extent. The neuroprotection by PREF and selected flavonoids may involve maintenance of antioxidant defense mechanism including glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). Conclusively, we demonstrate the R. vernciflua bark extract and its active flavonoids with potent neuroprotective and anti-inflammatory effects might be good therapeutic candidates as cognitive-enhancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Investigation of repressive and enhancive effects of fruit extracts on the activity of glucose-6-phophatase.

    Science.gov (United States)

    Zahoor, Muhammad; Jan, Muhammad Rasul; Naz, Sumaira

    2016-11-01

    Glucose-6-phosphatase is a key enzyme of glucose metabolic pathways. Deficiency of this enzyme leads to glycogen storage disease. This enzyme also plays a negative role in diabetes mellitus disorder in which the catalytic activity of this enzyme increases. Thus there is need for activators to enhance the activity of glucose-6-phosphatase in glycogen storage disease of type 1b while in diabetes mellitus repressors are needed to reduce its activity. Crude extracts of apricot, fig, mulberry and apple fruits were investigated for their repressive/enhancive effects on glucose-6-phosphatase in vivo. Albino mice were used as experimental animal. All the selected extracts showed depressive effects on glucose-6-phosphatase, which shows that all these extracts can be used as antidiabetic supplement of food. The inhibitory pattern was competitive one, which was evident from the effect of increasing dose from 1g/Kg body weight to 3g/Kg body weight for all the selected fruit extracts. However fig and apple fruit extracts showed high repressive effects for high doses as compared to apricot and mulberry fruit extracts. None of these selected fruit extracts showed enhancive effect on glucose-6-phosphatase activity. All these fruits or their extracts can be used as antidiabetic dietary supplement for diabetes mellitus.

  9. RNA cleaving '10-23' DNAzymes with enhanced stability and activity.

    Science.gov (United States)

    Schubert, Steffen; Gül, Deniz C; Grunert, Hans-Peter; Zeichhardt, Heinz; Erdmann, Volker A; Kurreck, Jens

    2003-10-15

    '10-23' DNAzymes can be used to cleave any target RNA in a sequence-specific manner. For applications in vivo, they have to be stabilised against nucleolytic attack by the introduction of modified nucleotides without obstructing cleavage activity. In this study, we optimise the design of a DNAzyme targeting the 5'-non-translated region of the human rhinovirus 14, a common cold virus, with regard to its kinetic properties and its stability against nucleases. We compare a large number of DNAzymes against the same target site that are stabilised by the use of a 3'-3'-inverted thymidine, phosphorothioate linkages, 2'-O-methyl RNA and locked nucleic acids, respectively. Both cleavage activity and nuclease stability were significantly enhanced by optimisation of arm length and content of modified nucleotides. Furthermore, we introduced modified nucleotides into the catalytic core to enhance stability against endonucleolytic degradation without abolishing catalytic activity. Our findings enabled us to establish a design for DNAzymes containing nucleotide modifications both in the binding arms and in the catalytic core, yielding a species with up to 10-fold enhanced activity and significantly elevated stability against nucleolytic cleavage. When transferring the design to a DNAzyme against a different target, only a slight modification was necessary to retain activity.

  10. Strategies to enhance biologically active-secondary metabolites in cell cultures of Artemisia - current trends.

    Science.gov (United States)

    Ali, Mohammad; Abbasi, Bilal Haider; Ahmad, Nisar; Khan, Haji; Ali, Gul Shad

    2017-11-01

    The genus Artemisia has been utilized worldwide due to its immense potential for protection against various diseases, especially malaria. Artemisia absinthium, previously renowned for its utilization in the popular beverage absinthe, is gaining resurgence due to its extensive pharmacological activities. Like A. annua, this species exhibits strong biological activities like antimalarial, anticancer and antioxidant. Although artemisinin was found to be the major metabolite for its antimalarial effects, several flavonoids and terpenoids are considered to possess biological activities when used alone and also to synergistically boost the bioavailability of artemisinin. However, due to the limited quantities of these metabolites in wild plants, in vitro cultures were established and strategies have been adopted to enhance medicinally important secondary metabolites in these cultures. This review elaborates on the traditional medicinal uses of Artemisia species and explains current trends to establish cell cultures of A. annua and A. absinthium for enhanced production of medicinally important secondary metabolites.

  11. Enhancer of Acetyltransferase Chameau (EAChm Is a Novel Transcriptional Co-Activator.

    Directory of Open Access Journals (Sweden)

    Takeya Nakagawa

    Full Text Available Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm family. EAChm is a negatively charged acidic protein retaining aspartate and glutamate. Furthermore, we identified that Chameau and EAChm stimulate transcription in vitro together with purified general transcription factors. In addition, RNA-seq analysis of Chameu KD and EAChm KD S2 cells suggest that Chameau and EAChm regulate transcription of common genes in vivo. Our results suggest that EAChm regulates gene transcription in Drosophila embryos by enhancing Acetyltransferase Chameau activity.

  12. Enhancer of Acetyltransferase Chameau (EAChm) Is a Novel Transcriptional Co-Activator.

    Science.gov (United States)

    Nakagawa, Takeya; Ikehara, Tsuyoshi; Doiguchi, Masamichi; Imamura, Yuko; Higashi, Miki; Yoneda, Mitsuhiro; Ito, Takashi

    2015-01-01

    Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT) plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm) family. EAChm is a negatively charged acidic protein retaining aspartate and glutamate. Furthermore, we identified that Chameau and EAChm stimulate transcription in vitro together with purified general transcription factors. In addition, RNA-seq analysis of Chameu KD and EAChm KD S2 cells suggest that Chameau and EAChm regulate transcription of common genes in vivo. Our results suggest that EAChm regulates gene transcription in Drosophila embryos by enhancing Acetyltransferase Chameau activity.

  13. A general approach toward enhancement of pseudocapacitive performance of conducting polymers by redox-active electrolytes

    KAUST Repository

    Chen, Wei

    2014-12-01

    A general approach is demonstrated where the pseudocapacitive performance of different conducting polymers is enhanced in redox-active electrolytes. The concept is demonstrated using several electroactive conducting polymers, including polyaniline, polypyrrole, and poly(3,4-ethylenedioxythiophene). As compared to conventional electrolytes, the redox-active electrolytes, prepared by simply adding a redox mediator to the conventional electrolyte, can significantly improve the energy storage capacity of pseudocapacitors with different conducting polymers. The results show that the specific capacitance of conducting polymer based pseudocapacitors can be increased by a factor of two by utilization of the redox-active electrolytes. In fact, this approach gives some of the highest reported specific capacitance values for electroactive conducting polymers. Moreover, our findings present a general and effective approach for the enhancement of energy storage performance of pseudocapacitors using a variety of polymeric electrode materials. © 2014 Elsevier B.V. All rights reserved.

  14. Immune-enhancing activity of extracellular polysaccharides isolated from Rhizopus nigricans.

    Science.gov (United States)

    Yu, Zhidan; Kong, Mengli; Zhang, Pengying; Sun, Qingjie; Chen, Kaoshan

    2016-09-05

    Extracellular polysaccharides (EPS1-1) was extracted from fermentation liquor of Rhizopus nigricans and evaluated its immune-enhancing activities in vitro and in vivo. Results suggested that the proliferation of lymphocyte was stimulated after treated with EPS1-1. Moreover, the activities of macrophages were enhanced by increasing the activities of phagocytosis and acid phosphatase, the production of NO and the mRNA levels of IL-2, TNF-α and iNOS. Furthermore, EPS1-1 could significantly boost the immunity of normal and immunosuppressed mice, which included the increase of loaded swimming time, footpad swelling, organ index and the secretion of IL-2 and TNF-α in serum, thus suggesting that EPS1-1 could improve the body immunity through cellular immunity and humoral immunity. These findings provided further insights into the potential use of EPS1-1 as immunopotentiator or new function food. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Triterpenoids Isolated from Ziziphus jujuba Enhance Glucose Uptake Activity in Skeletal Muscle Cells.

    Science.gov (United States)

    Kawabata, Kyuichi; Kitamura, Kenji; Irie, Kazuhiro; Naruse, Shoma; Matsuura, Tomohiro; Uemae, Tomoyuki; Taira, Shu; Ohigashi, Hajime; Murakami, Shigeru; Takahashi, Masakazu; Kaido, Yoko; Kawakami, Bunsei

    2017-01-01

    Jujube (Ziziphus jujuba Mill.), a traditional folk medicine and functional food in China and South Korea, is known for its beneficial properties, which include anti-cancer, anti-oxidative, and anti-obesity effects. To assess the anti-hyperglycemic effect of jujube in this study, we investigated the glucose uptake-promoting activity of jujube in rat L6 myotubes. After determining that the jujube extract induces muscle glucose uptake, we identified the following active compounds by bioassay-guided fractionation: betulonic acid, betulinic acid, and oleanonic acid. Ursonic acid, known to be present in jujube, was semi-synthesized from ursolic acid and also observed to enhance glucose uptake. These four triterpenic acids induced glucose uptake in a glucose transporter 4-dependent manner. Comparison experiments of jujube fruits from three countries, namely, China, South Korea, and Japan, revealed that Japanese jujube has a higher content of active triterpenoids and is the most potent enhancer of glucose uptake.

  16. Enhancement Experiment on Cementitious Activity of Copper-Mine Tailings in a Geopolymer System

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2017-12-01

    Full Text Available Copper-mine tailings are the residual products after the extraction of precious copper metal from copper ores, and their storage can create numerous environmental problems. Many researchers have used copper-mine tailings for the preparation of geopolymers. This paper studies the enhancement of the cementitious activity of copper-mine tailings in geopolymer systems. First, copper-mine tailings are activated through mechanical grinding activation. Then, the mechanically activated copper-mine tailings are further processed through thermal activation and alkaline-roasting activation. The cementitious activity index of copper-mine tailings is characterized through the degree of leaching concentration of Si and Al. It was observed that the Si and Al leaching concentration of mechanically activated tailings was increased by 26.03% and 93.33%, respectively. The concentration of Si and Al was increased by 54.19% and 119.92%, respectively. For alkaline-roasting activation, roasting time, temperature and the mass ratio of copper-mine tailings to NaOH (C/N ratio were evaluated through orthogonal tests, and the best condition for activation was 120 min at 600 °C with a C/N ratio of 5:1. In this study, scanning electron microscopy (SEM, X-ray diffraction (XRD and infra-red (IR analysis show that mechanical, thermal and alkaline-roasting activation could be used to improve the cementitious activity index of copper-mine tailings.

  17. Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles.

    Science.gov (United States)

    Bernela, Manju; Ahuja, Munish; Thakur, Rajesh

    2016-06-05

    Bromelain-loaded katira gum nanoparticles were synthesized using 3 level optimization process and desirability approach. Nanoparticles of the optimized batch were characterized using particle size analysis, zeta potential, transmission electron microscopy and Fourier-transform infrared spectroscopy. Investigation of their in vivo anti-inflammatory activity by employing carrageenan induced rat-paw oedema method showed that encapsulation of bromelain in katira gum nanoparticles substantially enhanced its anti-inflammatory potential. This may be attributed to enhanced absorption owing to reduced particle size or to protection of bromelain from acid proteases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Active enhancement methods for intra- and transdermal drug delivery: a review

    Directory of Open Access Journals (Sweden)

    Barbara Zorec

    2013-05-01

    Full Text Available Transdermal route has some advantages over other drug administration routes. These include avoidance of first pass effect (hepatic metabolism, better pharmacokinetic profile, reduction of side effects and good patient compliance. The greatest obstacle for the drugs to be delivered through the skin is overcoming the impermeable outermost layer of the skin – the stratum corneum. Quite a few enhancement techniques can be used to overcome the stratum corneum barrier and facilitate transdermal drug delivery. These include various passive (penetration enhancers, liposomes and active approaches (electroporation, iontophoresis, microneedles, which are of prime interest for transdermal drug delivery research area.

  19. The Effect of a Voice Activity Detector on the Speech Enhancement

    DEFF Research Database (Denmark)

    Dau, Torsten; Catic, Jasmina; Buchholz, Jörg

    2010-01-01

    of a VAD on the speech enhancement of this algorithm was evaluated using an envelopebased VAD, and the performance was compared to that achieved using an ideal error-free VAD. The performance was considered for stationary directional noise and nonstationary diffuse noise interferers at input SNRs from −10......A multimicrophone speech enhancement algorithm for binaural hearing aids that preserves interaural time delays was proposed recently. The algorithm is based on multichannel Wiener filtering and relies on a voice activity detector (VAD) for estimation of second-order statistics. Here, the effect...

  20. Investigation of effects of terpene skin penetration enhancers on stability and biological activity of lysozyme.

    Science.gov (United States)

    Varman, Rahul M; Singh, Somnath

    2012-12-01

    The transport of proteins through skin can be facilitated potentially by using terpenes as chemical enhancers. However, we do not know about the effects of these enhancers on the stability and biological activity of proteins which is crucial for the development of safe and efficient formulations. Therefore, this project investigated the effects of terpene-based skin penetration enhancers which are reported as nontoxic to the skin (e.g., limonene, p-cymene, geraniol, farnesol, eugenol, menthol, terpineol, carveol, carvone, fenchone, and verbenone), on the conformational stability and biological activity of a model protein lysozyme. Terpene (5% v/v) was added to lysozyme solution and kept for 24 h (the time normally a transdermal patch remains) for investigating conformational stability profiles and biological activity. Fourier transform infrared spectrophotometer was used to analyze different secondary structures, e.g., α-helix, β-sheet, β-turn, and random coil. Conformational changes were also monitored by differential scanning calorimeter by determining midpoint transition temperature (Tm) and calorimetric enthalpy (ΔH). Biological activity of lysozyme was determined by measuring decrease in A (450) when it was added to a suspension of Micrococcus lysodeikticus. The results of this study indicate that terpenes 9, 10, and 11 (carvone, L-fenchone, and L-verbenone) decreased conformational stability and biological activity of lysozyme significantly (p terpenes used in this study. It is concluded that smaller terpenes containing ketones with low lipophilicity (log K (ow) ∼2.00) would be optimal for preserving conformational stability and biological activity of lysozyme in a transdermal formulation containing terpene as permeation enhancer.

  1. Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer

    Directory of Open Access Journals (Sweden)

    Tai Phillip WL

    2011-07-01

    Full Text Available Abstract Background Hundreds of genes, including muscle creatine kinase (MCK, are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood. Results Modulatory region 1 (MR1 is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE containing a paired E-box/myocyte enhancer factor 2 (MEF2 regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively, but is not required for expression in fast-twitch muscle fibers (types IIb and IId. Conclusions In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

  2. Health game interventions to enhance physical activity self-efficacy of children: a quantitative systematic review.

    Science.gov (United States)

    Pakarinen, Anni; Parisod, Heidi; Smed, Jouni; Salanterä, Sanna

    2017-04-01

    To describe and explore health game interventions that enhance the physical activity self-efficacy of children and to evaluate the effectiveness of these interventions. Physical inactivity among children has increased globally. Self-efficacy is one of the key determinants of physical activity engagement in children. There is a need to explore new and innovative interventions to enhance physical activity self-efficacy that are also acceptable for today's children. Quantitative systematic review. MEDLINE (Ovid), CINAHL, PsychInfo, EMBASE and the Cochrane Library between 1996-2016. A review was conducted in accordance with the Cochrane Collaboration guidelines. A systematic search was done in June 2016 by two independent reviewers according to the eligibility criteria as follows: controlled trial, comparison of digital game intervention with no game intervention control condition, participants younger than 18 years of age and reported statistical analyses of a physical activity self-efficacy outcome measure. Altogether, five studies met the eligibility criteria. Four game interventions, employing three active games and one educational game, had positive effects on children's physical activity self-efficacy. An intervention, employing a game-themed mobile application, showed no intervention effects. The variation between intervention characteristics was significant and the quality of the studies was found to be at a medium level. Although health game interventions seemingly enhance the physical activity self-efficacy of children and have potential as a means of increasing physical activity, more rigorous research is needed to clarify how effective such interventions are in the longer run to contribute to the development of game-based interventions. © 2016 John Wiley & Sons Ltd.

  3. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.

    Science.gov (United States)

    Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

    2012-11-01

    We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥ 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.

  4. Memory-Enhancing Activity of Palmatine in Mice Using Elevated Plus Maze and Morris Water Maze

    Directory of Open Access Journals (Sweden)

    Dinesh Dhingra

    2012-01-01

    Full Text Available The present study was designed to evaluate the effect of palmatine on memory of Swiss young male albino mice. Palmatine (0.1, 0.5, 1 mg/kg, i.p. and physostigmine (0.1 mg/kg, i.p. per se were administered for 10 successive days to separate groups of mice. Effect of drugs on learning and memory of mice was evaluated using elevated plus maze and Morris water maze. Brain acetylcholinesterase activity was also estimated. Effect of palmatine on scopolamine- and diazepam-induced amnesia was also investigated. Palmatine (0.5 and 1 mg/kg and physostigmine significantly improved learning and memory of mice, as indicated by decrease in transfer latency using elevated plus maze, and decrease in escape latency during training and increase in time spent in target quadrant during retrieval using Morris water maze. The drugs did not show any significant effect on locomotor activity of the mice. Memory-enhancing activity of palmatine (1 mg/kg was comparable to physostigmine. Palmatine (1 mg/kg significantly reversed scopolamine- and diazepam-induced amnesia in mice. Palmatine and physostigmine also significantly reduced brain acetylcholinesterase activity of mice. Thus, palmatine showed memory-enhancing activity in mice probably by inhibiting brain acetylcholinesterase activity, through involvement of GABA-benzodiazepine pathway, and due to its antioxidant activity.

  5. Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

    Science.gov (United States)

    Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

    2015-12-01

    Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

    Science.gov (United States)

    Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

    2011-01-01

    Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

  7. Enhancement of collaboration activities utilizing 21st century learning design rubric

    Science.gov (United States)

    Cubero, Dave D.; Gargar, Clare V., Lady; Nallano, Gerlett Grace D.; Magsayo, Joy R.; Guarin, Rica Mae B.; Lahoylahoy, Myrna E.

    2018-01-01

    Twenty first century learners have incredibly diverse learning interests, needs, and aspirations. Engaging middle school students and sculpting successful, confident, and creative learners is a constant endeavor for educators [4]. In the 21st century classroom environments in which students can develop the skills they need in workplace. Collaboration occurs when students work together to create, discuss challenge and develop deeper critical thinking. In today's workplace, collaboration is essential as only few tasks are completed alone (Calgary and Park, 2016). The collaborative project-based curriculum used in this classroom develops the higher order thinking skills, effective communication skills, and knowledge of technology that students will need in the 21st century workplace. The study therefore aims to promote collaboration skills among learners as it is deemed as one of the top 21st century skills. Collaborative learning unleashes a unique intellectual and social synergy. This study aims to enhance the collaborative skills of students through conducting collaboration activities in learning the Ecosystem. This research utilizes pretest-posttest and employs descriptive research designs. It uses modified activities about the lesson on Ecosystem and utilizes a Collaboration Rubric to rate the modified activities. The activities were rated by ten In-Service teachers and there are 105 students who participated in doing the activities. The paired t-test is then used to analyze the data. The In-Service teachers evaluated the 1st and 2nd adapted activity and are rated as fair. Thus, the modified activities were enhanced since the ratings of each activity did not meet the criterion of the collaboration rubric. As for the 3rd adapted activity is rated as excellent and is ready for implementation. The evaluators provided comments and suggestions such as producing colored pictures on the activities, omitting some questions, and making the words simpler to enhance the

  8. The theory of expanded, extended, and enhanced opportunities for youth physical activity promotion.

    Science.gov (United States)

    Beets, Michael W; Okely, Anthony; Weaver, R Glenn; Webster, Collin; Lubans, David; Brusseau, Tim; Carson, Russ; Cliff, Dylan P

    2016-11-16

    Physical activity interventions targeting children and adolescents (≤18 years) often focus on complex intra- and inter-personal behavioral constructs, social-ecological frameworks, or some combination of both. Recently published meta-analytical reviews and large-scale randomized controlled trials have demonstrated that these intervention approaches have largely produced minimal or no improvements in young people's physical activity levels. In this paper, we propose that the main reason for previous studies' limited effects is that fundamental mechanisms that lead to change in youth physical activity have often been overlooked or misunderstood. Evidence from observational and experimental studies is presented to support the development of a new theory positing that the primary mechanisms of change in many youth physical activity interventions are approaches that fall into one of the following three categories: (a) the expansion of opportunities for youth to be active by the inclusion of a new occasion to be active, (b) the extension of an existing physical activity opportunity by increasing the amount of time allocated for that opportunity, and/or (c) the enhancement of existing physical activity opportunities through strategies designed to increase physical activity above routine practice. Their application and considerations for intervention design and interpretation are presented. The utility of these mechanisms, referred to as the Theory of Expanded, Extended, and Enhanced Opportunities (TEO), is demonstrated in their parsimony, logical appeal, support with empirical evidence, and the direct and immediate application to numerous settings and contexts. The TEO offers a new way to understand youth physical activity behaviors and provides a common taxonomy by which interventionists can identify appropriate targets for interventions across different settings and contexts. We believe the formalization of the TEO concepts will propel them to the forefront in the

  9. The transcriptional regulator Aire binds to and activates super-enhancers.

    Science.gov (United States)

    Bansal, Kushagra; Yoshida, Hideyuki; Benoist, Christophe; Mathis, Diane

    2017-03-01

    Aire is a transcription factor that controls T cell tolerance by inducing the expression of a large repertoire of genes specifically in thymic stromal cells. It interacts with scores of protein partners of diverse functional classes. We found that Aire and some of its partners, notably those implicated in the DNA-damage response, preferentially localized to and activated long chromatin stretches that were overloaded with transcriptional regulators, known as super-enhancers. We also identified topoisomerase 1 as a cardinal Aire partner that colocalized on super-enhancers and was required for the interaction of Aire with all of its other associates. We propose a model that entails looping of super-enhancers to efficiently deliver Aire-containing complexes to local and distal transcriptional start sites.

  10. Surface modification of activated carbon for enhanced adsorption of perfluoroalkyl acids from aqueous solutions.

    Science.gov (United States)

    Zhi, Yue; Liu, Jinxia

    2016-02-01

    The objective of the research was to examine the effect of increasing carbon surface basicity on uptake of perfluorooctane sulfonic (PFOS) and carboxylic acids (PFOA) by activated carbon. Granular activated carbons made from coal, coconut shell, wood, and phenolic-polymer-based activated carbon fibers were modified through high-temperature and ammonia gas treatments to facilitate systematical evaluation of the impact of basicity of different origins. Comparison of adsorption isotherms and adsorption distribution coefficients showed that the ammonia gas treatment was more effective than the high-temperature treatment in enhancing surface basicity. The resultant higher point of zero charges and total basicity (measured by total HCl uptake) correlated with improved adsorption affinity for PFOS and PFOA. The effectiveness of surface modification to enhance adsorption varied with carbon raw material. Wood-based carbons and activated carbon fibers showed enhancement by one to three orders of magnitudes while other materials could experience reduction in adsorption towards either PFOS or PFOA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Enhanced pharmacological activity of vitamin B₁₂ and penicillin as nanoparticles.

    Science.gov (United States)

    Yariv, Inbar; Lipovsky, Anat; Gedanken, Aharon; Lubart, Rachel; Fixler, Dror

    2015-01-01

    Sonochemistry has become a well-known technique for fabricating nanomaterials. Since one of the advantages of nanomaterials is that they have higher chemical activities compared with particles in the bulk form, efforts are being made to produce nano organic compounds with enhanced biological activities that could be exploited in the medical area. This study uses the sonication technique to prepare nano Vitamin B12 and nano Penicillin, and demonstrates their enhanced biological and pharmacological activity. The size and morphology of the nano Penicillin and nano Vitamin B12 were investigated using electron microscopy as well as dynamic light scattering techniques. The sizes of Penicillin and Vitamin B12 nanoparticles (NPs) were found to be 70 and 120-180 nm, respectively. The bactericidal effect of nano Penicillin was studied and found to be higher than that of the bulk form. Reducing the size of Vitamin B12 resulted in their enhanced antioxidative activity as observed using the electron paramagnetic spectroscopy technique. The penetration depth of these organic NPs can be detected by an optical iterative method. It is believed that nano organic drugs fabrication will have a great impact on the medical field.

  12. Kernel-Based Relevance Analysis with Enhanced Interpretability for Detection of Brain Activity Patterns

    Directory of Open Access Journals (Sweden)

    Andres M. Alvarez-Meza

    2017-10-01

    Full Text Available We introduce Enhanced Kernel-based Relevance Analysis (EKRA that aims to support the automatic identification of brain activity patterns using electroencephalographic recordings. EKRA is a data-driven strategy that incorporates two kernel functions to take advantage of the available joint information, associating neural responses to a given stimulus condition. Regarding this, a Centered Kernel Alignment functional is adjusted to learning the linear projection that best discriminates the input feature set, optimizing the required free parameters automatically. Our approach is carried out in two scenarios: (i feature selection by computing a relevance vector from extracted neural features to facilitating the physiological interpretation of a given brain activity task, and (ii enhanced feature selection to perform an additional transformation of relevant features aiming to improve the overall identification accuracy. Accordingly, we provide an alternative feature relevance analysis strategy that allows improving the system performance while favoring the data interpretability. For the validation purpose, EKRA is tested in two well-known tasks of brain activity: motor imagery discrimination and epileptic seizure detection. The obtained results show that the EKRA approach estimates a relevant representation space extracted from the provided supervised information, emphasizing the salient input features. As a result, our proposal outperforms the state-of-the-art methods regarding brain activity discrimination accuracy with the benefit of enhanced physiological interpretation about the task at hand.

  13. Enhancement of alpha- and beta-galactosidase activity in Lactobacillus reuteri by different metal ions.

    Science.gov (United States)

    Ibrahim, Salam A; Alazzeh, Awfa Y; Awaisheh, Saddam S; Song, Danfeng; Shahbazi, Abolghasem; AbuGhazaleh, Amer A

    2010-07-01

    The hydrolysis of oligosaccharides and lactose is of great importance to the food industry. Normally, oligosaccharides like raffinose, stachyose, and verbascose which are rich in different plants like soy bean are considered indigestible by the human gut. Moreover, many humans suffer from lactose intolerance due to the absence of effective enzyme that can digest lactose. alpha-Galactosidase can digest oligosaccharides like raffinose, while beta-galactosidases can hydrolyze lactose. Therefore, selection of microorganisms safe for human use and capable of producing high levels of enzymes becomes an attractive task. The objective of this study was to investigate the enhancement of alpha- and beta-galactosidase activity in Lactobacillus reuteri by different metal ions. Ten millimolar of Na(+), K(+), Fe(2+), and Mg(2+) and 1 mM of Mn(2+) were added separately to the growth culture of six strains of L. reuteri (CF2-7F, DSM20016, MF14-C, MM2-3, MM7, and SD2112). Results showed that L. reuteri CF2-7F had the highest alpha- and beta-galactosidase activity when grown in the medium with added Mn(2+) ions (22.7 and 19.3 Gal U/ml, respectively). 0.0274% of Mn(2+) ions lead to 27, 18% enhancement of alpha- and beta-galactosidase activity over the control group, and therefore, it could be added to the growth culture of CF2-7F to produce enhanced levels of alpha- and beta-galactosidase activity. The addition of Fe(2+) led to a significant (P production for alpha- and beta-galactosidase in L. reuteri CF2-7F, which may lead to enhancement of alpha- and beta-galactosidase activity and have a good potential to be used in the food industry.

  14. Syndecan-4 enhances PDGF-BB activity in diabetic wound healing.

    Science.gov (United States)

    Das, Subhamoy; Majid, Marjan; Baker, Aaron B

    2016-09-15

    Non-healing ulcers are a common consequence of long-term diabetes and severe peripheral vascular disease. These non-healing wounds are a major source of morbidity in patients with diabetes and place a heavy financial burden on the healthcare system. Growth factor therapies are an attractive strategy for enhancing wound closure in non-healing wounds but have only achieved mixed results in clinical trials. Platelet derived growth factor-BB (PDGF-BB) is the only currently approved growth factor therapy for non-healing wounds. However, PDGF-BB therapy is not effective in many patients and requires high doses that increase the potential for side effects. In this work, we demonstrate that syndecan-4 delivered in a proteoliposomal formulation enhances PDGF-BB activity in diabetic wound healing. In particular, syndecan-4 proteoliposomes enhance the migration of keratinocytes derived from patients with diabetes. In addition, syndecan-4 proteoliposomes sensitize keratinocytes to PDGF-BB stimulation, enhancing the intracellular signaling response to PDGF-BB. We further demonstrated that co-therapy with syndecan-4 proteoliposomes enhanced wound closure in diabetic, hyperlipidemic ob/ob mice. Wounds treated with both syndecan-4 proteoliposomes and PDGF-BB had increased re-epithelization and angiogenesis in comparison to wounds treated with PDGF-BB alone. Moreover, the wounds treated with syndecan-4 proteoliposomes and PDGF-BB also had increased M2 macrophages and reduced M1 macrophages, suggesting syndecan-4 delivery induces immunomodulation within the healing wounds. Together our findings support that syndecan-4 proteoliposomes markedly improve PDGF-BB efficacy for wound healing and may be useful in enhancing treatments for non-healing wounds. Non-healing wounds are major healthcare issue for patients with diabetes and peripheral vascular disease. Growth factor therapies have potential for healing chronic wounds but have not been effective for many patients. PDGF-BB is

  15. Enhancement of cloud-to-ground lightning activity over Taipei, Taiwan in relation to urbanization

    Science.gov (United States)

    Kar, S. K.; Liou, Y. A.

    2014-10-01

    Collecting the cloud-to-ground (CG) lightning flash data from Tai-Power Company of Taiwan, a long term study has been performed to investigate the enhancement of lightning activity in and around Taipei City, the largest metropolitan city of Taiwan, in relation to urbanization, for the period of 2005-2010. Results reveal that negative flash density is enhanced by approximately 64% while the positive flash density is enhanced by 48%, over and downwind of the city compared with other neighboring areas. On the other hand a decrease of nearly 24% in the percentage of positive flashes occurs over and downwind of Taipei compared to upwind values. We have also investigated the effect of urbanization on peak current of both polarities but no significant effect is noticed. Possible influence of urban particulate matter on the enhancement of CG lightning activity has been analyzed utilizing the annual averages of PM10 (particulate matter with aerodynamic diameter smaller than 10 μm) and SO2 (sulfur dioxide) concentrations data. Interesting results are found, indicating the higher concentrations of PM10 and SO2 contributes to the CG lightning enhancement. Both the concentrations exhibit a positive linear correlation with the percent change in CG flashes from the upwind to the urban area and from the upwind to the downwind area. However, the correlation coefficient for PM10 concentrations is comparatively much lower than SO2 concentrations. Positive correlations of 0.55 and 0.68 are found for the PM10 and SO2 concentrations, respectively, when compared separately with the percent change in CG flashes from the upwind to the downwind area, indicating the influence of aerosols on urban CG lightning enhancement. Hourly variation of lightning flashes show that the urban effects on CG lightning is prominent in the afternoon and early evening hours. The results obtained from the present analysis corroborate the results reported in the literature by other researchers.

  16. Ag-loaded MgSrFe-layered double hydroxide/chitosan composite scaffold with enhanced osteogenic and antibacterial property for bone engineering tissue.

    Science.gov (United States)

    Cao, Dandan; Xu, Zhengliang; Chen, Yixuan; Ke, Qinfei; Zhang, Changqing; Guo, Yaping

    2018-02-01

    Bone tissue engineering scaffolds for the reconstruction of large bone defects should simultaneously promote osteogenic differentiation and avoid postoperative infection. Herein, we develop, for the first time, Ag-loaded MgSrFe-layered double hydroxide/chitosan (Ag-MgSrFe/CS) composite scaffold. This scaffold exhibits three-dimensional interconnected macroporous structure with a pore size of 100-300 μm. The layered double hydroxide nanoplates in the Ag-MgSrFe/CS show lateral sizes of 200-400 nm and thicknesses of ∼50 nm, and the Ag nanoparticles with particle sizes of ∼20 nm are uniformly dispersed on the scaffold surfaces. Human bone marrow-derived mesenchymal stem cells (hBMSCs) present good adhesion, spreading, and proliferation on the Ag-MgSrFe/CS composite scaffold, suggesting that the Ag and Sr elements in the composite scaffold have no toxicity to hBMSCs. When compared with MgFe/CS composite scaffold, the Ag-MgSrFe/CS composite scaffold has better osteogenic property. The released Sr2+ ions from the composite scaffold enhance the alkaline phosphatase activity of hBMSCs, promote the extracellular matrix mineralization, and increase the expression levels of osteogenic-related RUNX2 and BMP-2. Moreover, the Ag-MgSrFe/CS composite scaffold possesses good antibacterial property because the Ag nanoparticles in the composite scaffold effectively prevent biofilm formation against S. aureus. Hence, the Ag-MgSrFe/CS composite scaffold with excellent osteoinductivity and antibacterial property has a great potential for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 863-873, 2018. © 2017 Wiley Periodicals, Inc.

  17. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders

    2016-01-01

    -ray crystallography, we show that the introduced 170 loop from trypsin directly interacts with the FVIIa active site, stabilizing segment 215-217 and activation loop 3, leading to enhanced activity. Molecular dynamics simulations and novel fluorescence quenching studies support that segment 215-217 conformation...... is pivotal to the enhanced activity of the FVIIa variants. We speculate that the allosteric regulation of FVIIa activity by TF binding follows a similar path in conjunction with protease domain N terminus insertion, suggesting a more complete molecular basis of TF-mediated allosteric enhancement of FVIIa...

  18. Examining factors affecting beginning teachers' transfer of learning of ICT-enhanced learning activities in their teaching practice

    NARCIS (Netherlands)

    Agyei, D.D.; Voogt, J.

    2014-01-01

    This study examined 100 beginning teachers’ transfer of learning when utilising Information Communication Technology-enhanced activity-based learning activities. The beginning teachers had participated in a professional development program that was characterised by ‘learning technology by

  19. Examining factors affecting beginning teachers’ transfer of learning of ICT-enhanced learning activities in their teaching practice

    NARCIS (Netherlands)

    Voogt, Joke; Agyei, Douglas; McBride, Ron; Searson, Michael

    2013-01-01

    This study examined 100 beginning teachers’ transfer of learning in utilizing Information Communication Technology-enhanced activity-based learning activities. The beginning teachers had participated in a professional development program characterized by ‘learning technology by collaborative design’

  20. Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Ring-Larsen, H; Christensen, N J

    1987-01-01

    spillover represents a minimum value. Our results indicate that the augmented circulating catecholamines in cirrhosis do not result from diminished removal but are contributed to from increased sympathetic nervous activity in the hepatic intestinal area (enhanced mesenteric sympathetic nervous activity)....

  1. Pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes

    NARCIS (Netherlands)

    Faas, MM; Bakker, WW; Baller, JFW; Schuiling, GA

    To test the hypothesis that pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes, cryostat-cut kidney sections of pregnant and cycling rats were exposed to activated polymorphonuclear leukocytes and

  2. Zero-valent iron enhanced methanogenic activity in anaerobic digestion of waste activated sludge after heat and alkali pretreatment.

    Science.gov (United States)

    Zhang, Yaobin; Feng, Yinghong; Quan, Xie

    2015-04-01

    Heat or alkali pretreatment is the effective method to improve hydrolysis of waste sludge and then enhance anaerobic sludge digestion. However the pretreatment may inactivate the methanogens in the sludge. In the present work, zero-valent iron (ZVI) was used to enhance the methanogenic activity in anaerobic sludge digester under two methanogens-suppressing conditions, i.e. heat-pretreatment and alkali condition respectively. With the addition of ZVI, the lag time of methane production was shortened, and the methane yield increased by 91.5% compared to the control group. The consumption of VFA was accelerated by ZVI, especially for acetate, indicating that the acetoclastic methanogenesis was enhanced. In the alkali-condition experiment, the hydrogen produced decreased from 27.6 to 18.8 mL when increasing the ZVI dosage from 0 to 10 g/L. Correspondingly, the methane yield increased from 1.9 to 32.2 mL, which meant that the H2-utilizing methanogenes was enriched. These results suggested that the addition of ZVI into anaerobic digestion of sludge after pretreated by the heat or alkali process could efficiently recover the methanogenic activity and increase the methane production and sludge reduction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Enhancement of photocatalytic and photoelectrocatalytic activity of Ag modified Mpg-C3N4 composites

    Science.gov (United States)

    He, Qiuchen; Zhou, Feng; Zhan, Su; Yang, Yifan; Liu, Yujun; Tian, Yu; Huang, Naibao

    2017-01-01

    In this study, mpg-C3N4/Ag composites of surface plasmon resonance structures were fabricated to improve the photocatalytic and photoelectrocatalytic activities of g-C3N4 via photo-assisted reduction method, which were characterized by XRD, EDS, XPS, FT-IR, FE-SEM, TEM, DRS and BET. The photocatalytic and photoelectrocatalytic activities were evaluated by the degradation of methylene blue (MB) and the oxygen reduction experiment under visible light. The results showed the photocatalytic and photoelectrocatalytic activities were dependent on the weight ratio of Ag and the optimum photocatalytic activity of mpg-C3N4/Ag at a weight ratio of 3% is almost 3 times as high as that of mpg-C3N4. Additionally, mpg-C3N4/Ag exhibited a significantly enhanced oxygen reduction performance under visible light. The limit current density was increased about 2 times by the modification of Ag nanoparticles, compared with that of pristine mpg-C3N4. Finally, based on the first principle, the enhancement mechanism of the photocatalytic and photoelectrocatalytic activities was discussed by the calculation on the band structure and density of states in the mpg-C3N4/Ag composites. The appropriate amount of Ag modification would cause the surface plasmon resonance effect, which improved the photocatalytic, photoelectrocatalytic, and oxygen reduction activities of mpg-C3N4.

  4. Aminoglycosylation can enhance the G-quadruplex binding activity of epigallocatechin.

    Directory of Open Access Journals (Sweden)

    Li-Ping Bai

    Full Text Available With the aim of enhancing G-quadruplex binding activity, two new glucosaminosides (16, 18 of penta-methylated epigallocatechin were synthesized by chemical glycosylation. Subsequent ESI-TOF-MS analysis demonstrated that these two glucosaminoside derivatives exhibit much stronger binding activity to human telomeric DNA and RNA G-quadruplexes than their parent structure (i.e., methylated EGC (14 as well as natural epigallocatechin (EGC, 6. The DNA G-quadruplex binding activity of 16 and 18 is even more potent than strong G-quadruplex binder quercetin, which has a more planar structure. These two synthetic compounds also showed a higher binding strength to human telomeric RNA G-quadruplex than its DNA counterpart. Analysis of the structure-activity relationship revealed that the more basic compound, 16, has a higher binding capacity with DNA and RNA G-quadruplexes than its N-acetyl derivative, 18, suggesting the importance of the basicity of the aminoglycoside for G-quadruplex binding activity. Molecular docking simulation predicted that the aromatic ring of 16 π-stacks with the aromatic ring of guanine nucleotides, with the glucosamine moiety residing in the groove of G-quadruplex. This research indicates that glycosylation of natural products with aminosugar can significantly enhance their G-quadruplex binding activities, thus is an effective way to generate small molecules targeting G-quadruplexes in nucleic acids. In addition, this is the first report that green tea catechin can bind to nucleic acid G-quadruplex structures.

  5. Activation of Cannabinoid Receptor 2 Enhances Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Yong-Xin Sun

    2015-01-01

    Full Text Available Bone marrow derived mesenchymal stem cells (BM-MSCs are considered as the most promising cells source for bone engineering. Cannabinoid (CB receptors play important roles in bone mass turnover. The aim of this study is to test if activation of CB2 receptor by chemical agonist could enhance the osteogenic differentiation and mineralization in bone BM-MSCs. Alkaline phosphatase (ALP activity staining and real time PCR were performed to test the osteogenic differentiation. Alizarin red staining was carried out to examine the mineralization. Small interference RNA (siRNA was used to study the role of CB2 receptor in osteogenic differentiation. Results showed activation of CB2 receptor increased ALP activity, promoted expression of osteogenic genes, and enhanced deposition of calcium in extracellular matrix. Knockdown of CB2 receptor by siRNA inhibited ALP activity and mineralization. Results of immunofluorescent staining showed that phosphorylation of p38 MAP kinase is reduced by knocking down of CB2 receptor. Finally, bone marrow samples demonstrated that expression of CB2 receptor is much lower in osteoporotic patients than in healthy donors. Taken together, data from this study suggested that activation of CB2 receptor plays important role in osteogenic differentiation of BM-MSCs. Lack of CB2 receptor may be related to osteoporosis.

  6. Oridonin Loaded Solid Lipid Nanoparticles Enhanced Antitumor Activity in MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2014-01-01

    Full Text Available Oridonin (ORI, a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs. ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.

  7. Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats.

    Science.gov (United States)

    Tallarida, Christopher S; Tallarida, Ronald J; Rawls, Scott M

    2015-04-01

    The Drug Enforcement Agency estimates that 80% of cocaine seized in the United States contains the veterinary pharmaceutical levamisole (LVM). One problem with LVM is that it is producing life-threatening neutropenia in an alarming number of cocaine abusers. The neuropharmacological profile of LVM is also suggestive of an agent with modest reinforcing and stimulant effects that could enhance cocaine's addictive effects. We tested the hypothesis that LVM (ip) enhances the rewarding and locomotor stimulant effects of cocaine (ip) using rat conditioned place preference (CPP) and locomotor assays. Effects of LVM by itself were also tested. LVM (0-10 mg/kg) produced CPP at 1mg/kg (P 0.05); however, the combination of LVM and cocaine produced enhanced CPP compared to saline or either drug by itself (P 0.05). LVM can enhance rewarding and locomotor-activating effects of low doses of cocaine in rats while possessing modest activity of its own. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Evaluation of skin permeation and analgesic activity effects of carbopol lornoxicam topical gels containing penetration enhancer.

    Science.gov (United States)

    Al-Suwayeh, Saleh A; Taha, Ehab I; Al-Qahtani, Fahad M; Ahmed, Mahrous O; Badran, Mohamed M

    2014-01-01

    The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 μg/cm(2)/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation.

  9. Evaluation of Skin Permeation and Analgesic Activity Effects of Carbopol Lornoxicam Topical Gels Containing Penetration Enhancer

    Directory of Open Access Journals (Sweden)

    Saleh A. Al-Suwayeh

    2014-01-01

    Full Text Available The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC and carbopol. The carbopol gels in presence of propylene glycol (PG and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD, beta-cyclodextrin (β-CD, Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8 showed the highest flux (14.31 μg/cm2/h with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8 enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo. This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation.

  10. Enhanced high-solids anaerobic digestion of waste activated sludge by the addition of scrap iron.

    Science.gov (United States)

    Zhang, Yaobin; Feng, Yinghong; Yu, Qilin; Xu, Zibin; Quan, Xie

    2014-05-01

    Anaerobic digestion of waste activated sludge usually requires pretreatment procedure to improve the bioavailability of sludge, which involves considerable energy and high expenditures. This study proposes a cost-effective method for enhanced anaerobic digestion of sludge without a pretreatment by directly adding iron into the digester. The results showed that addition of Fe(0) powder could enhance 14.46% methane yield, and Fe scrap (clean scrap) could further enhance methane yield (improving rate 21.28%) because the scrap has better mass transfer efficiency with sludge and liquid than Fe(0) powder. The scrap of Fe with rust (rusty scrap) could induce microbial Fe(III) reduction, which resulted in achieving the highest methane yield (improving rate 29.51%), and the reduction rate of volatile suspended solids (VSS) was also highest (48.27%) among Fe powder, clean scrap and rusty scrap. PCR-DGGE proved that the addition of rusty scrap could enhance diversity of acetobacteria and enrich iron-reducing bacteria to enhance degradation of complex substrates. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Enhanced adsorption of perfluorooctane sulfonate and perfluorooctanoate by bamboo-derived granular activated carbon.

    Science.gov (United States)

    Deng, Shubo; Nie, Yao; Du, Ziwen; Huang, Qian; Meng, Pingping; Wang, Bin; Huang, Jun; Yu, Gang

    2015-01-23

    A bamboo-derived granular activated carbon with large pores was successfully prepared by KOH activation, and used to remove perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from aqueous solution. The granular activated carbon prepared at the KOH/C mass ratio of 4 and activation temperature of 900°C had fast and high adsorption for PFOS and PFOA. Their adsorption equilibrium was achieved within 24h, which was attributed to their fast diffusion in the micron-sized pores of activated carbon. This granular activated carbon exhibited the maximum adsorbed amount of 2.32mmol/g for PFOS and 1.15mmol/g for PFOA at pH 5.0, much higher than other granular and powdered activated carbons reported. The activated carbon prepared under the severe activation condition contained many enlarged pores, favorable for the adsorption of PFOS and PFOA. In addition, the spent activated carbon was hardly regenerated in NaOH/NaCl solution, while the regeneration efficiency was significantly enhanced in hot water and methanol/ethanol solution, indicating that hydrophobic interaction was mainly responsible for the adsorption. The regeneration percent was up to 98% using 50% ethanol solution at 45°C. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Role of drop distortion in enhancing the lightning activity in clouds formed over cities

    Science.gov (United States)

    Bhalwankar, Rohini; Kamra, A. K.

    2013-03-01

    Atmospheric pollutants can modify the electrification and lightning activity in thunderclouds. Laboratory simulation experiments show that distortion of water drops is more when drops are formed from water polluted with Sulfate/Nitrate salts than that from distilled water and the difference in distortions is more in a higher electric field. Further, the polluted water drops falling in a horizontal electric field can trigger a discharge on their surface and the discharge can propagate as a streamer in lower electric fields as compared to that from distilled water drops. The difference in electrical conductivities of polluted and unpolluted water drops is most likely the key factor for manifestation of these differences. It is proposed that the enhanced distortion of polluted drops coupled with the change in their characteristics to trigger and propagate a discharge in lower electric fields may significantly contribute to the enhancement of lightning activity observed in clouds formed over big cities.

  13. Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Lorenzen, I; Henriksen, O

    1994-01-01

    intensity increase on early dynamic FLASH images higher by far than the CIG knees, while no significant difference was found on spin-echo images obtained 5 to 15 min after contrast injection. The early signal enhancement probably reflects the perfusion and capillary permeability of the synovium. The area...... of synovium could differentiate between healthy and arthritic knees. Gadolinium-enhanced dynamic FLASH imaging may provide clinically useful information about the actual inflammatory activity of arthritic joints.......Dynamic T1-weighted FLASH MR imaging, obtained just after i.v. gadopentetate dimeglumine injection, and pre- and postcontrast T1-weighted spin-echo (T1-SE) MR imaging were performed to compare their information value with respect to inflammatory activity in immunoinflammatory gonarthritis. We...

  14. Proximity does not contribute to activity enhancement in the glucose oxidase-horseradish peroxidase cascade

    Science.gov (United States)

    Zhang, Yifei; Tsitkov, Stanislav; Hess, Henry

    2016-12-01

    A proximity effect has been invoked to explain the enhanced activity of enzyme cascades on DNA scaffolds. Using the cascade reaction carried out by glucose oxidase and horseradish peroxidase as a model system, here we study the kinetics of the cascade reaction when the enzymes are free in solution, when they are conjugated to each other and when a competing enzyme is present. No proximity effect is found, which is in agreement with models predicting that the rapidly diffusing hydrogen peroxide intermediate is well mixed. We suggest that the reason for the activity enhancement of enzymes localized by DNA scaffolds is that the pH near the surface of the negatively charged DNA nanostructures is lower than that in the bulk solution, creating a more optimal pH environment for the anchored enzymes. Our findings challenge the notion of a proximity effect and provide new insights into the role of DNA scaffolds.

  15. Sensitivity-Enhanced Wearable Active Voiceprint Sensor Based on Cellular Polypropylene Piezoelectret.

    Science.gov (United States)

    Li, Wenbo; Zhao, Sheng; Wu, Nan; Zhong, Junwen; Wang, Bo; Lin, Shizhe; Chen, Shuwen; Yuan, Fang; Jiang, Hulin; Xiao, Yongjun; Hu, Bin; Zhou, Jun

    2017-07-19

    Wearable active sensors have extensive applications in mobile biosensing and human-machine interaction but require good flexibility, high sensitivity, excellent stability, and self-powered feature. In this work, cellular polypropylene (PP) piezoelectret was chosen as the core material of a sensitivity-enhanced wearable active voiceprint sensor (SWAVS) to realize voiceprint recognition. By virtue of the dipole orientation control method, the air layers in the piezoelectret were efficiently utilized, and the current sensitivity was enhanced (from 1.98 pA/Hz to 5.81 pA/Hz at 115 dB). The SWAVS exhibited the superiorities of high sensitivity, accurate frequency response, and excellent stability. The voiceprint recognition system could make correct reactions to human voices by judging both the password and speaker. This study presented a voiceprint sensor with potential applications in noncontact biometric recognition and safety guarantee systems, promoting the progress of wearable sensor networks.

  16. Grounding Activity in People-Centered Smart Territories by Enhancing Community Awareness

    Directory of Open Access Journals (Sweden)

    John M. Carroll

    2014-05-01

    Full Text Available Contemporary life can seem rushed and overloaded. We argue this may be due not to merely having too much to do, but rather with experiencing fragmentation and inadequate meaning in one’s own activity. We suggest that a design approach to this challenge is to enhance awareness of significant and persistent activity, and the themes, values, places, and motivations that unifies it and gives it greater meaning. Specifically, we suggest that people-centered smart territories can enhance community awareness by reminding people of placed-based history, heritage, current issues and discussions, and plans for the future in the community through a smart social grid of community information services.

  17. Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity.

    Science.gov (United States)

    Lucarini, Simone; Fagioli, Laura; Campana, Raffaella; Cole, Hannah; Duranti, Andrea; Baffone, Wally; Vllasaliu, Driton; Casettari, Luca

    2016-10-01

    Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. SOFT MALLEABLE VESICLES TAILORED FOR ENHANCED DELIVERY OF ACTIVE AGENTS THROUGH THE SKIN: AN UPDATE

    OpenAIRE

    Sandeep Kumar Parihar*, Mithun Bhowmick, Rajeev Kumar and Balkrishna Dubey

    2013-01-01

    Ethosomes are noninvasive delivery carriers that enable drugs to reach the deep skin layers and/or the systemic circulation. These are soft, malleable vesicles tailored for enhanced delivery of active agents. They are composed mainly of phospholipids, high concentration of ethanol and water. The high concentration of ethanol makes the ethosomes unique, as ethanol is known for its disturbance of skin lipid bilayer organization; therefore, when integrated into ...

  19. Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells†

    OpenAIRE

    Huh, Yun Suk; Chung, Aram J.; Cordovez, Bernardo; Erickson, David

    2008-01-01

    Here we present a novel microfluidic technique for on-chip surface enhanced Raman spectroscopy (SERS) based biomolecular detection, exploiting the use of electrokinetically active microwells. Briefly, the chip comprises of a series of microfluidic channels containing embedded microwells that, when electrically actuated, either locally attract or repulse species from solution through a combination of electrokinetic effects. We demonstrate that the approach combines the advantages of existing h...

  20. Intervention-induced enhancement in intrinsic brain activity in healthy older adults

    OpenAIRE

    Shufei Yin; Xinyi Zhu; Rui Li; Yanan Niu; Baoxi Wang; Zhiwei Zheng; Xin Huang; Lijuan Huo; Juan Li

    2014-01-01

    This study examined the effects of a multimodal intervention on spontaneous brain activity in healthy older adults. Seventeen older adults received a six-week intervention that consisted of cognitive training, Tai Chi exercise, and group counseling, while 17 older adults in a control group attended health knowledge lectures. The intervention group demonstrated enhanced memory and social support compared to the control group. The amplitude of low frequency fluctuations (ALFF) in the middle fro...

  1. Application of contact stabilization activated sludge for enhancing biological phosphorus removal (EBPR) in domestic wastewater

    OpenAIRE

    Ehab M. Rashed; Maha M. El-Shafei; Heikal, Mohamed A; Noureldin, Ahmed M.

    2014-01-01

    The experiment has been performed in order to investigate the effect of using contact stabilization activated sludge as an application of enhancing biological phosphorous removal (EBPR) by using contact tank as a phosphorus uptake zone and using thickening tank as a phosphorus release zone. The study involved the construction of a pilot plant which was setup in Quhafa waste water treatment plant (WWTP) that included contact, final sedimentation, stabilization and thickening tanks, respectivel...

  2. Dramatization at Extracurricular Activities as a Means to Enhance Foreign Language Teaching

    Directory of Open Access Journals (Sweden)

    Marina Valeryevna Kuimova

    2015-02-01

    Full Text Available The main purpose of foreign language teaching is to learn to communicate and overcome the language barrier. The article studies dramatization and its appropriateness in foreign language teaching, provides criteria for choosing a literary work for dramatization. The use of dramatization at extracurricular activities develops communication abilities, creativity; enhances motivation to learn a foreign language and strengthens students’ confidence in a foreign language.

  3. Enhancing learning with the social media: student teachers’ perceptions on Twitter in a debate activity

    OpenAIRE

    Gemma Tur; Victoria I. Marín

    2015-01-01

    This paper presents research focused on the educational experience of students using the microblogging platform Twitter for debate activities in three groups in different teacher education programmes at the University of the Balearic Islands, Spain. The implementation of this technology-based task in a face-to-face class was introduced as an innovative experience as a way of enhancing student learning and fostering participation in the context of formal learning. The educational objectives of...

  4. Aging Enhances the Production of Reactive Oxygen Species and Bactericidal Activity in Peritoneal Macrophages by Upregulating Classical Activation Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Smallwood, Heather S.; López-Ferrer, Daniel; Squier, Thomas C.

    2011-10-07

    Maintenance of macrophages in their basal state and their rapid activation in response to pathogen detection are central to the innate immune system, acting to limit nonspecific oxidative damage and promote pathogen killing following infection. To identify possible age-related alterations in macrophage function, we have assayed the function of peritoneal macrophages from young (3–4 months) and aged (14–15 months) Balb/c mice. In agreement with prior suggestions, we observe age-dependent increases in the extent of recruitment of macrophages into the peritoneum, as well as ex vivo functional changes involving enhanced nitric oxide production under resting conditions that contribute to a reduction in the time needed for full activation of senescent macrophages following exposure to lipopolysaccharides (LPS). Further, we observe enhanced bactericidal activity following Salmonella uptake by macrophages isolated from aged Balb/c mice in comparison with those isolated from young animals. Pathways responsible for observed phenotypic changes were interrogated using tandem mass spectrometry, which identified age-dependent increases in levels of proteins linked to immune cell pathways under basal conditions and following LPS activation. Immune pathways upregulated in macrophages isolated from aged mice include proteins critical to the formation of the immunoproteasome. Detection of these latter proteins is dramatically enhanced following LPS exposure for macrophages isolated from aged animals; in comparison, the identification of immunoproteasome subunits is insensitive to LPS exposure for macrophages isolated from young animals. Consistent with observed global changes in the proteome, quantitative proteomic measurements indicate that there are age-dependent abundance changes involving specific proteins linked to immune cell function under basal conditions. LPS exposure selectively increases the levels of many proteins involved in immune cell function in aged Balb/c mice

  5. Gaming is related to enhanced working memory performance and task-related cortical activity.

    Science.gov (United States)

    Moisala, M; Salmela, V; Hietajärvi, L; Carlson, S; Vuontela, V; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

    2017-01-15

    Gaming experience has been suggested to lead to performance enhancements in a wide variety of working memory tasks. Previous studies have, however, mostly focused on adult expert gamers and have not included measurements of both behavioral performance and brain activity. In the current study, 167 adolescents and young adults (aged 13-24 years) with different amounts of gaming experience performed an n-back working memory task with vowels, with the sensory modality of the vowel stream switching between audition and vision at random intervals. We studied the relationship between self-reported daily gaming activity, working memory (n-back) task performance and related brain activity measured using functional magnetic resonance imaging (fMRI). The results revealed that the extent of daily gaming activity was related to enhancements in both performance accuracy and speed during the most demanding (2-back) level of the working memory task. This improved working memory performance was accompanied by enhanced recruitment of a fronto-parietal cortical network, especially the dorsolateral prefrontal cortex. In contrast, during the less demanding (1-back) level of the task, gaming was associated with decreased activity in the same cortical regions. Our results suggest that a greater degree of daily gaming experience is associated with better working memory functioning and task difficulty-dependent modulation in fronto-parietal brain activity already in adolescence and even when non-expert gamers are studied. The direction of causality within this association cannot be inferred with certainty due to the correlational nature of the current study. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Osteopontin Peptide Icosamer Containing RGD and SLAYGLR Motifs Enhances the Motility and Phagocytic Activity of Microglia.

    Science.gov (United States)

    Kim, Il-Doo; Lee, Hahnbie; Jin, Yin-Chuan; Lee, Ja-Kyeong

    2017-12-01

    Osteopontin (OPN) is a secreted glycoprotein that is expressed in various tissues, including brain, and mediates a wide range of cellular activities. In a previous study, the authors observed the robust neuroprotective effects of recombinant OPN and of RGD and SLAYGLR-containing OPN-peptide icosamer (OPNpt20) in an animal model of transient focal ischemia, and demonstrated anti-inflammatory and pro-angiogenic effects of OPNpt20 in the postischemic brain. In the present study, we investigated the effects of OPNpt20 on the motility and phagocytic activity of BV2 cells (a microglia cell line). F-actin polymerization and cell motility were significantly enhanced in OPNpt20-treated BV2 cells, and numbers of filopodia-like processes increased and lamellipodia-like structures enlarged and thickened. In addition, treatment of cells with either of three mutant OPN icosamers containing mutation within RGD, SLAY, or RGDSLAY showed that the RGD and SLAY motifs of OPNpt20 play critical roles in the enhancement of cell motility, and the interaction between exogenous OPNpt20 and endogenous αv and α4 integrin and the activations of FAK, Erk, and Akt signaling pathways were found to be involved in the OPNpt20-mediated induction of cell motility. Furthermore, phagocytic activity of microglia was also significantly enhanced by OPNpt20 in a RGD and SLAY dependent manner. These results indicate OPNpt20 containing RGD and SLAY motifs triggers microglial motility and phagocytic activity and OPNpt20-integrin mediated signaling plays a critical role in these activities.

  7. Nitric oxide facilitates active avoidance learning via enhancement of glutamate levels in the hippocampal dentate gyrus.

    Science.gov (United States)

    Wang, Shi; Pan, De-Xi; Wang, Dan; Wan, Peng; Qiu, De-Lai; Jin, Qing-Hua

    2014-09-01

    The hippocampus is a key structure for learning and memory in mammals, and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. Despite a number of studies indicating that nitric oxide (NO) is involved in the formation and maintenance of LTP as a retrograde messenger, few studies have used neurotransmitter release as a visual indicator in awake animals to explore the role of NO in learning-dependent long-term enhancement of synaptic efficiency. Therefore, in the present study, the effects of l-NMMA (a NO synthase inhibitor) and SNP (a NO donor) on extracellular glutamate (Glu) concentrations and amplitudes of field excitatory postsynaptic potential (fEPSP) were measured in the hippocampal dentate gyrus (DG) region during the acquisition and extinction of active-avoidance behavior in freely-moving conscious rats. In the control group, the extracellular concentration of Glu in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to baseline levels following extinction training. In the experimental group, the change in Glu concentration was significantly reduced by local microinjection of l-NMMA, as was the acquisition of the active-avoidance behavior. In contrast, the change in Glu concentration was significantly enhanced by SNP, and the acquisition of the active-avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in extracellular Glu were accompanied by corresponding changes in fEPSP amplitude and active-avoidance behavior. Our results suggest that NO in the hippocampal DG facilitates active avoidance learning via enhancements of glutamate levels and synaptic efficiency in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. A Novel Serine Protease Secreted by Medicinal Maggots Enhances Plasminogen Activator-Induced Fibrinolysis

    Science.gov (United States)

    van der Plas, Mariena J. A.; Andersen, Anders S.; Nazir, Sheresma; van Tilburg, Nico H.; Oestergaard, Peter R.; Krogfelt, Karen A.; van Dissel, Jaap T.; Hensbergen, Paul J.

    2014-01-01

    Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As haemostatic processes play an important role in wound healing, this study focused on the effects of maggot secretions on coagulation and fibrinolysis. The results showed that maggot secretions enhance plasminogen activator-induced formation of plasmin and fibrinolysis in a dose- and time-dependent manner. By contrast, coagulation was not affected by secretions. Biochemical studies indicated that a novel serine protease within secretions, designated Sericase, cleaved plasminogen to several fragments. Recombinant Sericase degraded plasminogen leading amongst others to the formation of the mini-plasminogen like fragment Val454-plasminogen. In addition, the presence of a non-proteolytic cofactor in secretions was discovered, which plays a role in the enhancement of plasminogen activator-induced fibrinolysis by Sericase. We conclude from our in vitro studies that the novel serine protease Sericase, with the aid of a non-proteolytic cofactor, enhances plasminogen activator-induced fibrinolysis. PMID:24647546

  9. Enhanced oxygen reduction activity on surface-decorated perovskite thin films for solid oxide fuel cells

    KAUST Repository

    Mutoro, Eva

    2011-01-01

    Surface-decoration of perovskites can strongly affect the oxygen reduction activity, and therefore is a new and promising approach to improve SOFC cathode materials. In this study, we demonstrate that a small amount of secondary phase on a (001) La 0.8Sr 0.2CoO 3-δ (LSC) surface can either significantly activate or passivate the electrode. LSC (001) microelectrodes prepared by pulsed laser deposition on a (001)-oriented yttria-stabilized zirconia (YSZ) substrate were decorated with La-, Co-, and Sr-(hydr)oxides/carbonates. "Sr"-decoration with nanoparticle coverage in the range from 50% to 80% of the LSC surface enhanced the surface exchange coefficient, k q, by an order of magnitude while "La"- decoration and "Co"-decoration led to no change and reduction in k q, respectively. Although the physical origin for the enhancement is not fully understood, results from atomic force microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy suggest that the observed k q enhancement for "Sr"-decorated surfaces can be attributed largely to catalytically active interface regions between surface Sr-enriched particles and the LSC surface. © 2011 The Royal Society of Chemistry.

  10. CAMKII activation is not required for maintenance of learning-induced enhancement of neuronal excitability.

    Directory of Open Access Journals (Sweden)

    Ori Liraz

    Full Text Available Pyramidal neurons in the piriform cortex from olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP which is generated by repetitive spike firing. AHP reduction is due to decreased conductance of a calcium-dependent potassium current, the sI(AHP. We have previously shown that learning-induced AHP reduction is maintained by persistent protein kinase C (PKC and extracellular regulated kinase (ERK activation. However, the molecular machinery underlying this long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the CaMKII, which is known to be crucial in learning, memory and synaptic plasticity processes, is instrumental for the maintenance of learning-induced AHP reduction. KN93, that selectively blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from trained and control rat to the same extent. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls remained. Accordingly, the level of activated CaMKII was similar in pirifrom cortex samples taken form trained and control rats. Our data show that although CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform cortex, its activation is not required for maintaining learning-induced enhancement of neuronal excitability.

  11. Lactic acid bacteria: promising supplements for enhancing the biological activities of kombucha.

    Science.gov (United States)

    Nguyen, Nguyen Khoi; Dong, Ngan Thi Ngoc; Nguyen, Huong Thuy; Le, Phu Hong

    2015-01-01

    Kombucha is sweetened black tea that is fermented by a symbiosis of bacteria and yeast embedded within a cellulose membrane. It is considered a health drink in many countries because it is a rich source of vitamins and may have other health benefits. It has previously been reported that adding lactic acid bacteria (Lactobacillus) strains to kombucha can enhance its biological functions, but in that study only lactic acid bacteria isolated from kefir grains were tested. There are many other natural sources of lactic acid bacteria. In this study, we examined the effects of lactic acid bacteria from various fermented Vietnamese food sources (pickled cabbage, kefir and kombucha) on kombucha's three main biological functions: glucuronic acid production, antibacterial activity and antioxidant ability. Glucuronic acid production was determined by high-performance liquid chromatography-mass spectrometry, antibacterial activity was assessed by the agar-well diffusion method and antioxidant ability was evaluated by determining the 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity. Four strains of food-borne pathogenic bacteria were used in our antibacterial experiments: Listeria monocytogenes ATCC 19111, Escherichia coli ATCC 8739, Salmonella typhimurium ATCC 14028 and Bacillus cereus ATCC 11778. Our findings showed that lactic acid bacteria strains isolated from kefir are superior to those from other sources for improving glucuronic acid production and enhancing the antibacterial and antioxidant activities of kombucha. This study illustrates the potential of Lactobacillus casei and Lactobacillus plantarum isolated from kefir as biosupplements for enhancing the bioactivities of kombucha.

  12. Enhanced oxidation of naphthalene using plasma activation of TiO2/diatomite catalyst.

    Science.gov (United States)

    Wu, Zuliang; Zhu, Zhoubin; Hao, Xiaodong; Zhou, Weili; Han, Jingyi; Tang, Xiujuan; Yao, Shuiliang; Zhang, Xuming

    2018-04-05

    Non-thermal plasma technology has great potential in reducing polycyclic aromatic hydrocarbons (PAHs) emission. But in plasma-alone process, various undesired by-products are produced, which causes secondary pollutions. Here, a dielectric barrier discharge (DBD) reactor has been developed for the oxidation of naphthalene over a TiO 2 /diatomite catalyst at low temperature. In comparison to plasma-alone process, the combination of plasma and TiO 2 /diatomite catalyst significantly enhanced naphthalene conversion (up to 40%) and CO x selectivity (up to 92%), and substantially reduced the formation of aerosol (up to 90%) and secondary volatile organic compounds (up to near 100%). The mechanistic study suggested that the presence of the TiO 2 /diatomite catalyst intensified the electron energy in the DBD. Meantime, the energized electrons generated in the discharge activated TiO 2 , while the presence of ozone enhanced the activity of the TiO 2 /diatomite catalyst. This plasma-catalyst interaction led to the synergetic effect resulting from the combination of plasma and TiO 2 /diatomite catalyst, consequently enhanced the oxidation of naphthalene. Importantly, we have demonstrated the effectiveness of plasma to activate the photocatalyst for the deep oxidation of PAH without external heating, which is potentially valuable in the development of cost-effective gas cleaning process for the removal of PAHs in vehicle applications during cold start conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis.

    Directory of Open Access Journals (Sweden)

    Mariena J A van der Plas

    Full Text Available Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As haemostatic processes play an important role in wound healing, this study focused on the effects of maggot secretions on coagulation and fibrinolysis. The results showed that maggot secretions enhance plasminogen activator-induced formation of plasmin and fibrinolysis in a dose- and time-dependent manner. By contrast, coagulation was not affected by secretions. Biochemical studies indicated that a novel serine protease within secretions, designated Sericase, cleaved plasminogen to several fragments. Recombinant Sericase degraded plasminogen leading amongst others to the formation of the mini-plasminogen like fragment Val454-plasminogen. In addition, the presence of a non-proteolytic cofactor in secretions was discovered, which plays a role in the enhancement of plasminogen activator-induced fibrinolysis by Sericase. We conclude from our in vitro studies that the novel serine protease Sericase, with the aid of a non-proteolytic cofactor, enhances plasminogen activator-induced fibrinolysis.

  14. Studies on lipidification of streptokinase: a novel strategy to enhance the stability and activity.

    Science.gov (United States)

    Suthakaran, Pichaimuthu; Balasubramanian, Jaiiamadhumithaa; Ravichandran, Mirunalini; Murugan, Vidhyapriya; Ramya, Lanka Naga; Pulicherla, Krishna Kanth

    2014-01-01

    Thrombotic disorders and their associated problems are extensively prevalent in developed and developing countries. Streptokinase (SK) is a well-known thrombolytic agent, which is very useful in treating coronary thrombosis and acute myocardial infarction. Several attempts have been made to date to make improvements of this wonderful molecule in terms of reducing or eliminating the problems of eliciting immunogenicity and enhancing the half-life of the molecule. The present research is focused to produce a recombinant SK with enhanced stability and biological activity by the methodology of lipid modification. SK was targeted successfully to the membrane with the help of modified apyrase signal sequence. Higher expression was reported for GJ1158 strain in LBON medium when compared with BL21 (DE3). The obtained recombinant SK was tested for its biological activity by the method of caseinolytic assay. The higher clearance zone was observed in recombinant lipid-modified streptokinase, which denotes the enhanced activity of the protein. The present trial of lipid modification of therapeutics, particularly SK, could help for its superior use as a thrombolytic agent and also paves way for many of the other clinical applications.

  15. A tumor-penetrating peptide modification enhances the antitumor activity of thymosin alpha 1.

    Directory of Open Access Journals (Sweden)

    Xingzhen Lao

    Full Text Available A serious limitation of numerous antitumor drugs is the incapacity to penetrate solid tumors. However, addition of an RGD fragment to peptide drugs might solve this problem. In this study, we explored whether the introduction of a permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC fragments, would enhance the activity of thymosin alpha 1 (Tα1. The modified Tα1 (Tα1-iRGD was successfully expressed and purified, and the in vitro assay showed that Tα1-iRGD presented a similar activity as Tα1 in promoting proliferation of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that Tα1-iRGD exhibited more specific and greater binding with tumor cells compared with Tα1. Furthermore, the iRGD fragment evidently enhanced the basal ability of Tα1 to inhibit proliferation of cancer cells in vitro, particularly of mouse melanoma cell line B16F10 and human lung cancer cell line H460. Our findings indicated that the addition of an iRGD fragment increased the anti-proliferative activity of Tα1 against cancer cells by improving the ability of Tα1 to penetrate the tumor cells. This study highlighted the important roles of an iRGD sequence in the therapeutic strategy of Tα1-iRGD. Thus, Tα1-iRGD could be a novel drug candidate for cancer treatment.

  16. A tumor-penetrating peptide modification enhances the antitumor activity of thymosin alpha 1.

    Science.gov (United States)

    Lao, Xingzhen; Liu, Meng; Chen, Jiao; Zheng, Heng

    2013-01-01

    A serious limitation of numerous antitumor drugs is the incapacity to penetrate solid tumors. However, addition of an RGD fragment to peptide drugs might solve this problem. In this study, we explored whether the introduction of a permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC) fragments, would enhance the activity of thymosin alpha 1 (Tα1). The modified Tα1 (Tα1-iRGD) was successfully expressed and purified, and the in vitro assay showed that Tα1-iRGD presented a similar activity as Tα1 in promoting proliferation of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that Tα1-iRGD exhibited more specific and greater binding with tumor cells compared with Tα1. Furthermore, the iRGD fragment evidently enhanced the basal ability of Tα1 to inhibit proliferation of cancer cells in vitro, particularly of mouse melanoma cell line B16F10 and human lung cancer cell line H460. Our findings indicated that the addition of an iRGD fragment increased the anti-proliferative activity of Tα1 against cancer cells by improving the ability of Tα1 to penetrate the tumor cells. This study highlighted the important roles of an iRGD sequence in the therapeutic strategy of Tα1-iRGD. Thus, Tα1-iRGD could be a novel drug candidate for cancer treatment.

  17. GM-CSF Enhances Macrophage Glycolytic Activity In Vitro and Improves Detection of Inflammation In Vivo.

    Science.gov (United States)

    Singh, Parmanand; González-Ramos, Silvia; Mojena, Marina; Rosales-Mendoza, César Eduardo; Emami, Hamed; Swanson, Jeffrey; Morss, Alex; Fayad, Zahi A; Rudd, James H F; Gelfand, Jeffrey; Paz-García, Marta; Martín-Sanz, Paloma; Boscá, Lisardo; Tawakol, Ahmed

    2016-09-01

    (18)F-FDG accumulates in glycolytically active tissues and is known to concentrate in tissues that are rich in activated macrophages. In this study, we tested the hypotheses that human granulocyte-macrophage colony-stimulating factor (GM-CSF), a clinically used cytokine, increases macrophage glycolysis and deoxyglucose uptake in vitro and acutely enhances (18)F-FDG uptake within inflamed tissues such as atherosclerotic plaques in vivo. In vitro experiments were conducted on human macrophages whereby inflammatory activation and uptake of radiolabeled 2-deoxyglucose was assessed before and after GM-CSF exposure. In vivo studies were performed on mice and New Zealand White rabbits to assess the effect of GM-CSF on (18)F-FDG uptake in normal versus inflamed arteries, using PET. Incubation of human macrophages with GM-CSF resulted in increased glycolysis and increased 2-deoxyglucose uptake (P GM-CSF administration resulted in a 70% and 73% increase (P GM-CSF substantially augments glycolytic flux in vitro (via a mechanism dependent on ubiquitous type 6-phosphofructo-2-kinase and tumor necrosis factor-α) and increases (18)F-FDG uptake within inflamed atheroma in vivo. These findings demonstrate that GM-CSF can be used to enhance detection of inflammation. Further studies should explore the role of GM-CSF stimulation to enhance the detection of inflammatory foci in other disease states. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  18. Silver nanoparticles anchored reduced graphene oxide for enhanced electrocatalytic activity towards methanol oxidation

    Science.gov (United States)

    Kumar, Sanjeev; Mahajan, Mani; Singh, Rajinder; Mahajan, Aman

    2018-02-01

    In this report, silver nanoparticles (Ag NPs) anchored reduced graphene oxide (rGO) sheets (rGO/Ag) nanohybrid has been explored as anode material in direct methanol fuel cells (DMFCs). The synthesized rGO/Ag nanohybrid is characterized by XRD, XPS, FTIR spectroscopy and HRTEM techniques. Cyclic voltammograms demonstrate that the rGO/Ag nanohybrid exhibits higher electrocatalytic activity in comparison to rGO sheets for methanol oxidation reaction (MOR). This enhancement is attributed to the synergetic effect produced by the presence of more active sites provided by Ag NPs anchored on a conducting network of large surface area rGO sheets.

  19. Cellulosic carbon fibers with branching carbon nanotubes for enhanced electrochemical activities for bioprocessing applications.

    Science.gov (United States)

    Zhao, Xueyan; Lu, Xin; Tze, William Tai Yin; Kim, Jungbae; Wang, Ping

    2013-09-25

    Renewable biobased carbon fibers are promising materials for large-scale electrochemical applications including chemical processing, energy storage, and biofuel cells. Their performance is, however, often limited by low activity. Herein we report that branching carbon nanotubes can enhance the activity of carbonized cellulosic fibers, such that the oxidation potential of NAD(H) was reduced to 0.55 V from 0.9 V when applied for bioprocessing. Coordinating with enzyme catalysts, such hierarchical carbon materials effectively facilitated the biotransformation of glycerol, with the total turnover number of NAD(H) over 3500 within 5 h of reaction.

  20. Promoting Active Learning in Calculus and General Physics through Interactive and Media-Enhanced Lectures

    Directory of Open Access Journals (Sweden)

    Guoqing Tang

    2004-02-01

    Full Text Available In this paper we present an approach of incorporating interactive and media-enhanced lectures to promote active learning in Calculus and General Physics courses. The pedagogical practice of using interactive techniques in lectures to require "heads-on" and "hands-on" learning, and involve students more as active participants than passive receivers is a part of academic curricular reform efforts undertaken currently by the mathematics, physics and chemistry departments at North Carolina A&T State University under the NSF funded project "Talent-21: Gateway for Advancing Science and Mathematics Talents."

  1. Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Hasselbalch, Hans C; Nielsen, Claus H

    2013-01-01

    ), Escherichia coli LPS, or intact Porphyromonas gingivalis. Addition of platelets activated by thrombin-receptor-activating peptide enhanced IL-10 production induced by LPS (p ....05), and P. gingivalis (p IL-10 and TNF-α production were observed on addition of platelet supernatant to mononuclear cells, whereas addition of recombinant soluble CD40L mimicked the effects on IL-10...... production. Moreover, Ab-mediated blockade of CD40L counteracted the effect of platelets and platelet supernatants on TNF-α production. Monocytes separated into two populations with respect to IL-10 production induced by TG; the high-secreting fraction increased from 0.8 to 2.1% (p

  2. Effects of Pulsed Electric Field (PEF) Treatment on Enhancing Activity and Conformation of α-Amylase.

    Science.gov (United States)

    Tian, Mei-ling; Fang, Ting; Du, Mu-ying; Zhang, Fu-sheng

    2016-04-01

    To explore an efficient, safe, and speedy application of pulsed electric field (PEF) technology for enzymatic modification, effects of PEF treatment on the enzymatic activity, property and kinetic parameters of α-amylase were investigated. Conformational transitions were also studied with the aid of circular dichroism (CD) and fluorescence spectra. The maximum enzymatic activity of α-amylase was obtained under 15 kV/cm electric field intensity and 100 mL/min flow velocity PEF treatment, in which the enzymatic activity increased by 22.13 ± 1.14% compared with control. The activation effect could last for 18 h at 4 °C. PEF treatment could widen the range of optimum temperature for α-amylase, however, it barely exerted any effect on the optimum pH. On the other hand, α-amylase treated by PEF showed an increase of Vmax, t1/2 and ΔG, whereas a decrease of Km and k were observed. Furthermore, it can be observed from fluorescence and CD spectra that PEF treatment had increased the number of amino acid residues, especially that of tryptophan, on α-amylase surface with enhanced α-helices by 34.76% and decreased random coil by 12.04% on α-amylase when compared with that of untreated. These changes in structure had positive effect on enhancing α-amylase activity and property.

  3. Rhythmic arm swing enhances patterned locomotor-like muscle activity in passively moved lower extremities

    Science.gov (United States)

    Ogawa, Tetsuya; Sato, Takahiko; Ogata, Toru; Yamamoto, Shin-Ichiro; Nakazawa, Kimitaka; Kawashima, Noritaka

    2015-01-01

    The use of driven gait orthosis (DGO) has drawn attention in gait rehabilitation for patients after central nervous system (CNS) lesions. By imposing a passive locomotor-like kinematic pattern, the neural mechanisms responsible for locomotion can be activated as in a normal gait. To further enhance this activity, discussions on possible intervention are necessary. Given the possible functional linkages between the upper and lower limbs, we investigated in healthy subjects the degree of modification in the lower limb muscles during DGO-induced passive gait by the addition of swing movement in the upper extremity. The results clearly showed that muscle activity in the ankle dorsiflexor TA muscle was significantly enhanced when the passive locomotor-like movement was accompanied by arm swing movement. The modifications in the TA activity were not a general increase through the stride cycles, but were observed under particular phases as in normal gaits. Voluntary effort to swing the arms may have certain effects on the modification of the muscle activity. The results provide clinical implications regarding the usefulness of voluntary arm swing movement as a possible intervention in passive gait training using DGO, since ordinary gait training using DGO does not induce spontaneous arm swing movement despite its known influence on the lower limb movement. PMID:25742956

  4. Thiourea-Modified TiO2 Nanorods with Enhanced Photocatalytic Activity.

    Science.gov (United States)

    Wu, Xiaofeng; Fang, Shun; Zheng, Yang; Sun, Jie; Lv, Kangle

    2016-02-01

    Semiconductor TiO2 photocatalysis has attracted much attention due to its potential application in solving the problems of environmental pollution. In this paper, thiourea (CH4N2S) modified anatase TiO2 nanorods were fabricated by calcination of the mixture of TiO2 nanorods and thiourea at 600 °C for 2 h. It was found that only N element was doped into the lattice of TiO2 nanorods. With increasing the weight ratio of thiourea to TiO2 (R) from 0 to 8, the light-harvesting ability of the photocatalyst steady increases. Both the crystallization and photocatalytic activity of TiO2 nanorods increase first and then decrease with increase in R value, and R2 sample showed the highest crystallization and photocatalytic activity in degradation of Brilliant Red X3B (X3B) and Rhodamine B (RhB) dyes under visible light irradiation (λ > 420 nm). The increased visible-light photocatalytic activity of the prepared N-doped TiO2 nanorods is due to the synergistic effects of the enhanced crystallization, improved light-harvesting ability and reduced recombination rate of photo-generated electron-hole pairs. Note that the enhanced visible photocatalytic activity of N-doped nanorods is not based on the scarification of their UV photocatalytic activity.

  5. Enhancement of the hydrolysis activity of F0F1-ATPases using 60 Hz magnetic fields.

    Science.gov (United States)

    Chen, Chuanfang; Cui, Yuanbo; Yue, Jiachang; Huo, Xiaolin; Song, Tao

    2009-12-01

    The effects of extremely low frequency (ELF) magnetic fields on membrane F(0)F(1)-ATPase activity have been studied. When the F(0)F(1)-ATPase was exposed to 60 Hz magnetic fields of different magnetic intensities, 0.3 and 0.5 mT magnetic fields enhanced the hydrolysis activity, whereas 0.1 mT exposure caused no significant changes. Even if the F(0)F(1)-ATPase was inhibited by N,N-dicyclohexylcarbodiimide, its hydrolysis activity was enhanced by a 0.5 mT 60 Hz magnetic field. Moreover, when the chromatophores which were labeled with F-DHPE were exposed to a 0.5 mT, 60 Hz magnetic field, it was found that the pH of the outer membrane of the chromatophore was unchanged, which suggested that the magnetic fields used in this work did not affect the activity of F0. Taken together, our results show that the effects of magnetic fields on the hydrolysis activity of the membrane F(0)F(1)-ATPases were dependent on magnetic intensity and the threshold intensity is between 0.1 and 0.3 mT, and suggested that the F1 part of F(0)F(1)-ATPase may be an end-point affected by magnetic fields.

  6. Thiourea-Modified TiO2 Nanorods with Enhanced Photocatalytic Activity

    Directory of Open Access Journals (Sweden)

    Xiaofeng Wu

    2016-02-01

    Full Text Available Semiconductor TiO2 photocatalysis has attracted much attention due to its potential application in solving the problems of environmental pollution. In this paper, thiourea (CH4N2S modified anatase TiO2 nanorods were fabricated by calcination of the mixture of TiO2 nanorods and thiourea at 600 °C for 2 h. It was found that only N element was doped into the lattice of TiO2 nanorods. With increasing the weight ratio of thiourea to TiO2 (R from 0 to 8, the light-harvesting ability of the photocatalyst steady increases. Both the crystallization and photocatalytic activity of TiO2 nanorods increase first and then decrease with increase in R value, and R2 sample showed the highest crystallization and photocatalytic activity in degradation of Brilliant Red X3B (X3B and Rhodamine B (RhB dyes under visible light irradiation (λ > 420 nm. The increased visible-light photocatalytic activity of the prepared N-doped TiO2 nanorods is due to the synergistic effects of the enhanced crystallization, improved light-harvesting ability and reduced recombination rate of photo-generated electron-hole pairs. Note that the enhanced visible photocatalytic activity of N-doped nanorods is not based on the scarification of their UV photocatalytic activity.

  7. Enhancing catalytic activity of a hybrid xylanase through single substitution of Leu to Pro near the active site.

    Science.gov (United States)

    Wang, Qian; Zhao, Li-Li; Sun, Jian-Yi; Liu, Jian-Xin; Weng, Xiao-Yan

    2012-03-01

    A modified error-prone PCR and high-throughout screening system based on 96-well plate were employed to improve catalytic activity of a hybrid xylanase (ATx). The mutant (FSI-A124) with enhanced activity was further heterologously expressed in Pichia pastoris under the control of GAP promoter. The recombinant xylanase driven by the Saccharomyces cerevisiae α-mating factor was secreted into culture medium. After growth in YPD medium for 96 h, xylanase activity in the culture supernatant reached 66.1 U ml(-1), which was 2.92 times as that of its parent. 6 × His-tagged purification increased the specific activity to 1557.61 U mg(-1). The optimum temperature and pH of recombinant xylanase were 55°C and 6.0, respectively. A single amino acid substitution (L49P) was observed within sequence of the mutant. Insight of the three dimensional structure revealed that proline possibly produced weaker hydrogen bond, van der Waals force and hydrophobic interaction with other residues nearby than leucine, especially for V174, contributing to the flexibility of catalytic residue E177. In this study, FSI-A124 exhibited higher xylanase activity but poorer thermostability than its parent, indicating that activity and stability might be negatively correlated.

  8. Active music classes in infancy enhance musical, communicative and social development.

    Science.gov (United States)

    Gerry, David; Unrau, Andrea; Trainor, Laurel J

    2012-05-01

    Previous studies suggest that musical training in children can positively affect various aspects of development. However, it remains unknown as to how early in development musical experience can have an effect, the nature of any such effects, and whether different types of music experience affect development differently. We found that random assignment to 6 months of active participatory musical experience beginning at 6 months of age accelerates acquisition of culture-specific knowledge of Western tonality in comparison to a similar amount of passive exposure to music. Furthermore, infants assigned to the active musical experience showed superior development of prelinguistic communicative gestures and social behaviour compared to infants assigned to the passive musical experience. These results indicate that (1) infants can engage in meaningful musical training when appropriate pedagogical approaches are used, (2) active musical participation in infancy enhances culture-specific musical acquisition, and (3) active musical participation in infancy impacts social and communication development. © 2012 Blackwell Publishing Ltd.

  9. Macrophage activation induced by Brucella DNA suppresses bacterial intracellular replication via enhancing NO production.

    Science.gov (United States)

    Liu, Ning; Wang, Lin; Sun, Changjiang; Yang, Li; Tang, Bin; Sun, Wanchun; Peng, Qisheng

    2015-12-01

    Brucella DNA can be sensed by TLR9 on endosomal membrane and by cytosolic AIM2-inflammasome to induce proinflammatory cytokine production that contributes to partially activate innate immunity. Additionally, Brucella DNA has been identified to be able to act as a major bacterial component to induce type I IFN. However, the role of Brucella DNA in Brucella intracellular growth remains unknown. Here, we showed that stimulation with Brucella DNA promote macrophage activation in TLR9-dependent manner. Activated macrophages can suppresses wild type Brucella intracellular replication at early stage of infection via enhancing NO production. We also reported that activated macrophage promotes bactericidal function of macrophages infected with VirB-deficient Brucella at the early or late stage of infection. This study uncovers a novel function of Brucella DNA, which can help us further elucidate the mechanism of Brucella intracellular survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Surface enhanced Raman scattering, antibacterial and antifungal active triangular gold nanoparticles

    Science.gov (United States)

    Smitha, S. L.; Gopchandran, K. G.

    2013-02-01

    Shape controlled syntheses of gold nanoparticles have attracted a great deal of attention as their optical, electronic, magnetic and biological properties are strongly dependent on the size and shape of the particles. Here is a report on the surface enhanced Raman scattering (SERS) activity of Cinnamomum zeylanicum leaf broth reduced gold nanoparticles consisting of triangular and spherical like particles, using 2-aminothiophenol (2-ATP) and crystal violet (CV) as probe molecules. Nanoparticles prepared with a minimum leaf broth concentration, having a greater number of triangular like particles exhibit a SERS activity of the order of 107. The synthesized nanoparticles exhibit efficient antibacterial activity against the tested gram negative bacterium Escherichia coli and gram positive bacterium Staphylococcus aureus. Investigations on the antifungal activity of the synthesized nanoparticles against Aspergillus niger and Fusarium oxysporum positive is also discussed.

  11. HSPB1 Enhances SIRT2-Mediated G6PD Activation and Promotes Glioma Cell Proliferation.

    Directory of Open Access Journals (Sweden)

    Hongxing Ye

    Full Text Available Heat shock proteins belong to a conserved protein family and are involved in multiple cellular processes. Heat shock protein 27 (Hsp27, also known as heat HSPB1, participates in cellular responses to not only heat shock, but also oxidative or chemical stresses. However, the contribution of HSPB1 to anti-oxidative response remains unclear. Here, we show that HSPB1 activates G6PD in response to oxidative stress or DNA damage. HSPB1 enhances the binding between G6PD and SIRT2, leading to deacetylation and activation of G6PD. Besides, HSPB1 activates G6PD to sustain cellular NADPH and pentose production in glioma cells. High expression of HSPB1 correlates with poor survivalrate of glioma patients. Together, our study uncovers the molecular mechanism by which HSPB1 activates G6PD to protect cells from oxidative and DNA damage stress.

  12. Passivity enhancement by series LC filtered active damper with zero current reference

    DEFF Research Database (Denmark)

    Bai, Haofeng; Wang, Xiongfei; Blaabjerg, Frede

    2016-01-01

    Grid connected converters with the LCL filters suffer from the instability problems when they are connected to grid with non-negligible impedance. The active damper is an effective tool for improving the stability of the grid connected converters against the various grid conditions. The operation...... principle of the active damper in previous study is mimicking a damping resistance at the resonance frequencies, which is an intuitive approach but requires a complicated current reference generation algorithm and a high-bandwidth current control loop. However, the stability of the grid connected converters...... can be improved by enhancing the passivity of the total admittance seen by the grid, which allows for a zero current reference and a much simpler current controller for the active damper. To show the performance of the active damper with zero reference, this paper first carries out the impedance based...

  13. Low intensity laser therapy speeds wound healing in hemophilia by enhancing platelet procoagulant activity.

    Science.gov (United States)

    Hoffman, Maureane; Monroe, Dougald M

    2012-01-01

    Our group has previously shown that cutaneous wound healing is delayed and histologically abnormal in a mouse model of hemophilia. Hemostasis is not only required to stop bleeding at the time of wounding, but also produces bioactive substances that promote appropriate inflammatory and proliferative responses during healing. Low intensity laser therapy (LILT) has been reported to enhance impaired wound healing in a variety of animal and human studies. The current studies were conducted to test the hypothesis that LILT can improve healing in a hemophilia B mouse model. Three daily treatments with 12 J/sq cm of 650 nm laser illumination reduced the time to closure of a 3-mm cutaneous punch biopsy wound in the hemophilic mice. All wounds were closed at 13 days in the sham-treated hemophilic mice, compared with 10 days in the LILT-treated hemophilic mice, and 9 days in wild-type mice. While LILT can speed healing by enhancing proliferation of cutaneous cells, we found that an additional mechanism likely contributes to the efficacy of LILT in the hemophilic mice. LILT enhanced the mechanical rigidity and platelet activity of clots formed from human platelet-rich plasma. Illumination of isolated platelets increased the mitochondrial membrane potential and enhanced binding of coagulation factors to the surface of activated platelets. Thus, while LILT can directly promote proliferative responses during healing, it also appears to enhance hemostasis in an animal model with impaired coagulation. These data suggest that trials of LILT as an adjunct to the usual hemostatic therapies in hemophilia are warranted. © 2012 by the Wound Healing Society.

  14. Cyclin-dependent kinase activity enhances phosphatidylcholine biosynthesis in Arabidopsis by repressing phosphatidic acid phosphohydrolase activity.

    Science.gov (United States)

    Craddock, Christian P; Adams, Nicolette; Kroon, Johan T M; Bryant, Fiona M; Hussey, Patrick J; Kurup, Smita; Eastmond, Peter J

    2017-01-01

    Coordination of endomembrane biogenesis with cell cycle progression is considered to be important in maintaining cell function during growth and development. We previously showed that the disruption of PHOSPHATIDIC ACID PHOSPHOHYDROLASE (PAH) activity in Arabidopsis thaliana stimulates biosynthesis of the major phospholipid phosphatidylcholine (PC) and causes expansion of the endoplasmic reticulum. Here we show that PC biosynthesis is repressed by disruption of the core cell cycle regulator CYCLIN-DEPENDENT KINASE A;1 (CDKA;1) and that this repression is reliant on PAH. Furthermore, we show that cyclin-dependent kinases (CDKs) phosphorylate PAH1 at serine 162, which reduces both its activity and membrane association. Expression of a CDK-insensitive version of PAH1 with a serine 162 to alanine substitution represses PC biosynthesis and also reduces the rate of cell division in early leaf development. Together our findings reveal a physiologically important mechanism that couples the rate of phospholipid biosynthesis and endomembrane biogenesis to cell cycle progression in Arabidopsis. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  15. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Larson, Janet L; Covey, Margaret K; Kapella, Mary C; Alex, Charles G; McAuley, Edward

    2014-01-01

    People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. IN THIS RANDOMIZED CONTROLLED TRIAL, SUBJECTS WERE ASSIGNED TO: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR), health education with upper body resistance training (ED-UBR), or health education with gentle chair exercises (ED-Chair). Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Differences were observed in light physical activity (LPA) after 4 months of training, time by group interaction effect (P=0.045). The SE-UBR group increased time spent in LPA by +20.68±29.30 minutes/day and the other groups decreased time spent in LPA by -22.43±47.88 minutes/day and -25.73±51.76 minutes/day. Changes in LPA were not sustained at 12-month follow-up. There were no significant changes in moderate-to-vigorous physical activity, sedentary time, or functional performance. Subjects spent most of their waking hours sedentary: 72%±9% for SE-UBR, 68%±10% for ED-UBR, and 74%±9% for ED-Chair. The self-efficacy enhancing intervention produced a modest short-term increase in LPA. Further work is needed to increase the magnitude and duration of effect, possibly by targeting LPA.

  16. DNA–PKcs–SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yong; Fang, Shi-ji [The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000 (China); Zhu, Li-juan [Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215021 (China); Zhu, Lun-qing, E-mail: xiaodongwangsz@163.com [The Center of Diagnosis and Treatment for Children’s Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215000 (China); Zhou, Xiao-zhong, E-mail: zhouxz@suda.edu.cn [The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000 (China)

    2014-10-24

    Highlights: • LDI increases ALP activity, promotes type I collagen (Col I)/Runx2 mRNA expression. • LDI induces DNA–PKcs activation, which is required for osteoblast differentiation. • Akt activation mediates LDI-induced ALP activity and Col I/Runx2 mRNA increase. • DNA–PKcs–SIN1 complexation mediates LDI-induced Akt Ser-473 phosphorylation. • DNA–PKcs–SIN1 complexation is important for osteoblast differentiation. - Abstract: Low-dose irradiation (LDI) induces osteoblast differentiation, however the underlying mechanisms are not fully understood. In this study, we explored the potential role of DNA-dependent protein kinase catalytic subunit (DNA–PKcs)–Akt signaling in LDI-induced osteoblast differentiation. We confirmed that LDI promoted mouse calvarial osteoblast differentiation, which was detected by increased alkaline phosphatase (ALP) activity as well as mRNA expression of type I collagen (Col I) and runt-related transcription factor 2 (Runx2). In mouse osteoblasts, LDI (1 Gy) induced phosphorylation of DNA–PKcs and Akt (mainly at Ser-473). The kinase inhibitors against DNA–PKcs (NU-7026 and NU-7441) or Akt (LY294002, perifosine and MK-2206), as well as partial depletion of DNA–PKcs or Akt1 by targeted-shRNA, dramatically inhibited LDI-induced Akt activation and mouse osteoblast differentiation. Further, siRNA-knockdown of SIN1, a key component of mTOR complex 2 (mTORC2), also inhibited LDI-induced Akt Ser-473 phosphorylation as well as ALP activity increase and Col I/Runx2 expression in mouse osteoblasts. Co-immunoprecipitation (Co-IP) assay results demonstrated that LDI-induced DNA–PKcs–SIN1 complexation, which was inhibited by NU-7441 or SIN1 siRNA-knockdown in mouse osteoblasts. In summary, our data suggest that DNA–PKcs–SIN1 complexation-mediated Akt activation (Ser-473 phosphorylation) is required for mouse osteoblast differentiation.

  17. Receptor-mediated enhancement of beta adrenergic drug activity by ascorbate in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Patrick F Dillon

    Full Text Available RATIONALE: Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. OBJECTIVES: Extending this work to beta 2 adrenergic systems in vitro and in vivo. METHODS: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol with and without ascorbate was tested on horses with heaves and sheep with carbachol-induced bronchoconstriction. MEASUREMENTS: Binding constants for ascorbate binding to beta adrenergic receptor were derived from concentration-dependent spectral shifts. Dose- dependence curves were obtained for the relaxation of pre-contracted trachealis preparations due to beta agonists in the presence and absence of varied ascorbate. Tachyphylaxis and fade were also measured. Dose response curves were determined for the effect of albuterol plus-and-minus ascorbate on airway resistance in horses and sheep. MAIN RESULTS: Ascorbate binds to the beta 2 adrenergic receptor at physiological concentrations. The receptor recycles dehydroascorbate. Physiological and supra-physiological concentrations of ascorbate enhance submaximal epinephrine and isoproterenol relaxation of trachealis, producing a 3-10-fold increase in sensitivity, preventing tachyphylaxis, and reversing fade. In vivo, ascorbate improves albuterol's effect on heaves and produces a 10-fold enhancement of albuterol activity in "asthmatic" sheep. CONCLUSIONS: Ascorbate enhances beta-adrenergic activity via a novel receptor-mediated mechanism; increases potency and duration of beta adrenergic agonists effective in asthma and COPD; prevents tachyphylaxis; and reverses fade. These novel effects are

  18. Glutamate transporter activity promotes enhanced Na+/K+-ATPase-mediated extracellular K+ management during neuronal activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Holm, Rikke; Vilsen, Bente

    2016-01-01

    Neuronal activity is associated with transient [K+]o increases. The excess K+ is cleared by surrounding astrocytes, partly by the Na+/K+-ATPase of which several subunit isoform combinations exist. The astrocytic Na+/K+-ATPase α2β2 isoform constellation responds directly to increased [K+]o but...... Na+ affinity of isoform constellations involving the astrocytic β2 has remained elusive as a result of inherent expression of β1 in most cell systems, as well as technical challenges involved in measuring intracellular affinity in intact cells. We therefore expressed the different astrocytic isoform...... constellations in Xenopus oocytes and determined their apparent Na+ affinity in intact oocytes and isolated membranes. The Na+/K+-ATPase was not fully saturated at basal astrocytic [Na+]i, irrespective of isoform constellation, although the β1 subunit conferred lower apparent Na+ affinity to the α1 and α2...

  19. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

    Science.gov (United States)

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  20. Apoferritin Nanoparticle: A Novel and Biocompatible Carrier for Enzyme Immobilization with Enhanced Activity and Stability

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Youyu; Tang, Zhiwen; Wang, Jun; Wu, Hong J.; Lin, Chiann Tso; Lin, Yuehe

    2011-11-01

    Apoferritin is a nanostructured material with a uniform size and spherical structure, and it has excellent bio-compatibility. In this work, we report the use of apoferritin as a novel and biocompatible carrier for stabilizing enzymes and their activities. We used glucose oxidase (GOx) as a model enzyme. GOx was immobilized on the surface of the apoferritin through a green synthetic approach taking advantage of bioaffinity binding between streptavidin and biotin. As a result, a glucose oxidase-biotin/streptavidin/biotin-apoferritin conjugate (Apo-GOx) was prepared using streptavidin as a bridge. The synthesized Apo-GOx was characterized with transmission electron microscopy, ultraviolet, and fluorescence spectroscopy. The activity and stability of GOx on the surface of the apoferritin were studied in different environments, such as temperature, chemicals, and pH, in comparison with the biotinylated GOx (B-GOx). The results showed that the activity of GOx on the apoferritin surface was significantly enhanced. The thermal and chemical stability of the GOx on the apoferritin was also greatly improved compared to free B-GOx in a solution. It was found that the activity of the GOx on the apoferritin only lost 30% in comparison to a 70% loss of free B-GOx after a 2 h incubation at 50oC. There was almost no decrease in activity for the GOx on the apoferritin as compared to an 80% activity decrease for free B-GOx after 30 min incubation in a 5 M urea solution. Glucose detection was used as a model application for the enzyme immobilization method developed in this work. The GOx immobilized apoferritin nanoparticles exhibited high sensitivity for glucose detection with a detection limit of 3 nM glucose. This work offers a novel approach for immobilizing enzymes with enhanced stability and activity, and this method may find a number of applications, such as in enzyme catalysis, DNA assays and immunoassays.

  1. Activity Enhancement Based on the Chemical Equilibrium of Multiple-Subunit Nitrile Hydratase from Bordetella petrii.

    Science.gov (United States)

    Liu, Yi; Liu, Ping; Lin, Lu; Zhao, Yueqin; Zhong, Wenjuan; Wu, Lunjie; Zhou, Zhemin; Sun, Weifeng

    2016-09-01

    The maturation mechanism of nitrile hydratase (NHase) of Pseudomonas putida NRRL-18668 was discovered and named as "self-subunit swapping." Since the NHase of Bordetella petrii DSM 12804 is similar to that of P. putida, the NHase maturation of B. petrii is proposed to be the same as that of P. putida. However, there is no further information on the application of NHase according to these findings. We successfully rapidly purified NHase and its activator through affinity his tag, and found that the cell extracts of NHase possessed multiple types of protein ingredients including α, β, α2β2, and α(P14K)2 who were in a state of chemical equilibrium. Furthermore, the activity was significantly enhanced through adding extra α(P14K)2 to the cell extracts of NHase according to the chemical equilibrium. Our findings are useful for the activity enhancement of multiple-subunit enzyme and for the first time significantly increased the NHase activity according to the chemical equilibrium.

  2. Extraction optimization and nanoencapsulation of jujube pulp and seed for enhancing antioxidant activity.

    Science.gov (United States)

    Han, Hye Jung; Lee, Ji-Soo; Park, Sun-Ah; Ahn, Jun-Bae; Lee, Hyeon Gyu

    2015-06-01

    The aim of this study was to optimize extraction conditions for jujube pulp and seed in order to obtain maximum active ingredient yield and antioxidant activity, as well as to prepare chitosan nanoparticles loaded with jujube pulp and seed extracts for enhancing stability. The extraction conditions, i.e. temperature, time, and ethanol concentration, were optimized at the following respective values: 61.2 °C, 38 h, and 60.4% for pulp, and 58 °C, 34 h, and 59.2% for seed. The jujube nanoparticle size significantly increased with a higher chitosan/sodium tripolyphosphate ratio and extract concentration. Entrapment efficiency was greater than 80% regardless of preparation conditions. The stabilities of jujube pulp and seed extract in terms of total phenolic content and antioxidant activity were effectively enhanced by nanoencapsulation. In conclusion, jujube pulp and seed extracts prepared using optimal conditions could be useful as a natural functional food ingredient with antioxidant activity, and nanoencapsulation can be used to improve the stability of jujube extract. Therefore, these results could be used to promote the utilization of not only jujube pulp but also seed, by product. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Design, Synthesis and Evaluation of the Antibacterial Enhancement Activities of Amino Dihydroartemisinin Derivatives

    Directory of Open Access Journals (Sweden)

    Dacheng Yang

    2013-06-01

    Full Text Available Artemisinin (ART and its derivatives artesunate (AS, dihydroartemisinin (DHA are a group of drugs containing a sesquiterpene lactone used to treat malaria. Previously, AS was shown to not have antibacterial activity but to significantly increase the antibacterial activities of β-lactam antibiotics against E. coli. Herein, molecular docking experiments showed that ART, AS and DHA could dock into AcrB very well, especially DHA and AS; both DHA and AS had the same docking pose. The affinity between AS and AcrB seemed weaker than that of DHA, while the succinate tail of AS, which was like a “bug”, could extend in the binding pocket very well. Imitating the parent nucleus of DHA and the succinate tail of AS, twenty-one DHA derivatives 4a–u were designed and synthesized. Among them, seventeen were new compounds. The synergistic effects against E. coli AG100A/pET28a-AcrB showed among the new structures 4k, 4l, 4m, 4n, and 4r exhibited significant synergism with β-lactam antibiotics although they had no direct antibacterial activities themelves. The bacterial growth assay showed that only 4k in combination with ampicillin or cefuroxime could totally inhibit bacterial growth from 0 to 12 h, demonstrating that 4k had the best antibacterial enhancement effect. In conclusion, our results provided a new idea and several candidate compounds for antibacterial activity enhancers against multidrug resistant E. coli.

  4. Pin1 enhances adipocyte differentiation by positively regulating the transcriptional activity of PPARγ.

    Science.gov (United States)

    Han, Younho; Lee, Sung Ho; Bahn, Minjin; Yeo, Chang-Yeol; Lee, Kwang Youl

    2016-11-15

    Pin1 is a peptidylprolyl cis/trans isomerase and it has a unique enzymatic activity of catalyzing isomerization of the peptide bond between phospho-serine/threonine and proline. Through the conformational change of its substrates, Pin1 regulates diverse biological processes including adipogenesis. In mouse embryonic fibroblasts and 3T3-L1 preadipocytes, overexpression of Pin1 enhances adipocyte differentiation whereas inhibition of Pin1 activity suppresses it. However, the precise functions of Pin1 during adipogenesis are not clear. In the present study, we investigated the potential targets of Pin1 during adipogenesis. We found that Pin1 interacts directly with and regulates the transcriptional activity of PPARγ, a key regulator of adipogenesis. In addition, ERK activity and Ser273 of PPARγ, a potential ERK phosphorylation target site, are important for the regulation of PPARγ function by Pin1 in 3T3-L1 cells. Taken together our results suggest a novel regulatory mechanism of Pin1 during adipogenesis, in which Pin1 enhances adipocyte differentiation by regulating the function of PPARγ. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Enhancing learning with the social media: student teachers’ perceptions on Twitter in a debate activity

    Directory of Open Access Journals (Sweden)

    Gemma Tur

    2015-01-01

    Full Text Available This paper presents research focused on the educational experience of students using the microblogging platform Twitter for debate activities in three groups in different teacher education programmes at the University of the Balearic Islands, Spain. The implementation of this technology-based task in a face-to-face class was introduced as an innovative experience as a way of enhancing student learning and fostering participation in the context of formal learning. The educational objectives of these activities, besides working on the topics of the debate, were to empower student teachers’ Personal Learning Environments, engage student participation and enhance their use of social media and mobile devices for learning. Student perceptions were assessed by means of a questionnaire completed by them at the end of the courses. Tweets related to the debate were also collected in order to obtain some statistical data on student participation. Data collected allowed the researchers to observe student teacher engagement with the use of Twitter for the debate activity and its impact on their learning and understanding of the debate topic. Results also showed positive perceptions towards the use of social media in education and students’ willingness for future use, learning opportunities from Twitter and the use of mobile technology were also envisioned. Finally, conclusions argue the implications for practice of the current study and highlight some issues for further research, such as the exploration of new and innovative uses for teachers’ professional development and the empowerment of new activities and habits in learning on the move.

  6. Expression of CCL19 from Oncolytic Vaccinia Enhances Immunotherapeutic Potential while Maintaining Oncolytic Activity

    Directory of Open Access Journals (Sweden)

    Jun Li

    2012-12-01

    Full Text Available Promising phase II clinical results have been reported recently for several oncolytic viral therapeutics, including strains based on vaccinia virus. One reason for this has been an increased appreciation of the critical therapeutic importance of the immune response raised by these viruses. However, the most commonly used approaches to enhance these immunotherapeutic effects in oncolytic viruses, typically though expression of cytokine transgenes, often also result in a reduction in oncolytic activity and premature clearance of the virotherapy from the tumor. Approaches that enhance the immunotherapeutic effects while maintaining oncolytic activity would therefore be beneficial. Here, it is demonstrated that the expression of the chemokine CCL19 (ELC from an oncolytic vaccinia virus (vvCCL19 results in increased antitumor effects in syngeneic mouse tumor models. This corresponded with increased t cell and dendritic cell infiltration into the tumor. However, vvCCL19 persisted in the tumor at equivalent levels to a control virus without CCL19, demonstrating that oncolytic activity was not curtailed. Instead, vvCCL19 was cleared rapidly and selectively from normal tissues and organs, indicating a potentially increased safety profile. The therapeutic activity of vvCCL19 could be further significantly increased through combination with adoptive transfer of therapeutic immune cells expressing CCR7, the receptor for CCL19. This approach therefore represents a means to increase the safety and therapeutic benefit of oncolytic viruses, used alone or in combination with immune cell therapies.

  7. Negative emotional experiences during navigation enhance parahippocampal activity during recall of place information.

    Science.gov (United States)

    Chan, Edgar; Baumann, Oliver; Bellgrove, Mark A; Mattingley, Jason B

    2014-01-01

    It is known that the parahippocampal cortex is involved in object-place associations in spatial learning, but it remains unknown whether activity within this region is modulated by affective signals during navigation. Here we used fMRI to measure the neural consequences of emotional experiences on place memory during navigation. A day before scanning, participants undertook an active object location memory task within a virtual house in which each room was associated with a different schedule of task-irrelevant emotional events. The events varied in valence (positive, negative, or neutral) and in their rate of occurrence (intermittent vs. constant). On a subsequent day, we measured neural activity while participants were shown static images of the previously learned virtual environment, now in the absence of any affective stimuli. Our results showed that parahippocampal activity was significantly enhanced bilaterally when participants viewed images of a room in which they had previously encountered negatively arousing events. We conclude that such automatic enhancement of place representations by aversive emotional events serves as an important adaptive mechanism for avoiding future threats.

  8. Enhanced catalytic activity of solid and hollow platinum-cobalt nanoparticles towards reduction of 4-nitrophenol

    Science.gov (United States)

    Krajczewski, Jan; Kołątaj, Karol; Kudelski, Andrzej

    2016-12-01

    Previous investigations of hollow platinum nanoparticles have shown that such nanostructures are more active catalysts than their solid counterparts towards the following electrochemical reactions: reduction of oxygen, evolution of hydrogen, and oxidation of borohydride, methanol and formic acid. In this work we show that synthesised using standard galvanic replacement reaction (with Co templates) hollow platinum nanoparticles exhibit enhanced catalytic activity also towards reduction of 4-nitrophenol by sodium borohydride in water. Unlike in the case of procedures involving hollow platinum catalysts employed so far to carry out this reaction it is not necessary to couple analysed platinum nanoparticles to the surface of an electrode. Simplification of the analyzed reaction may eliminate same experimental errors. We found that the enhanced catalytic activity of hollow Pt nanoparticles is not only connected with generally observed larger surface area of hollow nanostructures, but is also due to the contamination of formed hollow nanostructures with cobalt, from which sacrificial templates used in the synthesis of hollow Pt nanostrustures have been formed. Because using sacrificial templates is a typical method of synthesis of hollow metal nanostructures, formed hollow nanoparticles are probably often contaminated, which may significantly influence their catalytic activity.

  9. Sophoraflavanone G from sophora pachycarpa enhanced the antibacterial activity of gentamycin against Staphylococcus aureus.

    Science.gov (United States)

    Fakhimi, Ali; Iranshahi, Mehrdad; Emami, Seyed Ahmad; Amin-Ar-Ramimeh, Esam; Zarrini, Gholamreza; Shahverdi, Ahmad Reza

    2006-01-01

    In this study the enhancement effect of Sophora pachycarpa roots' acetone extract on the antibacterial activity of gentamycin was evaluated against Staphylococcus aureus. Disc diffusion and broth dilution methods were used to determine the antibacterial activity of gentamycin in the absence and presence of plant extract and its various fractions separated by TLC. A clinical isolate of S. aureus was used as test strain. The active component of the plant extract involved in enhancement of gentamycin's activity had Rf = 0.72 on a TLC plate. The spectral data (1H NMR, 13C NMR) of this compound revealed that this compound was 5,7,2',4'-tetrahydroxy-8-lavandulylflavanone (sophoraflavanone G), previously isolated from Sophora exigua. In the presence of 0.03 microg/ mL of sophoraflavanone G the MIC value of gentamycin for S. aureus decreased from 32 to 8 microg/mL (a four-fold decrease). These results signify that the ultra-low concentration of sophoraflavanone G potentiates the antimicrobial action of gentamycin suggesting a possible utilization of this compound in combination therapy against Staphylococcus aureus.

  10. Enhancement of knowledge construction activities utilizing 21st century learning design rubric

    Science.gov (United States)

    Pedoche, Margarette Anne U.; Taladua, Janica Mae M.; Panal, Geicky Pearl C.; Magsayo, Joy R.; Guarin, Rica Mae B.; Myrna, H. Lahoylahoy

    2018-01-01

    The main objective of the study was to enhance knowledge construction activities on its design particularly the objectives, support materials, student activities and assessment tools. Activities from the 2nd Quarter of Science Learners Material were the basis in the adaptation of activities. The adapted activities were evaluated by the In-service Science teachers and undergone modification by the researchers based on the teacher's comments and suggestions. It was then evaluated, revised, and validated, tried-out using the 21st CLD Rubric. Subjects of the study were 110 students from Grade 7-B, Grade 7-D, Grade 7-F in Geronima Cabrera National High School, Kolambugan, Lanao del Norte during the academic year 2016-2017, the study to determine their learning capabilities investigated by the use of Knowledge Construction Activities in the 21st Century Classroom, to investigate how the lessons were understood and appreciated by students, to stimulate interpretation, analysis, synthesizing, or evaluating ideas and develop critical thinking. Both quantitative and qualitative data were obtained from the students' scores in three activities. Results showed that there was a significant difference between the pretest and posttest scores of students. Mean scores between the pretest and posttest showed a mean difference of 3.35, thus the null hypothesis was rejected. It could be concluded with sufficient evidence to show that the students had basically low prior knowledge about the topic ecosystem. A significant difference was seen in the pretest and posttest, scores of the activities and Ecosystem model results after the implementation phase that a knowledge construction type of activity was better than the traditional one for it promoted meaningful learning and active engagement of students. Based on the results, it was clear that the use of knowledge construction activities had an effect on student's achievement in comparison to traditional teaching method. Thus, it was

  11. In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation.

    Science.gov (United States)

    Martínez-Moreno, Julio M; Muñoz-Castañeda, Juan R; Herencia, Carmen; Oca, Addy Montes de; Estepa, Jose C; Canalejo, Rocio; Rodríguez-Ortiz, Maria E; Perez-Martinez, Pablo; Aguilera-Tejero, Escolástico; Canalejo, Antonio; Rodríguez, Mariano; Almadén, Yolanda

    2012-10-15

    The present study investigates the differential effect of two vitamin D receptor agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells calcification in vitro. Human vascular smooth muscle cells were incubated in a high phosphate (HP) medium alone or supplemented with either calcitriol 10(-8)M (HP + CTR) or paricalcitol 3·10(-8) M (HP + PC). HP medium induced calcification, which was associated with the upregulation of mRNA expression of osteogenic factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and osteocalcin. In these cells, activation of Wnt/β-catenin signaling was evidenced by the translocation of β-catenin into the nucleus and the increase in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican. Addition of calcitriol to HP medium (HP + CTR) further increased calcification and also enhanced the expression of osteogenic factors together with a significant elevation of nuclear β-catenin levels and the expression of cyclin D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not only reduced calcification but also downregulated the expression of BMP2 and other osteoblastic phenotype markers as well as the levels of nuclear β-catenin and the expression of its target genes. The role of Wnt/β-catenin on phosphate- and calcitriol-induced calcification was further demonstrated by the inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1), a specific natural antagonist of the Wnt/β-catenin signaling pathway. In conclusion, the differential effect of calcitriol and paricalcitol on vascular calcification appears to be mediated by a distinct regulation of the BMP and Wnt/β-catenin signaling pathways.

  12. Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from Pholidota articulata Lindley.

    Science.gov (United States)

    Sharma, Chetan; Dixit, Manisha; Singh, Rohit; Agrawal, Manali; Mansoori, Mohd Nizam; Kureel, Jyoti; Singh, Divya; Narender, Tadigoppula; Arya, Kamal Ram

    2015-07-21

    Pholidota articulata Lindley (PA) locally known as Hadjojen (bone jointer) belongs to family Orchidaceae is used for healing fractures in folklore tradition of Kumaon region of Uttarakhand, Himalaya, India. Bone is a dynamic organ and is constantly being remodeled in order to facilitate growth and repair. This process requires the involvement of bone forming osteoblast and bone resorbing osteoclast cells, which function in generating and mineralizing bone, giving strength and rigidity to the skeletal system. Present study was aimed to determine the therapeutic potential of ethanolic extract of PA and its isolated compound oxoflavidin, by characterizing their fracture healing properties. Ovariectomized (Ovx) estrogen deficient adult female Balb/c mice were used for in vivo evaluation of osteogenic or bone healing potential of ethanolic extract of PA. Further, its isolated compounds were tested for their osteogenic efficacy using alkaline phosphatase assay and mineralization assay in vitro in mice calvarial osteoblasts. The ethanolic extract of PA exhibited significant restoration of trabecular micro-architecture in both femoral and tibial bones. Additionally, treatment with PA extract led to better bone quality and devoid of any uterine estrogenicity in ovariectomized estrogen deficient mice. One of the isolated compound, oxoflavidin enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen, RUNX-2 and osteocalcin. These results warrant that ethanolic extract of PA and it's pure compound oxoflavidin have fracture healing properties. The extract and oxoflavidin exhibit a strong threapeutical potential for the treatment and management of postmenopausal osteoporosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells.

    Science.gov (United States)

    Huh, Yun Suk; Chung, Aram J; Cordovez, Bernardo; Erickson, David

    2009-02-07

    Here we present a novel microfluidic technique for on-chip surface enhanced Raman spectroscopy (SERS) based biomolecular detection, exploiting the use of electrokinetically active microwells. Briefly, the chip comprises of a series of microfluidic channels containing embedded microwells that, when electrically actuated, either locally attract or repulse species from solution through a combination of electrokinetic effects. We demonstrate that the approach combines the advantages of existing homogeneous (solution phase) and heterogeneous (surface phase) on-chip techniques by enabling active mixing to enhance the rate of binding between the SERS enhancers and the biomolecular targets as well as rapid concentration of the product for surface phase optical interrogation. This paper describes the chip design and fabrication procedure, experimental results illustrating the optimal conditions for our concentration and mixing processes, and a numerical analysis of the flow pattern. To demonstrate the usefulness of the device we apply it to the quantitative detection of nucleic acid sequences associated with Dengue virus serotype 2. We report a limit of detection for Dengue sequences of 30 pM and show excellent specificity against other serotypes.

  14. Effects of glucose on the performance of enhanced biological phosphorus removal activated sludge enriched with acetate.

    Science.gov (United States)

    Gebremariam, Seyoum Yami; Beutel, Marc W; Christian, David; Hess, Thomas F

    2012-10-01

    The effects of glucose on enhanced biological phosphorus removal (EBPR) activated sludge enriched with acetate was investigated using sequencing batch reactors. A glucose/acetate mixture was serially added to the test reactor in ratios of 25/75%, 50/50%, and 75/25% and the EBPR activity was compared to the control reactor fed with 100% acetate. P removal increased at a statistically significant level to a near-complete in the test reactor when the mixture increased to 50/50%. However, EBPR deteriorated when the glucose/acetate mixture increased to 75/25% in the test reactor and when the control reactor abruptly switched to 100% glucose. These results, in contrast to the EBPR conventional wisdom, suggest that the addition of glucose at moderate levels in wastewaters does not impede and may enhance EBPR, and that glucose waste products should be explored as an economical sustainable alternative when COD enhancement of EBPR is needed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Plasminogen Activator Inhibitor-1 Is Critical in Alcohol-Enhanced Acute Lung Injury in Mice.

    Science.gov (United States)

    Poole, Lauren G; Massey, Veronica L; Siow, Deanna L; Torres-Gonzáles, Edilson; Warner, Nikole L; Luyendyk, James P; Ritzenthaler, Jeffrey D; Roman, Jesse; Arteel, Gavin E

    2017-09-01

    Chronic alcohol exposure is a clinically important risk factor for the development of acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). However, the mechanisms by which alcohol sensitizes the lung to development of this disease are poorly understood. We determined the role of the antifibrinolytic protein plasminogen activator inhibitor-1 (PAI-1) in alcohol enhancement of experimental endotoxin-induced ALI. Wild-type, PAI-1-/-, and integrin β3-/- mice were fed ethanol-containing Lieber-DeCarli liquid or a control diet for 6 weeks, followed by systemic LPS challenge. LPS administration triggered coagulation cascade activation as evidenced by increased plasma thrombin-antithrombin levels and pulmonary fibrin deposition. Ethanol-exposed animals showed enhanced PAI-1 expression and pulmonary fibrin deposition with coincident exaggeration of pulmonary inflammatory edematous injury. PAI-1 deficiency markedly reduced pulmonary fibrin deposition and greatly reduced inflammation and injury without impacting upstream coagulation. Interestingly, pulmonary platelet accumulation was effectively abolished by PAI-1 deficiency in ethanol/LPS-challenged mice. Moreover, mice lacking integrin αIIBβ3, the primary platelet receptor for fibrinogen, displayed a dramatic reduction in early inflammatory changes after ethanol/LPS challenge. These results indicate that the mechanism whereby alcohol exaggerates LPS-induced lung injury requires PAI-1-mediated pulmonary fibrin accumulation, and suggest a novel mechanism whereby alcohol contributes to inflammatory ALI by enhancing fibrinogen-platelet engagement.

  16. Enhancing active learning in microbiology through case based learning: experiences from an Indian medical school.

    Science.gov (United States)

    Ciraj, A M; Vinod, P; Ramnarayan, K

    2010-01-01

    Case-based learning (CBL) is an interactive student-centered exploration of real life situations. This paper describes the use of CBL as an educational strategy for promoting active learning in microbiology. CBL was introduced in the microbiology curriculum for the second year medical students after an orientation program for faculty and students. After intervention, the average student scores in CBL topics were compared with scores obtained in lecture topics. An attempt was also made to find the effect of CBL on the academic performance. Student and faculty perception on CBL were also recorded. In a cross sectional survey conducted to assess the effectiveness of CBL, students responded that, apart from helping them acquire substantive knowledge in microbiology, CBL sessions enhanced their analytic, collaborative, and communication skills. The block examination scores in CBL topics were significantly higher than those obtained for lecture topics. Faculty rated the process to be highly effective in stimulating student interest and long term retention of microbiology knowledge. The student scores were significantly higher in the group that used CBL, compared to the group that had not used CBL as a learning strategy. Our experience indicated that CBL sessions enhanced active learning in microbiology. More frequent use of CBL sessions would not only help the student gain requisite knowledge in microbiology but also enhance their analytic and communication skills.

  17. Star-shaped ZnO/Ag hybrid nanostructures for enhanced photocatalysis and antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, George R.S., E-mail: grsandrade@hotmail.com [Postgraduate Program in Materials Science and Engineering, Federal University of Sergipe, São Cristóvão, SE (Brazil); Nascimento, Cristiane C. [Postgraduate Program in Materials Science and Engineering, Federal University of Sergipe, São Cristóvão, SE (Brazil); Federal Institute of Education, Science and Technology of Sergipe, Glória Campus, Nossa Senhora da Glória, SE (Brazil); Lima, Zenon M. [Postgraduate Program in Industrial Biochemistry, Tiradentes University, Aracaju, SE (Brazil); Teixeira-Neto, Erico [LNNano − Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, SP (Brazil); Costa, Luiz P. [Postgraduate Program in Industrial Biochemistry, Tiradentes University, Aracaju, SE (Brazil); ITPS − Technological and Research Institute of Sergipe, Aracaju, SE (Brazil); Gimenez, Iara F. [Postgraduate Program in Materials Science and Engineering, Federal University of Sergipe, São Cristóvão, SE (Brazil); Department of Chemistry, Federal University of Sergipe, São Cristóvão, SE (Brazil)

    2017-03-31

    Highlights: • A new and simple one-pot method for preparing star-shaped ZnO particles was reported. • ZnO particles were decorated with Ag nanoparticles (SNPs) by a photodeposition method. • The presence of SNC{sup −} ions on ZnO surface prevented uncontrollable growth of SNPs. • ZnO/Ag particles showed plasmon-enhanced photocatalytic activity toward an AZO dye. • SNP improved 16 times the antibacterial activity of ZnO toward 4 bacterial strains. - Abstract: Zinc oxide (ZnO) particles with a star-shaped morphology have been synthesized by a novel and simple room-temperature method and decorated with silver nanoparticles (SNPs) for enhanced photocatalysis and bactericide applications. The presence of thiourea during the precipitation of ZnO in alkaline conditions allowed the control of morphological features (e.g. average size and shape) and the surface functionalization with thiocyanate ions (SCN{sup −}). SNPs were deposited into the ZnO surface by a photoreduction method and their sizes could be easily controlled by changing the ZnO/AgNO{sub 3} ratio. The presence of SCN{sup −} on the semiconductor surface prevents uncontrollable growth of Ag nanoparticles into different morphologies and high degrees of polydispersity. XRD, SEM, TEM, FTIR, UV-vis-NIR and PL were employed for characterizing the structure, morphology and optical properties of the as-obtained pure and hybrid nanostructures. Finally, the hybrid ZnO/Ag particles have shown plasmon-enhanced performance for applications in photocatalysis and antibacterial activity compared to the pure ZnO counterpart. In this work, evaluation of the photodegradation of an aqueous methylene blue solution under UV-A irradiation and the antibacterial activity toward 4 bacterial strains, including Gram-positive bacteria Staphylococcus aureus (ATCC 43300, ATCC 25923 and ATCC 33591) and Gram-negative bacteria Pseudomonas aeruginosa (ATCC 27853).

  18. Enhanced exo-inulinase activity and stability by fusion of an inulin-binding module.

    Science.gov (United States)

    Zhou, Shun-Hua; Liu, Yuan; Zhao, Yu-Juan; Chi, Zhe; Chi, Zhen-Ming; Liu, Guang-Lei

    2016-09-01

    In this study, an inulin-binding module from Bacillus macerans was successfully fused to an exo-inulinase from Kluyveromyces marxianus, creating a hybrid functional enzyme. The recombinant exo-inulinase (rINU), the hybrid enzyme (rINUIBM), and the recombinant inulin-binding module (rIBM) were, respectively, heterologously expressed and biochemically characterized. It was found that both the inulinase activity and the catalytic efficiency (k cat/K m(app)) of the rINUIBM were considerably higher than those of rINU. Though the rINU and the rINUIBM shared the same optimum pH of 4.5, the optimum temperature of the rINUIBM (60 °C) was 5 °C higher than that of the rINU. Notably, the fused IBM significantly enhanced both the pH stability and the thermostability of the rINUIBM, suggesting that the rINUIBM obtained would have more extensive potential applications. Furthermore, the fusion of the IBM could substantially improve the inulin-binding capability of the rINUIBM, which was consistent with the determination of the K m(app). This meant that the fused IBM could play a critical role in the recognition of polysaccharides and enhanced the hydrolase activity of the associated inulinase by increasing enzyme-substrate proximity. Besides, the extra supplement of the independent non-catalytic rIBM could also improve the inulinase activity of the rINU. However, this improvement was much better in case of the fusion. Consequently, the IBM could be designated as a multifunctional domain that was responsible for the activity enhancement, the stabilization, and the substrate binding of the rINUIBM. All these features obtained in this study make the rINUIBM become an attractive candidate for an efficient inulin hydrolysis.

  19. Gamma radiation induced mutagenesis of lysobacter enzymogenes for enhanced chitinolytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Keun; Kim, Kyoung Youl; Senthilkumar, M. [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2010-03-15

    Two chitinase producing strains CHI2 and CHI4 were isolated from soybean rhizosphere soil. Both the strains belonged to Lysobacter enzymogenes as indicated by 16S rDNA sequence analysis. Though strain CHI2 and CHI4 produced extracellular chitinase, they differ in their chitinolytic activity. CHI4 produced approximately three times the higher amounts of enzyme than that of CHI2 under specified conditions. CHI2 produced 535.67 U I{sup -1} of chitinase after 48 h incubation with a specific activity of 3.91 U mg{sup -1} of protein while strain CHI4 produced 1584.13 U I{sup -1} of chitinase with a specific activity of 10.88 U mg{sup -1} protein. SDS-PAGE analysis indicated that the molecular weight of chitinase enzyme was approximately 45 kDa. A faint band with a molecular weight of 55 kDa reveals the possibility for the isolates to gamma rays at their LD{sub 99} value (0.23 kGy). Totally, 11 mutants of CHI2 and CHI4 are reported to have enhanced chitinase activity. Several leaky mutant clones with decreased enzyme activity and a defective mutant (CHI2-M16) with complete loss of chitinase activity were also dentified. CHI4-M18, CHI4-M8 and CHI4-M29 showed 78.8, 41.5, and 31.9% increased chitinase activity over type CHI4.

  20. Enhanced leavening properties of baker's yeast by reducing sucrase activity in sweet dough.

    Science.gov (United States)

    Zhang, Cui-Ying; Lin, Xue; Feng, Bing; Liu, Xiao-Er; Bai, Xiao-Wen; Xu, Jia; Pi, Li; Xiao, Dong-Guang

    2016-07-01

    Leavening ability in sweet dough is required for the commercial applications of baker's yeast. This property depends on many factors, such as glycolytic activity, sucrase activity, and osmotolerance. This study explored the importance of sucrase level on the leavening ability of baker's yeast in sweet dough. Furthermore, the baker's yeast strains with varying sucrase activities were constructed by deleting SUC2, which encodes sucrase or replacing the SUC2 promoter with the VPS8/TEF1 promoter. The results verify that the sucrase activity negatively affects the leavening ability of baker's yeast strains under high-sucrose conditions. Based on a certain level of osmotolerance, sucrase level plays a significant role in the fermentation performance of baker's yeast, and appropriate sucrase activity is an important determinant for the leavening property of baker's yeast in sweet dough. Therefore, modification on sucrase activity is an effective method for improving the leavening properties of baker's yeast in sweet dough. This finding provides guidance for the breeding of industrial baker's yeast strains for sweet dough leavening. The transformants BS1 with deleted SUC2 genetic background provided decreased sucrase activity (a decrease of 39.3 %) and exhibited enhanced leavening property (an increase of 12.4 %). Such a strain could be useful for industrial applications.

  1. Development of microalgae biomaterials with enhanced antioxidant activity using electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Younghwa; Park, Hyunjin; Choi, Soojeong; Lee, Jaehwa [Silla Univ., Busan (Korea, Republic of)

    2013-07-01

    By increasing the antioxidant products (e. g. antioxidant enzyme, carotenoid, phycobiliproteins, chlorophyll, lipid phenolic compounds, etc.) in microalgae, it could be useful for industry. In this study, mutants of fresh water microalgae Arthrospira platensis (A. platensis) by high energy electron beam were isolated and characterized. Those selected mutants showed higher growth rate than parental strain. The antioxidant enzyme activity (SOD and POD), flavonoid, phenolic compound and phycocyanin of mutants were increased about 2 times compared to wild type. Moreover, DPPH radical scavenging activity was increased about 20%. Microalgae species with improved growth rate and enhanced active compounds make the commercial process more feasible in industry. Using microalgae mutants with increased antioxidant products, it is useful to develop microalgae biomaterials for neutraceuticals.

  2. Enhancement of active corrosion protection via combination of inhibitor-loaded nanocontainers.

    Science.gov (United States)

    Tedim, J; Poznyak, S K; Kuznetsova, A; Raps, D; Hack, T; Zheludkevich, M L; Ferreira, M G S

    2010-05-01

    The present work reports the synthesis of layered double hydroxides (LDHs) nanocontainers loaded with different corrosion inhibitors (vanadate, phosphate, and 2-mercaptobenzothiazolate) and the characterization of the resulting pigments by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The anticorrosion activity of these nanocontainers with respect to aluminum alloy AA2024 was investigated by electrochemical impedance spectroscopy (EIS). The bare metallic substrates were immersed in dispersions of nanocontainers in sodium chloride solution and tested to understand the inhibition mechanisms and efficiency. The nanocontainers were also incorporated into commercial coatings used for aeronautical applications to study the active corrosion protection properties in systems of industrial relevance. The results show that an enhancement of the active protection effect can be reached when nanocontainers loaded with different inhibitors are combined in the same protective coating system.

  3. Characteristics and enhanced antioxidant activity of glycated Morchella esculenta protein isolate

    Directory of Open Access Journals (Sweden)

    Qiang ZHANG

    Full Text Available Abstract Morchella esculenta (L Pers. is a highly valued edible and medicinal fungus that remains underutilized. For this study, the effects of glycation treatment on antioxidant activity and characteristics of the M. esculenta protein isolate (MPI were investigated via the Maillard reaction. Conjugation between MPI and xylose was proven via UV-vis, FT-IR, intrinsic fluorescence analysis, and SDS-PAGE. Amino acid analysis revealed involvement of lysine, arginine and tyrosine in MPI, forming a covalent cross-link with xylose. Differential scanning calorimetry (DSC results showed that glycated MPI (MPIG possesses a more favorable thermal stability compared to native MPI (MPIN, heated MPI (MPIH and an unheated mixture of MPI and xylose (MPI-XM. MPIG exhibited significantly enhanced antioxidant activity compared to MPIN, MPIH, and MPI-XM. These results indicate MPIG can serve as a promising novel source of nutraceutical and functional ingredients that exert antioxidant activity.

  4. Peripheral chemoreceptor activation enhances 5-hydroxytryptamine release in the locus coeruleus of conscious rats.

    Science.gov (United States)

    Singewald, N; Kouvelas, D; Kaehler, S T; Sinner, C; Philippu, A

    2000-07-28

    Intravenous bolus injection of KCN (40 microg) elicited brief but pronounced tachypnea, bradycardia and pressor response, and led to a 37% increase in 5-hydroxytryptamine (serotonin) (5-HT) release in the locus coeruleus (LC) of freely moving rats. Slow infusion of KCN (15 microg/min) for 10 min induced only a slight pressor response, but increased the respiration rate (+39 breaths/min), as well as 5-HT release in the LC (+60%) throughout the infusion. In rats with transected chemoreceptor afferents, neither injection or infusion of KCN changed 5-HT release, suggesting that in intact animals, the effect on extracellular 5-HT was due to activation of peripheral chemoreceptors. In summary, we report that peripheral chemoreceptor activation enhances 5-HT release in the LC, indicating that 5-HT might be involved in the modulation of LC activity by ascending chemosensory information.

  5. Lithium Enhances Axonal Regeneration in Peripheral Nerve by Inhibiting Glycogen Synthase Kinase 3β Activation

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    Huanxing Su

    2014-01-01

    Full Text Available Brachial plexus injury often involves traumatic root avulsion resulting in permanent paralysis of the innervated muscles. The lack of sufficient regeneration from spinal motoneurons to the peripheral nerve (PN is considered to be one of the major causes of the unsatisfactory outcome of various surgical interventions for repair of the devastating injury. The present study was undertaken to investigate potential inhibitory signals which influence axonal regeneration after root avulsion injury. The results of the study showed that root avulsion triggered GSK-3β activation in the injured motoneurons and remaining axons in the ventral funiculus. Systemic application of a clinical dose of lithium suppressed activated GSK-3β in the lesioned spinal cord to the normal level and induced extensive axonal regeneration into replanted ventral roots. Our study suggests that GSK-3β activity is involved in negative regulation for axonal elongation and regeneration and lithium, the specific GSK-3β inhibitor, enhances motoneuron regeneration from CNS to PNS.

  6. Model Integrating Fuzzy Argument with Neural Network Enhancing the Performance of Active Queue Management

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    Nguyen Kim Quoc

    2015-08-01

    Full Text Available The bottleneck control by active queue management mechanisms at network nodes is essential. In recent years, some researchers have used fuzzy argument to improve the active queue management mechanisms to enhance the network performance. However, the projects using the fuzzy controller depend heavily on professionals and their parameters cannot be updated according to changes in the network, so the effectiveness of this mechanism is not high. Therefore, we propose a model combining the fuzzy controller with neural network (FNN to overcome the limitations above. Results of the training of the neural networks will find the optimal parameters for the adaptive fuzzy controller well to changes of the network. This improves the operational efficiency of the active queue management mechanisms at network nodes.

  7. Solvothermal synthesis of hierarchical TiO2 nanostructures with tunable morphology and enhanced photocatalytic activity

    Science.gov (United States)

    Fan, Zhenghua; Meng, Fanming; Zhang, Miao; Wu, Zhenyu; Sun, Zhaoqi; Li, Aixia

    2016-01-01

    This paper presents controllable growth and photocatalytic activity of TiO2 hierarchical nanostructures by solvothermal method at different temperatures. It is revealed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) that the morphology of TiO2 can be effectively controlled as rose-like, chrysanthemum-like and sea-urchin-like only changing solvothermal temperature. BET surface area analysis confirms the presence of a mesoporous network in all the nanostructures, and shows high surface area at relatively high temperature. The photocatalytic activities of the photocatalysts are evaluated by the photodegradation of RhB under UV light irradiation. The TiO2 samples exhibit high activity on the photodegradation of RhB, which is higher than that of the commercial P25. The enhancement in photocatalytic performance can be attributed to the synergetic effect of the surface area, crystallinity, band gap and crystalline size.

  8. Activation of β-adrenoceptor facilitates active avoidance learning through enhancement of glutamate levels in the hippocampal dentate gyrus.

    Science.gov (United States)

    Lv, Jing; Feng, Hao; Chen, Ling; Wang, Wei-Yao; Yue, Xue-Ling; Jin, Qing-Hua

    2017-10-18

    Long-term potentiation (LTP) is widely accepted as the best studied model for neurophysiological mechanisms that could underlie learning and memory formation. Despite a number of studies indicating that β-adrenoceptors in the hippocampal dentate gyrus (DG) is involved in the modulation of learning and memory as well as LTP, few studies have used glutamate release as a visual indicator in awake animals to explore the role of β-adrenoceptors in learning-dependent LTP. Therefore, in the present study, the effects of propranolol (an antagonist of β-adrenoceptor) and isoproterenol (an agonist of β-adrenoceptor) on extracellular concentrations of glutamate and amplitudes of field excitatory postsynaptic potential were measured in the DG region during active avoidance learning in freely moving conscious rats. In the control group, the glutamate level in the DG was significantly increased during the acquisition of active avoidance behavior and returned to basal level following extinction training. In propranolol group, antagonism of β-adrenoceptors in the DG significantly reduced the change in glutamate level, and the acquisition of the active avoidance behavior was significantly inhibited. In contrast, the change in glutamate level was significantly enhanced by isoproterenol, and the acquisition of the active avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in glutamate level were accompanied by corresponding changes in field excitatory postsynaptic potential amplitude and active avoidance behavior. Our results suggest that activation of β-adrenoceptors in the hippocampal DG facilitates active avoidance learning by modulations of glutamate level and synaptic efficiency in rats.

  9. Neoamphimedine Circumvents Metnase-Enhanced DNA Topoisomerase IIα Activity Through ATP-Competitive Inhibition

    Science.gov (United States)

    Ponder, Jessica; Yoo, Byong Hoon; Abraham, Adedoyin D.; Li, Qun; Ashley, Amanda K.; Amerin, Courtney L.; Zhou, Qiong; Reid, Brian G.; Reigan, Philip; Hromas, Robert; Nickoloff, Jac A.; LaBarbera, Daniel V.

    2011-01-01

    Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase was shown to enhance TopoIIα activity and increase resistance to TopoIIα poisons. Using in vitro DNA decatenation assays we show that neoamphimedine potently inhibits TopoIIα-dependent DNA decatenation in the presence of Metnase. Cell proliferation assays demonstrate that neoamphimedine can inhibit Metnase-enhanced cell growth with an IC50 of 0.5 μM. Additionally, we find that the apparent Km of TopoIIα for ATP increases linearly with higher concentrations of neoamphimedine, indicating ATP-competitive inhibition, which is substantiated by molecular modeling. These findings support the continued development of neoamphimedine as an anticancer agent, particularly in solid tumors that over-express Metnase. PMID:22163192

  10. Collective Behavior of Chiral Active Matter: Pattern Formation and Enhanced Flocking

    Science.gov (United States)

    Liebchen, Benno; Levis, Demian

    2017-08-01

    We generalize the Vicsek model to describe the collective behavior of polar circle swimmers with local alignment interactions. While the phase transition leading to collective motion in 2D (flocking) occurs at the same interaction to noise ratio as for linear swimmers, as we show, circular motion enhances the polarization in the ordered phase (enhanced flocking) and induces secondary instabilities leading to structure formation. Slow rotations promote macroscopic droplets with late time sizes proportional to the system size (indicating phase separation) whereas fast rotations generate patterns consisting of phase synchronized microflocks with a controllable characteristic size proportional to the average single-particle swimming radius. Our results defy the viewpoint that monofrequent rotations form a vapid extension of the Vicsek model and establish a generic route to pattern formation in chiral active matter with possible applications for understanding and designing rotating microflocks.

  11. Enhancing physical activity in older adults receiving hospital based rehabilitation: a phase II feasibility study

    Directory of Open Access Journals (Sweden)

    Said Catherine M

    2012-06-01

    Full Text Available Abstract Background Older adults receiving inpatient rehabilitation have low activity levels and poor mobility outcomes. Increased physical activity may improve mobility. The objective of this Phase II study was to evaluate the feasibility of a randomized controlled trial (RCT of enhanced physical activity in older adults receiving rehabilitation. Methods Patients admitted to aged care rehabilitation with reduced mobility were randomized to receive usual care or usual care plus additional physical activity, which was delivered by a physiotherapist or physiotherapy assistant. The feasibility and safety of the proposed RCT protocol was evaluated. The primary clinical outcome was mobility, which was assessed on hospital admission and discharge by an assessor blinded to group assignment. To determine the most appropriate measure of mobility, three measures were trialled; the Timed Up and Go, the Elderly Mobility Scale and the de Morton Mobility Index. Results The protocol was feasible. Thirty-four percent of people admitted to the ward were recruited, with 47 participants randomised to a control (n = 25 or intervention group (n = 22. The rates of adverse events (death, falls and readmission to an acute service did not differ between the groups. Usual care therapists remained blind to group allocation, with no change in usual practice. Physical activity targets were met on weekdays but not weekends and the intervention was acceptable to participants. The de Morton Mobility Index was the most appropriate measure of mobility. Conclusions The proposed RCT of enhanced physical activity in older adults receiving rehabilitation was feasible. A larger multi-centre RCT to establish whether this intervention is cost effective and improves mobility is warranted. Trial registration The trial was registered with the ANZTCR (ACTRN12608000427370.

  12. Senescence-induced loss in photosynthesis enhances cell wall beta-glucosidase activity.

    Science.gov (United States)

    Mohapatra, Pranab Kishor; Patro, Lichita; Raval, Mukesh Kumar; Ramaswamy, Nemmara Krishnan; Biswal, Udaya Chand; Biswal, Basanti

    2010-03-01

    A link between senescence-induced decline in photosynthesis and activity of beta-glucosidase is examined in the leaves of Arabidopsis. The enzyme is purified and characterized. The molecular weight of the enzyme is 58 kDa. It shows maximum activity at pH 5.5 and at temperature of 50 degrees C. Photosynthetic measurements and activity of the enzyme are conducted at different developmental stages including senescence of leaves. Senescence causes a significant loss in total chlorophyll, stomatal conductance, rate of evaporation and in the ability of the leaves for carbon dioxide fixation. The process also brings about a decline in oxygen evolution, quantum yield of photosystem II (PS II) and quantum efficiency of PS II photochemistry of thylakoid membrane. The loss in photosynthesis is accompanied by a significant increase in the activity of the cell wall-bound beta-glucosidase that breaks down polysaccharides to soluble sugars. The loss in photosynthesis as a signal for the enhancement in the activity of the enzyme is confirmed from the observation that incubation of excised mature leaves in continuous dark or in light with a photosynthesis inhibitor 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) that leads to sugar starvation enhances the activity of the enzyme. The work suggests that in the background of photosynthetic decline, the polysaccharides bound to cell wall that remains intact even during late phase of senescence may be the last target of senescing leaves for a possible source of sugar for remobilization and completion of the energy-dependent senescence program.

  13. Florfenicol As a Modulator Enhancing Antimicrobial Activity: Example Using Combination with Thiamphenicol against Pasteurella multocida

    Science.gov (United States)

    Wei, Chia-Fong; Shien, Jui-Hung; Chang, Shao-Kuang; Chou, Chi-Chung

    2016-01-01

    Synergistic effects between the same class of antibiotics are rarely reported. Our previous study found synergistic-like interaction between florfenicol (FFC) and thiamphenicol (TAP) against Staphylococcus aureus. Here, the enhanced antimicrobial activity was evaluated in 97 clinical isolates of both Gram-negative and Gram-positive bacteria. Susceptible strains were initially identified by checkerboard microdilution assay (fractional inhibitory concentration index [FICI] ≤ 0.625), followed by confirmation of synergism using the time-kill methodology (≥2 log10 CFU/ml reduction). In all, 43% of Pasteurella multocida tested were susceptible to the enhanced bactericidal effect. In chicken fowl cholera models, FFC and TAP combination at much lower dosage that is correspondent to their MIC deduction provided maximum protection in vivo. Furthermore, synergistic combination of FFC with oxytetracycline (OTC) against Pseudomonas aeruginosa in vitro was also demonstrated. Based on the enhanced uptake of TAP and OTC, FFC presumably elicits enhanced antimicrobial activity in an orderly manner through alteration of bacterial membrane permeability or efflux systems and subsequent increase of intracellular concentration of the antibiotics used in combination. Results of ethidium bromide accumulation assay and RNA-seq showed little evidence for the involvement of efflux pumps in the synergy but further investigation is required. This study suggests the potentiality of a novel combination regimen involving FFC as an initiating modulator effective against both Gram-positive and Gram-negative bacteria depending on the antibiotics that are combined. The observed improvement of bacteriostatic effect to bactericidal, and the extended effectiveness against FFC-resistant bacterial strains warrant further studies. PMID:27065961

  14. Florfenicol as a modulator enhancing antimicrobial activity: example using combination with thiamphenicol against Pasteurella multocida

    Directory of Open Access Journals (Sweden)

    Chia-Fong eWei

    2016-03-01

    Full Text Available Synergistic effects between the same class of antibiotics are rarely reported. Our previous study found synergistic-like interaction between florfenicol (FFC and thiamphenicol (TAP against Staphylococcus aureus. Here, the enhanced antimicrobial activity was evaluated in 97 clinical isolates of both Gram-negative and Gram-positive bacteria. Susceptible strains were initially identified by checkerboard microdilution assay (fractional inhibitory concentration index [FICI] ≤0.625, followed by confirmation of synergism using the time-kill methodology (≥2 log10 CFU/ml reduction. In all, 43% of Pasteurella multocida tested were susceptible to the enhanced bactericidal effect. In chicken fowl cholera models, FFC and TAP combination at much lower dosage that is correspondent to their MIC deduction provided maximum protection in vivo. Furthermore, synergistic combination of FFC with oxytetracycline (OTC against Pseudomonas aeruginosa in vitro was also demonstrated. Based on the enhanced uptake of TAP and OTC, FFC presumably elicits enhanced antimicrobial activity in an orderly manner through alteration of bacterial membrane permeability or efflux systems and subsequent increase of intracellular concentration of the antibiotics used in combination. Results of ethidium bromide accumulation assay and RNA-seq showed little evidence for the involvement of efflux pumps in the synergy but further investigation is required. This study suggests the potentiality of a novel combination regimen involving FFC as an initiating modulator effective against both Gram-positive and Gram-negative bacteria depending on the antibiotics that are combined. The observed improvement of bacteriostatic effect to bactericidal, and the extended effectiveness against FFC-resistant bacterial strains warrant further studies.

  15. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells

    Science.gov (United States)

    Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-01-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction. PMID:27144291

  16. Chemical enhanced oil recovery (EOR) activities in Indonesia: How it's future

    Science.gov (United States)

    Abdurrahman, Muslim

    2017-05-01

    Enhanced oil recovery (EOR) is a proven method for increasing oil production in many oil fields in the world. Huge oil remaining in the reservoir after primary and secondary recovery stage are the main reason for developing EOR methods. Approximately of 49.50 billion barrels oil as a candidate for EOR activities in Indonesia. This present study focuses on the chemical EOR activities involved surfactant and polymer. This research based on pertinent information from various resources such as journal papers, conference papers, and report from the government. Based on this information, this paper explain in detail the progress of each project and it shows the potential oil field employ chemical EOR in the near future. Generally, the EOR activities can be categorized into two phases such as preliminary study phase and field implementation phase. In the preliminary study, the activities simply involve experimental and/or simulation works. Following the preliminary is the field implementation phase which can be categorized into three phases such as field trial, pilot project, and full-scale. In fact, several activities have been conducted by Lemigas (government oil and gas research center), Institut Teknologi Bandung, Institut Pertanian Bogor. These activities focused on laboratory and simulation work. Those institutions have been developing the chemical formula collaborating with oil companies for applying the EOR method in their oil fields. Currently, status of chemical EOR activities include 5 oil fields under pilot project and 12 oil fields under field trial. There are 7 oil fields applying surfactant, 4 oil fields by alkaline-surfactant-polymer (ASP), 2 oil fields by polymer, 1 oil field by surfactant polymer (SP), and 1 oil field by caustic. According to this information, we will have insight knowledge about the EOR current activities, the main issues, future activities on chemical EOR in Indonesia. Moreover, this study can became the preliminary information for

  17. Enhanced IPC by activation of pertussis toxin-sensitive and -insensitive G protein-coupled purinoceptors.

    Science.gov (United States)

    Ninomiya, Hideki; Otani, Hajime; Lu, Kejie; Uchiyama, Takamichi; Kido, Masakuni; Imamura, Hiroji

    2002-05-01

    Extracellular ATP plays an important role in ischemic preconditioning (IPC) through the activation of P(2y) purinoceptors. This study examined whether ATP-stimulated P(2y) purinoceptors are coupled to pertussis toxin (PTX)-insensitive G protein and whether activation of this pathway enhances myocardial protection afforded by IPC. The rat was treated with PTX for 48 h, and the heart was then isolated and buffer perfused. The heart underwent IPC by three cycles of 5-min ischemia and 5-min reperfusion before 25 min of global ischemia. Isovolumic left ventricular function was measured, and functional recovery at 30 min after reperfusion was taken as an end point of myocardial protection. PTX pretreatment partially inhibited functional protection by IPC. Treatment with 100 microM 8-(p-sulfophenyl) theophylline (SPT) during IPC had no further effect on PTX-induced inhibition of functional protection by IPC, whereas suramin (300 microM) or reactive blue (RB) (10 microM) completely abolished myocardial protection in the preconditioned heart pretreated with PTX. Supplementation with adenosine (30 microM), ATP (30 microM), or UTP (50 microM) significantly enhanced IPC-induced functional protection, although preconditioning with these nucleotides without IPC had no protective effect. Adenosine-enhanced IPC was inhibited by pretreatment with PTX and SPT but not by suramin or RB, whereas ATP-enhanced IPC was inhibited by suramin or RB in combination with PTX pretreatment. On the other hand, UTP-enhanced IPC was not affected by PTX pretreatment but was inhibited by suramin or RB. Adenosine supplemented IPC without PTX pretreatment and ATP supplemented IPC with PTX pretreatment were not affected by nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM). Although the protein kinase C inhibitor Ro318425 (0.3 microM) or tyrosine kinase inhibitor genistein (50 microM) had no significant effect on the functional protection afforded by adenosine

  18. Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities.

    Science.gov (United States)

    Kusuyama, Joji; Kamisono, Ai; ChangHwan, Seong; Amir, Muhammad S; Bandow, Kenjiro; Eiraku, Nahoko; Ohnishi, Tomokazu; Matsuguchi, Tetsuya

    2018-03-01

    Bone marrow stromal cells (BMSCs) are multipotent cells that can differentiate into adipocytes and osteoblasts. Inadequate BMSC differentiation is occasionally implicated in chronic bone metabolic disorders. However, specific signaling pathways directing BMSC differentiation have not been elucidated. Here, we explored the roles of spleen tyrosine kinase (Syk) in BMSC differentiation into adipocytes and osteoblasts. We found that Syk phosphorylation was increased in the early stage, whereas its protein expression was gradually decreased during the adipogenic and osteogenic differentiation of two mouse mesenchymal stromal cell lines, ST2 and 10T(1/2), and a human BMSC line, UE6E-7-16. Syk inactivation with either a pharmacological inhibitor or Syk-specific siRNA suppressed adipogenic differentiation, characterized by decreased lipid droplet appearance and the gene expression of fatty acid protein 4 (Fabp4), peroxisome proliferator-activated receptor γ2 (Pparg2), CCAAT/enhancer binding proteins α (C/EBPα), and C/EBPβ. In contrast, Syk inhibition promoted osteogenic differentiation, represented by increase in matrix mineralization and alkaline phosphatase (ALP) activity, as well as the expression levels of osteocalcin, runt-related transcription factor 2 (Runx2), and distal-less homeobox 5 (Dlx5) mRNAs. We also found that Syk-induced signals are mediated by phospholipase C γ1 (PLCγ1) in osteogenesis and PLCγ2 in adipogenesis. Notably, Syk-activated PLCγ2 signaling was partly modulated through B-cell linker protein (BLNK) in adipogenic differentiation. On the other hand, growth factor receptor-binding protein 2 (Grb2) was involved in Syk-PLCγ1 axis in osteogenic differentiation. Taken together, these results indicate that Syk-PLCγ signaling has a dual role in regulating the initial stage of adipogenic and osteogenic differentiation of BMSCs. © 2017 Wiley Periodicals, Inc.

  19. Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancer.

    Science.gov (United States)

    Bernard, Pascal; Ryan, Janelle; Sim, Helena; Czech, Daniel P; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

    2012-02-01

    Genome analysis of patients with disorders of sex development, and gain- and loss-of-function studies in mice indicate that gonadal development is regulated by opposing signals. In females, the Wnt/β-catenin canonical pathway blocks testicular differentiation by repressing the expression of the Sertoli cell-specific gene Sox9 by an unknown mechanism. Using cell and embryonic gonad culture models, we show that activation of the Wnt/β-catenin pathway inhibits the expression of Sox9 and Amh, whereas mRNA and protein levels of Sry and steroidogenic factor 1 (Sf1), two key transcriptional regulators of Sox9, are not altered. Ectopic activation of Wnt/β-catenin signaling in male gonads led to a loss of Sf1 binding to the Tesco enhancer and absent Sox9 expression that we also observed in wild-type ovaries. Moreover, ectopic Wnt/β-catenin signaling induced the expression of the female somatic cell markers, Bmp2 and Rspo1, as a likely consequence of Sox9 loss. Wnt/β-catenin signaling in XY gonads did not, however, affect gene expression of the steroidogenic Leydig cell Sf1 target gene, Cyp11a1, or Sf1 binding to the Cyp11a1 promoter. Our data support a model in ovary development whereby activation of β-catenin prevents Sf1 binding to the Sox9 enhancer, thereby inhibiting Sox9 expression and Sertoli cell differentiation.

  20. Non-Hematopoietic MLKL Protects Against Salmonella Mucosal Infection by Enhancing Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Shui-Xing Yu

    2018-02-01

    Full Text Available The intestinal mucosal barrier is critical for host defense against pathogens infection. Here, we demonstrate that the mixed lineage kinase-like protein (MLKL, a necroptosis effector, promotes intestinal epithelial barrier function by enhancing inflammasome activation. MLKL−/− mice were more susceptible to Salmonella infection compared with wild-type counterparts, with higher mortality rates, increased body weight loss, exacerbated intestinal inflammation, more bacterial colonization, and severe epithelial barrier disruption. MLKL deficiency promoted early epithelial colonization of Salmonella prior to developing apparent intestinal pathology. Active MLKL was predominantly expressed in crypt epithelial cells, and experiments using bone marrow chimeras found that the protective effects of MLKL were dependent on its expression in non-hematopoietic cells. Intestinal mucosa of MLKL−/− mice had impaired caspase-1 and gasdermin D cleavages and decreased interleukin (IL-18 release. Moreover, administration of exogenous recombinant IL-18 rescued the phenotype of increased bacterial colonization in MLKL−/− mice. Thus, our results uncover the role of MLKL in enhancing inflammasome activation in intestinal epithelial cells to inhibit early bacterial colonization.

  1. Regulating Water-Reduction Kinetics in Cobalt Phosphide for Enhancing HER Catalytic Activity in Alkaline Solution.

    Science.gov (United States)

    Xu, Kun; Ding, Hui; Zhang, Mengxing; Chen, Min; Hao, Zikai; Zhang, Lidong; Wu, Changzheng; Xie, Yi

    2017-07-01

    Electrochemical water splitting to produce hydrogen renders a promising pathway for renewable energy storage. Considering limited electrocatalysts have good oxygen-evolution reaction (OER) catalytic activity in acid solution while numerous economical materials show excellent OER catalytic performance in alkaline solution, developing new strategies that enhance the alkaline hydrogen-evolution reaction (HER) catalytic activity of cost-effective catalysts is highly desirable for achieving highly efficient overall water splitting. Herein, it is demonstrated that synergistic regulation of water dissociation and optimization of hydrogen adsorption free energy on electrocatalysts can significantly promote alkaline HER catalysis. Using oxygen-incorporated Co 2 P as an example, the synergistic effect brings about 15-fold enhancement of alkaline HER activity. Theory calculations confirm that the water dissociation free energy of Co 2 P decreases significantly after oxygen incorporation, and the hydrogen adsorption free energy can also be optimized simultaneously. The finding suggests the powerful effectiveness of synergetic regulation of water dissociation and optimization of hydrogen adsorption free energy on electrocatalysts for alkaline HER catalysis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles.

    Science.gov (United States)

    Aggarwal, Mayank; Kondeti, Bhargav; Tu, Chingkuang; Maupin, C Mark; Silverman, David N; McKenna, Robert

    2014-03-01

    Human carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the hydration and dehydration of CO2 and HCO3 (-), respectively. The reaction follows a ping-pong mechanism, in which the rate-limiting step is the transfer of a proton from the zinc-bound solvent (OH(-)/H2O) in/out of the active site via His64, which is widely believed to be the proton-shuttling residue. The decreased catalytic activity (∼20-fold lower with respect to the wild type) of a variant of CA II in which His64 is replaced with Ala (H64A CA II) can be enhanced by exogenous proton donors/acceptors, usually derivatives of imidazoles and pyridines, to almost the wild-type level. X-ray crystal structures of H64A CA II in complex with four imidazole derivatives (imidazole, 1--methylimidazole, 2--methylimidazole and 4-methylimidazole) have been determined and reveal multiple binding sites. Two of these imidazole binding sites have been identified that mimic the positions of the 'in' and 'out' rotamers of His64 in wild-type CA II, while another directly inhibits catalysis by displacing the zinc-bound solvent. The data presented here not only corroborate the importance of the imidazole side chain of His64 in proton transfer during CA catalysis, but also provide a complete structural understanding of the mechanism by which imidazoles enhance (and inhibit when used at higher concentrations) the activity of H64A CA II.

  3. Enhanced photocurrent density in graphene/Si based solar cell (GSSC) by optimizing active layer thickness

    Energy Technology Data Exchange (ETDEWEB)

    Rosikhin, Ahmad, E-mail: a.rosikhin86@yahoo.co.id; Hidayat, Aulia Fikri; Syuhada, Ibnu; Winata, Toto, E-mail: toto@fi.itb.ac.id [Department of physics, physics of electronic materials research division Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung Jl. Ganesha 10, Bandung 40132, Jawa Barat – Indonesia (Indonesia)

    2015-12-29

    Thickness dependent photocurrent density in active layer of graphene/Si based solar cell has been investigated via analytical – simulation study. This report is a preliminary comparison of experimental and analytical investigation of graphene/Si based solar cell. Graphene sheet was interfaced with Si thin film forming heterojunction solar cell that was treated as a device model for photocurrent generator. Such current can be enhanced by optimizing active layer thickness and involving metal oxide as supporting layer to shift photons absorption. In this case there are two type of devices model with and without TiO{sub 2} in which the silicon thickness varied at 20 – 100 nm. All of them have examined and also compared with each other to obtain an optimum value. From this calculation it found that generated currents almost linear with thickness but there are saturated conditions that no more enhancements will be achieved. Furthermore TiO{sub 2} layer is effectively increases photon absorption but reducing device stability, maximum current is fluctuates enough. This may caused by the disturbance of excitons diffusion and resistivity inside each layer. Finally by controlling active layer thickness, it is quite useful to estimate optimization in order to develop the next solar cell devices.

  4. Oral administration of submerged cultivated Grifola frondosa enhances phagocytic activity in normal mice.

    Science.gov (United States)

    Wang, Lisu; Ha, Choi-Lan; Cheng, Tso-Lin; Cheng, Su-Yun; Lian, Tzi-Wei; Wu, Ming-Jiuan

    2008-02-01

    Grifola frondosa fruiting body (Maitake) has been used as a dietary supplement due to its antitumour and immunomodulatory properties. The aim of this study was to evaluate the immunomodulatory effects of orally administered submerged cultivated G. frondosa mixture, including both mycelium and culture broth, in a healthy murine model. Composition analyses showed that submerged cultivated G. frondosa mixture contained only 32.48% carbohydrate, which was less than half of fruiting bodies. The content of adenosine, a potential immunomodulatory agent in medicinal mushrooms, was 2.8 mg g(-1). After feeding 8-week-old female BALB/cByJ mice with AIN-93G diet containing 0% (C), 1% (G1), 3% (G3) or 5% (G5) (wt/wt) G. frondosa mixture for 31 days, neither body weight nor the outward appearance of organs showed any significant difference among different diet groups. Splenocyte subpopulation, mitogen-activated cytokine release and splenic NK activity were not affected by G. frondosa administration, either. On the other hand, the phagocytic activity was enhanced in leucocytes of groups G3 and G5, without exerting detectable levels of serum proinflammatory cytokines. These results suggested that oral administration of submerged cultivated G. frondosa mixture may enhance host innate immunity against foreign pathogens without eliciting adverse inflammatory response.

  5. A Stability Enhancement Method for Centrifugal Compressors using Active Control Casing Treatment System

    Science.gov (United States)

    Zhao, Yuanyang; Xiao, Jun; Li, Liansheng; Yang, Qichao; Liu, Guangbin; Wang, Le

    2015-08-01

    The centrifugal compressors are widely used in many fields. When the centrifugal compressors operate at the edge of the surge line, the compressor will be unstable. In addition, if the centrifugal compressor runs at this situation long time, the damage will be occurred on compressor. There are some kinds of method to improve and enlarge the range of the centrifugal compressors, such as inlet guide vane, and casing treatment. For casing treatment method, some structures have been researched, such as holed recirculation, basic slot casing treatment and groove casing treatment. All these researches are the passive methods. This paper present a new stability enhancement method based Active Control Casing Treatment (ACCT). All parts of this new method are introduced in detail. The control strategy of the system is mentioned in the paper. As a research sample, a centrifugal compressor having this system is researched using CFD method. The study focuses on the effect of the active control system on the impeller flow. The vortex in impeller is changed by the active control system. And this leads to the suppression of the extension of vortex blockage in impeller and to contribute to the enhancement of the compressor operating range.

  6. Antibiotic-decorated titanium with enhanced antibacterial activity through adhesive polydopamine for dental/bone implant

    Science.gov (United States)

    He, Shu; Zhou, Ping; Wang, Linxin; Xiong, Xiaoling; Zhang, Yifei; Deng, Yi; Wei, Shicheng

    2014-01-01

    Implant-associated infections, which are normally induced by microbial adhesion and subsequent biofilm formation, are a major cause of morbidity and mortality. Therefore, practical approaches to prevent implant-associated infections are in great demand. Inspired by adhesive proteins in mussels, here we have developed a novel antibiotic-decorated titanium (Ti) material with enhanced antibacterial activity. In this study, Ti substrate was coated by one-step pH-induced polymerization of dopamine followed by immobilization of the antibiotic cefotaxime sodium (CS) onto the polydopamine-coated Ti through catechol chemistry. Contact angle measurement and X-ray photoelectron spectroscopy confirmed the presence of CS grafted on the Ti surface. Our results demonstrated that the antibiotic-grafted Ti substrate showed good biocompatibility and well-behaved haemocompatibility. In addition, the antibiotic-grafted Ti could effectively prevent adhesion and proliferation of Escherichia coli (Gram-negative) and Streptococcus mutans (Gram-positive). Moreover, the inhibition of biofilm formation on the antibiotic-decorated Ti indicated that the grafted CS could maintain its long-term antibacterial activity. This modified Ti substrate with enhanced antibacterial activity holds great potential as implant material for applications in dental and bone graft substitutes. PMID:24647910

  7. Enhanced photocurrent density in graphene/Si based solar cell (GSSC) by optimizing active layer thickness

    Science.gov (United States)

    Rosikhin, Ahmad; Hidayat, Aulia Fikri; Syuhada, Ibnu; Winata, Toto

    2015-12-01

    Thickness dependent photocurrent density in active layer of graphene/Si based solar cell has been investigated via analytical - simulation study. This report is a preliminary comparison of experimental and analytical investigation of graphene/Si based solar cell. Graphene sheet was interfaced with Si thin film forming heterojunction solar cell that was treated as a device model for photocurrent generator. Such current can be enhanced by optimizing active layer thickness and involving metal oxide as supporting layer to shift photons absorption. In this case there are two type of devices model with and without TiO2 in which the silicon thickness varied at 20 - 100 nm. All of them have examined and also compared with each other to obtain an optimum value. From this calculation it found that generated currents almost linear with thickness but there are saturated conditions that no more enhancements will be achieved. Furthermore TiO2 layer is effectively increases photon absorption but reducing device stability, maximum current is fluctuates enough. This may caused by the disturbance of excitons diffusion and resistivity inside each layer. Finally by controlling active layer thickness, it is quite useful to estimate optimization in order to develop the next solar cell devices.

  8. Photocatalytic reduction synthesis of SrTiO3-graphene nanocomposites and their enhanced photocatalytic activity.

    Science.gov (United States)

    Xian, Tao; Yang, Hua; Di, Lijing; Ma, Jinyuan; Zhang, Haimin; Dai, Jianfeng

    2014-01-01

    SrTiO3-graphene nanocomposites were prepared via photocatalytic reduction of graphene oxide by UV light-irradiated SrTiO3 nanoparticles. Fourier transformed infrared spectroscopy analysis indicates that graphene oxide is reduced into graphene. Transmission electron microscope observation shows that SrTiO3 nanoparticles are well assembled onto graphene sheets. The photocatalytic activity of as-prepared SrTiO3-graphene composites was evaluated by the degradation of acid orange 7 (AO7) under a 254-nm UV irradiation, revealing that the composites exhibit significantly enhanced photocatalytic activity compared to the bare SrTiO3 nanoparticles. This can be explained by the fact that photogenerated electrons are captured by graphene, leading to an increased separation and availability of electrons and holes for the photocatalytic reaction. Hydroxyl (·OH) radicals were detected by the photoluminescence technique using terephthalic acid as a probe molecule and were found to be produced over the irradiated SrTiO3 nanoparticles and SrTiO3-graphene composites; especially, an enhanced yield is observed for the latter. The influence of ethanol, KI, and N2 on the photocatalytic efficiency was also investigated. Based on the experimental results, ·OH, h(+), and H2O2 are suggested to be the main active species in the photocatalytic degradation of AO7 by SrTiO3-graphene composites. 61.46. + w; 78.67.Bf; 78.66.Sq.

  9. Toward Multimodal Human-Robot Interaction to Enhance Active Participation of Users in Gait Rehabilitation.

    Science.gov (United States)

    Gui, Kai; Liu, Honghai; Zhang, Dingguo

    2017-11-01

    Robotic exoskeletons for physical rehabilitation have been utilized for retraining patients suffering from paraplegia and enhancing motor recovery in recent years. However, users are not voluntarily involved in most systems. This paper aims to develop a locomotion trainer with multiple gait patterns, which can be controlled by the active motion intention of users. A multimodal human-robot interaction (HRI) system is established to enhance subject's active participation during gait rehabilitation, which includes cognitive HRI (cHRI) and physical HRI (pHRI). The cHRI adopts brain-computer interface based on steady-state visual evoked potential. The pHRI is realized via admittance control based on electromyography. A central pattern generator is utilized to produce rhythmic and continuous lower joint trajectories, and its state variables are regulated by cHRI and pHRI. A custom-made leg exoskeleton prototype with the proposed multimodal HRI is tested on healthy subjects and stroke patients. The results show that voluntary and active participation can be effectively involved to achieve various assistive gait patterns.

  10. On the Enhanced Antibacterial Activity of Antibiotics Mixed with Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shantrokha AN

    2009-01-01

    Full Text Available Abstract The bacterial action of gentamicin and that of a mixture of gentamicin and 15-nm colloidal-gold particles onEscherichia coliK12 was examined by the agar-well-diffusion method, enumeration of colony-forming units, and turbidimetry. Addition of gentamicin to colloidal gold changed the gold color and extinction spectrum. Within the experimental errors, there were no significant differences in antibacterial activity between pure gentamicin and its mixture with gold nanoparticles (NPs. Atomic absorption spectroscopy showed that upon application of the gentamicin-particle mixture, there were no gold NPs in the zone of bacterial-growth suppression in agar. Yet, free NPs diffused into the agar. These facts are in conflict with the earlier findings indicating an enhancement of the bacterial activity of similar gentamicin–gold nanoparticle mixtures. The possible causes for these discrepancies are discussed, and the suggestion is made that a necessary condition for enhancement of antibacterial activity is the preparation of stable conjugates of NPs coated with the antibiotic molecules.

  11. Auto-ubiquitination of Mdm2 Enhances Its Substrate Ubiquitin Ligase Activity*

    Science.gov (United States)

    Ranaweera, Ruchira S.; Yang, Xiaolu

    2013-01-01

    The RING domain E3 ubiquitin ligase Mdm2 is the master regulator of the tumor suppressor p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. Like most E3 ligases, Mdm2 can also ubiquitinate itself. How Mdm2 auto-ubiquitination may influence its substrate ubiquitin ligase activity is undefined. Here we show that auto-ubiquitination of Mdm2 is an activating event. Mdm2 that has been conjugated to polyubiquitin chains, but not to single ubiquitins, exhibits substantially enhanced activity to polyubiquitinate p53. Mechanistically, auto-ubiquitination of Mdm2 facilitates the recruitment of the E2 ubiquitin-conjugating enzyme. This occurs through noncovalent interactions between the ubiquitin chains on Mdm2 and the ubiquitin binding domain on E2s. Mutations that diminish the noncovalent interactions render auto-ubiquitination unable to stimulate Mdm2 substrate E3 activity. These results suggest a model in which polyubiquitin chains on an E3 increase the local concentration of E2 enzymes and permit the processivity of substrate ubiquitination. They also support the notion that autocatalysis may be a prevalent mode for turning on the activity of latent enzymes. PMID:23671280

  12. Respiratory modulation of sympathetic nerve activity is enhanced in male rat offspring following uteroplacental insufficiency.

    Science.gov (United States)

    Menuet, C; Wlodek, M E; Fong, A Y; Allen, A M

    2016-06-01

    Sympathetic nerve activity to the cardiovascular system displays prominent respiratory-related modulation which leads to the generation of rhythmic oscillations in blood pressure called Traube-Hering waves. An amplification of this respiratory modulation of sympathetic activity is observed in hypertension of both genetic, the spontaneously hypertensive rat, and induced, chronic intermittent hypoxia or maternal protein restriction during gestation, origin. Male offspring of mothers with uteroplacental insufficiency, induced by bilateral uterine vessel ligation at 18 days of gestation, are also hypertensive in adulthood. In this study we examined whether these male offspring display altered respiratory modulation of sympathetic activity at pre-hypertensive ages compared to controls. Respiratory, cardiovascular and sympathetic parameters were examined using the working heart-brainstem preparation in 35 day old male rats that had reduced birth weight due to uteroplacental insufficiency. Whilst all respiratory parameters were not different between groups, we observed an enhanced respiratory-related burst of thoracic sympathetic nerve activity and amplified Traube-Hering waves in the growth-restricted group. This group also showed an increased sympathetic and bradycardic response to activation of peripheral chemoreceptors. The observations add support to the view that altered respiratory modulation of sympathetic activity represents a common mechanism involved in the development of several forms of hypertension. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Voriconazole Enhances the Osteogenic Activity of Human Osteoblasts In Vitro through a Fluoride-Independent Mechanism

    Science.gov (United States)

    Allen, Kahtonna C.; Sanchez, Carlos J.; Niece, Krista L.; Wenke, Joseph C.

    2015-01-01

    Periostitis, which is characterized by bony pain and diffuse periosteal ossification, has been increasingly reported with prolonged clinical use of voriconazole. While resolution of clinical symptoms following discontinuation of therapy suggests a causative role for voriconazole, the biological mechanisms contributing to voriconazole-induced periostitis are unknown. To elucidate potential mechanisms, we exposed human osteoblasts in vitro to voriconazole or fluconazole at 15 or 200 μg/ml (reflecting systemic or local administration, respectively), under nonosteogenic or osteogenic conditions, for 1, 3, or 7 days and evaluated the effects on cell proliferation (reflected by total cellular DNA) and osteogenic differentiation (reflected by alkaline phosphatase activity, calcium accumulation, and expression of genes involved in osteogenic differentiation). Release of free fluoride, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) was also measured in cell supernatants of osteoblasts exposed to triazoles, with an ion-selective electrode (for free fluoride) and enzyme-linked immunosorbent assays (ELISAs) (for VEGF and PDGF). Voriconazole but not fluconazole significantly enhanced the proliferation and differentiation of osteoblasts. In contrast to clinical observations, no increases in free fluoride levels were detected following exposure to either voriconazole or fluconazole; however, significant increases in the expression of VEGF and PDGF by osteoblasts were observed following exposure to voriconazole. Our results demonstrate that voriconazole can induce osteoblast proliferation and enhance osteogenic activity in vitro. Importantly, and in contrast to the previously proposed mechanism of fluoride-stimulated osteogenesis, our findings suggest that voriconazole-induced periostitis may also occur through fluoride-independent mechanisms that enhance the expression of cytokines that can augment osteoblastic activity. PMID:26324277

  14. Voriconazole Enhances the Osteogenic Activity of Human Osteoblasts In Vitro through a Fluoride-Independent Mechanism.

    Science.gov (United States)

    Allen, Kahtonna C; Sanchez, Carlos J; Niece, Krista L; Wenke, Joseph C; Akers, Kevin S

    2015-12-01

    Periostitis, which is characterized by bony pain and diffuse periosteal ossification, has been increasingly reported with prolonged clinical use of voriconazole. While resolution of clinical symptoms following discontinuation of therapy suggests a causative role for voriconazole, the biological mechanisms contributing to voriconazole-induced periostitis are unknown. To elucidate potential mechanisms, we exposed human osteoblasts in vitro to voriconazole or fluconazole at 15 or 200 μg/ml (reflecting systemic or local administration, respectively), under nonosteogenic or osteogenic conditions, for 1, 3, or 7 days and evaluated the effects on cell proliferation (reflected by total cellular DNA) and osteogenic differentiation (reflected by alkaline phosphatase activity, calcium accumulation, and expression of genes involved in osteogenic differentiation). Release of free fluoride, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) was also measured in cell supernatants of osteoblasts exposed to triazoles, with an ion-selective electrode (for free fluoride) and enzyme-linked immunosorbent assays (ELISAs) (for VEGF and PDGF). Voriconazole but not fluconazole significantly enhanced the proliferation and differentiation of osteoblasts. In contrast to clinical observations, no increases in free fluoride levels were detected following exposure to either voriconazole or fluconazole; however, significant increases in the expression of VEGF and PDGF by osteoblasts were observed following exposure to voriconazole. Our results demonstrate that voriconazole can induce osteoblast proliferation and enhance osteogenic activity in vitro. Importantly, and in contrast to the previously proposed mechanism of fluoride-stimulated osteogenesis, our findings suggest that voriconazole-induced periostitis may also occur through fluoride-independent mechanisms that enhance the expression of cytokines that can augment osteoblastic activity. Copyright © 2015

  15. Building novel Ag/CeO{sub 2} heterostructure for enhancing photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Leng, Qiang; Yang, Dezhi; Yang, Qi [Department of Applied Physics, Chongqing University, Chongqing 400044 (China); Hu, Chenguo, E-mail: hucg@cqu.edu.cn [Department of Applied Physics, Chongqing University, Chongqing 400044 (China); Kang, Yue; Wang, Mingjun [Department of Applied Physics, Chongqing University, Chongqing 400044 (China); Hashim, Muhammad [Department of Applied Physics, Chongqing University, Chongqing 400044 (China); Applied Physics Department, Federal Urdu University of Arts Science and Technology, Islamabad (Pakistan)

    2015-05-15

    Highlights: • Ag nanoparticle is designed to building Schottky heterojunction on CeO{sub 2} nanocube. • The photocatalytic activity of Ag/CeO{sub 2} heterostructure is much enhanced. • 95.33% of MB can be effectively degraded within half an hour. • Ag as acceptor of photoelectrons blocks the recombination of electron–hole pairs. - Abstract: Stable and recyclable photocatalysts with high efficiency to degrade organic contamination are important and widely demanded under the threat of the environment pollution. Ag/CeO{sub 2} heterostructure is designed as a photocatalyst to degrade organic dye under the simulated sunlight. The catalytic activity of CeO{sub 2} nanocubes (NCs) to degrade methylene blue (MB) is obviously enhanced when Ag nanoparticles (NPs) are deposited on the surface of them. The weight ratio of Ag and CeO{sub 2} in forming high efficiency catalyst, the amount of Ag/CeO{sub 2} catalyst used in degradation process, and the dye concentration and pH value of the initial MB solution are examined systematically. 95.33% of MB can be effectively degraded within half an hour when 50 mg of Ag/CeO{sub 2} catalyst in an optimal weight ratio of 1:3, is added to the 100 mL of MB solution (c{sub 0} = 1 × 10{sup −5} mol L{sup −1}, pH 6.2). The mechanism of the enhanced catalytic activity of Ag/CeO{sub 2} heterostructure is discussed. The photocatalytic degradation rate is found to obey pseudo-first-order kinetics equations according to Langmuir–Hinshelwood model. The intermediate products in different stages during the degradation of MB are analyzed.

  16. Surface modification of Cobalt ferrite nano-hollowspheres for inherent multiple photoluminescence and enhanced photocatalytic activities

    Science.gov (United States)

    Talukdar, Souvanik; Mandal, Dipika; Mandal, Kalyan

    2017-03-01

    Nano-hollow spheres (NHSs) are the new drift in magnetic nanostructures as they provide more surface area at nano length scale with enhanced magnetic properties compared to their nanoparticle counterpart. Here we reported the synthesis of biocompatible CoFe2O4 NHSs of diameter around 250 nm and emergence of intrinsic multiple photoluminescence from blue, green to red on modifying their surface with small organic ligands like tartrate. The surface modified NHSs also showed notable photocatalytic activity towards the degradation of environmentally malefic dyes like Methylene Blue and Rhodamine B. The surface modified NHSs are found to exhibit superior magnetic properties.

  17. INTEGRAL/JEM-X reports enhanced activity from the HMXB 4U 1036-56

    DEFF Research Database (Denmark)

    Chenevez, Jérôme; Fiocchi, M.; Bazzano, A.

    2015-01-01

    During the Galactic Plane Scanning performed by INTEGRAL on December 11th, 2015, the X-ray monitor JEM-X has detected enhanced activity from the high mass X-ray binary (HMXB) 4U 1036-56, aka RX J1037.5-5647. The position of the source was covered by the JEM-X field of view two times between UTC 6...... 1036-56 is a Be X-ray pulsar (e.g. Torres et al. 2012, ApJ 761, 49), whose last outburst was reported by Swift in February 2012 (Krimm et al. ATel #3936)....

  18. Enhanced biological phosphorus removal from activated sludge system; Eliminacion biologica del fosfor en aguas residuales

    Energy Technology Data Exchange (ETDEWEB)

    Pidre Bocardo, J. R.; Toja Santillana, J.; Alonso Alvarez, E. [Sevilla (Spain)

    1999-06-01

    A literature review of enhanced biological phosphorus removal was performed. This biological removal is based on the selective enrichment of bacteria accumulating inorganic polyphosphate, obtained at a cyclic regime of alternating anaerobic and aerobic conditions; or anaerobic, anoxic and aerobic zones for combined nitrogen and phosphorus removal. Some bacterial groups may to be implicate in this process, the gen Acinetobacter has been the most studied. In this paper a study of phosphorate forms from wastewater for a conventional activated sludge system is presented. (Author) 40 refs.

  19. Facile Solvothermal Synthesis of BiOCl/ZnO Heterostructures with Enhanced Photocatalytic Activity

    Directory of Open Access Journals (Sweden)

    Yong-Fang Li

    2014-01-01

    Full Text Available Well-defined nanosheet-assembled (BiOClx(ZnO1−x nanoflowers were synthesized by a solvothermal method. It was found that ZnO nanoparticles were anchored on the flower-like BiOCl nanostructures, as demonstrated by varying the initial compositions of the Bi precursor and the volume ratios of mixed solvents (ethylene glycol to water. The as-prepared (BiOCl0.6(ZnO0.4 nanocomposites showed enhanced photocatalytic activity toward rhodamine B degradation under ultraviolet (UV irradiation. And the photocatalytic mechanism was discussed in detail.

  20. Oleylamine-functionalized palladium nanoparticles with enhanced electrocatalytic activity for the oxygen reduction reaction

    Science.gov (United States)

    Shi, Yi; Yin, Shengkang; Ma, Yanrong; Lu, Dingkun; Chen, Yu; Tang, Yawen; Lu, Tianhong

    2014-01-01

    The oleylamine (OAm)-functionalized Pd nanoparticles (Pd-OAm) have been conveniently synthesized through direct thermal decomposition method of low cost palladium acetate. The morphology, crystalline structure and composition of the Pd-OAm are investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Fourier transform infrared (FT-IR) spectroscopy, XPS and zeta potential analysis confirm the successful immobilization of OAm molecules on the Pd nanoparticles surface. The Pd-OAm displays an enhanced electrocatalytic activity and formic acid-tolerant ability for the oxygen reduction reaction (ORR), suggesting a potential application in cathodic catalyst for direct formic acid fuel cells.

  1. Acotiamide hydrochloride (Z-338) enhances gastric motility and emptying by inhibiting acetylcholinesterase activity in rats.

    Science.gov (United States)

    Kawachi, Masanao; Matsunaga, Yugo; Tanaka, Takao; Hori, Yuko; Ito, Katsunori; Nagahama, Kenji; Ozaki, Tomoko; Inoue, Naonori; Toda, Ryoko; Yoshii, Kazuyoshi; Hirayama, Masamichi; Kawabata, Yoshihiro; Takei, Mineo

    2011-09-01

    In clinical trials, acotiamide hydrochloride (acotiamide: Z-338) has been reported to be useful in the treatment of functional dyspepsia. Here, we investigated the effects of acotiamide on gastric contraction and emptying activities in rats in comparison with itopride hydrochloride (itopride) and mosapride citrate (mosapride). We also examined in vitro the compound's inhibitory effect on acetylcholinesterase (AChE) activity derived from rat stomach. In in vivo studies, acotiamide (30 and 100mg/kg s.c.) and itopride (100mg/kg s.c.) markedly enhanced normal gastric antral motility in rats. In gastric motility dysfunction models, acotiamide (100mg/kg s.c.) and itopride (100mg/kg s.c.) improved both gastric antral hypomotility and the delayed gastric emptying induced by clonidine, an α(2)-adrenoceptor agonist. In contrast, mosapride (10mg/kg s.c.) had no effect on these models. Like the AChE inhibitors itopride (30 mg/kg s.c.) and neostigmine (10 μg/kg s.c.), acotiamide (10mg/kg s.c.) also clearly enhanced gastric body contractions induced by electrical stimulation of the vagus, which were abolished by atropine and hexamethonium, whereas mosapride (3 and 10mg/kg s.c.) did not. In in vitro studies, acotiamide concentration-dependently inhibited rat stomach-derived AChE activity (IC(50)=2.3 μmol/l). In addition, stomach tissue concentrations of acotiamide after administration at 10mg/kg s.c. were sufficient to produce inhibition of AChE activity in rat stomach. These results suggest that acotiamide stimulates gastric motility and improves gastric motility dysfunction in rats by inhibiting AChE activity, and may suggest a role for acotiamide in improving gastric motility dysfunction in patients with functional dyspepsia. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Construction and surface enhanced Raman scattering activity of gold nanoparticles array on boron doped diamond film

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Y.S., E-mail: yshzou75@gmail.com; He, L.L.; Zhang, Y.C.; Li, Z.X.; Wang, H.P.; Gu, L.; Tu, C.J.; Zeng, H.B.

    2013-09-16

    Surface functionalization of diamond with amine groups and immobilization of gold nanoparticles (AuNPs) on boron doped nanocrystalline diamond (BDND) films deposited by microwave plasma chemical vapor deposition were investigated. Hydrogen-terminated BDND film surfaces were activated through bonding with allylamine molecules under UV light irradiation. The resulting diamond surfaces were characterized by using X-ray photoelectron spectroscopy and water contact angle measurement. The amine groups were successfully bonded covalently on the BDND diamond surface via a direct photochemical reaction with allylamine. Gold nanoparticles with the average size of 15 nm were then further self-assembled on the amine-terminated diamond surface by immersing the film surface into the gold colloidal solution, and a dense and well distributed AuNPs array in two dimensions with controlled density was obtained. Standard Rhodamine 6G probe molecules were used to access the surface enhanced Raman scattering (SERS) activity of the prepared new SERS substrate based on AuNPs modified BDND film. The results indicated that such AuNPs modified BDND film showed an excellent and stable SERS activity in the low concentration detection of R6G due to the electromagnetic enhancement mechanism. - Highlights: • A homogeneous layer of amine groups was bonded covalently on BDND surface via a photochemical reaction with allylamine. • A dense and well distributed AuNPs array with controlled density was self-assembled on the amine-terminated BDND film surface. • A new and highly efficient SERS active substrate based on AuNPs modified BDND film was constructed. • The AuNPs modified BDND film exhibited good SERS performance with stable and reproducible SERS activity for detection of R6G.

  3. Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy.

    Science.gov (United States)

    Reddy, D S; Rogawski, M A

    2001-03-01

    Perimenstrual catamenial epilepsy may in part be due to withdrawal of the endogenous progesterone-derived neurosteroid allopregnanolone that potentiates gamma-aminobutyric acidA (GABA(A)) receptor-mediated inhibition. Here we sought to determine whether the anticonvulsant potencies of neuroactive steroids, benzodiazepines, phenobarbital (PB), and valproate (VPA) are altered during the heightened seizure susceptibility accompanying neurosteroid withdrawal in a rat model of perimenstrual catamenial epilepsy. Test drugs were evaluated for their ability to alter the convulsant activity of pentylenetetrazol (PTZ) in young adult female rats, in pseudopregnant rats with prolonged exposure to high levels of progesterone (and its neurosteroid metabolites), and in pseudopregnant rats 24 h after acute withdrawal of neurosteroids by treatment with the 5alpha-reductase inhibitor finasteride. Test drugs were administered at doses equivalent to twice their ED50 values for protection against PTZ-induced clonic seizures in naive young adult female rats. The anticonvulsant activity of allopregnanolone (5 mg/kg, s.c.), pregnanolone (5 mg/kg, s.c.), allotetrahydrodeoxycorticosterone (15 mg/kg, s.c.), and tetrahydrodeoxycorticosterone (10 mg/kg, s.c.) were enhanced by 34-127% after neurosteroid withdrawal. The anticonvulsant activity of PB (65 mg/kg, i.p.) was also enhanced by 24% in neurosteroid-withdrawn animals. In contrast, the anticonvulsant activity of diazepam (4 mg/kg, i.p.), bretazenil (0.106 mg/kg, i.p.), and VPA (560 mg/kg, i.p.) were reduced or unchanged in neurosteroid-withdrawn animals. The anticonvulsant activity of neuroactive steroids is potentiated after neurosteroid withdrawal, supporting the use of such agents in the treatment of perimenstrual catamenial epilepsy.

  4. Development of a cellulolytic Saccharomyces cerevisiae strain with enhanced cellobiohydrolase activity.

    Science.gov (United States)

    Hong, Jiefang; Yang, Huajun; Zhang, Kun; Liu, Cheng; Zou, Shaolan; Zhang, Minhua

    2014-11-01

    Consolidated bioprocessing (CBP) is a promising technology for lignocellulosic ethanol production, and the key is the engineering of a microorganism that can efficiently utilize cellulose. Development of Saccharomyces cerevisiae for CBP requires high level expression of cellulases, particularly cellobiohydrolases (CBH). In this study, to construct a CBP-enabling yeast with enhanced CBH activity, three cassettes containing constitutively expressed CBH-encoding genes (cbh1 from Aspergillus aculeatus, cbh1 and cbh2 from Trichoderma reesei) were constructed. T. reesei eg2, A. aculeatus bgl1, and the three CBH-encoding genes were then sequentially integrated into the S. cerevisiae W303-1A chromosome via δ-sequence-mediated integration. The resultant strains W1, W2, and W3, expressing uni-, bi-, and trifunctional cellulases, respectively, exhibited corresponding cellulase activities. Furthermore, both the activities and glucose producing activity ascended. The growth test on cellulose containing plates indicated that CBH was a necessary component for successful utilization of crystalline cellulose. The three recombinant strains and the control strains W303-1A and AADY were evaluated in acid- and alkali-pretreated corncob containing media with 5 FPU exogenous cellulase/g biomass loading. The highest ethanol titer (g/l) within 7 days was 5.92 ± 0.51, 18.60 ± 0.81, 28.20 ± 0.84, 1.40 ± 0.12, and 2.12 ± 0.35, respectively. Compared with the control strains, W3 efficiently fermented pretreated corncob to ethanol. To our knowledge, this is the first study aimed at creating cellulolytic yeast with enhanced CBH activity by integrating three types of CBH-encoding gene with a strong constitutive promoter Ptpi.

  5. Enhanced Virulence Gene Activity of Agrobacterium in Muskmelon (Cucumis melo L. cv. ‘Birdie’

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    Abul K.M. MOHIUDDIN

    2011-05-01

    Full Text Available Muskmelon (Cucumis melo L. cultivar ‘Birdie’, was evaluated for its response to the tumorigenic Agrobacterium tumefaciens and the oncogenic A. rhizogenes strains. Stem and petiole of three week-old in vitro-grown muskmelon plants were inoculated with five strains of A. tumefaciens and A. rhizogenes each and observed phenotypic expressions i.e. induction of crown galls and hairy roots. This phenotypic expression was efficaciously increased when virulence gene activity of different strains of two Agrobacterium species was enhanced. Intensive studies on enhancement of virulence gene activity of Agrobacterium found to be correlated to the appropriate light intensity (39.3 μmol m-2 s-1 with a specific concentration of monocyclic phenolic compound, acetosyringone (20 μM. The gene activity was also influenced by several other physical factors e.g. plant tissue type, Agrobacterium species and their strains, and plant tissue-Agrobacterium interaction. Among the different A. tumefaciens strains, LBA4404 showed the best virulence gene activity in both stem and petiole through the formation of higher rate of crown galls. On the other hand, strain 15834 of A. rhizogenes showed better gene activity in stem and 8196 in petiole through the formation of higher rate of hairy roots as well as higher average number of hairy roots. Among the two different types of explants, petiole was more susceptible to both Agrobacterium species. Thus it was concluded that future muskmelon transformation study can efficiently be carried out with LBA4404, 15834 and 8196 strains using petiole explants by adding 20 μM of acetosyringone in the medium.

  6. Fullerene (C{sub 60})/CdS nanocomposite with enhanced photocatalytic activity and stability

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Qiang [Key Laboratory of Advanced Ceramics and Machining Technology, Ministry of Education, School of Materials Science and Engineering, Tianjin University, Tianjin 300072 (China); Hu, Zhuofeng, E-mail: st04hzhf@gmail.com [Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong (China); Zhang, Qian; Li, Boyuan [Key Laboratory of Advanced Ceramics and Machining Technology, Ministry of Education, School of Materials Science and Engineering, Tianjin University, Tianjin 300072 (China); Shen, Zhurui, E-mail: shenzhurui@tju.edu.cn [Key Laboratory of Advanced Ceramics and Machining Technology, Ministry of Education, School of Materials Science and Engineering, Tianjin University, Tianjin 300072 (China)

    2017-05-01

    Highlights: • C{sub 60}/CdS nanocomposite has been fabricated as a novel visible-light-driven photocatalyst. • It exhibits enhanced photocatalytic activity and photostability than that of pure CdS reference. • The C{sub 60} improved the charge separation and transfer of nanocomposite due to its high electron affinity. - Abstract: Herein, the fullerene (C{sub 60})/CdS nanocomposite has been fabricated by a facile one-pot hydrothermal method. Its photocatatlytic hydrogen (H{sub 2}) evolution rate and degradation efficiency of Rhodamine B (Rh B) are evaluated under visible light irradiation (λ ≥ 420 nm). The content of C{sub 60} has been changed from 0.4 wt% to 8 wt%, and the optimal value for photocatalytic activity is determined to be 0.4 wt%. The H{sub 2} evolution rate over this optimal sample reaches 1.73 mmol h{sup −1} g{sup −1} and its apparent degradation rate of Rh B is 0.089 min{sup −1} (degradation efficiency of 97% within 40 min), which is 2.3 times and 1.5 times compared to that of pure CdS reference. Moreover, the photocorrosion of CdS in composite is effectively suppressed, and its photocatalytic activity can be well maintained after three recycles (97.8% retaining for composite vs. 84.4% retaining for CdS). Then, the enhanced photocatalytic activity and stability of C{sub 60}/CdS nanocomposite are further studied by spectroscopic and electrochemical methods. Results show that the C{sub 60} species covering on the surface of CdS can efficiently accelerate the separation and transfer of photoexcited charge carriers, which can improve its activity, and reduce the photocorrosion of CdS.

  7. Inactivation of the MDM2 RING domain enhances p53 transcriptional activity in mice.

    Science.gov (United States)

    Tian, Hui; Tackmann, Nicole R; Jin, Aiwen; Zheng, Junnian; Zhang, Yanping

    2017-11-09

    The MDM2 RING domain harbors E3 ubiquitin ligase activity critical for regulating the degradation of tumor suppressor p53, which controls many cellular pathways. The MDM2 RING domain also is required for an interaction with MDMX. Mice containing a substitution in the MDM2 RING domain, MDM2C462A, disrupting MDM2 E3 function and the MDMX interaction, die during early embryogenesis that can be rescued by p53 deletion. To investigate whether MDM2C462A, which retains p53 binding, has p53-suppressing activity, we generated Mdm2C462A/C462A;p53ER/- mice, in which we replaced the endogenous p53 alleles with an inducible p53ER/- allele, and compared survival with that of similarly generated Mdm2-/-;p53ER/- mice. Adult Mdm2-null mice died ~7 days after tamoxifen-induced p53 activation, indicating that in the absence of MDM2, MDMX cannot suppress p53. Surprisingly, Mdm2C462A/C462A;p53ER/- mice died ~5 days after tamoxifen injection, suggesting that p53 activity is higher in the presence of MDM2C462A than in the absence of MDM2. Indeed, in MDM2C462A-expressing mouse tissues and embryonic fibroblasts, p53 exhibited higher transcriptional activity than in those expressing no MDM2 or no MDM2 and MDMX. This observation indicated that MDM2C462A not only is unable to suppress p53 but may have gained the ability to enhance p53 activity. We also found that p53 acetylation, a measure of p53 transcriptional activity, was higher in the presence of MDM2C462A than in the absence of MDM2. These results reveal an unexpected role of MDM2C462A in enhancing p53 activity and suggest the possibility that compounds targeting MDM2 RING domain function could produce even more robust p53 activation. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  8. Checkpoint Kinase 1 Activation Enhances Intestinal Epithelial Barrier Function via Regulation of Claudin-5 Expression.

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    Akihiro Watari

    Full Text Available Several stressors are known to influence epithelial tight junction (TJ integrity, but the association between DNA damage and TJ integrity remains unclear. Here we examined the effects of daunorubicin and rebeccamycin, two anti-tumor chemicals that induce DNA damage, on TJ integrity in human intestinal epithelial cells. Daunorubicin and rebeccamycin dose-dependently enhanced transepithelial electrical resistance (TER and decreased flux of the 4 kDa FITC-dextran in Caco-2 cell monolayer. Daunorubicin- or rebeccamycin-induced enhancement of the TJ barrier function partly rescued attenuation of the barrier function by the inflammatory cytokines TNF-α and IFN-γ. Daunorubicin and rebeccamycin increased claudin-5 expression and the product was distributed in the actin cytoskeleton fraction, which was enriched with TJ proteins. Caffeine, which is an inhibitor of ataxia telangiectasia mutated protein (ATM and ataxia telangiectasia mutated and Rad3-related protein (ATR, and the Chk1 inhibitor inhibited the TER increases induced by daunorubicin and rebeccamycin, whereas a Chk2 inhibitor did not. Treatment with Chk1 siRNA also significantly inhibited the TER increases. Induction of claudin-5 expression was inhibited by Chk1 inhibitor and by siRNA treatment. Our results suggest that Chk1 activation by daunorubicin and rebeccamycin induced claudin-5 expression and enhanced TJ barrier function in Caco-2 cell monolayer, which suggests a link between DNA damage and TJ integrity in the human intestine.

  9. Application of ascorbic acid to enhance trichloroethene degradation by Fe(III)-activated calcium peroxide.

    Science.gov (United States)

    Zhang, Xiang; Gu, Xiaogang; Lu, Shuguang; Brusseau, Mark L; Xu, Minhui; Fu, Xiaori; Qiu, Zhaofu; Sui, Qian

    2017-10-01

    The enhancement effect of an environmentally friendly reducing agent, ascorbic acid (AA), on trichloroethene (TCE) degradation by Fe(III)-activated calcium peroxide (CP) was evaluated. The addition of AA accelerated the transformation of Fe(III) to Fe(II), and the complexation of Fe(III)/Fe(II) with AA and its products alleviated the precipitation of dissolved iron. These impacts enhanced the generation of reactive oxygen species (ROSs). Investigation of ROSs using chemical probe tests, electron paramagnetic resonance (EPR) tests, and radical scavenger tests strongly confirm large production of hydroxyl radicals (HO•) that is responsible for TCE degradation. The generation of Cl(-) from the degraded TCE was complete in the enhanced CP/Fe(III)/AA system. The investigation of solution matrix effects showed that the TCE degradation rate decreases with the increase in solution pH, while Cl(-), SO4(2-) and NO3(-) anions have minor impact. Conversely, HCO3(-) significantly inhibited TCE degradation due to pH elevation and HO• scavenging. The results of experiments performed using actual groundwater indicated that an increase in reagent doses are required for effective TCE removal. In summary, the potential effectiveness of the CP/Fe(III)/AA oxidation system for remediation of TCE contaminated groundwater has been demonstrated. Additional research is needed to develop the system for practical implementation.

  10. Effects of selenylation modification on immune-enhancing activity of garlic polysaccharide.

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    Shulei Qiu

    Full Text Available The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(3(4 to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h.

  11. Effectiveness and Student Perceptions of an Active Learning Activity Using a Headline News Story to Enhance In-Class Learning of Cell Cycle Regulation

    Science.gov (United States)

    Dirks-Naylor, Amie J.

    2016-01-01

    An active learning activity was used to engage students and enhance in-class learning of cell cycle regulation in a PharmD level integrated biological sciences course. The aim of the present study was to determine the effectiveness and perception of the in-class activity. After completion of a lecture on the topic of cell cycle regulation,…

  12. Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

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    Guillaume Dalmasso

    Full Text Available BACKGROUND: PepT1, an intestinal epithelial apical d