WorldWideScience

Sample records for ires activities enhances

  1. Loss of p53 enhances the function of the endoplasmic reticulum through activation of the IRE1α/XBP1 pathway

    Science.gov (United States)

    Kodama, Rika; Byun, Sanguine; Yoon, Kyoung Wan; Hiraki, Masatsugu; Mandinova, Anna; Lee, Sam W.

    2015-01-01

    Altered regulation of ER stress response has been implicated in a variety of human diseases, such as cancer and metabolic diseases. Excessive ER function contributes to malignant phenotypes, such as chemoresistance and metastasis. Here we report that the tumor suppressor p53 regulates ER function in response to stress. We found that loss of p53 function activates the IRE1α/XBP1 pathway to enhance protein folding and secretion through upregulation of IRE1α and subsequent activation of its target XBP1. We also show that wild-type p53 interacts with synoviolin (SYVN1)/HRD1/DER3, a transmembrane E3 ubiquitin ligase localized to ER during ER stress and removes unfolded proteins by reversing transport to the cytosol from the ER, and its interaction stimulates IRE1α degradation. Moreover, IRE1α inhibitor suppressed protein secretion, induced cell death in p53-deficient cells, and strongly suppressed the formation of tumors by p53-deficient human tumor cells in vivo compared with those that expressed wild-type p53. Therefore, our data imply that the IRE1α/XBP1 pathway serves as a target for therapy of chemoresistant tumors that express mutant p53. PMID:26254280

  2. Brucella Rough Mutant Induce Macrophage Death via Activating IRE1α Pathway of Endoplasmic Reticulum Stress by Enhanced T4SS Secretion.

    Science.gov (United States)

    Li, Peng; Tian, Mingxing; Bao, Yanqing; Hu, Hai; Liu, Jiameng; Yin, Yi; Ding, Chan; Wang, Shaohui; Yu, Shengqing

    2017-01-01

    Brucella is a Gram-negative facultative intracellular pathogen that causes the worldwide zoonosis, known as brucellosis. Brucella virulence relies mostly on its ability to invade and replicate within phagocytic cells. The type IV secretion system (T4SS) and lipopolysaccharide are two major Brucella virulence factors. Brucella rough mutants reportedly induce the death of infected macrophages, which is T4SS dependent. However, the underlying molecular mechanism remains unclear. In this study, the T4SS secretion capacities of Brucella rough mutant and its smooth wild-type strain were comparatively investigated, by constructing the firefly luciferase fused T4SS effector, BPE123 and VceC. In addition, quantitative real-time PCR and western blotting were used to analyze the T4SS expression. The results showed that T4SS expression and secretion were enhanced significantly in the Brucella rough mutant. We also found that the activity of the T4SS virB operon promoter was notably increased in the Brucella rough mutant, which depends on quorum sensing-related regulators of VjbR upregulation. Cell infection and cell death assays revealed that deletion of vjbR in the Brucella rough mutant absolutely abolished cytotoxicity within macrophages by downregulating T4SS expression. This suggests that up-regulation of T4SS promoted by VjbR in rough mutant Δ rfbE contribute to macrophage death. In addition, we found that the Brucella rough mutant induce macrophage death via activating IRE1α pathway of endoplasmic reticulum stress. Taken together, our study provide evidence that in comparison to the Brucella smooth wild-type strain, VjbR upregulation in the Brucella rough mutant increases transcription of the virB operon, resulting in overexpression of the T4SS gene, accompanied by the over-secretion of effecter proteins, thereby causing the death of infected macrophages via activating IRE1α pathway of endoplasmic reticulum stress, suggesting novel insights into the molecular

  3. Brucella Rough Mutant Induce Macrophage Death via Activating IRE1α Pathway of Endoplasmic Reticulum Stress by Enhanced T4SS Secretion

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-09-01

    Full Text Available Brucella is a Gram-negative facultative intracellular pathogen that causes the worldwide zoonosis, known as brucellosis. Brucella virulence relies mostly on its ability to invade and replicate within phagocytic cells. The type IV secretion system (T4SS and lipopolysaccharide are two major Brucella virulence factors. Brucella rough mutants reportedly induce the death of infected macrophages, which is T4SS dependent. However, the underlying molecular mechanism remains unclear. In this study, the T4SS secretion capacities of Brucella rough mutant and its smooth wild-type strain were comparatively investigated, by constructing the firefly luciferase fused T4SS effector, BPE123 and VceC. In addition, quantitative real-time PCR and western blotting were used to analyze the T4SS expression. The results showed that T4SS expression and secretion were enhanced significantly in the Brucella rough mutant. We also found that the activity of the T4SS virB operon promoter was notably increased in the Brucella rough mutant, which depends on quorum sensing-related regulators of VjbR upregulation. Cell infection and cell death assays revealed that deletion of vjbR in the Brucella rough mutant absolutely abolished cytotoxicity within macrophages by downregulating T4SS expression. This suggests that up-regulation of T4SS promoted by VjbR in rough mutant ΔrfbE contribute to macrophage death. In addition, we found that the Brucella rough mutant induce macrophage death via activating IRE1α pathway of endoplasmic reticulum stress. Taken together, our study provide evidence that in comparison to the Brucella smooth wild-type strain, VjbR upregulation in the Brucella rough mutant increases transcription of the virB operon, resulting in overexpression of the T4SS gene, accompanied by the over-secretion of effecter proteins, thereby causing the death of infected macrophages via activating IRE1α pathway of endoplasmic reticulum stress, suggesting novel insights into the

  4. Arabidopsis IRE1 catalyses unconventional splicing of bZIP60 mRNA to produce the active transcription factor

    KAUST Repository

    Nagashima, Yukihiro; Mishiba, Kei-ichiro; Suzuki, Eiji; Shimada, Yukihisa; Iwata, Yuji; Koizumi, Nozomu

    2011-01-01

    -type. Transcriptome analysis revealed that genes whose induction was reduced in ire1a/ire1b largely overlapped those in the bzip60 mutant. We observed that the active form of bZIP60 protein detected in the wild-type was missing in ire1a/ire1b. We further demonstrated

  5. Endoplasmic Reticulum Stress Sensor IREEnhances IL-23 Expression by Human Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Saioa Márquez

    2017-06-01

    Full Text Available Human monocyte-derived dendritic cells (DCs exposed to pathogen-associated molecular patterns (PAMPs undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.

  6. Arabidopsis IRE1 catalyses unconventional splicing of bZIP60 mRNA to produce the active transcription factor

    KAUST Repository

    Nagashima, Yukihiro

    2011-07-01

    IRE1 plays an essential role in the endoplasmic reticulum (ER) stress response in yeast and mammals. We found that a double mutant of Arabidopsis IRE1A and IRE1B (ire1a/ire1b) is more sensitive to the ER stress inducer tunicamycin than the wild-type. Transcriptome analysis revealed that genes whose induction was reduced in ire1a/ire1b largely overlapped those in the bzip60 mutant. We observed that the active form of bZIP60 protein detected in the wild-type was missing in ire1a/ire1b. We further demonstrated that bZIP60 mRNA is spliced by ER stress, removing 23 ribonucleotides and therefore causing a frameshift that replaces the C-terminal region of bZIP60 including the transmembrane domain (TMD) with a shorter region without a TMD. This splicing was detected in ire1a and ire1b single mutants, but not in the ire1a/ire1b double mutant. We conclude that IRE1A and IRE1B catalyse unconventional splicing of bZIP60 mRNA to produce the active transcription factor.

  7. The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity.

    Science.gov (United States)

    Shan, Bo; Wang, Xiaoxia; Wu, Ying; Xu, Chi; Xia, Zhixiong; Dai, Jianli; Shao, Mengle; Zhao, Feng; He, Shengqi; Yang, Liu; Zhang, Mingliang; Nan, Fajun; Li, Jia; Liu, Jianmiao; Liu, Jianfeng; Jia, Weiping; Qiu, Yifu; Song, Baoliang; Han, Jing-Dong J; Rui, Liangyou; Duan, Sheng-Zhong; Liu, Yong

    2017-05-01

    Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance. Myeloid-specific IRE1α abrogation in Ern1 f/f ; Lyz2-Cre mice largely reversed high-fat diet (HFD)-induced M1-M2 imbalance in white adipose tissue (WAT) and blocked HFD-induced obesity, insulin resistance, hyperlipidemia and hepatic steatosis. Brown adipose tissue (BAT) activity, WAT browning and energy expenditure were significantly higher in Ern1 f/f ; Lyz2-Cre mice. Furthermore, IRE1α ablation augmented M2 polarization of macrophages in a cell-autonomous manner. Thus, IRE1α senses protein unfolding and metabolic and immunological states, and consequently guides ATM polarization. The macrophage IRE1α pathway drives obesity and metabolic syndrome through impairing BAT activity and WAT browning.

  8. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    LENUS (Irish Health Repository)

    Gupta, Sanjeev

    2010-01-01

    Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha\\/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  9. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    Directory of Open Access Journals (Sweden)

    Sanjeev Gupta

    2010-07-01

    Full Text Available Endoplasmic reticulum (ER stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR. Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  10. Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Chun [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Jin, Zhao [Department of Coloproctology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 325000 (China); Chen, Nian-zhao [Department of Medicine, The Chinese Medicine Hospital of Wenzhou, Wenzhou 325000 (China); Lu, Min; Liu, Chang-bao; Hu, Wan-Le [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Zheng, Chen-guo, E-mail: zhengchenguo80@163.com [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China)

    2016-01-29

    Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. - Highlights: • IRE1 was determined to be an independent predictor of overall survival in CRC patient. • IRE1-XBP1 pathway promoted CRC cell proliferation through regulating Cyclin D1 expression. • IRE1-XBP1 pathway played important role in EMT of CRC cells.

  11. Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

    International Nuclear Information System (INIS)

    Jin, Chun; Jin, Zhao; Chen, Nian-zhao; Lu, Min; Liu, Chang-bao; Hu, Wan-Le; Zheng, Chen-guo

    2016-01-01

    Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. - Highlights: • IRE1 was determined to be an independent predictor of overall survival in CRC patient. • IRE1-XBP1 pathway promoted CRC cell proliferation through regulating Cyclin D1 expression. • IRE1-XBP1 pathway played important role in EMT of CRC cells.

  12. Activation of Host IRE1α-Dependent Signaling Axis Contributes the Intracellular Parasitism of Brucella melitensis

    Directory of Open Access Journals (Sweden)

    Aseem Pandey

    2018-04-01

    Full Text Available Brucella spp. are intracellular vacuolar pathogens that causes brucellosis, a worldwide zoonosis of profound importance. We previously demonstrated that the activity of host unfolded protein response (UPR sensor IRE1α (inositol-requiring enzyme 1 and ER-associated autophagy confer susceptibility to Brucella melitensis and Brucella abortus intracellular replication. However, the mechanism by which host IRE1α regulates the pathogen intracellular lifestyle remains elusive. In this study, by employing a diverse array of molecular approaches, including biochemical analyses, fluorescence microscopy imaging, and infection assays using primary cells derived from Ern1 (encoding IRE1 conditional knockout mice, we address this gap in our understanding by demonstrating that a novel IRE1α to ULK1, an important component for autophagy initiation, signaling axis confers susceptibility to Brucella intracellular parasitism. Importantly, deletion or inactivation of key signaling components along this axis, including IRE1α, BAK/BAX, ASK1, and JNK as well as components of the host autophagy system ULK1, Atg9a, and Beclin 1, resulted in striking disruption of Brucella intracellular trafficking and replication. Host kinases in the IRE1α-ULK1 axis, including IRE1α, ASK1, JNK1, and/or AMPKα as well as ULK1, were also coordinately phosphorylated in an IRE1α-dependent fashion upon the pathogen infection. Taken together, our findings demonstrate that the IRE1α-ULK1 signaling axis is subverted by the bacterium to promote intracellular parasitism, and provide new insight into our understanding of the molecular mechanisms of intracellular lifestyle of Brucella.

  13. MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy

    International Nuclear Information System (INIS)

    Bos, Willemien van den; Bruin, D.M. de; Randen, A. van; Engelbrecht, M.R.W.; Postema, A.W.; Muller, B.G.; Zondervan, P.J.; Laguna Pes, M.P.; Reijke, T.M. de; Rosette, J.J.M.C.H. de la; Varkarakis, I.M.; Skolarikos, A.; Savci-Heijink, C.D.; Jurhill, R.R.; Wijkstra, H.

    2016-01-01

    Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H and E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. (orig.)

  14. RITA enhances irradiation-induced apoptosis in p53-defective cervical cancer cells via upregulation of IRE1α/XBP1 signaling.

    Science.gov (United States)

    Zhu, Hong; Abulimiti, Muyasha; Liu, Huan; Su, Xiang-Jiang; Liu, Cai-Hong; Pei, Hai-Ping

    2015-09-01

    Radiation therapy is the most widely used treatment for patients with cervical cancer. Recent studies have shown that endoplasmic reticulum (ER) stress induces apoptosis and sensitizes tumor cells to radiotherapy, which reportedly induces ER stress in cells. Classical key tumor suppressor p53 is involved in the response to a variety of cellular stresses, including those incurred by ionizing irradiation. A recent study demonstrated that small-molecule RITA (reactivation of p53 and induction of tumor cell apoptosis) increased the radiosensitivity of tumor cells expressing mutant p53 (mtp53). In the present study, we explored the effects and the underlying mechanisms of RITA in regards to the radiosensitivity and ER stress in mtp53-expressing human cervix cancer cells. Treatment with 1 µM of RITA for 24 h before irradiation markedly decreased survival and increased apoptosis in C-33A and HT-3 cells; the effects were not significantly altered by knockdown of p53. In the irradiated C-33A and HT-3 cells, RITA significantly increased the expression of IRE1α, the spliced XBP1 mRNA level, as well as apoptosis; the effects were abolished by knockdown of IRE1α. Transcriptional pulse-chase assays revealed that RITA significantly increased the stability of IRE1α mRNA in the irradiated C-33A and HT-3 cells. In contrast, the same RITA treatment did not show any significant effect on sham-irradiated cells. In conclusion, the present study provides initial evidence that RITA upregulates the expression level of IRE1α by increasing the stability of IRE1α mRNA in irradiated mtp53-expressing cervical cancer cells; the effect leads to enhanced IRE1α/XBP1 ER stress signaling and increased apoptosis in the cells. The present study offers novel insight into the pharmacological potential of RITA in the radiotherapy for cervical cancer.

  15. New small molecule inhibitors of UPR activation demonstrate that PERK, but not IRE1α signaling is essential for promoting adaptation and survival to hypoxia

    International Nuclear Information System (INIS)

    Cojocari, Dan; Vellanki, Ravi N.; Sit, Brandon; Uehling, David; Koritzinsky, Marianne; Wouters, Bradly G.

    2013-01-01

    Background and purpose: The unfolded protein response (UPR) is activated in response to hypoxia-induced stress in the endoplasmic reticulum (ER) and consists of three distinct signaling arms. Here we explore the potential of targeting two of these arms with new potent small-molecule inhibitors designed against IRE1α and PERK. Methods: We utilized shRNAs and small-molecule inhibitors of IRE1α (4μ8c) and PERK (GSK-compound 39). XBP1 splicing and DNAJB9 mRNA was measured by qPCR and was used to monitor IREactivity. PERK activity was monitored by immunoblotting eIF2α phosphorylation and qPCR of DDIT3 mRNA. Hypoxia tolerance was measured using proliferation and clonogenic cell survival assays of cells exposed to mild or severe hypoxia in the presence of the inhibitors. Results: Using knockdown experiments we show that PERK is essential for survival of KP4 cells while knockdown of IRE1α dramatically decreases the proliferation and survival of HCT116 during hypoxia. Further, we show that in response to both hypoxia and other ER stress-inducing agents both 4μ8c and the PERK inhibitor are selective and potent inhibitors of IRE1α and PERK activation, respectively. However, despite potent inhibition of IREactivation, 4μ8c had no effect on cell proliferation or clonogenic survival of cells exposed to hypoxia. This was in contrast to the inactivation of PERK signaling with the PERK inhibitor, which reduced tolerance to hypoxia and other ER stress inducing agents. Conclusions: Our results demonstrate that IRE1α but not its splicing activity is important for hypoxic cell survival. The PERK signaling arm is uniquely important for promoting adaptation and survival during hypoxia-induced ER stress and should be the focus of future therapeutic efforts

  16. Yip1A, a Novel Host Factor for the Activation of the IRE1 Pathway of the Unfolded Protein Response during Brucella Infection

    Science.gov (United States)

    Taguchi, Yuki; Imaoka, Koichi; Kataoka, Michiyo; Uda, Akihiko; Nakatsu, Daiki; Horii-Okazaki, Sakuya; Kunishige, Rina; Kano, Fumi; Murata, Masayuki

    2015-01-01

    Brucella species replicate within host cells in the form of endoplasmic reticulum (ER)-derived vacuoles. The mechanisms by which the bacteria are sequestered into such vacuoles and obtain a continuous membrane supply for their replication remain to be elucidated. In the present study, we provided several lines of evidence that demonstrate the mechanism by which B. abortus acquires the ER-derived membrane. First, during Brucella infection, the IRE1 pathway, but not the PERK and ATF6 pathways, of the unfolded protein response (UPR) was activated in a time-dependent manner, and the COPII vesicle components Sar1, Sec23, and Sec24D were upregulated. Second, a marked accretion of ER-derived vacuoles was observed around replicating bacteria using fluorescent microscopy and electron microscopy. Third, we identified a novel host factor, Yip1A, for the activation of the IRE1 pathway in response to both tunicamycin treatment and infection with B. abortus. We found that Yip1A is responsible for the phosphorylation of IRE1 through high-order assembly of Ire1 molecules at ER exit sites (ERES) under the UPR conditions. In Yip1A-knockdown cells, B. abortus failed to generate the ER-derived vacuoles, and remained in endosomal/lysosomal compartments. These results indicate that the activation of the IRE1 pathway and the subsequent formation of ER-derived vacuoles are critical for B. abortus to establish a safe replication niche, and that Yip1A is indispensable for these processes. Furthermore, we showed that the autophagy-related proteins Atg9 and WIPI1, but not DFCP1, were required for the biogenesis of the ER-derived membrane compartments.  On the basis of our findings, we propose a model for intracellular Brucella replication that exploits the host UPR and ER-derived vacuole formation machineries, both of which depend on Yip1A-mediated IRE1 activation. PMID:25742138

  17. The IRES electronic seal

    International Nuclear Information System (INIS)

    Autrusson, B.; Brochard, D.; Moreau, J.F.; Martin, J.C.

    2001-01-01

    In the framework of the French Support Program for the IAEA Safeguards, the 'Institut de Protection et de Surete Nucleaire' (IPSN), developed an electronic seal called Integrated and Reusable Electronic Seal (IRES) that enables independent verification by different inspectorates (IAEA, Euratom, and National Inspectorate). The seal can be remotely interrogated by radio frequency and integrated to other Containment/surveillance systems by serial line RS 485. Data are authenticated and the IRESMAG software manages in the seal reader all functionalities of the seal and records inspection data compatible with the IAEA's Seal Database. To perform this development, IPSN relies on industrial partners: SAPHYMO for the general architecture of the seal and the electronics, THALES for the authentication of data and the security of transmission. The main features of the IRES seal are the following: Interrogation by different inspectorate, allowing independent conclusions; Recording of events, including tampering, in a non-volatile memory; Authentication of data and enhanced security of the communication between the seal and the seal reader; Remote interrogation by an inspector or/and automatic for unattended systems or remote monitoring; Reusable after erasing the seal memory and replacement of the batteries

  18. Divergent picornavirus IRES elements

    DEFF Research Database (Denmark)

    Belsham, Graham

    2009-01-01

    Internal ribosome entry site (IRES) elements were first identified about 20 years ago within the 5' untranslated region of picornavirus RNAs. They direct a cap-independent mechanism of translation initiation on the viral RNA. Within the picornavirus family it is now known that there are four...... classes of IRES element which vary in size (450-270nt), they also have different, complex, secondary structures and distinct requirements for cellular proteins to allow them to function. This review describes the features of each class of picornavirus IRES element but focuses on the characteristics...... of the most recently described group, initially identified within the porcine teschovirus-1 RNA, which has strong similarities to the IRES elements from within the genomes of hepatitis C virus and the pestiviruses which are members of the flavivirus family. The selection of the initiation codon...

  19. Apigenin Restricts FMDV Infection and Inhibits Viral IRES Driven Translational Activity

    Directory of Open Access Journals (Sweden)

    Suhong Qian

    2015-03-01

    Full Text Available Foot-and-mouth disease (FMD is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV. FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i apigenin inhibits FMDV infection at the viral post-entry stage; (ii apigenin does not exhibit direct extracellular virucidal activity; and (iii apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection.

  20. Apigenin restricts FMDV infection and inhibits viral IRES driven translational activity.

    Science.gov (United States)

    Qian, Suhong; Fan, Wenchun; Qian, Ping; Zhang, Dong; Wei, Yurong; Chen, Huanchun; Li, Xiangmin

    2015-03-31

    Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV). FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i) apigenin inhibits FMDV infection at the viral post-entry stage; (ii) apigenin does not exhibit direct extracellular virucidal activity; and (iii) apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection.

  1. IRE1: ER stress sensor and cell fate executor.

    Science.gov (United States)

    Chen, Yani; Brandizzi, Federica

    2013-11-01

    Cells operate a signaling network termed the unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to maintain the ER and cellular function. Although mammalian IRE1 promotes cell survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Translational Control Protein 80 Stimulates IRES-Mediated Translation of p53 mRNA in Response to DNA Damage

    Directory of Open Access Journals (Sweden)

    Marie-Jo Halaby

    2015-01-01

    Full Text Available Synthesis of the p53 tumor suppressor increases following DNA damage. This increase and subsequent activation of p53 are essential for the protection of normal cells against tumorigenesis. We previously discovered an internal ribosome entry site (IRES that is located at the 5′-untranslated region (UTR of p53 mRNA and found that the IRES activity increases following DNA damage. However, the mechanism underlying IRES-mediated p53 translation in response to DNA damage is still poorly understood. In this study, we discovered that translational control protein 80 (TCP80 has increased binding to the p53 mRNA in vivo following DNA damage. Overexpression of TCP80 also leads to increased p53 IRES activity in response to DNA damage. TCP80 has increased association with RNA helicase A (RHA following DNA damage and overexpression of TCP80, along with RHA, leads to enhanced expression of p53. Moreover, we found that MCF-7 breast cancer cells with decreased expression of TCP80 and RHA exhibit defective p53 induction following DNA damage and diminished expression of its downstream target PUMA, a proapoptotic protein. Taken together, our discovery of the function of TCP80 and RHA in regulating p53 IRES and p53 induction following DNA damage provides a better understanding of the mechanisms that regulate IRES-mediated p53 translation in response to genotoxic stress.

  3. HCV IRES-mediated core expression in zebrafish.

    Directory of Open Access Journals (Sweden)

    Ye Zhao

    Full Text Available The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism.

  4. Structural and functional basis for RNA cleavage by Ire1

    Directory of Open Access Journals (Sweden)

    Stroud Robert M

    2011-07-01

    Full Text Available Abstract Background The unfolded protein response (UPR controls the protein folding capacity of the endoplasmic reticulum (ER. Central to this signaling pathway is the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The endoribonuclease (RNase domain of Ire1 initiates a non-conventional mRNA splicing reaction, leading to the production of a transcription factor that controls UPR target genes. The mRNA splicing reaction is an obligatory step of Ire1 signaling, yet its mechanism has remained poorly understood due to the absence of substrate-bound crystal structures of Ire1, the lack of structural similarity between Ire1 and other RNases, and a scarcity of quantitative enzymological data. Here, we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis. Results This analysis and two new crystal structures suggest that Ire1 RNase uses histidine H1061 and tyrosine Y1043 as the general acid-general base pair contributing ≥ 7.6 kcal/mol and 1.4 kcal/mol to transition state stabilization, respectively, and asparagine N1057 and arginine R1056 for coordination of the scissile phosphate. Investigation of the stem-loop recognition revealed that additionally to the stem-loops derived from the classic Ire1 substrates HAC1 and Xbp1 mRNA, Ire1 can site-specifically and rapidly cleave anticodon stem-loop (ASL of unmodified tRNAPhe, extending known substrate specificity of Ire1 RNase. Conclusions Our data define the catalytic center of Ire1 RNase and suggest a mechanism of RNA cleavage: each RNase monomer apparently contains a separate catalytic apparatus for RNA cleavage, whereas two RNase subunits contribute to RNA stem-loop docking. Conservation of the key residues among Ire1 homologues suggests that the mechanism elucidated here for yeast Ire1 applies to Ire1 in metazoan cells, and to the only known Ire1 homologue RNase L.

  5. Enterovirus 71 contains a type I IRES element that functions when eukaryotic initiation factor eIF4G is cleaved

    International Nuclear Information System (INIS)

    Thompson, Sunnie R.; Sarnow, Peter

    2003-01-01

    Human enterovirus 71 (EV71) is a member of the Enterovirus genus of the Picornaviridae family. Other members of this family utilize an unusual mechanism of translation initiation whereby ribosomes are recruited internally to the viral RNA by an internal ribosome site (IRES) located in their 5' noncoding regions (5' NCR). Using dicistronic reporter constructs, we demonstrate that the 5' NCRs of the 7423/MS/87 and BrCr strains of EV71 function as an IRES both in extracts and in cultured cells. Preincubation of translation extracts with purified coxsackievirus 2A protease cleaved elF4G, a component of the cap binding complex, resulting in a significant decrease in translation of capped mRNAs. In contrast, the translational efficiency of the EV71 IRES was enhanced under this condition, demonstrating that the EV71 IRES functions similar to other enterovirus IRES elements when components of the cap binding protein complex are cleaved. Finally, insertion of an upstream, out-of-frame start codon in the 5' NCR of the EV71 genome inhibited IRES activity, suggesting that EV71 can be classified as a type I IRES, in which ribosomes first bind upstream of the initiation codon and then scan the mRNA until an appropriate downstream AUG start codon is encountered and protein synthesis commences

  6. Rapid kinetics of iron responsive element (IRE) RNA/iron regulatory protein 1 and IRE-RNA/eIF4F complexes respond differently to metal ions.

    Science.gov (United States)

    Khan, Mateen A; Ma, Jia; Walden, William E; Merrick, William C; Theil, Elizabeth C; Goss, Dixie J

    2014-06-01

    Metal ion binding was previously shown to destabilize IRE-RNA/IRP1 equilibria and enhanced IRE-RNA/eIF4F equilibria. In order to understand the relative importance of kinetics and stability, we now report rapid rates of protein/RNA complex assembly and dissociation for two IRE-RNAs with IRP1, and quantitatively different metal ion response kinetics that coincide with the different iron responses in vivo. kon, for FRT IRE-RNA binding to IRP1 was eight times faster than ACO2 IRE-RNA. Mn(2+) decreased kon and increased koff for IRP1 binding to both FRT and ACO2 IRE-RNA, with a larger effect for FRT IRE-RNA. In order to further understand IRE-mRNA regulation in terms of kinetics and stability, eIF4F kinetics with FRT IRE-RNA were determined. kon for eIF4F binding to FRT IRE-RNA in the absence of metal ions was 5-times slower than the IRP1 binding to FRT IRE-RNA. Mn(2+) increased the association rate for eIF4F binding to FRT IRE-RNA, so that at 50 µM Mn(2+) eIF4F bound more than 3-times faster than IRP1. IRP1/IRE-RNA complex has a much shorter life-time than the eIF4F/IRE-RNA complex, which suggests that both rate of assembly and stability of the complexes are important, and that allows this regulatory system to respond rapidly to change in cellular iron. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Ire1 Has Distinct Catalytic Mechanisms for XBP1/HAC1 Splicing and RIDD

    Directory of Open Access Journals (Sweden)

    Arvin B. Tam

    2014-11-01

    Full Text Available An evolutionarily conserved unfolded protein response (UPR component, IRE1, cleaves XBP1/HAC1 introns in order to generate spliced mRNAs that are translated into potent transcription factors. IRE1 also cleaves endoplasmic-reticulum-associated RNAs leading to their decay, an activity termed regulated IRE1-dependent decay (RIDD; however, the mechanism by which IRE1 differentiates intron cleavage from RIDD is not well understood. Using in vitro experiments, we found that IRE1 has two different modes of action: XBP1/HAC1 is cleaved by IRE1 subunits acting cooperatively within IRE1 oligomers, whereas a single subunit of IRE1 performs RIDD without cooperativity. Furthermore, these distinct activities can be separated by complementation of catalytically inactive IRE1 RNase and mutations at oligomerization interfaces. Using an IRE1 RNase inhibitor, STF-083010, selective inhibition of XBP1 splicing indicates that XBP1 promotes cell survival, whereas RIDD leads to cell death, revealing modulation of IRE1 activities as a drug-development strategy.

  8. Inflammatory conditions induce IRES-dependent translation of cyp24a1.

    Directory of Open Access Journals (Sweden)

    Daniela Rübsamen

    Full Text Available Rapid alterations in protein expression are commonly regulated by adjusting translation. In addition to cap-dependent translation, which is e.g. induced by pro-proliferative signaling via the mammalian target of rapamycin (mTOR-kinase, alternative modes of translation, such as internal ribosome entry site (IRES-dependent translation, are often enhanced under stress conditions, even if cap-dependent translation is attenuated. Common stress stimuli comprise nutrient deprivation, hypoxia, but also inflammatory signals supplied by infiltrating immune cells. Yet, the impact of inflammatory microenvironments on translation in tumor cells still remains largely elusive. In the present study, we aimed at identifying translationally deregulated targets in tumor cells under inflammatory conditions. Using polysome profiling and microarray analysis, we identified cyp24a1 (1,25-dihydroxyvitamin D3 24-hydroxylase to be translationally upregulated in breast tumor cells co-cultured with conditioned medium of activated monocyte-derived macrophages (CM. Using bicistronic reporter assays, we identified and validated an IRES within the 5' untranslated region (5'UTR of cyp24a1, which enhances translation of cyp24a1 upon CM treatment. Furthermore, IRES-dependent translation of cyp24a1 by CM was sensitive to phosphatidyl-inositol-3-kinase (PI3K inhibition, while constitutive activation of Akt sufficed to induce its IRES activity. Our data provide evidence that cyp24a1 expression is translationally regulated via an IRES element, which is responsive to an inflammatory environment. Considering the negative feedback impact of cyp24a1 on the vitamin D responses, the identification of a novel, translational mechanism of cyp24a1 regulation might open new possibilities to overcome the current limitations of vitamin D as tumor therapeutic option.

  9. The IRES electronic seal

    International Nuclear Information System (INIS)

    Gourlez, P.; Funk, P.; Brochard, D.; Moreau, J.F.; Martin, J.C.

    2001-01-01

    In the framework of the French Support Program for the IAEA Safeguards, the 'Institut de Protection et de Surete Nucleaire' (IPSN), developed an electronic seal called Integrated and Reusable Electronic Seal (IRES) that enables independent verification by different inspectorates (IAEA, Euratom, and National Inspectorate) Furthermore, a bilateral co-ordination between Euratom and French domestic safeguards takes place in some French facilities regarding a common approach concerning the seals especially in case of crisis situation. The seal can be remotely interrogated by radio frequency and integrated to other Containment/surveillance systems by serial line RS 485. Data are authenticated and the IRESMAG software manages in the seal reader all functionalities of the seal and records inspection data compatible with the IAEA's Seal Database

  10. Insights into the Biology of IRES Elements through Riboproteomic Approaches

    Directory of Open Access Journals (Sweden)

    Almudena Pacheco

    2010-01-01

    Full Text Available Translation initiation is a highly regulated process that exerts a strong influence on the posttranscriptional control of gene expression. Two alternative mechanisms govern translation initiation in eukaryotic mRNAs, the cap-dependent initiation mechanism operating in most mRNAs, and the internal ribosome entry site (IRES-dependent mechanism, first discovered in picornaviruses. IRES elements are highly structured RNA sequences that, in most instances, require specific proteins for recruitment of the translation machinery. Some of these proteins are eukaryotic initiation factors. In addition, RNA-binding proteins (RBPs play a key role in internal initiation control. RBPs are pivotal regulators of gene expression in response to numerous stresses, including virus infection. This review discusses recent advances on riboproteomic approaches to identify IRES transacting factors (ITAFs and the relationship between RNA-protein interaction and IRES activity, highlighting the most relevant features on picornavirus and hepatitis C virus IRESs.

  11. IRE1α links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.

    Science.gov (United States)

    Li, Hui; Li, Bing; Larose, Louise

    2017-08-01

    PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear. In this study, we found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down-regulation of IRE1α. Indeed, we show that silencing Nck1 in HepG2 cells leads to decreased IRE1α expression and signaling. Accordingly, IRE1α depletion using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation, reproducing the effects of silencing Nck1 on activation of this pathway. In addition, depletion of IRE1α also leads to reduced PTP1B expression, which was rescued by ectopic expression of IRE1α in Nck1-depleted cells. Mechanistically, we found that silencing either Nck1 or IRE1α in HepG2 cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels, a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2 cells, are increased in both Nck1- and IRE1α-depleted HepG2 cells, a miR-122 antagomir did not rescue PTP1B expression in these cells. Overall, this study highlights an important role for Nck1 in fine-tuning IRE1α expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia.

    Directory of Open Access Journals (Sweden)

    Maria Licursi

    Full Text Available Internal ribosome entry site (IRES-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV, foot-and-mouth disease virus (FMDV, hepatitis C virus (HCV, human rhinovirus (HRV or poliovirus (PV. Under mild hypothermic conditions (30 and 35°C, we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB and upstream of N-Ras (unr, the IRES trans-acting factors (ITAFs of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent.

  13. Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition.

    Science.gov (United States)

    Minchenko, D O; Riabovol, O O; Ratushna, O O; Minchenko, O H

    2017-01-01

    The aim of the present study was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of glioma cells proliferation. The expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by a quantitative polymerase chain reaction. Inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 signaling enzyme function up-regulates the expression of EBBP, E2IG5, PGRMC2, and SLC39A6 genes is in U87 glioma cells in comparison with the control glioma cells, with more significant changes for E2IG5 and PGRMC2 genes. At the same time, the expression of NRIP1 and ESRRA genes is strongly down-regulated in glioma cells upon inhibition of IRE1. We also showed that hypoxia increases the expression of E2IG5, PGRMC2, and EBBP genes and decreases NRIP1 and ESRRA genes expression in control glioma cells. Furthermore, the inhibition of IRE1 in U87 glioma cells decreases the eff ect of hypoxia on the expression of E2IG5 and PGRMC2 genes, eliminates hypoxic regulation of NRIP1 gene, and enhances the sensitivity of ESRRA gene to hypoxic condition. Furthermore, the expression of SLC39A6 gene is resistant to hypoxia in both the glioma cells with and without IRE1 signaling enzyme function. Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells in gene specific manner and these changes

  14. Structural Features of the Seneca Valley Virus Internal Ribosome Entry Site (IRES) Element: a Picornavirus with a Pestivirus-Like IRES

    DEFF Research Database (Denmark)

    Willcocks, Margaret M.; Locker, Nicolas; Gomwalk, Zarmwa

    2011-01-01

    The RNA genome of Seneca Valley virus (SVV), a recently identified picornavirus, contains an internal ribosome entry site (IRES) element which has structural and functional similarity to that from classical swine fever virus (CSFV) and hepatitis C virus, members of the FLAVIVIRIDAE: The SVV IRES...... has an absolute requirement for the presence of a short region of virus-coding sequence to allow it to function either in cells or in rabbit reticulocyte lysate. The IRES activity does not require the translation initiation factor eIF4A or intact eIF4G. The predicted secondary structure indicates...

  15. Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata.

    Directory of Open Access Journals (Sweden)

    Taiga Miyazaki

    2013-01-01

    Full Text Available Proper protein folding in the endoplasmic reticulum (ER is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR, is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata.

  16. Physiological roles of Regulated Ire1 Dependent Decay

    Directory of Open Access Journals (Sweden)

    Dina S. Coelho

    2014-04-01

    Full Text Available Ire1 is an important transducer of the Unfolded Protein Response (UPR that is activated by the accumulation of misfolded proteins in the Endoplamic Reticulum (ER stress. Activated Ire1 mediates the splicing of an intron from the mRNA of Xbp1, causing a frame-shift during translation and introducing a new carboxyl domain in the Xbp1 protein, which only then becomes a fully functional transcription factor. Studies using cell culture systems demonstrated that Ire1 also promotes the degradation of mRNAs encoding mostly ER-targeted proteins, to reduce the load of incoming ER client proteins during ER stress. This process was called RIDD (regulated Ire1-dependent decay, but its physiological significance remained poorly characterized beyond cell culture systems. Here we review several recent studies that have highlighted the physiological roles of RIDD in specific biological paradigms, such as photoreceptor differentiation in Drosophila or mammalian liver and endocrine pancreas function. These studies demonstrate the importance of RIDD in tissues undergoing intense secretory function and highlight the physiologic role of RIDD during UPR activation in cells and organisms.

  17. Viral IRES prediction system - a web server for prediction of the IRES secondary structure in silico.

    Directory of Open Access Journals (Sweden)

    Jun-Jie Hong

    Full Text Available The internal ribosomal entry site (IRES functions as cap-independent translation initiation sites in eukaryotic cells. IRES elements have been applied as useful tools for bi-cistronic expression vectors. Current RNA structure prediction programs are unable to predict precisely the potential IRES element. We have designed a viral IRES prediction system (VIPS to perform the IRES secondary structure prediction. In order to obtain better results for the IRES prediction, the VIPS can evaluate and predict for all four different groups of IRESs with a higher accuracy. RNA secondary structure prediction, comparison, and pseudoknot prediction programs were implemented to form the three-stage procedure for the VIPS. The backbone of VIPS includes: the RNAL fold program, aimed to predict local RNA secondary structures by minimum free energy method; the RNA Align program, intended to compare predicted structures; and pknotsRG program, used to calculate the pseudoknot structure. VIPS was evaluated by using UTR database, IRES database and Virus database, and the accuracy rate of VIPS was assessed as 98.53%, 90.80%, 82.36% and 80.41% for IRES groups 1, 2, 3, and 4, respectively. This advance useful search approach for IRES structures will facilitate IRES related studies. The VIPS on-line website service is available at http://140.135.61.250/vips/.

  18. Xbp1-Independent Ire1 Signaling Is Required for Photoreceptor Differentiation and Rhabdomere Morphogenesis in Drosophila

    Directory of Open Access Journals (Sweden)

    Dina S. Coelho

    2013-11-01

    Full Text Available The unfolded protein response (UPR is composed by homeostatic signaling pathways that are activated by excessive protein misfolding in the endoplasmic reticulum. Ire1 signaling is an important mediator of the UPR, leading to the activation of the transcription factor Xbp1. Here, we show that Drosophila Ire1 mutant photoreceptors have defects in the delivery of rhodopsin-1 to the rhabdomere and in the secretion of Spacemaker/Eyes Shut into the interrhabdomeral space. However, these defects are not observed in Xbp1 mutant photoreceptors. Ire1 mutant retinas have higher mRNA levels for targets of regulated Ire1-dependent decay (RIDD, including for the fatty acid transport protein (fatp. Importantly, the downregulation of fatp by RNAi rescues the rhodopsin-1 delivery defects observed in Ire1 mutant photoreceptors. Our results show that the role of Ire1 during photoreceptor differentiation is independent of Xbp1 function and demonstrate the physiological relevance of the RIDD mechanism in this specific paradigm.

  19. IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals.

    Science.gov (United States)

    Kanda, Takehiro; Ozawa, Makoto; Tsukiyama-Kohara, Kyoko

    2016-03-31

    Foot-and-mouth disease virus (FMDV) possess a positive sense, single stranded RNA genome. Internal ribosomal entry site (IRES) element exists within its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA is initiated by internal entry of the 40S ribosome within the IRES element. This process is facilitated by cellular factors known as IRES trans-acting factors (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven-hoofed animals such as cattle and pigs, but the factors determining the host range have not been identified yet. Although, ITAFs are known to promote IRES-mediated translation, these findings were confirmed only in cells derived from FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated translation activities among cell lines derived from four different animal species using bicistronic luciferase reporter plasmid, which possesses an FMDV-IRES element between Renilla and Firefly luciferase genes. Furthermore, we analyzed the effect of the cellular factors on IRES-mediated translation by silencing the cellular factors using siRNA in both FMDV-susceptible and -insusceptible animal cells. Our data indicated that IRES-mediated translational activity was not linked to FMDV host range. ITAF45 promoted IRES-mediated translation in all cell lines, and the effects of poly-pyrimidine tract binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may influence the host range of FMDV. IRES-mediated translation activity of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated translation in all cells, and the effects of PTB and 4E-BP1 were observed only in FMDV-susceptible cells.

  20. Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression.

    Science.gov (United States)

    Reineke, Lucas C; Merrick, William C

    2009-12-01

    Cap-independent initiation of translation is thought to promote protein synthesis on some mRNAs during times when cap-dependent initiation is down-regulated. However, the mechanism of cap-independent initiation is poorly understood. We have previously reported the secondary structure within the yeast minimal URE2 IRES element. In this study, we sought to investigate the mechanism of internal initiation in yeast by assessing the functional role of nucleotides within the minimal URE2 IRES element, and delineating the cis-sequences that modulate levels of internal initiation using a monocistronic reporter vector. Furthermore, we compared the eIF2A sensitivity of the URE2 IRES element with some of the invasive growth IRES elements using DeltaeIF2A yeast. We found that the stability of the stem-loop structure within the minimal URE2 IRES element is not a critical determinant of optimal IRES activity, and the downstream sequences that modulate URE2 IRES-mediated translation can be defined to discrete regions within the URE2 coding region. Repression of internal initiation on the URE2 minimal IRES element by eIF2A is not dependent on the stability of the secondary structure within the URE2 IRES element. Our data also indicate that eIF2A-mediated repression is not specific to the URE2 IRES element, as both the GIC1 and PAB1 IRES elements are repressed by eIF2A. These data provide valuable insights into the mRNA requirements for internal initiation in yeast, and insights into the mechanism of eIF2A-mediated suppression.

  1. IRES-dependent translational control during virus-induced endoplasmic reticulum stress and apoptosis

    Directory of Open Access Journals (Sweden)

    Paul eHanson

    2012-03-01

    Full Text Available Many virus infections and stresses can induce endoplasmic reticulum (ER stress response, a host self defense mechanism against viral invasion and stress. During this event, viral and cellular gene expression is actively regulated and often encounters a switching of the translation initiation from cap-dependent to IRES (internal ribosome entry sites-dependent. This switching is largely dependent on the mRNA structure of the 5’untranslated region (5’UTR and on the particular stress stimuli. Picornviruses and some other viruses contain an IRES within their 5’UTR of viral genome and employ an IRES-driven mechanism for translation initiation. Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5’UTRs. These genes initiate translation usually by a cap-dependent mechanism under normal physiological conditions; however, in certain environments, such as infection, starvation and heat shock they shift translation initiation to an IRES-dependent modality. Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent. These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation of host factors for translation initiation, over-production of homologous proteins of cap-binding protein eIF4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others. Here, we summarize the recent advances in our understanding of the molecular mechanisms for the switching of translation initiation, particularly for the proteins involved in cell survival and apoptosis in the ER stress pathways during viral infections.

  2. Alphavirus replicon approach to promoterless analysis of IRES elements.

    Science.gov (United States)

    Kamrud, K I; Custer, M; Dudek, J M; Owens, G; Alterson, K D; Lee, J S; Groebner, J L; Smith, J F

    2007-04-10

    Here we describe a system for promoterless analysis of putative internal ribosome entry site (IRES) elements using an alphavirus (family Togaviridae) replicon vector. The system uses the alphavirus subgenomic promoter to produce transcripts that, when modified to contain a spacer region upstream of an IRES element, allow analysis of cap-independent translation of genes of interest (GOI). If the IRES element is removed, translation of the subgenomic transcript can be reduced >95% compared to the same transcript containing a functional IRES element. Alphavirus replicons, used in this manner, offer an alternative to standard dicistronic DNA vectors or in vitro translation systems currently used to analyze putative IRES elements. In addition, protein expression levels varied depending on the spacer element located upstream of each IRES. The ability to modulate the level of expression from alphavirus vectors should extend the utility of these vectors in vaccine development.

  3. The IRE1α/XBP1s Pathway Is Essential for the Glucose Response and Protection of β Cells.

    Directory of Open Access Journals (Sweden)

    Justin R Hassler

    2015-10-01

    Full Text Available Although glucose uniquely stimulates proinsulin biosynthesis in β cells, surprisingly little is known of the underlying mechanism(s. Here, we demonstrate that glucose activates the unfolded protein response transducer inositol-requiring enzyme 1 alpha (IRE1α to initiate X-box-binding protein 1 (Xbp1 mRNA splicing in adult primary β cells. Using mRNA sequencing (mRNA-Seq, we show that unconventional Xbp1 mRNA splicing is required to increase and decrease the expression of several hundred mRNAs encoding functions that expand the protein secretory capacity for increased insulin production and protect from oxidative damage, respectively. At 2 wk after tamoxifen-mediated Ire1α deletion, mice develop hyperglycemia and hypoinsulinemia, due to defective β cell function that was exacerbated upon feeding and glucose stimulation. Although previous reports suggest IRE1α degrades insulin mRNAs, Ire1α deletion did not alter insulin mRNA expression either in the presence or absence of glucose stimulation. Instead, β cell failure upon Ire1α deletion was primarily due to reduced proinsulin mRNA translation primarily because of defective glucose-stimulated induction of a dozen genes required for the signal recognition particle (SRP, SRP receptors, the translocon, the signal peptidase complex, and over 100 other genes with many other intracellular functions. In contrast, Ire1α deletion in β cells increased the expression of over 300 mRNAs encoding functions that cause inflammation and oxidative stress, yet only a few of these accumulated during high glucose. Antioxidant treatment significantly reduced glucose intolerance and markers of inflammation and oxidative stress in mice with β cell-specific Ire1α deletion. The results demonstrate that glucose activates IRE1α-mediated Xbp1 splicing to expand the secretory capacity of the β cell for increased proinsulin synthesis and to limit oxidative stress that leads to β cell failure.

  4. The UPR reduces glucose metabolism via IRE1 signaling.

    Science.gov (United States)

    van der Harg, Judith M; van Heest, Jessica C; Bangel, Fabian N; Patiwael, Sanne; van Weering, Jan R T; Scheper, Wiep

    2017-04-01

    Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis. Since the UPR is strategically positioned to sense and integrate metabolic stress signals, it is likely that - apart from its adaptive response to restore proteostasis - it also directly affects metabolic pathways. Here we investigate the direct role of the UPR in glucose homeostasis. O-GlcNAc is a post-translational modification that is highly responsive to glucose fluctuations. We find that UPR activation results in decreased O-GlcNAc modification, in line with reduced glucose metabolism. Our data indicate that UPR activation has no direct impact on the upstream processes in glucose metabolism; glucose transporter expression, glucose uptake and hexokinase activity. In contrast, prolonged UPR activation decreases glycolysis and mitochondrial metabolism. Decreased mitochondrial respiration is not accompanied by apoptosis or a structural change in mitochondria indicating that the reduction in metabolic rate upon UPR activation is a physiological non-apoptotic response. Metabolic decrease is prevented if the IRE1 pathway of the UPR is inhibited. This indicates that activation of IRE1 signaling induces a reduction in glucose metabolism, as part of an adaptive response. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Generation and analysis of an improved Foxg1-IRES-Cre driver mouse line.

    Science.gov (United States)

    Kawaguchi, Daichi; Sahara, Setsuko; Zembrzycki, Andreas; O'Leary, Dennis D M

    2016-04-01

    Foxg1 expression is highly restricted to the telencephalon and other head structures in the early embryo. This expression pattern has been exploited to generate conditional knockout mice, based on a widely used Foxg1-Cre knock-in line (Foxg1(tm1(cre)Skm)), in which the Foxg1 coding region was replaced by the Cre gene. The utility of this line, however, is severely hampered for two reasons: (1) Foxg1-Cre mice display ectopic and unpredictable Cre activity, and (2) Foxg1 haploinsufficiency can produce neurodevelopmental phenotypes. To overcome these issues, we have generated a new Foxg1-IRES-Cre knock-in mouse line, in which an IRES-Cre cassette was inserted in the 3'UTR of Foxg1 locus, thus preserving the endogenous Foxg1 coding region and un-translated gene regulatory sequences in the 3'UTR, including recently discovered microRNA target sites. We further demonstrate that the new Foxg1-IRES-Cre line displays consistent Cre activity patterns that recapitulated the endogenous Foxg1 expression at embryonic and postnatal stages without causing defects in cortical development. We conclude that the new Foxg1-IRES-Cre mouse line is a unique and advanced tool for studying genes involved in the development of the telencephalon and other Foxg1-expressing regions starting from early embryonic stages. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. hNIS-IRES-eGFP Dual Reporter Gene Imaging

    Directory of Open Access Journals (Sweden)

    Jiantu Che

    2005-04-01

    Full Text Available The human and rodent sodium iodide symporters (NIS have recently been cloned and are being investigated as potential therapeutic and reporter genes. We have extended this effort by constructing an internal ribosomal entry site (IRES-linked human NIS (hNIS-enhanced green fluorescent protein (eGFP hybrid reporter gene for both nuclear and optical imaging. A self-inactivating retroviral vector, termed pQCNIG, containing hNIS-IRES-eGFP dual reporter gene, driven by a constitutive CMV promoter, was constructed and used to generate RG2-pQCNIG cells and RG2-pQCNIG tumors. 131I-iodide and 99mTcO4-pertechnetate accumulation studies plus fluorescence microscopy and intensity assays were performed in vitro, and gamma camera imaging studies in RG2-pQCNIG and RG2 tumor-bearing athymic rats were performed. RG2-pQCNIG cells expressed high levels of hNIS protein and showed high intensity of eGFP fluorescence compared with RG2 wild-type cells. RG2-pQCNIG cells accumulated Na131I and 99mTcO4– to a 50:1 and a 170:1 tissue/medium ratio at 10 min, compared with 0.8:1.2 tissue/medium ratio in wild-type RG2 cells. A significant correlation between radiotracer accumulation and eGFP fluorescence intensity was demonstrated. RG2-pQCNIG and RG2 tumors were readily differentiated by in vivo gamma camera imaging; radiotracer uptake increased in RG2-pQCNIG but declined in RG2 tumors over the 50-min imaging period. Stomach and thyroid were the major organs of radionuclide accumulation. The IRES-linked hNIS-eGFP dual reporter gene is functional and stable in transduced RG2-pQCNIG cells. Optical and nuclear imaging of tumors produced from these cell lines provides the opportunity to monitor tumor growth and response to therapy. These studies indicate the potential for a wider application of hNIS reporter imaging and translation into patient studies using radioisotopes that are currently available for human use for both SPECT and PET imaging.

  7. Characterization of Hepatitis C Virus IRES Quasispecies – From the Individual to the Pool

    Directory of Open Access Journals (Sweden)

    Václav Vopálenský

    2018-04-01

    Full Text Available Hepatitis C virus (HCV is a single-stranded positive-sense RNA virus from the genus Hepacivirus. The viral genomic +RNA is 9.6 kb long and contains highly structured 5′ and 3′ untranslated regions (UTRs and codes for a single large polyprotein, which is co- and post-translationally processed by viral and cellular proteases into at least 11 different polypeptides. Most of the 5′ UTR and an initial part of the polyprotein gene are occupied by an internal ribosome entry site (IRES, which mediates cap-independent translation of the viral proteins and allows the virus to overcome cellular antiviral defense based on the overall reduction of the cap-dependent translation initiation. We reconsidered published results concerning a search for possible correlation between patient response to interferon-based antiviral therapy and accumulation of nucleotide changes within the HCV IRES. However, we were unable to identify any such correlation. Rather than searching for individual mutations, we suggest to focus on determination of individual and collective activities of the HCV IRESs found in patient specimens. We developed a combined, fast, and undemanding approach based on high-throughput cloning of the HCV IRES species to a bicistronic plasmid followed by determination of the HCV IRES activity by flow cytometry. This approach can be adjusted for measurement of the individual HCV IRES activity and for estimation of the aggregate ability of the whole HCV population present in the specimen to synthesize viral proteins. To detect nucleotide variations in the individual IRESs, we used denaturing gradient gel electrophoresis (DGGE analysis that greatly improved identification and classification of HCV IRES variants in the sample. We suggest that determination of the collective activity of the majority of HCV IRES variants present in one patient specimen in a given time represents possible functional relations among variant sequences within the complex

  8. The effects of irreversible electroporation (IRE on nerves.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available BACKGROUND: If a critical nerve is circumferentially involved with tumor, radical surgery intended to cure the cancer must sacrifice the nerve. Loss of critical nerves may lead to serious consequences. In spite of the impressive technical advancements in nerve reconstruction, complete recovery and normalization of nerve function is difficult to achieve. Though irreversible electroporation (IRE might be a promising choice to treat tumors near or involved critical nerve, the pathophysiology of the nerve after IRE treatment has not be clearly defined. METHODS: We applied IRE directly to a rat sciatic nerve to study the long term effects of IRE on the nerve. A sequence of 10 square pulses of 3800 V/cm, each 100 µs long was applied directly to rat sciatic nerves. In each animal of group I (IRE the procedure was applied to produce a treated length of about 10 mm. In each animal of group II (Control the electrodes were only applied directly on the sciatic nerve for the same time. Electrophysiological, histological, and functional studies were performed on immediately after and 3 days, 1 week, 3, 5, 7 and 10 weeks following surgery. FINDINGS: Electrophysiological, histological, and functional results show the nerve treated with IRE can attain full recovery after 7 weeks. CONCLUSION: This finding is indicative of the preservation of nerve involving malignant tumors with respect to the application of IRE pulses to ablate tumors completely. In summary, IRE may be a promising treatment tool for any tumor involving nerves.

  9. Structure of the hepatitis C virus IRES bound to the human 80S ribosome: remodeling of the HCV IRES.

    Science.gov (United States)

    Boehringer, Daniel; Thermann, Rolf; Ostareck-Lederer, Antje; Lewis, Joe D; Stark, Holger

    2005-11-01

    Initiation of translation of the hepatitis C virus (HCV) polyprotein is driven by an internal ribosome entry site (IRES) RNA that bypasses much of the eukaryotic translation initiation machinery. Here, single-particle electron cryomicroscopy has been used to study the mechanism of HCV IRES-mediated initiation. A HeLa in vitro translation system was used to assemble human IRES-80S ribosome complexes under near physiological conditions; these were stalled before elongation. Domain 2 of the HCV IRES is bound to the tRNA exit site, touching the L1 stalk of the 60S subunit, suggesting a mechanism for the removal of the HCV IRES in the progression to elongation. Domain 3 of the HCV IRES positions the initiation codon in the ribosomal mRNA binding cleft by binding helix 28 at the head of the 40S subunit. The comparison with the previously published binary 40S-HCV IRES complex reveals structural rearrangements in the two pseudoknot structures of the HCV IRES in translation initiation.

  10. The mechanism of translation initiation on Aichivirus RNA mediated by a novel type of picornavirus IRES.

    Science.gov (United States)

    Yu, Yingpu; Sweeney, Trevor R; Kafasla, Panagiota; Jackson, Richard J; Pestova, Tatyana V; Hellen, Christopher Ut

    2011-08-26

    Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G-interacting domain is structurally distinct, although it contains an apical eIF4G-interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin.

  11. Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Carla M. P. Ribeiro

    2017-01-01

    Full Text Available Cystic fibrosis (CF pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR. This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease.

  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. High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor

    International Nuclear Information System (INIS)

    Auf, Gregor; Vajkoczy, Peter; Seno, Masaharu; Bikfalvi, Andreas; Minchenko, Dmitri; Minchenko, Oleksandr; Moenner, Michel; Jabouille, Arnaud; Delugin, Maylis; Guérit, Sylvaine; Pineau, Raphael; North, Sophie; Platonova, Natalia; Maitre, Marlène; Favereaux, Alexandre

    2013-01-01

    Epidermal growth factor (EGF) receptors contribute to the development of malignant glioma. Here we considered the possible implication of the EGFR ligand epiregulin (EREG) in glioma development in relation to the activity of the unfolded protein response (UPR) sensor IRE1α. We also examined EREG status in several glioblastoma cell lines and in malignant glioma. Expression and biological properties of EREG were analyzed in human glioma cells in vitro and in human tumor xenografts with regard to the presence of ErbB proteins and to the blockade of IRE1α. Inactivation of IRE1α was achieved by using either the dominant-negative strategy or siRNA-mediated knockdown. EREG was secreted in high amounts by U87 cells, which also expressed its cognate EGF receptor (ErbB1). A stimulatory autocrine loop mediated by EREG was evidenced by the decrease in cell proliferation using specific blocking antibodies directed against either ErbB1 (cetuximab) or EREG itself. In comparison, anti-ErbB2 antibodies (trastuzumab) had no significant effect. Inhibition of IRE1α dramatically reduced EREG expression both in cell culture and in human xenograft tumor models. The high-expression rate of EREG in U87 cells was therefore linked to IRE1α, although being modestly affected by chemical inducers of the endoplasmic reticulum stress. In addition, IRE1-mediated production of EREG did not depend on IRE1 RNase domain, as neither the selective dominant-negative invalidation of the RNase activity (IRE1 kinase active) nor the siRNA-mediated knockdown of XBP1 had significant effect on EREG expression. Finally, chemical inhibition of c-Jun N-terminal kinases (JNK) using the SP600125 compound reduced the ability of cells to express EREG, demonstrating a link between the growth factor production and JNK activation under the dependence of IRE1α. EREG may contribute to glioma progression under the control of IRE1α, as exemplified here by the autocrine proliferation loop mediated in U87 cells by the

  14. AtLa1 protein initiates IRES-dependent translation of WUSCHEL mRNA and regulates the stem cell homeostasis of Arabidopsis in response to environmental hazards.

    Science.gov (United States)

    Cui, Yuchao; Rao, Shaofei; Chang, Beibei; Wang, Xiaoshuang; Zhang, Kaidian; Hou, Xueliang; Zhu, Xueyi; Wu, Haijun; Tian, Zhaoxia; Zhao, Zhong; Yang, Chengwei; Huang, Tao

    2015-10-01

    Plant stem cells are hypersensitive to environmental hazards throughout their life cycle, but the mechanism by which plants safeguard stem cell homeostasis in response to environmental hazards is largely unknown. The homeodomain transcription factor WUSCHEL (WUS) protein maintains the stem cell pool in the shoot apical meristem of Arabidopsis. Here, we demonstrate that the translation of WUS mRNA is directed by an internal ribosomal entry site (IRES) located in the 5'-untranslated region. The AtLa1 protein, an RNA-binding factor, binds to the 5'-untranslated region and initiates the IRES-dependent translation of WUS mRNA. Knockdown of AtLa1 expression represses the WUS IRES-dependent translation and leads to the arrest of growth and development. The AtLa1 protein is mainly located in the nucleoplasm. However, environmental hazards promote the nuclear-to-cytoplasmic translocation of the AtLa1 protein, which further enhances the IRES-dependent translation of WUS mRNA. Genetic evidence indicates that the WUS protein increases the tolerance of the shoot apical meristem to environmental hazards. Based on these results, we conclude that the stem cell niche in Arabidopsis copes with environmental hazards by enhancing the IRES-dependent translation of WUS mRNA under the control of the AtLa1 protein. © 2015 John Wiley & Sons Ltd.

  15. Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE).

    Science.gov (United States)

    Kos, Bor; Voigt, Peter; Miklavcic, Damijan; Moche, Michael

    2015-09-01

    Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated. The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy. Output of the numerical treatment planning method shows that a 19.9 cm3 irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months. Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

  16. Specificity in endoplasmic reticulum-stress signaling in yeast entails a step-wise engagement of HAC1 mRNA to clusters of the stress sensor Ire1.

    Science.gov (United States)

    van Anken, Eelco; Pincus, David; Coyle, Scott; Aragón, Tomás; Osman, Christof; Lari, Federica; Gómez Puerta, Silvia; Korennykh, Alexei V; Walter, Peter

    2014-12-30

    Insufficient protein-folding capacity in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR). In the ER lumen, accumulation of unfolded proteins activates the transmembrane ER-stress sensor Ire1 and drives its oligomerization. In the cytosol, Ire1 recruits HAC1 mRNA, mediating its non-conventional splicing. The spliced mRNA is translated into Hac1, the key transcription activator of UPR target genes that mitigate ER-stress. In this study, we report that oligomeric assembly of the ER-lumenal domain is sufficient to drive Ire1 clustering. Clustering facilitates Ire1's cytosolic oligomeric assembly and HAC1 mRNA docking onto a positively charged motif in Ire1's cytosolic linker domain that tethers the kinase/RNase to the transmembrane domain. By the use of a synthetic bypass, we demonstrate that mRNA docking per se is a pre-requisite for initiating Ire1's RNase activity and, hence, splicing. We posit that such step-wise engagement between Ire1 and its mRNA substrate contributes to selectivity and efficiency in UPR signaling.

  17. Endoplasmic reticulum stress and IRE-1 signaling cause apoptosis in colon cancer cells in response to andrographolide treatment.

    Science.gov (United States)

    Banerjee, Aditi; Ahmed, Hafiz; Yang, Peixin; Czinn, Steven J; Blanchard, Thomas G

    2016-07-05

    The plant metabolite andrographolide induces cell cycle arrest and apoptosis in cancer cells. The mechanism(s) by which andrographolide induces apoptosis however, have not been elucidated. The present study was performed to determine the molecular events that promote apoptosis in andrographolide treated cells using T84, HCT116 and COLO 205 colon cancer cell lines. Andrographolide was determined to limit colony formation and Ki67 expression, alter nuclear morphology, increase cytoplasmic histone-associated-DNA-fragments, and increase cleaved caspase-3 levels. Andrographolide also induced significantly higher expression of endoplasmic reticulum (ER) stress proteins GRP-78 and IRE-1 by 48 h but not PERK or ATF6. Apoptosis signaling molecules BAX, spliced XBP-1 and CHOP were also significantly increased. Moreover, chemical inhibition of ER stress or IRE-1 depletion with siRNA in andrographolide treated cells significantly limited expression of IRE-1 and CHOP as determined by immunofluorescence staining, real time PCR, or immunobloting. This was accompanied by a decreased BAX/Bcl-2 ratio. Andrographolide significantly promotes cancer cell death compared to normal cells. These data demonstrate that andrographolide associated ER stress contributes to apoptosis through the activation of a pro-apoptotic GRP-78/IRE-1/XBP-1/CHOP signaling pathway.

  18. Crystallization and preliminary X-ray diffraction analysis of iron regulatory protein 1 in complex with ferritin IRE RNA

    International Nuclear Information System (INIS)

    Selezneva, Anna I.; Cavigiolio, Giorgio; Theil, Elizabeth C.; Walden, William E.; Volz, Karl

    2006-01-01

    The iron regulatory protein IRP1 has been crystallized in a complex with ferritin IRE RNA and a complete data set has been collected to 2.8 Å resolution. Iron regulatory protein 1 (IRP1) is a bifunctional protein with activity as an RNA-binding protein or as a cytoplasmic aconitase. Interconversion of IRP1 between these mutually exclusive states is central to cellular iron regulation and is accomplished through iron-responsive assembly and disassembly of a [4Fe–4S] cluster. When in its apo form, IRP1 binds to iron responsive elements (IREs) found in mRNAs encoding proteins of iron storage and transport and either prevents translation or degradation of the bound mRNA. Excess cellular iron stimulates the assembly of a [4Fe–4S] cluster in IRP1, inhibiting its IRE-binding ability and converting it to an aconitase. The three-dimensional structure of IRP1 in its different active forms will provide details of the interconversion process and clarify the selective recognition of mRNA, Fe–S sites and catalytic activity. To this end, the apo form of IRP1 bound to a ferritin IRE was crystallized. Crystals belong to the monoclinic space group P2 1 , with unit-cell parameters a = 109.6, b = 80.9, c = 142.9 Å, β = 92.0°. Native data sets have been collected from several crystals with resolution extending to 2.8 Å and the structure has been solved by molecular replacement

  19. Inhibition of Hepatitis C Virus in Mice by a Small Interfering RNA Targeting a Highly Conserved Sequence in Viral IRES Pseudoknot.

    Directory of Open Access Journals (Sweden)

    Jae-Su Moon

    Full Text Available The hepatitis C virus (HCV internal ribosome entry site (IRES that directs cap-independent viral translation is a primary target for small interfering RNA (siRNA-based HCV antiviral therapy. However, identification of potent siRNAs against HCV IRES by bioinformatics-based siRNA design is a challenging task given the complexity of HCV IRES secondary and tertiary structures and association with multiple proteins, which can also dynamically change the structure of this cis-acting RNA element. In this work, we utilized siRNA tiling approach whereby siRNAs were tiled with overlapping sequences that were shifted by one or two nucleotides over the HCV IRES stem-loop structures III and IV spanning nucleotides (nts 277-343. Based on their antiviral activity, we mapped a druggable region (nts 313-343 where the targets of potent siRNAs were enriched. siIE22, which showed the greatest anti-HCV potency, targeted a highly conserved sequence across diverse HCV genotypes, locating within the IRES subdomain IIIf involved in pseudoknot formation. Stepwise target shifting toward the 5' or 3' direction by 1 or 2 nucleotides reduced the antiviral potency of siIE22, demonstrating the importance of siRNA accessibility to this highly structured and sequence-conserved region of HCV IRES for RNA interference. Nanoparticle-mediated systemic delivery of the stability-improved siIE22 derivative gs_PS1 siIE22, which contains a single phosphorothioate linkage on the guide strand, reduced the serum HCV genome titer by more than 4 log10 in a xenograft mouse model for HCV replication without generation of resistant variants. Our results provide a strategy for identifying potent siRNA species against a highly structured RNA target and offer a potential pan-HCV genotypic siRNA therapy that might be beneficial for patients resistant to current treatment regimens.

  20. Beam Simulations for IRE and Driver-Status and Strategy

    International Nuclear Information System (INIS)

    Friedman, A.; Grote, D.P.; Lee, E.P.; Sonnendrucker, E.

    2000-01-01

    The methods and codes employed in the U.S. Heavy Ion Fusion program to simulate the beams in an Integrated Research Experiments (IRE) facility and a fusion driver are presented in overview. A new family of models incorporating accelerating module impedance, multi-beam, and self-magnetic effects is described, and initial WARP3d particle simulations of beams using these models are presented. Finally, plans for streamlining the machine-design simulation sequence, and for simulating beam dynamics from the source to the target in a consistent and comprehensive manner, are described

  1. IRE/F as a Cross-Curricular Collaborative Genre of Implicit Argumentation

    Science.gov (United States)

    Lawrence, Ann M.; Crespo, Sandra

    2016-01-01

    We contend that the classroom-discourse routine of IRE/F (teacher initiation, student response, teacher evaluation/follow-up) is a genre of argumentation that is both collaborative and implicit because teachers and students cooperate during IRE/F exchanges not only to make and mirror knowledge claims but also to suppress justification for those…

  2. 42 CFR 423.2010 - When CMS, the IRE, or Part D plan sponsors may participate in an ALJ hearing.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false When CMS, the IRE, or Part D plan sponsors may... PRESCRIPTION DRUG BENEFIT Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2010 When CMS, the IRE... require, CMS, the IRE, and/or the Part D plan sponsor to participate in any proceedings before the ALJ...

  3. PRMT5 regulates IRES-dependent translation via methylation of hnRNP A1

    Science.gov (United States)

    Gao, Guozhen; Dhar, Surbhi

    2017-01-01

    Abstract The type II arginine methyltransferase PRMT5 is responsible for the symmetric dimethylation of histone to generate the H3R8me2s and H4R3me2s marks, which correlate with the repression of transcription. However, the protein level of a number of genes (MEP50, CCND1, MYC, HIF1a, MTIF and CDKN1B) are reported to be downregulated by the loss of PRMT5, while their mRNA levels remain unchanged, which is counterintuitive for PRMT5's proposed role as a transcription repressor. We noticed that the majority of the genes regulated by PRMT5, at the posttranscriptional level, express mRNA containing an internal ribosome entry site (IRES). Using an IRES-dependent reporter system, we established that PRMT5 facilitates the translation of a subset of IRES-containing genes. The heterogeneous nuclear ribonucleoprotein, hnRNP A1, is an IRES transacting factor (ITAF) that regulates the IRES-dependent translation of Cyclin D1 and c-Myc. We showed that hnRNP A1 is methylated by PRMT5 on two residues, R218 and R225, and that this methylation facilitates the interaction of hnRNP A1 with IRES RNA to promote IRES-dependent translation. This study defines a new role for PRMT5 regulation of cellular protein levels, which goes beyond the known functions of PRMT5 as a transcription and splicing regulator. PMID:28115626

  4. 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.

  5. BECCS Market Launch Strategy Aiming to Help Ensure Reliable Grid Power at High Penetrations of IRE (Intermittent Renewable Electricity)

    Science.gov (United States)

    WIlliams, R. H.

    2017-12-01

    Despite its recognized importance for carbon (C)-mitigation, progress in advancing biomass energy with CO2 capture and sequestration (BECCS) has been slow. A BECCS market launch strategy based on technologies ready for commercial-scale demonstration is discussed—based on co-gasification of coal and biomass to make H2 with CCS. H2 so produced would be a key element of a H2 balancing capacity (H2-BC) strategy for ensuring reliable grid power at high IRE penetrations. High grid penetrations of IRE must be complemented by fast-ramping balancing (backup and/or storage) capacity (BC) to ensure reliable grid power. BC provided now by natural gas-fired gas turbine combined cycle and combustion turbine units would eventually have to be decarbonized to realize C-mitigation goals, via CCS or other means. Capital-intensive CCS energy systems require baseload operation to realize favourable economics, but at high IRE penetrations, BC plants must be operated at low capacity factors. A H2-BC strategy is a promising way to address this challenge. The elements of a H2-BC system are: (a) H2 production from carbonaceous feedstocks in baseload plants with CCS; (b) H2 consumption in fast-ramping BC units that operate at low capacity factors; (c) Buffer underground H2 storage to enable decoupling baseload H2 production from highly variable H2 consumption by BC units. The concept is likely to "work" because underground H2 storage is expected to be inexpensive. A H2 production analysis is presented for a negative GHG-emitting H2-BC system based on cogasification of corn stover and coal, with captured CO2 used for enhanced oil recovery. The technical readiness of each system component is discussed, and preliminary insights are offered as to the conditions under which the corresponding H2-BC system might compete with natural gas in providing backup for IRE on US electric grids. Public policy to help advance this strategy might be forthcoming, because 2 US Senate bills with broad

  6. Muudatused tulekahjuhäiresüsteemide ehitamisel / Veiko Jürisson

    Index Scriptorium Estoniae

    Jürisson, Veiko, 1956-2008

    2005-01-01

    Tulekahju-signalisatsioonisüsteemi ehitusele eelneva kirjaliku nõusoleku taotlemisest kohalikult omavalitsuselt, valminud süsteemi üleandmisest omanikule ning automaatse tulekahjuhäiresüsteemi kasutusloa andmisest

  7. IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES)

    Science.gov (United States)

    Kolekar, Pandurang; Pataskar, Abhijeet; Kulkarni-Kale, Urmila; Pal, Jayanta; Kulkarni, Abhijeet

    2016-01-01

    Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5′ untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/. PMID:27264539

  8. An approach to modeling and optimization of integrated renewable energy system (ires)

    Science.gov (United States)

    Maheshwari, Zeel

    The purpose of this study was to cost optimize electrical part of IRES (Integrated Renewable Energy Systems) using HOMER and maximize the utilization of resources using MATLAB programming. IRES is an effective and a viable strategy that can be employed to harness renewable energy resources to energize remote rural areas of developing countries. The resource- need matching, which is the basis for IRES makes it possible to provide energy in an efficient and cost effective manner. Modeling and optimization of IRES for a selected study area makes IRES more advantageous when compared to hybrid concepts. A remote rural area with a population of 700 in 120 households and 450 cattle is considered as an example for cost analysis and optimization. Mathematical models for key components of IRES such as biogas generator, hydropower generator, wind turbine, PV system and battery banks are developed. A discussion of the size of water reservoir required is also presented. Modeling of IRES on the basis of need to resource and resource to need matching is pursued to help in optimum use of resources for the needs. Fixed resources such as biogas and water are used in prioritized order whereas movable resources such as wind and solar can be used simultaneously for different priorities. IRES is cost optimized for electricity demand using HOMER software that is developed by the NREL (National Renewable Energy Laboratory). HOMER optimizes configuration for electrical demand only and does not consider other demands such as biogas for cooking and water for domestic and irrigation purposes. Hence an optimization program based on the need-resource modeling of IRES is performed in MATLAB. Optimization of the utilization of resources for several needs is performed. Results obtained from MATLAB clearly show that the available resources can fulfill the demand of the rural areas. Introduction of IRES in rural communities has many socio-economic implications. It brings about improvement in living

  9. Effect of CD34+ cord blood stem cell transfected by plasmid vector pIRES2-FL-IL-3 on the mice after irradiation

    International Nuclear Information System (INIS)

    Zhang Yong; Zhang Linsheng; Zhang Hongbing; Guo Chaohua; Tong Shiwu

    2008-01-01

    Objective: To observe the effect of CD34 cord blood stem cell transfected by plasmid vector plRES2-FL-IL-3 on the mouse after irradiation and to investigate its mechanisms. Methods: In the co-expressed group (12 mice), CD 34 + cord blood stem cells were transfected by plasmid vector pIRES2-FL-IL-3.5 x lO 5 cells were injected intravenously in the mouse. The hemogram changes in mice were detected 2, 4 and 6 weeks after radiation. At 6 weeks after irradiation, the expression of the CD 34 in spleen was detected by immumofluorescence method. The mRNA level and the activity of IL-3 and FL were detected by RT-PCR and Western blot. Other 3 groups were CD 34 + cell group (CD 34 group), pIRES2-IL-3 group(IL 3 group) and pIRES2-FL group(FL group), and there were 12 mice in each group. Results: The survival rate of CD 34 group, IL3 group and FL group at the 6th week were 25.0% (3/12), 50.0% (6/12) and 50.0% (6/12), respectively. It was 91.7% (11/12) in the co-expressed group, which was higher than those in the other groups. The expression of the CD 34 of spleen in the co-expressed group was higher than those of the other groups. The mRNA level and the activity of IL-3 and FL of spleen in the co-expressed group were higher than those in the other groups too. Conclusions: The CD 34 '+ cord blood stem cells transfected by plasmid vector pIRES2-FL-IL-3 have hemogenesis promotion effect on the mice after irradiation, which was related with the aggregation, proliferation of stem cells and the high expression of the interest proteins.. (authors)

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

    Science.gov (United States)

    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.

  11. Structural Analysis of PTM Hotspots (SAPH-ire)--A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families.

    Science.gov (United States)

    Dewhurst, Henry M; Choudhury, Shilpa; Torres, Matthew P

    2015-08-01

    Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)--a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits--conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit-N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. © 2015 by The American

  12. Structural Analysis of PTM Hotspots (SAPH-ire) – A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families*

    Science.gov (United States)

    Dewhurst, Henry M.; Choudhury, Shilpa; Torres, Matthew P.

    2015-01-01

    Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)—a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits—conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit–N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. PMID:26070665

  13. Minimal-length Synthetic shRNAs Formulated with Lipid Nanoparticles are Potent Inhibitors of Hepatitis C Virus IRES-linked Gene Expression in Mice

    Directory of Open Access Journals (Sweden)

    Anne Dallas

    2013-01-01

    Full Text Available We previously identified short synthetic shRNAs (sshRNAs that target a conserved hepatitis C virus (HCV sequence within the internal ribosome entry site (IRES of HCV and potently inhibit HCV IRES-linked gene expression. To assess in vivo liver delivery and activity, the HCV-directed sshRNA, SG220 was formulated into lipid nanoparticles (LNP and injected i.v. into mice whose livers supported stable HCV IRES-luciferase expression from a liver-specific promoter. After a single injection, RNase protection assays for the sshRNA and 3H labeling of a lipid component of the nanoparticles showed efficient liver uptake of both components and long-lasting survival of a significant fraction of the sshRNA in the liver. In vivo imaging showed a dose-dependent inhibition of luciferase expression (>90% 1 day after injection of 2.5 mg/kg sshRNA with t1/2 for recovery of about 3 weeks. These results demonstrate the ability of moderate levels of i.v.-injected, LNP-formulated sshRNAs to be taken up by liver hepatocytes at a level sufficient to substantially suppress gene expression. Suppression is rapid and durable, suggesting that sshRNAs may have promise as therapeutic agents for liver indications.

  14. Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction.

    Science.gov (United States)

    Luis, Nuno Miguel; Wang, Lifen; Ortega, Mauricio; Deng, Hansong; Katewa, Subhash D; Li, Patrick Wai-Lun; Karpac, Jason; Jasper, Heinrich; Kapahi, Pankaj

    2016-10-25

    Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut. Consistently, IRE1/XBP1 function in ECs is required for increased longevity upon DR. We further identify sugarbabe, a Gli-like zinc-finger transcription factor, as a key mediator of the IRE1/XBP1-regulated induction of de novo lipogenesis in ECs. Overexpression of sugarbabe rescues metabolic and lifespan phenotypes of IRE1 loss-of-function conditions. Our study highlights the critical role of metabolic adaptation of the intestinal epithelium for DR-induced lifespan extension and explores the IRE1/XBP1 signaling pathway regulating this adaptation and influencing lifespan. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Hydrolytic enzyme activity enhanced by Barium supplementation

    Directory of Open Access Journals (Sweden)

    Camilo Muñoz

    2016-10-01

    Full Text Available Hydrolysis of polymers is a first and often limiting step during the degradation of plant residues. Plant biomass is generally a major component of waste residues and a major renewable resource to obtain a variety of secondary products including biofuels. Improving the performance of enzymatic hydrolysis of plant material with minimum costs and limiting the use of additional microbial biomass or hydrolytic enzymes directly influences competitiveness of these green biotechnological processes. In this study, we cloned and expressed a cellulase and two esterases recovered from environmental thermophilic soil bacterial communities and characterize their optimum activity conditions including the effect of several metal ions. Results showed that supplementing these hydrolytic reactions with Barium increases the activity of these extracellular hydrolytic enzymes. This observation represents a simple but major improvement to enhance the efficiency and competitiveness of this process within an increasingly important biotechnological sector.

  16. Initiation of translation in bacteria by a structured eukaryotic IRES RNA.

    Science.gov (United States)

    Colussi, Timothy M; Costantino, David A; Zhu, Jianyu; Donohue, John Paul; Korostelev, Andrei A; Jaafar, Zane A; Plank, Terra-Dawn M; Noller, Harry F; Kieft, Jeffrey S

    2015-03-05

    The central dogma of gene expression (DNA to RNA to protein) is universal, but in different domains of life there are fundamental mechanistic differences within this pathway. For example, the canonical molecular signals used to initiate protein synthesis in bacteria and eukaryotes are mutually exclusive. However, the core structures and conformational dynamics of ribosomes that are responsible for the translation steps that take place after initiation are ancient and conserved across the domains of life. We wanted to explore whether an undiscovered RNA-based signal might be able to use these conserved features, bypassing mechanisms specific to each domain of life, and initiate protein synthesis in both bacteria and eukaryotes. Although structured internal ribosome entry site (IRES) RNAs can manipulate ribosomes to initiate translation in eukaryotic cells, an analogous RNA structure-based mechanism has not been observed in bacteria. Here we report our discovery that a eukaryotic viral IRES can initiate translation in live bacteria. We solved the crystal structure of this IRES bound to a bacterial ribosome to 3.8 Å resolution, revealing that despite differences between bacterial and eukaryotic ribosomes this IRES binds directly to both and occupies the space normally used by transfer RNAs. Initiation in both bacteria and eukaryotes depends on the structure of the IRES RNA, but in bacteria this RNA uses a different mechanism that includes a form of ribosome repositioning after initial recruitment. This IRES RNA bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.

  17. A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy.

    Science.gov (United States)

    Deegan, Shane; Koryga, Izabela; Glynn, Sharon A; Gupta, Sanjeev; Gorman, Adrienne M; Samali, Afshin

    2015-01-02

    Endoplasmic reticulum (ER) stress is known to lead to activation of both the unfolded protein response (UPR) and autophagy. Although regulatory connections have been identified between the UPR and autophagy, it is still unclear to what extent the UPR regulates the genes involved at the different stages of the autophagy pathway. Here, we carried out a microarray analysis of HCT116 cells subjected to ER stress and observed the transcriptional upregulation of a large cohort of autophagy-related genes. Of particular interest, we identified the transcriptional upregulation of the autophagy receptor genes SQSTM1/p62, NBR1 and BNIP3L/NIX in response to ER stress and show that the inhibition of the UPR transmembrane receptors, PERK and IRE1, abrogates this upregulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Accidental release of iodine 131 by the IRE of the Fleurus site: return on experience by the Belgian safety authority

    International Nuclear Information System (INIS)

    Vandecasteele, C.M.; Sonck, M.; Degueldre, D.

    2010-01-01

    After a presentation of the activities of the IRE, the Belgian National Institute of Radio-elements, i.e. the production of radionuclides used in nuclear medicine, this report describes the process and chemical reaction which caused an accidental release of iodine 131. It analyzes the causes of this incident, and how the incident has been managed by the Belgian safety authority. It discusses the first assessment of radiological consequences, describes how the incident has been managed at the federal level, and how population and media have been informed. It discusses the actual radiological consequences through measurements performed on grass and vegetables (graphs and maps indicate contamination levels and contaminated areas), and through the assessment of exposure of adults and children by different ways. Lessons learned are then discussed

  19. The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins.

    Science.gov (United States)

    Gao, Meng; Duan, Hao; Liu, Jing; Zhang, Hao; Wang, Xin; Zhu, Meng; Guo, Jitao; Zhao, Zhenlong; Meng, Lirong; Peng, Yihong

    2014-06-01

    The activation of ERK and p38 signal cascade in host cells has been demonstrated to be essential for picornavirus enterovirus 71 (EV71) replication and up-regulation of virus-induced cyclooxygenase-2 (COX-2)/prostaglandins E2 (PGE2) expression. The aim of this study was to examine the effects of sorafenib, a clinically approved anti-cancer multi-targeted kinase inhibitor, on the propagation and pathogenesis of EV71, with a view to its possible mechanism and potential use in the design of therapy regimes for Hand foot and mouth disease (HFMD) patients with life threatening neurological complications. In this study, non-toxic concentrations of sorafenib were shown to inhibit the yield of infectious progeny EV71 (clinical BC08 strain) by about 90% in three different cell types. A similar inhibitory effect of sorafenib was observed on the synthesis of both viral genomic RNA and the VP1 protein. Interestingly, sorafenib exerted obvious inhibition of the EV71 internal ribosomal entry site (IRES)-mediated translation, the first step in picornavirus replication, by linking it to a firefly luciferase reporter gene. Sorafenib was also able to prevent both EV71-induced CPE and the activation of ERK and p38, which contributes to up-regulation COX-2/PGE2 expression induced by the virus. Overall, this study shows that sorafenib strongly inhibits EV71 replication at least in part by regulating viral IRES-dependent translation of viral proteins, indicating a novel potential strategy for the treatment of HFMD patients with severe neurological complications. To our knowledge, this is the first report that investigates the mechanism by which sorafenib inhibits EV71 replication. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Phanerochaete mutants with enhanced ligninolytic activity

    International Nuclear Information System (INIS)

    Kakar, S.N.; Perez, A.; Gonzales, J.

    1994-01-01

    In addition to lignin, the white rot fungus Phanerochaete chrysosporium has the ability to degrade a wide spectrum of recalcitrant organo pollutants in soils and aqueous media. Most of the organic compounds are degraded under ligninolytic conditions with the involvement of the extracellular enzymes, lignin peroxidases, and manganese-dependent peroxidases, which are produced as secondary metabolites triggered by conditions of nutrient starvation (e.g., nitrogen limitation). The fungus and its enzymes can thus provide alternative technologies for bioremediation, bio pulping, bio bleaching, and other industrial applications. The efficiency and effectiveness of the fungus can be enhanced by increasing production and secretion of the important enzymes in large quantities and as primary metabolites under enriched conditions. One way this can be achieved is through isolation of mutants that are deregulated, or are hyper producers or super secretors of key enzymes under enriched conditions. Through UV-light and γ-ray mutagenesis, we have isolated a variety of mutants, some of which produce key enzymes of the ligninolytic system under high-nitrogen growth conditions. One of the mutants, 76UV, produced 272 U of lignin peroxidases enzyme activity/L after 9 d under high nitrogen (although the parent strain does not produce this enzyme under these conditions). The mutant and the parent strains produced up to 54 and 62 U/L, respectively, of the enzyme activity under low nitrogen growth conditions during this period. In some experiments, the mutant showed 281 U/L of enzyme activity under high nitrogen after 17 d

  1. Analysis of Factors Affecting System Performance in the ASpIRE Challenge

    Science.gov (United States)

    2015-12-13

    performance in the ASpIRE ( Automatic Speech recognition In Reverberant Environments) challenge. In particular, overall word error rate (WER) of the solver...in mismatched conditions. Index Terms: speech recognition, reverberant rooms, microphone audio 1. Introduction The development of automatic ...IEEE Workshop on Automatic Speech Recognition and Understanding, 2005. [7] Harper, M., The Automatic Speech Recognition in Reverberant

  2. Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation

    NARCIS (Netherlands)

    Fernandez, James; Yaman, Ibrahim; Huang, Charles; Liu, Haiyan; Lopez, Alex B.; Komar, Anton A.; Caprara, Mark G.; Merrick, William C.; Snider, Martin D.; Kaufman, Randal J.; Lamers, Wouter H.; Hatzoglou, Maria

    2005-01-01

    It was previously shown that the mRNA for the cat-1 Arg/Lys transporter is translated from an internal ribosome entry site (IRES) that is regulated by cellular stress. Amino acid starvation stimulated cat-1 translation via a mechanism that requires translation of an ORF in the mRNA leader and

  3. Switch from cap- to factorless IRES-dependent 0 and +1 frame translation during cellular stress and dicistrovirus infection.

    Directory of Open Access Journals (Sweden)

    Qing S Wang

    Full Text Available Internal ribosome entry sites (IRES are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A "stop-go" peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.

  4. Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE

    Directory of Open Access Journals (Sweden)

    Kos Bor

    2015-09-01

    Full Text Available Background. Irreversible electroporation (IRE is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated.

  5. The use of IRE in multi-modality treatment for oligometastatic pancreatic cancer.

    Science.gov (United States)

    Hong, Young; Rice, Jonathan; Sharma, Divyansh; Martin, Robert C G

    2018-03-02

    Pancreatic ductal adenocarcinoma (PDAC) often presents late with only 20% of patients being candidates for resection while majority already have advanced metastases with median overall survival of 3-6 months. Currently, the role of oligometastasectomy and local therapy options in PDAC is unknown in patients who have favorable response to systemic chemotherapy. The aim of this study is to analyze the survival outcome of oligometastasectomy and local IRE therapy in select patients who are treated with systemic chemotherapy for PDAC metastases. We utilized a prospective database from 2010 to 2016 to identify patients with local surgical therapy after induction systemic chemotherapy for oligometastatic PDAC (Stage 4). The initial local therapy treatment of distant metastatic lesions was followed by adjuvant chemotherapy. Subsequently, resection of the primary PDAC in conjunction with irreversible electroporation (IRE) was performed after favorable response by RECIST criteria. Seven patients were identified with metastatic PDAC treated with oligometastasectomy and/or local therapy. There was single metastatic lesion in 43% (3/7) of which 57% (4/7) were localized in the liver. The treatment of the primary pancreatic cancer was performed utilizing IRE in situ in 6/7 (86%) of patients in our study with resection or radiation of oligometastasis. The median survival in our study group was 16 months with 28% (2/7) patients who remain NED (range 16-41 months). Combination of systemic chemotherapy and oligometastasectomy with adjunctive local IRE therapy is a feasible treatment strategy in highly select patients with oligometastatic PDAC that demonstrate favorable tumor biology with objective response to systemic therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. 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.

  7. Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-Å resolution.

    Science.gov (United States)

    Quade, Nick; Boehringer, Daniel; Leibundgut, Marc; van den Heuvel, Joop; Ban, Nenad

    2015-07-08

    Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 5'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 Å resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs.

  8. HCV IRES domain IIb affects the configuration of coding RNA in the 40S subunit's decoding groove.

    Science.gov (United States)

    Filbin, Megan E; Kieft, Jeffrey S

    2011-07-01

    Hepatitis C virus (HCV) uses a structured internal ribosome entry site (IRES) RNA to recruit the translation machinery to the viral RNA and begin protein synthesis without the ribosomal scanning process required for canonical translation initiation. Different IRES structural domains are used in this process, which begins with direct binding of the 40S ribosomal subunit to the IRES RNA and involves specific manipulation of the translational machinery. We have found that upon initial 40S subunit binding, the stem-loop domain of the IRES that contains the start codon unwinds and adopts a stable configuration within the subunit's decoding groove. This configuration depends on the sequence and structure of a different stem-loop domain (domain IIb) located far from the start codon in sequence, but spatially proximal in the IRES•40S complex. Mutation of domain IIb results in misconfiguration of the HCV RNA in the decoding groove that includes changes in the placement of the AUG start codon, and a substantial decrease in the ability of the IRES to initiate translation. Our results show that two distal regions of the IRES are structurally communicating at the initial step of 40S subunit binding and suggest that this is an important step in driving protein synthesis.

  9. Biomonitoring of intermittent rivers and ephemeral streams in Europe: Current practice and priorities to enhance ecological status assessments.

    Science.gov (United States)

    Stubbington, Rachel; Chadd, Richard; Cid, Núria; Csabai, Zoltán; Miliša, Marko; Morais, Manuela; Munné, Antoni; Pařil, Petr; Pešić, Vladimir; Tziortzis, Iakovos; Verdonschot, Ralf C M; Datry, Thibault

    2018-03-15

    Intermittent rivers and ephemeral streams (IRES) are common across Europe and dominate some Mediterranean river networks. In all climate zones, IRES support high biodiversity and provide ecosystem services. As dynamic ecosystems that transition between flowing, pool, and dry states, IRES are typically poorly represented in biomonitoring programmes implemented to characterize EU Water Framework Directive ecological status. We report the results of a survey completed by representatives from 20 European countries to identify current challenges to IRES status assessment, examples of best practice, and priorities for future research. We identify five major barriers to effective ecological status classification in IRES: 1. the exclusion of IRES from Water Framework Directive biomonitoring based on their small catchment size; 2. the lack of river typologies that distinguish between contrasting IRES; 3. difficulties in defining the 'reference conditions' that represent unimpacted dynamic ecosystems; 4. classification of IRES ecological status based on lotic communities sampled using methods developed for perennial rivers; and 5. a reliance on taxonomic characterization of local communities. Despite these challenges, we recognize examples of innovative practice that can inform modification of current biomonitoring activity to promote effective IRES status classification. Priorities for future research include reconceptualization of the reference condition approach to accommodate spatiotemporal fluctuations in community composition, and modification of indices of ecosystem health to recognize both taxon-specific sensitivities to intermittence and dispersal abilities, within a landscape context. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Enhanced activation of the left hemisphere promotes normative decision making.

    Science.gov (United States)

    Corser, Ryan; Jasper, John D

    2014-01-01

    Previous studies have reported that enhanced activation of the left cerebral hemisphere reduces risky-choice, attribute, and goal-framing effects relative to enhanced activation of the right cerebral hemisphere. The present study sought to extend these findings and show that enhanced activation of the left hemisphere also reduces violations of other normative principles, besides the invariance principle. Participants completed ratio bias (Experiment 1, N = 296) and base rate neglect problems (Experiment 2, N = 145) under normal (control) viewing or with the right or left hemisphere primarily activated by imposing a unidirectional gaze. In Experiment 1 we found that enhanced left hemispheric activation reduced the ratio bias relative to normal viewing and a group experiencing enhanced right hemispheric activation. In Experiment 2 enhanced left hemispheric activation resulted in using base rates more than normal viewing, but not significantly more than enhanced right hemispheric activation. Results suggest that hemispheric asymmetries can affect higher-order cognitive processes, such as decision-making biases. Possible theoretical accounts are discussed as well as implications for dual-process theories.

  11. Enhancement of the Electrocatalytic Activity of Gold Nanoparticles via Anodic Treatment and the Decrease of the Enhanced Activity with Aging

    International Nuclear Information System (INIS)

    Jo, Kyung Min; Kang, Hyun Ju; Yang, Hae Sik

    2011-01-01

    We have recently shown that the electrocatalytic activity of Au nanoparticles (AuNPs) can be enhanced via NaBH 4 treatment and cathodic treatment and that the enhanced activity slowly decreases with aging. We have also demonstrated that the electrocatalytic activity of the AuNPs freshly prepared by electrochemical or chemical reduction slowly decreases with aging in both air and solution. Likewise, the electrocatalytic activity of anodically treated Au electrodes or AuNPs might change with aging. Herein, we report that the electrocatalytic activity of long-aged AuNPs can be enhanced via anodic treatment and that the enhanced electrocatalytic activity decreases with aging in air. The change in the electrocatalytic activity of AuNPs was evaluated by comparing cyclic voltammograms for the electrooxi-dation of hydrogen peroxide (H 2 O 2 ) and formic acid

  12. Targeting the CACNA1A IRES as a Treatment for Spinocerebellar Ataxia Type 6.

    Science.gov (United States)

    Pastor, Parviz Daniel Hejazi; Du, Xiaofei; Fazal, Sarah; Davies, Andre N; Gomez, Christopher M

    2018-02-01

    We have discovered that the P/Q-type voltage-gated Ca 2+ channel (VGCC) gene, CACNA1A, encodes both the α1A (Cav2.1) subunit and a newly recognized transcription factor, α1ACT, by means of a novel internal ribosomal entry site (IRES) within the α1A C-terminal coding region. α1ACT, when mutated with an expansion of the polyglutamine tract in the C-terminus, gives rise to spinocerebellar ataxia type 6 (SCA6). Because silencing of the entire CACNA1A gene would result in the loss of the essential Cav2.1 channel, the IRES controlling α1ACT expression is an excellent target for selective silencing of α1ACT as a therapeutic intervention for SCA6. We performed a high-throughput screen of FDA-approved small molecules using a dual luciferase reporter system and identified ten hits able to selectively inhibit the IRES. We identified four main candidates that showed selective suppression of α1ACT relative to α1A in HEK cells expressing a native CACNA1A vector. We previously pursued another avenue of molecular intervention through miRNA silencing. We studied three human miRNAs (miRNA-711, -3191-5p, -4786) that would potentially bind to sequences within the CACNA1A IRES region, based on an miRNA prediction program. Only miRNA-3191-5p was found to selectively inhibit the translation of α1ACT in cells. We developed a hyperacute model of SCA6 in mice by injecting a pathogenic form of the IRES-mediated α1ACT (AAV9-α1ACTQ33). Finally, we tested the effectiveness of the miRNA therapy by co-expressing either control miRNA or miRNA-3191-5p and found that miRNA-3191-5p decreased the levels of α1ACTQ33 and prevented the hyperacute disease in mice. These studies provide the proof of principle that a therapy directed at selectively preventing α1ACT expression could be used to treat SCA6.

  13. Modeling cancer registration processes with an enhanced activity diagram.

    Science.gov (United States)

    Lyalin, D; Williams, W

    2005-01-01

    Adequate instruments are needed to reflect the complexity of routine cancer registry operations properly in a business model. The activity diagram is a key instrument of the Unified Modeling Language (UML) for the modeling of business processes. The authors aim to improve descriptions of processes in cancer registration, as well as in other public health domains, through the enhancements of an activity diagram notation within the standard semantics of UML. The authors introduced the practical approach to enhance a conventional UML activity diagram, complementing it with the following business process concepts: timeline, duration for individual activities, responsibilities for individual activities within swimlanes, and descriptive text. The authors used an enhanced activity diagram for modeling surveillance processes in the cancer registration domain. Specific example illustrates the use of an enhanced activity diagram to visualize a process of linking cancer registry records with external mortality files. Enhanced activity diagram allows for the addition of more business concepts to a single diagram and can improve descriptions of processes in cancer registration, as well as in other domains. Additional features of an enhanced activity diagram allow to advance the visualization of cancer registration processes. That, in turn, promotes the clarification of issues related to the process timeline, responsibilities for particular operations, and collaborations among process participants. Our first experiences in a cancer registry best practices development workshop setting support the usefulness of such an approach.

  14. Enhancing Activity for the Oxygen Evolution Reaction

    DEFF Research Database (Denmark)

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

    2014-01-01

    Electrochemical production of hydrogen, facilitated in electrolyzers, holds great promise for energy storage and solar fuel production. A bottleneck in the process is the catalysis of the oxygen evolution reaction, involving the transfer of four electrons. The challenge is that the binding energies...... 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...... that the oxygen evolution reaction overpotential decreases by 100–300 mV for manganese oxides and 100 mV for cobalt oxides....

  15. 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.

  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. 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.

  18. 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.

  19. Surface enhanced Raman optical activity (SEROA)

    DEFF Research Database (Denmark)

    Abdali, Salim; Blanch, E.W.

    2008-01-01

    Raman optical activity (ROA) directly monitors the stereochemistry of chiral molecules and is now an incisive probe of biomolecular structure. ROA spectra contain a wealth of information on tertiary folding, secondary structure and even the orientation of individual residues in proteins and nucleic...

  20. Enhancement of immunological activity after mild hyperthermia

    International Nuclear Information System (INIS)

    Noguchi, Kenichi; Hasegawa, Takeo; Takahashi, Tohru

    2002-01-01

    At present, hyperthermia is clinically very important as interdisciplinary therapeutic method, and studies are being performed on combined effects with surgical treatment, radiotherapy, chemotherapy and gene therapy for the treatment of malignant tumors. We evaluated the effects of hyperthermia under temperature of 42.5C and demonstrated that the activation of immunological response is increased and anti-tumor effect cabn be obtained in this studies. We used animals were C3H mice (male,7W) bearing SCC-VII tumor on femur skin. Then, the mice were divided to 10 mice in each group, and only femur region was immersed in warm water for thermal treatment. Also we measured the tumor growth, changes of blood cell fraction and NK cell activity. The results of the present study confirmed: (1) Anti-tumor effect can be given by thermal treatment at relatively mild temperature (mild temperature at 39C-42C); (2) The increase of neutrophils is dependent on the quantity of heat added; (3) Immunological response of monocytes and lymphocytes is associated with it; (4) Activity of the immunological potency as a whole such as activation of NK cells was also confirmed

  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. The unfolded protein response in melanocytes: activation in response to chemical stressors of the endoplasmic reticulum and tyrosinase misfolding.

    Science.gov (United States)

    Manga, Prashiela; Bis, Sabina; Knoll, Kristen; Perez, Beremis; Orlow, Seth J

    2010-10-01

    Accumulation of proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), comprising three signaling pathways initiated by Ire1, Perk and Atf6 respectively. Unfolded protein response activation was compared in chemically stressed murine wildtype melanocytes and mutant melanocytes that retain tyrosinase in the ER. Thapsigargin, an ER stressor, activated all pathways in wildtype melanocytes, triggering Caspase 12-mediated apoptosis at toxic doses. Albino melanocytes expressing mutant tyrosinase showed evidence of ER stress with increased Ire1 expression, but the downstream effector, Xbp1, was not activated even following thapsigargin treatment. Attenuation of Ire1 signaling was recapitulated in wildtype melanocytes treated with thapsigargin for 8 days, with diminished Xbp1 activation observed after 4 days. Atf6 was also activated in albino melanocytes, with no response to thapsigargin, while the Perk pathway was not activated and thapsigargin treatment elicited robust expression of the downstream effector CCAAT-enhancer-binding protein homologous protein. Thus, melanocytes adapt to ER stress by attenuating two UPR pathways.

  3. 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.

  4. Translational control of ceruloplasmin gene expression: Beyond the IRE

    Directory of Open Access Journals (Sweden)

    BARSANJIT MAZUMDER

    2006-01-01

    Full Text Available Translational control is a common regulatory mechanism for the expression of iron-related proteins. For example, three enzymes involved in erythrocyte development are regulated by three different control mechanisms: globin synthesis is modulated by heme-regulated translational inhibitor; erythroid 5-aminolevulinate synthase translation is inhibited by binding of the iron regulatory protein to the iron response element in the 5'-untranslated region (UTR; and 15-lipoxygenase is regulated by specific proteins binding to the 3'-UTR. Ceruloplasmin (Cp is a multi-functional, copper protein made primarily by the liver and by activated macrophages. Cp has important roles in iron homeostasis and in inflammation. Its role in iron metabolism was originally proposed because of its ferroxidase activity and because of its ability to stimulate iron loading into apo-transferrin and iron efflux from liver. We have shown that Cp mRNA is induced by interferon (IFN-γ in U937 monocytic cells, but synthesis of Cp protein is halted by translational silencing. The silencing mechanism requires binding of a cytosolic inhibitor complex, IFN-Gamma-Activated Inhibitor of Translation (GAIT, to a specific GAIT element in the Cp 3'-UTR. Here, we describe our studies that define and characterize the GAIT element and elucidate the specific trans-acting proteins that bind the GAIT element. Our experiments describe a new mechanism of translational control of an iron-related protein and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.

  5. Is enhanced physical activity possible using active videogames?

    Science.gov (United States)

    Our research indicated that 10– to 12-year-old children receiving two active Wii (TM)(Nintendo (R); 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 phys...

  6. Environmental Education Activities to Enhance Decision-Making.

    Science.gov (United States)

    Yambert, Paul A.; And Others

    This document contains a set of 10 activities that teachers may use with students (ages 10 to adult) to enhance environmental knowledge and environmentally responsible behavior. Sample worksheets are included when applicable. The activities focus on: renewable and nonrenewable resources; recycling; population growth; wildlife; recycling in a…

  7. Enhancement of internal ribosome entry site-mediated translation and replication of hepatitis C virus by PD98059

    International Nuclear Information System (INIS)

    Murata, Takayuki; Hijikata, Makoto; Shimotohno, Kunitada

    2005-01-01

    Translation initiation of hepatitis C virus (HCV) occurs in an internal ribosome entry site (IRES)-dependent manner. We found that HCV IRES-dependent protein synthesis is enhanced by PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) signaling pathway, while cellular cap-dependent translation was relatively unaffected by the compound. Treatment of cells with PD98059 allowed for robust HCV replication following cellular incubation with HCV-positive serum. Though the molecular mechanism underlying IRES enhancement remains elusive, PD98059 is a potent accelerator of HCV RNA replication

  8. Gramicidin D enhances the antibacterial activity of fluoride

    OpenAIRE

    Nelson, James W.; Zhou, Zhiyuan; Breaker, Ronald R.

    2014-01-01

    Fluoride is a toxic anion found in many natural environments. One of the major bacterial defenses against fluoride is the cell envelope, which limits passage of the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the permeability of bacterial membranes to fluoride should also enhance fluoride toxicity. In this study, we demonstrate that the pore-forming antibiotic gramicidin D increases fluoride uptake in B. subtilis and that the antibacterial activity of this compound...

  9. Gamma background radiation monitoring results (1990-95) in the environs around IRE OSCOM, Orissa using TLDs

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, N K; Bapat, V N; Nambi, K S.V. [Bhabha Atomic Research Centre, Mumbai (India). Environmental Assessment Div.; Saha, S C [Bhabha Atomic Research Centre, Bombay (India). Health Physics Div.

    1997-09-01

    Quarterly environmental radiation monitoring data using TLDs in about 28 locations in and around IRE-OSCOM covering a six year period 1990-95 is presented in the report. While the indoor radiation levels in beach areas having monazite deposits recorded annual average of 653{+-}230 mR/y, that in IRE residential colony gave a value of 240 {+-}30 mR/y. The radiation levels recorded inside the OSCOM plant are well within the limits prescribed for occupational radiation exposures. (author). 3 refs., 7 figs., 1 tab.

  10. Gamma background radiation monitoring results (1990-95) in the environs around IRE OSCOM, Orissa using TLDs

    International Nuclear Information System (INIS)

    Mehta, N.K.; Bapat, V.N.; Nambi, K.S.V.; Saha, S.C.

    1997-01-01

    Quarterly environmental radiation monitoring data using TLDs in about 28 locations in and around IRE-OSCOM covering a six year period 1990-95 is presented in the report. While the indoor radiation levels in beach areas having monazite deposits recorded annual average of 653±230 mR/y, that in IRE residential colony gave a value of 240 ±30 mR/y. The radiation levels recorded inside the OSCOM plant are well within the limits prescribed for occupational radiation exposures. (author). 3 refs., 7 figs., 1 tab

  11. Reduced IRE1α mediates apoptotic cell death by disrupting calcium homeostasis via the InsP3 receptor.

    Science.gov (United States)

    Son, S M; Byun, J; Roh, S-E; Kim, S J; Mook-Jung, I

    2014-04-17

    The endoplasmic reticulum (ER) is not only a home for folding and posttranslational modifications of secretory proteins but also a reservoir for intracellular Ca(2+). Perturbation of ER homeostasis contributes to the pathogenesis of various neurodegenerative diseases, such as Alzheimer's and Parkinson diseases. One key regulator that underlies cell survival and Ca(2+) homeostasis during ER stress responses is inositol-requiring enzyme 1α (IRE1α). Despite extensive studies on this ER membrane-associated protein, little is known about the molecular mechanisms by which excessive ER stress triggers cell death and Ca(2+) dysregulation via the IRE1α-dependent signaling pathway. In this study, we show that inactivation of IRE1α by RNA interference increases cytosolic Ca(2+) concentration in SH-SY5Y cells, leading to cell death. This dysregulation is caused by an accelerated ER-to-cytosolic efflux of Ca(2+) through the InsP3 receptor (InsP3R). The Ca(2+) efflux in IRE1α-deficient cells correlates with dissociation of the Ca(2+)-binding InsP3R inhibitor CIB1 and increased complex formation of CIB1 with the pro-apoptotic kinase ASK1, which otherwise remains inactivated in the IRE1α-TRAF2-ASK1 complex. The increased cytosolic concentration of Ca(2+) induces mitochondrial production of reactive oxygen species (ROS), in particular superoxide, resulting in severe mitochondrial abnormalities, such as fragmentation and depolarization of membrane potential. These Ca(2+) dysregulation-induced mitochondrial abnormalities and cell death in IRE1α-deficient cells can be blocked by depleting ROS or inhibiting Ca(2+) influx into the mitochondria. These results demonstrate the importance of IRE1α in Ca(2+) homeostasis and cell survival during ER stress and reveal a previously unknown Ca(2+)-mediated cell death signaling between the IRE1α-InsP3R pathway in the ER and the redox-dependent apoptotic pathway in the mitochondrion.

  12. Ficus Deltoidea Enhance Glucose Uptake Activity in Cultured Muscle Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Shafii Khamis; Amin Ismail; Muhajir Hamid

    2015-01-01

    Ficus deltoidea or locally known as Mas cotek is one of the common medicinal plants used in Malaysia. Our previous studies showed that this plant have blood glucose lowering effect. Glucose uptake into muscle and adipocytes cells is one of the known mechanisms of blood glucose lowering effect. This study was performed to evaluate the effect of Ficus deltoidea on glucose uptake activity into muscle cells. The cells were incubated with Ficus deltoidea extracts either alone or combination with insulin. Amount of glucose uptake by L6 myotubes was determined using glucose tracer, 2-deoxy-(1- 3 H 1 )-glucose. The results showed that Ficus deltoidea extracts at particular doses enhanced basal or insulin-mediated glucose uptake into muscle cells significantly. Hot aqueous extract enhanced glucose uptake at the low concentration (10 μg/ ml) whereas methanolic extract enhanced glucose uptake at low and high concentrations. Methanolic extract also mimicked insulin activity during enhancing glucose uptake into L^ muscle cells. Glucose uptake activity of Ficus deltoidea could be attributed by the phenolic compound presence in the plant. This study had shown that Ficus deltoidea has the ability to enhance glucose uptake into muscle cells which is partly contributed the antidiabetic activity of this plant. (author)

  13. Roles of different IRES-dependent FGF2 isoforms in the acquisition of the major aggressive features of human metastatic melanoma.

    Science.gov (United States)

    Andreucci, Elena; Bianchini, Francesca; Biagioni, Alessio; Del Rosso, Mario; Papucci, Laura; Schiavone, Nicola; Magnelli, Lucia

    2017-01-01

    Fibroblast growth factor 2 (FGF2) is involved in many physiological and pathological processes. Fgf2 deregulation contributes to the acquisition of malignant features of melanoma and other cancers. FGF2 is an alternative translation product expressed as five isoforms, a low-molecular-weight (18 KDa) and four high-molecular-weight (22, 22.5, 24, 34 KDa) isoforms, with different subcellular distributions. An internal ribosomal entry site (IRES) in its mRNA controls the translation of all the isoforms with the exception for the cap-dependent 34 KDa. The 18-KDa isoform has been extensively studied, while very few is known about the roles of high molecular weight isoforms. FGF2 is known to promote melanoma development and progression. To disclose the differential contribution of FGF2 isoforms in melanoma, we forced the expression of IRES-dependent low-molecular-weight (LMW, 18 KDa) and high-molecular-weight (HMW, 22, 22.5, 24 KDa) isoforms in a human metastatic melanoma cell line. This comparative study highlights that, while LMW isoform confers stem-like features to melanoma cells and promotes angiogenesis, HMW isoforms induce higher migratory ability and contribute to tumor perfusion by promoting vasculogenic mimicry (VM) when endothelial cell-driven angiogenesis is lacking. To conclude, FGF2 isoforms mainly behave in specific, antithetical manners, but can cooperate in different steps of tumor progression, providing melanoma cells with major malignant features. FGF2 is an alternative translation product expressed as different isoforms termed LMW and HMW. FGF2 is involved in melanoma development and progression. HMW FGF2 isoforms enhance in vitro motility of melanoma cells. LMW FGF2 confers stem-like features and increases in vivo metastasization. LMW FGF2 promotes angiogenesis while HMW FGF2 induces vasculogenic mimicry.

  14. Chimeric polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Science.gov (United States)

    Wogulis, Mark; Sweeney, Matthew; Heu, Tia

    2017-06-14

    The present invention relates to chimeric GH61 polypeptides having cellulolytic enhancing activity. The present invention also relates to polynucleotides encoding the chimeric GH61 polypeptides; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the chimeric GH61 polypeptides.

  15. 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 ...

  16. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Science.gov (United States)

    Maiyuran, Suchindra; Kramer, Randall; Harris, Paul

    2013-10-29

    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.

  17. Can aquatic worms enhance methane production from waste activated sludge?

    NARCIS (Netherlands)

    Serrano, Antonio; Hendrickx, Tim L.G.; Elissen, Hellen; Laarhoven, Bob; Buisman, Cees J.N.; Temmink, Hardy

    2016-01-01

    Although literature suggests that aquatic worms can help to enhance the methane production from excess activated sludge, clear evidence for this is missing. Therefore, anaerobic digestion tests were performed at 20 and at 30 °C with sludge from a high-loaded membrane bioreactor, the aquatic worm

  18. Insight into the recognition, binding, and reactivity of catalytic metallodrugs targeting stem loop IIb of hepatitis C IRES RNA.

    Science.gov (United States)

    Bradford, Seth S; Ross, Martin James; Fidai, Insiya; Cowan, James A

    2014-06-01

    The complex Cu-GGHYrFK-amide (1-Cu) was previously reported as a novel metallotherapeutic that catalytically inactivates stem loop IIb (SLIIb) of the hepatitis C virus (HCV) internal ribosomal entry site (IRES) RNA and demonstrates significant antiviral activity in a cellular HCV replicon assay. Herein we describe additional studies focused on understanding the cleavage mechanism as well as the relationship of catalyst configuration to structural recognition and site-selective cleavage of the structured RNA motif. These are advanced by use of a combination of MALDI-TOF mass spectrometry, melting temperature determinations, and computational analysis to develop a structural model for binding and reactivity toward SLIIb of the IRES RNA. In addition, the binding, reactivity, and structural chemistry of the all-D-amino acid form of this metallopeptide, complex 2-Cu, are reported and compared with those of complex 1-Cu. In vitro RNA binding and cleavage assays for complex 2-Cu show a KD value of 76 ± 3 nM, and Michaelis-Menten parameters of kcat =0.14 ± 0.01 min(-1) and KM =7.9 ± 1.2 μM, with a turnover number exceeding 40. In a luciferase-based cellular replicon assay Cu-GGhyrfk-amide shows activity similar to that of the 1-Cu parent peptide, with an IC50 value of 1.9 ± 0.4 μM and cytotoxicity exceeding 100 μM. RT-PCR experiments confirm a significant decrease in HCV RNA levels in replicon assays for up to nine days when treated with complex 1-Cu in three-day dosing increments. This study shows the influence that the α-carbon stereocenter has for this new class of compounds, while detailed mass spectrometry and computational analyses provide new insight into the mechanisms of recognition, binding, and reactivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Ire1 mediated mRNA splicing in a C-terminus deletion mutant of Drosophila Xbp1.

    Directory of Open Access Journals (Sweden)

    Dina S Coelho

    Full Text Available The Unfolded Protein Response is a homeostatic mechanism that permits eukaryotic cells to cope with Endoplasmic Reticulum (ER stress caused by excessive accumulation of misfolded proteins in the ER lumen. The more conserved branch of the UPR relies on an ER transmembrane enzyme, Ire1, which, upon ER stress, promotes the unconventional splicing of a small intron from the mRNA encoding the transcription factor Xbp1. In mammals, two specific regions (the hydrophobic region 2--HR2--and the C-terminal translational pausing site present in the Xbp1unspliced protein mediate the recruitment of the Xbp1 mRNA-ribosome-nascent chain complex to the ER membrane, so that Xbp1 mRNA can be spliced by Ire1. Here, we generated a Drosophila Xbp1 deletion mutant (Excision101 lacking both HR2 and C-terminal region, but not the Ire1 splicing site. We show that Ire1-dependent splicing of Xbp1 mRNA is reduced, but not abolished in Excision101. Our results suggest the existence of additional mechanisms for ER membrane targeting of Xbp1 mRNA that are independent of the C-terminal domain of Drosophila Xbp1unspliced.

  20. Generation of Oxtr cDNA(HA)-Ires-Cre Mice for Gene Expression in an Oxytocin Receptor Specific Manner.

    Science.gov (United States)

    Hidema, Shizu; Fukuda, Tomokazu; Hiraoka, Yuichi; Mizukami, Hiroaki; Hayashi, Ryotaro; Otsuka, Ayano; Suzuki, Shingo; Miyazaki, Shinji; Nishimori, Katsuhiko

    2016-05-01

    The neurohypophysial hormone oxytocin (OXT) and its receptor (OXTR) have critical roles in the regulation of pro-social behaviors, including social recognition, pair bonding, parental behavior, and stress-related responses. Supporting this hypothesis, a portion of patients suffering from autism spectrum disorder have mutations, such as single nucleotide polymorphisms, or epigenetic modifications in their OXTR gene. We previously reported that OXTR-deficient mice exhibit pervasive social deficits, indicating the critical role of OXTR in social behaviors. In the present study, we generated Oxtr cDNA(HA)-Ires-Cre knock-in mice, expressing both OXTR and Cre recombinase under the control of the endogenous Oxtr promoter. Knock-in cassette of Oxtr cDNA(HA)-Ires-Cre consisted of Oxtr cDNA tagged with the hemagglutinin epitope at the 3' end (Oxtr cDNA(HA)), internal ribosomal entry site (Ires), and Cre. Cre was expressed in the uterus, mammary gland, kidney, and brain of Oxtr cDNA(HA)-Ires-Cre knock-in mice. Furthermore, the distribution of Cre in the brain was similar to that observed in Oxtr-Venus fluorescent protein expressing mice (Oxtr-Venus), another animal model previously generated by our group. Social behavior of Oxtr cDNA(HA)-Ires-Cre knock-in mice was similar to that of wild-type animals. We demonstrated that this construct is expressed in OXTR-expressing neurons specifically after an infection with the recombinant adeno-associated virus carrying the flip-excision switch vector. Using this system, we showed the transport of the wheat-germ agglutinin tracing molecule from the OXTR-expressing neurons to the innervated neurons in knock-in mice. This study might contribute to the monosynaptic analysis of neuronal circuits and to the optogenetic analysis of neurons expressing OXTR. © 2015 Wiley Periodicals, Inc.

  1. Irreversible Electroporation (IRE) Fails to Demonstrate Efficacy in a Prospective Multicenter Phase II Trial on Lung Malignancies: The ALICE Trial

    Energy Technology Data Exchange (ETDEWEB)

    Ricke, Jens, E-mail: jens.ricke@med.ovgu.de; Jürgens, Julian H. W., E-mail: julian.juergens@med.ovgu.de [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany); Deschamps, Frederic; Tselikas, Lambros [Institut de Cancérologie Gustave Roussy, Department of Image Guided Therapy (France); Uhde, Katja; Kosiek, Ortrud [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany); Baere, Thierry De [Institut de Cancérologie Gustave Roussy, Department of Image Guided Therapy (France)

    2015-04-15

    PurposeTo assess safety and efficacy of irreversible electroporation (IRE) of lung malignancies.Materials and MethodsPatients with primary and secondary lung malignancies and preserved lung function were included in this prospective single arm trial. Primary and secondary endpoints were safety and efficacy. Recruitment goal was 36 subjects in 2 centers. Patients underwent IRE under general anesthesia with probe placement performed in Fluoroscopy-CT. The IRE system employed was NanoKnife{sup ®} (Angiodynamics). System settings for the ablation procedure followed the manufacturer’s recommendations. The Mann–Whitney U test was used to evaluate the correlation of nine technical parameters with local tumor control. Median follow up was 12 months.ResultsThe expected efficacy was not met at interim analysis and the trial was stopped prematurely after inclusion of 23 patients (13/10 between both centers). The dominant tumor entity was colorectal (n = 13). The median tumor diameter was 16 mm (8–27 mm). Pneumothoraces were observed in 11 of 23 patients with chest tubes required in 8 (35 %). Frequently observed alveolar hemorrhage never led to significant hemoptysis. 14/23 showed progressive disease (61 %). Stable disease was found in 1 (4 %), partial remission in 1 (4 %) and complete remission in 7 (30 %) patients. The relative increase of the current during ablation was significantly higher in the group treated successfully as compared to the group presenting local recurrence (p < 0.05). Needle tract seeding was found in three cases (13 %).ConclusionsIRE is not effective for the treatment of lung malignancies. We hypothesize that the energy deposition with current IRE probes is highly sensitive to air exposure.

  2. IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico

    Directory of Open Access Journals (Sweden)

    Hong Jun-Jie

    2009-05-01

    Full Text Available Abstract Background Internal ribosomal entry sites (IRESs provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. Results We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. Conclusion IRSS is freely available at this website http://140.135.61.9/ires/. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.

  3. Gramicidin D enhances the antibacterial activity of fluoride.

    Science.gov (United States)

    Nelson, James W; Zhou, Zhiyuan; Breaker, Ronald R

    2014-07-01

    Fluoride is a toxic anion found in many natural environments. One of the major bacterial defenses against fluoride is the cell envelope, which limits passage of the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the permeability of bacterial membranes to fluoride should also enhance fluoride toxicity. In this study, we demonstrate that the pore-forming antibiotic gramicidin D increases fluoride uptake in Bacillus subtilis and that the antibacterial activity of this compound is potentiated by fluoride. Polymyxin B, another membrane-targeting antibiotic with a different mechanism of action, shows no such improvement. These results, along with previous findings, indicate that certain compounds that destabilize bacterial cell envelopes can enhance the toxicity of fluoride. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. "A Separation Theorem of Active Management and Synthetic Enhanced Active Strategies"(in Japanese)

    OpenAIRE

    Takao Kobayashi; Seiji Minami

    2008-01-01

    We propose a Separation Theorem of Active Management. It asserts that in the so-called Enhanced Active Portfolio framework the efficient frontier is linear in the active return/active risk space, and one can separate the determination of optimal active portfolio weights from the determination of optimal leverage ratio. The risk preference of investors does not play any role in the former decision. The theorem holds under a fairly general set of conditions on portfolio restrictions. As such it...

  5. 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.

  6. Enhanced supercapacitance of activated vertical graphene nanosheets in hybrid electrolyte

    Science.gov (United States)

    Ghosh, Subrata; Sahoo, Gopinath; Polaki, S. R.; Krishna, Nanda Gopala; Kamruddin, M.; Mathews, Tom

    2017-12-01

    Supercapacitors are becoming the workhorse for emerging energy storage applications due to their higher power density and superior cycle life compared to conventional batteries. The performance of supercapacitors depends on the electrode material, type of electrolyte, and interaction between them. Owing to the beneficial interconnected porous structure with multiple conducting channels, vertical graphene nanosheets (VGN) have proved to be leading supercapacitor electrode materials. Herein, we demonstrate a novel approach based on the combination of surface activation and a new organo-aqueous hybrid electrolyte, tetraethylammonium tetrafluoroborate in H2SO4, to achieve significant enhancement in supercapacitor performance of VGN. As-synthesized VGN exhibits an excellent supercapacitance of 0.64 mF/cm2 in H2SO4. However, identification of a novel electrolyte for performance enhancement is the subject of current research. The present manuscript demonstrates the potential of the hybrid electrolyte in enhancing the areal capacitance (1.99 mF/cm2) with excellent retention (only 5.4% loss after 5000 cycles) and Coulombic efficiency (93.1%). In addition, a five-fold enhancement in the capacitance of VGNs (0.64 to 3.31 mF/cm2) with a reduced internal resistance is achieved by the combination of KOH activation and the hybrid electrolyte.

  7. Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling

    Science.gov (United States)

    Urbano, Francisco J.; Leznik, Elena; Llinás, Rodolfo R.

    2007-01-01

    Modafinil (Provigil, Modiodal), an antinarcoleptic and mood-enhancing drug, is shown here to sharpen thalamocortical activity and to increase electrical coupling between cortical interneurons and between nerve cells in the inferior olivary nucleus. After irreversible pharmacological block of connexin permeability (i.e., by using either 18β-glycyrrhetinic derivatives or mefloquine), modafinil restored electrotonic coupling within 30 min. It was further established that this restoration is implemented through a Ca2+/calmodulin protein kinase II-dependent step. PMID:17640897

  8. Enhanced natural radiation exposure enhanced by human activity: the largest contributor to the Chinese population dose

    International Nuclear Information System (INIS)

    Pan Ziqiang; Liu Yanyang

    2011-01-01

    For the radiation exposure caused by human activities, the enhanced natural radiation exposure is the largest contributor to Chinese population dose. This problem has attracted social attention in recent years. Efforts have been made in several fields, such as radon indoors and in workplace, environmental problems associated with NORMs, occupational radiation hazards of non-uranium mine, and radiation dose evaluation for energy chain, but there are still many problems to be solved. In order to protect the health of workers and the public, while ensuring industrial production and economic development, it is also necessary to continue to strengthen research in all aspects above mentioned, and gradually promote the control of natural radiation exposure enhanced by human activities. (authors)

  9. Intelligent Architecture for Enhanced Observability for Active Distribution System

    DEFF Research Database (Denmark)

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

    2017-01-01

    There is a rapid increase of renewable energy resources (RE) and demand response resources (DRR) in the distribution networks. This is challenging for the reliable and stable operation of the grid. So, to ensure secure, optimized and economical operation in such active distribution grids they need...... 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...

  10. Mechanisms of morphine enhancement of spontaneous seizure activity.

    Science.gov (United States)

    Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

    2007-12-01

    High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

  11. Psychosocial Practices that Enhance Cognitive Activity in Dementia

    Directory of Open Access Journals (Sweden)

    Neslihan Lok

    2014-09-01

    Full Text Available The daily lives of individuals with dementia, cognitive aspects need to be strengthened in order to maintain the quality. For this reason, dementia, cognitive, psycho-social applications there is a need to increase activity. Dementia drug treatment interventions used as an aid to increase cognitive activity. These interventions, behavior, emotion, perception and stimulation-oriented approaches can be classified into four groups. Dementia cognitive enhancer activity and an older group, this intervention and dissemination practices for selecting the most appropriate method to be applied. All psychosocial practices to increase cognitive activity psychiatrist, psychiatric nurse specialists, psychologists, social workers, occupational therapists can with the condition to study the relevant therapy. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 210-216

  12. Irreversible electroporation ablation (IRE of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated.

    Directory of Open Access Journals (Sweden)

    Prejesh Philips

    Full Text Available BACKGROUND: Irreversible electroporation (IRE is a novel technology that uses peri-target discrete probes to deliver high-voltage localized electric current to induce cell death without thermal-induced coagulative necrosis. "Learnability" and consistently effective results by novice practitioners is essential for determining acceptance of novel techniques. This multi-center prospectively-collected database study evaluates the learning curve of IRE. METHODS: Analysis of 150 consecutive patients over 7 institutions from 9/2010-7/2012 was performed with patients treated divided into 3 groups A (1(st 50 patients treated, B (2(nd 50 and C (3(rd 50 patients treated chronologically and analyzed for outcomes. RESULTS: A total of 167 IRE procedures were performed, with a majority being liver(39.5% and pancreatic(35.5% lesions. The three groups were similar with respect to co-morbidities and demographics. Group C had larger lesions (3.9 vs 3 cm,p=0.001, more numerous lesions (3.2 vs 2.2,p=0.07, more vascular invasion(p=0.001, underwent more associated procedures(p=0.001 and had longer operative times(p<0.001. Despite this, they had similar complication and high-grade complication rates(p=0.24. Attributable morbidity rate was 13.3%(total 29.3% and high-grade complications were seen in 4.19%(total 12.6%. Pancreatic lesions(p=0.001 and laparotomy(p=0.001 were associated with complications. CONCLUSION: The review represents that single largest review of IRE soft tissue ablation demonstrating initial patient selection and safety. Over time, complex treatments of larger lesions and lesions with greater vascular involvement were performed without a significant increase in adverse effects or impact on local relapse free survival. This evolution demonstrates the safety profile of IRE and speed of graduation to more complex lesions, which was greater than 5 cases by institution. IRE is a safe and effective alternative to conventional ablation with a demonstrable

  13. Thrombopoietin contributes to enhanced platelet activation in cigarette smokers.

    Science.gov (United States)

    Lupia, Enrico; Bosco, Ornella; Goffi, Alberto; Poletto, Cesare; Locatelli, Stefania; Spatola, Tiziana; Cuccurullo, Alessandra; Montrucchio, Giuseppe

    2010-05-01

    Thrombopoietin (TPO) is a humoral growth factor that primes platelet activation in response to several agonists. We recently showed that TPO enhances platelet activation in unstable angina and sepsis. Aim of this study was to investigate the role of TPO in platelet function abnormalities described in cigarette smokers. In a case-control study we enrolled 20 healthy cigarette smokers and 20 nonsmokers, and measured TPO and C-reactive protein (CRP), as well as platelet-leukocyte binding and P-selectin expression. In vitro we evaluated the priming activity of smoker or control plasma on platelet activation, and the role of TPO in this effect. We then studied the effects of acute smoking and smoking cessation on TPO levels and platelet activation indices. Chronic cigarette smokers had higher circulating TPO levels than nonsmoking controls, as well as increased platelet-leukocyte binding, P-selectin expression, and CRP levels. Serum cotinine concentrations correlated with TPO concentrations, platelet-monocyte aggregates and P-selectin expression. In addition, TPO levels significantly correlated with ex vivo platelet-monocyte aggregation and P-selectin expression. In vitro, the plasma from cigarette smokers, but not from nonsmoking controls, primed platelet-monocyte binding, which was reduced when an inhibitor of TPO was used. We also found that acute smoking slightly increased TPO levels, but did not affect platelet-leukocyte binding, whereas smoking cessation induced a significant decrease in both circulating TPO and platelet-leukocyte aggregation. Elevated TPO contributes to enhance platelet activation and platelet-monocyte cross-talk in cigarette smokers. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  14. The IRP/IRE system in vivo: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Nicole eWilkinson

    2014-07-01

    Full Text Available Iron regulatory proteins 1 and 2 (IRP1 and IRP2 post-transcriptionally control the expression of several mRNAs encoding proteins of iron, oxygen and energy metabolism. The mechanism involves their binding to iron responsive elements (IREs in the untranslated regions of target mRNAs, thereby controlling mRNA translation or stability. Whereas IRP2 functions solely as an RNA-binding protein, IRP1 operates as either an RNA-binding protein or a cytosolic aconitase. Early experiments in cultured cells established a crucial role of IRPs in regulation of cellular iron metabolism. More recently, studies in mouse models with global or localized Irp1 and/or Irp2 deficiencies uncovered new physiological functions of IRPs in the context of systemic iron homeostasis. Thus, IRP1 emerged as a key regulator of erythropoiesis and iron absorption by controlling hypoxia inducible factor 2α (HIF2α mRNA translation, while IRP2 appears to dominate the control of iron uptake and heme biosynthesis in erythroid progenitor cells by regulating the expression of transferrin receptor 1 (TfR1 and 5-aminolevulinic acid synthase 2 (ALAS2 mRNAs, respectively. Targeted disruption of either Irp1 or Irp2 in mice is associated with distinct phenotypic abnormalities. Thus, Irp1-/- mice develop polycythemia and pulmonary hypertension, while Irp2-/- mice present with microcytic anemia, iron overload in the intestine and the liver, and neurologic defects. Combined disruption of both Irp1 and Irp2 is incombatible with life and leads to early embryonic lethality. Mice with intestinal- or liver-specific disruption of both Irps are viable at birth but die later on due to malabsorption or liver failure, respectively. Adult mice lacking both Irps in the intestine exhibit a profound defect in dietary iron absorption due to a mucosal block that is caused by the de-repression of ferritin mRNA translation. Herein, we discuss the physiological function of the IRE/IRP regulatory system.

  15. First Delayed Resection Findings After Irreversible Electroporation (IRE) of Human Localised Renal Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Trial

    Energy Technology Data Exchange (ETDEWEB)

    Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Ricke, Jens, E-mail: jens.Ricke@med.ovgu.de; Pech, Maciej, E-mail: macej.pech@med.ovgu.de; Fischbach, Frank, E-mail: frank.fischbach@med.ovgu.de; Jürgens, Julian, E-mail: julian.juergens@med.ovgu.de [University of Magdeburg, Department of Radiology (Germany); Siedentopf, Sandra, E-mail: sandra.siedentopf@med.ovgu.de; Roessner, Albert, E-mail: albert.roessner@med.ovgu.de [University of Magdeburg, Institute of Pathology (Germany); Porsch, Markus, E-mail: markus.porsch@med.ovgu.de; Baumunk, Daniel, E-mail: daniel.baumunk@med.ovgu.de; Schostak, Martin, E-mail: martin.schostak@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Köllermann, Jens, E-mail: jens.koellermann@sana.de [Sana Klinikum Offenbach Am Main, Institute of Pathology (Germany); Liehr, Uwe-Bernd, E-mail: uwe-bernd.liehr@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany)

    2016-02-15

    IntroductionIt is postulated that focal IRE affords complete ablation of soft-tissue tumours while protecting the healthy peritumoral tissue. Therefore, IRE may be an interesting option for minimally invasive, kidney-tissue-sparing, non-thermal ablation of renal tumours.AimWith this current pilot study (“IRENE trial”), we present the first detailed histopathological data of IRE of human RCC followed by delayed tumour resection. The aim of this interim analysis of the first three patients was to investigate the ablation efficiency of percutaneous image-guided focal IRE in RCC, to assess whether a complete ablation of T1a RCC and tissue preservation with the NanoKnife system is possible and to decide whether the ablation parameters need to be altered.MethodsFollowing resection 4 weeks after percutaneous IRE, the success of ablation and detailed histopathological description were used to check the ablation parameters.ResultsThe IRE led to a high degree of damage to the renal tumours (1 central, 2 peripheral; size range 15–17 mm). The postulated homogeneous, isomorphic damage was only partly confirmed. We found a zonal structuring of the ablation zone, negative margins and, enclosed within the ablation zone, very small tumour residues of unclear malignancy.ConclusionAccording to these initial, preliminary study results of the first three renal cases, a new zonal distribution of IRE damage was described and the curative intended, renal saving focal ablation of localised RCC below <3 cm by percutaneous IRE by the NanoKnife system appears to be possible, but needs further, systematic evaluation for this treatment method and treatment protocol.

  16. Chicago section activities to enhance public acceptance of nuclear power

    International Nuclear Information System (INIS)

    Snyder, T.L.; Keffer, J.W.

    1992-01-01

    The Chicago section of the American Nuclear Society (ANS) is an active organization with ∼450 members. The local section territory encompasses northern Illinois and includes in its territory all six of Commonwealth Edison Company's (CECo's) nuclear generating stations as well as Argonne National Laboratory (ANL). Included in the territory are several large engineering firms - ABB Impell, Bechtel, Fluor Daniel, and Sargent ampersand Lundy. The national headquarters of the ANS is also located within the local section boundaries. All these organizations are represented in the local section membership and provide access to abundant technical resources that can be used to enhance public acceptance of nuclear power. An important attribute of any local section that enables it to perform interesting programs and be active in the community is its financial resources. The Chicago section has a strong financial base because of its ability to raise funds by participating in and sponsoring ANS topical and other meetings. For instance, in 1991, they sponsored and were actively involved in the Emergency Preparedness Topical Meeting held in Chicago. In 1992, they were actively involved in sponsoring the organizational activities of the ANS/ENS International Meeting, which will celebrate the 50th year of nuclear fission. The financial and technical resources of the Chicago section continue to contribute to a successful program of public education and public acceptance activities regarding the nuclear industry

  17. Enhancement of DNA polymerase activity in potato tuber slices

    International Nuclear Information System (INIS)

    Watanabe, Akira; Imaseki, Hidemasa

    1977-01-01

    DNA polymerase was extracted from potato (Soleum tuberosum L.) tuber discs and the temporal correlation of its activity change to DNA synthesis in vivo was examined during aging of the discs. Most of the DNA polymerase was recovered as a bound form in the 18,000 x g precipitate. Reaction with the bound-form enzyme was dependent on the presence of four deoxynucleoside triphosphates, Mg 2+ , and a template. ''Activated'' DNA and heat-denatured DNA, but not native DNA, were utilized as templates. The polymerase activity was sensitive to SH reagents. Fresh discs, which do not synthesize DNA in vivo, contained a significant amount of DNA polymerase and its activity increased linearly with time until 48 hr after slicing and became four times that of fresh discs after 72 hr, whereas the activity of DNA synthesis in vivo increased with time and decreased after reaching a maximum at 30 hr. Cycloheximide inhibited the enhancement of polymerase activity. DNA polymerase from aged and fresh discs had identical requirements for deoxynucleotides and a template in their reactions, sensitivity to SH reagent, and affinity to thymidine triphosphate. (auth.)

  18. Resonance Raman Optical Activity and Surface Enhanced Resonance Raman Optical Activity analysis of Cytochrome C

    DEFF Research Database (Denmark)

    Johannessen, Christian; Abdali, Salim; White, Peter C.

    2007-01-01

    High quality Resonance Raman (RR) and resonance Raman Optical Activity (ROA) spectra of cytochrome c were obtained in order to perform full assignment of spectral features of the resonance ROA spectrum. The resonance ROA spectrum of cytochrome c revealed a distinct spectral signature pattern due...... to resonance enhanced skeletal porphyrin vibrations, more pronounced than any contribution from the protein back-bone. Combining the intrinsic resonance enhancement of cytochrome c with surface plasmon enhancement by colloidal silver particles, the Surface Enhanced Resonance Raman Scattering (SERRS) and Chiral...... Enhanced Raman Spectroscopy (ChERS) spectra of the protein were successfully obtained at very low concentration (as low as 1 µM). The assignment of spectral features was based on the information obtained from the RR and resonance ROA spectra. Excellent agreement between RR and SERRS spectra is reported...

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Dor Vadas

    2017-09-01

    Full Text Available Background: The Brain uses 20% of the total oxygen supply consumed by the entire body. Even though, <10% of the brain is active at any given time, it utilizes almost all the oxygen delivered. In order to perform complex tasks or more than one task (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 < 0.001 for both. 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.

  1. Increased expression of IRE1α and stress-related signal transduction proteins in ischemia-reperfusion injured retina

    Directory of Open Access Journals (Sweden)

    Natsuyo Hata

    2008-08-01

    Full Text Available Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1, SAPK/ERK kinase 1 (SEK1 and c-Jun N-terminal kinase (JNK is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

  2. 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.

  3. Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1α.

    Science.gov (United States)

    Sepulveda, Denisse; Rojas-Rivera, Diego; Rodríguez, Diego A; Groenendyk, Jody; Köhler, Andres; Lebeaupin, Cynthia; Ito, Shinya; Urra, Hery; Carreras-Sureda, Amado; Hazari, Younis; Vasseur-Cognet, Mireille; Ali, Maruf M U; Chevet, Eric; Campos, Gisela; Godoy, Patricio; Vaisar, Tomas; Bailly-Maitre, Béatrice; Nagata, Kazuhiro; Michalak, Marek; Sierralta, Jimena; Hetz, Claudio

    2018-01-18

    Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization. The regulation of IRE1α signaling by Hsp47 is evolutionarily conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency sensitized cells and animals to experimental ER stress, revealing the significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47 adjusts IRE1α signaling by fine-tuning the threshold to engage an adaptive UPR. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Psychopaths show enhanced amygdala activation during fear conditioning

    Directory of Open Access Journals (Sweden)

    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.

  5. Enhancement of activated sludge disintegration and dewaterability by Fenton process

    Science.gov (United States)

    Heng, G. C.; Isa, M. H.

    2016-06-01

    Municipal and industrial wastewater treatment plants produce large amounts of sludge. This excess sludge is an inevitable drawback inherent to the activated sludge process. In this study, the waste activated sludge was obtained from the campus wastewater treatment plant at Universiti Teknologi PETRONAS (UTP), Malaysia. Fenton pretreatment was optimized by using the response surface methodology (RSM) to study the effects of three operating conditions including the dosage of H2O2 (g H2O2/kg TS), the molar ratio of H2O2/Fe2+ and reaction time. The optimum operating variables to achieve MLVSS removal 65%, CST reduction 28%, sCOD 11000 mg/L and EPS 500 mg/L were: 1000 g H2O2/kg TS, H2O2/Fe2+ molar ratio 70 and reaction time 45 min. Fenton process was proved to be able to enhance the sludge disintegration and dewaterability.

  6. MWCNT/CdS hybrid nanocomposite for enhanced photocatalytic activity

    International Nuclear Information System (INIS)

    Chaudhary, Deepti; Khare, Neeraj; Vankar, V. D.

    2016-01-01

    Multi-walled carbon nanotubes (MWCNT)/CdS hybrid nanocomposite were synthesized by one step hydrothermal method. MWCNTs were used as a substrate for the growth of CdS nanoparticles. MWCNT/CdS nanocomposite and pure CdS were characterized by XRD, TEM, UV-vis and photoluminescence spectroscopy. HRTEM study confirms the intimate contact of CdS with MWCNT. The photocatalytic activity of nanocomposite was studied for the degradation of methylene blue dye under UV irradiation. The enhanced photocatalytic activity of MWCNT/CdS nanocomposite as compared to pure CdS has been attributed to reduced recombination of photogenerated charge carriers due to interfacial electron transfer from CdS to MWCNT.

  7. Somatostatin-IRES-Cre Mice: Between Knockout and Wild-Type?

    Science.gov (United States)

    Viollet, Cécile; Simon, Axelle; Tolle, Virginie; Labarthe, Alexandra; Grouselle, Dominique; Loe-Mie, Yann; Simonneau, Michel; Martel, Guillaume; Epelbaum, Jacques

    2017-01-01

    The neuropeptide somatostatin (SOM) is widely expressed in rodent brain and somatostatin-IRES-Cre (SOM-cre) mouse strains are increasingly used to unravel the physiology of SOM-containing neurons. However, while knock-in targeting strategy greatly improves Cre-Lox system accuracy, recent reports have shown that genomic insertion of Cre construct per se can markedly affect physiological function. We show that Cre transgene insertion into the 3'UTR of the somatostatin gene leads to the selective and massive depletion of endogenous SOM in all tested brain regions. It also strongly impacts SOM-related neuroendocrine responses in a similar manner to what has been reported for SST KO mice: increased corticosterone levels after 30-min restraint stress, decreased amplitude and regularity of ultradian growth hormone secretory patterns accompanied by changes in sexually dimorphic liver gene expression ( serpina1, Cyp2b9, Cyp2a4, Cyp2d9, and Cyp7b1 ). In addition to demonstrating the need for examination of the consequences of Cre transgenesis, these results also reveal how this SOM-cre strain may be a useful tool in studying the functional consequences of moderate to low SOM levels as reported in neurological and psychiatric disorders.

  8. Undergraduate Student Involvement in International Research - The IRES Program at MAX-lab, Sweden

    Science.gov (United States)

    Briscoe, William; O'Rielly, Grant; Fissum, Kevin

    2014-03-01

    Undergraduate students associated with The George Washington University and UMass Dartmouth have had the opportunity to participate in nuclear physics research as a part of the PIONS@MAXLAB Collaboration performing experiments at MAX-lab at Lund University in Sweden. This project has supported thirteen undergraduate students during 2009 - 2011. The student researchers are involved with all aspects of the experiments performed at the laboratory, from set-up to analysis and presentation at national conferences. These experiments investigate the dynamics responsible for the internal structure of the nucleon through the study of pion photoproduction off the nucleon and high-energy Compton scattering. Along with the US and Swedish project leaders, members of the collaboration (from four different countries) have contributed to the training and mentoring of these students. This program provides students with international research experiences that prepare them to operate successfully in a global environment and encourages them to stay in areas of science, technology, engineering and math (STEM) that are crucial for our modern, technology-dependent society. We will present the history, goals and outcomes in both physics results and student success that have come from this program. This work supported by NSF OISE/IRES award 0553467.

  9. Gamma irradiation enhances biological activities of mulberry leaf extract

    International Nuclear Information System (INIS)

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

    2017-01-01

    The purpose of this study was to investigate the influence of irradiation on the anti-oxidative, anti-inflammatory and whitening effects of mulberry leaf extract. This was done by comparing the phenolic contents; 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effects; 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) radical scavenging effects; in vitro tyrosinase inhibitory effects and the production of IL-6, TNF-α, PGE 2 , and NO in lipopolysaccharide-stimulated RAW264.7 macrophages and the production of IL-6 and TNF-α in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 cells, respectively. The results showed that irradiated mulberry leaf extract possesses more anti-oxidant, anti-inflammatory, and tyrosinase inhibitory activities than their non-irradiated counterpart, probably due to increase in phenolic contents induced by gamma irradiation at dose of 10kGy. This research stresses on the importance of irradiation in functional foods. - Highlights: • Gamma-irradiated mulberry leaf extract enhanced in vitro antioxidant activities. • Gamma-irradiated mulberry leaf extract enhanced in vitro tyrosinase inhibitory effects. • Gamma-irradiated mulberry leaf extract treatment reduced the production of IL-6, TNF-α, PGE 2 , and NO.

  10. 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.

  11. 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.

  12. 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.

  13. PERSPECTIVE: Electrical activity enhances neuronal survival and regeneration

    Science.gov (United States)

    Corredor, Raul G.; Goldberg, Jeffrey L.

    2009-10-01

    The failure of regeneration in the central nervous system (CNS) remains an enormous scientific and clinical challenge. After injury or in degenerative diseases, neurons in the adult mammalian CNS fail to regrow their axons and reconnect with their normal targets, and furthermore the neurons frequently die and are not normally replaced. While significant progress has been made in understanding the molecular basis for this lack of regenerative ability, a second approach has gained momentum: replacing lost neurons or lost connections with artificial electrical circuits that interface with the nervous system. In the visual system, gene therapy-based 'optogenetics' prostheses represent a competing technology. Now, the two approaches are converging, as recent data suggest that electrical activity itself, via the molecular signaling pathways such activity stimulates, is sufficient to induce neuronal survival and regeneration, particularly in retinal ganglion cells. Here, we review these data, discuss the effects of electrical activity on neurons' molecular signaling pathways and propose specific mechanisms by which exogenous electrical activity may be acting to enhance survival and regeneration.

  14. Reliability and responsiveness of dynamic contrast-enhanced magnetic resonance imaging in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Axelsen, M.B.; Poggenborg, R.P.; Stoltenberg, M.

    2013-01-01

    intraarticular injection with 80 mg methylprednisolone. Using semi-automated image processing software, DCE-MRI parameters, including the initial rate of enhancement (IRE) and maximal enhancement (ME), were generated for three regions of interest (ROIs): ‘Whole slice’, ‘Quick ROI’, and ‘Precise ROI......Objectives: To investigate the responsiveness to treatment and the reliability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rheumatoid arthritis (RA) knee joints. Methods: DCE-MRI was performed in 12 clinically active RA knee joints before and 1, 7, 30, and 180 days after......’. The smallest detectable difference (SDD), the smallest detectable change (SDC), and intra- and inter-reader intraclass correlation coefficients (ICCs) were used to assess the reliability of DCE-MRI. Responsiveness to treatment was assessed by the standardized response mean (SRM). Results: In all patients...

  15. Enhanced multimaterial 4D printing with active hinges

    Science.gov (United States)

    Akbari, Saeed; Hosein Sakhaei, Amir; Kowsari, Kavin; Yang, Bill; Serjouei, Ahmad; Yuanfang, Zhang; Ge, Qi

    2018-06-01

    Despite great progress in four-dimensional (4D) printing, i.e. three-dimensional (3D) printing of active (stimuli-responsive) materials, the relatively low actuation force of the 4D printed structures often impedes their engineering applications. In this study, we use multimaterial inkjet 3D printing technology to fabricate shape memory structures, including a morphing wing flap and a deployable structure, which consist of active and flexible hinges joining rigid (non-active) parts. The active hinges, printed from a shape memory polymer (SMP), lock the structure into a second temporary shape during a thermomechanical programming process, while the flexible hinges, printed from an elastomer, effectively increase the actuation force and the load-bearing capacity of the printed structure as reflected in the recovery ratio. A broad range of mechanical properties such as modulus and failure strain can be achieved for both active and flexible hinges by varying the composition of the two base materials, i.e. the SMP and the elastomer, to accommodate large deformation induced during programming step, and enhance the recovery in the actuating step. To find the important design parameters, including local deformation, shape fixity and recovery ratio, we conduct high fidelity finite element simulations, which are able to accurately predict the nonlinear deformation of the printed structures. In addition, a coupled thermal-electrical finite element analysis was performed to model the heat transfer within the active hinges during the localized Joule heating process. The model predictions showed good agreement with the measured temperature data and were used to find the major parameters affecting temperature distribution including the applied voltage and the convection rate.

  16. 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.

  17. 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

    production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes....

  18. Slow-light-enhanced gain in active photonic crystal waveguides

    DEFF Research Database (Denmark)

    Ek, Sara; Hansen, Per Lunnemann; Chen, Yaohui

    2014-01-01

    Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material......, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experi- mentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic...... crystal structural parameters, the maximum value of the gain coefficient can be increased compared with a ridge waveguide structure and at the same time the spectral position of the peak gain be controlled. The experimental results are in qualitative agreement with theory and show that gain values similar...

  19. Autophagic machinery activated by dengue virus enhances virus replication

    International Nuclear Information System (INIS)

    Lee, Y.-R.; Lei, H.-Y.; Liu, M.-T.; Wang, J.-R.; Chen, S.-H.; Jiang-Shieh, Y.-F.; Lin, Y.-S.; Yeh, T.-M.; Liu, C.-C.; Liu, H.-S.

    2008-01-01

    Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, our data show that ATG5 protein is required to execute DV2-induced autophagy. All together, we are the first to demonstrate that DV can activate autophagic machinery that is favorable for viral replication

  20. Ultrasound enhanced activation of peroxydisulfate by activated carbon fiber for decolorization of azo dye.

    Science.gov (United States)

    Huang, Tianyin; Zhang, Ke; Qian, Yajie; Fang, Cong; Chen, Jiabin

    2018-02-20

    Activated carbon fiber (ACF) has become an emerging activator for peroxydisulfate (PDS) to generate sulfate radical (SO 4 •- ). However, the relative low activation efficiency and poor contaminant mineralization limited its widespread application. Herein, ultrasound (US) was introduced to the ACF activated PDS system, and the synergistic effect of US and ACF in PDS activation and the enhancement of contaminant mineralization were investigated. The synergistic effect of US and ACF was observed in the PDS activation to decolorize orange G (OG). The decolorization efficiency increased with increasing ACF loading and US power, and PDS/OG ratio from 1 to 40. The activation energy was determined to be 24.065 kJ/mol. The radical-induced decolorization of OG took place on the surface of ACF, and both SO 4 •- and hydroxyl radical ( • OH) contributed to OG decolorization. The azo bond and naphthalene ring on OG were destructed to other aromatic intermediates and finally mineralized to CO 2 and H 2 O. The introduction of US in the ACF/PDS system significantly enhanced the mineralization of OG. The combination of US and PDS was highly efficient to activate PDS to decolorize azo dyes. Moreover, the introduction of US remarkably improved the contaminant mineralization.

  1. 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.

  2. Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1 inhibition.

    Science.gov (United States)

    Meng, Fanying; Bhupathi, Deepthi; Sun, Jessica D; Liu, Qian; Ahluwalia, Dharmendra; Wang, Yan; Matteucci, Mark D; Hart, Charles P

    2015-05-21

    The hypoxia-activated prodrug TH-302 is reduced at its nitroimidazole group and selectively under hypoxic conditions releases the DNA cross-linker bromo-isophosphoramide mustard (Br-IPM). Here, we have explored the effect of Chk1 inhibition on TH-302-mediated pharmacological activities. We employed in vitro cell viability, DNA damage, cellular signaling assays and the in vivo HT29 human tumor xenograft model to study the effect of Chk1inhibition on TH-302 antitumor activities. TH-302 cytotoxicity is greatly enhanced by Chk1 inhibition in p53-deficient but not in p53-proficient human cancer cell lines. Chk1 inhibitors reduced TH-302-induced cell cycle arrest via blocking TH-302-induced decrease of phosphorylation of histone H3 and increasing Cdc2-Y15 phosphorylation. Employing the single-cell gel electrophoresis (comet) assay, we observed a potentiation of the TH-302 dependent tail moment. TH-302 induced γH2AX and apoptosis were also increased upon the addition of Chk1 inhibitor. Potentiation of TH-302 cytotoxicity by Chk1 inhibitor was only observed in cell lines proficient in, but not deficient in homology-directed DNA repair. We also show that combination treatment led to lowering of Rad51 expression levels as compared to either agent alone. In vivo data demonstrate that Chk1 inhibitor enhances TH-302 anti-tumor activity in p53 mutant HT-29 human tumor xenografts, supporting the hypothesis that these in vitro results can translate to enhanced in vivo efficacy of the combination. TH-302-mediated in vitro and in vivo anti-tumor activities were greatly enhanced by the addition of Chk1 inhibitors. The preclinical data presented in this study support a new approach for the treatment of p53-deficient hypoxic cancers by combining Chk1 inhibitors with the hypoxia-activated prodrug TH-302.

  3. Human PrimPol activity is enhanced by RPA.

    Science.gov (United States)

    Martínez-Jiménez, María I; Lahera, Antonio; Blanco, Luis

    2017-04-10

    Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.

  4. Active screen plasma nitriding enhances cell attachment to polymer surfaces

    International Nuclear Information System (INIS)

    Kaklamani, Georgia; Bowen, James; Mehrban, Nazia; Dong, Hanshan; Grover, Liam M.; Stamboulis, Artemis

    2013-01-01

    Active screen plasma nitriding (ASPN) is a well-established technique used for the surface modification of materials, the result of which is often a product with enhanced functional performance. Here we report the modification of the chemical and mechanical properties of ultra-high molecular weight poly(ethylene) (UHMWPE) using 80:20 (v/v) N 2 /H 2 ASPN, followed by growth of 3T3 fibroblasts on the treated and untreated polymer surfaces. ASPN-treated UHMWPE showed extensive fibroblast attachment within 3 h of seeding, whereas fibroblasts did not successfully attach to untreated UHMWPE. Fibroblast-coated surfaces were maintained for up to 28 days, monitoring their metabolic activity and morphology throughout. The chemical properties of the ASPN-treated UHMWPE surface were studied using X-ray photoelectron spectroscopy, revealing the presence of C-N, C=N, and C≡N chemical bonds. The elastic modulus, surface topography, and adhesion properties of the ASPN-treated UHMWPE surface were studied over 28 days during sample storage under ambient conditions and during immersion in two commonly used cell culture media.

  5. Porous platinum mesoflowers with enhanced activity for methanol oxidation reaction

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang Lina; Wang Wenjin; Hong Feng [School of Science, MOE Key Laboratory for Non-equilibrium Synthesis and Modulation of Condensed Matter, Xi' an Jiaotong University, Xi' an 710049 (China); Yang Shengchun, E-mail: ysch1209@mail.xjtu.edu.cn [School of Science, MOE Key Laboratory for Non-equilibrium Synthesis and Modulation of Condensed Matter, Xi' an Jiaotong University, Xi' an 710049 (China); You Hongjun, E-mail: hjyou@mail.xjtu.edu.cn [School of Science, MOE Key Laboratory for Non-equilibrium Synthesis and Modulation of Condensed Matter, Xi' an Jiaotong University, Xi' an 710049 (China); Fang Jixiang; Ding Bingjun [School of Science, MOE Key Laboratory for Non-equilibrium Synthesis and Modulation of Condensed Matter, Xi' an Jiaotong University, Xi' an 710049 (China)

    2012-07-15

    Porous Pt and Pt-Ag alloy mesoflowers (MFs) with about 2 {mu}m in diameter and high porosity were synthesized using Ag mesoflowers as sacrificial template by galvanic reaction. The silver content in Pt-Ag alloys can be facilely controlled by nitric acid treatment. And the pure Pt MFs can be obtained by selective removal of silver element from Pt{sub 72}Ag{sub 28} MFs electrochemically. Both Pt{sub 45}Ag{sub 55}, Pt{sub 72}Ag{sub 28} and pure Pt show a high catalytic performance in methanol oxidation reaction (MOR). Especially, pure Pt MFs exhibited a 2 to 3 times current density enhancement in MOR compared with the commercial used Pt black, which can be attributed to their porous nanostructure with 3-dimentional nature and small crystal sizes. - Graphical Abstract: The CVs of MOR on Pt (red) and Pt black (green) catalysts in 0.1 M HClO{sub 4} and 0.5 M CH{sub 3}OH for specific mass current. The insert shows the SEM images of two porous Pt MFs. Platinum mesoflowers (MFs) with about 2 {mu}m in diameter and high porosity were synthesised with Ag mesoflowers as sacrificial template by galvanic replacement. The porous Pt MFs exhibited a more than 3 times enhancement in electrocatalytic performance for methanol oxidation reaction compared the commercial used Pt black. Highlights: Black-Right-Pointing-Pointer Porous Pt and Pt-Ag mesoflowers (MFs) were synthesized using Ag MFs sacrifical template. Black-Right-Pointing-Pointer Pt MFs presents an improved catalytic activity in MOR compared with Pt black. Black-Right-Pointing-Pointer We provided a facile approach for the development of high performance Pt electrocatalysts for fuel cells.

  6. An adenine-to-guanine nucleotide change in the IRES SL-IV domain of picornavirus/hepatitis C chimeric viruses leads to a nonviable phenotype

    International Nuclear Information System (INIS)

    McKnight, Kevin L.; Sandefur, Stephanie; Phipps, Krista M.; Heinz, Beverly A.

    2003-01-01

    The inability for the internal ribosomal entry site (IRES) of hepatitis C virus (HCV) to be readily studied in the context of viral replication has been circumvented by constructing chimeras such as with poliovirus (PV), in which translation of the genome polyprotein is under control of the HCV IRES. During our attempts to configure the PV/HCV chimera for our drug discovery efforts, we discovered that an adenine- (A) to-guanine (G) change at nt 350 in domain IV of the HCV IRES resulted in a nonviable phenotype. Similarly, a mengovirus (MV)/HCV chimera using the same configuration with a G at nt 350 (G-350) was found to be nonviable. In contrast, a bovine viral diarrhea virus (BVDV)/HCV chimera remained viable with G-350 in the HCV IRES insert. Second-site, resuscitating mutations were identified from the G-350 PV/HCV and MV/HCV viruses after blind passaging. For both viruses, the resuscitating mutations involved destabilization of domain IV in the HCV IRES. The nonviability of G-350 in the picornavirus/HCV chimeric background might be linked to translation efficiency as indicated by analyses with dual reporter and PV/HCV replicon constructs

  7. Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology

    DEFF Research Database (Denmark)

    Axelsen, Mette Bjørndal; Stoltenberg, M.; Poggenborg, R.

    2012-01-01

    , the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T(1)-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement...... capsule of the knee joint (Precise ROI). Intra- and interreader agreement was assessed using the intra-class correlation coefficient (ICC). Results: The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman's correlation coefficient (rho......) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intraand inter-reader ICCs were very high (0.93-1.00). No Whole slice parameters were correlated to histology. Conclusion: DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint...

  8. 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

    2017-09-01

    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

  9. Nanostructured porous ZnO film with enhanced photocatalytic activity

    International Nuclear Information System (INIS)

    Wang Lina; Zheng Yingying; Li Xiaoyun; Dong Wenjun; Tang Weihua; Chen Benyong; Li Chaorong; Li Xiao; Zhang Tierui

    2011-01-01

    Well-defined ZnO nanostructured films have been fabricated directly on Zn foil via hydrothermal synthesis. During the fabrication of the ZnO nanostructured films, the Zn foil serves as the Zn source and also the substrate. Porous nanosheet-based, nanotube-based and nanoflower-based ZnO films can all be easily prepared by adjusting the alkali type, reaction time and reaction temperature. The composition, morphology and structure of ZnO films are characterized by X-ray diffraction, scanning electron microscope and high-resolution transmission electron microscope. The porous ZnO nanosheet-based film exhibits enhanced photocatalytic activity in the degradation of Rhodamine B under UV light irradiation. This can be attributed to the high surface area of the ZnO nanosheet and the large percentage of the exposed [001] facet. Moreover, the self-supporting, recyclable and stable ZnO photocatalytic film can be readily recovered and potentially applied for pollution disposal.

  10. Optical manipulation and catalytic activity enhanced by surface plasmon effect

    Science.gov (United States)

    Zou, Ningmu; Min, Jiang; Jiao, Wenxiang; Wang, Guanghui

    2017-02-01

    For optical manipulation, a nano-optical conveyor belt consisting of an array of gold plasmonic non-concentric nano-rings (PNNRs) is demonstrated for the realization of trapping and unidirectional transportation of nanoparticles by polarization rotation of excitation beam. These hot spots of an asymmetric plasmonic nanostructure are polarization dependent, therefore, one can use the incident polarization state to manipulate the trapped targets. Trapped particles could be transferred between adjacent PNNRs in a given direction just by rotating the polarization of incident beam due to unbalanced potential. The angular dependent distribution of electric field around PNNR has been solved using the three- dimensional finite-difference time-domain (FDTD) technique. For optical enhanced catalytic activity, the spectral properties of dimers of Au nanorod-Au nanorod nanostructures under the excitation of 532nm photons have been investigated. With a super-resolution catalytic mapping technique, we identified the existence of "hot spot" in terms of catalytic reactivity at the gap region within the twined plasmonic nanostructure. Also, FDTD calculation has revealed an intrinsic correlation between hot electron transfer.

  11. 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.

  12. Does small-bodied salmon spawning activity enhance streambed mobility?

    Science.gov (United States)

    Hassan, Marwan A.; Tonina, Daniele; Buxton, Todd H.

    2015-09-01

    Female salmonids bury and lay their eggs in streambeds by digging a pit, which is then covered with sediment from a second pit that is dug immediately upstream. The spawning process alters streambed topography, winnows fine sediment, and mixes sediment in the active layer. The resulting egg nests (redds) contain coarser and looser sediments than those of unspawned streambed areas, and display a dune-like shape with an amplitude and length that vary with fish size, substrate conditions, and flow conditions. Redds increase local bed surface roughness (drag, resulting in lower grain shear stress and less particle mobility. Spawning, also prevents streambed armoring by mixing surface and subsurface material, potentially increasing particle mobility. Here we use two-dimensional hydraulic modeling with detailed prespawning and postspawning bathymetries and field observations to test the effect of spawning by small-bodied salmonids on sediment transport. Our results show that topographical roughness from small salmon redds has negligible effects on shear stress at the reach-unit scale, and limited effects at the local scale. Conversely, results indicate sediment mixing reduces armoring and enhances sediment mobility, which increases potential bed load transport by subsequent floods. River restoration in fish-bearing streams should take into consideration the effects of redd excavation on channel stability. This is particularly important for streams that historically supported salmonids and are the focus of habitat restoration actions.

  13. Photon activation therapy: a Monte Carlo study on dose enhancement by various sources and activation media

    International Nuclear Information System (INIS)

    Bakhshabadi, Mahdi; Ghorbani, Mahdi; Meigooni, Ali Soleimani

    2013-01-01

    In the present study, a number of brachytherapy sources and activation media were simulated using MCNPX code and the results were analyzed based on the dose enhancement factor values. Furthermore, two new brachytherapy sources ( 131 Cs and a hypothetical 170 Tm) were evaluated for their application in photon activation therapy (PAT). 125 I, 103 Pd, 131 Cs and hypothetical 170 Tm brachytherapy sources were simulated in water and their dose rate constant and the radial dose functions were compared with previously published data. The sources were then simulated in a soft tissue phantom which was composed of Ag, I, Pt or Au as activation media uniformly distributed in the tumour volume. These simulations were performed using the MCNPX code, and dose enhancement factor (DEF) was obtained for 7, 18 and 30 mg/ml concentrations of the activation media. Each source, activation medium and concentration was evaluated separately in a separate simulation. The calculated dose rate constant and radial dose functions were in agreement with the published data for the aforementioned sources. The maximum DEF was found to be 5.58 for a combination of the 170 Tm source with 30 mg/ml concentration of I. The DEFs for 131 Cs and 170 Tm sources for all the four activation media were higher than those for other sources and activation media. From this point of view, these two sources can be more useful in photon activation therapy with photon emitter sources. Furthermore, 131 Cs and 170 Tm brachytherapy sources can be proposed as new options for use in the field of PAT.

  14. Enhanced persistency of resting and active periods of locomotor activity in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Wataru Sano

    Full Text Available Patients with schizophrenia frequently exhibit behavioral abnormalities associated with its pathological symptoms. Therefore, a quantitative evaluation of behavioral dynamics could contribute to objective diagnoses of schizophrenia. However, such an approach has not been fully established because of the absence of quantitative biobehavioral measures. Recently, we studied the dynamical properties of locomotor activity, specifically how resting and active periods are interwoven in daily life. We discovered universal statistical laws ("behavioral organization" and their alterations in patients with major depressive disorder. In this study, we evaluated behavioral organization of schizophrenic patients (n = 19 and healthy subjects (n = 11 using locomotor activity data, acquired by actigraphy, to investigate whether the laws could provide objective and quantitative measures for a possible diagnosis and assessment of symptoms. Specifically, we evaluated the cumulative distributions of resting and active periods, defined as the periods with physical activity counts successively below and above a predefined threshold, respectively. Here we report alterations in the laws governing resting and active periods; resting periods obeyed a power-law cumulative distribution with significantly lower parameter values (power-law scaling exponents, whereas active periods followed a stretched exponential distribution with significantly lower parameter values (stretching exponents, in patients. Our findings indicate enhanced persistency of both lower and higher locomotor activity periods in patients with schizophrenia, probably reflecting schizophrenic pathophysiology.

  15. Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

    Science.gov (United States)

    Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

    1994-11-15

    Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

  16. Ground Reaction Force and Mechanical Differences Between the Interim Resistive Exercise Device (iRED) and Smith Machine While Performing a Squat

    Science.gov (United States)

    Amonette, William E.; Bentley, Jason R.; Lee, Stuart M. C.; Loehr, James A.; Schneider, Suzanne

    2004-01-01

    Musculoskeletal unloading in microgravity has been shown to induce losses in bone mineral density, muscle cross-sectional area, and muscle strength. Currently, an Interim Resistive Exercise Device (iRED) is being flown on board the ISS to help counteract these losses. Free weight training has shown successful positive musculoskeletal adaptations. In biomechanical research, ground reaction forces (GRF) trajectories are used to define differences between exercise devices. The purpose of this evaluation is to quantify the differences in GRF between the iRED and free weight exercise performed on a Smith machine during a squat. Due to the differences in resistance properties, inertial loading and load application to the body between the two devices, we hypothesize that subjects using iRED will produce GRF that are significantly different from the Smith machine. There will be differences in bar/harness range of motion and the time when peak GRF occurred in the ROMbar. Three male subjects performed three sets of ten squats on the iRED and on the Smith Machine on two separate days at a 2-second cadence. Statistically significant differences were found between the two devices in all measured GRF variables. Average Fz and Fx during the Smith machine squat were significantly higher than iRED. Average Fy (16.82 plus or minus.23; p less than .043) was significantly lower during the Smith machine squat. The mean descent/ascent ratio of the magnitude of the resultant force vector of all three axes for the Smith machine and iRED was 0.95 and 0.72, respectively. Also, the point at which maximum Fz occurred in the range of motion (Dzpeak) was at different locations with the two devices.

  17. 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.

  18. Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins.

    OpenAIRE

    Martin, M E; Piette, J; Yaniv, M; Tang, W J; Folk, W R

    1988-01-01

    The polyomavirus enhancer is composed of multiple DNA sequence elements serving as binding sites for proteins present in mouse nuclear extracts that activate transcription and DNA replication. We have identified three such proteins and their binding sites and correlate them with enhancer function. Mutation of nucleotide (nt) 5140 in the enhancer alters the binding site (TGACTAA, nt 5139-5145) for polyomavirus enhancer A binding protein 1 (PEA1), a murine homolog of the human transcription fac...

  19. Glutamate transporter activity promotes enhanced Na+/K+-ATPase -mediated extracellular K+ management during neuronal activity

    DEFF Research Database (Denmark)

    Larsen, Brian R; Holm, Rikke; Vilsen, Bente

    2016-01-01

    , in addition, Na+ /K+ -ATPase-mediated K+ clearance could be governed by astrocytic [Na+ ]i . During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+ -coupled glutamate transporters, thereby elevating [Na+ ]i . It thus remains unresolved whether...... the different Na+ /K+ -ATPase isoforms are controlled by [K+ ]o or [Na+ ]i during neuronal activity. Hippocampal slice recordings of stimulus-induced [K+ ]o transients with ion-sensitive microelectrodes revealed reduced Na+ /K+ -ATPase-mediated K+ management upon parallel inhibition of the glutamate transporter......+ affinity to the α1 and α2 isoforms than the β2 isoform. In summary, enhanced astrocytic Na+ /K+ -ATPase-dependent K+ clearance was obtained with parallel glutamate transport activity. The astrocytic Na+ /K+ -ATPase isoform constellation α2β1 appeared to be specifically geared to respond to the [Na+ ]i...

  20. Tat-haFGF14–154 Upregulates ADAM10 to Attenuate the Alzheimer Phenotype of APP/PS1 Mice through the PI3K-CREB-IRE1α/XBP1 Pathway

    Directory of Open Access Journals (Sweden)

    Tian Meng

    2017-06-01

    Full Text Available Acid fibroblast growth factor (aFGF has shown neuroprotection in Alzheimer’s disease (AD models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14–154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14–154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10 in the brain. Tat-haFGF14–154 antagonized Aβ1–42-induced cell death and structural damage in rat primary neurons in an ADAM10-dependent manner, which, in turn, was promoted by the activation of XBP1 splicing and modulated by the PI3K-CREB pathway. Both knockdown of ADAM10 and inhibition of PI3K (LY294002 negated Tat-haFGF14–154 rescue. Thus, Tat-haFGF14–154 activates the IRE1α/XBP1 pathway of the unfolded protein response (UPR against the endoplasmic reticulum (ER stress induced by Aβ, and, subsequently, the nuclear translocation of spliced XBP1 (XBP1s promotes transcription of ADAM10. These results highlight the important role of ADAM10 and its activation through the PI3K-CREB-IRE1α/XBP1 pathway as a key factor in the mechanism of neuroprotection for Tat-haFGF14–154.

  1. Growth enhancement and gene expression of Arabidopsis thaliana irradiated with active oxygen species

    Science.gov (United States)

    Watanabe, Satoshi; Ono, Reoto; Hayashi, Nobuya; Shiratani, Masaharu; Tashiro, Kosuke; Kuhara, Satoru; Inoue, Asami; Yasuda, Kaori; Hagiwara, Hiroko

    2016-07-01

    The characteristics of plant growth enhancement effect and the mechanism of the enhancement induced by plasma irradiation are investigated using various active species in plasma. Active oxygen species in oxygen plasma are effective for growth enhancement of plants. DNA microarray analysis of Arabidopsis thaliana indicates that the genes coding proteins that counter oxidative stresses by eliminating active oxygen species are expressed at significantly high levels. The size of plant cells increases owing to oxygen plasma irradiation. The increases in gene expression levels and cell size suggest that the increase in the expression level of the expansin protein is essential for plant growth enhancement phenomena.

  2. Back to basics: the untreated rabbit reticulocyte lysate as a competitive system to recapitulate cap/poly(A) synergy and the selective advantage of IRES-driven translation.

    Science.gov (United States)

    Soto Rifo, Ricardo; Ricci, Emiliano P; Décimo, Didier; Moncorgé, Olivier; Ohlmann, Théophile

    2007-01-01

    Translation of most eukaryotic mRNAs involves the synergistic action between the 5' cap structure and the 3' poly(A) tail at the initiation step. The poly(A) tail has also been shown to stimulate translation of picornavirus internal ribosome entry sites (IRES)-directed translation. These effects have been attributed principally to interactions between eIF4G and poly(A)-binding protein (PABP) but also to the participation of PABP in other steps during translation initiation. As the rabbit reticulocyte lysate (RRL) does not recapitulate this cap/poly(A) synergy, several systems based on cellular cell-free extracts have been developed to study the effects of poly(A) tail in vitro but they generally exhibit low translational efficiency. Here, we describe that the non-nuclease-treated RRL (untreated RRL) is able to recapitulate the effects of poly(A) tail on translation in vitro. In this system, translation of a capped/polyadenylated RNA was specifically inhibited by either Paip2 or poly(rA), whereas translation directed by HCV IRES remained unaffected. Moreover, cleavage of eIF4G by FMDV L protease strongly stimulated translation directed by the EMCV IRES, thus recapitulating the competitive advantage that the proteolytic processing of eIF4G confers to IRES-driven RNAs.

  3. 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…

  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. Focus on Freshman: Basic Instruction Programs Enhancing Physical Activity

    Science.gov (United States)

    Curry, Jarred; Jenkins, Jayne M.; Weatherford, Jennifer

    2015-01-01

    Physical activity sharply decreases after different life stages, particularly high school graduation to beginning university education. The purpose of this study was to investigate the effect of a specifically designed university physical activity class, Exercise Planning for Freshman (EPF), on students' physical activity and group cohesion…

  6. Accidental release of iodine-131 by IRE at Fleurus: back experience of Belgium safety authority; Rejet accidentel d'iode-131 par l'IRE sur le site de Fleurus: retour d'experience de l'autorite de surete belge

    Energy Technology Data Exchange (ETDEWEB)

    Vandecasteele, C.M.; Sonck, M. [AFCN - Agence federale de controle nucleaire, Bruxelles (Belgium); Degueldre, D. [Bel V, Anderlecht (Belgium)

    2011-04-15

    The IRE (National institute for radioelements) produces radionuclides for nuclear medicine from highly enriched uranium irradiated targets. On 22/08/2008, fresh production wastes were transferred into an almost empty decay tank. The mixing of these liquids led to the release of approximately 47 GBq of molecular iodine-131 into the atmosphere. The first conservative assessments of the radiological consequences did not require taking direct protective actions for the population, such as sheltering or stable iodine intake. However, the estimated iodine-131 deposits could locally reach or exceed the derived reference levels for the contamination of milk (4 kBq/m2) and leafy vegetables (10 kBq/m2). For this reason, and because there was a threat of a further release, the federal emergency plan was activated on 28/08 and the population potentially concerned was recommended to avoid consumption of locally produced fruits, vegetables and fresh milk. These protective actions were lifted on 7/09 and the emergency plan was lifted on 12/09. The main lesson learned from this event concerns the paramount importance of the rapid exchange of information that is as accurate and complete as possible between the different stakeholders: from the operator up to the population, through federal and local authorities. (authors)

  7. Enhanced Gamma Oscillatory Activity in Rats with Chronic Inflammatory Pain

    OpenAIRE

    Wang, Jing; Wang, Jing; Xing, Guo-Gang; Li, Xiaoli; Wan, You

    2016-01-01

    It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic infla...

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

    OpenAIRE

    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,...

  9. 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 (IO 4 - ) to degrade organic contaminants at ambient temperature. The physicochemical properties of GAC and I-GAC were examined using scanning electron microscopy, N 2 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 (I 3 - ) and pentaiodide (I 5 - ) on I-GAC. The catalytic activity of I-GAC towards IO 4 - 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 IO 3 was the predominant reactive species in the I-GAC/IO 4 - system. The mechanism underlying the enhanced catalytic performance of I-GAC could be explained by the introduction of negatively charged I 3 - and I 5 - into I-GAC, which induced positive charge density on the surface of I-GAC. This accelerated the interaction between I-GAC and IO 4 - , and subsequently mediated the increasing generation of iodyl radicals (IO 3 ). 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.

  10. Active and Inactive Enhancers Cooperate 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

    2016-06-07

    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 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. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. 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.

  12. Allosteric activation of midazolam CYP3A5 hydroxylase activity by icotinib - Enhancement by ketoconazole.

    Science.gov (United States)

    Zhuang, XiaoMei; Zhang, TianHong; Yue, SiJia; Wang, Juan; Luo, Huan; Zhang, YunXia; Li, Zheng; Che, JinJing; Yang, HaiYing; Li, Hua; Zhu, MingShe; Lu, Chuang

    2016-12-01

    Icotinib (ICO), a novel small molecule and a tyrosine kinase inhibitor, was developed and approved recently in China for non-small cell lung cancer. During screening for CYP inhibition potential in human liver microsomes (HLM), heterotropic activation toward CYP3A5 was revealed. Activation by icotinib was observed with CYP3A-mediated midazolam hydroxylase activity in HLM (∼40% over the baseline) or recombinant human CYP3A5 (rhCYP3A5) (∼70% over the baseline), but not in the other major CYPs including rhCYP3A4. When co-incubated with selective CYP3A4 inhibitor CYP3cide or monoclonal human CYP3A4 inhibitory antibody in HLM, the activation was extended to ∼60%, suggesting CYP3A5 might be the isozyme involved. Further, the relative activation was enhanced to ∼270% in rhCYP3A5 in the presence of ketoconazole. The activation was substrate and pathway dependent and observed only in the formation of 1'-OH-midazolam, and not 4-OH-midazolam, 6β-OH-testosterone, or oxidized nifedipine. The activation requires the presence of cytochrome b5 and it is only observed in the liver microsomes of dogs, monkeys, and humans, but not in rats and mice. Kinetic analyses of 1'-OH-midazolam formation showed that ICO increased the V max values in HLM and rhCYP3A5 with no significant changes in K m values. By adding CYP3cide with ICO to the incubation, the V max values increased 2-fold over the CYP3cide control. Addition of ketoconazole with ICO alone or ICO plus CYP3cide resulted in an increase in V max values and decrease in K m values compared to their controls. This phenomenon may be attributed to a new mechanism of CYP3A5 heterotropic activation, which warrants further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. 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 ...

  14. Enhancing Learning Outcomes through Application Driven Activities in Marketing

    Science.gov (United States)

    Stegemann, Nicole; Sutton-Brady, Catherine

    2013-01-01

    This paper introduces an activity used in class to allow students to apply previously acquired information to a hands-on task. As the authors have previously shown active learning is a way to effectively facilitate and improve students' learning outcomes. As a result to improve learning outcomes we have overtime developed a series of learning…

  15. Enhancement of antimicrobial activity of chitosan by irradiation

    International Nuclear Information System (INIS)

    Matsuhashi, S.; Kume, T.

    1997-01-01

    Antimicrobial activity of irradiated chitosan was studied against Escherichia coli B/r. Irradiation of chitosan at 100 kGy under dry conditions was effective in increasing the activity, and inhibited the growth of E. coli completely. The molecular weight of chitosan significantly decreased with the increase in irradiation dose, whereas the relative surface charge of chitosan was decreased only 3% by 100 kGy irradiation. Antimicrobial activity assay of chitosan fractionated according to molecular weight showed that 1 x 10 5 -3 x 10 5 fraction was most effective in suppressing the growth of E coli. This fraction comprised only 8% of the 100 kGy irradiated chitosan. On the other hand, chitosan whose molecular weight was less than 1 x 10 5 had no activity. The results show that low dose irradiation, specifically 100 kGy, of chitosan gives enough degradation to increase its antimicrobial activity as a result of a change in molecular weight. (Author)

  16. High salt intake enhances swim stress-induced PVN vasopressin cell activation and active stress coping.

    Science.gov (United States)

    Mitchell, N C; Gilman, T L; Daws, L C; Toney, G M

    2018-07-01

    Stress contributes to many psychiatric disorders; however, responsivity to stressors can vary depending on previous or current stress exposure. Relatively innocuous heterotypic (differing in type) stressors can summate to result in exaggerated neuronal and behavioral responses. Here we investigated the ability of prior high dietary sodium chloride (salt) intake, a dehydrating osmotic stressor, to enhance neuronal and behavioral responses of mice to an acute psychogenic swim stress (SS). Further, we evaluated the contribution of the osmo-regulatory stress-related neuropeptide arginine vasopressin (VP) in the hypothalamic paraventricular nucleus (PVN), one of only a few brain regions that synthesize VP. The purpose of this study was to determine the impact of high dietary salt intake on responsivity to heterotypic stress and the potential contribution of VPergic-mediated neuronal activity on high salt-induced stress modulation, thereby providing insight into how dietary (homeostatic) and environmental (psychogenic) stressors might interact to facilitate psychiatric disorder vulnerability. Salt loading (SL) with 4% saline for 7 days was used to dehydrate and osmotically stress mice prior to exposure to an acute SS. Fluid intake and hematological measurements were taken to quantify osmotic dehydration, and serum corticosterone levels were measured to index stress axis activation. Immunohistochemistry (IHC) was used to stain for the immediate early gene product c-Fos to quantify effects of SL on SS-induced activation of neurons in the PVN and extended amygdala - brain regions that are synaptically connected and implicated in responding to osmotic stress and in modulation of SS behavior, respectively. Lastly, the role of VPergic PVN neurons and VP type 1 receptor (V1R) activity in the amygdala in mediating effects of SL on SS behavior was evaluated by quantifying c-Fos activation of VPergic PVN neurons and, in functional experiments, by nano-injecting the V1R selective

  17. 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

  18. Reduced graphene oxide wrapped Ag nanostructures for enhanced SERS activity

    Science.gov (United States)

    Nair, Anju K.; Kala, M. S.; Thomas, Sabu; Kalarikkal, Nandakumar

    2018-04-01

    Graphene - metal nanoparticle hybrids have received great attention due to their unique electronic properties, large specific surface area, very high conductivity and more charge transfer. Thus, it is extremely advantages to develop a simple and efficient process to disperse metal nanostructures over the surface of graphene sheets. Herein, we report a hydrothermal assisted strategy for developing reduced graphene oxide /Ag nanomorphotypes (cube, wire) for surface enhanced Raman scattering (SERS) applications, considering the advantages of synergistic effect of graphene and plasmonic properties of Ag nanomorphotypes.

  19. Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress.

    Science.gov (United States)

    Kanemoto, Soshi; Nitani, Ryota; Murakami, Tatsuhiko; Kaneko, Masayuki; Asada, Rie; Matsuhisa, Koji; Saito, Atsushi; Imaizumi, Kazunori

    2016-11-11

    The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular homeostasis. However, numerous environmental and genetic factors give rise to ER stress by inducing an accumulation of unfolded proteins. Under ER stress conditions, cells initiate the unfolded protein response (UPR). Here, we demonstrate a novel aspect of the UPR by electron microscopy and immunostaining analyses, whereby multivesicular body (MVB) formation was enhanced after ER stress. This MVB formation was influenced by inhibition of ER stress transducers inositol required enzyme 1 (IRE1) and PKR-like ER kinase (PERK). Furthermore, exosome release was also increased during ER stress. However, in IRE1 or PERK deficient cells, exosome release was not upregulated, indicating that IRE1- and PERK-mediated pathways are involved in ER stress-dependent exosome release. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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 ...

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

    Science.gov (United States)

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

    2018-05-01

    TiO 2 (Degussa P25) photocatalysts harboring 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 3 h) reach 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 vacancy states can produce vacancy energy level located below the conduction band minimum, which resulting in the bandgap 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 photogenerated electron-hole pair separation efficiency, which leads to an obvious enhancement of the visible photocatalytic activities of Vacuum P25. © 2017 The American Society of Photobiology.

  2. Slow self-activation enhances the potency of viridin prodrugs.

    Science.gov (United States)

    Blois, Joseph; Yuan, Hushan; Smith, Adam; Pacold, Michael E; Weissleder, Ralph; Cantley, Lewis C; Josephson, Lee

    2008-08-14

    When the viridin wortmannin (Wm) is modified by reaction with certain nucleophiles at the C20 position, the compounds obtained exhibit an improved antiproliferative activity even though a covalent reaction between C20 and a lysine in the active site of PI3 kinase is essential to Wm's ability to inhibit this enzyme. Here we show that this improved potency results from an intramolecular attack by the C6 hydroxyl group that slowly converts these inactive prodrugs to the active species Wm over the 48 h duration of the antiproliferative assay. Our results provide a guide for selecting Wm-like compounds to maximize kinase inhibition with the variety of protocols used to assess the role of PI3 kinase in biological systems, or for achieving optimal therapeutic effects in vivo . In addition, the slow self-activation of WmC20 derivatives provides a mechanism that can be exploited to obtain kinase inhibitors endowed with physical and pharmacokinetic properties far different from man-made kinase inhibitors because they do not bind to kinase active sites.

  3. Evaluating automated dynamic contrast enhanced wrist 3 T MRI in healthy volunteers: One-year longitudinal observational study

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Anshul, E-mail: anshul.rastogi@bartshealth.nhs.uk [Kennedy Institute of Rheumatology, Imperial College London (United Kingdom); Kubassova, Olga, E-mail: olga@imageanalysis.org.uk [Image Analysis, Leeds (United Kingdom); Krasnosselskaia, Lada V., E-mail: solaguz@yahoo.com [Imaging Sciences Department, Imperial College London (United Kingdom); Lim, Adrian K.P., E-mail: a.lim@imperial.ac.uk [Department of Radiology, Imperial College Healthcare NHS Trust, London (United Kingdom); Satchithananda, Keshthra, E-mail: keshthra.satchithananda@imperial.nhs.uk [Department of Radiology, Imperial College Healthcare NHS Trust, London (United Kingdom); Boesen, Mikael, E-mail: mikael.boesen@gmail.com [Department of Radiology and the Parker Institute, Frederiksberg and Bispebjerg Hospitals (Denmark); Binks, Michael, E-mail: michael.h.binks@gsk.com [GlaxoSmithKline, Stevenage, SG1 2NY (United Kingdom); Hajnal, Joseph V., E-mail: jo.hajnal@kcl.ac.uk [Imaging Sciences Department, Imperial College London (United Kingdom); Taylor, Peter C., E-mail: peter.taylor@kennedy.ox.ac.uk [Kennedy Institute of Rheumatology, Imperial College London (United Kingdom)

    2013-08-15

    Rational and Objective: Dynamic contrast enhanced (DCE)-MRI has great potential to provide quantitative measure of inflammatory activity in rheumatoid arthritis. There is no current benchmark to establish the stability of signal in the joints of healthy subjects when imaged with DCE-MRI longitudinally, which is crucial so as to differentiate changes induced by treatment from the inherent variability of perfusion measures. The objective of this study was to test a pixel-by-pixel parametric map based approach for analysis of DCE-MRI (Dynamika) and to investigate the variability in signal characteristics over time in healthy controls using longitudinally acquired images. Materials and Methods: 10 healthy volunteers enrolled, dominant wrists were imaged with contrast enhanced 3T MRI at baseline, week 12, 24 and 52 and scored with RAMRIS, DCE-MRI was analysed using a novel quantification parametric map based approach. Radiographs were obtained at baseline and week 52 and scored using modified Sharp van der Heidje method. RAMRIS scores and dynamic MRI measures were correlated. Results: No erosions were seen on radiographs, whereas MRI showed erosion-like changes, low grade bone marrow oedema and low-moderate synovial enhancement. The DCE-MRI parameters were stable (baseline scores, variability) (mean ± st.dev); in whole wrist analysis, ME{sub mean} (1.3 ± 0.07, −0.08 ± 0.1 at week 24) and IRE{sub mean} (0.008 ± 0.004, −0.002 ± 0.005 at week 12 and 24). In the rough wrist ROI, ME{sub mean} (1.2 ± 0.07, 0.04 ± 0.02 at week 52) and IRE{sub mean} (0.001 ± 0.0008, 0.0006 ± 0.0009 at week 52) and precise wrist ROI, ME{sub mean} (1.2 ± 0.09, 0.04 ± 0.04 at week 52) and IRE{sub mean} (0.001 ± 0.0008, 0.0008 ± 0.001 at week 24 and 52). The Dynamic parameters obtained using fully automated analysis demonstrated strong, statistically significant correlations with RAMRIS synovitis scores. Conclusion: The study demonstrated that contrast enhancement does occur in

  4. Business oriented educational experiments enhance active learning by engineering students

    DEFF Research Database (Denmark)

    Christiansen, Nynne Mia; Schjær-Jacobsen, Hans; Simon, Jens

    2012-01-01

    It is generally agreed that one of the keys to recreating industrial growth after the financial crisis is to mobilize universities and engineering schools to be more actively involved in innovation and entrepreneurship activities in cooperation with industrial companies. This active learning...... exploration symposium on bridging the gap between engineering education and business is proposed on the basis of the Copenhagen University College of Engineering (IHK) being involved in a DKK 50m ongoing project “Business Oriented Educational Experiments” financed by the Capital Region of Denmark...... and the European Social Fund. The project is carried out with other major educational institutions in the Copenhagen area and organized in five themes: 1) world class competences, 2) new interactions between education and business, 3) the experimenting organization, 4) education on demand, and 5) new career paths...

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

    DEFF Research Database (Denmark)

    Hoffmann, Christian

    Enzyme immobilization is an important concept for the development of improved biocatalytic processes, primarily through facilitated separation procedures. However, enzyme immobilization usually comes at a price of reduced biocatalytic activity. For this reason, different immobilization methods have...... 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...... on their tailored surface modification in order to obtain improved enzyme-support systems. Firstly, an off-stoichiometric thiol-ene (OSTE) thermosetting material was used for the development of a screening platform allowing the investigation of micro-environmental effects and their impact on the activity...

  6. Protein kinase A activation enhances β-catenin transcriptional activity through nuclear localization to PML bodies.

    Directory of Open Access Journals (Sweden)

    Mei Zhang

    Full Text Available The Protein Kinase A (PKA and Wnt signaling cascades are fundamental pathways involved in cellular development and maintenance. In the osteoblast lineage, these pathways have been demonstrated functionally to be essential for the production of mineralized bone. Evidence for PKA-Wnt crosstalk has been reported both during tumorigenesis and during organogenesis, and the nature of the interaction is thought to rely on tissue and cell context. In this manuscript, we analyzed bone tumors arising from mice with activated PKA caused by mutation of the PKA regulatory subunit Prkar1a. In primary cells from these tumors, we observed relocalization of β-catenin to intranuclear punctuate structures, which were identified as PML bodies. Cellular redistribution of β-catenin could be recapitulated by pharmacologic activation of PKA. Using 3T3-E1 pre-osteoblasts as a model system, we found that PKA phosphorylation sites on β-catenin were required for nuclear re-localization. Further, β-catenin's transport to the nucleus was accompanied by an increase in canonical Wnt-dependent transcription, which also required the PKA sites. PKA-Wnt crosstalk in the cells was bi-directional, including enhanced interactions between β-catenin and the cAMP-responsive element binding protein (CREB and transcriptional crosstalk between the Wnt and PKA signaling pathways. Increases in canonical Wnt/β-catenin signaling were associated with a decrease in the activity of the non-canonical Wnt/Ror2 pathway, which has been shown to antagonize canonical Wnt signaling. Taken together, this study provides a new understanding of the complex regulation of the subcellular distribution of β-catenin and its differential protein-protein interaction that can be modulated by PKA signaling.

  7. 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.

  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. Protecting patients’ electronic health records using enhanced active bundles

    NARCIS (Netherlands)

    Salih, R.M.; Lilien, L.T.; Ben Othmane, L.; Arriaga, R.; Matic, A.

    2012-01-01

    We propose a solution that provides protection for patients' electronic health/medical records disseminated among different authorized healthcare information systems. The solution is known as Active Bundles using a Trusted Third Party (ABTTP). It is based on the use of trusted third parties, and the

  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 antioxidant activity of polyolefin films integrated with grape tannins.

    Science.gov (United States)

    Olejar, Kenneth J; Ray, Sudip; Kilmartin, Paul A

    2016-06-01

    A natural antioxidant derived from an agro-waste of the wine industry, grape tannin, was incorporated by melt blending into three different polyolefins (high-density polyethylene, linear low-density polyethylene and polypropylene) to introduce antioxidant functionality. Significant antioxidant activity was observed at 1% tannin inclusion in all polymer blends. The antioxidant activity was observed to increase steadily with a greater concentration of grape tannins, the highest increases being seen with polypropylene. The mechanical and thermal properties of the polymer films following antioxidant incorporation were minimally altered with up to 3% grape tannins. All of the polyolefin-grape tannin films successfully passed the leachability test following USP661 standard protocol. Superior antioxidant activity was established in polyolefin thin films by utilization of a bulk grape extract obtained from winery waste. Significant increases in antioxidant activity were seen with 1% extract inclusion. This not only demonstrates the potential for food packaging applications of the polyolefin blends, but also valorizes the agro-waste. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  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. Intense synaptic activity enhances temporal resolution in spinal motoneurons.

    Directory of Open Access Journals (Sweden)

    Rune W Berg

    Full Text Available In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, 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 of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory and excitatory synaptic activity. By shortening the effective integration time, this intense synaptic input may serve to facilitate the generation of rapid changes in movements.

  14. Enhanced Passive and Active Processing of Syllables in Musician Children

    Science.gov (United States)

    Chobert, Julie; Marie, Celine; Francois, Clement; Schon, Daniele; Besson, Mireille

    2011-01-01

    The aim of this study was to examine the influence of musical expertise in 9-year-old children on passive (as reflected by MMN) and active (as reflected by discrimination accuracy) processing of speech sounds. Musician and nonmusician children were presented with a sequence of syllables that included standards and deviants in vowel frequency,…

  15. 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

  16. 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…

  17. 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 gingivalis (p ....05), and P. gingivalis (p gingivalis-stimulated cultures (p ... of activated platelets. Adherence of platelets increased TG- and TT-induced IL-10 secretion by monocytes (p gingivalis (p

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

    KAUST Repository

    Chen, Wei; Baby, Rakhi Raghavan; Alshareef, Husam N.

    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

  19. 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...... results for future compact devices for terabit/s communication, such as miniaturised semiconductor optical amplifiers and mode-locked lasers....

  20. 77 FR 25188 - Extension of Agency Information Collection Activity Under OMB Review: Enhanced Security...

    Science.gov (United States)

    2012-04-27

    ... general aviation (GA) aircraft operators who wish to fly into and/or out of Ronald Reagan Washington.... Information Collection Requirement Title: Enhanced Security Procedures at Ronald Reagan Washington National...] Extension of Agency Information Collection Activity Under OMB Review: Enhanced Security Procedures at Ronald...

  1. Novel Chiroptical Analysis of Hemoglobin by Surface Enhanced Resonance Raman Optical Activity Spectroscopy

    DEFF Research Database (Denmark)

    Brazhe, Nadezda; Brazhe, Alexey; Sosnovtseva, Olga

    2010-01-01

    The metalloprotein hemoglobin (Hb) was studied using surface enhanced resonance Raman spectroscopy (SERRS) and surface enhanced resonance Raman optical activity (SERROA). The SERROA results are analyzed and compared with the SERRS, and the later to the resonance Raman (RRS) performed on Hb...

  2. 78 FR 47676 - Agency Information Collection Activities; Comment Request; Credit Enhancement for Charter School...

    Science.gov (United States)

    2013-08-06

    ... the use of information technology. Please note that written comments received in response to this... DEPARTMENT OF EDUCATION [Docket No. ED-2013-ICCD-0101] Agency Information Collection Activities; Comment Request; Credit Enhancement for Charter School Facilities Program Performance Report AGENCY...

  3. 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

  4. Self-Assembled Complexes of Horseradish Peroxidase with Magnetic Nanoparticles Showing Enhanced Peroxidase Activity

    KAUST Repository

    Corgié , Sté phane C.; Kahawong, Patarawan; Duan, Xiaonan; Bowser, Daniel; Edward, Joseph B.; Walker, Larry P.; Giannelis, Emmanuel P.

    2012-01-01

    Bio-nanocatalysts (BNCs) consisting of horseradish peroxidase (HRP) self-assembled with magnetic nanoparticles (MNPs) enhance enzymatic activity due to the faster turnover and lower inhibition of the enzyme. The size and magnetization of the MNPs

  5. 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.

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

    KAUST Repository

    Chen, Wei; Xia, Chuan; Baby, Rakhi Raghavan; Alshareef, Husam N.

    2014-01-01

    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

  7. 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.

  8. Enhancement of Antibacterial activity of Chitosan by gamma irradiation

    International Nuclear Information System (INIS)

    Bashandy, A.S.; Ibrahim, H.M.M.

    2006-01-01

    The antibacterial activity of irradiated and non-irradiated chitosan against E.coli, S.aureus, Salmonella, Strep. fecalis,Closteridium and P. aerugenosa was studied. Up to 1.25 mg/l, chitosan hardly suppressed the growth of all the strains while 3 mg/l of chitosan clearly inhibited the growth of all the studied strains. Therefore, the concentration of 3 mg/l of chitosan in the medium was adopted in this study. Irradiation at 100 KGy under dry conditions was effective in increasing the activity of chitosan and the growth of bacterial strains which was completely inhibited. It was also found that the addition of chitosan to dressing membranes present good barrier properties against microbes especially that irradiated at 100 KGy

  9. Silver-enhanced block copolymer membranes with biocidal activity

    KAUST Repository

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

    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.

  10. Enhanced Efflux Pump Activity in Old Candida glabrata Cells.

    Science.gov (United States)

    Bhattacharya, Somanon; Fries, Bettina C

    2018-03-01

    We investigated the effect of replicative aging on antifungal resistance in Candida glabrata Our studies demonstrate significantly increased transcription of ABC transporters and efflux pump activity in old versus young C. glabrata cells of a fluconazole-sensitive and -resistant strain. In addition, higher tolerance to killing by micafungin and amphotericin B was noted and is associated with higher transcription of glucan synthase gene FKS1 and lower ergosterol content in older cells. Copyright © 2018 American Society for Microbiology.

  11. Lipase Activity Enhancement by SC-CO2 Treatment

    Czech Academy of Sciences Publication Activity Database

    Hlavsová, K.; Wimmer, Zdeněk; Xanthakis, E.; Bernášek, Prokop; Sovová, Helena; Zarevúcka, Marie

    63b, č. 6 (2008), s. 779-784 ISSN 0932-0776 R&D Projects: GA MŠk OC D30.001 Institutional research plan: CEZ:AV0Z50380511; CEZ:AV0Z40720504; CEZ:AV0Z40550506 Keywords : lipase activity * supercritical carbon dioxide * enantioselectivity Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 0.852, year: 2008 www.znaturforsch.com/ab/v63b/63b0779.pdf

  12. Enhancement of antibiotic activity by Cordia verbenacea DC

    OpenAIRE

    Matias, Edinardo F.F.; Santos, Karla K. A.; Almeida, Thiago S.; Costa, José G.M. da; Coutinho, Henrique D.M.

    2010-01-01

    Escherichia coli is known to produce enterotoxins whose properties and its role in diarrheal disease has been extensively investigated. Some species of Staphylococcus are often recognized as etiological agents of many animal and human opportunistic infections. This study is the first test of change in resistance of antibiotic activity by Cordia verbenacea DC. against multiresistant strains of Escherichia coli and Staphylococcus aureus. In this study, the hexane and methanol extract of Cordia ...

  13. Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement.

    Science.gov (United States)

    Tsao, Nadia H; Hall, Elizabeth A H

    2017-11-14

    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 were 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 an additional multilayer uptake that leads to a much higher loading for the SiPCL system (∼280 μg/2.4 × 10 9 microcapsules compared with ∼135 μg/2.4 × 10 9 microcapsules for S/M/S). Whereas the 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 toward diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (T d ) increases from 1 to 2 days for the S/M/S and for the low concentration, loaded SiPCl vehicles to ∼10 days for the high loaded microcapsules. However, T d can be reduced on insonation to 2 days, indicating the potential to gain control over the local enhanced release with ultrasound. This was tested for a docetaxel model and its effect on C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC 50 in solution.

  14. 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

  15. 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.

  16. Intense synaptic activity enhances temporal resolution in spinal motoneurons

    DEFF Research Database (Denmark)

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

    2008-01-01

    In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems...... of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory...

  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 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.

  19. The second extracellular loop of the adenosine A1 receptor mediates activity of allosteric enhancers.

    Science.gov (United States)

    Kennedy, Dylan P; McRobb, Fiona M; Leonhardt, Susan A; Purdy, Michael; Figler, Heidi; Marshall, Melissa A; Chordia, Mahendra; Figler, Robert; Linden, Joel; Abagyan, Ruben; Yeager, Mark

    2014-02-01

    Allosteric enhancers of the adenosine A1 receptor amplify signaling by orthosteric agonists. Allosteric enhancers are appealing drug candidates because their activity requires that the orthosteric site be occupied by an agonist, thereby conferring specificity to stressed or injured tissues that produce adenosine. To explore the mechanism of allosteric enhancer activity, we examined their action on several A1 receptor constructs, including (1) species variants, (2) species chimeras, (3) alanine scanning mutants, and (4) site-specific mutants. These findings were combined with homology modeling of the A1 receptor and in silico screening of an allosteric enhancer library. The binding modes of known docked allosteric enhancers correlated with the known structure-activity relationship, suggesting that these allosteric enhancers bind to a pocket formed by the second extracellular loop, flanked by residues S150 and M162. We propose a model in which this vestibule controls the entry and efflux of agonists from the orthosteric site and agonist binding elicits a conformational change that enables allosteric enhancer binding. This model provides a mechanism for the observations that allosteric enhancers slow the dissociation of orthosteric agonists but not antagonists.

  20. Amygdala activity related to enhanced memory for pleasant and aversive stimuli.

    Science.gov (United States)

    Hamann, S B; Ely, T D; Grafton, S T; Kilts, C D

    1999-03-01

    Pleasant or aversive events are better remembered than neutral events. Emotional enhancement of episodic memory has been linked to the amygdala in animal and neuropsychological studies. Using positron emission tomography, we show that bilateral amygdala activity during memory encoding is correlated with enhanced episodic recognition memory for both pleasant and aversive visual stimuli relative to neutral stimuli, and that this relationship is specific to emotional stimuli. Furthermore, data suggest that the amygdala enhances episodic memory in part through modulation of hippocampal activity. The human amygdala seems to modulate the strength of conscious memory for events according to emotional importance, regardless of whether the emotion is pleasant or aversive.

  1. 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.

  2. Enhancing laboratory activity with computer-based tutorials

    Directory of Open Access Journals (Sweden)

    Gordon Ritchie

    1995-12-01

    Full Text Available In a degree course in electronic engineering, great importance is attached to laboratory work, in which students have the opportunity to develop their creative skills in a practical environment. For example, in the first year of the course they are expected to design and test some basic circuits using data available on the characteristics of the semiconductor devices to be used. Many of the students cannot be prepared sufficiently for this activity by attendance at lectures, in which basic principles are expounded to large classes. Firstyear students have widely differing knowledge, experience and ability in circuit design. Therefore, without individual tuition many of them are insufficiently prepared for their laboratory work. Weaker students often neglect to study the laboratory documentation thoroughly in advance and they make poor progress in the laboratory.

  3. Active sampling technique to enhance chemical signature of buried explosives

    Science.gov (United States)

    Lovell, John S.; French, Patrick D.

    2004-09-01

    Deminers and dismounted countermine engineers commonly use metal detectors, ground penetrating radar and probes to locate mines. Many modern landmines have a very low metal content, which severely limits the effectiveness of metal detectors. Canines have also been used for landmine detection for decades. Experiments have shown that canines smell the explosives which are known to leak from most types of landmines. The fact that dogs can detect landmines indicates that vapor sensing is a viable approach to landmine detection. Several groups are currently developing systems to detect landmines by "sniffing" for the ultra-trace explosive vapors above the soil. The amount of material that is available to passive vapor sensing systems is limited to no more than the vapor in equilibrium with the explosive related chemicals (ERCs) distributed in the surface soils over and near the landmine. The low equilibrium vapor pressure of TNT in the soil/atmosphere boundary layer and the limited volume of the boundary layer air imply that passive chemical vapor sensing systems require sensitivities in the picogram range, or lower. ADA is working to overcome many of the limitations of passive sampling methods, by the use of an active sampling method that employs a high-powered (1,200+ joules) strobe lamp to create a highly amplified plume of vapor and/or ERC-bearing fine particulates. Initial investigations have demonstrated that this approach can amplify the detectability of TNT by two or three orders of magnitude. This new active sampling technique could be used with any suitable explosive sensor.

  4. Hollow mesoporous titania microspheres: New technology and enhanced photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Zhenliang; Wei, Wenrui; Wang, Litong [School of Chemical Engineering, Fuzhou University, Fuzhou 350108 (China); Hong, Ruoyu, E-mail: rhong@suda.edu.cn [School of Chemical Engineering, Fuzhou University, Fuzhou 350108 (China); College of Chemistry, Chemical Engineering and Materials Science & Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China)

    2015-12-01

    Graphical abstract: Schematic of the formation process of HTS. - Highlights: • Amino modified porous PS-DVB microspheres were used as templates to coat TiO{sub 2.} • The coating of TiO{sub 2} was conducted under regular changing atmospheric pressure. • The PS-DVB@TiO{sub 2} was calcinated first under nitrogen and then under air to get HTS. • The resultant products were provided with high surface area and excellent photocatalytic activity under UV irradiation. - Abstract: Hollow titania microspheres (HTS) were fabricated via a sol–gel process by coating the hydrolysis product of titanium tetrabutoxide (TBOT) onto the amino (–NH{sub 2}) modified porous polystyrene cross-linked divinyl benzene (PS-DVB) microspheres under changing atmospheric pressure, followed by calcination in nitrogen and air atmosphere. Particularly, the atmospheric pressure was continuously and regularly changed during the formation process of PS-DVB@TiO{sub 2} microspheres. Then the TiO{sub 2} particles were absorbed into the pores and onto the surface of PS-DVB as well. The resultant HTS (around 2 μm in diameter) featured a high specific surface area (84.37 m{sup 2}/g), anatase crystal and stable hollow microsphere structure, which led to high photocatalysis activity. The photocatalytic degradation of malachite green (MG) organic dye solution was conducted under ultraviolet (UV) light irradiation, which showed a high photocatalytic ability (81% of MG was degraded after UV irradiation for 88 min). Therefore, it could be potentially applied for the treatment of wastewater contaminated by organic pollutants.

  5. 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.

  6. 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.

  7. Highly reproducible surface-enhanced Raman scattering-active Au nanostructures prepared by simple electrodeposition: origin of surface-enhanced Raman scattering activity and applications as electrochemical substrates.

    Science.gov (United States)

    Choi, Suhee; Ahn, Miri; Kim, Jongwon

    2013-05-24

    The fabrication of effective surface-enhanced Raman scattering (SERS) substrates has been the subject of intensive research because of their useful applications. In this paper, dendritic gold (Au) rod (DAR) structures prepared by simple one-step electrodeposition in a short time were examined as an effective SERS-active substrate. The SERS activity of the DAR surfaces was compared to that of other nanostructured Au surfaces with different morphologies, and its dependence on the structural variation of DAR structures was examined. These comparisonal investigations revealed that highly faceted sharp edge sites present on the DAR surfaces play a critical role in inducing a high SERS activity. The SERS enhancement factor was estimated to be greater than 10(5), and the detection limit of rhodamine 6G at DAR surfaces was 10(-8)M. The DAR surfaces exhibit excellent spot-to-spot and substrate-to-substrate SERS enhancement reproducibility, and their long-term stability is very good. It was also demonstrated that the DAR surfaces can be effectively utilized in electrochemical SERS systems, wherein a reversible SERS behavior was obtained during the cycling to cathodic potential regions. Considering the straightforward preparation of DAR substrates and the clean nature of SERS-active Au surfaces prepared in the absence of additives, we expect that DAR surfaces can be used as cost-effective SERS substrates in analytical and electrochemical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Metabolic factors affecting enhanced phosphorus uptake by activated sludge.

    Science.gov (United States)

    Boughton, W H; Gottfried, R J; Sinclair, N A; Yall, I

    1971-10-01

    Activated sludges obtained from the Rilling Road plant located at San Antonio, Tex., and from the Hyperion treatment plant located at Los Angeles, Calif., have the ability to remove all of the orthophosphate normally present in Tucson sewage within 3 hr after being added to the waste water. Phosphorus removal was independent of externally supplied sources of energy and ions, since orthophosphate and (32)P radioactivity were readily removed from tap water, glass-distilled water, and deionized water. Phosphorus uptake by Rilling sludge in the laboratory appears to be wholly biological, as it has an optimum pH range (7.7 to 9.7) and an optimum temperature range (24 to 37 C). It was inhibited by HgCl(2), iodoacetic acid, p-chloromercuribenzoic acid, NaN(3), and 2, 4-dinitrophenol (compounds that affect bacterial membrane permeability, sulfhydryl enzymes, and adenosine triphosphate synthesis). Uptake was inhibited by 1% NaCl but was not affected by 10(-3)m ethylenediaminetetraacetic acid disodium salt (a chelating agent for many metallic ions).

  9. The enhancement of immunological activity by mild hypothermia

    International Nuclear Information System (INIS)

    Hasegawal, Takeo; Gu, Yeun Hwa; Miyata, Katuyuki

    2004-01-01

    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. 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.

  11. Contemplation of wheat genotypes for enhanced antioxidant enzyme activity

    International Nuclear Information System (INIS)

    Nasim, S.; Shabbir, G.; Ilyas, M.

    2017-01-01

    Wheat (Triticum aestivum L.) is leading cereal crop in Pakistan but its yield is highly affected due to various abiotic factors especially drought stress, which affects the metabolism of plants. The present study was conducted at Pir Mehr Ali Shah Arid Agriculture University Rawalpindi, using thirty three genotypes during 2011 to investigate the response of anti oxidative enzymes. Seedlings were subjected to stress condition with 30 % PEG 6000 solution along with control (irrigated with water) under in vitro conditions. The experiment was conducted in pots following Complete Randomized Design in Laboratory. Results revealed that under control conditions the maximum values for Guaiacol peroxidase were found in Punjab-96 and Auqab-2000 (2.523), for superoxide in C-273 (0.294), for ascorbate peroxide in PAK-81 (2.523) and for catalase in Kohsar-95 (0.487). Under moisture stress condition the maximum value for Guaiacol peroxidase were recorded for Kohsar-95 (2.699), for superoxide in Kohsar-95 (1.259), for ascorbate peroxide in Pak-81, SA-75, Mexipak-65 and PARI-73 (3.000) and for catalase in Mexipak-65 (0.640). The genotypes which showed higher antioxidant enzyme activity under drought stress have the ability to perform better under adverse soil moisture condition. Such potential genotypes can be utilized in the future breeding programs and also in improving the wheat varieties against drought stress. (author)

  12. 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.

  13. Microwave activation of palladium nanoparticles for enhanced ethanol electrocatalytic oxidation reaction in alkaline medium

    CSIR Research Space (South Africa)

    Rohwer, MB

    2015-02-01

    Full Text Available in alkaline medium (in terms of high mass activity stability and fast reaction kinetics). The remarkable microwave-induced properties on the Pd catalyst promise to revolutionize the use of microwave for catalyst activation for enhanced heterogeneous catalysis...

  14. 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

  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

    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, ...

  17. Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1

    Directory of Open Access Journals (Sweden)

    Karla A. Mark

    2016-10-01

    Full Text Available Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1. Vitamin D3 (D3 induced expression of SKN-1 target genes but not canonical targets of XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.

  18. 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

    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...... stability analysis of grid converters in the weak grid. Based on the impedance model of the series LC filtered active damper, the real part of its output admittance is investigated and shown to be able to enhance the passivity of the admittance of the converters seen by the grid. Finally, simulation...

  19. Xenobiotics enhance laccase activity in alkali-tolerant γ-proteobacterium JB.

    Science.gov (United States)

    Singh, Gursharan; Batish, Mona; Sharma, Prince; Capalash, Neena

    2009-01-01

    Various genotoxic textile dyes, xenobiotics, substrates (10 µM) and agrochemicals (100 µg/ml) were tested for enhancement of alkalophilic laccase activity in γ-proteobacterium JB. Neutral Red, Indigo Carmine, Naphthol Base Bordears and Sulphast Ruby dyes increased the activity by 3.7, 2.7, 2.6 and 2.3 fold respectively. Xenobiotics/substrates like p-toluidine, 8-hydroxyquinoline and anthracine increased it by 3.4, 2.8 and 2.3 fold respectively. Atrazine and trycyclozole pesticides enhanced the activity by 1.95 and 1.5 fold respectively.

  20. 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.

  1. Contrast-enhanced ultrasonography for the determination of Crohn’s disease activity – preliminary experience

    Science.gov (United States)

    Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Kłopocka, Maria; Liebert, Ariel; Lemanowicz, Adam; Serafin, Zbigniew

    2014-01-01

    Summary Background Contrast-enhanced ultrasound (CEUS) is a recent non-invasive modality, which may partially replace currently used techniques (endoscopy, CT enterography and MR enterography) in the diagnostics and assessment of Crohn’s disease (CD). The aim of the study was to analyze early experience in the use of CEUS for the measurement of activity and staging of CD. Material/Methods Eleven patients previously diagnosed with CD were included in the study. They underwent contrast-enhanced ultrasonography (SonoVue, Bracco), low-dose CT enterography (LDCTE), assessment of laboratory markers of inflammation and clinical CD activity index (CDAI). Contrast enhancement was evaluated using a semi-quantitative method and a quantitative method that included measurement of peak enhancement (PE), enhancement curve rise time (RT) and wash-in-rate (WiR). Results Ileal wall thickening was observed in all patients. Semi-quantitative method was used to observe CD activity in CEUS in 10 cases that perfectly matched LDCTE findings. There was a moderate positive correlation between PE and CDAI (r=0.65, p<0.001). There was no significant relationship between perfusion parameters and laboratory markers of inflammation. Conclusions CEUS is a promising modality for non-invasive assessment of pathologic ileal vascularization in the course of Crohn’s disease. Intensity of enhancement in CEUS reflects activity of the disease detected in LDCTE and correlates with CDAI. PMID:24723988

  2. Contrast-enhanced ultrasonography for the determination of Crohn's disease activity - preliminary experience.

    Science.gov (United States)

    Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Kłopocka, Maria; Liebert, Ariel; Lemanowicz, Adam; Serafin, Zbigniew

    2014-01-01

    Contrast-enhanced ultrasound (CEUS) is a recent non-invasive modality, which may partially replace currently used techniques (endoscopy, CT enterography and MR enterography) in the diagnostics and assessment of Crohn's disease (CD). The aim of the study was to analyze early experience in the use of CEUS for the measurement of activity and staging of CD. Eleven patients previously diagnosed with CD were included in the study. They underwent contrast-enhanced ultrasonography (SonoVue, Bracco), low-dose CT enterography (LDCTE), assessment of laboratory markers of inflammation and clinical CD activity index (CDAI). Contrast enhancement was evaluated using a semi-quantitative method and a quantitative method that included measurement of peak enhancement (PE), enhancement curve rise time (RT) and wash-in-rate (WiR). Ileal wall thickening was observed in all patients. Semi-quantitative method was used to observe CD activity in CEUS in 10 cases that perfectly matched LDCTE findings. There was a moderate positive correlation between PE and CDAI (r=0.65, p<0.001). There was no significant relationship between perfusion parameters and laboratory markers of inflammation. CEUS is a promising modality for non-invasive assessment of pathologic ileal vascularization in the course of Crohn's disease. Intensity of enhancement in CEUS reflects activity of the disease detected in LDCTE and correlates with CDAI.

  3. Contrast-enhanced ultrasonography for the determination of Crohn’s disease activity – preliminary experience

    International Nuclear Information System (INIS)

    Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Kłopocka, Maria; Liebert, Ariel; Lemanowicz, Adam; Serafin, Zbigniew

    2014-01-01

    Contrast-enhanced ultrasound (CEUS) is a recent non-invasive modality, which may partially replace currently used techniques (endoscopy, CT enterography and MR enterography) in the diagnostics and assessment of Crohn’s disease (CD). The aim of the study was to analyze early experience in the use of CEUS for the measurement of activity and staging of CD. Eleven patients previously diagnosed with CD were included in the study. They underwent contrast-enhanced ultrasonography (SonoVue, Bracco), low-dose CT enterography (LDCTE), assessment of laboratory markers of inflammation and clinical CD activity index (CDAI). Contrast enhancement was evaluated using a semi-quantitative method and a quantitative method that included measurement of peak enhancement (PE), enhancement curve rise time (RT) and wash-in-rate (WiR). Ileal wall thickening was observed in all patients. Semi-quantitative method was used to observe CD activity in CEUS in 10 cases that perfectly matched LDCTE findings. There was a moderate positive correlation between PE and CDAI (r=0.65, p<0.001). There was no significant relationship between perfusion parameters and laboratory markers of inflammation. CEUS is a promising modality for non-invasive assessment of pathologic ileal vascularization in the course of Crohn’s disease. Intensity of enhancement in CEUS reflects activity of the disease detected in LDCTE and correlates with CDAI

  4. 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).

  5. 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.

  6. The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

    OpenAIRE

    Hernández-García, Susana; San-Segundo, Laura; González-Méndez, Lorena; Corchete, Luis A; Misiewicz-Krzeminska, Irena; Martín-Sánchez, Montserrat; López-Iglesias, Ana-Alicia; Algarín, Esperanza Macarena; Mogollón, Pedro; Díaz-Tejedor, Andrea; Paíno, Teresa; Tunquist, Brian; Mateos, María-Victoria; Gutiérrez, Norma C; Díaz-Rodriguez, Elena

    2017-01-01

    [EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomali...

  7. Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers

    Science.gov (United States)

    Sérandour, Aurélien A.; Avner, Stéphane; Percevault, Frédéric; Demay, Florence; Bizot, Maud; Lucchetti-Miganeh, Céline; Barloy-Hubler, Frédérique; Brown, Myles; Lupien, Mathieu; Métivier, Raphaël; Salbert, Gilles; Eeckhoute, Jérôme

    2011-01-01

    Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation. PMID:21233399

  8. 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.

  9. Enhanced bag of words using multilevel k-means for human activity recognition

    Directory of Open Access Journals (Sweden)

    Motasem Elshourbagy

    2016-07-01

    Full Text Available This paper aims to enhance the bag of features in order to improve the accuracy of human activity recognition. In this paper, human activity recognition process consists of four stages: local space time features detection, feature description, bag of features representation, and SVMs classification. The k-means step in the bag of features is enhanced by applying three levels of clustering: clustering per video, clustering per action class, and clustering for the final code book. The experimental results show that the proposed method of enhancement reduces the time and memory requirements, and enables the use of all training data in the k-means clustering algorithm. The evaluation of accuracy of action classification on two popular datasets (KTH and Weizmann has been performed. In addition, the proposed method improves the human activity recognition accuracy by 5.57% on the KTH dataset using the same detector, descriptor, and classifier.

  10. 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

  11. Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid β-oxidation and ketogenesis via activating XBP1 signaling in liver

    Directory of Open Access Journals (Sweden)

    Meiyuan Zhang

    2018-06-01

    Full Text Available Liver coordinates a series of metabolic adaptations to maintain systemic energy balance and provide adequate nutrients for critical organs, tissues and cells during starvation. However, the mediator(s implicated in orchestrating these fasting-induced adaptive responses and the underlying molecular mechanisms are still obscure. Here we show that hepatic growth differentiation factor 15 (GDF15 is regulated by IRE1α-XBP1s branch and promotes hepatic fatty acids β-oxidation and ketogenesis upon fasting. GDF15 expression was exacerbated in liver of mice subjected to long-term fasted or ketogenic diet feeding. Abrogation of hepatic Gdf15 dramatically attenuated hepatic β-oxidation and ketogenesis in fasted mice or mice with STZ-initiated type I diabetes. Further study revealed that XBP1s activated Gdf15 transcription via binding to its promoter. Elevated GDF15 in liver reduced lipid accumulation and impaired NALFD development in obese mice through enhancing fatty acids oxidation in liver. Therefore, our results demonstrate a novel and critical role of hepatic GDF15 activated by IRE1α-XBP1s branch in regulating adaptive responses of liver upon starvation stress. Keywords: Fasting, Fatty acid β-oxidation, Ketogenesis, GDF15, XBP1, NAFLD

  12. Porous-ZnO-Nanobelt Film as Recyclable Photocatalysts with Enhanced Photocatalytic Activity

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-01-01

    Full Text Available Abstract In this article, the porous-ZnO-nanobelt film was synthesized by oxidizing the ZnSe-nanobelt film in air. The experiment results show that the porous-ZnO-nanobelt film possesses enhanced photocatalytic activity compared with the ZnO-nanobelt film, and can be used as recyclable photocatalysts. The enhanced photocatalytic activity of the porous-ZnO-nanobelt film is attributed to the increased surface area. Therefore, turning the 1D-nanostructure film into porous one may be a feasible approach to meet the demand of photocatalyst application.

  13. 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.

  14. 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.

  15. Activation of peroxisome proliferator-activated receptor-α enhances fatty acid oxidation in human adipocytes

    International Nuclear Information System (INIS)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki; Kawada, Teruo

    2011-01-01

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

  16. 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

    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...... 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...

  17. 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.

  18. Mast cells enhance T cell activation: Importance of mast cell-derived TNF

    Science.gov (United States)

    Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

    2005-05-01

    Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

  19. Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory.

    Science.gov (United States)

    Liu, Yu-Zhang; Wang, Yao; Shen, Weida; Wang, Zhiru

    2017-08-01

    Learning and memory storage requires neuronal plasticity induced in the hippocampus and other related brain areas, and this process is thought to rely on synchronized activity in neural networks. We used paired whole-cell recording in vivo to examine the synchronized activity that was induced in hippocampal CA1 neurons by associative fear learning. We found that both membrane potential synchronization and spike synchronization of CA1 neurons could be transiently enhanced after task learning, as observed on day 1 but not day 5. On day 1 after learning, CA1 neurons showed a decrease in firing threshold and rise times of suprathreshold membrane potential changes as well as an increase in spontaneous firing rates, possibly contributing to the enhancement of spike synchronization. The transient enhancement of CA1 neuronal synchronization may play important roles in the induction of neuronal plasticity for initial storage and consolidation of associative memory. The hippocampus is critical for memory acquisition and consolidation. This function requires activity- and experience-induced neuronal plasticity. It is known that neuronal plasticity is largely dependent on synchronized activity. As has been well characterized, repetitive correlated activity of presynaptic and postsynaptic neurons can lead to long-term modifications at their synapses. Studies on network activity have also suggested that memory processing in the hippocampus may involve learning-induced changes of neuronal synchronization, as observed in vivo between hippocampal CA3 and CA1 networks as well as between the rhinal cortex and the hippocampus. However, further investigation of learning-induced synchronized activity in the hippocampus is needed for a full understanding of hippocampal memory processing. In this study, by performing paired whole-cell recording in vivo on CA1 pyramidal cells (PCs) in anaesthetized adult rats, we examined CA1 neuronal synchronization before and after associative fear

  20. Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

    Science.gov (United States)

    Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

    2016-01-01

    Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms

  1. Gamma radiation induced enhancement in the antioxidant and radioprotective activities of flavonoids

    International Nuclear Information System (INIS)

    Arul Anantha Kumar, A.; Sonwani, Swetha; Bakkiam, D.

    2018-01-01

    Recently γ-radiation has been used as a tool to induce structural changes in natural biomolecules to enhance their biological and physiological properties. Flavonoids are a family of plant derived polyphenolic compounds having considerable scientific and therapeutic importance. Structurally they are the benzo-γ-pyrone derivatives containing phenolic and pyrane rings. Flavonoid radioprotection is an intense area of research thanks to features like natural origin, effectiveness at non-toxic dose levels and lack of side effects. But till date no report is available on the effect of γ-radiation mediated enhancement in radioprotection activity of flavonoids. In view of this the present study was carried out to determine the γ-radiation induced structural changes in selected flavonoids i.e. apigenin, naringenin and genistein and also to explore the possibility of enhancement in their antioxidant and radioprotective activities

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

    KAUST Repository

    Rahal, Raed; Wankhade, Atul V.; Cha, Dong Kyu; Fihri, Aziz; Ould-Chikh, Samy; Patil, Umesh; Polshettiwar, Vivek

    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.

  3. 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.

  4. 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.

  5. The Effectiveness of Cooperative Learning Activities in Enhancing EFL Learners' Fluency

    Science.gov (United States)

    Alrayah, Hassan

    2018-01-01

    This research-paper aims at examining the effectiveness of cooperative learning activities in enhancing EFL learners' fluency. The researcher has used the descriptive approach, recorded interviews for testing fluency as tools of data collection and the software program SPSS as a tool for the statistical treatment of data. Research sample consists…

  6. Enhanced coagulation activation in preeclampsia: the role of APC resistance, microparticles and other plasma constituents

    NARCIS (Netherlands)

    VanWijk, Marja J.; Boer, Kees; Berckmans, René J.; Meijers, Joost C. M.; van der Post, Joris A. M.; Sturk, Augueste; VanBavel, Ed; Nieuwland, Rienk

    2002-01-01

    Coagulation activation in pregnancy is further enhanced in preeclampsia. We investigated whether this results from increased thrombin generation by the plasma itself or its cell-derived microparticles. Plasma samples were obtained from preeclamptic, normal pregnant and nonpregnant women (each n =

  7. Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

    NARCIS (Netherlands)

    Muris, A.H.; Rolf, L.; Damoiseaux, J.; Koeman, E.; Hupperts, R.

    2014-01-01

    Background: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNβ) or placebo. The effect of

  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. 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...

  10. Photon activation therapy with 127I-deoxyuridine: measurement of dose enhancement in cultured mammalian cells

    International Nuclear Information System (INIS)

    Fairchild, R.G.; Laster, B.H.; Commerford, S.L.; Furcinitti, P.S.; Sylvester, B.; Gabel, D.; Popenoe, E.; Foster, S.

    1985-01-01

    A technique for radiation enhancement of conventional photon radiotherapy is outlined which has been called photon activation therapy (PAT) (6). High linear energy transfer (LET) radiations in the form of Auger electron distributions are generated by photons of appropriate energies, through photon activation of stable iodine incorporated as an analog of thymidine (Tyd) in DNA. Of the several halogenated deoxyribonucleosides evaluated, iodinated deoxyuridine (IdUrd) has been chosen as the only Tyd analog providing effective photon activation. This mechanism is combined with radiation sensitization produced by IdUrd to produce an overall radiation enhancement. Calculations show that at 5% replacement (IdUrd for Tyd) therapeutic (TG) will vary from ∼2 (single acute dose) to ∼17 (low dose rates associated with permanent implant brachytherapy). Parameters used in the calculation of TG have been evaluated in cell culture; dose enhancements obtained with x-rays (including photon activation) were found to be significantly higher than values measured with γ-rays (no photon activation). Comparison is made between theoretical and measured values. Because of the evident lack of repair of damage produced by both sensitization and photon activation, significant gains are expected to be realized following protracted irradiations. Exchanges (IdUrd for Tyd) for 105 have been obtained in vivo (murine tumors). The authors believe that the application of PAT would be most advantageous in the treatment of brain tumors (grade IV astrocytomas) with implanted 145 Sm sources

  11. 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.

  12. 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

  13. Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

    International Nuclear Information System (INIS)

    Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

    2006-01-01

    Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

  14. 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.

  15. 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.

  16. 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

  17. Metal-chelating active packaging film enhances lysozyme inhibition of Listeria monocytogenes.

    Science.gov (United States)

    Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2014-07-01

    Several studies have demonstrated that metal chelators enhance the antimicrobial activity of lysozyme. This study examined the effect of metal-chelating active packaging film on the antimicrobial activity of lysozyme against Listeria monocytogenes. Polypropylene films were surface modified by photoinitiated graft polymerization of acrylic acid (PP-g-PAA) from the food contact surface of the films to impart chelating activity based on electrostatic interactions. PP-g-PAA exhibited a carboxylic acid density of 113 ± 5.4 nmol cm(-2) and an iron chelating activity of 53.7 ± 9.8 nmol cm(-2). The antimicrobial interaction of lysozyme and PP-g-PAA depended on growth media composition. PP-g-PAA hindered lysozyme activity at low ionic strength (2.48-log increase at 64.4 mM total ionic strength) and enhanced lysozyme activity at moderate ionic strength (5.22-log reduction at 120 mM total ionic strength). These data support the hypothesis that at neutral pH, synergy between carboxylate metal-chelating films (pKa(bulk) 6.45) and lysozyme (pI 11.35) is optimal in solutions of moderate to high ionic strength to minimize undesirable charge interactions, such as lysozyme absorption onto film. These findings suggest that active packaging, which chelates metal ions based on ligand-specific interactions, in contrast to electrostatic interactions, may improve antimicrobial synergy. This work demonstrates the potential application of metal-chelating active packaging films to enhance the antimicrobial activity of membrane-disrupting antimicrobials, such as lysozyme.

  18. 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

  19. Enhancing the water oxidation activity of Ni2P nanocatalysts by iron-doping and electrochemical activation

    International Nuclear Information System (INIS)

    Liu, Guang; He, Dongying; Yao, Rui; Zhao, Yong; Li, Jinping

    2017-01-01

    Highlights: •A sol-gel method for synthesis of Fe-doping Ni 2 P nanocatalysts was present. •Fe-doping Ni 2 P sample exhibited high OER activity after electrochemical activation. •In situ formed Fe-NiOOH layer on activated Fe-Ni 2 P provided more active OER sites. -- Abstract: In this work, we reported a facile and safe route for synthesis of Ni 2 P nanocatalysts by sol-gel method and demonstrated that the oxygen evolution reaction (OER) activity of Ni 2 P nanocatalysts can be dramatically enhanced by iron-doping and electrochemical activation. Compared with the fresh Fe-doped Ni 2 P nanocatalysts, a stable Fe-NiOOH layer was formed on the surface of Fe-doped Ni 2 P nanoparticles by electrochemical activation, thus promoting the charge transfer ability and surface electrochemically active sites generation for the electrochemical activated Fe-doped Ni 2 P nanocatalysts, ultimately accounting for the improvement of water oxidation activity, which was evidenced by cyclic voltammograms (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectra (XPS) as well as high-resolution transmission electron microscopy (HR-TEM) measurements. For water oxidation reaction in 1 M KOH solution, the electrochemical activated Fe-doped Ni 2 P nanocatalysts can attain 10 mA/cm 2 at an overpotential of 292 mV with Tafel slope of 50 mV/dec, which was also much better than that of individual Ni 2 P, Fe 2 P nanocatalysts as well as commercial RuO 2 electrocatalyst. Moreover, long-term stability performance by chronoamperometric and chronopotentiometric tests for the activated Fe-doped Ni 2 P nanocatalysts exhibited no obvious decline within 56 h. It was demonstrated that modulating the OER catalytic activity for metal phosphide by iron-doping and electrochemical activation may provide new opportunities and avenues to engineer high performance electrocatalysts for water splitting.

  20. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    Science.gov (United States)

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  1. Health physics experience on the decommissioning of Thorium plant of IRE Ltd. at Trombay

    International Nuclear Information System (INIS)

    Savant, P.B.; Venkata Rao, D.V.; Rangarajan, R.; Pushparaja

    2003-01-01

    Thorium plant which was in operation for the last 45 years at Trombay, was decommissioned during the period 1999-2001. The decommissioning operation was spread over a period of 18 months. Over the years of operations, considerable activity was build-up was on the plant equipment and supporting structures. A new plant is erected at OSCOM to meet the thorium nitrate requirement. In view of the aging of the process equipment and resulting increase in the Person-Sv expenditure, it was decided to decommission the plant at Trombay. Decommissioning work is a voluminous job and hence required a careful planning of manpower, budgeting of personnel exposures and safe transfer of radioactive wastes. A considerable reduction in the budgeted man- days was achieved by using appropriate machinery and modern gadgets. A total of 3465 man-days were utilised for the work. 40 contract labourers were engaged in two phases. The total dose received was 123.32 Person-mSv as against the budgeted 189.29 Person-mSv for the entire operation. The maximum individual whole body dose received was 4.5 mSv. Around 2000 m 3 of low level radioactive solid waste was disposed off. Chipping of walls and floor has resulted in reduction of the volume of low level waste by as much as 766 m 3 as compared-to estimated volume of 4000 m 3 . This paper discusses briefly the experience gained by the RHC Unit in providing RHC surveillance for the decommissioning work. (author)

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

    Science.gov (United States)

    Chen, Wei; Rakhi, R. B.; Alshareef, H. N.

    2013-05-01

    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).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). Electronic supplementary information (ESI) available: Experimental section, supporting figures including SEM, TEM, XPS, BET, CV and CD curves and a summary table of capacitance. See DOI: 10.1039/c3nr00773a

  3. 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.

  4. 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.

  5. Robust Identification of Developmentally Active Endothelial Enhancers in Zebrafish Using FANS-Assisted ATAC-Seq.

    Science.gov (United States)

    Quillien, Aurelie; Abdalla, Mary; Yu, Jun; Ou, Jianhong; Zhu, Lihua Julie; Lawson, Nathan D

    2017-07-18

    Identification of tissue-specific and developmentally active enhancers provides insights into mechanisms that control gene expression during embryogenesis. However, robust detection of these regulatory elements remains challenging, especially in vertebrate genomes. Here, we apply fluorescent-activated nuclei sorting (FANS) followed by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to identify developmentally active endothelial enhancers in the zebrafish genome. ATAC-seq of nuclei from Tg(fli1a:egfp) y1 transgenic embryos revealed expected patterns of nucleosomal positioning at transcriptional start sites throughout the genome and association with active histone modifications. Comparison of ATAC-seq from GFP-positive and -negative nuclei identified more than 5,000 open elements specific to endothelial cells. These elements flanked genes functionally important for vascular development and that displayed endothelial-specific gene expression. Importantly, a majority of tested elements drove endothelial gene expression in zebrafish embryos. Thus, FANS-assisted ATAC-seq using transgenic zebrafish embryos provides a robust approach for genome-wide identification of active tissue-specific enhancer elements. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. 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.

  7. Study on CO{sub 2} absorption enhancement by adding active carbon particles into MEA solution

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Juan; Sun, Rui; Ma, Lian; Sun, Shaozeng [Harbin Institute of Technology, Harbin (China). School of Energy Science and Engineering

    2013-07-01

    The chemical absorption of CO{sub 2} is generally recognized as the most efficient post-combustion technology of CO{sub 2} separation at present. A study on CO{sub 2} absorption enhancement by adding small particles of active carbon into MEA solution is investigated within a self-designed glass stirring tank. Experiments of different particle loadings and different particle sizes have been conducted. When active carbon particle concentration is fewer, compared to the absorption rate of CO{sub 2} gas absorbed by MEA aqueous solution, the role of active carbon adsorption CO{sub 2} gas is negligible. The enhancement efficiency of CO{sub 2} absorption could be improved by 10% to the upmost in this liquid-particle system.

  8. Antimicrobial activity of Bacillus amyloliquefaciens LBM 5006 is enhanced in the presence of Escherichia coli.

    Science.gov (United States)

    Benitez, Lisianne; Correa, AnaPaula; Daroit, Daniel; Brandelli, Adriano

    2011-03-01

    Increased antimicrobial activity was observed when Bacillus amyloliquefaciens LBM 5006 strain was cultivated in the presence of thermally inactivated cells of Escherichia coli, but not with Staphylococcus aureus, Listeria monocytogenes, or Bacillus cereus. E. coli also enhanced the antimicrobial activity when it was added to the medium in the form of living cells or as cell debris after cellular fractionation. No inducing activity was observed with addition of cell-free supernatant of E. coli cultures, suggesting that inducing factor is associated to the cells. Polyacrylamide gel electrophoresis revealed that additional peptide bands are secreted when B. amyloliquefaciens was cultivated in the presence of cell debris of E. coli. These results suggest that the presence of intact or inactivated E. coli enhanced the synthesis of antimicrobial peptides by B. amyloliquefaciens LBM 5006.

  9. 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.

  10. 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.

  11. Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae.

    Science.gov (United States)

    Ioannou, Petros; Andrianaki, Aggeliki; Akoumianaki, Tonia; Kyrmizi, Irene; Albert, Nathaniel; Perlin, David; Samonis, George; Kontoyiannis, Dimitrios P; Chamilos, Georgios

    2015-12-07

    The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin with Aspergillus hyphae (P hyphae. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae

    Science.gov (United States)

    Ioannou, Petros; Andrianaki, Aggeliki; Akoumianaki, Tonia; Kyrmizi, Irene; Albert, Nathaniel; Perlin, David; Samonis, George

    2015-01-01

    The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin with Aspergillus hyphae (P Aspergillus hyphae. PMID:26643329

  13. Memory-enhancing activity of Anacyclus pyrethrum in albino Wistar rats

    Directory of Open Access Journals (Sweden)

    K Sujith

    2012-08-01

    Full Text Available Objective: To explore the potential effect of ethanolic extract of Anacyclus pyrethrum (A. pyrethrum in memory dysfunction. Methods: Memory impairment was produced by administration of scopolamine (1mg/kg i. p in rats. Passive avoidance paradigms, elevated plus maze and social learning task was used to assess learning and memory. Results: A. pyrethrum extract treated group decreased transfer latency in elevated plus maze model paradigm which is an indicative of cognition improvement. In case of passive avoidance paradigm extract treated group exhibited prounced effect in reversal of scopolamine induced amnesia which was revealed by increase in step down latency. Social learning task also revealed the memory enhancing activity of A. pyrethrum extract. Conclusions: Ethanolic extract of A. pyrethrum has been demonstrated to improve cognitive processes by enhancing memory in different experimental paradigms such as passive avoidance paradigms, elevated plus maze and social learning task when administered orallyBrain cholinesterase level was measured to assess central cholinergic activity. The treatment with drugs, which increase cholinergic neurotransmission, causes an improvement in cognitive deficits. The present study suggest that ethanolic extract of A. pyrethrum increased brain cholinesterase level and hence it possess memory enhancing activity in scopolamine induced amnesia model by enhancing central cholinergic neurotransmission.

  14. Enhanced photocatalytic activity of SrTiO3 photocatalyst by topotactic preparation

    Science.gov (United States)

    Cao, Jiafeng; Huang, Xianshan; Liu, Yi; Wu, Jianguang; Ji, Yuexia

    2016-11-01

    Novel SrTiO3 (ST) photocatalysts with different shapes such as plates, rods and cubes were successfully synthesized based on a topotactic approach. The rod-like ST particles formed in situ at the plates show superior photocatalytic activities towards the decomposition of Rhodamine B than the plate-like and the cubic particles under visible-light irradiation, which could be attributed to the crystal orientation exposing highly active sites accompanied by the crystallite growth in molten salt. The results reveal an effective approach for fabrication of novel photocatalysts of perovskite structure with enhanced photocatalytic activities.

  15. Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

    International Nuclear Information System (INIS)

    Rainio, Eeva-Marja; Ahlfors, Helena; Carter, Kara L.; Ruuska, Marja; Matikainen, Sampsa; Kieff, Elliott; Koskinen, Paeivi J.

    2005-01-01

    Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth

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

    DEFF Research Database (Denmark)

    Dau, Torsten; Catic, Jasmina; Buchholz, Jörg

    2010-01-01

    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...... 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...

  18. Contrast-enhanced ultrasound imaging of active bleeding associated with hepatic and splenic trauma.

    Science.gov (United States)

    Lv, F; Tang, J; Luo, Y; Li, Z; Meng, X; Zhu, Z; Li, T

    2011-10-01

    The aim of this study was to evaluate contrast-enhanced ultrasound (CEUS) imaging of active bleeding from hepatic and splenic trauma. Three hundred and ninety-two patients with liver or/and spleen trauma (179 liver and 217 spleen injuries), who underwent CEUS examinations following contrast-enhanced computed tomography (CT), were enrolled in this retrospective study over a period of >4 years. CEUS detected contrast medium extravasation or pooling in 16% (63/396) of liver or spleen lesions in 61 patients, which was confirmed by contrast-enhanced CT. Special attention was paid to observing the presence, location, and characteristics of the extravasated or pooled contrast medium. The CEUS detection rate for active bleeding was not different from that of contrast-enhanced CT (p=0.333). Information from surgery, minimally invasive treatment and conservative treatment was used as reference standard, and the sensitivities of the two techniques were not different (p=0.122). Of 63 lesions in 61 patients, CEUS showed that 74.6% (47/63) (21 liver lesions and 26 spleen lesions) presented contrast medium extravasation or pooling, both in the organ and out the capsule, in 14.3% (9/63) and only outside the capsule in 11.1% (7/63). CEUS imaging of active bleeding from hepatic and splenic trauma presented various characteristics, and the sizes and shapes of the active bleeding due to contrast medium extravasation or pooling were variable. CEUS can show the active bleeding associated with hepatic and splenic trauma with various imaging characteristics, thus making it possible to diagnose active bleeding using CEUS.

  19. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

    Directory of Open Access Journals (Sweden)

    Takashi Watanabe

    Full Text Available Mastermind-like 1 (MAML1 is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2, a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2 from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1(-/- embryos at embryonic day 16.5 (E16.5 had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1 and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1 expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1(-/- mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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…

  5. Activation of the canonical Wnt/β-catenin pathway enhances monocyte adhesion to endothelial cells

    International Nuclear Information System (INIS)

    Lee, Dong Kun; Nathan Grantham, R.; Trachte, Aaron L.; Mannion, John D.; Wilson, Colleen L.

    2006-01-01

    Monocyte adhesion to vascular endothelium has been reported to be one of the early processes in the development of atherosclerosis. In an attempt to develop strategies to prevent or delay atherosclerosis progression, we analyzed effects of the Wnt/β-catenin signaling pathway on monocyte adhesion to various human endothelial cells. Adhesion of fluorescein-labeled monocytes to various human endothelial cells was analyzed under a fluorescent microscope. Unlike sodium chloride, lithium chloride enhanced monocyte adhesion to endothelial cells in a dose-dependent manner. We further demonstrated that inhibitors for glycogen synthase kinase (GSK)-3β or proteosome enhanced monocyte-endothelial cell adhesion. Results of semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) indicated that activation of Wnt/β-catenin pathway did not change expression levels of mRNA for adhesion molecules. In conclusion, the canonical Wnt/β-catenin pathway enhanced monocyte-endothelial cell adhesion without changing expression levels of adhesion molecules

  6. 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.

  7. Fraction From Lycium barbarum Polysaccharides Reduces Immunotoxicity and Enhances Antitumor Activity of Doxorubicin in Mice.

    Science.gov (United States)

    Deng, Xiangliang; Luo, Shuang; Luo, Xia; Hu, Minghua; Ma, Fangli; Wang, Yuanyuan; Zhou, Lian; Huang, Rongrong

    2018-01-01

    The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.

  8. A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.

    Science.gov (United States)

    Liu, Yan; Wang, Yubin; Zhu, Guoqi; Sun, Jiandong; Bi, Xiaoning; Baudry, Michel

    2016-06-01

    While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

    Science.gov (United States)

    Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

    2016-07-01

    Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

  10. Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.

    Science.gov (United States)

    Siefert, S A; Chabasse, C; Mukhopadhyay, S; Hoofnagle, M H; Strickland, D K; Sarkar, R; Antalis, T M

    2014-10-01

    The resolution of deep vein thrombosis requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. To investigate the role of PAI-2 in venous thrombus formation and resolution. Venous thrombus resolution was compared in wild-type C57BL/6, PAI-2(-/-) , and PAI-1(-/-) mice using the stasis model of deep vein thrombosis. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. We found that the absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2(-/-) mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2-deficient thrombi had increased levels of the neutrophil chemoattractant CXCL2, which was associated with early enhanced neutrophil recruitment. These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. © 2014 International Society on Thrombosis and Haemostasis.

  11. 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.

  12. THE ROLES OF TED TALKS AND VLOG IN ENHANCING STUDENTS‘ ACTIVENESS IN SPEAKING CLASS

    Directory of Open Access Journals (Sweden)

    Candradewi Wahyu Anggraeni

    2017-12-01

    Full Text Available The aims of this research are to describe the roles of TED Talks and Vlog in enhancing students‘ activeness in speaking class and to explain the students‘ perspectives toward the use of TED Talks and Vlog in speaking class. The research method used in this research is qualitative research design in the form of case study. The instruments of data collection are documents of students‘ vlog, observation, questionnaire, and interview. The participants of this research are the students of speaking class. This research has three significances which consist of theoretical, practical, and pedagogical significances. The theoretical significance is the research contributes to prove and add the speaking theories, whereas the practical significance is the research can be conducted by teachers, lecturers, or researchers to figure out the roles and the ways to improve students‘ participation in speaking class. In addition, the pedagogical significance shows that this research provides a reference of the use TED Talks and Vlog in enhancing students‘ activeness in speaking class, helps the students to be active in speaking class by following the lecturer‘s instruction toward the speaking activities given, and can be used as the empirical research finding toward students‘ activeness in speaking class. The findings show that TED Talks and Vlog have seven roles in order to help the students to be more active in speaking class and reveal the students‘ perceptions about virtues and hurdles toward the use of TED Talks and Vlog in speaking class.

  13. 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.

  14. Enhanced neutrophil chemotactic activity after bronchial challenge in subjects with grain dust-induced asthma.

    Science.gov (United States)

    Park, H S; Jung, K S

    1998-03-01

    There have been few reports suggesting involvement of neutrophils in induction of bronchoconstriction after inhalation of grain dust. To understand the role of neutrophils in pathogenesis of grain dust-induced asthma. We observed serum neutrophil chemotactic activity during grain dust-bronchoprovocation tests in six asthmatic subjects with positive bronchial challenges (group I). They were compared with those of six symptomatic subjects from the same workplace with negative bronchial challenges (group II). After grain dust inhalation, serum neutrophil chemotactic activity significantly increased at 30 minutes (P = .028), and then decreased to baseline level at 240 minutes (P = .028) in five subjects of group I having isolated early asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for up to 240 minutes in one asthmatic subject having both early and late asthmatic responses. There was, however, no significant change in serum neutrophil chemotactic activity during bronchial challenges in subjects of group II. Pre-incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the neutrophil chemotactic activity results of group I subjects. These results suggest that enhanced neutrophil chemotactic activity distinct from IL-8 may contribute to significant bronchoconstriction induced by grain dust.

  15. Facile synthesis of phosphorus doped graphitic carbon nitride polymers with enhanced visible-light photocatalytic activity

    International Nuclear Information System (INIS)

    Zhang, Ligang; Chen, Xiufang; Guan, Jing; Jiang, Yijun; Hou, Tonggang; Mu, Xindong

    2013-01-01

    Graphical abstract: - Highlights: • P-doped g-C 3 N 4 has been prepared by a one-pot green synthetic approach. • The incorporation of P resulted in favorable textural and electronic properties. • Doping with P enhanced the visible-light photocatalytic activity of g-C 3 N 4 . • A postannealing treatment further enhanced the activity of P-doped g-C 3 N 4 . • Photogenerated holes were the main species responsible for the activity. - Abstract: Phosphorus-doped carbon nitride materials were prepared by a one-pot green synthetic approach using dicyandiamide monomer and a phosphorus containing ionic liquid as precursors. The as-prepared materials were subjected to several characterizations and investigated as metal-free photocatalysts for the degradation of organic pollutants (dyes like Rhodamine B, Methyl orange) in aqueous solution under visible light. Results revealed that phosphorus-doped carbon nitride have a higher photocatalytic activity for decomposing Rhodamine B and Methyl orange in aqueous solution than undoped g-C 3 N 4 , which was attributed to the favorable textural, optical and electronic properties caused by doping with phosphorus heteroatoms into carbon nitride host. A facile postannealing treatment further improved the activity of the photocatalytic system, due to the higher surface area and smaller structural size in the postcalcined catalysts. The phosphorus-doped carbon nitride showed high visible-light photocatalytic activity, making them promising materials for a wide range of potential applications in photochemistry

  16. Enhancement of antibacterial activity of ciprofloxacin hydrochloride by complexation with sodium cholate

    Directory of Open Access Journals (Sweden)

    Uduma E. Osonwa

    2017-12-01

    Full Text Available Ciprofloxacin is a broad spectrum bactericidal anti-infective agent of the fluoroquinolones class used in treatment of many bacterial infections. In recent times, there has been increasing resistance to the antibiotic. In this work, we investigated the effect of making an ion- pair complex of Ciprofloxacin – hydrochloride with Sodium cholate on bacterial activity. The optimal ratio of the reactants and pH were determined using UV spectrometry. The complex was characterized by octanol-water partitioning, melting point, and IR spectrometry. The antibacterial activity of the complex was determined against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae by the agar-well diffusion method. The complex was whitish to off-white in color and crystalline, with a melting point of 238 °C. The stoichiometry of the complex shows a molar ratio of 1:1 of sodium cholate to ciprofloxacin. The best pH for complexation was pH 9. The complex partitioned 3.38 times into octanol than in water. The FTIR revealed interaction between the 4-nitrogen atom in the 7-piperazinyl group of ciprofloxacin and the carbonyl of the cholate. The drug in complex form gave double the antibacterial activity of the uncomplexed drug. This study showed that development of hydrophobic ion pair complex enhances antibacterial activity of ciprofloxacin hydrochloride. Keywords: Ciprofloxacin, Sodium cholate, Ion-pair complex, Antibacterial activity, Enhanced activity

  17. Daily physical activity enhances resilient resources for symptom management in middle-aged women.

    Science.gov (United States)

    Kishida, Moé; Elavsky, Steriani

    2015-07-01

    The aim of the present study was to evaluate the direct and indirect associations between physical activity and menopausal symptoms. Community-dwelling middle-aged women (N = 103; age range 40-60 years) completed daily Internet surveys at the end of the day and wore an accelerometer for the objective assessment of physical activity for 21-days. 1-1-1 multilevel mediation models were estimated to test whether resilient resources (i.e., positive affect and coping efficacy) mediated the association between physical activity and symptom burden at the between- and within-person level. Analyses demonstrated physical activity had an indirect effect (-0.16) on symptom burden through the enhancement of positive affect at the within-person level (p physical activity on symptom burden at the within-person level was -0.08 (p physical activity may help a woman to cope with her symptoms is through the enhancement of positive affect and coping efficacy on a day-to-day basis. (c) 2015 APA, all rights reserved.

  18. Morphine withdrawal enhances constitutive μ-opioid receptor activity in the ventral tegmental area.

    Science.gov (United States)

    Meye, Frank J; van Zessen, Ruud; Smidt, Marten P; Adan, Roger A H; Ramakers, Geert M J

    2012-11-14

    μ-Opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive activity is highly relevant in the mouse VTA, as it regulates GABAergic input to dopamine neurons. Specifically, suppression of MOR constitutive activity with the inverse agonist KC-2-009 enhanced GABAergic neurotransmission onto VTA dopamine neurons. This inverse agonistic effect was fully blocked by the specific MOR neutral antagonist CTOP, which had no effect on GABAergic transmission itself. We next show that withdrawal from chronic morphine further increases the magnitude of inverse agonistic effects at the MOR, suggesting enhanced MOR constitutive activity. We demonstrate that this increase can be an adaptive response to the detrimental elevation in cAMP levels known to occur during morphine withdrawal. These findings offer important insights in the physiological occurrence and function of MOR constitutive activity, and have important implications for therapeutic strategies aimed at normalizing MOR signaling during addiction and opioid overdose.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Apitherapeutics and phage-loaded nanofibers as wound dressings with enhanced wound healing and antibacterial activity.

    Science.gov (United States)

    Sarhan, Wessam A; Azzazy, Hassan Me

    2017-09-01

    Develop green wound dressings which exhibit enhanced wound-healing ability and potent antibacterial effects. Honey, polyvinyl alcohol, chitosan nanofibers were electrospun and loaded with bee venom, propolis and/or bacteriophage against the multidrug-resistant Pseudomonas aeruginosa and examined for their antibacterial, wound-healing ability and cytotoxicity. Among different formulations of nanofibers, honey, polyvinyl alcohol, chitosan-bee venom/bacteriophage exhibited the most potent antibacterial activity against all tested bacterial strains (Gram-positive and -negative strains) and achieved nearly complete killing of multidrug-resistant P. aeruginosa. In vivo testing revealed enhanced wound-healing results and cytotoxicity testing proved improved biocompatibility. The developed biocompatible nanofibers represent competitive wound-healing dressings with potent antibacterial and wound-healing activity.

  6. 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.

  7. 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.

  8. The IAEA activities towards enhanced utilisation, sustainability and applications of research reactors

    International Nuclear Information System (INIS)

    Ridikas, D.; Mank, G.; Adelfang, P.; Alldred, K.; Bradley, E.E.; Goldman, I.N.; Khvan, A.; Peld, N.

    2010-01-01

    This paper will give a brief introduction to the programmatic structure of the Research Reactor (RR) related activities of the IAEA sub-programme 'Research Reactors', under which the project on 'Enhancement of utilization and applications of RRs' will be presented in more detail. Both recent achievements and future planed actions will be reported with the major emphasis on RR utilisation related issues, specific applications of RRs, networks and coalitions, and assistance to the Member States (MS) planning their 1st RR. (author)

  9. Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure.

    Science.gov (United States)

    Xu, Bo; Zheng, Hong; Patel, Kaushik P

    2012-04-15

    Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 ± 0.6 vs. 2.6 ± 0.3 spikes/s, P neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 ± 7% vs. +184 ± 61%) or an increase in MAP (-42 ± 8% vs. -71 ± 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 ± 15% vs. 92 ± 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to baroreceptor and osmotic challenges observed during CHF.

  10. PTP1B Inhibition Causes Rac1 Activation by Enhancing Receptor Tyrosine Kinase Signaling

    Directory of Open Access Journals (Sweden)

    Ayako Tsuchiya

    2014-04-01

    Full Text Available Background/Aims: The present study investigated the signaling pathway underlying Rac1 activation induced by the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl-cyclopropyl]-octanoic acid (DCP-LA. Methods: Activity of protein tyrosine phosphatase 1B (PTP1B was assayed under cell-free conditions. Western blot was carried out to quantify phosphorylation of insulin receptor substrate-1 (IRS-1 and Akt in PC-12 cells. Rac1 activity was monitored in the föerster resonance energy transfer (FRET analysis using living and fixed PC-12 cells. Results: DCP-LA markedly suppressed PTP1B activity in a concentration (100 pM-100 µM-dependent manner. In the DCP-LA binding assay, fluorescein-conjugated DCP-LA produced a single fluorescent signal band at 60 kDa, corresponding to the molecule of PTP1B, and the signal was attenuated or abolished by co-treatment or pretreatment with non-conjugated DCP-LA. DCP-LA significantly enhanced nerve growth factor (NGF-stimulated phosphorylation of IRS-1 at Tyr1222 and Akt1/2 at Thr308/309 and Ser473/474 in PC-12 cells. In the FRET analysis, DCP-LA significantly enhanced NGF-stimulated Rac1 activation, which is abrogated by the phosphatidylinositol 3 kinase (PI3K inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase-1 (PDK1 inhibitor BX912, or the Akt inhibitor MK2206. Conclusion: The results of the present study show that DCP-LA-induced PTP1B inhibition, possibly through its direct binding, causes Rac1 activation by enhancing a pathway along a receptor tyrosine kinase (RTK/IRS-1/PI3K/Akt/Rac1 axis.

  11. Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung

    Science.gov (United States)

    Jandl, Katharina; Stacher, Elvira; Bálint, Zoltán; Sturm, Eva Maria; Maric, Jovana; Peinhaupt, Miriam; Luschnig, Petra; Aringer, Ida; Fauland, Alexander; Konya, Viktoria; Dahlen, Sven-Erik; Wheelock, Craig E.; Kratky, Dagmar; Olschewski, Andrea; Marsche, Gunther; Schuligoi, Rufina; Heinemann, Akos

    2016-01-01

    Background Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of the 2 D-type prostanoid receptors (DPs) DP1 and DP2 (also called chemoattractant receptor–homologous molecule expressed on TH2 cells) in regulating macrophages have not been elucidated to date. Objective We investigated the role of PGD2 receptors on primary human macrophages, as well as primary murine lung macrophages, and their ability to influence neutrophil action in vitro and in vivo. Methods In vitro studies, including migration, Ca2+ flux, and cytokine secretion, were conducted with primary human monocyte-derived macrophages and neutrophils and freshly isolated murine alveolar and pulmonary interstitial macrophages. In vivo pulmonary inflammation was assessed in male BALB/c mice. Results Activation of DP1, DP2, or both receptors on human macrophages induced strong intracellular Ca2+ flux, cytokine release, and migration of macrophages. In a murine model of LPS-induced pulmonary inflammation, activation of each PGD2 receptor resulted in aggravated airway neutrophilia, tissue myeloperoxidase activity, cytokine contents, and decreased lung compliance. Selective depletion of alveolar macrophages abolished the PGD2-enhanced inflammatory response. Activation of PGD2 receptors on human macrophages enhanced the migratory capacity and prolonged the survival of neutrophils in vitro. In human lung tissue specimens both DP1 and DP2 receptors were located on alveolar macrophages along with hematopoietic PGD synthase, the rate-limiting enzyme of PGD2 synthesis. Conclusion For the first time, our results show that PGD2 markedly augments disease activity through its ability to enhance the proinflammatory actions of macrophages and subsequent neutrophil activation. PMID:26792210

  12. 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.

  13. 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.

  14. Enhanced oxygen reduction activity on surface-decorated perovskite thin films for solid oxide fuel cells

    KAUST Repository

    Mutoro, Eva; Crumlin, Ethan J.; Biegalski, Michael D.; Christen, Hans M.; Shao-Horn, Yang

    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.

  15. 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.

  16. 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.

  17. 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.

  18. Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

    Science.gov (United States)

    Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

    2016-12-01

    Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

  19. 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.

  20. Voc enhancement of a solar cell with doped Li+-PbS as the active layer

    Science.gov (United States)

    Chávez Portillo, M.; Alvarado Pulido, J.; Gallardo Hernández, S.; Soto Cruz, B. S.; Alcántara Iniesta, S.; Gutiérrez Pérez, R.; Portillo Moreno, O.

    2018-06-01

    In this report, we investigate the fabrication of solar cells obtained by chemical bath technique, based on CdS as window layer and PbS and PbS-Li+-doped as the active layer. We report open-circuit-voltage Voc values of ∼392 meV for PbS and ∼630 meV for PbSLi+-doped, a remarkable enhanced in the open circuit voltage is shown for solar cells with doped active layer. Li+ ion passivate the dangling bonds in PbS-metal layer interface in consequence reducing the recombination centers.

  1. 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."

  2. Enhancement of Immune Activation Activities of Spirulina maxima Grown in Deep-Sea Water

    Science.gov (United States)

    Choi, Woon Yong; Kang, Do Hyung; Lee, Hyeon Yong

    2013-01-01

    In this study, the immuno-modulatory and anticancer activities of marine algae, Spirulina maxima grown in deep-sea water (DSW), were investigated. It was found that the extract of S. maxima, cultured in DSW, effectively suppressed the expression of Bcl2 in A549 cells as well as inhibiting various human cancer cells with concentration dependency, which possibly implies that the extracts may play more important roles in controlling cancer cell growth. The secretion of cytokines IL-6 and TNF-α from human B cells was also greatly increased, compared to those of the extract grown in conventional sea-water. The growth of Human Natural Killer (NK) cells in the presence of the extracts from DSW was significantly higher (12.2 × 104 viable cells/mL) when compared to the control (1.1 × 104 viable cells/mL). Based on HPLC analysis, the increase in the biological activities of the extracts from DSW was caused by considerably high amounts of β-carotene and ascorbic acid because the DSW contained high concentrations and good ratios of several key minerals for biosynthesizing β-carotene and ascorbic acid, as well as maintaining high cell growth. PMID:23743830

  3. 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.

  4. Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of Mycobacterium tuberculosis MazF Toxins

    Science.gov (United States)

    Nigam, Akanksha; Kumar, Sathish

    2018-01-01

    ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis. PMID:29717013

  5. Increased p21ras activity in human fibroblasts transduced with survivin enhances cell proliferation

    International Nuclear Information System (INIS)

    Temme, Achim; Diestelkoetter-Bachert, Petra; Schmitz, Marc; Morgenroth, Agnieszka; Weigle, Bernd; Rieger, Michael A.; Kiessling, Andrea; Rieber, E. Peter

    2005-01-01

    Survivin is critically involved in mitosis and when overexpressed enhances the activity of the Aurora B kinase, a serine-threonine kinase belonging to the family of oncogenic Aurora/IpI1p-related kinases. Both proteins interact with Ras GTPase-activating protein suggesting an impact on the Ras pathway. This study aimed at defining the role of survivin in proliferation and potential transformation of cells. When survivin was overexpressed in normal human lung fibroblasts, the characteristic track lanes of fibroblasts were disturbed and the rate of cell proliferation was increased. An enhanced level of p21 ras mRNA and protein expression and concomitant rise in levels of activated p21 ras were observed. Despite increased proliferation cell survival remained dependent on serum and cells were not able to form colonies in soft agar assays. These data suggest that overexpression of survivin increases cell growth but, despite the increase in active p21 ras , is not sufficient to transform primary cells. Yet, in addition to its anti-apoptotic function it might contribute to the accelerated growth of tumour cells by increasing p21 ras activity

  6. 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.

  7. 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.

  8. Mechanism, kinetics and application studies on enhanced activated sludge by interior microelectrolysis.

    Science.gov (United States)

    Yang, Xiaoyi; Xue, Yu; Wang, Wenna

    2009-01-01

    Enhanced activated sludge by interior microelectrolysis (EAIM) was studied to treat textile wastewater, kinetics, mechanism and application of which were also discussed in comparison with traditional activated sludge and interior microelectrolysis, respectively. The results of kinetics study indicated three different processes all followed first-order kinetics well. In EAIM, three impact factors take effects on COD removal, which are flocculation, activated sludge and electrophoresis and redox. In terms of assumption of no interaction among three COD removal mechanisms, 49.6% of the total COD removal is ascribed to flocculation, 30.1% to activated sludge and 20.3% to electrophoresis and redox. EAIM showed its advantages in COD removal efficiency, extensive adaptability to complex composition and wide range of pH. EAIM-aerobic process provided an efficient and economic performance for dealing with textile wastewater.

  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. 6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1alpha resulting in new vessel formation.

    Science.gov (United States)

    Yoo, Y-G; Na, T-Y; Yang, W-K; Kim, H-J; Lee, I-K; Kong, G; Chung, J-H; Lee, M-O

    2007-05-31

    Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis. Previously, we reported that the orphan nuclear receptor Nur77 functions in stabilizing HIF-1alpha. Here, we demonstrate that 6-mercaptopurine (6-MP), an activator of the NR4A family members, enhances transcriptional activity of HIF-1. 6-MP enhanced the protein-level of HIF-1alpha as well as vascular endothelial growth factor (VEGF) in a dose- and time-dependent manner. The induction of HIF-1alpha was abolished by the transfection of either a dominant-negative Nur77 mutant or si-Nur77, indicating a critical role of Nur77 in the 6-MP action. The HIF-1alpha protein level remained up to 60 min in the presence of 6-MP when de novo protein synthesis was blocked by cycloheximide, suggesting that 6-MP induces stabilization of the HIF-1alpha protein. The fact that 6-MP decreased the association of HIF-1alpha with von Hippel-Lindau protein and the acetylation of HIF-1alpha, may explain how 6-MP induced stability of HIF-1alpha. Further, 6-MP induced the transactivation function of HIF-1alpha by recruiting co-activator cyclic-AMP-response-element-binding protein. Finally, 6-MP enhanced the expression of HIF-1alpha and VEGF, and the formation of capillary tubes in human umbilical vascular endothelial cells. Together, our results provide a new insight for 6-MP action in the stabilization of HIF-1alpha and imply a potential application of 6-MP in hypoxia-associated human vascular diseases.

  11. Mechanical stress activates Smad pathway through PKCδ to enhance interleukin-11 gene transcription in osteoblasts.

    Directory of Open Access Journals (Sweden)

    Shinsuke Kido

    Full Text Available BACKGROUND: Mechanical stress rapidly induces ΔFosB expression in osteoblasts, which binds to interleukin (IL-11 gene promoter to enhance IL-11 expression, and IL-11 enhances osteoblast differentiation. Because bone morphogenetic proteins (BMPs also stimulate IL-11 expression in osteoblasts, there is a possibility that BMP-Smad signaling is involved in the enhancement of osteoblast differentiation by mechanical stress. The present study was undertaken to clarify whether mechanical stress affects BMP-Smad signaling, and if so, to elucidate the role of Smad signaling in mechanical stress-induced enhancement of IL-11 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Mechanical loading by fluid shear stress (FSS induced phosphorylation of BMP-specific receptor-regulated Smads (BR-Smads, Smad1/5, in murine primary osteoblasts (mPOBs. FSS rapidly phosphorylated Y311 of protein kinase C (PKCδ, and phosphorylated PKCδ interacted with BR-Smads to phosphorylate BR-Smads. Transfection of PKCδ siRNA or Y311F mutant PKCδ abrogated BR-Smads phosphorylation and suppressed IL-11 gene transcription enhanced by FSS. Activated BR-Smads bound to the Smad-binding element (SBE of IL-11 gene promoter and formed complex with ΔFosB/JunD heterodimer via binding to the C-terminal region of JunD. Site-directed mutagenesis in the SBE and the AP-1 site revealed that both SBE and AP-1 sites were required for full activation of IL-11 gene promoter by FSS. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that PKCδ-BR-Smads pathway plays an important role in the intracellular signaling in response to mechanical stress, and that a cross-talk between PKCδ-BR-Smads and ΔFosB/JunD pathways synergistically stimulates IL-11 gene transcription in response to mechanical stress.

  12. Webcams, Crowdsourcing, and Enhanced Crosswalks: Developing a Novel Method to Analyze Active Transportation.

    Science.gov (United States)

    Hipp, J Aaron; Manteiga, Alicia; Burgess, Amanda; Stylianou, Abby; Pless, Robert

    2016-01-01

    Active transportation opportunities and infrastructure are an important component of a community's design, livability, and health. Features of the built environment influence active transportation, but objective study of the natural experiment effects of built environment improvements on active transportation is challenging. The purpose of this study was to develop and present a novel method of active transportation research using webcams and crowdsourcing, and to determine if crosswalk enhancement was associated with changes in active transportation rates, including across a variety of weather conditions. The 20,529 publicly available webcam images from two street intersections in Washington, DC, USA were used to examine the impact of an improved crosswalk on active transportation. A crowdsource, Amazon Mechanical Turk, annotated image data. Temperature data were collected from the National Oceanic and Atmospheric Administration, and precipitation data were annotated from images by trained research assistants. Summary analyses demonstrated slight, bi-directional differences in the percent of images with pedestrians and bicyclists captured before and after the enhancement of the crosswalks. Chi-square analyses revealed these changes were not significant. In general, pedestrian presence increased in images captured during moderate temperatures compared to images captured during hot or cold temperatures. Chi-square analyses indicated the crosswalk improvement may have encouraged walking and biking in uncomfortable outdoor conditions (P < 0.5). The methods employed provide an objective, cost-effective alternative to traditional means of examining the effects of built environment changes on active transportation. The use of webcams to collect active transportation data has applications for community policymakers, planners, and health professionals. Future research will work to validate this method in a variety of settings as well as across different built

  13. Webcams, crowdsourcing, and enhanced crosswalks: Developing a novel method to analyze active transportation

    Directory of Open Access Journals (Sweden)

    J. Aaron eHipp

    2016-05-01

    Full Text Available Introduction: Active transportation opportunities and infrastructure are an important component of a community’s design, livability, and health. Features of the built environment influence active transportation, but objective study of the natural experiment effects of built environment improvements on active transportation is challenging. The purpose of this study was to develop and present a novel method of active transportation research using webcams and crowdsourcing, and to determine if crosswalk enhancement was associated with changes in active transportation rates, including across a variety of weather conditions. Methods: 20,529 publicly available webcam images from two street intersections in Washington, D.C., were used to examine the impact of an improved crosswalk on active transportation. A crowdsource, Amazon Mechanical Turk, annotated image data. Temperature data was collected from the National Oceanic and Atmospheric Administration, and precipitation data was annotated from images by trained research assistants. Results: Summary analyses demonstrated slight, bi-directional differences in the percent of images with pedestrians and bicyclists captured before and after the enhancement of the crosswalks. Chi-square analyses revealed these changes were not significant. In general, pedestrian presence increased in images captured during moderate temperatures compared to images captured during hot or cold temperatures. Chi-square analyses indicated the crosswalk improvement may have encouraged walking and biking in uncomfortable outdoor conditions (p<0.5. Conclusion: The methods employed provide an objective, cost-effective alternative to traditional means of examining the effects of built environment changes on active transportation. The use of webcams to collect active transportation data has applications for community policymakers, planners, and health professionals. Future research will work to validate this method in a variety of

  14. 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.

  15. Ultrasonic synthesis of fern-like ZnO nanoleaves and their enhanced photocatalytic activity

    International Nuclear Information System (INIS)

    Ma, Qing Lan; Xiong, Rui; Zhai, Bao-gai; Huang, Yuan Ming

    2015-01-01

    Graphical abstract: - Highlights: • Fern-like ZnO nanoleaves were synthesized by ultrasonicating Zn microcrystals in water. • A fern-like ZnO nanoleaf is a self-assembly of ZnO nanoplates along one ZnO nanorod. • Fern-like ZnO nanoleaves exhibit enhanced photocatalytic activity than ZnO nanocrystals. • The branched hierarchical structures are responsible for the enhanced photocatalytic activity. - Abstract: Two-dimensional fern-like ZnO nanoleaves were synthesized by ultrasonicating zinc microcrystals in water. The morphology, crystal structure, optical property and photocatalytic activity of the fern-like ZnO nanoleaves were characterized with scanning electron microscopy, X-ray diffraction, transmission electron microscopy, photoluminescence spectroscopy and ultraviolet–visible spectroscopy, respectively. It is found that one fern-like ZnO nanoleaf is composed of one ZnO nanorod as the central trunk and a number of ZnO nanoplates as the side branches in opposite pairs along the central ZnO nanorod. The central ZnO nanorod in the fern-like nanoleaves is about 1 μm long while the side-branching ZnO nanoplates are about 100 nm long and 20 nm wide. Further analysis has revealed that ZnO nanocrystals are the building blocks of the central ZnO nanorod and the side-branching ZnO nanoplates. Under identical conditions, fern-like ZnO nanoleaves exhibit higher photocatalytic activity in photodegrading methyl orange in aqueous solution than spherical ZnO nanocrystals. The first-order photocatalytic rate constant of the fern-like ZnO nanoleaves is about four times as large as that of the ZnO nanoparticles. The branched architecture of the hierarchical nanoleaves is suggested be responsible for the enhanced photocatalytic activity of the fern-like ZnO nanoleaves

  16. Select polyphenolic fractions from dried plum enhance osteoblast activity through BMP-2 signaling.

    Science.gov (United States)

    Graef, Jennifer L; Rendina-Ruedy, Elizabeth; Crockett, Erica K; Ouyang, Ping; King, Jarrod B; Cichewicz, Robert H; Lucas, Edralin A; Smith, Brenda J

    2018-05-01

    Dried plum supplementation has been shown to enhance bone formation while suppressing bone resorption. Evidence from previous studies has demonstrated that these responses can be attributed in part to the fruit's polyphenolic compounds. The purpose of this study was to identify the most bioactive polyphenolic fractions of dried plum with a focus on their osteogenic activity and to investigate their mechanisms of action under normal and inflammatory conditions. Utilizing chromatographic techniques, six fractions of polyphenolic compounds were prepared from a crude extract of dried plum. Initial screening assays revealed that two fractions (DP-FrA and DP-FrB) had the greatest osteogenic potential. Subsequent experiments using primary bone-marrow-derived osteoblast cultures demonstrated these two fractions enhanced extracellular alkaline phosphatase (ALP), an indicator of osteoblast activity, and mineralized nodule formation under normal conditions. Both fractions enhanced bone morphogenetic protein (BMP) signaling, as indicated by increased Bmp2 and Runx2 gene expression and protein levels of phosphorylated Smad1/5. DP-FrB was most effective at up-regulating Tak1 and Smad1, as well as protein levels of phospho-p38. Under inflammatory conditions, TNF-α suppressed ALP and tended to decrease nodule formation (P=.0674). This response coincided with suppressed gene expression of Bmp2 and the up-regulation of Smad6, an inhibitor of BMP signaling. DP-FrA and DP-FrB partially normalized these responses. Our results show that certain fractions of polyphenolic compounds in dried plum up-regulate osteoblast activity by enhancing BMP signaling, and when this pathway is inhibited by TNF-α, the osteogenic response is attenuated. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Hydrogen adsorption-mediated synthesis of concave Pt nanocubes and their enhanced electrocatalytic activity

    Science.gov (United States)

    Lu, Bang-An; Du, Jia-Huan; Sheng, Tian; Tian, Na; Xiao, Jing; Liu, Li; Xu, Bin-Bin; Zhou, Zhi-You; Sun, Shi-Gang

    2016-06-01

    Concave nanocubes are enclosed by high-index facets and have negative curvature; they are expected to have enhanced reactivity, as compared to nanocubes with flat surfaces. Herein, we propose and demonstrate a new strategy for the synthesis of concave Pt nanocubes with {hk0} high-index facets, by using a hydrogen adsorption-mediated electrochemical square-wave potential method. It was found that Pt atoms prefer to deposit on edge sites rather than terrace sites on Pt surfaces with intensive hydrogen adsorption, resulting in the formation of concave structures. The as-prepared concave Pt nanocubes exhibit enhanced catalytic activity and stability towards oxidation of ethanol and formic acid in acidic solutions, compared to commercial Pt/C catalysts.Concave nanocubes are enclosed by high-index facets and have negative curvature; they are expected to have enhanced reactivity, as compared to nanocubes with flat surfaces. Herein, we propose and demonstrate a new strategy for the synthesis of concave Pt nanocubes with {hk0} high-index facets, by using a hydrogen adsorption-mediated electrochemical square-wave potential method. It was found that Pt atoms prefer to deposit on edge sites rather than terrace sites on Pt surfaces with intensive hydrogen adsorption, resulting in the formation of concave structures. The as-prepared concave Pt nanocubes exhibit enhanced catalytic activity and stability towards oxidation of ethanol and formic acid in acidic solutions, compared to commercial Pt/C catalysts. Electronic supplementary information (ESI) available: Details of DFT calculation, SEM images of concave Pt nanocubes, mass activity and stability characterization of the catalysts. See DOI: 10.1039/c6nr02349e

  18. Single Channel Analysis of Isoflurane and Ethanol Enhancement of Taurine-Activated Glycine Receptors.

    Science.gov (United States)

    Kirson, Dean; Todorovic, Jelena; Mihic, S John

    2018-01-01

    The amino acid taurine is an endogenous ligand acting on glycine receptors (GlyRs), which is released by astrocytes in many brain regions, such as the nucleus accumbens and prefrontal cortex. Taurine is a partial agonist with an efficacy significantly lower than that of glycine. Allosteric modulators such as ethanol and isoflurane produce leftward shifts of glycine concentration-response curves but have no effects at saturating glycine concentrations. In contrast, in whole-cell electrophysiology studies these modulators increase the effects of saturating taurine concentrations. A number of possible mechanisms may explain these enhancing effects, including modulator effects on conductance, channel open times, or channel closed times. We used outside-out patch-clamp single channel electrophysiology to investigate the mechanism of action of 200 mM ethanol and 0.55 mM isoflurane in enhancing the effects of a saturating concentration of taurine. Neither modulator enhanced taurine-mediated conductance. Isoflurane increased the probability of channel opening. Isoflurane also increased the lifetimes of the two shortest open dwell times while both agents decreased the likelihood of occurrence of the longest-lived intracluster channel-closing events. The mechanism of enhancement of GlyR functioning by these modulators is dependent on the efficacy of the agonist activating the receptor and the concentration of agonist tested. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Surface-enhanced Raman scattering active gold nanoparticle/nanohole arrays fabricated through electron beam lithography

    Science.gov (United States)

    Wu, Tsunghsueh; Lin, Yang-Wei

    2018-03-01

    Effective surface-enhanced Raman scattering (SERS)-active substrates from gold nanoparticle and gold nanohole arrays were successfully fabricated through electron beam lithography with precise computer-aided control of the unit size and intergap distance. Their SERS performance was evaluated using 4-mercaptobenzoic acid (4-MBA). These gold arrays yielded strong SERS signals under 785 nm laser excitation. The enhancement factors for 4-MBA molecules on the prepared gold nanoparticle and nanohole arrays maxed at 1.08 × 107 and 8.61 × 106, respectively. The observed increase in SERS enhancement was attributed to the localized surface plasmon resonance (LSPR) wavelength shifting toward the near-infrared regime when the gold nanohole diameter increased, in agreement with the theoretical prediction in this study. The contribution of LSPR to the Raman enhancement from nanohole arrays deposited on fluorine-doped tin oxide glass was elucidated by comparing SERS and transmission spectra. This simple fabrication procedure, which entails employing electron beam lithography and the controllability of the intergap distance, suggests highly promising uses of nanohole arrays as functional components in sensing and photonic devices.

  20. 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

  1. 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.

  2. Handling and safety enhancement of race cars using active aerodynamic systems

    Science.gov (United States)

    Diba, Fereydoon; Barari, Ahmad; Esmailzadeh, Ebrahim

    2014-09-01

    A methodology is presented in this work that employs the active inverted wings to enhance the road holding by increasing the downward force on the tyres. In the proposed active system, the angles of attack of the vehicle's wings are adjusted by using a real-time controller to increase the road holding and hence improve the vehicle handling. The handling of the race car and safety of the driver are two important concerns in the design of race cars. The handling of a vehicle depends on the dynamic capabilities of the vehicle and also the pneumatic tyres' limitations. The vehicle side-slip angle, as a measure of the vehicle dynamic safety, should be narrowed into an acceptable range. This paper demonstrates that active inverted wings can provide noteworthy dynamic capabilities and enhance the safety features of race cars. Detailed analytical study and formulations of the race car nonlinear model with the airfoils are presented. Computer simulations are carried out to evaluate the performance of the proposed active aerodynamic system.

  3. NSCT BASED LOCAL ENHANCEMENT FOR ACTIVE CONTOUR BASED IMAGE SEGMENTATION APPLICATION

    Directory of Open Access Journals (Sweden)

    Hiren Mewada

    2010-08-01

    Full Text Available Because of cross-disciplinary nature, Active Contour modeling techniques have been utilized extensively for the image segmentation. In traditional active contour based segmentation techniques based on level set methods, the energy functions are defined based on the intensity gradient. This makes them highly sensitive to the situation where the underlying image content is characterized by image nonhomogeneities due to illumination and contrast condition. This is the most difficult problem to make them as fully automatic image segmentation techniques. This paper introduces one of the approaches based on image enhancement to this problem. The enhanced image is obtained using NonSubsampled Contourlet Transform, which improves the edges strengths in the direction where the illumination is not proper and then active contour model based on level set technique is utilized to segment the object. Experiment results demonstrate that proposed method can be utilized along with existing active contour model based segmentation method under situation characterized by intensity non-homogeneity to make them fully automatic.

  4. 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.

  5. 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

  6. Exploration of the Role of Heat Activation in Enhancing Serpentine Carbon Sequestration Reactions

    International Nuclear Information System (INIS)

    McKelvy, M.J.; Chizmeshya, A.V.G.; Diefenbacher, J.; Bearat, H.; Wolf, G.

    2005-01-01

    As compared with other candidate carbon sequestration technologies, mineral carbonation offers the unique advantage of permanent disposal via geologically stable and environmentally benign carbonates. The primary challenge is the development of an economically viable process. Enhancing feedstock carbonation reactivity is key. Heat activation dramatically enhances aqueous serpentine carbonation reactivity. Although the present process is too expensive to implement, the materials characteristics and mechanisms that enhance carbonation are of keen interest for further reducing cost. Simultaneous thermogravimetric and differential thermal analysis (TGA/DTA) of the serpentine mineral lizardite was used to isolate a series of heat-activated materials as a function of residual hydroxide content at progressively higher temperatures. Their structure and composition are evaluated via TGA/DTA, X-ray powder diffraction (including phase analysis), and infrared analysis. The meta-serpentine materials that were observed to form ranged from those with longer range ordering, consistent with diffuse stage-2 like interlamellar order, to an amorphous component that preferentially forms at higher temperatures. The aqueous carbonation reaction process was investigated for representative materials via in situ synchrotron X-ray diffraction. Magnesite was observed to form directly at 15 MPa CO 2 and at temperatures ranging from 100 to 125 C. Carbonation reactivity is generally correlated with the extent of meta-serpentine formation and structural disorder.

  7. Enhancement of sludge reduction and methane production by removing extracellular polymeric substances from waste activated sludge.

    Science.gov (United States)

    Nguyen, Minh Tuan; Mohd Yasin, Nazlina Haiza; Miyazaki, Toshiki; Maeda, Toshinari

    2014-12-01

    The management of waste activated sludge (WAS) recycling is a concern that affects the development of the future low-carbon society, particularly sludge reduction and biomass utilization. In this study, we investigated the effect of removing extracellular polymeric substances (EPS), which play important roles in the adhesion and flocculation of WAS, on increased sludge disintegration, thereby enhancing sludge reduction and methane production by anaerobic digestion. EPS removal from WAS by ethylenediaminetetraacetic acid (EDTA) significantly enhanced sludge reduction, i.e., 49 ± 5% compared with 27 ± 1% of the control at the end the digestion process. Methane production was also improved in WAS without EPS by 8881 ± 109 CH4 μmol g(-1) dry-weight of sludge. Microbial activity was determined by denaturing gradient gel electrophoresis and real-time polymerase chain reaction, which showed that the hydrolysis and acetogenesis stages were enhanced by pretreatment with 2% EDTA, with a larger methanogenic community and better methane production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 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.

  9. The nucleosome assembly activity of NAP1 is enhanced by Alien.

    Science.gov (United States)

    Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

    2007-05-01

    The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitamin D receptor (VDR), binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. Furthermore, Alien reduces the accessibility of the histones H3 and H4 for NAP1-promoted assembly reaction. This indicates that Alien sustains and reinforces the formation of nucleosomes. Employing deletion mutants of Alien suggests that different regions of Alien are involved in enhancement of NAP1-mediated nucleosome assembly and in inhibiting the accessibility of the histones H3 and H4. In addition, we provide evidence that Alien is associated with chromatin and with micrococcus nuclease-prepared nucleosome fractions and interacts with the histones H3 and H4. Furthermore, chromatin immunoprecipitation and reimmunoprecipitation experiments suggest that NAP1 and Alien localize to the endogenous CYP24 promoter in vivo, a VDR target gene. Based on these findings, we present here a novel pathway linking corepressor function with nucleosome assembly activity.

  10. Enhanced photocatalytic activity of ZnO–graphene nanocomposites prepared by microwave synthesis

    International Nuclear Information System (INIS)

    Herring, Natalie P.; Almahoudi, Serial H.; Olson, Chelsea R.; El-Shall, M. Samy

    2012-01-01

    This work reports a simple one-step synthesis of ZnO nanopyramids supported on reduced graphene oxide (RGO) nanosheets using microwave irradiation (MWI) of zinc acetate and GO in the presence of a mixture of oleic acid and oleylamine. The rapid decomposition of zinc acetate by MWI in the presence of the mixture of oleic acid and oleylamine results in the formation of hexagonal ZnO nanopyramids. GO has a high affinity for absorbing MWI, which results in a high local heating effect around the GO nanosheets and facilitates the reduction of GO by the oleylamine. The RGO nanosheets act as heterogeneous surface sites for the nucleation and growth of the ZnO nanopyramids. Using ligand exchange, the ZnO–RGO nanocomposites can be dispersed in an aqueous medium, thus allowing their use as photocatalysts for the degradation of the malachite green dye in water. The ZnO–RGO nanocomposites show enhanced photocatalytic activity for the degradation of the dye over the unsupported ZnO nanopyramids. The enhanced activity is attributed to efficient charge transfer of the photogenerated electrons in the conduction band of ZnO to graphene. This enhances the oxidative pathway of the holes generated in the valence band of ZnO which can effectively lead to the degradation and mineralization of the malachite green. The ZnO nanopyramids supported on RGO could have improved performance in other photocatalytic reactions and also in solar energy conversion.

  11. Enhanced electrochemomechanical activity of polyaniline films towards high pH region: contribution of Donnan effect

    International Nuclear Information System (INIS)

    Takashima, Wataru; Nakashima, Megumi; Pandey, Shyam S.; Kaneto, Keiichi

    2004-01-01

    Enhancement of electrochemomechanical deformation (ECMD) and expansion of ECMD activity towards high pH have been simultaneously achieved in the electrolytes equilibrated with HCl and NaCl solutions for polyaniline (PANI) film. The maximum deformation has been reached to 6.7% in the mixture of 3 M HCl and 3 M NaCl equilibrated at pH 3 at ambient temperature. By comparing the fact that the ECMD magnitude is 3.2% in 1 M HCl equilibrated at pH 0.5, the simple judicious selection of electrolyte condition leads to the enhancement of ECMD magnitude by around two times. The concentration dependence on both electrical conductivity and absorption spectra elucidates the increase of protonation ratio as a function of electrolyte concentration. The results indicate that the high concentration retains both the electrochemical and ECMD activities in PANI film towards high pH region, which is the enhanced functionality of PANI supported by Donnan effect

  12. Acute stress enhances learning and memory by activating acid-sensing ion channels in rats.

    Science.gov (United States)

    Ye, Shunjie; Yang, Rong; Xiong, Qiuju; Yang, Youhua; Zhou, Lianying; Gong, Yeli; Li, Changlei; Ding, Zhenhan; Ye, Guohai; Xiong, Zhe

    2018-04-15

    Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs. We found that corticosterone (CORT) induced by acute stress caused a potentiation of ASICs current via glucocorticoid receptors (GRs) not mineralocorticoid receptors (MRs). Meanwhile, CORT did not produce an increase of ASICs current by pretreated with GF109203X, an antagonist of protein kinase C (PKC), whereas CORT did result in a markedly enhancement of ASICs current by bryostatin 1, an agonist of PKC, suggesting that potentiation of ASICs function may be depended on PKC activating. More importantly, an antagonist of ASICs, amiloride (10 μM) reduced the performance of learning and memory induced by acute stress, which is further suggesting that ASICs as the key components involves in cognitive processes induced by acute stress. These results indicate that acute stress causes the enhancement of ASICs function by activating PKC signaling pathway, which leads to potentiated learning and memory. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. BFV activates the NF-κB pathway through its transactivator (BTas) to enhance viral transcription

    International Nuclear Information System (INIS)

    Wang Jian; Tan Juan; Zhang Xihui; Guo Hongyan; Zhang Qicheng; Guo Tingting; Geng Yunqi; Qiao Wentao

    2010-01-01

    Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-κB (NF-κB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-κB pathway through the action of its transactivator, BTas. Both cellular IKKβ and IκBα also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-κB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKα and IKKβ), which may be responsible for regulation of IKK kinase activity and persistent NF-κB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-κB. Together, this study suggests that BFV activates the NF-κB pathway through BTas to enhance viral transcription.

  14. 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).

  15. 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.

  16. 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.

  17. Enhanced Photocatalytic Activity of La3+-Doped TiO2 Nanotubes with Full Wave-Band Absorption

    Science.gov (United States)

    Xia, Minghao; Huang, Lingling; Zhang, Yubo; Wang, Yongqian

    2018-06-01

    TiO2 nanotubes doped with La3+ were synthesized by anodic oxidation method and the photocatalytic activity was detected by photodegrading methylene blue. As-prepared samples improved the absorption of both ultraviolet light and visible light and have a great enhancement on the photocatalytic activity while contrasting with the pristine TiO2 nanotubes. A tentative mechanism for the enhancement of photocatalytic activity with full wave-band absorption is proposed.

  18. Model Integrating Fuzzy Argument with Neural Network Enhancing the Performance of Active Queue Management

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. Enhanced photoelectrochemical and photocatalytic activity of WO3-surface modified TiO2 thin film

    Science.gov (United States)

    Qamar, Mohammad; Drmosh, Qasem; Ahmed, Muhammad I.; Qamaruddin, Muhammad; Yamani, Zain H.

    2015-02-01

    Development of nanostructured photocatalysts for harnessing solar energy in energy-efficient and environmentally benign way remains an important area of research. Pure and WO3-surface modified thin films of TiO2 were prepared by magnetron sputtering on indium tin oxide glass, and photoelectrochemical and photocatalytic activities of these films were studied. TiO2 particles were <50 nm, while deposited WO3 particles were <20 nm in size. An enhancement in the photocurrent was observed when the TiO2 surface was modified WO3 nanoparticles. Effect of potential, WO3 amount, and radiations of different wavelengths on the photoelectrochemical activity of TiO2 electrodes was investigated. Photocatalytic activity of TiO2 and WO3-modified TiO2 for the decolorization of methyl orange was tested.

  1. Development of microalgae biomaterials with enhanced antioxidant activity using electron beam

    International Nuclear Information System (INIS)

    Kim, Younghwa; Park, Hyunjin; Choi, Soojeong; Lee, Jaehwa

    2013-01-01

    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. 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.

  3. Microbial activity in subsurface samples before and during nitrate-enhanced bioremediation

    International Nuclear Information System (INIS)

    Thomas, J.M.; Gordy, V.R.; Bruce, C.L.; Ward, C.H.; Hutchins, S.R.; Sinclair, J.L.

    1995-01-01

    A study was conducted to determine the microbial activity at a site contaminated with JP-4 jet fuel before and during nitrate-enhanced bioremediation. Samples at three depths from six different locations were collected aseptically under anaerobic conditions before and during treatment. Cores were located in or close to the source of contamination, downgradient of the source, or outside the zone of contamination. Parameters for microbial characterization included (1) viable counts of aerobic heterotrophic, JP-4 degrading, and oligotrophic bacteria; (2) the most probable number (MPN) of aerobic and anaerobic protozoa; (3) the MPN of total denitrifiers; and (4) the MPN of denitrifiers in hydrocarbon-amended microcosms. The results indicate that the total number of denitrifiers increased by an order of magnitude during nitrate-enhanced bioremediation in most samples. The number of total heterotrophs and JP-4-degrading microorganisms growing aerobically also increased. In addition, the first anaerobic protozoa associated with hydrocarbon-contaminated subsurface materials were detected

  4. 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.

  5. Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity.

    Science.gov (United States)

    Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho

    2017-08-08

    Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.

  6. Amination of activated carbon for enhancing phenol adsorption: Effect of nitrogen-containing functional groups

    International Nuclear Information System (INIS)

    Yang, Guo; Chen, Honglin; Qin, Hangdao; Feng, Yujun

    2014-01-01

    To study the contribution of different nitrogen-containing functional groups to enhancement of phenol adsorption, the aminated activated carbons (AC) were characterized by N2 adsorption/desorption, XPS, Boehm titration, and pH drift method and tested for adsorption behaviors of phenol. Adsorption isotherm fitting revealed that the Langmuir model was preferred for the aminated ACs. The adsorption capacity per unit surface area (q m /SSA BET ) was linearly correlated with the amount of pyridinic and pyrrolic N, which suggested that these two functional groups played a critical role in phenol adsorption. The enhancement of adsorption capacity was attributed to the strengthened π–π dispersion between phenol and basal plane of AC by pyridinic, pyrrolic N. The adsorption kinetics was found to follow the pseudo-second-order kinetic model, and intraparticle diffusion was one of the rate-controlling steps in the adsorption process.

  7. 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.

  8. Circadian variations of interferon-induced enhancement of human natural killer (NK) cell activity.

    Science.gov (United States)

    Gatti, G; Cavallo, R; Sartori, M L; Carignola, R; Masera, R; Delponte, D; Salvadori, A; Angeli, A

    1988-01-01

    We searched for circadian changes in the enhancement of the NK activity after exposure to IFN-gamma of peripheral blood mononuclear (PBM) cells obtained serially throughout the 24-h cycle. In August-October 1986, blood was drawn from 7 healthy, diurnally active and nocturnally resting male volunteers (22-34 yr) at 4-h intervals for 24 h starting at 08:00. PBM cells were immediately separated and assayed for NK cell activity, using K 562 cultured cells as a target in a 4-h 51Cr release assay after prior incubation for 20 h with buffer or 300 IU rIFN-gamma. Circadian variations of the spontaneous NK cell cytotoxicity were apparent; the activity was at its maximum at the end of the night or in the early morning and then declined in the afternoon. The 24-h rhythmic pattern was validated with statistical significance by the Cosinor method (p less than 0.02; acrophase 04:22). Maximum enhancement by IFN-gamma was attained in the second part of the night or in the early morning, i.e. in phase with the peak of the spontaneous NK cell activity. A significant circadian rhythm of the percent increase above control levels was validated by the Cosinor method (p less than 0.01; acrophase 04:03). Our findings may be of relevance to a better understanding of the mechanisms of control of human NK activity and warrant consideration as an approach to improve the effectiveness of time-qualified immunotherapy.

  9. Methyl jasmonate enhances memory performance through inhibition of oxidative stress and acetylcholinesterase activity in mice.

    Science.gov (United States)

    Eduviere, Anthony T; Umukoro, S; Aderibigbe, Adegbuyi O; Ajayi, Abayomi M; Adewole, Folashade A

    2015-07-01

    Current research effort focuses on the development of safer natural compounds with multipronged mechanisms of action that could be used to ameliorate memory deficits in patients with Alzheimer's disease, as cure for the disease still remains elusive. In this study, we evaluated the effect of methyl jasmonate (MJ), a naturally occurring bioactive compound on memory, acetylcholinesterase activity and biomarkers of oxidative stress in mice. Male Swiss mice were treated with intraperitoneal injection of MJ (10-40 mg/kg) alone or in combination with scopolamine (3mg/kg) once daily for 7 days. Thirty minutes after the last treatment, memory functions were assessed using Y-maze and object recognition tests. Thereafter, acetylcholinesterase activity and levels of biomarkers of oxidative stress were assessed in mice brains using standard biochemical procedures. MJ significantly enhanced memory performance and reversed scopolamine-induced cognitive impairment in mice. MJ demonstrated significant inhibition of acetylcholinesterase activity suggesting increased cholinergic neurotransmission. It further decreased malondialdehyde concentrations in mouse brain indicating antioxidant activity. Moreover, MJ significantly increased glutathione levels and activity of antioxidant enzymes (catalase and superoxide dismutase) in mice brains. The increased oxidative stress; evidenced by elevated levels of malondialdehyde and decreased antioxidant defense systems in scopolamine-treated mice was attenuated by MJ. The results of this study suggest that MJ may be useful in conditions associated with memory dysfunctions or age-related cognitive decline. The positive effect of MJ on memory may be related to inhibition of oxidative stress and enhancement of cholinergic neurotransmission through inhibition of acetylcholinesterase activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Activating RNAs associate with Mediator to enhance chromatin architecture and transcription.

    Science.gov (United States)

    Lai, Fan; Orom, Ulf A; Cesaroni, Matteo; Beringer, Malte; Taatjes, Dylan J; Blobel, Gerd A; Shiekhattar, Ramin

    2013-02-28

    Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of lncRNAs may have varied biological functions. We and others have identified a class of lncRNAs, termed ncRNA-activating (ncRNA-a), that function to activate their neighbouring genes using a cis-mediated mechanism. To define the precise mode by which such enhancer-like RNAs function, we depleted factors with known roles in transcriptional activation and assessed their role in RNA-dependent activation. Here we report that depletion of the components of the co-activator complex, Mediator, specifically and potently diminished the ncRNA-induced activation of transcription in a heterologous reporter assay using human HEK293 cells. In vivo, Mediator is recruited to ncRNA-a target genes and regulates their expression. We show that ncRNA-a interact with Mediator to regulate its chromatin localization and kinase activity towards histone H3 serine 10. The Mediator complex harbouring disease- displays diminished ability to associate with activating ncRNAs. Chromosome conformation capture confirmed the presence of DNA looping between the ncRNA-a loci and its targets. Importantly, depletion of Mediator subunits or ncRNA-a reduced the chromatin looping between the two loci. Our results identify the human Mediator complex as the transducer of activating ncRNAs and highlight the importance of Mediator and activating ncRNA association in human disease.

  11. 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

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

    International Nuclear Information System (INIS)

    Sato, Chieri; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime

    2012-01-01

    Highlights: ► We investigated the role of S1P signaling for osteoblast differentiation. ► Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. ► S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. ► 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 receptor-mediated signaling plays a crucial role for osteoblast differentiation.

  13. 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.

  14. Enhanced photocurrent density in graphene/Si based solar cell (GSSC) by optimizing active layer thickness

    International Nuclear Information System (INIS)

    Rosikhin, Ahmad; Hidayat, Aulia Fikri; Syuhada, Ibnu; Winata, Toto

    2015-01-01

    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 TiO 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 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

  15. Assessment of inflammatory activity in Crohn's disease by means of dynamic contrast-enhanced MRI.

    Science.gov (United States)

    Pupillo, V A; Di Cesare, E; Frieri, G; Limbucci, N; Tanga, M; Masciocchi, C

    2007-09-01

    Our aim was to perform a dynamic study of contrast enhancement of the intestinal wall in patients with Crohn's disease to quantitatively assess local inflammatory activity. We studied a population of 50 patients with histologically proven Crohn's disease. Magnetic resonance imaging (MRI) was performed using a 1.5-T magnet with a phased-array coil and acquisition of T2-weighted single-shot fast spin echo (SSFSE) half Fourier sequences before intravenous administration of gadolinium, and T1-weighted fast spoiled gradient (FSPGR) fat-saturated sequences before and after contrast administration. Before the examination, patents received oral polyethylene glycol (PEG) (1,000 ml for adults; 10 ml/Kg of body weight for children). Regions of interest (ROI) were placed on the normal and diseased intestinal wall to assess signal intensity and rate of increase in contrast enhancement over time. Data were compared with the Crohn's Disease Activity Index (CDAI). The diseased bowel wall showed early and intense uptake of contrast that increases over time until a plateau is reached. In patients in the remission phase after treatment, signal intensity was only slightly higher in diseased bowel loops than in healthy loops. There was a significant correlation between the peak of contrast uptake and CDAI. Dynamic MRI is a good technique for quantifying local inflammatory activity of bowel wall in patients with Crohn's disease.

  16. 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.

  17. Enhanced photocatalytic activity of titania-silica mixed oxide prepared via basic hydrolyzation

    International Nuclear Information System (INIS)

    Xie Chao; Xu Zili; Yang Qiujing; Xue Baoyong; Du Yaoguo; Zhang Jiahua

    2004-01-01

    Two different synthesis routes were applied to prepare TiO 2 -XSiO 2 (X denotes mol% of silica in titania-silica mixed oxides) with different silica concentrations by using ammonia water as hydrolysis catalyst. Through comparing the photocatalytic performance of two sets of mixed oxides, we found that the photocatalytic activity of mixed oxides prepared via the route which can promote homogeneity, was significantly enhanced as compared with that of counterparts prepared via the another route, and the highest photocatalytic activity obtained by adding about 9.1 mol% silica into titania was much higher than that of pure TiO 2 . The mixed oxides were investigated by means of XRD, thermal analysis, UV-vis, FT-IR and XPS. The characterization results suggest that, in comparison with pure TiO 2 , the mixed oxides exhibit smaller crystallite size and higher thermal stability which can elevate the temperature of anatase to rutile phase transformation due to the addition of silica. Furthermore, Broensted acidity, which is associated with the formation of Ti-O-Si hetero linkages where tetrahedrally coordinated silica is chemically mixed with the octahedral titania matrix, may be a very important contribution to the enhanced photocatalytic activity of titania-silica mixed oxides as well

  18. 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.

  19. Insulin receptor substrate-3, interacting with Bcl-3, enhances p50 NF-{kappa}B activity

    Energy Technology Data Exchange (ETDEWEB)

    Kabuta, Tomohiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Hakuno, Fumihiko; Cho, Yoshitake; Yamanaka, Daisuke; Chida, Kazuhiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Asano, Tomoichiro [Graduate School of Biomedical Science, Hiroshima University, Hiroshima 734-8551 (Japan); Wada, Keiji [Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Takahashi, Shin-Ichiro, E-mail: atkshin@mail.ecc.u-tokyo.ac.jp [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan)

    2010-04-09

    The insulin receptor substrate (IRS) proteins are major substrates of both insulin receptor and insulin-like growth factor (IGF)-I receptor tyrosine kinases. Previously, we reported that IRS-3 is localized to both cytosol and nucleus, and possesses transcriptional activity. In the present study, we identified Bcl-3 as a novel binding protein to IRS-3. Bcl-3 is a nuclear protein, which forms a complex with the homodimer of p50 NF-{kappa}B, leading to enhancement of transcription through p50 NF-{kappa}B. We found that Bcl-3 interacts with the pleckstrin homology domain and the phosphotyrosine binding domain of IRS-3, and that IRS-3 interacts with the ankyrin repeat domain of Bcl-3. In addition, IRS-3 augmented the binding activity of p50 to the NF-{kappa}B DNA binding site, as well as the tumor necrosis factor (TNF)-{alpha}-induced transcriptional activity of NF-{kappa}B. Lastly, IRS-3 enhanced NF-{kappa}B-dependent anti-apoptotic gene induction and consequently inhibited TNF-{alpha}-induced cell death. This series of results proposes a novel function for IRS-3 as a transcriptional regulator in TNF-{alpha} signaling, distinct from its function as a substrate of insulin/IGF receptor kinases.

  20. 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.

  1. Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

    Science.gov (United States)

    Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Camire, Rodney M.; Arruda, Valder R.

    2016-01-01

    Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity. Inhibition of furin increases the secretion and decreases the intracellular retention of FVIII-BDD protein in mammalian cells. Our new variant (FVIII-ΔF), in which this recognition motif is removed, efficiently circumvents furin. FVIII-ΔF demonstrates increased recombinant protein yields, enhanced clotting activity, and higher circulating FVIII levels after adeno-associated viral vector–based liver gene therapy in a murine model of severe hemophilia A (HA) compared with FVIII-BDD. Moreover, we observed an amelioration of the bleeding phenotype in severe HA dogs with sustained therapeutic FVIII levels after FVIII-ΔF gene therapy at a lower vector dose than previously employed in this model. The immunogenicity of FVIII-ΔF did not differ from that of FVIII-BDD as a protein or a gene therapeutic. Thus, contrary to previous suppositions, FVIII variants that can avoid furin processing are likely to have enhanced translational potential for HA therapy. PMID:27734034

  2. Enhancement of Th1 type cytokine production and primary T cell activation by PBI-1393.

    Science.gov (United States)

    Allam, Mustapha; Julien, Nathalie; Zacharie, Boulos; Penney, Christopher; Gagnon, Lyne

    2007-12-01

    In previous reports, we have shown that PBI-1393 (formerly BCH-1393), N,N-Dimethylaminopurine pentoxycarbonyl D-arginine, stimulates cytotoxic T-lymphocyte (CTL) responses both in vitro and in vivo in normal immune status and immunosuppressed mice. Additionally, PBI-1393 was tested for anticancer activity in syngeneic mouse experimental tumor models and it displayed significant inhibition of tumor outgrowths when given in combination with sub-therapeutic doses of cytotoxic drugs (cyclophosphamide, 5-fluorouracil, doxorubicin and cis-platinum). However, the mechanism of action of PBI-1393 was still unknown. Here, we report that PBI-1393 enhances IL-2 and IFN-gamma production in human activated T cells by 51% and 46% respectively. PBI-1393 increases also IL-2 and IFN-gamma mRNA expression as shown by RT-PCR. The physiological relevance of IL-2 and IFN-gamma gene modulation by PBI-1393 is illustrated by the advantageous increase of T cell proliferation (39+/-0.3% above control) and human CTL response against prostate (PC-3) cancer cells (42+/-0.03%). The enhancement of human T cell proliferation and CTL activation by PBI-1393 demonstrates that this compound potentiates the immune response and in this regard, it could be used as an alternative approach to IL-2 and/or IFN-gamma therapy against cancer.

  3. 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

  4. Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Mu-Yun [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Shen, Yuh-Chiang [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); National Research Institute of Chinese Medicine, Taipei, Taiwan (China); Lu, Chien-Hsing [Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yang, Shu-Yi [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Ho, Tsing-Fen [Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Peng, Yu-Ta [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chang, Chia-Che, E-mail: chia_che@dragon.nchu.edu.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China)

    2012-12-15

    Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified

  5. Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

    International Nuclear Information System (INIS)

    Pan, Mu-Yun; Shen, Yuh-Chiang; Lu, Chien-Hsing; Yang, Shu-Yi; Ho, Tsing-Fen; Peng, Yu-Ta; Chang, Chia-Che

    2012-01-01

    Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified as an

  6. Isikult vabaduse võtmine põhjendusel, et ta on psüühikahäire tõttu endale või teistele ohtlik / Sten Lind, Katrin Eino

    Index Scriptorium Estoniae

    Lind, Sten, 1979-

    2014-01-01

    Psüühikahäire määratlemine ning isiku ohtlikkus psühhiaatrilise abi seaduse § 11, sotsiaalhoolekande seaduse § 19 ja karistusseadustiku § 86 kontekstis. Riigikohtu lahenditest 3-2-1-81-07 ja 3-2-1-155-13

  7. Building novel Ag/CeO2 heterostructure for enhancing photocatalytic activity

    International Nuclear Information System (INIS)

    Leng, Qiang; Yang, Dezhi; Yang, Qi; Hu, Chenguo; Kang, Yue; Wang, Mingjun; Hashim, Muhammad

    2015-01-01

    Highlights: • Ag nanoparticle is designed to building Schottky heterojunction on CeO 2 nanocube. • The photocatalytic activity of Ag/CeO 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 2 heterostructure is designed as a photocatalyst to degrade organic dye under the simulated sunlight. The catalytic activity of CeO 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 2 in forming high efficiency catalyst, the amount of Ag/CeO 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 2 catalyst in an optimal weight ratio of 1:3, is added to the 100 mL of MB solution (c 0 = 1 × 10 −5 mol L −1 , pH 6.2). The mechanism of the enhanced catalytic activity of Ag/CeO 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

  8. 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.

  9. High quantum yield graphene quantum dots decorated TiO_2 nanotubes for enhancing photocatalytic activity

    International Nuclear Information System (INIS)

    Qu, Ailan; Xie, Haolong; Xu, Xinmei; Zhang, Yangyu; Wen, Shengwu; Cui, Yifan

    2016-01-01

    Highlights: • High concentration yellow GQDs and TiO_2 nanotubes were achieved by a simple and green method. • High quantum yield GQDs enhanced the photodegradation capacity of TiO_2 nanotube. • The catalytic performance of GQDs/TiO_2 depends on the GQDs loading. • The improved photocatalytic activity of GQDs/TiO_2 was attributed to three aspects. - Abstract: Graphene quantum dots (GQDs) with high quantum yield (about 23.6% at an excitation wavelength of 320 nm) and GQDs/TiO_2 nanotubes (GQDs/TiO_2 NTs) composites were achieved by a simple hydrothermal method at low temperature. Photoluminescence characterization showed that the GQDs exhibited the down-conversion PL features at excitation from 300 to 420 nm and up-conversion photoluminescence in the range of 600–800 nm. The photocatalytic activity of prepared GQDs/TiO_2 NTs composites on the degradation of methyl orange (MO) was significantly enhanced compared with that of pure TiO_2 nanotubes (TiO_2 NTs). For the composites coupling with 1.5%, 2.5% and 3.5% GQDs, the degradation of MO after 20 min irradiation under UV–vis light irradiation (λ = 380–780 nm) were 80.52%, 94.64% and 51.91%, respectively, which are much higher than that of pure TiO_2 NTs (35.41%). It was inferred from the results of characterization that the improved photocatalytic activity of the GQDs/TiO_2 NTs composites was attributed to the synergetic effect of up-conversion properties of the GQDs, enhanced visible light absorption and efficient separation of photogenerated electron-holes of the GQDs/TiO_2 composite.

  10. Enhanced Virulence Gene Activity of Agrobacterium in Muskmelon (Cucumis melo L. cv. ‘Birdie’

    Directory of Open Access Journals (Sweden)

    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.

  11. Eviction of linker histone H1 by NAP-family histone chaperones enhances activated transcription.

    Science.gov (United States)

    Zhang, Qian; Giebler, Holli A; Isaacson, Marisa K; Nyborg, Jennifer K

    2015-01-01

    In the Metazoan nucleus, core histones assemble the genomic DNA to form nucleosome arrays, which are further compacted into dense chromatin structures by the linker histone H1. The extraordinary density of chromatin creates an obstacle for accessing the genetic information. Regulation of chromatin dynamics is therefore critical to cellular homeostasis, and histone chaperones serve as prominent players in these processes. In the current study, we examined the role of specific histone chaperones in negotiating the inherently repressive chromatin structure during transcriptional activation. Using a model promoter, we demonstrate that the human nucleosome assembly protein family members hNap1 and SET/Taf1β stimulate transcription in vitro during pre-initiation complex formation, prior to elongation. This stimulatory effect is dependent upon the presence of activators, p300, and Acetyl-CoA. We show that transcription from our chromatin template is strongly repressed by H1, and that both histone chaperones enhance RNA synthesis by overcoming H1-induced repression. Importantly, both hNap1 and SET/Taf1β directly bind H1, and function to enhance transcription by evicting the linker histone from chromatin reconstituted with H1. In vivo studies demonstrate that SET/Taf1β, but not hNap1, strongly stimulates activated transcription from the chromosomally-integrated model promoter, consistent with the observation that SET/Taf1β is nuclear, whereas hNap1 is primarily cytoplasmic. Together, these observations indicate that SET/Taf1β may serve as a critical regulator of H1 dynamics and gene activation in vivo. These studies uncover a novel function for SET that mechanistically couples transcriptional derepression with H1 dynamics. Furthermore, they underscore the significance of chaperone-dependent H1 displacement as an essential early step in the transition of a promoter from a dense chromatin state into one that is permissive to transcription factor binding and robust

  12. 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.

  13. 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.

  14. Enhanced activation of motor execution networks using action observation combined with imagination of lower limb movements.

    Directory of Open Access Journals (Sweden)

    Michael Villiger

    Full Text Available The combination of first-person observation and motor imagery, i.e. first-person observation of limbs with online motor imagination, is commonly used in interactive 3D computer gaming and in some movie scenes. These scenarios are designed to induce a cognitive process in which a subject imagines himself/herself acting as the agent in the displayed movement situation. Despite the ubiquity of this type of interaction and its therapeutic potential, its relationship to passive observation and imitation during observation has not been directly studied using an interactive paradigm. In the present study we show activation resulting from observation, coupled with online imagination and with online imitation of a goal-directed lower limb movement using functional MRI (fMRI in a mixed block/event-related design. Healthy volunteers viewed a video (first-person perspective of a foot kicking a ball. They were instructed to observe-only the action (O, observe and simultaneously imagine performing the action (O-MI, or imitate the action (O-IMIT. We found that when O-MI was compared to O, activation was enhanced in the ventralpremotor cortex bilaterally, left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions shared many activation foci in motor relevant areas as confirmed by conjunction analysis. These results show that (i combining observation with motor imagery (O-MI enhances activation compared to observation-only (O in the relevant foot motor network and in regions responsible for attention, for control of goal-directed movements and for the awareness of causing an action, and (ii it is possible to extensively activate the motor execution network using O-MI, even in the absence of overt movement. Our results may have implications for the development of novel virtual reality interactions for neurorehabilitation interventions and other applications involving training of motor tasks.

  15. Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior.

    Science.gov (United States)

    Takeda, Atsushi; Itoh, Hiromasa; Yamada, Kohei; Tamano, Haruna; Oku, Naoto

    2008-10-01

    The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency. The extracellular signal of ZnAF-2, a membrane-impermeable zinc indicator, was also lower in the hippocampal CA3, suggesting that the basal extracellular concentrations of zinc are lower maintained in zinc deficiency. To check mossy fiber activity after 4-week zinc deprivation, the decrease in the signal of FM4-64, an indicator of presynaptic activity (exocytosis), at mossy fiber synapses was measured under the condition of spontaneous depolarization. The decrease was significantly facilitated by zinc deficiency, suggesting that the basal exocytosis at mossy fiber synapses is enhanced by zinc deficiency. On the other hand, the increase in anxiety-like behavior was observed in the open-field test after 4-week zinc deprivation. The present study demonstrates that the decrease in the basal extracellular concentrations of zinc may be linked to the enhancement of the basal mossy fiber activity in zinc deficiency. This decrease seems to be also involved in neuropsychological behavior in zinc deficiency.

  16. 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.

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

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Lorenzen, I; Henriksen, O

    1994-01-01

    examined 16 clinically active (CAG), 7 clinically inactive (CIG) and 4 healthy knees. The synovium of a preselected slice was outlined. Its area and relative signal intensity increase after gadopentetate dimeglumine on T1-SE and FLASH (at each time t) were calculated. The CAG knees showed a mean signal...... 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...

  18. Chronic alcohol consumption enhances iNKT cell maturation and activation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hui, E-mail: hzhang@wsu.edu; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1{sup −} iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1{sup +}CD44{sup hi} mature iNKT cells but does not alter the number of NK1.1{sup −} immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1{sup −} iNKT cells, especially the NK1.1{sup −}CD44{sup lo} Stage I iNKT cells. The percentage of NKG2A{sup +} iNKT cells increases in all of the tissues and organs examined; whereas CXCR3{sup +} iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol

  19. 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)....

  20. Chronic alcohol consumption enhances iNKT cell maturation and activation

    International Nuclear Information System (INIS)

    Zhang, Hui; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-01

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1 − iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1 + CD44 hi mature iNKT cells but does not alter the number of NK1.1 − immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1 − iNKT cells, especially the NK1.1 − CD44 lo Stage I iNKT cells. The percentage of NKG2A + iNKT cells increases in all of the tissues and organs examined; whereas CXCR3 + iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol consumption induces Th1 immune response upon i

  1. Understanding how environmental enhancement and conservation activities may benefit health and wellbeing: a systematic review.

    Science.gov (United States)

    Lovell, Rebecca; Husk, Kerryn; Cooper, Chris; Stahl-Timmins, Will; Garside, Ruth

    2015-09-07

    Action taken to enhance or conserve outdoor environments may benefit health and wellbeing through the process of participation but also through improving the environment. There is interest, amongst both health and environmental organisations, in using such activities as health promotion interventions. The objective of this systematic review was to investigate the health and wellbeing impacts of participation in environmental enhancement and conservation activities and to understand how these activities may be beneficial, to whom and in what circumstances or contexts. A theory-led mixed-method systematic review was used to assess evidence of effect and to identify pathways to change (protocol: http://onlinelibrary.wiley.com/doi/ 10.1002/14651858.CD010351/full ). Due to the multi-disciplinary, dispersed and disparate body of evidence an extensive multi-stage search strategy was devised and undertaken. Twenty-seven databases and multiple sources of grey literature were searched and over 200 relevant organisations were contacted. The heterogenous evidence was synthesised using a narrative approach and a conceptual model was developed to illustrate the mechanisms of effect. Due to the limited nature of the evidence additional higher order evidence was sought to assess the plausibility of the proposed mechanisms of effect through which health and wellbeing may accrue. The majority of the quantitative evidence (13 studies; all poor quality and lower-order study designs) was inconclusive, though a small number of positive and negative associations were observed. The qualitative evidence (13 studies; 10 poor quality, 3 good) indicated that the activities were perceived to have value to health and wellbeing through a number of key mechanisms; including exposure to natural environments, achievement, enjoyment and social contact. Additional high level evidence indicated that these pathways were plausible. Despite interest in the use of environmental enhancement activities as a

  2. Enhancer elements upstream of the SHOX gene are active in the developing limb.

    Science.gov (United States)

    Durand, Claudia; Bangs, Fiona; Signolet, Jason; Decker, Eva; Tickle, Cheryll; Rappold, Gudrun

    2010-05-01

    Léri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.

  3. Effects of selenylation modification on immune-enhancing activity of garlic polysaccharide.

    Directory of Open Access Journals (Sweden)

    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.

  4. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure

    International Nuclear Information System (INIS)

    Jessop, Forrest; Hamilton, Raymond F.; Rhoderick, Joseph F.; Shaw, Pamela K.; Holian, Andrij

    2016-01-01

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5 fl/fl LysM-Cre + mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5 fl/fl LysM-Cre + mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis. - Highlights: • Silica exposure increases autophagy in macrophages. • Autophagy deficient mice have enhanced inflammation and silicosis. • Autophagy deficiency in macrophages results in greater silica-induced cytotoxicity. • Autophagy deficiency in macrophages increases extracellular IL-18 and HMGB1.

  5. Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

    Directory of Open Access Journals (Sweden)

    Guillaume Dalmasso

    Full Text Available BACKGROUND: PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. RESULTS: We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1 promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by approximately 2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles. CONCLUSIONS: Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.

  6. Mechanism of salt-induced activity enhancement of a marine-derived laccase, Lac15.

    Science.gov (United States)

    Li, Jie; Xie, Yanan; Wang, Rui; Fang, Zemin; Fang, Wei; Zhang, Xuecheng; Xiao, Yazhong

    2018-04-01

    Laccase (benzenediol: oxygen oxidoreductases, EC1.10.3.2) is a multi-copper oxidase capable of oxidizing a variety of phenolic and other aromatic organic compounds. The catalytic power of laccase makes it an attractive candidate for potential applications in many areas of industry including biodegradation of organic pollutants and synthesis of novel drugs. Most laccases are vulnerable to high salt and have limited applications. However, some laccases are not only tolerant to but also activated by certain concentrations of salt and thus have great application potential. The mechanisms of salt-induced activity enhancement of laccases are unclear as yet. In this study, we used dynamic light scattering, size exclusion chromatography, analytical ultracentrifugation, intrinsic fluorescence emission, circular dichroism, ultraviolet-visible light absorption, and an enzymatic assay to investigate the potential correlation between the structure and activity of the marine-derived laccase, Lac15, whose activity is promoted by low concentrations of NaCl. The results showed that low concentrations of NaCl exert little influence on the protein structure, which was partially folded in the absence of the salt; moreover, the partially folded rather than the fully folded state seemed to be favorable for enzyme activity, and this partially folded state was distinctive from the so-called 'molten globule' occasionally observed in active enzymes. More data indicated that salt might promote laccase activity through mechanisms involving perturbation of specific local sites rather than a change in global structure. Potential binding sites for chloride ions and their roles in enzyme activity promotion are proposed.

  7. Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-κB activation and enhancing autophagy.

    Directory of Open Access Journals (Sweden)

    Yolanda Williams-Bey

    Full Text Available The omega-3 (ω3 fatty acid docosahexaenoic acid (DHA can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR 4 (also known as GPR120, a G-protein coupled receptor (GPR known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity.

  8. Papel da via de sinalização mediada por Ire1 e Xbp1 na diferenciação de fotoreceptores em Drosophila

    OpenAIRE

    Coelho, Dina Raquel da Silva, 1984-

    2009-01-01

    Tese de mestrado. Biologia (Biologia Molecular Humana). Universidade de Lisboa, Faculdade de Ciências, 2009 O mecanismo de Unfolded Protein Response (UPR) protege as células do stress no retículo endoplasmático (RE) causado pela acumulação de proteínas misfolded no seu lúmen. Este mecanismo leva à activação de um conjunto de vias de sinalização que aumenta a capacidade de folding de proteínas no RE. No presente trabalho, analisámos o papel da via do UPR mediada por Ire1 e Xbp1 no desenvolv...

  9. Which learning activities enhance physiotherapy practice? A systematic review protocol of quantitative and qualitative studies.

    Science.gov (United States)

    Leahy, Edmund; Chipchase, Lucy; Blackstock, Felicity

    2017-04-17

    Learning activities are fundamental for the development of expertise in physiotherapy practice. Continuing professional development (CPD) encompasses formal and informal learning activities undertaken by physiotherapists. Identifying the most efficient and effective learning activities is essential to enable the profession to assimilate research findings and improve clinical skills to ensure the most efficacious care for clients. To date, systematic reviews on the effectiveness of CPD provide limited guidance on the most efficacious models of professional development for physiotherapists. The aim of this systematic review is to evaluate which learning activities enhance physiotherapy practice. A search of Ovid MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO (Psychological Abstracts), PEDro, Cochrane Library, AMED and Educational Resources and Information Center (ERIC) will be completed. Citation searching and reference list searching will be undertaken to locate additional studies. Quantitative and qualitative studies will be included if they examine the impact of learning activities on clinician's behaviour, attitude, knowledge, beliefs, skills, self-efficacy, work satisfaction and patient outcomes. Risk of bias will be assessed by two independent researchers. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and Confidence in the Evidence from Reviews of Qualitative research (CERQual) will be used to synthesise results where a meta-analysis is possible. Where a meta-analysis is not possible, a narrative synthesis will be conducted. PROSPERO CRD42016050157.

  10. Urease immobilized polymer hydrogel: Long-term stability and enhancement of enzymatic activity.

    Science.gov (United States)

    Kutcherlapati, S N Raju; Yeole, Niranjan; Jana, Tushar

    2016-02-01

    A method has been developed in which an enzyme namely urease was immobilized inside hydrogel matrix to study the stability and enzymatic activity in room temperature (∼27-30°C). This urease coupled hydrogel (UCG) was obtained by amine-acid coupling reaction and this procedure is such that it ensured the wider opening of mobile flap of enzyme active site. A systematic comparison of urea-urease assay and the detailed kinetic data clearly revealed that the urease shows activity for more than a month when stored at ∼27-30°C in case of UCG whereas it becomes inactive in case of free urease (enzyme in buffer solution). The aqueous microenvironment inside the hydrogel, unusual morphological features and thermal behaviour were believed to be the reasons for unexpected behaviour. UCG displayed enzyme activity at basic pH and up to 60°C. UCG showed significant enhancement in activity against thermal degradation compared to free urease. In summary, this method is a suitable process to stabilize the biomacromolecules in standard room temperature for many practical uses. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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

    between the loop and Lys(161) in the N-terminal tail. In support of the first mechanism, the mutations E296V and D212N resulted in similar, about 2-fold, enhancements of the amidolytic activity. Moreover, mutation of the Lys(161)-interactive residue Asp(217) or Asp(219) to Ala reduced the amidolytic...... activity by 40-50%, whereas the K161A mutation resulted in 80% reduction. Hence one of these Asp residues in the Ca(2+)-binding loop appears to suffice for some residual interaction with Lys(161), whereas the more severe effect upon replacement of Lys(161) is due to abrogation of the interaction with the N......-terminal tail. However, Ca(2+) attenuation of the repulsion between Asp(212) and Glu(296) keeps the activity above that of apoFVIIa. Altogether, our data suggest that repulsion involving Asp(212) in the Ca(2+)-binding loop suppresses FVIIa activity and that optimal activity requires a favorable interaction...

  12. Plant carbohydrate binding module enhances activity of hybrid microbial cellulase enzyme

    Directory of Open Access Journals (Sweden)

    Caitlin Siobhan Byrt

    2012-11-01

    Full Text Available A synthetic, highly active cellulase enzyme suitable for in planta production may be a valuable tool for biotechnological approaches to develop transgenic biofuel crops with improved digestibility. Here, we demonstrate that the addition of a plant derived carbohydrate binding module (CBM to a synthetic glycosyl hydrolase (GH improved the activity of the hydrolase in releasing sugar from plant biomass. A CEL-HYB1-CBM enzyme was generated by fusing a hybrid microbial cellulase, CEL-HYB1, with the carbohydrate-binding module (CBM of the tomato (Solanum lycopersicum SlCel9C1 cellulase. CEL-HYB1 and CEL-HYB1-CBM enzymes were produced in vitro using Pichia pastoris and the activity of these enzymes was tested using CMC, MUC and native crystalline cellulose assays. The presence of the CBM substantially improved the endo-glucanase activity of CEL-HYB1, especially against the native crystalline cellulose encountered in Sorghum plant cell walls. These results indicate that addition of an endogenous plant derived CBM to cellulase enzymes may enhance hydrolytic activity.

  13. A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media.

    Science.gov (United States)

    Madusanka, Nadeesh; de Silva, K M Nalin; Amaratunga, Gehan

    2015-12-10

    A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used as an emulsifier for curcumin which is a turmeric derived water insoluble polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite (MMT) nanoclay was incorporated in the formulation as a matrix material which also plays a role in release kinetics. It was observed that water solubility of curcumin in the nanocomposite has significantly increased (60% release within 2h and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is suitable as a curcumin carrier having enhanced release and structural properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Enhanced oxygen reduction activity and solid oxide fuel cell performance with a nanoparticles-loaded cathode.

    Science.gov (United States)

    Zhang, Xiaomin; Liu, Li; Zhao, Zhe; Tu, Baofeng; Ou, Dingrong; Cui, Daan; Wei, Xuming; Chen, Xiaobo; Cheng, Mojie

    2015-03-11

    Reluctant oxygen-reduction-reaction (ORR) activity has been a long-standing challenge limiting cell performance for solid oxide fuel cells (SOFCs) in both centralized and distributed power applications. We report here that this challenge has been tackled with coloading of (La,Sr)MnO3 (LSM) and Y2O3 stabilized zirconia (YSZ) nanoparticles within a porous YSZ framework. This design dramatically improves ORR activity, enhances fuel cell output (200-300% power improvement), and enables superior stability (no observed degradation within 500 h of operation) from 600 to 800 °C. The improved performance is attributed to the intimate contacts between nanoparticulate YSZ and LSM particles in the three-phase boundaries in the cathode.

  15. Developing technology-enhanced active learning for medical education: challenges, solutions, and future directions.

    Science.gov (United States)

    McCoy, Lise; Pettit, Robin K; Lewis, Joy H; Bennett, Thomas; Carrasco, Noel; Brysacz, Stanley; Makin, Inder Raj S; Hutman, Ryan; Schwartz, Frederic N

    2015-04-01

    Growing up in an era of video games and Web-based applications has primed current medical students to expect rapid, interactive feedback. To address this need, the A.T. Still University-School of Osteopathic Medicine in Arizona (Mesa) has developed and integrated a variety of approaches using technology-enhanced active learning for medical education (TEAL-MEd) into its curriculum. Over the course of 3 years (2010-2013), the authors facilitated more than 80 implementations of games and virtual patient simulations into the education of 550 osteopathic medical students. The authors report on 4 key aspects of the TEAL-MEd initiative, including purpose, portfolio of tools, progress to date regarding challenges and solutions, and future directions. Lessons learned may be of benefit to medical educators at academic and clinical training sites who wish to implement TEAL-MEd activities.

  16. Street football is a feasible health-enhancing activity for homeless men

    DEFF Research Database (Denmark)

    Helge, Eva Wulff; Randers, Morten Bredsgaard; Hornstrup, Therese

    2014-01-01

    This case-control study investigated the feasibility of street football as a health-enhancing activity for homeless men, specifically the musculoskeletal effects of 12 weeks of training. Twenty-two homeless men participated in the football group (FG) and 10 served as controls (C). Plasma.......095 to 0.969 ± 0.090 g/cm(2) (P = 0.02). No effects were observed in C. In conclusion, street football appears to be a feasible training activity with musculoskeletal health benefits for homeless men. The attendance rate and the training intensity were high, and 12 weeks of training resulted...... in a substantial anabolic response in bone metabolism. Postural balance improved markedly, and the overall risk of falling, and hospitalization due to sudden trauma, could be reduced by street football for homeless men....

  17. Solid state fermentation of Trichoderma viride for enhancement phenolic content, antioxidant and antimicrobial activities in ginger.

    Science.gov (United States)

    Saleh, Rashad M; Kabli, Saleh A; Al-Garni, Saleh M; Al-Ghamdi, Maryam A; Abdel-Aty, Azza M; Mohamed, Saleh A

    2018-05-04

    The phenolic content of methanolic and water extracts of ginger fermented by Trichoderma spp. during solid state fermentation (SSF) was detected as compared with unfermented ginger. The total phenolic content of fermented ginger increased several times. The highest phenolic content of ginger was detected after SSF by T. viride. The optimal physiological conditions for the maximum production of the phenolic content and β-glucosidase activity of fermented ginger by T. viride were detected at day 7 incubation, pH 6.0, 30°C and 30% moisture. There are consistent between the maximum production of β-glucosidase and phenolic content. The SSF of ginger by T. viride greatly enhanced the antioxidant potency of phenolic compounds by using DPPH and ABTS assays. Potent antibacterial activity was appeared by phenolic compounds of fermented ginger against all the tested human-pathogenic bacteria. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Facile Synthesis of Au Nanocube-CdS Core-Shell Nanocomposites with Enhanced Photocatalytic Activity

    Science.gov (United States)

    Liu, Xiao-Li; Liang, Shan; Li, Min; Yu, Xue-Feng; Zhou, Li; Wang, Qu-Qua

    2014-06-01

    Au nanocube-CdS core-shell nanocomposites are prepared by using a one-pot method in aqueous phase with cetyltrimethylammonium bromide as the surfactant. The extinction properties and photocatalytic activity of Au-CdS nanocomposites are investigated. Compared with the pure Au nanocubes, the Au-CdS nanocomposites exhibit enhanced extinction intensity. Compared with CdS nanoparticles, the Au-CdS nanocomposites exhibit improved photocatalytic activity. Furthermore, the photocatalytic efficiency is even better with the increase in the core size of the Au-CdS nanocomposites. Typically, the photocatalytic efficiency of the Au-CdS with 62 nm sized Au nanocubes is about two times higher than that of the pure CdS. It is believed that the Au-CdS nanocomposites may find potential applications in environmental fields, and this synthesis method can be extended to prepare a wide variety of functional composites with Au cores.

  19. Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury

    Science.gov (United States)

    Hormigo, Kristiina M.; Zholudeva, Lyandysha V.; Spruance, Victoria M.; Marchenko, Vitaliy; Cote, Marie-Pascale; Vinit, Stephane; Giszter, Simon; Bezdudnaya, Tatiana; Lane, Michael A.

    2016-01-01

    Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals. One strategy with demonstrated therapeutic potential is the use of treatments that increase neural and muscular activity (e.g. locomotor training, neural and muscular stimulation) and promote plasticity. With a focus on respiratory function post-SCI, this review will discuss advances in the use of neural interfacing strategies and activity-based treatments, and highlights some recent results from our own research. PMID:27582085

  20. PAPP-A proteolytic activity enhances IGF bioactivity in ascites from women with ovarian carcinoma

    DEFF Research Database (Denmark)

    Thomsen, Jacob; Hjortebjerg, Rikke; Espelund, Ulrick

    2015-01-01

    Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF) action through proteolysis of IGF-binding protein (IGFBP)-4. In experimental animals, PAPP-A accelerates ovarian tumor growth by this mechanism. To investigate the effect of PAPP-A in humans, we compared.......03). Ascites was more potent than serum in activating the IGF-I receptor (IGF-IR) in vitro (+31%, P IGF-I, and lower levels of IGF-II (P ... of IGF-IR in all but one tumor, whereas all tumors expressed PAPP-A, IGFBP-4, IGF-I and IGF-II. Addition of recombinant PAPP-A to ascites increased the cleavage of IGFBP-4 and enhanced IGF-IR activation (P IGFs and these proteins...

  1. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Larson JL

    2014-10-01

    Full Text Available Janet L Larson,1,2 Margaret K Covey,2 Mary C Kapella,2 Charles G Alex,3,4 Edward McAuley,5 1Division of Acute, Critical and Long-Term Care Programs, School of Nursing, University of Michigan, Ann Arbor, MI, 2Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, 3Division of Pulmonary and Critical Care Medicine, Edward Hines Jr VA Hospital, Hines, IL, 4Advocate Christ Medical Center, Oaklawn, IL, 5Department of Kinesiology and Community Health, College of Applied Health Sciences, University of Illinois Urbana-Champagne, Urbana, IL, USA Background: 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. Methods: 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. Results: 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

  2. Facile synthesis of polyaniline-modified CuS with enhanced adsorbtion and photocatalytic activity

    Science.gov (United States)

    Wang, Xiufang; Chen, Shaohua; Shuai, Ying

    2016-10-01

    Novel hierarchical polyaniline-modified CuS (PANI-CuS) has been synthesized by simple assembling PANI on the surface of flower-like CuS spheres. The PANI modification enhances the adsorption properties of flower-like CuS. The prepared PANI-CuS composites exhibit higher visible-light-driven photocatalytic activities in degradation of rhodamine B (RhB) than that of neat CuS. The unusual photocatalytic activity could be attributed to the great adsorptivity of dyes, the extended photoresponse range, and the high migration efficiency of photoinduced electrons, which may effectively suppress the charge recombination. This work not only provides a simple strategy for fabricating highly efficient and stable CuS-based composites, but also proves that these unique structures are excellent platforms for significantly improving their visible- light-driven photoactivities, holding great promise for their applications in the field of purifying polluted water resources.

  3. Enhanced osteogenic activity of poly ether ether ketone using calcium plasma immersion ion implantation.

    Science.gov (United States)

    Lu, Tao; Qian, Shi; Meng, Fanhao; Ning, Congqin; Liu, Xuanyong

    2016-06-01

    As a promising implantable material, poly ether ether ketone (PEEK) possesses similar elastic modulus to that of cortical bones yet suffers from bio-inertness and poor osteogenic properties, which limits its application as orthopedic implants. In this work, calcium is introduced onto PEEK surface using calcium plasma immersion ion implantation (Ca-PIII). The results obtained from scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) confirm the modified layer with varying contents of calcium are formed on PEEK surfaces. Water contact angle measurements reveal the increasing hydrophobicity of both Ca-PIII treated surfaces. In vitro cell adhesion, viability assay, alkaline phosphatase activity and collagen secretion analyses disclose improved the adhesion, proliferation, and osteo-differentiation of rat bone mesenchymal stem cells (bMSCs) on Ca-PIII treated surfaces. The obtained results indicate that PEEK surface with enhanced osteogenic activity can be produced by calcium incorporation. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Impact of slow-light enhancement on optical propagation in active semiconductor photonic crystal waveguides

    DEFF Research Database (Denmark)

    Chen, Yaohui; de Lasson, Jakob Rosenkrantz; Gregersen, Niels

    2015-01-01

    We derive and validate a set of coupled Bloch wave equations for analyzing the reflection and transmission properties of active semiconductor photonic crystal waveguides. In such devices, slow-light propagation can be used to enhance the material gain per unit length, enabling, for example......, the realization of short optical amplifiers compatible with photonic integration. The coupled wave analysis is compared to numerical approaches based on the Fourier modal method and a frequency domain finite element technique. The presence of material gain leads to the build-up of a backscattered field, which...... is interpreted as distributed feedback effects or reflection at passive-active interfaces, depending on the approach taken. For very large material gain values, the band structure of the waveguide is perturbed, and deviations from the simple coupled Bloch wave model are found....

  5. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

    Science.gov (United States)

    Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

    1990-01-01

    The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

  6. 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

    . The group that recovered in virtual nature without sound and the control group displayed no particular autonomic activation or deactivation. The results demonstrate a potential mechanistic link between nature, the sounds of nature, and stress recovery, and suggest the potential importance of virtual reality......Experimental research on stress recovery in natural environments is limited, as is study of the effect of sounds of nature. After inducing stress by means of a virtual stress test, we explored physiological recovery in two different virtual natural environments (with and without exposure to sounds...... 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...

  7. Pt3Co concave nanocubes: synthesis, formation understanding, and enhanced catalytic activity toward hydrogenation of styrene.

    Science.gov (United States)

    Wang, Chenyu; Lin, Cuikun; Zhang, Lihua; Quan, Zewei; Sun, Kai; Zhao, Bo; Wang, Feng; Porter, Nathan; Wang, Yuxuan; Fang, Jiye

    2014-02-03

    We report a facile synthesis route to prepare high-quality Pt3Co nanocubes with a concave structure, and further demonstrate that these concave Pt3Co nanocubes are terminated with high-index crystal facets. The success of this preparation is highly dependent on an appropriate nucleation process with a successively anisotropic overgrowth and a preservation of the resultant high-index planes by control binding of oleyl-amine/oleic acid with a fine-tuned composition. Using a hydrogenation of styrene as a model reaction, these Pt3Co concave nanocubes as a new class of nanocatalysts with more open structure and active atomic sites located on their high-index crystallographic planes exhibit an enhanced catalytic activity in comparison with low-indexed surface terminated Pt3Co nanocubes in similar size. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Using Laboratory Activities Enhanced with Concept Cartoons to Support Progression in Students' Understanding of Acid-Base Concepts

    Science.gov (United States)

    Ozmen, Haluk; Demircioglu, Gokhan; Burhan, Yasemin; Naseriazar, Akbar; Demircioglu, Hulya

    2012-01-01

    The aim of this study is to examine the effectiveness of an intervention based on a series of laboratory activities enhanced with concept cartoons. The purpose of the intervention was to enhance students' understanding of acid-base chemistry for eight grade students' from two classes in a Turkish primary school. A pretest-posttest non-equivalent…

  9. Re-localization of Cellular Protein SRp20 during Poliovirus Infection: Bridging a Viral IRES to the Host Cell Translation Apparatus

    Science.gov (United States)

    Fitzgerald, Kerry D.; Semler, Bert L.

    2011-01-01

    Poliovirus IRES-mediated translation requires the functions of certain canonical as well as non-canonical factors for the recruitment of ribosomes to the viral RNA. The interaction of cellular proteins PCBP2 and SRp20 in extracts from poliovirus-infected cells has been previously described, and these two proteins were shown to function synergistically in viral translation. To further define the mechanism of ribosome recruitment for the initiation of poliovirus IRES-dependent translation, we focused on the role of the interaction between cellular proteins PCBP2 and SRp20. Work described here demonstrates that SRp20 dramatically re-localizes from the nucleus to the cytoplasm of poliovirus-infected neuroblastoma cells during the course of infection. Importantly, SRp20 partially co-localizes with PCBP2 in the cytoplasm of infected cells, corroborating our previous in vitro interaction data. In addition, the data presented implicate the presence of these two proteins in viral translation initiation complexes. We show that in extracts from poliovirus-infected cells, SRp20 is associated with PCBP2 bound to poliovirus RNA, indicating that this interaction occurs on the viral RNA. Finally, we generated a mutated version of SRp20 lacking the RNA recognition motif (SRp20ΔRRM) and found that this protein is localized similar to the full length SRp20, and also partially co-localizes with PCBP2 during poliovirus infection. Expression of this mutated version of SRp20 results in a ∼100 fold decrease in virus yield for poliovirus when compared to expression of wild type SRp20, possibly via a dominant negative effect. Taken together, these results are consistent with a model in which SRp20 interacts with PCBP2 bound to the viral RNA, and this interaction functions to recruit ribosomes to the viral RNA in a direct or indirect manner, with the participation of additional protein-protein or protein-RNA interactions. PMID:21779168

  10. Generation of Pax6-IRES-EGFP knock-in mouse via the cloning-free CRISPR/Cas9 system to reliably visualize neurodevelopmental dynamics.

    Science.gov (United States)

    Inoue, Yukiko U; Morimoto, Yuki; Hoshino, Mikio; Inoue, Takayoshi

    2018-07-01

    Pax6 encodes a transcription factor that plays pivotal roles in eye development, early brain patterning, neocortical arealization, and so forth. Visualization of Pax6 expression dynamics in these events could offer numerous advantages to neurodevelopmental studies. While CRISPR/Cas9 system has dramatically accelerated one-step generation of knock-out mouse, establishment of gene-cassette knock-in mouse via zygote injection has been considered insufficient due to its low efficiency. Recently, an improved CRISPR/Cas9 system for effective gene-cassette knock-in has been reported, where the native form of guide RNAs (crRNA and tracrRNA) assembled with recombinant Cas9 protein are directly delivered into mouse fertilized eggs. Here we apply this strategy to insert IRES-EGFP-pA cassette into Pax6 locus and achieve efficient targeted insertions of the 1.8 kb reporter gene. In Pax6-IRES-EGFP mouse we have generated, EGFP-positive cells reside in the eyes and cerebellum as endogenous Pax6 expressing cells at postnatal day 2. At the early embryonic stages when the embryos are transparent, EGFP-positive regions can be easily identified without PCR-based genotyping, precisely recapitulating the endogenous Pax6 expression patterns. Remarkably, at E12.5, the graded expression patterns of Pax6 in the developing neocortex now become recognizable in our knock-in mice, serving a sufficiently sensitive and useful tool to precisely visualize neurodevelopmental processes. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

  11. Optical filter finesses enhancement based on nested coupled cavities and active medium

    Science.gov (United States)

    Adib, George A.; Sabry, Yasser M.; Khalil, Diaa

    2016-04-01

    Optical filters with relatively large FSR and narrow linewidth are simultaneously needed for different applications. The ratio between the FSR and the 3-dB linewidth is given by finesse of the filter, which is solely determined by the different energy loss mechanisms limited by the technology advancement. In this work, we present a novel coupled-cavity configuration embedding an optical filter and a gain medium; allowing an overall finesse enhancement and simultaneous FSR and 3-dB linewidth engineering beyond the technological limits of the filter fabrication method. The configuration consists of two resonators. An active ring resonator comprises an optical gain medium and a passive resonator. In one configuration, the optical filter is the passive resonator itself. In a second configuration, the passive resonator is another ring resonator that embeds the optical filter. The presented configurations using a semiconductor optical amplifier are applied one time to a mechanically Fabry-Perot filter in the first presented configuration; and a second time to a fiber ring filter in the second presented configuration. The mechanical filter has an original 3-dB linewidth of 1nm and an FSR that is larger than 100nm while the enhanced linewidth is about 0.3nm. The fiber ring filter length is 4 m and directional coupler ratios of 90/10corresponding to a 3-dBlinewidth of about 4MHz and an FSR of 47 MHz. The enhanced 3- dBlinewidth of the overall filter configuration is 200kHz, demonstrating finesse enhancement up to20 times the original finesse of the filter.

  12. DNP-enhanced solid-state NMR spectroscopy of active pharmaceutical ingredients.

    Science.gov (United States)

    Zhao, Li; Pinon, Arthur C; Emsley, Lyndon; Rossini, Aaron J

    2017-11-28

    Solid-state NMR spectroscopy has become a valuable tool for the characterization of both pure and formulated active pharmaceutical ingredients (APIs). However, NMR generally suffers from poor sensitivity that often restricts NMR experiments to nuclei with favorable properties, concentrated samples, and acquisition of one-dimensional (1D) NMR spectra. Here, we review how dynamic nuclear polarization (DNP) can be applied to routinely enhance the sensitivity of solid-state NMR experiments by one to two orders of magnitude for both pure and formulated APIs. Sample preparation protocols for relayed DNP experiments and experiments on directly doped APIs are detailed. Numerical spin diffusion models illustrate the dependence of relayed DNP enhancements on the relaxation properties and particle size of the solids and can be used for particle size determination when the other factors are known. We then describe the advanced solid-state NMR experiments that have been enabled by DNP and how they provide unique insight into the molecular and macroscopic structure of APIs. For example, with large sensitivity gains provided by DNP, natural isotopic abundance, 13 C- 13 C double-quantum single-quantum homonuclear correlation NMR spectra of pure APIs can be routinely acquired. DNP also enables solid-state NMR experiments with unreceptive quadrupolar nuclei such as 2 H, 14 N, and 35 Cl that are commonly found in APIs. Applications of DNP-enhanced solid-state NMR spectroscopy for the molecular level characterization of low API load formulations such as commercial tablets and amorphous solid dispersions are described. Future perspectives for DNP-enhanced solid-state NMR experiments on APIs are briefly discussed. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Reactive magnetron sputtering deposition of bismuth tungstate onto titania nanoparticles for enhancing visible light photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Ratova, Marina, E-mail: marina_ratova@hotmail.com [Surface Engineering Group, School of Engineering, Manchester Metropolitan University, Manchester, M1 5GD (United Kingdom); Kelly, Peter J.; West, Glen T. [Surface Engineering Group, School of Engineering, Manchester Metropolitan University, Manchester, M1 5GD (United Kingdom); Tosheva, Lubomira; Edge, Michele [School of Science and the Environment, Manchester Metropolitan University, Manchester M1 5GD (United Kingdom)

    2017-01-15

    Highlights: • Bismuth tungstate coatings were deposited by reactive magnetron sputtering. • Oscillating bowl was introduced to the system to enable coating of nanopartulates. • Deposition of Bi{sub 2}WO{sub 6} enhanced visible light activity of titania nanoparticles. • The best results were obtained for coating with Bi:W ratio of approximately 2:1. • Deposition of Bi{sub 2}WO{sub 6} onto TiO{sub 2} resulted in more efficient electron-hole separation. - Abstract: Titanium dioxide − bismuth tungstate composite materials were prepared by pulsed DC reactive magnetron sputtering of bismuth and tungsten metallic targets in argon/oxygen atmosphere onto anatase and rutile titania nanoparticles. The use of an oscillating bowl placed beneath the two magnetrons arranged in a co-planar closed field configuration enabled the deposition of bismuth tungstate onto loose powders, rather than a solid substrate. The atomic ratio of the bismuth/tungsten coatings was controlled by varying the power applied to each target. The effect of the bismuth tungstate coatings on the phase, optical and photocatalytic properties of titania was investigated by X-ray diffraction, energy-dispersive X-ray spectroscopy (EDX), Brunauer–Emmett–Teller (BET) surface area measurements, transmission electron microscopy (TEM), UV–vis diffuse reflectance spectroscopy and an acetone degradation test. The latter involved measurements of the rate of CO{sub 2} evolution under visible light irradiation of the photocatalysts, which indicated that the deposition of bismuth tungstate resulted in a significant enhancement of visible light activity, for both anatase and rutile titania particles. The best results were achieved for coatings with a bismuth to tungsten atomic ratio of 2:1. In addition, the mechanism by which the photocatalytic activity of the TiO{sub 2} nanoparticles was enhanced by compounding it with bismuth tungstate was studied by microwave cavity perturbation. The results of these

  14. Microbial Consortium with High Cellulolytic Activity (MCHCA for enhanced biogas production.

    Directory of Open Access Journals (Sweden)

    Krzysztof ePoszytek

    2016-03-01

    Full Text Available The use of lignocellulosic biomass as a substrate in agricultural biogas plants is very popular and yields good results. However, the efficiency of anaerobic digestion, and thus biogas production, is not always satisfactory due to the slow or incomplete degradation (hydrolysis of plant matter. To enhance the solubilization of the lignocellulosic biomass various physical, chemical and biological pretreatment methods are used.The aim of this study was to select and characterize cellulose-degrading bacteria, and to construct a microbial consortium, dedicated for degradation of maize silage and enhancing biogas production from this substrate.Over one hundred strains of cellulose-degrading bacteria were isolated from: sewage sludge, hydrolyzer from an agricultural biogas plant, cattle slurry and manure. After physiological characterization of the isolates, sixteen strains (representatives of Bacillus, Providencia and Ochrobactrum genera were chosen for the construction of a Microbial Consortium with High Cellulolytic Activity, called MCHCA. The selected strains had a high endoglucanase activity (exceeding 0.21 IU/mL CMCase activity and a wide range of tolerance to various physical and chemical conditions. Lab-scale simulation of biogas production using the selected strains for degradation of maize silage was carried out in a two-bioreactor system, similar to those used in agricultural biogas plants.The obtained results showed that the constructed MCHCA consortium is capable of efficient hydrolysis of maize silage, and increases biogas production by even 38%, depending on the inoculum used for methane fermentation. The results in this work indicate that the mesophilic Microbial Consortium with High Cellulolytic Activity has a great potential for application on industrial scale in agricultural biogas plants.

  15. Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation.

    Science.gov (United States)

    Lupia, E; Bosco, O; Mariano, F; Dondi, A E; Goffi, A; Spatola, T; Cuccurullo, A; Tizzani, P; Brondino, G; Stella, M; Montrucchio, G

    2009-06-01

    Thrombopoietin (TPO) is a humoral growth factor that does not induce platelet aggregation per se, but enhances platelet activation in response to several agonists. Circulating levels of TPO are increased in patients with sepsis and are mainly related to sepsis severity. To investigate the potential contribution of elevated TPO levels in platelet activation during burn injury complicated or not by sepsis. We studied 22 burned patients, 10 without and 12 with sepsis, and 10 healthy subjects. We measured plasma levels of TPO, as well as leukocyte-platelet binding and P-selectin expression. The priming activity of plasma from burned patients or healthy subjects on platelet aggregation and leukocyte-platelet binding, and the role of TPO in these effects were also studied in vitro. Burned patients without and with sepsis showed higher circulating TPO levels and increased monocyte-platelet binding compared with healthy subjects. Moreover, TPO levels, monocyte-platelet binding and P-selectin expression were significantly higher in burned patients with sepsis than in burned patients without sepsis. In vitro, plasma from burned patients without and with sepsis, but not from healthy subjects, primed platelet aggregation, monocyte-platelet binding and platelet P-selectin expression. The effect of plasma from burned patients with sepsis was significantly higher than that of plasma from burned patients without sepsis. An inhibitor of TPO prevented the priming effect of plasma from burned patients. Increased TPO levels may enhance platelet activation during burn injury and sepsis, potentially participating in the pathogenesis of multi-organ failure in these diseases.

  16. Synthesis of 2.5 nm colloidal iridium nanoparticles with strong surface enhanced Raman scattering activity

    International Nuclear Information System (INIS)

    Cui, Malin; Zhao, Yuan; Wang, Chan; Song, Qijun

    2016-01-01

    Colloidal iridium nanoparticles (IrNPs) were synthesized through an environmentally friendly approach by using trisodium citrate as the capping molecule in an aqueous medium. The resulting colloidal IrNPs have a typical diameter of