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Sample records for cd133 promoter reveals

  1. hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

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    Shunsuke Ohnishi

    Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

  2. Galectin-1 is overexpressed in CD133+ human lung adenocarcinoma cells and promotes their growth and invasiveness

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    Zhou, Xuefeng; Li, Dan; Wang, Xianguo; Zhang, Bo; Zhu, Hua; Zhao, Jinping

    2015-01-01

    Previous studies demonstrated that a subpopulation of cancer cells, which are CD133 positive (CD133+) feature higher invasive and metastatic abilities, are called cancer stem cells (CSCs). By using tumor cells derived from patients with lung adenocarcinoma, we found that galectin-1 is highly overexpressed in the CD133+ cancer cells as compared to the normal cancer cells (CD133−) from the same patients. We overexpressed galectin-1 in CD133− cancer cells and downregulated it in CSCs. We found that overexpression of galectin-1 promoted invasiveness of CD133− cells, while knockdown of galectin-1 suppressed proliferation, colony formation and invasiveness of CSCs. Furthermore, tumor growth was significantly inhibited in CSCs xenografts with knockdown of galectin-1 as compared to CSCs treated with scramble siRNAs. Biochemical studies revealed that galectin-1 knockdown led to the suppression of COX-2/PGE2 and AKT/mTOR pathways, indicating galectin-1 might control the phenotypes of CSCs by regulating these signaling pathways. Finally, a retrospective study revealed that galectin-1 levels in blood circulation negatively correlates with overall survival and positively correlates with lymph node metastasis of the patients. Taken together, these findings suggested that galectin-1 plays a major role on the tumorigenesis and invasiveness of CD133+ cancer cells and might serve as a potential therapeutic target for treatment of human patients with lung adenocarcinoma. PMID:25605013

  3. G protein-coupled receptor 87 (GPR87 promotes the growth and metastasis of CD133⁺ cancer stem-like cells in hepatocellular carcinoma.

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    Mingxia Yan

    Full Text Available Hepatocellular carcinoma (HCC is a prevalent disease worldwide, and the majority of HCC-related deaths occur due to local invasion and distant metastasis. Cancer stem cells (CSCs are a small subpopulation of cancer cells that have been hypothesized to be responsible for metastatic disease. Recently, we and others have identified a CSC population from human HCC cell lines and xenograft tumors characterized by their expression of CD133. However, the precise molecular mechanisms by which CD133(+ cancer stem-like cells mediate HCC metastasis have not been sufficiently analyzed. Here, we have sorted HCC cells using CD133 as a cancer stem cell (CSC marker by magnetic-activated cell sorting (MACS and demonstrated that the CD133(+ HCC cells not only possess greater migratory and invasive capacity in vitro but are also endowed with enhanced metastatic capacity in vivo and in human HCC specimens when compared to CD133(- HCC cells. Gene expression analysis of the CD133(+ and CD133(- cells of the HCC line SMMC-7721 revealed that G protein-coupled receptor 87 (GPR87 is highly expressed in CD133(+ HCC cells. In this study, we explored the role of GPR87 in the regulation of CD133 expression. We demonstrated that the overexpression of GPR87 up-regulated CD133 expression, promoted CSC-associated migratory and invasive properties in vitro, and increased tumor initiation in vivo. Conversely, silencing of GPR87 expression reduced the levels of CD133 expression.GPR87 promotes the growth and metastasis of CD133(+ cancer stem-like cells, and our findings may reveal new targets for HCC prevention or therapy.

  4. Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

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    2014-01-01

    Background New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients. Methods MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade. Results Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes. Conclusions Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility. PMID:25015560

  5. The Interaction between Cancer Stem Cell Marker CD133 and Src Protein Promotes Focal Adhesion Kinase (FAK) Phosphorylation and Cell Migration.

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    Liu, Chanjuan; Li, Yinan; Xing, Yang; Cao, Benjin; Yang, Fan; Yang, Tianxiao; Ai, Zhilong; Wei, Yuanyan; Jiang, Jianhai

    2016-07-22

    CD133, a widely known cancer stem cell marker, has been proved to promote tumor metastasis. However, the mechanism by which CD133 regulates metastasis remains largely unknown. Here, we report that CD133 knockdown inhibits cancer cell migration, and CD133 overexpression promotes cell migration. CD133 expression is beneficial to activate the Src-focal adhesion kinase (FAK) signaling pathway. Further studies show that CD133 could interact with Src, and the region between amino acids 845 and 857 in the CD133 C-terminal domain is indispensable for its interaction with Src. The interaction activates Src to phosphorylate its substrate FAK and to promote cell migration. Likewise, a Src binding-deficient CD133 mutant loses the abilities to increase Src and FAK phosphorylation and to promote cell migration. Inhibition of Src activity by PP2, a known Src activity inhibitor, could block the activation of FAK phosphorylation and cell migration induced by CD133. In summary, our data suggest that activation of FAK by the interaction between CD133 and Src promotes cell migration, providing clues to understand the migratory mechanism of CD133(+) tumor cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells.

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    Long, Qifang; Yang, Ru; Lu, Weixian; Zhu, Weipei; Zhou, Jundong; Zheng, Cui; Zhou, Dongmei; Yu, Ling; Wu, Jinchang

    2017-01-01

    Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133+ ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.

  7. MGMT promoter methylation status and MGMT and CD133 immunohistochemical expression as prognostic markers in glioblastoma patients treated with temozolomide plus radiotherapy

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    2012-01-01

    Background The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. Methods Seventy-eight patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan–Meier method. Results The MGMT gene promoter was found to be methylated in 34 patients (44.7%) and unmethylated in 42 patients (55.3%). A significant correlation was observed between MGMT promoter methylation and patients’ survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative. Conclusions Our results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these patients. Future studies

  8. MGMT promoter methylation status and MGMT and CD133 immunohistochemical expression as prognostic markers in glioblastoma patients treated with temozolomide plus radiotherapy

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    Melguizo Consolación

    2012-12-01

    Full Text Available Abstract Background The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM. The O6-methylguanine DNA methyltransferase (MGMT enzyme is related with temozolomide (TMZ resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. Methods Seventy-eight patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan–Meier method. Results The MGMT gene promoter was found to be methylated in 34 patients (44.7% and unmethylated in 42 patients (55.3%. A significant correlation was observed between MGMT promoter methylation and patients’ survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative. Conclusions Our results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these

  9. Differential characteristics of CD133(+) and CD133 (-) Jurkat cells.

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    Anbarlou, Azadeh; Atashi, Amir; Soleimani, Masoud; AkhavanRahnama, Mahshid; Bohloli, Mahbobeh; Mossahebi-Mohammadi, Majid

    2015-06-01

    T cell acute lymphoblastic leukemia (T-ALL) is a hematological disease including malignancy of T cell precursors. There are some T-ALL patients that are drug-resistant. A major cause of treatment failure in cancers can be associated with the existence of cancer stem cells. The identification of these cell populations helps us to clarify resistance mechanisms and rely on special markers for recognizing cancer stem cells. CD133 is one of the markers that is used for the identification of cancer stem cells. In this study, we evaluated CD133(+) and CD133(-) characteristic cells in Jurkat cells by assay proliferation, invasion, and apoptosis. CD133(+) and CD133(-) Jurkat cells were separated and immediately analyzed for proliferation, invasion, and doxorubicin-induced apoptosis. Proliferation, invasion, and resistance to chemotherapy of CD133(+) Jurkat cells were significantly more than CD133(-) Jurkat cells. Also, our results showed that CD133(+) Jurkat cells expressed ABCG2 gene more than CD133(-) Jurkat cells. In conclusion, CD133 marker could be introduced as a specific marker of cancer stem cells in Jurkat cell line.

  10. Biomarker screening of oral cancer cell lines revealed sub-populations of CD133-, CD44-, CD24- and ALDH1- positive cancer stem cells

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    Kendall K

    2013-05-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth worldwide for cancer-related mortality. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation, although more recent trials combining chemotherapy and radiation have demonstrated improvements. However, cancer recurrence and treatment failures continue to occur in a significant percentage of patients. Recent advances in tumor biology have led to the discovery that many cancers, including HNSCC, may contain subpopulations of cells with stem cell-like properties that may explain relapse and recurrence. The objective of this study was to screen existing oral cancer cell lines for biomarkers specific for cells with stem cell-like properties. RNA was isolated for RT-PCR screening using primers for specific mRNA of the biomarkers: CD44, CD24, CD133, NANOG, Nestin, ALDH1, and ABCG2 in CAL27, SCC25 and SCC15 cells. This analysis revealed that some oral cancer cell lines (CAL27 and SCC25 may contain small subpopulations of adhesion- and contact-independent cells (AiDC that also express tumor stem cell markers, including CD44, CD133, and CD24. In addition, CAL27 cells also expressed the intracellular tumor stem cell markers, ALDH1 and ABCG2. Isolation and culture of the adhesion- and contact-independent cells from CAL27 and SCC25 populations revealed differential proliferation rates and more robust inhibition by the MEK inhibitor PD98059, as well as the chemotherapeutic agents Cisplatin and Paclitaxel, within the AiDC CAL27 cells. At least one oral cancer cell line (CAL27 contained subpopulations of cells that express specific biomarkers associated with tumor stem cells which were morphologically and phenotypically distinct from other cells within this cell line.

  11. CD133 expression in chemo-resistant Ewing sarcoma cells

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    Kovar Heinrich

    2010-03-01

    lines the CD133+ fraction is relatively more drug-resistant, while in others there is no apparent difference between CD133+ and CD133- cells. These studies reveal heterogeneity in PROM1/CD133 expression in ESFT tumors and cell lines and confirm that high levels of PROM1 expression are, in at least some cases, associated with chemo-resistant disease. Further studies are required to elucidate the contribution of PROM1/CD133 expressing cells to therapeutic resistance in a large, prospective cohort of primary ESFT.

  12. Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas

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    Garcia Juan L

    2010-08-01

    Full Text Available Abstract Background Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Methods Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; Results Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders. Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups

  13. Selected CD133⁺ progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial.

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    Jimenez-Quevedo, Pilar; Gonzalez-Ferrer, Juan Jose; Sabate, Manel; Garcia-Moll, Xavier; Delgado-Bolton, Roberto; Llorente, Leopoldo; Bernardo, Esther; Ortega-Pozzi, Aranzazu; Hernandez-Antolin, Rosana; Alfonso, Fernando; Gonzalo, Nieves; Escaned, Javier; Bañuelos, Camino; Regueiro, Ander; Marin, Pedro; Fernandez-Ortiz, Antonio; Neves, Barbara Das; Del Trigo, Maria; Fernandez, Cristina; Tejerina, Teresa; Redondo, Santiago; Garcia, Eulogio; Macaya, Carlos

    2014-11-07

    Refractory angina constitutes a clinical problem. The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133(+) cells to foster angiogenesis in patients with refractory angina. In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133(+) cells or no treatment. The primary end point was the safety of transendocardial injection of CD133(+) cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, -8.5 [95% confidence interval, -15.0 to -4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, -1.0 [95% confidence interval, -1.9 to -0.1]) but not in the control arm. Our findings support feasibility and safety of transendocardial injection of CD133(+) cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial. © 2014 American Heart Association, Inc.

  14. The biological difference between CD13+CD133+ and CD13¬CD133¬liver cancer cells and its clinical significance

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    Shi-long JIN

    2013-09-01

    Full Text Available Objective To compare the biological difference between CD13+CD133+ and CD13-CD133- hepatocellular carcinoma (HCC cells in HuH7 cell line and its clinical significance. Methods The status of proliferation, phase of the cell cycle, tumor formation in vivo, differentiation, and their chemoresistance to 5-FU and pirarubicin of CD13+CD133+ and CD13-CD133-HCC cells were studied to analyze the clinical implication of CD13+CD133+HCC cell subset. Results The proliferation rate of CD13+CD133+HCC cells was significantly higher than that of CD13-CD133-HCC cells. The cell-cycle phase study showed that 78.45% of the CD13+CD133+HCC cells were in the G0/G1 phase, 2.19% in G2/M phase, and 19.36% in S phase, while 62.18% CD13-CD133-HCC cells were in the G0/G1 phase, 11.88% in G2/M phase, and 25.95% in S phase. Limiting dilution analysis of HuH7 cells revealed that 1×103 CD13+CD133+ cells could form the tumor, while 1×105 CD13-CD133- cells did. CD13+CD133+ cells showed chemoresistance to 5-FU and pirarubicin, while other three subsets succumbed to the drugs. Conclusion CD13+CD133+ cancer cells in HuH7 showed the characteristics of cancer stem cells (CSCs, which might contribute to the relapse and metastasis of liver cancer, and they may be the main target for chemotherapy in human liver cancer.

  15. CD133, Selectively Targeting the Root of Cancer

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    Jörg U. Schmohl

    2016-05-01

    Full Text Available Cancer stem cells (CSC are capable of promoting tumor initiation and self-renewal, two important hallmarks of carcinoma formation. This population comprises a small percentage of the tumor mass and is highly resistant to chemotherapy, causing the most difficult problem in the field of cancer research, drug refractory relapse. Many CSC markers have been reported. One of the most promising and perhaps least ubiquitous is CD133, a membrane-bound pentaspan glycoprotein that is frequently expressed on CSC. There is evidence that directly targeting CD133 with biological drugs might be the most effective way to eliminate CSC. We have investigated two entirely unrelated, but highly effective approaches for selectively targeting CD133. The first involves using a special anti-CD133 single chain variable fragment (scFv to deliver a catalytic toxin. The second utilizes this same scFv to deliver components of the immune system. In this review, we discuss the development and current status of these CD133 associated biological agents. Together, they show exceptional promise by specific and efficient CSC elimination.

  16. Expression of CD133 in acute leukemia.

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    Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

    2013-06-01

    There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients.

  17. Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia

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    Blazek, Ed R.; Foutch, Jennifer L.; Maki, Guitta

    2007-01-01

    Purpose: Primary medulloblastoma and glioblastoma multiforme tumor cells that express the surface marker CD133 are believed to be enriched for brain tumor stem cells because of their unique ability to initiate or reconstitute tumors in immunodeficient mice. This study sought to characterize the radiobiological properties and marker expression changes of CD133+ vs. CD133- cells of an established medulloblastoma cell line. Methods and Materials: Daoy and D283 Med cell lines were stained with fluorescently labeled anti-CD133 antibody and sorted into CD133+ and CD133- populations. The effect of oxygen (2% vs. 20%) on CD133 expression was measured. Both populations were analyzed for marker stability, cell cycle distribution, and radiosensitivity. Results: CD133+ Daoy cells restored nearly native CD133+ and CD133- populations within 18 days, whereas CD133- cells remained overwhelmingly CD133-. Culturing Daoy cells in 2% oxygen rather than the standard 20% oxygen increased their CD133 expression 1.6-fold. CD133+ Daoy cells were radioresistant via the β-parameter of the linear-quadratic model relative to CD133- Daoy cells, although their α-parameters and cell cycle distributions were identical. Conclusions: Restoration of the original CD133+ and CD133- populations from CD133+ Daoy cells in serum is further evidence that CD133+ cells are functionally distinct from CD133- cells. The radioresistance of CD133+ compared with CD133- Daoy cells is consistent with better repair of sublethal damage. Enlargement of the CD133+ sector is a new feature of the hypoxic response

  18. Presence of pluripotent CD133+ cells correlates with malignancy of gliomas.

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    Thon, Niklas; Damianoff, Karin; Hegermann, Jemima; Grau, Stefan; Krebs, Bjarne; Schnell, Oliver; Tonn, Jörg-Christian; Goldbrunner, Roland

    2010-01-01

    Presence of CD133(+) cancer stem cells has been demonstrated within glioblastoma multiforme (GBM), the most malignant phenotype of gliomas (WHO grade IV). Since GBM frequently develops from low grade gliomas (WHO grade II) we assessed a possible qualitative or quantitative correlation of CD133(+) cells and glioma grade to get new insights in gliomagenesis. The amount of CD133(+) cells within the bulk tumor mass, analyzed by immunostaining and Western blotting, showed a clear quantitative correlation with glioma grade (WHO degrees II, III and IV). Most of CD133(+) cells were arranged in clusters frequently associated to tumor vessels. Protein analysis revealed high cellular coexpression of CD133 with Musashi-I but not CD34 indicating a neural, i.e. local origin of these cells. In vitro, no differences in stem cell properties concerning self-renewal and multi-lineage differentiation have been found for CD133(+) cells isolated from gliomas of different grades. These findings indicate a solely quantitative correlation of glioma grade with the presence of neural CD133(+) cells within tumors supporting the concept of a CD133(+) stem cell dependent gliomagenesis. Copyright 2008. Published by Elsevier Inc.

  19. Enhancing the Oncolytic Activity of CD133-Targeted Measles Virus: Receptor Extension or Chimerism with Vesicular Stomatitis Virus Are Most Effective

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    Dina Kleinlützum

    2017-06-01

    Full Text Available Therapy resistance and tumor recurrence are often linked to a small refractory and highly tumorigenic subpopulation of neoplastic cells, known as cancer stem cells (CSCs. A putative marker of CSCs is CD133 (prominin-1. We have previously described a CD133-targeted oncolytic measles virus (MV-CD133 as a promising approach to specifically eliminate CD133-positive tumor cells. Selectivity was introduced at the level of cell entry by an engineered MV hemagglutinin (H. The H protein was blinded for its native receptors and displayed a CD133-specific single-chain antibody fragment (scFv as targeting domain. Interestingly, MV-CD133 was more active in killing CD133-positive tumors than the unmodified MV-NSe despite being highly selective for its target cells. To further enhance the antitumoral activity of MV-CD133, we here pursued arming technologies, receptor extension, and chimeras between MV-CD133 and vesicular stomatitis virus (VSV. All newly generated viruses including VSV-CD133 were highly selective in eliminating CD133-positive cells. MV-CD46/CD133 killed in addition CD133-negative cells being positive for the MV receptors. In an orthotopic glioma model, MV-CD46/CD133 and MVSCD-CD133, which encodes the super cytosine deaminase, were most effective. Notably, VSV-CD133 caused fatal neurotoxicity in this tumor model. Use of CD133 as receptor could be excluded as being causative. In a subcutaneous tumor model of hepatocellular cancer, VSV-CD133 revealed the most potent oncolytic activity and also significantly prolonged survival of the mice when injected intravenously. Compared to MV-CD133, VSV-CD133 infected a more than 104-fold larger area of the tumor within the same time period. Our data not only suggest new concepts and approaches toward enhancing the oncolytic activity of CD133-targeted oncolytic viruses but also raise awareness about careful toxicity testing of novel virus types.

  20. CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth.

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    Zhou, Linli; Yang, Kun; Carpenter, April; Lang, Richard A; Andl, Thomas; Zhang, Yuhang

    2016-10-01

    Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. CD133 is essential for glioblastoma stem cell maintenance.

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    Brescia, Paola; Ortensi, Barbara; Fornasari, Lorenzo; Levi, Daniel; Broggi, Giovanni; Pelicci, Giuliana

    2013-05-01

    The role of the cell surface CD133 as a cancer stem cell marker in glioblastoma (GBM) has been widely investigated, since it identifies cells that are able to initiate neurosphere growth and form heterogeneous tumors when transplanted in immune-compromised mice. However, evidences of CD133-negative cells exhibiting similar properties have also been reported. Moreover, the functional role of CD133 in cancer stem/progenitor cells remains poorly understood. We studied the biological effects of CD133 downregulation in GBM patient-derived neurospheres. Our results indicate that there is not a hierarchical relation between CD133-positive and CD133-negative cells composing the neurospheres. Indeed, CD133 appears in an interconvertible state, changing its subcellular localization between the cytoplasm and the plasmamembrane of neurosphere cells. Silencing of CD133 in human GBM neurospheres using lentivirus-mediated short hairpin RNA impairs the self-renewal and tumorigenic capacity of neurosphere cells. These results imply that CD133 could be used as a therapeutic target in GBMs. Copyright © 2013 AlphaMed Press.

  2. Label-free quantitative proteomics of CD133-positive liver cancer stem cells

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    Tsai Sheng-Ta

    2012-11-01

    Full Text Available Abstract Background CD133-positive liver cancer stem cells, which are characterized by their resistance to conventional chemotherapy and their tumor initiation ability at limited dilutions, have been recognized as a critical target in liver cancer therapeutics. In the current work, we developed a label-free quantitative method to investigate the proteome of CD133-positive liver cancer stem cells for the purpose of identifying unique biomarkers that can be utilized for targeting liver cancer stem cells. Label-free quantitation was performed in combination with ID-based Elution time Alignment by Linear regression Quantitation (IDEAL-Q and MaxQuant. Results Initially, IDEAL-Q analysis revealed that 151 proteins were differentially expressed in the CD133-positive hepatoma cells when compared with CD133-negative cells. We then analyzed these 151 differentially expressed proteins by MaxQuant software and identified 10 significantly up-regulated proteins. The results were further validated by RT-PCR, western blot, flow cytometry or immunofluorescent staining which revealed that prominin-1, annexin A1, annexin A3, transgelin, creatine kinase B, vimentin, and EpCAM were indeed highly expressed in the CD133-positive hepatoma cells. Conclusions These findings confirmed that mass spectrometry-based label-free quantitative proteomics can be used to gain insights into liver cancer stem cells.

  3. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

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    Zhang Xin

    2009-07-01

    Full Text Available Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors. Patients and methods Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed. Results The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5% were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%. Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth. Conclusion The fact that a higher percentage CD133+ cells were strongly associated

  4. Expression of Nestin and CD133 in serous ovarian carcinoma.

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    Onisim, Andrea; Iancu, Mihaela; Vlad, Catalin; Kubelac, Paul; Fetica, Bogdan; Fulop, Annamaria; Achimas-Cadariu, Andrei; Achimas-Cadariu, Patriciu

    2016-01-01

    Pupose: Nestin and CD133 are regarded as putative markers of cancer stem cells (CSCs) and related to poor prognosis in various cancer sites. Since few studies have focused on their role in ovarian cancer, we aimed to investigate their predictive value and association with neoangiogenesis. Immunohistochemical analysis for nestin and CD133 was performed on 85 serous ovarian carcinoma tumor samples using tissue microarray technique. Nestin immunoreactivity was detected in both tumor and endothelial cells, whilst CD133 was only identified in tumor cells. CD34 endothelial expression was used to assess intratumor microvessel density (MVD). Of the tissue samples 49.4% were nestin-positive and 24.7% were positive for CD133. In both univariate and multivariate analysis nestin or CD133 expressions in tumor cells were not significantly associated with clinicopathological parameters (age, serum CA125, peritoneal carcinomatosis, malignant ascites, tumor grade). However, in multivariate analysis nestin expression in tumor cells proved to be an independent prognostic factor, associated with poorer survival and time to progression (p=0.025 and p=0.05, respectively). This has not been achieved for CD133. Furthermore, a significant concordance between nestin endothelial expression (nestin-determined MVD) and CD34-determined MVD was achieved. In addition to the well-known clinicopathological characteristics, tumor expression of nestin might be a valuable prognostic factor for survival in patients with advanced ovarian cancer. With regard to its endothelial expression, nestin might be as reliable as CD34 for quantifying tumor angiogenesis. Further investigation is justified in order to better clarify the role of these biomarkers.

  5. CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy

    International Nuclear Information System (INIS)

    Mia-Jan, Khalilullah; Jung, So Young; Kim, Ik-Yong; Oh, Sung Soo; Choi, EunHee; Chang, Sei Jin; Kang, Tae Young; Cho, Mee-Yon

    2013-01-01

    Cancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet. We assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing. The CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015). In stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor

  6. Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients

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    Yang Zhuanyi

    2008-12-01

    Full Text Available Abstract Aim Gliomas represent the most frequent neoplasm of the central nervous system. Unfortunately, surgical cure of it is practically impossible and their clinical course is primarily determined by the biological behaviors of the tumor cells. The aim of this study was to investigate the correlation of the stem cell markers Nestin and CD133 expression with the grading of gliomas, and to evaluate their prognostic value. Methods The tissue samples consisted of 56 low- (WHO grade II, 69 high- (WHO grade III, IV grade gliomas, and 10 normal brain tissues. The expression levels of Nestin and CD133 proteins were detected using SABC immunohistochemical analysis. Then, the correlation of the two markers' expression with gliomas' grading of patients and their prognostic value were determined. Results Immunohistochemical analysis with anti-Nestin and anti-CD133 antibodies revealed dense and spotty staining in the tumor cells and their expression levels became significantly higher as the glioma grade advanced (p p p p Conclusion These results collectively suggest that Nestin and CD133 expression may be an important feature of human gliomas. A combined detection of Nestin/CD133 co-expression may benefit us in the prediction of aggressive nature of this tumor.

  7. CD133+ brain tumor-initiating cells are dependent on STAT3 signaling to drive medulloblastoma recurrence.

    Science.gov (United States)

    Garg, N; Bakhshinyan, D; Venugopal, C; Mahendram, S; Rosa, D A; Vijayakumar, T; Manoranjan, B; Hallett, R; McFarlane, N; Delaney, K H; Kwiecien, J M; Arpin, C C; Lai, P-S; Gómez-Biagi, R F; Ali, A M; de Araujo, E D; Ajani, O A; Hassell, J A; Gunning, P T; Singh, S K

    2017-02-02

    Medulloblastoma (MB), the most common malignant paediatric brain tumor, is currently treated using a combination of surgery, craniospinal radiotherapy and chemotherapy. Owing to MB stem cells (MBSCs), a subset of MB patients remains untreatable despite standard therapy. CD133 is used to identify MBSCs although its functional role in tumorigenesis has yet to be determined. In this work, we showed enrichment of CD133 in Group 3 MB is associated with increased rate of metastasis and poor clinical outcome. The signal transducers and activators of transcription-3 (STAT3) pathway are selectively activated in CD133 + MBSCs and promote tumorigenesis through regulation of c-MYC, a key genetic driver of Group 3 MB. We screened compound libraries for STAT3 inhibitors and treatment with the selected STAT3 inhibitors resulted in tumor size reduction in vivo. We propose that inhibition of STAT3 signaling in MBSCs may represent a potential therapeutic strategy to treat patients with recurrent MB.

  8. Differential number of CD34+, CD133+ and CD34+/CD133+ cells in peripheral blood of patients with congestive heart failure

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    Fritzenwanger M

    2009-03-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPC which are characterised by the simulateous expression of CD34, CD133 and vascular endothelial growth receptor 2 (VEGF 2 are involved in the pathophysiology of congestive heart failure (CHF and their number and function is reduced in CHF. But so far our knowledge about the number of circulating hematopoietic stem/progenitor cells (CPC expressing the early hematopoietic marker CD133 and CD34 in CHF is spares and therefore we determined their number and correlated them with New York Heart Association (NYHA functional class. Methods CD34 and CD133 surface expression was quantified by flow cytometry in the peripheral venous blood of 41 healthy adults and 101 patients with various degrees of CHF. Results CD34+, CD133+ and CD34+/CD133+ cells correlated inversely with age. Both the number of CD34+ and of CD34+/CD133+ cells inversely correlated with NYHA functional class. The number of CD133+ cells was not affected by NYHA class. Furthermore the number of CD133+ cells did not differ between control and CHF patients. Conclusion In CHF the release of CD34+, CD133+ and CD34+/CD133+ cells from the bone marrow seems to be regulated differently. Modulating the releasing process in CHF may be a tool in CHF treatment.

  9. Eukaryotic Initiation Factor 5A2 Contributes to the Maintenance of CD133(+) Hepatocellular Carcinoma Cells via the c-Myc/microRNA-29b Axis.

    Science.gov (United States)

    Bai, Hai-Yan; Liao, Yi-Ji; Cai, Mu-Yan; Ma, Ning-Fang; Zhang, Qi; Chen, Jie-Wei; Zhang, Jia-Xing; Wang, Feng-Wei; Wang, Chen-Yuan; Chen, Wen-Hui; Jin, Xiao-Han; Xu, Rui-Hua; Guan, Xin-Yuan; Xie, Dan

    2018-02-01

    Cancer stem cells (CSCs)/cancer-initiating cells (CICs) are suggested responsible for driving cancer resistance to conventional therapies and for cancer recurrence and/or metastasis. CD133 is served as a key biomarker to identify and characterize this subpopulation of cells in hepatocellular carcinoma (HCC). Our previous study indicated that overexpression of eukaryotic initiation factor 5A2 (EIF5A2) promotes HCC cell metastasis and angiogenesis. In this study, we demonstrated that EIF5A2 might play a crucial role in CSCs regulation and investigated its potential molecular mechanisms. Using quantitative real-time polymerase chain reaction assay, we observed that the expression of EIF5A2 positively correlated with CD133 levels in a cohort of cancerous and noncancerous liver tissues and cells. Next, HCC cells with high expression of EIF5A2 have a strong capacity to form undifferentiated tumor spheres in vitro and show elevated levels of stem cell-related genes, leading to an increased ability to develop tumors when subcutaneously injected into nude mice. Furthermore, differential microRNA expression was profiling between two EIF5A2-depleted HCC cell lines and their control one identified a decreased expression of miR-29b in EIF5A2-depleted cell lines. Further functional studies illustrated that downregulated miR-29b level is responsible for EIF5A2-maintained HCC cell stemness either in vitro or in vivo. Moreover, enforced expression of EIF5A2 in HCC cells largely enhanced the binding of c-Myc on the promoter of miR-29b and downregulation of miR-29b by EIF5A2 was dependent on c-Myc. Our findings, collectively, reveal that EIF5A2 contributes to the maintenance of CD133+ HCC cells via the c-Myc/miR-29b axis. Stem Cells 2018;36:180-191. © 2017 AlphaMed Press.

  10. Intracoronary Infusion of Autologous CD133+ Cells in Myocardial Infarction and Tracing by Tc99m MIBI Scintigraphy of the Heart Areas Involved in Cell Homing

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    Ubaidullo Kurbonov

    2013-01-01

    Full Text Available CD133 mesenchymal cells were enriched using magnetic microbead anti-CD133 antibody from bone marrow mononuclear cells (BMMNCs. Flow cytometry and immunocytochemistry analysis using specific antibodies revealed that these cells were essentially 89 ± 4% CD133+ and 8 ± 5% CD34+. CD133+/CD34+ BMMNCs secrete important bioactive proteins such as cardiotrophin-1, angiogenic and neurogenic factors, morphogenetic proteins, and proinflammatory and remodeling factors in vitro. Single intracoronary infusions of autologous CD133+/CD34+ BMMNCs are effective and reduce infarct size in patients as analyzed by Tc99m MIBI myocardial scintigraphy. The majority of patients were treated via left coronary artery. Nine months after cell therapy, 5 out of 8 patients showed a net positive response to therapy in different regions of the heart. Uptake of Tc99 isotope and revitalization of the heart area in inferoseptal region are more pronounced (P=0.016 as compared to apex and anterosptal regions after intracoronary injection of the stem cells. The cells chosen here have the properties essential for their potential use in cell therapy and their homing can be followed without major difficulty by the scintigraphy. The cell therapy proposed here is safe and should be practiced, as we found, in conjunction with scintigraphic observation of areas of heart which respond optimally to the infusion of autologous CD133+/CD34+ BMMNCs.

  11. Chemoresistance of CD133(+) colon cancer may be related with increased survivin expression.

    Science.gov (United States)

    Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah; Cho, Mee-Yon

    2015-07-31

    CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133(+) colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133(-) cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133(+) and siRNA-induced CD133(-) cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133(+) cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133(+) cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133(+) cells at 96 h after siRNA transfection. From this study, we conclude that CD133(+) cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133(+) colon cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Chemoresistance of CD133+ colon cancer may be related with increased survivin expression

    International Nuclear Information System (INIS)

    Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah; Cho, Mee-Yon

    2015-01-01

    CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133 + colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133 − cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133 + and siRNA-induced CD133 − cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133 + cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133 + cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133 + cells at 96 h after siRNA transfection. From this study, we conclude that CD133 + cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133 + colon cancer. - Highlights: • We evaluate the role of CD133 in chemoresistance of colon cancer. • We compared the chemoresistance of CD133 + cells and siRNA-induced CD133 − cells. • CD133 had little to no effect on MDR1, ABCG2 and AKT1 expression. • Survivin expression and chemoresistance were increased in CD133 + colon cancer cells

  13. Chemoresistance of CD133{sup +} colon cancer may be related with increased survivin expression

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    Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Cho, Mee-Yon, E-mail: meeyon@yonsei.ac.kr [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Institute of Genomic Cohort, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of)

    2015-07-31

    CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133{sup +} colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133{sup −} cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133{sup +} and siRNA-induced CD133{sup −} cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133{sup +} cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133{sup +} cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133{sup +} cells at 96 h after siRNA transfection. From this study, we conclude that CD133{sup +} cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133{sup +} colon cancer. - Highlights: • We evaluate the role of CD133 in chemoresistance of colon cancer. • We compared the chemoresistance of CD133{sup +} cells and siRNA-induced CD133{sup −} cells. • CD133 had little to no effect on MDR1, ABCG2 and AKT1 expression. • Survivin expression and chemoresistance were increased in CD133{sup +} colon cancer cells.

  14. Chemoresistance to 5-FU inhibited by 635 nm LED irradiation in CD133+ KB cell line.

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    Kim, Donghwi; Park, Mineon; Jang, Hyunwoong; Hyun, Hoon; Lim, Wonbong

    2018-01-01

    Consistent with cancer stem cell theory, a small fraction of cancer cells, described as cancer stem cells (CSCs), may promote tumor recurrence and anti-cancer drug resistance. Therefore, much effort has been devoted to the development of CSC targeted therapy to vanquish drug resistance. In this study, we have investigated the effect of multiple light-emitting diode (LED) irradiation treatments with conventional anti-cancer drugs on CSC-like oral cancer cells that acquired stemness by ectopic over expression of CD133. To evaluate combined LED irradiation anti-cancer drug effects, we investigated the chemosensitizing effect of 635 nm irradiation on 5-fluorouracil (5FU)-treated KB CD133+ and KB Vec cells, interrogating the underlying molecular mechanisms associated with stemness and apoptosis that are responsible for chemopreventive activity. In addition, combination therapy with LED irradiation and 5-FU treatment was carried out in KB CD133+ and KB Vec cell-inoculated mouse models. LED irradiation of 635 nm inhibited CSC-like properties consistent with a decrease in OCT4 and NANOG protein expression, reducing colony-forming ability. In addition, LED irradiation enhanced 5-FU-induced cytotoxicity and improved 5-FU chemosensitivity in KB CD133+ via enhancement of apoptosis. These findings were validated in vivo, wherein LED irradiation combined with 5-FU treatment inhibited tumor growth in KB CD133+ -inoculated mice. Collectively, our results provide novel evidence for 635 nm irradiation-induced 5-FU chemosensitization of CSC in oral cancer. In addition, this research highlights that 635 nm LED irradiation may serve as an adjunct treatment to conventional chemotherapeutic drugs in patients with oral cancer.

  15. Distinctive effects of CD34- and CD133-specific antibody-coated stents on re-endothelialization and in-stent restenosis at the early phase of vascular injury

    DEFF Research Database (Denmark)

    Wu, Xue; Yin, Tieying; Tian, Jie

    2015-01-01

    It is not clear what effects of CD34- and CD133-specific antibody-coated stents have on re-endothelialization and in-stent restenosis (ISR) at the early phase of vascular injury. This study aims at determining the capabilities of different coatings on stents (e.g. gelatin, anti-CD133 and anti-CD34......-coated stents, the time of cells adhesion was longer and earlier present in the anti-CD133 antibody-coated stents and anti-CD133 antibody-coated stents have superiority in re-endothelialization and inhibition of ISR. In conclusion, this study demonstrated that anti-CD133 antibody as a stent coating...... for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR....

  16. CD133 is a marker of bioenergetic stress in human glioma.

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    Corinne E Griguer

    Full Text Available Mitochondria dysfunction and hypoxic microenvironment are hallmarks of cancer cell biology. Recently, many studies have focused on isolation of brain cancer stem cells using CD133 expression. In this study, we investigated whether CD133 expression is regulated by bioenergetic stresses affecting mitochondrial functions in human glioma cells. First, we determined that hypoxia induced a reversible up-regulation of CD133 expression. Second, mitochondrial dysfunction through pharmacological inhibition of the Electron Transport Chain (ETC produced an up-regulation of CD133 expression that was inversely correlated with changes in mitochondrial membrane potential. Third, generation of stable glioma cells depleted of mitochondrial DNA showed significant and stable increases in CD133 expression. These glioma cells, termed rho(0 or rho(0, are characterized by an exaggerated, uncoupled glycolytic phenotype and by constitutive and stable up-regulation of CD133 through many cell passages. Moreover, these rho(0 cells display the ability to form "tumor spheroids" in serumless medium and are positive for CD133 and the neural progenitor cell marker, nestin. Under differentiating conditions, rho(0 cells expressed multi-lineage properties. Reversibility of CD133 expression was demonstrated by transfering parental mitochondria to rho(0 cells resulting in stable trans-mitochondrial "cybrid" clones. This study provides a novel mechanistic insight about the regulation of CD133 by environmental conditions (hypoxia and mitochondrial dysfunction (genetic and chemical. Considering these new findings, the concept that CD133 is a marker of brain tumor stem cells may need to be revised.

  17. A new methodological sequence to expand and transdifferentiate human umbilical cord blood derived CD133+ cells into a cardiomyocyte-like phenotype.

    Science.gov (United States)

    Cui, Yu-Xin; Kafienah, Wael; Suleiman, M-S; Ascione, Raimondo

    2013-06-01

    Transplantation of antigenic-separated stem cells for human cardiovascular diseases such as myocardial infarction needs to be supported by experimental studies that allow refinement of the procedure. In this study we investigated optimising a protocol for the expansion and subsequent differentiation of human umbilical cord blood (HUCB) derived CD133(+) stem cells into a cardiomyocyte-like lineage. CD133(+) cells from HUCB were selected first by immunomagnetic separation and their purity was confirmed by flow cytometry analysis. For expansion and differentiation we developed a novel culture medium recipe that involves sequential signalling factors. Briefly, CD133(+) cells were expanded for 6 days under optimal serum-free conditions in combination with fibronectin and assessed by microscopy and AlamarBlue proliferation assay. Expanded CD133(+) cells were then plated in a cardiac differentiation promoting medium and cultured up to 4 weeks. With this protocol HUCB-CD133(+) cells can be regularly expanded in serum-free medium to obtain recovery and growth in vitro up to 6 folds. The addition of recombinant human thrombopoietin to the remaining factors of the expanding medium was associated with larger cell expansion. Expanded UCB CD133(+) cells showed a cardiomyocyte-like phenotype following differentiation in vitro through expressing intracellular cardiac specific markers including cardiac-specific α-actin, myosin heavy chain and troponin I. This change in phenotype was associated with the expression of cardiac-specific transcription factors Gata-4 and MEF2C. In addition, the change in phenotype was associated with an upregulation of nuclear receptor transcription factors including PPAR α, PPARγ, RXR α and RXRβ. We believe our protocol represents a significant advancement and overcome the technical hurdle of deriving cardiomyogenic-like cells from HUCB CD133(+) stem cells. In addition, it has the required attributes of simplicity and consistency. This will

  18. CD133 Immunohistochemisty in Glioblastoma – Identification of Tumor Stem Cells or a Matter of Coincidence?

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Christensen, Karina Garnier; Jensen, Stine Skov

    The putative stem cell marker CD133 is the marker of choice for identifying brain tumor stem cells in gliomas, but the use of different antibody clones recognizing different epitopes with different glycosylation status, confuses the field. In this study, we sat out to highlight if current...... suggest that CD133 immunohistochemical studies take this in to consideration by using different CD133 antibody clones together with other stem cell markers and e.g. PCR techniques before too firm conclusions are drawn....

  19. Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.

    Science.gov (United States)

    Sansone, Pasquale; Ceccarelli, Claudio; Berishaj, Marjan; Chang, Qing; Rajasekhar, Vinagolu K; Perna, Fabiana; Bowman, Robert L; Vidone, Michele; Daly, Laura; Nnoli, Jennifer; Santini, Donatella; Taffurelli, Mario; Shih, Natalie N C; Feldman, Michael; Mao, Jun J; Colameco, Christopher; Chen, Jinbo; DeMichele, Angela; Fabbri, Nicola; Healey, John H; Cricca, Monica; Gasparre, Giuseppe; Lyden, David; Bonafé, Massimiliano; Bromberg, Jacqueline

    2016-02-09

    The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133(hi)/ER(lo)/OXPHOS(lo). These cells exit metabolic dormancy via an IL6-driven feed-forward ER(lo)-IL6(hi)-Notch(hi) loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133(hi) CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy.

  20. CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Chien-Chih [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Liu, Ren-Shyan [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, National PET/Cyclotron Center, Taipei (China); National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China); Yang, An-Hang [Taipei Veterans General Hospital, Department of Pathology and Laboratory Medicine, Taipei (China); National Yang-Ming University, Department of Pathology, School of Medicine, Taipei (China); Liu, Ching-Sheng [National Yang-Ming University Medical School, Department of Nuclear Medicine, School of Medicine, Taipei (China); Chi, Chin-Wen [National Yang-Ming University, Institute of Pharmacology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China); Tseng, Ling-Ming [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Tsai, Yi-Fan [Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Ho, Jennifer H. [Taipei Medical University, Graduate Institute of Clinical Medicine, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Department of Ophthalmology, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Center for Stem Cell Research, Taipei (China); Lee, Chen-Hsen [NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Lee, Oscar K. [Taipei Veterans General Hospital, Department of Orthopedics, Taipei (China); National Yang-Ming University, Stem Cell Research Center, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China)

    2013-01-15

    {sup 131}I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133{sup +} cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133{sup +} cells and higher radioresistance. After {gamma}-irradiation of the cells, the CD133{sup +} population was enriched due to the higher apoptotic rate of CD133{sup -} cells. In vivo {sup 131}I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133{sup +} cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133{sup +} cells. (orig.)

  1. CD133(+) niches and single cells in glioblastoma have different phenotypes

    DEFF Research Database (Denmark)

    Christensen, Karina; Schrøder, Henrik Daa; Kristensen, Bjarne Winther

    2011-01-01

    with CD133 and the candidate stem cell markers Sox2, Bmi-1, EGFR, podoplanin and nestin, the proliferation marker Ki67 and the endothelial cell markers CD31, CD34, and VWF. Cell counting showed that the CD133(+) cells in the niches had a significantly higher expression of Sox2, EGFR and nestin compared...

  2. CD133 and BMI1 expressions and its prognostic role in primary ...

    Indian Academy of Sciences (India)

    mutations in newly diagnosed glioblastoma patients and its role in prognosis. Overexpression of CD133 mRNA and BMI1 protein was found in 47.6 and 76.2% patients respectively and TP53 mutations was seen in 57.1% of patients in our study. There was no correlation among TP53 mutations and expressions of CD133 ...

  3. Transcatheter Arterial Infusion of Autologous CD133+ Cells for Diabetic Peripheral Artery Disease

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    Xiaoping Zhang

    2016-01-01

    Full Text Available Microvascular lesion in diabetic peripheral arterial disease (PAD still cannot be resolved by current surgical and interventional technique. Endothelial cells have the therapeutic potential to cure microvascular lesion. To evaluate the efficacy and immune-regulatory impact of intra-arterial infusion of autologous CD133+ cells, we recruited 53 patients with diabetic PAD (27 of CD133+ group and 26 of control group. CD133+ cells enriched from patients’ PB-MNCs were reinfused intra-arterially. The ulcer healing followed up till 18 months was 100% (3/3 in CD133+ group and 60% (3/5 in control group. The amputation rate was 0 (0/27 in CD133+ group and 11.54% (3/26 in control group. Compared with the control group, TcPO2 and ABI showed obvious improvement at 18 months and significant increasing VEGF and decreasing IL-6 level in the CD133+ group within 4 weeks. A reducing trend of proangiogenesis and anti-inflammatory regulation function at 4 weeks after the cells infusion was also found. These results indicated that autologous CD133+ cell treatment can effectively improve the perfusion of morbid limb and exert proangiogenesis and anti-inflammatory immune-regulatory impacts by paracrine on tissue microenvironment. The CD133+ progenitor cell therapy may be repeated at a fixed interval according to cell life span and immune-regulatory function.

  4. The cancer stem cell marker CD133 interacts with plakoglobin and controls desmoglein-2 protein levels.

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    Ryo Koyama-Nasu

    Full Text Available The pentaspan membrane glycoprotein CD133 (also known as prominin-1 has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC and show that CD133 interacts with plakoglobin (also known as γ-catenin, a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.

  5. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma

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    Lu Lizhi

    2006-12-01

    Full Text Available Abstract Background Recently, a small population of cancer stem cells in adult and pediatric brain tumors has been identified. Some evidence has suggested that CD133 is a marker for a subset of leukemia and glioblastoma cancer stem cells. Especially, CD133 positive cells isolated from human glioblastoma may initiate tumors and represent novel targets for therapeutics. The gene expression and the drug resistance property of CD133 positive cancer stem cells, however, are still unknown. Results In this study, by FACS analysis we determined the percentage of CD133 positive cells in three primary cultured cell lines established from glioblastoma patients 10.2%, 69.7% and 27.5%, respectively. We also determined the average mRNA levels of markers associated with neural precursors. For example, CD90, CD44, CXCR4, Nestin, Msi1 and MELK mRNA on CD133 positive cells increased to 15.6, 5.7, 337.8, 21.4, 84 and 1351 times, respectively, compared to autologous CD133 negative cells derived from cell line No. 66. Additionally, CD133 positive cells express higher levels of BCRP1 and MGMT mRNA, as well as higher mRNA levels of genes that inhibit apoptosis. Furthermore, CD133 positive cells were significantly resistant to chemotherapeutic agents including temozolomide, carboplatin, paclitaxel (Taxol and etoposide (VP16 compared to autologous CD133 negative cells. Finally, CD133 expression was significantly higher in recurrent GBM tissue obtained from five patients as compared to their respective newly diagnosed tumors. Conclusion Our study for the first time provided evidence that CD133 positive cancer stem cells display strong capability on tumor's resistance to chemotherapy. This resistance is probably contributed by the CD133 positive cell with higher expression of on BCRP1 and MGMT, as well as the anti-apoptosis protein and inhibitors of apoptosis protein families. Future treatment should target this small population of CD133 positive cancer stem cells in

  6. Overactivation of Ras signaling pathway in CD133+ MPNST cells.

    Science.gov (United States)

    Borrego-Diaz, Emma; Terai, Kaoru; Lialyte, Kristina; Wise, Amanda L; Esfandyari, Tuba; Behbod, Fariba; Mautner, Victor F; Spyra, Melanie; Taylor, Sarah; Parada, Luis F; Upadhyaya, Meena; Farassati, Faris

    2012-07-01

    Cancer stem cells (CSCs) are believed to be the regenerative pool of cells responsible for repopulating tumors. Gaining knowledge about the signaling characteristics of CSCs is important for understanding the biology of tumors and developing novel anti-cancer therapies. We have identified a subpopulation of cells positive for CD133 (a CSC marker) from human primary malignant peripheral nerve sheath tumor (MPNST) cells which were absent in non-malignant Schwann cells. CD133 was also found to be expressed in human tissue samples and mouse MPNST cells. CD133+ cells were capable of forming spheres in non-adherent/serum-free conditions. The activation levels of Ras and its downstream effectors such as ERK, JNK, PI3K, p38K, and RalA were significantly increased in this population. Moreover, the CD133+ cells showed enhanced invasiveness which was linked to the increased expression of β-Catenin and Snail, two important proteins involved in the epithelial to mesenchymal transition, and Paxilin, a focal adhesion protein. Among other important characteristics of the CD133+ population, endoplasmic reticulum stress marker IRE1α was decreased, implying the potential sensitivity of CD133+ to the accumulation of unfolded proteins. Apoptotic indicators seemed to be unchanged in CD133+ cells when compared to the wild (unsorted) cells. Finally, in order to test the possibility of targeting CD133+ MPNST cells with Ras pathway pharmacological inhibitors, we exposed these cells to an ERK inhibitor. The wild population was more sensitive to inhibition of proliferation by this inhibitor as compared with the CD133+ cells supporting previous studies observing enhanced chemoresistance of these cells.

  7. Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

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    Wen-Shin Song

    2016-10-01

    Conclusion: SOX2 plays a crucial role in regulating tumorigenicity in CD133+ GBM cells. Our results not only revealed the genetic plasticity contributing to drug resistance and stemness but also demonstrated the dominant role of SOX2 in maintenance of GBM CSCs, which may provide a novel therapeutic target to overcome the conundrum of poor survival of brain cancers.

  8. Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury

    DEFF Research Database (Denmark)

    Schmelzle, Moritz; Splith, Katrin; Wiuff Andersen, Lars

    2013-01-01

    BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block...... sacrificed and plasma MP were isolated by ultracentrifugation. HSC and CD133 MP levels were analyzed by fluorescence-activated cell sorting. Patients were enrolled with acute (n=5) and acute on chronic (n=5) liver injury with matched controls (n=7). Blood was collected at admission and plasma CD133 and CD39...... MP subsets were analyzed by fluorescence-activated cell sorting. RESULTS: HSC and CD133 MP levels were significantly increased only in the plasma of wild-type mice with acetaminophen hepatotoxicity (P

  9. Gene expression profiling of circulating CD133+cells of hepatocellular carcinoma patients associated with HCV infection.

    Science.gov (United States)

    Zekri, Abdel-Rahman N; El-Sisi, Enas R; Abdallah, Zeinab F; Ismail, Alaa; Barakat Barakat, Ahmed

    2017-03-01

    Identifying the genetic expression profile of CD133 + cells from HCC patients compared to CD133 + cells from healthy volunteers that may contribute in hepatocarcinogenesis process. Circulating CD133 + cells were sorted from the peripheral blood of HCC patients as well as from healthy volunteers using magnetic activated cell sorting. The differential expression profile of stem cell related genes was performed using the Stem Cell PCR profiling assay. Data analysis of stem cells related genes in CD133 + cells of the HCC group compared to the control group showed that; CCND2, COL1A1, CTNNA1, DLL3, JAG1, KRT15, MYC, NOTCH2, T and TERT were up-regulated (fold change=80, 68.6, 6.67, 7.22, 3.8, 15.2, 14.5, 105.6, 26.6 and 99 respectively while only CD3D was down-regulated (fold change=0.055) in HCC patients. However, after application of Beferroni correction to adjust P-value; KRT15 was the only gene that was significantly over expressed in CD133 + cells of HCC compared to control group (P-value=0.012). KRT15 can be used to differentiate between circulating CD133 + cells from HCC group and control group. However, further study may be needed to confirm on the protein level. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  10. CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

    International Nuclear Information System (INIS)

    Seidel, Claudia; Dietrich, Antje; Wondrak, Marit; Kunz-Schughart, Leoni A.; Grade, Marian; Ried, Thomas

    2009-01-01

    The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133 + ) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133 + subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133 + cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133 + / CD133 - subpopulations

  11. Aberrant expression of CD133 in non-small cell lung cancer and its relationship to vasculogenic mimicry

    Directory of Open Access Journals (Sweden)

    Wu Shiwu

    2012-11-01

    Full Text Available Abstract Background To investigate on expressions and clinical significances of CD133 protein and vasculogenic mimicry (VM in primary non-small cell lung cancer (NSCLC. Methods The specimens of NSCLC from 305 Chinese patients with follow-up were analyzed for CD133 protein expression and VM by immunohistochemical and histochemical staining. Results In NSCLC, positive rates of 48.9% and 35.7% were obtained for CD133 and VM, respectively. The VM and expression of CD133 were significantly higher in carcinoma than in normal. There were a positive relationship between the VM and expression of CD133 and the tumor grade, lymph node metastasis and clinical stage (all P Conclusions VM, MVD and expression of CD133 are related to differentiation, lymph node metastasis, clinical stage, and prognosis. It is suggested that CD133, VM and MVD should be considered as a potential marker for the prognosis.

  12. Inhibition of CREB binding protein-beta-catenin signaling down regulates CD133 expression and activates PP2A-PTEN signaling in tumor initiating liver cancer cells.

    Science.gov (United States)

    Tang, Yuanyuan; Berlind, Joshua; Mavila, Nirmala

    2018-03-12

    promotes stemness via CD133 induction and cell proliferation in TICs. We found a novel functional link between CBP-beta-catenin and PP2A-PTEN-AKT pathway in liver TICs. Therefore, CBP-beta-catenin-PP2A-PTEN-AKT signaling axis could be a novel therapeutic target to prevent liver tumor initiation and cancer recurrence.

  13. CD133+CXCR4+ colon cancer cells exhibit metastatic potential and predict poor prognosis of patients

    Directory of Open Access Journals (Sweden)

    Zhang Shan-shan

    2012-08-01

    Full Text Available Abstract Background Colorectal cancer (CRC, which frequently metastasizes to the liver, is one of the three leading causes of cancer-related deaths worldwide. Growing evidence suggests that a subset of cells exists among cancer stem cells. This distinct subpopulation is thought to contribute to liver metastasis; however, it has not been fully explored in CRC yet. Methods Flow cytometry analysis was performed to detect distinct subsets with CD133 and CXCR4 markers in human primary and metastatic CRC tissues. The 'stemness' and metastatic capacities of different subpopulations derived from the colon cancer cell line HCT116 were compared in vitro and in vivo. The roles of epithelial-mesenchymal transition (EMT and stromal-cell derived factor-1 (SDF-1 in the metastatic process were also investigated. A survival curve was used to explore the correlation between the content of CD133+CXCR4+ cancer cells and patient survival. Results In human specimens, the content of CD133+CXCR4+ cells was higher in liver metastases than in primary colorectal tumors. Clonogenic and tumorigenic cells were restricted to CD133+ cells in the HCT116 cell line, with CXCR4 expression having no impact on the 'stemness' properties. We found that CD133+CXCR4+ cancer cells had a high metastatic capacity in vitro and in vivo. Compared with CD133+CXCR4- cells, CD133+CXCR4+ cancer cells experienced EMT, which contributed partly to their metastatic phenotype. We then determined that SDF-1/CXCL12 treatment could further induce EMT in CD133+CXCR4+ cancer cells and enhance their invasive behavior, while this could not be observed in CD133+CXCR4- cancer cells. Blocking SDF-1/CXCR4 interaction with a CXCR4 antagonist, AMD3100 (1,10-[1,4-phenylenebis(methylene]bis-1,4,8,11 -tetraazacyclotetradecane octahydrochloride, inhibited metastatic tumor growth in a mouse hepatic metastasis model. Finally, a high percentage of CD133+CXCR4+ cells in human primary CRC was associated with a reduced two

  14. Rapid selection and proliferation of CD133+ cells from cancer cell lines: chemotherapeutic implications.

    Directory of Open Access Journals (Sweden)

    Sarah E Kelly

    2010-04-01

    Full Text Available Cancer stem cells (CSCs are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133+] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB (Celdyne, Houston, TX. For comparison, another bioreactor, the rotary cell culture system (RCCS manufactured by Synthecon (Houston, TX was used. Both the HFB and the RCCS bioreactors simulate aspects of hypogravity. In our study, the HFB increased CD133+ cell growth from various cell lines compared to the RCCS vessel and to normal gravity control. We observed a +15-fold proliferation of the CD133+ cellular fraction with cancer cells that were cultured for 7-days at optimized conditions. The RCCS vessel instead yielded a (-4.8-fold decrease in the CD133+cellular fraction respect to the HFB after 7-days of culture. Interestingly, we also found that the hypogravity environment of the HFB greatly sensitized the CD133+ cancer cells, which are normally resistant to chemo treatment, to become susceptible to various chemotherapeutic agents, paving the way to less toxic and more effective chemotherapeutic treatment in patients. To be able to test the efficacy of cytotoxic agents in vitro prior to their use in clinical setting on cancer cells as well as on cancer stem cells may pave the way to more effective chemotherapeutic strategies in patients. This could be an important advancement in the therapeutic options of oncologic patients, allowing for more targeted and personalized chemotherapy regimens as well as for higher response rates.

  15. Significance of CD133 positive cells in four novel HPV-16 positive cervical cancer-derived cell lines and biopsies of invasive cervical cancer.

    Science.gov (United States)

    Javed, Shifa; Sharma, Bal Krishan; Sood, Swati; Sharma, Sanjeev; Bagga, Rashmi; Bhattacharyya, Shalmoli; Rayat, Charan Singh; Dhaliwal, Lakhbir; Srinivasan, Radhika

    2018-04-02

    Cervical cancer is a major cause of cancer-related mortality in women in the developing world. Cancer Stem cells (CSC) have been implicated in treatment resistance and metastases development; hence understanding their significance is important. Primary culture from tissue biopsies of invasive cervical cancer and serial passaging was performed for establishing cell lines. Variable Number Tandem Repeat (VNTR) assay was performed for comparison of cell lines with their parental tissue. Tumorsphere and Aldefluor assays enabled isolation of cancer stem cells (CSC); immunofluorescence and flow cytometry were performed for their surface phenotypic expression in cell lines and in 28 tissue samples. Quantitative real-time PCR for stemness and epithelial-mesenchymal transition (EMT) markers, MTT cytotoxicity assay, cell cycle analysis and cell kinetic studies were performed. Four low-passage novel cell lines designated RSBS-9, - 14 and - 23 from squamous cell carcinoma and RSBS-43 from adenocarcinoma of the uterine cervix were established. All were HPV16+. VNTR assay confirmed their uniqueness and derivation from respective parental tissue. CSC isolated from these cell lines showed CD133 + phenotype. In tissue samples of untreated invasive cervical cancer, CD133 + CSCs ranged from 1.3-23% of the total population which increased 2.8-fold in radiation-resistant cases. Comparison of CD133 + with CD133 - bulk population cells revealed increased tumorsphere formation and upregulation of stemness and epithelial-mesenchymal transition (EMT) markers with no significant difference in cisplatin sensitivity. Low-passage cell lines developed would serve as models for studying tumor biology. Cancer Stem Cells in cervical cancer display CD133 + phenotype and are increased in relapsed cases and hence should be targeted for achieving remission.

  16. DNA Damage in CD133-Positive Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma

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    Raynoo Thanan

    2016-01-01

    Full Text Available Barrett’s esophagus (BE caused by gastroesophageal reflux is a major risk factor of Barrett’s esophageal adenocarcinoma (BEA, an inflammation-related cancer. Chronic inflammation and following tissue damage may activate progenitor cells under reactive oxygen/nitrogen species-rich environment. We previously reported the formation of oxidative/nitrative stress-mediated mutagenic DNA lesions, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG and 8-nitroguanine, in columnar epithelial cells of BE tissues and cancer cells of BEA tissues. We investigated the mechanisms of BEA development in relation to oxidative/nitrative DNA damage and stem cell hypothesis. We examined 8-nitroguanine and 8-oxodG formation and the expression of stem cell marker (CD133 in biopsy specimens of patients with BE and BEA by immunohistochemical analysis in comparison with those of normal subjects. CD133 was detected at apical surface of columnar epithelial cells of BE and BEA tissues, and the cytoplasm and cell membrane of cancer cells in BEA tissues. DNA lesions and CD133 were colocalized in columnar epithelial cells and cancer cells. Their relative staining intensities in these tissues were significantly higher than those in normal subjects. Our results suggest that BE columnar epithelial cells with CD133 expression in apical surface undergo inflammation-mediated DNA damage, and mutated cells acquire the property of cancer stem cells with cytoplasmic CD133 expression.

  17. Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.

    Directory of Open Access Journals (Sweden)

    Shanmiao Gou

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133⁺ but not CD24⁺CD44⁺ESA⁺ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133⁺ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease.

  18. Paclitaxel-loaded nanoparticles decorated with anti-CD133 antibody: a targeted therapy for liver cancer stem cells

    Science.gov (United States)

    Jin, Cheng; Yang, Zhaoxu; Yang, Jingyue; Li, Haimin; He, Yong; An, Jiaze; Bai, Ling; Dou, Kefeng

    2014-01-01

    Recent studies have revealed the existence of liver cancer stem cells (CSCs). Therefore, there is an urgent need for new and effective treatment strategies specific to liver CSCs. In this work, the poly( d, l-lactide-coglycolide) nanoparticles containing paclitaxel were prepared by emulsification-solvent evaporation method. The nanoparticles decorated with anti-CD133 antibody, termed targeted nanoparticles, were prepared by carbodiimide chemistry for liver CSCs. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, and in vitro release) were investigated. Cellular uptake and accumulation in tumor tissue of nanoparticles were observed. To assess anti-tumor activity of nanoparticles in vitro and in vivo, cell survival assay and tumor regression study were carried out using liver cancer cell lines (Huh7 and HepG2) and their xenografts. Particle size of targeted nanoparticles was 429.26 ± 41.53 nm with zeta potential of -11.2 mV. Targeted nanoparticles possessed spherical morphology and high encapsulation efficiency (87.53 ± 5.9 %). The accumulation of targeted nanoparticles depends on dual effects of passive and active targeting. Drug-loaded nanoparticles showed cytotoxicity on the tumor cells in vitro and in vivo. Targeted nanoparticles resulted in significant improvement in therapeutic response through selectively eliminating CD133 positive subpopulation. These results suggested that the novel nanoparticles could be a promising candidate with excellent therapeutic efficacy for targeting liver CSCs.

  19. The Protein Content of Extracellular Vesicles Derived from Expanded Human Umbilical Cord Blood-Derived CD133+ and Human Bone Marrow-Derived Mesenchymal Stem Cells Partially Explains Why both Sources are Advantageous for Regenerative Medicine.

    Science.gov (United States)

    Angulski, Addeli B B; Capriglione, Luiz G; Batista, Michel; Marcon, Bruna H; Senegaglia, Alexandra C; Stimamiglio, Marco A; Correa, Alejandro

    2017-04-01

    Adult stem cells have beneficial effects when exposed to damaged tissue due, at least in part, to their paracrine activity, which includes soluble factors and extracellular vesicles (EVs). Given the multiplicity of signals carried by these vesicles through the horizontal transfer of functional molecules, human mesenchymal stem cell (hMSCs) and CD133 + cell-derived EVs have been tested in various disease models and shown to recover damaged tissues. In this study, we profiled the protein content of EVs derived from expanded human CD133 + cells and bone marrow-derived hMSCs with the intention of better understanding the functions performed by these vesicles/cells and delineating the most appropriate use of each EV in future therapeutic procedures. Using LC-MS/MS analysis, we identified 623 proteins for expanded CD133 + -EVs and 797 proteins for hMSCs-EVs. Although the EVs from both origins were qualitatively similar, when protein abundance was considered, hMSCs-EVs and CD133 + -EVs were different. Gene Ontology (GO) enrichment analysis in CD133 + -EVs revealed proteins involved in a variety of angiogenesis-related functions as well proteins related to the cytoskeleton and highly implicated in cell motility and cellular activation. In contrast, when overrepresented proteins in hMSCs-EVs were analyzed, a GO cluster of immune response-related genes involved with immune response-regulating factors acting on phagocytosis and innate immunity was identified. Together our data demonstrate that from the point of view of protein content, expanded CD133 + -EVs and hMSCs-EVs are in part similar but also sufficiently different to reflect the main beneficial paracrine effects widely reported in pre-clinical studies using expanded CD133 + cells and/or hBM-MSCs.

  20. CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

    Science.gov (United States)

    Paschall, Amy V.; Yang, Dafeng; Lu, Chunwan; Redd, Priscilla S.; Choi, Jeong-Hyeon; Heaton, Christopher M.; Lee, Jeffrey R.; Nayak-Kapoor, Asha; Liu, Kebin

    2016-01-01

    The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5-FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133+ colon cancer cells in vitro. 5-FU chemotherapy also increases CD133+ tumor cells in human colon cancer patients. However, sorted CD133+ colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133+ colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133+ and 5-FU-resistant colon cancer cells as compared to CD133+ and 5-FU-sensitive colon cancer cells. Consequently, CD133+CD24lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133+CD24lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells. PMID:27659530

  1. Detection of the Hematopoietic Stem and Progenitor Cell Marker CD133 during Angiogenesis in Three-Dimensional Collagen Gel Culture

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    Masumi Akita

    2013-01-01

    Full Text Available We detected the hematopoietic stem and progenitor cell marker CD133 using immunogold labeling during angiogenesis in a three-dimensional collagen gel culture. CD133-positive cells were present in capillary tubes newly formed from aortic explants in vitro. The CD133-positive cell population had the capacity to form capillary tubes. Lovastatin strongly inhibited cell migration from aortic explants and caused the degradation of the capillary tubes. The present study provides insight into the function of CD133 during angiogenesis as well as an explanation for the antiangiogenic effect of statins.

  2. Tumour-initiating cells vs. cancer "stem" cells and CD133: What's in the name?

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Stantic, M.; Zobalová, Renata; Chladová, Jaromíra; Wang, X. F.; Procházka, L.; Dong, L.; Anděra, Ladislav; Ralph, S.J.

    2007-01-01

    Roč. 255, č. 4 (2007), s. 855-859 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : tumour-initiating cells * CD133 * resistance to treatment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.749, year: 2007

  3. Effects of metformin on CD133+ colorectal cancer cells in diabetic patients.

    Directory of Open Access Journals (Sweden)

    Yanfei Zhang

    Full Text Available In diabetic patients complicated with colorectal cancer (CRC, metformin treatment was reported to have diverse correlation with CRC-specific mortality. In laboratory studies, metformin was reported to affect the survival of cancer stem cells (CSCs in breast and pancreatic cancers and glioblastoma. Although cscs play a critical role in the resistance to 5-fluorouracil (5-FU chemotherapy in CRC patients, the effect of metformin on cscs in CRC patients and the synergistic effect of metformin in combination with 5-FU on cscs are not reported. In the present study pathological examinations were performed in 86 CRC patients complicated with type 2 DM who had been divided into a metformin group and a non-metformin group. Comparisons regarding pathological type, incidence of metastasis, expression of CD133 and β-catenin were conducted between the two groups. We explored the synergistic effects of metformin in combination with 5-FU on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of SW620 human colorectal cancer cell lines. The results show that metformin treatment had reverse correlations with the proportion of patients with poorly differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+ cscs in SW620 cells. These findings provide an important complement to previous study. Inhibition of the proliferation of CD133+ cscs may be a potential mechanism responsible for the association of metformin use with improved CRC outcomes in CRC patients with type 2 diabetes.

  4. Neuronal hypoxia in vitro: Investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells

    Directory of Open Access Journals (Sweden)

    Emmrich Frank

    2008-09-01

    Full Text Available Abstract Background The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. Methods A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC, a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y. Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9 and growth factors (G-CSF, GM-CSF, VEGF, bFGF were analyzed using fluorescence microscopy, FACS and cytometric bead array. Results tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% ± 3%. Untreated post-hypoxic control cultures showed apoptosis rates of 85% ± 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. Conclusion Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes.

  5. Clinical value of CD133 and nestin in patients with glioma

    DEFF Research Database (Denmark)

    Dahlrot, Rikke H; Hansen, Steinbjørn; Jensen, Stine S

    2014-01-01

    Cancer stem cell-related (CSC) markers have been suggested to have promising potentials as novel types of prognostic and predictive markers in gliomas. However no single CSC-related marker is currently used in clinical decisions. The aim of this study was to investigate the prognostic value of CD...... 2005 and 2009. We found that the expression of CD133 did not correlate with WHO grade, and there was no association with overall survival (OS). The level of nestin correlated positively with WHO grade. In patients with WHO grade II tumors, a high level of nestin was associated with short progression......-free survival (PFS) in multivariate analysis. High levels of co-localization were associated with poor PFS in patients with WHO grade II tumors, but not with OS. We conclude that CD133 was not an independent prognostic factor, but a high level of nestin was associated with poor PFS in patients with WHO grade II...

  6. Adult Human CD133/1+ Kidney Cells Isolated from Papilla Integrate into Developing Kidney Tubules

    Science.gov (United States)

    Ward, Heather H.; Romero, Elsa; Welford, Angela; Pickett, Gavin; Bacallao, Robert; Gattone, Vincent H.; Ness, Scott A.; Wandinger-Ness, Angela; Roitbak, Tamara

    2011-01-01

    Approximately 60,000 patients in the US are waiting for a kidney transplant due to genetic, immunologic and environmentally caused kidney failure. Adult human renal stem cells could offer opportunities for autologous transplant and repair of damaged organs. Current data suggest that there are multiple progenitor types in the kidney with distinct localizations. In the present study, we characterize cells derived from human kidney papilla and show their capacity for tubulogenesis. In situ, nestin+ and CD133/1+ cells were found extensively intercalated between tubular epithelia in the loops of Henle of renal papilla, but not of the cortex. Populations of primary cells from the renal cortex and renal papilla were isolated by enzymatic digestion from human kidneys unsuited for transplant and immuno-enriched for CD133/1+ cells. Isolated CD133/1+ papillary cells were positive for nestin, as well as several human embryonic stem cell markers (SSEA4, Nanog, SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial and neuronal like phenotypes. Isolated papillary cells exhibited morphologic plasticity upon modulation of culture conditions and inhibition of asymmetric cell division. Labeled papillary cells readily associated with cortical tubular epithelia in co-culture and 3-dimensional collagen gel cultures. Heterologous organ culture demonstrated that CD133/1+ progenitors from the papilla and cortex, became integrated into developing kidney tubules. Tubular epithelia did not participate in tubulogenesis. Human renal papilla harbor cells with the hallmarks of adult kidney stem/progenitor cells that can be amplified and phenotypically modulated in culture while retaining the capacity to form new kidney tubules. PMID:21255643

  7. Adult human CD133/1(+) kidney cells isolated from papilla integrate into developing kidney tubules.

    Science.gov (United States)

    Ward, Heather H; Romero, Elsa; Welford, Angela; Pickett, Gavin; Bacallao, Robert; Gattone, Vincent H; Ness, Scott A; Wandinger-Ness, Angela; Roitbak, Tamara

    2011-10-01

    Approximately 60,000 patients in the United States are waiting for a kidney transplant due to genetic, immunologic and environmentally caused kidney failure. Adult human renal stem cells could offer opportunities for autologous transplant and repair of damaged organs. Current data suggest that there are multiple progenitor types in the kidney with distinct localizations. In the present study, we characterize cells derived from human kidney papilla and show their capacity for tubulogenesis. In situ, nestin(+) and CD133/1(+) cells were found extensively intercalated between tubular epithelia in the loops of Henle of renal papilla, but not of the cortex. Populations of primary cells from the renal cortex and renal papilla were isolated by enzymatic digestion from human kidneys unsuited for transplant and immuno-enriched for CD133/1(+) cells. Isolated CD133/1(+) papillary cells were positive for nestin, as well as several human embryonic stem cell markers (SSEA4, Nanog, SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial and neuronal-like phenotypes. Isolated papillary cells exhibited morphologic plasticity upon modulation of culture conditions and inhibition of asymmetric cell division. Labeled papillary cells readily associated with cortical tubular epithelia in co-culture and 3-dimensional collagen gel cultures. Heterologous organ culture demonstrated that CD133/1(+) progenitors from the papilla and cortex became integrated into developing kidney tubules. Tubular epithelia did not participate in tubulogenesis. Human renal papilla harbor cells with the hallmarks of adult kidney stem/progenitor cells that can be amplified and phenotypically modulated in culture while retaining the capacity to form new kidney tubules. This article is part of a Special Issue entitled: Polycystic Kidney Disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. The Potential Role of CD133 in Immune Surveillance and Apoptosis: A Mitochondrial Connection?

    Czech Academy of Sciences Publication Activity Database

    Zobalová, Renata; Prokopová, Kateřina; Stantic, M.; Stapelberg, M.; Dong, L.-F.; Ralph, S.J.; Akporiaye, E.; Neužil, Jiří

    2011-01-01

    Roč. 15, č. 12 (2011), s. 2989-3002 ISSN 1523-0864 R&D Projects: GA ČR(CZ) GA204/08/0811; GA ČR(CZ) GA305/07/1008 Institutional research plan: CEZ:AV0Z50520701 Keywords : Cancer stem-like cells * protein CD133 * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.456, year: 2011

  9. MPEG-CS/Bmi-1RNAi Nanoparticles Synthesis and Its Targeted Inhibition Effect on CD133+ Laryngeal Stem Cells.

    Science.gov (United States)

    Wei, Xudong; He, Jian; Wang, Jingyu; Wang, Wei

    2018-03-01

    Previous studies have confirmed that CD133+ cells in laryngeal tumor tissue have the characteristics of cancer stem cells. Bmi-1 gene expression is central to the tumorigenicity of CD133+ cells. In this study, we tried to develop a new siRNA carrier system using chitosan-methoxypolyethylene nanoparticles (CS-mPEG-NPs) that exhibit higher tumor-targeting ability and enhanced gene silencing efficacy in CD133+ tumor stem cells. It is hoped to block the self-renewal and kill the stem cells of laryngeal carcinoma. The mPEG-CS-Bmi-1RNAi-NPs were synthesized and their characters were checked. The changes in invasion ability and sensitivity to radiotherapy and chemotherapy of CD133+Hep-2 tumor cells were observed after Bmi-1 gene silencing. The mPEG-CS-Bmi-1RNAi-NPs synthesized in this experiment have a regular spherical form, a mean size of 139.70 ±6.40 nm, an encapsulation efficiency of 85.21 ± 1.94%, with drug loading capacity of 18.47 ± 1.83%, as well as low cytotoxicity, providing good protection to the loaded gene, strong resistance to nuclease degradation and high gene transfection efficiency. After Bmi-1 gene silencing, the invasion ability of CD133+ cells was weakened. Co-cultured with paclitaxel, the survival rates of CD133+Bmi-1RNAi cells were lower. After radiotherapy, the mean growth inhibition rate of CD133+/Bmi-1RNAi cells was significantly lower than CD133+ cells. In conclusion, the mPEG-CS nano-carrier is an ideal vector in gene therapy, while silencing the Bmi-1 gene can enhance the sensitivity of CD133+ tumor stem cells to chemoradiotherapy and abate their invasion ability.

  10. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

    International Nuclear Information System (INIS)

    Kim, Ki Hyung; Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo; Park, Eun-Sil; Jeong, Namkung; Eo, Wan-Kyu; Kim, Heung Yeol; Cha, Hee-Jae

    2014-01-01

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker

  11. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Hyung [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Park, Eun-Sil [Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, MA (United States); Jeong, Namkung [Department of Obstetrics and Gynecology, The Catholic University, Seoul (Korea, Republic of); Eo, Wan-Kyu [Department of Internal Medicine, Kyung Hee University, Seoul (Korea, Republic of); Kim, Heung Yeol, E-mail: hykyale@yahoo.com [Department of Obstetrics and Gynecology, Kosin University College of Medicine, Busan (Korea, Republic of); Cha, Hee-Jae, E-mail: hcha@kosin.ac.kr [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Institute for Medical Science, Kosin University College of Medicine, Busan (Korea, Republic of)

    2014-05-02

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker.

  12. Expressions of ABCG2, CD133, and Podoplanin in Salivary Adenoid Cystic Carcinoma

    Directory of Open Access Journals (Sweden)

    Wuwei Li

    2014-01-01

    Full Text Available Adenoid cystic carcinoma (ACC is one of the most common salivary gland malignant tumors with a high risk of recurrence and metastasis. Current studies on cancer stem cells (CSCs have verified that CSCs are the driving force behind tumor initiation and progression, suggesting that new cancer therapies may be established by effectively targeting and killing the CSCs. The primary goal of this study is to investigate the expression patterns of ABCG2, CD133, and podoplanin in ACC of minor salivary glands by immunohistochemistry analysis. We found that ABCG2 was weakly expressed in normal looking salivary gland tissues. A significant upregulation of ABCG2 expression in ACC was observed with a similar expression pattern of Ki-67. CD133 was detected in apical membrane of epithelial cells and podoplanin was expressed positively in myoepithelial cells of both normal looking tissue and ACC. However, no significant difference was found of the expression pattern of CD133 and podoplanin between normal looking tissues and ACC. Our observations suggest that CSCs may exist in quiescent cells with ABCG2 positive staining, which are surrounded by cells with positive expression of ABCG2 and Ki-67 in ACC, and costaining with ABCG2 and Ki-67 may help predict the location of CSCs.

  13. Evaluation of the expansion of umbilical cord blood derived from CD133+ cells on biocompatible microwells

    Directory of Open Access Journals (Sweden)

    Mina Soufizomorrod

    2016-05-01

    Full Text Available Background: Hematopoietic stem cell transplantation (HSCT is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB has known as an alternative for hematopoietic stem/progenitor cells (HPSC in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB. Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells’ proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.

  14. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rappa, Germana [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Mercapide, Javier; Anzanello, Fabio [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Le, Thuc T. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Johlfs, Mary G. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Fiscus, Ronald R. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Wilsch-Bräuninger, Michaela [Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden (Germany); Corbeil, Denis [Tissue Engineering Laboratories (BIOTEC) and DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany Technische Universitat Dresden, Dresden (Germany); Lorico, Aurelio, E-mail: alorico@roseman.edu [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States)

    2013-04-01

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in

  15. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    International Nuclear Information System (INIS)

    Rappa, Germana; Mercapide, Javier; Anzanello, Fabio; Le, Thuc T.; Johlfs, Mary G.; Fiscus, Ronald R.; Wilsch-Bräuninger, Michaela; Corbeil, Denis; Lorico, Aurelio

    2013-01-01

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in

  16. CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC cell lines HCT-116

    International Nuclear Information System (INIS)

    Dittfeld, Claudia; Dietrich, Antje; Peickert, Susann; Hering, Sandra; Baumann, Michael; Grade, Marian; Ried, Thomas; Kunz-Schughart, Leoni A.

    2009-01-01

    Background and purpose: CD133 is controversially discussed as putative (surrogate) marker for cancer stem/tumor-initiating cell populations (CSC/TIC) in epithelial tumors including colorectal carcinomas (CRCs). We studied CD133 expression in established CRC cell lines and examined in vitro behavior, radioresponse and in vivo tumor formation of CD133 +/- subpopulations of one cell line of interest. Materials and methods: Ten CRC cell lines were analyzed for CD133 expression using flow cytometry and Western blotting. CD133 + and CD133 - HCT-116 subpopulations were separated by FACS and studied in 2-D and 3-D culture and colony formation assays after irradiation. Subcutaneous xenograft formation was monitored in NMRI (nu/nu) mice. Results and conclusions: CRC cell lines could be classified into three groups: (i) CD133 - , (ii) CD133 + and (iii) those with two distinct CD133 + and CD133 - subpopulations. Isolated CD133 +/- HCT-116 subpopulations were studied relative to the original fraction. No difference was found in 2-D growth, spheroid formation or radioresponse in vitro. Also, tumor formation and growth rate did not differ for the sorted subpopulations. However, a subset of xenografts originated from CD133 - HCT-116 showed a striking enrichment in the CD133 + fraction. Our data show that CD133 expression is not selective for sphere forming, tumor-initiating or radioresistant subpopulations in the HCT-116 CRC cell lines. This implies that CD133 cannot be regarded as a CSC/TIC marker in all CRC cell lines and that functional measurements of tumor formation have to generally accompany CSC/TIC-directed mechanistic or therapeutic studies.

  17. Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression

    Science.gov (United States)

    Prados, Jose; Caba, Octavio; Cabeza, Laura; Berdasco, Maria; Gónzalez, Beatriz; Melguizo, Consolación

    2015-01-01

    Background The use of temozolomide (TMZ) has improved the prognosis for glioblastoma multiforme patients. However, TMZ resistance may be one of the main reasons why treatment fails. Although this resistance has frequently been linked to the expression of O6-methylguanine-DNA methyltransferase (MGMT) it seems that this enzyme is not the only molecular mechanism that may account for the appearance of drug resistance in glioblastoma multiforme patients as the mismatch repair (MMR) complex, P-glycoprotein, and/or the presence of cancer stem cells may also be implicated. Methods Four nervous system tumor cell lines were used to analyze the modulation of MGMT expression and MGMT promoter methylation by TMZ treatment. Furthermore, 5-aza-2’-deoxycytidine was used to demethylate the MGMT promoter and O(6)-benzylguanine to block GMT activity. In addition, MMR complex and P-glycoprotein expression were studied before and after TMZ exposure and correlated with MGMT expression. Finally, the effect of TMZ exposure on CD133 expression was analyzed. Results Our results showed two clearly differentiated groups of tumor cells characterized by low (A172 and LN229) and high (SF268 and SK-N-SH) basal MGMT expression. Interestingly, cell lines with no MGMT expression and low TMZ IC50 showed a high MMR complex expression, whereas cell lines with high MGMT expression and high TMZ IC50 did not express the MMR complex. In addition, modulation of MGMT expression in A172 and LN229 cell lines was accompanied by a significant increase in the TMZ IC50, whereas no differences were observed in SF268 and SK-N-SH cell lines. In contrast, P-glycoprotein and CD133 was found to be unrelated to TMZ resistance in these cell lines. Conclusions These results may be relevant in understanding the phenomenon of TMZ resistance, especially in glioblastoma multiforme patients laking MGMT expression, and may also aid in the design of new therapeutic strategies to improve the efficacy of TMZ in glioblastoma

  18. Dual-targeting immunoliposomes using angiopep-2 and CD133 antibody for glioblastoma stem cells.

    Science.gov (United States)

    Kim, Jung Seok; Shin, Dae Hwan; Kim, Jin-Seok

    2018-01-10

    Glioblastoma stem cells (GSCs), which are identified as subpopulation of CD133 + /ALDH1 + , are known to show resistance to the most of chemotherapy and radiation therapy, leading to the recurrence of tumor in glioblastoma multiforme (GBM) patients. Also, delivery of temozolomide (TMZ), a mainline treatment of GBM, to the GBM site is hampered by various barriers including the blood-brain barrier (BBB). A dual-targeting immunoliposome encapsulating TMZ (Dual-LP-TMZ) was developed by using angiopep-2 (An2) and anti-CD133 monoclonal antibody (CD133 mAb) for BBB transcytosis and specific delivery to GSCs, respectively. The size, zeta potential and drug encapsulation efficiency of Dual-LP-TMZ were 203.4nm in diameter, -1.6mV and 99.2%, respectively. The in vitro cytotoxicity of Dual-LP-TMZ against U87MG GSCs was increased by 425- and 181-folds when compared with that of free TMZ and non-targeted TMZ liposome (LP-TMZ) (10.3μM vs. 4380μM and 1869μM in IC 50 , respectively). Apoptosis and anti-migration ability of Dual-LP-TMZ in U87MG GSCs were also significantly enhanced comparing with those of free TMZ or LP-TMZ. In vivo study clearly showed a significant reduction in tumor size after intravenous administrations of Dual-LP-TMZ to the orthotopically-implanted brain tumor mice when compared with free TMZ or LP-TMZ. Increased life span (ILS) and median survival time (MST) of tumor-bearing mice were also increased when treated with Dual-LP-TMZ (211.2% in ILS and 49.2days in MST) than with free TMZ (0% in ILS and 23.3day in MST). These data indicate that conjugation of both An2 peptide and CD133 mAb to TMZ-encapsulating liposome is very effective in delivering the TMZ to GSCs via BBB, suggesting a potential use of Dual-LP-TMZ as a therapeutic modality for GBM. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Regeneration of rat corpora cavernosa tissue by transplantation of CD133+ cells derived from human bone marrow and placement of biodegradable gel sponge sheet

    Directory of Open Access Journals (Sweden)

    Shogo Inoue

    2017-01-01

    Full Text Available The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133 + cells into a rat corpora cavernosa defect model. We excised 2 mm × 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. Alginate gel sponge sheets supplemented with 1 × 10 4 CD133 + cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats (0.34258 ± 0.0831 was significantly higher than that for eight rats with only the excision (0.0580 ± 0.0831, P = 0.0238 and similar to that for five rats for which the penis was exposed, and there was no excision (0.37228 ± 0.1051, P = 0.8266. Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor (NGF, and vascular endothelial growth factor (VEGF were significantly higher than those for rats treated with alginate gel sheets without cell supplementation (NGF: P = 0.0309; VEGF: P < 0.0001. These findings show that transplantation of CD133 + cells accelerates functional and histological recovery in the corpora cavernosa defect model.

  20. The importance of the stem cell marker prominin-1/CD133 in the uptake of transferrin and in iron metabolism in human colon cancer Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Erika Bourseau-Guilmain

    Full Text Available As the pentaspan stem cell marker CD133 was shown to bind cholesterol and to localize in plasma membrane protrusions, we investigated a possible function for CD133 in endocytosis. Using the CD133 siRNA knockdown strategy and non-differentiated human colon cancer Caco-2 cells that constitutively over-expressed CD133, we provide for the first time direct evidence for a role of CD133 in the intracellular accumulation of fluorescently labeled extracellular compounds. Assessed using AC133 monoclonal antibody, CD133 knockdown was shown to improve Alexa488-transferrin (Tf uptake in Caco-2 cells but had no impact on FITC-dextran or FITC-cholera-toxin. Absence of effect of the CD133 knockdown on Tf recycling established a role for CD133 in inhibiting Tf endocytosis rather than in stimulating Tf exocytosis. Use of previously identified inhibitors of known endocytic pathways and the positive impact of CD133 knockdown on cellular uptake of clathrin-endocytosed synthetic lipid nanocapsules supported that CD133 impact on endocytosis was primarily ascribed to the clathrin pathway. Also, cholesterol extraction with methyl-β-cyclodextrine up regulated Tf uptake at greater intensity in the CD133(high situation than in the CD133(low situation, thus suggesting a role for cholesterol in the inhibitory effect of CD133 on endocytosis. Interestingly, cell treatment with the AC133 antibody down regulated Tf uptake, thus demonstrating that direct extracellular binding to CD133 could affect endocytosis. Moreover, flow cytometry and confocal microscopy established that down regulation of CD133 improved the accessibility to the TfR from the extracellular space, providing a mechanism by which CD133 inhibited Tf uptake. As Tf is involved in supplying iron to the cell, effects of iron supplementation and deprivation on CD133/AC133 expression were investigated. Both demonstrated a dose-dependent down regulation here discussed to the light of transcriptional and post

  1. Immunocapture of CD133-positive cells from human cancer cell lines by using monodisperse magnetic poly(glycidyl methacrylate) microspheres containing amino groups

    Energy Technology Data Exchange (ETDEWEB)

    Kuan, Wei-Chih [Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhisung 621, Taiwan (China); Horák, Daniel, E-mail: horak@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Plichta, Zdeněk [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Lee, Wen-Chien [Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhisung 621, Taiwan (China)

    2014-01-01

    Magnetic poly(glycidyl methacrylate)-based macroporous microspheres with an average particle size of 4.2 μm were prepared using a modified multi-step swelling polymerization method and by introducing amino functionality on their surfaces. Antibody molecules were oxidized on their carbohydrate moieties and bound to the amino-containing magnetic microspheres via a site-directed procedure. CD133-positive cells could be effectively captured from human cancer cell lines (HepG2, HCT116, MCF7, and IMR-32) by using magnetic microspheres conjugated to an anti-human CD133 antibody. After further culture, the immunocaptured CD133-expressing cells from IMR-32 proliferated and gradually detached from the magnetic microspheres. Flow-cytometric analysis confirmed the enrichment of CD133-expressing cells by using the antibody-bound magnetic microspheres. Such microspheres suitable for immunocapture are very promising for cancer diagnosis because the CD133-expressing cells in cancer cell lines have been suggested to be cancer stem cells. - Highlights: • Multi-step swelling polymerization produced poly(glycidyl methacrylate) microspheres. • Anti-human CD133 antibodies were bound to the amino-containing magnetic microspheres. • CD133-positive cells were effectively captured from human cancer cell lines. • Immunocaptured CD133-expressing cells proliferated and were detached from microspheres. • Enrichment of CD133-expressing cells was confirmed by flow-cytometric analysis.

  2. Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133-positive cells by knockdown of SirT1 expression

    International Nuclear Information System (INIS)

    Chang, C.-J.; Hsu, C.-C.; Yung, M.-C.; Chen, K.-Y.; Tzao Ching; Wu, W.-F.; Chou, H.-Y.; Lee, Y.-Y.; Lu, K.-H.; Chiou, S.-H.; Ma, H.-I

    2009-01-01

    CD133-expressing glioma cells play a critical role in tumor recovery after treatment and are resistant to radiotherapy. Herein, we demonstrated that glioblastoma-derived CD133-positive cells (GBM-CD133 + ) are capable of self-renewal and express high levels of embryonic stem cell genes and SirT1 compared to GBM-CD133 - cells. To evaluate the role of SirT1 in GBM-CD133 + , we used a lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in GBM-CD133 + . Silencing of SirT1 significantly enhanced the sensitivity of GBM-CD133 + to radiation and increased the level of radiation-mediated apoptosis. Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in the inhibition of tumor growth in nude mice transplanted with GBM-CD133 + . Kaplan-Meier survival analysis indicated that the mean survival rate of GBM-CD133 + mice treated with radiotherapy was significantly improved by Sh-SirT1 as well. In sum, these results suggest that SirT1 is a potential target for increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells to radiotherapy.

  3. GMP-conformant on-site manufacturing of a CD133+ stem cell product for cardiovascular regeneration.

    Science.gov (United States)

    Skorska, Anna; Müller, Paula; Gaebel, Ralf; Große, Jana; Lemcke, Heiko; Lux, Cornelia A; Bastian, Manuela; Hausburg, Frauke; Zarniko, Nicole; Bubritzki, Sandra; Ruch, Ulrike; Tiedemann, Gudrun; David, Robert; Steinhoff, Gustav

    2017-02-10

    CD133 + stem cells represent a promising subpopulation for innovative cell-based therapies in cardiovascular regeneration. Several clinical trials have shown remarkable beneficial effects following their intramyocardial transplantation. Yet, the purification of CD133 + stem cells is typically performed in centralized clean room facilities using semi-automatic manufacturing processes based on magnetic cell sorting (MACS®). However, this requires time-consuming and cost-intensive logistics. CD133 + stem cells were purified from patient-derived sternal bone marrow using the recently developed automatic CliniMACS Prodigy® BM-133 System (Prodigy). The entire manufacturing process, as well as the subsequent quality control of the final cell product (CP), were realized on-site and in compliance with EU guidelines for Good Manufacturing Practice. The biological activity of automatically isolated CD133 + cells was evaluated and compared to manually isolated CD133 + cells via functional assays as well as immunofluorescence microscopy. In addition, the regenerative potential of purified stem cells was assessed 3 weeks after transplantation in immunodeficient mice which had been subjected to experimental myocardial infarction. We established for the first time an on-site manufacturing procedure for stem CPs intended for the treatment of ischemic heart diseases using an automatized system. On average, 0.88 × 10 6 viable CD133 + cells with a mean log 10 depletion of 3.23 ± 0.19 of non-target cells were isolated. Furthermore, we demonstrated that these automatically isolated cells bear proliferation and differentiation capacities comparable to manually isolated cells in vitro. Moreover, the automatically generated CP shows equal cardiac regeneration potential in vivo. Our results indicate that the Prodigy is a powerful system for automatic manufacturing of a CD133 + CP within few hours. Compared to conventional manufacturing processes, future clinical application of

  4. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

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    Coco Claudio

    2012-09-01

    Full Text Available Abstract Background Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG complex, have been previously reported to be altered in colorectal cancers. Methods Expression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated. Results Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0–80. A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002 and overall (p = 0.008 survival. Expression of α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02 and overall (p = 0.02 survival. Increased expression of CD133, but not loss of α-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002 and death (RR = 2.3; p = 0.003. Conclusions Loss of α-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.

  5. Omega-3 Eicosapentaenoic Acid Decreases CD133 Colon Cancer Stem-Like Cell Marker Expression While Increasing Sensitivity to Chemotherapy

    Science.gov (United States)

    De Carlo, Flavia; Witte, Theodore R.; Hardman, W. Elaine; Claudio, Pier Paolo

    2013-01-01

    Colorectal cancer is the third leading cause of cancer-related death in the western world. In vitro and in vivo experiments showed that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer cells, including colon cancer, and increase the efficacy of various anticancer drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs) that are responsible for tumor formation and maintenance. CSLCs have also been linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon CSLCs have been immunophenotyped using several antibodies against cellular markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to isolate a population of colon cancer cells that retains stem cells properties (CSLCs) from both established cell lines and primary cell cultures. We demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased the cell number of the overall population of cancer cells, but not of the CD133 (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20 (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the sensitivity of COLO 320 DM cells (total population) to both standard-of-care chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil. PMID:23874993

  6. Engineered matrix coatings to modulate the adhesion of CD133+ human hematopoietic progenitor cells.

    Science.gov (United States)

    Franke, Katja; Pompe, Tilo; Bornhäuser, Martin; Werner, Carsten

    2007-02-01

    Interactions of hematopoietic progenitor cells (HPC) with their local microenvironments in the bone marrow are thought to control homing, differentiation, and self-renewal of the cells. To dissect the role of extracellular matrix (ECM) components of the niche microenvironment, a set of well-defined ECM coatings including fibronectin, heparin, heparan sulphate, hyaluronic acid, tropocollagen I, and co-fibrils of collagen I with heparin or hyaluronic acid was prepared and analysed with respect to the attachment of human CD133+ HPC in vitro. The extension of the adhesion areas of individual cells as well as the fraction of adherent cells were assessed by reflection interference contrast microscopy (RICM). Intense cell-matrix interactions were found on surfaces coated with fibronectin, heparin, heparan sulphate, and on the collagen I based co-fibrils. Insignificant adhesion was found for tropocollagen I and hyaluronic acid. The strongest adhesion of HPC was observed on fibronectin with contact areas of about 7 microm(2). Interaction of HPC with coatings consisting of heparin, heparan sulphate, and co-fibrils result in small circular shaped contact zones of 3 microm(2) pointing to another, less efficient, adhesion mechanism. Analysing the specificity of cell-matrix interaction by antibody blocking experiments suggests an integrin(alpha(5)beta(1))-specific adhesion on fibronectin, while adhesion on heparin was shown to be mediated by selectins (CD62L). Taken together, our data provide a basis for the design of advanced culture carriers supporting site-specific proliferation or differentiation of HPC.

  7. Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1–6 cells

    Directory of Open Access Journals (Sweden)

    Jeng KS

    2013-08-01

    Full Text Available Kuo-Shyang Jeng,1 I-Shyan Sheen,2 Wen-Juei Jeng,2 Ming-Che Yu,3 Hsin-I Hsiau,3 Fang-Yu Chang,3 Hsin-Hua Tsai31Department of Surgery, Far Eastern Memorial Hospital, Taipei, 2Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, 3Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan, Republic of ChinaBackground: The important role of cancer stem cells in carcinogenesis has been emphasized in research. CD133+ cells have been mentioned as liver cancer stem cells in hepatocellular carcinoma (HCC. Some researchers have proposed that the sonic hedgehog (Shh pathway contributes to hepatocarcinogenesis and that the pathway activation occurs mainly in cancer stem cells. We investigated whether the activation of the Shh pathway occurs in CD133+ cells from liver cancer.Materials and methods: We used magnetic sorting to isolate CD133+ cells from mouse cancer Hepa 1–6 cells. To examine the clonogenicity, cell culture and soft agar colony formation assay were performed between CD133+ and CD133- cells. To study the activation of the Shh pathway, we examined the mRNA expressions of Shh, patched homolog 1 (Ptch-1, glioma-associated oncogene homolog 1 (Gli-1, and smoothened homolog (Smoh by real-time polymerase chain reaction of both CD133+ and CD133- cells.Results: The number (mean ± standard deviation of colonies of CD133+ cells and CD133- cells was 1,031.0 ± 104.7 and 119.7 ± 17.6 respectively. This difference was statistically significant (P < 0.001. Their clonogenicity was 13.7% ± 1.4% and 1.6% ± 0.2% respectively with a statistically significant difference found (P < 0.001. CD133+ cells and CD133– cells were found to have statistically significant differences in Shh mRNA and Smoh mRNA (P = 0.005 and P = 0.043 respectively.Conclusion: CD133+ Hepa 1–6 cells have a significantly higher colony proliferation and clonogenicity. The Shh pathway is activated in these

  8. Spatial distribution of prominin-1 (CD133-positive cells within germinative zones of the vertebrate brain.

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    József Jászai

    Full Text Available In mammals, embryonic neural progenitors as well as adult neural stem cells can be prospectively isolated based on the cell surface expression of prominin-1 (CD133, a plasma membrane glycoprotein. In contrast, characterization of neural progenitors in non-mammalian vertebrates endowed with significant constitutive neurogenesis and inherent self-repair ability is hampered by the lack of suitable cell surface markers. Here, we have investigated whether prominin-1-orthologues of the major non-mammalian vertebrate model organisms show any degree of conservation as for their association with neurogenic geminative zones within the central nervous system (CNS as they do in mammals or associated with activated neural progenitors during provoked neurogenesis in the regenerating CNS.We have recently identified prominin-1 orthologues from zebrafish, axolotl and chicken. The spatial distribution of prominin-1-positive cells--in comparison to those of mice--was mapped in the intact brain in these organisms by non-radioactive in situ hybridization combined with detection of proliferating neural progenitors, marked either by proliferating cell nuclear antigen or 5-bromo-deoxyuridine. Furthermore, distribution of prominin-1 transcripts was investigated in the regenerating spinal cord of injured axolotl.Remarkably, a conserved association of prominin-1 with germinative zones of the CNS was uncovered as manifested in a significant co-localization with cell proliferation markers during normal constitutive neurogenesis in all species investigated. Moreover, an enhanced expression of prominin-1 became evident associated with provoked, compensatory neurogenesis during the epimorphic regeneration of the axolotl spinal cord. Interestingly, significant prominin-1-expressing cell populations were also detected at distinct extraventricular (parenchymal locations in the CNS of all vertebrate species being suggestive of further, non-neurogenic neural function

  9. Prominin-1/CD133+ lung epithelial progenitors protect from bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Germano, Davide; Blyszczuk, Przemyslaw; Valaperti, Alan; Kania, Gabriela; Dirnhofer, Stephan; Landmesser, Ulf; Lüscher, Thomas F; Hunziker, Lukas; Zulewski, Henryk; Eriksson, Urs

    2009-05-15

    The mouse model of bleomycin-induced lung injury offers an approach to study idiopathic pulmonary fibrosis, a progressive interstitial lung disease with poor prognosis. Progenitor cell-based treatment strategies might combine antiinflammatory effects and the capacity for tissue repair. To expand progenitor cells with reparative and regenerative capacities and to evaluate their protective effects on pulmonary fibrosis in vivo. Prominin-1/CD133(+) epithelial progenitor cells (PEPs) were expanded from adult mouse lungs after digestion and culture of distal airways. Lung fibrosis was induced in C57Bl/6 mice by instillation of bleomycin. Two hours later, animals were transplanted with PEPs. Inflammation and fibrosis were assessed by immunohistochemistry, bronchoalveolar lavage fluid differentials, and real-time polymerase chain reaction. PEPs expanded from mouse lungs were of bone marrow origin, coexpressed stem and hematopoietic cell markers, and differentiated in vitro into alveolar type II surfactant protein-C(+) epithelial cells. In bleomycin-challenged mice, intratracheally injected PEPs engrafted into the lungs and differentiated into type II pneumocytes. Furthermore, PEPs suppressed proinflammatory and profibrotic gene expression, prevented the recruitment of inflammatory cells, and protected bleomycin-challenged mice from pulmonary fibrosis. Mechanistically, the protective effect depended on upregulation of inducible nitric oxide synthase in PEPs and nitric oxide-mediated suppression of alveolar macrophage proliferation. Accordingly, PEPs from iNOS(-/-) but not iNOS(+/+) mice failed to protect from bleomycin-induced lung injury. The combined antiinflammatory and regenerative capacity of bone marrow-derived pulmonary epithelial progenitors offers a promising approach for development of cell-based therapeutic strategies against pulmonary fibrosis.

  10. Full GMP-Compliant Validation of Bone Marrow-Derived Human CD133+ Cells as Advanced Therapy Medicinal Product for Refractory Ischemic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Daniela Belotti

    2015-01-01

    Full Text Available According to the European Medicine Agency (EMA regulatory frameworks, Advanced Therapy Medicinal Products (ATMP represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+ cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs. In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM, ATMP-CD133 manufacturing output yielded a median of 6.66 × 106 of CD133+ cells (range 2.85 × 106–30.84 × 106, with a viability ranged between 96,03% and 99,97% (median 99,87% and a median purity of CD133+ cells of 90,60% (range 81,40%–96,20%. Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106 cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial.

  11. Full GMP-compliant validation of bone marrow-derived human CD133(+) cells as advanced therapy medicinal product for refractory ischemic cardiomyopathy.

    Science.gov (United States)

    Belotti, Daniela; Gaipa, Giuseppe; Bassetti, Beatrice; Cabiati, Benedetta; Spaltro, Gabriella; Biagi, Ettore; Parma, Matteo; Biondi, Andrea; Cavallotti, Laura; Gambini, Elisa; Pompilio, Giulio

    2015-01-01

    According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133(+) cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 10(6) of CD133(+) cells (range 2.85 × 10(6)-30.84 × 10(6)), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133(+) cells of 90,60% (range 81,40%-96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 10(6) cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).

  12. Full GMP-Compliant Validation of Bone Marrow-Derived Human CD133+ Cells as Advanced Therapy Medicinal Product for Refractory Ischemic Cardiomyopathy

    Science.gov (United States)

    Belotti, Daniela; Gaipa, Giuseppe; Bassetti, Beatrice; Cabiati, Benedetta; Spaltro, Gabriella; Biagi, Ettore; Parma, Matteo; Biondi, Andrea; Cavallotti, Laura; Gambini, Elisa; Pompilio, Giulio

    2015-01-01

    According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+ cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 106 of CD133+ cells (range 2.85 × 106–30.84 × 106), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133+ cells of 90,60% (range 81,40%–96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106 cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial). PMID:26495296

  13. Cancer cells with high expression of CD133 exert FLIP upregulation and resistance to TRAIL-induced apoptosis

    Czech Academy of Sciences Publication Activity Database

    Zobalová, Renata; Stantic, M.; Prokopová, Kateřina; Dong, L. F.; Neužil, Jiří

    2009-01-01

    Roč. 34, č. 3 (2009), s. 231-235 ISSN 0951-6433 R&D Projects: GA AV ČR(CZ) IAA500520702; GA ČR GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Cancer stem cells * CD 133 * FLIP Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.912, year: 2009

  14. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

    OpenAIRE

    Li, Chun-Yan; Li, Bao-Xiu; Liang, Yi; Peng, Rui-Qing; Ding, Ya; Xu, Da-Zhi; Zhang, Xin; Pan, Zhi-Zhong; Wan, De-Sen; Zeng, Yi-Xin; Zhu, Xiao-Feng; Zhang, Xiao-Shi

    2009-01-01

    Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was inves...

  15. Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells

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    Ade Kallas-Kivi

    2016-01-01

    Full Text Available The lipophilic statin lovastatin decreases cholesterol synthesis and is a safe and effective treatment for the prevention of cardiovascular diseases. Growing evidence points at antitumor potential of lovastatin. Therefore, understanding the molecular mechanism of lovastatin function in different cell types is critical to effective therapy design. In this study, we investigated the effects of lovastatin on the differentiation potential of human embryonic stem (hES cells (H9 cell line. Multiparameter flow cytometric assay was used to detect changes in the expression of transcription factors characteristic of hES cells. We found that lovastatin treatment delayed NANOG downregulation during ectodermal and endodermal differentiation. Likewise, expression of ectodermal (SOX1 and OTX2 and endodermal (GATA4 and FOXA2 markers was higher in treated cells. Exposure of hES cells to lovastatin led to a minor decrease in the expression of SSEA-3 and a significant reduction in CD133 expression. Treated cells also formed fewer embryoid bodies than control cells. By analyzing hES with and without CD133, we discovered that CD133 expression is required for proper formation of embryoid bodies. In conclusion, lovastatin reduced the heterogeneity of hES cells and impaired their differentiation potential.

  16. Intrathecal injection of CD133-positive enriched bone marrow progenitor cells in children with cerebral palsy: feasibility and safety.

    Science.gov (United States)

    Zali, Alireza; Arab, Leila; Ashrafi, Farzad; Mardpour, Soura; Niknejhadi, Maryam; Hedayati-Asl, Amir Abbas; Halimi-Asl, Aliasghar; Ommi, Davood; Hosseini, Seyyedeh-Esmat; Baharvand, Hossein; Aghdami, Nasser

    2015-02-01

    Recent studies have proposed that cellular transplantation may have some regenerative and functional efficacy in the treatment of cerebral palsy (CP); however, much remains to be understood regarding its safety, feasibility and efficacy. This study was initiated to evaluate the safety of autologous bone marrow-derived CD133(+) cell intrathecal injection. Children (n = 12), aged 4 to 12 years, who were diagnosed with different types of CP underwent BM aspiration. CD133(+) cells were enriched from the BM samples and intrathecally injected. The Gross Motor Function Measure (GMFM-66), Gross Motor Function Classification System (GMFCS), UK FIM+FAM, Functional Independence Measure (FIM) and Functional Assessment Measure (FAM) were assessed at baseline and 6 months after the procedure. Patients' ability to balance was measured by the Berg Balance Scale (BBS), and severity of spasticity was evaluated by the Modified Ashworth Scale. Magnetic resonance imaging was done at baseline and 6 months after therapy. This study was registered in ClinicalTrials.gov (NCT01404663). There were no adverse events detected by clinical and laboratory tests or imaging studies, with the exception of a seizure in 1 patient. A significant improvement was observed 6 months after cell transplantation versus baseline according to GMFM, GMFCS, FIM+FAM, Ashworth Scale, and BBS outcomes. Subarachnoid injection of CD133-positive enriched bone marrow progenitor cells in children with CP is a safe approach. The results suggest a possible short-term improvement in neurological function. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. The stem cell marker CD133 is highly expressed in sessile serrated adenoma and its borderline variant compared with hyperplastic polyp

    DEFF Research Database (Denmark)

    Mohammadi, Mahin; Bzorek, Michael; Bonde, Jesper Hansen

    2013-01-01

    in their histological typing, the identification of reliable markers that assist in the characterisation is warranted. Most important is the identification of polyp qualities that may reflect the patients' risk of developing colorectal cancer. To address these issues, CD133 may represent a potential adjunct. Here we......Non-dysplastic serrated polyps (ND-SP) represent a heterogeneous group of colorectal lesions that comprise hyperplastic polyp (HP) and the non-dysplastic subset of sessile serrated adenoma/polyp/lesion (SSA/P/L) and its borderline variant (BSSA/P/L). Given the observer variation...... studied the discriminatory value of CD133 expression in the classification of ND-SPs and its distribution pattern in relation to synchronous colorectal carcinoma (SCRC). 39 SSA/P/Ls, 27 BSSA/P/Ls and 21 matched HPs were immunostained for CD133. The data were further correlated to the presence of SCRC...

  18. Characterization of a GM7 glioblastoma cell line showing CD133 positivity and both cytoplasmic and nuclear localization of nestin.

    Science.gov (United States)

    Loja, Tomas; Chlapek, Petr; Kuglik, Petr; Pesakova, Martina; Oltova, Alexandra; Cejpek, Pavel; Veselska, Renata

    2009-01-01

    A newly established GM7 cell line was derived from the tumor tissue of a 65-year-old man surgically treated for a relapse of glioblastoma multiforme that occurred 10 months after first surgery following radiotherapy. GM7 cells exhibit spindle or glia-like morphology, and multinucleated giant cells are also present in the culture. The cells proliferate rapidly (PDT is about 18 h) and tend to grow in multilayer without contact inhibition. Using G-banding and SKY, the GM7 cell line was identified as near-triploid with a large number of structural and numerical abnormalities. Repeated karyotyping during long-term cultivation confirmed a chromosome number of 70+/-3 chromosomes per cell. Special attention was paid to the immunocytochemical analysis of protein markers in this cell line; GM7 cells showed strong positivity for CD133, vimentin, nestin, NF-160 and S-100 protein and weak positivity for GFAP and NSE, but were negative for synaptophysin. The most important features of the GM7 cell line are its stable phenotype CD133+/nestin+, which are accepted as stem cell markers in neural stem/progenitor cells, and especially unusual intracellular localization of the IF protein nestin, which was detected and repeatedly confirmed both in the cytoplasm and cell nucleus. For this reason, the new GM7 glioblastoma cell line represents an important model suitable not only for further studies on glioblastoma biology and cancer stem cells, but particularly for the detailed investigation of the role of nestin in transformed cells.

  19. Expression and Significance of Stem Cell Markers CK19, Notch3, CD133, P75NTR, STRO-1 and ABCG2 in Pulmonary Squamous Carcinomas

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    Xuyong LIN, , , , ,

    2009-04-01

    Full Text Available Background and objective Increasing reports showed that some tumor stem cells were selfrenewal and multi-lineage differentiated in tumors, similar to the normal stem cells in human body. The aim of this study is to observe the expression of stem cell markers in lung squamous carcinoma tissues. Methods Fifty-four lung cancer specimens from surgery were analyzed for CK19, Notch3, CD133, P75NTR, STRO-1 and ABCG2 expression by using S-P immunohistochemistry. In addition, ten normal lung tissue samples were included as control. Results CK19, Notch3, CD133 and ABCG2 were expressed in 54 Lung cancer tissues, without expression of P75NTR and STRO-1. The expressionrate of CK19, Notch3, CD133 and ABCG2 was 66.67% (36/54, 87.04% (47/54, 50% (27/54, and 61.11% (33/54 respectively. The levels of expression of Notch3, CD133 and ABCG2 were significantly lower in high differentiation group than those in moderate and low differentiation group (P <0.05. The levels of expression of CK19, CD133 and ABCG2 were significantly higher in lymph node metastasis group than those in non-metastasis group (P <0.05. The percentage of total positive cells of four stem cell markers in serial tissue sections was lower than 2%. Conclusion There was expression ofsome stem cell markers in pulmonary squamous carcinomas, and there was relationship between expression degree withdifferentiation degree and lymph node metastasis.

  20. Effect of taxanes combined with platinum chemotherapy on serum HE4, AFP, DDX4, CD133, CEA and T lymphocyte subsets in patients with epithelial ovarian cancer

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    Lu Wang

    2016-09-01

    Full Text Available Objective: To study the effect of taxanes combined with platinum chemotherapy on serum human epididymal protein 4 (HE4, 毩-fetoprotein (AFP, DEAD box polypeptide 4 (DDX4, cluster of differentiation 133 (CD133, carcinoembryonic antigen (CEA and T lymphocyte subsets in patients with epithelial ovarian cancer (EOC. Methods: A total of 80 EOC patients in our hospital from October 2014 to January 2016 were enrolled in this study. The subjects were divided into control group (n=40 and experiment group (n=40 randomly. Patients in control group were treated with platinum, the experiment group were treated with taxanes combined with platinum chemotherapy. With 21 days as a course of treatment, the two groups were treated for 4 courses. The clinical curative effect after treatment of the two groups was compared. The serum HE4, AFP, DDX4, CD133, CEA levels and peripheral blood CD3+, CD4+, CD8+ cells of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum HE4, AFP, DDX4, CD133, CEA level and peripheral blood CD3+, CD4+, CD8+ cells of the two groups before treatment (P>0.05. The serum HE4, AFP, DDX4, CD133 and CEA level of the two groups after treatment were significantly lower than before treatment (P<0.05, and that of experiment were significantly lower than control group (P<0.05. The peripheral blood CD3+, CD4+ and CD8+ cells of the two groups after treatment were significantly lower than before treatment (P<0.05, and that of experiment were significantly higher than control group (P<0.05. Conclusions: Taxanes combined with platinum chemotherapy can significantly reduce the serum HE4, AFP, DDX4, CD133 and CEA levels, improve peripheral blood CD3+, CD4+ and CD8+ levels of patients with epithelial ovarian cancer, and it is worthy clinical application.

  1. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

    Science.gov (United States)

    Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

    2015-05-28

    The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. Copyright © 2015

  2. Platelet released growth factors boost expansion of bone marrow derived CD34(+) and CD133(+) endothelial progenitor cells for autologous grafting.

    Science.gov (United States)

    Lippross, Sebastian; Loibl, Markus; Hoppe, Sven; Meury, Thomas; Benneker, Lorin; Alini, Mauro; Verrier, Sophie

    2011-01-01

    Stem cell based autologous grafting has recently gained mayor interest in various surgical fields for the treatment of extensive tissue defects. CD34(+) and CD133(+) cells that can be isolated from the pool of bone marrow mononuclear cells (BMC) are capable of differentiating into mature endothelial cells in vivo. These endothelial progenitor cells (EPC) are believed to represent a major portion of the angiogenic regenerative cells that are released from bone marrow when tissue injury has occurred. In recent years tissue engineers increasingly looked at the process of vessel neoformation because of its major importance for successful cell grafting to replace damaged tissue. Up to now one of the greatest problems preventing a clinical application is the large scale of expansion that is required for such purpose. We established a method to effectively enhance the expansion of CD34(+) and CD133(+) cells by the use of platelet-released growth factors (PRGF) as a media supplement. PRGF were prepared from thrombocyte concentrates and used as a media supplement to iscove's modified dulbecco's media (IMDM). EPC were immunomagnetically separated from human bone morrow monocyte cells and cultured in IMDM + 10% fetal calf serum (FCS), IMDM + 5%, FCS + 5% PRGF and IMDM + 10% PRGF. We clearly demonstrate a statistically significant higher and faster cell proliferation rate at 7, 14, 21, and 28 days of culture when both PRGF and FCS were added to the medium as opposed to 10% FCS or 10% PRGF alone. The addition of 10% PRGF to IMDM in the absence of FCS leads to a growth arrest from day 14 on. In histochemical, immunocytochemical, and gene-expression analysis we showed that angiogenic and precursor markers of CD34(+) and CD133(+) cells are maintained during long-term culture. In summary, we established a protocol to boost the expansion of CD34(+) and CD133(+) cells. Thereby we provide a technical step towards the clinical application of autologous stem cell

  3. Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses.

    Science.gov (United States)

    Friedman, Gregory K; Moore, Blake P; Nan, Li; Kelly, Virginia M; Etminan, Tina; Langford, Catherine P; Xu, Hui; Han, Xiaosi; Markert, James M; Beierle, Elizabeth A; Gillespie, G Yancey

    2016-02-01

    Childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15. Using 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies. We demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002. Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Long-term clinical results of autologous bone marrow CD 133+ cell transplantation in patients with ST-elevation myocardial infarction

    Science.gov (United States)

    Kirgizova, M. A.; Suslova, T. E.; Markov, V. A.; Karpov, R. S.; Ryabov, V. V.

    2015-11-01

    The aim of the study was investigate the long-term results of autologous bone marrow CD 133+ cell transplantation in patients with primary ST-Elevation Myocardial Infarction (STEMI). Methods and results: From 2006 to 2007, 26 patients with primary STEMI were included in an open randomized study. Patients were randomized to two groups: 1st - included patients underwent PCI and transplantation of autologous bone marrow CD 133+ cell (n = 10); 2nd - patients with only PCI (n = 16). Follow-up study was performed 7.70±0.42 years after STEMI and consisted in physical examination, 6-min walking test, Echo exam. Total and cardiovascular mortality in group 1 was lower (20% (n = 2) vs. 44% (n = 7), p = 0.1 and 22% (n = 2) vs. 25% (n = 4), (p=0.53), respectively). Analysis of cardiac volumetric parameters shows significant differences between groups: EDV of 100.7 ± 50.2 mL vs. 144.40±42.7 mL, ESV of 56.3 ± 37.8 mL vs. 89.7 ± 38.7 mL in 1st and 2nd groups, respectively. Data of the study showed positive effects of autologous bone marrow CD 133+ cell transplantation on the long-term survival of patients and structural status of the heart.

  5. MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Pasqualino de Antonellis

    Full Text Available Through negative regulation of gene expression, microRNAs (miRNAs can function as oncosuppressors in cancers, and can themselves show altered expression in various tumor types. Here, we have investigated medulloblastoma tumors (MBs, which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many of the cell-fate-determining stages. Notch regulates a subset of MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulate these phenomena, and can be used in anti-cancer therapies.In a screening of potential targets within Notch signaling, miR-34a was seen to be a regulator of the Notch pathway through its targeting of Notch ligand Delta-like 1 (Dll1. Down-regulation of Dll1 expression by miR-34a negatively regulates cell proliferation, and induces apoptosis and neural differentiation in MB cells. Using an inducible tetracycline on-off model of miR-34a expression, we show that in Daoy MB cells, Dll1 is the first target that is regulated in MB, as compared to the other targets analyzed here: Cyclin D1, cMyc and CDK4. MiR-34a expression negatively affects CD133(+/CD15(+ tumor-propagating cells, then we assay through reverse-phase proteomic arrays, Akt and Stat3 signaling hypo-phosphorylation. Adenoviruses carrying the precursor miR-34a induce neurogenesis of tumor spheres derived from a genetic animal model of MB (Patch1(+/- p53(-/-, thus providing further evidence that the miR-34a/Dll1 axis controls both autonomous and non autonomous signaling of Notch. In vivo, miR-34a overexpression carried by adenoviruses reduces tumor burden in cerebellum xenografts of athymic mice, thus demonstrating an anti-tumorigenic role of miR-34a in vivo.Despite advances in our understanding of the pathogenesis of MB, one-third of patients with MB remain incurable. Here, we show that stable nucleic

  6. Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133+ human colorectal cancer cells

    International Nuclear Information System (INIS)

    Klose, Johannes; Eissele, Jana; Volz, Claudia; Schmitt, Steffen; Ritter, Alina; Ying, Shen; Schmidt, Thomas; Heger, Ulrike; Schneider, Martin; Ulrich, Alexis

    2016-01-01

    The polyether antibiotic Salinomycin (Sal) is regarded as an inhibitor of cancer stem cells. Its effectiveness on human colorectal cancer (CRC) cells in vitro has been demonstrated before. The aim of this study was to establish a murine model to investigate the effectiveness of Sal in vivo. Furthermore, we investigated the impact of Sal on Wnt/β-catenin signaling in human CD133 + CRC cells. The two murine CRC cell lines MC38 and CT26 were used to analyze the impact of Sal on tumor cell proliferation, viability, migration, cell cycle progression and cell death in vitro. For in vivo studies, CT26 cells were injected into syngeneic BALB/c mice to initiate (i) subcutaneous, (ii) orthotopic, or (iii) metastatic CRC growth. Sal was administered daily, 5-Fluoruracil served as a control. For mechanistic studies, the CD133 + and CD133 - subpopulations of human CRC cells were separated by flow cytometry and separately exposed to increasing concentrations of Sal. The impact on Wnt/β-catenin signaling was determined by Western blotting and quantitative PCR. Sal markedly impaired tumor cell viability, proliferation and migration, and induced necrotic cell death in vitro. CRC growth in vivo was likewise inhibited upon Sal treatment. Interference with Wnt signaling and reduced expression of the Wnt target genes Fibronectin and Lgr5 indicates a novel molecular mechanism, mediating anti-tumoral effects of Sal in CRC. Sal effectively impairs CRC growth in vivo. Furthermore, Sal acts as an inhibitor of Wnt/β-catenin signaling. Thus, Salinomycin represents a promising candidate for clinical CRC treatment. The online version of this article (doi:10.1186/s12885-016-2879-8) contains supplementary material, which is available to authorized users

  7. Up-modulation of PLC-β2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+phenotype: a promising target for preventing progression of TNBC.

    Science.gov (United States)

    Brugnoli, Federica; Grassilli, Silvia; Lanuti, Paola; Marchisio, Marco; Al-Qassab, Yasamin; Vezzali, Federica; Capitani, Silvano; Bertagnolo, Valeria

    2017-09-04

    The malignant potential of triple negative breast cancer (TNBC) is also dependent on a sub-population of cells with a stem-like phenotype. Among the cancer stem cell markers, CD133 and EpCAM strongly correlate with breast tumor aggressiveness, suggesting that simultaneous targeting of the two surface antigens may be beneficial in treatment of TNBC. Since in TNBC-derived cells we demonstrated that PLC-β2 induces the conversion of CD133 high to CD133 low cells, here we explored its possible role in down-modulating the expression of both CD133 and EpCAM and, ultimately, in reducing the number of TNBC cells with a stem-like phenotype. A magnetic step-by-step cell isolation with antibodies directed against CD133 and/or EpCAM was performed on the TNBC-derived MDA-MB-231 cell line. In the same cell model, PLC-β2 was over-expressed or down-modulated and cell proliferation and invasion capability were evaluated by Real-time cell assays. The surface expression of CD133, EpCAM and CD44 in the different experimental conditions were measured by multi-color flow cytometry immunophenotyping. A CD133 + /EpCAM + sub-population with high proliferation rate and invasion capability is present in the MDA-MB-231 cell line. Over-expression of PLC-β2 in CD133 + /EpCAM + cells reduced the surface expression of both CD133 and EpCAM, as well as proliferation and invasion capability of this cellular subset. On the other hand, the up-modulation of PLC-β2 in the whole MDA-MB-231 cell population reduced the number of cells with a CD44 + /CD133 + /EpCAM + stem-like phenotype. Since selective targeting of the cells with the highest aggressive potential may have a great clinical importance for TNBC, the up-modulation of PLC-β2, reducing the number of cells with a stem-like phenotype, may be a promising goal for novel therapies aimed to prevent the progression of aggressive breast tumors.

  8. Flow cytometry data analysis of CD34+/CD133+ stem cells in bone marrow and peripheral blood and T, B, and NK cells after hematopoietic grafting

    Directory of Open Access Journals (Sweden)

    José C. Jaime-Pérez

    2016-06-01

    Full Text Available This article provides flow cytometry information regarding levels of expression for hematopoietic stem cell markers CD34 and CD133 obtained simultaneously of the bone marrow and peripheral blood from recipients of allogeneic and autologous transplants of PB hematoprogenitors for treating hematological malignancies and who were clinically healthy after ≥100 days following the procedure. CD34 and CD133 expression is compared regarding type of transplant (autologous vs. allogeneic and sample cell source (bone marrow vs. peripheral blood. Patients were conditioned with a reduced-intensity conditioning regimen. Also shown is the flow cytometry analysis of mononuclear cell and lymphocyte populations in the peripheral blood of both types of recipients, as well as the characterization of immune cells, including T lymphocyte antigenic make up markers CD3, CD4 and CD8, B lymphocytes and NK cells, including total NK, bright and dim subtypes in the peripheral blood of both types of recipients. For further information and discussion regarding interpretation and meaning of post-transplant flow cytometry analysis, please refer to the article “Assessment of immune reconstitution status in recipients of a successful hematopoietic stem cell transplant from peripheral blood after reduced intensity conditioning” [1].

  9. The construction of a library of synthetic promoters revealed some specific features of strong Streptomyces promoters

    DEFF Research Database (Denmark)

    Seghezzi, Nicolas; Amar, Patrick; Købmann, Brian

    2011-01-01

    projects. Thirty-eight promoters were sequenced, and the sequences of the 14 weakest and 14 strongest promoters were compared using the WebLogo software with small sample correction. This comparison revealed that the −10 box, the −10 extended motif as well as the spacer of the strong Streptomyces promoters......Streptomyces are bacteria of industrial interest whose genome contains more than 73% of bases GC. In order to define, in these GC-rich bacteria, specific sequence features of strong promoters, a library of synthetic promoters of various sequence composition was constructed in Streptomyces. To do so...... concentrations of neomycin (20, 50, and 100 μg ml−1). Promoter strengths varied up to 12-fold, in small increments of activity increase, as determined by reverse transcriptase-PCR. This collection of promoters of various strengths can be useful for the fine-tuning of gene expression in genetic engineering...

  10. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study.

    Science.gov (United States)

    Santamaria, Xavier; Cabanillas, Sergio; Cervelló, Irene; Arbona, Cristina; Raga, Francisco; Ferro, Jaime; Palmero, Julio; Remohí, Jose; Pellicer, Antonio; Simón, Carlos

    2016-05-01

    Could cell therapy using autologous peripheral blood CD133+ bone marrow-derived stem cells (BMDSCs) offer a safe and efficient therapeutic approach for patients with refractory Asherman's syndrome (AS) and/or endometrial atrophy (EA) and a wish to conceive? In the first 3 months, autologous cell therapy, using CD133+ BMDSCs in conjunction with hormonal replacement therapy, increased the volume and duration of menses as well as the thickness and angiogenesis processes of the endometrium while decreasing intrauterine adhesion scores. AS is characterized by the presence of intrauterine adhesions and EA prevents the endometrium from growing thicker than 5 mm, resulting in menstruation disorders and infertility. Many therapies have been attempted for these conditions, but none have proved effective. This was a prospective, experimental, non-controlled study. There were 18 patients aged 30-45 years with refractory AS or EA were recruited, and 16 of these completed the study. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and neoangiogenesis were assessed before and 3 and 6 months after cell therapy. After the initial hysteroscopic diagnosis, BMDSC mobilization was performed by granulocyte-CSF injection, then CD133+ cells were isolated through peripheral blood aphaeresis to obtain a mean of 124.39 million cells (range 42-236), which were immediately delivered into the spiral arterioles by catheterization. Subsequently, endometrial treatment after stem cell therapy was assessed in terms of restoration of menses, endometrial thickness (by vaginal ultrasound), adhesion score (by hysteroscopy), neoangiogenesis and ongoing pregnancy rate. The study was conducted at Hospital Clínico Universitario of Valencia and IVI Valencia (Spain). All 11 AS patients exhibited an improved uterine cavity 2 months after stem cell therapy. Endometrial thickness increased from an average of 4.3 mm (range 2.7-5) to 6.7 mm (range 3.1-12) ( ITALIC! P = 0

  11. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH{sup +}/CD133{sup +} stem cell-like human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Li, E-mail: lin.796@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Fuchs, James; Li, Chenglong [Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210 (United States); Olson, Veronica [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Bekaii-Saab, Tanios [Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210 (United States); Lin, Jiayuh, E-mail: lin.674@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. Black-Right-Pointing-Pointer STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. Black-Right-Pointing-Pointer Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. Black-Right-Pointing-Pointer STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. Black-Right-Pointing-Pointer Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH{sup +}/CD133{sup +}). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower

  12. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH+/CD133+ stem cell-like human colon cancer cells

    International Nuclear Information System (INIS)

    Lin, Li; Fuchs, James; Li, Chenglong; Olson, Veronica; Bekaii-Saab, Tanios; Lin, Jiayuh

    2011-01-01

    Highlights: ► The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. ► STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. ► Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. ► STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. ► Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH + /CD133 + ). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem

  13. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  14. CD133-enriched Xeno-Free human embryonic-derived neural stem cells expand rapidly in culture and do not form teratomas in immunodeficient mice

    Directory of Open Access Journals (Sweden)

    Daniel L. Haus

    2014-09-01

    Full Text Available Common methods for the generation of human embryonic-derived neural stem cells (hNSCs result in cells with potentially compromised safety profiles due to maintenance of cells in conditions containing non-human proteins (e.g. in bovine serum or on mouse fibroblast feeders. Additionally, sufficient expansion of resulting hNSCs for scaling out or up in a clinically relevant time frame has proven to be difficult. Here, we report a strategy that produces hNSCs in completely “Xeno-Free” culture conditions. Furthermore, we have enriched the hNSCs for the cell surface marker CD133 via magnetic sorting, which has led to an increase in the expansion rate and neuronal fate specification of the hNSCs in vitro. Critically, we have also confirmed neural lineage specificity upon sorted hNSC transplantation into the immunodeficient NOD-scid mouse brain. The future use or adaptation of these protocols has the potential to better facilitate the advancement of pre-clinical strategies from the bench to the bedside.

  15. Monoclonal Antibodies 13A4 and AC133 Do Not Recognize the Canine Ortholog of Mouse and Human Stem Cell Antigen Prominin-1 (CD133.

    Directory of Open Access Journals (Sweden)

    Kristina Thamm

    Full Text Available The pentaspan membrane glycoprotein prominin-1 (CD133 is widely used in medicine as a cell surface marker of stem and cancer stem cells. It has opened new avenues in stem cell-based regenerative therapy and oncology. This molecule is largely used with human samples or the mouse model, and consequently most biological tools including antibodies are directed against human and murine prominin-1. Although the general structure of prominin-1 including its membrane topology is conserved throughout the animal kingdom, its primary sequence is poorly conserved. Thus, it is unclear if anti-human and -mouse prominin-1 antibodies cross-react with their orthologs in other species, especially dog. Answering this issue is imperative in light of the growing number of studies using canine prominin-1 as an antigenic marker. Here, we address this issue by cloning the canine prominin-1 and use its overexpression as a green fluorescent protein fusion protein in Madin-Darby canine kidney cells to determine its immunoreactivity with antibodies against human or mouse prominin-1. We used immunocytochemistry, flow cytometry and immunoblotting techniques and surprisingly found no cross-species immunoreactivity. These results raise some caution in data interpretation when anti-prominin-1 antibodies are used in interspecies studies.

  16. Human prominin-1 (CD133 is detected in both neoplastic and non-neoplastic salivary gland diseases and released into saliva in a ubiquitinated form.

    Directory of Open Access Journals (Sweden)

    Jana Karbanová

    Full Text Available Prominin-1 (CD133 is physiologically expressed at the apical membranes of secretory (serous and mucous and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133 applied on paraffin-embedded sections and characterized its occurrence in saliva. The 80B258 epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid carcinoma. The 80B258 immunoreactivity was predominately detected at the apical membrane of tumor cells showing acinar or intercalated duct cell differentiation, which lined duct- or cyst-like structures, and in luminal secretions. It was observed on the whole cell membrane in non-luminal structures present in the vicinity of thin-walled blood vessels and hemorrhagic areas in adenoid cystic carcinoma. Of note, AC133 labeled only a subset of 80B258-positive structures. In peritumoral salivary gland tissues as well as in obstructive sialadenitis, an up-regulation of prominin-1 (both 80B258 and AC133 immunoreactivities was observed in intercalated duct cells. In most tissues, prominin-1 was partially co-expressed with two cancer markers: carcinoembryonic antigen (CEA and mucin-1 (MUC1. Differential centrifugation of saliva followed by immunoblotting indicated that all three markers were released in association with small membrane vesicles. Immuno-isolated prominin-1-positive vesicles contained CEA and MUC1, but also exosome-related proteins CD63, flotillin-1, flotillin-2 and the adaptor protein syntenin-1. The latter protein was shown to interact with prominin-1 as demonstrated by its co-immunoisolation. A fraction of saliva-associated prominin-1 appeared to be ubiquitinated. Collectively, our findings bring new insights into the biochemistry and trafficking of prominin-1 as well as its immunohistochemical profile in

  17. Human prominin-1 (CD133) is detected in both neoplastic and non-neoplastic salivary gland diseases and released into saliva in a ubiquitinated form.

    Science.gov (United States)

    Karbanová, Jana; Laco, Jan; Marzesco, Anne-Marie; Janich, Peggy; Voborníková, Magda; Mokrý, Jaroslav; Fargeas, Christine A; Huttner, Wieland B; Corbeil, Denis

    2014-01-01

    Prominin-1 (CD133) is physiologically expressed at the apical membranes of secretory (serous and mucous) and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133) applied on paraffin-embedded sections and characterized its occurrence in saliva. The 80B258 epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid carcinoma. The 80B258 immunoreactivity was predominately detected at the apical membrane of tumor cells showing acinar or intercalated duct cell differentiation, which lined duct- or cyst-like structures, and in luminal secretions. It was observed on the whole cell membrane in non-luminal structures present in the vicinity of thin-walled blood vessels and hemorrhagic areas in adenoid cystic carcinoma. Of note, AC133 labeled only a subset of 80B258-positive structures. In peritumoral salivary gland tissues as well as in obstructive sialadenitis, an up-regulation of prominin-1 (both 80B258 and AC133 immunoreactivities) was observed in intercalated duct cells. In most tissues, prominin-1 was partially co-expressed with two cancer markers: carcinoembryonic antigen (CEA) and mucin-1 (MUC1). Differential centrifugation of saliva followed by immunoblotting indicated that all three markers were released in association with small membrane vesicles. Immuno-isolated prominin-1-positive vesicles contained CEA and MUC1, but also exosome-related proteins CD63, flotillin-1, flotillin-2 and the adaptor protein syntenin-1. The latter protein was shown to interact with prominin-1 as demonstrated by its co-immunoisolation. A fraction of saliva-associated prominin-1 appeared to be ubiquitinated. Collectively, our findings bring new insights into the biochemistry and trafficking of prominin-1 as well as its immunohistochemical profile in certain types

  18. Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.

    Science.gov (United States)

    Ruscito, Ilary; Cacsire Castillo-Tong, Dan; Vergote, Ignace; Ignat, Iulia; Stanske, Mandy; Vanderstichele, Adriaan; Ganapathi, Ram N; Glajzer, Jacek; Kulbe, Hagen; Trillsch, Fabian; Mustea, Alexander; Kreuzinger, Caroline; Benedetti Panici, Pierluigi; Gourley, Charlie; Gabra, Hani; Kessler, Mirjana; Sehouli, Jalid; Darb-Esfahani, Silvia; Braicu, Elena Ioana

    2017-07-01

    High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

    Science.gov (United States)

    Grunseich, Christopher; Wang, Isabel X; Watts, Jason A; Burdick, Joshua T; Guber, Robert D; Zhu, Zhengwei; Bruzel, Alan; Lanman, Tyler; Chen, Kelian; Schindler, Alice B; Edwards, Nancy; Ray-Chaudhury, Abhik; Yao, Jianhua; Lehky, Tanya; Piszczek, Grzegorz; Crain, Barbara; Fischbeck, Kenneth H; Cheung, Vivian G

    2018-02-01

    R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

    International Nuclear Information System (INIS)

    Patru, Cristina; Berhneim, Alain; Mihalescu-Maingot, Maria; Haiech, Jacques; Bièche, Ivan; Moura-Neto, Vivaldo; Daumas-Duport, Catherine; Junier, Marie-Pierre; Chneiweiss, Hervé; Romao, Luciana; Varlet, Pascale; Coulombel, Laure; Raponi, Eric; Cadusseau, Josette; Renault-Mihara, François; Thirant, Cécile; Leonard, Nadine

    2010-01-01

    Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies. We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies

  1. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    Science.gov (United States)

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Characterization of KIR intermediate promoters reveals four promoter types associated with distinct expression patterns of KIR subtypes.

    Science.gov (United States)

    Li, H; Wright, P W; McCullen, M; Anderson, S K

    2016-01-01

    The human killer cell immunoglobulin-like receptor (KIR) genes contain multiple promoters that control the process of gene activation and variegated expression of KIR on natural killer (NK) and T cells. Specific subfamilies of KIR genes have differences in the timing and tissue specificity of expression: however, previous studies of the proximal KIR promoters have not shown significant differences in activity between differentially expressed KIR gene subsets. The recent identification of an intermediate KIR promoter (ProI) associated with KIR2DL1 expression suggested a central role for this element in KIR expression. The current study identifies ProI elements in all of the KIR genes, revealing four classes of ProI that correspond with four distinct expression phenotypes of KIR subgroups: KIR2DL2/S2/L3 that are expressed early in reconstituting NK after transplant; KIR2DL4 that is expressed by CD56-bright NK in a non-variegated manner; KIR3DL3 that is not expressed by circulating NK cells; and the remaining KIR that are expressed by subsets of CD56-dim NK. The four classes of ProI are structurally diverse and display distinct functional properties. Altogether, these results indicate that KIR ProI elements contribute to the tissue/cell-type specificity of KIR transcription and cooperate with the probabilistic proximal promoter to control KIR expression.

  3. A Multi-Scale Model of Hepcidin Promoter Regulation Reveals Factors Controlling Systemic Iron Homeostasis

    Science.gov (United States)

    Muckenthaler, Martina U.; Legewie, Stefan

    2014-01-01

    Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF) phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease. PMID:24391488

  4. A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Guillem Casanovas

    2014-01-01

    Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

  5. Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes.

    Science.gov (United States)

    Farthing, Cassandra R; Ficz, Gabriella; Ng, Ray Kit; Chan, Chun-Fung; Andrews, Simon; Dean, Wendy; Hemberger, Myriam; Reik, Wolf

    2008-06-27

    DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, sperm, trophoblast stem (TS) cells, and primary embryonic fibroblasts (pMEFs). Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency genes in the early

  6. Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes.

    Directory of Open Access Journals (Sweden)

    Cassandra R Farthing

    2008-06-01

    Full Text Available DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES cells, embryonic germ (EG cells, sperm, trophoblast stem (TS cells, and primary embryonic fibroblasts (pMEFs. Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency

  7. Genome-wide Single-Molecule Footprinting Reveals High RNA Polymerase II Turnover at Paused Promoters.

    Science.gov (United States)

    Krebs, Arnaud R; Imanci, Dilek; Hoerner, Leslie; Gaidatzis, Dimos; Burger, Lukas; Schübeler, Dirk

    2017-08-03

    Transcription initiation entails chromatin opening followed by pre-initiation complex formation and RNA polymerase II recruitment. Subsequent polymerase elongation requires additional signals, resulting in increased residence time downstream of the start site, a phenomenon referred to as pausing. Here, we harnessed single-molecule footprinting to quantify distinct steps of initiation in vivo throughout the Drosophila genome. This identifies the impact of promoter structure on initiation dynamics in relation to nucleosomal occupancy. Additionally, perturbation of transcriptional initiation reveals an unexpectedly high turnover of polymerases at paused promoters-an observation confirmed at the level of nascent RNAs. These observations argue that absence of elongation is largely caused by premature termination rather than by stable polymerase stalling. In support of this non-processive model, we observe that induction of the paused heat shock promoter depends on continuous initiation. Our study provides a framework to quantify protein binding at single-molecule resolution and refines concepts of transcriptional pausing. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Jing Qin Wu

    Full Text Available While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression.The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22 from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05. Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1 gene.This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia.

  9. The Structure of Neurexin 1[alpha] Reveals Features Promoting a Role as Synaptic Organizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fang; Venugopal, Vandavasi; Murray, Beverly; Rudenko, Gabby (Michigan)

    2014-10-02

    {alpha}-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The {alpha}-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how {alpha}-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1{alpha} extracellular domain (n1{alpha}) to 2.65 {angstrom}. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 {angstrom} structure of n1{alpha} carrying splice insert SS3 in LNS4 reveals that SS3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables {alpha}-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

  10. Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

    Science.gov (United States)

    Baena, Andres; Ligeiro, Filipa; Diop, Ousmane M.; Brieva, Claudia; Gagneux, Pascal; O'Brien, Stephen J.; Ryder, Oliver A.; Goldfeld, Anne E.

    2007-01-01

    Background Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF. PMID:17637837

  11. Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness.

    Science.gov (United States)

    Conkright, Michael D; Guzmán, Ernesto; Flechner, Lawrence; Su, Andrew I; Hogenesch, John B; Montminy, Marc

    2003-04-01

    We have employed a hidden Markov model (HMM) based on known cAMP responsive elements to search for putative CREB target genes. The best scoring sites were positionally conserved between mouse and human orthologs, suggesting that this parameter can be used to enrich for true CREB targets. Target validation experiments revealed a core promoter requirement for transcriptional induction via CREB; TATA-less promoters were unresponsive to cAMP compared to TATA-containing genes, despite comparable binding of CREB to both sets of genes in vivo. Indeed, insertion of a TATA box motif rescued cAMP responsiveness on a TATA-less promoter. These results illustrate a mechanism by which subsets of target genes for a transcription factor are differentially regulated depending on core promoter configuration.

  12. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters.

    Science.gov (United States)

    Core, Leighton J; Waterfall, Joshua J; Lis, John T

    2008-12-19

    RNA polymerases are highly regulated molecular machines. We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome. We show that peaks of promoter-proximal polymerase reside on approximately 30% of human genes, transcription extends beyond pre-messenger RNA 3' cleavage, and antisense transcription is prevalent. Additionally, most promoters have an engaged polymerase upstream and in an orientation opposite to the annotated gene. This divergent polymerase is associated with active genes but does not elongate effectively beyond the promoter. These results imply that the interplay between polymerases and regulators over broad promoter regions dictates the orientation and efficiency of productive transcription.

  13. Multiple novel promoter-architectures revealed by decoding the hidden heterogeneity within the genome

    Science.gov (United States)

    Narlikar, Leelavati

    2014-01-01

    An important question in biology is how different promoter-architectures contribute to the diversity in regulation of transcription initiation. A step forward has been the production of genome-wide maps of transcription start sites (TSSs) using high-throughput sequencing. However, the subsequent step of characterizing promoters and their functions is still largely done on the basis of previously established promoter-elements like the TATA-box in eukaryotes or the -10 box in bacteria. Unfortunately, a majority of promoters and their activities cannot be explained by these few elements. Traditional motif discovery methods that identify novel elements also fail here, because TSS neighborhoods are often highly heterogeneous containing no overrepresented motif. We present a new, organism-independent method that explicitly models this heterogeneity while unraveling different promoter-architectures. For example, in five bacteria, we detect the presence of a pyrimidine preceding the TSS under very specific circumstances. In tuberculosis, we show for the first time that the spacing between the bacterial 10-motif and TSS is utilized by the pathogen for dynamic gene-regulation. In eukaryotes, we identify several new elements that are important for development. Identified promoter-architectures show differential patterns of evolution, chromatin structure and TSS spread, suggesting distinct regulatory functions. This work highlights the importance of characterizing heterogeneity within high-throughput genomic data rather than analyzing average patterns of nucleotide composition. PMID:25326324

  14. The MTP1 promoters from Arabidopsis halleri reveal cis-regulating elements for the evolution of metal tolerance.

    Science.gov (United States)

    Fasani, Elisa; DalCorso, Giovanni; Varotto, Claudio; Li, Mingai; Visioli, Giovanna; Mattarozzi, Monica; Furini, Antonella

    2017-06-01

    In the hyperaccumulator Arabidopsis halleri, the zinc (Zn) vacuolar transporter MTP1 is a key component of hypertolerance. Because protein sequences and functions are highly conserved between A. halleri and Arabidopsis thaliana, Zn tolerance in A. halleri may reflect the constitutively higher MTP1 expression compared with A. thaliana, based on copy number expansion and different cis regulation. Three MTP1 promoters were characterized in A. halleri ecotype I16. The comparison with the A. thaliana MTP1 promoter revealed different expression profiles correlated with specific cis-acting regulatory elements. The MTP1 5' untranslated region, highly conserved among A. thaliana, Arabidopsis lyrata and A. halleri, contains a dimer of MYB-binding motifs in the A. halleri promoters absent in the A. thaliana and A. lyrata sequences. Site-directed mutagenesis of these motifs revealed their role for expression in trichomes. A. thaliana mtp1 transgenic lines expressing AtMTP1 controlled by the native A. halleri promoter were more Zn-tolerant than lines carrying mutations on MYB-binding motifs. Differences in Zn tolerance were associated with different distribution of Zn among plant organs and in trichomes. The different cis-acting elements in the MTP1 promoters of A. halleri, particularly the MYB-binding sites, are probably involved in the evolution of Zn tolerance. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  15. Mesenchymal stem cells promote formation of colorectal tumors in mice.

    Science.gov (United States)

    Tsai, Kuo-Shu; Yang, Shung-Haur; Lei, Yen-Ping; Tsai, Chih-Chien; Chen, Hsin-Wei; Hsu, Chih-Yuan; Chen, Ling-Lan; Wang, Hsei-Wei; Miller, Stephanie A; Chiou, Shih-Hwa; Hung, Mien-Chie; Hung, Shih-Chieh

    2011-09-01

    Tumor-initiating cells are a subset of tumor cells with the ability to form new tumors; however, they account for less than 0.001% of the cells in colorectal or other types of tumors. Mesenchymal stem cells (MSCs) integrate into the colorectal tumor stroma; we investigated their involvement in tumor initiation. Human colorectal cancer cells, MSCs, and a mixture of both cell types were injected subcutaneously into immunodeficient mice. We compared the ability of each injection to form tumors and investigated the signaling pathway involved in tumor initiation. A small number (≤ 10) of unsorted, CD133⁻, CD166⁻, epithelial cell adhesion molecule⁻(EpCAM⁻), or CD133⁻/CD166⁻/EpCAM⁻ colorectal cancer cells, when mixed with otherwise nontumorigenic MSCs, formed tumors in mice. Secretion of interleukin (IL)-6 by MSCs increased the expression of CD133 and activation of Janus kinase 2-signal transducer and activator of transcription 3 (STAT3) in the cancer cells, and promoted sphere and tumor formation. An antibody against IL-6 or lentiviral-mediated transduction of an interfering RNA against IL-6 in MSCs or STAT3 in cancer cells prevented the ability of MSCs to promote sphere formation and tumor initiation. IL-6, secreted by MSCs, signals through STAT3 to increase the numbers of colorectal tumor-initiating cells and promote tumor formation. Reagents developed to disrupt this process might be developed to treat patients with colorectal cancer. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Polycomb complex protein BMI-1 promotes invasion and metastasis of pancreatic cancer stem cells by activating PI3K/AKT signaling, an ex vivo, in vitro, and in vivo study

    Science.gov (United States)

    Wang, Min-Cong; Jiao, Min; Wu, Tao; Jing, Li; Cui, Jie; Guo, Hui; Tian, Tao; Ruan, Zhi-ping; Wei, Yong-Chang; Jiang, Li-Li; Sun, Hai-Feng; Huang, Lan-Xuan; Nan, Ke-Jun; Li, Chun-Li

    2016-01-01

    Cancer stem cell theory indicates cancer stem cells are the key to promote tumor invasion and metastasis. Studies showed that BMI-1 could promote self-renew, differentiation and tumor formation of CSCs and invasion/metastasis of human cancer. However, whether BMI-1 could regulate invasion and metastasis ability of CSCs is still unclear. In our study, we found that up-regulated expression of BMI-1 was associated with tumor invasion, metastasis and poor survival of pancreatic cancer patients. CD133+ cells were obtained by using magnetic cell sorting and identified of CSCs properties such as self-renew, multi-differentiation and tumor formation ability. Then, we found that BMI-1 expression was up-regulated in pancreatic cancer stem cells. Knockdown of BMI-1 expression attenuated invasion ability of pancreatic cancer stem cells in Transwell system and liver metastasis capacity in nude mice which were injected CSCs through the caudal vein. We are the first to reveal that BMI-1 could promote invasion and metastasis ability of pancreatic cancer stem cells. Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs. In summary, our findings indicate that BMI-1 could be used as the therapeutic target to inhibiting CSCs-mediated pancreatic cancer metastasis. PMID:26840020

  17. XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation

    DEFF Research Database (Denmark)

    Mortuza, Gulnahar B; Cavazza, Tommaso; Garcia-Mayoral, Maria Flor

    2014-01-01

    215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215. Our data suggest that one TD and two XMAP215...... molecules associate to form a four-helix coiled-coil complex. A hybrid methods approach was used to define the precise regions of the TACC heptad repeat and the XMAP215 C terminus required for assembly and functioning of the complex. We show that XTACC3 can induce the recruitment of larger amounts of XMAP...

  18. Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration.

    Science.gov (United States)

    Lai, Shih-Lei; Marín-Juez, Rubén; Moura, Pedro Luís; Kuenne, Carsten; Lai, Jason Kuan Han; Tsedeke, Ayele Taddese; Guenther, Stefan; Looso, Mario; Stainier, Didier Yr

    2017-06-20

    Zebrafish display a distinct ability to regenerate their heart following injury. However, this ability is not shared by another teleost, the medaka. In order to identify cellular and molecular bases for this difference, we performed comparative transcriptomic analyses following cardiac cryoinjury. This comparison points to major differences in immune cell dynamics between these models. Upon closer examination, we observed delayed and reduced macrophage recruitment in medaka, along with delayed neutrophil clearance. To investigate the role of immune responses in cardiac regeneration, we delayed macrophage recruitment in zebrafish and observed compromised neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. In contrast, stimulating Toll-like receptor signaling in medaka enhanced immune cell dynamics and promoted neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. Altogether, these data provide further insight into the complex role of the immune response during regeneration, and serve as a platform to identify and test additional regulators of cardiac repair.

  19. Faculty verbal evaluations reveal strategies used to promote medical student performance

    Directory of Open Access Journals (Sweden)

    Lowell Tong

    2011-05-01

    Full Text Available Background: Preceptors rarely follow medical students’ developing clinical performance over time and across disciplines. This study analyzes preceptors’ descriptions of longitudinal integrated clerkship (LIC students’ clinical development and their identification of strategies to guide students’ progress. Methods: We used a common evaluation framework, reporter-interpreter-manager-educator, to guide multidisciplinary LIC preceptors’ discussions of students’ progress. We conducted thematic analysis of transcripts from preceptors’ (seven longitudinal ambulatory preceptors per student quarterly group discussions of 15 students’ performance over one year. Results: All students’ clinical development progressed, although most experienced obstacles. Lack of structure in the history and physical exam commonly obstructed progression. Preceptors used templates for data gathering, and modeling or experiences in the inpatient setting to provide time and solidify structure. To advance students’ knowledge acquisition, many preceptors identified focused learning topics with their students; to promote application of knowledge, preceptors used reasoning strategies to teach the steps involved in synthesizing clinical data. Preceptors shared accountability for helping students advance as the LIC allowed them to follow students’ response to teaching strategies. Discussion: These results depict preceptors’ perceptions of LIC students’ developmental continuum and illustrate how multidisciplinary preceptors can use a common evaluation framework to identify strategies to improve performance and follow students’ performance longitudinally.

  20. Wine metabolomics reveals new sulfonated products in bottled white wines, promoted by small amounts of oxygen.

    Science.gov (United States)

    Arapitsas, Panagiotis; Ugliano, Maurizio; Perenzoni, Daniele; Angeli, Andrea; Pangrazzi, Paolo; Mattivi, Fulvio

    2016-01-15

    The impact of minute amounts of oxygen in the headspace on the post-bottling development of wine is generally considered to be very important, since oxygen can either damage or improve the quality of wine. This project aimed to gain new experimental evidence about the chemistry of the interaction between wine and oxygen. The experimental design included 216 bottles of 12 different white wines produced from 6 different cultivars (Inzolia, Muller Thurgau, Chardonnay, Grillo, Traminer and Pinot gris). Half of them were bottled using the standard industrial process with inert headspace and the other half without inert gas and with extra headspace. After 60 days of storage at room temperature, the wines were analysed using an untargeted LC-MS method. The use of a detailed holistic analysis workflow, with several levels of quality control and marker selection, gave 35 metabolites putatively induced by the different amounts of oxygen. These metabolite markers included ascorbic acid, tartaric acid and various sulfonated compounds observed in wine for the first time (e.g. S-sulfonated cysteine, glutathione and pantetheine; and sulfonated indole-3-lactic acid hexoside and tryptophol). The consumption of SO2 mediated by these sulfonation reactions was promoted by the presence of higher levels of oxygen on bottling. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation.

    Science.gov (United States)

    Song, Jing; Ma, Dongshen; Xing, Yun; Tang, Shanshan; Alahdal, Murad; Guo, Jiamin; Pan, Yi; Zhang, Yanfeng; Shen, Yumeng; Wu, Qiong; Lu, Zhou; Jin, Liang

    2018-03-22

    A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133⁺ and CD133 - cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133⁺ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  2. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Jing Song

    2018-03-01

    Full Text Available A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG, a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133+ and CD133− cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133+ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet. αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  3. Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization.

    Science.gov (United States)

    Yang, Jr-M; Schiapparelli, P; Nguyen, H-N; Igarashi, A; Zhang, Q; Abbadi, S; Amzel, L M; Sesaki, H; Quiñones-Hinojosa, A; Iijima, M

    2017-06-29

    PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity. Cellular and biochemical analyses as well as structural modelling revealed that two mutations disrupt intramolecular interaction of PTEN and open its conformation, enhancing polyubiquitination of PTEN and decreasing protein stability. Moreover, promoting mono-ubiquitination increases protein stability and nuclear localization of mutant PTEN. Thus, our findings provide a molecular mechanism for cancer-associated PTEN defects and may lead to a brain cancer treatment that targets PTEN mono-ubiquitination.

  4. The prognostic value of cancer stem-like cell markers SOX2 and CD133 in stage III colon cancer is modified by expression of the immune-related markers FoxP3, PD-L1 and CD3.

    Science.gov (United States)

    Miller, T J; McCoy, M J; Hemmings, C; Bulsara, M K; Iacopetta, B; Platell, C F

    2017-12-01

    Cancer stem-like cells are highly tumourigenic cells that can repopulate entire tumours after apparent successful treatment. Recent evidence suggests they interact with other cells in the tumour microenvironment, including immune cell subsets, to enhance their survival. The aim of this study was to determine whether the expression of immune cell markers in primary colon cancer impacts the prognostic significance of cancer stem-like cell marker expression. Immunohistochemistry was used to assess the expression of putative stem cell markers (ALDH1, CD44v6, CD133, Lgr5, SOX2) and immune cell related markers (CD3, CD8, FoxP3, PD-L1) in 104 patients with stage III colon cancer. Associations of marker expression with overall and cancer-specific survival were determined using Kaplan-Meier analysis. High SOX2 expression in the central tumour area was found to be an independent factor for poor cancer-specific survival [hazard ratio (HR) 6.19; 95% confidence interval (CI) 2.24-17.14; p=0.001]. When immune-related factors were taken into account, patients categorised as SOX2 low /FoxP3 high had good outcome (HR 0.164; 95%CI 0.066-0.406; p<0.0001) whereas patients categorised as SOX2 high /PD-L1 low had poor outcome (HR 8.992; 95%CI 3.397-23.803; p<0.0001). The prognostic value of the SOX2 cancer stem-like cell marker in colon cancer is modified by expression of immune-cell related factors FoxP3 and PD-L1. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  5. Mutational analysis of the mycobacteriophage BPs promoter PR reveals context-dependent sequences for mycobacterial gene expression.

    Science.gov (United States)

    Oldfield, Lauren M; Hatfull, Graham F

    2014-10-01

    The PR promoter of mycobacteriophage BPs directs early lytic gene expression and is under the control of the BPs repressor, gp33. Reporter gene fusions showed that PR has modest activity in an extrachromosomal context but has activity that is barely detectable in an integrated context, even in the absence of its repressor. Mutational dissection of PR showed that it uses a canonical -10 hexamer recognized by SigA, and mutants with mutations to the sequence 5'-TATAMT had the greatest activities. It does not contain a 5'-TGN-extended -10 sequence, although mutants with mutations creating an extended -10 sequence had substantially increased promoter activity. Mutations in the -35 hexamer also influenced promoter activity but were strongly context dependent, and similar substitutions in the -35 hexamer differentially affected promoter activity, depending on the -10 and extended -10 motifs. This warrants caution in the construction of synthetic promoters or the bioinformatic prediction of promoter activity. Combinations of mutations throughout PR generated a calibrated series of promoters for expression of stably integrated recombinant genes in both Mycobacterium smegmatis and M. tuberculosis, with maximal promoter activity being more than 2-fold that of the strong hsp60 promoter. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Chromatin immunoprecipitation assays revealed CREB and serine 133 phospho-CREB binding to the CART gene proximal promoter.

    Science.gov (United States)

    Rogge, George A; Shen, Li-Ling; Kuhar, Michael J

    2010-07-16

    Both over expression of cyclic AMP response element binding protein (CREB) in the nucleus accumbens (NAc), and intra-accumbal injection of cocaine- and amphetamine-regulated transcript (CART) peptides, have been shown to decrease cocaine reward. Also, over expression of CREB in the rat NAc increased CART mRNA and peptide levels, but it is not known if this was due to a direct action of P-CREB on the CART gene promoter. The goal of this study was to test if CREB and P-CREB bound directly to the CRE site in the CART promoter, using chromatin immunoprecipitation (ChIP) assays. ChIP assay with anti-CREB antibodies showed an enrichment of the CART promoter fragment containing the CRE region over IgG precipitated material, a non-specific control. Forskolin, which was known to increase CART mRNA levels in GH3 cells, was utilized to show that the drug increased levels of P-CREB protein and P-CREB binding to the CART promoter CRE-containing region. A region of the c-Fos promoter containing a CRE cis-regulatory element was previously shown to bind P-CREB, and it was used here as a positive control. These data suggest that the effects of CREB over expression on blunting cocaine reward could be, at least in part, attributed to the increased expression of the CART gene by direct interaction of P-CREB with the CART promoter CRE site, rather than by some indirect action. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes

    KAUST Repository

    Alam, Tanvir

    2014-10-02

    Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.

  8. Lethal factor VII deficiency due to novel mutations in the F7 promoter: functional analysis reveals disruption of HNF4 binding site.

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Lopez, Estelle; Viart, Victoria; Chafa, Ouerdia; Tapon-Bretaudière, Jacqueline; Claustres, Mireille; Taulan, Magali

    2012-08-01

    Hereditary factor VII (FVII) deficiency is a rare autosomal recessive disorder. Deleterious mutations that prevent the synthesis of any amount of functional FVII have been associated with life-threatening haemorrhage in neonates. Here we report two infants, of Maghrebian origin, who suffered a fatal spontaneous cerebral haemorrhage. Investigation of the molecular basis for their severe FVII deficiency revealed novel mutations in a homozygous state within the F7 gene promoter: a single nucleotide substitution (c.-65G>C) and a 2bp deletion (c.-60_-59delTT). To determine whether these promoter variants were responsible for the FVII deficiency, computer-assisted sequence analyses were performed. The data predicted a disrupted binding of both HNF4 and COUP-TF transcription factors with each variant. Concordantly, experimental results revealed an altered HNF4-induced transactivation in the promoter mutated variants. The execution of functional tests is critical to ensuring a complete understanding of the effect of any promoter mutant on FVII deficiency. Only then can an accurate molecular diagnosis be made and further genetic counselling and prenatal diagnosis be offered.

  9. Genome-scale regression analysis reveals a linear relationship for promoters and enhancers after combinatorial drug treatment

    KAUST Repository

    Rapakoulia, Trisevgeni

    2017-08-09

    Motivation: Drug combination therapy for treatment of cancers and other multifactorial diseases has the potential of increasing the therapeutic effect, while reducing the likelihood of drug resistance. In order to reduce time and cost spent in comprehensive screens, methods are needed which can model additive effects of possible drug combinations. Results: We here show that the transcriptional response to combinatorial drug treatment at promoters, as measured by single molecule CAGE technology, is accurately described by a linear combination of the responses of the individual drugs at a genome wide scale. We also find that the same linear relationship holds for transcription at enhancer elements. We conclude that the described approach is promising for eliciting the transcriptional response to multidrug treatment at promoters and enhancers in an unbiased genome wide way, which may minimize the need for exhaustive combinatorial screens.

  10. Slug overexpression induces stemness and promotes hepatocellular carcinoma cell invasion and metastasis.

    Science.gov (United States)

    Sun, Yu; Song, Guo-Dong; Sun, Ning; Chen, Jian-Qiu; Yang, Shao-Shi

    2014-06-01

    Detection of metastasis of hepatocellular carcinoma (HCC) is crucial for early diagnosis. Epithelial-mesenchymal transition (EMT) is a common event in the metastasis of tumor cells. Slug and Snail are homologous proteins, which play an important role in EMT. The present study aimed to investigate whether Slug and Snail overexpression is associated with the invasiveness of HCC in vitro and in vivo . Invasion, colony formation and wound healing assays, as well as flow cytometry analysis, were performed to examine the invasiveness and proliferation capabilities of HepG2 cells following transfection with cNDA or the siRNA of Slug or Snail. The effects of Slug on HCC in vivo were examined using a xenograft model. Slug upregulation increased the percentage of cluster of differentiation (CD)133 + cells among HepG2 cells, and induced cell invasion and proliferation; whereas Snail upregulation did not affect the cells in vitro . The Slug overexpression group exhibited the highest rate of tumor growth compared with the Snail overexpression and control groups in vivo . These findings demonstrated that Slug increases the percentage of CD133 + cells, promotes the clonigenicity of HCC cells and induces a stronger stemness in Slug-overexpressing cells. These changes activate dormant developmental pathways in invading tumor cells. Thus, Slug may serve as a novel target for HCC prognosis and therapy.

  11. Comparative and genetic analysis of the four sequenced Paenibacillus polymyxa genomes reveals a diverse metabolism and conservation of genes relevant to plant-growth promotion and competitiveness.

    Science.gov (United States)

    Eastman, Alexander W; Heinrichs, David E; Yuan, Ze-Chun

    2014-10-03

    Members of the genus Paenibacillus are important plant growth-promoting rhizobacteria that can serve as bio-reactors. Paenibacillus polymyxa promotes the growth of a variety of economically important crops. Our lab recently completed the genome sequence of Paenibacillus polymyxa CR1. As of January 2014, four P. polymyxa genomes have been completely sequenced but no comparative genomic analyses have been reported. Here we report the comparative and genetic analyses of four sequenced P. polymyxa genomes, which revealed a significantly conserved core genome. Complex metabolic pathways and regulatory networks were highly conserved and allow P. polymyxa to rapidly respond to dynamic environmental cues. Genes responsible for phytohormone synthesis, phosphate solubilization, iron acquisition, transcriptional regulation, σ-factors, stress responses, transporters and biomass degradation were well conserved, indicating an intimate association with plant hosts and the rhizosphere niche. In addition, genes responsible for antimicrobial resistance and non-ribosomal peptide/polyketide synthesis are present in both the core and accessory genome of each strain. Comparative analyses also reveal variations in the accessory genome, including large plasmids present in strains M1 and SC2. Furthermore, a considerable number of strain-specific genes and genomic islands are irregularly distributed throughout each genome. Although a variety of plant-growth promoting traits are encoded by all strains, only P. polymyxa CR1 encodes the unique nitrogen fixation cluster found in other Paenibacillus sp. Our study revealed that genomic loci relevant to host interaction and ecological fitness are highly conserved within the P. polymyxa genomes analysed, despite variations in the accessory genome. This work suggets that plant-growth promotion by P. polymyxa is mediated largely through phytohormone production, increased nutrient availability and bio-control mechanisms. This study provides an in

  12. Transcriptomic analyses of RNA-binding proteins reveal eIF3c promotes cell proliferation in hepatocellular carcinoma.

    Science.gov (United States)

    Li, Tangjian; Li, Shengli; Chen, Di; Chen, Bing; Yu, Tao; Zhao, Fangyu; Wang, Qifeng; Yao, Ming; Huang, Shenglin; Chen, Zhiao; He, Xianghuo

    2017-05-01

    RNA-binding proteins (RBPs) play fundamental roles in the RNA life cycle. The aberrant expression of RBPs is often observed in human disease, including cancer. In this study, we screened for the expression levels of 1542 human RBPs in The Cancer Genome Atlas liver hepatocellular carcinoma samples and found 92 consistently upregulated RBP genes in HCC compared with normal samples. Additionally, we undertook a Kaplan-Meier analysis and found that high expression of 15 RBP genes was associated with poor prognosis in patients with HCC. Furthermore, we found that eIF3c promotes HCC cell proliferation in vitro as well as tumorigenicity in vivo. Gene Set Enrichment Analysis showed that high eIF3c expression is positively associated with KRAS, vascular endothelial growth factor, and Hedgehog signaling pathways, all of which are closely associated with specific cancer-related gene sets. Our study provides the basis for further investigation of the molecular mechanism by which eIF3c promotes the development and progression of HCC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  13. Specific interactions between arbuscular mycorrhizal fungi and plant growth-promoting bacteria--as revealed by different combinations

    Energy Technology Data Exchange (ETDEWEB)

    Jaderlund, Lotta; Arthurson, Veronica; Granhall, Ulf; Jansson, Janet K.

    2008-05-15

    The interactions between two plant growth promoting rhizobacteria (PGPR), Pseudomonas fluorescens SBW25 and Paenibacillus brasilensis PB177, two arbuscular mycorrhizal (AM) fungi (Glomus mosseae and G. intraradices) and one pathogenic fungus (Microdochium nivale) were investigated on winter wheat (Triticum aestivum cultivar Tarso) in a greenhouse trial. PB177, but not SBW25, had strong inhibitory effects on M. nivale in dual culture plate assays. The results from the greenhouse experiment show very specific interactions; e.g. the two AM fungi react differently when interacting with the same bacteria on plants. G. intraradices (single inoculation or together with SBW25) increased plant dry weight on M. nivale infested plants, suggesting that the pathogenic fungus is counteracted by G. intraradices, but PB177 inhibited this positive effect. This is an example of two completely different reactions between the same AM fungus and two species of bacteria, previously known to enhance plant growth and inhibit pathogens. When searching for plant growth promoting microorganisms it is therefore important to test for the most suitable combination of plant, bacteria and fungi in order to get satisfactory plant growth benefits.

  14. Social cognitive aspects of the participation in workplace health promotion as revealed by the theory of planned behavior.

    Science.gov (United States)

    Röttger, Stefan; Maier, Johanna; Krex-Brinkmann, Larissa; Kowalski, Jens T; Krick, Annika; Felfe, Jörg; Stein, Michael

    2017-12-01

    Health-promoting efforts strongly depend on individual cognitions such as attitudes as well as social cognitive aspects of the work environment such as leadership and support. Using the theory of planned behavior (TPB) as a theoretical frame, participation behavior of employees in courses offered by the workplace health promotion (WHP) program of the German Armed Forces was investigated. Social cognitive aspects of the work environment, such as leadership behaviors by setting an example or optimizing organization of work, were included in the TPB components of subjective norm and perceived behavioral control, which allowed for an investigation of the specific effects of leadership on WHP participation. A survey study with N=1385 members of the German Armed Forces was conducted in 2015 in Germany. Results showed that perceived behavioral control and attitudes towards WHP were the strongest predictors for WHP participation. While subjective norm was positively related to attitudes, it had a slightly negative effect on intention to participate in WHP activities. These findings suggest that the most effective way for leadership to increase WHP participation is to enhance perceived behavioral control. Quite contrary, creating a positive subjective norm regarding WHP participation may even result in psychological reactance. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. In situ hybridization and promoter analysis reveal that cotton leaf curl Multan betasatellite localizes in the phloem.

    Science.gov (United States)

    Eini, O; Rasheed, M S; Randles, J W

    Begomoviruses (the family Geminiviridae) have either a monopartite or a bipartite (DNA A and DNA B) single-stranded DNA genome. DNA B contains the open reading frame for movement protein and enables some bipartite begomoviruses to invade non-phloem tissues, whereas monopartite begomoviruses are limited to the phloem. Betasatellite DNA replicates in association with some monopartite begomoviruses to produce severe symptoms and enhance replication of helper virus in some hosts. The cotton leaf curl Multan betasatellite (CLCuMuB) has been shown to substitute for the DNA B of a bipartite begomovirus by permitting systemic infection, but the tissue tropism and the role of betasatellites in releasing monopartite begomoviruses from the phloem to adjacent tissue has not been described. In this study, the tissue tropism of CLCuMuB and a monopartite helper virus, tomato leaf curl virus (ToLCV), has been investigated using in situ hybridization, promoter localization and analysis of transgenic 2β plants, which contain a dimer of the CLCuMuB genome. In situ hybridization showed that CLCuMuB and ToLCV were localized into the vascular tissue of infected plants. In addition, CLCuMuB was detected only in the vascular tissue of 2β transgenic plants after infection with ToLCV. β-glucuronidase (GUS) expression under the βC1 promoter was also limited to the phloem tissues. In conclusion, we showed for the first time that CLCuMuB localizes only in the phloem tissues and unlike the DNA B component, CLCuMuB is unable to release the monopartite helper virus out of phloem tissues.

  16. Comprehensive analysis of transcript start sites in ly49 genes reveals an unexpected relationship with gene function and a lack of upstream promoters.

    Science.gov (United States)

    Gays, Frances; Koh, Alan S C; Mickiewicz, Katarzyna M; Aust, Jonathan G; Brooks, Colin G

    2011-03-31

    Comprehensive analysis of the transcription start sites of the Ly49 genes of C57BL/6 mice using the oligo-capping 5'-RACE technique revealed that the genes encoding the "missing self" inhibitory receptors, Ly49A, C, G, and I, were transcribed from multiple broad regions in exon 1, in the intron1/exon2 region, and upstream of exon -1b. Ly49E was also transcribed in this manner, and uniquely showed a transcriptional shift from exon1 to exon 2 when NK cells were activated in vitro with IL2. Remarkably, a large proportion of Ly49E transcripts was then initiated from downstream of the translational start codon. By contrast, the genes encoding Ly49B and Q in myeloid cells, the activating Ly49D and H receptors in NK cells, and Ly49F in activated T cells, were predominantly transcribed from a conserved site in a pyrimidine-rich region upstream of exon 1. An ∼200 bp fragment from upstream of the Ly49B start site displayed tissue-specific promoter activity in dendritic cell lines, but the corresponding upstream fragments from all other Ly49 genes lacked detectable tissue-specific promoter activity. In particular, none displayed any significant activity in a newly developed adult NK cell line that expressed multiple Ly49 receptors. Similarly, no promoter activity could be found in fragments upstream of intron1/exon2. Collectively, these findings reveal a previously unrecognized relationship between the pattern of transcription and the expression/function of Ly49 receptors, and indicate that transcription of the Ly49 genes expressed in lymphoid cells is achieved in a manner that does not require classical upstream promoters.

  17. Increased sensitivity of transforming growth factor (TGF) beta 1 null cells to alkylating agents reveals a novel link between TGFbeta signaling and O(6)-methylguanine methyltransferase promoter hypermethylation.

    Science.gov (United States)

    Yamada, H; Vijayachandra, K; Penner, C; Glick, A

    2001-06-01

    Inactivation of the transforming growth factor beta (TGFbeta)-signaling pathway and gene silencing through hypermethylation of promoter CpG islands are two frequent alterations in human and experimental cancers. Here we report that nonneoplastic TGFbeta1-/- keratinocyte cell lines exhibit increased sensitivity to cell killing by alkylating agents, and this is due to lack of expression of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT). In TGFbeta1-/- but not TGFbeta1+/- cell lines, the CpG dinucleotides in the MGMT promoter are hypermethylated, as measured by restriction enzyme analysis and methylation specific polymerase chain reaction. In one unstable TGFbeta1+/- cell line, loss of the wild type TGFbeta1 allele correlates with the appearance of methylation in the MGMT promoter. Bisulfite sequencing shows that in the KO3 TGFbeta1-/- cell line nearly all of the 28 CpG sites in the MGMT promoter 475 base pairs upstream of the start site of transcription are methylated, whereas most are unmethylated in the H1 TGFbeta1+/- line. Treatment of the TGFbeta1-/- cell lines with 5-azacytidine causes reexpression of MGMT mRNA and demethylation of CpG islands in the promoter. Analysis of the time course of methylation using methylation-specific polymerase chain reaction shows a lack of methylation in primary TGFbeta1-/- keratinocytes and increasing methylation with passage number of immortalized clones. Subcloning of early passage clones reveals a remarkable heterogeneity and instability of the methylation state in the TGFbeta1-/- keratinocytes. Thus, the TGFbeta1-/- genotype does not directly regulate MGMT methylation but predisposes cells to immortalization-associated MGMT hypermethylation.

  18. Genetic basis of olfactory cognition: extremely high level of DNA sequence polymorphism in promoter regions of the human olfactory receptor genes revealed using the 1000 Genomes Project dataset.

    Science.gov (United States)

    Ignatieva, Elena V; Levitsky, Victor G; Yudin, Nikolay S; Moshkin, Mikhail P; Kolchanov, Nikolay A

    2014-01-01

    The molecular mechanism of olfactory cognition is very complicated. Olfactory cognition is initiated by olfactory receptor proteins (odorant receptors), which are activated by olfactory stimuli (ligands). Olfactory receptors are the initial player in the signal transduction cascade producing a nerve impulse, which is transmitted to the brain. The sensitivity to a particular ligand depends on the expression level of multiple proteins involved in the process of olfactory cognition: olfactory receptor proteins, proteins that participate in signal transduction cascade, etc. The expression level of each gene is controlled by its regulatory regions, and especially, by the promoter [a region of DNA about 100-1000 base pairs long located upstream of the transcription start site (TSS)]. We analyzed single nucleotide polymorphisms using human whole-genome data from the 1000 Genomes Project and revealed an extremely high level of single nucleotide polymorphisms in promoter regions of olfactory receptor genes and HLA genes. We hypothesized that the high level of polymorphisms in olfactory receptor promoters was responsible for the diversity in regulatory mechanisms controlling the expression levels of olfactory receptor proteins. Such diversity of regulatory mechanisms may cause the great variability of olfactory cognition of numerous environmental olfactory stimuli perceived by human beings (air pollutants, human body odors, odors in culinary etc.). In turn, this variability may provide a wide range of emotional and behavioral reactions related to the vast variety of olfactory stimuli.

  19. Single-cell profiling reveals that eRNA accumulation at enhancer-promoter loops is not required to sustain transcription.

    Science.gov (United States)

    Rahman, Samir; Zorca, Cornelia E; Traboulsi, Tatiana; Noutahi, Emmanuel; Krause, Matthew R; Mader, Sylvie; Zenklusen, Daniel

    2017-04-07

    Enhancers are intergenic DNA elements that regulate the transcription of target genes in response to signaling pathways by interacting with promoters over large genomic distances. Recent studies have revealed that enhancers are bi-directionally transcribed into enhancer RNAs (eRNAs). Using single-molecule fluorescence in situ hybridization (smFISH), we investigated the eRNA-mediated regulation of transcription during estrogen induction in MCF-7 cells. We demonstrate that eRNAs are localized exclusively in the nucleus and are induced with similar kinetics as target mRNAs. However, eRNAs are mostly nascent at enhancers and their steady-state levels remain lower than those of their cognate mRNAs. Surprisingly, at the single-allele level, eRNAs are rarely co-expressed with their target loci, demonstrating that active gene transcription does not require the continuous transcription of eRNAs or their accumulation at enhancers. When co-expressed, sub-diffraction distance measurements between nascent mRNA and eRNA signals reveal that co-transcription of eRNAs and mRNAs rarely occurs within closed enhancer-promoter loops. Lastly, basal eRNA transcription at enhancers, but not E2-induced transcription, is maintained upon depletion of MLL1 and ERα, suggesting some degree of chromatin accessibility prior to signal-dependent activation of transcription. Together, our findings suggest that eRNA accumulation at enhancer-promoter loops is not required to sustain target gene transcription. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Media audit reveals inappropriate promotion of products under the scope of the International Code of Marketing of Breast-milk Substitutes in South-East Asia.

    Science.gov (United States)

    Vinje, Kristine Hansen; Phan, Linh Thi Hong; Nguyen, Tuan Thanh; Henjum, Sigrun; Ribe, Lovise Omoijuanfo; Mathisen, Roger

    2017-06-01

    To review regulations and to perform a media audit of promotion of products under the scope of the International Code of Marketing of Breast-milk Substitutes ('the Code') in South-East Asia. We reviewed national regulations relating to the Code and 800 clips of editorial content, 387 advertisements and 217 Facebook posts from January 2015 to January 2016. We explored the ecological association between regulations and market size, and between the number of advertisements and market size and growth of milk formula. Cambodia, Indonesia, Myanmar, Thailand and Vietnam. Regulations on the child's age for inappropriate marketing of products are all below the Code's updated recommendation of 36 months (i.e. 12 months in Thailand and Indonesia; 24 months in the other three countries) and are voluntary in Thailand. Although the advertisements complied with the national regulations on the age limit, they had content (e.g. stages of milk formula; messages about the benefit; pictures of a child) that confused audiences. Market size and growth of milk formula were positively associated with the number of newborns and the number of advertisements, and were not affected by the current level of implementation of breast-milk substitute laws and regulations. The present media audit reveals inappropriate promotion and insufficient national regulation of products under the scope of the Code in South-East Asia. Strengthened implementation of regulations aligned with the Code's updated recommendation should be part of comprehensive strategies to minimize the harmful effects of advertisements of breast-milk substitutes on maternal and child nutrition and health.

  1. Conspecific plants are better 'nurses' than rocks: consistent results revealing intraspecific facilitation as a process that promotes establishment in a hyper-arid environment.

    Science.gov (United States)

    Loayza, Andrea P; Herrera-Madariaga, Marisol A; Carvajal, Danny E; García-Guzmán, Patricio; Squeo, Francisco A

    2017-11-01

    Harsh environmental conditions in arid ecosystems limit seedling recruitment to microhabitats under nurse structures, such as shrubs or rocks. These structures, however, do not necessarily afford the same benefits to plants because nurse rocks provide only physical nurse effects, whereas nurse plants can provide both physical and biological nurse effects. Nevertheless, if the nurse plant is a conspecific, the benefits it provides may be outweighed by higher mortality due to negative density-dependent processes; consequently, negative density-dependence is expected to limit plants from acting as nurses to their own seedlings. The degree to which an abiotic nurse may be more beneficial than a conspecific one remains largely unexplored. Here, we examine the role and elucidate the mechanisms by which conspecific plants and rocks promote plant establishment in a hyper-arid desert. For 4 years, we examined establishment patterns of Myrcianthes coquimbensis (Myrtaceae), a threatened desert shrub that recruits solely in rock cavities and under conspecific shrubs. Specifically, we characterized these microhabitats, as well as open interspaces for comparison, and conducted germination, seed removal and seedling survival experiments. Our results revealed that conspecific shrubs and nurse rocks modified environmental conditions in similar ways; soil and air temperatures were lower, and water availability was higher than in open interspaces. We found no evidence on negative density-dependent recruitment: seed removal was lowest and seedling emergence highest under conspecific plants, moreover seedling survival probabilities were similar in rock cavities and under conspecific plants. We conclude that the probability of establishment was highest under conspecific plants than in other microhabitats, contrasting what is expected under the Janzen-Connell recruitment model. We suggest that for species living in stressful environments, population regulation may be a function of

  2. Phylogenetic surveys on the newt genus Tylototriton sensu lato (Salamandridae, Caudata reveal cryptic diversity and novel diversification promoted by historical climatic shifts

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2018-03-01

    Full Text Available Global climatic transitions and Tibetan Plateau uplifts are hypothesized to have profoundly impacted biodiversity in southeastern Asia. To further test the hypotheses related to the impacts of these incidents, we investigated the diversification patterns of the newt genus Tylototriton sensu lato, distributed across the mountain ranges of southeastern Asia. Gene-tree and species-tree analyses of two mitochondrial genes and two nuclear genes revealed five major clades in the genus, and suggested several cryptic species. Dating estimates suggested that the genus originated in the early-to-middle Miocene. Under different species delimitating scenarios, diversification analyses with birth-death likelihood tests indicated that the genus held a higher diversification rate in the late Miocene-to-Pliocene era than that in the Pleistocene. Ancestral area reconstructions indicated that the genus originated from the northern Indochina Peninsula. Accordingly, we hypothesized that the Miocene Climatic Transition triggered the diversification of the genus, and the reinforcement of East Asian monsoons associated with the stepwise uplifts of the Tibetan Plateau promoted the radiation of the genus in southeastern Asia during the Miocene-to-Pliocene period. Quaternary glacial cycles likely had limited effects on speciation events in the genus, but mainly had contributions on their intraspecific differentiations.

  3. Comparative analysis of the ATRX promoter and 5' regulatory region reveals conserved regulatory elements which are linked to roles in neurodevelopment, alpha-globin regulation and testicular function

    Directory of Open Access Journals (Sweden)

    Argentaro Anthony

    2011-06-01

    Full Text Available Abstract Background ATRX is a tightly-regulated multifunctional protein with crucial roles in mammalian development. Mutations in the ATRX gene cause ATR-X syndrome, an X-linked recessive developmental disorder resulting in severe mental retardation and mild alpha-thalassemia with facial, skeletal and genital abnormalities. Although ubiquitously expressed the clinical features of the syndrome indicate that ATRX is not likely to be a global regulator of gene expression but involved in regulating specific target genes. The regulation of ATRX expression is not well understood and this is reflected by the current lack of identified upstream regulators. The availability of genomic data from a range of species and the very highly conserved 5' regulatory regions of the ATRX gene has allowed us to investigate putative transcription factor binding sites (TFBSs in evolutionarily conserved regions of the mammalian ATRX promoter. Results We identified 12 highly conserved TFBSs of key gene regulators involved in biologically relevant processes such as neural and testis development and alpha-globin regulation. Conclusions Our results reveal potentially important regulatory elements in the ATRX gene which may lead to the identification of upstream regulators of ATRX and aid in the understanding of the molecular mechanisms that underlie ATR-X syndrome.

  4. Phylogenetic surveys on the newt genus Tylototriton sensu lato (Salamandridae, Caudata) reveal cryptic diversity and novel diversification promoted by historical climatic shifts.

    Science.gov (United States)

    Wang, Bin; Nishikawa, Kanto; Matsui, Masafumi; Nguyen, Truong Quang; Xie, Feng; Li, Cheng; Khatiwada, Janak Raj; Zhang, Baowei; Gong, Dajie; Mo, Yunming; Wei, Gang; Chen, Xiaohong; Shen, Youhui; Yang, Daode; Xiong, Rongchuan; Jiang, Jianping

    2018-01-01

    Global climatic transitions and Tibetan Plateau uplifts are hypothesized to have profoundly impacted biodiversity in southeastern Asia. To further test the hypotheses related to the impacts of these incidents, we investigated the diversification patterns of the newt genus Tylototriton sensu lato , distributed across the mountain ranges of southeastern Asia. Gene-tree and species-tree analyses of two mitochondrial genes and two nuclear genes revealed five major clades in the genus, and suggested several cryptic species. Dating estimates suggested that the genus originated in the early-to-middle Miocene. Under different species delimitating scenarios, diversification analyses with birth-death likelihood tests indicated that the genus held a higher diversification rate in the late Miocene-to-Pliocene era than that in the Pleistocene. Ancestral area reconstructions indicated that the genus originated from the northern Indochina Peninsula. Accordingly, we hypothesized that the Miocene Climatic Transition triggered the diversification of the genus, and the reinforcement of East Asian monsoons associated with the stepwise uplifts of the Tibetan Plateau promoted the radiation of the genus in southeastern Asia during the Miocene-to-Pliocene period. Quaternary glacial cycles likely had limited effects on speciation events in the genus, but mainly had contributions on their intraspecific differentiations.

  5. Clonal analysis of kit ligand a functional expression reveals lineage-specific competence to promote melanocyte rescue in the mutant regenerating caudal fin.

    Directory of Open Access Journals (Sweden)

    Robert C Tryon

    Full Text Available The study of regeneration in an in vivo vertebrate system has the potential to reveal targetable genes and pathways that could improve our ability to heal and repair damaged tissue. We have developed a system for clonal labeling of discrete cell lineages and independently inducing gene expression under control of the heat shock promoter in the zebrafish caudal fin. Consequently we are able to test the affects of overexpressing a single gene in the context of regeneration within each of the nine different cell lineage classes that comprise the caudal fin. This can test which lineage is necessary or sufficient to provide gene function. As a first example to demonstrate this approach, we explored which lineages were competent to functionally express the kit ligand a protein as assessed by the local complementation of the mutation in the sparse-like (kitlgatc244b background. We show that dermal fibroblast expression of kit ligand a robustly supports the rescue of melanocytes in the regenerating caudal fin. kit ligand a expression from skin and osteoblasts results in more modest and variable rescue of melanocytes, while lateral line expression was unable to complement the mutation.

  6. R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters.

    Science.gov (United States)

    Chen, Liang; Chen, Jia-Yu; Zhang, Xuan; Gu, Ying; Xiao, Rui; Shao, Changwei; Tang, Peng; Qian, Hao; Luo, Daji; Li, Hairi; Zhou, Yu; Zhang, Dong-Er; Fu, Xiang-Dong

    2017-11-16

    R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-quadruplex in non-template DNA, corroborating with all biochemically established properties of R-loops. Transcription perturbation experiments further indicate that R-loop induction correlates to transcriptional pausing. Interestingly, we note that most mapped R-loops are each linked to a nearby free RNA end; by using a ribozyme to co-transcriptionally cleave nascent RNA, we demonstrate that such a free RNA end coupled with a G/C-skewed sequence is necessary and sufficient to induce R-loop. These findings provide a topological solution for RNA invasion into duplex DNA and suggest an order for R-loop initiation and elongation in an opposite direction to that previously proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The C. elegans DSB-2 protein reveals a regulatory network that controls competence for meiotic DSB formation and promotes crossover assurance.

    Directory of Open Access Journals (Sweden)

    Simona Rosu

    Full Text Available For most organisms, chromosome segregation during meiosis relies on deliberate induction of DNA double-strand breaks (DSBs and repair of a subset of these DSBs as inter-homolog crossovers (COs. However, timing and levels of DSB formation must be tightly controlled to avoid jeopardizing genome integrity. Here we identify the DSB-2 protein, which is required for efficient DSB formation during C. elegans meiosis but is dispensable for later steps of meiotic recombination. DSB-2 localizes to chromatin during the time of DSB formation, and its disappearance coincides with a decline in RAD-51 foci marking early recombination intermediates and precedes appearance of COSA-1 foci marking CO-designated sites. These and other data suggest that DSB-2 and its paralog DSB-1 promote competence for DSB formation. Further, immunofluorescence analyses of wild-type gonads and various meiotic mutants reveal that association of DSB-2 with chromatin is coordinated with multiple distinct aspects of the meiotic program, including the phosphorylation state of nuclear envelope protein SUN-1 and dependence on RAD-50 to load the RAD-51 recombinase at DSB sites. Moreover, association of DSB-2 with chromatin is prolonged in mutants impaired for either DSB formation or formation of downstream CO intermediates. These and other data suggest that association of DSB-2 with chromatin is an indicator of competence for DSB formation, and that cells respond to a deficit of CO-competent recombination intermediates by prolonging the DSB-competent state. In the context of this model, we propose that formation of sufficient CO-competent intermediates engages a negative feedback response that leads to cessation of DSB formation as part of a major coordinated transition in meiotic prophase progression. The proposed negative feedback regulation of DSB formation simultaneously (1 ensures that sufficient DSBs are made to guarantee CO formation and (2 prevents excessive DSB levels that could

  8. Functional dissection of the promoter of the pollen-specific gene NTP303 reveals a novel pollen-specific, and conserved cis-regulatory element.

    Science.gov (United States)

    Weterings, K; Schrauwen, J; Wullems, G; Twell, D

    1995-07-01

    Regulatory elements within the promoter of the pollen-specific NTP303 gene from tobacco were analysed by transient and stable expression analyses. Analysis of precisely targeted mutations showed that the NTP303 promoter is not regulated by any of the previously described pollen-specific cis-regulatory elements. However, two adjacent regions from -103 to -86 bp and from -86 to -59 bp were shown to contain sequences which positively regulated the NTP303 promoter. Both of these regions were capable of driving pollen-specific expression from a heterologous promoter, independent of orientation and in an additive manner. The boundaries of the minimal, functional NTP303 promoter were determined to lie within the region -86 to -51 bp. The sequence AAATGA localized from -94 to -89 bp was identified as a novel cis-acting element, of which the TGA triplet was shown to comprise an active part. This element was shown to be completely conserved in the similarly regulated promoter of the Bp 10 gene from Brassica napus encoding a homologue of the NTP303 gene.

  9. The power of direct context as revealed by eye tracking: A model tracks relative attention to competing editorial and promotional content

    NARCIS (Netherlands)

    Smit, E.G.; Boerman, S.C.; van Meurs, L.

    2015-01-01

    Many previous studies on attention have ignored the eye-catching potential of 'direct context'—the entire promotional and editorial content an observer can view at the same time—in print media. In the current study, characteristics of 183 magazine advertisements and their direct context were coded

  10. Promoter engineering reveals the importance of heptameric direct repeats for DNA-binding by SARP-LAL regulators inStreptomyces.

    Science.gov (United States)

    Barreales, Eva G; Vicente, Cláudia M; de Pedro, Antonio; Santos-Aberturas, Javier; Aparicio, Jesús F

    2018-03-02

    The biosynthesis of small size polyene macrolides is ultimately controlled by a couple of transcriptional regulators that act in a hierarchical way. A SARP-LAL regulator binds the promoter of a PAS-LuxR regulator-encoding gene and activates its transcription, and in turn, the gene product of the latter activates transcription from various promoters of the polyene gene cluster directly. The primary operator of PimR, archetype of SARP-LAL regulators, contains three heptameric direct repeats separated by four nucleotide spacers, but the regulator can also bind a secondary operator with only two direct repeats separated by a 3 nucleotide spacer, both located in the promoter region of its unique target gene pimM Similar arrangement of operators has been identified for PimR counterparts encoded by gene clusters for different antifungal secondary metabolites, including not only polyene macrolides but peptidyl nucleosides, phoslactomycins, or cycloheximide. Here we have used promoter engineering and quantitative transcriptional analyses to determine the contribution of the different heptameric repeats to transcriptional activation and final polyene production. Optimized promoters have thus been developed. Deletion studies and electrophoretic mobility assays have been used for the definition of DNA-binding boxes formed by 22-nucleotide sequences comprising two conserved heptameric direct repeats separated by four-nucleotide less conserved spacers. A cooperative binding of PimR SARP appears to be the mechanism involved in binding of regulator monomers to operators, and at least two protein monomers are required for efficient binding. IMPORTANCE: Here we have shown that modulation of the production of antifungal pimaricin in Streptomyces natalensis can be accomplished via promoter engineering of the PAS-LuxR transcriptional activator pimM Expression of this gene is controlled by the SARP-LAL regulator PimR, which binds a series of heptameric direct repeats in its promoter

  11. Systems Biology Reveals Cigarette Smoke-Induced Concentration-Dependent Direct and Indirect Mechanisms That Promote Monocyte-Endothelial Cell Adhesion.

    Science.gov (United States)

    Poussin, Carine; Laurent, Alexandra; Peitsch, Manuel C; Hoeng, Julia; De Leon, Hector

    2015-10-01

    Cigarette smoke (CS) affects the adhesion of monocytes to endothelial cells, a critical step in atherogenesis. Using an in vitro adhesion assay together with innovative computational systems biology approaches to analyze omics data, our study aimed at investigating CS-induced mechanisms by which monocyte-endothelial cell adhesion is promoted. Primary human coronary artery endothelial cells (HCAECs) were treated for 4 h with (1) conditioned media of human monocytic Mono Mac-6 (MM6) cells preincubated with low or high concentrations of aqueous CS extract (sbPBS) from reference cigarette 3R4F for 2 h (indirect treatment, I), (2) unconditioned media similarly prepared without MM6 cells (direct treatment, D), or (3) freshly generated sbPBS (fresh direct treatment, FD). sbPBS promoted MM6 cells-HCAECs adhesion following I and FD, but not D. In I, the effect was mediated at a low concentration through activation of vascular inflammation processes promoted in HCAECs by a paracrine effect of the soluble mediators secreted by sbPBS-treated MM6 cells. Tumor necrosis factor α (TNFα), a major inducer, was actually shed by unstable CS compound-activated TNFα-converting enzyme. In FD, the effect was triggered at a high concentration that also induced some toxicity. This effect was mediated through an yet unknown mechanism associated with a stress damage response promoted in HCAECs by unstable CS compounds present in freshly generated sbPBS, which had decayed in D unconditioned media. Aqueous CS extract directly and indirectly promotes monocytic cell-endothelial cell adhesion in vitro via distinct concentration-dependent mechanisms. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion

    Science.gov (United States)

    Foo, Chwan Hong; Rootes, Christina L.; Marsh, Glenn A.; Gould, Cathryn M.; Klein, Reuben; Riddell, Sarah J.; Middleton, Deborah; Simpson, Kaylene J.; Bean, Andrew G. D.; Stewart, Cameron R.

    2016-01-01

    Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs) impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection. miR-181 also promoted Nipah virus infection, but did not affect infection by paramyxoviruses from other genera, indicating specificity in the virus-host interaction. Infection promotion was primarily mediated via the ability of miR-181 to significantly enhance henipavirus-induced membrane fusion. Cell signalling receptors of ephrins, namely EphA5 and EphA7, were identified as novel negative regulators of henipavirus fusion. The expression of these receptors, as well as EphB4, were suppressed by miR-181 overexpression, suggesting that simultaneous inhibition of several Ephs by the miRNA contributes to enhanced infection and fusion. Immune-responsive miR-181 levels was also up-regulated in the biofluids of ferrets and horses infected with Hendra virus, suggesting that the host innate immune response may promote henipavirus spread and exacerbate disease severity. This study is the first genome-wide screen of miRNAs influencing infection by a clinically significant mononegavirus and nominates select miRNAs as targets for future anti-viral therapy development. PMID:27783670

  13. Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion.

    Directory of Open Access Journals (Sweden)

    Chwan Hong Foo

    2016-10-01

    Full Text Available Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection. miR-181 also promoted Nipah virus infection, but did not affect infection by paramyxoviruses from other genera, indicating specificity in the virus-host interaction. Infection promotion was primarily mediated via the ability of miR-181 to significantly enhance henipavirus-induced membrane fusion. Cell signalling receptors of ephrins, namely EphA5 and EphA7, were identified as novel negative regulators of henipavirus fusion. The expression of these receptors, as well as EphB4, were suppressed by miR-181 overexpression, suggesting that simultaneous inhibition of several Ephs by the miRNA contributes to enhanced infection and fusion. Immune-responsive miR-181 levels was also up-regulated in the biofluids of ferrets and horses infected with Hendra virus, suggesting that the host innate immune response may promote henipavirus spread and exacerbate disease severity. This study is the first genome-wide screen of miRNAs influencing infection by a clinically significant mononegavirus and nominates select miRNAs as targets for future anti-viral therapy development.

  14. Epitope-tagged yeast strains reveal promoter driven changes to 3′-end formation and convergent antisense-transcription from common 3′ UTRs

    Science.gov (United States)

    Swaminathan, Angavai; Beilharz, Traude H.

    2016-01-01

    Epitope-tagging by homologous recombination is ubiquitously used to study gene expression, protein localization and function in yeast. This is generally thought to insulate the regulation of gene expression to that mediated by the promoter and coding regions because native 3′ UTR are replaced. Here we show that the 3′ UTRs, CYC1 and ADH1, contain cryptic promoters that generate abundant convergent antisense-transcription in Saccharomyces cerevisiae. Moreover we show that aberrant, truncating 3′ –end formation is often associated with regulated transcription in TAP-tagged strains. Importantly, the steady-state level of both 3′ –truncated and antisense transcription products is locus dependent. Using TAP and GFP-tagged strains we show that the transcriptional state of the gene-of-interest induces changes to 3′ –end formation by alternative polyadenylation and antisense transcription from a universal 3′ UTR. This means that these 3′ UTRs contains plastic features that can be molded to reflect the regulatory architecture of the locus rather than bringing their own regulatory paradigm to the gene-fusions as would be expected. Our work holds a cautionary note for studies utilizing tagged strains for quantitative biology, but also provides a new model for the study of promoter driven rewiring of 3′ –end formation and regulatory non-coding transcription. PMID:26481348

  15. Epitope-tagged yeast strains reveal promoter driven changes to 3'-end formation and convergent antisense-transcription from common 3' UTRs.

    Science.gov (United States)

    Swaminathan, Angavai; Beilharz, Traude H

    2016-01-08

    Epitope-tagging by homologous recombination is ubiquitously used to study gene expression, protein localization and function in yeast. This is generally thought to insulate the regulation of gene expression to that mediated by the promoter and coding regions because native 3' UTR are replaced. Here we show that the 3' UTRs, CYC1 and ADH1, contain cryptic promoters that generate abundant convergent antisense-transcription in Saccharomyces cerevisiae. Moreover we show that aberrant, truncating 3' -end formation is often associated with regulated transcription in TAP-tagged strains. Importantly, the steady-state level of both 3' -truncated and antisense transcription products is locus dependent. Using TAP and GFP-tagged strains we show that the transcriptional state of the gene-of-interest induces changes to 3' -end formation by alternative polyadenylation and antisense transcription from a universal 3' UTR. This means that these 3' UTRs contains plastic features that can be molded to reflect the regulatory architecture of the locus rather than bringing their own regulatory paradigm to the gene-fusions as would be expected. Our work holds a cautionary note for studies utilizing tagged strains for quantitative biology, but also provides a new model for the study of promoter driven rewiring of 3' -end formation and regulatory non-coding transcription. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Involvement of histone acetylation of Sox17 and Foxa2 promoters during mouse definitive endoderm differentiation revealed by microRNA profiling.

    Directory of Open Access Journals (Sweden)

    Shijun Fu

    Full Text Available Generation of hepatocyte from embryonic stem cells (ESCs holds great promise for hepatocyte replacement therapy to treat liver diseases. Achieving high efficiency of directed differentiation of ESCs to hepatocyte is of critical importance. Previously, Wnt3a has been reported to promote Activin A-induced human definitive endoderm (DE differentiation, the early stage of hepatocyte differentiation. However, the underlying molecular mechanisms are not clear. Growing evidence demonstrated that microRNAs (miRNAs are key regulators involved in various important biological processes including the regulation of stem cell differentiation. In the present study, we profiled genome wide miRNA expression during Wnt3a and Activin A induced mouse DE differentiation. We uncovered distinct miRNA expression patterns during DE differentiation with the identification of a subset of miRNAs whose expression is synergistically regulated by Wnt3a/Activin A treatment at different stages of DE differentiation. Forced expression of a pool of such synergistically regulated miRNAs alone could partially promote DE differentiation, indicating a regulatory role of them. Using TargetScan and GeneGO pathway analyses, the synergistically regulated miRNAs are predicted to regulate key pathways involved in DE differentiation; among them includes the regulation of histone acetylation. Consistently, Wnt3a and Activin A treatment increased global histone acetylation which can be partially mimicked by over expression of the pooled miRNAs. Chromatin IP (ChIP experiments demonstrated that the promoter regions of Sox17 and Foxa2 are subjected to histone acetylation regulation. Administration of Hdac inhibitors greatly augmented DE differentiation. Our data uncovered a novel epigenetic mechanism of Wnt3a and Activin A induced DE differentiation, whereby the treatment of growth factors induced histone acetylation at least in part by the regulation of miRNA expression.

  17. In Vitro Functional Analyses of Infrequent Nucleotide Variants in the Lactase Enhancer Reveal Different Molecular Routes to Increased Lactase Promoter Activity and Lactase Persistence

    DEFF Research Database (Denmark)

    Liebert, A.; Jones, B.L.; Danielsen, Erik Thomas

    2016-01-01

    The genetic trait that allows intestinal lactase to persist into adulthood in some 35% of humans worldwide operates at the level of transcription, the effect being caused by cis-acting nucleotide changes upstream of the lactase gene (LCT). A single nucleotide substitution, -13910 C>T, the first...... causal variant to be identified, accounts for lactase persistence over most of Europe. Located in a region shown to have enhancer function in vitro, it causes increased activity of the LCT promoter in Caco-2 cells, and altered transcription factor binding. Three other variants in close proximity, -13907...

  18. CD133 and BMI1 expressions and its prognostic role in primary ...

    Indian Academy of Sciences (India)

    lysis buffer (50 mM Tris, 150 mM NaCl, 1 mol/L EDTA,. 0.1% sodium dodecyl sulphate, 1% Triton X-100, 1 mol/L phenylmethylsulphonyl fluoride (pH 8)). The protein con- tent in the lysates was measured using Bradford assay. For. Western blot analysis, 50 μg protein was resolved in 12%. SDS-PAGE gels, transferred onto ...

  19. CD133-positive cells are resistant to TRAIL due to up-regulation of FLIP

    Czech Academy of Sciences Publication Activity Database

    Zobalová, Renata; McDermott, L.; Stantic, M.; Prokopová, Kateřina; Dong, L.-F.; Neužil, Jiří

    2008-01-01

    Roč. 373, č. 4 (2008), s. 567-571 ISSN 0006-291X R&D Projects: GA AV ČR(CZ) IAA500520702 Institutional research plan: CEZ:AV0Z50520701 Keywords : Cancer stem cells * apoptosis * resistance to apoptosis induction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.648, year: 2008

  20. Systems approach to characterize the metabolism of liver cancer stem cells expressing CD133

    Science.gov (United States)

    Hur, Wonhee; Ryu, Jae Yong; Kim, Hyun Uk; Hong, Sung Woo; Lee, Eun Byul; Lee, Sang Yup; Yoon, Seung Kew

    2017-04-01

    Liver cancer stem cells (LCSCs) have attracted attention because they cause therapeutic resistance in hepatocellular carcinoma (HCC). Understanding the metabolism of LCSCs can be a key to developing therapeutic strategy, but metabolic characteristics have not yet been studied. Here, we systematically analyzed and compared the global metabolic phenotype between LCSCs and non-LCSCs using transcriptome and metabolome data. We also reconstructed genome-scale metabolic models (GEMs) for LCSC and non-LCSC to comparatively examine differences in their metabolism at genome-scale. We demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. We also confirmed that MYC, a central point of regulation in cancer metabolism, was significantly up-regulated in LCSCs compared with non-LCSCs. Moreover, LCSCs tend to have less active fatty acid oxidation. In this study, the metabolic characteristics of LCSCs were identified using integrative systems analysis, and these characteristics could be potential cures for the resistance of liver cancer cells to anticancer treatments.

  1. Valproic Acid Increases CD133 Positive Cells that Show Low Sensitivity to Cytostatics in Neuroblastoma

    Czech Academy of Sciences Publication Activity Database

    Khalil, M.A.; Hraběta, J.; Groh, T.; Procházka, Pavel; Doktorová, H.; Eckschlager, T.

    2016-01-01

    Roč. 11, č. 9 (2016), e0162916 E-ISSN 1932-6203 R&D Projects: GA ČR GAP301/12/1734 Institutional support: RVO:68378041 Keywords : cancer stem-cells * histone deacetylase * colon-cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

  2. CD133 and BMI1 expressions and its prognostic role in primary ...

    Indian Academy of Sciences (India)

    M. K. Sibin1 C. H. Lavanya1 Dhananjaya I. Bhat2 Narasinga Rao2 N. Geethashree1 W. Vibhuti1 G. K. Chetan1. Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bengaluru 560 029, India; Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru 560 029, India ...

  3. Transcriptome Response to Heavy Metals in Sinorhizobium meliloti CCNWSX0020 Reveals New Metal Resistance Determinants That Also Promote Bioremediation by Medicago lupulina in Metal-Contaminated Soil.

    Science.gov (United States)

    Lu, Mingmei; Jiao, Shuo; Gao, Enting; Song, Xiuyong; Li, Zhefei; Hao, Xiuli; Rensing, Christopher; Wei, Gehong

    2017-10-15

    The symbiosis of the highly metal-resistant Sinorhizobium meliloti CCNWSX0020 and Medicago lupulina has been considered an efficient tool for bioremediation of heavy metal-polluted soils. However, the metal resistance mechanisms of S. meliloti CCNWSX00200 have not been elucidated in detail. Here we employed a comparative transcriptome approach to analyze the defense mechanisms of S. meliloti CCNWSX00200 against Cu or Zn exposure. Six highly upregulated transcripts involved in Cu and Zn resistance were identified through deletion mutagenesis, including genes encoding a multicopper oxidase (CueO), an outer membrane protein (Omp), sulfite oxidoreductases (YedYZ), and three hypothetical proteins (a CusA-like protein, a FixH-like protein, and an unknown protein), and the corresponding mutant strains showed various degrees of sensitivity to multiple metals. The Cu-sensitive mutant (Δ cueO ) and three mutants that were both Cu and Zn sensitive (Δ yedYZ , Δ cusA -like, and Δ fixH -like) were selected for further study of the effects of these metal resistance determinants on bioremediation. The results showed that inoculation with the Δ cueO mutant severely inhibited infection establishment and nodulation of M. lupulina under Cu stress, while inoculation with the Δ yedYZ and Δ fixH -like mutants decreased just the early infection frequency and nodulation under Cu and Zn stresses. In contrast, inoculation with the Δ cusA -like mutant almost led to loss of the symbiotic capacity of M. lupulina to even grow in uncontaminated soil. Moreover, the antioxidant enzyme activity and metal accumulation in roots of M. lupulina inoculated with all mutants were lower than those with the wild-type strain. These results suggest that heavy metal resistance determinants may promote bioremediation by directly or indirectly influencing formation of the rhizobium-legume symbiosis. IMPORTANCE Rhizobium-legume symbiosis has been promoted as an appropriate tool for bioremediation of heavy

  4. Genomic Analyses Reveal Global Functional Alterations That Promote Tumor Growth and Novel Tumor Suppressor Genes in Natural Killer-Cell Malignancies

    DEFF Research Database (Denmark)

    Kucuk, Can; Iqbal, Javeed; J. deLeeuw, Ronald

    in the gene expression profile, we performed GEP and array-CGH studies on seven clinically well defined cases and eight well characterized cell lines derived from NKL patients. Methods: Array-CGH was performed on a tiling BAC array and GEP on an Affymetrix 133 plus2 array.The two data sets were correlated...... to identify functional alterations associated with the genetic abnormalities.Candidate genes on del 6q21 were identified and further studied for mutations and promoter methylation. Results: Our aCGH study identified frequent recurrent gains (> 25 %) in 1q, 2p, 7q, 13q, 17q and 20pter-qter. Regions of loss...

  5. Interleukin-6 Induced "Acute" Phenotypic Microenvironment Promotes Th1 Anti-Tumor Immunity in Cryo-Thermal Therapy Revealed By Shotgun and Parallel Reaction Monitoring Proteomics.

    Science.gov (United States)

    Xue, Ting; Liu, Ping; Zhou, Yong; Liu, Kun; Yang, Li; Moritz, Robert L; Yan, Wei; Xu, Lisa X

    2016-01-01

    Cryo-thermal therapy has been emerged as a promising novel therapeutic strategy for advanced breast cancer, triggering higher incidence of tumor regression and enhanced remission of metastasis than routine treatments. To better understand its anti-tumor mechanism, we utilized a spontaneous metastatic mouse model and quantitative proteomics to compare N-glycoproteome changes in 94 serum samples with and without treatment. We quantified 231 highly confident N-glycosylated proteins using iTRAQ shotgun proteomics. Among them, 53 showed significantly discriminated regulatory patterns over the time course, in which the acute phase response emerged as the most enhanced pathway. The anti-tumor feature of the acute response was further investigated using parallel reaction monitoring target proteomics and flow cytometry on 23 of the 53 significant proteins. We found that cryo-thermal therapy reset the tumor chronic inflammation to an "acute" phenotype, with up-regulation of acute phase proteins including IL-6 as a key regulator. The IL-6 mediated "acute" phenotype transformed IL-4 and Treg-promoting ICOSL expression to Th1-promoting IFN-γ and IL-12 production, augmented complement system activation and CD86(+)MHCII(+) dendritic cells maturation and enhanced the proliferation of Th1 memory cells. In addition, we found an increased production of tumor progression and metastatic inhibitory proteins under such "acute" environment, favoring the anti-metastatic effect. Moreover, cryo-thermal on tumors induced the strongest "acute" response compared to cryo/hyperthermia alone or cryo-thermal on healthy tissues, accompanying by the most pronounced anti-tumor immunological effect. In summary, we demonstrated that cryo-thermal therapy induced, IL-6 mediated "acute" microenvironment shifted the tumor chronic microenvironment from Th2 immunosuppressive and pro-tumorigenic to Th1 immunostimulatory and tumoricidal state. Moreover, the magnitude of "acute" and "danger" signals play a key

  6. Biomaterial-enabled delivery of SDF-1α at the ventral side of breast cancer cells reveals a crosstalk between cell receptors to promote the invasive phenotype.

    Science.gov (United States)

    Liu, Xi Qiu; Fourel, Laure; Dalonneau, Fabien; Sadir, Rabia; Leal, Salome; Lortat-Jacob, Hugues; Weidenhaupt, Marianne; Albiges-Rizo, Corinne; Picart, Catherine

    2017-05-01

    The SDF-1α chemokine (CXCL12) is a potent bioactive chemoattractant known to be involved in hematopoietic stem cell homing and cancer progression. The associated SDF-1α/CXCR4 receptor signaling is a hallmark of aggressive tumors, which can metastasize to distant sites such as lymph nodes, lung and bone. Here, we engineered a biomimetic tumoral niche made of a thin and soft polyelectrolyte film that can retain SDF-1α to present it, in a spatially-controlled manner, at the ventral side of the breast cancer cells. Matrix-bound SDF-1α but not soluble SDF-1α induced a striking increase in cell spreading and migration in a serum-containing medium, which was associated with the formation of lamellipodia and filopodia in MDA-MB231 cells and specifically mediated by CXCR4. Other Knockdown and inhibition experiments revealed that CD44, the major hyaluronan receptor, acted in concert, via a spatial coincidence, to drive a specific matrix-bound SDFα-induced cell response associated with ERK signaling. In contrast, the β1 integrin adhesion receptor played only a minor role on cell polarity. The CXCR4/CD44 mediated cellular response to matrix-bound SDF-1α involved the Rac1 RhoGTPase and was sustained solely in the presence of matrix-bound SDFα, in contrast with the transient signaling observed in response to soluble SDF-1α. Our results highlight that a biomimetic tumoral niche enables to reveal potent cellular effects and so far hidden molecular mechanisms underlying the breast cancer response to chemokines. These results open new insights for the design of future innovative therapies in metastatic cancers, by inhibiting CXCR4-mediated signaling in the tumoral niche via dual targeting of receptors (CXCR4 and CD44) or of associated signaling molecules (CXCR4 and Rac1). Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. High-resolution three-dimensional NMR structure of the KRAS proto-oncogene promoter reveals key features of a G-quadruplex involved in transcriptional regulation.

    Science.gov (United States)

    Kerkour, Abdelaziz; Marquevielle, Julien; Ivashchenko, Stefaniia; Yatsunyk, Liliya A; Mergny, Jean-Louis; Salgado, Gilmar F

    2017-05-12

    Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element located upstream of the major transcription start site. The KRAS nuclease-hypersensitive element (NHE) region contains a G-rich element (22RT; 5'-AGGGCGGTGTGGGAATAGGGAA-3') and encompasses a Myc-associated zinc finger-binding site that regulates KRAS transcription. The NEH region therefore has been proposed as a target for new drugs that control KRAS transcription, which requires detailed knowledge of the NHE structure. In this study, we report a high-resolution NMR structure of the G-rich element within the KRAS NHE. We found that the G-rich element forms a parallel structure with three G-quartets connected by a four-nucleotide loop and two short one-nucleotide double-chain reversal loops. In addition, a thymine bulge is found between G8 and G9. The loops of different lengths and the presence of a bulge between the G-quartets are structural elements that potentially can be targeted by small chemical ligands that would further stabilize the structure and interfere or block transcriptional regulators such as Myc-associated zinc finger from accessing their binding sites on the KRAS promoter. In conclusion, our work suggests a possible new route for the development of anticancer agents that could suppress KRAS expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome.

    Directory of Open Access Journals (Sweden)

    Yi-Hsuan Wu

    Full Text Available The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5' end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5' UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5' UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5' UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome.

  9. Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators.

    Directory of Open Access Journals (Sweden)

    So Yeon Kwon

    2016-04-01

    Full Text Available NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF is able to alter chromatin dynamics to control transcription and genome organization. Previous biochemical and genetic analysis of the specificity-subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx has defined NURF as a critical regulator of homeotic, heat-shock and steroid-responsive gene transcription. It has been speculated that NURF controls pathway specific transcription by co-operating with sequence-specific transcription factors to remodel chromatin at dedicated enhancers. However, conclusive in vivo demonstration of this is lacking and precise regulatory elements targeted by NURF are poorly defined. To address this, we have generated a comprehensive map of in vivo NURF activity, using MNase-sequencing to determine at base pair resolution NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment. Our data show that, besides anticipated roles at enhancers, NURF interacts physically and functionally with the TRF2/DREF basal transcription factor to organize nucleosomes downstream of active promoters. Moreover, we detect NURF remodeling and recruitment at distal insulator sites, where NURF functionally interacts with and co-localizes with DREF and insulator proteins including CP190 to establish nucleosome-depleted domains. This insulator function of NURF is most apparent at subclasses of insulators that mark the boundaries of chromatin domains, where multiple insulator proteins co-associate. By visualizing the complete repertoire of in vivo NURF chromatin targets, our data provide new insights into how chromatin remodeling can control genome organization and regulatory interactions.

  10. Global gene expression in muscle from fasted/refed trout reveals up-regulation of genes promoting myofibre hypertrophy but not myofibre production.

    Science.gov (United States)

    Rescan, Pierre-Yves; Le Cam, Aurelie; Rallière, Cécile; Montfort, Jérôme

    2017-06-07

    Compensatory growth is a phase of rapid growth, greater than the growth rate of control animals, that occurs after a period of growth-stunting conditions. Fish show a capacity for compensatory growth after alleviation of dietary restriction, but the underlying cellular mechanisms are unknown. To learn more about the contribution of genes regulating hypertrophy (an increase in muscle fibre size) and hyperplasia (the generation of new muscle fibres) in the compensatory muscle growth response in fish, we used high-density microarray analysis to investigate the global gene expression in muscle of trout during a fasting-refeeding schedule and in muscle of control-fed trout displaying normal growth. The compensatory muscle growth signature, as defined by genes up-regulated in muscles of refed trout compared with control-fed trout, showed enrichment in functional categories related to protein biosynthesis and maturation, such as RNA processing, ribonucleoprotein complex biogenesis, ribosome biogenesis, translation and protein folding. This signature was also enriched in chromatin-remodelling factors of the protein arginine N-methyl transferase family. Unexpectedly, functional categories related to cell division and DNA replication were not inferred from the molecular signature of compensatory muscle growth, and this signature contained virtually none of the genes previously reported to be up-regulated in hyperplastic growth zones of the late trout embryo myotome and to potentially be involved in production of new myofibres, notably genes encoding myogenic regulatory factors, transmembrane receptors essential for myoblast fusion or myofibrillar proteins predominant in nascent myofibres. Genes promoting myofibre growth, but not myofibre formation, were up-regulated in muscles of refed trout compared with continually fed trout. This suggests that a compensatory muscle growth response, resulting from the stimulation of hypertrophy but not the stimulation of hyperplasia

  11. Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells.

    Science.gov (United States)

    Dey, Swatee; Bakthavatchalu, Vasudevan; Tseng, Michael T; Wu, Peng; Florence, Rebecca L; Grulke, Eric A; Yokel, Robert A; Dhar, Sanjit Kumar; Yang, Hsin-Sheng; Chen, Yumin; St Clair, Daret K

    2008-10-01

    The physicochemical properties of nanomaterials differ from those of the bulk material of the same composition. However, little is known about the underlying effects of these particles in carcinogenesis. The purpose of this study was to determine the mechanisms involved in the carcinogenic properties of nanoparticles using aluminum oxide (Al(2)O(3)/alumina) nanoparticles as the prototype. Well-established mouse epithelial JB6 cells, sensitive to neoplastic transformation, were used as the experimental model. We demonstrate that alumina was internalized and maintained its physicochemical composition inside the cells. Alumina increased cell proliferation (53%), proliferating cell nuclear antigen (PCNA) levels, cell viability and growth in soft agar. The level of manganese superoxide dismutase, a key mitochondrial antioxidant enzyme, was elevated, suggesting a redox signaling event. In addition, the levels of reactive oxygen species and the activities of the redox sensitive transcription factor activator protein-1 (AP-1) and a longevity-related protein, sirtuin 1 (SIRT1), were increased. SIRT1 knockdown reduces DNA synthesis, cell viability, PCNA levels, AP-1 transcriptional activity and protein levels of its targets, JunD, c-Jun and BcL-xl, more than controls do. Immunoprecipitation studies revealed that SIRT1 interacts with the AP-1 components c-Jun and JunD but not with c-Fos. The results identify SIRT1 as an AP-1 modulator and suggest a novel mechanism by which alumina nanoparticles may function as a potential carcinogen.

  12. Comprehensive profile of differentially expressed circular RNAs reveals that hsa_circ_0000069 is upregulated and promotes cell proliferation, migration, and invasion in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Guo J

    2016-12-01

    Full Text Available Jia-ni Guo,* Jin Li,* Chang-li Zhu,* Wan-ting Feng, Jing-xian Shao, Li Wan, Ming-de Huang, Jing-dong He Department of Medical Oncology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an City, Jiangsu Province, People’s Republic of China *These authors contributed equally to this work Background: Nowadays, despite great progress in cancer research, the detailed mechanisms of colorectal cancer (CRC are still poorly understood. Circular RNAs (circRNAs, a new star of the non-coding RNA network, have been identified as critical regulators in various cancers, including CRC. Methods and results: In this study, by using unsupervised hierarchical clustering analysis, a novel dysregulated circRNA, hsa_circ_0000069, was found. The expression of hsa_circ_0000069 was measured in 30 paired CRC tissues and adjacent noncancerous tissues using quantitative polymerase chain reaction. A high expression of hsa_circ_0000069 was observed in CRC tissues and correlated with patients’ age and tumor, node, metastasis (TNM stage (P<0.05. Furthermore, by using specifically designed siRNAs in CRC cells, a functional analysis was performed which revealed that hsa_circ_0000069 knockdown could notably inhibit cell proliferation, migration, and invasion, and induce G0/G1 phase arrest of cell cycle in vitro. Conclusion: This study’s findings are the first to demonstrate that hsa_circ_0000069, an important regulator in cancer progression, could be a promising target in the diagnosis and therapy in colorectal cancer. Keywords: circular RNA, colorectal cancer, regulation, hsa_circ_0000069

  13. Single-molecule tracking in live Vibrio cholerae reveals that ToxR recruits the membrane-bound virulence regulator TcpP to the toxT promoter.

    Science.gov (United States)

    Haas, Beth L; Matson, Jyl S; DiRita, Victor J; Biteen, Julie S

    2015-04-01

    Vibrio cholerae causes the human disease cholera by producing a potent toxin. The V. cholerae virulence pathway involves an unusual transcription step: the bitopic inner-membrane proteins TcpP and ToxR activate toxT transcription. As ToxT is the primary direct transcription activator in V. cholerae pathogenicity, its regulation by membrane-localized activators is key in the disease process. However, the molecular mechanisms by which membrane-localized activators engage the transcription process have yet to be uncovered in live cells. Here we report the use of super-resolution microscopy, single-molecule tracking, and gene knockouts to examine the dynamics of individual TcpP proteins in live V. cholerae cells with < 40 nm spatial resolution on a 50 ms timescale. Single-molecule trajectory analysis reveals that TcpP diffusion is heterogeneous and can be described by three populations of TcpP motion: one fast, one slow, and one immobile. By comparing TcpP diffusion in wild-type V. cholerae to that in mutant strains lacking either toxR or the toxT promoter, we determine that TcpP mobility is greater in the presence of its interaction partners than in their absence. Our findings support a mechanism in which ToxR recruits TcpP to the toxT promoter for transcription activation. © 2014 John Wiley & Sons Ltd.

  14. Gemcitabine treatment promotes pancreatic cancer stemness through the Nox/ROS/NF-κB/STAT3 signaling cascade.

    Science.gov (United States)

    Zhang, Zhengle; Duan, Qingke; Zhao, Hengqiang; Liu, Tao; Wu, Heshui; Shen, Qiang; Wang, Chunyou; Yin, Tao

    2016-11-01

    Gemcitabine, the standard chemotherapy drug for advanced pancreatic cancer, has shown limited benefits because of profound chemoresistance. However, the mechanism involved remains unclear. Cancer stem cells exhibit great tumorigenicity and are closely correlated with drug resistance and tumor relapse. In this study, we demonstrated that certain doses of gemcitabine increased the ratios of CD24 + and CD133 + cells and the expression of stemness-associated genes such as Bmi1, Nanog, and Sox2. The enhancement of stemness after gemcitabine treatment was accompanied by increased cell migration, chemoresistance, and tumorigenesis. Moreover, we found that gemcitabine promoted the binding of phosphorylated STAT3 to the promoter of Bmi1, Nanog, and Sox2 genes. Furthermore, inhibition of STAT3 partially reversed gemcitabine-induced sphere formation, migration, chemoresistance, and tumor relapse. We also demonstrated that the activation of STAT3 and gemcitabine-enhanced stemness was NADPH oxidase (Nox)-generated, ROS-dependent, and NF-κB partially mediated the process. Together, our results suggest a pivotal role of pancreatic cancer stem cells in developing chemoresistance toward gemcitabine treatment through the Nox/ROS/NF-κB/STAT3 signaling pathway. These findings will provide new insight for identifying potential targets that can be used to sensitize pancreatic cancer cells to chemotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Analysis of the sfaX(II) locus in the Escherichia coli meningitis isolate IHE3034 reveals two novel regulatory genes within the promoter-distal region of the main S fimbrial operon.

    Science.gov (United States)

    Sjöström, Annika E; Sondén, Berit; Müller, Claudia; Rydström, Anna; Dobrindt, Ulrich; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2009-03-01

    We describe the expression and regulation of the gene sfaX(II) located near the Sfa(II) fimbrial determinant in the newborn meningitis Escherichia coli (NMEC) isolate IHE3034. sfaX(II) belongs to a gene family, the 17-kDa genes, typically located downstream (300-3000bp) of different fimbrial operons found in E. coli isolates of uropathogenic and newborn meningitis origin. Using transcriptional sfaX(II) reporter gene fusions we found that different environmental conditions commonly affecting expression of fimbrial genes also affected sfaX(II) expression. Analysis of the sfaX(II) transcripts showed that the gene is part of the main fimbrial operon as it is transcribed together with the rest of the fimbrial genes. In addition, the sfaX(II) gene can be expressed from a more proximal promoter and is found to be subject to strong down-regulation by the nucleoid protein H-NS. Studies with an sfaX(II) mutant derivative of IHE3034 did not reveal effects on Sfa(II) fimbrial biogenesis as monitored by e.g. immunofluorescence microscopy. Nevertheless, a mutation in sfaX(II) resulted in altered expression of other surface components. Moreover, we define a new gene, sfaY(II), coding for a putative phosphodiesterase that is located in between the sfaX(II) gene and the fimbrial biogenesis genes. Our studies by ectopic expression of sfaY(II) in Vibrio cholerae showed that the gene product caused reduced biofilm formation and it is proposed that sfaY(II) can influence cyclic-di-GMP turnover in the bacteria. Our findings demonstrate that the operons typical for S-fimbriae of extraintestinal pathogenic E. coli include previously unrecognized novel regulatory genes.

  16. Structure of the Escherichia coli Antitoxin MqsA (YgiT/b3021) Bound to Its Gene Promoter Reveals Extensive Domain Rearrangements and the Specificity of Transcriptional Regulation

    Energy Technology Data Exchange (ETDEWEB)

    B Brown; T Wood; W Peti; R Page

    2011-12-31

    Bacterial cultures, especially biofilms, produce a small number of persister cells, a genetically identical subpopulation of wild type cells that are metabolically dormant, exhibit multidrug tolerance, and are highly enriched in bacterial toxins. The gene most highly up-regulated in Escherichia coli persisters is mqsR, a ribonuclease toxin that, along with mqsA, forms a novel toxin-antitoxin (TA) system. Like all known TA systems, both the MqsR-MqsA complex and MqsA alone regulate their own transcription. Despite the importance of TA systems in persistence and biofilms, very little is known about how TA modules, and antitoxins in particular, bind and recognize DNA at a molecular level. Here, we report the crystal structure of MqsA bound to a 26-bp fragment from the mqsRA promoter. We show that MqsA binds DNA predominantly via its C-terminal helix-turn-helix domain, with direct binding of recognition helix residues Asn{sup 97} and Arg{sup 010} to the DNA major groove. Unexpectedly, the structure also revealed that the MqsA N-terminal domain interacts with the DNA phosphate backbone. This results in a more than 105{sup o} rotation of the N-terminal domains between the free and complexed states, an unprecedented rearrangement for an antitoxin. The structure also shows that MqsA bends the DNA by more than 55{sup o} in order to achieve symmetrical binding. Finally, using a combination of biochemical and NMR studies, we show that the DNA sequence specificity of MqsA is mediated by direct readout.

  17. Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer.

    Directory of Open Access Journals (Sweden)

    Steven Kregel

    Full Text Available Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR, has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5 expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways.

  18. Absence of DAB2IP promotes cancer stem cell like signatures and indicates poor survival outcome in colorectal cancer.

    Science.gov (United States)

    Min, Jiang; Liu, Liang; Li, Xiaolan; Jiang, Jianwu; Wang, Jingtao; Zhang, Bo; Cao, Dengyi; Yu, Dongdong; Tao, Deding; Hu, Junbo; Gong, Jianping; Xie, Daxing

    2015-11-13

    Metastasis is a critical factor for the high mortality of colorectal cancer (CRC), but its mechanism is not completely understood. Epithelial-mesenchymal transition (EMT) is thought to play a key role in metastasis and also increases the cancer stem cell (CSC) feature that facilitates metastatic colonization. In this study, we investigated the biological roles of DAB2IP regulating EMT and stem cell-like features in human CRC. We demonstrate that DAB2IP suppresses NF-κB-mediated EMT and CSC features in CRC cells. In DAB2IP knockout mice, we discovered the hyperplasia in colonic epithelium which aberrantly represents the mesenchymal feature and NF-κB pathway activation. In clinic CRC tissue, we also reveal that reduced DAB2IP can enrich the CD133(+) subpopulation. DAB2IP expression was inversely correlated with tumor differentiation and metastasis, and patients with lower DAB2IP expression had shorter overall survival time. Taken together, our study demonstrates that DAB2IP inhibits NF-κB-inducing EMT and CSC to suppress the CRC progression, and also suggests that DAB2IP is a beneficial prediction factor for CRC patient prognosis.

  19. M e Multidr enriche rug-res ed for sistant CD133 of TG t hepa 3 subp ...

    African Journals Online (AJOL)

    SAM

    erapy, cancer mmon cancer. 92-2993160. hepatocellular e terms of the can Journ arcinom hrough way g Lin1,2 and en 361004, Pe. 61005, People. 4 istance is t m cells or c esistant to th by chemoth erefore, we. (HCC) cells markers. In t eloped by ex counting kit- ow cytometry s used to an. HCC cells in le MDR phen.

  20. Modulation of Chemokine Gene Expression in CD133 Cord Blood-Derived Human Mast Cells by Cyclosporin A and Dexamethasone

    DEFF Research Database (Denmark)

    Holm, Mette; Kvistgaard, Helene; Dahl, Christine

    2006-01-01

    following receptor mediated mast cell activation or following pharmacological activation of specific signal transduction cascades that become activated upon classical FcepsilonRI receptor crosslinking. We demonstrate that chemokine genes encoding IL-8, MCP-1, MIP-1alpha, and MIP-1beta are induced...... 150-fold, which vastly exceeds the yields of conventional protocols using CD34(+) cells as a source of progenitors. Taking advantage of the large quantities of in vitro differentiated mast cells, here we assess at the levels of transcription and translation the kinetics of chemokine gene induction...

  1. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  2. A Random Screen Using a Novel Reporter Assay System Reveals a Set of Sequences That Are Preferred as the TATA or TATA-Like Elements in the CYC1 Promoter of Saccharomyces cerevisiae.

    Science.gov (United States)

    Watanabe, Kiyoshi; Yabe, Makoto; Kasahara, Koji; Kokubo, Tetsuro

    2015-01-01

    In Saccharomyces cerevisiae, the core promoters of class II genes contain either TATA or TATA-like elements to direct accurate transcriptional initiation. Genome-wide analyses show that the consensus sequence of the TATA element is TATAWAWR (8 bp), whereas TATA-like elements carry one or two mismatches to this consensus. The fact that several functionally distinct TATA sequences have been identified indicates that these elements may function, at least to some extent, in a gene-specific manner. The purpose of the present study was to identify functional TATA sequences enriched in one particular core promoter and compare them with the TATA or TATA-like elements that serve as the pre-initiation complex (PIC) assembly sites on the yeast genome. For this purpose, we conducted a randomized screen of the TATA element in the CYC1 promoter by using a novel reporter assay system and identified several hundreds of unique sequences that were tentatively classified into nine groups. The results indicated that the 7 bp TATA element (i.e., TATAWAD) and several sets of TATA-like sequences are preferred specifically by this promoter. Furthermore, we find that the most frequently isolated TATA-like sequence, i.e., TATTTAAA, is actually utilized as a functional core promoter element for the endogenous genes, e.g., ADE5,7 and ADE6. Collectively, these results indicate that the sequence requirements for the functional TATA or TATA-like elements in one particular core promoter are not as stringent. However, the variation of these sequences differs significantly from that of the PIC assembly sites on the genome, presumably depending on promoter structures and reflecting the gene-specific function of these sequences.

  3. Analyses of Ca2+ dynamics using a ubiquitin-10 promoter-driven Yellow Cameleon 3.6 indicator reveal reliable transgene expression and differences in cytoplasmic Ca2+ responses in Arabidopsis and rice (Oryza sativa) roots.

    Science.gov (United States)

    Behera, Smrutisanjita; Wang, Nili; Zhang, Chunxia; Schmitz-Thom, Ina; Strohkamp, Sarah; Schültke, Stefanie; Hashimoto, Kenji; Xiong, Lizhong; Kudla, Jörg

    2015-04-01

    Ca(2+) signatures are central to developmental processes and adaptive responses in plants. However, high-resolution studies of Ca(2+) dynamics using genetically encoded Ca(2+) indicators (GECIs) such as Yellow Cameleon (YC) proteins have so far not been conducted in important model crops such as rice (Oryza sativa). We conducted a comparative study of 35S and ubiquitin-10 (UBQ10) promoter functionality in Arabidopsis thaliana and O. sativa plants expressing the Ca(2+) indicator Yellow Cameleon 3.6 (YC3.6) under control of the UBQ10 or 35S promoter. Ca(2+) signatures in roots of both species were analyzed during exposure to hyperpolarization/depolarization cycles or in response to application of the amino acid glutamate. We found a superior performance of the UBQ10 promoter with regard to expression pattern, levels and expression stabilities in both species. We observed remarkable differences between the two species in the spatiotemporal parameters of the observed Ca(2+) signatures. Rice appeared in general to respond with a lower maximal signal amplitude but greatly increased signal duration when compared with Arabidopsis. Our results identify important advantages to using the UBQ10 promoter in Arabidopsis and rice and in T-DNA mutant backgrounds. Moreover, the observed differences in Ca(2+) signaling in the two species underscore the need for comparative studies to achieve a comprehensive understanding of Ca(2+) signaling in plants. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  4. Metazoan promoters

    DEFF Research Database (Denmark)

    Lenhard, Boris; Sandelin, Albin Gustav; Carninci, Piero

    2012-01-01

    Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters ...

  5. Health Promotion

    DEFF Research Database (Denmark)

    Povlsen, Lene; Borup, I.

    2015-01-01

    , the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation......In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986...... - an associate professorship was established with a focus on health promotion. Nevertheless, the concept of health promotion had been integrated with or mentioned in courses run prior to the new post. Subsequently, a wide spectrum of courses in health promotion was introduced, such as Empowerment for Child...

  6. ANTIGENIC PROMOTION

    Science.gov (United States)

    Wu, Chin-Yu; Cinader, Bernard

    1971-01-01

    Rabbits were immunized with p-azobenzene arsonic acid derivatives of human serum albumin (HA-As) or of dissociated keyhole limpet hemocyanin. The IgM response to the hapten was evaluated in terms of the number of hapten-specific plaque-forming cells in the lymph node draining the injection site. In some experiments, antibody was measured by agglutination of tanned and sensitized erythrocytes. The hapten response of animals immunized with HA-As was increased (promoting effect) when the animals were injected with one of several structurally unrelated macromolecules: keyhole limpet hemocyanin (KLH), horse spleen ferritin (HSF), lysozyme (Lys), alum-precipitated human gamma globulin (alum-precipitated HGG). Different macromolecules differed in the magnitude of the promoting effect they induced, e.g., promotion by the associated form of KLH was greater than that by the dissociated form; alum-precipitated HGG was a better promoter than was soluble HGG. The relative magnitude of promotion by different macromolecules (associated vs. dissociated KLH, alum-precipitated vs. soluble HGG) correlated with the relative magnitude of the carrier effect, as judged by the hapten response induced by p-azobenzene arsonic acid conjugated to various proteins. Promotion was detected by agglutination assay of circulating antibody, by plaque assay of cells from the popliteal lymph node draining the site of preinjection, but not by plaque assay of cells from the contralateral lymph node. Promotion was dependent on the dose of the promoting macromolecule and on the dose of the hapten-protein conjugate. It was not observed in animals tolerant to the promoting macromolecule. Inhibition (i.e. antigenic competition), rather than promotion, was observed upon a secondary response to the preinjected macromolecule or when the hapten-protein conjugate was incorporated in Freund's adjuvant. PMID:15776570

  7. The co-stimulatory molecule B7-H3 promotes the epithelial-mesenchymal transition in colorectal cancer.

    Science.gov (United States)

    Jiang, Bo; Zhang, Ting; Liu, Fen; Sun, Zhangzhang; Shi, Hanping; Hua, Dong; Yang, Chen

    2016-05-31

    B7-H3, first recognized as a co-stimulatory molecule, is abnormally expressed in cancer tissues and is associated with cancer metastasis and a poor prognosis. However, as an initial event of metastasis, the relationship between the Epithelial-Mesenchymal Transition (EMT ) in cancer cells and B7-H3 has still not been investigated. In this study, we first analyzed B7-H3 expression by immunohistochemistry in colorectal cancer tissues. B7-H3 was expressed in the cancer cell membrane and was associated with the T stage of colorectal cancer; it also showed a positive correlation with MMP2 and MMP9 expression in cancer tissues. Over-expression of B7-H3 in SW480 cells allowed cancer cells to invade and metastasize more than the control cells, whereas invasion and metastasis capabilities were decreased after B7-H3 was knocked down in Caco-2 cells. We further showed that B7-H3 down-regulated the expression of E-cadherin and β-catenin and up-regulated N-cadherin and Vimentin expression, implying that B7-H3 promoted the EMT in colorectal cancer cells. We also checked another character of the EMT, the stemness of cancer cells. CD133, CD44 and Oct4 were significantly elevated after the SW480 cells were transfected with B7-H3 and reduced in Caco-2 cells after B7-H3 was inhibited. In subsequent studies, we proved that B7-H3 upregulated the expression of Smad1 via PI3K-Akt. In conclusion, B7-H3 promotes the EMT in colorectal cancer cells by activating the PI3K-Akt pathway and upregulating the expression of Smad1.

  8. Paracrine Secretion of Transforming Growth Factor β by Ductal Cells Promotes Acinar-to-Ductal Metaplasia in Cultured Human Exocrine Pancreas Tissues.

    Science.gov (United States)

    Akanuma, Naoki; Liu, Jun; Liou, Geou-Yarh; Yin, Xue; Bejar, Kaitlyn R; Liu, Chengyang; Sun, Lu-Zhe; Storz, Peter; Wang, Pei

    2017-10-01

    We aimed to evaluate the contribution of acinar-to-ductal metaplasia (ADM) to the accumulation of cells with a ductal phenotype in cultured human exocrine pancreatic tissues and reveal the underlying mechanism. We sorted and cultured viable cell populations in human exocrine pancreatic tissues with a flow cytometry-based lineage tracing method to evaluate possible mechanisms of ADM. Cell surface markers, gene expression pattern, and sphere formation assay were used to examine ADM. A large proportion of acinar cells gained CD133 expression during the 2-dimensional culture and showed down-regulation of acinar markers and up-regulation of ductal markers, assuming an ADM phenotype. In a serum-free culture condition, ADM induction was mainly dependent on transforming growth factor β (TGF-β) secreted from cultured ductal cells. Human acinar cells when cultured alone for a week in a serum-free condition do not undergo ADM. However, serum may contain other factors besides TGF-β to induce ADM in human acinar cells. In addition, we found that TGF-β cannot induce ADM of murine acinar cells. Ductal cells are the major source of TGF-β that induces ADM in cultured human exocrine pancreatic tissues. This culture system might be a useful model to investigate the mechanism of ADM in human cells.

  9. CRISPR Technology Reveals RAD(51)-ical Mechanisms of Repair in Roundworms: An Educational Primer for Use with "Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans".

    Science.gov (United States)

    Turcotte, Carolyn A; Andrews, Nicolas P; Sloat, Solomon A; Checchi, Paula M

    2016-11-01

    The mechanisms cells use to maintain genetic fidelity via DNA repair and the accuracy of these processes have garnered interest from scientists engaged in basic research to clinicians seeking improved treatment for cancer patients. Despite the continued advances, many details of DNA repair are still incompletely understood. In addition, the inherent complexity of DNA repair processes, even at the most fundamental level, makes it a challenging topic. This primer is meant to assist both educators and students in using a recent paper, "Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in Caenorhabditis elegans," to understand mechanisms of DNA repair. The goals of this primer are to highlight and clarify several key techniques utilized, with special emphasis on the clustered, regularly interspaced, short palindromic repeats technique and the ways in which it has revolutionized genetics research, as well as to provide questions for deeper in-class discussion. Copyright © 2016 by the Genetics Society of America.

  10. Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model.

    Directory of Open Access Journals (Sweden)

    Desirée L Salazar

    2010-08-01

    Full Text Available Traumatic spinal cord injury (SCI results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+ and CD24(-/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention.

  11. Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens.

    Science.gov (United States)

    Karatas, Omer Faruk; Suer, Ilknur; Yuceturk, Betul; Yilmaz, Mehmet; Oz, Buge; Guven, Gulgun; Cansiz, Harun; Creighton, Chad J; Ittmann, Michael; Ozen, Mustafa

    2016-11-05

    Emerging evidences proposed that microRNAs are associated with regulation of distinct physio-pathological processes including development of normal stem cells and carcinogenesis. In this study we aimed to investigate microRNA profile of cancer stem-like cells (CSLCs) isolated form freshly resected larynx cancer (LCa) tissue samples. CD133 positive (CD133 + ) stem-like cells were isolated from freshly resected LCa tumor specimens. MicroRNA profile of 12 pair of CD133 + and CD133 - cells was determined using microRNA microarray and differential expressions of selvected microRNAs were validated by quantitative real time PCR (qRT-PCR). MicroRNA profiling of CD133 + and CD133 - LCa samples with microarray revealed that miR-26b, miR-203, miR-200c, and miR-363-3p were significantly downregulated and miR-1825 was upregulated in CD133 + larynx CSLCs. qRT-PCR analysis in a total of 25 CD133 + /CD133 - sample pairs confirmed the altered expressions of these five microRNAs. Expressions of miR-26b, miR-200c, and miR-203 were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively. Furthermore, in silico analysis revealed that these microRNAs target both cancer and stem-cell associated signaling pathways. Our results showed that certain microRNAs in CD133 + cells could be used as cancer stem cell markers. Based on these results, we propose that this panel of microRNAs might carry crucial roles in LCa pathogenesis through regulating stem cell properties of tumor cells.

  12. Melatonin disturbs SUMOylation mediated crosstalk between c-Myc and Nestin via MT1 activation and promotes the sensitivity of Paclitaxel in brain cancer stem cells.

    Science.gov (United States)

    Lee, Hyemin; Lee, Hyo-Jung; Jung, Ji Hoon; Shin, Eun Ah; Kim, Sung-Hoon

    2018-04-14

    Here the underlying antitumor mechanism of melatonin and its potency as a sensitizer of Paclitaxel was investigated in X02 cancer stem cells. Melatonin suppressed sphere formation and induced G2/M arrest in X02 cells expressing Nestin, CD133, CXCR4 and SOX-2 as biomarkers of stemness. Furthermore, melatonin reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and upregulated cyclin B1 in X02 cells. Notably, genes of c-Myc related mRNAs were differentially expressed in melatonin treated X02 cells by microarray analysis. Consistently, melatonin reduced the expression of c-Myc at mRNA and protein levels, which was blocked by MG132. Of note, overexpression of c-Myc increased the expression of Nestin, while overexpression of Nestin enhanced c-Myc through crosstalk despite different locations, nucleus and cytoplasm. Interestingly, melatonin attenuated small ubiquitin-related modifier-1 (SUMO-1) more than SUMO-2 or SUMO-3 and disturbed nuclear translocation of Nestin for direct binding to c-Myc by SUMOylation of SUMO-1 protein by immunofluorescence and immunoprecipitation. Also, melatonin reduced trimethylated histone H3K4me3 and H3K36me3 more than dimethylation in X02 cells by Western blotting and Chromatin immunoprecipitation assay. Notably, melatonin upregulated MT1, not MT2, in X02 cells and melatonin receptor inhibitor Luzindole blocked the ability of melatonin to decrease the expression of Nestin, p-c-Myc(S62) and c-Myc. Furthermore, melatonin promoted cytotoxicity, sub G1 accumulation and apoptotic body formation by Paclitaxcel in X02 cells. Taken together, these findings suggest that melatonin inhibits stemness via suppression of c-Myc, Nestin, and histone methylation via MT1 activation and promotes anticancer effect of Paclitaxcel in brain cancer stem cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Promoting industrialisation

    International Nuclear Information System (INIS)

    Hayfield, F.

    1986-04-01

    When the first nuclear power programme is decided upon, automatically the country has to initiate in parallel a programme to modify or add to its current industrial structure and resources. The extent of this new industrialisation depends upon many factors which both, the Government and the Industries have to consider. The Government has a vital role which includes the setting up of the background against which the industrial promotion should take place and in many cases may have also to play an active role all along this programme. Equally, the existing industries have an important role so as to achieve the most efficient participation in the nuclear programme. Invariably the industrial promotional programme will incur a certain degree of transfer of technology, the extent depending on the policies adopted. For this technology transfer to take place efficiently, both the donor and the receiver have to recognise each other's legitimate ambitions and fears. The transfer of technology is a process having a high human content and both donor and receiver have to take this into account. This can be further complicated when there is a difference in culture between them. Technology transfer is carried out within a contractual and organisational framework which will identify the donor (licensor) and the receiver (licensee). This framework may take various forms from a simple cooperative agreement, through a joint-venture organisation right to a standard contract between two separate entities. Each arrangement has its advantages and drawbacks and requires investment of different degrees. One of the keys to a successful industrial promotion is having it carried out in a timely fashion which will be parallel with the nuclear power programme. Experience in some countries has shown the problems when the industrialisation is out of phase with the programme whilst in other cases this industrialisation was at a level and scale unjustified. (author)

  14. Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis.

    Science.gov (United States)

    Zhou, Xin; Patel, Darshan; Sen, Sabyasachi; Shanmugam, Victoria; Sidawy, Anton; Mishra, Lopa; Nguyen, Bao-Ngoc

    2017-04-01

    analysis of peripheral blood mononuclear cells showed that PARP inhibition increased mobilization of endothelial progenitor cells (VEGFR2 + /CD133 + and VEGFR2 + /CD34 + ) into the systemic circulation. Furthermore, under in vitro hyperglycemia and hypoxia conditions, PARP inhibition enhanced HUVEC migration and invasion in Boyden chamber assays by 80% and 180% (P < .05), respectively. Delayed healing in ischemic and diabetic wounds is caused by PARP hyperactivity, and PARP inhibition significantly enhanced ischemic and diabetic wound healing by promoting angiogenesis. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  15. Perceptions of health promoters about health promotion ...

    African Journals Online (AJOL)

    2013-02-11

    Feb 11, 2013 ... Original Research http://www.hsag.co.za doi:10.4102/hsag.v18i1.648. Perceptions of health promoters about health promotion programmes for ... Providing health promotion in the communities is one of the many strategies that were introduced ... will therefore assist in improving and developing health.

  16. The role of promotion in alcoholism treatment marketing.

    Science.gov (United States)

    Jones, M A; Self, D R; Owens, C A; Kline, T A

    1988-01-01

    This article is an overview of the promotion function as a part of the ATM's marketing mix. It approaches various promotion decision areas from a managerial perspective, focusing upon some key components of promotion planning. Rather than provide specific operational or implementation details (how to write a brochure) it is more conceptual in nature and offers a framework for promotion planners. The article addresses promotion management, promotion objectives, analysis for promotion planning, the promotion mix, and addresses the benefits and limitations of some specific promotion tools available to the ATM manager. It treats ATMs as a service and reveals specific implications for promotion strategy dictated by services. The article also reports promotion tools employed by Alabama ATMs citing data from the Alabama study.

  17. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

    Directory of Open Access Journals (Sweden)

    Shekoufeh Atashpour

    2015-07-01

    Conclusion:The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells.

  18. Immunocapture of CD133-positive cells from human cancer cell lines by using monodisperse magnetic poly(glycidyl methacrylate) microspheres containing amino groups

    Czech Academy of Sciences Publication Activity Database

    Kuan, W.-C.; Horák, Daniel; Plichta, Zdeněk; Lee, W.-C.

    2014-01-01

    Roč. 34, 1 January (2014), s. 193-200 ISSN 0928-4931 R&D Projects: GA ČR GCP207/12/J013 Institutional support: RVO:61389013 Keywords : magnetic * poly(glycidyl methacrylate) * microspheres Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.088, year: 2014

  19. In Vivo 5FU-Exposed Human Medullary Thyroid Carcinoma Cells Contain a Chemoresistant CD133+Tumor-Initiating Cell Subset

    Czech Academy of Sciences Publication Activity Database

    Kučerová, L.; Feketeová, L.; Kozovská, Z.; Poturnajová, M.; Matusková, M.; Nencka, Radim; Babál, P.

    2014-01-01

    Roč. 24, č. 3 (2014), s. 520-532 ISSN 1050-7256 Institutional support: RVO:61388963 Keywords : cancer stem cells * thymidylate synthase * colorectal cancer Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.493, year: 2014

  20. What Is a Promotion?

    Science.gov (United States)

    Pergamit, Michael R.; Veum, Jonathan R.

    1999-01-01

    For a sample of young workers, "promotion" involved no change in position or duties; promotion was more likely for males than females and Whites than Blacks or Hispanics. Company training and prior promotions were important predictors. Promotion did not appear to have a direct impact on job satisfaction. (SK)

  1. Dearth of School Library Collection: Inhibition to Reading Promotion ...

    African Journals Online (AJOL)

    The findings of the study revealed a dearth of learning resources such as periodical literature and audiovisual resources to be used in promoting and developing favourable reading culture among pupils in Nigerian schools. Also, the study revealed a dearth of reading promotion programmes such as story hour and book ...

  2. Promoting preschool reading

    OpenAIRE

    Istenič, Vesna

    2013-01-01

    The thesis titled Promoting preschool reading consists of a theoretiral and an empirical part. In the theoretical part I wrote about reading, the importance of reading, types of reading, about reading motivation, promoting reading motivation, internal and external motivation, influence of reading motivation on the child's reading activity, reading and familial literacy, the role of adults in promotion reading literacy, reading to a child and promoting reading in pre-school years, where I ...

  3. Developing a Promotional Video

    Science.gov (United States)

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  4. What do health-promoting schools promote?

    DEFF Research Database (Denmark)

    Simovska, Venka

    2012-01-01

    review process, nine submissions were accepted for publication. Five of these are selected to be published in this issue and the rest will be published in a future issue of the journal. Findings – The five articles in this issue take a comprehensive approach to health promotion in schools and reflect......Purpose – The editorial aims to provide a brief overview of the individual contributions to the special issue, and a commentary positioning the contributions within research relating to the health-promoting schools initiative in Europe. Design/methodology/approach – The members of the Schools...... for Health in Europe Research Group were invited to submit their work addressing processes and outcomes in school health promotion to this special issue of Health Education. Additionally, an open call for papers was published on the Health Education web site. Following the traditional double blind peer...

  5. Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

    Science.gov (United States)

    Sagrinati, Costanza; Netti, Giuseppe Stefano; Mazzinghi, Benedetta; Lazzeri, Elena; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Meini, Claudia; Gacci, Mauro; Squecco, Roberta; Carini, Marco; Gesualdo, Loreto; Francini, Fabio; Maggi, Enrico; Annunziato, Francesco; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

    2006-09-01

    Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

  6. Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

    Directory of Open Access Journals (Sweden)

    Jian-jun Sun

    2015-01-01

    Full Text Available This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133 + and CD133− cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133 + cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133− cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133 + astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133− astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.

  7. SPORT PROMOTION STRATEGIES

    Directory of Open Access Journals (Sweden)

    Alexandru Lucian MIHAI

    2013-10-01

    Full Text Available In sport marketing, the word promotion covers a range of interrelated activities. All of these activities are designed to attract attention, stimulate the interest and awareness of consumers, and of course, encourage them to purchase a sport product. Promotion is about communicating with and educating consumers. The purpose of a sport promotional strategy is to build brand loyalty and product credibility, develop image, and position the brand. A promotional strategy is similar to a marketing strategy, but the promotional strategy seeks short-term objectives, both direct and indirect. Promotional objectives usually include increased sales, stimulate impulse buying, raise customer traffic, and present and reinforce image. It also provides information about products and services, publicizes new stores or websites, and creates and enhances customer satisfaction.

  8. Health promotion in globalization

    Directory of Open Access Journals (Sweden)

    Álvaro Franco-Giraldo

    2012-10-01

    Full Text Available Objective: to unravel some theoretical and factual elements required to implement more effective health promotion strategies and practices in the field of health services whilst following the great challenges that globalization has imposed on the health systems, which are inevitably expressed in the local context (glocalization. Methodology: a narrative review taking into account the concepts of globalization and health promotion in relation to health determinants. The authors approach some courses of action and strategies for health promotion based on the social principles and universal values that guide health promotion, health service reorientation and primary healthcare, empowerment, social participation, and inter-sectoral and social mobilization. Discussion: the discussion focuses on the redirection of health promotion services in relation to the wave of health reforms that has spread throughout the world under the neoliberal rule. The author also discusses health promotion, its ineffectiveness, and the quest for renewal. Likewise, the author sets priorities for health promotion in relation to social determinants. Conclusion: the current global order, in terms of international relations, is not consistent with the ethical principles of health promotion. In this paper, the author advocates for the implementation of actions to change the social and physical life conditions of people based on changes in the use of power in society and the appropriate practice of politics in the context of globalization in order to achieve the effectiveness of the actions of health promotion.

  9. Physical activity and health promotion strategies among ...

    African Journals Online (AJOL)

    Results: The findings revealed that 64% of the participants were physically active both within the work and recreation domains and 65% of the participants had good physical activity promoting practices. Discussing physical activity and giving out information regarding physical activity were most common methods used in ...

  10. Promoter reuse in prokaryotes

    NARCIS (Netherlands)

    Nijveen, H.; Matus-Garcia, M.; Passel, van M.W.J.

    2012-01-01

    Anecdotal evidence shows promoters being reused separate from their downstream gene, thus providing a mechanism for the efficient and rapid rewiring of a gene’s transcriptional regulation. We have identified over 4000 groups of highly similar promoters using a conservative sequence similarity search

  11. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    IAS Admin

    Plant Growth Promoting Rhizobacteria (PGPR) are a group of bacteria that enhances plant growth and yield via various plant growth promoting substances as well as biofertilizers. Given the negative environmental impact of artificial fertiliz- ers and their increasing costs, the use of beneficial soil micro- organisms such as ...

  12. Health-promoting schools

    DEFF Research Database (Denmark)

    Kwan, Stella Y L; Petersen, Poul Erik; Pine, Cynthia M

    2005-01-01

    them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School......Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling...... Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated...

  13. Hunting happiness or promoting health? Why positive psychology deserves a place in health promotion.

    Science.gov (United States)

    Bull, Torill

    2008-09-01

    This commentary asks the question of whether positive psychology represents an egoistic pursuit of happiness, which is in conflict with basic values within health promotion. A look at key concepts and research findings within positive psychology reveals common ground with health promotion. Similarities are evident in conceptualization of health, resource focus, value focus and consequences for policy. Some influences of happiness on health and functioning are described.

  14. TypeScript revealed

    CERN Document Server

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  15. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...

  16. TLR4 Signaling via NANOG Cooperates With STAT3 to Activate Twist1 and Promote Formation of Tumor-Initiating Stem-Like Cells in Livers of Mice.

    Science.gov (United States)

    Uthaya Kumar, Dinesh Babu; Chen, Chia-Lin; Liu, Jian-Chang; Feldman, Douglas E; Sher, Linda S; French, Samuel; DiNorcia, Joseph; French, Samuel W; Naini, Bita V; Junrungsee, Sunhawit; Agopian, Vatche Garen; Zarrinpar, Ali; Machida, Keigo

    2016-03-01

    Obesity and alcohol consumption contribute to steatohepatitis, which increases the risk for hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCCs). Mouse hepatocytes that express HCV-NS5A in liver up-regulate the expression of Toll-like receptor 4 (TLR4), and develop liver tumors containing tumor-initiating stem-like cells (TICs) that express NANOG. We investigated whether the TLR4 signals to NANOG to promote the development of TICs and tumorigenesis in mice placed on a Western diet high in cholesterol and saturated fat (HCFD). We expressed HCV-NS5A from a transgene (NS5A Tg) in Tlr4-/- (C57Bl6/10ScN), and wild-type control mice. Mice were fed a HCFD for 12 months. TICs were identified and isolated based on being CD133+, CD49f+, and CD45-. We obtained 142 paraffin-embedded sections of different stage HCCs and adjacent nontumor areas from the same patients, and performed gene expression, immunofluorescence, and immunohistochemical analyses. A higher proportion of NS5A Tg mice developed liver tumors (39%) than mice that did not express HCV NS5A after the HCFD (6%); only 9% of Tlr4-/- NS5A Tg mice fed HCFD developed liver tumors. Livers from NS5A Tg mice fed the HCFD had increased levels of TLR4, NANOG, phosphorylated signal transducer and activator of transcription (pSTAT3), and TWIST1 proteins, and increases in Tlr4, Nanog, Stat3, and Twist1 messenger RNAs. In TICs from NS5A Tg mice, NANOG and pSTAT3 directly interact to activate expression of Twist1. Levels of TLR4, NANOG, pSTAT3, and TWIST were increased in HCC compared with nontumor tissues from patients. HCFD and HCV-NS5A together stimulated TLR4-NANOG and the leptin receptor (OB-R)-pSTAT3 signaling pathways, resulting in liver tumorigenesis through an exaggerated mesenchymal phenotype with prominent Twist1-expressing TICs. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Profilin 2 promotes migration, invasion, and stemness of HT29 human colorectal cancer stem cells.

    Science.gov (United States)

    Kim, Min-Jung; Lee, Yoo-Sun; Han, Gi-Yeon; Lee, Han-Na; Ahn, Chiyoung; Kim, Chan-Wha

    2015-01-01

    We investigated the role of profilin 2 in the stemness, migration, and invasion of HT29 cancer stem cells (CSCs). Increased and decreased levels of profilin 2 significantly enhanced and suppressed the self-renewal, migration, and invasion ability of HT29 CSCs, respectively. Moreover, profilin 2 directly regulated the expression of stemness markers (CD133, SOX2, and β-catenin) and epithelial mesenchymal transition (EMT) markers (E-cadherin and snail). CD133 and β-catenin were up-regulated by overexpression of profilin 2 and down-regulated by depletion of profilin 2. SOX2 was decreased by profilin 2 depletion. E-cadherin was not influenced by profilin 2- overexpression but increased by profilin 2- knockdown. The expression of snail was suppressed by profilin 2- knockdown. We speculated that stemness and the EMT are closely linked through profilin 2-related pathways. Therefore, this study indicates that profilin 2 affects the metastatic potential and stemness of colorectal CSCs by regulating EMT- and stemness-related proteins.

  18. Nurses and teachers: partnerships for green health promotion.

    Science.gov (United States)

    Sendall, Marguerite C; Lidstone, John; Fleming, Marylou; Domocol, Michelle

    2013-07-01

    The term green health promotion is given to health promotion underpinned by the principles of ecological health and sustainability. Green health promotion is supported philosophically by global health promotion documents such as the 1986 Ottawa Charter for Health Promotion and the ecological public health movement. Green health promotion in schools means the practice, the principles of ecological health, and sustainability. A literature review revealed a paucity of publications about green health promotion in schools. Literature about nurses and health promotion in schools is generally found in nursing publications. Literature about ecological sustainability in schools is mostly found in teaching publications. This article explores the nexus between nursing and health promotion, and teachers and ecological sustainability. Collaborative partnerships between health and education do not capitalize on programs such as Health Promoting Schools and the School Based Youth Health Nurse Program in Queensland, Australia. The authors consider how collaborative partnerships between health and education in schools can work toward green health promotion. Nursing's approach to health promotion and education's approach to ecological sustainability need to be aligned to enhance green health promotion in schools. © 2013, American School Health Association.

  19. Health-promoting schools

    DEFF Research Database (Denmark)

    Kwan, Stella Y L; Petersen, Poul Erik; Pine, Cynthia M

    2005-01-01

    them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School...... Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated...... framework and appropriate methodologies for the evaluation of school oral health projects is emphasized....

  20. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test...... in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even...

  1. Chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1992-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. In this paper the work carried out at Berkeley from the spring of 1942 to the summer of 1945 is described briefly. The aqueous chemistry of plutonium is quite remarkable. Important insights were obtained from tracer experiments, but the full complexity was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were based on aqueous solutions, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, an equilibrium was rapidly established among the four aqueous oxidation states, while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element are reported

  2. Promoting and Protecting the Sexual and Reproductive Health of ...

    African Journals Online (AJOL)

    Nekky Umera

    advocate the use of these strategies in promoting sexuality education. The study also reveals that significant difference does not exist in the means scores of male and female counsellors on the ways to promote and protect the sexual and reproductive health of adolescents as shown in table III. Implications for Counselling.

  3. Assessing Preschool Teachers' Practices to Promote Self-Regulated Learning

    Science.gov (United States)

    Adagideli, Fahretdin Hasan; Saraç, Seda; Ader, Engin

    2015-01-01

    Recent research reveals that in preschool years, through pedagogical interventions, preschool teachers can and should promote self-regulated learning. The main aim of this study is to develop a self-report instrument to assess preschool teachers' practices to promote self-regulated learning. A pool of 50 items was recruited through literature…

  4. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    IAS Admin

    PGPR genera exhibiting plant growth promoting activity are: Pseudomonas, Azospirillum, Azotobacter, Bacillus, Burkholdaria,. Enterobacter, Rhizobium, Erwinia, Mycobacterium, Mesorhizo- bium, Flavobacterium, etc. This article presents perspectives on the role of PGPR in agriculture sustainability. Jay Shankar Singh is an.

  5. Researching health promotion

    National Research Council Canada - National Science Library

    Platt, Stephen David; Watson, Jonathan

    2000-01-01

    ... the progress towards developing and implementing health promotion interventions that: * * * * are theoretically grounded, socio-culturally appropriate and sustainable involve the redistribution of resources towards those most in need reflect the principles of equity, participation and empowerment incorporate rigorous, methodologically ...

  6. Health promotion in context:

    DEFF Research Database (Denmark)

    Liveng, Anne; Andersen, Heidi Myglegård; Lehn Christiansen, Sine

    2018-01-01

    Health promotion constitutes a complex field of study, as it addresses multifaceted problems and involves a range of methods and theories. Students in the field of health promotion can find this challenging. To raise their level of reflexivity and support learning we have developed the “context...... model,” which is presented in this article. The model provides a framework for the analysis of health-promotion initiatives, employing eight perspectives each intertwined with the others. It is based on the assumption that health and health inequities are contextual and that the theoretically inspired...... understanding of contexts is central for health promoters. Contexts for health are seen as more than the local setting; they are embedded in societal and global conditions—which, vice versa, influence the local setting. A Danish community health project is used to exemplify how the model can be used in relation...

  7. Promoting Your Web Site.

    Science.gov (United States)

    Raeder, Aggi

    1997-01-01

    Discussion of ways to promote sites on the World Wide Web focuses on how search engines work and how they retrieve and identify sites. Appropriate Web links for submitting new sites and for Internet marketing are included. (LRW)

  8. Health Promotion Education

    DEFF Research Database (Denmark)

    Lehn-Christiansen, Sine

    The paper discusses the implications of health promotion in education. The paper is based on my PhD project entitled “Health promotion education seen through a power/knowledge and subjectification perspective” (in prep). The PhD project explores how professional health promotion skills...... are conceived in a specific educational setting; namely the Danish social and health education programme. Here, health promotion is formally conceived as a qualification aimed at citizens and patients - and not at the students themselves. However, as the paper will demonstrate, conceptions of student......’s and citizen’s health, health habits and health concerns merge within the educational framework. Through empirical findings, based on 20 qualitative interviews and participatory observation studies from four schools, I show that there are widespread ideas, among teachers as well as students, that professional...

  9. Plant Growth Promoting Rhizobacteria

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 3. Plant Growth Promoting Rhizobacteria - Potential Microbes for Sustainable Agriculture. Jay Shankar Singh. General Article Volume 18 Issue 3 March 2013 pp 275-281 ...

  10. Health promotion in globalization

    OpenAIRE

    Álvaro Franco-Giraldo

    2012-01-01

    Objective: to unravel some theoretical and factual elements required to implement more effective health promotion strategies and practices in the field of health services whilst following the great challenges that globalization has imposed on the health systems, which are inevitably expressed in the local context (glocalization). Methodology: a narrative review taking into account the concepts of globalization and health promotion in relation to health determinants. The authors approach some...

  11. Promoting Global Health

    Directory of Open Access Journals (Sweden)

    Margaret A. Winker, MD

    2015-11-01

    Full Text Available The Editor-in-Chief of the International Journal of MCH and AIDS (IJMA is a member of the World Association of Medical Editors (WAME. The Editorial Board of IJMA believes it is important that the statement on promoting global health and this accompanying editorial is brought to the attention of our readers. Medical journal editors have a social responsibility to promote global health by publishing, whenever possible, research that furthers health worldwide.

  12. Astroglial networks promote neuronal coordination.

    Science.gov (United States)

    Chever, Oana; Dossi, Elena; Pannasch, Ulrike; Derangeon, Mickael; Rouach, Nathalie

    2016-01-12

    Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30- and connexin 43-deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior. Our data thus provide molecular and biophysical evidence predicting selective astroglial gap junction inhibitors as anticonvulsive drugs. Copyright © 2016, American Association for the Advancement of Science.

  13. Promotion of intercultural dialogue

    Directory of Open Access Journals (Sweden)

    Tina Baloh

    2015-10-01

    Full Text Available The Vklopi se (“Integrate” project (January 5 – June 30, 2015 is a programme for promotion of intercultural dialogue between third-country nationals and their host society. Its aim is to promote the co-operation between the home country and third-country nationals in different fields of everyday life as well as the promotion of ethnic diversity and raising awareness about the importance of intercultural dialogue and tolerance. The project is co-financed by the EU through the European Fund for the Integration of Third-Country Nationals and the Slovenian Ministry of the Interior, and represents one of the integration policy measures that facilitate integration of non-EU migrants into cultural, economic and social life in the Republic of Slovenia. The following activities were prepared or carried out within the project: intercultural cooking workshops, radio shows, intercultural stands, a survey, and a brochure.

  14. ROMANIAN TOURISM PROMOTION

    Directory of Open Access Journals (Sweden)

    Alexandru-Mircea NEDELEA

    2017-12-01

    Full Text Available The tourism industry is unlike any other because, instead of a product, you are selling a place and all the things it has to offer. You are competing with the entire world every time you promote tourism in a given destination, and this high level of competition demands a creative and unique approach. To be successful, your marketing should constantly put forth the best possible image of your destination, while creating interest on a broad scale in as many ways as possible. Romania has to conceive an efficient promotional mix in order to attract more tourists.

  15. A future task for Health Promotion research: Integration of Health Promotion and sustainable development

    DEFF Research Database (Denmark)

    Jelsøe, Erling; Thualagant, Nicole; Holm, Jesper

    2018-01-01

    Based on previous studies and reflections collected from participants in a workshop at the 8th Nordic Health Promotion Research Network conference, we reveal current tendencies and discuss future challenges for health promotion research regarding integration of sustainable development principles....... Despite obvious interfaces and interactions between the two, our contention is that strategies for health promotion are not sufficiently integrated with strategies for sustainable development and that policies aimed at solving health or sustainability problems may therefore cause new, undesired...... and unforeseen environmental and health problems. As illustrated in previous research and as deliberated in the above-mentioned workshop, a number of barriers are identified: these are believed to be related to historical segregation, the conceptual understandings of health promotion and sustainable development...

  16. A future task for health-promotion research: Integration of health promotion and sustainable development.

    Science.gov (United States)

    Jelsøe, Erling; Thualagant, Nicole; Holm, Jesper; Kjærgård, Bente; Andersen, Heidi Myglegård; From, Ditte-Marie; Land, Birgit; Pedersen, Kirsten Bransholm

    2018-02-01

    Based on previous studies and reflections collected from participants in a workshop at the 8th Nordic Health Promotion Research Network conference, we reveal current tendencies and discuss future challenges for health-promotion research regarding integration of sustainable development principles. Despite obvious interfaces and interactions between the two, our contention is that strategies for health promotion are not sufficiently integrated with strategies for sustainable development and that policies aimed at solving health or sustainability problems may therefore cause new, undesired and unforeseen environmental and health problems. As illustrated in previous research and as deliberated in the above-mentioned workshop, a number of barriers are identified. These are believed to be related to historical segregation, the conceptual understandings of health promotion and sustainable development, as well as the politics and implementation of policy goals in both areas. Three focal points are proposed as important challenges to address in future research: (a) the duality of health promotion and sustainability and how it can be handled in order to enhance mutually supportive processes between them; (b) the social dimension of sustainability and how it can be strengthened in the development of strategies for health promotion and sustainable development; and (c) exploring and identifying policy approaches and strategies for integrating health promotion and sustainable development.

  17. Promoting Healthy Dietary Behaviors.

    Science.gov (United States)

    Perry, Cheryl L.; Story, Mary; Lytle, Leslie A.

    This chapter reviews the research on promoting healthy dietary behaviors in all youth, not just those who exhibit problems such as obesity or eating disorders. The first section of this chapter presents a rationale for addressing healthy dietary behavior with children and adolescents, on the basis of the impact of these behaviors on short- and…

  18. Buying time promotes happiness

    NARCIS (Netherlands)

    Whillans, Ashley; Dunn, Elizabeth; Smeets, Paul M.; Bekkers, R.H.F.P.; Norton, M.I.

    2017-01-01

    Around the world, increases in wealth have produced an unintended consequence: a rising sense of time scarcity. We provide evidence that using money to buy time can provide a buffer against this time famine, thereby promoting happiness. Using large, diverse samples from the United States, Canada,

  19. National promotional campaign

    Directory of Open Access Journals (Sweden)

    Pekevski Siniša

    2008-01-01

    Full Text Available Taking an attention to promotion as operational variable in marketing effort, author focused on so called ways of creating national images. As a case of very interesting activity paper discuss an experience of regional chamber of Croatia with activities in upgrading international recognition of national products as well as country as destination in such context.

  20. Promoting tourism destination image

    NARCIS (Netherlands)

    R. Govers (Robert); F.M. Go (Frank); K. Kumar (Kuldeep)

    2007-01-01

    textabstractThis article examines the role of tourism promotion as a component of destination image formation. It reports the findings of a study in which 1,100 respondents from around the globe described their previsit perceived image of seven sample destinations, as well as the information sources

  1. Promoting La Cultura Hispana

    Science.gov (United States)

    Pluviose, David

    2007-01-01

    Launched in 1985 at Arizona State University, the Hispanic Research Center's (HRC) efforts to promote Latino and Chicano art and issues have flourished in recent years. In 2004, the HRC hosted the Arizona International Latina/o Arts Festival in collaboration with the Mesa Southwest Museum. The HRC has also founded a mentoring institute for…

  2. Mexico: health promotion initiatives.

    Science.gov (United States)

    Cardaci, D

    2000-01-01

    Mexico is currently undergoing a Health Sector Reform to address the country's epidemiologic and demographic changes, deep socio-economic inequalities and their consequences on health. The Government and a diversified set of actors, mainly NGOs, are taking up health promotion initiatives.

  3. Dynamic usage of transcription start sites within core promoters

    DEFF Research Database (Denmark)

    Kawaji, Hideya; Frith, Martin C; Katayama, Shintaro

    2006-01-01

    BACKGROUND: Mammalian promoters do not initiate transcription at single, well defined base pairs, but rather at multiple, alternative start sites spread across a region. We previously characterized the static structures of transcription start site usage within promoters at the base pair level......, based on large-scale sequencing of transcript 5' ends. RESULTS: In the present study we begin to explore the internal dynamics of mammalian promoters, and demonstrate that start site selection within many mouse core promoters varies among tissues. We also show that this dynamic usage of start sites...... is associated with CpG islands, broad and multimodal promoter structures, and imprinting. CONCLUSION: Our results reveal a new level of biologic complexity within promoters--fine-scale regulation of transcription starting events at the base pair level. These events are likely to be related to epigenetic...

  4. Promoting Linguistic Diversity

    DEFF Research Database (Denmark)

    Daryai-Hansen, Petra Gilliyard

    2005-01-01

    To face up to the omnipresence of ‘Anglo-American’, conferences on language policy today address the issue of promoting linguistic diversity. This especially applies to contemporary Europe. Nevertheless, these conferences, which can be regarded as a kind of laboratories or academic microcosm, do ...... not subscribe to clear language policies. Consequently, the predominant language is here, as elsewhere, the Anglo-American. This article outlines the deep division between the postulate of linguistic diversity and reality, and is a call for soul-searching.......To face up to the omnipresence of ‘Anglo-American’, conferences on language policy today address the issue of promoting linguistic diversity. This especially applies to contemporary Europe. Nevertheless, these conferences, which can be regarded as a kind of laboratories or academic microcosm, do...

  5. Promoting renewable energy technologies

    International Nuclear Information System (INIS)

    Grenaa Jensen, S.

    2004-06-01

    Technologies using renewable energy sources are receiving increasing interest from both public authorities and power producing companies, mainly because of the environmental advantages they procure in comparison with conventional energy sources. These technologies can be substitution for conventional energy sources and limit damage to the environment. Furthermore, several of the renewable energy technologies satisfy an increasing political goal of self-sufficiency within energy production. The subject of this thesis is promotion of renewable technologies. The primary goal is to increase understanding on how technological development takes place, and establish a theoretical framework that can assist in the construction of policy strategies including instruments for promotion of renewable energy technologies. Technological development is analysed by through quantitative and qualitative methods. (BA)

  6. [Promoting Living Kidney Transplantation].

    Science.gov (United States)

    Lin, Chiu-Chu

    2016-04-01

    Kidney transplantation is the best approach for treating patients with end stage renal disease, offering patients the best chance of returning to normal health. While the techniques used in kidney transplantation surgery are mature and highly successful, there is a severe shortage of donor organs. Statistics show a serious imbalance between organ donations and patients on the waiting list for organ transplantation. Moreover, evidence from empirical studies has shown a better transplantation outcome for patients who receive living donor transplantation than for those who receive organs from cadavers. Although using relatives as donors offers an effective way to reduce the problem of organ shortage, this strategy faces many challenges and many other factors affect the promotion of living donor transplantation. This article elaborates how cultural and psychological factors, kidney transplantation awareness, and ethics and laws impact upon living kidney donations and then proposes coping strategies for promoting living kidney transplantation.

  7. Advancement & Promotion Review: 2003

    CERN Multimedia

    2003-01-01

    Advancement, exceptional advancement and promotion decisions were made at the end of June, following the procedures published in Weekly Bulletin No. 13/2003. These decisions were included, where applicable, in the salaries for the month of July 2003. The award of the periodic step was communicated to staff by the salary shown on the July salary slip. All other decisions are communicated by separate notification. The names of staff receiving exceptional advancements or promotions are now published on the HR Division website and are accessible for consultation only at the following address: http://cern.ch/hr-div/internal/personnel/advlist_2003.asp It is recalled that change of career path proposals submitted to the Technical Engineers and Administrative Careers Committee (TEACC) or to Human Resources Division are being examined with a view to preparing the latters' recommendations by the end of September 2003. Final decisions will be applied retroactively to 1 July 2003. Human Resources Division Tel:...

  8. ADVANCEMENT & PROMOTION REVIEW: 2002

    CERN Multimedia

    2002-01-01

    Advancement, exceptional advancement and promotion decisions were made at the beginning of July, under the new career structure scheme and following the procedures published in Weekly Bulletin No. 11/2002. These decisions were included, where applicable, in the salaries for the month of July 2002. The award of the periodic step was communicated to staff by the salary shown on the July salary slip. All other decisions are communicated by separate notification. The names of staff receiving exceptional advancements or promotions will be published this year on the HR Division website and are accessible for consultation only at the following address : http://cern.ch/hr-div/internal/personnel/advlist.asp It is recalled that change of career path proposals submitted to the Technical Engineers and Administrative Careers Committee (TEACC) or to Human Resources Division are being examined with a view to preparing the latters' recommendations by the end of September 2002. Final decisions will be applied retroactivel...

  9. Promoting renewable energy technologies

    DEFF Research Database (Denmark)

    Olsen, O.J.; Skytte, K.

    2004-01-01

    % of its annual electricity production. In this paper, we present and discuss the Danish experience as a case of promoting renewable energy technologies. The development path of the two technologies has been very different. Wind power is considered an outright success with fast deployment to decreasing...... technology and its particular context, it is possible to formulate some general principles that can help to create an effective and efficient policy for promoting new renewable energy technologies.......Wind power and combined heat and power (CHP) using biomass (for combustion, gasification or fermentation) are two of the most promising renewable technologies for generation of electricity. Denmark has a long and well-established tradition for these technologies that now account for approx. 25...

  10. Promoting Health, Producing Moralisms?

    DEFF Research Database (Denmark)

    Brogaard Kristensen, Dorthe; Askegaard, Søren; Hauge Jeppesen, Lene

    2010-01-01

    Based on an ethnographic study of 25 Danish consumers, the aim of this paper is threefold. Firstly, based on a critique of traditional approaches to consumer health campaigning, it argues for a more socially diversified approach for understanding consumer construction and pursuit of healthy...... behaviour. Secondly, it presents a typology of discourses that are employed by consumers in constructing their (health oriented) food consumption. Thirdly, it addresses certain social and moral dilemmas inherent in consumer health promotional campaigns....

  11. : Healthy lifestyles’ promotion

    OpenAIRE

    Fernández Gómez, Erika; Díaz-Campo, Jesús

    2014-01-01

    International audience; The goal of this research was to analyse the advertising of food broadcast by the two Spanish private thematic channels aimed at children with more audience in Spain (Neox and Boing). A content analysis was made in order to study the commercials showed during the hours of children’s enhanced protection established by the normative of this country. The paper presents the increasing concern about kids´ obesity and the role of food industry. Healthy lifestyles are promote...

  12. Health Promotion Education in India: Present Landscape and Future Vistas

    Science.gov (United States)

    Pati, Sanghamitra; Sharma, Kavya; Zodpey, Sanjay; Chauhan, Kavita; Dobe, Madhumita

    2012-01-01

    ‘Health promotion is the process of enabling people to increase control over and to improve their health’. This stream of public health is emerging as a critical domain within the realm of disease prevention. Over the last two decades, the curative model of health care has begun a subtle shift towards a participatory model of health promotion emphasizing upon practice of healthy lifestyles and creating healthy communities. Health promotion encompasses five key strategies with health communication and education as its cornerstones. Present study is an attempt to explore the current situation of health promotion education in India with an aim to provide a background for capacity building in health promotion. A systematic predefined method was adopted to collect and compile information on existing academic programs pertaining to health promotion and health education/communication. Results of the study reveal that currently health promotion education in India is fragmented and not uniform across institutes. It is yet to be recognized as a critical domain of public health education. Mostly teaching of health promotion is limited to health education and communication. There is a need for designing programmes for short-term and long-term capacity building, with focus on innovative methods and approaches. Public health institutes and associations could play a proactive role in designing and imparting academic programs on health promotion. Enhancing alliances with various institutes involved in health promotion activities and networking among public health and medical institutes as well as health services delivery systems would be more productive. PMID:22980352

  13. MetaProm: a neural network based meta-predictor for alternative human promoter prediction.

    Science.gov (United States)

    Wang, Junwen; Ungar, Lyle H; Tseng, Hung; Hannenhalli, Sridhar

    2007-10-17

    De novo eukaryotic promoter prediction is important for discovering novel genes and understanding gene regulation. In spite of the great advances made in the past decade, recent studies revealed that the overall performances of the current promoter prediction programs (PPPs) are still poor, and predictions made by individual PPPs do not overlap each other. Furthermore, most PPPs are trained and tested on the most-upstream promoters; their performances on alternative promoters have not been assessed. In this paper, we evaluate the performances of current major promoter prediction programs (i.e., PSPA, FirstEF, McPromoter, DragonGSF, DragonPF, and FProm) using 42,536 distinct human gene promoters on a genome-wide scale, and with emphasis on alternative promoters. We describe an artificial neural network (ANN) based meta-predictor program that integrates predictions from the current PPPs and the predicted promoters' relation to CpG islands. Our specific analysis of recently discovered alternative promoters reveals that although only 41% of the 3' most promoters overlap a CpG island, 74% of 5' most promoters overlap a CpG island. Our assessment of six PPPs on 1.06 x 109 bps of human genome sequence reveals the specific strengths and weaknesses of individual PPPs. Our meta-predictor outperforms any individual PPP in sensitivity and specificity. Furthermore, we discovered that the 5' alternative promoters are more likely to be associated with a CpG island.

  14. Novel characterisation of the gene encoding conglutinin reveals that previously characterised promoter corresponds to the CL-43 promoter

    DEFF Research Database (Denmark)

    Hansen, Soren; Moeller, Vivi; Holm, Dorte

    2002-01-01

    Conglutinin, a collectin found in bovine serum, is an opsonin that binds to glycoconjugates on the surface of microorganisms or on deposited iC3b, and acts in concert with phagocytes to establish a first-line of immune defense. We have isolated a genomic conglutinin phage clone and found that the 5...... of CL-43. Comparison of potential cis-regulatory elements in relation to the functional studies indicates that the two genes are regulated by different mechanisms....

  15. The study on Egr-1 promoter which is radioactive promoter

    International Nuclear Information System (INIS)

    Zhang Chunzhi; Guo Yang; Lv Zhonghong

    2006-01-01

    Radiogenetic therapy is a heated reaseach on oncotherapy. Early growth response gene-1 (Egr-1) gene promoter is a probably means in radiogenetic therapy. The article review studying on Egr-1 gene promoter and constructing regulating gene expressing system by radiation-inducible Egr-1 gene promoter. (authors)

  16. Promoting women's health.

    Science.gov (United States)

    Doyal, L

    1991-01-01

    The male-dominated medical establishment continues to make health promotion policies for women. Women must have access to a more accurate information base about women's health and the link between their health and socioeconomic roles. They must be full partners in formulating and implementing health promotion strategies. Yet, such a database does not exist due to systemic bias in research. For example, research shows alcoholism affects men and women differently, but prevention and treatment strategies and evaluation of their outcomes do not take this into account. Further, men do not understand subjective aspects of female conditions. In addition, even though women provide most care in our society, health promotion policies do not incorporate their knowledge. Moreover, care of the sick can damage the health of the care giver. Statistics on women's health are lacking, e.g., exhaustion and depression as consequences of child care and housework, especially among poor women. Developed countries continue to use maternal mortality as a means of measuring reproductive hazard, but maternal death is a rarity. In fact, a reproductive mortality rate would be more applicable, which would include deaths from abortions, pregnancy, and contraception. Besides, birth control has real disadvantages, e.g., a painful medical procedure is needed to insert IUDs and they increase the risk of pelvic inflammatory disease. Paid employment has positive and negative effects depending on whether women are alone or have a partner and have children, their income, and educational level. Women in industry face considerable health hazards, e.g., textile workers at increased risk of several lung diseases. Appropriate expenditure on health and social services and sound economic policies at the central level will benefit women's health. Besides, when society values and supports all aspects of women's work and roles, women's health will achieve its potential.

  17. The Promoted Sibling

    DEFF Research Database (Denmark)

    Visholm, Steen

    to the psychodynamic understanding of families, groups and organisations. With a point of departure in a study of self-governing groups in a factory the paper introduces the concept: ‘the promoted sibling’ which provide quite some understanding of the middle managers challenges in his or her role and the challenges...... to understand challenges to leaders in postmodern organisations. Theories about leadership has until now been occupied with the vertical relations in the organisations. To lead a team of creative people the leader has to pay attention both to the relations between leader and followers and to the relations...

  18. Leadership Styles Promote Teamwork

    Directory of Open Access Journals (Sweden)

    Khater Aldoshan

    2015-08-01

    Full Text Available This paper will evaluate the importance of learning leadership styles and the explanation of when and how each one is used in the workforce. In this paper many experts have been cited that are well-known in the field of leadership. Also this paper will concentrate on the importance of teamwork in the workforce and there are many examples of how teamwork is effective for creating the best possible outcomes for creativity and productivity. In the television industry creativity is an essential component of the job description and inspirational leadership that promotes teamwork is essential.

  19. Guarded Type Promotion

    DEFF Research Database (Denmark)

    Winther, Johnni

    2011-01-01

    In Java, explicit casts are ubiquitous since they bridge the gap between compile-time and runtime type safety. Since casts potentially throw a ClassCastException, many programmers use a defensive programming style of guarded casts. In this programming style casts are protected by a preceding...... in a Java 6 compiler. Through our extensive testing of real-life code we show that guarded casts account for approximately one fourth of all casts and that Guarded Type Promotion can eliminate the need for 95 percent of these guarded casts....

  20. Renewable energy sources (promotion)

    International Nuclear Information System (INIS)

    Cook, F.

    1986-01-01

    Permission to present a Bill to establish an independent commission directly responsible for the research, development and demonstration of clean, renewable, alternative sources of energy (to nuclear energy) is requested. The paragraphs of the preamble to the Bill are summarized by the Member seeking permission. The main reason for promoting renewable energy sources is opposition to the nuclear industry. One objection was raised. However, permission was granted to present the Bill and it was read for the first time with a second reading ordered for 7 March 1986. The Bill itself is not reprinted but the permission and question are reported verbatim. (U.K.)

  1. Promotion and resignation in employee networks

    Science.gov (United States)

    Yuan, Jia; Zhang, Qian-Ming; Gao, Jian; Zhang, Linyan; Wan, Xue-Song; Yu, Xiao-Jun; Zhou, Tao

    2016-02-01

    Enterprises have put more and more emphasis on data analysis so as to obtain effective management advices. Managers and researchers are trying to dig out the major factors that lead to employees' promotion and resignation. Most previous analyses are based on questionnaire survey, which usually consists of a small fraction of samples and contains biases caused by psychological defense. In this paper, we successfully collect a data set consisting of all the employees' work-related interactions (action network, AN for short) and online social connections (social network, SN for short) of a company, which inspires us to reveal the correlations between structural features and employees' career development, namely promotion and resignation. Through statistical analysis, we show that the structural features of both AN and SN are correlated and predictive to employees' promotion and resignation, and the AN has higher correlation and predictability. More specifically, the in-degree in AN is the most relevant indicator for promotion, while the k-shell index in AN and in-degree in SN are both very predictive to resignation. Our results provide a novel and actionable understanding of enterprise management and suggest that to enhance the interplays among employees, no matter work-related or social interplays, can be helpful to reduce staffs' turnover risk.

  2. Time series clustering analysis of health-promoting behavior

    Science.gov (United States)

    Yang, Chi-Ta; Hung, Yu-Shiang; Deng, Guang-Feng

    2013-10-01

    Health promotion must be emphasized to achieve the World Health Organization goal of health for all. Since the global population is aging rapidly, ComCare elder health-promoting service was developed by the Taiwan Institute for Information Industry in 2011. Based on the Pender health promotion model, ComCare service offers five categories of health-promoting functions to address the everyday needs of seniors: nutrition management, social support, exercise management, health responsibility, stress management. To assess the overall ComCare service and to improve understanding of the health-promoting behavior of elders, this study analyzed health-promoting behavioral data automatically collected by the ComCare monitoring system. In the 30638 session records collected for 249 elders from January, 2012 to March, 2013, behavior patterns were identified by fuzzy c-mean time series clustering algorithm combined with autocorrelation-based representation schemes. The analysis showed that time series data for elder health-promoting behavior can be classified into four different clusters. Each type reveals different health-promoting needs, frequencies, function numbers and behaviors. The data analysis result can assist policymakers, health-care providers, and experts in medicine, public health, nursing and psychology and has been provided to Taiwan National Health Insurance Administration to assess the elder health-promoting behavior.

  3. Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Mitrugno Valentina

    2010-11-01

    Full Text Available Abstract Background Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6, a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells. Results Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions. Conclusion We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.

  4. Health promotion and prevention strategies.

    Science.gov (United States)

    Bradbury-Golas, Kathleen

    2013-09-01

    Opiate dependency is a medical disorder that requires treatment intervention. Primary health care not only entails treatment of illness but also involves disease prevention and health promotion. Based on Pender's revised Health Promotion Model, a descriptive study comparing the health promoting behaviors/practices in abusing and recovering opiate-dependent drug users is analyzed. Using the Health Promoting Lifestyle Profile II, a comparative descriptive, exploratory, nonexperimental design study was conducted to identify key health-promoting behaviors in recovering opiate-dependent drug users. Prevention strategy recommendations are discussed, along with future research recommendations. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Buying time promotes happiness

    OpenAIRE

    Whillans, Ashley V.; Dunn, Elizabeth W.; Smeets, Paul; Bekkers, Rene; Norton, Michael I.

    2017-01-01

    Despite rising incomes, people around the world are feeling increasingly pressed for time, undermining well-being. We show that the time famine of modern life can be reduced by using money to buy time. Surveys of large, diverse samples from four countries reveal that spending money on time-saving services is linked to greater life satisfaction. To establish causality, we show that working adults report greater happiness after spending money on a time-saving purchase than on a material purchas...

  6. Ambient oxygen promotes tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Ho Joong Sung

    2011-05-01

    Full Text Available Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also cause genomic instability in cultured mammalian cells, its effect on de novo tumorigenesis at the organismal level is unclear. Herein, by decreasing ambient oxygen exposure, we report a ∼50% increase in the median tumor-free survival time of p53-/- mice. In the thymus, reducing oxygen exposure decreased the levels of oxidative DNA damage and RAG recombinase, both of which are known to promote lymphomagenesis in p53-/- mice. Oxygen is further shown to be associated with genomic instability in two additional cancer models involving the APC tumor suppressor gene and chemical carcinogenesis. Together, these observations represent the first report directly testing the effect of ambient oxygen on de novo tumorigenesis and provide important physiologic evidence demonstrating its critical role in increasing genomic instability in vivo.

  7. Buying time promotes happiness.

    Science.gov (United States)

    Whillans, Ashley V; Dunn, Elizabeth W; Smeets, Paul; Bekkers, Rene; Norton, Michael I

    2017-08-08

    Around the world, increases in wealth have produced an unintended consequence: a rising sense of time scarcity. We provide evidence that using money to buy time can provide a buffer against this time famine, thereby promoting happiness. Using large, diverse samples from the United States, Canada, Denmark, and The Netherlands ( n = 6,271), we show that individuals who spend money on time-saving services report greater life satisfaction. A field experiment provides causal evidence that working adults report greater happiness after spending money on a time-saving purchase than on a material purchase. Together, these results suggest that using money to buy time can protect people from the detrimental effects of time pressure on life satisfaction.

  8. Anger Promotes Economic Conservatism.

    Science.gov (United States)

    Kettle, Keri L; Salerno, Anthony

    2017-10-01

    Research suggests that certain facets of people's political ideals can be motivated by different goals. Although it is widely accepted that emotions motivate goal-directed behavior, less is known about how emotion-specific goals may influence different facets of ideology. In this research, we examine how anger affects political ideology and through what mechanisms such effects occur. Drawing on the dual-process motivational model of ideology and the functionalist perspective of emotion, we propose that anger leads people to support conservative economic ideals, which promote economic independence and discourage societal resource sharing. Four studies support our hypothesis that anger can enhance support for an election candidate espousing conservative economic ideals. We find that anger shifts people toward economic conservatism by orienting them toward competition for resources. Implications and future research on the relationship between emotions and political ideology are discussed.

  9. TRYPTOPHAN PROMOTES CHARITABLE DONATING

    Directory of Open Access Journals (Sweden)

    Laura eSteenbergen

    2014-12-01

    Full Text Available The link between serotonin (5-HT and one of the most important elements of prosocial behavior, charity, has remained largely uninvestigated. In the present study, we tested whether charitable donating can be promoted by administering the food supplement L-Tryptophan (TRP, the biochemical precursor of 5-HT. Participants were compared with respect to the amount of money they donated when given the opportunity to make a charitable donation. As expected, compared to a neutral placebo, TRP appears to increase the participants’ willingness to donate money to a charity. This result supports the idea that the food we eat may act as a cognitive enhancer modulating the way we think and perceive the world and others.

  10. Promoting household energy conservation

    International Nuclear Information System (INIS)

    Steg, Linda

    2008-01-01

    It is commonly assumed that households must change their behaviour to reduce the problems caused by increasing levels of fossil energy use. Strategies for behaviour change will be more effective if they target the most important causes of the behaviour in question. Therefore, this paper first discusses the factors influencing household energy use. Three barriers to fossil fuel energy conservation are discussed: insufficient knowledge of effective ways to reduce household energy use, the low priority and high costs of energy savings, and the lack of feasible alternatives. Next, the paper elaborates on the effectiveness and acceptability of strategies aimed to promote household energy savings. Informational strategies aimed at changing individuals' knowledge, perceptions, cognitions, motivations and norms, as well as structural strategies aimed at changing the context in which decisions are made, are discussed. This paper focuses on the psychological literature on household energy conservation, which mostly examined the effects of informational strategies. Finally, this paper lists important topics for future research

  11. A pattern-based nearest neighbor search approach for promoter prediction using DNA structural profiles.

    Science.gov (United States)

    Gan, Yanglan; Guan, Jihong; Zhou, Shuigeng

    2009-08-15

    Identification of core promoters is a key clue in understanding gene regulations. However, due to the diverse nature of promoter sequences, the accuracy of existing prediction approaches for non-CpG island (simply CGI)-related promoters is not as high as that for CGI-related promoters. This consequently leads to a low genome-wide promoter prediction accuracy. In this article, we first systematically analyze the similarities and differences between the two types of promoters (CGI- and non-CGI-related) from a novel structural perspective, and then devise a unified framework, called PNNP (Pattern-based Nearest Neighbor search for Promoter), to predict both CGI- and non-CGI-related promoters based on their structural features. Our comparative analysis on the structural characteristics of promoters reveals two interesting facts: (i) the structural values of CGI- and non-CGI-related promoters are quite different, but they exhibit nearly similar structural patterns; (ii) the structural patterns of promoters are obviously different from that of non-promoter sequences though the sequences have almost similar structural values. Extensive experiments demonstrate that the proposed PNNP approach is effective in capturing the structural patterns of promoters, and can significantly improve genome-wide performance of promoters prediction, especially non-CGI-related promoters prediction. The implementation of the program PNNP is available at http://admis.tongji.edu.cn/Projects/pnnp.aspx.

  12. Early 20th century conceptualization of health promotion.

    Science.gov (United States)

    Madsen, Wendy

    2017-12-01

    This historical analysis of the term 'health promotion' during the early 20th century in North American journal articles revealed concepts that strongly resonate with those of the 21st century. However, the lineage between these two time periods is not clear, and indeed, this paper supports contentions health promotion has a disrupted history. This paper traces the conceptualizations of health promotion during the 1920s, attempts to operationalize health promotion in the 1930s resulting in a narrowing of the concept to one of health education, and the disappearance of the term from the 1940s. In doing so, it argues a number of factors influenced the changing conceptualization and utilization of health promotion during the first half of the 20th century, many of which continue to present times, including issues around what health promotion is and what it means, ongoing tensions between individual and collective actions, tensions between specific and general causes of health and ill health, and between expert and societal contributions. The paper concludes the lack of clarity around these issues contributed to health promotion disappearing in the mid-20th century and thus resolution of these would be worthwhile for the continuation and development of health promotion as a discipline into the 21st century. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Oxytocin promotes human ethnocentrism.

    Science.gov (United States)

    De Dreu, Carsten K W; Greer, Lindred L; Van Kleef, Gerben A; Shalvi, Shaul; Handgraaf, Michel J J

    2011-01-25

    Human ethnocentrism--the tendency to view one's group as centrally important and superior to other groups--creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence.

  14. Ethnopoly promotes tolerance

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    On Friday 23 April, 225 primary school children from the eight schools in Meyrin-Cointrin and their accompanying adults took part in a big game of Ethnopoly. Private individuals, associations, administrations, shopkeepers and CERN all opened their doors to them to talk about their countries, their customs and what they are doing to promote tolerance and integration.   The CERN stand set up at ForumMeyrin for the Ethnopoly game. Scurrying from one place to another, the 10 and 11 year olds were made aware of the rich cultural diversity of their commune, which is home to 130 different nationalities. Physicists and engineers from CERN took up residence in the Forum Meyrin for the day in order to talk to the children about the advantages of international collaboration, a subject dear to the Organization's heart. They welcomed around fifty children in the course of the day, conveying to them a message of tolerance: despite their differences, the 10,000 scientists and other members of the CERN...

  15. Health promotion in the workplace

    OpenAIRE

    Sultan T Al-Otaibi

    2016-01-01

    The objective of this review was to describe the scientific evidence for coordinating health promotion at the workplace and to discuss the required future research in this field. Literature review from March 1990 to November 2014 was performed. Using the keywords ′health, promotion, worksite and workplace′, literature was searched in the following databases: Medline, PubMed and Google Scholar; with no time limit. There is emerging evidence that workplace health promotion enhances the effectiv...

  16. Promoting mental health in men

    OpenAIRE

    Haddad, M.

    2013-01-01

    Health promotion is essential to improve the health status and quality of life of individuals. Promoting mental health at an individual, community and policy level is central to reducing the incidence of mental health problems, including self-harm and suicide. Men may be particularly vulnerable to mental health problems, in part because they are less likely to seek help from healthcare professionals. Although this article discusses mental health promotion and related strategies in general, th...

  17. Promotion and Fast Food Demand

    OpenAIRE

    Timothy J. Richards; Luis Padilla

    2009-01-01

    Many believe that fast food promotion is a significant cause of the obesity epidemic in North America. Industry members argue that promotion only reallocates brand shares and does not increase overall demand. We study the effect of fast food promotion on market share and total demand by estimating a discrete / continuous model of fast food restaurant choice and food expenditure that explicitly accounts for both spatial and temporal determinants of demand. Estimates are obtained using a unique...

  18. Transcriptional Auto-Regulation of RUNX1 P1 Promoter

    Science.gov (United States)

    Martinez, Milka; Hinojosa, Marcela; Trombly, Daniel; Morin, Violeta; Stein, Janet; Stein, Gary; Javed, Amjad; Gutierrez, Soraya E.

    2016-01-01

    RUNX1 a member of the family of runt related transcription factors (RUNX), is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5’UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription. PMID:26901859

  19. Transcriptional Auto-Regulation of RUNX1 P1 Promoter.

    Directory of Open Access Journals (Sweden)

    Milka Martinez

    Full Text Available RUNX1 a member of the family of runt related transcription factors (RUNX, is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  20. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R

    2014-03-26

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  1. Decision Making and Revealed Preference

    DEFF Research Database (Denmark)

    de la Rosa, Leonidas Enrique

    If our decision-making processes are to some extent shaped by evolutionary pressures and our environment is different from that to which we adapted, some of our choices will not be in our best interest. But revealed preference is the only tool that we have so far to conduct a normative analysis...

  2. Revealing and Concealing in Antiquity

    DEFF Research Database (Denmark)

    Secrecy and the act of concealing and revealing knowledge effectually segregate the initiated and the uninitiated. The act of sharing or hiding knowledge plays a central role in all human relations private or public, political or religious. This volume explores the concept of secrecy and its...

  3. Revealed preference with limited consideration

    NARCIS (Netherlands)

    Demuynck, T.; Seel, C.

    2014-01-01

    We derive revealed preference tests for models where individuals use consideration sets to simplify their consumption problem. Our basic test provides necessary and sufficient conditions for consistency of observed choices with the existence of consideration set restrictions. The same conditions can

  4. Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes

    DEFF Research Database (Denmark)

    Lindvall, Therese; Karlsson, Jenny; Holmdahl, Rikard

    2009-01-01

    in different experimental arthritis models were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to experimental autoimmune encephalomyelitis , control development of collagen induced arthritis (CIA). METHODS: Collagen induced arthritis, induced...

  5. Tracking of chromosome dynamics in live Streptococcus pneumoniae reveals that transcription promotes chromosome segregation

    NARCIS (Netherlands)

    Kjos, Morten; Veening, Jan-Willem

    Chromosome segregation is an essential part of the bacterial cell cycle but is poorly characterized in oval-shaped streptococci. Using time-lapse fluorescence microscopy and total internal reflection fluorescence microscopy, we have tracked the dynamics of chromosome segregation in live cells of the

  6. Non-native acylated homoserine lactones reveal that LuxIR quorum sensing promotes symbiont stability.

    Science.gov (United States)

    Studer, Sarah V; Schwartzman, Julia A; Ho, Jessica S; Geske, Grant D; Blackwell, Helen E; Ruby, Edward G

    2014-08-01

    Quorum sensing, a group behaviour coordinated by a diffusible pheromone signal and a cognate receptor, is typical of bacteria that form symbioses with plants and animals. LuxIR-type N-acyl L-homoserine (AHL) quorum sensing is common in Gram-negative Proteobacteria, and many members of this group have additional quorum-sensing networks. The bioluminescent symbiont Vibrio fischeri encodes two AHL signal synthases: AinS and LuxI. AinS-dependent quorum sensing converges with LuxI-dependent quorum sensing at the LuxR regulatory element. Both AinS- and LuxI-mediated signalling are required for efficient and persistent colonization of the squid host, Euprymna scolopes. The basis of the mutualism is symbiont bioluminescence, which is regulated by both LuxI- and AinS-dependent quorum sensing, and is essential for maintaining a colonization of the host. Here, we used chemical and genetic approaches to probe the dynamics of LuxI- and AinS-mediated regulation of bioluminescence during symbiosis. We demonstrate that both native AHLs and non-native AHL analogues can be used to non-invasively and specifically modulate induction of symbiotic bioluminescence via LuxI-dependent quorum sensing. Our data suggest that the first day of colonization, during which symbiont bioluminescence is induced by LuxIR, is a critical period that determines the stability of the V. fischeri population once symbiosis is established. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  7. Burning reveals cryptic diversity and promotes coexistence of native species in a restored California prairie

    Science.gov (United States)

    Grassland and prairie restoration projects in California often result in long-term establishment of only a few native plant species, even when they begin with a diverse palette of species. A likely explanation for the disappearance of certain native species over time is that they are outcompeted by ...

  8. Burning reveals cryptic plant diversity and promotes coexistence in a California prairie restoration experiment

    Science.gov (United States)

    Grassland and prairie restoration projects in California often result in long-term establishment of only a few native plant species, even when they begin with a diverse seed palette. A likely explanation for the disappearance of certain native species over time is that they are excluded through comp...

  9. Promotion mix and industrial marketing

    Directory of Open Access Journals (Sweden)

    Jovičić Dragoljub

    2007-01-01

    Full Text Available Promotion activities are very important and irreplaceable marketing instrument in placement of production goods. In contrast to final consumption goods, where advertising has an absolute priority compared to another promotion activities, personal sale and development of sale dominate during placement of production goods.

  10. Integrative approaches: promoting socioecological resilience

    Science.gov (United States)

    J.W. Long; Carl Skinner; M. North; C.T. Hunsaker; L. Quinn-Davidson

    2014-01-01

    This chapter begins by discussing current challenges for ecosystem management that emerged from multiple chapters of the full synthesis. It then considers integrative approaches to promote resilience, including general strategies that recognize the integrated nature of socioecological systems, the importance of promoting disturbance regimes upon which these systems...

  11. Health Education and Health Promotion

    NARCIS (Netherlands)

    Koelen, M.A.; Ban, van den A.W.

    2004-01-01

    This book is a comprehensive resource for theory, research and action in health education and health promotion. The authors describe strategies and actions for health education and health promotion based on theories for understanding, predicting and changing behavioural, social and environmental

  12. PROMOTION STRATEGIES IN WINE MARKETING

    Directory of Open Access Journals (Sweden)

    Ştefan MATEI

    2014-06-01

    Full Text Available Marketing has proven to be very useful instrument in the wine industry, in fostering comprehensive, cohesive and effective strategies which wineries require to effectively compete in today’s almost saturated wine market. But within wine marketing, the promotion strategy, from our point of view, is the most important component of the winery that can ensure the success in the market or can shorten the life cycle of the product. This being said, the aim of the paper is twofold. Firstly, to determine and analyze the steps that are required to create a promotion strategy in the wine industry, by comparing different approaches. Secondly, to identify the instruments of the promotional mix that helps a winery to implement its promotional strategy. Bearing that in mind, the paper starts with some theoretical aspects regarding the promotion strategy and ends by providing a brief overview of the main findings.

  13. Literature promotion in Public Libraries

    DEFF Research Database (Denmark)

    Kann-Christensen, Nanna; Balling, Gitte

    2011-01-01

    This article discusses a model that can be used in order to analyse notions on literature promotion in public libraries. The model integrates different issues which interact with how literature promotion is understood and thought of in public libraries. Besides cultural policy we regard the logics...... of new public management (NPM) and professional logics in the field of public libraries. Cultural policy along with the identification of underlying logics present among politicians, government officials, managers and librarians/promoters of literature, play an important part in creating an understanding...... of literature promotion in Danish libraries. Thus the basic premise for the development of the model is that cultural policy (Policy) has an important influence on notions on literature promotion and other activities in public libraries, but that cultural policy must be seen in some kind of interaction...

  14. The invisibilization of health promotion in Australian public health initiatives.

    Science.gov (United States)

    O'Hara, Lily; Taylor, Jane; Barnes, Margaret

    2018-02-01

    The field of health promotion has arguably shifted over the past thirty years from being socially proactive to biomedically defensive. In many countries this has been accompanied by a gradual decline, or in some cases the almost complete removal of health promotion designated positions within Government health departments. The language or discourse used to describe the practice and discipline of health promotion is reflective of such changes. In this study, critical discourse analysis was used to determine the representation of health promotion as a practice and a discipline within 10 Australian Government weight-related public health initiatives. The analysis revealed the invisibilization of critical health promotion in favour of an agenda described as 'preventive health'. This was achieved primarily through the textual practices of overlexicalization and lexical suppression. Excluding document titles, there were 437 uses of the terms health promotion, illness prevention, disease prevention, preventive health, preventative health in the documents analysed. The term 'health promotion' was used sparingly (16% of total terms), and in many instances was coupled with the term 'illness prevention'. Conversely, the terms 'preventive health' and 'preventative health' were used extensively, and primarily used alone. The progressive invisibilization of critical health promotion has implications for the perceptions and practice of those identifying as health promotion professionals and for people with whom we work to address the social and structural determinants of health and wellbeing. Language matters, and the language and intent of critical health promotion will struggle to survive if its speakers are professionally unidentifiable or invisible. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Molecular mechanisms that distinguish TFIID housekeeping from regulatable SAGA promoters.

    Science.gov (United States)

    de Jonge, Wim J; O'Duibhir, Eoghan; Lijnzaad, Philip; van Leenen, Dik; Groot Koerkamp, Marian Ja; Kemmeren, Patrick; Holstege, Frank Cp

    2017-02-01

    An important distinction is frequently made between constitutively expressed housekeeping genes versus regulated genes. Although generally characterized by different DNA elements, chromatin architecture and cofactors, it is not known to what degree promoter classes strictly follow regulatability rules and which molecular mechanisms dictate such differences. We show that SAGA-dominated/TATA-box promoters are more responsive to changes in the amount of activator, even compared to TFIID/TATA-like promoters that depend on the same activator Hsf1. Regulatability is therefore an inherent property of promoter class. Further analyses show that SAGA/TATA-box promoters are more dynamic because TATA-binding protein recruitment through SAGA is susceptible to removal by Mot1. In addition, the nucleosome configuration upon activator depletion shifts on SAGA/TATA-box promoters and seems less amenable to preinitiation complex formation. The results explain the fundamental difference between housekeeping and regulatable genes, revealing an additional facet of combinatorial control: an activator can elicit a different response dependent on core promoter class. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  16. Latexin exhibits tumor-suppressor potential in pancreatic ductal adenocarcinoma

    Science.gov (United States)

    XUE, ZHANXIONG; ZHOU, YUHUI; WANG, CHENG; ZHENG, JIHANG; ZHANG, PU; ZHOU, LINGLING; WU, LIANG; SHAN, YUNFENG; YE, MENGSI; HE, YUN; CAI, ZHENZHAI

    2016-01-01

    Recent studies suggest that latexin (Lxn) expression is involved in stem cell regulation and that it plays significant roles in tumor cell migration and invasion. The clinicopathological significance of Lxn expression and its possible correlation with CD133 expression in pancreatic ductal adenocarcinoma (PDAC) is currently unknown. In the present study, immunohistochemical analysis was performed to determine Lxn and CD133 expression in 43 PDAC patient samples and in 32 corresponding adjacent non-cancerous samples. The results were analyzed and compared with patient age, gender, tumor site and size, histological grade, clinical stage and overall mean survival time. Lxn expression was clearly decreased in the PDAC tissues compared with that in the adjacent non-cancerous tissues, while CD133 expression was increased. Low Lxn expression in the PDAC tissues was significantly correlated with tumor size (P=0.002), histological grade (P=0.000), metastasis (P=0.007) and clinical stage (P=0.018), but not with age (P=0.451), gender (P=0.395) or tumor site (P=0.697). Kaplan-Meier survival analysis revealed that low Lxn expression was significantly correlated with reduced overall survival time (P=0.000). Furthermore, Lxn expression was found to be inversely correlated with CD133 expression (r=−0.485, P=0.001). Furthermore, CD133-positive MIA PaCa-2 pancreatic tumor cells were sorted by magnetic-activated cell sorting (MACS), and those that overexpressed Lxn exhibited a significantly higher rate of apoptosis and lower proliferative activity. Our findings suggest that Lxn may function as a tumor suppressor that targets CD133-positive pancreatic cancer cells. PMID:26530530

  17. Edutainment's Impact on Health Promotion: Viewing The Biggest Loser Through the Social Cognitive Theory.

    Science.gov (United States)

    Mocarski, Richard; Bissell, Kimberly

    2016-01-01

    Through a critical rhetorical analysis using Bandura's social cognitive theory as a lens to view The Biggest Loser (TBL), this article illustrates the contradictions between the show's health promotional aims and its entertainment aims, which show the problems the show creates for health promotion practitioners working on obesity. The social cognitive theory constructs of observational learning, psychological determinants, and environmental determinants emerged from this reading of TBL as central to how the show masquerades as a health promotion tool. This reading reveals that TBL promotes a neoliberal construction of health and obesity that challenges the worldview that many health promotion campaigns take and, therefore, complicates our own efforts to combat obesity. With this revealed, it is suggested that TBL be incorporated into health promotion campaigns only as a foil. © 2015 Society for Public Health Education.

  18. Health promotion in the workplace

    Directory of Open Access Journals (Sweden)

    Sultan T Al-Otaibi

    2016-01-01

    Full Text Available The objective of this review was to describe the scientific evidence for coordinating health promotion at the workplace and to discuss the required future research in this field. Literature review from March 1990 to November 2014 was performed. Using the keywords ′health, promotion, worksite and workplace′, literature was searched in the following databases: Medline, PubMed and Google Scholar; with no time limit. There is emerging evidence that workplace health promotion enhances the effectiveness of effort to promote and protect workers′ health. It proves both cost-effective and cost-beneficial to health promotion at the worksite and subsequently further reduces absenteeism. However, future research is needed to identify the impact of other factors such as age, gender and race on workers′ exposure. There is also a need to develop valid tests to measure the outcome of these programmes at the workplace. Health promotion should be central to workplace planning and should be recognised as an integral part of proactive occupational health. Indeed, the workplace is viewed as one of the most popular venues for promoting health and preventing diseases among employees.

  19. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Petranovic, Dina; Jensen, Peter Ruhdal

    2005-01-01

    The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how...... does one choose the correct promoter and what are the appropriate methods for reading promoter strength? Furthermore, how fine should the tuning of gene expression be for some specific applications and how can the simultaneous and individual tuning of multiple genes be achieved? Some recent studies...

  20. Photovoltaic module with adhesion promoter

    Science.gov (United States)

    Xavier, Grace

    2013-10-08

    Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.

  1. Stress Managment and Health Promotion

    Directory of Open Access Journals (Sweden)

    Asghar Dadkhah

    2004-09-01

    Full Text Available Health promotion approach is utilized to address the prevention, management and early intervention for stress management and also to promote positive mental and psychological health. Stress affects everyone and must be managed effectively to reduce its chronic and deleterious effects this study consists of two sections: in first section the principals of health promotion in different human existence levels, prevention of disease related to stress, the effect of stress on human well-being, and stress management were discussed. In second section the role of rehabilitation specialists (Medical technologist, nurses, occupational therapists, physiotherapists, respiratory therapists, and social workers in stress management were counted.

  2. Transparency masters for mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1980-01-01

    Transparency Masters for Mathematics Revealed focuses on master diagrams that can be used for transparencies for an overhead projector or duplicator masters for worksheets. The book offers information on a compilation of master diagrams prepared by John R. Stafford, Jr., audiovisual supervisor at the University of Missouri at Kansas City. Some of the transparencies are designed to be shown horizontally. The initial three masters are number lines and grids that can be used in a mathematics course, while the others are adaptations of text figures which are slightly altered in some instances. The

  3. Collegewide Promotion of E-Learning/Active Learning and Faculty Development

    Science.gov (United States)

    Ogawa, Nobuyuki; Shimizu, Akira

    2016-01-01

    Japanese National Institutes of Technology have revealed a plan to strongly promote e-Learning and active learning under the common schematization of education in over 50 campuses nationwide. Our e-Learning and ICT-driven education practiced for more than fifteen years were highly evaluated, and is playing a leading role in promoting e-Learning…

  4. To Reveal Thy Heart Perchance to Reveal the World

    Directory of Open Access Journals (Sweden)

    Robert B. Faux

    2005-05-01

    Full Text Available Ronald PELIAS, a professor of speech communications, employs a variety of writing methods as examples of alternative ways to do research and to share with the reader a seldom seen and seldom considered aspect of academic life: Heart. In the early chapters of the book, PELIAS sets out to establish a way to place his Heart in the foreground; baring his emotional vulnerability, his humanness, his being in the world. Later chapters of the book encompass an autoethnographic study of academic life in which the previously revealed Heart is placed in context. In this review essay I discuss PELIAS' book in relation to the larger literature on autoethnography and subjectivist research; I follow this by discussing the need for and usefulness of such alternative methods using PELIAS' autoethnography of academic life as a context. URN: urn:nbn:de:0114-fqs050279

  5. Nutritional Recommendation Should Promote Sustainability.

    Science.gov (United States)

    Reber, Robert J.

    1991-01-01

    Any process or event that disrupts the flow of nutrients and energy becomes a nutrition problem. Nutritionists should promote practices that protect the integrity, stability, and beauty of the land community (soil, water, air, all biological species). (Author)

  6. Oral health promotion at worksites

    DEFF Research Database (Denmark)

    Schou, L

    1989-01-01

    Many workplace-based health promotion programmes have been reported but only a few include or focus specifically on oral health. Although certain obstacles to oral health promotion in the workplace exist from the management side, from the dental profession and from the employees, these seem...... is at present sparse and there are few guidelines to actual strategies for effective oral health promotion. However, elements of strategies that have been successful in various geographical and economic environments include: active involvement of the work force, the use of dental auxiliaries, voluntary daily...... mouthrinsing, screening activities, use of mass media, oral hygiene instruction and prophylaxis and paraprofessional training. It is recommended that future research concentrates on these elements to build up a meaningful and relevant data base upon which effective oral health promotion programmes can...

  7. PARTICULARITIES OF MODERN PHARMACEUTICAL PROMOTION

    Directory of Open Access Journals (Sweden)

    Юрий Владимирович Тарасов

    2014-02-01

    Full Text Available Pharmaceutical products market is one of the most saturated consumers’ markets. Characteristic features of it are: high competition, fierce struggle for the customer, specific technologies of promotion. In conditions of globalization and increase in competition both in world pharmaceutical market and in the market of medicines and goods of medical purpose in Russia modern marketing techniques of promotion of the products to the end consumers are the key tools for strengthening market positions – both of producers of pharmaceutical goods and their suppliers, distributors, big whole-sale companies. Among main tools of promotion are: advertising, public relations, stimulation of sales on the market of medicines, personal sales, computer technologies. The article describes different technologies of promotion of medicines: indoor-advertising, hot lines, pharmaceutical exhibitions, packing. DOI: http://dx.doi.org/10.12731/2218-7405-2013-12-1

  8. Does Labor Diversity Promote Entrepreneurship?

    DEFF Research Database (Denmark)

    Marino, Marianna; Parrotta, Pierpaolo; Pozzoli, Dario

    We find evidence that workforce educational diversity promotes entrepreneurial behavior of employees as well as the formation of new firms, whereas diversity in demographics hinders transitions to selfemployment. Ethnic diversity favors entrepreneurship in financial and business services....

  9. [Five paradoxes in health promotion].

    Science.gov (United States)

    López-Dicastillo, Olga; Canga-Armayor, Navidad; Mujika, Agurtzane; Pardavila-Belio, Miren Idoia; Belintxon, Maider; Serrano-Monzó, Inmaculada; Pumar-Méndez, María J

    The World Health Organization states that health promotion is a key strategy to improve health, and it is conceived as a global process of enabling people to increase control over, and to improve, their health. Health promotion does not focus solely on empowering individuals dealing with their knowledge, attitudes and skills, but it also takes political, social, economic and environmental aspects influencing health and wellbeing into account. The complexity of applying these concepts is reflected in the five paradoxes in health promotion; these arise in between the rhetoric in health promotion and implementation. The detected paradoxes which are described herein involve the patient versus the person, the individual versus the group, disease professionals versus health professionals, disease indicators versus health indicators, and health as an expense versus health as an investment. Making these contradictions explicit can help determine why it is so complex to put the concepts related to health promotion into practice. It can also help to put forward aspects that need further work if health promotion is to put into practice. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Promotion of development and introduction

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    In order to promote effectively and smoothly development and introduction of oil substituting energies, comprehensive investigations for improving the energy demand and supply structures and investigations on development infrastructures will be conducted. Investigations will also be given on promoting improvements in overseas coal import base infrastructures, and demand/supply improvement, development and utilization of overseas energies. Investigations and guidance will be given on forming visions to improve demand/supply structures and to introduce and promote technologies thereof. In order to deepen further the understanding and recognition by the nation on oil substituting energies, such publicity activities will be carried out as provision of information, and promotion on popularization and education of energy demand/supply improving systems. For the purpose of promoting international exchanges, information exchange will be promoted on improving the energy demand/supply structures, so is on international information exchange. International cooperative operations on coal utilization, international cooperation on alcohol utilization technologies, and assistance to holding the world energy conferences will be carried out, and an Asia-Pacific Coal Demand and Supply Seminar will be held. In addition, training operations for coal engineers will be performed.

  11. Health promotion and prison settings.

    Science.gov (United States)

    Santora, Lidia; Arild Espnes, Geir; Lillefjell, Monica

    2014-01-01

    The purpose of this paper is to examine the contribution of modern correctional service in health promotion exemplified by the case study of Norwegian health promotion policies in prison settings. This paper applies a two-fold methodology. First a narrative systematic literature review based on the Norwegian policy documents relevant for correctional settings is conducted. This is followed by a general review of the literature on the principles of humane service delivery in offender rehabilitation. Alongside the contribution of the Risk-Need-Responsivity Model in corrections and prevention of reoffending, the findings demonstrate an evident involvement of Norway in health promotion through authentic health promoting actions applied in prison settings. The actions are anchored in health policy's overarching goals of equity and "health in all public policy" aiming to reduce social inequalities in population health. In order to achieve a potential success of promoting health in correctional settings, policy makers have much to gain from endorsing a dialogue that respects the unique contributions of correctional research and health promotion. Focussing on inter-agency partnership and interdisciplinary collaboration between humane services may result in promising outcomes for individual, community and public health gain. The organizational factors and community involvement may be a significant aspect in prisoner rehabilitation, reentry and reintegration.

  12. Effective services promotion management in Far North (Russia

    Directory of Open Access Journals (Sweden)

    Grabar Anna

    2017-01-01

    Full Text Available The problem of the effective management of services promotion in the Far North (Russia is topical due to the severe weather and climatic conditions and the high price barrier in this industry. The objective of the article is the analysis of consumer market characteristics and the formation of specific recommendations on services promotion for the industries. Statistical methods and methods of analysis, synthesis, decomposition and expert assessments used in the study revealed the features of the consumer market. The article highlights the factors and patterns of communication services market functioning and its development dynamics. Specific recommendations on the actions in competitive market are given to the companies providing communications services.

  13. Religion and health-promoting behaviors among emerging adults.

    Science.gov (United States)

    Horton, Shalonda E B

    2015-02-01

    Studies suggest we capitalize upon religion's health benefits to prevent obesity. The purpose of this qualitative descriptive study was to determine how emerging adults used religion to manage their health. Two focus groups were conducted among White and African American participants. Content analysis of the data revealed categories about their attitudes regarding parental and religious influences, religion's influence on behavior, negative health effects of religion, barriers, obesity prevention, and health promotion programs. Society sends out "easy" solutions for unhealthy behaviors, but we should focus on healthy behavior benefits, remove barriers, and consider religion's part in health promotion (obesity prevention).

  14. Mechanosensitive promoter region in the human HB-GAM gene

    DEFF Research Database (Denmark)

    Liedert, Astrid; Kassem, Moustapha; Claes, Lutz

    2009-01-01

    expression through specific transcription factor binding sites in the promoter region of mechanosensitive genes. In the present study, we demonstrate that the expression of HB-GAM, which is known to have stimulating effects on osteogenic differentiation, is rapidly induced by mechanical loading in hMSC-TERT4...... cells. Analysis of the human HB-GAM gene upstream regulatory region with luciferase reporter gene assays revealed that the upregulation of HB-GAM expression occurred at the transcriptional level and was mainly dependent on the HB-GAM promoter region most upstream containing three potential AP-1 binding...

  15. Cultural influences on health-promoting behaviors of older African-American women.

    Science.gov (United States)

    Baker, Janelle R

    2011-12-01

    Culture is an integral component of health-promoting behaviors that can no longer be ignored. Using Pender's Revised Health Promotion Model as a guide, this correlational predictive study explored the cultural influences on the health-promoting behaviors of 201 (N = 201) older African-American women in the southeastern United States. Findings revealed that older African-American women who were acculturated towards the dominant society had significantly higher scores on the Modified African American Acculturation Scale Revised (AAAS-R), were highly educated with high socioeconomic resources, and were more likely to engage in health-promoting behaviors. Culture significantly predicted health-promoting behaviors (b = .27, t(198), p health-promoting behaviors among older African-American women (R2 = .22, F[2, 198] = 27.31, p health disparities and to encourage health-promoting behaviors and longevity.

  16. Development of a conceptual model of the role of hospital nurses in health promotion in Jordan.

    Science.gov (United States)

    Shoqirat, N

    2015-05-19

    International evidence reveals that hospital nurses have not been able to incorporate health promotion effectively into the framework of their care. This can be attributed to unclear conceptualizing of the barriers and facilitators to the role of nurses in health promotion. An integrative review was carried out to develop a conceptual model to assist hospital nurses in Jordan to understand how health promotion activities can be developed. Factors affecting the involvement of nurses in health promotion - ranging from limited knowledge about health promotion to the social image of nursing - can be structured into three levels: the micro (individual), meso (organizational) and macro (population). By understanding the interplay of factors between and within the levels, nurses and other health professionals can draw on the individual, social and organizational factors that influence nurses' role in health promotion. The proposed model can be considered as a springboard for developing health promotion activities related to hospitals in other Muslim-majority contexts.

  17. Plan competitions reveal entrepreneurial talent

    Energy Technology Data Exchange (ETDEWEB)

    Madison, Alison L.

    2011-05-15

    Monthly economic diversity column for Tri-City Herald business section. Excerpt below: There’s something to be said for gaining valuable real-world experience in a structured, nurturing environment. Take for instance learning to scuba dive in the comfort of my resort pool rather than immediately hanging out with sharks while I figure out little things like oxygen tanks and avoiding underwater panic attacks. Likewise, graduate students are getting some excellent, supportive real-world training through university business plan competitions. These competitions are places where smart minds, new technologies, months of preparation and coaching, and some healthy pre-presentation jitters collide to reveal not only solid new business ideas, but also some promising entrepreneurial talent. In fact, professionals from around our region descend upon college campuses every spring to judge these events, which help to bridge the gap between academics and the real technology and business-driven economy.

  18. Communication Games Reveal Preparation Contextuality

    Science.gov (United States)

    Hameedi, Alley; Tavakoli, Armin; Marques, Breno; Bourennane, Mohamed

    2017-12-01

    A communication game consists of distributed parties attempting to jointly complete a task with restricted communication. Such games are useful tools for studying limitations of physical theories. A theory exhibits preparation contextuality whenever its predictions cannot be explained by a preparation noncontextual model. Here, we show that communication games performed in operational theories reveal the preparation contextuality of that theory. For statistics obtained in a particular family of communication games, we show a direct correspondence with correlations in spacelike separated events obeying the no-signaling principle. Using this, we prove that all mixed quantum states of any finite dimension are preparation contextual. We report on an experimental realization of a communication game involving three-level quantum systems from which we observe a strong violation of the constraints of preparation noncontextuality.

  19. Communication Games Reveal Preparation Contextuality.

    Science.gov (United States)

    Hameedi, Alley; Tavakoli, Armin; Marques, Breno; Bourennane, Mohamed

    2017-12-01

    A communication game consists of distributed parties attempting to jointly complete a task with restricted communication. Such games are useful tools for studying limitations of physical theories. A theory exhibits preparation contextuality whenever its predictions cannot be explained by a preparation noncontextual model. Here, we show that communication games performed in operational theories reveal the preparation contextuality of that theory. For statistics obtained in a particular family of communication games, we show a direct correspondence with correlations in spacelike separated events obeying the no-signaling principle. Using this, we prove that all mixed quantum states of any finite dimension are preparation contextual. We report on an experimental realization of a communication game involving three-level quantum systems from which we observe a strong violation of the constraints of preparation noncontextuality.

  20. The chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1990-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. Important insights were obtained from tracer experiments, but the full complexity of plutonium chemistry was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were aqueous solution based, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, it was found that an equilibrium was rapidly established among the four aqueous oxidation states while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element will be reported

  1. Revealing ontological commitments by magic.

    Science.gov (United States)

    Griffiths, Thomas L

    2015-03-01

    Considering the appeal of different magical transformations exposes some systematic asymmetries. For example, it is more interesting to transform a vase into a rose than a rose into a vase. An experiment in which people judged how interesting they found different magic tricks showed that these asymmetries reflect the direction a transformation moves in an ontological hierarchy: transformations in the direction of animacy and intelligence are favored over the opposite. A second and third experiment demonstrated that judgments of the plausibility of machines that perform the same transformations do not show the same asymmetries, but judgments of the interestingness of such machines do. A formal argument relates this sense of interestingness to evidence for an alternative to our current physical theory, with magic tricks being a particularly pure source of such evidence. These results suggest that people's intuitions about magic tricks can reveal the ontological commitments that underlie human cognition. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Local enactments of national health promotion policies

    DEFF Research Database (Denmark)

    Wimmelmann, Camilla Lawaetz

    2017-01-01

    Governments of welfare states are firmly committed to public health, resulting in a substantial number of public health policies. Given the multi-level structure of most welfare systems, the influence of a public health policy is related to its ability to spread geographically and move across...... organisational levels. Visiting, observing and interviewing 15 policy workers from 10 municipalities during a two-year period, this study investigated what happened to a Danish national health promotion policy as it was put into practice and managed in the Danish municipalities. The analysis reveals...... the concrete enactments and their locally experienced effects, our understanding of national public health policies risks becoming detached from praxis and unproductive. Public health policy-makers must pay methodological and analytical attention to the policies' multimodality and their concrete locally...

  3. Promotional Strategy Impacts on Organizational Market Share and Profitability

    Directory of Open Access Journals (Sweden)

    Adesoga Dada Adefulu

    2015-12-01

    Full Text Available The paper examined promotional strategy impacts on market share and profitability in Coca-Cola and 7up companies in Lagos State, Nigeria. Survey research method was adopted. The study population was the staff in marketing positions in the selected companies. Questionnaire was administered on the samples from Coca-Cola and 7UP companies. The statistical tool employed was the univariate analysis of variance (ANOVA to determine the statistical significance and the extent to which promotional strategy brings about variation in market share and profitability in the selected companies The study revealed the need for a better understanding of the organizational factors that determine the commitment of organizational resources to drive the achievement of marketing goals. In addition, promotional strategy measured by advertising, publicity and sales promotion affected market share and profitability at different percentage rates while Personal selling did not .The study concluded that promotional strategy suitable to a business caused variations in market share and profitability. Managers concerned about maintaining competitive edge in the market may find it appropriate to begin by examining promotional strategy adoption. Suggestions are also made for further research and study limitations are denoted. Researchers are encouraged to devote efforts to identifying what variables may modify the nature of relationship?

  4. 'Troubling' moments in health promotion: unpacking the ethics of empowerment.

    Science.gov (United States)

    Spencer, Grace

    2015-12-01

    Concepts of empowerment feature strongly in global health discourses. Empowerment is frequently advocated as a positive approach to addressing individual and community-level health needs. Despite its popularity, relatively little has been said about the unintended consequences of empowerment, which may give rise to some troubling ethical issues or, indeed, result in outcomes that may not be considered health promoting. Drawing on current uses of empowerment within health promotion, along with insights from an ethnographic study on young people's health, this paper raises some critical questions about the ethics of empowerment. By doing so, the paper troubles the idea that empowerment is a 'good thing' without some careful attention to the varying ways in which the ethics of empowerment may unfold in practice. Findings revealed young people's different perspectives on health and priorities for health promotion. The present analysis highlights how these alternative framings prompt a number of ethical tensions for understanding and operationalising empowerment. In conclusion, the findings underscore the importance of promoting ethical reflexivity in health promotion and, crucially, attending to the unintended and potentially ethically problematic consequences of empowerment. So what? This paper raises some critical questions about the ethics of empowerment and calls for a more thorough engagement with the unintended consequences of empowerment within health promotion.

  5. Sport promotion in USA and Europe

    Directory of Open Access Journals (Sweden)

    Ognjenov Gajina

    2002-01-01

    Full Text Available Promotion as most viewable marketing activity is in sports for years. Many companies invest lots of funds for promotion of sport. Investing funds in sports they can promote their companies. This is called sponsorship.

  6. Oxytocin promotes group-serving dishonesty.

    Science.gov (United States)

    Shalvi, Shaul; De Dreu, Carsten K W

    2014-04-15

    To protect and promote the well-being of others, humans may bend the truth and behave unethically. Here we link such tendencies to oxytocin, a neuropeptide known to promote affiliation and cooperation with others. Using a simple coin-toss prediction task in which participants could dishonestly report their performance levels to benefit their group's outcome, we tested the prediction that oxytocin increases group-serving dishonesty. A double-blind, placebo-controlled experiment allowing individuals to lie privately and anonymously to benefit themselves and fellow group members showed that healthy males (n = 60) receiving intranasal oxytocin, rather than placebo, lied more to benefit their group, and did so faster, yet did not necessarily do so because they expected reciprocal dishonesty from fellow group members. Treatment effects emerged when lying had financial consequences and money could be gained; when losses were at stake, individuals in placebo and oxytocin conditions lied to similar degrees. In a control condition (n = 60) in which dishonesty only benefited participants themselves, but not fellow group members, oxytocin did not influence lying. Together, these findings fit a functional perspective on morality revealing dishonesty to be plastic and rooted in evolved neurobiological circuitries, and align with work showing that oxytocin shifts the decision-maker's focus from self to group interests. These findings highlight the role of bonding and cooperation in shaping dishonesty, providing insight into when and why collaboration turns into corruption.

  7. Loss of HLTF function promotes intestinal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sandhu Sumit

    2012-03-01

    Full Text Available Abstract Background HLTF (Helicase-like Transcription Factor is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.

  8. [A study of factors influencing on health promoting lifestyle in the elderly--application of Pender's health promotion model].

    Science.gov (United States)

    Seo, Hyun Mi; Hah, Yang Sook

    2004-12-01

    The purpose of this study was to investigate the factors influencing health promoting lifestyle in the elderly. The subject of this study was 305 elderly person over the age of 60, living in rural and urban, Korea. For the analysis of collected data, descriptive statistics, t-test, analysis of variance and stepwise multiple regression were used for statistical analysis with SPSS statistical program. The average item score for the health promoting lifestyle was 2.46. The higher score on the subscale was nutrition(2.65). The lowest score on the subscale were physical activity(2.36) and stress management(2.36). General characteristics showing statistically significant difference in health promoting lifestyle were age, residential district, live together spouse, education, religion and pocket money in the elderly. Stepwise multiple regression analysis revealed that the most powerful predictor of health promoting lifestyle in the elderly was prior related behavior(R2=.554). A combination of prior related behavior, perceived benefits of action, perceived self-efficacy, commitment to a plan of action, and interpersonal influences accounted for 64.3% of the variance in health promoting lifestyle in the elderly. The factors influencing on health promoting lifestyle for elderly were prior related behavior, perceived benefits of action, perceived self-efficacy, commitment to a plan of action, and interpersonal influences.

  9. Hubble Images Reveal Jupiter's Auroras

    Science.gov (United States)

    1996-01-01

    These images, taken by the Hubble Space Telescope, reveal changes in Jupiter's auroral emissions and how small auroral spots just outside the emission rings are linked to the planet's volcanic moon, Io. The images represent the most sensitive and sharply-detailed views ever taken of Jovian auroras.The top panel pinpoints the effects of emissions from Io, which is about the size of Earth's moon. The black-and-white image on the left, taken in visible light, shows how Io and Jupiter are linked by an invisible electrical current of charged particles called a 'flux tube.' The particles - ejected from Io (the bright spot on Jupiter's right) by volcanic eruptions - flow along Jupiter's magnetic field lines, which thread through Io, to the planet's north and south magnetic poles. This image also shows the belts of clouds surrounding Jupiter as well as the Great Red Spot.The black-and-white image on the right, taken in ultraviolet light about 15 minutes later, shows Jupiter's auroral emissions at the north and south poles. Just outside these emissions are the auroral spots. Called 'footprints,' the spots are created when the particles in Io's 'flux tube' reach Jupiter's upper atmosphere and interact with hydrogen gas, making it fluoresce. In this image, Io is not observable because it is faint in the ultraviolet.The two ultraviolet images at the bottom of the picture show how the auroral emissions change in brightness and structure as Jupiter rotates. These false-color images also reveal how the magnetic field is offset from Jupiter's spin axis by 10 to 15 degrees. In the right image, the north auroral emission is rising over the left limb; the south auroral oval is beginning to set. The image on the left, obtained on a different date, shows a full view of the north aurora, with a strong emission inside the main auroral oval.The images were taken by the telescope's Wide Field and Planetary Camera 2 between May 1994 and September 1995.This image and other images and data

  10. In silico comparative analysis of promoters derived from plant pararetroviruses.

    Science.gov (United States)

    Gupta, Dipinte; Ranjan, Rajiv

    2017-12-01

    Promoters are specific sequence of nucleotides present upstream of gene coding region involved in initiation and regulation of transcription. Multiple cis-acting element forms the architecture of promoter to which trans-acting nucleic binding factors bind and regulates its activity. Since 1980 genome of pararetrovirus, are being exploited for developing efficient promoters. Among all of them Cauliflower mosaic virus is the most widely used promoter for gene expression. The basic rational behind the strength of promoter lies in the sequence of cis elements and the spacer nucleotide elements between them, thereby strength of these promoter fragments can be regulated by altering these nucleotide sequences. In the present study sequence of eight putative promoters of plant pararetrovirus are retrieved from National Centre for Biotechnology Information (NCBI) website. These sequence are subjected to various bioinformatics tools comprises of Clustal W, Plant Care, Mathinspector, ModelInspector for establishing the phylogenetic similarity, to identify the quantity and quality of present cis-elements, to find the various common transcription factors binding sites and to determine the presence of module for various specific functions respectively. A range of 28.80-56.0 percentage identification was observed in phylogenetic analysis, with the greatest similarity in Mirabilis mosaic virus and Dahlia mosaic virus. A broad range of cis-elements (51), transcription factor binding site (512) was obtained and 60% observed module are in combination with DOFF motif which shows a function relevance with abiotic stress inducibility. The present study had revealed the functional significance of these elements in gene regulation of pararetrovirus genome and also gives a overall idea for designing novel synthetic promoter.

  11. Characterization of promoter sequence of toll-like receptor genes in Vechur cattle

    Directory of Open Access Journals (Sweden)

    R. Lakshmi

    2016-06-01

    Full Text Available Aim: To analyze the promoter sequence of toll-like receptor (TLR genes in Vechur cattle, an indigenous breed of Kerala with the sequence of Bos taurus and access the differences that could be attributed to innate immune responses against bovine mastitis. Materials and Methods: Blood samples were collected from Jugular vein of Vechur cattle, maintained at Vechur cattle conservation center of Kerala Veterinary and Animal Sciences University, using an acid-citrate-dextrose anticoagulant. The genomic DNA was extracted, and polymerase chain reaction was carried out to amplify the promoter region of TLRs. The amplified product of TLR2, 4, and 9 promoter regions was sequenced by Sanger enzymatic DNA sequencing technique. Results: The sequence of promoter region of TLR2 of Vechur cattle with the B. taurus sequence present in GenBank showed 98% similarity and revealed variants for four sequence motifs. The sequence of the promoter region of TLR4 of Vechur cattle revealed 99% similarity with that of B. taurus sequence but not reveals significant variant in motifregions. However, two heterozygous loci were observed from the chromatogram. Promoter sequence of TLR9 gene also showed 99% similarity to B. taurus sequence and revealed variants for four sequence motifs. Conclusion: The results of this study indicate that significant variation in the promoter of TLR2 and 9 genes in Vechur cattle breed and may potentially link the influence the innate immunity response against mastitis diseases.

  12. Isolation and characterization of cardiogenic, stem-like cardiac precursors from heart samples of patients with congenital heart disease.

    Science.gov (United States)

    Ghazizadeh, Zaniar; Vahdat, Sadaf; Fattahi, Faranak; Fonoudi, Hananeh; Omrani, Gholamreza; Gholampour, Maziar; Aghdami, Nasser

    2015-09-15

    Regenerative therapies based on resident human cardiac progenitor cells (hCPCs) are a promising alternative to medical treatments for patients with myocardial infarction. However, hCPCs are rare in human heart and finding efficient source and proper surface marker for isolation of these cells would make them a good candidate for therapy. We have isolated 5.34∗10(6)±2.04∗10(5)/g viable cells from 35 heart tissue samples of 23 patients with congenital heart disease obtained during their heart surgery along with 6 samples from 3 normal subjects during cardiac biopsy. According to FACS analysis, younger ages, atrial specimen and disease with increased pulmonary vascular resistance were associated with higher percentage of c-kit(+) (CD117) hCPCs. Analysis for other stemness markers revealed increased CD133(+) cells in the hearts of patients with congenital heart disease. By using both immune-labeling and PCR, we demonstrated that these cells express key cardiac lineage and endothelial transcription factors and structural proteins during in vitro differentiation and do express stemness transcription factors in undifferentiated state. Another novel datum of potentially relevant interest is their ability in promoting greater myocardial regeneration and better survival in rat model of myocardial infarction following transplantation. Our results could provide evidence for conditions associated with enriched hCPCs in patients with congenital heart disease. Moreover, we showed presence of a significant number of CD133 expressing cardiogenic stem-like cardiac precursors in the heart of patients with congenital heart disease, which could be isolated and stored for future regenerative therapies in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. AAHD's Health Promotion and Wellness, Part 2: Health Promotion Programs

    Science.gov (United States)

    Exceptional Parent, 2011

    2011-01-01

    This article is part 2 of a 4-part series on "Health Promotion and Wellness" from the American Association on Health and Disability (AAHD). According to the U.S. Census Bureau, more than 54 million people--one in five Americans--have a disability, and these Americans are more likely to report: (1) Being in poorer overall health; (2) Having less…

  14. Characterization of galactose-dependent promoters from an oleaginous fungus Mortierella alpina 1S-4.

    OpenAIRE

    Okuda, Tomoyo; Ando, Akinori; Sakuradani, Eiji; Kikukawa, Hiroshi; Kamada, Nozomu; Ochiai, Misa; Shima, Jun; Ogawa, Jun

    2014-01-01

    An inducible promoter is a useful tool for the controlled expression of a given gene. In this report, we describe galactose-dependent promoters for potential use in an oleaginous fungus Mortierella alpina. We cloned the putative promoter regions of two genes encoding galactose metabolic enzymes, GAL1 and GAL10, from the genome of M. alpina 1S-4. The β-glucuronidase (GUS) reporter gene assay in M. alpina 1S-4 revealed that regulation of these promoters was dependent on the presence of galactos...

  15. Assessing Preschool Teachers’ Practices to Promote Self-Regulated Learning

    Directory of Open Access Journals (Sweden)

    Fahretdin Hasan ADAGİDELİ

    2015-06-01

    Full Text Available Recent research reveals that in preschool years, through pedagogical interventions, preschool teachers can and should promote self-regulated learning. The main aim of this study is to develop a self-report instrument to assess preschool teachers’ practices to promote self-regulated learning. A pool of 50 items was recruited through literature review. Items, then, were formulated as statements, to which the teachers could respond on a Likert-scale. In line with the expert and teacher opinions, twenty statements were removed from the original pool and some statements were reformulated. The latest version of the scale consisted of 21 statements. The participants were preschool teacher (N=169 from Istanbul. Empirical testing at item and scale level showed that T-SRL is a reliable and a valid instrument to assess preschool teachers’ classroom practices promoting self-regulated learning of their children at the age of 3-6.

  16. Assessing preschool teachers’ practices to promote self-regulated learning

    Directory of Open Access Journals (Sweden)

    Fahretdin Hasan Adagideli

    2015-07-01

    Full Text Available Recent research reveals that in preschool years, through pedagogical interventions, preschool teachers can and should promote self-regulated learning. The main aim of this study is to develop a self-report instrument to assess preschool teachers’ practices to promote self-regulated learning. A pool of 50 items was recruited through literature review. Items, then, were formulated as statements, to which the teachers could respond on a Likert-scale. In line with the expert and teacher opinions, twenty statements were removed from the original pool and some statements were reformulated. The latest version of the scale consisted of 21 statements. The participants were preschool teacher (N=169 from Istanbul. Empirical testing at item and scale level showed that T-SRL is a reliable and a valid instrument to assess preschool teachers’ classroom practices promoting self-regulated learning of their children at the age of 3-6.

  17. Artificial Promoters for Metabolic Optimization

    DEFF Research Database (Denmark)

    Jensen, Peter Ruhdal; Hammer, Karin

    1998-01-01

    In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms......In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro...

  18. TERT promoter mutations and prognosis in solitary fibrous tumor.

    Science.gov (United States)

    Bahrami, Armita; Lee, Seungjae; Schaefer, Inga-Marie; Boland, Jennifer M; Patton, Kurt T; Pounds, Stanley; Fletcher, Christopher D

    2016-12-01

    Solitary fibrous tumor is a mesenchymal neoplasm exhibiting a broad spectrum of biological behavior and harboring the NAB2-STAT6 fusion. Clinicopathologic parameters are currently used in risk-prediction models for solitary fibrous tumor, but the molecular determinants of malignancy in solitary fibrous tumors remain unknown. We proposed that the activation of telomere maintenance pathways confers a perpetual malignant phenotype to these tumors. Therefore, we investigated telomerase reverse transcriptase (TERT) reactivation induced by promoter mutations as a potential molecular mechanism for aggressive clinical behavior in solitary fibrous tumor. The retrospective study included tumor samples from 94 patients with solitary fibrous tumor (31 thoracic and 63 extra-thoracic). Follow-up information was available for 68 patients (median, 46 months). TERT promoter mutation analysis was performed by PCR and Sanger sequencing, and TERT mRNA expression was assessed by real-time quantitative reverse transcription PCR. Patients were stratified into clinicopathologic subgroups (high-risk (n=20), moderate-risk (n=28), and low-risk (n=46)) according to the risk-stratification model proposed by Demicco et al. TERT promoter mutations were identified in 26 of 94 (28%) solitary fibrous tumors: -124C>T in 23 tumors (88%), -124C>A in 1 tumor (4%), and -146C>T in 2 tumors (8%). Real-time quantitative reverse transcription PCR revealed that TERT mRNA expression was higher in all solitary fibrous tumors with the mutant TERT promoter than those with the wild-type TERT promoter. TERT promoter mutations were strongly associated with high-risk clinicopathologic characteristics and outcome. An adverse event (relapse, death) occurred in 16 of 68 (24%) patients, 12 with solitary fibrous tumors with TERT promoter mutations and 4 with the wild-type TERT promoter. TERT promoter mutations were strongly associated with older age (P=0.006), larger tumor size (P=0.000002), higher risk classifications

  19. INVESTIGATION INTO CONSUMER RESPONSE TO SALES PROMOTIONAL ACTIVITIES: THE CASE OF UNILEVER GHANA LIMITED

    Directory of Open Access Journals (Sweden)

    Martin Owusu Ansah

    2013-10-01

    Full Text Available The promotional activities have become more sophisticated and an increasing number of companies are using them to ensure their survival in today’s competitive market. Essentially, the study analyzed the nature of sales promotional activities of Unilever Ghana Limited; determined factors that influence the consumption of Unilever products in Kumasi and finally examined the relationship between sales promotions and the consumption of Unilever products. Primary and secondary data sources were used to select 220 consumers of Unilever in Kumasi and an in-depth interview with the Managers of the companies in Kumasi. Convenient sampling technique was employed in the study. Cross tabulation was done on the demographics whilst a regression model was used to establish the relationship between sales promotions and consumption of products. The findings revealed that Personalities in promotions, Prices in promotions, Messages in promotions and Promotional tools have strong influence on consumption but the Medium in promotion did not have influence on consumption during promotions. It was therefore recommended for celebrities to be used in the company’s promotions.

  20. Health Promotion at the Ballpark.

    Science.gov (United States)

    Hodges, Bonni C

    2017-03-01

    The arrival of a new summer collegiate baseball league franchise to a small central New York city was seen as an opportunity for health promotion. The initiative was set up to explore two overarching questions: (1) Are summer collegiate baseball events acceptable to local public health organizations as viable places for health promotion activities addressing local health issues? (2) Are summer collegiate baseball organizations amenable to health promotion activities built in to their fan and/or player experiences? Planning and implementation were guided by precede-proceed, social cognitive theory, social marketing, and diffusion of innovations constructs. Environmental changes were implemented to support healthy eating and nontobacco use by players and fans; four health awareness nights were implemented at home games corresponding to local public health priorities and included public service announcements, between inning quizzes, information dissemination at concession and team market locations, and special guests. Sales and fan feedback support mostly healthy concession offerings and a tobacco-free ballpark; postseason evaluations from team staff and public health partners support continuing the trials of this sports event as a venue for health promotion.

  1. Local wisdom and health promotion

    DEFF Research Database (Denmark)

    Demaio, Alessandro Rhyll

    2011-01-01

    served are the goal for public health physicians in our modern, globalized world. This meta-analysis reviewed literature from the past 18 years drawn from a wide range of sources. This investigations proposes a grassroots, material shift toward regarding health promotion interventions as partnerships...

  2. How Bureaucracy Promotes Inclusive Organizing

    DEFF Research Database (Denmark)

    Holck, Lotte

    Diversity literature in general and Feminist in particular have long promoted alternatives to bureaucracy on the premise that this form of governance is far from gender- and race-neutral, and that inclusive organizing necessitate a flatter, decentralized and more ‘organic’ set-up (Ferguson 1984...

  3. Advertising and Sales Promotion Guide.

    Science.gov (United States)

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Vocational Education.

    This document contains teacher materials for a 4-unit, 1-year marketing education course in advertising and sales promotion offered in grades 11 and 12 in North Carolina. The preface contains a rationale for the development of the course, a course description, course objectives, a list of the instructional units of the course, and a list of the…

  4. Sales promotion and channel coordination

    NARCIS (Netherlands)

    Wierenga, B.; Soethoudt, J.M.

    2010-01-01

    Consumer sales promotions are usually the result of the decisions of two marketing channel parties, the manufacturer and the retailer. In making these decisions, each party normally follows its own interest: i.e. maximizes its own profit. Unfortunately, this results in a suboptimal outcome for the

  5. Promoting Metacognition in Music Classes

    Science.gov (United States)

    Benton, Carol W.

    2013-01-01

    Metacognition is a type of thinking in which learners think about their own cognitive processes. Because it transcends disciplines and grade levels, metacognition is useful in many educational settings and can be transferred from the music classroom to other subject areas. Music educators can promote metacognition by designing and implementing…

  6. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Petranovic, Dina; Jensen, Peter Ruhdal

    2005-01-01

    The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how...

  7. University Festival Promotes STEM Education

    Science.gov (United States)

    Quagliata, Andrew B.

    2015-01-01

    STEM education is argued as an essential ingredient in preparing our children for careers of the future. This study describes a university festival that includes the promotion of STEM-related career interests in young people among its goals. A total of 203 participants between the age of 7 and 17 completed both pre-event and post-event surveys. In…

  8. 7 CFR 1219.22 - Promotion.

    Science.gov (United States)

    2010-01-01

    ... in the United States, including paid advertising, sales promotion, and publicity. Promotion... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1219.22 Section 1219.22 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH...

  9. 7 CFR 1150.114 - Promotion.

    Science.gov (United States)

    2010-01-01

    ... promotion, and publicity to advance the image and sales of, and demand for, dairy products generally. ... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1150.114 Section 1150.114 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research...

  10. Sex Discrimination in the Promotion Process.

    Science.gov (United States)

    Olson, Craig A.; Becker, Brian E.

    1983-01-01

    Examines the extent of gender differences in the incidence of and returns to promotions. Concludes that the returns to promotion are comparable for men and women, but that women are held to higher promotion standards than men and therefore receive fewer promotions than men with equal measured abilities. (NRJ)

  11. Health promotion for older Americans.

    Science.gov (United States)

    Heckler, M M

    1985-01-01

    As American lifespans increase, there is greater concern for the quality of those longer lives. The Department of Health and Human Services, through its many component agencies, has inaugurated a major initiative to promote health and fitness among older Americans to improve life quality and to reduce health care costs. The older population is a fertile ground for such an initiative, because studies indicate that the elderly are extremely health-conscious and very willing to adopt habits that will maintain good health. Investigation disclosed six target areas of concentration at which the health promotion initiative could be aimed: fitness-exercise, nutrition, safe and proper use of drugs and alcohol, accident prevention, other preventive services, and smoking cessation. The initiative includes cooperative programs with States; dissemination of printed information; nutritious meals for the elderly; a Food and Drug Administration consumer education program; Centers for Disease Control programs on accident prevention; a special task force to deal with Alzheimer's disease; and, in cooperation with states, a media campaign of health promotion for the elderly. At least three national health and senior citizens organizations are working closely with HHS agencies on the initiative. A separate Department effort involves the encouragement of fast-growing health maintenance organizations to promote health and prevention for their Medicare members and the persuasion of Medicare beneficiaries generally to seek second medical or surgical opinions. State and local government and the private sector, responding to Department initiatives, have also been developing programs for the aging. Their interest and participation ensures that special health promotion and disease prevention efforts directed toward elderly Americans will continue and proliferate.

  12. IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells.

    Science.gov (United States)

    Cao, Hui; Zhang, Jing; Liu, Hong; Wan, Ledong; Zhang, Honghe; Huang, Qiong; Xu, Enping; Lai, Maode

    2016-09-20

    Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide due to the distant metastases. Compelling evidence has reported that epithelial-mesenchymal transition (EMT) is involved in promoting cancer invasion and metastasis. However, the precise molecular events that initiate this complex EMT process remain poorly understood. Here, we showed that the pleiotropic cytokine interleukin-13 (IL-13) could induce an aggressive phenotype displaying EMT by enhancing the expression of EMT-promoting factor ZEB1. Importantly, STAT6 signaling inhibitor and STAT6 knockdown significantly reversed IL-13-induced EMT and ZEB1 induction in CRC cells, whereas ectopic STAT6 expression in STAT6null CRC cell line markedly promoted EMT in the present of IL-13. ChIP-PCR and Luciferase assays revealed that activated STAT6 directly bound to the promoter of ZEB1. Otherwise, we found IL-13 also up-regulated the stem cell markers (nanog, CD44, CD133 and CD166) and promoted cell migration and invasion through STAT6 pathway. We also found that siRNA-mediated knockdown of IL-13Rα1 could reverse IL-13-induced ZEB1 and EMT changes by preventing STAT6 signaling. Finally, we demonstrated positive correlation between IL-13Rα1 and ZEB1 at mRNA levels in human CRC samples. Taken together, our findings first demonstrated that IL-13/IL-13Rα1/STAT6/ZEB1 pathway plays a critical role in promoting EMT and aggressiveness of CRC.

  13. Measuring the Cost of Supermarket Promotions

    DEFF Research Database (Denmark)

    Gao, Cixiu

    2014-01-01

    The widespread use of retail promotions and the magnitude of dollars spent on them call economists to examine the role of promotional costs in shaping the coordination of pricing and promotion decisions. In this study, I estimate the marginal cost of price promotion in the retail industry. The es...... expensive promotions. Stores with higher promotion costs, however, would have to offer deeper price discounts in order to attract more store visits........ The estimates imply that the marginal cost of promotion ranges from $0.97 to $4.98 per promotion, and the total promotion cost comprises 3.6 to 17.1 percent of store revenues, or 10.4 to 23.7 percent of profits. The results also indicate that stores with higher promotion elasticities are able to afford more...

  14. Promoters active in interphase are bookmarked during mitosis by ubiquitination

    Science.gov (United States)

    Arora, Mansi; Zhang, Jie; Heine, George F.; Ozer, Gulcin; Liu, Hui-wen; Huang, Kun; Parvin, Jeffrey D.

    2012-01-01

    We analyzed modification of chromatin by ubiquitination in human cells and whether this mark changes through the cell cycle. HeLa cells were synchronized at different stages and regions of the genome with ubiquitinated chromatin were identified by affinity purification coupled with next-generation sequencing. During interphase, ubiquitin marked the chromatin on the transcribed regions of ∼70% of highly active genes and deposition of this mark was sensitive to transcriptional inhibition. Promoters of nearly half of the active genes were highly ubiquitinated specifically during mitosis. The ubiquitination at the coding regions in interphase but not at promoters during mitosis was enriched for ubH2B and dependent on the presence of RNF20. Ubiquitin labeling of both promoters during mitosis and transcribed regions during interphase, correlated with active histone marks H3K4me3 and H3K36me3 but not a repressive histone modification, H3K27me3. The high level of ubiquitination at the promoter chromatin during mitosis was transient and was removed within 2 h after the cells exited mitosis and entered the next cell cycle. These results reveal that the ubiquitination of promoter chromatin during mitosis is a bookmark identifying active genes during chromosomal condensation in mitosis, and we suggest that this process facilitates transcriptional reactivation post-mitosis. PMID:22941662

  15. STRATEGIC APPROACH TO PROMOTION OF CONSTRUCTION PRODUCTS IN THE MARKET

    Directory of Open Access Journals (Sweden)

    Fatima M. Ramazanova

    2017-01-01

    Full Text Available Abstract. Objectives The aim of the study is to develop a system of practical measures to ensure the most effective promotion of construction products to the market. Method During the process of research, methods of logical, statistical and comparative analysis as well as expert evaluations were used. Results Analysis and assessment of the construction market situation enabled a group of factors that affect the sales of construction products – in particular, building materials – to be identified, which constituted an empirical basis for developing a strategy for their promotion, aimed at maximum satisfaction of solvent demand and profit. It is determined that as an instrument of the communication policy of a construction enterprise, the promotion of construction products is a system of incentive measures and techniques designed to stimulate sales. A characterisation of the promotional system of construction products as an instrument of marketing communications is presented, revealing the target dependence of measures to stimulate sales from stages of the life cycle. The criteria for selecting the promotion channels have been systematised, serving as the basis for the strategic approach to the organisation of the distribution logistic system in construction and the steady positioning of construction products on the market. Conclusion A strategic approach to the promotion of construction products in the market ensures the creation of a system of effectively integrated marketing communications, implemented in the form of a strategic bridging partnership. Realisation of the strategy of construction product promotion comprises a reliable basis for strengthening the market positions of construction companies under the harsh conditions of a competitive environment. 

  16. Two independent transcription initiation codes overlap on vertebrate core promoters

    Science.gov (United States)

    Haberle, Vanja; Li, Nan; Hadzhiev, Yavor; Plessy, Charles; Previti, Christopher; Nepal, Chirag; Gehrig, Jochen; Dong, Xianjun; Akalin, Altuna; Suzuki, Ana Maria; van Ijcken, Wilfred F. J.; Armant, Olivier; Ferg, Marco; Strähle, Uwe; Carninci, Piero; Müller, Ferenc; Lenhard, Boris

    2014-03-01

    A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs and recruits general transcription factors to initiate transcription. The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle. Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition. This transition provides a unique opportunity to study the rules of TSS selection and the hierarchy of events linking transcription initiation with key chromatin modifications. We analysed TSS usage during zebrafish early embryonic development at high resolution using cap analysis of gene expression, and determined the positions of H3K4me3-marked promoter-associated nucleosomes. Here we show that the transition from the maternal to zygotic transcriptome is characterized by a switch between two fundamentally different modes of defining transcription initiation, which drive the dynamic change of TSS usage and promoter shape. A maternal-specific TSS selection, which requires an A/T-rich (W-box) motif, is replaced with a zygotic TSS selection grammar characterized by broader patterns of dinucleotide enrichments, precisely aligned with the first downstream (+1) nucleosome. The developmental dynamics of the H3K4me3-marked nucleosomes reveal their DNA-sequence-associated positioning at promoters before zygotic transcription and subsequent transcription-independent adjustment to the final position downstream of the zygotic TSS. The two TSS-defining grammars coexist, often physically overlapping, in core promoters of constitutively expressed genes to enable

  17. Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects their Survival.

    Science.gov (United States)

    Müller-Greven, Gaëlle; Carlin, Cathleen R; Burgett, Monica E; Ahluwalia, Manmeet S; Lauko, Adam; Nowacki, Amy S; Herting, Cameron J; Qadan, Maha A; Bredel, Markus; Toms, Steven A; Lathia, Justin D; Hambardzumyan, Dolores; Sarkaria, Jann N; Hamerlik, Petra; Gladson, Candece L

    2017-11-15

    Purpose: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors. Experimental Design: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133 + cells derived from GBM tumors in vitro Bevacizumab internalization, trafficking, and effects on cell survival were analyzed using multilabel confocal microscopy, immunoblotting, and cytotoxicity assays in the presence/absence of inhibitors. Results: In the GBM mouse models, administered anti-mouse-VEGF-A entered the perivascular tumor niche and was internalized by Sox2 + /CD44 + tumor cells. In the perivascular tumor cells, bevacizumab was detected in the recycling compartment or the lysosomes, and increased autophagy was found. Bevacizumab was internalized rapidly by CD133 + /Sox2 + -GBM cells in vitro through macropinocytosis with a fraction being trafficked to a recycling compartment, independent of FcRn, and a fraction to lysosomes. Bevacizumab treatment of CD133 + GBM cells depleted VEGF-A and induced autophagy thereby improving cell survival. An inhibitor of lysosomal acidification decreased bevacizumab-induced autophagy and increased cell death. Inhibition of macropinocytosis increased cell death, suggesting macropinocytosis of bevacizumab promotes CD133 + cell survival. Conclusions: We demonstrate that bevacizumab is internalized by Sox2 + /CD44 + -GBM tumor cells residing in the perivascular tumor niche. Macropinocytosis of bevacizumab and trafficking to the lysosomes promotes CD133 + cell survival, as does the autophagy induced by bevacizumab depletion of VEGF-A. Clin Cancer Res; 23(22); 7059-71. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Predicting the strength of UP-elements and full-length E. coli σE promoters

    Science.gov (United States)

    Rhodius, Virgil A.; Mutalik, Vivek K.; Gross, Carol A.

    2012-01-01

    Predicting the location and strength of promoters from genomic sequence requires accurate sequenced-based promoter models. We present the first model of a full-length bacterial promoter, encompassing both upstream sequences (UP-elements) and core promoter modules, based on a set of 60 promoters dependent on σE, an alternative ECF-type σ factor. UP-element contribution, best described by the length and frequency of A- and T-tracts, in combination with a PWM-based core promoter model, accurately predicted promoter strength both in vivo and in vitro. This model also distinguished active from weak/inactive promoters. Systematic examination of promoter strength as a function of RNA polymerase (RNAP) concentration revealed that UP-element contribution varied with RNAP availability and that the σE regulon is comprised of two promoter types, one of which is active only at high concentrations of RNAP. Distinct promoter types may be a general mechanism for increasing the regulatory capacity of the ECF group of alternative σ's. Our findings provide important insights into the sequence requirements for the strength and function of full-length promoters and establish guidelines for promoter prediction and for forward engineering promoters of specific strengths. PMID:22156164

  19. Puerto Rico Revealed Preference Survey Data 2004

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Revealed preference models provide insights into recreational angler behavior and the economic value of recreational fishing trips. Revealed preference data is...

  20. Conceptualization and measurement of mental health providers' recovery-promoting competence: the recovery promoting relationships scale (RPRS).

    Science.gov (United States)

    Russinova, Zlatka; Rogers, E Sally; Cook, Karon F; Ellison, Marsha Langer; Lyass, Asya

    2013-03-01

    The purpose of this study was to construct and validate an instrument that measures practitioners' competence to promote the recovery among individuals with psychiatric disabilities from the perspective of the person served. Items were developed based upon input from individuals served and practitioners as well as the extant literature on recovery. "Recovery-promoting competence" was conceptualized as a set of practitioner capabilities that promote the recovery process and enhance the working alliance. A scale was developed using a two-stage process that initially identified specific recovery-promoting competencies and then tested candidate items measuring those competencies. Item Response Theory and Classical Test Theory approaches were used to validate the instrument and assess its psychometric properties with a national sample of 382 individuals with psychiatric disabilities. Analyses revealed two distinct sets of recovery-promoting competencies: (a) competencies that enhance clients' recovery, and (b) competencies that build and maintain a strong therapeutic or working alliance. The first set further differentiated into subcompetencies-enhancing clients' hopefulness, empowerment, and self-acceptance. The instrument had high internal consistency and acceptable stability over time, convergent, criterion, and known groups' validity. This scale is a tool for assessing mental health and rehabilitation practitioners' competencies from the perspective of the individual served which can be used both in research and program evaluation of agencies serving individuals with psychiatric disabilities. PsycINFO Database Record (c) 2013 APA, all rights reserved

  1. Oral health promotion at worksites

    DEFF Research Database (Denmark)

    Schou, L

    1989-01-01

    Many workplace-based health promotion programmes have been reported but only a few include or focus specifically on oral health. Although certain obstacles to oral health promotion in the workplace exist from the management side, from the dental profession and from the employees, these seem...... to be of a scale that can easily be overcome: moreover, numerous potential benefits exist. From the employer's point of view, the main arguments in favour are reduced health care costs, increased productivity and reduced absenteeism. The benefits to the dental profession are possible increases in utilization...... of services and less restraint from fee payment structures and physical environments. The immediate benefit to the employees is easy access to dental services. In addition, work-related dental hazards can be compensated for or prevented and screening activities can be more easily organized. The literature...

  2. Electrochemical promotion of catalytic reactions

    Science.gov (United States)

    Imbihl, R.

    2010-05-01

    The electrochemical promotion of heterogeneously catalyzed reactions (EPOC) became feasible through the use of porous metal electrodes interfaced to a solid electrolyte. With the O 2- conducting yttrium stabilized zirconia (YSZ), the Na + conducting β″-Al 2O 3 (β-alumina), and several other types of solid electrolytes the EPOC effect has been demonstrated for about 100 reaction systems in studies conducted mainly in the mbar range. Surface science investigations showed that the physical basis for the EPOC effect lies in the electrochemically induced spillover of oxygen and alkali metal, respectively, onto the surface of the metal electrodes. For the catalytic promotion effect general concepts and mechanistic schemes were proposed but these concepts and schemes are largely speculative. Applying surface analytical tools to EPOC systems the proposed mechanistic schemes can be verified or invalidated. This report summarizes the progress which has been achieved in the mechanistic understanding of the EPOC effect.

  3. EXPERIENCES WITH IDEA PROMOTING INITIATIVES

    DEFF Research Database (Denmark)

    Gish, Liv

    2011-01-01

    In new product development a central activity is to provide new ideas. Over the last decades experiences with stimulating employee creativity and establishing idea promoting initiatives have been made in industrial practice. Such initiatives are often labeled Idea Management – a research field...... with a growing interest. In this paper I examine three different idea promoting initiatives carried out in Grundfos, a leading pump manufacturer. In the analysis I address what understandings of idea work are inscribed in the initiatives and what role these initiatives play in the organization with respect...... to idea work. Furthermore I look into what makes these initiatives ‘work’ or ‘not work’. The analysis builds on an in-depth case study made in Grundfos based on 40 interviews with R&D professionals and managers. The managerial implications of the study are that managers should be aware of what...

  4. South Asia's health promotion kaleidoscope.

    Science.gov (United States)

    Mukhopadhyay, Alok

    2007-01-01

    South Asia has 22 percent of the world's population but only 1.3 percent of the global income. Consequently 40 percent of the population is living in absolute poverty. However the health transition in some of its countries including India and Sri Lanka is a testimony to the fact that there are proven solutions to the problems of health and development within the region. The countries of the region have much in common, including a democratic political system, four major religions, a vibrant and living tradition of voluntarism and an extensive health infrastructure which is operating well below par. Despite the underlying unity, South Asia enjoys enormous cultural, linguistic and ethnic diversity. In this large, complex and vibrant region, health promotion is a challenging task, but it also holds the key to a dramatic change in the global health situation. Many of these solutions lie in wider areas of socio-political action. There are much needed shifts in the health promotion and development efforts, particularly in the area of poverty and social justice; gender inequity; population stabilisation; health and environment; control of communicable and non-communicable diseases; and urban health strategies. The principle of cooperation, partnership and intersectoral collaboration for health will be explored. Developing an appropriate, sustainable and people centred health and development strategy in the coming decades is an enormous challenge. There has been an attempt to focus on the emerging needs of the region, which call for health promotion, and involvement of civil society, private sector and the governments bestowed with the increased responsibility of ensuring health security for people. Strengthening the existing health systems, allocating adequate resources for health development and ensuring community participation are all prerequisites to the success of health promotion in the region.

  5. Mistakes the newly promoted make.

    Science.gov (United States)

    Kennedy, M M

    1999-01-01

    Many newly promoted managers make identical mistakes, most of them preventable. Physician executives who are thinking of taking on a bigger job should consider the following eight mistakes: (1) misreading top management's agenda, (2) micromanaging your successor, (3) not updating technical skills, (4) assuming customs and taboos are negotiable, (5) not rewriting your job description to mirror your new role, (6) not mentally moving from management to leadership, (7) not adjusting to relationships, and (8) not identifying a likely successor.

  6. Promoting university interaction with industry

    DEFF Research Database (Denmark)

    Vestergaard, Jakob

    The present working paper reports the results of a study of experiences with the agenda of promoting science-based economic growth in Finland. With the objective of gathering information on best practices, the overall research question of this study was dual: (1) Which institutions, rules and pol...... and policies have been introduced to stimulate university interaction with industry? (2) Which of these seem, so far, to have been the most successful ones?...

  7. Promoting university interaction with industry

    DEFF Research Database (Denmark)

    Vestergaard, Jakob

    The present working paper reports the results of a study of experiences with the agenda of promoting science-based economic growth in Finland. With the objective of gathering information on best practices, the overall research question of this study was dual: (1) Which institutions, rules...... and policies have been introduced to stimulate university interaction with industry? (2) Which of these seem, so far, to have been the most successful ones?...

  8. Health promotion for older Americans.

    OpenAIRE

    Heckler, M M

    1985-01-01

    As American lifespans increase, there is greater concern for the quality of those longer lives. The Department of Health and Human Services, through its many component agencies, has inaugurated a major initiative to promote health and fitness among older Americans to improve life quality and to reduce health care costs. The older population is a fertile ground for such an initiative, because studies indicate that the elderly are extremely health-conscious and very willing to adopt habits that...

  9. Pull Promotions and Channel Coordination

    OpenAIRE

    Eitan Gerstner; James D. Hess

    1995-01-01

    This paper recommends that manufacturers consider a pull price promotion as a coordination device in an independent channel of distribution. Uncoordinated decisions of both manufacturer and retailer to charge high prices can break down the effort to expand the market, resulting in losses to the channel as a whole. We show that manufacturers can enhance channel price coordination by designing pull price discounts that target price-conscious consumers. The increased price coordination improves ...

  10. Opportunities for administrators to promote disease management.

    Science.gov (United States)

    Kash, Bita A; Gamm, Larry D; Bolin, Jane Nelson; Peck, B Mitchell

    2005-01-01

    Studies of disease management (DM) have shown that patients who participate in such programs achieve better health status and make fewer emergency room visits. Private and government payers have recently increased their efforts to promote DM initiatives through financial incentives to healthcare providers. This article explores opportunities for administrators of health services organizations (HSO) to promote DM in the current political and economic environment. Our survey of professionals (DM leaders, physicians, and DM nurses) in six DM programs reveals these professionals' assessments of the key players and resources that they deem important to their respective DM programs. They view DM programs as heavily dependent on the support of physicians, nurses, and health plan leaders but relatively less so on the support of HSO administrators- a situation that may suggest opportunities for administrators to take on greater leadership in moving the HSO toward developing DM programs. Survey results also indicate a strong need for the integration of resources such as communication systems, electronic medical records, and DM reporting. Taken collectively, these needs suggest a number of strategies for the administrator to play a larger role in supporting the adoption and effective implementation of DM. In the article, we propose that DM programs can benefit substantially from an administrator who can demonstrate a thorough knowledge of DM-related government and private-payer initiatives and who has the ability to provide leadership to develop and implement viable DM programs. Valued contributions that the administrator should bring to the table include support of standardized DM processes, use of practice guidelines, and provision of pertinent information systems.

  11. Sport promotion and sales management

    Directory of Open Access Journals (Sweden)

    Zahra Aminiroshan

    2014-06-01

    Full Text Available At the beginning of third millennium, the world of sport has been experiencing new marketing techniques to introduce products and services. The purpose of this study was to compare advertising and sales promotion strategies, the effects of different strategies in sport production companies to retain or to gain market share among selected firms, which were active in Iran. The method of survey was descriptive – analytical and some questionnaires were used for collecting data in Likert scale. The validity of the questionnaire were estimated by interview with professors and exports in marketing and sport marketing and the reliability was assessed by using Cronbach's alpha (α= 0.89. Statistical population of the study includes Sport Goods-Producing companies in Iran (N= 180 and 122 firms formed the study sample. For testing the hypothesis, we have used Paired Samples T-Test. The analysis of findings showed that there was a meaningful difference between using advertising and sales promotion strategies. In general, we can say, there are some limited applications of using techniques and methods of sales promotion strategies in Iranian sport industry and methods of advertising. Consequently, regarding the intense competition among companies as well as fast growth of markets and fast changes in consumer’s behavior, identifying the best methods for corresponding relationship to customer would be required.

  12. Incentives to promote family planning.

    Science.gov (United States)

    Heil, Sarah H; Gaalema, Diann E; Herrmann, Evan S

    2012-11-01

    Over the past 60 years, population control has become an increasingly urgent issue worldwide as a growing population strains already limited resources. The use of financial incentives to promote family planning is an innovative approach that has potential to make a contribution to efforts to better manage population growth. This report reviews eight studies that examined the effect of incentives on family planning. Published studies that tested the impact of incentives to promote some aspect of family planning and included an appropriate control or comparison condition were reviewed. Incentives have been used to promote attendance at contraceptive education sessions, adoption and continuation of contraceptive methods, sterilization, and to limit family size. All but one of the eight studies reviewed reported positive outcomes, but weaknesses in study design and execution limit the strength of the conclusions that can be drawn. Review of this literature suggests that family planning behaviors, like other behaviors, are sensitive to incentives. Given the tremendous need for efficacious interventions in global efforts to manage population growth, further research on this topic using more rigorous experimental methods is warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Analysis of Promoters of Arabidopsis thaliana Divergent Gene Pair SERAT3;2 and IDH-III Shows SERAT3;2 Promoter is Nested Within the IDH-III Promoter.

    Science.gov (United States)

    Raipuria, Ritesh Kumar; Kumar, Vajinder; Guruprasad, Kadur Narayan; Bhat, Shripad Ramachandra

    2017-07-01

    Intergenic regions of divergent gene pairs show bidirectional promoter activity but whether regulatory sequences for gene expression in opposite directions are shared is not established. In this study, promoters of divergently arranged gene pair At4g35640-At4g35650 (SERAT3;2-IDH-III) of Arabidopsis thaliana were analyzed to identify overlapping regulatory regions. Both genes showed the highest expression in flower buds and flowers. 5' RACE experiments extended the intergenic region from 161 bp shown in TAIR annotation to 512 bp. GUS analysis of transgenic A. thaliana plants carrying the 691 bp fragment (512 bp intergenic region plus 5' UTR of both the genes) linked to uidA gene revealed that SERAT3;2 promoter drives gene expression in the tapetum, whereas IDH-III promoter functions specifically in microspores/pollen. Serial 5' deletion of the 691 bp fragment showed SERAT3;2 promoter extends up to -355 position, whereas IDH-III promoter encompasses the 512 bp intergenic region. In transgenics, uidA transcript levels were lower than native SERAT3;2 and IDH-III transcripts indicating presence of additional cis regulatory elements beyond the 691 bp fragment. The present study demonstrated for the first time occurrence of a nested promoter in plants and identified a novel bidirectional promoter capable of driving gene expression in tapetum and microspores/pollen.

  14. Engineered Promoters for Potent Transient Overexpression.

    Directory of Open Access Journals (Sweden)

    Dan Y Even

    Full Text Available The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional properties to each promoter. Earlier studies that examined the ability to modulate gene expression levels via the core promoter, led to the design of strong synthetic core promoters, which combine different core elements into a single core promoter. Here, we designed a new core promoter, termed super core promoter 3 (SCP3, which combines four core promoter elements (the TATA box, Inr, MTE and DPE into a single promoter that drives prolonged and potent gene expression. We analyzed the effect of core promoter architecture on the temporal dynamics of reporter gene expression by engineering EGFP expression vectors that are driven by distinct core promoters. We used live cell imaging and flow cytometric analyses in different human cell lines to demonstrate that SCPs, particularly the novel SCP3, drive unusually strong long-term EGFP expression. Importantly, this is the first demonstration of long-term expression in transiently transfected mammalian cells, indicating that engineered core promoters can provide a novel non-viral strategy for biotechnological as well as gene-therapy-related applications that require potent expression for extended time periods.

  15. Revealing Shifts and Diversity in Understandings of Self Access Language Learning

    Science.gov (United States)

    Adamson, John L.; Brown, Howard G.; Fujimoto-Adamson, Naoki

    2012-01-01

    This study has traced the growth of a new facility intended to promote independent language study in a Japanese university. The study traces this Self Access Learning Center (SALC) from its inception through the first two years of its development. It has revealed how key qualitative insights from an archive of semi-structured interviews,…

  16. VISTA Reveals the Secret of the Unicorn

    Science.gov (United States)

    2010-10-01

    A new infrared image from ESO's VISTA survey telescope reveals an extraordinary landscape of glowing tendrils of gas, dark clouds and young stars within the constellation of Monoceros (the Unicorn). This star-forming region, known as Monoceros R2, is embedded within a huge dark cloud. The region is almost completely obscured by interstellar dust when viewed in visible light, but is spectacular in the infrared. An active stellar nursery lies hidden inside a massive dark cloud rich in molecules and dust in the constellation of Monoceros. Although it appears close in the sky to the more familiar Orion Nebula it is actually almost twice as far from Earth, at a distance of about 2700 light-years. In visible light a grouping of massive hot stars creates a beautiful collection of reflection nebulae where the bluish starlight is scattered from parts of the dark, foggy outer layers of the molecular cloud. However, most of the new-born massive stars remain hidden as the thick interstellar dust strongly absorbs their ultraviolet and visible light. In this gorgeous infrared image taken from ESO's Paranal Observatory in northern Chile, the Visible and Infrared Survey Telescope for Astronomy (VISTA [1], eso0949) penetrates the dark curtain of cosmic dust and reveals in astonishing detail the folds, loops and filaments sculpted from the dusty interstellar matter by intense particle winds and the radiation emitted by hot young stars. "When I first saw this image I just said 'Wow!' I was amazed to see all the dust streamers so clearly around the Monoceros R2 cluster, as well as the jets from highly embedded young stellar objects. There is such a great wealth of exciting detail revealed in these VISTA images," says Jim Emerson, of Queen Mary, University of London and leader of the VISTA consortium. With its huge field of view, large mirror and sensitive camera, VISTA is ideal for obtaining deep, high quality infrared images of large areas of the sky, such as the Monoceros R2 region

  17. Natural selection promotes antigenic evolvability.

    Science.gov (United States)

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  18. Promoting collaboration in emergency medicine.

    Science.gov (United States)

    Nagraj, Shobhana; Harrison, Juliet; Hill, Lawrence; Bowker, Lesley; Lindqvist, Susanne

    2018-02-23

    Collaborative practice between paramedics and medical staff is essential for ensuring the safe handover of patients. Handover of care is a critical time in the patient journey, when effective communication and collaborative practice are central to promoting patient safety and to avoiding medical error. To encourage effective collaboration between paramedic and medical students, an innovative, practice-based simulation exercise, known as interprofessional clinical skills (ICS) was developed at the University of East Anglia, UK. Emphasising patient safety, effective handover of care and teamwork, within the context of emergency medicine, the ICS promotes collaborative practice amongst health care students through the use of high- and low-fidelity simulation, human factors and values-based practice. A total of 123 undergraduate students from paramedic (60) and medical backgrounds (63) took part in the ICS. Evaluation data were collected from all students through the completion of an internal feedback/satisfaction questionnaire with 13 statements and one open-ended comment box. The response rate for the questionnaire was 100%. Of the 123 students from paramedic and medical disciplines, 99% agreed or strongly agreed with the statement 'I enjoyed this session'. Students also felt that the ICS helped them to build mutual respect (98%), enhance understanding of roles (94%) and develop as collaborative practitioners (92%). Collaborative practice between paramedics and medical staff is essential CONCLUSION: The ICS is an innovative, enjoyable and meaningful intervention for promoting interprofessional collaborative practice between paramedic and medical students in a simulated practice setting. It encourages students to gain core training in clinical skills and patient safety, within a safe, supervised environment. © 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

  19. Pender's health promotion model in medical research.

    Science.gov (United States)

    Heydari, Abbas; Khorashadizadeh, Fatemeh

    2014-09-01

    This review shows how researchers use pander's health promotion model. We included all articles in which Pender's health promotion has been used for theoretical framework. Eligible articles were selected according to review of abstracts. Search was conducted using the electronic database from 1990 to 2012. Based on our search, 74 articles with various methodologies were relevant for review. Their aims of these studies were to predict effective factors/barriers in health promotion behaviours, to detect effects of intervention programme for improving health promotion behaviours, test the model, identify quality of life and health promotion behaviour, predict stage of change in related factors that affect health promotion behaviour, prevent the events that interfere with health promotion behaviour, develop another model similar to this model, compare this model with another model, determine the relationship of variables associated to health promotion behaviours.

  20. Health promotion capacity mapping: the Korean situation.

    Science.gov (United States)

    Nam, Eun Woo; Engelhardt, Katrin

    2007-06-01

    Ten years ago the Republic of Korea enacted the National Health Promotion Act, setting the stage for health promotion action in the country. A National Health Promotion Fund was established, financed through tobacco taxes, which is now one of the largest in the world. However, despite abundant financial resources, the infrastructure needed to plan, implement, coordinate and evaluate health promotion efforts is still underdeveloped. Currently, health promotion capacity mapping efforts are emerging in Korea. Two international capacity mapping tools have been used to assess the Korean situation, namely HP-Source and the Health Promotion Capacity Profile, which was developed prior to the sixth Global Conference of Health Promotion, held in August 2005 in Bangkok, Thailand. The article summarizes and discusses the results of the capacity mapping exercise, highlights its challenges and suggest ways to improve the accuracy of health promotion capacity mapping.

  1. Promoting Racial Equality in the Nursing Curriculum.

    Science.gov (United States)

    Foolchand, M. K.

    1995-01-01

    Equality in nursing education and the profession can be promoted in the following ways: a working policy on racism and equal opportunities; curriculum content that explores stereotypes, values, attitudes, and prejudices; and multicultural health research, education, and promotion. (SK)

  2. Trade promotion of irradiated food

    International Nuclear Information System (INIS)

    1986-10-01

    The meeting carried out by the Group was attended by invited specialists on legislation, marketing, consumer attitudes and industry interested in the application of food irradiation. The major objectives of the meeting were to identify barriers and constraints to trade in irradiated food and to recommend actions to be carried out by the Group to promote trade in such foods. The report of the meeting and selected 9 background papers used at the meeting are presented. A separate abstract was prepared for each of these papers

  3. PROMOTION OF MONTENEGRO THROUGH SPORTS

    Directory of Open Access Journals (Sweden)

    Dervis Selhanovic

    2011-03-01

    Full Text Available Modern social structures of Montenegro exist in a hypercomplex and very dynamic environment. The complexity and dynamism are, in part, a consequence of the general characteristics of the modern age, and in part, of the transition processes which have affected the Montenegrin society. The transition processes are taking place at all levels and subsystems of the community, and its sociological milieu is facing inevitability of adaptation and immersion in such processes and trends. There is no more positive promotion for a country than a sports promotion. There is no expert team, public relations agency or a lawyer than can win Montenegro a front page. We can talk about the importance of sports for the promotion of Montenegro from another point of view. If we compare the number of occurrences of names of the selected Montenegrin athletes with that of politicians, scientists or artists in different internet search engines, we will realize how great is the capacity of marketing potential that lies in Montenegrin sports and top athletes as representatives of the products and services with the label - Made in Montenegro. In addition to the success of the Montenegrin athletes globally, the promotion of Montenegro through sports is directly contributed by the major sporting events and contests, on account of which Montenegro presented itself not only as an excellent host and organizer, but also demonstrated the remarkable state and marketing capabilities and competencies. Reputation (image is not achieved overnight. Its semiological and symbolic charge includes all (visual, vocal, environmental, personal, active inputs, which need to be channelled and created. Indeed, continual work in creating and maintaining the image of Montenegro is a public relations function. With efficiently and professionally developed media and PR strategy, the modern state of Montenegro may expect to favourably position its image at the international scene, and to present its

  4. Phosphazene-promoted anionic polymerization

    KAUST Repository

    Zhao, Junpeng

    2014-01-01

    In the recent surge of metal-free polymerization techniques, phosphazene bases have shown their remarkable potential as organic promoters/catalysts for the anionic polymerization of various types of monomers. By complexation with the counterion (e.g. proton or lithium cation), phosphazene base significantly improve the nucleophilicity of the initiator/chain-end resulting in rapid and usually controlled anionic/quasi-anionic polymerization. In this review, we will introduce the general mechanism, i.e. in situ activation (of initiating sites) and polymerization, and summarize the applications of such a mechanism on macromolecular engineering toward functionalized polymers, block copolymers and complex macromolecular architectures.

  5. Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer

    International Nuclear Information System (INIS)

    Vulcano, Francesca; Milazzo, Luisa; Ciccarelli, Carmela; Eramo, Adriana; Sette, Giovanni; Mauro, Annunziata; Macioce, Giampiero; Martinelli, Andrea; La Torre, Renato; Casalbore, Patrizia; Hassan, Hamisa Jane

    2016-01-01

    Studies on the role of multipotent mesenchymal stromal cells (MSC) on tumor growth have reported both a tumor promoting and a suppressive effect. The aim of the present study was to determine the effect of MSC isolated from Wharton's jelly of umbilical cord (WJMSC) on lung cancer stem cells (LCSC) derived from human lung tumors: two adenocarcinomas (AC) and two squamous cell carcinomas (SCC). LCSC derived from SCC and AC expressed, to varying extents, the more relevant stem cell markers. The effect of WJMSC on LCSC was investigated in vitro using conditioned medium (WJ-CM): a proliferation increase in AC-LCSC was observed, with an increase in the ALDH+ and in the CD133+ cell population. By contrast, WJ-CM hampered the growth of SCC-LCSC, with an increase in the pre-G1 phase indicating the induction of apoptosis. Furthermore, the ALDH+ and CD133+ population was also reduced. In vivo, subcutaneous co-transplantation of AC-LCSC/WJMSC generated larger tumors than AC-LCSC alone, characterized by an increased percentage of CD133+ and CD166+ cells. By contrast, co-transplantation of WJMSC and SCC-LCSC did not affect the tumor size. Our results strongly suggest that WJMSC exert, both in vitro and in vivo, contrasting effects on LCSC derived from different lung tumor subtypes. - Highlights: • CM from WJMSC induces apoptosis of SCC-LCSC and reduction of ALDH+ and CD133+ cells. • Specificity of SCC-LCSC inhibition by WJ-CM is proved by the use of a CM from NHDF. • WJ-CM enhance AC-LCSC proliferation and increase CD133+ and ALDH+ cell fractions. • Coinjection of WJMSC with AC-LCSC increase tumor growth with SCC-LCSC has no effect.

  6. Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Vulcano, Francesca, E-mail: francesca.vulcano@iss.it [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome (Italy); Milazzo, Luisa, E-mail: luisa.milazzo@iss.it [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome (Italy); Ciccarelli, Carmela, E-mail: carmela.ciccarelli@univaq.it [Department of Biotechnological and Applied Clinical Sciences, University of L' Aquila (Italy); Eramo, Adriana, E-mail: adriana.eramo@iss.it [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome (Italy); Sette, Giovanni, E-mail: giovanni.sette@gmail.com [Regina Elena National Cancer Institute, Rome (Italy); Mauro, Annunziata, E-mail: amauro@unite.it [Faculty of Veterinary Medicine, University of Teramo (Italy); Macioce, Giampiero, E-mail: giampiero.macioce@iss.it [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome (Italy); Martinelli, Andrea, E-mail: andrea.martinelli@iss.it [Experimental Animal Welfare Sector of the Istituto Superiore di Sanità, Rome (Italy); La Torre, Renato, E-mail: renato.latorre@uniroma1.it [Department of Gynecology, Obstetrics and Urological Sciences, Sapienza University of Rome (Italy); Casalbore, Patrizia, E-mail: patrizia.casalbore@cnr.it [Institute of Cell Biology and Neurobiology, National Research Council, Rome (Italy); Hassan, Hamisa Jane, E-mail: jane.hassan@iss.it [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome (Italy); and others

    2016-07-15

    Studies on the role of multipotent mesenchymal stromal cells (MSC) on tumor growth have reported both a tumor promoting and a suppressive effect. The aim of the present study was to determine the effect of MSC isolated from Wharton's jelly of umbilical cord (WJMSC) on lung cancer stem cells (LCSC) derived from human lung tumors: two adenocarcinomas (AC) and two squamous cell carcinomas (SCC). LCSC derived from SCC and AC expressed, to varying extents, the more relevant stem cell markers. The effect of WJMSC on LCSC was investigated in vitro using conditioned medium (WJ-CM): a proliferation increase in AC-LCSC was observed, with an increase in the ALDH+ and in the CD133+ cell population. By contrast, WJ-CM hampered the growth of SCC-LCSC, with an increase in the pre-G1 phase indicating the induction of apoptosis. Furthermore, the ALDH+ and CD133+ population was also reduced. In vivo, subcutaneous co-transplantation of AC-LCSC/WJMSC generated larger tumors than AC-LCSC alone, characterized by an increased percentage of CD133+ and CD166+ cells. By contrast, co-transplantation of WJMSC and SCC-LCSC did not affect the tumor size. Our results strongly suggest that WJMSC exert, both in vitro and in vivo, contrasting effects on LCSC derived from different lung tumor subtypes. - Highlights: • CM from WJMSC induces apoptosis of SCC-LCSC and reduction of ALDH+ and CD133+ cells. • Specificity of SCC-LCSC inhibition by WJ-CM is proved by the use of a CM from NHDF. • WJ-CM enhance AC-LCSC proliferation and increase CD133+ and ALDH+ cell fractions. • Coinjection of WJMSC with AC-LCSC increase tumor growth with SCC-LCSC has no effect.

  7. A novel BDNF gene promoter directs expression to skeletal muscle

    Directory of Open Access Journals (Sweden)

    Heinrich Gerhard

    2003-06-01

    Full Text Available Abstract Background Cell-specific expression of the gene that encodes brain-derived neurotrophic factor (BDNF is required for the normal development of peripheral sensory neurons and efficient synaptic transmission in the mature central and peripheral nervous system. The control of BDNF gene expression involves multiple tissue and cell-specific promoters that are differentially regulated. The molecular mechanisms that are responsible for tissue and cell-specific expression of these promoters are still incompletely understood. Results The cloning and analysis of three additional zebrafish (Danio rerio BDNF gene exons and two associated promoters, is reported. Among them are two exons that generate a novel tripartite mature transcript. The exons were located on the transcription unit, whose overall organization was determined by cloning, Southern blot hybridization and sequence analysis, and compared with the pufferfish (Fugu rubripes and mammalian BDNF loci, revealing a conserved but more compact organization. Structural and functional analysis of the exons, their adjacent promoters and 5' flanks, showed that they are expressed cell-specifically. The promoter associated with the 5' exon of the tripartite transcript is GC-rich, TATA-less and the 5' flank adjacent to it contains multiple Sp1, Mef2, and AP1 elements. A fusion gene containing the promoter and 1.5 KB of 5' flank is directed exclusively to skeletal muscle of transiently transfected embryos. The second promoter, whose associated 5' exon contains a 25-nucleotide segment of identity with a mammalian BDNF gene exon, was transiently expressed in yolk of the early embryo. RT-PCR analysis of total RNA from whole juvenile fish and adult female skeletal muscle revealed tissue-specific expression of the 5' exons but the novel exon could not be detected even after two rounds of nested PCR. Conclusion The zebrafish BDNF gene is as complex as the mammalian gene yet much more compact. Its exons are

  8. Promotion Signal: Proxy for a Price Cut?

    OpenAIRE

    Inman, J Jeffrey; McAlister, Leigh; Hoyer, Wayne D

    1990-01-01

    Evidence suggests that some consumers react to promotion signals without considering relative price information. We adopt Petty and Cacioppo's Elaboration Likelihood Model (ELM) to explain this behavior in terms of the ELM's peripheral route to pursuasion in which the promotion signal is taken as a cue for a price cut. Experimental results show that low need for cognition individuals react to the simple presence of a promotion signal whether or not the price of the promoted brand is reduced, ...

  9. Sales promotion strategies in Procter&Gamble

    OpenAIRE

    Šebesta, Miroslav

    2017-01-01

    The thesis gives comprehensive overview on the topic of sales promotions. The special focus is devoted to activities of Procter & Gamble on the Czech market. With increasing importance of sales promotions on the Czech market, the thesis aims to introduce main academic findings concerning sales promotions and test them on brands of Procter & Gamble. The next goal is to find out whether sales promotion strategies of Procter & Gamble provide a competitive advantage for the company on the Czech m...

  10. Adhesion rings surround invadopodia and promote maturation

    Directory of Open Access Journals (Sweden)

    Kevin M. Branch

    2012-06-01

    Invasion and metastasis are aggressive cancer phenotypes that are highly related to the ability of cancer cells to degrade extracellular matrix (ECM. At the cellular level, specialized actin-rich structures called invadopodia mediate focal matrix degradation by serving as exocytic sites for ECM-degrading proteinases. Adhesion signaling is likely to be a critical regulatory input to invadopodia, but the mechanism and location of such adhesion signaling events are poorly understood. Here, we report that adhesion rings surround invadopodia shortly after formation and correlate strongly with invadopodium activity on a cell-by-cell basis. By contrast, there was little correlation of focal adhesion number or size with cellular invadopodium activity. Prevention of adhesion ring formation by inhibition of RGD-binding integrins or knockdown (KD of integrin-linked kinase (ILK reduced the number of ECM-degrading invadopodia and reduced recruitment of IQGAP to invadopodium actin puncta. Furthermore, live cell imaging revealed that the rate of extracellular MT1-MMP accumulation at invadopodia was greatly reduced in both integrin-inhibited and ILK-KD cells. Conversely, KD of MT1-MMP reduced invadopodium activity and dynamics but not the number of adhesion-ringed invadopodia. These results suggest a model in which adhesion rings are recruited to invadopodia shortly after formation and promote invadopodium maturation by enhancing proteinase secretion. Since adhesion rings are a defining characteristic of podosomes, similar structures formed by normal cells, our data also suggest further similarities between invadopodia and podosomes.

  11. SOCIAL NETWORKS - KEY TOOL USED BY EMPLOYEES FOR PROMOTING THE IMAGE OF BUCHAREST MUSEUMS

    OpenAIRE

    Ruxandra-Irina POPESCU; Razvan-Andrei CORBOS; Laura MINA-RAIU; Gianina Nicoleta STAN

    2014-01-01

    Social networks are a strong instrument for promoting for free the image of a product, service or organization. The present study is aimed at determining the impact of social networks on attracting tourists to big museums of Bucharest city. Thus, the research carried out reveals that museum employees use social platforms for promoting the image of the institutions they represent, posting several information about (1) permanent or temporary exhibitions, (2) additional services (movie evenings,...

  12. The 'revealed preferences' theory: Assumptions and conjectures

    International Nuclear Information System (INIS)

    Green, C.H.

    1983-01-01

    Being kind of intuitive psychology the 'Revealed-Preferences'- theory based approaches towards determining the acceptable risks are a useful method for the generation of hypotheses. In view of the fact that reliability engineering develops faster than methods for the determination of reliability aims the Revealed-Preferences approach is a necessary preliminary help. Some of the assumptions on which the 'Revealed-Preferences' theory is based will be identified and analysed and afterwards compared with experimentally obtained results. (orig./DG) [de

  13. 5 CFR 532.407 - Promotion.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Promotion. 532.407 Section 532.407 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Pay Administration § 532.407 Promotion. (a) An employee who is promoted is entitled to be paid at the lowest...

  14. 29 CFR 541.503 - Promotion work.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Promotion work. 541.503 Section 541.503 Labor Regulations... Outside Sales Employees § 541.503 Promotion work. (a) Promotion work is one type of activity often performed by persons who make sales, which may or may not be exempt outside sales work, depending upon the...

  15. 7 CFR 1212.20 - Promotion.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion, Consumer Education, and Industry Information Order Definitions § 1212.20 Promotion. “Promotion” means any...

  16. 48 CFR 13.104 - Promoting competition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Promoting competition. 13... METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Procedures 13.104 Promoting competition. The contracting officer must promote competition to the maximum extent practicable to obtain supplies and services...

  17. Do Promotions Benefit Manufacturers, Retailers or Both?

    NARCIS (Netherlands)

    S. Srinivasan (Shuba); K.H. Pauwels (Koen); D.M. Hanssens (Dominique); M.G. Dekimpe (Marnik)

    2002-01-01

    textabstractWhile there has been strong managerial and academic interest in price promotions, much of the focus has been on the impact of such promotions on category sales, brand sales and brand choice. In contrast, little is known about the long-run impact of price promotions on manufacturer and

  18. Culture Connection Project: promoting multiculturalism in elementary schools.

    Science.gov (United States)

    Matuk, Lucia Yiu; Ruggirello, Tina

    2007-01-01

    To promote multiculturalism among grade school students through drama education. Grade 3-6 students (N = 665) from 6 targeted schools including lead-class students (n = 158) representing each school. Elementary schools in Windsor-Essex County, Ontario, Canada. In this non-experimental design study, group discussions conducted with each lead class to explore students' understanding of multiculturalism were developed into an interactive drama performance and performed for all grades 3-6 students in their respective schools. A follow-up drama workshop was offered to each lead class one week after the drama performance. All students completed a 7-item questionnaire before and after the drama performance and after the drama workshop. Pre-test and post-test data collected were analyzed using T-test and ANOVA to determine the effects of drama education on students' attitudes toward multiculturalism. Statistical analysis at 0.05 significance level revealed that both the performance and the drama workshop heightened students' awareness of racism, and instilled cultural respect through "talking with others", "accepting others", and "believing that they can make a difference" in multiculturalism promotion. Drama education was an effective experiential tool for promoting multiculturalism in a school setting. The key to promoting inter-racial harmony is to respect and accept individual differences and to broaden the social determinants of health by providing culture safety care.

  19. Community capacity building and health promotion in a globalized world.

    Science.gov (United States)

    Raeburn, John; Akerman, Marco; Chuengsatiansup, Komatra; Mejia, Fanny; Oladepo, Oladimeji

    2006-12-01

    In this paper, community capacity building (CCB) is seen as part of a long-standing health promotion tradition involving community action in health promotion. The conceptual context of the term CCB is presented, and compared with other community approaches. The usage of the term is variable. It is submitted that its common features are (i) the concepts of capacity and empowerment (versus disease and deficiency), (ii) bottom-up, community-determined agendas and actions and (iii) processes for developing competence. A brief literature review looks at some of the main contributions from the 1990 s on, which reveal an emphasis on building competencies, the measurement of community capacity and the attempt to break CCB down into operational components. Academic research on the impact of CCB on health is lacking, but multiple case studies documented in the 'grey literature' suggest CCB is highly effective, as does research in related areas, such as community empowerment. Five contemporary case studies submitted by the contributing authors show both the range and efficacy of CCB applications. The concluding synthesis and recommendations say that what is needed for health promotion in a globalized world is a balance between global macro (policy, regulatory, etc.) actions and those of the human and local scale represented by CCB. It is concluded that action centred on empowered and capable communities, in synergistic collaboration with other key players, may be the most powerful instrument available for the future of health promotion in a globalized world.

  20. Condom ads promote illicit sex.

    Science.gov (United States)

    Kippley, J F

    1994-01-01

    Written in 1987, this opinion was republished in the wake of US President Bill Clinton's AIDS prevention media campaign promoting condom use which began January 1994, targeted at young adults aged 18-25. The author staunchly opposes condom use even though he admits that people do not consider abstinence from sex to be a serious option for the prevention of HIV/STD infection. He believes that there is no moral use of sex with a condom and that condoms have always been a sign of immorality, be it prostitution, adultery, fornication, or marital contraception. Likewise, the author laments the success enjoyed by Planned Parenthood in achieving the social acceptance of marital contraception and sex outside of marriage. The complete social acceptance of homosexual activity, however, remains to be achieved. Magazines, newspapers, and television receive income in exchange for publishing or airing advertisements. Finding offensive advertisements which promote the use of condoms against HIV infection, the author recommends writing letters of complaint to the responsible media sources. If the television stations or publications in question continue to advertise condoms to the public, stop watching them or end one's subscriptions to the particular printed media. Such action taken collectively among many individuals will reduce product sales and income, and potentially sway corporate policy against condom ads.

  1. The epidemiology of drug promotion.

    Science.gov (United States)

    Silverman, M

    1977-01-01

    A survey was conducted on the promotion of 28 prescription drugs in the form of 40 different products marketed in the United States and Latin America by 23 multinational pharmaceutical companies. Striking differences were found in the manner in which the identical drug, marketed by the identical company or its foreign affiliate, was described to physicians in the United States and to physicians in Latin America. In the United States, the listed indications were usually few in number, while the contraindications, warnings, and potential adverse reactions were given in extensive detail. In Latin America, the listed indications were far more numerous, while the hazards were usually minimized, glossed over, or totally ignored. The differences were not simply between the United States on the one hand and all the Latin American countries on the other. There were substantial differences within Latin America, with the same global company telling one story in Mexico, another in Central America, a third in Ecuador and Colombia, and yet another in Brazil. The companies have sought to defend these practices by contending that they are not breaking any Latin American laws. In some countries, however, such promotion is in clear violation of the law. The corporate ethics and social responsibilities concerned here call for examination and action.

  2. International energy-promotion-activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Comprehensive promotion of energy and environmental measures are demanded in order to realize improvement in energy demand/supply structures in developing countries where increase in energy demand is anticipated. To achieve this goal, technical transfer related to energy saving technologies and clean coal as well as international energy promotion activities are implemented in China and Indonesia since fiscal 1993. In the field of energy saving, model operations are performed to improve efficiency in such energy consuming fields as steel making, power generation, and oil refining, in addition to cooperation in structuring databases and establishing master plans. In the clean coal field, model operations are conducted to reduce environmental load in coal utilizing areas, in addition to cooperation in establishing master plans for coal utilization. This paper describes feasibility studies on environmentally harmonious coal utilization systems in developing countries, assistance to introduction thereof, and joint verification operations. To rationalize international energy usage, basic surveys on energy utilization efficiency improvement and model operations are carried out mainly in the Asia-Pacific countries.

  3. Do online gossipers promote brands?

    Science.gov (United States)

    Okazaki, Shintaro; Rubio, Natalia; Campo, Sara

    2013-02-01

    Online gossip has been recognized as small talk on social networking sites (SNSs) that influences consumer behavior, but little attention has been paid to its role. This study makes three theoretical predictions: (a) propensity to gossip online leads to greater information value, entertainment value, and friendship value; (b) upon exposure to a high-involvement product, online gossipers are more willing to spread such information through electronic word-of-mouth (eWOM) in search of prestige or fame as a knowledge expert; and (c) this tendency will be more pronounced when they are connected with strong ties (rather than weak ties) and belong to a large network (rather than a small network). An experimental survey was conducted with a scenario method. In total, 818 general consumers participated in the survey. A multivariate analysis of variance (ANOVA) provides empirical support for prediction (1). With regard to predictions (2) and (3), a series of three-way and two-way between-subjective ANOVAs were performed. When a high-involvement product is promoted, gossipers, rather than nongossipers, are more willing to participate in eWOM on an SNS. Furthermore, a significant interaction effect indicates that online gossipers' willingness to particiapte in eWOM would be more pronounced if they belonged to a large network rather than a small network. However, when a low-involvement product is promoted, no interaction effect is found between online gossip and network size. In closing, theoretical and managerial implications are discussed, while important limitations are recognized.

  4. Promoting breast screening in Glasgow.

    Science.gov (United States)

    Cohen, L; Dobson, H; McGuire, F

    2000-03-01

    To establish whether there is a role for advertising in the promotion of the Breast Screening Programme and what the role of advertising might be. Four hundred and sixty questionnaires were completed by women attending their breast screening appointment. Quantitative and qualitative data were collected from the static unit at Calder Street and the mobile unit in Govan. The advertising (budget 30,000 Pounds) campaign ran over an eight week period in the Govan, Paisley Road West and Cardonald areas of Glasgow. Media used included press advertising, The Glasgow Underground, adshells, bus advertising (interiors) and poster distribution via local outlets. Forty-two per cent of the sample were aware of the campaign. Ninety-seven per cent liked the campaign images. Eighty eight per cent felt that breast screening should be advertised more. Screening uptake increased in the areas covered by the advertising campaign. Govan -58%-71% and Ibrox (Paisley Road West and Cardonald) -59%-61%. Women were very supportive of the role of advertising for the Breast Screening Programme. In particular they found the campaign images and messages reassuring, supportive and credible. Their views suggest that the role of advertising should be: To raise awareness of the service To make women more conscious of the benefits of screening To change public perceptions of the screening process However, it is recognised that a fully integrated approach is required for the promotion of the service to account for the improvement in uptake, as advertising cannot be expected to work in isolation.

  5. Triad pattern algorithm for predicting strong promoter candidates in bacterial genomes

    Directory of Open Access Journals (Sweden)

    Sakanyan Vehary

    2008-05-01

    Full Text Available Abstract Background Bacterial promoters, which increase the efficiency of gene expression, differ from other promoters by several characteristics. This difference, not yet widely exploited in bioinformatics, looks promising for the development of relevant computational tools to search for strong promoters in bacterial genomes. Results We describe a new triad pattern algorithm that predicts strong promoter candidates in annotated bacterial genomes by matching specific patterns for the group I σ70 factors of Escherichia coli RNA polymerase. It detects promoter-specific motifs by consecutively matching three patterns, consisting of an UP-element, required for interaction with the α subunit, and then optimally-separated patterns of -35 and -10 boxes, required for interaction with the σ70 subunit of RNA polymerase. Analysis of 43 bacterial genomes revealed that the frequency of candidate sequences depends on the A+T content of the DNA under examination. The accuracy of in silico prediction was experimentally validated for the genome of a hyperthermophilic bacterium, Thermotoga maritima, by applying a cell-free expression assay using the predicted strong promoters. In this organism, the strong promoters govern genes for translation, energy metabolism, transport, cell movement, and other as-yet unidentified functions. Conclusion The triad pattern algorithm developed for predicting strong bacterial promoters is well suited for analyzing bacterial genomes with an A+T content of less than 62%. This computational tool opens new prospects for investigating global gene expression, and individual strong promoters in bacteria of medical and/or economic significance.

  6. A novel baculovirus-derived promoter with high activity in the baculovirus expression system.

    Science.gov (United States)

    Martínez-Solís, María; Gómez-Sebastián, Silvia; Escribano, José M; Jakubowska, Agata K; Herrero, Salvador

    2016-01-01

    The baculovirus expression vector system (BEVS) has been widely used to produce a large number of recombinant proteins, and is becoming one of the most powerful, robust, and cost-effective systems for the production of eukaryotic proteins. Nevertheless, as in any other protein expression system, it is important to improve the production capabilities of this vector. The orf46 viral gene was identified among the most highly abundant sequences in the transcriptome of Spodoptera exigua larvae infected with its native baculovirus, the S. exigua multiple nucleopolyhedrovirus (SeMNPV). Different sequences upstream of the orf46 gene were cloned, and their promoter activities were tested by the expression of the GFP reporter gene using the Autographa californica nucleopolyhedrovirus (AcMNPV) vector system in different insect cell lines (Sf21, Se301, and Hi5) and in larvae from S. exigua and Trichoplusia ni. The strongest promoter activity was defined by a 120 nt sequence upstream of the ATG start codon for the orf46 gene. On average, GFP expression under this new promoter was more than two fold higher than the expression obtained with the standard polyhedrin (polh) promoter. Additionally, the orf46 promoter was also tested in combination with the polh promoter, revealing an additive effect over the polh promoter activity. In conclusion, this new characterized promoter represents an excellent alternative to the most commonly used baculovirus promoters for the efficient expression of recombinant proteins using the BEVS.

  7. A novel baculovirus-derived promoter with high activity in the baculovirus expression system

    Directory of Open Access Journals (Sweden)

    María Martínez-Solís

    2016-06-01

    Full Text Available The baculovirus expression vector system (BEVS has been widely used to produce a large number of recombinant proteins, and is becoming one of the most powerful, robust, and cost-effective systems for the production of eukaryotic proteins. Nevertheless, as in any other protein expression system, it is important to improve the production capabilities of this vector. The orf46 viral gene was identified among the most highly abundant sequences in the transcriptome of Spodoptera exigua larvae infected with its native baculovirus, the S. exigua multiple nucleopolyhedrovirus (SeMNPV. Different sequences upstream of the orf46 gene were cloned, and their promoter activities were tested by the expression of the GFP reporter gene using the Autographa californica nucleopolyhedrovirus (AcMNPV vector system in different insect cell lines (Sf21, Se301, and Hi5 and in larvae from S. exigua and Trichoplusia ni. The strongest promoter activity was defined by a 120 nt sequence upstream of the ATG start codon for the orf46 gene. On average, GFP expression under this new promoter was more than two fold higher than the expression obtained with the standard polyhedrin (polh promoter. Additionally, the orf46 promoter was also tested in combination with the polh promoter, revealing an additive effect over the polh promoter activity. In conclusion, this new characterized promoter represents an excellent alternative to the most commonly used baculovirus promoters for the efficient expression of recombinant proteins using the BEVS.

  8. Methylation of ras association domain protein 10 (RASSF10) promoter negative association with the survival of gastric cancer.

    Science.gov (United States)

    Deng, Jingyu; Liang, Han; Ying, Guoguang; Li, Haixin; Xie, Xingming; Yu, Jun; Fan, Daiming; Hao, Xishan

    2014-01-01

    The present study was conducted to elucidate the prognostic prediction value of the methylation of the RASSF10 promoter in gastric cancer (GC). A total of 300 patients with GC revealed the methylation degrees of the DNA of the RASSF10 promoter. Methylation-specific PCR (MSP) analysis was performed to qualitatively detect the methylated degrees of the DNA of the RASSF10 promoter of 300 patients with GC. Associations between molecular, clinicopathological and survival data were analyzed. The protein and mRNA expressions of RASSF10 in GC tissues were lower than those in normal gastric mucosal tissues. In the MSP analysis cohort, patients with methylated RASSF10 promoter exhibited significantly shorter median OS than those with unmethylated RASSF10 promoter (P promoter was an independent predictor of the survival of patients with GC. The methylation of the RASSF10 promoter could be applied for the clinical prediction of the prognosis of GC.

  9. Health promotion viewed as processes of subjectification in the education of Danish Social and Healthcare Workers

    DEFF Research Database (Denmark)

    Lehn-Christiansen, Sine

    2011-01-01

    This article explores how health promotion is practised within a specific educational setting: the Danish Social and Health Education Programme. Here, health promotion is formally conceived as a strategy aimed at citizens - not at the students themselves. However, the students are generally...... perceived as being incapable of taking care of their own health and therefore also as being too far from the role model figure inherent in the discourse of professional health promotion work. Practices targeting students' physical health are induced both in- and outside the curriculum. Based on empirical...... analysis and post-structuralist theory, the article explores the processes of subjectification that result from the practices of health promotion within this particular educational setting. The article reveals how health promotion is transformed into an educational technology and is thus utilised to solve...

  10. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells

    International Nuclear Information System (INIS)

    Oka, Naoki; Soeda, Akio; Inagaki, Akihito; Onodera, Masafumi; Maruyama, Hidekazu; Hara, Akira; Kunisada, Takahiro; Mori, Hideki; Iwama, Toru

    2007-01-01

    There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche

  11. PAF promotes stemness and radioresistance of glioma stem cells.

    Science.gov (United States)

    Ong, Derrick Sek Tong; Hu, Baoli; Ho, Yan Wing; Sauvé, Charles-Etienne Gabriel; Bristow, Christopher A; Wang, Qianghu; Multani, Asha S; Chen, Peiwen; Nezi, Luigi; Jiang, Shan; Gorman, Claire Elizabeth; Monasterio, Marta Moreno; Koul, Dimpy; Marchesini, Matteo; Colla, Simona; Jin, Eun-Jung; Sulman, Erik P; Spring, Denise J; Yung, Wai-Kwan Alfred; Verhaak, Roel G W; Chin, Lynda; Wang, Y Alan; DePinho, Ronald A

    2017-10-24

    An integrated genomic and functional analysis to elucidate DNA damage signaling factors promoting self-renewal of glioma stem cells (GSCs) identified proliferating cell nuclear antigen (PCNA)-associated factor ( PAF ) up-regulation in glioblastoma. PAF is preferentially overexpressed in GSCs. Its depletion impairs maintenance of self-renewal without promoting differentiation and reduces tumor-initiating cell frequency. Combined transcriptomic and metabolomic analyses revealed that PAF supports GSC maintenance, in part, by influencing DNA replication and pyrimidine metabolism pathways. PAF interacts with PCNA and regulates PCNA-associated DNA translesion synthesis (TLS); consequently, PAF depletion in combination with radiation generated fewer tumorspheres compared with radiation alone. Correspondingly, pharmacological impairment of DNA replication and TLS phenocopied the effect of PAF depletion in compromising GSC self-renewal and radioresistance, providing preclinical proof of principle that combined TLS inhibition and radiation therapy may be a viable therapeutic option in the treatment of glioblastoma multiforme (GBM). Published under the PNAS license.

  12. Pochonia chlamydosporia promotes the growth of tomato and lettuce plants

    Directory of Open Access Journals (Sweden)

    Rosangela Dallemole-Giaretta

    2015-10-01

    Full Text Available The fungus Pochonia chlamydosporia is one of the most studied biological agents used to control plant-parasitic nematodes. This study found that the isolates Pc-3, Pc-10 and Pc-19 of this fungus promote the growth of tomato and lettuce seedlings. The isolate Pc-19 colonized the rhizoplane of tomato seedlings in only 15 days and produced a large quantity of chlamydospores. This isolate was able to use cellulose as a carbon source, in addition to glucose and sucrose. Scanning electron microscopy (SEM revealed that hyphae of the P. chlamydosporia isolate Pc-10 penetrated the epidermal cells of the tomato roots. These three P. chlamydosporia isolates promote the growth of tomato and lettuce.

  13. Alterations in HIV-1 LTR promoter activity during AIDS progression

    International Nuclear Information System (INIS)

    Hiebenthal-Millow, Kirsten; Greenough, Thomas C.; Bretttler, Doreen B.; Schindler, Michael; Wildum, Steffen; Sullivan, John L.; Kirchhoff, Frank

    2003-01-01

    HIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression

  14. Synthetic promoter libraries- tuning of gene expression

    DEFF Research Database (Denmark)

    Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal

    2006-01-01

    The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene...... be met by using promoter libraries. This approach generally consists of inserting a library of promoters in front of the gene to be studied, whereby the individual promoters might deviate either in their spacer sequences or bear slight deviations from the consensus sequence of a vegetative promoter. Here......, we describe the two different methods for obtaining promoter libraries and compare their applicability....

  15. Location and coordination of promoter atoms in Co- and Ni-promoted MoS2-based hydrotreating catalysts

    DEFF Research Database (Denmark)

    Lauritsen, Jeppe V.; Kibsgaard, Jakob; Olesen, Georg H.

    2007-01-01

    In this study, we used scanning tunneling microscopy (STM) and density functional theory (DFT) to investigate the atomic-scale structure of the active Co- or Ni-promoted MoS2 nanoclusters in hydrotreating catalysts. Co-promoted MoS2 nanoclusters (Co–Mo–S) are found to adopt a hexagonal shape...... on the nanocluster size. Larger clusters (type A) are structurally similar to Co–Mo–S exposing fully Ni-substituted (1010) edges with a 50% S coverage. Smaller clusters (type B) show dodecagonal shapes terminated by three different edges, all of which contain Ni-promoter atoms fully or partially substituting the Mo......, with Co atoms preferentially located at (1010) edges with a 50% sulfur coverage. The first atom-resolved STM images of the Ni-promoted MoS2 nanoclusters (Ni–Mo–S) reveal that the addition of Ni also leads to truncated morphologies, but the degree of truncation and the Ni sites are observed to depend...

  16. Experimental evolution reveals hidden diversity in evolutionary pathways.

    Science.gov (United States)

    Lind, Peter A; Farr, Andrew D; Rainey, Paul B

    2015-03-25

    Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans.

  17. A composite method based on formal grammar and DNA structural features in detecting human polymerase II promoter region.

    Directory of Open Access Journals (Sweden)

    Sutapa Datta

    Full Text Available An important step in understanding gene regulation is to identify the promoter regions where the transcription factor binding takes place. Predicting a promoter region de novo has been a theoretical goal for many researchers for a long time. There exists a number of in silico methods to predict the promoter region de novo but most of these methods are still suffering from various shortcomings, a major one being the selection of appropriate features of promoter region distinguishing them from non-promoters. In this communication, we have proposed a new composite method that predicts promoter sequences based on the interrelationship between structural profiles of DNA and primary sequence elements of the promoter regions. We have shown that a Context Free Grammar (CFG can formalize the relationships between different primary sequence features and by utilizing the CFG, we demonstrate that an efficient parser can be constructed for extracting these relationships from DNA sequences to distinguish the true promoter sequences from non-promoter sequences. Along with CFG, we have extracted the structural features of the promoter region to improve upon the efficiency of our prediction system. Extensive experiments performed on different datasets reveals that our method is effective in predicting promoter sequences on a genome-wide scale and performs satisfactorily as compared to other promoter prediction techniques.

  18. A Composite Method Based on Formal Grammar and DNA Structural Features in Detecting Human Polymerase II Promoter Region

    Science.gov (United States)

    Datta, Sutapa; Mukhopadhyay, Subhasis

    2013-01-01

    An important step in understanding gene regulation is to identify the promoter regions where the transcription factor binding takes place. Predicting a promoter region de novo has been a theoretical goal for many researchers for a long time. There exists a number of in silico methods to predict the promoter region de novo but most of these methods are still suffering from various shortcomings, a major one being the selection of appropriate features of promoter region distinguishing them from non-promoters. In this communication, we have proposed a new composite method that predicts promoter sequences based on the interrelationship between structural profiles of DNA and primary sequence elements of the promoter regions. We have shown that a Context Free Grammar (CFG) can formalize the relationships between different primary sequence features and by utilizing the CFG, we demonstrate that an efficient parser can be constructed for extracting these relationships from DNA sequences to distinguish the true promoter sequences from non-promoter sequences. Along with CFG, we have extracted the structural features of the promoter region to improve upon the efficiency of our prediction system. Extensive experiments performed on different datasets reveals that our method is effective in predicting promoter sequences on a genome-wide scale and performs satisfactorily as compared to other promoter prediction techniques. PMID:23437045

  19. Revealing Conceptual Understanding of International Business

    Science.gov (United States)

    Ashley, Sue; Schaap, Harmen; de Bruijn, Elly

    2017-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students' conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual understanding in higher education. Essays and concept…

  20. REVEAL: Software Documentation and Platform Migration

    Science.gov (United States)

    Wilson, Michael A.; Veibell, Victoir T.; Freudinger, Lawrence C.

    2008-01-01

    The Research Environment for Vehicle Embedded Analysis on Linux (REVEAL) is reconfigurable data acquisition software designed for network-distributed test and measurement applications. In development since 2001, it has been successfully demonstrated in support of a number of actual missions within NASA s Suborbital Science Program. Improvements to software configuration control were needed to properly support both an ongoing transition to operational status and continued evolution of REVEAL capabilities. For this reason the project described in this report targets REVEAL software source documentation and deployment of the software on a small set of hardware platforms different from what is currently used in the baseline system implementation. This report specifically describes the actions taken over a ten week period by two undergraduate student interns and serves as a final report for that internship. The topics discussed include: the documentation of REVEAL source code; the migration of REVEAL to other platforms; and an end-to-end field test that successfully validates the efforts.

  1. Promoting sustainability through green chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Kirchhoff, Mary M. [American Chemical Society, 1155 Sixteenth Street, NW, Washington, DC 20036 (United States)

    2005-06-15

    Green chemistry is an important tool in achieving sustainability. The implementation of green chemistry, the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances, is essential if the expanding global population is to enjoy an increased standard of living without having a negative impact on the health of the planet. Cleaner technologies will allow the chemical enterprise to provide society with the goods and services on which it depends in an environmentally responsible manner. Green chemistry provides solutions to such global challenges as climate change, sustainable agriculture, energy, toxics in the environment, and the depletion of natural resources. A collaborative effort by industry, academia, and government is needed to promote the adoption of the green chemistry technologies necessary to achieve a sustainable society.

  2. How Bureaucracy Promotes Inclusive Organizing

    DEFF Research Database (Denmark)

    Holck, Lotte

    and informality struggle with membership perceptions of partiality and unfairness on the basis of ethnicity and professional background, then the bureaucratic structured organization characterized by structural stability and formality is more successful in generating the necessary membership perception fairness......Diversity literature in general and Feminist in particular have long promoted alternatives to bureaucracy on the premise that this form of governance is far from gender- and race-neutral, and that inclusive organizing necessitate a flatter, decentralized and more ‘organic’ set-up (Ferguson 1984......, Martin P.Y 1987, Ashcraft 2001, 2006, 2013, Acker 1990, Ghorashi & Sabelis 2012, Dai 2014). My ethnographic research in two case organizations both championed for their diversity work in a Danish context, shows a different pattern: While the organization characterized by structural flexibility...

  3. Promoting Teen Mothers' Mental Health.

    Science.gov (United States)

    Freed, Patricia; SmithBattle, Lee

    2016-01-01

    In this second article in a two-part series, we call for the integration of strengths-based and trauma-informed care into services for teen mothers. Nurses working with teen mothers in health clinics, schools and home visiting programs can play a pivotal role in promoting their mental health. Many teen mothers have high levels of psychological distress and histories of adverse experiences that cannot be ignored, and cannot solely be addressed by referral to mental health services. Nurses must be prepared to assess for trauma and be open to listening to teen mothers' experiences. Principles of strengths-based and trauma-informed care are complementary and can be integrated in clinical services so that teen mothers' distress is addressed and their strengths and aspirations are supported. Potential screening tools, interviewing skills and basic strategies to alleviate teen mothers' distress are discussed.

  4. Public Relations as Promotional Activity

    Directory of Open Access Journals (Sweden)

    Almira CURRI-MEMETI

    2011-11-01

    Full Text Available Public relations give opportunity to the organization to present its image and personality to its own “public”- users, supporters, sponsors, donors, local community and other public.It is about transferring the message to the public, but that is a twoway street. You must communicate with your public, but at the same time you must give opportunity to the public to communicate easier with you. The real public relations include dialog – you should listen to the others, to see things through their perspective. This elaborate is made with the purpose to be useful for every organization, not for the sensational promotion of its achievements, but to become more critical towards its work. Seeing the organization in the way that the other see it, you can become better and sure that you are giving to your users the best service possible.

  5. Ecklonia cava promotes hair growth.

    Science.gov (United States)

    Bak, S S; Ahn, B N; Kim, J A; Shin, S H; Kim, J C; Kim, M K; Sung, Y K; Kim, S K

    2013-12-01

    Previous studies have reported the protective effects on skin elasticity of the edible marine seaweed Ecklonia cava, which acts through regulation of both antioxidative and anti-inflammatory responses. We evaluated the effect of E. cava and one of its components, dioxinodehydroeckol, on hair-shaft growth in cultured human hair follicles and on hair growth in mice. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to check cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells after treatment with E. cava and its metabolite, dioxinodehydroeckol. Hair-shaft growth was measured using the in vitro hair-follicle organ-culture system, in the presence or absence of E. cava and dioxinodehydroeckol. Anagen induction activity was examined by topical application of E. cava to the dorsal skin of C57BL/6 mice. Insulin-like growth factor (IGF)-1 expression was measured by reverse transcriptase PCR and ELISA. The proliferation activity was found to be highest for the ethyl acetate-soluble fraction of E. cava (EAFE) in DPCs and in ORS cells. Treatment with EAFE resulted in elongation of the hair shaft in cultured human hair follicles, and promoted transition of the hair cycle from the telogen to the anagen phase in the dorsal skin of C57BL/6 mice. In addition, EAFE induced an increase in IGF-1 expression in DPCs. Dioxinodehydroeckol, a component of E. cava, induced elongation of the hair shaft, an increase in proliferation of DPCs and ORS cells, and an increase in expression of IGF-1 in DPCs. These results suggest that E. cava containing dioxinodehydroeckol promotes hair growth through stimulation of DPCs and ORS cells. © 2013 British Association of Dermatologists.

  6. Phytoextraction to promote sustainable development

    Directory of Open Access Journals (Sweden)

    C.W.N. Anderson

    2013-10-01

    Full Text Available Mining makes a positive contribution to the economy of Indonesia. Significant earnings accrue through the export of tin, coal, copper, nickel and gold. Of these commodities, gold carries the highest unit value. But not all gold mining is regulated. Indonesia has a significant Artisanal and Small Scale Gold Mining (ASGM industry, defined as any informal and unregulated system of gold mining. These operations are often illegal, unsafe and are environmentally and socially destructive. New technology is needed to support the sustainable exploitation of gold and other precious metal resources in locations where ASGM is currently practised. This technology must be simple, cheap, easy to operate and financially rewarding. A proven option that needs to be promoted is phytoextraction. This is technology where plants are used to extract metals from waste rock, soil or water. These metals can subsequently be recovered from the plant in pure form, and sold or recycled. Gold phytoextraction is a commercially available technology, while international research has shown that phytoextraction will also work for mercury. In the context of ASGM operations, tailings could be contained in specific ‘farming areas’ and cropped using phytoextraction technology. The banning of ASGM operations is not practicable or viable. Poverty would likely become more extreme if a ban were enforced. Instead, new technology options are essential to promote the sustainable development of this industry. Phytoextraction would involve community and worker engagement, education and employment. New skills in agriculture created through application of the technology would be transferrable to the production of food, fibre and timber crops on land adjacent to the mining operations. Phytoextraction could therefore catalyse sustainable development in artisanal gold mining areas throughout Indonesia.

  7. Preconception care: promoting reproductive planning.

    Science.gov (United States)

    Dean, Sohni V; Lassi, Zohra S; Imam, Ayesha M; Bhutta, Zulfiqar A

    2014-09-26

    Preconception care recognizes that many adolescent girls and young women will be thrust into motherhood without the knowledge, skills or support they need. Sixty million adolescents give birth each year worldwide, even though pregnancy in adolescence has mortality rates at least twice as high as pregnancy in women aged 20-29 years. Reproductive planning and contraceptive use can prevent unintended pregnancies, unsafe abortions and sexually-transmitted infections in adolescent girls and women. Smaller families also mean better nutrition and development opportunities, yet 222 million couples continue to lack access to modern contraception. A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. Comprehensive interventions can prevent first pregnancy in adolescence by 15% and repeat adolescent pregnancy by 37%. Such interventions should address underlying social and community factors, include sexual and reproductive health services, contraceptive provision; personal development programs and emphasizes completion of education. Appropriate birth spacing (18-24 months from birth to next pregnancy compared to short intervals <6 months) can significantly lower maternal mortality, preterm births, stillbirths, low birth weight and early neonatal deaths. Improving adolescent health and preventing adolescent pregnancy; and promotion of birth spacing through increasing correct and consistent use of effective contraception are fundamental to preconception care. Promoting reproductive planning on a wider scale is closely interlinked with the reliable provision of effective

  8. Health promotion and dental caries

    Directory of Open Access Journals (Sweden)

    Marisa Maltz

    2010-01-01

    Full Text Available The central idea of the Brazilian health system is to prevent the establishment of disease or detect it as early as possible. Prevention and treatment of dental caries are related to behavioral factors, including dietary and oral hygiene habits, which are related to many chronic diseases. Dental health promotion therefore should be fully integrated into broadly based health-promoting strategies and actions such as food and health policies, and general hygiene (including oral hygiene, among others. For decades, a linear relationship between sugar consumption and caries has been observed. Recent data has indicated that this relationship is not as strong as it used to be before the widespread use of fluoride. However, diet is still a key factor acting in the carious process. Oral hygiene is a major aspect when it comes to caries, since dental biofilm is its etiological factor. Oral hygiene procedures are effective in controlling dental caries, especially if plaque removal is performed adequately and associated with fluoride. An alternative to a more efficient biofilm control in occlusal areas is the use of dental sealants, which are only indicated for caries-active individuals. If a cavity is formed as a consequence of the metabolic activity of the biofilm, a restorative material or a sealant can be placed to block access of the biofilm to the oral environment in order to prevent caries progress. The prevention of dental caries based on common risk-factor strategies (diet and hygiene should be supplemented by more disease-specific policies such as rational use of fluoride, and evidence-based dental health care.

  9. Does sleep promote false memories?

    Science.gov (United States)

    Darsaud, Annabelle; Dehon, Hedwige; Lahl, Olaf; Sterpenich, Virginie; Boly, Mélanie; Dang-Vu, Thanh; Desseilles, Martin; Gais, Stephen; Matarazzo, Luca; Peters, Frédéric; Schabus, Manuel; Schmidt, Christina; Tinguely, Gilberte; Vandewalle, Gilles; Luxen, André; Maquet, Pierre; Collette, Fabienne

    2011-01-01

    Memory is constructive in nature so that it may sometimes lead to the retrieval of distorted or illusory information. Sleep facilitates accurate declarative memory consolidation but might also promote such memory distortions. We examined the influence of sleep and lack of sleep on the cerebral correlates of accurate and false recollections using fMRI. After encoding lists of semantically related word associates, half of the participants were allowed to sleep, whereas the others were totally sleep deprived on the first postencoding night. During a subsequent retest fMRI session taking place 3 days later, participants made recognition memory judgments about the previously studied associates, critical theme words (which had not been previously presented during encoding), and new words unrelated to the studied items. Sleep, relative to sleep deprivation, enhanced accurate and false recollections. No significant difference was observed in brain responses to false or illusory recollection between sleep and sleep deprivation conditions. However, after sleep but not after sleep deprivation (exclusive masking), accurate and illusory recollections were both associated with responses in the hippocampus and retrosplenial cortex. The data suggest that sleep does not selectively enhance illusory memories but rather tends to promote systems-level consolidation in hippocampo-neocortical circuits of memories subsequently associated with both accurate and illusory recollections. We further observed that during encoding, hippocampal responses were selectively larger for items subsequently accurately retrieved than for material leading to illusory memories. The data indicate that the early organization of memory during encoding is a major factor influencing subsequent production of accurate or false memories.

  10. DNA Topoisomerases Maintain Promoters in a State Competent for Transcriptional Activation in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Pedersen, Jakob Madsen; Fredsøe, Jacob Christian; Rødgaard, Morten Terpager

    2012-01-01

    -depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation...... and elongation of PHO5, as well as the nuclear entrance of Pho4p. Finally, we provide evidence that topoisomerases are required to maintain the PHO5 promoter in a superhelical state, which is competent for proper activation. In conclusion, our results reveal a hitherto unknown function of topoisomerases during...

  11. How Nonfiction Reveals the Nature of Science

    Science.gov (United States)

    Zarnowski, Myra; Turkel, Susan

    2013-01-01

    In this article, the authors consider whether children's trade books promote an authentic understanding of the nature of science. They begin by discussing the characteristics of the nature of science and then examine existing research in children's science books for evidence of the visibility of these features. They describe the problems…

  12. Conformational biosensors reveal GPCR signalling from endosomes

    DEFF Research Database (Denmark)

    Irannejad, R; Tomshine, Jin C; Tomshine, Jon R

    2013-01-01

    -domain antibodies (nanobodies) to directly probe activation of the β2-adrenoceptor, a prototypical GPCR, and its cognate G protein, Gs (ref. 12), in living mammalian cells. We show that the adrenergic agonist isoprenaline promotes receptor and G protein activation in the plasma membrane as expected, but also...

  13. Solid-Phase S-Alkylation Promoted by Molecular Sieves.

    Science.gov (United States)

    Calce, Enrica; Leone, Marilisa; Mercurio, Flavia Anna; Monfregola, Luca; De Luca, Stefania

    2015-11-20

    A solid-phase S-alkylation procedure to introduce chemical modification on the cysteine sulfhydryl group of a peptidyl resin is reported. The reaction is promoted by activated molecular sieves and consists of a solid-solid process, since both the catalyst and the substrate are in a solid state. The procedure was revealed to be efficient and versatile, particularly when used in combination with the solution S-alkylation approach, allowing for the introduction of different molecular diversities on the same peptide molecule.

  14. Digital Citizenship and Health Promotion Programs: The Power of Knowing.

    Science.gov (United States)

    Hicks, Elaine R

    2016-11-03

    Patterns of Internet access and use among disadvantaged subgroups of Americans reveal that not all disparities are the same, a distinction crucial for appropriate public policies and health promotion program planning. In their book, Digital Citizenship: The Internet, Society, and Participation, authors Karen Mossberger, Caroline Tolbert, and Ramona McNeal deconstructed national opinion surveys and used multivariate methods of data analysis to demonstrate the impact of exclusion from online society economically, socially, and politically among disadvantaged Americans. © 2016 Society for Public Health Education.

  15. GSTT2 promoter polymorphisms and colorectal cancer risk

    Directory of Open Access Journals (Sweden)

    Ahn Sun-A

    2007-01-01

    Full Text Available Abstract Background Glutathione S-transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs are associated with colorectal cancer risk. Methods A total of 436 colorectal cancer patients and 568 healthy controls were genotyped for three GSTT2 promoter SNPs (-537G>A, -277T>C and -158G>A, using real-time TaqMan assay and direct sequencing. An electrophoretic mobility shift assay (EMSA was performed to determine the effects of polymorphisms on protein binding to the GSTT2 promoter. Results The -537A allele (-537G/A or A/A was significantly associated with colorectal cancer risk (OR = 1.373, p = 0.025, while the -158A allele (-158G/A or A/A was involved in protection against colorectal cancer (OR = 0.539, p = 0.032. Haplotype 2 (-537A, -277T, -158G was significantly associated with colorectal cancer risk (OR = 1.386, p = 0.021, while haplotype 4 (-537G, -277C, -158A protected against colorectal cancer (OR = 0.539, p = 0.032. EMSA data revealed lower promoter binding activity in the -537A allele than its -537G counterpart. Conclusion Our results collectively suggest that SNPs and haplotypes of the GSTT2 promoter region are associated with colorectal cancer risk in the Korean population.

  16. Analysis and prediction of baculovirus promoter sequences.

    Science.gov (United States)

    Xing, Ke; Deng, Riqiang; Wang, Jinwen; Feng, Jinghua; Huang, Mingsong; Wang, Xunzhang

    2005-10-01

    Consensus patterns of baculovirus sequences upstream from the translational initiation sites have been analyzed and a web tool, Local Alignment Promoter Predictor (LAPP), for the prediction of baculovirus promoter sequences has also been developed. Potential consensus sequences, i.e., TCATTGT, TCTTGTA, CTCGTAA, TCCATTT and TCATT plus TCGT in approximately 30 bp spacing context, have been found in baculovirus promoter regions, in addition to well-characterized late and early promoter elements G/T/ATAAG and TATAA, which is accompanied about 30-bp downstream by a transcriptional initiation sequence CAGT or CATT. Promoter prediction is performed by a dynamic programming algorithm based on maximal segment pair measure with scores above some cutoff against each sequence in a refined promoter database. The algorithm was able to discriminate between promoter and non-promoter sequences in a test set of baculovirus sequences with prediction specificity and sensitivity superior to that using five other eukaryotic promoter recognition programs available on the Internet. A web server that implements the LAPP with continually updated promoter database is freely available at http://life.zsu.edu.cn/LAPP/.

  17. Single promoters as regulatory network motifs

    Science.gov (United States)

    Zopf, Christopher; Maheshri, Narendra

    2012-02-01

    At eukaryotic promoters, chromatin can influence the relationship between a gene's expression and transcription factor (TF) activity. This additional complexity might allow single promoters to exhibit dynamical behavior commonly attributed to regulatory motifs involving multiple genes. We investigate the role of promoter chromatin architecture in the kinetics of gene activation using a previously described set of promoter variants based on the phosphate-regulated PHO5 promoter in S. cerevisiae. Accurate quantitative measurement of transcription activation kinetics is facilitated by a controllable and observable TF input to a promoter of interest leading to an observable expression output in single cells. We find the particular architecture of these promoters can result in a significant delay in activation, filtering of noisy TF signals, and a memory of previous activation -- dynamical behaviors reminiscent of a feed-forward loop but only requiring a single promoter. We suggest this is a consequence of chromatin transactions at the promoter, likely passing through a long-lived ``primed'' state between its inactive and competent states. Finally, we show our experimental setup can be generalized as a ``gene oscilloscope'' to probe the kinetics of heterologous promoter architectures.

  18. The Microbiome of Brazilian Mangrove Sediments as Revealed by Metagenomics

    Science.gov (United States)

    Andreote, Fernando Dini; Jiménez, Diego Javier; Chaves, Diego; Dias, Armando Cavalcante Franco; Luvizotto, Danice Mazzer; Dini-Andreote, Francisco; Fasanella, Cristiane Cipola; Lopez, Maryeimy Varon; Baena, Sandra; Taketani, Rodrigo Gouvêa; de Melo, Itamar Soares

    2012-01-01

    Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct mangrove areas (BrMgv01 to 04) in Brazil. The taxonomic approaches applied revealed the dominance of Deltaproteobacteria and Gammaproteobacteria in the samples. Paired statistical analysis showed higher proportions of specific taxonomic groups in each dataset. The metabolic reconstruction indicated the possible occurrence of processes modulated by the prevailing conditions found in mangrove sediments. In terms of carbon cycling, the sequences indicated the prevalence of genes involved in the metabolism of methane, formaldehyde, and carbon dioxide. With respect to the nitrogen cycle, evidence for sequences associated with dissimilatory reduction of nitrate, nitrogen immobilization, and denitrification was detected. Sequences related to the production of adenylsulfate, sulfite, and H2S were relevant to the sulphur cycle. These data indicate that the microbial core involved in methane, nitrogen, and sulphur metabolism consists mainly of Burkholderiaceae, Planctomycetaceae, Rhodobacteraceae, and Desulfobacteraceae. Comparison of our data to datasets from soil and sea samples resulted in the allotment of the mangrove sediments between those samples. The results of this study add valuable data about the composition of microbial communities in mangroves and also shed light on possible transformations promoted by microbial organisms in mangrove sediments. PMID:22737213

  19. The microbiome of Brazilian mangrove sediments as revealed by metagenomics.

    Directory of Open Access Journals (Sweden)

    Fernando Dini Andreote

    Full Text Available Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct mangrove areas (BrMgv01 to 04 in Brazil. The taxonomic approaches applied revealed the dominance of Deltaproteobacteria and Gammaproteobacteria in the samples. Paired statistical analysis showed higher proportions of specific taxonomic groups in each dataset. The metabolic reconstruction indicated the possible occurrence of processes modulated by the prevailing conditions found in mangrove sediments. In terms of carbon cycling, the sequences indicated the prevalence of genes involved in the metabolism of methane, formaldehyde, and carbon dioxide. With respect to the nitrogen cycle, evidence for sequences associated with dissimilatory reduction of nitrate, nitrogen immobilization, and denitrification was detected. Sequences related to the production of adenylsulfate, sulfite, and H(2S were relevant to the sulphur cycle. These data indicate that the microbial core involved in methane, nitrogen, and sulphur metabolism consists mainly of Burkholderiaceae, Planctomycetaceae, Rhodobacteraceae, and Desulfobacteraceae. Comparison of our data to datasets from soil and sea samples resulted in the allotment of the mangrove sediments between those samples. The results of this study add valuable data about the composition of microbial communities in mangroves and also shed light on possible transformations promoted by microbial organisms in mangrove sediments.

  20. Use of marketing to disseminate brief alcohol intervention to general practitioners: promoting health care interventions to health promoters.

    Science.gov (United States)

    Lock, C A; Kaner, E F

    2000-11-01

    Health research findings are of little benefit to patients or society if they do not reach the audience they are intended to influence. Thus, a dissemination strategy is needed to target new findings at its user group and encourage a process of consideration and adoption or rejection. Social marketing techniques can be utilized to aid successful dissemination of research findings and to speed the process by which new information reaches practice. Principles of social marketing include manipulating the marketing mix of product, price, place and promotion. This paper describes the development of a marketing approach and the outcomes from a trial evaluating the effectiveness and cost-effectiveness of manipulating promotional strategies to disseminate actively a screening and brief alcohol intervention (SBI) programme to general practitioners (GPs). The promotional strategies consisted of postal marketing, telemarketing and personal marketing. The study took place in general practices across the Northern and Yorkshire Regional Health Authority. Of the 614 GPs eligible for the study, one per practice, 321 (52%) took the programme and of those available to use it for 3 months (315), 128 (41%) actively considered doing so, 73 (23%) actually went on to use it. Analysis of the specific impact of the three different promotional strategies revealed that while personal marketing was the most effective overall dissemination and implementation strategy, telemarketing was more cost-effective. The findings of our work show that using a marketing approach is promising for conveying research findings to GPs and in particular a focus on promotional strategies can facilitate high levels of uptake and consideration in this target group.

  1. An innovative model of culturally tailored health promotion groups for Cambodian survivors of torture.

    Science.gov (United States)

    Berkson, Sarah Y; Tor, Svang; Mollica, Richard; Lavelle, James; Cosenza, Carol

    2014-01-01

    Cambodians living in the U.S.A. suffer from depression, posttraumatic stress disorder (PTSD), and chronic medical disease at rates far in excess of national averages. The Harvard Program in Refugee Trauma's Cambodian Health Promotion Program seeks to address this burden of disease by offering them culturally tailored health education in a group setting. A health professional and a bicultural health educator co-facilitated a five-session health promotion group for Cambodian survivors of torture from 2007 to 2011. The program covered five major topics from Western and Cambodian worldviews. They included the meaning of health promotion, nutrition, exercise, stress management and sleep hygiene, and health practitioner-patient communication. The bicultural worker administered Pre and Post semi-structured Health Promotion Questionnaires. The data presented here are the results from 126 participants. Changes between the Pre and Post health promotion groups demonstrated significant improvements in health status, lifestyle activities, sleep, and depression. Participants revealed greater confidence in communicating with their primary health care practitioner. Culturally tailored Cambodian health promotion education administered in a small group setting may improve health and mental health behaviors. Culturally tailored health promotion education in a small group setting may promote healing in survivors of torture. It is an intervention worthy of further research and development.

  2. Palytoxin: exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis.

    Science.gov (United States)

    Wattenberg, Elizabeth V

    2007-01-01

    Palytoxin is a novel skin tumor promoter, which has been used to help probe the role of different types of signaling mechanisms in carcinogenesis. The multistage mouse skin model indicates that tumor promotion is an early, prolonged, and reversible phase of carcinogenesis. Understanding the molecular mechanisms underlying tumor promotion is therefore important for developing strategies to prevent and treat cancer. Naturally occurring tumor promoters that bind to specific cellular receptors have proven to be useful tools for investigating important biochemical events in multistage carcinogenesis. For example, the identification of protein kinase C as the receptor for the prototypical skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (also called phorbol 12-myristate 13-acetate, PMA) provided key evidence that tumor promotion involves the aberrant modulation of signaling cascades that govern cell fate and function. The subsequent discovery that palytoxin, a marine toxin isolated from zoanthids (genus Palythoa), is a potent skin tumor promoter yet does not activate protein kinase C indicated that investigating palytoxin action could help reveal new aspects of tumor promotion. Interestingly, the putative receptor for palytoxin is the Na(+),K(+)-ATPase. This review focuses on palytoxin-stimulated signaling and how palytoxin has been used to investigate alternate biochemical mechanisms by which important targets in carcinogenesis can be modulated.

  3. Characterization and identification of microRNA core promoters in four model species.

    Directory of Open Access Journals (Sweden)

    Xuefeng Zhou

    2007-03-01

    Full Text Available MicroRNAs are short, noncoding RNAs that play important roles in post-transcriptional gene regulation. Although many functions of microRNAs in plants and animals have been revealed in recent years, the transcriptional mechanism of microRNA genes is not well-understood. To elucidate the transcriptional regulation of microRNA genes, we study and characterize, in a genome scale, the promoters of intergenic microRNA genes in Caenorhabditis elegans, Homo sapiens, Arabidopsis thaliana, and Oryza sativa. We show that most known microRNA genes in these four species have the same type of promoters as protein-coding genes have. To further characterize the promoters of microRNA genes, we developed a novel promoter prediction method, called common query voting (CoVote, which is more effective than available promoter prediction methods. Using this new method, we identify putative core promoters of most known microRNA genes in the four model species. Moreover, we characterize the promoters of microRNA genes in these four species. We discover many significant, characteristic sequence motifs in these core promoters, several of which match or resemble the known cis-acting elements for transcription initiation. Among these motifs, some are conserved across different species while some are specific to microRNA genes of individual species.

  4. Self-tracking as Health promotion

    DEFF Research Database (Denmark)

    Jelsøe, Erling

    conditions for improving health and initiatives in social settings (as represented for example by the WHO Ottawa Charter). On the other hand, there is also an element of community orientation among many self-trackers through e.g. sharing and comparison of data via social media. This presentation will provide...... though this is not the only incentive for self-tracking). Even though health promotion is often seen as an activity, which resonates with a focus on individual responsibility, such a conception of health promotion contrasts with a broader critical concept of health promotion that emphasize social...... an analysis of social and community oriented dimensions of self-tracking as a form of health promotion compared to the above mentioned broad critical approach to health promotion in order to identify the contradictions as well as common traits and discuss implications for health promoting initiatives...

  5. Smartphones Promote Autonomous Learning in ESL Classrooms

    Directory of Open Access Journals (Sweden)

    Viji Ramamuruthy

    2015-10-01

    Full Text Available The rapid development of high-technology has caused new inventions of gadgets for all walks of life regardless age. In this rapidly advancing technology era many individuals possess hi-tech gadgets such as laptops, tablets, iPad, android phones and smart phones. Adult learners in higher learning institution especially are fond of using smart phones. Students become passive in the classrooms as they are glued to their smart phones. This situation triggers the question of whether learning really takes place while the students are too engaged with their smart phones in the ESL classroom. In this context, the following questions are framed to investigate this issue: What type of learning skills are gained by using smartphones in ESL classrooms? Does smartphone use promote the autonomous learning process? To what extent do learners rely on the lecturers in addition to the usage of smartphones? What are the learning satisfactions gained by ESL learners using smartphones? A total of 70 smartphone users in the age range 18 to 26 years participated in this quantitative study. Questionnaires eliciting demographic details of the respondents, learning skills, learning satisfaction, students' perception on teacher's role in the ESL classroom and autonomous learning were distributed to all the randomly chosen samples. The data were then analyzed by using SPSS version 16. The findings revealed that smartphone use boosted learners’ critical thinking, creative thinking, communication and collaboration skills. In fact, learners gain great satisfaction in the learning process through smartphones. Although learners have moved toward autonomous learning, they are still reliant on the teachers to achieve their learning goals.

  6. Using art to promote democracy

    Directory of Open Access Journals (Sweden)

    Nena Mijoč

    2006-12-01

    Full Text Available The author presents and supports with case studies international practice of adult learning, which uses rather unusual and innovative approaches to motivate and train groups of people, who live on the margin of events and decision-making processes, for democratic citizenship. We speak about informal training, which through music, art and literature enriches the process of mutual learning. This encourages selfconfidence of individuals and groups and helps developing competencies, which are important for active and democratic citizenship. International conferences, which are very often prepared for the first time also for members of minor organizations and societies, such as within Grundtvig projects, are for many a learning experience and opportunity to promote and meet >>good solutions« for problems of adult learning. Using immediate experience of planning and cooperation in projects and also on basis of mistakes, problems and conflicts people learn to contribute. At the same time relationships are enriched and friendships built between trainers/educators, participants and volunteers from different European countries.

  7. Promoting innovation in pediatric nutrition.

    Science.gov (United States)

    Bier, Dennis M

    2010-01-01

    Truly impactful innovation can only be recognized in retrospect. Moreover, almost by definition, developing algorithmic paths on roadmaps for innovation are likely to be unsuccessful because innovators do not generally follow established routes. Nonetheless, environments can be established within Departments of Pediatrics that promote innovating thinking. The environmental factors necessary to do so include: (1) demand that academic Pediatrics Departments function in an aggressively scholarly mode; (2) capture the most fundamental science in postnatal developmental biology; (3) focus education and training on the boundaries of our knowledge, rather than the almost exclusive attention to what we think we already know; (4) devote mentoring, time and resources to only the most compelling unanswered questions in the pediatric sciences, including nutrition; (5) accept only systematic, evidence-based answers to clinical questions; (6) if systematic, evidence-based data are not available, design the proper studies to get them; (7) prize questioning the answers to further move beyond the knowledge limit; (8) support the principle that experiments in children will be required to convincingly answer clinical questions important to children, and (9) establish the multicenter resources in pediatric scientist training, clinical study design and implementation, and laboratory and instrument technologies required to answer today's questions with tomorrow's methods. Copyright © 2010 S. Karger AG, Basel.

  8. Towards a relational health promotion.

    Science.gov (United States)

    Veenstra, Gerry; Burnett, Patrick John

    2016-03-01

    The Ottawa Charter for Health Promotion exhibits a substantialist approach to the agency-structure dichotomy. From a substantialist point of view, both individual agency and social structure come preformed and subsequently relate to and influence one another, starkly positioning the choices made by individuals against the structured sets of opportunities and constraints in reference to which choices are made. From a relational perspective, however, relations between elements, not the elements themselves, are the primary ontological focus. We advocate for a relational approach to the structure-agency dichotomy, one that locates both agency and structure in social relations and thereby dissolves the stark distinction between them, suggesting that relational theories can provide useful insights into how and why people 'choose' to engage in health-related behaviours. Pierre Bourdieu's theory of practice, predicated upon the notions of field, capital and habitus, is exemplary in this regard. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Promotional Tool of Marketing: An Islamic Perspective

    OpenAIRE

    Muhammad Anwar; Mohammad Saeed

    1996-01-01

    Promotional tools of marketing, (e.g., personal selling, advertising, sales promotion, public relations, promotional games as well as contests), play a key role in creating consumer awareness about the qualities of various products and services available on the market, and can go a long way in contributing to economic progress and social development. Muslim marketers have to be conscious of their position and role in managing marketing activities. The Qur'anic view about man and his resources...

  10. Promoter Sequences for Defining Transgene Expression

    Science.gov (United States)

    Jones, Huw D.; Sparks, Caroline A.

    The design of reverse genetic experiments that utilize transgenic approaches often requires transgenes to be expressed in a predefined pattern and there is limited information regarding the gene expression profile for specific promoters. It is important that expression patterns are predetermined in the specific genotype targeted for transformation because the same promoter-transgene construct can produce different expression patterns in different host species. This chapter compares constitutive, targeted, or inducible promoters that have been characterized in specific cereal species.

  11. Managing workplace health promotion in municipal organizations

    OpenAIRE

    Larsson, Robert

    2015-01-01

    The workplace is a suitable setting for health promotion, not least due to the amount of time employees spend at work. Previous research indicates large variations in employers' handling of workplace health promotion (WHP) efforts. However, more empirical knowledge of how WHP is handled in public sector organizations is needed. The overall aim of the thesis was to explore how WHP is managed and implemented in municipal organizations. The thesis draws on health promotion as the point of depart...

  12. Health Promotion and Wellness Staffing Methods

    National Research Council Canada - National Science Library

    Thomsen, Kim

    1999-01-01

    .... Health promotion and wellness programs positively influence the military mission readiness and force protection, increase productivity, reduce health care costs, minimize illness and non-battle...

  13. Promoting Chiaro Hotel Using a Website

    OpenAIRE

    Kurniawati, Ivana; Ibrahim, Jusuf I

    2017-01-01

    Chiaro Hotel is a one-star hotel in Sidoarjo that is located at a strategic location. It is clean and comfortable family hotel. The problem of Chiaro Hotel is lack of promotion. Even though Chiaro Hotel has had some promotional tools, such as short promotional video, marketing booklet, and flyer, those promotional tools do not give good impact for the hotel because they do not show the uniqueness of Chiaro Hotel. Therefore, I make a website to solve Chiaro Hotel's problem. This website can re...

  14. Comparative analyses of bidirectional promoters in vertebrates

    Directory of Open Access Journals (Sweden)

    Taylor James

    2008-05-01

    Full Text Available Abstract Background Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated by bidirectional promoters to map the ancestral history of the promoter regions. Results Our mapping of bidirectional promoters from humans to fish shows that many such promoters emerged after the divergence of chickens and fish. Furthermore, annotations of promoters in deep phylogenies enable detection of missing data or assembly problems present in higher vertebrates. The functional importance of bidirectional promoters is indicated by selective pressure to maintain the arrangement of genes regulated by the promoter over long evolutionary time spans. Characteristics unique to bidirectional promoters are further elucidated using a technique for unsupervised classification, known as ESPERR. Conclusion Results of these analyses will aid in our understanding of the evolution of bidirectional promoters, including whether the regulation of two genes evolved as a consequence of their proximity or if function dictated their co-regulation.

  15. Effectiveness of Social Marketing Interventions to Promote Physical Activity Among Adults: A Systematic Review.

    Science.gov (United States)

    Xia, Yuan; Deshpande, Sameer; Bonates, Tiberius

    2016-11-01

    Social marketing managers promote desired behaviors to an audience by making them tangible in the form of environmental opportunities to enhance benefits and reduce barriers. This study proposed "benchmarks," modified from those found in the past literature, that would match important concepts of the social marketing framework and the inclusion of which would ensure behavior change effectiveness. In addition, we analyzed behavior change interventions on a "social marketing continuum" to assess whether the number of benchmarks and the role of specific benchmarks influence the effectiveness of physical activity promotion efforts. A systematic review of social marketing interventions available in academic studies published between 1997 and 2013 revealed 173 conditions in 92 interventions. Findings based on χ 2 , Mallows' Cp, and Logical Analysis of Data tests revealed that the presence of more benchmarks in interventions increased the likelihood of success in promoting physical activity. The presence of more than 3 benchmarks improved the success of the interventions; specifically, all interventions were successful when more than 7.5 benchmarks were present. Further, primary formative research, core product, actual product, augmented product, promotion, and behavioral competition all had a significant influence on the effectiveness of interventions. Social marketing is an effective approach in promoting physical activity among adults when a substantial number of benchmarks are used and when managers understand the audience, make the desired behavior tangible, and promote the desired behavior persuasively.

  16. Pericyte–fibroblast transition promotes tumor growth and metastasis

    Science.gov (United States)

    Hosaka, Kayoko; Yang, Yunlong; Seki, Takahiro; Fischer, Carina; Dubey, Olivier; Fredlund, Erik; Hartman, Johan; Religa, Piotr; Ishii, Yoko; Sasahara, Masakiyo; Larsson, Ola; Cossu, Giulio; Cao, Renhai; Lim, Sharon; Cao, Yihai

    2016-01-01

    Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte–fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that PDGF-BB-PDGFRβ signaling promotes PFT both in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB–activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB–induced PFT. Genetic tracing of pericytes with two independent mouse strains, TN-AP-CreERT2:R26R-tdTomato and NG2-CreERT2:R26R-tdTomato, shows that PFT cells gain stromal fibroblast and myofibroblast markers in tumors. Importantly, coimplantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells and metastasis. Our findings reveal a mechanism of vascular pericytes in PDGF-BB–promoted cancer invasion and metastasis by inducing PFT, and thus targeting PFT may offer a new treatment option of cancer metastasis. PMID:27608497

  17. TWIST is Expressed in Human Gliomas, Promotes Invasion

    Directory of Open Access Journals (Sweden)

    Maria C. Elias

    2005-09-01

    Full Text Available TWIST is a basic helix-loop-helix (bHLH transcription factor that regulates mesodermal development, promotes tumor cell metastasis, and, in response to cytotoxic stress, enhances cell survival. Our screen for bHLH gene expression in rat C6 glioma revealed TWIST. To delineate a possible oncogenic role for TWIST in the human central nervous system (CNS, we analyzed TWIST message, protein expression in gliomas, normal brain. TWIST was detected in the large majority of human glioma-derived cell lines, human gliomas examined. Increased TWIST mRNA levels were associated with the highest grade gliomas, increased TWIST expression accompanied transition from low grade to high grade in vivo, suggesting a role for TWIST in promoting malignant progression. In accord, elevated TWIST mRNA abundance preceded the spontaneous malignant transformation of cultured mouse astrocytes hemizygous for p53. Overexpression of TWIST protein in a human glioma cell line significantly enhanced tumor cell invasion, a hallmark of high-grade gliomas. These findings support roles for TWIST both in early glial tumorigenesis, subsequent malignant progression. TWIST was also expressed in embryonic, fetal human brain, in neurons, but not glia, of mature brain, indicating that, in gliomas, TWIST may promote the functions also critical for CNS development or normal neuronal physiology.

  18. Promoting Strong Written Communication Skills

    Science.gov (United States)

    Narayanan, M.

    2015-12-01

    The reason that an improvement in the quality of technical writing is still needed in the classroom is due to the fact that universities are facing challenging problems not only on the technological front but also on the socio-economic front. The universities are actively responding to the changes that are taking place in the global consumer marketplace. Obviously, there are numerous benefits of promoting strong written communication skills. They can be summarized into the following six categories. First, and perhaps the most important: The University achieves learner satisfaction. The learner has documented verbally, that the necessary knowledge has been successfully acquired. This results in learner loyalty that in turn will attract more qualified learners.Second, quality communication lowers the cost per pupil, consequently resulting in increased productivity backed by a stronger economic structure and forecast. Third, quality communications help to improve the cash flow and cash reserves of the university. Fourth, having high quality communication enables the university to justify the need for high costs of tuition and fees. Fifth, better quality in written communication skills result in attracting top-quality learners. This will lead to happier and satisfied learners, not to mention greater prosperity for the university as a whole. Sixth, quality written communication skills result in reduced complaints, thus meaning fewer hours spent on answering or correcting the situation. The University faculty and staff are thus able to devote more time on scholarly activities, meaningful research and productive community service. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate.Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., & Winter, J. (1997). Mastering change: Learning the lessons of the enterprise.London: Department for Education and Employment. Buzzel, Robert D., and Bradley T. Gale. (1987

  19. The zebrafish spi1 promoter drives myeloid-specific expression in stable transgenic fish

    NARCIS (Netherlands)

    Ward, AC; McPhee, DO; Condron, MM; Varma, S; Cody, SH; Onnebo, SMN; Paw, BH; Zon, LI; Lieschke, GJ

    2003-01-01

    The spi1 (pu.1) gene has recently been identified as a useful marker of early myeloid cells in zebrafish. To enhance the versatility of this organism as a model for studying myeloid development, the promoter of this gene has been isolated and characterized. Transient transgenesis revealed that a 5.3

  20. Promoting Reflective Thinking Skills by Using Web 2.0 Application

    Science.gov (United States)

    Abdullah, Mohamed

    2015-01-01

    The study aims to investigate are using Web 2.0 applications promoting reflective thinking skills for higher education student in faculty for education. Although the literature reveals that technology integration is a trend in higher education and researchers and educators have increasingly shared their ideas and examples of implementations of Web…

  1. Buying in multiple stores : Shopping strategies beyond price promotions and their effects on Store Competition

    NARCIS (Netherlands)

    Gijsbrechts, E.; Campo, K.; Nisol, P.

    2013-01-01

    Grocery-store switching has typically been viewed as evidence of cherry-picking behavior, with consumers switching stores to benefit from temporary promotional offers. However, research reveals that it may also result from a longer-term planning process based on stable store characteristics. Even in

  2. Promoting Well-Being and Gerotranscendence in an Art Therapy Program for Older Adults

    Science.gov (United States)

    Stephenson, Raquel Chapin

    2013-01-01

    This article describes a community art therapy program that was designed to promote health and well-being in old age. Observations of diverse participant interactions in the nondirective therapy studio over the course of 6 years revealed the benefits of art making and how it may influence well-being during the process of advancing age. Program…

  3. Wireless Laptops as Means for Promoting Active Learning in Large Lecture Halls

    Science.gov (United States)

    Barak, Miri; Lipson, Alberta; Lerman, Steven

    2006-01-01

    This paper reports on a study that examined the use of wireless laptops for promoting active learning in lecture halls. The study examined students' behavior in class and their perceptions of the new learning environment throughout three consecutive semesters. An online survey revealed that students have highly positive perceptions about the use…

  4. Promotion of a Ti-Mediated Mannich Reaction by a Proton Source.

    Science.gov (United States)

    Limanto, John; Yoshikawa, Naoki; Reamer, Robert A; Tan, Lushi; Brunskill, Andrew; Reibarkh, Mikhail

    2016-01-15

    Low temperature NMR studies revealed that a diastereoselective Mannich reaction between a phenyl oxazolidone-derived titanium enolate and an aromatic aldimine was found to occur only after introduction of a proton source. While various protic additives could be used to promote the transformation, the best results were obtained using AcOH to afford the corresponding Mannich products in high diastereoselectivities and yields.

  5. Hydrogen Promoted Oxygen Activation by Free Gold Cluster Cations

    Science.gov (United States)

    Barnett, Robert N.; Yoon, Bokwon; Landman, Uzi; Lang, Sandra M.; Bernhardt, Thorsten M.

    2009-03-01

    In this contribution we present experiments and first-principles density functional theory calculations on gas-phase reaction of small gold clusters, aiming at elucidation of the role of hydrogen in the activation of molecular oxygen for the selective oxidation of hydrocarbons. Positively charged gold clusters. Au4^+ and Au6^+. were chosen because electronic factors and experimental data suggest them to be most suitable for promoting the oxidation of unsaturated hydrocarbons. Our investigations show that, although small gas phase gold cluster cations are inert toward molecular oxygen, the pre-adsorption of molecular hydrogen cooperatively activates the adsorption of O2 on Au4^+ and Au6^+. Temperature and reaction time dependent investigations in an octopole ion trap under multi-collision conditions reveal that hydrogen promotes the activation and dissociation of molecular oxygen on the gold clusters at temperatures as low as 200 K. The detailed mechanism of the hydrogen induced oxygen activation, involving an intermediate hydro-peroxy-complex is revealed by the DFT calculations.

  6. DNA structural features of eukaryotic TATA-containing and TATA-less promoters.

    Science.gov (United States)

    Yella, Venkata Rajesh; Bansal, Manju

    2017-03-01

    Eukaryotic genes can be broadly classified as TATA-containing and TATA-less based on the presence of TATA box in their promoters. Experiments on both classes of genes have revealed a disparity in the regulation of gene expression and cellular functions between the two classes. In this study, we report characteristic differences in promoter sequences and associated structural properties of the two categories of genes in six different eukaryotes. We have analyzed three structural features, DNA duplex stability, bendability, and curvature along with the distribution of A-tracts, G-quadruplex motifs, and CpG islands. The structural feature analyses reveal that while the two classes of gene promoters are distinctly different from each other, the properties are also distinguishable across the six organisms.

  7. Social work with families at social risk promoting gender equality

    Directory of Open Access Journals (Sweden)

    Pivoriene J.

    2016-01-01

    Full Text Available The article is based on the research whose aim is to find out the attitudes of social workers toward gender equality. The qualitative research was carried out in 2014 in order to find out social workers' attitudes to gender equality in families and families at social risk, as well as obstacles and possibilities for implementation of gender equality in families at social risk. Eight social workers working with families at social risk were interviewed using semi-structured interview and content analysis for research data analysis. The research data reveals that gender equality in the family can be reached by mutual agreement, when the division of duties and responsibilities is in accordance with needs and abilities of family members. Good family relations are emphasized as a prerequisite for gender equality. Families at social risk with unbalanced social functioning and relationships are affected by stereotyped thinking about gender roles. As informants point out, this makes gender equality impossible in families at social risk. Social workers reveal that they do not directly relate the gender dimension with social work practice, and as a result it becomes problematic to promote gender equality in families at social risk. The main obstacles for implementation of gender equality are clients' resistance to change, too much responsibilities put on women-mother by social workers and other institutions that deal with social risk families, lack of information on gender equality and tools for promoting gender equality in the family. However, the informants provide solutions for promotion of gender equality in micro, mezzo and macro practice that correspond to the guidelines presented in the documents and strategies on gender equality at national and EU level.

  8. Faculty Members’ Views on Academic Promotion and Appointment Process

    Directory of Open Access Journals (Sweden)

    Engin DEMİR

    2017-04-01

    Full Text Available Despite the changes made related to academic promotion and appointment over the years in Turkey, there have been two main criteria: academic publications after PhD and foreign language proficiency. It commonly known that faculty members come across several problems during the process of attaining the title of associate professorship and these problems affect the academic environment in several ways. The purpose of this study is to reveal the faculty members’ views on the academic promotion in postdoctoral process and provide further suggestions.. Data were gathered through a semi-structured interview form including 10 items prepared by the researcher and analyzed through content analysis. In addition, a criterion table comprised of 25 items was applied to the participants before the interview. These criteria were determined by the InteruniversityBoard of Turkey and other universities. 18 faculty members marked the criteria they consider essential. Participants consisted of faculty members from science, social and medical fields. Results of the study revealed that faculty members considered associate professorship exam and foreign language exam necessary. According to the faculty members, the criteria related to publishing international articles and lecturing at undergraduate and graduate levels were especially very important among all criteria and the current system had a determinant role in the faculty members’ behaviors and academic publications. Faculty members stated that foreign language exam did not measure language proficiency accurately ; academic positions were not assigned fairly; there were some problems about the quality of academic publications, ethics and being a scientist. Similarly, they clearly stated that the society did not rely on scientists. The results gained in the study corroborate the need to review the academic promotion and appointment process. An increase in the number of such studies that examine faculty members

  9. REVEAL: Software Documentation and Platform Migration

    Science.gov (United States)

    Wilson, Michael A.; Veibell, Victoir T.

    2011-01-01

    The Research Environment for Vehicle Embedded Analysis on Linux (REVEAL) is reconfigurable data acquisition software designed for network-distributed test and measurement applications. In development since 2001, it has been successfully demonstrated in support of a number of actual missions within NASA's Suborbital Science Program. Improvements to software configuration control were needed to properly support both an ongoing transition to operational status and continued evolution of REVEAL capabilities. For this reason the project described in this report targets REVEAL software source documentation and deployment of the software on a small set of hardware platforms different from what is currently used in the baseline system implementation. This presentation specifically describes the actions taken over a ten week period by two undergraduate student interns and serves as an overview of the content of the final report for that internship.

  10. The double jeopardy of sales promotions.

    Science.gov (United States)

    Jones, J P

    1990-01-01

    The maturing of most consumer markets in the United States has put great pressure on manufacturers in their search for growth. They have concentrated on building sales and expanding share proportions in the stagnant markets with devices like niche products, product extensions, mergers, and international ventures. They have shifted emphasis to sales promotions at the expense of advertising. But promotions, when you come right down to it, mean price reductions. Trade promotions are almost always rebates, and consumer promotions are usually temporary price reductions or coupons. The cost in reduced profit, demonstrated mathematically through calculations of price elasticity, is severe. Besides, when the promotion is over, the manufacturer has not moved forward an inch in shoring up the brand franchise. Promotions bring volatile demand, whereas the producer seeks stable demand. By sustaining a brand image and building customer loyalty, on the other hand, theme advertising can stabilize demand. Moreover, this type of advertising is less likely than promotion is to invite destructive competitive retaliation. Calculation of the advertising elasticity of a brand indicates that sometimes even modest sales increases can produce healthy profit improvement. In a well-planned marketing campaign, there is often good reason to include trade or consumer promotion--to counter a leading competitor's moves, for example. But there is no point in carrying out wild swings at rivals in a struggle for market share. Mathematical techniques can aid the efficiency of marketing planning and put on a more rational basis the decision on where to put the dollars.

  11. 76 FR 34871 - Mobile Barcode Promotion

    Science.gov (United States)

    2011-06-15

    .... The mobile barcodes must be used for marketing, promotional or educational purposes. They may not be... POSTAL SERVICE 39 CFR Part 111 Mobile Barcode Promotion AGENCY: Postal Service TM . ACTION: Final... and flats, and Standard Mail[reg] letters and flats bearing two-dimensional mobile barcodes. DATES...

  12. Mental health promotion: paradigms and practice

    National Research Council Canada - National Science Library

    Tudor, Keith

    1996-01-01

    ... concept which is clearly differentiated from mental illness and psychopathology. The second part of the book focuses on the theory and practice of mental health promotion through applications to policy, assessment, consultation, and to education and training in mental health promotion. Drawing on a wealth of international literature Keith Tudor offe...

  13. 78 FR 24239 - Temporary Mailing Promotion

    Science.gov (United States)

    2013-04-24

    ... Temporary Mailing Promotion AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is... with offering a Technology Credit Promotion. This notice informs the public of the Postal Service's filing and takes other administrative steps. DATES: Comment Date: May 6, 2013. ADDRESSES: Submit comments...

  14. Marketing instruments of foreign trade promotion

    Directory of Open Access Journals (Sweden)

    Bjelić Predrag

    2011-01-01

    Full Text Available Instruments of promotion as a part of marketing mix are usually associated with companies but more and more countries use this instrument in order to boost their exports. These foreign trade promotion instruments are now popular in many countries in the world since their use is not opposed to any World Trade Organization rules. Marketing instruments of trade promotions are the most important. They include National Exhibitions and National labels of origin and quality. In order to coordinate the application of these instruments countries have established national bodies for trade promotion. Many studies in the past had argued that national Agencies established to promote export did not had any real success, but recent studies indicate that they could have a significant impact on country export promotion. The result of this rise in impact of national export promotion agencies is due to international effort spearheaded by International Trade Center. The aim of this paper is to point out types and methods of marketing instruments application in trade promotion and to present the effectiveness of these instruments applications.

  15. 17 CFR 200.70 - Business promotions.

    Science.gov (United States)

    2010-04-01

    ... AND ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.70 Business promotions. A member must not engage in any other business, employment or vocation while in office, nor may he ever use the... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Business promotions. 200.70...

  16. PROMOTION