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Sample records for ezh2 expression group

  1. Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

    Science.gov (United States)

    Xie, Qiang; Wang, Hongbei; Heilman, Edward R; Walsh, Michael G; Haseeb, M A; Gupta, Raavi

    2014-01-01

    Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

  2. Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis

    NARCIS (Netherlands)

    Fluge, Ø.; Gravdal, K.; Carlsen, E.; Vonen, B.; Kjellevold, K.; Refsum, S.; Lilleng, R.; Eide, T.J.; Halvorsen, T.B.; Tveit, K.M.; Otte, A.P.; Akslen, L.A.; Dahl, O.

    2009-01-01

    Background: Enhancer of zeste homologue 2 (EZH2) is a member of the Polycomb group of genes that is involved in epigenetic silencing and cell cycle regulation. Methods: We studied EZH2 expression in 409 patients with colorectal cancer stages II and III. The patients were included in a randomised

  3. High expression of Polycomb group protein EZH2 predicts poor survival in salivary gland adenoid cystic carcinoma

    NARCIS (Netherlands)

    Vékony, H.; Raaphorst, F.M.; Otte, A.P.; van Lohuizen, M.; Leemans, C.R.; van der Waal, I.; Bloemena, E.

    2008-01-01

    Background: The prognosis of adenoid cystic carcinoma (ACC), a malignant salivary gland tumour, depends on clinicopathological parameters. To decipher the biological behaviour of ACC, and to identify patients at risk of developing metastases, additional markers are needed. Methods: Expression of the

  4. MUC1-C activates EZH2 expression and function in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Tagde, Ashujit; Alam, Maroof; Bouillez, Audrey; Christensen, Camilla L; Samur, Mehmet; Wong, Kwok-Kin; Kufe, Donald

    2017-08-07

    The EZH2 histone methyltransferase is a member of the polycomb repressive complex 2 (PRC2) that is highly expressed in diverse human cancers and is associated with a poor prognosis. MUC1-C is an oncoprotein that is similarly overexpressed in carcinomas and has been linked to epigenetic regulation. A role for MUC1-C in regulating EZH2 and histone methylation is not known. Here, we demonstrate that targeting MUC1-C in diverse human carcinoma cells downregulates EZH2 and other PRC2 components. MUC1-C activates (i) the EZH2 promoter through induction of the pRB→E2F pathway, and (ii) an NF-κB p65 driven enhancer in exon 1. We also show that MUC1-C binds directly to the EZH2 CXC region adjacent to the catalytic SET domain and associates with EZH2 on the CDH1 and BRCA1 promoters. In concert with these results, targeting MUC1-C downregulates EZH2 function as evidenced by (i) global and promoter-specific decreases in H3K27 trimethylation (H3K27me3), and (ii) activation of tumor suppressor genes, including BRCA1. These findings highlight a previously unreported role for MUC1-C in activating EZH2 expression and function in cancer cells.

  5. Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

    Science.gov (United States)

    Harms, Kelly L; Chubb, Heather; Zhao, Lili; Fullen, Douglas R; Bichakjian, Christopher K; Johnson, Timothy M; Carskadon, Shannon; Palanisamy, Nallasivam; Harms, Paul W

    2017-09-01

    Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Ezh2 regulates transcriptional and post-translational expression of T-bet and promotes Th1 cell responses mediating aplastic anemia in mice1

    Science.gov (United States)

    Tong, Qing; He, Shan; Xie, Fang; Mochizuki, Kazuhiro; Liu, Yongnian; Mochizuki, Izumi; Meng, Lijun; Sun, Hongxing; Zhang, Yanyun; Guo, Yajun; Hexner, Elizabeth; Zhang, Yi

    2014-01-01

    Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-γ-producing T helper (Th)1 CD4+ T cells mediate the immune destruction of hematopoietic cells, and are central to the pathogenesis. However, the molecular events that control the development of BM-destructive Th1 cells remain largely unknown. Ezh2 is a chromatin-modifying enzyme that regulates multiple cellular processes primarily by silencing gene expression. We recently reported that Ezh2 is crucial for inflammatory T cell responses after allogeneic BM transplantation. To elucidate whether Ezh2 mediates pathogenic Th1 responses in AA and the mechanism of Ezh2 action in regulating Th1 cells, we studied the effects of Ezh2 inhibition in CD4+ T cells using a mouse model of human AA. Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. Ezh2 inhibition resulted in significant decrease in the expression of Tbx21 and Stat4 (which encode transcription factors T-bet and STAT4, respectively). Introduction of T-bet but not STAT4 into Ezh2-deficient T cells fully rescued their differentiation into Th1 cells mediating AA. Ezh2 bound to the Tbx21 promoter in Th1 cells, and directly activated Tbx21 transcription. Unexpectedly, Ezh2 was also required to prevent proteasome-mediated degradation of T-bet protein in Th1 cells. Our results identify T-bet as the transcriptional and post-translational Ezh2 target that acts together to generate BM-destructive Th1 cells, and highlight the therapeutic potential of Ezh2 inhibition in reducing AA and other autoimmune diseases. PMID:24760151

  7. TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p.

    Science.gov (United States)

    Cao, Jiaqing; Han, Xinyou; Qi, Xin; Jin, Xiangyun; Li, Xiaolin

    2017-10-01

    lncRNA-TUG1 (Taurine upregulated 1) is up-regulated and highly correlated with poor prognosis and disease status in osteosarcoma. TUG1 knockdown inhibits osteosarcoma cell proliferation, migration and invasion, and promotes apoptosis. However, its mechanism of action has not been well addressed. Growing evidence documented that lncRNA works as competing endogenous (ce)RNAs to modulate the expression and biological functions of miRNA. As a putative combining target of TUG1, miR-144-3p has been associated with the progress of osteosarcoma. To verify whether TUG1 functions through regulating miR-144-3p, the expression levels of TUG1 and miR-144-3p in osteosarcoma tissues and cell lines were determined. TUG1 was upregulated in osteosarcoma tissues and cell lines, and negatively correlated with miR-144-3p. TUG1 knockdown induced miR-144-3p expression in MG63 and U2OS cell lines. Results from dual luciferase reporter assay, RNA-binding protein immuno-precipitation (RIP) and applied biotin-avidin pull-down system confirmed TUG1 regulated miR-144-3p expression through direct binding. EZH2, a verified target of miR-144-3p was upregulated in osteosarcoma tissues and negatively correlated with miR-144-3p. EZH2 was negatively regulated by miR-144-3p and positively regulated by TUG1. Gain-and loss-of-function experiments were performed to analyze the role of TUG1, miR-144-3p and EZH2 in the migration and EMT of osteosarcoma cells. EZH2 over-expression partly abolished TUG1 knockdown or miR-144-3p overexpression induced inhibition of migration and EMT in osteosarcoma cells. In addition, TUG1 knockdown represses the activation of Wnt/β-catenin pathway, which was reversed by EZH2 over-expression. The activator of Wnt/β-catenin pathway LiCl could partially block the TUG1-knockdown induced osteosarcoma cell migration and EMT inhibition. In conclusion, our results showed that TUG1 plays an important role in osteosarcoma development through miRNA-144-3p/EZH2/Wnt/β-catenin pathway.

  8. Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

    Science.gov (United States)

    Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

    2009-09-01

    The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

  9. The Effect of Sodium Valproate on the Glioblastoma U87 Cell Line Tumor Development on the Chicken Embryo Chorioallantoic Membrane and on EZH2 and p53 Expression

    Directory of Open Access Journals (Sweden)

    Dovilė Kavaliauskaitė

    2017-01-01

    Full Text Available Literature data support evidences that glioblastoma (GBM patients experience prolonged survival due to sodium valproate (NaVP treatment. The study assessed the human GBM cell U87 xenograft studied in the chicken embryo chorioallantoic membrane (CAM model evaluating NaVP effect on tumor. Three groups of tumors (each n = 10 were studied: nontreated, treated with 4 mM, and treated with 8 mM of NaVP. The majority of tumors without NaVP treatment during tumor growth destroyed the chorionic epithelium, invaded the mesenchyme, and induced angiogenesis. Incidence of tumor formation on CAM without invasion into the mesenchyme was higher when U87 cells were treated with NaVP; the effect significantly increased with NaVP concentration. Treatment with 8 mM of NaVP did not show clear dynamics of tumor growth during 5 days; at the same time, the angiogenesis failed. With a strong staining of EZH2, p53 in tumors without NaVP treatment was found, and NaVP significantly decreased the expression of EZH2- and p53-positive cells; the effect was significantly higher at its 8 mM concentration. NaVP has a function in blocking the growth, invasion, and angiogenesis of tumor in the CAM model; tumor growth interferes with EZH2 and p53 molecular pathways, supporting the NaVP potential in GBM therapy.

  10. Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification.

    Science.gov (United States)

    Gherardi, Samuele; Ripoche, Doriane; Mikaelian, Ivan; Chanal, Marie; Teinturier, Romain; Goehrig, Delphine; Cordier-Bussat, Martine; Zhang, Chang X; Hennino, Ana; Bertolino, Philippe

    2017-04-01

    Although Men1 is a well-known tumour suppressor gene, little is known about the functions of Menin, the protein it encodes for. Since few years, numerous publications support a major role of Menin in the control of epigenetics gene regulation. While Menin interaction with MLL complex favours transcriptional activation of target genes through H3K4me3 marks, Menin also represses gene expression via mechanisms involving the Polycomb repressing complex (PRC). Interestingly, Ezh2, the PRC-methyltransferase that catalyses H3K27me3 repressive marks and Menin have been shown to co-occupy a large number of promoters. However, lack of binding between Menin and Ezh2 suggests that another member of the PRC complex is mediating this indirect interaction. Having found that ActivinB - a TGFβ superfamily member encoded by the Inhbb gene - is upregulated in insulinoma tumours caused by Men1 invalidation, we hypothesize that Menin could directly participate in the epigenetic-repression of Inhbb gene expression. Using Animal model and cell lines, we report that loss of Menin is directly associated with ActivinB-induced expression both in vivo and in vitro. Our work further reveals that ActivinB expression is mediated through a direct modulation of H3K27me3 marks on the Inhbb locus in Menin-KO cell lines. More importantly, we show that Menin binds on the promoter of Inhbb gene where it favours the recruitment of Ezh2 via an indirect mechanism involving Akt-phosphorylation. Our data suggests therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. PCI-24781 down-regulates EZH2 expression and then promotes glioma apoptosis by suppressing the PIK3K/Akt/mTOR pathway.

    Science.gov (United States)

    Zhang, Wei; Lv, Shengqing; Liu, Jun; Zang, Zhenle; Yin, Junyi; An, Ning; Yang, Hui; Song, Yechun

    2014-10-01

    PCI-24781 is a novel histone deacetylase inhibitor that inhibits tumor proliferation and promotes cell apoptosis. However, it is unclear whether PCI-24781 inhibits Enhancer of Zeste 2 (EZH2) expression in malignant gliomas. In this work, three glioma cell lines were incubated with various concentrations of PCI-24781 (0, 0.25, 0.5, 1, 2.5 and 5 μM) and analyzed for cell proliferation by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay and colony formation, and cell cycle and apoptosis were assessed by flow cytometry. The expression of EZH2 and apoptosis-related proteins was assessed by western blotting. Malignant glioma cells were also transfected with EZH2 siRNA to examine how PCI-24781 suppresses tumor cells. EZH2 was highly expressed in the three glioma cell lines. Incubation with PCI-24781 reduced cell proliferation and increased cell apoptosis by down-regulating EZH2 in a concentration-dependent manner. These effects were simulated by EZH2 siRNA. In addition, PCI-24781 or EZH2 siRNA accelerated cell apoptosis by down-regulating the expression of AKT, mTOR, p70 ribosomal protein S6 kinase (p70s6k), glycogen synthase kinase 3A and B (GSK3a/b) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). These data suggest that PCI-24781 may be a promising therapeutic agent for treating gliomas by down-regulating EZH2 which promotes cell apoptosis by suppressing the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway.

  12. Inhibitory Effect of Berberine on Zeste Homolog 2 (Ezh2 ...

    African Journals Online (AJOL)

    homolog 2 (Ezh2) expressions in KYSE450 human esophageal cancer cells. Methods: ... of the AXL receptor kinase. The results of ... effects of estrogen receptor antagonists on ..... protein EZH2 is involved in progression of prostate cancer.

  13. MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1α/HIF-1β

    Directory of Open Access Journals (Sweden)

    Xu Jianfeng

    2010-05-01

    Full Text Available Abstract Background In prostate cancer (PCa, the common treatment involving androgen ablation alleviates the disease temporarily, but results in the recurrence of highly aggressive and androgen-independent metastatic cancer. Therefore, more effective therapeutic approaches are needed. It is known that aberrant epigenetics contributes to prostate malignancy. Unlike genetic changes, these epigenetic alterations are reversible, which makes them attractive targets in PCa therapy to impede cancer progression. As a histone methyltransferease, Ezh2 plays an essential role in epigenetic regulation. Since Ezh2 is overexpressed and acts as an oncogene in PCa, it has been proposed as a bona fide target of PCa therapy. MicroRNAs (miRNAs regulate gene expression through modulating protein translation. Recently, the contribution of miRNAs in cancer development is increasingly appreciated. In this report, we present our study showing that microRNA-101 (miR-101 inhibits Ezh2 expression and differentially regulates prostate cancer cells. In addition, the expression of miR-101 alters upon androgen treatment and HIF-1α/HIF-1β induction. Result In our reporter assays, both miR-101 and miR-26a inhibit the expression of a reporter construct containing the 3'-UTR of Ezh2. When ectopically expressed in PC-3, DU145 and LNCaP cells, miR-101 inhibits endogenous Ezh2 expression in all three cell lines, while miR-26a only decreases Ezh2 in DU145. Ectopic miR-101 reduces the invasion ability of PC-3 cells, while restored Ezh2 expression rescues the invasiveness of PC-3 cells. Similarly, miR-101 also inhibits cell invasion and migration of DU145 and LNCaP cells, respectively. Interestingly, ectopic miR-101 exhibits differential effects on the proliferation of PC-3, DU-145 and LNCaP cells and also causes morphological changes of LNCaP cells. In addition, the expression of miR-101 is regulated by androgen receptor and HIF-1α/HIF-1β. While HIF-1α/HIF-1β induced by

  14. Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2.

    Science.gov (United States)

    Christofides, Anthos; Karantanos, Theodoros; Bardhan, Kankana; Boussiotis, Vassiliki A

    2016-12-20

    Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure. Numerous studies have highlighted the role of the PRC2 catalytic component enhancer of zeste homolog 2 (EZH2) in neoplastic development and progression, and EZH2 mutations have been identified in various malignancies. Through modulating the expression of critical genes, EZH2 is actively involved in fundamental cellular processes such as cell cycle progression, cell proliferation, differentiation and apoptosis. In addition to cancer cells, EZH2 also has a decisive role in the differentiation and function of T effector and T regulatory cells. In this review we summarize the recent progress regarding the role of EZH2 in human malignancies, highlight the molecular mechanisms by which EZH2 aberrations promote the pathogenesis of cancer, and discuss the anti-tumor effects of EZH2 targeting via activating direct anti-cancer mechanisms and anti-tumor immunity.

  15. Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2*

    Science.gov (United States)

    Dudakovic, Amel; Camilleri, Emily T.; Xu, Fuhua; Riester, Scott M.; McGee-Lawrence, Meghan E.; Bradley, Elizabeth W.; Paradise, Christopher R.; Lewallen, Eric A.; Thaler, Roman; Deyle, David R.; Larson, A. Noelle; Lewallen, David G.; Dietz, Allan B.; Stein, Gary S.; Montecino, Martin A.; Westendorf, Jennifer J.; van Wijnen, Andre J.

    2015-01-01

    Epigenetic control of gene expression is critical for normal fetal development. However, chromatin-related mechanisms that activate bone-specific programs during osteogenesis have remained underexplored. Therefore, we investigated the expression profiles of a large cohort of epigenetic regulators (>300) during osteogenic differentiation of human mesenchymal cells derived from the stromal vascular fraction of adipose tissue (AMSCs). Molecular analyses establish that the polycomb group protein EZH2 (enhancer of zeste homolog 2) is down-regulated during osteoblastic differentiation of AMSCs. Chemical inhibitor and siRNA knockdown studies show that EZH2, a histone methyltransferase that catalyzes trimethylation of histone 3 lysine 27 (H3K27me3), suppresses osteogenic differentiation. Blocking EZH2 activity promotes osteoblast differentiation and suppresses adipogenic differentiation of AMSCs. High throughput RNA sequence (mRNASeq) analysis reveals that EZH2 inhibition stimulates cell cycle inhibitory proteins and enhances the production of extracellular matrix proteins. Conditional genetic loss of Ezh2 in uncommitted mesenchymal cells (Prrx1-Cre) results in multiple defects in skeletal patterning and bone formation, including shortened forelimbs, craniosynostosis, and clinodactyly. Histological analysis and mRNASeq profiling suggest that these effects are attributable to growth plate abnormalities and premature cranial suture closure because of precocious maturation of osteoblasts. We conclude that the epigenetic activity of EZH2 is required for skeletal patterning and development, but EZH2 expression declines during terminal osteoblast differentiation and matrix production. PMID:26424790

  16. Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells.

    Science.gov (United States)

    Hua, Wen-Feng; Fu, Yong-Shui; Liao, Yi-Ji; Xia, Wen-Jie; Chen, Yang-Chao; Zeng, Yi-Xin; Kung, Hsiang-Fu; Xie, Dan

    2010-07-10

    Curcumin, a natural compound isolated from turmeric, may inhibit cell proliferation in various tumor cells through a mechanism that is not fully understood. The enhancer of zeste homolog 2 (EZH2) gene is overexpressed in human breast cancers with poor prognosis. In this study, we observed a dose- and time-dependent down-regulation of expression of EZH2 by curcumin that correlates with decreased proliferation in the MDA-MB-435 breast cancer cell line. The curcumin treatment resulted in an accumulation of cells in the G(1) phase of the cell cycle. Further investigation revealed that curcumin-induced down-regulation of EZH2 through stimulation of three major members of the mitogen-activated protein kinase (MAPK) pathway: c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase. These data suggest that an underlying mechanism of the MAPK pathway mediates the down-regulation of EZH2, thus contributing to the anti-proliferative effects of curcumin against breast cancer. Copyright 2010 Elsevier B.V. All rights reserved.

  17. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    OpenAIRE

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2...

  18. Sodium arsenite represses the expression of myogenin in C2C12 mouse myoblast cells through histone modifications and altered expression of Ezh2, Glp, and Igf-1

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Gia-Ming [Environmental Toxicology Graduate Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Present address: The University of Chicago, Section of Hematology/Oncology, 900 E. 57th Street, Room 7134, Chicago, IL 60637 (United States); Bain, Lisa J., E-mail: lbain@clemson.edu [Environmental Toxicology Graduate Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States)

    2012-05-01

    Arsenic is a toxicant commonly found in water systems and chronic exposure can result in adverse developmental effects including increased neonatal death, stillbirths, and miscarriages, low birth weight, and altered locomotor activity. Previous studies indicate that 20 nM sodium arsenite exposure to C2C12 mouse myocyte cells delayed myoblast differentiation due to reduced myogenin expression, the transcription factor that differentiates myoblasts into myotubes. In this study, several mechanisms by which arsenic could alter myogenin expression were examined. Exposing differentiating C2C12 cells to 20 nM arsenic increased H3K9 dimethylation (H3K9me2) and H3K9 trimethylation (H3K9me3) by 3-fold near the transcription start site of myogenin, which is indicative of increased repressive marks, and reduced H3K9 acetylation (H3K9Ac) by 0.5-fold, indicative of reduced permissive marks. Protein expression of Glp or Ehmt1, a H3-K9 methyltransferase, was also increased by 1.6-fold in arsenic-exposed cells. In addition to the altered histone remodeling status on the myogenin promoter, protein and mRNA levels of Igf-1, a myogenic growth factor, were significantly repressed by arsenic exposure. Moreover, a 2-fold induction of Ezh2 expression, and an increased recruitment of Ezh2 (3.3-fold) and Dnmt3a (∼ 2-fold) to the myogenin promoter at the transcription start site (− 40 to + 42), were detected in the arsenic-treated cells. Together, we conclude that the repressed myogenin expression in arsenic-exposed C2C12 cells was likely due to a combination of reduced expression of Igf-1, enhanced nuclear expression and promoter recruitment of Ezh2, and altered histone remodeling status on myogenin promoter (− 40 to + 42). -- Highlights: ► Igf-1 expression is decreased in C2C12 cells after 20 nM arsenite exposure. ► Arsenic exposure alters histone remodeling on the myogenin promoter. ► Glp expression, a H3–K9 methyltransferase, was increased in arsenic-exposed cells. ► Ezh2

  19. The histone methyltransferase EZH2 as a novel prosurvival factor in clinically aggressive chronic lymphocytic leukemia.

    Science.gov (United States)

    Papakonstantinou, Nikos; Ntoufa, Stavroula; Chartomatsidou, Elisavet; Kotta, Konstantia; Agathangelidis, Andreas; Giassafaki, Lefki; Karamanli, Tzeni; Bele, Panagiota; Moysiadis, Theodoros; Baliakas, Panagiotis; Sutton, Lesley Ann; Stavroyianni, Niki; Anagnostopoulos, Achilles; Makris, Antonios M; Ghia, Paolo; Rosenquist, Richard; Stamatopoulos, Kostas

    2016-06-14

    The histone methyltransferase EZH2 induces gene repression through trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 overexpression has been reported in many types of cancer and associated with poor prognosis. Here we investigated the expression and functionality of EZH2 in chronic lymphocytic leukemia (CLL). Aggressive cases with unmutated IGHV genes (U-CLL) displayed significantly higher EZH2 expression compared to indolent CLL cases with mutated IGHV genes (M-CLL); furthermore, in U-CLL EZH2 expression was upregulated with disease progression. Within U-CLL, EZH2high cases harbored significantly fewer (p = 0.033) TP53 gene abnormalities compared to EZH2low cases. EZH2high cases displayed high H3K27me3 levels and increased viability suggesting that EZH2 is functional and likely confers a survival advantage to CLL cells. This argument was further supported by siRNA-mediated downmodulation of EZH2 which resulted in increased apoptosis. Notably, at the intraclonal level, cell proliferation was significantly associated with EZH2 expression. Treatment of primary CLL cells with EZH2 inhibitors induced downregulation of H3K27me3 levels leading to increased cell apoptosis. In conclusion, EZH2 is overexpressed in adverse-prognosis CLL and associated with increased cell survival and proliferation. Pharmacologic inhibition of EZH2 catalytic activity promotes apoptosis, highlighting EZH2 as a novel potential therapeutic target for specific subgroups of patients with CLL.

  20. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    Science.gov (United States)

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future. PMID:21865393

  1. Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes.

    Science.gov (United States)

    Hyland, Paula L; McDade, Simon S; McCloskey, Rachel; Dickson, Glenda J; Arthur, Ken; McCance, Dennis J; Patel, Daksha

    2011-11-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

  2. EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice

    Directory of Open Access Journals (Sweden)

    Zhan-Li Shi

    2018-01-01

    Full Text Available Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks. On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP. Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

  3. Regulation of T cell differentiation and function by EZH2

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    THEODOROS KARANTANOS

    2016-05-01

    Full Text Available The enhancer of zeste homologue 2 (EZH2, one of the polycomb group (PcG proteins, is the catalytic subunit of Polycomb-repressive complex 2 (PRC2 and induces the trimethylation of the histone H3 lysine 27 (H3K27me3 promoting epigenetic gene silencing. EZH2 contains a SET domain promoting the methyltransferase activity while the three other protein components of PRC2, namely EED, SUZ12 and RpAp46/48 induce compaction of the chromatin permitting EZH2 enzymatic activity. Numerous studies highlight the role of this evolutionary conserved protein as a master regulator of differentiation in humans involved in the repression of the homeotic (Hox gene and the inactivation of X-chromosome. Through its effects in the epigenetic regulation of critical genes, EZH2 has been strongly linked to cell cycle progression, stem cell pluripotency and cancer biology. Most recently, EZH2 has been associated with hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis. Several studies have evaluated the role of EZH2 in the regulation of T cell differentiation and plasticity as well as its implications in the development of autoimmune diseases and graft versus host disease (GvHD. In this review we will briefly summarize the current knowledge regarding the role of EZH2 in the regulation of T cell differentiation, effector function and homing in the tumor microenvironment and we will discuss possible therapeutic targeting of EZH2 in order to alter T cell immune functions.

  4. Regulation of T Cell Differentiation and Function by EZH2

    Science.gov (United States)

    Karantanos, Theodoros; Christofides, Anthos; Bardhan, Kankana; Li, Lequn; Boussiotis, Vassiliki A.

    2016-01-01

    The enhancer of zeste homolog 2 (EZH2), one of the polycomb-group proteins, is the catalytic subunit of Polycomb-repressive complex 2 (PRC2) and induces the trimethylation of the histone H3 lysine 27 (H3K27me3) promoting epigenetic gene silencing. EZH2 contains a SET domain promoting the methyltransferase activity, while the three other protein components of PRC2, namely EED, SUZ12, and RpAp46/48, induce compaction of the chromatin permitting EZH2 enzymatic activity. Numerous studies highlight the role of this evolutionary conserved protein as a master regulator of differentiation in humans involved in the repression of the homeotic gene and the inactivation of X-chromosome. Through its effects in the epigenetic regulation of critical genes, EZH2 has been strongly linked to cell cycle progression, stem cell pluripotency, and cancer biology, being currently at the cutting edge of research. Most recently, EZH2 has been associated with hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis. Several studies have evaluated the role of EZH2 in the regulation of T cell differentiation and plasticity as well as its implications in the development of autoimmune diseases and graft-versus-host disease (GVHD). The aim of this review is to summarize the current knowledge regarding the role of EZH2 in the regulation of the differentiation and function of T cells focusing on possible applications in various immune-mediated conditions, including autoimmune disorders and GVHD. PMID:27199994

  5. EZH2 regulates dental pulp inflammation by direct effect on inflammatory factors.

    Science.gov (United States)

    Hui, Tianqian; A, Peng; Zhao, Yuan; Yang, Jing; Ye, Ling; Wang, Chenglin

    2018-01-01

    Pulpitis is a multi-factorial disease that could be caused by complex interactions between genetics, epigenetics and environmental factors. We aimed to evaluate the role of Enhancer of Zeste Homolog 2 (EZH2) in the inflammatory response of human dental pulp cells (HDPCs) and dental pulp tissues. The expressions of inflammatory cytokines in HDPCs treated by EZH2 complex or EZH2 siRNA with or without rhTNF-α were examined by quantitative real-time polymerase chain reaction (q-PCR). The levels of secreted inflammatory cytokines including IL-6, IL-8, IL-15, CCL2 and CXCL12 in culture supernatants were measured by Luminex assay. In rat pulpitis model, the effects of EZH2 on dental pulp tissues were verified by histology. We invested the mechanisms of the effect of EZH2 on the inflammatory factors by ChIP assay. EZH2 down-regulation inhibited the expression of inflammatory factors, including IL-6, IL-8, IL-15, CCL2 and CXCL12 in HDPCs. EZH2 complex promoted the expression and secretion of these inflammatory factors in HDPCs, while EZH2 silencing could attenuate the promotion of inflammatory factors that were induced by rhTNF-α. In pulpitis models of rats, EZH2 down-regulation inhibited the inflammatory process of dental pulp while EZH2 complex showed no significant facilitation of pulpal inflammation. In addition, EZH2 could bind on the promoters of IL-6, IL-8 and CCL2, but not IL-15 and CXCL12, to affect the transcription of these proinflammatory cytokines. In HDPCs, EZH2 could induce inflammation, while EZH2 down-regulation could attenuate the inflammatory responses. EZH2 plays an important role in this inflammatory process of dental pulp. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Comprehensive Evaluation of the Role of EZH2 in the Growth, Invasion, and Aggression of a Panel of Prostate Cancer Cell Lines

    Science.gov (United States)

    Karanikolas, Breanne D.W.; Figueiredo, Marxa L.; Wu, Lily

    2010-01-01

    Background Although most prostate cancers respond well to initial treatments, a fraction of prostate cancers are more aggressive and will recur and metastasize. At that point, there are few treatment options available. Significant efforts have been made to identify biomarkers that will identify these more aggressive cancers to tailor a more vigorous treatment in order to improve outcome. Polycomb Group protein Enhancer of Zeste 2 (EZH2) was found to be overexpressed in metastatic prostate tumors, and is considered an excellent candidate for such a biomarker. Scattered studies have found that EZH2 overexpression causes neoplastic transformation, invasion, and growth of prostate cells. However, these studies utilized different systems and cell lines, and so are difficult to correlate with one another. Methods In this study, a comprehensive evaluation of the phenotypic effects of EZH2 in a panel of five prostate cancer cell lines was performed. By using multiple cell lines, and examining overexpression and knockdown of EZH2 concurrently, a broad view of EZH2's role in prostate cancer was achieved. Results Overexpression of EZH2 led to more aggressive behaviors in all prostate cell lines tested. In contrast, downregulation of EZH2 reduced invasion and tumorigenicity of androgen-independent cell lines CWR22Rv1, PC3, and DU145, but not of androgen-dependent cell lines LAPC4 and LNCaP. Conclusions Findings from this study suggest androgen-independent prostate tumors are more dependent on EZH2 expression than androgen-dependent tumors. Our observations provide an explanation for the strong correlation between EZH2 overexpression and advanced stage, aggressive prostate cancers. PMID:20087897

  7. EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?

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    Ke-Sin Yan

    2017-05-01

    Full Text Available Enhancer of zeste homolog 2 (EZH2, a histone methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3 to regulate gene expression through epigenetic machinery. EZH2 functions as a double-facet molecule in regulation of gene expression via repression or activation mechanisms, depending on the different cellular contexts. EZH2 interacts with both histone and non-histone proteins to modulate diverse physiological functions including cancer progression and malignancy. In this review article, we focused on the updated information regarding microRNAs (miRNAs and long non coding RNAs (lncRNAs in regulation of EZH2, the oncogenic and tumor suppressive roles of EZH2 in cancer progression and malignancy, as well as current pre-clinical and clinical trials of EZH2 inhibitors.

  8. EZH2 Impairs Human Dental Pulp Cell Mineralization via the Wnt/β-Catenin Pathway.

    Science.gov (United States)

    Li, B; Yu, F; Wu, F; Hui, T; A, P; Liao, X; Yin, B; Wang, C; Ye, L

    2018-05-01

    The enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of PRC2 (polycomb repressor complex 2). It mediates gene silencing via methyltransferase activity and is involved in the determination of cell lineage. However, the function of EZH2 and the underlying mechanisms by which it affects the differentiation of human dental pulp cell (hDPC) have remained underexplored. In this research, we found that EZH2 expression decreased during the mineralization of hDPCs, with attenuated H3K27me3 (trimethylation on lysine 27 in histone H3). Overexpression of EZH2 impaired the odontogenic differentiation of hDPCs, while EZH2 without methyltransferase activity mutation (mutation of suppressed variegation of 3 to 9, enhancer of zeste and trithorax domain, EZH2ΔSET) did not display this phenotype. In addition, siRNA knockdown studies showed that EZH2 negatively modulated hDPC differentiation in vitro and inhibited mineralized nodule formation in transplanted β-tricalcium phosphate / hDPC composites. To further investigate the underlying mechanisms, we explored the Wnt/β-catenin signaling pathway in view of the fact that previous research had documented the essential role that it plays during hDPC mineralization, as well as its links to EZH2 in other cells. We demonstrated for the first time that EZH2 depletion activated the Wnt/β-catenin signaling pathway and enhanced the accumulation of β-catenin in hDPCs. Chromatin immunoprecipitation analysis suggested that these effects are attributable to the level of the EZH2-regulated H3K27me3 on the β-catenin promoter. We conclude that EZH2 plays a negative role during the odontogenic differentiation of hDPCs. Suppression of EZH2 could promote hDPC mineralization by epigenetically regulating the expression of β-catenin and activating the Wnt canonical signaling pathway.

  9. EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications.

    Science.gov (United States)

    Li, Zhenghao; Takenobu, Hisanori; Setyawati, Amallia Nuggetsiana; Akita, Nobuhiro; Haruta, Masayuki; Satoh, Shunpei; Shinno, Yoshitaka; Chikaraishi, Koji; Mukae, Kyosuke; Akter, Jesmin; Sugino, Ryuichi P; Nakazawa, Atsuko; Nakagawara, Akira; Aburatani, Hiroyuki; Ohira, Miki; Kamijo, Takehiko

    2018-05-01

    The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported. A Kaplan-Meier analysis on the event free survival and overall survival of NB patients indicated that the high expression of EZH2 correlated with an unfavorable prognosis. In order to elucidate the functional roles of EZH2 in NB tumorigenesis and its aggressiveness, we knocked down EZH2 in NB cell lines using lentivirus systems. The knockdown of EZH2 significantly induced NB cell differentiation, e.g., neurite extension, and the neuronal differentiation markers, NF68 and GAP43. EZH2 inhibitors also induced NB cell differentiation. We performed a comprehensive transcriptome analysis using Human Gene Expression Microarrays and found that NTRK1 (TrkA) is one of the EZH2-related suppression targets. The depletion of NTRK1 canceled EZH2 knockdown-induced NB cell differentiation. Our integrative methylome, transcriptome, and chromatin immunoprecipitation assays using NB cell lines and clinical samples clarified that the NTRK1 P1 and P2 promoter regions were regulated differently by DNA methylation and EZH2-related histone modifications. The NTRK1 transcript variants 1/2, which were regulated by EZH2-related H3K27me3 modifications at the P1 promoter region, were strongly expressed in favorable, but not unfavorable NB. The depletion and inhibition of EZH2 successfully induced NTRK1 transcripts and functional proteins. Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also

  10. TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p

    OpenAIRE

    Cao, Jiaqing; Han, Xinyou; Qi, Xin; Jin, Xiangyun; Li, Xiaolin

    2017-01-01

    lncRNA-TUG1 (Taurine upregulated 1) is up regulated and highly correlated with poor prognosis and disease status in osteosarcoma. TUG1 knockdown inhibits osteosarcoma cell proliferation, migration and invasion, and promotes apoptosis. However, its mechanism of action has not been well addressed. Growing evidence documented that lncRNA works as competing endogenous (ce)RNAs to modulate the expression and biological functions of miRNA. As a putative combining target of TUG1, miR-144-3p has been...

  11. Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity

    DEFF Research Database (Denmark)

    Pasini, Diego; Bracken, Adrian P; Jensen, Michael R

    2004-01-01

    SUZ12 is a recently identified Polycomb group (PcG) protein, which together with EZH2 and EED forms different Polycomb repressive complexes (PRC2/3). These complexes contain histone H3 lysine (K) 27/9 and histone H1 K26 methyltransferase activity specified by the EZH2 SET domain. Here we show...

  12. A non-canonical function of Ezh2 preserves immune homeostasis.

    Science.gov (United States)

    Vasanthakumar, Ajithkumar; Xu, Dakang; Lun, Aaron Tl; Kueh, Andrew J; van Gisbergen, Klaas Pjm; Iannarella, Nadia; Li, Xiaofang; Yu, Liang; Wang, Die; Williams, Bryan Rg; Lee, Stanley Cw; Majewski, Ian J; Godfrey, Dale I; Smyth, Gordon K; Alexander, Warren S; Herold, Marco J; Kallies, Axel; Nutt, Stephen L; Allan, Rhys S

    2017-04-01

    Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We further show that Ezh2 directly methylates the NKT cell lineage defining transcription factor PLZF, leading to its ubiquitination and subsequent degradation. Sustained PLZF expression in Ezh2-deficient mice is associated with the expansion of a subset of NKT cells that cause immune perturbation. Taken together, we have identified a chromatin-independent function of Ezh2 that impacts on the development of the immune system. © 2017 The Authors.

  13. Multifaceted role of EZH2 in breast and prostate tumorigenesis: epigenetics and beyond.

    Science.gov (United States)

    Deb, Gauri; Thakur, Vijay S; Gupta, Sanjay

    2013-05-01

    Overexpression of EZH2 and other PRC2 subunits, such as SUZ12, is associated with tumor progression and poor prognosis in several human malignancies. Nevertheless, the underlying mechanisms driving aberrant EZH2 expression are poorly understood. This review provides molecular insights into the essential role of EZH2 in breast and prostate tumorigenesis. We addressed the current understanding on the oncogenic role of EZH2, with an emphasis on: (1) the less known PRC2-independent role of EZH2 in gene activation, in addition to its canonical role in transcriptional silencing as a histone methyltransferase catalyzing the trimethylation of histone H3 at lysine 27; (2) causes and consequences of its deregulation in tumor cells and; (3) collaboration of EZH2 with other epigenetic and hormone receptor-mediated oncogenic signaling pathways. We also summarize how EZH2 has emerged as a promising therapeutic target in hormone-refractory cancers and the prospects for integrating EZH2 blockade with available pharmacological inhibitors.

  14. Update of research on the role of EZH2 in cancer progression

    Directory of Open Access Journals (Sweden)

    Shen L

    2013-04-01

    Full Text Available Liang Shen,1 Jing Cui,2 Shumei Liang,3 Yingxin Pang,1 Peishu Liu11Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 2Department of Oral and Maxillofacial Surgery, Jinan Stomatologic Hospital, 3Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of ChinaAbstract: Accumulating evidence shows that enhancer of zeste homolog 2 (E2H2 is upregulated in a broad range of cancer types, such as breast cancer, prostate cancer, ovarian cancer, and colon cancer. Therefore, inhibiting EZH2 expression may be a promising strategy for anticancer therapy. This review focuses on the current understanding of the mechanisms underlying EZH2 regulation that are involved in cancer progression. Also, it introduces two EZH2 inhibitors that target EZH2 and could be potentially applied in the treatment of cancer in the future.Keywords: EZH2, PRC2, cancer

  15. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  16. Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury.

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    Lin Cheng

    Full Text Available Epigenetic predisposition is thought to critically contribute to adult-onset disorders, such as retinal neurodegeneration. The histone methyltransferase, enhancer of zeste homolog 2 (Ezh2, is transiently expressed in the perinatal retina, particularly enriched in retinal ganglion cells (RGCs. We previously showed that embryonic deletion of Ezh2 from retinal progenitors led to progressive photoreceptor degeneration throughout life, demonstrating a role for embryonic predisposition of Ezh2-mediated repressive mark in maintaining the survival and function of photoreceptors in the adult. Enrichment of Ezh2 in RGCs leads to the question if Ezh2 also mediates gene expression and function in postnatal RGCs, and if its deficiency changes RGC susceptibility to cell death under injury or disease in the adult. To test this, we generated mice carrying targeted deletion of Ezh2 from RGC progenitors driven by Math5-Cre (mKO. mKO mice showed no detectable defect in RGC development, survival, or cell homeostasis as determined by physiological analysis, live imaging, histology, and immunohistochemistry. Moreover, RGCs of Ezh2 deficient mice revealed similar susceptibility against glaucomatous and acute optic nerve trauma-induced neurodegeneration compared to littermate floxed or wild-type control mice. In agreement with the above findings, analysis of RNA sequencing of RGCs purified from Ezh2 deficient mice revealed few gene changes that were related to RGC development, survival and function. These results, together with our previous report, support a cell lineage-specific mechanism of Ezh2-mediated gene repression, especially those critically involved in cellular function and homeostasis.

  17. Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically in melanoma as a promising target for combination therapy.

    Science.gov (United States)

    Yu, Huan; Ma, Meng; Yan, Junya; Xu, Longwen; Yu, Jiayi; Dai, Jie; Xu, Tianxiao; Tang, Huan; Wu, Xiaowen; Li, Siming; Lian, Bin; Mao, Lili; Chi, Zhihong; Cui, Chuanliang; Guo, Jun; Kong, Yan

    2017-12-04

    Coexistence of enhancer of zeste homolog 2 (EZH2) and BRAF gene aberrations has been described in many cancer types. In this study, we aim to explore the coexistence status of BRAF V600E mutation and the copy number variation of EZH2 and explore the potential of this combination as a therapeutic target. A total of 138 cases of melanoma samples harboring BRAF V600E mutation were included, and EZH2 copy numbers were examined by QuantiGenePlex DNA Assays. Clinical pathological distinction between patient groups with or without EZH2 amplification (hereafter referred to as EZH2 gain) was statistically analyzed. The sensitivity of melanoma cell lines and patient-derived xenograft (PDX) models containing BRAF V600E mutation with or without EZH2 gain to vemurafenib (BRAF inhibitor), GSK2816126 (EZH2 inhibitor) and a combination of both agents was evaluated. In our cohort, the coexistence rate of BRAF V600E mutation and EZH2 gain was up to 29.0%, and significant differences in overall survival and disease-free survival were found between no EZH2 copy number gain and gain groups (P = 0.038, P = 0.030), gain and high EZH2 copy number gain groups (P = 0.006, P = 0.010). Combination with BRAF and EZH2 inhibition showed better inhibitory efficacy in melanoma prevention compared with vemurafenib monotherapy. More importantly, this improved therapeutic effect was observed especially in melanoma cell lines and PDX models containing concurrently BRAF V600E mutation and EZH2 gain. Coexistence of BRAF V600E mutation and EZH2 gain is rather prevalent in melanoma. Our findings provided evidence for the feasibility of combination therapy with EZH2 and BRAF inhibitors in melanoma with concurrent BRAF V600E mutation and EZH2 gain.

  18. GSK126 (EZH2 inhibitor) interferes with ultraviolet A radiation-induced photoaging of human skin fibroblast cells

    Science.gov (United States)

    Qin, Haiyan; Zhang, Guang; Zhang, Lianbo

    2018-01-01

    Polycomb group genes (PcG) encode chromatin modification proteins that are involved in the epigenetic regulation of cell differentiation, proliferation and the aging processes. The key subunit of the PcG complex, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), has a central role in a variety of mechanisms, such as the formation of chromatin structure, gene expression regulation and DNA damage. In the present study, ultraviolet A (UVA) was used to radiate human dermal fibroblasts in order to construct a photo-aged cell model. Subsequently, the cell viability assay, Hoechst staining, apoptosis detection using flow cytometry, senescence-associated β-galactosidase (SA-β-gal) staining and erythrocyte exclusion experiments were performed. GSK126, a histone methylation enzyme inhibitor of EZH2, was used as an experimental factor. Results suggested that GSK126 downregulated the mRNA expression levels of EZH2 and upregulated the mRNA expression levels of BMI-1. Notably, GSK126 affected the transcription of various photoaging-related genes and thus protected against photoaging induced by UVA radiation. PMID:29545866

  19. Ezh2 represses the basal cell lineage during lung endoderm development.

    Science.gov (United States)

    Snitow, Melinda E; Li, Shanru; Morley, Michael P; Rathi, Komal; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Morrisey, Edward E

    2015-01-01

    The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway. Loss of Ezh2 also leads to reduced secretory cell differentiation. In their place, morphologically similar cells develop that express a subset of basal cell genes, including keratin 5, but no longer express high levels of either Trp63 or of standard secretory cell markers. This suggests that Ezh2 regulates the phenotypic switch between basal cells and secretory cells. Together, these findings show that Ezh2 restricts the basal cell lineage during normal lung endoderm development to allow the proper patterning of epithelial lineages during lung formation. © 2015. Published by The Company of Biologists Ltd.

  20. A chimeric fusion of the hASH1 and EZH2 promoters mediates high and specific reporter and suicide gene expression and cytotoxicity in small cell lung cancer cells

    DEFF Research Database (Denmark)

    Poulsen, T.T.; Pedersen, N.; Juel, H.

    2008-01-01

    Transcriptionally targeted gene therapy is a promising experimental modality for treatment of systemic malignancies such as small cell lung cancer (SCLC). We have identified the human achaete-scute homolog 1 (hASH1) and enhancer of zeste homolog 2 (EZH2) genes as highly upregulated in SCLC compar...

  1. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Etienne Danis

    2016-03-01

    Full Text Available Early T cell precursor acute lymphoblastic leukemia (ETP-ALL is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients.

  2. EZH2 Protects Glioma Stem Cells from Radiation-Induced Cell Death in a MELK/FOXM1-Dependent Manner

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    Sung-Hak Kim

    2015-02-01

    Full Text Available Glioblastoma (GBM-derived tumorigenic stem-like cells (GSCs may play a key role in therapy resistance. Previously, we reported that the mitotic kinase MELK binds and phosphorylates the oncogenic transcription factor FOXM1 in GSCs. Here, we demonstrate that the catalytic subunit of Polycomb repressive complex 2, EZH2, is targeted by the MELK-FOXM1 complex, which in turn promotes resistance to radiation in GSCs. Clinically, EZH2 and MELK are coexpressed in GBM and significantly induced in postirradiation recurrent tumors whose expression is inversely correlated with patient prognosis. Through a gain-and loss-of-function study, we show that MELK or FOXM1 contributes to GSC radioresistance by regulation of EZH2. We further demonstrate that the MELK-EZH2 axis is evolutionarily conserved in Caenorhabditis elegans. Collectively, these data suggest that the MELK-FOXM1-EZH2 signaling axis is essential for GSC radioresistance and therefore raise the possibility that MELK-FOXM1-driven EZH2 signaling can serve as a therapeutic target in irradiation-resistant GBM tumors.

  3. Transcriptome and H3K27 tri-methylation profiling of Ezh2-deficient lung epithelium

    Directory of Open Access Journals (Sweden)

    Aliaksei Z. Holik

    2015-09-01

    Full Text Available The adaptation of the lungs to air breathing at birth requires the fine orchestration of different processes to control lung morphogenesis and progenitor cell differentiation. However, there is little understanding of the role that epigenetic modifiers play in the control of lung development. We found that the histone methyl transferase Ezh2 plays a critical role in lung lineage specification and survival at birth. We performed a genome-wide transcriptome study combined with a genome-wide analysis of the distribution of H3K27 tri-methylation marks to interrogate the role of Ezh2 in lung epithelial cells. Lung cells isolated from Ezh2-deficient and control mice at embryonic day E16.5 were sorted into epithelial and mesenchymal populations based on EpCAM expression. This enabled us to dissect the transcriptional and epigenetic changes induced by the loss of Ezh2 specifically in the lung epithelium. Here we provide a detailed description of the analysis of the RNA-seq and ChIP-seq data, including quality control, read mapping, differential expression and differential binding analyses, as well as visualisation methods used to present the data. These data can be accessed from the Gene Expression Omnibus database (super-series accession number GSE57393.

  4. EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer

    NARCIS (Netherlands)

    Pietersen, Alexandra M.; Horlings, Hugo M.; Hauptmann, Michael; Langerod, Anita; Ajouaou, Abderrahim; Cornelissen-Steijger, Paulien; Wessels, Lodewijk F.; Jonkers, Jos; van de Vijver, Marc J.; van Lohuizen, Maarten

    2008-01-01

    Introduction PolycombGroup (PcG) proteins maintain gene repression through histone modifications and have been implicated in stem cell regulation and cancer. EZH2 is part of Polycomb Repressive Complex 2 (PRC2) and trimethylates H3K27. This histone mark recruits the BMI1-containing PRC1 that

  5. Interplay between EZH2 and G9a Regulates CXCL10 Gene Repression in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Coward, William R; Brand, Oliver J; Pasini, Alice; Jenkins, Gisli; Knox, Alan J; Pang, Linhua

    2018-04-01

    Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodeling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 repression. In this study, we explored the role of H3K27 methylation and the interplay between the two histone lysine methyltransferases enhancer of zest homolog 2 (EZH2) and G9a in CXCL10 repression in IPF. By applying chromatin immunoprecipitation, Re-ChIP, and proximity ligation assays, we demonstrated that, like G9a-mediated H3K9 methylation, EZH2-mediated histone H3 lysine 27 trimethylation (H3K27me3) was significantly enriched at the CXCL10 promoter in fibroblasts from IPF lungs (F-IPF) compared with fibroblasts from nonfibrotic lungs, and we also found that EZH2 and G9a physically interacted with each other. EZH2 knockdown reduced not only EZH2 and H3K27me3 but also G9a and H3K9me3, and G9a knockdown reduced not only G9 and H3K9me3 but also EZH2 and H3K27me3. Depletion and inhibition of EZH2 and G9a also reversed histone deacetylation and restored CXCL10 expression in F-IPF. Furthermore, treatment of fibroblasts from nonfibrotic lungs with the profibrotic cytokine transforming growth factor-β1 increased EZH2, G9a, H3K27me3, H3K9me3, and histone deacetylation at the CXCL10 promoter, similar to that observed in F-IPF, which was correlated with CXCL10 repression and was prevented by EZH2 and G9a knockdown. These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other antifibrotic genes in IPF.

  6. Altered expression of polycomb group genes in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available The Polycomb group (PcG proteins play a critical role in histone mediated epigenetics which has been implicated in the malignant evolution of glioblastoma multiforme (GBM. By systematically interrogating The Cancer Genome Atlas (TCGA, we discovered widespread aberrant expression of the PcG members in GBM samples compared to normal brain. The most striking differences were upregulation of EZH2, PHF19, CBX8 and PHC2 and downregulation of CBX7, CBX6, EZH1 and RYBP. Interestingly, changes in EZH2, PHF19, CBX7, CBX6 and EZH1 occurred progressively as astrocytoma grade increased. We validated the aberrant expression of CBX6, CBX7, CBX8 and EZH2 in GBM cell lines by Western blotting and qRT-PCR, and further the aberrant expression of CBX6 in GBM tissue samples by immunohistochemical staining. To determine if there was functional significance to the diminished CBX6 levels in GBM, CBX6 was overexpressed in GBM cells resulting in decreased proliferative capacity. In conclusion, aberrant expression of PcG proteins in GBMs may play a role in the development or maintenance of the malignancy.

  7. Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor.

    Science.gov (United States)

    Honma, Daisuke; Kanno, Osamu; Watanabe, Jun; Kinoshita, Junzo; Hirasawa, Makoto; Nosaka, Emi; Shiroishi, Machiko; Takizawa, Takeshi; Yasumatsu, Isao; Horiuchi, Takao; Nakao, Akira; Suzuki, Keisuke; Yamasaki, Tomonori; Nakajima, Katsuyoshi; Hayakawa, Miho; Yamazaki, Takanori; Yadav, Ajay Singh; Adachi, Nobuaki

    2017-10-01

    Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B-cell lymphoma cells harboring gain-of-function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL-AF9, MLL-AF4, and AML1-ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  8. NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF

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    Mitchell E. Fane

    2017-02-01

    Full Text Available While invasion and metastasis of tumour cells are the principle factor responsible for cancer related deaths, the mechanisms governing the process remain poorly defined. Moreover, phenotypic divergence of sub-populations of tumour cells is known to underpin alternative behaviors linked to tumour progression such as proliferation, survival and invasion. In the context of melanoma, heterogeneity between two transcription factors, BRN2 and MITF, has been associated with phenotypic switching between predominantly invasive and proliferative behaviors respectively. Epigenetic changes, in response to external cues, have been proposed to underpin this process, however the mechanism by which the phenotypic switch occurs is unclear. Here we report the identification of the NFIB transcription factor as a novel downstream effector of BRN2 function in melanoma cells linked to the migratory and invasive characteristics of these cells. Furthermore, the function of NFIB appears to drive an invasive phenotype through an epigenetic mechanism achieved via the upregulation of the polycomb group protein EZH2. A notable target of NFIB mediated up-regulation of EZH2 is decreased MITF expression, which further promotes a less proliferative, more invasive phenotype. Together our data reveal that NFIB has the ability to promote dynamic changes in the chromatin state of melanoma cells to facilitate migration, invasion and metastasis.

  9. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin | Office of Cancer Genomics

    Science.gov (United States)

    Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays.

  10. EZH2: a pivotal regulator in controlling cell differentiation.

    Science.gov (United States)

    Chen, Ya-Huey; Hung, Mien-Chie; Li, Long-Yuan

    2012-01-01

    Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin structures, contributing to tumor progression and the regulation of development and lineage commitment both in embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4, resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its targets as well as their roles in stem cell maintenance and cell differentiation.

  11. SAH derived potent and selective EZH2 inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Kung, Pei-Pei; Huang, Buwen; Zehnder, Luke; Tatlock, John; Bingham, Patrick; Krivacic, Cody; Gajiwala, Ketan; Diehl, Wade; Yu, Xiu; Maegley, Karen A.

    2015-04-01

    A series of novel enhancer of zeste homolog 2 (EZH2) inhibitors was designed based on the chemical structure of the histone methyltransferase (HMT) inhibitor SAH (S-adenosyl-l-homocysteine). These nucleoside-based EZH2 inhibitors blocked the methylation of nucleosomes at H3K27 in biochemical assays employing both WT PRC2 complex as well as a Y641N mutant PRC2 complex. The most potent compound, 27, displayed IC50’s against both complexes of 270 nM and 70 nM, respectively. To our knowledge, compound 27 is the most potent SAH-derived inhibitor of the EZH2 PRC2 complex yet identified. This compound also displayed improved potency, lipophilic efficiency (LipE), and selectivity profile against other lysine methyltransferases compared with SAH.

  12. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM.

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    Dejuan Kong

    Full Text Available The emergence of castrate-resistant prostate cancer (CRPC contributes to the high mortality of patients diagnosed with prostate cancer (PCa, which in part could be attributed to the existence and the emergence of cancer stem cells (CSCs. Recent studies have shown that deregulated expression of microRNAs (miRNAs contributes to the initiation and progression of PCa. Among several known miRNAs, let-7 family appears to play a key role in the recurrence and progression of PCa by regulating CSCs; however, the mechanism by which let-7 family contributes to PCa aggressiveness is unclear. Enhancer of Zeste homolog 2 (EZH2, a putative target of let-7 family, was demonstrated to control stem cell function. In this study, we found loss of let-7 family with corresponding over-expression of EZH2 in human PCa tissue specimens, especially in higher Gleason grade tumors. Overexpression of let-7 by transfection of let-7 precursors decreased EZH2 expression and repressed clonogenic ability and sphere-forming capacity of PCa cells, which was consistent with inhibition of EZH2 3'UTR luciferase activity. We also found that the treatment of PCa cells with BR-DIM (formulated DIM: 3,3'-diindolylmethane by Bio Response, Boulder, CO, abbreviated as BR-DIM up-regulated let-7 and down-regulated EZH2 expression, consistent with inhibition of self-renewal and clonogenic capacity. Moreover, BR-DIM intervention in our on-going phase II clinical trial in patients prior to radical prostatectomy showed upregulation of let-7 consistent with down-regulation of EZH2 expression in PCa tissue specimens after BR-DIM intervention. These results suggest that the loss of let-7 mediated increased expression of EZH2 contributes to PCa aggressiveness, which could be attenuated by BR-DIM treatment, and thus BR-DIM is likely to have clinical impact.

  13. EZH2-mediated α-actin methylation needs lncRNA TUG1, and promotes the cortex cytoskeleton formation in VSMCs.

    Science.gov (United States)

    Chen, Rong; Kong, Peng; Zhang, Fan; Shu, Ya-Nan; Nie, Xi; Dong, Li-Hua; Lin, Yan-Ling; Xie, Xiao-Li; Zhao, Li-Li; Zhang, Xiang-Jian; Han, Mei

    2017-06-15

    Recent studies have revealed that long non-coding RNAs (lncRNAs) participate in vascular homeostasis and pathophysiological conditions development. But still very few literatures elucidate the regulatory mechanism of non-coding RNAs in this biological process. Here we identified lncRNA taurine up-regulated gene 1 (TUG1) in rat vascular smooth muscle cells (VSMCs), and got 4612bp nucleotide sequence. The expression level of TUG1 RNA was increased in synthetic VSMCs by real-time PCR analysis. Meanwhile, the expression of enhancer of zeste homolog 2 (EZH2) (TUG1 binding protein) increased in cytoplasm of VSMCs under the same conditions. Immunofluoresce analysis displayed the colocalization of EZH2 with α-actin in cytoplasm and F-actin in cell edge ruffles. This leads us to hypothesize the existence of cytoplasmic TUG1/EZH2/α-actin complex. Using RNA pull down assay, we found that TUG1 interacted with both EZH2 and α-actin. Disruption of TUG1 abolished the interaction of EZH2 with α-actin, and accelerated depolymerization of F-actin in VSMCs. Based on EZH2 methyltransferase activity and the potential methylation sites in α-actin structure, we revealed that α-actin was lysine-methylated. Furthermore, the methylation of α-actin was inhibited by knockdown of TUG1. In conclusion, these findings partly suggested that EZH2-mediated methylation of α-actin may be dependent on TUG1, and thereby promotes cortex F-actin polymerization in synthetic VSMCs. Copyright © 2017. Published by Elsevier B.V.

  14. Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.

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    Satoshi Kawano

    Full Text Available The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2 methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1 has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma-a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein-display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers.

  15. Involvement of EZH2, SUV39H1, G9a and associated molecules in pathogenesis of urethane induced mouse lung tumors: Potential targets for cancer control

    International Nuclear Information System (INIS)

    Pandey, Manuraj; Sahay, Satya; Tiwari, Prakash; Upadhyay, Daya S.; Sultana, Sarwat; Gupta, Krishna P.

    2014-01-01

    In the present study, we showed the correlation of EZH2, SUV39H1 or G9a expression and histone modifications with the urethane induced mouse lung tumorigenesis in the presence or absence of antitumor agent, inositol hexaphosphate (IP6). Tumorigenesis and the molecular events involved therein were studied at 1, 4, 12 or 36 weeks after the exposure. There were no tumors at 1 or 4 weeks but tumors started appearing at 12 weeks and grew further till 36 weeks after urethane exposure. Among the molecular events, upregulation of EZH2 and SUV39H1 expressions appeared to be time dependent, but G9a expression was altered significantly only at later stages of 12 or 36 weeks. Alteration in miR-138 expression supports the upregulation of its target, EZH2. H3K9me2, H3K27me3 or H4K20me3 was found to be altered at 12 or 36 weeks. However, ChIP analysis of p16 and MLH1 promoters showed their binding with H3K9me2 and H3K27me3 which was maximum at 36 weeks. Thus, histone modification and their interactions with gene promoter resulted in the reduced expression of p16 and MLH1. IP6 prevented the incidence and the size of urethane induced lung tumors. IP6 also prevented the urethane induced alterations in EZH2, SUV39H1, G9a expressions and histone modifications. Our results suggest that the alterations in the histone modification pathways involving EZH2 and SUV39H1 expressions are among the early events in urethane induced mouse lung tumorigenesis and could be exploited for cancer control. - Highlights: • Urethane induces mouse lung tumor in a time dependent manner. • EZH2, SUV39H1, G9a induced by urethane and progress with time • Downregulation of miRNA-138 supports the EZH2 upregulation. • Methylation of histones showed a consequence of upregulated EZH2, SUV39H1 and G9a. • IP6 inhibits urethane induced changes and prevents tumor development

  16. Involvement of EZH2, SUV39H1, G9a and associated molecules in pathogenesis of urethane induced mouse lung tumors: Potential targets for cancer control

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Manuraj; Sahay, Satya; Tiwari, Prakash [Carcinogenesis Laboratory, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow –226001 (India); Upadhyay, Daya S. [Laboratory Animals Services, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow (India); Sultana, Sarwat [Dept. Medical Elementology and Toxicology, Jamia Hamdard, Hamdard Nagar, New Delhi (India); Gupta, Krishna P., E-mail: krishnag522@yahoo.co.in [Carcinogenesis Laboratory, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow –226001 (India)

    2014-10-15

    In the present study, we showed the correlation of EZH2, SUV39H1 or G9a expression and histone modifications with the urethane induced mouse lung tumorigenesis in the presence or absence of antitumor agent, inositol hexaphosphate (IP6). Tumorigenesis and the molecular events involved therein were studied at 1, 4, 12 or 36 weeks after the exposure. There were no tumors at 1 or 4 weeks but tumors started appearing at 12 weeks and grew further till 36 weeks after urethane exposure. Among the molecular events, upregulation of EZH2 and SUV39H1 expressions appeared to be time dependent, but G9a expression was altered significantly only at later stages of 12 or 36 weeks. Alteration in miR-138 expression supports the upregulation of its target, EZH2. H3K9me2, H3K27me3 or H4K20me3 was found to be altered at 12 or 36 weeks. However, ChIP analysis of p16 and MLH1 promoters showed their binding with H3K9me2 and H3K27me3 which was maximum at 36 weeks. Thus, histone modification and their interactions with gene promoter resulted in the reduced expression of p16 and MLH1. IP6 prevented the incidence and the size of urethane induced lung tumors. IP6 also prevented the urethane induced alterations in EZH2, SUV39H1, G9a expressions and histone modifications. Our results suggest that the alterations in the histone modification pathways involving EZH2 and SUV39H1 expressions are among the early events in urethane induced mouse lung tumorigenesis and could be exploited for cancer control. - Highlights: • Urethane induces mouse lung tumor in a time dependent manner. • EZH2, SUV39H1, G9a induced by urethane and progress with time • Downregulation of miRNA-138 supports the EZH2 upregulation. • Methylation of histones showed a consequence of upregulated EZH2, SUV39H1 and G9a. • IP6 inhibits urethane induced changes and prevents tumor development.

  17. A non-canonical function of Ezh2 preserves immune homeostasis

    NARCIS (Netherlands)

    Vasanthakumar, Ajithkumar; Xu, Dakang; Lun, Aaron Tl; Kueh, Andrew J.; van Gisbergen, Klaas Pjm; Iannarella, Nadia; Li, Xiaofang; Yu, Liang; Wang, Die; Williams, Bryan Rg; Lee, Stanley Cw; Majewski, Ian J.; Godfrey, Dale I.; Smyth, Gordon K.; Alexander, Warren S.; Herold, Marco J.; Kallies, Axel; Nutt, Stephen L.; Allan, Rhys S.

    2017-01-01

    Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histoneH3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we

  18. ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer.

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    Paolo Kunderfranco

    2010-05-01

    Full Text Available ETS transcription factors regulate important signaling pathways involved in cell differentiation and development in many tissues and have emerged as important players in prostate cancer. However, the biological impact of ETS factors in prostate tumorigenesis is still debated.We performed an analysis of the ETS gene family using microarray data and real-time PCR in normal and tumor tissues along with functional studies in normal and cancer cell lines to understand the impact in prostate tumorigenesis and identify key targets of these transcription factors. We found frequent dysregulation of ETS genes with oncogenic (i.e., ERG and ESE1 and tumor suppressor (i.e., ESE3 properties in prostate tumors compared to normal prostate. Tumor subgroups (i.e., ERG(high, ESE1(high, ESE3(low and NoETS tumors were identified on the basis of their ETS expression status and showed distinct transcriptional and biological features. ERG(high and ESE3(low tumors had the most robust gene signatures with both distinct and overlapping features. Integrating genomic data with functional studies in multiple cell lines, we demonstrated that ERG and ESE3 controlled in opposite direction transcription of the Polycomb Group protein EZH2, a key gene in development, differentiation, stem cell biology and tumorigenesis. We further demonstrated that the prostate-specific tumor suppressor gene Nkx3.1 was controlled by ERG and ESE3 both directly and through induction of EZH2.These findings provide new insights into the role of the ETS transcriptional network in prostate tumorigenesis and uncover previously unrecognized links between aberrant expression of ETS factors, deregulation of epigenetic effectors and silencing of tumor suppressor genes. The link between aberrant ETS activity and epigenetic gene silencing may be relevant for the clinical management of prostate cancer and design of new therapeutic strategies.

  19. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Göllner, Stefanie; Oellerich, Thomas; Agrawal-Singh, Shuchi

    2017-01-01

    In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction...

  20. Lineage specific expression of Polycomb Group Proteins in human embryonic stem cells in vitro.

    Science.gov (United States)

    Pethe, Prasad; Pursani, Varsha; Bhartiya, Deepa

    2015-05-01

    Human embryonic (hES) stem cells are an excellent model to study lineage specification and differentiation into various cell types. Differentiation necessitates repression of specific genes not required for a particular lineage. Polycomb Group (PcG) proteins are key histone modifiers, whose primary function is gene repression. PcG proteins form complexes called Polycomb Repressive Complexes (PRCs), which catalyze histone modifications such as H2AK119ub1, H3K27me3, and H3K9me3. PcG proteins play a crucial role during differentiation of stem cells. The expression of PcG transcripts during differentiation of hES cells into endoderm, mesoderm, and ectoderm lineage is yet to be shown. In-house derived hES cell line KIND1 was differentiated into endoderm, mesoderm, and ectoderm lineages; followed by characterization using RT-PCR for HNF4A, CDX2, MEF2C, TBX5, SOX1, and MAP2. qRT-PCR and western blotting was performed to compare expression of PcG transcripts and proteins across all the three lineages. We observed that cells differentiated into endoderm showed upregulation of RING1B, BMI1, EZH2, and EED transcripts. Mesoderm differentiation was characterized by significant downregulation of all PcG transcripts during later stages. BMI1 and RING1B were upregulated while EZH2, SUZ12, and EED remained low during ectoderm differentiation. Western blotting also showed distinct expression of BMI1 and EZH2 during differentiation into three germ layers. Our study shows that hES cells differentiating into endoderm, mesoderm, and ectoderm lineages show distinct PcG expression profile at transcript and protein level. © 2015 International Federation for Cell Biology.

  1. High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

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    Ji Young Oh

    2018-04-01

    Full Text Available Background/Aims: Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC migration, and analyze the mechanism accompanied by this effect. Methods: Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. Results: High concentration glucose (25 mM elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS promotes two signaling; JNK which regulates γ–secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. Conclusion: This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways.

  2. Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2018-03-01

    Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382.

    Science.gov (United States)

    Zhao, Liang; Sun, Hongwei; Kong, Hongru; Chen, Zongjing; Chen, Bicheng; Zhou, Mengtao

    2017-01-01

    Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT) phenotype. RNA-binding protein immunoprecipitation (RIP) and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2) was a target of miR-382 in PC. In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous 'sponge' and competing for miR-382 binding to the miRNA target EZH2. © 2017 The Author(s). Published by S. Karger AG, Basel.

  4. The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382

    Directory of Open Access Journals (Sweden)

    Liang Zhao

    2017-08-01

    Full Text Available Background/Aims: Pancreatic carcinoma (PC is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1 was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Methods: Quantitative real-time PCR (qRT-PCR was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT phenotype. RNA-binding protein immunoprecipitation (RIP and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2 was a target of miR-382 in PC. Results: In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Conclusion: Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous ‘sponge’ and competing for miR-382 binding to the miRNA target EZH2.

  5. Long non-coding RNA profile in mantle cell lymphoma identifies a functional lncRNA ROR1-AS1 associated with EZH2/PRC2 complex

    Science.gov (United States)

    Hu, Guangzhen; Gupta, Shiv K.; Troska, Tammy P.; Nair, Asha; Gupta, Mamta

    2017-01-01

    Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed. As a result, several novel lncRNAs were found significantly overexpressed in the MCL samples with lncRNA ROR1-AS1 the most significant one. We cloned the ROR1-AS1 lncRNA in expression vector and ectopically transfected in MCL cell lines. Results showed that overexpression of ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone. ROR-AS1 overexpression also decreased the mRNA expression of P16 (P = 0.21), and SOX11 (p = 0.017), without much effect on P53, ATM and P14 mRNA. RNA-immunoprecipitation assays demonstrated high affinity binding of lncRNA ROR1-AS1 with EZH2 and SUZ12 proteins of the polycomb repressive complex-2 (PRC2). Suppressing EZH2 activity with pharmacological inhibitor GSK343 abolished binding of ROR1-AS1 with EZH2. Taken together, this study identified a functional lncRNA ROR-AS1 involved with regulation of gene transcription via associating with PRC2 complex, and may serve as a novel biomarker in MCL patients. PMID:29113297

  6. Short-Chain Fatty Acids from Periodontal Pathogens Suppress Histone Deacetylases, EZH2, and SUV39H1 To Promote Kaposi's Sarcoma-Associated Herpesvirus Replication

    Science.gov (United States)

    Yu, Xiaolan; Shahir, Abdel-Malek; Sha, Jingfeng; Feng, Zhimin; Eapen, Betty; Nithianantham, Stanley; Das, Biswajit; Karn, Jonathan; Weinberg, Aaron; Bissada, Nabil F.

    2014-01-01

    ABSTRACT Periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum produce five different short-chain fatty acids (SCFAs) as metabolic by-products. We detect significantly higher levels of SCFAs in the saliva of patients with severe periodontal disease. The different SCFAs stimulate lytic gene expression of Kaposi's sarcoma-associated herpesvirus (KSHV) dose dependently and synergistically. SCFAs inhibit class-1/2 histone deacetylases (HDACs) and downregulate expression of silent information regulator-1 (SIRT1). SCFAs also downregulate expression of enhancer of zeste homolog2 (EZH2) and suppressor of variegation 3-9 homolog1 (SUV39H1), which are two histone N-lysine methyltransferases (HLMTs). By suppressing the different components of host epigenetic regulatory machinery, SCFAs increase histone acetylation and decrease repressive histone trimethylations to transactivate the viral chromatin. These new findings provide mechanistic support that SCFAs from periodontal pathogens stimulate KSHV replication and infection in the oral cavity and are potential risk factors for development of oral Kaposi's sarcoma (KS). IMPORTANCE About 20% of KS patients develop KS lesions first in the oral cavity, while other patients never develop oral KS. It is not known if the oral microenvironment plays a role in oral KS tumor development. In this work, we demonstrate that a group of metabolic by-products, namely, short-chain fatty acids, from bacteria that cause periodontal disease promote lytic replication of KSHV, the etiological agent associated with KS. These new findings provide mechanistic support that periodontal pathogens create a unique microenvironment in the oral cavity that contributes to KSHV replication and development of oral KS. PMID:24501407

  7. Long Intergenic Noncoding RNA 00511 Acts as an Oncogene in Non–small-cell Lung Cancer by Binding to EZH2 and Suppressing p57

    Directory of Open Access Journals (Sweden)

    Cheng-Cao Sun

    2016-01-01

    Full Text Available Long noncoding RNAs (lncRNAs play crucial roles in carcinogenesis. However, the function and mechanism of lncRNAs in human non–small-cell lung cancer (NSCLC are still remaining largely unknown. Long intergenic noncoding RNA 00511 (LINC00511 has been found to be upregulated and acts as an oncogene in breast cancer, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Herein, we identified LINC00511 as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found LINC00511 was upregulated and associated with oncogenesis, tumor size, metastasis, and poor prognosis in NSCLC. Moreover, LINC00511 affected cell proliferation, invasiveness, metastasis, and apoptosis in multiple NSCLC cell lines. Mechanistically, LINC00511 bound histone methyltransferase enhancer of zeste homolog 2 ((EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2, a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3, and acted as a modular scaffold of EZH2/PRC2 complexes, coordinated their localization, and specified the histone modification pattern on the target genes, including p57, and consequently altered NSCLC cell biology. Thus, LINC00511 is mechanistically, functionally, and clinically oncogenic in NSCLC. Targeting LINC00511 and its pathway may be meaningful for treating patients with NSCLC.

  8. Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2.

    Science.gov (United States)

    Niu, Yuchun; Ma, Feng; Huang, Weimei; Fang, Shun; Li, Man; Wei, Ting; Guo, Linlang

    2017-01-09

    Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC and its possible molecular mechanism. The expression of TUG1 in thirty-three cases of SCLC tissues and SCLC cell line were examined by quantitative RT-PCR (qRT-PCR). The functional roles of TUG1 in SCLC were demonstrated by CCK8 assay, colony formation assay, wound healing assay and transwell assay, flow cytometry analysis and in vivo study through siRNA or shRNA mediated knockdown. Western blot assays were used to evaluate gene and protein expression in cell lines. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular mechanism of TUG1 involved in cell growth and chemoresistance of small cell lung cancer. We found that TUG1 was overexpressed in SCLC tissues, and its expression was correlated with the clinical stage and the shorter survival time of SCLC patients. Moreover, downregulation of TUG1 expression could impair cell proliferation and increased cell sensitivity to anticancer drugs both in vitro and in vivo. We also discovered that TUG1 knockdown significantly promoted cell apoptosis and cell cycle arrest, and inhibited cell migration and invasion in vitro . We further demonstrated that TUG1 can regulate the expression of LIMK2b (a splice variant of LIM-kinase 2) via binding with enhancer of zeste homolog 2 (EZH2), and then promoted cell growth and chemoresistance of SCLC. Together, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.

  9. Tissue Microarray Assessment of Novel Prostate Cancer Biomarkers AMACR and EZH2 and Immunologic Response to Them in African-American and Caucasian Men

    National Research Council Canada - National Science Library

    Mehra, Rohit

    2007-01-01

    .... We constructed 5 tissue microarrays representing 40 African-American and 159 Caucasian prostate cancer patients and performed immunohistochemistry on these arrays using antibody to AMACR and EZH2...

  10. Tissue Microarray Assessment of Novel Prostate Cancer Biomarkers AMACR and EZH2 and Immunologic Response to them in African-American and Caucasian Men

    National Research Council Canada - National Science Library

    Mehra, Rohit

    2006-01-01

    .... We constructed 5 tissue microarrays representing 40 African-American and 159 Caucasian prostate cancer patients and performed immunohistochemistry on these arrays using antibodies to AMACR and EZH2...

  11. Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

    Science.gov (United States)

    Oricchio, Elisa; Katanayeva, Natalya; Donaldson, Maria Christine; Sungalee, Stephanie; Pasion, Joyce P; Béguelin, Wendy; Battistello, Elena; Sanghvi, Viraj R; Jiang, Man; Jiang, Yanwen; Teater, Matt; Parmigiani, Anita; Budanov, Andrei V; Chan, Fong Chun; Shah, Sohrab P; Kridel, Robert; Melnick, Ari M; Ciriello, Giovanni; Wendel, Hans-Guido

    2017-06-28

    Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2 Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  12. Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas.

    Directory of Open Access Journals (Sweden)

    Sarah K Knutson

    Full Text Available Patients with non-Hodgkin lymphoma (NHL are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone. Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone - a glucocorticoid receptor agonist (GRag component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting.

  13. Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas.

    Science.gov (United States)

    Knutson, Sarah K; Warholic, Natalie M; Johnston, L Danielle; Klaus, Christine R; Wigle, Tim J; Iwanowicz, Dorothy; Littlefield, Bruce A; Porter-Scott, Margaret; Smith, Jesse J; Moyer, Mikel P; Copeland, Robert A; Pollock, Roy M; Kuntz, Kevin W; Raimondi, Alejandra; Keilhack, Heike

    2014-01-01

    Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone). Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone - a glucocorticoid receptor agonist (GRag) component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting.

  14. Effects of four single nucleotide polymorphisms of EZH2 on cancer risk: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ling Z

    2018-02-01

    Full Text Available Zhixin Ling,1,2,* Zonghao You,1,2,* Ling Hu,3 Lei Zhang,1,2 Yiduo Wang,1,2 Minhao Zhang,1,2 Guangyuan Zhang,1,2 Shuqiu Chen,1,2 Bin Xu,1,2 Ming Chen1,2 1Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China; 2Surgical Research Center, Institute of Urology, Medical School of Southeast University, Nanjing, China; 3Department of Nephrology, People’s Hospital of Wuxi City, Wuxi, China *These authors contributed equally to this work Background: Although the relationship between several single nucleotide polymorphisms (SNPs of the oncogene EZH2 and cancer risk has been assessed by some case–control studies, results of subsequent studies are controversial. Sample sizes from single-center studies are also limited, thereby providing unreliable findings. Hence, we conducted a comprehensive search and meta-analysis to evaluate the associations between EZH2 SNPs and cancer risk.Materials and methods: A comprehensive literature search for studies focusing on EZH2 SNPs and cancer risk was conducted on PubMed, Web of Science, Embase, and China National Knowledge Infrastructure online databases. Genotype data were extracted and examined through a meta-analysis, and pooled odds ratios (ORs with 95% CIs were used to assess the corresponding associations. Sensitivity analysis, publication bias assessment, and heterogeneity test were performed using STATA 12.0.Results: Twelve eligible studies were included in this meta-analysis. The association of 4 SNPs, namely, rs887569, rs2302427, rs3757441, and rs41277434, in the EZH2 locus with cancer risk was evaluated. Five studies (1,794 cases and 1,878 controls indicated that rs887569 was related to a decreased cancer risk (CTTT/CC: OR =0.849, 95% CI: [0.740 to 0.973], P=0.019; TT/CCCT: OR =0.793, 95% CI: [0.654 to 0.962], P=0.019. Seven studies (2,408 cases and 2,910 controls showed that rs2302427 was linked to a decreased cancer risk (GG/CC: OR =0.562, 95% CI: [0.400 to 0.792], P

  15. EZH2 and CD79B mutational status over time in B-cell non-Hodgkin lymphomas detected by high-throughput sequencing using minimal samples

    Science.gov (United States)

    Saieg, Mauro Ajaj; Geddie, William R; Boerner, Scott L; Bailey, Denis; Crump, Michael; da Cunha Santos, Gilda

    2013-01-01

    BACKGROUND: Numerous genomic abnormalities in B-cell non-Hodgkin lymphomas (NHLs) have been revealed by novel high-throughput technologies, including recurrent mutations in EZH2 (enhancer of zeste homolog 2) and CD79B (B cell antigen receptor complex-associated protein beta chain) genes. This study sought to determine the evolution of the mutational status of EZH2 and CD79B over time in different samples from the same patient in a cohort of B-cell NHLs, through use of a customized multiplex mutation assay. METHODS: DNA that was extracted from cytological material stored on FTA cards as well as from additional specimens, including archived frozen and formalin-fixed histological specimens, archived stained smears, and cytospin preparations, were submitted to a multiplex mutation assay specifically designed for the detection of point mutations involving EZH2 and CD79B, using MassARRAY spectrometry followed by Sanger sequencing. RESULTS: All 121 samples from 80 B-cell NHL cases were successfully analyzed. Mutations in EZH2 (Y646) and CD79B (Y196) were detected in 13.2% and 8% of the samples, respectively, almost exclusively in follicular lymphomas and diffuse large B-cell lymphomas. In one-third of the positive cases, a wild type was detected in a different sample from the same patient during follow-up. CONCLUSIONS: Testing multiple minimal tissue samples using a high-throughput multiplex platform exponentially increases tissue availability for molecular analysis and might facilitate future studies of tumor progression and the related molecular events. Mutational status of EZH2 and CD79B may vary in B-cell NHL samples over time and support the concept that individualized therapy should be based on molecular findings at the time of treatment, rather than on results obtained from previous specimens. Cancer (Cancer Cytopathol) 2013;121:377–386. © 2013 American Cancer Society. PMID:23361872

  16. Epigenetic control of hematopoietic stem cell aging - The case of Ezh2

    NARCIS (Netherlands)

    de Haan, Gerald; Gerrits, Alice; Kanz, L; Weisel, KC; Dick, JE; Fibbe, WE

    2007-01-01

    Hematopoietic stem cells have potent, but not unlimited, selfrenewal potential. The mechanisms that restrict selfrenewal are likely to play a role during aging. Recent data suggest that the regulation of histone modifications by Polycomb group genes may be of crucial relevance to balance selfrenewal

  17. TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation mediated repression: implications in duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Swarnali Acharyya

    2010-08-01

    Full Text Available Classical NF-kappaB signaling functions as a negative regulator of skeletal myogenesis through potentially multiple mechanisms. The inhibitory actions of TNFalpha on skeletal muscle differentiation are mediated in part through sustained NF-kappaB activity. In dystrophic muscles, NF-kappaB activity is compartmentalized to myofibers to inhibit regeneration by limiting the number of myogenic progenitor cells. This regulation coincides with elevated levels of muscle derived TNFalpha that is also under IKKbeta and NF-kappaB control.Based on these findings we speculated that in DMD, TNFalpha secreted from myotubes inhibits regeneration by directly acting on satellite cells. Analysis of several satellite cell regulators revealed that TNFalpha is capable of inhibiting Notch-1 in satellite cells and C2C12 myoblasts, which was also found to be dependent on NF-kappaB. Notch-1 inhibition occurred at the mRNA level suggesting a transcriptional repression mechanism. Unlike its classical mode of action, TNFalpha stimulated the recruitment of Ezh2 and Dnmt-3b to coordinate histone and DNA methylation, respectively. Dnmt-3b recruitment was dependent on Ezh2.We propose that in dystrophic muscles, elevated levels of TNFalpha and NF-kappaB inhibit the regenerative potential of satellite cells via epigenetic silencing of the Notch-1 gene.

  18. TNF Inhibits Notch-1 in Skeletal Muscle Cells by Ezh2 and DNA Methylation Mediated Repression: Implications in Duchenne Muscular Dystrophy

    Science.gov (United States)

    Acharyya, Swarnali; Sharma, Sudarshana M.; Cheng, Alfred S.; Ladner, Katherine J.; He, Wei; Kline, William; Wang, Huating; Ostrowski, Michael C.; Huang, Tim H.; Guttridge, Denis C.

    2010-01-01

    Background Classical NF-κB signaling functions as a negative regulator of skeletal myogenesis through potentially multiple mechanisms. The inhibitory actions of TNFα on skeletal muscle differentiation are mediated in part through sustained NF-κB activity. In dystrophic muscles, NF-κB activity is compartmentalized to myofibers to inhibit regeneration by limiting the number of myogenic progenitor cells. This regulation coincides with elevated levels of muscle derived TNFα that is also under IKKβ and NF-κB control. Methodology/Principal Findings Based on these findings we speculated that in DMD, TNFα secreted from myotubes inhibits regeneration by directly acting on satellite cells. Analysis of several satellite cell regulators revealed that TNFα is capable of inhibiting Notch-1 in satellite cells and C2C12 myoblasts, which was also found to be dependent on NF-κB. Notch-1 inhibition occurred at the mRNA level suggesting a transcriptional repression mechanism. Unlike its classical mode of action, TNFα stimulated the recruitment of Ezh2 and Dnmt-3b to coordinate histone and DNA methylation, respectively. Dnmt-3b recruitment was dependent on Ezh2. Conclusions/Significance We propose that in dystrophic muscles, elevated levels of TNFα and NF-κB inhibit the regenerative potential of satellite cells via epigenetic silencing of the Notch-1 gene. PMID:20814569

  19. Signals of Ezh2, Src, and Akt Involve in Myostatin-Pax7 Pathways Regulating the Myogenic Fate Determination during the Sheep Myoblast Proliferation and Differentiation

    Science.gov (United States)

    Li, Li; Liu, Ruizao; Zhang, Li; Zhao, Fuping; Lu, Jian; Zhang, Xiaoning; Du, Lixin

    2015-01-01

    Myostatin and Pax7 have been well documented individually, however, the mechanism by which Myostatin regulates Pax7 is seldom reported. Here, based on muscle transcriptome analysis in Texel (Myostatin mutant) and Ujumqin (wild type) sheep across the five fetal stages, we constructed and examined the Myostatin-Pax7 pathways in muscle. Then we validated the signals by RNAi in the proliferating and differentiating sheep myoblasts in vitro at mRNA, protein, and cell morphological levels. We reveal that Myostatin signals to Pax7 at least through Ezh2, Src, and Akt during the sheep myoblast proliferation and differentiation. Other signals such as p38MAPK, mTOR, Erk1/2, Wnt, Bmp2, Smad, Tgfb1, and p21 are most probably involved in the Myostatin-affected myogenic events. Myostatin knockdown significantly reduces the counts of nucleus and myotube, but not the fusion index of myoblasts during cell differentiation. In addition, findings also indicate that Myostatin is required for normal myogenic differentiation of the sheep myoblasts, which is different from the C2C12 myoblasts. We expand the regulatory network of Myostatin-Pax7 pathways and first illustrate that Myostatin as a global regulator participates in the epigenetic events involved in myogenesis, which contributes to understand the molecular mechanism of Myostatin in regulation of myogenesis. PMID:25811841

  20. MiR302 regulates SNAI1 expression to control mesangial cell plasticity

    DEFF Research Database (Denmark)

    De Chiara, L.; Andrews, D.; Watson, A.

    2017-01-01

    Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor...... and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation. esiRNA silencing of each component suggest that Smad3 and EZH2 are part...... of a complex that regulates plasticity and that miR302 regulates EZH2 and Snail independently. Subsequent manipulation of miR302 overexpressing cells demonstrated the potential of using this approach for reprogramming as evidenced by de novo expression of the tight junction components ZO-1 and E...

  1. Transcriptional response of polycomb group genes to status epilepticus in mice is modified by prior exposure to epileptic preconditioning

    Directory of Open Access Journals (Sweden)

    James eReynolds

    2015-03-01

    Full Text Available Exposure of the brain to brief, non-harmful seizures can activate protective mechanisms that temporarily generate a damage-refractory state. This process, termed epileptic tolerance, is associated with large-scale down-regulation of gene expression. Polycomb group proteins are master controllers of gene silencing during development that are re-activated by injury to the brain. Here we explored the transcriptional response of genes associated with polycomb repressor complex (PRC 1 (Ring1A and Ring1B and Bmi1 and PRC2 (Ezh1, Ezh2 and Suz12, as well as additional transcriptional regulators Sirt1, Yy1 and Yy2, in a mouse model of status epilepticus. Findings were contrasted to changes after status epilepticus in mice previously given brief seizures to evoke tolerance. Real-time quantitative PCR showed status epilepticus prompted an early (1 h increase in expression of several genes in PRC1 and PRC2 in the hippocampus, followed by down-regulation of many of the same genes at later times points (4 , 8 and 24 h. Spatio-temporal differences were found among PRC2 genes in epileptic tolerance, including increased expression of Ezh2, Suz12 and Yy2 relative to the normal injury response to status epilepticus. In contrast, PRC1 complex genes including Ring 1B and Bmi1 displayed differential down-regulation in epileptic tolerance. The present study characterizes polycomb group gene expression following status epilepticus and shows prior seizure exposure produces select changes to PRC1 and PRC2 composition that may influence differential gene expression in epileptic tolerance.

  2. SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Relster, Mette Marie; Greve, Katrine Buch Viden

    2014-01-01

    Polycomb group (PcG) complexes regulate cellular identity through epigenetic programming of chromatin. Here, we show that SSX2, a germline-specific protein ectopically expressed in melanoma and other types of human cancers, is a chromatin-associated protein that antagonizes BMI1 and EZH2 PcG body...... formation and derepresses PcG target genes. SSX2 further negatively regulates the level of the PcG-associated histone mark H3K27me3 in melanoma cells, and there is a clear inverse correlation between SSX2/3 expression and H3K27me3 in spermatogenesis. However, SSX2 does not affect the overall composition...

  3. Memory effect in expressed emotions during long term group interactions

    NARCIS (Netherlands)

    Gorbunov, R.; Barakova, E.I.; Rauterberg, M.; Ferrández Vicente, J.M.; Álvarez-Sánchez, J.R.; de la Paz López, F.; Toledo Moreo, J.; Adeli, H.

    2017-01-01

    Long-term interactions in groups can be monitored through games in which the participants need to show their social preferences by making choice to help or to use egoistic game strategy. In this paper we analyse the facial expressions of a group of isolated individuals (astronauts) during repeated

  4. Expressed satisfaction with the nominal group technique among change agents

    NARCIS (Netherlands)

    Gresham, J.N.

    1986-01-01

    Expressed Satisfaction with the Nominal Group Technique Among Change Agents. Jon Neal Gresham The purpose of this study was to determine whether or not policymakers and change agents with differing professional backgrounds and responsibilities, who participated in the structured process of a

  5. An expressive art group intervention for sexually abused adolescent ...

    African Journals Online (AJOL)

    Objective: South Africa has a high prevalence of sexual abuse of children and adolescents. Among the numerous adverse consequences of sexual abuse is the difficulty survivors may experience in developing positive self-esteem and maintaining positive relationships. In a low resource setting, an expressive art group ...

  6. Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497).

    Science.gov (United States)

    Kung, Pei-Pei; Bingham, Patrick; Brooun, Alexei; Collins, Michael; Deng, Ya-Li; Dinh, Dac; Fan, Connie; Gajiwala, Ketan S; Grantner, Rita; Gukasyan, Hovhannes J; Hu, Wenyue; Huang, Buwen; Kania, Robert; Kephart, Susan E; Krivacic, Cody; Kumpf, Robert A; Khamphavong, Penney; Kraus, Manfred; Liu, Wei; Maegley, Karen A; Nguyen, Lisa; Ren, Shijian; Richter, Dan; Rollins, Robert A; Sach, Neal; Sharma, Shikhar; Sherrill, John; Spangler, Jillian; Stewart, Albert E; Sutton, Scott; Uryu, Sean; Verhelle, Dominique; Wang, Hui; Wang, Shuiwang; Wythes, Martin; Xin, Shuibo; Yamazaki, Shinji; Zhu, Huichun; Zhu, JinJiang; Zehnder, Luke; Edwards, Martin

    2018-02-08

    A new series of lactam-derived EZH2 inhibitors was designed via ligand-based and physicochemical-property-based strategies to address metabolic stability and thermodynamic solubility issues associated with previous lead compound 1. The new inhibitors incorporated an sp 3 hybridized carbon atom at the 7-position of the lactam moiety present in lead compound 1 as a replacement for a dimethylisoxazole group. This transformation enabled optimization of the physicochemical properties and potency compared to compound 1. Analysis of relationships between calculated log D (clogD) values and in vitro metabolic stability and permeability parameters identified a clogD range that afforded an increased probability of achieving favorable ADME data in a single molecule. Compound 23a exhibited the best overlap of potency and pharmaceutical properties as well as robust tumor growth inhibition in vivo and was therefore advanced as a development candidate (PF-06821497). A crystal structure of 23a in complex with the three-protein PRC2 complex enabled understanding of the key structural features required for optimal binding.

  7. Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

    Science.gov (United States)

    Luan, Jinwei; Li, Xianglan; Guo, Rutao; Liu, Shanshan; Luo, Hongyu; You, Qingshan

    2016-06-01

    Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray.

  8. Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu)

    International Nuclear Information System (INIS)

    Luan, Jinwei; Li, Xianglan; Guo, Rutao; Liu, Shanshan; Luo, Hongyu; You, Qingshan

    2016-01-01

    Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray

  9. Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms

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    Takuro Kameda

    2015-06-01

    Full Text Available Myeloproliferative neoplasms (MPNs are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling and the autonomous growth of differentiated cells therefore they are considered as “driver” gene mutations. In addition to the above driver gene mutations mutations in epigenetic regulators such as TET2 DNMT3A ASXL1 EZH2 or IDH1/2 are detected in about 5%–30% of cases respectively [3]. Mutations in TET2 DNMT3A EZH2 or IDH1/2 commonly confer the increased self-renewal capacity on normal hematopoietic stem cells (HSCs but they do not lead to the autonomous growth of differentiated cells and only exhibit subtle clinical phenotypes [4,6–8,5]. It was unclear how mutations in such epigenetic regulators influenced abnormal HSCs with driver gene mutations how they influenced the disease phenotype or whether a single driver gene mutation was sufficient for the initiation of human MPNs. Therefore we focused on JAK2V617F and loss of TET2—the former as a representative of driver gene mutations and the latter as a representative of mutations in epigenetic regulators—and examined the influence of single or double mutations on HSCs (Lineage−Sca-1+c-Kit+ cells (LSKs by functional analyses and microarray whole-genome expression analyses [9]. Gene expression profiling showed that the HSC fingerprint genes [10] was statistically equally enriched in TET2-knockdown-LSKs but negatively enriched in JAK2V617F–LSKs compared to that in wild-type-LSKs. Double-mutant-LSKs showed the same tendency as JAK2V617F–LSKs in terms of their HSC fingerprint genes but the expression of individual genes differed between the two groups. Among 245 HSC fingerprint genes 100 were more

  10. Polycomb Group Protein PHF1 Regulates p53-dependent Cell Growth Arrest and Apoptosis*

    Science.gov (United States)

    Yang, Yang; Wang, Chenji; Zhang, Pingzhao; Gao, Kun; Wang, Dejie; Yu, Hongxiu; Zhang, Ting; Jiang, Sirui; Hexige, Saiyin; Hong, Zehui; Yasui, Akira; Liu, Jun O.; Huang, Haojie; Yu, Long

    2013-01-01

    Polycomb group protein PHF1 is well known as a component of a novel EED-EZH2·Polycomb repressive complex 2 complex and plays important roles in H3K27 methylation and Hox gene silencing. PHF1 is also involved in the response to DNA double-strand breaks in human cells, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1 as a potential p53 pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1 directly interacts with p53 proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and its target gene expression both in normal state and DNA damage response. Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression was significantly down-regulated in human breast cancer samples. Taken together, we establish PHF1 as a novel positive regulator of the p53 pathway. These data shed light on the potential roles of PHF1 in tumorigenesis and/or tumor progression. PMID:23150668

  11. DZNep, inhibitor of S-adenosylhomocysteine hydrolase, down-regulates expression of SETDB1 H3K9me3 HMTase in human lung cancer cells.

    Science.gov (United States)

    Lee, Ju-Kyung; Kim, Keun-Cheol

    2013-09-06

    3-Deazaneplanocin A (DZNep), an epigenetic anticancer drug, leads to the indirect suppression of S-adenosyl methionine-dependent cellular methylations by inhibiting S-adenosyl homocystein (AdoHcy) hydrolase. Although it is well known that DZNep targets the degradation of EZH2 protein, H3K27me3 HMTase, there are still uncertainties about the regulation of other types of HMTases during cell death. In this study, we describe that SETDB1 gene expression was regulated by DZNep treatment in human lung cancer cells. We confirm that DZNep induced growth inhibition and increased the dead cell population of lung cancer cells. DZNep treatment affected histone methylations, including H3K27me3 and H3K9me3, but not H3K4me3. Reduced levels of H3K27me3 and H3K9me3 were related with the decreased EZH2 and SETDB1 proteins. Real time PCR analysis showed that SETDB1 gene expression was decreased by DZNep treatment, but no effect was observed for EZH2 gene expression. We cloned the promoter region of SETDB1 and SUV39H1 genes, and performed luciferase assays. The promoter activity of SETDB1 gene was down regulated by DZNep treatment, whereas no effect on SUV39H1 promoter activity was observed. In conclusion, we suggest that DZNep regulates not only on H3K27me3 HMTase EZH2, but also H3K9 HMTase SETDB1 gene expression at the transcription level, implicating that the mechanism of action of DZNep targets multiple HMTases during the death of lung cancer cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. The immediate early gene product EGR1 and polycomb group proteins interact in epigenetic programming during chondrogenesis.

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    Frank Spaapen

    Full Text Available Initiation of and progression through chondrogenesis is driven by changes in the cellular microenvironment. At the onset of chondrogenesis, resting mesenchymal stem cells are mobilized in vivo and a complex, step-wise chondrogenic differentiation program is initiated. Differentiation requires coordinated transcriptomic reprogramming and increased progenitor proliferation; both processes require chromatin remodeling. The nature of early molecular responses that relay differentiation signals to chromatin is poorly understood. We here show that immediate early genes are rapidly and transiently induced in response to differentiation stimuli in vitro. Functional ablation of the immediate early factor EGR1 severely deregulates expression of key chondrogenic control genes at the onset of differentiation. In addition, differentiating cells accumulate DNA damage, activate a DNA damage response and undergo a cell cycle arrest and prevent differentiation associated hyper-proliferation. Failed differentiation in the absence of EGR1 affects global acetylation and terminates in overall histone hypermethylation. We report novel molecular connections between EGR1 and Polycomb Group function: Polycomb associated histone H3 lysine27 trimethylation (H3K27me3 blocks chromatin access of EGR1. In addition, EGR1 ablation results in abnormal Ezh2 and Bmi1 expression. Consistent with this functional interaction, we identify a number of co-regulated targets genes in a chondrogenic gene network. We here describe an important role for EGR1 in early chondrogenic epigenetic programming to accommodate early gene-environment interactions in chondrogenesis.

  13. Mitis group streptococci express variable pilus islet 2 pili.

    Science.gov (United States)

    Zähner, Dorothea; Gandhi, Ashish R; Yi, Hong; Stephens, David S

    2011-01-01

    Streptococcus oralis, Streptococcus mitis, and Streptococcus sanguinis are members of the Mitis group of streptococci and agents of oral biofilm, dental plaque and infective endocarditis, disease processes that involve bacteria-bacteria and bacteria-host interactions. Their close relative, the human pathogen S. pneumoniae uses pilus-islet 2 (PI-2)-encoded pili to facilitate adhesion to eukaryotic cells. PI-2 pilus-encoding genetic islets were identified in S. oralis, S. mitis, and S. sanguinis, but were absent from other isolates of these species. The PI-2 islets resembled the genetic organization of the PI-2 islet of S. pneumoniae, but differed in the genes encoding the structural pilus proteins PitA and PitB. Two and three variants of pitA (a pseudogene in S. pneumoniae) and pitB, respectively, were identified that showed ≈20% difference in nucleotide as well as corresponding protein sequence. Species-independent combinations of pitA and pitB variants indicated prior intra- and interspecies horizontal gene transfer events. Polyclonal antisera developed against PitA and PitB of S. oralis type strain ATCC35037 revealed that PI-2 pili in oral streptococci were composed of PitA and PitB. Electronmicrographs showed pilus structures radiating >700 nm from the bacterial surface in the wild type strain, but not in an isogenic PI-2 deletion mutant. Anti-PitB-antiserum only reacted with pili containing the same PitB variant, whereas anti-PitA antiserum was cross-reactive with the other PitA variant. Electronic multilocus sequence analysis revealed that all PI-2-encoding oral streptococci were closely-related and cluster with non-PI-2-encoding S. oralis strains. This is the first identification of PI-2 pili in Mitis group oral streptococci. The findings provide a striking example of intra- and interspecies horizontal gene transfer. The PI-2 pilus diversity provides a possible key to link strain-specific bacterial interactions and/or tissue tropisms with pathogenic traits

  14. Mitis group streptococci express variable pilus islet 2 pili.

    Directory of Open Access Journals (Sweden)

    Dorothea Zähner

    Full Text Available Streptococcus oralis, Streptococcus mitis, and Streptococcus sanguinis are members of the Mitis group of streptococci and agents of oral biofilm, dental plaque and infective endocarditis, disease processes that involve bacteria-bacteria and bacteria-host interactions. Their close relative, the human pathogen S. pneumoniae uses pilus-islet 2 (PI-2-encoded pili to facilitate adhesion to eukaryotic cells.PI-2 pilus-encoding genetic islets were identified in S. oralis, S. mitis, and S. sanguinis, but were absent from other isolates of these species. The PI-2 islets resembled the genetic organization of the PI-2 islet of S. pneumoniae, but differed in the genes encoding the structural pilus proteins PitA and PitB. Two and three variants of pitA (a pseudogene in S. pneumoniae and pitB, respectively, were identified that showed ≈20% difference in nucleotide as well as corresponding protein sequence. Species-independent combinations of pitA and pitB variants indicated prior intra- and interspecies horizontal gene transfer events. Polyclonal antisera developed against PitA and PitB of S. oralis type strain ATCC35037 revealed that PI-2 pili in oral streptococci were composed of PitA and PitB. Electronmicrographs showed pilus structures radiating >700 nm from the bacterial surface in the wild type strain, but not in an isogenic PI-2 deletion mutant. Anti-PitB-antiserum only reacted with pili containing the same PitB variant, whereas anti-PitA antiserum was cross-reactive with the other PitA variant. Electronic multilocus sequence analysis revealed that all PI-2-encoding oral streptococci were closely-related and cluster with non-PI-2-encoding S. oralis strains.This is the first identification of PI-2 pili in Mitis group oral streptococci. The findings provide a striking example of intra- and interspecies horizontal gene transfer. The PI-2 pilus diversity provides a possible key to link strain-specific bacterial interactions and/or tissue tropisms with

  15. Role Differentiation in Groups: The Relationship Between Instrumental and Expressive Leadership.

    Science.gov (United States)

    Rees, C. Roger; Segal, Mady Wechsler

    1984-01-01

    Examined the degree of differentiation between instrumental and expressive leadership roles in two natural groups (N=101). Results showed a relatively high degree of leadership role integration with several members of each group fulfilling both instrumental and expressive leadership roles. (LLL)

  16. A Phenomenological Exploration of the Experiences of Master's Level Counselor Trainees in Expressive Arts Group Supervision

    Science.gov (United States)

    Rossi, Martha Howe

    2010-01-01

    Expressive arts group supervision is the use of music, stories, movement, poetry or prose, role-play or psychodrama, art, guided imagery, or play to help trainees develop reflective skills (Wilkins, 1995), express thoughts and feelings (Knill, Levine & Levine, 2005; Lahad, 2000), develop new perspectives (Gladding, 2005), increase communication…

  17. Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis

    NARCIS (Netherlands)

    Geurts, J. J. G.; Wolswijk, G.; Bö, L.; van der Valk, P.; Polman, C. H.; Troost, D.; Aronica, E.

    2003-01-01

    Recent evidence supports a role for glutamate receptors in the pathophysiology of multiple sclerosis. In the present study, we have focused specifically on the expression of metabotropic glutamate receptors (mGluRs) in multiple sclerosis brain tissue. The expression of group I (mGluR1alpha and

  18. Classification Formula and Generation Algorithm of Cycle Decomposition Expression for Dihedral Groups

    Directory of Open Access Journals (Sweden)

    Dakun Zhang

    2013-01-01

    Full Text Available The necessary of classification research on common formula of group (dihedral group cycle decomposition expression is illustrated. It includes the reflection and rotation conversion, which derived six common formulae on cycle decomposition expressions of group; it designed the generation algorithm on the cycle decomposition expressions of group, which is based on the method of replacement conversion and the classification formula; algorithm analysis and the results of the process show that the generation algorithm which is based on the classification formula is outperformed by the general algorithm which is based on replacement conversion; it has great significance to solve the enumeration of the necklace combinational scheme, especially the structural problems of combinational scheme, by using group theory and computer.

  19. Blood group antigen A type 3 expression is a favorable prognostic factor in advanced NSCLC.

    Science.gov (United States)

    Schmidt, L H; Kuemmel, A; Schliemann, C; Schulze, A; Humberg, J; Mohr, M; Görlich, D; Hartmann, W; Bröckling, S; Marra, A; Hillejan, L; Goletz, S; Karsten, U; Berdel, W E; Spieker, T; Wiewrodt, R

    2016-02-01

    Several blood group-related carbohydrate antigens are prognosis-relevant markers of tumor tissues. A type 3 (repetitive A) is a blood group antigen specific for A1 erythrocytes. Its potential expression in tumor tissues has so far not been examined. We have evaluated its expression in normal lung and in lung cancer using a novel antibody (A69-A/E8). For comparison an anti-A antibody specific to A types 1 and 2 was used, because its expression on lung cancer tissue has been previously reported to be of prognostic relevance. Resected tissue samples of 398 NSCLC patients were analyzed in immunohistochemistry using tissue microarrays. Expression of A type 3 was not observed in non-malignant lung tissues. A type 3 was expressed on tumor cells of around half of NSCLC patients of blood group A1 (ptype 1/2 antigen was observed (p=0.562), the expression of A type 3 by tumor cells indicated a highly significant favorable prognosis among advanced NSCLC patients (p=0.011) and in NSCLC patients with lymphatic spread (p=0.014). Univariate prognostic results were confirmed in a Cox proportional hazards model. In this study we present for the first time prognostic data for A type 3 antigen expression in lung cancer patients. Prospective studies should be performed to confirm the prognostic value of A type 3 expression for an improved risk stratification in NSCLC patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Expression of the Fanconi anemia group A gene (Fanca) during mouse embryogenesis.

    Science.gov (United States)

    Abu-Issa, R; Eichele, G; Youssoufian, H

    1999-07-15

    About 80% of all cases of Fanconi anemia (FA) can be accounted for by complementation groups A and C. To understand the relationship between these groups, we analyzed the expression pattern of the mouse FA group-A gene (Fanca) during embryogenesis and compared it with the known pattern of the group-C gene (Fancc). Northern analysis of RNA from mouse embryos at embryonic days 7, 11, 15, and 17 showed a predominant 4.5 kb band in all stages. By in situ hybridization, Fanca transcripts were found in the whisker follicles, teeth, brain, retina, kidney, liver, and limbs. There was also stage-specific variation in Fanca expression, particularly within the developing whiskers and the brain. Some tissues known to express Fancc (eg, gut) failed to show Fanca expression. These observations show that (1) Fanca is under both tissue- and stage-specific regulation in several tissues; (2) the expression pattern of Fanca is consistent with the phenotype of the human disease; and (3) Fanca expression is not necessarily coupled to that of Fancc. The presence of distinct tissue targets for FA genes suggests that some of the variability in the clinical phenotype can be attributed to the complementation group assignment.

  1. Who wants to know? The effect of audience on identity expression among minority group members

    NARCIS (Netherlands)

    Barreto, M; Spears, R; Ellemers, N; Shahinper, K

    Statements of social identification among ethnic minority members were examined as a function of group membership of the participants, group membership of the audience, and personal identifiability. In Study 1, Turkish migrants and Iranian refugees in the Netherlands expressed their identification

  2. 3-Deazaneplanocin A suppresses aggressive phenotype-related gene expression in an oral squamous cell carcinoma cell line

    International Nuclear Information System (INIS)

    Hatta, Mitsutoki; Naganuma, Kaori; Kato, Kenichi; Yamazaki, Jun

    2015-01-01

    In tumor tissues, alterations of gene expression caused by aberrant epigenetic modifications confer phenotypic diversity on malignant cells. Although 3-deazaneplanocin A (DZNep) has been shown to reactivate tumor suppressor genes in several cancer cells, it remains unclear whether DZNep attenuates the malignant phenotypes of oral squamous cell carcinoma (OSCC) cells. In this study, we investigated the effect of DZNep on the expression of genes related to aggressive phenotypes, such as epithelial–mesenchymal transition, in OSCC cells. We found that DZNep reduced the cellular levels of polycomb group proteins (EZH2, SUZ12, BMI1, and RING1A) and the associated trimethylation of Lys27 on histone H3 and monoubiquitination of Lys119 on histone H2A in the poorly differentiated OSCC cell line SAS. Immunocytochemical staining demonstrated that DZNep induced the reorganization of filamentous actin and the membrane localization of E-cadherin associated with cell–cell adhesions. We also found an inhibitory effect of DZNep on cell proliferation using a WST assay. Finally, quantitative RT-PCR analysis demonstrated that genes involved in the aggressive phenotypes (TWIST2, EGFR, ACTA2, TGFB1, WNT5B, and APLIN) were down-regulated, whereas epithelial phenotype genes (CDH1, CLDN4, IVL, and TGM1) were up-regulated in SAS cells treated with DZNep. Collectively, our findings suggest that DZNep reverses the aggressive characteristics of OSCC cells through the dynamic regulation of epithelial plasticity via the reprogramming of gene expression patterns. - Highlights: • DZNep reduced PcG proteins and associated histone modifications in OSCC cells. • DZNep enhanced cell–cell adhesion indicative of epithelial phenotype in OSCC cells. • DZNep suppressed the aggressive phenotype-related gene expression in OSCC cells. • DZNep activated the gene expression of epithelial markers in OSCC cells.

  3. 3-Deazaneplanocin A suppresses aggressive phenotype-related gene expression in an oral squamous cell carcinoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Hatta, Mitsutoki, E-mail: hatta@college.fdcnet.ac.jp [Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka (Japan); Naganuma, Kaori [Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka (Japan); Kato, Kenichi; Yamazaki, Jun [Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka (Japan)

    2015-12-04

    In tumor tissues, alterations of gene expression caused by aberrant epigenetic modifications confer phenotypic diversity on malignant cells. Although 3-deazaneplanocin A (DZNep) has been shown to reactivate tumor suppressor genes in several cancer cells, it remains unclear whether DZNep attenuates the malignant phenotypes of oral squamous cell carcinoma (OSCC) cells. In this study, we investigated the effect of DZNep on the expression of genes related to aggressive phenotypes, such as epithelial–mesenchymal transition, in OSCC cells. We found that DZNep reduced the cellular levels of polycomb group proteins (EZH2, SUZ12, BMI1, and RING1A) and the associated trimethylation of Lys27 on histone H3 and monoubiquitination of Lys119 on histone H2A in the poorly differentiated OSCC cell line SAS. Immunocytochemical staining demonstrated that DZNep induced the reorganization of filamentous actin and the membrane localization of E-cadherin associated with cell–cell adhesions. We also found an inhibitory effect of DZNep on cell proliferation using a WST assay. Finally, quantitative RT-PCR analysis demonstrated that genes involved in the aggressive phenotypes (TWIST2, EGFR, ACTA2, TGFB1, WNT5B, and APLIN) were down-regulated, whereas epithelial phenotype genes (CDH1, CLDN4, IVL, and TGM1) were up-regulated in SAS cells treated with DZNep. Collectively, our findings suggest that DZNep reverses the aggressive characteristics of OSCC cells through the dynamic regulation of epithelial plasticity via the reprogramming of gene expression patterns. - Highlights: • DZNep reduced PcG proteins and associated histone modifications in OSCC cells. • DZNep enhanced cell–cell adhesion indicative of epithelial phenotype in OSCC cells. • DZNep suppressed the aggressive phenotype-related gene expression in OSCC cells. • DZNep activated the gene expression of epithelial markers in OSCC cells.

  4. P2-31: In-Group Advantage in Negative Facial Expressions

    Directory of Open Access Journals (Sweden)

    Li-Chuan Hsu

    2012-10-01

    Full Text Available To perceive facial expressions is suggested to be universal. However, studies have shown the in-group advantage (IGA in recognition of facial expressions (e.g., Matsumoto, 1989, 1992 which is that people understand emotions more accurately when these emotions are expressed by members of their own culture group. A balanced design was used to investigate whether this IGA was showed in Western people and as well as in Asian people (Taiwanese. An emotional identification task was adopted to ask participants to identify positive (happy and negative (sadness, fear, and anger faces among Eastern and Western faces. We used Eastern faces from the Taiwanese Facial Expression Image Database (Chen, 2007 and Western faces from Ekman & Frisen (1979. Both reaction times and accuracies of performance were measured. Results showed that even all participants can identify positive and negative faces accurately; Asia participants responded significantly faster to negative Eastern faces than to negative Western faces. The similar IGA effect was also shown in Western participants. However, no such culture difference was found to positive faces. The results revealed the in-group advantage of the perception of facial expressions was specific to negative emotions and question the universality of perceiving facial expressions.

  5. Expression of LacdiNAc Groups on N-Glycans among Human Tumors Is Complex

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    Kiyoko Hirano

    2014-01-01

    Full Text Available Aberrant glycosylation of proteins and lipids is one of the characteristic features of malignantly transformed cells. The GalNAcβ1 → 4GlcNAc (LacdiNAc or LDN group at the nonreducing termini of both N- and O-glycans is not generally found in mammalian cells. We previously showed that the expression level of the LacdiNAc group in N-glycans decreases dramatically during the progression of human breast cancer. In contrast, the enhanced expression of the LacdiNAc group has been shown to be associated with the progression of human prostate, ovarian, and pancreatic cancers. Therefore, the expression of the disaccharide group appears to be dependent on types of tumors. The mechanism of formation of the LacdiNAc group in human tumors and cancer cells has been studied, and two β4-N-acetylgalacto-saminyltransferases (β4GalNAcTs, β4GalNAcT3 and β4GalNAcT4, have been shown to be involved in the biosynthesis of this disaccharide group in a tissue-dependent manner. Transfection of the β4GalNAcT3 gene brought about significant changes in the malignant phenotypes of human neuroblastoma, indicating that this disaccharide group is important for suppressing the tumor growth.

  6. Expression and mechanism of high mobility group box protein-1 in retinal tissue of diabetic rats

    Directory of Open Access Journals (Sweden)

    Shuang Jiang

    2016-05-01

    Full Text Available AIM:To investigate the expression and mechanism of high mobility group box protein-1(HMGB1in the retina of diabetic rats. METHODS:Sixty SD rats were randomly divided into diabetic group and control group. Diabetic rat model was produced by intraperitioneal injection of 1% STZ with 60mg/Kg weight. The rats in control group received intraperitioneal injection of normal saline with same dosage. After injection, the rats were sacrificed and eyeballs were enucleated for HE staining, the retina fluorescence angiography, TUNEL and Western Blot detection at 1, 2 and 4mo for the expressions of HMGB1 and NF-κB. RESULTS:Compared with the control group, the retinal cells disorder, cell densities decreases, microvasculars occlusion were founded with inner and outer nuclear layer thinning and ganglion cell apoptosis. The fluorescence angiography showed that peripheral capillaries became circuitous and vascular occlusion and non-perfusion area could be seen. The expressions of HMGB1 and NF-κB were higher than those of control with time dependence and they had significant positive correlations(PCONCLUSION:The expression of HMGB1 increases in diabetic rat retina, which may involve in the occurrence of diabetic retinopathy through the NF- κB pathway.

  7. Entitativity and intergroup bias: How belonging to a cohesive group allows people to express their prejudices.

    Science.gov (United States)

    Effron, Daniel A; Knowles, Eric D

    2015-02-01

    We propose that people treat prejudice as more legitimate when it seems rationalistic-that is, linked to a group's pursuit of collective interests. Groups that appear to be coherent and unified wholes (entitative groups) are most likely to have such interests. We thus predicted that belonging to an entitative group licenses people to express prejudice against outgroups. Support for this idea came from 3 correlational studies and 5 experiments examining racial, national, and religious prejudice. The first 4 studies found that prejudice and discrimination seemed more socially acceptable to third parties when committed by members of highly entitative groups, because people could more easily explain entitative groups' biases as a defense of collective interests. Moreover, ingroup entitativity only lent legitimacy to outgroup prejudice when an interests-based explanation was plausible-namely, when the outgroup could possibly threaten the ingroup's interests. The last 4 studies found that people were more willing to express private prejudices when they perceived themselves as belonging to an entitative group. Participants' perceptions of their own race's entitativity were associated with a greater tendency to give explicit voice to their implicit prejudice against other races. Furthermore, experimentally raising participants' perceptions of ingroup entitativity increased explicit expressions of outgroup prejudice, particularly among people most likely to privately harbor such prejudices (i.e., highly identified group members). Together, these findings demonstrate that entitativity can lend a veneer of legitimacy to prejudice and disinhibit its expression. We discuss implications for intergroup relations and shifting national demographics. (PsycINFO Database Record (c) 2015 APA, all rights reserved). PsycINFO Database Record (c) 2015 APA, all rights reserved.

  8. Abnormal expression of blood group-related antigens in uterine endometrial cancers.

    Science.gov (United States)

    Tsukazaki, K; Sakayori, M; Arai, H; Yamaoka, K; Kurihara, S; Nozawa, S

    1991-08-01

    The expression of A, B, and H group antigens, Lewis group antigens (Lewis(a), Lewis(b), Lewis(x), and Lewis(y)), and Lc4 and nLc4 antigens, the precursor antigens of both groups, was examined immunohistochemically with monoclonal antibodies in 9 normal endometria, 6 endometrial hyperplasias, and 31 endometrial cancers. 1) A, B and/or H antigens were detected in endometrial cancers at an incidence of 51.6%, while no distinct localization of these antigens was observed in normal endometria. H antigen, the precursor of A and B antigens, was particularly frequently detected in endometrial cancers. 2) An increased rate of expression of Lewis group antigens, particularly Lewis(b) antigen, was observed in endometrial cancers compared with its expression in normal endometria. 3) Lc4 and nLc4 antigens were detected in endometrial cancers at rates of 41.9% and 38.7%, respectively, these expressions being increased compared with those in normal endometria. 4) These results suggest that a highly abnormal expression of blood group-related antigens in endometrial cancers occurs not only at the level of A, B, and H antigens and Lewis group antigens, but also at the level of their precursor Lc4 and nLc4 antigens. 5) Lewis(a), Lewis(b), and Lc4 antigens, built on the type-1 chain, are more specific to endometrial cancers than their respective positional isomers, Lewis(x), Lewis(y), and nLc4 antigens, built on the type-2 chain.

  9. Network-based group variable selection for detecting expression quantitative trait loci (eQTL

    Directory of Open Access Journals (Sweden)

    Zhang Xuegong

    2011-06-01

    Full Text Available Abstract Background Analysis of expression quantitative trait loci (eQTL aims to identify the genetic loci associated with the expression level of genes. Penalized regression with a proper penalty is suitable for the high-dimensional biological data. Its performance should be enhanced when we incorporate biological knowledge of gene expression network and linkage disequilibrium (LD structure between loci in high-noise background. Results We propose a network-based group variable selection (NGVS method for QTL detection. Our method simultaneously maps highly correlated expression traits sharing the same biological function to marker sets formed by LD. By grouping markers, complex joint activity of multiple SNPs can be considered and the dimensionality of eQTL problem is reduced dramatically. In order to demonstrate the power and flexibility of our method, we used it to analyze two simulations and a mouse obesity and diabetes dataset. We considered the gene co-expression network, grouped markers into marker sets and treated the additive and dominant effect of each locus as a group: as a consequence, we were able to replicate results previously obtained on the mouse linkage dataset. Furthermore, we observed several possible sex-dependent loci and interactions of multiple SNPs. Conclusions The proposed NGVS method is appropriate for problems with high-dimensional data and high-noise background. On eQTL problem it outperforms the classical Lasso method, which does not consider biological knowledge. Introduction of proper gene expression and loci correlation information makes detecting causal markers more accurate. With reasonable model settings, NGVS can lead to novel biological findings.

  10. VE-Cadherin–Mediated Epigenetic Regulation of Endothelial Gene Expression

    Science.gov (United States)

    Morini, Marco F.; Giampietro, Costanza; Corada, Monica; Pisati, Federica; Lavarone, Elisa; Cunha, Sara I.; Conze, Lei L.; O’Reilly, Nicola; Joshi, Dhira; Kjaer, Svend; George, Roger; Nye, Emma; Ma, Anqi; Jin, Jian; Mitter, Richard; Lupia, Michela; Cavallaro, Ugo; Pasini, Diego; Calado, Dinis P.

    2018-01-01

    Rationale: The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumors, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular interendothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, VEC (vascular endothelial cadherin), upregulate genes with key roles in endothelial differentiation and stability. Objective: We aim at understanding the molecular mechanisms through which VEC triggers the expression of a set of genes involved in endothelial differentiation and vascular stabilization. Methods and Results: We compared a VEC-null cell line with the same line reconstituted with VEC wild-type cDNA. VEC expression and clustering upregulated endothelial-specific genes with key roles in vascular stabilization including claudin-5, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and von Willebrand factor (vWf). Mechanistically, VEC exerts this effect by inhibiting polycomb protein activity on the specific gene promoters. This is achieved by preventing nuclear translocation of FoxO1 (Forkhead box protein O1) and β-catenin, which contribute to PRC2 (polycomb repressive complex-2) binding to promoter regions of claudin-5, VE-PTP, and vWf. VEC/β-catenin complex also sequesters a core subunit of PRC2 (Ezh2 [enhancer of zeste homolog 2]) at the cell membrane, preventing its nuclear translocation. Inhibition of Ezh2/VEC association increases Ezh2 recruitment to claudin-5, VE-PTP, and vWf promoters, causing gene downregulation. RNA sequencing comparison of VEC-null and VEC-positive cells suggested a more general role of VEC in activating endothelial genes and triggering a vascular stability-related gene expression program. In pathological angiogenesis of human ovarian carcinomas, reduced VEC expression paralleled decreased

  11. VE-Cadherin-Mediated Epigenetic Regulation of Endothelial Gene Expression.

    Science.gov (United States)

    Morini, Marco F; Giampietro, Costanza; Corada, Monica; Pisati, Federica; Lavarone, Elisa; Cunha, Sara I; Conze, Lei L; O'Reilly, Nicola; Joshi, Dhira; Kjaer, Svend; George, Roger; Nye, Emma; Ma, Anqi; Jin, Jian; Mitter, Richard; Lupia, Michela; Cavallaro, Ugo; Pasini, Diego; Calado, Dinis P; Dejana, Elisabetta; Taddei, Andrea

    2018-01-19

    The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumors, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular interendothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, VEC (vascular endothelial cadherin), upregulate genes with key roles in endothelial differentiation and stability. We aim at understanding the molecular mechanisms through which VEC triggers the expression of a set of genes involved in endothelial differentiation and vascular stabilization. We compared a VEC-null cell line with the same line reconstituted with VEC wild-type cDNA. VEC expression and clustering upregulated endothelial-specific genes with key roles in vascular stabilization including claudin-5 , vascular endothelial-protein tyrosine phosphatase ( VE-PTP ), and von Willebrand factor ( vWf ). Mechanistically, VEC exerts this effect by inhibiting polycomb protein activity on the specific gene promoters. This is achieved by preventing nuclear translocation of FoxO1 (Forkhead box protein O1) and β-catenin, which contribute to PRC2 (polycomb repressive complex-2) binding to promoter regions of claudin-5 , VE-PTP , and vWf . VEC/β-catenin complex also sequesters a core subunit of PRC2 (Ezh2 [enhancer of zeste homolog 2]) at the cell membrane, preventing its nuclear translocation. Inhibition of Ezh2/VEC association increases Ezh2 recruitment to claudin-5 , VE-PTP , and vWf promoters, causing gene downregulation. RNA sequencing comparison of VEC-null and VEC-positive cells suggested a more general role of VEC in activating endothelial genes and triggering a vascular stability-related gene expression program. In pathological angiogenesis of human ovarian carcinomas, reduced VEC expression paralleled decreased levels of claudin-5 and VE-PTP. These

  12. Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells

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    Chia-I Ko

    2014-01-01

    Full Text Available The aryl hydrocarbon receptor (AHR is a transcription factor and environmental sensor that regulates expression of genes involved in drug-metabolism and cell cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice and studies with orthologous genes in invertebrates suggest that AHR may also play a significant role in embryonic development. To address this hypothesis, we studied the regulation of Ahr expression in mouse embryonic stem cells and their differentiated progeny. In ES cells, interactions between OCT3/4, NANOG, SOX2 and Polycomb Group proteins at the Ahr promoter repress AHR expression, which can also be repressed by ectopic expression of reprogramming factors in hepatoma cells. In ES cells, unproductive RNA polymerase II binds at the Ahr transcription start site and drives the synthesis of short abortive transcripts. Activation of Ahr expression during differentiation follows from reversal of repressive marks in Ahr promoter chromatin, release of pluripotency factors and PcG proteins, binding of Sp factors, establishment of histone marks of open chromatin, and engagement of active RNAPII to drive full-length RNA transcript elongation. Our results suggest that reversible Ahr repression in ES cells holds the gene poised for expression and allows for a quick switch to activation during embryonic development.

  13. Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer

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    Xiaoao Pang

    2014-05-01

    Full Text Available We investigated the significance of high- mobility group box1 (HMGB1 and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3, IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN, and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05. In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05. HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05. HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05. Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment.

  14. Nitrogen Fixation Aligns with nifH Abundance and Expression in Two Coral Trophic Functional Groups

    KAUST Repository

    Pogoreutz, Claudia

    2017-06-28

    Microbial nitrogen fixation (diazotrophy) is a functional trait widely associated with tropical reef-building (scleractinian) corals. While the integral role of nitrogen fixation in coral nutrient dynamics is recognized, its ecological significance across different coral functional groups remains yet to be evaluated. Here we set out to compare molecular and physiological patterns of diazotrophy (i.e., nifH gene abundance and expression as well as nitrogen fixation rates) in two coral families with contrasting trophic strategies: highly heterotrophic, free-living members of the family Fungiidae (Pleuractis granulosa, Ctenactis echinata), and mostly autotrophic coral holobionts with low heterotrophic capacity (Pocilloporidae: Pocillopora verrucosa, Stylophora pistillata). The Fungiidae exhibited low diazotroph abundance (based on nifH gene copy numbers) and activity (based on nifH gene expression and the absence of detectable nitrogen fixation rates). In contrast, the mostly autotrophic Pocilloporidae exhibited nifH gene copy numbers and gene expression two orders of magnitude higher than in the Fungiidae, which coincided with detectable nitrogen fixation activity. Based on these data, we suggest that nitrogen fixation compensates for the low heterotrophic nitrogen uptake in autotrophic corals. Consequently, the ecological importance of diazotrophy in coral holobionts may be determined by the trophic functional group of the host.

  15. Nitrogen Fixation Aligns with nifH Abundance and Expression in Two Coral Trophic Functional Groups

    KAUST Repository

    Pogoreutz, Claudia; Radecker, Nils; Cardenas, Anny; Gä rdes, Astrid; Wild, Christian; Voolstra, Christian R.

    2017-01-01

    Microbial nitrogen fixation (diazotrophy) is a functional trait widely associated with tropical reef-building (scleractinian) corals. While the integral role of nitrogen fixation in coral nutrient dynamics is recognized, its ecological significance across different coral functional groups remains yet to be evaluated. Here we set out to compare molecular and physiological patterns of diazotrophy (i.e., nifH gene abundance and expression as well as nitrogen fixation rates) in two coral families with contrasting trophic strategies: highly heterotrophic, free-living members of the family Fungiidae (Pleuractis granulosa, Ctenactis echinata), and mostly autotrophic coral holobionts with low heterotrophic capacity (Pocilloporidae: Pocillopora verrucosa, Stylophora pistillata). The Fungiidae exhibited low diazotroph abundance (based on nifH gene copy numbers) and activity (based on nifH gene expression and the absence of detectable nitrogen fixation rates). In contrast, the mostly autotrophic Pocilloporidae exhibited nifH gene copy numbers and gene expression two orders of magnitude higher than in the Fungiidae, which coincided with detectable nitrogen fixation activity. Based on these data, we suggest that nitrogen fixation compensates for the low heterotrophic nitrogen uptake in autotrophic corals. Consequently, the ecological importance of diazotrophy in coral holobionts may be determined by the trophic functional group of the host.

  16. Expression of blood group antigens A and B in pancreas of vertebrates

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    ELENKA GEORGIEVA

    2012-01-01

    Full Text Available The biological role of blood group antigens (BGA A and B in tissues of different vertebrates is still controversial. There are few investigations on vertebrate pancreas and no obvious explanation of their tissue expression. The aim of the present study is to follow and compare the pancreatic expression of BGA A and B in representatives of five vertebrate classes. The biotin-streptavidin-proxidase labeling system was used for immunohistochemical detection of BGA by monoclonal antibodies to human A and B antigens. The present study reveals specific immunoreactivity in acinar and epithelial cells of pancreatic efferent ducts in species free-living vertebrates. The immunoperoxidase staining shows antigenic heterogeneity in the cellular localization. The number of positive cells and the intensity of expression vary in different species. Endothelial cells are positive only in the pancreas of Emys orbicularis. The lack of BGA A and B in some species suggests that the expression of these antigens is dependent not only on the evolutionary level of the species, but mainly on some genetic control mechanisms. The production of BGA A and B and the variability in their cellular localization probably reflect the stage of cell differentiation and the mechanisms of pancreatic secretor function. The presence of histo BGA in endodermal acinar pancreatic cells confirms the assumption for the high antigenic stability and conservatism of these molecules in vertebrate histogenesis and evolution.

  17. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

    Science.gov (United States)

    Yui, Daishi; Nishida, Yoichiro; Nishina, Tomoko; Mogushi, Kaoru; Tajiri, Mio; Ishibashi, Satoru; Ajioka, Itsuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Murayama, Shigeo; Yokota, Takanori

    2015-01-01

    Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa -/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa -/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa -/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. PMID:26637123

  18. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme.

    Directory of Open Access Journals (Sweden)

    Daishi Yui

    Full Text Available Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD model mice showed decreased insulin-degrading enzyme (IDE levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/- mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3; Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD.

  19. Group II intron inhibits conjugative relaxase expression in bacteria by mRNA targeting

    Science.gov (United States)

    Piazza, Carol Lyn; Smith, Dorie

    2018-01-01

    Group II introns are mobile ribozymes that are rare in bacterial genomes, often cohabiting with various mobile elements, and seldom interrupting housekeeping genes. What accounts for this distribution has not been well understood. Here, we demonstrate that Ll.LtrB, the group II intron residing in a relaxase gene on a conjugative plasmid from Lactococcus lactis, inhibits its host gene expression and restrains the naturally cohabiting mobile element from conjugative horizontal transfer. We show that reduction in gene expression is mainly at the mRNA level, and results from the interaction between exon-binding sequences (EBSs) in the intron and intron-binding sequences (IBSs) in the mRNA. The spliced intron targets the relaxase mRNA and reopens ligated exons, causing major mRNA loss. Taken together, this study provides an explanation for the distribution and paucity of group II introns in bacteria, and suggests a potential force for those introns to evolve into spliceosomal introns. PMID:29905149

  20. Establishing the National Expression in the Work of the Independent Group of Slovenian Artists (The Independents

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    Asta Vrečko

    2015-12-01

    Full Text Available The interwar period was ripe with political crises connected to the national question in the Kingdom of SHS and the Kingdom of Yugoslavia. The relationship between Yugoslav and Slovene identity again became central for the question of national emancipation within an increasing supranational conflict and became the focus of visual arts in the 1930s. After a decade marked by Expressionism and New Objectivity in the thirties, values of moderate modernism and the quest for national expression re-emerged. At the time a new group of artists emerged on the Slovene artistic scene. They were schooled in Zagreb, the cultural centre of the Kingdom of Yugoslavia, where intense polemics regarding national expression in art were taking place. This contribution outlines the search for “our expression” in art as understood by the central protagonists of the art scene in Croatia, Krsto Hegedušić and Ljubo Babić. The latter especially was of central importance to the formation of the young Slovene art, because he was a prolific writer and one of the most important professors at the Academy of Fine Arts in Zagreb. The former Slovenian students, who formed the Independent group of Slovenian artists (Klub neodvisnih slovenskih likovnih umetnikov emerged in the turbulent years before the outbreak of World War II. In art, so they claimed, they were seeking their own, Slovenian national visual expression. In this search they took inspiration from Croatian artists, whose ideas they adapted to the Slovenian situation. At the same time, they legitimised their efforts with references to Slovene impressionists, who were regarded as the founding fathers of Slovene national art. In this way the Independents (Neodvisni sought to highlight the continuity in their search for Slovene national expression in art despite the transformed historical context. They based their national expression in art on a modernist version of Slovene impressionism. They combined this with

  1. 77 FR 7601 - Notice of Segregation of Public Lands for the Pattern Energy Group Ocotillo Express Wind Energy...

    Science.gov (United States)

    2012-02-13

    ... LVRWB10B3980] Notice of Segregation of Public Lands for the Pattern Energy Group Ocotillo Express Wind Energy... Acts, for a period of 2 years for the purpose of processing a wind energy right-of-way (ROW... filed by Pattern Energy Group for the Ocotillo Express Wind Project on the above described lands while...

  2. The Modulation of Mimicry by Ethnic Group-Membership and Emotional Expressions.

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    Birgit Rauchbauer

    Full Text Available Mimicry has been ascribed affiliative functions. In three experiments, we used a newly developed social-affective mimicry task (SAMT to investigate mimicry´s modulation by emotional facial expressions (happy, angry and ethnic group-membership (White in-group, Black out-group. Experiment 1 established the main consistent effect across experiments, which was enhanced mimicry to angry out-group faces compared to angry in-group faces. Hence the SAMT was useful for experimentally investigating the modulation of mimicry. Experiment 2 demonstrated that these effects were not confounded by general aspects of response conflict, as a Simon task resulted in different response patterns than the SAMT. Experiment 2 and pooled analysis of Experiments 1 and 2 also corroborated the finding of enhanced mimicry to angry out-group faces. Experiment 3 tested whether this effect was related to perceptions of threat, by framing angry persons as physically threatening, or not. Selective enhancement of mimicry to out-group persons framed as physically threatening confirmed this hypothesis. Further support for the role of threat was derived from implicit measures showing, in all experiments, that black persons were more strongly associated with threat. Furthermore, enhanced mimicry was consistently related to response facilitation in the execution of congruent movements. This suggests that mimicry acted as a social congruency signal. Our findings suggest that mimicry may serve as an appeasement signal in response to negative affiliative intent. This extends previous models of mimicry, which have predominantly focused on its role in reciprocating affiliation. It suggests that mimicry might not only be used to maintain and establish affiliative bonds, but also to ameliorate a negative social situation.

  3. High Expression of High-Mobility Group Box 1 in Menstrual Blood: Implications for Endometriosis.

    Science.gov (United States)

    Shimizu, Keiko; Kamada, Yasuhiko; Sakamoto, Ai; Matsuda, Miwa; Nakatsuka, Mikiya; Hiramatsu, Yuji

    2017-11-01

    Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor ( VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid ( P endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.

  4. Expression of group III metabotropic glutamate receptors in the reproductive system of male mice.

    Science.gov (United States)

    Marciniak, Marcin; Chruścicka, Barbara; Lech, Tomasz; Burnat, Grzegorz; Pilc, Andrzej

    2016-03-01

    Although the presence of metabotropic glutamate (mGlu) receptors in the central nervous system is well documented, they have recently been found in peripheral and non-neuronal tissues. In the present study we investigated the expression of group III mGlu receptors in the reproductive system of male mice. Reverse transcription-polymerase chain reaction analysis revealed the presence of mGlu6, mGlu7 and mGlu8 (but not mGlu4) receptor transcripts in testes and epididymides from adult mice. In addition, expression of mGlu6 (Grm6) and mGlu8 receptor (Grm8) mRNA was detected in spermatozoa isolated from the vas deferens. The vas deferens was found to contain only mGlu7 receptor (Grm7) mRNA, which was particularly intense in 21-day-old male mice. In penile homogenates, only the mGlu7 receptor signal was detected. Genetic ablation of the mGlu7 receptor in males led to fertility disorders manifested by decreased insemination capability as well as deterioration of sperm parameters, particularly sperm motility, vitality, sperm membrane integrity and morphology, with a simultaneous increase in sperm concentration. These results indicate that constitutively expressed mGlu receptors in the male reproductive system may play an important role in ejaculation and/or erection processes, as well as in the formation and maturation of spermatozoa.

  5. Impaired Recognition of Facially Expressed Emotions in Different Groups of Patients with Sleep Disorders.

    Science.gov (United States)

    Crönlein, Tatjana; Langguth, Berthold; Eichhammer, Peter; Busch, Volker

    2016-01-01

    Recently it has been shown that acute sleep loss has a direct impact on emotional processing in healthy individuals. Here we studied the effect of chronically disturbed sleep on emotional processing by investigating two samples of patients with sleep disorders. 25 patients with psychophysiologic insomnia (23 women and 2 men, mean age: 51.6 SD; 10.9 years), 19 patients with sleep apnea syndrome (4 women and 15 men, mean age: 51.9; SD 11.1) and a control sample of 24 subjects with normal sleep (15 women and 9 men, mean age 45.3; SD 8.8) completed a Facial Expressed Emotion Labelling (FEEL) task, requiring participants to categorize and rate the intensity of six emotional expression categories: anger, anxiety, fear, happiness, disgust and sadness. Differences in FEEL score and its subscales among the three samples were analysed using ANOVA with gender as a covariate. Both patients with psychophysiologic insomnia and patients with sleep apnea showed significantly lower performance in the FEEL test as compared to the control group. Differences were seen in the scales happiness and sadness. Patient groups did not differ from each other. By demonstrating that previously known effects of acute sleep deprivation on emotional processing can be extended to persons experiencing chronically disturbed sleep, our data contribute to a deeper understanding of the relationship between sleep loss and emotions.

  6. Impaired Recognition of Facially Expressed Emotions in Different Groups of Patients with Sleep Disorders.

    Directory of Open Access Journals (Sweden)

    Tatjana Crönlein

    Full Text Available Recently it has been shown that acute sleep loss has a direct impact on emotional processing in healthy individuals. Here we studied the effect of chronically disturbed sleep on emotional processing by investigating two samples of patients with sleep disorders.25 patients with psychophysiologic insomnia (23 women and 2 men, mean age: 51.6 SD; 10.9 years, 19 patients with sleep apnea syndrome (4 women and 15 men, mean age: 51.9; SD 11.1 and a control sample of 24 subjects with normal sleep (15 women and 9 men, mean age 45.3; SD 8.8 completed a Facial Expressed Emotion Labelling (FEEL task, requiring participants to categorize and rate the intensity of six emotional expression categories: anger, anxiety, fear, happiness, disgust and sadness. Differences in FEEL score and its subscales among the three samples were analysed using ANOVA with gender as a covariate.Both patients with psychophysiologic insomnia and patients with sleep apnea showed significantly lower performance in the FEEL test as compared to the control group. Differences were seen in the scales happiness and sadness. Patient groups did not differ from each other.By demonstrating that previously known effects of acute sleep deprivation on emotional processing can be extended to persons experiencing chronically disturbed sleep, our data contribute to a deeper understanding of the relationship between sleep loss and emotions.

  7. Imitation of in-group versus out-group members' facial expressions of anger: a test with a time perception task.

    Science.gov (United States)

    Mondillon, Laurie; Niedenthal, Paula M; Gil, Sandrine; Droit-Volet, Sylvie

    2007-01-01

    This research investigated the automatic imitation of facial expressions of anger by in-group and out-group members, using a temporal estimation task. Individuals typically overestimate duration represented by angry faces, probably due to increases in arousal (Droit-Volet, Brunot, & Niedenthal, 2004). Overestimation is not observed when imitation of the facial expressions is inhibited, suggesting that embodied simulation mediates the changes in arousal (Effron, Niedenthal, Gil, & Droit-Volet, 2006). This method thus provides an implicit measure of imitation and was used to test the hypothesis that individuals imitate in-group, but not out-group members' facial expressions of emotion. In separate studies Chinese and French Caucasian participants were presented with short (400 ms) and long (1600 ms) standard durations in a temporal bisection task. They then categorized standard and intermediate durations, represented by angry and neutral faces, in terms of similarity to the short and long standard durations. Half of the face stimuli were Chinese, and half Caucasian. Results revealed a bias in the temporal perception of emotion for the Caucasian participants when they were presented with Caucasian facial expressions and not Chinese ones. In contrast, this bias in time perception was observed when Chinese individuals imitated faces of both in- and out-group members. The results of the Chinese participants are interpreted in terms of familiarity with and motivations to understand the emotional expressions of members of a host culture.

  8. Expression

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    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  9. Energy Cost Expression for a Youth Compendium of Physical Activities: Rationale for Using Age Groups.

    Science.gov (United States)

    Pfeiffer, Karin A; Watson, Kathleen B; McMurray, Robert G; Bassett, David R; Butte, Nancy F; Crouter, Scott E; Herrmann, Stephen D; Trost, Stewart G; Ainsworth, Barbara E; Fulton, Janet E; Berrigan, David

    2018-02-01

    This study compared the accuracy of physical activity energy expenditure (PAEE) prediction using 2 methods of accounting for age dependency versus 1 standard (single) value across all ages. PAEE estimates were derived by pooling data from 5 studies. Participants, 6-18 years (n = 929), engaged in 14 activities while in a room calorimeter or wearing a portable metabolic analyzer. Linear regression was used to estimate the measurement error in PAEE (expressed as youth metabolic equivalent) associated with using age groups (6-9, 10-12, 13-15, and 16-18 y) and age-in-years [each year of chronological age (eg, 12 = 12.0-12.99 y)] versus the standard (a single value across all ages). Age groups and age-in-years showed similar error, and both showed less error than the standard method for cycling, skilled, and moderate- to vigorous-intensity activities. For sedentary and light activities, the standard had similar error to the other 2 methods. Mean values for root mean square error ranged from 0.2 to 1.7 youth metabolic equivalent across all activities. Error reduction ranged from -0.2% to 21.7% for age groups and -0.23% to 18.2% for age-in-years compared with the standard. Accounting for age showed lower errors than a standard (single) value; using an age-dependent model in the Youth Compendium is recommended.

  10. Understanding Xeroderma Pigmentosum Complementation Groups Using Gene Expression Profiling after UV-Light Exposure.

    Science.gov (United States)

    Bowden, Nikola A; Beveridge, Natalie J; Ashton, Katie A; Baines, Katherine J; Scott, Rodney J

    2015-07-14

    Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease.

  11. The Dermatophagoides farinae group 22 allergen: cloning and expression in Escherichia coli.

    Science.gov (United States)

    Cui, Yu-bao; Cai, Hong-xing; Zhou, Ying; Wang, Nan; Yu, Li-li; Yang, Li; Zhang, Cheng-bo

    2015-09-01

    Dermatophagoides farinae (Hughes) (Acari: Pyroglyphidae) and other domestic mites produce allergens that affect people worldwide. Here, the complementary DNA (cDNA) coding for group 22 allergen of D. farinae (Der f 22) from China was cloned, sequenced, and expressed successfully. The cDNA encoding Der f 22 was synthesized by reverse transcription polymerase chain reaction (RT-PCR), then ligated to the pCold-TF for expression in Escherichia coli BL21 cells. The purified recombinant fusion protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western-blotting, and tandem matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF/TOF). The full-length cDNA comprised 468 nucleotides and was 99.57% (466/468) identical with the reference sequence (GenBank: DQ643992). After the plasmid pCold-TF-Der f 22 was transformed into E. coli BL21 and expressed with the induction of IPTG, SDS-PAGE showed a specific band for the recombinant fusion protein. The recombinant fusion protein, which was purified by chromatography, bound with a His-tagged antibody by Western blotting. MALDI-TOF/TOF mass spectrometry revealed that the structure of the recombinant protein was identical to the predicted Der f 22 structure. The hydrophilic protein contains a signal peptide of 20 amino acids, and the mature Der f 22 consists of 135 amino acid residues with a molecular weight of 14.7 kDa and theoretical isoelectric points (pI) of 6.38. Its secondary structure comprises an alpha helix (38.5%), beta-sheet (45.9%), random coils (11.85%), and beta-turns (11.1%). This work represents the first reported full-length sequence and successful cloning of Der f 22 from D. farinae in China; bioinformatics analysis can be used to further study the allergenicity and clinical utility of the recombinant Der f 22. © 2015 ARS-AAOA, LLC.

  12. Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs

    International Nuclear Information System (INIS)

    Erdmann, Kati; Kaulke, Knut; Thomae, Cathleen; Huebner, Doreen; Sergon, Mildred; Froehner, Michael; Wirth, Manfred P; Fuessel, Susanne

    2014-01-01

    Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA). In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation. The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a. The findings of this study indicate that the expression of specific miRNAs is decreased in PCa and inversely correlates with the up-regulation of their putative target genes. Consequently, miRNAs could contribute to oncogenesis and progression of PCa via an altered miRNA-target gene-interaction

  13. One angry woman: Anger expression increases influence for men, but decreases influence for women, during group deliberation.

    Science.gov (United States)

    Salerno, Jessica M; Peter-Hagene, Liana C

    2015-12-01

    We investigated whether expressing anger increases social influence for men, but diminishes social influence for women, during group deliberation. In a deception paradigm, participants believed they were engaged in a computer-mediated mock jury deliberation about a murder case. In actuality, the interaction was scripted. The script included 5 other mock jurors who provided verdicts and comments in support of the verdicts; 4 agreed with the participant and 1 was a "holdout" dissenter. Holdouts expressed their opinions with no emotion, anger, or fear and had either male or female names. Holdouts exerted no influence on participants' opinions when they expressed no emotion or fear. Participants' confidence in their own verdict dropped significantly, however, after male holdouts expressed anger. Yet, anger expression undermined female holdouts: Participants became significantly more confident in their original verdicts after female holdouts expressed anger-even though they were expressing the exact same opinion and emotion as the male holdouts. Mediation analyses revealed that participants drew different inferences from male versus female anger, which created a gender gap in influence during group deliberation. The current study has implications for group decisions in general, and jury deliberations in particular, by suggesting that expressing anger might lead men to gain influence, but women to lose influence over others (even when making identical arguments). These diverging consequences might result in women potentially having less influence on societally important decisions than men, such as jury verdicts. (c) 2015 APA, all rights reserved).

  14. Feasibility of an expressive-disclosure group intervention for post-treatment colorectal cancer patients: results of the Healthy Expressions study.

    Science.gov (United States)

    Carmack, Cindy L; Basen-Engquist, Karen; Yuan, Ying; Greisinger, Anthony; Rodriguez-Bigas, Miguel; Wolff, Robert A; Barker, Trina; Baum, George; Pennebaker, James W

    2011-11-01

    Adjusting to cancer requires effective cognitive and emotional processing. Written and verbal disclosure facilitate processing and have been studied independently in cancer survivors. Combined written and verbal expression may be more effective than either alone, particularly for patients with difficult to discuss or embarrassing side effects. Thus, the authors developed and tested the efficacy of a 12-session combined written and verbal expression group program for psychologically distressed colorectal cancer (CRC) patients. Forty post-treatment patients with CRC (stages I-III) identified as psychologically distressed using the Brief Symptom Inventory (BSI) were randomized to an intervention group (Healthy Expressions; n = 25) or standard care (control group; n = 15). Assessments were completed at baseline, Month 2, and Month 4 (postintervention). Primary outcomes were psychological functioning and quality of life (QOL). Most participants were women (63%), white (63%), and non-Hispanic (75%). The Healthy Expressions group demonstrated significantly greater changes in distress compared with the control group at Month 2 on the BSI Global Severity Index (GSI) and the Centers for Epidemiologic Studies Depression scale (CES-D) scores (P psychological functioning in CRC patients who reported experiencing distress. Findings demonstrate the program's feasibility and provide strong support for conducting a larger randomized trial. Copyright © 2011 American Cancer Society.

  15. Expression and characterization of human group C rotavirus virus-like particles in insect cells

    International Nuclear Information System (INIS)

    Clark, Kristina B.; Lin, S.-C.; Humphrey, Charles; Foytich, Kimberly; Esona, Mathew; Wang Yuhuan; Liu, Merry; Jiang Baoming

    2009-01-01

    Group C rotavirus (GpC RV) is a causative agent of acute gastroenteritis in children and adults. We expressed the three major capsid proteins VP2, VP6 and VP7 of human GpC RV in baculovirus and demonstrated the self-assembly of VP2/6/7 or VP6/7 virus-like particles (VLPs) in insect cells. We examined a number of parameters, including the kinetics of protein synthesis in different cell lines and media, to optimize the most favorable conditions for the synthesis of recombinant viral proteins and the production of VLPs in Sf9 cells. Hyperimmune serum to VP2/6/7 and VP6/7 VLPs recognized individual recombinant proteins of human GpC RV by Western blot analysis. This serum also showed specific reactivities with the corresponding GpC VLPs but not GpA RV by using immune electron microscopy (IEM) and enzyme immunoassay (EIA). The ability to produce an unlimited amount of GpC RV antigen and the availability of high quality antibody will allow us to develop sensitive and specific diagnostic assays to better determine the epidemiology and disease burden of GpC RV in humans.

  16. Social Integration and Religious Identity Expression among Dutch Muslims: The Role of Minority and Majority Group Contact

    Science.gov (United States)

    Maliepaard, Mieke; Phalet, Karen

    2012-01-01

    Against the background of contrasting religious versus secular norms in immigrant communities and in Dutch society, this study examines how religious identity expression is related to the social integration of Dutch Muslims within (a) Turkish or Moroccan minority groups and (b) Dutch majority groups. Using nationally representative survey data (N…

  17. Cultural expressions of social class and their implications for group-related beliefs and behaviors

    OpenAIRE

    Rheinschmidt-Same, Michelle; Becker, Julia; Kraus, Michael

    2017-01-01

    In the wake of the Great Recession, rising inequality has increased social class disparities between people in society. In this research, we examine how differences in social class shape unique patterns of cultural expression, and how these cultural expressions affirm ingroup beliefs. In Study 1 (N=113), we provide evidence that cultural expressions of social class on an online social network can signal the social class of targets: by simply viewing the cultural practices of individuals captu...

  18. Biosynthetic basis of incompatible histo-blood group A antigen expression

    DEFF Research Database (Denmark)

    David, L; Leitao, D; Sobrinho-Simoes, M

    1993-01-01

    The expression of incompatible A carbohydrate antigens in some adenocarcinomas may provide an explanation for the generally observed lower incidence of adenocarcinoma among types O and B versus type A individuals. The chemistry and genetic basis of incompatible A expression is largely unknown. He...

  19. An asymptotic expression for the eigenvalues of the normalization kernel of the resonating group method

    International Nuclear Information System (INIS)

    Lomnitz-Adler, J.; Brink, D.M.

    1976-01-01

    A generating function for the eigenvalues of the RGM Normalization Kernel is expressed in terms of the diagonal matrix elements of thw GCM Overlap Kernel. An asymptotic expression for the eigenvalues is obtained by using the Method of Steepest Descent. (Auth.)

  20. Using Group II Introns for Attenuating the In Vitro and In Vivo Expression of a Homing Endonuclease.

    Directory of Open Access Journals (Sweden)

    Tuhin Kumar Guha

    Full Text Available In Chaetomium thermophilum (DSM 1495 within the mitochondrial DNA (mtDNA small ribosomal subunit (rns gene a group IIA1 intron interrupts an open reading frame (ORF encoded within a group I intron (mS1247. This arrangement offers the opportunity to examine if the nested group II intron could be utilized as a regulatory element for the expression of the homing endonuclease (HEase. Constructs were generated where the codon-optimized ORF was interrupted with either the native group IIA1 intron or a group IIB type intron. This study showed that the expression of the HEase (in vivo in Escherichia coli can be regulated by manipulating the splicing efficiency of the HEase ORF-embedded group II introns. Exogenous magnesium chloride (MgCl2 stimulated the expression of a functional HEase but the addition of cobalt chloride (CoCl2 to growth media antagonized the expression of HEase activity. Ultimately the ability to attenuate HEase activity might be useful in precision genome engineering, minimizing off target activities, or where pathways have to be altered during a specific growth phase.

  1. Expression of blood group-related glycoconjugates in the junctional and other oral epithelia of rodents

    DEFF Research Database (Denmark)

    Mackenzie, I C; Dabelsteen, Erik; Rittman, G

    1995-01-01

    BACKGROUND: The junctional epithelium (JE) attaches the gingiva to the non-vital tooth surface and has other unusual properties which protect the underlying periodontal tissues. The JE differs from other gingival and oral epithelia in its unusual expression of cytokeratins typical of both...... and provide an alternative marker system for regionally-differing patterns of cell maturation. RESULTS: Markers that are typical of basal cells in other stratifying epithelia were expressed by all cell strata of JE. JE lacked differentiation markers typical of other stratifying oral epithelial but showed...... suprabasal expression of markers typically expressed by simple epithelia and specialized epithelia, such as taste buds. CONCLUSIONS: The phenotype of rodent JE differs from that of other oral epithelia and the pattern of differentiation assessed by its expression of glycoconjugates parallels that for other...

  2. Self-expression, group affiliation, pleasure and memory as predictors of consumer product attachment and satisfaction among mobile phone users

    Directory of Open Access Journals (Sweden)

    Kagiso Tlhabano

    2013-03-01

    Full Text Available In the post-purchase behaviour of a product, there are challenges with change in the degree of consumer product attachment, and these challenges affect consumer product satisfaction overtime. This study investigated how self-expression, group affiliation, memory, and demographic variables predicted consumer product attachment and satisfaction among mobile phone users in Ibadan. Three hundred students of the University of Ibadan were selected using convenient random selection. Their mean age was 20.7 and standard deviation of 2.52. A structured questionnaire consisting of the socio demographic section, measure of self-expression, group affiliation, memory, pleasure, consumer attachment and product satisfaction was used to collect the data. Using multiple regression analysis, the results showed that self-expression, group affiliation, memories and pleasure jointly predicted consumer attachment among mobile phone users, F (4,299 = 48.47; P<0.05 and they contributed 40% to the variance of consumer attachment. Self-expression (β = 0.26, t = 4.44, P<0.05, memory (β = 0.29, t = 4.97, P<0.05, and pleasure (β = 0.28, t =5.01, P<0.05 independently predicted consumer attachment while group affiliation did not. In addition, self- expression, group affiliation, memories and pleasure jointly predicted product satisfaction, F (4,299 =39.79; P<0.05 and they contributed 35% to the variance of product satisfaction. Pleasure (β=0.596, t =10.35, P<0.05 independently predicted product satisfaction while self-expression, group affiliation and memory did not. Furthermore, age, gender, mobile type, ethnicity and religion did not jointly and independently predict consumer product satisfaction. These findings have implication for mobile phone manufacturers in terms of product improvement and building a strategic marketing channel that would meet the needs of global consumers.

  3. Blood-group-related carbohydrates are expressed in organotypic cultures of human skin and oral mucosa

    DEFF Research Database (Denmark)

    Grøn, B; Andersson, A; Dabelsteen, Erik

    1999-01-01

    cultures. The organotypic skin and oral mucosa cultures showed a histological differentiation pattern analogous to that of normal skin and buccal mucosa, and a tissue-specific expression of carbohydrate structures and cytokeratins. However, both types of organotypic cultures also expressed markers which...... are normally seen during wound healing, including Lewis y, cytokeratin 16, and cytokeratin 19. We conclude that the organotypic cultures of oral mucosa and skin are suitable models for future studies of the function of cell-surface carbohydrates, although the expression of wound healing markers has to be taken...... the function of cell-surface carbohydrates, we established organotypic cultures of skin and buccal mucosa. In these cultures, keratinocytes are grown at the air-liquid interface on a supporting matrix consisting of homologous fibroblasts embedded in a collagen type I gel. We examined the expression of blood...

  4. Expressed Sense of Self by People With Alzheimer's Disease in a Support Group Interpreted in Terms of Agency and Communion.

    Science.gov (United States)

    Hedman, Ragnhild; Hansebo, Görel; Ternestedt, Britt-Marie; Hellström, Ingrid; Norberg, Astrid

    2016-04-01

    The self is constructed in cooperation with other people and social context influences how people perceive and express it. People with Alzheimer's disease (AD) often receive insufficient support in constructing their preferred selves, but little is known about how they express themselves together with other people with AD. In accordance with Harré's social constructionist theory of self, this study aimed to describe how five people with mild and moderate AD express their Self 2 (i.e., their personal attributes and life histories) in a support group with a facilitator experienced in communicating with people with AD. The participants' expressions of their Self 2 were analyzed with qualitative abductive content analysis and interpreted in terms of agency and communion and a lack of agency and communion. The findings highlight the importance of supporting a sense of agency and communion when assisting people with AD in constructing their self. © The Author(s) 2014.

  5. Analytical expressions for group delay in the far field from an optical fiber having an arbitrary index profile

    OpenAIRE

    Danielsen, Per Lander

    1981-01-01

    A general and efficient model for optical fibers with a few modes and arbitrary index profiles is established. The model yields a solution of the vectorial wave equation and analytical expressions for the group delay and the far field. Convergence tests have shown that the dispersion can be calculated with an accuracy better than 0.2 ps/(km . nm).

  6. Analytical expressions for group delay in the far field from an optical fiber having an arbitrary index profile

    DEFF Research Database (Denmark)

    Danielsen, Per Lander

    1981-01-01

    A general and efficient model for optical fibers with a few modes and arbitrary index profiles is established. The model yields a solution of the vectorial wave equation and analytical expressions for the group delay and the far field. Convergence tests have shown that the dispersion can...

  7. Learning of Idiomatic Language Expressions in a Group Intervention for Children with Autism

    Science.gov (United States)

    Whyte, Elisabeth M.; Nelson, Keith E.; Khan, Kiren S.

    2013-01-01

    In typical development, children learn an extensive range of idioms and other figurative (non-literal) language expressions during childhood and adolescence. However, many children with autism fall far behind in their idiom comprehension and production and never fully reach adult levels. The current study measured the effectiveness of a group…

  8. Affective expressions in groups and inferences about members' relational well-being: The effects of socially engaging and disengaging emotions.

    Science.gov (United States)

    Rothman, Naomi B; Magee, Joe C

    2016-01-01

    Our findings draw attention to the interpersonal communication function of a relatively unexplored dimension of emotions-the level of social engagement versus disengagement. In four experiments, regardless of valence and target group gender, observers infer greater relational well-being (more cohesiveness and less conflict) between group members from socially engaging (sadness and appreciation) versus disengaging (anger and pride) emotion expressions. Supporting our argument that social (dis)engagement is a critical dimension communicated by these emotions, we demonstrate (1) that inferences about group members' self-interest mediate the effect of socially engaging emotions on cohesiveness and (2) that the influence of socially disengaging emotion expressions on inferences of conflict is attenuated when groups have collectivistic norms (i.e., members value a high level of social engagement). Furthermore, we show an important downstream consequence of these inferences of relational well-being: Groups that seem less cohesive because of their members' proud (versus appreciative) expressions are also expected to have worse task performance.

  9. Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Joshi NV

    2009-01-01

    Full Text Available Abstract Background Regulation of gene expression in Plasmodium falciparum (Pf remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS; this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

  10. Stabilization of Transfected Cells Expressing Low-Incidence Blood Group Antigens: Novel Methods Facilitating Their Use as Reagent-Cells.

    Directory of Open Access Journals (Sweden)

    Cecilia González

    Full Text Available The identification of erythrocyte antibodies in the serum of patients rely on panels of human red blood cells (RBCs, which coexpress many antigens and are not easily available for low-incidence blood group phenotypes. These problems have been addressed by generating cell lines expressing unique blood group antigens, which may be used as an alternative to human RBCs. However, the use of cell lines implies several drawbacks, like the requirement of cell culture facilities and the high cost of cryopreservation. The application of cell stabilization methods could facilitate their use as reagent cells in clinical laboratories.We generated stably-transfected cells expressing low-incidence blood group antigens (Dia and Lua. High-expresser clones were used to assess the effect of TransFix® treatment and lyophilization as cell preservation methods. Cells were kept at 4°C and cell morphology, membrane permeability and antigenic properties were evaluated at several time-points after treatment.TransFix® addition to cell suspensions allows cell stabilization and proper antigen detection for at least 120 days, despite an increase in membrane permeability and a reduction in antigen expression levels. Lyophilized cells showed minor morphological changes and antigen expression levels were rather conserved at days 1, 15 and 120, indicating a high stability of the freeze-dried product. These stabilized cells have been proved to react specifically with human sera containing alloantibodies.Both stabilization methods allow long-term preservation of the transfected cells antigenic properties and may facilitate their distribution and use as reagent-cells expressing low-incidence antigens, overcoming the limited availability of such rare RBCs.

  11. Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection.

    Directory of Open Access Journals (Sweden)

    Philipp Rausch

    2015-07-01

    Full Text Available Glycans play important roles in host-microbe interactions. Tissue-specific expression patterns of the blood group glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2 are variable in wild mouse populations, and loss of B4galnt2 expression is associated with altered intestinal microbiota. We hypothesized that variation in B4galnt2 expression alters susceptibility to intestinal pathogens. To test this, we challenged mice genetically engineered to express different B4galnt2 tissue-specific patterns with a Salmonella Typhimurium infection model. We found B4galnt2 intestinal expression was strongly associated with bacterial community composition and increased Salmonella susceptibility as evidenced by increased intestinal inflammatory cytokines and infiltrating immune cells. Fecal transfer experiments demonstrated a crucial role of the B4galnt2-dependent microbiota in conferring susceptibility to intestinal inflammation, while epithelial B4galnt2 expression facilitated epithelial invasion of S. Typhimurium. These data support a critical role for B4galnt2 in gastrointestinal infections. We speculate that B4galnt2-specific differences in host susceptibility to intestinal pathogens underlie the strong signatures of balancing selection observed at the B4galnt2 locus in wild mouse populations.

  12. Effects of an expressive writing intervention on a group of public employees subjected to work relocation.

    Science.gov (United States)

    Tarquini, Matteo; Di Trani, Michela; Solano, Luigi

    2016-02-15

    Pennebaker's writing technique has yielded good results on health, psychological and performance dimensions. In spite of the positive outcomes, the technique has rarely been applied directly within the workplace and its effects on burnout have never been tested. 18 public employees subjected to work relocation were asked to write about their present work situation or another difficult event of their life (Writing Group), while another 17 were not assigned any writing task (Control Group). To assess whether there was an improvement in burnout, alexithymia and psychological well-being in the Writing Group compared with the baseline measurement and the Control Group. While the baseline levels in the Writing and Control Groups in the 3 dimensions considered were similar, scores in the Writing Group at both a second (1 month after the end of the procedure) and third measurement (7 months after the end) improved when compared with the baseline, whereas those in the Control Group worsened. Pennebaker's writing technique appears to promote adaptive coping strategies in stressful situations, and to increase occupational and psychological well-being as well as the ability to process emotions. It also appears to buffer the negative effects of work-related stress.

  13. Regulation of expression of a select group of Bacillus anthracis spore coat proteins.

    Science.gov (United States)

    Aronson, Arthur

    2018-04-01

    The spore coat of Bacilli is a relatively complex structure comprised of about 70 species of proteins in 2 or 3 layers. While some are involved in assembly or protection, the regulation of many are not well defined so lacZ transcriptional fusions were constructed to six Bacillus anthracis spore coat genes in order to gain insight into their possible functions. The genes were selected on the basis of the location of the encoded proteins within the coat and distribution among spore forming species. Conditions tested were temperature and media either as solid or liquid. The most extensive differences were for the relatively well expressed fusions to the cotH and cotM genes, which were greatest at 30°C on plates of a nutrient rich medium. The cotJ operon was moderately expressed under all conditions although somewhat higher on enriched plates at 30°C. Cot S was low under all conditions except for a substantial increase in biofilm medium. Cot∝ and cotF were essentially invariant with a somewhat greater expression in the more enriched medium. The capacity of a subset of coat genes to respond to various conditions reflects a flexibility in spore coat structure that may be necessary for adaptation to environmental challenges. This could account, at least in part, for the complexity of this structure.

  14. OPERATIVE GROUP: EDUCATIONAL PRACTICE AS AN EXPRESSION FOR SELF-CARE IN DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    Mariana Almeida Maia

    2013-12-01

    Full Text Available The goal is to understand the views of users with type 2 diabetes about their participation in the operating groups and the impact of self-care practices. This is a qualitative descriptive- exploratory held in three basic health units of the sanitary district east of Belo Horizonte and involved the participation of 18 users in 2011. The speeches of the users were analyzed based on content analysis, identifying the categories: exchange of experience, education for self- care, assessment of user participation in the operative groups, Feelings and links between professionals and users. It was noted that the operational groups provided the construction of knowledge through listening, reflection and questioning of reality where the user identified the importance of knowledge about diet, physical activity and treatment. We found that health actions implemented through the operational groups encourage users to think about your lifestyle, characterized as a tool in health education from the perspective of promotion, prevention and control.

  15. Posttraumatic stress disorder and art group therapy: Self-expression of traumatic inner world of war veterans

    Directory of Open Access Journals (Sweden)

    Mandić-Gajić Gordana

    2016-01-01

    Full Text Available Background/Aim. Art therapy and drawings may serve as alternative means of expression and release from trauma among veterans diagnosed with posttraumatic stress disorder (PTSD. Methods. The retrospective clinical study of drawings of war veterans was performed. A total of 89 war veterans met the Diagnostics and Statistical Manual of Mental Disorders (DSM-IV PTSD criteria and were consecutively admitted to the Day Hospital during 5 years. Art group therapy as part of integrative treatment was performed once a week. The group was open and heterogeneous. Qualitative analysis of drawings content and group protocols were obtained. The drawings were made by free associations. War related themes were explored and descriptive statistics were applied. Results. The most frequent type of common themes of combat stress presented battle and witnessing wounded and killed combatants. Less frequent were themes of graves, destroyed cities and broken trees. The veterans preferred black and red colors with association to death, blood, wounds and destroyed objects. Conclusion. Drawing could provide a unique, complex, visual illustration of war traumatic experiences and memories of posttraumatic stress disorder veterans. Art group discussion might enhance war veterans’ verbal expression due to group support in safe setting. As adjuvant psychotherapy, art group therapy could enrich awareness and the ability of clinicians to treat hard posttraumatic stress disorder symptoms related to uncovered war trauma.

  16. Neurodevelopmental Expression Profile of Dimeric and Monomeric Group 1 mGluRs: Relevance to Schizophrenia Pathogenesis and Treatment.

    Science.gov (United States)

    Lum, Jeremy S; Fernandez, Francesca; Matosin, Natalie; Andrews, Jessica L; Huang, Xu-Feng; Ooi, Lezanne; Newell, Kelly A

    2016-10-10

    Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically declining at adolescence and adulthood (-97-99%). The mGluR regulators, Homer 1b/c and Norbin, significantly increased with age in the PFC and hippocampus. Perinatal PCP treatment significantly increased juvenile dimeric mGluR5 levels in the PFC and hippocampus (37-50%) but decreased hippocampal mGluR1α (-50-56%). Perinatal PCP treatment also reduced mGluR1α dimer levels in the PFC at adulthood (-31%). These results suggest that Group 1 mGluRs have distinct dimeric and monomeric neurodevelopmental patterns, which may impact their pharmacological profiles at specific ages. Perinatal PCP treatment disrupted the early expression of Group 1 mGluRs which may underlie neurodevelopmental alterations observed in this model.

  17. Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice.

    Science.gov (United States)

    Horii, Yasuyuki; Nagasawa, Tatsuhiro; Sakakibara, Hiroyuki; Takahashi, Aki; Tanave, Akira; Matsumoto, Yuki; Nagayama, Hiromichi; Yoshimi, Kazuto; Yasuda, Michiko T; Shimoi, Kayoko; Koide, Tsuyoshi

    2017-08-01

    Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

  18. Emotions as guardians of group norms: expressions of anger and disgust drive inferences about autonomy and purity violations.

    Science.gov (United States)

    Heerdink, Marc W; Koning, Lukas F; van Doorn, Evert A; van Kleef, Gerben A

    2018-05-18

    Other people's emotional reactions to a third person's behaviour are potentially informative about what is appropriate within a given situation. We investigated whether and how observers' inferences of such injunctive norms are shaped by expressions of anger and disgust. Building on the moral emotions literature, we hypothesised that angry and disgusted expressions produce relative differences in the strength of autonomy-based versus purity-based norm inferences. We report three studies (plus three supplementary studies) using different types of stimuli (vignette-based, video clips) to investigate how emotional reactions shape norms about potential norm violations (eating snacks, drinking alcohol), and contexts (groups of friends, a university, a company). Consistent with our theoretical argument, the results indicate that observers use others' emotional reactions not only to infer whether a particular behaviour is inappropriate, but also why it is inappropriate: because it primarily violates autonomy standards (as suggested relatively more strongly by expressions of anger) or purity standards (as suggested relatively more strongly by expressions of disgust). We conclude that the social functionality of emotions in groups extends to shaping norms based on moral standards.

  19. Perspective-taking: decreasing stereotype expression, stereotype accessibility, and in-group favoritism.

    Science.gov (United States)

    Galinsky, A D; Moskowitz, G B

    2000-04-01

    Using 3 experiments, the authors explored the role of perspective-taking in debiasing social thought. In the 1st 2 experiments, perspective-taking was contrasted with stereotype suppression as a possible strategy for achieving stereotype control. In Experiment 1, perspective-taking decreased stereotypic biases on both a conscious and a nonconscious task. In Experiment 2, perspective-taking led to both decreased stereotyping and increased overlap between representations of the self and representations of the elderly, suggesting activation and application of the self-concept in judgments of the elderly. In Experiment 3, perspective-taking reduced evidence of in-group bias in the minimal group paradigm by increasing evaluations of the out-group. The role of self-other overlap in producing prosocial outcomes and the separation of the conscious, explicit effects from the nonconscious, implicit effects of perspective-taking are discussed.

  20. Layer 5 Callosal Parvalbumin-Expressing Neurons: A Distinct Functional Group of GABAergic Neurons.

    Science.gov (United States)

    Zurita, Hector; Feyen, Paul L C; Apicella, Alfonso Junior

    2018-01-01

    Previous studies have shown that parvalbumin-expressing neurons (CC-Parv neurons) connect the two hemispheres of motor and sensory areas via the corpus callosum, and are a functional part of the cortical circuit. Here we test the hypothesis that layer 5 CC-Parv neurons possess anatomical and molecular mechanisms which dampen excitability and modulate the gating of interhemispheric inhibition. In order to investigate this hypothesis we use viral tracing to determine the anatomical and electrophysiological properties of layer 5 CC-Parv and parvalbumin-expressing (Parv) neurons of the mouse auditory cortex (AC). Here we show that layer 5 CC-Parv neurons had larger dendritic fields characterized by longer dendrites that branched farther from the soma, whereas layer 5 Parv neurons had smaller dendritic fields characterized by shorter dendrites that branched nearer to the soma. The layer 5 CC-Parv neurons are characterized by delayed action potential (AP) responses to threshold currents, lower firing rates, and lower instantaneous frequencies compared to the layer 5 Parv neurons. Kv1.1 containing K + channels are the main source of the AP repolarization of the layer 5 CC-Parv and have a major role in determining both the spike delayed response, firing rate and instantaneous frequency of these neurons.

  1. Posttraumatic stress disorder and art group therapy: Self-expression of traumatic inner world of war veterans

    OpenAIRE

    Mandić-Gajić Gordana; Špirić Željko

    2016-01-01

    Background/Aim. Art therapy and drawings may serve as alternative means of expression and release from trauma among veterans diagnosed with posttraumatic stress disorder (PTSD). Methods. The retrospective clinical study of drawings of war veterans was performed. A total of 89 war veterans met the Diagnostics and Statistical Manual of Mental Disorders (DSM-IV) PTSD criteria and were consecutively admitted to the Day Hospital during 5 years. Art group therapy...

  2. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    International Nuclear Information System (INIS)

    Zhang, Xufang; Jiang, Hongwei; Gong, Qimei; Fan, Chen; Huang, Yihua; Ling, Junqi

    2014-01-01

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration

  3. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xufang, E-mail: xufang.zhang@student.qut.edu.au [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Jiang, Hongwei, E-mail: jianghw@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Gong, Qimei, E-mail: gongqmei@gmail.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Fan, Chen, E-mail: c3.fan@student.qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Huang, Yihua, E-mail: enu0701@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Ling, Junqi, E-mail: lingjq@mail.sysu.edu.cn [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China)

    2014-08-08

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  4. Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

    Science.gov (United States)

    Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

    2011-01-01

    Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

  5. Increased Fos expression among midbrain dopaminergic cell groups during birdsong tutoring.

    Science.gov (United States)

    Nordeen, E J; Holtzman, D A; Nordeen, K W

    2009-08-01

    During avian vocal learning, birds memorize conspecific song patterns and then use auditory feedback to match their vocal output to this acquired template. Some models of song learning posit that during tutoring, conspecific visual, social and/or auditory cues activate neuromodulatory systems that encourage acquisition of the tutor's song and attach incentive value to that specific acoustic pattern. This hypothesis predicts that stimuli experienced during social tutoring activate cell populations capable of signaling reward. Using immunocytochemistry for the protein product of the immediate early gene c-Fos, we found that brief exposure of juvenile male zebra finches to a live familiar male tutor increased the density of Fos+ cells within two brain regions implicated in reward processing: the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). This activation of Fos appears to involve both dopaminergic and non-dopaminergic VTA/SNc neurons. Intriguingly, a familiar tutor was more effective than a novel tutor in stimulating Fos expression within these regions. In the periaqueductal gray, a dopamine-enriched cell population that has been implicated in emotional processing, Fos labeling also was increased after tutoring, with a familiar tutor again being more effective than a novel conspecific. As several neural regions implicated in song acquisition receive strong dopaminergic projections from these midbrain nuclei, their activation in conjunction with hearing the tutor's song could help to establish sensory representations that later guide motor sequence learning.

  6. Cloning, expression, and analysis of the group 2 allergen from Dermatophagoides farinae from China

    Directory of Open Access Journals (Sweden)

    Cui Yu-bao

    2010-12-01

    Full Text Available To obtain the recombinant group 2 allergen product of Dermatophagoides farinae (Der f 2, the Der f 2 gene was synthesized by RT-PCR. The full-length cDNA comprised 441 nucleotides and was 99.3% identical to the reference sequence (GenBank AB195580. The cDNA was bound to vector pET28a to construct plasmid pET28a(+-Der f 2, which was transformed into E. coli BL21 and induced by IPTG. SDS-PAGE showed a specific band of about 14kDa in the hole cell lysate. s estiated by chroatography, about 3.86 g of the recobinant product as obtained, which conjugated with serum IgE from asthmatic children. The protein had a signal peptide of 17 amino acids. Its secondary structure comprised an alpha helix (19.86%, an extended strand (30.82%, and a random coil (49.32%. The subcellular localization of this allergen was predicted to be at mitochondria. Furthermore, its function was shown to be associated with an MD-2-related lipid-recognition (ML domain. The results of this study provide a solid foundation for large-scale production of the allergen for clinical diagnosis and treatent of allergic disorders.Com a finalidade de obter o produto recombinante do alergeno grupo 2 do Dermatophagoides farinae (Der f2, o gene Der f2 foi sintetizado por RT-PCR. O cDNA continha 441 nucleotídeos e era idêntico em 99,3% à sequência de referência (GenBank AB195580. O cDNA foi ligado ao vetor pET28a para construir o plasmídeo pET28a(+-Der f2, o qual foi introduzido por transformação em E. coli BL21 e induzido por IPTG. Em SDS-PAGE foi vista mia banda específica de 14 kDa no lisado celular. Conforme estimado por cromatografia, cerca de 3,86 mg do produto recombinante foi obtido, que reagia com IgE sérica de crianças asmáticas. A proteína continha um peptídeo sinal de 17 amino ácidos. Sua estrutura secundária consistia de uma alfa hélice (19,86%, uma fita estendida (30,82%, e uma sequência randômica (49,32%. A localização subcelular desse alergeno foi predita

  7. Mucosal Blood Group Antigen Expression Profiles and HIV Infections: A Study among Female Sex Workers in Kenya.

    Directory of Open Access Journals (Sweden)

    Nadia Musimbi Chanzu

    Full Text Available The ABO blood group antigens are carbohydrate moieties expressed on human red blood cells however; these antigens can also be expressed on some other cells particularly the surface of epithelial cells and may be found in mucosal secretions. In many human populations 80% secrete ABO antigens (termed 'secretors' while 20% do not (termed 'non-secretors'. Furthermore, there are disease conditions that are associated with secretor status.To investigate correlations between secretor status and HIV infection among female sex workers in Nairobi, Kenya.This cross-sectional study recruited 280 female sex workers aged 18-65 years from the Pumwani Majengo cohort, Kenya. Blood typing was determined by serological techniques using monoclonal antibodies to the ABO blood group antigens. Secretor phenotyping was determined using anti-H specific lectins specific to salivary, vaginal and cervical blood group H antigen using the agglutination inhibition technique and correlated to individual HIV sero-status. Participants were additionally screened for Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis.Out of the 280 participants, 212 (75.7% were secretors and 68 (24.3% were non-secretors. The incidence of all infections: HIV, Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis was higher among secretors compared to non-secretors. However, this difference was only statistically significant for HIV infection incidence rates: HIV infected secretors (83.7% versus HIV un-infected secretors (71.8% (p = 0.029 Based on ABO phenotype stratification, the incidence of HIV infection was higher among blood group A secretors (26/52 = 50%, in comparison to B (12/39 = 33.3%: p = 0.066, AB (3/9 = 33.3%: p = 0.355, and O secretors (36/112 = 32.1%: p = 0.028.This is the first report to document the variable expression of the ABH blood group antigens profiling secretor and non-secretor phenotypes in the female genital tract among a high-risk population

  8. [Expression of high mobility group box-1 in the lung tissue and serum of patients with pulmonary tuberculosis].

    Science.gov (United States)

    Yang, Xiao-min; Yang, Hua

    2013-07-01

    To explore the expression of high mobility group box-1 (HMGB1) in the lung tissue and serum of patients with pulmonary tuberculosis and to explore its relationship with tumor necrosis factor (TNF)-α and interleukin(IL)-1β. Sixty samples of lung tissues were obtained from patients with pulmonary tuberculosis who had underwent pneumonectomy in Department of Chest Surgery, First Affiliated Hospital of Zunyi Medical College from June 2010 to December 2011. At the same period, 40 normal lung samples were also obtained from patients with pulmonary contusion and lung cancer by surgical resections as the control group. The mRNA expressions of HMGB1 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of HMGB1 was measured by immunohistochemical staining of tissue microarrays in lung tissue. Blood samples were taken from 89 patients with active pulmonary tuberculosis (pulmonary tuberculosis group), including hematogenous disseminated pulmonary tuberculosis (type II) in 35 cases and secondary pulmonary tuberculosis (type III) in 54 cases, and 50 healthy volunteers (control group). Furthermore, the 54 patients with secondary pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (35 cases) vs those with lung cavity (19 cases), patients with involvement of pulmonary tuberculosis (69 ± 29) was significantly higher than that in normal lung tissue (22 ± 12) (t = 2.389, P pulmonary tuberculosis (786 ± 86) was significantly higher than that in normal lung tissue (202 ± 60) (t = 3.872, P pulmonary tuberculosis group were (5.0 ± 3.2) µg/L, (118 ± 77) ng/L and (33 ± 20) ng/L, respectively, which were significantly higher than those in the control group [(1.7 ± 1.0) µg/L, (40 ± 11) ng/L and (18 ± 12) ng/L, respectively], the respective t values being -0.928, 4.268 and 11.064, all P pulmonary tuberculosis, the serum concentration of HMGB

  9. A statistical method for predicting splice variants between two groups of samples using GeneChip® expression array data

    Directory of Open Access Journals (Sweden)

    Olson James M

    2006-04-01

    Full Text Available Abstract Background Alternative splicing of pre-messenger RNA results in RNA variants with combinations of selected exons. It is one of the essential biological functions and regulatory components in higher eukaryotic cells. Some of these variants are detectable with the Affymetrix GeneChip® that uses multiple oligonucleotide probes (i.e. probe set, since the target sequences for the multiple probes are adjacent within each gene. Hybridization intensity from a probe correlates with abundance of the corresponding transcript. Although the multiple-probe feature in the current GeneChip® was designed to assess expression values of individual genes, it also measures transcriptional abundance for a sub-region of a gene sequence. This additional capacity motivated us to develop a method to predict alternative splicing, taking advance of extensive repositories of GeneChip® gene expression array data. Results We developed a two-step approach to predict alternative splicing from GeneChip® data. First, we clustered the probes from a probe set into pseudo-exons based on similarity of probe intensities and physical adjacency. A pseudo-exon is defined as a sequence in the gene within which multiple probes have comparable probe intensity values. Second, for each pseudo-exon, we assessed the statistical significance of the difference in probe intensity between two groups of samples. Differentially expressed pseudo-exons are predicted to be alternatively spliced. We applied our method to empirical data generated from GeneChip® Hu6800 arrays, which include 7129 probe sets and twenty probes per probe set. The dataset consists of sixty-nine medulloblastoma (27 metastatic and 42 non-metastatic samples and four cerebellum samples as normal controls. We predicted that 577 genes would be alternatively spliced when we compared normal cerebellum samples to medulloblastomas, and predicted that thirteen genes would be alternatively spliced when we compared metastatic

  10. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment.

    Directory of Open Access Journals (Sweden)

    Bin Bao

    Full Text Available Hypoxia is known to play critical roles in cell survival, angiogenesis, tumor invasion, and metastasis. Hypoxia mediated over-expression of hypoxia-inducible factor (HIF has been shown to be associated with therapeutic resistance, and contributes to poor prognosis of cancer patients. Emerging evidence suggest that hypoxia and HIF pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT, maintenance of cancer stem cell (CSC functions, and also maintains the vicious cycle of inflammation-all which lead to therapeutic resistance. However, the precise molecular mechanism(s by which hypoxia/HIF drives these events are not fully understood. Here, we show, for the first time, that hypoxia leads to increased expression of VEGF, IL-6, and CSC signature genes Nanog, Oct4 and EZH2 consistent with increased cell migration/invasion and angiogenesis, and the formation of pancreatospheres, concomitant with increased expression of miR-21 and miR-210 in human pancreatic cancer (PC cells. The treatment of PC cells with CDF, a novel synthetic compound inhibited the production of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 and miR-210 under hypoxia. CDF also led to decreased cell migration/invasion, angiogenesis, and formation of pancreatospheres under hypoxia. Moreover, CDF decreased gene expression of miR-21, miR-210, IL-6, HIF-1α, VEGF, and CSC signatures in vivo in a mouse orthotopic model of human PC. Collectively, these results suggest that the anti-tumor activity of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become a novel, and effective anti-tumor agent for PC therapy.

  11. Heat shock and prolonged heat stress attenuate neurotoxin and sporulation gene expression in group I Clostridium botulinum strain ATCC 3502.

    Science.gov (United States)

    Selby, Katja; Mascher, Gerald; Somervuo, Panu; Lindström, Miia; Korkeala, Hannu

    2017-01-01

    Foodborne pathogenic bacteria are exposed to a number of environmental stresses during food processing, storage, and preparation, and in the human body. In order to improve the safety of food, the understanding of molecular stress response mechanisms foodborne pathogens employ is essential. Many response mechanisms that are activated during heat shock may cross-protect bacteria against other environmental stresses. To better understand the molecular mechanisms Clostridium botulinum, the causative agent of botulism, utilizes during acute heat stress and during adaptation to stressfully high temperature, the C. botulinum Group I strain ATCC 3502 was grown in continuous culture at 39°C and exposed to heat shock at 45°C, followed by prolonged heat stress at 45°C to allow adaptation of the culture to the high temperature. Growth in continuous culture was performed to exclude secondary growth phase effects or other environmental impacts on bacterial gene transcription. Changes in global gene expression profiles were studied using DNA microarray hybridization. During acute heat stress, Class I and III heat shock genes as well as members of the SOS regulon were activated. The neurotoxin gene botA and genes encoding the neurotoxin-associated proteins were suppressed throughout the study. Prolonged heat stress led to suppression of the sporulation machinery whereas genes related to chemotaxis and motility were activated. Induced expression of a large proportion of prophage genes was detected, suggesting an important role of acquired genes in the stress resistance of C. botulinum. Finally, changes in the expression of a large number of genes related to carbohydrate and amino acid metabolism indicated remodeling of the cellular metabolism.

  12. Cloning and characterization of murine fanconi anemia group A gene: Fanca protein is expressed in lymphoid tissues, testis, and ovary.

    Science.gov (United States)

    van de Vrugt, H J; Cheng, N C; de Vries, Y; Rooimans, M A; de Groot, J; Scheper, R J; Zhi, Y; Hoatlin, M E; Joenje, H; Arwert, F

    2000-04-01

    Fanconi anemia (FA) is an autosomal recessive disorder in humans characterized by bone marrow failure, cancer predisposition, and cellular hypersensitivity to cross-linking agents such as mitomycin C and diepoxybutane. FA genes display a caretaker function essential for maintenance of genomic integrity. We have cloned the murine homolog of FANCA, the gene mutated in the major FA complementation group (FA-A). The full-length mouse Fanca cDNA consists of 4503 bp and encodes a protein with a predicted molecular weight of 161 kDa. The deduced Fanca mouse protein shares 81% amino acid sequence similarity and 66% identity with the human protein. The nuclear localization signal and partial leucine zipper consensus motifs found in the human FANCA protein were also present in the murine homolog. In spite of the species difference, the murine Fanca cDNA was capable of correcting the cross-linker sensitive phenotype of human FA-A cells, suggesting functional conservation. Based on Northern as well as Western blots, Fanca was mainly expressed in lymphoid tissues, testis, and ovary. This expression pattern correlates with some of the clinical symptoms observed in FA patients. The availability of the murine Fanca cDNA now allows the gene to be studied in experimental mouse models.

  13. EXPRESS

    International Nuclear Information System (INIS)

    Ancelin, C.; Le, P.; DeSaint-Quentin, S.; Villatte, N.

    1987-01-01

    This paper presents EXPRESS, an expert system developed for the automation of reliability studies. The first part consists in the description of the method for static thermohydraulic systems. In this step, the authors define the knowledge representation based on the two inference engines - ALOUETTE and LCR developed by EDF. They explain all the process to construct a fault tree from a topological and functional description of the system. Numerous examples are exhibited in illustration of the method. This is followed by the lessons derived from the studies performed on some safety systems of the PALUEL nuclear plant. The development of the same approach for electric power systems is described, insisting on the difference resulting from the sequential nature of these systems. Finally, they show the main advantages identified during the studies

  14. Prevalence of Enhancer of Zeste Homolog 2 in Patients with Resected Small Cell Lung Cancer.

    Science.gov (United States)

    Toyokawa, Gouji; Takada, Kazuki; Tagawa, Tetsuzo; Kinoshita, Fumihiko; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Takamori, Shinkichi; Akamine, Takaki; Hirai, Fumihiko; Yamada, Yuichi; Hamamoto, Ryuji; Oda, Yoshinao; Maehara, Yoshihiko

    2018-06-01

    Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. AB0 blood groups and rhesus factor expression as prognostic parameters in patients with epithelial ovarian cancer - a retrospective multi-centre study.

    Science.gov (United States)

    Seebacher, Veronika; Polterauer, Stephan; Reinthaller, Alexander; Koelbl, Heinz; Achleitner, Regina; Berger, Astrid; Concin, Nicole

    2018-04-19

    AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC). AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC. Their association with patients' survival was assessed using univariate and multivariable analyses. Neither AB0 blood groups nor Rhesus factor expression were associated with clinico-pathological parameters, recurrence-free, cancer-specific, or overall survival. In a subgroup of patients with high-grade serous adenocarcinoma, however, blood groups B and AB were associated with a better 5-year cancer-specific survival rate compared to blood groups A and 0 (60.3 ± 8.6% vs. 43.8 ± 3.6%, p = 0.04). Yet, this was not significant in multivariable analysis. AB0 blood groups and Rhesus factor expression are both neither associated with features of biologically aggressive disease nor clinical outcome in patients with EOC. Further investigation of the role of the blood group B antigen on cancer-specific survival in the subgroup of high-grade serous should be considered.

  16. Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

    International Nuclear Information System (INIS)

    Hwang, Chung-Feng; Huang, Hsuan-Ying; Chen, Chang-Han; Chien, Chih-Yen; Hsu, Yao-Chung; Li, Chien-Feng

    2012-01-01

    Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription–polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

  17. The effect of ω-fatty acids on the expression of phospholipase A2 group 2A in human gastric cancer patients.

    Science.gov (United States)

    Shariati, Mahboube; Aghaei, Mahmoud; Movahedian, Ahmad; Somi, Mohammad Hosein; Dolatkhah, Homayun; Aghazade, Ahmad Mirza

    2016-01-01

    Studies show that polyunsaturated fatty acids (PUFAs) may have an inhibitory role in carcinogenesis. It was previously shown that PLA2 group 2A (PLA2G2A) messenger RNA (mRNA) expression is associated with less frequent metastasis and longer survival in gastric adenocarcinoma. This study intends to investigate the effect of PUFAs on the expression of PLA2G2A in patients with gastric cancer. Thirty-four patients with gastric cancer (GC) were randomly divided into two groups. The first group received cisplatin medication. The second group received cisplatin medication and supplements of ω-fatty acids for three courses. The total RNA was extracted from the tissues and cDNA was synthesized. The gene expression of PLA2G2A was evaluated by the real-time polymerase chain reaction (PCR) method. To confirm the changes in gene expression, frozen section was utilized. The frozen tissue samples were sectioned and stained using the immunohistochemistry technique. After chemotherapy and chemotherapy plus supplement, the relative mean of PLA2G2A gene expression increased 1.5 ± 0.5-fold and 7.4 ± 2.6-fold, respectively ( P = 0.006). The relative mean of gene expression in patients who received cisplatin and ω-fatty acids supplement increased more significantly (7.5 ± 3.3-fold) than in patients who received only cisplatin ( P = 0.016). It was found that PUFAs increased the gene and protein expression of PLA2G2A in gastric cancer. Concerning the fact that studies reveal protective function of PLA2G2A in gastric cancer, it is suggested that increased expression of PLA2G2A is helpful. Furthermore, PUFAs can be considered as a useful therapeutic supplement for patients with gastric cancer.

  18. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

    International Nuclear Information System (INIS)

    Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K.; Kim, Grace E.; Lin, Lawrence; Giacomini, Kathy; Naranjo, Arlene; Van Ryn, Collin; Yanik, Gregory A.; Kreissman, Susan G.; Hogarty, Michael; DuBois, Steven G.

    2016-01-01

    Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

  19. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

    Energy Technology Data Exchange (ETDEWEB)

    Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); Kim, Grace E. [UCSF School of Medicine, Department of Pathology, San Francisco, CA (United States); Lin, Lawrence; Giacomini, Kathy [UCSF School of Pharmacy, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA (United States); Naranjo, Arlene; Van Ryn, Collin [University of Florida, Children' s Oncology Group Statistics and Data Center, Gainesville, FL (United States); Yanik, Gregory A. [University of Michigan, CS Mott Children' s Hospital, Ann Arbor, MI (United States); Kreissman, Susan G. [Duke University Medical Center, Durham, NC (United States); Hogarty, Michael [University of Pennsylvania, Children' s Hospital of Philadelphia and Perelman School of Medicine, Philadelphia, PA (United States); DuBois, Steven G. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); UCSF School of Medicine, San Francisco, CA (United States)

    2016-03-15

    Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

  20. Interplay between H1 and HMGN epigenetically regulates OLIG1&2 expression and oligodendrocyte differentiation.

    Science.gov (United States)

    Deng, Tao; Postnikov, Yuri; Zhang, Shaofei; Garrett, Lillian; Becker, Lore; Rácz, Ildikó; Hölter, Sabine M; Wurst, Wolfgang; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabe; Bustin, Michael

    2017-04-07

    An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination. Loss of HMGNs increases the chromatin binding of histone H1, thereby recruiting the histone methyltransferase EZH2 and elevating H3K27me3 levels, thus conferring a repressive epigenetic signature at Olig1&2 sites. Embryonic stem cells lacking HMGNs show reduced ability to differentiate towards the oligodendrocyte lineage, and mice lacking HMGNs show reduced oligodendrocyte count and decreased spinal cord myelination, and display related neurological phenotypes. Thus, the presence of HMGN proteins is required for proper expression of neural differentiation genes during embryonic stem cell differentiation. Specifically, we demonstrate that the dynamic interplay between HMGNs and H1 in chromatin epigenetically regulates the expression of OLIG1&2, thereby affecting oligodendrocyte development and myelination, and mouse behavior. Published by Oxford University Press on behalf of Nucleic Acids Research 2016.

  1. Quit Now! A Psychoeducational Expressive Therapy Group Work Approach for At-Risk and Delinquent Adolescent Smokers in Singapore

    Science.gov (United States)

    Kit, Phey Ling; Teo, Lan

    2012-01-01

    In this article, we review the risk and protective factors for adolescent smoking, as well as current research on evidence-based practices. The relevance of structured expressive therapy in meeting the maturational and emotional needs of at-risk and delinquent adolescents, and the multicultural context of adolescents in Singapore's Asian society…

  2. Deconstructing therapeutic mechanisms in cancer support groups: do we express more emotion when we tell stories or talk directly to each other?

    Science.gov (United States)

    Tamagawa, Rie; Li, Yong; Gravity, Theo; Piemme, Karen Altree; DiMiceli, Sue; Collie, Kate; Giese-Davis, Janine

    2015-02-01

    Studies indicate that story-telling and emotional expression may be important therapeutic mechanisms. This study examined how they work together over 1 year of supportive-expressive group therapy (SET). Participants were 41 women randomized to SET. We coded emotional expression and story types (story vs. non-story) at the initial session, 4, 8, and 12 months. Women engaged in more storytelling in their initial than later sessions. In later sessions, women expressed significantly more emotion, specifically compassion and high-arousal positive affect. Direct communication (non-story) allowed more positive but also more defensive expression as women supported and challenged each other. Greater hostility in non-story and greater constrained anger during story were associated with increasing depression. Greater high-arousal positive affect in non-story and greater primary negative affect in story were associated with increasing social network size. These results inform clinicians about cues they might use to improve the effectiveness of cancer support groups.

  3. Average correlation clustering algorithm (ACCA) for grouping of co-regulated genes with similar pattern of variation in their expression values.

    Science.gov (United States)

    Bhattacharya, Anindya; De, Rajat K

    2010-08-01

    Distance based clustering algorithms can group genes that show similar expression values under multiple experimental conditions. They are unable to identify a group of genes that have similar pattern of variation in their expression values. Previously we developed an algorithm called divisive correlation clustering algorithm (DCCA) to tackle this situation, which is based on the concept of correlation clustering. But this algorithm may also fail for certain cases. In order to overcome these situations, we propose a new clustering algorithm, called average correlation clustering algorithm (ACCA), which is able to produce better clustering solution than that produced by some others. ACCA is able to find groups of genes having more common transcription factors and similar pattern of variation in their expression values. Moreover, ACCA is more efficient than DCCA with respect to the time of execution. Like DCCA, we use the concept of correlation clustering concept introduced by Bansal et al. ACCA uses the correlation matrix in such a way that all genes in a cluster have the highest average correlation values with the genes in that cluster. We have applied ACCA and some well-known conventional methods including DCCA to two artificial and nine gene expression datasets, and compared the performance of the algorithms. The clustering results of ACCA are found to be more significantly relevant to the biological annotations than those of the other methods. Analysis of the results show the superiority of ACCA over some others in determining a group of genes having more common transcription factors and with similar pattern of variation in their expression profiles. Availability of the software: The software has been developed using C and Visual Basic languages, and can be executed on the Microsoft Windows platforms. The software may be downloaded as a zip file from http://www.isical.ac.in/~rajat. Then it needs to be installed. Two word files (included in the zip file) need to

  4. Optimatization of transient transformation methods to study gene expression in Musa acuminata (AAA group) cultivar Ambon Lumut

    Science.gov (United States)

    Prayuni, Kinasih; Dwivany, Fenny M.

    2015-09-01

    Banana is classified as a climateric fruit, whose ripening is regulated by ethylene. Ethylene is synthesized from ACC (1-aminocyclopropane-1-carboxylic acid) by ACC oxidase enzyme which is encoded by ACO gene. Controling an important gene expression in ethylene biosynthesis pathway has became a target to delay the ripening process. Therefore in the previous study we have designed a MaACO-RNAi construct to control MaACO gene expression. In this research, we study the effectiveness of different transient transformation methods to deliver the construct. Direct injection, with or no vaccum infiltration methods were used to deliver MaACO-RNAi construct. All of the methods succesfully deliver the construct into banana fruits based on RT-PCR result.

  5. Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10

    International Nuclear Information System (INIS)

    Khor, L.-Y.; De Silvio, Michelle; Li, Rile; McDonnell, Timothy J.; Hammond, M. Elizabeth H.; Sause, William T.; Pilepich, Miljenko V.; Okunieff, Paul; Sandler, Howard M.; Pollack, Alan

    2006-01-01

    Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium. Results: The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions: Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer

  6. Expression of blood group I and i active carbohydrate sequences on cultured human and animal cell lines assessed by radioimmunoassays with monoclonal cold agglutinins

    International Nuclear Information System (INIS)

    Childs, R.A.; Kapadia, A.; Feizi, T.

    1980-01-01

    Human monoclonal anti-I and anti-i, reactive with known carbohydrate sequences, have been used as reagents to quantitate (by radioimmunoassay) and visualize (by immunofluorescence) the expression of the various blood group I and i antigenic determinants in a variety of cultured cell lines commonly used in laboratory investigations. It has been shown that the antigens they recognize are widely distributed on the surface of human and animal cell lines, expressed in varying amounts in different cell lines and on individual cells within a given cell line. In two cell lines, a transformation-associated increase in the expression of I antigen was observed. Because of their precise specificity for defined carbohydrate chain domains, these autoantibodies have become valuable reagents in biological chemistry. (orig.) [de

  7. Habilidades expressivas de um grupo de alunos com paralisia cerebral na atividade de jogo Expressive abilities of a group of students with cerebral palsy during game activities

    Directory of Open Access Journals (Sweden)

    Fabiana Sayuri Sameshima

    2009-01-01

    Full Text Available OBJETIVO: Analisar as habilidades expressivas de um grupo de alunos com paralisia cerebral sem oralidade durante atividades de jogos. MÉTODOS: Participaram deste estudo três alunos com paralisia cerebral, do sexo masculino, com idades entre 13 e 16 anos, com severos distúrbios na comunicação oral, sem déficits visual, auditivo e cognitivo. Os alunos frequentavam classe especial e eram usuários de recursos de comunicação alternativa. Foi filmada a interação do grupo de alunos durante a realização de seis jogos adaptados. A partir das transcrições das fitas, foi possível definir oito categorias referentes às habilidades expressivas do grupo. RESULTADOS: Os resultados demonstraram que o grupo de alunos utilizou as expressões: verbal sem ajuda/vocal; verbal com ajuda/não-vocal; não-verbal/vocal; não-verbal/não-vocal; não-verbal/não-vocal + não-verbal/vocal; verbal sem ajuda/vocal + não-verbal/vocal; não-verbal/vocal + verbal com ajuda/não-vocal e não-verbal/não-vocal + verbal com ajuda/não-vocal para se comunicar, sendo que as categorias mais utilizadas foram não-verbal/não-vocal; verbal com ajuda/não-vocal e não-verbal/não-vocal + não-verbal/vocal. CONCLUSÕES: Os jogos propiciaram ao grupo de alunos com paralisia cerebral sem oralidade o uso das diferentes habilidades expressivas, como, por exemplo, uso de gestos representativos, expressões corporais e faciais, vocalizações, fala articulada, uso de pastas e pranchas de comunicação suplementar e alternativa, assim como as combinações destas habilidades. Os gestos representativos e as expressões corporais e faciais foram as habilidades mais utilizadas pelo grupo de alunos com paralisia cerebral sem oralidade, razão pela qual os profissionais devem estar atentos a estas possibilidades expressivas.PURPOSE: To analyze the expressive abilities of a group of nonspeaking students with cerebral palsy during game activities. METHODS: Three male students with

  8. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

    Science.gov (United States)

    Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

    2017-02-14

    Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Isthmin is a novel secreted protein expressed as part of the Fgf-8 synexpression group in the Xenopus midbrain-hindbrain organizer.

    Science.gov (United States)

    Pera, Edgar M; Kim, James I; Martinez, Sarah L; Brechner, Mariel; Li, Su Yu; Wessely, Oliver; De Robertis, E M

    2002-08-01

    Patterning of the central nervous system is regulated by a signaling center located at the midbrain-hindbrain boundary (MHB), or isthmus organizer. Fibroblast growth factors secreted from the MHB are required and sufficient to direct the ordered growth and regionalization of the midbrain and anterior hindbrain. In an unbiased secretion cloning screen of Xenopus gastrula embryos we identified a novel gene, which we designated as Isthmin (xIsm) due to its prominent expression at the MHB. xIsm encodes a secreted protein of 449 amino acids containing one copy of the thrombospondin type 1 repeat (TSR). We also found orthologous Isthmin genes in human (hIsm) and mouse (mIsm), as well as a gene encoding an Isthmin-like human unknown protein (hIsm-l). The conservation of a unique carboxy-terminal region between hIsm and hIsm-l suggests that Isthmin is the founding member of a new family of secreted proteins. xIsm was strongly expressed maternally in the Xenopus egg and showed zygotic expression in the ventral blastopore lip, notochord, and MHB. Additional expression domains were detected in neural crest, ear vesicle, and developing blood islands. Interestingly, xIsm was co-expressed with Fibroblast growth factor-8 (xFgf-8) at multiple sites including the MHB, indicating that these two genes are part of a synexpression group which also includes sprouty and sef homologs.

  10. DOC-2/DAB2 Interacting Protein Status in High-Risk Prostate Cancer Correlates With Outcome for Patients Treated With Radiation Therapy

    International Nuclear Information System (INIS)

    Jacobs, Corbin; Tumati, Vasu; Kapur, Payal; Yan, Jingsheng; Hong, David; Bhuiyan, Manzerul; Xie, Xian-Jin; Pistenmaa, David; Yu, Lan; Hsieh, Jer-Tsong; Saha, Debabrata; Kim, D. W. Nathan

    2014-01-01

    Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Methods and Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance–free survival (CRFS), and distant metastasis–free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Results: Fifty-four patients with high-risk prostate cancer (stage ≥T3a, or Gleason score ≥8, or prostate-specific antigen level ≥20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Conclusion: Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for

  11. DOC-2/DAB2 Interacting Protein Status in High-Risk Prostate Cancer Correlates With Outcome for Patients Treated With Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Corbin; Tumati, Vasu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Kapur, Payal [Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Yan, Jingsheng [Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hong, David; Bhuiyan, Manzerul [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Xie, Xian-Jin [Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Pistenmaa, David [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States); Yu, Lan [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong [Simmons Cancer Center, Dallas, Texas (United States); Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Saha, Debabrata [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States); Kim, D. W. Nathan, E-mail: Nathan.Kim@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States)

    2014-07-15

    Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Methods and Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance–free survival (CRFS), and distant metastasis–free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Results: Fifty-four patients with high-risk prostate cancer (stage ≥T3a, or Gleason score ≥8, or prostate-specific antigen level ≥20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Conclusion: Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for

  12. Enhancer of zeste homologue 2 plays an important role in neuroblastoma cell survival independent of its histone methyltransferase activity.

    Science.gov (United States)

    Bate-Eya, Laurel T; Gierman, Hinco J; Ebus, Marli E; Koster, Jan; Caron, Huib N; Versteeg, Rogier; Dolman, M Emmy M; Molenaar, Jan J

    2017-04-01

    Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer. High EZH2 expression correlated with poor prognosis and overall survival independent of MYCN amplification status. Unexpectedly, treatment of 3 EZH2-high expressing neuroblastoma cell lines (IMR32, CHP134 and NMB), with EZH2-specific inhibitors (GSK126 and EPZ6438) resulted in only a slight G1 arrest, despite maximum histone methyltransferase activity inhibition. Furthermore, colony formation in cell lines treated with the inhibitors was reduced only at concentrations much higher than necessary for complete inhibition of EZH2 histone methyltransferase activity. Knockdown of the complete protein with three independent shRNAs resulted in a strong apoptotic response and decreased cyclin D1 levels. This apoptotic response could be rescued by overexpressing EZH2ΔSET, a truncated form of wild-type EZH2 lacking the SET transactivation domain necessary for histone methyltransferase activity. Our findings suggest that high EZH2 expression, at least in neuroblastoma, has a survival function independent of its methyltransferase activity. This important finding highlights the need for studies on EZH2 beyond its methyltransferase function and the requirement for compounds that will target EZH2 as a complete protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Molecular cloning and expression of five glutathione S-transferase (GST) genes from Banana (Musa acuminata L. AAA group, cv. Cavendish).

    Science.gov (United States)

    Wang, Zhuo; Huang, Suzhen; Jia, Caihong; Liu, Juhua; Zhang, Jianbin; Xu, Biyu; Jin, Zhiqiang

    2013-09-01

    Three tau class MaGSTs responded to abiotic stress, MaGSTF1 and MaGSTL1 responded to signaling molecules, they may play an important role in the growth of banana plantlet. Glutathione S-transferases (GST) are multifunctional detoxification enzymes that participate in a variety of cellular processes, including stress responses. In this study, we report the molecular characteristics of five GST genes (MaGSTU1, MaGSTU2, MaGSTU3, MaGSTF1 and MaGSTL1) cloned from banana (Musa acuminate L. AAA group, cv. Cavendish) using a RACE-PCR-based strategy. The predicted molecular masses of these GSTs range from 23.4 to 27.7 kDa and their pIs are acidic. At the amino acid level, they share high sequence similarity with GSTs in the banana DH-Pahang (AA group) genome. Phylogenetic analysis showed that the deduced amino acid sequences of MaGSTs also have high similarity to GSTs of other plant species. Expression analysis by semi-quantitative RT-PCR revealed that these genes are differentially expressed in various tissues. In addition, their expression is regulated by various stress conditions, including exposure to signaling molecules, cold, salinity, drought and Fusarium oxysporum f specialis(f. Sp) cubense Tropical Race 4 (Foc TR4) infection. The expression of the tau class MaGSTs (MaGSTU1, MaGSTU2 and MaGSTU3) mainly responded to cold, salinity and drought while MaGSTF1 and MaGSTL1 expressions were upregulated by signaling molecules. Our findings suggest that MaGSTs play a key role in both development and abiotic stress responses.

  14. Xeroderma pigmentosum, complementation group D expression in H1299 lung cancer cells following benzo[a]pyrene exposure as well as in head and neck cancer patients.

    Science.gov (United States)

    Lin, Chang-Shen; Chiou, Wen-Yen; Lee, Ka-Wo; Chen, Tzu-Fen; Lin, Yuan-Jen; Huang, Jau-Ling

    2016-01-01

    DNA repair genes play critical roles in response to carcinogen-induced and anticancer therapy-induced DNA damage. Benzo[a]pyrene (BaP), the most carcinogenic polycyclic aromatic hydrocarbon (PAH), is classified as a group 1 carcinogen by International Agency for Research on Cancer. The aims of this study were to (1) evaluate the effects of BaP on DNA repair activity and expression of DNA repair genes in vitro and (2) examine the role of xeroderma pigmentosum, complementation group D (XPD) mRNA expression in human head and neck cancers. Host cell reactivation assay showed that BaP inhibited nucleotide excision repair in H1299 lung cancer cells. DNA repair through the non-homologous end-joining pathway was not affected by BaP. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot demonstrated that XPD was downregulated by BaP treatment. BaP exposure did not apparently affect expression of another 11 DNA repair genes. BaP treatment increased the DNA damage marker γ-H2AX and ultraviolet (UV) sensitivity, supporting an impairment of DNA repair in BaP-treated cells. XPD expression was also examined by quantitative RT-PCR in 68 head and neck cancers, and a lower XPD mRNA level was found in smokers' cancer specimens. Importantly, reduced XPD expression was correlated with patient 5-year overall survival rate (35 vs. 56%) and was an independent prognostic factor (hazard ratio: 2.27). Data demonstrated that XPD downregulation was correlated with BaP exposure and human head and neck cancer survival.

  15. Identification and expression analysis of four 14-3-3 genes during fruit ripening in banana (Musa acuminata L. AAA group, cv. Brazilian).

    Science.gov (United States)

    Li, Mei-Ying; Xu, Bi-Yu; Liu, Ju-Hua; Yang, Xiao-Liang; Zhang, Jian-Bin; Jia, Cai-Hong; Ren, Li-Cheng; Jin, Zhi-Qiang

    2012-02-01

    To investigate the regulation of 14-3-3 proteins in banana (Musa acuminata L. AAA group, cv. Brazilian) fruit postharvest ripening, four cDNAs encoding 14-3-3 proteins were isolated from banana and designated as Ma-14-3-3a, Ma-14-3-3c, Ma-14-3-3e, and Ma-14-3-3i, respectively. Amino acid sequence alignment showed that the four 14-3-3 proteins shared a highly conserved core structure and variable C-terminal as well as N-terminal regions with 14-3-3 proteins from other plant species. Phylogenetic analysis revealed that the four 14-3-3 genes belong to the non-ε groups. They were differentially and specifically expressed in various tissues. Real-time RT-PCR analysis indicated that these four genes function differentially during banana fruit postharvest ripening. Three genes, Ma-14-3-3a, Ma-14-3-3c, and Ma-14-3-3e, were significantly induced by exogenous ethylene treatment. However, gene function differed in naturally ripened fruits. Ethylene could induce Ma-14-3-3c expression during postharvest ripening, but expression patterns of Ma-14-3-3a and Ma-14-3-3e suggest that these two genes appear to be involved in regulating ethylene biosynthesis during fruit ripening. No obvious relationship emerged between Ma-14-3-3i expression in naturally ripened and 1-MCP (1-methylcyclopropene)-treated fruit groups during fruit ripening. These results indicate that the 14-3-3 proteins might be involved in various regulatory processes of banana fruit ripening. Further studies will mainly focus on revealing the detailed biological mechanisms of these four 14-3-3 genes in regulating banana fruit postharvest ripening.

  16. Counterbalancing patient demands with evidence: results from a pan-Canadian randomized clinical trial of brief supportive-expressive group psychotherapy for women with systemic lupus erythematosus.

    Science.gov (United States)

    Dobkin, Patricia L; Da Costa, Deborah; Joseph, Lawrence; Fortin, Paul R; Edworthy, Steven; Barr, Susan; Ensworth, Stephanie; Esdaile, John M; Beaulieu, André; Zummer, Michel; Senécal, Jean-Luc; Goulet, Jean-Richard; Choquette, Denis; Rich, Eric; Smith, Doug; Cividino, Alfred; Gladman, Dafna; St-Pierre, Yvan; Clarke, Ann E

    2002-01-01

    To evaluate the effect of Brief Supportive-Expressive Group Psychotherapy as an adjunct to standard medical care in reducing psychological distress, medical symptoms, and health care costs and improving quality of life in women with systemic lupus erythematosus (SLE). A randomized clinical trial was conducted with 133 SLE female patients from 9 clinics across Canada. Clinical and psychosocial measures were taken at baseline, posttreatment, and 6 and 12 months posttreatment. Outcomes assessed were psychological distress, quality of life, disease activity, health service utilization, and diminished productivity. Intention-to-treat analyses revealed that there were no clinically important group differences on any of the outcome measures. Although both groups improved over time on several measures (e.g., decreases in psychological distress, stress, and emotion-oriented coping), these changes could not be attributed to the psychotherapeutic intervention. Thus, evidence does not support the referral of these patients to this type of intervention.

  17. Extracellular Hsp90 as a Novel Epigenetic of EMT and Metastatic Risk in Prostate Cancer

    Science.gov (United States)

    2015-12-01

    effects of eHsp90. As expected, treatment with NPGA or UO126 restored E-cadherin expression in tan - dem with diminished P-ERK and EZH2 (Fig. 1D...co-occupy a cohort of EZH2 target sites and function as a repressive cofac- tor (43, 44). Therefore, additional studies are warranted to fur - ther

  18. The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus.

    Science.gov (United States)

    Danger, Jessica L; Makthal, Nishanth; Kumaraswami, Muthiah; Sumby, Paul

    2015-12-01

    The group A Streptococcus (GAS; Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the prtF1 and prtF2 mRNAs within their 5' untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the prtF1 and prtF2 mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection. More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small

  19. Association and Expression of Virulence from Plasmids of the Group B Strain in Pseudomonas syringae pv. eriobotryae

    Directory of Open Access Journals (Sweden)

    Tran Dang Khanh

    2018-04-01

    Full Text Available Pseudomonas syringae pv. eriobotryae causes serious stem canker in loquat (Eriobotrya japonica trees. This study was conducted to determine whether plasmids are involved with its virulence. The strain NAE89, which belonged to the B group, harbored two plasmids at approximately 6.2 and 50 Mdal that caused stem canker and halo leaf spots on loquat plants. Following digestion with BamHI and ligation into the BamHI cloning site of the broad range host cosmid pLAFR3, four DNA fragments at 3.8, 6.6, 12.3, and 22.8 kb were generated. Although the plasmid-encoded virulence gene psvA was undigested with the BamHI, the halo leaf spot gene may be adjacent to the psvA gene was digested. A pLAFR3 cosmid clone was introduced into the non-pathogenic PE0 and NAE89-1 strains by triparental matings and the pathogenicity was recovered. As a result, the pLAFR3 cosmid clone was introduced into the largest size DNA fragment of 22.8 kb and determined to be the causal agent of canker on the stem of the loquat. This study revealed that the psvA gene, previously found in the 50 Mdal plasmid, was also observed in the 22.8 kb DNA fragment.

  20. High expression of high-mobility group box 1 in the blood and lungs is associated with the development of chronic obstructive pulmonary disease in smokers.

    Science.gov (United States)

    Ko, Hsin-Kuo; Hsu, Wen-Hu; Hsieh, Chih-Cheng; Lien, Te-Cheng; Lee, Tzong-Shyuan; Kou, Yu Ru

    2014-02-01

    High-mobility group box 1 (HMGB1) is an important mediator in multiple pathological conditions, but the expression of HMGB1 in chronic obstructive pulmonary disease (COPD) has not yet been completely investigated. We aimed to analyze the relationship between HMGB1 expression in blood and lung tissue and the development of COPD. Twenty-eight patients admitted for single pulmonary surgical intervention were enrolled. The expression of HMGB1 in blood and lung tissue was evaluated by enzyme-linked immunosorbent assay analysis and immunohistochemistry stain, respectively. The study patients were divided into smokers with COPD (n = 11), smokers without COPD (n = 8) and non-smoker healthy controls (n = 9). Smokers with COPD compared with smokers without COPD and healthy controls were older in age, with lower post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) ratio (63.1 ± 5.5 vs 77.6 ± 3.6 and 84.5 ± 5.8, P vs 7.3 ± 4.8 and 17.0 ± 19.6 ng/mL, P = 0.016 and P = 0.021, respectively). In smokers with COPD, the numbers and portion of HMGB1-expressing cells in epithelium and submucosal areas were significantly increased. Notably, plasma HMGB1 levels negatively correlated with post-bronchodilator FEV1 /FVC ratio (r = -0.585, P = 0.008) in smokers, but not in non-smokers. In smokers, high expression of HMGB1 in the blood and lungs is related to the lung function impairment and appears to be associated with the development of COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  1. Targeting the Enhancer of Zeste Homologue 2 in Medulloblastoma

    Science.gov (United States)

    Alimova, Irina; Venkataraman, Sujatha; Harris, Peter; Marquez, Victor E.; Northcott, Paul A; Dubuc, Adrian; Taylor, Michael D; Foreman, Nicholas K; Vibhakar, Rajeev

    2012-01-01

    Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 that catalyzes the trimethylation of histone H3 on Lys 27, and represses gene transcription. EZH2 enhances cancer-cell proliferation and regulates stem cell maintenance and differentiation. Here, we demonstrate that EZH2 is highly expressed in medulloblastoma, a highly malignant brain tumor of childhood, and this altered expression is correlated with genomic gain of chromosome 7 in a subset of medulloblastoma. Inhibition of EZH2 by RNAi suppresses medulloblastoma tumor cell growth. We show that 3-deazaneplanocin A, a chemical inhibitor of EZH2, can suppress medulloblastoma cell growth partially by inducing apoptosis. Suppression of EZH2 expression diminishes the ability of tumor cells to form spheres in culture and strongly represses the ability of known oncogenes to transform neural stem cells. These findings establish a role of EZH2 in medulloblastoma and identify EZH2 as a potential therapeutic target especially in high-risk tumors. PMID:22287205

  2. Effects of supportive-expressive discussion groups on loneliness, hope and quality of life in breast cancer survivors: a randomized control trial.

    Science.gov (United States)

    Tabrizi, Fatemeh Moghaddam; Radfar, Moloud; Taei, Zeynab

    2016-09-01

    Evaluation of the effect of supportive expressive discussion groups on loneliness, hope and quality of life in breast cancer survivors. A randomized control trial including breast cancer patients who had completed chemotherapy and randomly allocated into two groups: intervention (n = 41) and control (n = 40). The intervention consisted of twelve weekly 90-min sessions for groups of six to eight breast cancer survivors. Data were obtained pre-to -post the intervention and at 8-week follow-up. The data were analyzed using a repeated-measures analysis of variance (ANOVA). The findings revealed a significant reduction in loneliness scores (F = 69.85, p hope (F = 20.8, p life from pre- to post-intervention, and then over the 8-week follow-up period in the intervention group, while scores of control participants did not show this pattern during the study. The strongest effects were found for global quality of life (effect size) = 0.59), for future perspectives (effect size = 0.51), emotional functioning (effect size = 0.35) and social functioning (effect size = 0.31). The intervention was effective on loneliness, hope and quality of life in the intervention group. The intervention needs further evaluation in a larger study and with other cancer types. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. The binding activity of Mel-18 at the Il17a promoter is regulated by the integrated signals of the TCR and polarizing cytokines.

    Science.gov (United States)

    Hod-Dvorai, Reut; Jacob, Eyal; Boyko, Yulia; Avni, Orly

    2011-08-01

    We have previously shown that in differentiated T-helper (Th)1 and Th2 cells, polycomb group (PcG) proteins are associated differentially with the promoters of the signature cytokine genes. The correlation of the binding activity of PcG proteins with gene expression is unusual, since they are well known as epigenetic regulators that maintain transcriptional silencing. Here we show that in Th17 cells, the more phenotypically flexible Th lineage, the PcG proteins Mel-18 and less strikingly Ezh2 are associated differentially with the Il17a promoter. Using the RNAi approach, we found that Mel-18 and Ezh2 positively regulate the expression of Il17a and Il17f. The inducible binding of Mel-18 and Ezh2 at the Il17a promoter was dependent on signaling pathways downstream of the TCR. However, a continuous presence of TGF-β, the cytokine that is necessary to maintain Il17a expression, was required to preserve the binding activity of Mel-18, but not of Ezh2, following restimulation. The binding of Mel-18 at the Il17a promoter was correlated with the recruitment of the lineage-specifying transcription factor RORγt. Altogether, our results suggest that in Th17 cells the TCR and polarizing cytokines synergize to modulate the binding activity of Mel-18 at the Il17a promoter, and consequently to facilitate Il17a expression. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth

    DEFF Research Database (Denmark)

    Jiang, Ning; Ke, Binghu; Hjort-Jensen, Kim

    2017-01-01

    Castration resistant prostate cancer (CRPC) is a stage of relapse that arises after various forms of androgen ablation therapy (ADT) and causes significant morbidity and mortality. However, the mechanism underlying progression to CRPC remains poorly understood. Here, we report that YAP1, which...... is negatively regulated by AR, influences prostate cancer (PCa) cell self-renewal and CRPC development. Specifically, we found that AR directly regulates the methylation of YAP1 gene promoter via the formation of a complex with Polycomb group protein EZH2 and DNMT3a. In normal conditions, AR recruits EZH2......-differentiation of PCa cells to stem/progenitor-like cells (PCSC), which potentially contribute to disease recurrence. Finally, the knock down of YAP1 expression or the inhibition of YAP1 function by Verteporfin in TRAMP prostate cancer mice significantly suppresses tumor recurrence following castration. In conclusion...

  5. Activity of metabolic enzymes and muscle-specific gene expression in parr and smolts Atlantic salmon Salmo salar L. of different age groups.

    Science.gov (United States)

    Churova, Maria V; Meshcheryakova, Olga V; Veselov, Aleksey E; Efremov, Denis A; Nemova, Nina N

    2017-08-01

    This study was conducted to characterize the energy metabolism level and the features of muscle growth regulation during the development of Atlantic salmon (Salmo salar) inhabiting the Indera River (Kola Peninsula, Russia). The activities of aerobic and anaerobic enzymes (cytochrome c oxidase and lactate dehydrogenase) and carbohydrate metabolism enzymes (glucose-6-phosphate dehydrogenase, glycerol-3-phosphate dehydrogenase, and aldolase) were measured in muscle and liver tissue. Gene expression levels of myosin heavy chain (MyHC), myostatin (MSTN-1a), and myogenic regulatory factors (MRFs-MyoD1a, MyoD1b, MyoD1c, Myf5, myogenin) were measured in the white muscles of salmon parr of ages 0+, 1+, 2+, and 3+ and smolts of ages 2+ and 3+. Multidirectional changes in the activity of enzymes involved in aerobic and anaerobic energy metabolism with age were shown in the white muscles of the parr. The cytochrome c oxidase activity was higher in muscles of underyearlings (0+) and yearlings (1+) and decreased in 2+ and 3+ age groups. The activity of lactate dehydrogenase, in contrast, increased with age. The patterns of changes in expression levels of MyoD1a, MyoD1b, myogenin, MyHC, and MSTN-1a at different ages of the parr were similar. Particularly, the expression of these genes peaked in the yearling parr (1+) and then decreased in elder groups. The differences were revealed in parameters studied between the parr and smolts. The level of aerobic and anaerobic metabolism enzyme activities was higher in the white muscles of smolts than in parr. The activity of carbohydrate metabolism enzymes was decreased in the smolts' livers. The expression levels of MyHC, MyoD1a, MyoD1b, and myogenin were lower in smolts at age 2+ compared to parr. These findings expand our knowledge of age-related and stage-related features of energy metabolism and muscle development regulation in young Atlantic salmon in their natural habitat. The results might be used for monitoring of the salmon

  6. Relationships between High-mobility Group Protein B1 and Triggering Receptor Expressed on Myeloid Cells Concentrations in Gingival Crevicular Fluid and Chronic Periodontitis.

    Science.gov (United States)

    Paknejad, Mojgan; Sattari, Mandana; Roozbahani, Zohreh; Ershadi, Morteza; Mehrfard, Ali

    2016-10-01

    One of the inflammatory mediators which is secreted by inflammatory cells is high-mobility group protein B1 (HMGB1). Interaction of HMGB1 and toll-like receptors (TLRs) leads to increased production of inflammatory cytokines. On the other hand, it was shown that triggering receptor expressed on myeloid cells (TREM-1) also can be activated by TLRs, and its soluble form (sTREM-1) can be formed by cleaving of membrane-bound form of TREM-1 proteinases. Since there is not enough knowledge about the precise role of HMGB1 and sTREM-1 in periodontal diseases, the aim of this study was to evaluate the concentration of HMGB1 and sTREM-1 in gingival crevicular fluid (GCF) samples of patients with chronic periodontitis. Gingival crevicular fluid (GCF) samples were obtained from a total of 24 individuals with clinically healthy gingiva and 24 patients with moderate to severe chronic periodontitis. For collecting GCF samples, periopapers were placed at the entrance of the crevice and left in position for 30 seconds. Then, they were stored at -80°C. Enzyme-linked immunosorbent assay (ELISA) was used for measuring the concentration of HMGB1 and sTREM-1 in GCF samples. The concentration of HMGB1 (pchronic periodontitis group. In addition, there was a significant positive correlation between HMGB1 and sTREM-1 concentration in chronic periodontitis group (pperiodontal tissues and they can promote inflammatory process, which leads to tissue destruction.

  7. The group A streptococcal collagen-like protein 1, Scl1, mediates biofilm formation by targeting the EDA-containing variant of cellular fibronectin expressed in wounded tissue

    Science.gov (United States)

    Oliver-Kozup, Heaven; Martin, Karen H.; Schwegler-Berry, Diane; Green, Brett J.; Betts, Courtney; Shinde, Arti V.; Van De Water, Livingston; Lukomski, Slawomir

    2012-01-01

    Summary Wounds are known to serve as portals of entry for group A Streptococcus (GAS). Subsequent tissue colonization is mediated by interactions between GAS surface proteins and host extracellular matrix components. We recently reported that the streptococcal collagen-like protein-1, Scl1, selectively binds the cellular form of fibronectin (cFn) and also contributes to GAS biofilm formation on abiotic surfaces. One structural feature of cFn, which is predominantly expressed in response to tissue injury, is the presence of a spliced variant containing extra domain A (EDA/EIIIA). We now report that GAS biofilm formation is mediated by the Scl1 interaction with EDA-containing cFn. Recombinant Scl1 proteins that bound cFn also bound recombinant EDA within the C-C′ loop region recognized by the α9β1 integrin. The extracellular 2-D matrix derived from human dermal fibroblasts supports GAS adherence and biofilm formation. Altogether, this work identifies and characterizes a novel molecular mechanism by which GAS utilizes Scl1 to specifically target an extracellular matrix component that is predominantly expressed at the site of injury in order to secure host tissue colonization. PMID:23217101

  8. A naturally occurring mutation in ropB suppresses SpeB expression and reduces M1T1 group A streptococcal systemic virulence.

    Directory of Open Access Journals (Sweden)

    Andrew Hollands

    Full Text Available Epidemiological studies of group A streptococcus (GAS have noted an inverse relationship between SpeB expression and invasive disease. However, the role of SpeB in the course of infection is still unclear. In this study we utilize a SpeB-negative M1T1 clinical isolate, 5628, with a naturally occurring mutation in the gene encoding the regulator RopB, to elucidate the role of RopB and SpeB in systemic virulence. Allelic exchange mutagenesis was used to replace the mutated ropB allele in 5628 with the intact allele from the well characterized isolate 5448. The inverse allelic exchange was also performed to replace the intact ropB in 5448 with the mutated allele from 5628. An intact ropB was found to be essential for SpeB expression. While the ropB mutation was shown to have no effect on hemolysis of RBC's, extracellular DNase activity or survival in the presence of neutrophils, strains with the mutated ropB allele were less virulent in murine systemic models of infection. An isogenic SpeB knockout strain containing an intact RopB showed similarly reduced virulence. Microarray analysis found genes of the SpeB operon to be the primary target of RopB regulation. These data show that an intact RopB and efficient SpeB production are necessary for systemic infection with GAS.

  9. Defects in the Zeta Chain Expression (ζ in a Group of Patients with SLE, Scleroderma and Late-onset Arthritis, Colombia 2014

    Directory of Open Access Journals (Sweden)

    Heber Siachoque-Montañez

    2014-09-01

    Full Text Available Introduction: Systemic Lupus Erythematosus (SLE, Scleroderma and late-onset arthritis are autoimmune inflammatory diseases (EIA characterized by autoantibody production and presence of abnormal T cells which generate defective immune response. The abnormal expression of key signaling molecules in the defective function of T-lymphocytes plays a significant role in the pathogenesis of autoimmune disease. The T-cells exhibit numerous abnormalities TCRζ1 signaling complex, these aberrations result in altered expression of cytokines and some biochemical events involved in the expression of surface molecules. Defects in the complex may be associated TCRζ to steroids used in autoimmune disease patients due to their powerful anti-inflammatory activity and immunosuppressive properties. The synthetic corticosteroids such as examethasone inhibit the transcriptional activity of some factors such as NFKB and AP-1, which regulate the synthesis of certain cytokines and could be involved in the TCRζ synthesis. Material and Methods: A case-control study, with a 1:1 ratio of cases and controls (13:13. Cases were patients with active autoimmune disease (6 patients with SLE, 5 patients with scleroderma and 2 patients with lateonset arthritis, who have not started treatment with corticosteroids. Controls were patients with no autoimmune disease. The diagnosis was made by the criteria established by the American College of Rheumatology for patients with SLE, scleroderma and late-onset arthritis. A 10 mL sample was obtained by venipuncture whole blood. Total RNA was extracted and RT-PCR was performed using a set of primers flanking a region of 138 base pairs involving exons 2, 3 and 4 of the ζ chain. Results: The values of Z chain amplification showed significant differences in patients with autoimmune disease (0.8214 } 0.1787, med = 0.7368 compared with the control group (0.9225 } 0.1272, med = 0.9830 (p = 0.045, Mann-Withney non-parametric one tailed exact

  10. An OMV Vaccine Derived from a Capsular Group B Meningococcus with Constitutive FetA Expression: Preclinical Evaluation of Immunogenicity and Toxicity.

    Directory of Open Access Journals (Sweden)

    Gunnstein Norheim

    Full Text Available Following the introduction of effective protein-polysaccharide conjugate vaccines against capsular group C meningococcal disease in Europe, meningococci of capsular group B remain a major cause of death and can result in debilitating sequelae. The outer membrane proteins PorA and FetA have previously been shown to induce bactericidal antibodies in humans. Despite considerable antigenic variation among PorA and FetA OMPs in meningococci, systematic molecular epidemiological studies revealed this variation is highly structured so that a limited repertoire of antigenic types is congruent with the hyperinvasive meningococcal lineages that have caused most of the meningococcal disease in Europe in recent decades. Here we describe the development of a prototype vaccine against capsular group B meningococcal infection based on a N. meningitidis isolate genetically engineered to have constitutive expression of the outer membrane protein FetA. Deoxycholate outer membrane vesicles (dOMVs extracted from cells cultivated in modified Frantz medium contained 21.8% PorA protein, 7.7% FetA protein and 0.03 μg LPS per μg protein (3%. The antibody response to the vaccine was tested in three mouse strains and the toxicological profile of the vaccine was tested in New Zealand white rabbits. Administration of the vaccine, MenPF-1, when given by intramuscular injection on 4 occasions over a 9 week period, was well tolerated in rabbits up to 50 μg/dose, with no evidence of systemic toxicity. These data indicated that the MenPF-1 vaccine had a toxicological profile suitable for testing in a phase I clinical trial.

  11. Mindfulness-Based Cancer Recovery (MBCR) versus Supportive Expressive Group Therapy (SET) for distressed breast cancer survivors: evaluating mindfulness and social support as mediators.

    Science.gov (United States)

    Schellekens, Melanie P J; Tamagawa, Rie; Labelle, Laura E; Speca, Michael; Stephen, Joanne; Drysdale, Elaine; Sample, Sarah; Pickering, Barbara; Dirkse, Dale; Savage, Linette Lawlor; Carlson, Linda E

    2017-06-01

    Despite growing evidence in support of mindfulness as an underlying mechanism of mindfulness-based interventions (MBIs), it has been suggested that nonspecific therapeutic factors, such as the experience of social support, may contribute to the positive effects of MBIs. In the present study, we examined whether change in mindfulness and/or social support mediated the effect of Mindfulness-Based Cancer Recovery (MBCR) compared to another active intervention (i.e. Supportive Expressive Group Therapy (SET)), on change in mood disturbance, stress symptoms and quality of life. A secondary analysis was conducted of a multi-site randomized clinical trial investigating the impacts of MBCR and SET on distressed breast cancer survivors (MINDSET). We applied the causal steps approach with bootstrapping to test mediation, using pre- and post-intervention questionnaire data of the participants who were randomised to MBCR (n = 69) or SET (n = 70). MBCR participants improved significantly more on mood disturbance, stress symptoms and social support, but not on quality of life or mindfulness, compared to SET participants. Increased social support partially mediated the impact of MBCR versus SET on mood disturbance and stress symptoms. Because no group differences on mindfulness and quality of life were observed, no mediation analyses were performed on these variables. Findings showed that increased social support was related to more improvement in mood and stress after MBCR compared to support groups, whereas changes in mindfulness were not. This suggests a more important role for social support in enhancing outcomes in MBCR than previously thought.

  12. Hotair mediates hepatocarcinogenesis through suppressing miRNA-218 expression and activating P14 and P16 signaling.

    Science.gov (United States)

    Fu, Wei-Ming; Zhu, Xiao; Wang, Wei-Mao; Lu, Ying-Fei; Hu, Bao-Guang; Wang, Hua; Liang, Wei-Cheng; Wang, Shan-Shan; Ko, Chun-Hay; Waye, Mary Miu-Yee; Kung, Hsiang-Fu; Li, Gang; Zhang, Jin-Fang

    2015-10-01

    Long non-coding RNA Hotair has been considered as a pro-oncogene in multiple cancers. Although there is emerging evidence that reveals its biological function and the association with clinical prognosis, the precise mechanism remains largely elusive. We investigated the function and mechanism of Hotair in hepatocellular carcinoma (HCC) cell models and a xenograft mouse model. The regulatory network between miR-218 and Hotair was elucidated by RNA immunoprecipitation and luciferase reporter assays. Finally, the correlation between Hotair, miR-218 and the target gene Bmi-1 were evaluated in 52 paired HCC specimens. In this study, we reported that Hotair negatively regulated miR-218 expression in HCC, which might be mediated through an EZH2-targeting-miR-218-2 promoter regulatory axis. Further investigation revealed that Hotair knockdown dramatically inhibited cell viability and induced G1-phase arrest in vitro and suppressed tumorigenicity in vivo by promoting miR-218 expression. Oncogene Bmi-1 was shown to be a functional target of miR-218, and the main downstream targets signaling, P16(Ink4a) and P14(ARF), were activated in Hotair-suppressed tumorigenesis. In primary human HCC specimens, Hotair and Bmi-1 were concordantly upregulated whereas miR-218 was downregulated in these tissues. Furthermore, Hotair was inversely associated with miR-218 expression and positively correlated with Bmi-1 expression in these clinical tissues. Hotair silence activates P16(Ink4a) and P14(ARF) signaling by enhancing miR-218 expression and suppressing Bmi-1 expression, resulting in the suppression of tumorigenesis in HCC. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

    Science.gov (United States)

    Kleb, Brittany; Estécio, Marcos R H; Zhang, Jiexin; Tzelepi, Vassiliki; Chung, Woonbok; Jelinek, Jaroslav; Navone, Nora M; Tahir, Salahaldin; Marquez, Victor E; Issa, Jean-Pierre; Maity, Sankar; Aparicio, Ana

    2016-03-03

    Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs.

  14. An XPA gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities.

    Science.gov (United States)

    Takahashi, Y; Endo, Y; Kusaka-Kikushima, A; Nakamaura, S; Nakazawa, Y; Ogi, T; Uryu, M; Tsuji, G; Furue, M; Moriwaki, S

    2017-07-01

    A certain relationship between XPA gene mutations and the severity of symptoms has been observed in patients with xeroderma pigmentosum group A (XP-A). Patients with mutations within the DNA-binding domain usually exhibit severe symptoms, whereas splicing mutations in the same domain sometimes cause very mild symptoms. This inconsistency can be explained by a small amount of functional XPA protein produced from normally spliced transcripts. We herein report the case of an adult Japanese patient with XP-A with unusually mild symptoms. We identified a homozygous c.529G>A mutation in exon 4 of the XPA gene, which resulted in aberrant splicing with a 29-bp deletion in exon 4 causing a frameshift. Intact mRNA was observable, but a Western blot analysis failed to detect any normal XPA protein. We therefore evaluated the DNA repair capacity in normal cells in which the XPA expression was artificially diminished. The repair capacity was still present in cells with trace levels of the XPA protein. The repair capacity of the cells derived from our patient with mild symptoms was poor by comparison, but still significant compared with that of the cells derived from a patient with XP-A with severe symptoms. These results provide strong evidence that a trace level of XPA protein can still exert a relatively strong repair capacity, resulting in only a mild phenotype. © 2016 British Association of Dermatologists.

  15. Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.

    Science.gov (United States)

    Wassef, Michel; Rodilla, Veronica; Teissandier, Aurélie; Zeitouni, Bruno; Gruel, Nadege; Sadacca, Benjamin; Irondelle, Marie; Charruel, Margaux; Ducos, Bertrand; Michaud, Audrey; Caron, Matthieu; Marangoni, Elisabetta; Chavrier, Philippe; Le Tourneau, Christophe; Kamal, Maud; Pasmant, Eric; Vidaud, Michel; Servant, Nicolas; Reyal, Fabien; Meseure, Dider; Vincent-Salomon, Anne; Fre, Silvia; Margueron, Raphaël

    2015-12-15

    Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications. © 2015 Wassef et al.; Published by Cold Spring Harbor Laboratory Press.

  16. FB-NOF is a non-autonomous transposable element, expressed in Drosophila melanogaster and present only in the melanogaster group.

    Science.gov (United States)

    Badal, Martí; Xamena, Noel; Cabré, Oriol

    2013-09-10

    Most foldback elements are defective due to the lack of coding sequences but some are associated with coding sequences and may represent the entire element. This is the case of the NOF sequences found in the FB of Drosophila melanogaster, formerly considered as an autonomous TE and currently proposed as part of the so-called FB-NOF element, the transposon that would be complete and fully functional. NOF is always associated with FB and never seen apart from the FB inverted repeats (IR). This is the reason why the FB-NOF composite element can be considered the complete element. At least one of its ORFs encodes a protein that has always been considered its transposase, but no detailed studies have been carried out to verify this. In this work we test the hypothesis that FB-NOF is an active transposon nowadays. We search for its expression product, obtaining its cDNA, and propose the ORF and the sequence of its potential protein. We found that the NOF protein is not a transposase as it lacks any of the motifs of known transposases and also shows structural homology with hydrolases, therefore FB-NOF cannot belong to the superfamily MuDR/foldback, as up to now it has been classified, and can be considered as a non-autonomous transposable element. The alignment with the published genomes of 12 Drosophila species shows that NOF presence is restricted only to the 6 Drosophila species belonging to the melanogaster group. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. The phytochemical 3,3'-diindolylmethane decreases expression of AR-controlled DNA damage repair genes through repressive chromatin modifications and is associated with DNA damage in prostate cancer cells.

    Science.gov (United States)

    Palomera-Sanchez, Zoraya; Watson, Gregory W; Wong, Carmen P; Beaver, Laura M; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2017-09-01

    Androgen receptor (AR) is a transcription factor involved in normal prostate physiology and prostate cancer (PCa) development. 3,3'-Diindolylmethane (DIM) is a promising phytochemical agent against PCa that affects AR activity and epigenetic regulators in PCa cells. However, whether DIM suppresses PCa via epigenetic regulation of AR target genes is unknown. We assessed epigenetic regulation of AR target genes in LNCaP PCa cells and showed that DIM treatment led to epigenetic suppression of AR target genes involved in DNA repair (PARP1, MRE11, DNA-PK). Decreased expression of these genes was accompanied by an increase in repressive chromatin marks, loss of AR occupancy and EZH2 recruitment to their regulatory regions. Decreased DNA repair gene expression was associated with an increase in DNA damage (γH2Ax) and up-regulation of genomic repeat elements LINE1 and α-satellite. Our results suggest that DIM suppresses AR-dependent gene transcription through epigenetic modulation, leading to DNA damage and genome instability in PCa cells. Published by Elsevier Inc.

  18. Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Rongna Wei

    2016-01-01

    Conclusions: High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.

  19. Lipocalin 2 expression is associated with aggressive features of endometrial cancer

    International Nuclear Information System (INIS)

    Mannelqvist, Monica; Akslen, Lars A; Stefansson, Ingunn M; Wik, Elisabeth; Kusonmano, Kanthida; Raeder, Maria B; Øyan, Anne M; Kalland, Karl-Henning; Moses, Marsha A; Salvesen, Helga B

    2012-01-01

    Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival. Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies. Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage

  20. Clinically Relevant Subsets Identified by Gene Expression Patterns Support a Revised Ontogenic Model of Wilms Tumor: A Children's Oncology Group Study

    Directory of Open Access Journals (Sweden)

    Samantha Gadd

    2012-08-01

    Full Text Available Wilms tumors (WT have provided broad insights into the interface between development and tumorigenesis. Further understanding is confounded by their genetic, histologic, and clinical heterogeneity, the basis of which remains largely unknown. We evaluated 224 WT for global gene expression patterns; WT1, CTNNB1, and WTX mutation; and 11p15 copy number and methylation patterns. Five subsets were identified showing distinct differences in their pathologic and clinical features: these findings were validated in 100 additional WT. The gene expression pattern of each subset was compared with published gene expression profiles during normal renal development. A novel subset of epithelial WT in infants lacked WT1, CTNNB1, and WTX mutations and nephrogenic rests and displayed a gene expression pattern of the postinduction nephron, and none recurred. Three subsets were characterized by a low expression of WT1 and intralobar nephrogenic rests. These differed in their frequency of WT1 and CTNNB1 mutations, in their age, in their relapse rate, and in their expression similarities with the intermediate mesoderm versus the metanephric mesenchyme. The largest subset was characterized by biallelic methylation of the imprint control region 1, a gene expression profile of the metanephric mesenchyme, and both interlunar and perilobar nephrogenic rests. These data provide a biologic explanation for the clinical and pathologic heterogeneity seen within WT and enable the future development of subset-specific therapeutic strategies. Further, these data support a revision of the current model of WT ontogeny, which allows for an interplay between the type of initiating event and the developmental stage in which it occurs.

  1. AMPK Signaling Involvement for the Repression of the IL-1β-Induced Group IIA Secretory Phospholipase A2 Expression in VSMCs.

    Directory of Open Access Journals (Sweden)

    Khadija El Hadri

    Full Text Available Secretory Phospholipase A2 of type IIA (sPLA2 IIA plays a crucial role in the production of lipid mediators by amplifying the neointimal inflammatory context of the vascular smooth muscle cells (VSMCs, especially during atherogenesis. Phenformin, a biguanide family member, by its anti-inflammatory properties presents potential for promoting beneficial effects upon vascular cells, however its impact upon the IL-1β-induced sPLA2 gene expression has not been deeply investigated so far. The present study was designed to determine the relationship between phenformin coupling AMP-activated protein kinase (AMPK function and the molecular mechanism by which the sPLA2 IIA expression was modulated in VSMCs. Here we find that 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR treatment strongly repressed IL-1β-induced sPLA2 expression at least at the transcriptional level. Our study reveals that phenformin elicited a dose-dependent inhibition of the sPLA2 IIA expression and transient overexpression experiments of constitutively active AMPK demonstrate clearly that AMPK signaling is involved in the transcriptional inhibition of sPLA2-IIA gene expression. Furthermore, although the expression of the transcriptional repressor B-cell lymphoma-6 protein (BCL-6 was markedly enhanced by phenformin and AICAR, the repression of sPLA2 gene occurs through a mechanism independent of BCL-6 DNA binding site. In addition we show that activation of AMPK limits IL-1β-induced NF-κB pathway activation. Our results indicate that BCL-6, once activated by AMPK, functions as a competitor of the IL-1β induced NF-κB transcription complex. Our findings provide insights on a new anti-inflammatory pathway linking phenformin, AMPK and molecular control of sPLA2 IIA gene expression in VSMCs.

  2. Fanzine as a Tool of Artistic Expression in Prison Contexts: Visual A/R/Tography with a Group of Prisoners in Module 6 at the Albolote Penitentiary Center in Spain

    Science.gov (United States)

    Martín-Andrés, Cristina; Manriquez, Natalia Villalobos

    2017-01-01

    This project was born with the intention of generating and recording the artistic expression of a group of inmates in module 6 of the Albolote (ES) penitentiary center through the creation of collaborative fanzines. A workshop was created, held once a week for 4 months. Through conceptual proposals and aesthetic tools, each participant in the…

  3. High-mobility group B1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in canine lymphoma.

    Science.gov (United States)

    Sterenczak, Katharina A; Joetzke, Alexa E; Willenbrock, Saskia; Eberle, Nina; Lange, Sandra; Junghanss, Christian; Nolte, Ingo; Bullerdiek, Jörn; Simon, Daniela; Murua Escobar, Hugo

    2010-12-01

    Canine lymphoma is a commonly occurring, spontaneously developing neoplasia similar to human non-Hodgkin's lymphoma and, thus, is used as a valuable model for human malignancy. HMGB1 and RAGE are strongly associated with tumour progression and vascularisation. Consequently, deregulated RAGE and HMGB1 may play an important role in the mechanisms involved in lymphoma progression. Expression patterns of HMGB1 and RAGE were analysed in 22 canine lymphoma and three canine non-neoplastic control samples via real time PCR and canine beta-glucuronidase gene (GUSB) as endogenous control. HMGB1 was up-regulated in the neoplastic samples, while RAGE expression remained inconspicuous. This study demonstrated similar mechanisms in lymphoma progression in humans and dogs due to overexpression of HMGB1, which was described in human lymphomas. RAGE remained stable in terms of expression indicating that the extracellular HMGB1-induced effects are regulated by HMGB1 itself.

  4. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression.

    Science.gov (United States)

    Zhang, E-b; Yin, D-d; Sun, M; Kong, R; Liu, X-h; You, L-h; Han, L; Xia, R; Wang, K-m; Yang, J-s; De, W; Shu, Y-q; Wang, Z-x

    2014-05-22

    Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (PTUG1 expression serves as an independent predictor for overall survival (PTUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy.

  5. Divergent Requirements for EZH1 in Heart Development Versus Regeneration.

    Science.gov (United States)

    Ai, Shanshan; Yu, Xianhong; Li, Yumei; Peng, Yong; Li, Chen; Yue, Yanzhu; Tao, Ge; Li, Chuanyun; Pu, William T; He, Aibin

    2017-07-07

    Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Heart development was normal in Ezh1 -/- ( Ezh 1 knockout) and Ezh2 f/f ::cTNT -Cre ( Ezh 2 knockout) embryos. Ablation of both genes in Ezh1 -/- ::Ezh2 f/f ::cTNT -Cre embryos caused lethal heart malformations, including hypertrabeculation, compact myocardial hypoplasia, and ventricular septal defect. Epigenome and transcriptome profiling showed that derepressed genes were upregulated in a manner consistent with total EZH dose. In neonatal heart regeneration, Ezh1 was required, but Ezh2 was dispensable. This finding was further supported by rescue experiments: cardiac myocyte-restricted re-expression of EZH1 but not EZH2 restored neonatal heart regeneration in Ezh 1 knockout. In myocardial infarction performed outside of the neonatal regenerative window, EZH1 but not EZH2 likewise improved heart function and stimulated cardiac myocyte proliferation. Mechanistically, EZH1 occupied and activated genes related to cardiac growth. Our work unravels divergent mechanisms of EZH1 in heart development and regeneration, which will empower efforts to overcome epigenetic barriers to heart regeneration. © 2017 American Heart Association, Inc.

  6. Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function

    DEFF Research Database (Denmark)

    Jorgensen, Stine; Have, Christian Theil; Underwood, Christina Rye

    2017-01-01

    -expressed murine and goldfish orthologs. The latter orthologs are Gq-coupled and lead to intracellular accumulation of inositol phosphates and calcium release. In the present study we cloned the bonobo chimpanzee GPRC6A receptor, which is 99% identical to the human receptor, and show that it is cell surface...

  7. Development of perturbation theory expressions for the evaluation of reactivity effects and sensitivity coefficient of reactivity effect to the group cross-sections on the basis of improved coarse mesh method for 3D diffusion problem

    International Nuclear Information System (INIS)

    Seregin, A.S.

    2000-01-01

    In the paper the formulae for perturbation theory functionals calculation are given and equations are based on improved coarse mesh discretization of diffusion problem in 3-dimensional geometry (Hex-Z). Expressions for the reactivity effect components and reactivity coefficients, written in the framework of the first order perturbation theory, are presented. On this basis the formulae for estimation of the sensitivity coefficients of different reactivity effects group cross-sections were derived. Expressions for the reactivity effect and its components obtained in the framework of the strict perturbation theory, are also presented in the paper. (author)

  8. Change of CD20 Expression in Diffuse Large B-Cell Lymphoma Treated with Rituximab, an Anti-CD20 Monoclonal Antibody: A Study of the Osaka Lymphoma Study Group

    Directory of Open Access Journals (Sweden)

    Naoki Wada

    2009-10-01

    Full Text Available Change of CD20 expression was examined in cases of diffuse large B-cell lymphoma (DLBCL. CD20 expression after treatment with anti-CD20 antibody (rituximab, Rx for DLBCL was examined in 23 cases who received serial biopsy by immunohistochemistry (IHC and flow cytometry (FCM. CD20– by IHC and/or FCM was defined as CD20–. Four cases were CD20– at initial biopsy but became CD20+ after chemotherapy with Rx (CH-R (group A. Recurrent tumors in three group A cases became resistant to CH-R. Initial and recurrent tumors were CD20+ before and after CH-R in 17 cases (group B. Tumors before CH-R were CD20– in two cases (group C and continued to be CD20– in one and turned CD20+ in the other with survival time after the relapse of 8 and 23 months, respectively. Evaluation of CD20 expression with immunohistochemical and flow cytometric methods is used for the prediction of responsiveness of relapsed DLBCL for CH-R.

  9. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas

    DEFF Research Database (Denmark)

    Mohammad, Faizaan; Weissmann, Simon; Leblanc, Benjamin Olivier

    2017-01-01

    Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor that is located in the pons and primarily affects children. Nearly 80% of DIPGs harbor mutations in histone H3 genes, wherein lysine 27 is substituted with methionine (H3K27M). H3K27M has been shown to inhibit polycomb repressiv...

  10. Epigenetic Therapy of Hematopoietic Malignancies: Novel Approaches for Tissue-Specific and Global Inhibition of EZH2 Enzymatic Activities

    Science.gov (United States)

    2017-10-01

    removed by Picard Tools, and base quality score recalibration and Indel (insert/deletion) realignment using the Genome Analysis Toolkit GATK (McKenna et...Analysis Toolkit : a MapReduce framework for analyzing next-generation DNA sequencing data. Genome research 20, 1297-1303. McLean, C. Y., Bristor, D...CA151683), a Department of Defense Career Development award (CA130247), and grants from Gabrielle’s Angel Foundation and Concern Foundation. GGW is also

  11. EZH2 Protects Glioma Stem Cells from Radiation-Induced Cell Death in a MELK/FOXM1-Dependent Manner

    DEFF Research Database (Denmark)

    Kim, Sung-Hak; Joshi, Kaushal; Ezhilarasan, Ravesanker

    2015-01-01

    Glioblastoma (GBM)-derived tumorigenic stem-like cells (GSCs) may play a key role in therapy resistance. Previously, we reported that the mitotic kinase MELK binds and phosphorylates the oncogenic transcription factor FOXM1 in GSCs. Here, we demonstrate that the catalytic subunit of Polycomb repr...

  12. EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival

    NARCIS (Netherlands)

    Smits, Michiel; van Rijn, Sjoerd; Hulleman, Esther; Biesmans, Dennis; van Vuurden, Dannis G.; Kool, Marcel; Haberler, Christine; Aronica, Eleonora; Vandertop, W. Peter; Noske, David P.; Würdinger, Thomas

    2012-01-01

    Purpose: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches. Experimental

  13. Developing Programmes to Promote Participation in Sport among Adolescents with Disabilities: Perceptions Expressed by a Group of South African Adolescents with Cerebral Palsy

    Science.gov (United States)

    Bantjes, Jason; Swartz, Leslie; Conchar, Lauren; Derman, Wayne

    2015-01-01

    Adolescents with disabilities in developing countries frequently have limited access to sporting opportunities and comparatively little is known of their lived experiences and preferences. We set out to understand what a group of adolescents with cerebral palsy (CP) living in South Africa perceive to be important components of programmes developed…

  14. Transcriptome Analysis of the Intracellular Facultative Pathogen Piscirickettsia salmonis: Expression of Putative Groups of Genes Associated with Virulence and Iron Metabolism.

    Directory of Open Access Journals (Sweden)

    Alvaro Machuca

    Full Text Available The intracellular facultative bacteria Piscirickettsia salmonis is one of the most important pathogens of the Chilean aquaculture. However, there is a lack of information regarding the whole genomic transcriptional response according to different extracellular environments. We used next generation sequencing (NGS of RNA (RNA-seq to study the whole transcriptome of an isolate of P. salmonis (FAVET-INBIOGEN using a cell line culture and a modified cell-free liquid medium, with or without iron supplementation. This was done in order to obtain information about the factors there are involved in virulence and iron acquisition. First, the isolate was grown in the Sf21 cell line; then, the bacteria were cultured into a cell-free liquid medium supplemented or not with iron. We identified in the transcriptome, genes associated with type IV secretion systems, genes related to flagellar structure assembly, several proteases and sigma factors, and genes related to the development of drug resistance. Additionally, we identified for the first time several iron-metabolism associated genes including at least two iron uptake pathways (ferrous iron and ferric iron uptake that are actually expressed in the different conditions analyzed. We further describe putative genes that are related with the use and storage of iron in the bacteria, which have not been previously described. Several sets of genes related to virulence were expressed in both the cell line and cell-free culture media (for example those related to flagellar structure; such as basal body, MS-ring, C-ring, proximal and distal rod, and filament, which may play roles in other basic processes rather than been restricted to virulence.

  15. Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

    Directory of Open Access Journals (Sweden)

    Takayoshi eMasuoka

    2016-03-01

    Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

  16. Beneficial Effects of Ethyl Pyruvate through Inhibiting High-Mobility Group Box 1 Expression and TLR4/NF-κB Pathway after Traumatic Brain Injury in the Rat

    Directory of Open Access Journals (Sweden)

    Xingfen Su

    2011-01-01

    Full Text Available Ethyl pyruvate (EP has demonstrated neuroprotective effects against acute brain injury through its anti-inflammatory action. The nuclear protein high-mobility group box 1 (HMGB1 can activate inflammatory pathways when released from dying cells. This study was designed to investigate the protective effects of EP against secondary brain injury in rats after Traumatic Brain Injury (TBI. Adult male rats were randomly divided into three groups: (1 Sham + vehicle group, (2 TBI + vehicle group, and (3 TBI + EP group (n=30 per group. Right parietal cortical contusion was made by using a weight-dropping TBI method. In TBI + EP group, EP was administered intraperitoneally at a dosage of 75 mg/kg at 5 min, 1 and 6 h after TBI. Brain samples were harvested at 24 h after TBI. We found that EP treatment markedly inhibited the expressions of HMGB1 and TLR4, NF-κB DNA binding activity and inflammatory mediators, such as IL-1β, TNF-α and IL-6. Also, EP treatment significantly ameliorated beam walking performance, brain edema, and cortical apoptotic cell death. These results suggest that the protective effects of EP may be mediated by the reduction of HMGB1/TLR4/NF-κB-mediated inflammatory response in the injured rat brain.

  17. Correlation analysis and prognostic impact of 18F-FDG PET and excision repair cross-complementation group 1 (ERCC-1) expression in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Jeong, Yong Hyu; Lee, Choong Kun; Jo, Kwan Hyeong; Hwang, Sang Hyun; Cha, Jong Tae; Lee, Jeong Won; Yun, Mi Jin; Cho, Arthur

    2015-01-01

    The aim of this study was to determine the relationship between [ 18 ]-2-fluoro-2-deoxy-D-glucose (FDG) uptake and excision repair cross-complementation group 1 (ERCC-1) expression and to evaluate the prognostic effect of these two factors in resectable non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed 212 patients with resectable NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) scan for cancer staging and ERCC-1 expression analysis between January 2008 to December 2011. All patients were then followed-up for survival analysis. Semiquantitative evaluation of ERCC-1 was performed with the H-scoring system and was correlated with maximum standardized uptake value (SUV max ) of NSCLC. Univariate and multivariate analyses were performed to evaluate for FDG uptake and ERCC-1 expression predicting overall survival. In 212 patients (139 male, median age 68 ± 9.11), 112 patients had ERCC-positive tumors and 100 patients had ERCC-negative tumors. There was no significant difference in SUV max between ERCC-1-positive tumors (8.02 ±5.40) and ERCC-1-negative tumors (7.57 ± 6.56, p = 0.584). All patients were followed-up for a median of 40.5 months (95 % confidence interval [CI], 38.5–42.2 months). Univariate analysis and multivariate analysis for all patients showed that both ERCC-1 expression (hazard ratio [HR], 2.78; 95 % CI, 1.20–6.47) and FDG uptake (HR, 4.50; 95 % CI, 2.07–9.77) independently predicted overall survival. We have found no statistical correlation between FDG uptake and ERCC-1 expression in NSCLC. However, both higher FDG uptake and positive ERCC-1 expression are independent predictive markers of prognosis, suggesting that both should be obtained during patient workup

  18. Correlation analysis and prognostic impact of {sup 18}F-FDG PET and excision repair cross-complementation group 1 (ERCC-1) expression in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yong Hyu; Lee, Choong Kun; Jo, Kwan Hyeong; Hwang, Sang Hyun; Cha, Jong Tae; Lee, Jeong Won; Yun, Mi Jin; Cho, Arthur [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The aim of this study was to determine the relationship between [{sup 18}]-2-fluoro-2-deoxy-D-glucose (FDG) uptake and excision repair cross-complementation group 1 (ERCC-1) expression and to evaluate the prognostic effect of these two factors in resectable non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed 212 patients with resectable NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) scan for cancer staging and ERCC-1 expression analysis between January 2008 to December 2011. All patients were then followed-up for survival analysis. Semiquantitative evaluation of ERCC-1 was performed with the H-scoring system and was correlated with maximum standardized uptake value (SUV{sub max}) of NSCLC. Univariate and multivariate analyses were performed to evaluate for FDG uptake and ERCC-1 expression predicting overall survival. In 212 patients (139 male, median age 68 ± 9.11), 112 patients had ERCC-positive tumors and 100 patients had ERCC-negative tumors. There was no significant difference in SUV{sub max} between ERCC-1-positive tumors (8.02 ±5.40) and ERCC-1-negative tumors (7.57 ± 6.56, p = 0.584). All patients were followed-up for a median of 40.5 months (95 % confidence interval [CI], 38.5–42.2 months). Univariate analysis and multivariate analysis for all patients showed that both ERCC-1 expression (hazard ratio [HR], 2.78; 95 % CI, 1.20–6.47) and FDG uptake (HR, 4.50; 95 % CI, 2.07–9.77) independently predicted overall survival. We have found no statistical correlation between FDG uptake and ERCC-1 expression in NSCLC. However, both higher FDG uptake and positive ERCC-1 expression are independent predictive markers of prognosis, suggesting that both should be obtained during patient workup.

  19. Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson’s Disease

    Science.gov (United States)

    Hossein-nezhad, Arash; Fatemi, Roya Pedram; Ahmad, Rili; Peskind, Elaine R.; Zabetian, Cyrus P.; Hu, Shu-Ching; Shi, Min; Wahlestedt, Claes; Zhang, Jing; Faghihi, Mohammad Ali

    2016-01-01

    Background: Parkinson’s disease (PD) is a debilitating neurological disorder for which prognostic and diagnostic biomarkers are lacking. Cerebrospinal fluid (CSF) is an accessible body fluid that comes into direct contact with the central nervous system (CNS) and acts as a nuclease-free repository where RNA transcripts shed by brain tissues can reside for extended periods of time. Objective: We studied the RNA species present in the CSF of PD patients to identify novel diagnostic biomarkers. Methods: Small volumes of CSF from 27 PD patients and 30 healthy age- and sex-matched controls were used for RNA extraction followed by next-generation sequencing (RNA-seq) using the Illumina platform. CSF contains a number of fragmented RNA species that were individually sequenced and analyzed. Comparing PD to control subjects, we observed a pool of dysregulated sequencing tags that were further analyzed and validated by quantitative real-time PCR (qRT-PCR). Results: A total of 201 differentially expressed sequencing tags (DETs), including 92 up-regulated and 109 down-regulated DETs were identified. We validated the following DETs by real time PCR in the patient samples: Dnmt1, Ezh2, CCR3, SSTR5,PTPRC, UBC, NDUFV2, BMP7, SCN9, SCN9 antisense (AC010127.3), and long noncoding RNAs AC079630 and UC001lva.4 (close to the LRRK2 gene locus), as potential PD biomarkers. Conclusions: The CSF is a unique environment that contains many species of RNA. Our work demonstrates that CSF can potentially be used to identify biomarkers for the detection and tracking of disease progression and evaluation of therapeutic outcomes. PMID:26889637

  20. Receptor for advanced glycation end products - membrane type1 matrix metalloproteinase axis regulates tissue factor expression via RhoA and Rac1 activation in high-mobility group box-1 stimulated endothelial cells.

    Directory of Open Access Journals (Sweden)

    Koichi Sugimoto

    Full Text Available BACKGROUND: Atherosclerosis is understood to be a blood vessel inflammation. High-mobility group box-1 (HMGB-1 plays a key role in the systemic inflammation. Tissue factor (TF is known to lead to inflammation which promotes thrombus formation. Membrane type1 matrix metalloprotease (MT1-MMP associates with advanced glycation endproducts (AGE triggered-TF protein expression and phosphorylation of NF-κB. However, it is still unclear about the correlation of MT1-MMP and HMBG-1-mediated TF expression. In this study, we investigated the molecular mechanisms of TF expression in response to HMGB-1 stimulation and the involvement of MT1-MMP in endothelial cells. METHODS AND RESULTS: Pull-down assays and Western blotting revealed that HMGB-1 induced RhoA/Rac1 activation and NF-kB phosphorylation in cultured human aortic endothelial cells. HMGB-1 increased the activity of MT1-MMP, and inhibition of RAGE or MT1-MMP by siRNA suppressed HMGB-1-induced TF upregulation as well as HMGB-1-triggered RhoA/Rac1 activation and NF-kB phosphorylation. CONCLUSIONS: The present study showed that RAGE/MT1-MMP axis modified HMBG-1-mediated TF expression through RhoA and Rac1 activation and NF-κB phosphorylation in endothelial cells. These results suggested that MT1-MMP was involved in vascular inflammation and might be a good target for treating atherosclerosis.

  1. Genetic, comparative genomic, and expression analyses of the Mc1r locus in the polychromatic Midas cichlid fish (Teleostei, Cichlidae Amphilophus sp.) species group.

    Science.gov (United States)

    Henning, Frederico; Renz, Adina Josepha; Fukamachi, Shoji; Meyer, Axel

    2010-05-01

    Natural populations of the Midas cichlid species in several different crater lakes in Nicaragua exhibit a conspicuous color polymorphism. Most individuals are dark and the remaining have a gold coloration. The color morphs mate assortatively and sympatric population differentiation has been shown based on neutral molecular data. We investigated the color polymorphism using segregation analysis and a candidate gene approach. The segregation patterns observed in a mapping cross between a gold and a dark individual were consistent with a single dominant gene as a cause of the gold phenotype. This suggests that a simple genetic architecture underlies some of the speciation events in the Midas cichlids. We compared the expression levels of several candidate color genes Mc1r, Ednrb1, Slc45a2, and Tfap1a between the color morphs. Mc1r was found to be up regulated in the gold morph. Given its widespread association in color evolution and role on melanin synthesis, the Mc1r locus was further investigated using sequences derived from a genomic library. Comparative analysis revealed conserved synteny in relation to the majority of teleosts and highlighted several previously unidentified conserved non-coding elements (CNEs) in the upstream and downstream regions in the vicinity of Mc1r. The identification of the CNEs regions allowed the comparison of sequences from gold and dark specimens of natural populations. No polymorphisms were found between in the population sample and Mc1r showed no linkage to the gold phenotype in the mapping cross, demonstrating that it is not causally related to the color polymorphism in the Midas cichlid.

  2. Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.

    Science.gov (United States)

    Yin, H; Medstrand, P; Kristofferson, A; Dietrich, U; Aman, P; Blomberg, J

    1999-03-30

    Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is reported here. It was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total DNA. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. Work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function. Copyright 1999 Academic Press.

  3. Combinations of Novel Histone Deacetylase and Bcr-Abl Inhibitors in the Therapy of Imatinib Mesylate-Sensitive and -Refractory Bcr-Abl Expressing Leukemia

    Science.gov (United States)

    2008-12-01

    Balasis,1Purva Bali,1Veronica Estrella ,1Sandhya Kumaraswamy,1 Rekha Rao,1Kathy Rocha,1Bryan Herger,1Francis Lee,2 Victoria Richon,3 and Kapil Bhalla1...Balasis M, Bali P, Estrella V, Kumaraswamy S, et al. Histone deacetylase inhibitors deplete EZH2 and associated Polycomb Repressive Complex 2 proteins

  4. Peptidoglycan Association of Murein Lipoprotein Is Required for KpsD-Dependent Group 2 Capsular Polysaccharide Expression and Serum Resistance in a Uropathogenic Escherichia coli Isolate.

    Science.gov (United States)

    Diao, Jingyu; Bouwman, Catrien; Yan, Donghong; Kang, Jing; Katakam, Anand K; Liu, Peter; Pantua, Homer; Abbas, Alexander R; Nickerson, Nicholas N; Austin, Cary; Reichelt, Mike; Sandoval, Wendy; Xu, Min; Whitfield, Chris; Kapadia, Sharookh B

    2017-05-23

    Murein lipoprotein (Lpp) and peptidoglycan-associated lipoprotein (Pal) are major outer membrane lipoproteins in Escherichia coli Their roles in cell-envelope integrity have been documented in E. coli laboratory strains, and while Lpp has been linked to serum resistance in vitro , the underlying mechanism has not been established. Here, lpp and pal mutants of uropathogenic E. coli strain CFT073 showed reduced survival in a mouse bacteremia model, but only the lpp mutant was sensitive to serum killing in vitro The peptidoglycan-bound Lpp form was specifically required for preventing complement-mediated bacterial lysis in vitro and complement-mediated clearance in vivo Compared to the wild-type strain, the lpp mutant had impaired K2 capsular polysaccharide production and was unable to respond to exposure to serum by elevating capsular polysaccharide amounts. These properties correlated with altered cellular distribution of KpsD, the predicted outer membrane translocon for "group 2" capsular polysaccharides. We identified a novel Lpp-dependent association between functional KpsD and peptidoglycan, highlighting important interplay between cell envelope components required for resistance to complement-mediated lysis in uropathogenic E. coli isolates. IMPORTANCE Uropathogenic E. coli (UPEC) isolates represent a significant cause of nosocomial urinary tract and bloodstream infections. Many UPEC isolates are resistant to serum killing. Here, we show that a major cell-envelope lipoprotein (murein lipoprotein) is required for serum resistance in vitro and for complement-mediated bacterial clearance in vivo This is mediated, in part, through a novel mechanism by which murein lipoprotein affects the proper assembly of a key component of the machinery involved in production of "group 2" capsules. The absence of murein lipoprotein results in impaired production of the capsule layer, a known participant in complement resistance. These results demonstrate an important role for

  5. Unique case of oligoastrocytoma with recurrence and grade progression: Exhibiting differential expression of high mobility group-A1 and human telomerase reverse transcriptase

    Science.gov (United States)

    Gandhi, Puneet; Khare, Richa; Niraj, Kavita; Garg, Nitin; Sorte, Sandeep K; Gulwani, Hanni

    2016-01-01

    Mixed gliomas, primarily oligoastrocytomas, account for about 5%-10% of all gliomas. Distinguishing oligoastrocytoma based on histological features alone has limitations in predicting the exact biological behavior, necessitating ancillary markers for greater specificity. In this case report, human telomerase reverse transcriptase (hTERT) and high mobility group-A1 (HMGA1); markers of proliferation and stemness, have been quantitatively analyzed in formalin-fixed paraffin-embedded tissue samples of a 34 years old patient with oligoastrocytoma. Customized florescence-based immunohistochemistry protocol with enhanced sensitivity and specificity is used in the study. The patient presented with a history of generalized seizures and his magnetic resonance imaging scans revealed infiltrative ill-defined mass lesion with calcified foci within the left frontal white matter, suggestive of glioma. He was surgically treated at our center for four consecutive clinical events. Histopathologically, the tumor was identified as oligoastrocytoma-grade II followed by two recurrence events and final progression to grade III. Overall survival of the patient without adjuvant therapy was more than 9 years. Glial fibrillary acidic protein, p53, Ki-67, nuclear atypia index, pre-operative neutrophil-lymphocyte ratio, are the other parameters assessed. Findings suggest that hTERT and HMGA1 are linked to tumor recurrence and progression. Established markers can assist in defining precise histopathological grade in conjuction with conventional markers in clinical setup. PMID:27672647

  6. Leaving out control groups: an internal contrast analysis of gene expression profiles in atrial fibrillation patients--a systems biology approach to clinical categorization.

    Science.gov (United States)

    Vanhoutte, Kurt; de Asmundis, Carlo; Francesconi, Anna; Figysl, Jurgen; Steurs, Griet; Boussy, Tim; Roos, Markus; Mueller, Andreas; Massimo, Lucio; Paparella, Gaetano; Van Caelenberg, Kristien; Chierchia, Gian Battista; Sarkozy, Andrea; Terradellas, Pedro Brugada Y; Zizi, Martin

    2009-01-01

    Atrial fibrillation (AF) is a frequent chronic dysrythmia with an incidence that increases with age (>40). Because of its medical and socio-economic impacts it is expected to become an increasing burden on most health care systems. AF is a multi-factorial disease for which the identification of subtypes is warranted. Novel approaches based on the broad concepts of systems biology may overcome the blurred notion of normal and pathological phenotype, which is inherent to high throughput molecular arrays analysis. Here we apply an internal contrast algorithm on AF patient data with an analytical focus on potential entry pathways into the disease. We used a RMA (Robust Multichip Average) normalized Affymetrix micro-array data set from 10 AF patients (geo_accession #GSE2240). Four series of probes were selected based on physiopathogenic links with AF entryways: apoptosis (remodeling), MAP kinase (cell remodeling), OXPHOS (ability to sustain hemodynamic workload) and glycolysis (ischemia). Annotated probe lists were polled with Bioconductor packages in R (version 2.7.1). Genetic profile contrasts were analysed with hierarchical clustering and principal component analysis. The analysis revealed distinct patient groups for all probe sets. A substantial part (54% till 67%) of the variance is explained in the first 2 principal components. Genes in PC1/2 with high discriminatory value were selected and analyzed in detail. We aim for reliable molecular stratification of AF. We show that stratification is possible based on physiologically relevant gene sets. Genes with high contrast value are likely to give pathophysiological insight into permanent AF subtypes.

  7. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells

    DEFF Research Database (Denmark)

    Bracken, Adrian P; Kleine-Kohlbrecher, Daniela; Dietrich, Nikolaj

    2007-01-01

    The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up-regulation are not well understood. Here, we show that the ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association...... and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 (PRC2) complex. Significantly, EZH2 is down-regulated in stressed and senescing populations of cells, coinciding with decreased levels of associated H3K27me3, displacement of BMI1, and activation of transcription...

  8. A phase 1 study of a group B meningococcal native outer membrane vesicle vaccine made from a strain with deleted lpxL2 and synX and stable expression of opcA.

    Science.gov (United States)

    Keiser, Paul B; Gibbs, Barnett T; Coster, Trinka S; Moran, E Ellen; Stoddard, Mark B; Labrie, Joseph E; Schmiel, Deborah H; Pinto, Valerian; Chen, Ping; Zollinger, Wendell D

    2010-10-08

    This phase 1 clinical trial assessed the safety and immunogenicity of a native outer membrane vesicle (NOMV) vaccine prepared from a lpxL2(-) synX(-) mutant of strain 44/76 with opcA expression stabilized. Thirty-four volunteers were assigned to one of the three dose groups (25 mcg, 25 mcg with aluminum hydroxide adjuvant, and 50 mcg) to receive three intramuscular injections at 0, 6 and 24 weeks. Specific local and systemic adverse events (AEs) were solicited by diary and at visits on days 1, 2, 7 and 14 after each vaccination and at the end of the study at 30 weeks. Blood chemistries, complete blood count, and coagulation studies were measured on each vaccination day and again two days later. Blood for antibody measurements and bactericidal assays were drawn 0, 14, and 42 days after each vaccination. The proportion of volunteers who developed a fourfold or greater increase in serum bactericidal activity (SBA) to the wild-type parent of the vaccine strain with high opcA expression at 6 weeks after the third dose was 12/26 (0.46, 95% confidence interval 0.27-0.65). Antibody levels to OpcA were significantly higher in vaccine responders than in non-responders (p=0.008), and there was a trend for higher antibody levels to the lipooligosaccharide (LOS) (p=0.059). Bactericidal depletion assays on sera from volunteers with high-titer responses also indicate a major contribution of anti-OpcA and anti-LOS antibodies to the bactericidal response.These results suggest that genetically modified NOMV vaccines can induce protection against group B meningococcus. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Jing Wan

    2017-04-01

    Full Text Available Objective: To study the correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion. Methods: A total of 128 patients with thyroid papillary carcinoma who received surgical treatment in the hospital between May 2013 and May 2016 were collected, CEUS was used to make clear the peak intensity (PI and area under the curve (AUC of tumor tissue and surrounding normal tissue, and the median of PI and AUC was referred to further divide the patients into high PI group and low PI group as well as high AUC group and low AUC group, 64 cases in each group. Fluorescent quantitative PCR was used to determine proliferation and invasion gene mRNA expression in tumor tissues. Results: PI and AUC levels in tumor tissue were lower than those in surrounding normal tissue; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low PI group were higher than those of high PI group, and invasion gene Ki-67 mRNA expression was higher than that of high PI group while P53 and MRP-1 mRNA expression were lower than those of high PI group; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low AUC group were higher than those of high AUC group, and invasion gene Ki-67 mRNA expression was higher than that of high AUC group while P53 and MRP-1 mRNA expression were lower than those of high AUC group. Conclusion: Thyroid papillary carcinoma CEUS parameters PI and AUC levels can quantifiably reflect the cancer cell proliferation and invasion activity.

  10. Emotional collectives: How groups shape emotions and emotions shape groups.

    Science.gov (United States)

    van Kleef, Gerben A; Fischer, Agneta H

    2016-01-01

    Group settings are epicentres of emotional activity. Yet, the role of emotions in groups is poorly understood. How do group-level phenomena shape group members' emotional experience and expression? How are emotional expressions recognised, interpreted and shared in group settings? And how do such expressions influence the emotions, cognitions and behaviours of fellow group members and outside observers? To answer these and other questions, we draw on relevant theoretical perspectives (e.g., intergroup emotions theory, social appraisal theory and emotions as social information theory) and recent empirical findings regarding the role of emotions in groups. We organise our review according to two overarching themes: how groups shape emotions and how emotions shape groups. We show how novel empirical approaches break important new ground in uncovering the role of emotions in groups. Research on emotional collectives is thriving and constitutes a key to understanding the social nature of emotions.

  11. Group X

    Energy Technology Data Exchange (ETDEWEB)

    Fields, Susannah

    2007-08-16

    This project is currently under contract for research through the Department of Homeland Security until 2011. The group I was responsible for studying has to remain confidential so as not to affect the current project. All dates, reference links and authors, and other distinguishing characteristics of the original group have been removed from this report. All references to the name of this group or the individual splinter groups has been changed to 'Group X'. I have been collecting texts from a variety of sources intended for the use of recruiting and radicalizing members for Group X splinter groups for the purpose of researching the motivation and intent of leaders of those groups and their influence over the likelihood of group radicalization. This work included visiting many Group X websites to find information on splinter group leaders and finding their statements to new and old members. This proved difficult because the splinter groups of Group X are united in beliefs, but differ in public opinion. They are eager to tear each other down, prove their superiority, and yet remain anonymous. After a few weeks of intense searching, a list of eight recruiting texts and eight radicalizing texts from a variety of Group X leaders were compiled.

  12. Group Flow and Group Genius

    Science.gov (United States)

    Sawyer, Keith

    2015-01-01

    Keith Sawyer views the spontaneous collaboration of group creativity and improvisation actions as "group flow," which organizations can use to function at optimum levels. Sawyer establishes ideal conditions for group flow: group goals, close listening, complete concentration, being in control, blending egos, equal participation, knowing…

  13. Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated down-regulation of E-cadherin.

    Science.gov (United States)

    Zhou, Zhen; Zhang, Hong-Sheng; Liu, Yang; Zhang, Zhong-Guo; Du, Guang-Yuan; Li, Hu; Yu, Xiao-Ying; Huang, Ying-Hui

    2018-02-01

    Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased EZH2 expression and reduced UTX-1 expression, thus increasing histone H3K27 tri-methylation causing repression of the target gene E-cadherin. Ectopic expression of the H3K27 demethylase UTX-1 or EZH2 depletion both impeded EZH2 binding caused a loss of H3K27 methylation at epithelial gene E-cadherin promoter, thereby suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX-1 depletion and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells. These findings provide insight into the regulation of TET1 and E-cadherin and identify EZH2 as a critical mediator of E-cadherin repression and tumor progression. © 2017 Wiley Periodicals, Inc.

  14. Permutation groups

    CERN Document Server

    Passman, Donald S

    2012-01-01

    This volume by a prominent authority on permutation groups consists of lecture notes that provide a self-contained account of distinct classification theorems. A ready source of frequently quoted but usually inaccessible theorems, it is ideally suited for professional group theorists as well as students with a solid background in modern algebra.The three-part treatment begins with an introductory chapter and advances to an economical development of the tools of basic group theory, including group extensions, transfer theorems, and group representations and characters. The final chapter feature

  15. Immunodetection of Helicobacter sp. and the associated expression of ABO blood group antigens in the gastric mucosa of captive and free-living New World primates in the Amazon region

    Directory of Open Access Journals (Sweden)

    Délia Cristina Figueira Aguiar

    2011-12-01

    Full Text Available The histo-blood group ABH antigens were first described in humans. These antigens are only present on erythrocytes from great apes and humans, while in more primitive animals they are found in tissues and body fluids. The ABH antigens are mainly distributed in tissues exposed to the external environment and potentially serve as ligands for pathogens or inhibitors of tissue connections. The objective of this paper was two-fold: (i to determine the presence of Helicobacter sp. in the gastric mucosa of 16 captive and 24 free-living New World monkeys and (ii to evaluate the presence of histopathological alterations related to bacterial infection and the associated expression of ABH antigens in the tissue. Stomach tissues from 13 species of monkey were assessed using haematoxylin-eosin and modified Gram staining (Hucker methods. An immunohistochemical analysis of the tissue revealed the presence of infectious bacteria that were characteristic of the genus Helicobacter sp. The results demonstrate that various species of monkey might be naturally infected with the Helicobacter sp. and that there is an increased susceptibility to infection. This study serves as a comparative analysis of infection between human and non-human primates and indicates the presence of a new species of Helicobacter.

  16. A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression.

    Science.gov (United States)

    Keiser, P B; Biggs-Cicatelli, S; Moran, E E; Schmiel, D H; Pinto, V B; Burden, R E; Miller, L B; Moon, J E; Bowden, R A; Cummings, J F; Zollinger, W D

    2011-02-04

    This phase I clinical trial assessed the safety and immunogenicity of a native outer membrane vesicle (NOMV) vaccine prepared from an lpxL1(-) synX(-) mutant of strain 8570(B:4:P1.19,15:L8-5) of Neisseria meningitidis. Additional mutations enhance the expression of factor H binding protein variant 1 (fHbp v.1), stabilize expression of OpcA and introduce a second PorA (P1.22,14). Thirty-six volunteers were assigned to one of four dose groups (10, 25, 50 and 75 mcg, based on protein content) to receive three intramuscular injections at six week intervals with aluminum hydroxide adjuvant. Specific local and systemic adverse events were solicited by diary and at visits on days 2, 7, and 14 after each vaccination. Blood chemistries, complete blood count, and coagulation studies were measured on each vaccination day and again 2 and 14 days later. Blood for ELISA and serum bactericidal assays was drawn two and six weeks after each vaccination. The proportion of volunteers who developed a fourfold or greater increase in bactericidal activity to the wild type parent of the vaccine strain at two weeks after the third dose was 27 out of 34 (0.79, 95% C.I. 0.65-0.93). Against four other group B strains the response rate ranged from 41% to 82% indicating a good cross reactive antibody response. Depletion assays show contributions to bactericidal activity from antibodies to lipooligosaccharide (LOS), fHbp v.1 and OpcA. Published by Elsevier Ltd.

  17. Concepts of epigenetics in prostate cancer development.

    Science.gov (United States)

    Cooper, C S; Foster, C S

    2009-01-27

    Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention.

  18. Group devaluation and group identification

    NARCIS (Netherlands)

    Leach, C.W.; Rodriguez Mosquera, P.M.; Vliek, M.L.W.; Hirt, E.

    2010-01-01

    In three studies, we showed that increased in-group identification after (perceived or actual) group devaluation is an assertion of a (preexisting) positive social identity that counters the negative social identity implied in societal devaluation. Two studies with real-world groups used order

  19. Lie groups and algebraic groups

    Indian Academy of Sciences (India)

    We give an exposition of certain topics in Lie groups and algebraic groups. This is not a complete ... of a polynomial equation is equivalent to the solva- bility of the equation ..... to a subgroup of the group of roots of unity in k (in particular, it is a ...

  20. Group Work

    Science.gov (United States)

    Wilson, Kristy J.; Brickman, Peggy; Brame, Cynthia J.

    2018-01-01

    Science, technology, engineering, and mathematics faculty are increasingly incorporating both formal and informal group work in their courses. Implementing group work can be improved by an understanding of the extensive body of educational research studies on this topic. This essay describes an online, evidence-based teaching guide published by…

  1. Reflection groups

    International Nuclear Information System (INIS)

    Eggermont, G.

    2006-01-01

    In 2005, PISA organised proactive meetings of reflection groups on involvement in decision making, expert culture and ethical aspects of radiation protection.All reflection group meetings address particular targeted audiences while the output publication in book form is put forward

  2. Group theory

    CERN Document Server

    Scott, W R

    2010-01-01

    Here is a clear, well-organized coverage of the most standard theorems, including isomorphism theorems, transformations and subgroups, direct sums, abelian groups, and more. This undergraduate-level text features more than 500 exercises.

  3. Group Grammar

    Science.gov (United States)

    Adams, Karen

    2015-01-01

    In this article Karen Adams demonstrates how to incorporate group grammar techniques into a classroom activity. In the activity, students practice using the target grammar to do something they naturally enjoy: learning about each other.

  4. Computer group

    International Nuclear Information System (INIS)

    Bauer, H.; Black, I.; Heusler, A.; Hoeptner, G.; Krafft, F.; Lang, R.; Moellenkamp, R.; Mueller, W.; Mueller, W.F.; Schati, C.; Schmidt, A.; Schwind, D.; Weber, G.

    1983-01-01

    The computer groups has been reorganized to take charge for the general purpose computers DEC10 and VAX and the computer network (Dataswitch, DECnet, IBM - connections to GSI and IPP, preparation for Datex-P). (orig.)

  5. Group learning

    DEFF Research Database (Denmark)

    Pimentel, Ricardo; Noguira, Eloy Eros da Silva; Elkjær, Bente

    The article presents a study that aims at the apprehension of the group learning in a top management team composed by teachers in a Brazilian Waldorf school whose management is collective. After deciding to extend the school, they had problems recruiting teachers who were already trained based...... on the Steiner´s ideas, which created practical problems for conducting management activities. The research seeks to understand how that group of teachers collectively manage the school, facing the lack of resources, a significant heterogeneity in the relationships, and the conflicts and contradictions......, and they are interrelated to the group learning as the construction, maintenance and reconstruction of the intelligibility of practices. From this perspective, it can be said that learning is a practice and not an exceptional phenomenon. Building, maintaining and rebuilding the intelligibility is the group learning...

  6. Group technology

    International Nuclear Information System (INIS)

    Rome, C.P.

    1976-01-01

    Group Technology has been conceptually applied to the manufacture of batch-lots of 554 machined electromechanical parts which now require 79 different types of metal-removal tools. The products have been grouped into 7 distinct families which require from 8 to 22 machines in each machine-cell. Throughput time can be significantly reduced and savings can be realized from tooling, direct-labor, and indirect-labor costs

  7. Abelian groups

    CERN Document Server

    Fuchs, László

    2015-01-01

    Written by one of the subject’s foremost experts, this book focuses on the central developments and modern methods of the advanced theory of abelian groups, while remaining accessible, as an introduction and reference, to the non-specialist. It provides a coherent source for results scattered throughout the research literature with lots of new proofs. The presentation highlights major trends that have radically changed the modern character of the subject, in particular, the use of homological methods in the structure theory of various classes of abelian groups, and the use of advanced set-theoretical methods in the study of undecidability problems. The treatment of the latter trend includes Shelah’s seminal work on the undecidability in ZFC of Whitehead’s Problem; while the treatment of the former trend includes an extensive (but non-exhaustive) study of p-groups, torsion-free groups, mixed groups, and important classes of groups arising from ring theory. To prepare the reader to tackle these topics, th...

  8. Group dynamics.

    Science.gov (United States)

    Scandiffio, A L

    1990-12-01

    Group dynamics play a significant role within any organization, culture, or unit. The important thing to remember with any of these structures is that they are made up of people--people with different ideas, motivations, background, and sometimes different agendas. Most groups, formal or informal, look for a leader in an effort to maintain cohesiveness of the unit. At times, that cultural bond must be developed; once developed, it must be nurtured. There are also times that one of the group no longer finds the culture comfortable and begins to act out behaviorally. It is these times that become trying for the leader as she or he attempts to remain objective when that which was once in the building phase of group cohesiveness starts to fall apart. At all times, the manager must continue to view the employee creating the disturbance as an integral part of the group. It is at this time that it is beneficial to perceive the employee exhibiting problem behaviors as a special employee, as one who needs the benefit of your experience and skills, as one who is still part of the group. It is also during this time that the manager should focus upon her or his own views in the area of power, communication, and the corporate culture of the unit that one has established before attempting to understand another's point of view. Once we understand our own motivation and accept ourselves, it is then that we may move on to offer assistance to another. Once we understand our insecurities recognizing staff dysfunction as a symptom of system dysfunction will not be so threatening to the concept of the manager that we perceive ourselves to be. It takes a secure person to admit that she or he favors staff before deciding to do something to change things. The important thing to know is that it can be done. The favored staff can find a new way of relating to others, the special employee can find new modes of behavior (and even find self-esteem in the process), the group can find new ways

  9. Group representations

    CERN Document Server

    Karpilovsky, G

    1994-01-01

    This third volume can be roughly divided into two parts. The first part is devoted to the investigation of various properties of projective characters. Special attention is drawn to spin representations and their character tables and to various correspondences for projective characters. Among other topics, projective Schur index and projective representations of abelian groups are covered. The last topic is investigated by introducing a symplectic geometry on finite abelian groups. The second part is devoted to Clifford theory for graded algebras and its application to the corresponding theory

  10. Lego Group

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Pedersen, Torben; Slepniov, Dmitrij

    2010-01-01

    The last years’ rather adventurous journey from 2004 to 2009 had taught the fifth-largest toy-maker in the world - the LEGO Group - the importance of managing the global supply chain effectively. In order to survive the largest internal financial crisis in its roughly 70 years of existence......, the management had, among many initiatives, decided to offshore and outsource a major chunk of its production to Flextronics. In this pursuit of rapid cost-cutting sourcing advantages, the LEGO Group planned to license out as much as 80 per cent of its production besides closing down major parts...

  11. Informal groups

    NARCIS (Netherlands)

    E. van den Berg; P. van Houwelingen; J. de Hart

    2011-01-01

    Original title: Informele groepen Going out running with a group of friends, rather than joining an official sports club. Individuals who decide to take action themselves rather than giving money to good causes. Maintaining contact with others not as a member of an association, but through an

  12. COMMUNICATIONS GROUP

    CERN Multimedia

    L. Taylor

    2011-01-01

    The CMS Communications Group, established at the start of 2010, has been busy in all three areas of its responsibility: (1) Communications Infrastructure, (2) Information Systems, and (3) Outreach and Education. Communications Infrastructure There are now 55 CMS Centres worldwide that are well used by physicists working on remote CMS shifts, Computing operations, data quality monitoring, data analysis and outreach. The CMS Centre@CERN in Meyrin, is the centre of the CMS offline and computing operations, hosting dedicated analysis efforts such as during the CMS Heavy Ion lead-lead running. With a majority of CMS sub-detectors now operating in a “shifterless” mode, many monitoring operations are now routinely performed from there, rather than in the main Control Room at P5. The CMS Communications Group, CERN IT and the EVO team are providing excellent videoconferencing support for the rapidly-increasing number of CMS meetings. In parallel, CERN IT and ...

  13. Group therapy

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Full text: In his review 'Genesis of Unified Gauge Theories' at the symposium in Honour of Abdus Salam (June, page 23), Tom Kibble of Imperial College, London, looked back to the physics events around Salam from 1959-67. He described how, in the early 1960s, people were pushing to enlarge the symmetry of strong interactions beyond the SU(2) of isospin and incorporate the additional strangeness quantum number. Kibble wrote - 'Salam had students working on every conceivable symmetry group. One of these was Yuval Ne'eman, who had the good fortune and/or prescience to work on SU(3). From that work, and of course from the independent work of Murray Gell- Mann, stemmed the Eightfold Way, with its triumphant vindication in the discovery of the omega-minus in 1964.' Yuval Ne'eman writes - 'I was the Defence Attaché at the Israeli Embassy in London and was admitted by Salam as a part-time graduate student when I arrived in 1958. I started research after resigning from the Embassy in May 1960. Salam suggested a problem: provide vector mesons with mass - the problem which was eventually solved by Higgs, Guralnik, Kibble,.... (as described by Kibble in his article). I explained to Salam that I had become interested in symmetry. Nobody at Imperial College at the time, other than Salam himself, was doing anything in groups, and attention further afield was focused on the rotation - SO(N) - groups. Reacting to my own half-baked schemes, Salam told me to forget about the rotation groups he taught us, and study group theory in depth, directing me to Eugene Dynkin's classification of Lie subalgebras, about which he had heard from Morton Hamermesh. I found Dynkin incomprehensible without first learning about Lie algebras from Henri Cartan's thesis, which luckily had been reproduced by Dynkin in his 1946 thesis, using his diagram method. From a copy of a translation of Dynkin's thesis which I found in the British Museum Library, I

  14. COMMUNICATIONS GROUP

    CERN Multimedia

    L. Taylor

    2010-01-01

    The CMS Communications Group, established at the start of 2010, has been strengthening the activities in all three areas of its responsibility: (1) Communications Infrastructure, (2) Information Systems, and (3) Outreach and Education. Communications Infrastructure The Communications Group has invested a lot of effort to support the operations needs of CMS. Hence, the CMS Centres where physicists work on remote CMS shifts, Data Quality Monitoring, and Data Analysis are running very smoothly. There are now 55 CMS Centres worldwide, up from just 16 at the start of CMS data-taking. The latest to join are Imperial College London, the University of Iowa, and the Università di Napoli. The CMS Centre@CERN in Meyrin, which is now full repaired after the major flooding at the beginning of the year, has been at the centre of CMS offline and computing operations, most recently hosting a large fraction of the CMS Heavy Ion community during the lead-lead run. A number of sub-detector shifts can now take pla...

  15. Group play

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects of the v......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...... of group dynamics, the influence of the fictional game characters and the comparative play experience between the two formats. The results indicate that group dynamics and the relationship between the players and their digital characters, are integral to the quality of the gaming experience in multiplayer...

  16. COMMUNICATIONS GROUP

    CERN Multimedia

    L. Taylor

    2011-01-01

    The CMS Communications Group has been busy in all three areas of its responsibility: (1) Communications Infrastructure, (2) Information Systems, and (3) Outreach and Education. Communications Infrastructure The 55 CMS Centres worldwide are well used by physicists working on remote CMS shifts, Computing operations, data quality monitoring, data analysis and outreach. The CMS Centre@CERN in Meyrin, is the centre of the CMS Offline and Computing operations, and a number of subdetector shifts can now take place there, rather than in the main Control Room at P5. A new CMS meeting room has been equipped for videoconferencing in building 42, next to building 40. Our building 28 meeting room and the facilities at P5 will be refurbished soon and plans are underway to steadily upgrade the ageing equipment in all 15 CMS meeting rooms at CERN. The CMS evaluation of the Vidyo tool indicates that it is not yet ready to be considered as a potential replacement for EVO. The Communications Group provides the CMS-TV (web) cha...

  17. HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

    DEFF Research Database (Denmark)

    Linge, Annett; Lohaus, Fabian; Löck, Steffen

    2016-01-01

    OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell...

  18. Path Expressions

    Science.gov (United States)

    1975-06-01

    Traditionally, synchronization of concurrent processes is coded in line by operations on semaphores or similar objects. Path expressions move the...discussion about a variety of synchronization primitives . An analysis of their relative power is found in [3]. Path expressions do not introduce yet...another synchronization primitive . A path expression relates to such primitives as a for- or while-statement of an ALGOL-like language relates to a JUMP

  19. LncRNA-TUG1/EZH2 Axis Promotes Cell Proliferation, Migration And The EMT Phenotype Formation Through Sponging miR-382

    OpenAIRE

    Chen, Zongjing; Chen, Bicheng; Zhou, Mengtao; Sun, Hongwei; Zhao, Liang; Kong, Hongru

    2017-01-01

    Pancreatic carcinoma (PC) is the one of the most common and malignant cancer in the world. Despite many effort have been made in recent years, the survival rate of PC still remains unsatisfied. Therefore, investigating the mechanisms underlying the progression of PC might facilitate the development of novel treatments that improve patient prognosis. LncRNA Taurine Up-regulated Gene 1 (TUG1) was initially identified as a transcript up- regulated by taurine, siRNA-based depletion of TUG1 suppre...

  20. Dual inhibition of DNMTs and EZH2 can overcome both intrinsic and acquired resistance of myeloma cells to IMiDs in a cereblon-independent manner

    DEFF Research Database (Denmark)

    Dimopoulos, Konstantinos; Søgaard Helbo, Alexandra; Fibiger Munch-Petersen, Helga

    2018-01-01

    Thalidomide and its derivatives, lenalidomide and pomalidomide (also known as IMiDs), have significantly changed the treatment landscape of multiple myeloma, and the recent discovery of cereblon (CRBN) as their direct biological target has led to a deeper understanding of their complex mechanism ...

  1. COMMUNICATIONS GROUP

    CERN Multimedia

    L. Taylor

    2010-01-01

    The recently established CMS Communications Group, led by Lucas Taylor, has been busy in all three of its main are areas of responsibility: Communications Infrastructure, Information Systems, and Outreach and Education Communications Infrastructure The damage caused by the flooding of the CMS Centre@CERN on 21st December has been completely repaired and all systems are back in operation. Major repairs were made to the roofs, ceilings and one third of the floor had to be completely replaced. Throughout these works, the CMS Centre was kept operating and even hosted a major press event for first 7 TeV collisions, as described below. Incremental work behind the scenes is steadily improving the quality of the CMS communications infrastructure, particularly Webcasting, video conferencing, and meeting rooms at CERN. CERN/IT is also deploying a pilot service of a new videoconference tool called Vidyo, to assess whether it might provide an enhanced service at a lower cost, compared to the EVO tool currently in w...

  2. COMMUNICATIONS GROUP

    CERN Multimedia

    L. Taylor

    2011-01-01

    Communications Infrastructure The 55 CMS Centres worldwide are well used by physicists working on remote CMS shifts, Computing operations, data quality monitoring, data analysis and outreach. The CMS Centre@CERN in Meyrin is particularly busy at the moment, hosting about 50 physicists taking part in the heavy-ion data-taking and analysis. Three new CMS meeting room will be equipped for videoconferencing in early 2012: 40/5B-08, 42/R-031, and 28/S-029. The CMS-TV service showing LHC Page 1, CMS Page 1, etc. (http://cmsdoc.cern.ch/cmscc/projector/index.jsp) is now also available for mobile devices: http://cern.ch/mcmstv. Figure 12: Screenshots of CMS-TV for mobile devices Information Systems CMS has a new web site: (http://cern.ch/cms) using a modern web Content Management System to ensure content and links are managed and updated easily and coherently. It covers all CMS sub-projects and groups, replacing the iCMS internal pages. It also incorporates the existing CMS public web site (http:/...

  3. COMMUNICATIONS GROUP

    CERN Multimedia

    L. Taylor

    2012-01-01

      Outreach and Education We are fortunate that our research has captured the public imagination, even though this inevitably puts us under the global media spotlight, as we saw with the Higgs seminar at CERN in December, which had 110,000 distinct webcast viewers. The media interest was huge with 71 media organisations registering to come to CERN to cover the Higgs seminar, which was followed by a press briefing with the DG and Spokespersons. This event resulted in about 2,000 generally positive stories in the global media. For this seminar, the CMS Communications Group prepared up-to-date news and public material, including links to the CMS results, animations and event displays [http://cern.ch/go/Ch8thttp://cern.ch/go/Ch8t]. There were 44,000 page-views on the CMS public website, with the Higgs news article being by far the most popular item. CMS event displays from iSpy are fast becoming the iconic media images, featuring on numerous major news outlets (BBC, CNN, MSN...) as well as in the sci...

  4. Caricaturing facial expressions.

    Science.gov (United States)

    Calder, A J; Rowland, D; Young, A W; Nimmo-Smith, I; Keane, J; Perrett, D I

    2000-08-14

    The physical differences between facial expressions (e.g. fear) and a reference norm (e.g. a neutral expression) were altered to produce photographic-quality caricatures. In Experiment 1, participants rated caricatures of fear, happiness and sadness for their intensity of these three emotions; a second group of participants rated how 'face-like' the caricatures appeared. With increasing levels of exaggeration the caricatures were rated as more emotionally intense, but less 'face-like'. Experiment 2 demonstrated a similar relationship between emotional intensity and level of caricature for six different facial expressions. Experiments 3 and 4 compared intensity ratings of facial expression caricatures prepared relative to a selection of reference norms - a neutral expression, an average expression, or a different facial expression (e.g. anger caricatured relative to fear). Each norm produced a linear relationship between caricature and rated intensity of emotion; this finding is inconsistent with two-dimensional models of the perceptual representation of facial expression. An exemplar-based multidimensional model is proposed as an alternative account.

  5. Group and representation theory

    CERN Document Server

    Vergados, J D

    2017-01-01

    This volume goes beyond the understanding of symmetries and exploits them in the study of the behavior of both classical and quantum physical systems. Thus it is important to study the symmetries described by continuous (Lie) groups of transformations. We then discuss how we get operators that form a Lie algebra. Of particular interest to physics is the representation of the elements of the algebra and the group in terms of matrices and, in particular, the irreducible representations. These representations can be identified with physical observables. This leads to the study of the classical Lie algebras, associated with unitary, unimodular, orthogonal and symplectic transformations. We also discuss some special algebras in some detail. The discussion proceeds along the lines of the Cartan-Weyl theory via the root vectors and root diagrams and, in particular, the Dynkin representation of the roots. Thus the representations are expressed in terms of weights, which are generated by the application of the elemen...

  6. Encountering Carl Rogers: His Views on Facilitating Groups.

    Science.gov (United States)

    Landreth, Garry L.

    1984-01-01

    Presents Carl Rogers' views on facilitating groups, as expressed in a telephone dialogue seminar with graduate students in counselor education at North Texas State University. Discusses extended group marathons, cocounseling, nonverbal group exercises and the future of group work. (JAC)

  7. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  8. Molecular invariants: atomic group valence

    International Nuclear Information System (INIS)

    Mundim, K.C.; Giambiagi, M.; Giambiagi, M.S. de.

    1988-01-01

    Molecular invariants may be deduced in a very compact way through Grassman algebra. In this work, a generalized valence is defined for an atomic group; it reduces to the Known expressions for the case of an atom in a molecule. It is the same of the correlations between the fluctions of the atomic charges qc and qd (C belongs to the group and D does not) around their average values. Numerical results agree with chemical expectation. (author) [pt

  9. A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein 160 (MN/LAI). The AGIS Group, and l'Agence Nationale de Recherche sur le SIDA.

    Science.gov (United States)

    Pialoux, G; Excler, J L; Rivière, Y; Gonzalez-Canali, G; Feuillie, V; Coulaud, P; Gluckman, J C; Matthews, T J; Meignier, B; Kieny, M P

    1995-03-01

    The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgp160), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgp160 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively. Six months after the last boost, only 55% were still positive. Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 and in all subjects after the first booster injection and 12 months after the first injection. An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3+, CD8+, MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Renormalization group and asymptotic freedom

    International Nuclear Information System (INIS)

    Morris, J.R.

    1978-01-01

    Several field theoretic models are presented which allow exact expressions of the renormalization constants and renormalized coupling constants. These models are analyzed as to their content of asymptotic free field behavior through the use of the Callan-Symanzik renormalization group equation. It is found that none of these models possesses asymptotic freedom in four dimensions

  11. Group Work with Abusive Parents.

    Science.gov (United States)

    Kruger, Lois; And Others

    1979-01-01

    Social work students conclude from an experience that parents can consider alternative means of disciplining children when they participate in a parent group that is comfortable and when attendance is promoted by provision of tangible services. Parents achieved increased sense of self-worth and learned appropriate ways of expressing anger. (Author)

  12. A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    Ioannis Anestopoulos

    2016-12-01

    Full Text Available Silibinin, extracted from milk thistle (Silybum marianum L., has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2 members Enhancer of Zeste Homolog 2 (EZH2, Suppressor of Zeste Homolog 12 (SUZ12, and Embryonic Ectoderm Development (EED in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR. Furthermore immunoblot and immunofluorescence analysis revealed that silibinin-mediated reduction of EZH2 levels was accompanied by an increase in trimethylation of histone H3 on lysine (Κ-27 residue (H3K27me3 levels and that such response was, in part, dependent on decreased expression levels of phosphorylated Akt (ser473 (pAkt and phosphorylated EZH2 (ser21 (pEZH2. Additionally silibinin exerted other epigenetic effects involving an increase in total DNA methyltransferase (DNMT activity while it decreased histone deacetylases 1-2 (HDACs1-2 expression levels. We conclude that silibinin induces epigenetic alterations in human prostate cancer cells, suggesting that subsequent disruptions of central processes in chromatin conformation may account for some of its diverse anticancer effects.

  13. Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options.

    Science.gov (United States)

    Brown, Robert E; Naqvi, Syed; McGuire, Mary F; Buryanek, Jamie; Karni, Ron J

    2017-08-17

    Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation. However, the EZH2 pathway is amenable to low toxicity therapies designed to promote differentiation to a more benign state and prevent recurrent disease by inhibiting the incorporation of HPV into the genome. This is the first study using clinical specimens to demonstrate EZH2 protein expression in oropharyngeal carcinoma (OPC). The study included eight patients with oropharyngeal carcinoma, confirmed p16INK4a- positive by immunohistochemistry (IHC). The tissue expression of E6/E7 messenger RNA (mRNA) was measured by RNAscope® in-situ hybridization technology. Expression of EZH2, Ki-67, and mitotic indices were assessed by morphoproteomic analysis. Biomedical analytics expanded the results with data from Ingenuity Pathway Analysis (IPA) and KEGG databases to construct a molecular network pathway for further insights. Expression of E6 and E7 oncogenes in p16INK4a- positive oropharyngeal carcinoma was confirmed. EZH2 and its correlates, including elevated proliferation index (Ki-67) and mitotic progression were also present. Biomedical analytics validated the relationship between HPV- E6 and E7 and the expression of the EZH2 pathway. There is morphoproteomic and mRNA evidence of the association of p16INK4a-HPV infection with the E6 and E7 oncogenes and the expression of EZH2, Ki-67 and mitotic progression in oropharyngeal carcinoma. The molecular network biology was confirmed by

  14. Which finite simple groups are unit groups?

    DEFF Research Database (Denmark)

    Davis, Christopher James; Occhipinti, Tommy

    2014-01-01

    We prove that if G is a finite simple group which is the unit group of a ring, then G is isomorphic to either (a) a cyclic group of order 2; (b) a cyclic group of prime order 2^k −1 for some k; or (c) a projective special linear group PSLn(F2) for some n ≥ 3. Moreover, these groups do all occur a...

  15. Mutual Group Hypnosis: A Social Interaction Analysis.

    Science.gov (United States)

    Sanders, Shirley

    Mutual Group Hypnosis is discussed in terms of its similarity to group dynamics in general and in terms of its similarity to a social interaction program (Role Modeling) designed to foster the expression of warmth and acceptance among group members. Hypnosis also fosters a regression to prelogical thought processes in the service of the ego. Group…

  16. VEGF expression in hepatectomized tumor-bearing mice.

    Science.gov (United States)

    Andrini, L; Blanco, A Fernandez; Inda, A; García, M; Garcia, A; Errecalde, A

    2011-01-01

    The experiments were designed in order to study the VEGF expression in intact (group I), hepatectomized (group II), and hepatectomized-tumor bearing mice (group III) throughout one complete circadian time span. Adult male mice were used for the VEGF expression study. The statistical analysis was performed using analysis of variance (ANOVA). The results showed statistical differences in the VEGF expression between groups I and II, but the most significant differences were found between groups I and III. In conclusion, these expressions have a circadian rhythm in all groups; moreover, in group III, this expression was higher and appeared before than in the others.

  17. Blood Groups in Infection and Host Susceptibility.

    Science.gov (United States)

    Cooling, Laura

    2015-07-01

    Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Blood Groups in Infection and Host Susceptibility

    Science.gov (United States)

    2015-01-01

    SUMMARY Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome. PMID:26085552

  19. Group Cohesion in Experiential Growth Groups

    Science.gov (United States)

    Steen, Sam; Vasserman-Stokes, Elaina; Vannatta, Rachel

    2014-01-01

    This article explores the effect of web-based journaling on changes in group cohesion within experiential growth groups. Master's students were divided into 2 groups. Both used a web-based platform to journal after each session; however, only 1 of the groups was able to read each other's journals. Quantitative data collected before and…

  20. Group Work Publication-1991.

    Science.gov (United States)

    Zimpfer, David G.

    1992-01-01

    Lists 21 new publications in group work, of which 9 are reviewed. Those discussed include publications on group counseling and psychotherapy, structured groups, support groups, psychodrama, and social group work. (Author/NB)

  1. Quantum isometry groups

    Indian Academy of Sciences (India)

    Jyotishman Bhowmick

    2015-11-07

    Nov 7, 2015 ... Classical. Quantum. Background. Compact Hausdorff space. Unital C∗ algebra. Gelfand-Naimark. Compact Group. Compact Quantum Group. Woronowicz. Group Action. Coaction. Woronowicz. Riemannian manifold. Spectral triple. Connes. Isometry group. Quantum Isometry Group. To be discussed.

  2. Group typicality, group loyalty and cognitive development.

    Science.gov (United States)

    Patterson, Meagan M

    2014-09-01

    Over the course of childhood, children's thinking about social groups changes in a variety of ways. Developmental Subjective Group Dynamics (DSGD) theory emphasizes children's understanding of the importance of conforming to group norms. Abrams et al.'s study, which uses DSGD theory as a framework, demonstrates the social cognitive skills underlying young elementary school children's thinking about group norms. Future research on children's thinking about groups and group norms should explore additional elements of this topic, including aspects of typicality beyond loyalty. © 2014 The British Psychological Society.

  3. MUC1-C activates polycomb repressive complexes and downregulates tumor suppressor genes in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Kufe, Donald

    2018-04-01

    The PRC2 and PRC1 complexes are aberrantly expressed in human cancers and have been linked to decreases in patient survival. MUC1-C is an oncoprotein that is also overexpressed in diverse human cancers and is associated with a poor prognosis. Recent studies have supported a previously unreported function for MUC1-C in activating PRC2 and PRC1 in cancer cells. In the regulation of PRC2, MUC1-C (i) drives transcription of the EZH2 gene, (ii) binds directly to EZH2, and (iii) enhances occupancy of EZH2 on target gene promoters with an increase in H3K27 trimethylation. Regarding PRC1, which is recruited to PRC2 sites in the hierarchical model, MUC1-C induces BMI1 transcription, forms a complex with BMI1, and promotes H2A ubiquitylation. MUC1-C thereby contributes to the integration of PRC2 and PRC1-mediated repression of tumor suppressor genes, such as CDH1, CDKN2A, PTEN and BRCA1. Like PRC2 and PRC1, MUC1-C is associated with the epithelial-mesenchymal transition (EMT) program, cancer stem cell (CSC) state, and acquisition of anticancer drug resistance. In concert with these observations, targeting MUC1-C downregulates EZH2 and BMI1, inhibits EMT and the CSC state, and reverses drug resistance. These findings emphasize the significance of MUC1-C as a therapeutic target for inhibiting aberrant PRC function and reprogramming the epigenome in human cancers.

  4. AREVA group overview; Presentation du groupe AREVA

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-02-08

    This document presents the Group Areva, a world nuclear industry leader, from a financial holding company to an industrial group, operating in two businesses: the nuclear energy and the components. The structure and the market of the group are discussed, as the financial assets. (A.L.B.)

  5. Overgroups of root groups in classical groups

    CERN Document Server

    Aschbacher, Michael

    2016-01-01

    The author extends results of McLaughlin and Kantor on overgroups of long root subgroups and long root elements in finite classical groups. In particular he determines the maximal subgroups of this form. He also determines the maximal overgroups of short root subgroups in finite classical groups and the maximal overgroups in finite orthogonal groups of c-root subgroups.

  6. Interagency mechanical operations group numerical systems group

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    This report consists of the minutes of the May 20-21, 1971 meeting of the Interagency Mechanical Operations Group (IMOG) Numerical Systems Group. This group looks at issues related to numerical control in the machining industry. Items discussed related to the use of CAD and CAM, EIA standards, data links, and numerical control.

  7. Electroacupuncture at the Wangu acupoint suppresses expression ...

    African Journals Online (AJOL)

    Materials and Methods: The 54 healthy, male, Sprague-Dawley (SD) rats, 9 months old, and of clean grade (300-450) g, were randomly divided into three groups: sham surgery group, VD group and electro-acupuncture group. The ethology scores of VD rats were evaluated and the mRNA expressions of inflammatory ...

  8. Theory of Lie groups

    CERN Document Server

    Chevalley, Claude

    2018-01-01

    The standard text on the subject for many years, this introductory treatment covers classical linear groups, topological groups, manifolds, analytic groups, differential calculus of Cartan, and compact Lie groups and their representations. 1946 edition.

  9. Multiple group membership and well-being

    DEFF Research Database (Denmark)

    Sønderlund, Anders L.; Morton, Thomas A.; Ryan, Michelle K.

    2017-01-01

    multiple group membership and well-being, but only for individuals high in SIC. This effect was mediated by perceived identity expression and access to social support. Study 2 (N = 104) also found that multiple group memberships indirectly contributed to well-being via perceived identity expression......A growing body of research points to the value of multiple group memberships for individual well-being. However, much of this work considers group memberships very broadly and in terms of number alone. We conducted two correlational studies exploring how the relationship between multiple group...... and social support, as well as identity compatibility and perceived social inclusion. But, in this study the relationship between multiple group memberships and well-being outcomes was moderated by the perceived value and visibility of group memberships to others. Specifically, possessing multiple, devalued...

  10. Managing parental groups: personal impact of a group leadership course for child healthcare nurses.

    OpenAIRE

    Lefevre, Åsa; Lundqvist, Pia; Drevenhorn, Eva; Hallström, Inger

    2017-01-01

    AIMS AND OBJECTIVES: To investigate the experience and personal impact of a group leadership course for child healthcare nurses.BACKGROUND: During their child's first year, all parents in Sweden are invited to participate in parental groups within the child health service; however, only 49% choose to participate. Despite extensive experience, child healthcare nurses find managing parental groups challenging and express a need for training in group dynamics and group leadership.DESIGN: The stu...

  11. Group Milieu in systemic and psychodynamic group therapy

    DEFF Research Database (Denmark)

    Lau, Marianne Engelbrecht

    Objectives: A recent meta-analysis also concluded that psychotherapeutic approaches are beneficial for adult with a history of CSA and maintained for at least six months follow-up. The results suggest that different characteristics of therapy moderate the therapeutic outcome. We found in a random......Objectives: A recent meta-analysis also concluded that psychotherapeutic approaches are beneficial for adult with a history of CSA and maintained for at least six months follow-up. The results suggest that different characteristics of therapy moderate the therapeutic outcome. We found....... Methods: This randomized prospective study included 106 women: 52 assigned to psychodynamic group psychotherapy and 54 assigned to systemic group psychotherapy. The Group Environment Scale (GES) was filled in the mid phase of therapy and analysed in three dimensions and 10 subscales. Results: The systemic...... subscales: Cohesion (pLeader support (p=0.001), Expressiveness (p

  12. Introduction to Sporadic Groups

    Directory of Open Access Journals (Sweden)

    Luis J. Boya

    2011-01-01

    Full Text Available This is an introduction to finite simple groups, in particular sporadic groups, intended for physicists. After a short review of group theory, we enumerate the 1+1+16=18 families of finite simple groups, as an introduction to the sporadic groups. These are described next, in three levels of increasing complexity, plus the six isolated ''pariah'' groups. The (old five Mathieu groups make up the first, smallest order level. The seven groups related to the Leech lattice, including the three Conway groups, constitute the second level. The third and highest level contains the Monster group M, plus seven other related groups. Next a brief mention is made of the remaining six pariah groups, thus completing the 5+7+8+6=26 sporadic groups. The review ends up with a brief discussion of a few of physical applications of finite groups in physics, including a couple of recent examples which use sporadic groups.

  13. Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: A report from the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Chakravarti, Arnab; Winter, Kathryn M.S.; Wu, C.-L.; Kaufman, Donald; Hammond, Elizabeth; Parliament, Matthew; Tester, William; Hagan, Michael; Grignon, David; Heney, Niall; Pollack, Alan; Sandler, Howard; Shipley, William

    2005-01-01

    Purpose: Erb-1 (epidermal growth factor receptor, EGFR) and Erb-2 (Her-2) are two of the best characterized members in the EGFR pathway. In many tumor types, overexpression of these proteins is associated with enhanced malignant potential. Our objective in this study was to investigate the clinical relevance of EGFR and Her-2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group (RTOG) bladder preservation trials using cisplatin-containing chemoradiation (RTOG 8802, 8903, 9506, and 9706). Methods and materials: Tumors from 73 cases from patients with muscle-invading T2-T4a bladder cancers had slides interpretable for EGFR staining; 55 cases had slides interpretable for Her-2 staining. Additionally, the respective prognostic values of p53, pRB, and p16 immunostaining were concomitantly examined. Staining and interpretation of staining were done in a blinded manner, without knowledge of clinical outcome. Staining was judged as positive or negative. Subsequently, staining was correlated with clinical outcome. Results: On univariate analysis, EGFR positivity was significantly associated with improved overall survival (p = 0.044); disease-specific survival (DSS) (p = 0.042); and DSS with intact bladder (p = 0.021). There was also a trend for association between EGFR expression and reduced frequency of distant metastasis (p = 0.06). On multivariate analysis adding tumor stage, tumor grade, whether a visibly complete transurethral resection of bladder tumor (TURBT) was done or not, and patient age to the model, EGFR positivity was significantly associated with improved DSS. On univariate analysis, Her-2 positivity was significantly associated with reduced complete response (CR) rates (50% vs. 81%, p = 0.026) after chemoradiation which remained significant on multivariate analysis. The other markers examined in this study were not found to have any prognostic value in this setting. Conclusion: Epidermal growth factor receptor expression

  14. Main Memory Implementations for Binary Grouping

    OpenAIRE

    May, Norman; Moerkotte, Guido

    2005-01-01

    An increasing number of applications depend on efficient storage and analysis features for XML data. Hence, query optimization and efficient evaluation techniques for the emerging XQuery standard become more and more important. Many XQuery queries require nested expressions. Unnesting them often introduces binary grouping. We introduce several algorithms implementing binary grouping and analyze their time and space complexity. Experiments demonstrate their performance.

  15. Me against we: in-group transgression, collective shame, and in-group-directed hostility.

    Science.gov (United States)

    Piff, Paul K; Martinez, Andres G; Keltner, Dacher

    2012-01-01

    People can experience great distress when a group to which they belong (in-group) is perceived to have committed an immoral act. We hypothesised that people would direct hostility toward a transgressing in-group whose actions threaten their self-image and evoke collective shame. Consistent with this theorising, three studies found that reminders of in-group transgression provoked several expressions of in-group-directed hostility, including in-group-directed hostile emotion (Studies 1 and 2), in-group-directed derogation (Study 2), and in-group-directed punishment (Study 3). Across studies, collective shame-but not the related group-based emotion collective guilt-mediated the relationship between in-group transgression and in-group-directed hostility. Implications for group-based emotion, social identity, and group behaviour are discussed.

  16. Group Work: How to Use Groups Effectively

    Science.gov (United States)

    Burke, Alison

    2011-01-01

    Many students cringe and groan when told that they will need to work in a group. However, group work has been found to be good for students and good for teachers. Employers want college graduates to have developed teamwork skills. Additionally, students who participate in collaborative learning get better grades, are more satisfied with their…

  17. Free Boolean Topological Groups

    Directory of Open Access Journals (Sweden)

    Ol’ga Sipacheva

    2015-11-01

    Full Text Available Known and new results on free Boolean topological groups are collected. An account of the properties that these groups share with free or free Abelian topological groups and properties specific to free Boolean groups is given. Special emphasis is placed on the application of set-theoretic methods to the study of Boolean topological groups.

  18. Small Group Research

    Science.gov (United States)

    McGrath, Joseph E.

    1978-01-01

    Summarizes research on small group processes by giving a comprehensive account of the types of variables primarily studied in the laboratory. These include group structure, group composition, group size, and group relations. Considers effects of power, leadership, conformity to social norms, and role relationships. (Author/AV)

  19. The motivation to express prejudice

    Science.gov (United States)

    Forscher, Patrick S.; Cox, William T. L.; Graetz, Nicholas; Devine, Patricia G.

    2015-01-01

    Contemporary prejudice research focuses primarily on people who are motivated to respond without prejudice and the ways in which unintentional bias can cause these people to act inconsistent with this motivation. However, some real-world phenomena (e.g., hate speech, hate crimes) and experimental findings (e.g., Plant & Devine, 2001; 2009) suggest that some expressions of prejudice are intentional. These phenomena and findings are difficult to explain solely from the motivations to respond without prejudice. We argue that some people are motivated to express prejudice, and we develop the motivation to express prejudice (MP) scale to measure this motivation. In seven studies involving more than 6,000 participants, we demonstrate that, across scale versions targeted at Black people and gay men, the MP scale has good reliability and convergent, discriminant, and predictive validity. In normative climates that prohibit prejudice, the internal and external motivations to express prejudice are functionally non-independent, but they become more independent when normative climates permit more prejudice toward a target group. People high in the motivation to express prejudice are relatively likely to resist pressure to support programs promoting intergroup contact and vote for political candidates who support oppressive policies. The motivation to express prejudice predicted these outcomes even when controlling for attitudes and the motivations to respond without prejudice. This work encourages contemporary prejudice researchers to broaden the range of samples, target groups, and phenomena that they study, and more generally to consider the intentional aspects of negative intergroup behavior. PMID:26479365

  20. Gene-Transformation-Induced Changes in Chemical Functional Group Features and Molecular Structure Conformation in Alfalfa Plants Co-Expressing Lc-bHLH and C1-MYB Transcriptive Flavanoid Regulatory Genes: Effects of Single-Gene and Two-Gene Insertion.

    Science.gov (United States)

    Heendeniya, Ravindra G; Yu, Peiqiang

    2017-03-20

    Alfalfa ( Medicago sativa L.) genotypes transformed with Lc-bHLH and Lc transcription genes were developed with the intention of stimulating proanthocyanidin synthesis in the aerial parts of the plant. To our knowledge, there are no studies on the effect of single-gene and two-gene transformation on chemical functional groups and molecular structure changes in these plants. The objective of this study was to use advanced molecular spectroscopy with multivariate chemometrics to determine chemical functional group intensity and molecular structure changes in alfalfa plants when co-expressing Lc-bHLH and C1-MYB transcriptive flavanoid regulatory genes in comparison with non-transgenic (NT) and AC Grazeland (ACGL) genotypes. The results showed that compared to NT genotype, the presence of double genes ( Lc and C1 ) increased ratios of both the area and peak height of protein structural Amide I/II and the height ratio of α-helix to β-sheet. In carbohydrate-related spectral analysis, the double gene-transformed alfalfa genotypes exhibited lower peak heights at 1370, 1240, 1153, and 1020 cm -1 compared to the NT genotype. Furthermore, the effect of double gene transformation on carbohydrate molecular structure was clearly revealed in the principal component analysis of the spectra. In conclusion, single or double transformation of Lc and C1 genes resulted in changing functional groups and molecular structure related to proteins and carbohydrates compared to the NT alfalfa genotype. The current study provided molecular structural information on the transgenic alfalfa plants and provided an insight into the impact of transgenes on protein and carbohydrate properties and their molecular structure's changes.

  1. Geometric group theory

    CERN Document Server

    Druţu, Cornelia

    2018-01-01

    The key idea in geometric group theory is to study infinite groups by endowing them with a metric and treating them as geometric spaces. This applies to many groups naturally appearing in topology, geometry, and algebra, such as fundamental groups of manifolds, groups of matrices with integer coefficients, etc. The primary focus of this book is to cover the foundations of geometric group theory, including coarse topology, ultralimits and asymptotic cones, hyperbolic groups, isoperimetric inequalities, growth of groups, amenability, Kazhdan's Property (T) and the Haagerup property, as well as their characterizations in terms of group actions on median spaces and spaces with walls. The book contains proofs of several fundamental results of geometric group theory, such as Gromov's theorem on groups of polynomial growth, Tits's alternative, Stallings's theorem on ends of groups, Dunwoody's accessibility theorem, the Mostow Rigidity Theorem, and quasiisometric rigidity theorems of Tukia and Schwartz. This is the f...

  2. Profinite graphs and groups

    CERN Document Server

    Ribes, Luis

    2017-01-01

    This book offers a detailed introduction to graph theoretic methods in profinite groups and applications to abstract groups. It is the first to provide a comprehensive treatment of the subject. The author begins by carefully developing relevant notions in topology, profinite groups and homology, including free products of profinite groups, cohomological methods in profinite groups, and fixed points of automorphisms of free pro-p groups. The final part of the book is dedicated to applications of the profinite theory to abstract groups, with sections on finitely generated subgroups of free groups, separability conditions in free and amalgamated products, and algorithms in free groups and finite monoids. Profinite Graphs and Groups will appeal to students and researchers interested in profinite groups, geometric group theory, graphs and connections with the theory of formal languages. A complete reference on the subject, the book includes historical and bibliographical notes as well as a discussion of open quest...

  3. Group purchasing: an overview.

    Science.gov (United States)

    Wetrich, J G

    1987-07-01

    The various types and operational methods of purchasing groups are described, and evaluation of groups is discussed. Since group purchasing is increasing in popularity as a method of controlling drug costs, community and hospital pharmacy managers may need to evaluate various groups to determine the appropriateness of their services. Groups are categorized as independent, system based, or alliance or association based. Instead of "purchasing," some groups develop contracts for hospitals, which then purchase directly from the vendor. Aside from this basic difference between groups that purchase and groups that contract, comparisons among groups are difficult because of the wide variation in sizes and services. Competition developing from diversification among groups has led to "super groups," formed from local and regional groups. In evaluating groups, advantages and disadvantages germane to accomplishing the member's objectives must be considered. To ensure a group's success, members must be committed and support the group's philosophies; hospital pharmacists must help to establish a strong formulary system. To select vendors, groups should develop formal qualification and selection criteria and should not base a decision solely on price. The method of solicitation (bidding or negotiating), as well as the role of the prime vendor, should be studied. Legal implications of group purchasing, especially in the areas of administrative fees and drug diversion, must also be considered. The most advantageous group for each organization will include members with common missions and will be able to implement strategies for future success.

  4. The SSETI-express Mission

    DEFF Research Database (Denmark)

    Alminde, Lars; Bisgaard, Morten; Melville, N.

    In January 2004 a group of students met at the European Space Technology and Research Centre (ESTEC) in Holland to discuss the feasibility of building a micro-satellite, dubbed SSETI-Express, from parts derived from other student satellite projects and launch it within one and a half year...

  5. The SSETI-Express Mission

    DEFF Research Database (Denmark)

    Alminde, Lars; Bisgaard, Morten; Melville, Neil

    2005-01-01

    In January 2004 a group of students met at the European Space Technology and Research Centre (ESTEC) in Holland to discuss the feasibility of building a micro-satellite, dubbed SSETI-Express, from parts derived from other student satellite projects and launch it within one and a half year...

  6. Ordered groups and infinite permutation groups

    CERN Document Server

    1996-01-01

    The subjects of ordered groups and of infinite permutation groups have long en­ joyed a symbiotic relationship. Although the two subjects come from very different sources, they have in certain ways come together, and each has derived considerable benefit from the other. My own personal contact with this interaction began in 1961. I had done Ph. D. work on sequence convergence in totally ordered groups under the direction of Paul Conrad. In the process, I had encountered "pseudo-convergent" sequences in an ordered group G, which are like Cauchy sequences, except that the differences be­ tween terms of large index approach not 0 but a convex subgroup G of G. If G is normal, then such sequences are conveniently described as Cauchy sequences in the quotient ordered group GIG. If G is not normal, of course GIG has no group structure, though it is still a totally ordered set. The best that can be said is that the elements of G permute GIG in an order-preserving fashion. In independent investigations around that t...

  7. ALIGNMENTS OF GROUP GALAXIES WITH NEIGHBORING GROUPS

    International Nuclear Information System (INIS)

    Wang Yougang; Chen Xuelei; Park, Changbom; Yang Xiaohu; Choi, Yun-Young

    2009-01-01

    Using a sample of galaxy groups found in the Sloan Digital Sky Survey Data Release 4, we measure the following four types of alignment signals: (1) the alignment between the distributions of the satellites of each group relative to the direction of the nearest neighbor group (NNG); (2) the alignment between the major axis direction of the central galaxy of the host group (HG) and the direction of the NNG; (3) the alignment between the major axes of the central galaxies of the HG and the NNG; and (4) the alignment between the major axes of the satellites of the HG and the direction of the NNG. We find strong signal of alignment between the satellite distribution and the orientation of central galaxy relative to the direction of the NNG, even when the NNG is located beyond 3r vir of the host group. The major axis of the central galaxy of the HG is aligned with the direction of the NNG. The alignment signals are more prominent for groups that are more massive and with early-type central galaxies. We also find that there is a preference for the two major axes of the central galaxies of the HG and NNG to be parallel for the system with both early central galaxies, however, not for the systems with both late-type central galaxies. For the orientation of satellite galaxies, we do not find any significant alignment signals relative to the direction of the NNG. From these four types of alignment measurements, we conclude that the large-scale environment traced by the nearby group affects primarily the shape of the host dark matter halo, and hence also affects the distribution of satellite galaxies and the orientation of central galaxies. In addition, the NNG directly affects the distribution of the satellite galaxies by inducing asymmetric alignment signals, and the NNG at very small separation may also contribute a second-order impact on the orientation of the central galaxy in the HG.

  8. Citizens' action group

    International Nuclear Information System (INIS)

    Andritzky, W.

    1978-01-01

    For the first empirical study of citizens' action groups 331 such groups were consulted. Important information was collected on the following aspects of these groups: their self-image, areas and forms of activities, objectives and their extent, how long the group has existed, successes and failures and their forms of organisation. (orig.) [de

  9. Communication in Organizational Groups

    OpenAIRE

    Monica RADU

    2007-01-01

    Organizational group can be defined as some persons between who exist interactive connections (functional, communication, affective, normative type). Classification of these groups can reflect the dimension, type of relationship or type of rules included. Organizational groups and their influence over the individual efficiency and the efficiency of the entire group are interconnected. Spontaneous roles in these groups sustain the structure of the relationship, and the personality of each indi...

  10. [Social crisis, spontaneous groups and group order].

    Science.gov (United States)

    Edelman, Lucila; Kordon, Diana

    2002-12-01

    Argentina has gone through very difficult times during the last years and, in particularly, new kinds of social practices have emerged in order to cope with the crisis. This situation demands and urges a new type of reflection upon the double role of groups, as tools to transform reality and as a way to elaborate those processes regarding subjectivity. In this paper we analyse some topics regarding the groupal field (considering spontaneous groups as well as groupal devices that allow to elaborate the crisis). We consider social bond to be the condition of possibility for the existence of the psyche and of time continuity, and that it also makes possible personal and social elaboration of trauma, crisis and social catastrophe. We develop some aspects of an specific device (the reflection group), which we have already depicted in another moment, showing it's usefulness to cope with social crisis and to promote the subjective elaboration of crisis.

  11. Quantum group and quantum symmetry

    International Nuclear Information System (INIS)

    Chang Zhe.

    1994-05-01

    This is a self-contained review on the theory of quantum group and its applications to modern physics. A brief introduction is given to the Yang-Baxter equation in integrable quantum field theory and lattice statistical physics. The quantum group is primarily introduced as a systematic method for solving the Yang-Baxter equation. Quantum group theory is presented within the framework of quantum double through quantizing Lie bi-algebra. Both the highest weight and the cyclic representations are investigated for the quantum group and emphasis is laid on the new features of representations for q being a root of unity. Quantum symmetries are explored in selected topics of modern physics. For a Hamiltonian system the quantum symmetry is an enlarged symmetry that maintains invariance of equations of motion and allows a deformation of the Hamiltonian and symplectic form. The configuration space of the integrable lattice model is analyzed in terms of the representation theory of quantum group. By means of constructing the Young operators of quantum group, the Schroedinger equation of the model is transformed to be a set of coupled linear equations that can be solved by the standard method. Quantum symmetry of the minimal model and the WZNW model in conformal field theory is a hidden symmetry expressed in terms of screened vertex operators, and has a deep interplay with the Virasoro algebra. In quantum group approach a complete description for vibrating and rotating diatomic molecules is given. The exact selection rules and wave functions are obtained. The Taylor expansion of the analytic formulas of the approach reproduces the famous Dunham expansion. (author). 133 refs, 20 figs

  12. Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the epithelial–mesenchymal transition via enhancer of zeste homolog 2 in the malignant transformation of HBE cells induced by cigarette smoke extract

    International Nuclear Information System (INIS)

    Lu, Lu; Luo, Fei; Liu, Yi; Liu, Xinlu; Shi, Le; Lu, Xiaolin; Liu, Qizhan

    2015-01-01

    Lung cancer is regarded as the leading cause of cancer-related deaths, and cigarette smoking is one of the strongest risk factors for the development of lung cancer. However, the mechanisms for cigarette smoke-induced lung carcinogenesis remain unclear. The present study investigated the effects of an miRNA (miR-217) on levels of an lncRNA (MALAT1) and examined the role of these factors in the epithelial–mesenchymal transition (EMT) induced by cigarette smoke extract (CSE) in human bronchial epithelial (HBE) cells. In these cells, CSE caused decreases of miR-217 levels and increases in lncRNA MALAT1 levels. Over-expression of miR-217 with a mimic attenuated the CSE-induced increase of MALAT1 levels, and reduction of miR-217 levels by an inhibitor enhanced expression of MALAT1. Moreover, the CSE-induced increase of MALAT1 expression was blocked by an miR-217 mimic, indicating that miR-217 negatively regulates MALAT1 expression. Knockdown of MALAT1 reversed CSE-induced increases of EZH2 (enhancer of zeste homolog 2) and H3K27me3 levels. In addition to the alteration from epithelial to spindle-like mesenchymal morphology, chronic exposure of HBE cells to CSE increased the levels of EZH2, H3K27me3, vimentin, and N-cadherin and decreased E-cadherin levels, effects that were reversed by MALAT1 siRNA or EZH2 siRNA. The results indicate that miR-217 regulation of EZH2/H3K27me3 via MALAT1 is involved in CSE-induced EMT and malignant transformation of HBE cells. The posttranscriptional silencing of MALAT1 by miR-217 provides a link, through EZH2, between ncRNAs and the EMT and establishes a mechanism for CSE-induced lung carcinogenesis. - Highlights: • CSE exposure decreases miR-217 levels and increases MALAT1 levels. • miR-217 negatively regulates MALAT1 expression. • MALAT1, via EZH2, is involved in the EMT of CSE-transformed HBE cells.

  13. Impaired detection of happy facial expressions in autism.

    Science.gov (United States)

    Sato, Wataru; Sawada, Reiko; Uono, Shota; Yoshimura, Sayaka; Kochiyama, Takanori; Kubota, Yasutaka; Sakihama, Morimitsu; Toichi, Motomi

    2017-10-17

    The detection of emotional facial expressions plays an indispensable role in social interaction. Psychological studies have shown that typically developing (TD) individuals more rapidly detect emotional expressions than neutral expressions. However, it remains unclear whether individuals with autistic phenotypes, such as autism spectrum disorder (ASD) and high levels of autistic traits (ATs), are impaired in this ability. We examined this by comparing TD and ASD individuals in Experiment 1 and individuals with low and high ATs in Experiment 2 using the visual search paradigm. Participants detected normal facial expressions of anger and happiness and their anti-expressions within crowds of neutral expressions. In Experiment 1, reaction times were shorter for normal angry expressions than for anti-expressions in both TD and ASD groups. This was also the case for normal happy expressions vs. anti-expressions in the TD group but not in the ASD group. Similarly, in Experiment 2, the detection of normal vs. anti-expressions was faster for angry expressions in both groups and for happy expressions in the low, but not high, ATs group. These results suggest that the detection of happy facial expressions is impaired in individuals with ASD and high ATs, which may contribute to their difficulty in creating and maintaining affiliative social relationships.

  14. Introduction to topological groups

    CERN Document Server

    Husain, Taqdir

    2018-01-01

    Concise treatment covers semitopological groups, locally compact groups, Harr measure, and duality theory and some of its applications. The volume concludes with a chapter that introduces Banach algebras. 1966 edition.

  15. MSUD Family Support Group

    Science.gov (United States)

    ... The Treatment Of MSUD The MSUD Family Support Group has provided funds to Buck Institute for its ... of the membership of the MSUD Family Support Group, research for improved treatments and potential cure was ...

  16. Nilpotent -local finite groups

    Science.gov (United States)

    Cantarero, José; Scherer, Jérôme; Viruel, Antonio

    2014-10-01

    We provide characterizations of -nilpotency for fusion systems and -local finite groups that are inspired by known result for finite groups. In particular, we generalize criteria by Atiyah, Brunetti, Frobenius, Quillen, Stammbach and Tate.

  17. UPIN Group File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Group Unique Physician Identifier Number (UPIN) File is the business entity file that contains the group practice UPIN and descriptive information. It does NOT...

  18. Group Decision Process Support

    DEFF Research Database (Denmark)

    Gøtze, John; Hijikata, Masao

    1997-01-01

    Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists.......Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists....

  19. Gestalt Interactional Groups

    Science.gov (United States)

    Harman, Robert L.; Franklin, Richard W.

    1975-01-01

    Gestalt therapy in groups is not limited to individual work in the presence of an audience. Describes several ways to involve gestalt groups interactionally. Interactions described focus on learning by doing and discovering, and are noninterpretive. (Author/EJT)

  20. Group B streptococcus - pregnancy

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000511.htm Group B streptococcus - pregnancy To use the sharing features on this page, please enable JavaScript. Group B streptococcus (GBS) is a type of bacteria that some ...

  1. Gene Expression and Microarray Investigation of Dendrobium ...

    African Journals Online (AJOL)

    blood glucose > 16.7 mmol/L were used as the model group and treated with Dendrobium mixture. (DEN ... Keywords: Diabetes, Gene expression, Dendrobium mixture, Microarray testing ..... homeostasis in airway smooth muscle. Am J.

  2. Finite groups and quantum physics

    International Nuclear Information System (INIS)

    Kornyak, V. V.

    2013-01-01

    Concepts of quantum theory are considered from the constructive “finite” point of view. The introduction of a continuum or other actual infinities in physics destroys constructiveness without any need for them in describing empirical observations. It is shown that quantum behavior is a natural consequence of symmetries of dynamical systems. The underlying reason is that it is impossible in principle to trace the identity of indistinguishable objects in their evolution—only information about invariant statements and values concerning such objects is available. General mathematical arguments indicate that any quantum dynamics is reducible to a sequence of permutations. Quantum phenomena, such as interference, arise in invariant subspaces of permutation representations of the symmetry group of a dynamical system. Observable quantities can be expressed in terms of permutation invariants. It is shown that nonconstructive number systems, such as complex numbers, are not needed for describing quantum phenomena. It is sufficient to employ cyclotomic numbers—a minimal extension of natural numbers that is appropriate for quantum mechanics. The use of finite groups in physics, which underlies the present approach, has an additional motivation. Numerous experiments and observations in the particle physics suggest the importance of finite groups of relatively small orders in some fundamental processes. The origin of these groups is unclear within the currently accepted theories—in particular, within the Standard Model.

  3. Multicultural group work

    DEFF Research Database (Denmark)

    Hansen, Annette Skovsted

    2014-01-01

    Motivation for the activity I use this strategy for forming groups to ensure diverse/multicultural groups that combine a variety of different strengths and resources based on student's academic, disciplinary, linguistic, national, personal and work backgrounds.......Motivation for the activity I use this strategy for forming groups to ensure diverse/multicultural groups that combine a variety of different strengths and resources based on student's academic, disciplinary, linguistic, national, personal and work backgrounds....

  4. Adaptive Evolution of Gene Expression in Drosophila

    Directory of Open Access Journals (Sweden)

    Armita Nourmohammad

    2017-08-01

    Full Text Available Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.

  5. The Areva Group; Le groupe Areva

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-08-01

    This document provides information on the Areva Group, a world nuclear industry leader, offering solutions for nuclear power generation, electricity transmission and distribution and interconnect systems to the telecommunications, computer and automotive markets. It presents successively the front end division including the group business lines involved in producing nuclear fuel for electric power generation (uranium mining, concentration, conversion and enrichment and nuclear fuel fabrication); the reactors and services division which designs and builds PWR, BWR and research reactors; the back end division which encompasses the management of the fuel that has been used in nuclear power plants; the transmission and distribution division which provides products, systems and services to the medium and high voltage energy markets; the connectors division which designs and manufactures electrical, electronic and optical connectors, flexible micro circuitry and interconnection systems. Areva is implemented in Europe, north and south america, africa and asia-pacific. (A.L.B.)

  6. Groups, combinatorics and geometry

    CERN Document Server

    Ivanov, A A; Saxl, J

    2003-01-01

    Over the past 20 years, the theory of groups in particular simplegroups, finite and algebraic has influenced a number of diverseareas of mathematics. Such areas include topics where groups have beentraditionally applied, such as algebraic combinatorics, finitegeometries, Galois theory and permutation groups, as well as severalmore recent developments.

  7. Working Group 7 Summary

    Energy Technology Data Exchange (ETDEWEB)

    Nagaitsev S.; Berg J.

    2012-06-10

    The primary subject of working group 7 at the 2012 Advanced Accelerator Concepts Workshop was muon accelerators for a muon collider or neutrino factory. Additionally, this working group included topics that did not fit well into other working groups. Two subjects were discussed by more than one speaker: lattices to create a perfectly integrable nonlinear lattice, and a Penning trap to create antihydrogen.

  8. AREVA group overview

    International Nuclear Information System (INIS)

    2002-01-01

    This document presents the Group Areva, a world nuclear industry leader, from a financial holding company to an industrial group, operating in two businesses: the nuclear energy and the components. The structure and the market of the group are discussed, as the financial assets. (A.L.B.)

  9. Group Psychotherapy in Denmark.

    Science.gov (United States)

    Jørgensen, Lars Bo; Thygesen, Bente; Aagaard, Søren

    2015-10-01

    This is a short article on the history and training standards in the Institute of Group Analysis in Copenhagen (IGA-CPH). We describe theoretical orientations and influences in the long-term training program and new initiatives, like courses in mentalization-based group treatment and a dynamic short-term group therapy course, as well as research in group psychotherapy in Denmark. Some group analytic initiatives in relation to social issues and social welfare are presented, as well as initiatives concerning the school system and unemployment.

  10. Group theory I essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Group Theory I includes sets and mapping, groupoids and semi-groups, groups, isomorphisms and homomorphisms, cyclic groups, the Sylow theorems, and finite p-groups.

  11. Lectures on Chevalley groups

    CERN Document Server

    Steinberg, Robert

    2016-01-01

    Robert Steinberg's Lectures on Chevalley Groups were delivered and written during the author's sabbatical visit to Yale University in the 1967-1968 academic year. The work presents the status of the theory of Chevalley groups as it was in the mid-1960s. Much of this material was instrumental in many areas of mathematics, in particular in the theory of algebraic groups and in the subsequent classification of finite groups. This posthumous edition incorporates additions and corrections prepared by the author during his retirement, including a new introductory chapter. A bibliography and editorial notes have also been added. This is a great unsurpassed introduction to the subject of Chevalley groups that influenced generations of mathematicians. I would recommend it to anybody whose interests include group theory. -Efim Zelmanov, University of California, San Diego Robert Steinberg's lectures on Chevalley groups were given at Yale University in 1967. The notes for the lectures contain a wonderful exposition of ...

  12. E-groups training

    CERN Multimedia

    HR Department

    2012-01-01

    There will be an e-groups training course on 16 March 2012 which will cover the main e-groups functionalities i.e.: creating and managing e-groups, difference between static and dynamic e-groups, configuring posting restrictions and archives, examples of where e-groups can be used in daily work. Even if you have already worked with e-groups, this may be a good opportunity to learn about the best practices and security related recommendations when using e-groups. You can find more details as well as enrolment form for the training (it’s free) here. The number of places is limited, so enrolling early is recommended.   Technical Training Tel. 72844

  13. Expression of CD133 in acute leukemia.

    Science.gov (United States)

    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.

  14. Filtrations of free groups as intersections

    OpenAIRE

    Efrat, Ido

    2013-01-01

    For several natural filtrations of a free group S we express the n-th term of the filtration as the intersection of all kernels of homomorphisms from S to certain groups of upper-triangular unipotent matrices. This generalizes a classical result of Grun for the lower central filtration. In particular, we do this for the n-th term in the lower p-central filtration of S.

  15. Group Psychotherapy in Italy.

    Science.gov (United States)

    Giannone, Francesca; Giordano, Cecilia; Di Blasi, Maria

    2015-10-01

    This article describes the history and the prevailing orientations of group psychotherapy in Italy (psychoanalytically oriented, psychodrama, CBT groups) and particularly group analysis. Provided free of charge by the Italian health system, group psychotherapy is growing, but its expansion is patchy. The main pathways of Italian training in the different group psychotherapy orientations are also presented. Clinical-theoretical elaboration on self development, psychopathology related to group experiences, and the methodological attention paid to objectives and methods in different clinical groups are issues related to group therapy in Italy. Difficulties in the relationship between research and clinical practice are discussed, as well as the empirical research network that tries to bridge the gap between research and clinical work in group psychotherapy. The economic crisis in Italy has led to massive cuts in health care and to an increasing demand for some forms of psychological treatment. For these reasons, and because of its positive cost-benefit ratio, group psychotherapy is now considered an important tool in the national health care system to expand the clinical response to different forms of psychological distress.

  16. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko

    2015-12-23

    Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

  17. Geometric group theory

    CERN Document Server

    Bestvina, Mladen; Vogtmann, Karen

    2014-01-01

    Geometric group theory refers to the study of discrete groups using tools from topology, geometry, dynamics and analysis. The field is evolving very rapidly and the present volume provides an introduction to and overview of various topics which have played critical roles in this evolution. The book contains lecture notes from courses given at the Park City Math Institute on Geometric Group Theory. The institute consists of a set of intensive short courses offered by leaders in the field, designed to introduce students to exciting, current research in mathematics. These lectures do not duplicate standard courses available elsewhere. The courses begin at an introductory level suitable for graduate students and lead up to currently active topics of research. The articles in this volume include introductions to CAT(0) cube complexes and groups, to modern small cancellation theory, to isometry groups of general CAT(0) spaces, and a discussion of nilpotent genus in the context of mapping class groups and CAT(0) gro...

  18. Asserive Training in Groups Using Video Feedback

    Science.gov (United States)

    Galassi, John P.; And Others

    1974-01-01

    The study investigated the effectiveness of group assertive training with nonassertive college students. Significant differences were found between experimental and control subjects on the College Self-Expression Scale, the Subjective Unit of Disturbance Scale, eye contact, length of scene, and assertive content but not on response latency.…

  19. Using Creative Group Techniques in High Schools

    Science.gov (United States)

    Veach, Laura J.; Gladding, Samuel T.

    2007-01-01

    Groups in high schools that use creative techniques help adolescents express their emotions appropriately, behave differently, and gain insight into themselves and others. This article looks at seven different creative arts media--music, movement, visual art, literature, drama, play, and humor--and offers examples of how they can be used in groups…

  20. CLASSIFICATION OF CRIMINAL GROUPS

    OpenAIRE

    Natalia Romanova

    2013-01-01

    New types of criminal groups are emerging in modern society.  These types have their special criminal subculture. The research objective is to develop new parameters of classification of modern criminal groups, create a new typology of criminal groups and identify some features of their subculture. Research methodology is based on the system approach that includes using the method of analysis of documentary sources (materials of a criminal case), method of conversations with themembers of the...

  1. Group therapy for adolescents

    OpenAIRE

    Nada Hribar

    2001-01-01

    The group included adolescents from secondary school and some students. The group had weekly sessions or twice on mounth. The adolescents had varied simptoms: depressive, anxiety, psychosomatic disorders, learning difficulties, cunduct problems. All of adolescents were common on many problems in social interactions. The goal of therapeutic work were: to increase assertiveness skills and to reduce the anxious in social situations. The adolescents in group raised a self-esteem and developed som...

  2. Presentations of groups

    CERN Document Server

    Johnson, D L

    1997-01-01

    The aim of this book is to provide an introduction to combinatorial group theory. Any reader who has completed first courses in linear algebra, group theory and ring theory will find this book accessible. The emphasis is on computational techniques but rigorous proofs of all theorems are supplied. This new edition has been revised throughout, including new exercises and an additional chapter on proving that certain groups are infinite.

  3. Group-Server Queues

    OpenAIRE

    Li, Quan-Lin; Ma, Jing-Yu; Xie, Mingzhou; Xia, Li

    2017-01-01

    By analyzing energy-efficient management of data centers, this paper proposes and develops a class of interesting {\\it Group-Server Queues}, and establishes two representative group-server queues through loss networks and impatient customers, respectively. Furthermore, such two group-server queues are given model descriptions and necessary interpretation. Also, simple mathematical discussion is provided, and simulations are made to study the expected queue lengths, the expected sojourn times ...

  4. Environmental groups in politics

    International Nuclear Information System (INIS)

    Lowe, P.; Goyder, J.

    1983-01-01

    The subject is covered in chapters, entitled: introduction; (Part I) the environmental movement (environmental groups and the attentive public; the episodic development of the environmental movement; the underlying values of environmentalism; the roots of environmental concern; the social limits to growth; elite manipulation of values); the organisation of environmental groups; environmental groups in national politics; environmental groups in local politics; (Part II) the Henley Society; Friends of the Earth; the National Trust; the Royal Society for Nature Conservation; the European Environmental Bureau. (U.K.)

  5. Complex quantum groups

    International Nuclear Information System (INIS)

    Drabant, B.; Schlieker, M.

    1993-01-01

    The complex quantum groups are constructed. They are q-deformations of the real Lie groups which are obtained as the complex groups corresponding to the Lie algebras of type A n-1 , B n , C n . Following the ideas of Faddeev, Reshetikhin and Takhtajan Hopf algebras of regular functionals U R for these complexified quantum groups are constructed. One has thus in particular found a construction scheme for the q-Lorentz algebra to be identified as U(sl q (2,C). (orig.)

  6. Explosive Technology Group

    Data.gov (United States)

    Federal Laboratory Consortium — The Explosive Technology Group (ETG) provides diverse technical expertise and an agile, integrated approach to solve complex challenges for all classes of energetic...

  7. Study Groups in Denmark

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    2007-01-01

    Since 1998 European Study Groups have been held in Denmark, and Danish companies from LEGO and NOVO to very small high-tech firms have participated. I briefly describe the history, the organisation and the format of the Danish Study Groups, and highlight a few problem solutions.......Since 1998 European Study Groups have been held in Denmark, and Danish companies from LEGO and NOVO to very small high-tech firms have participated. I briefly describe the history, the organisation and the format of the Danish Study Groups, and highlight a few problem solutions....

  8. Lie groups for pedestrians

    CERN Document Server

    Lipkin, Harry J

    2002-01-01

    According to the author of this concise, high-level study, physicists often shy away from group theory, perhaps because they are unsure which parts of the subject belong to the physicist and which belong to the mathematician. However, it is possible for physicists to understand and use many techniques which have a group theoretical basis without necessarily understanding all of group theory. This book is designed to familiarize physicists with those techniques. Specifically, the author aims to show how the well-known methods of angular momentum algebra can be extended to treat other Lie group

  9. The normal holonomy group

    International Nuclear Information System (INIS)

    Olmos, C.

    1990-05-01

    The restricted holonomy group of a Riemannian manifold is a compact Lie group and its representation on the tangent space is a product of irreducible representations and a trivial one. Each one of the non-trivial factors is either an orthogonal representation of a connected compact Lie group which acts transitively on the unit sphere or it is the isotropy representation of a single Riemannian symmetric space of rank ≥ 2. We prove that, all these properties are also true for the representation on the normal space of the restricted normal holonomy group of any submanifold of a space of constant curvature. 4 refs

  10. Youth Armed Groups in Colombia

    Directory of Open Access Journals (Sweden)

    Linda Dale

    2014-09-01

    Full Text Available For the many years of Colombia’s civil war, youth have been trying to find their way in complicated and dangerous situations. A central component of this is their relationship with armed groups, something that has evolved considerably over the past ten years. This practice note examines the context within which these connections are formed and the implications this has for self/social identity and meaningful resistance. The ideas in this practice note are based on consultations with young Colombians, particularly those displaced from 2000-2013. These sessions included art activities, focus groups and individual interviews. Art activities involved descriptive and expressive projects so that participants could explore their feelings and memories of situations and experiences. This provided a base for group discussions where youth exchanged information and debated issues. A total of 34 workshops were held over a twelve year period. These consultations revealed how war flows all over young people, touching every aspect of their identity. The boundaries between the personal and political no longer exist in today’s civil wars, if indeed they every truly did. Young people growing up inside Colombia’s war understand this at a deep level. An acknowledgement of this pain – showing the connections between the personal and political dimensions of war – is, they would maintain, the basis for their personal healing as well as an important tool for the building of sustainable peace.

  11. Trajectory grouping structure

    Directory of Open Access Journals (Sweden)

    Maike Buchin

    2015-03-01

    Full Text Available The collective motion of a set of moving entities like people, birds, or other animals, is characterized by groups arising, merging, splitting, and ending. Given the trajectories of these entities, we define and model a structure that captures all of such changes using the Reeb graph, a concept from topology. The trajectory grouping structure has three natural parameters that allow more global views of the data in group size, group duration, and entity inter-distance. We prove complexity bounds on the maximum number of maximal groups that can be present, and give algorithms to compute the grouping structure efficiently. We also study how the trajectory grouping structure can be made robust, that is, how brief interruptions of groups can be disregarded in the global structure, adding a notion of persistence to the structure. Furthermore, we showcase the results of experiments using data generated by the NetLogo flocking model and from the Starkey project. The Starkey data describe the movement of elk, deer, and cattle. Although there is no ground truth for the grouping structure in this data, the experiments show that the trajectory grouping structure is plausible and has the desired effects when changing the essential parameters. Our research provides the first complete study of trajectory group evolvement, including combinatorial,algorithmic, and experimental results.

  12. Express web application development

    CERN Document Server

    Yaapa, Hage

    2013-01-01

    Express Web Application Development is a practical introduction to learning about Express. Each chapter introduces you to a different area of Express, using screenshots and examples to get you up and running as quickly as possible.If you are looking to use Express to build your next web application, ""Express Web Application Development"" will help you get started and take you right through to Express' advanced features. You will need to have an intermediate knowledge of JavaScript to get the most out of this book.

  13. Computational methods working group

    International Nuclear Information System (INIS)

    Gabriel, T.A.

    1997-09-01

    During the Cold Moderator Workshop several working groups were established including one to discuss calculational methods. The charge for this working group was to identify problems in theory, data, program execution, etc., and to suggest solutions considering both deterministic and stochastic methods including acceleration procedures.

  14. GroupFinder

    DEFF Research Database (Denmark)

    Bøgh, Kenneth Sejdenfaden; Skovsgaard, Anders; Jensen, Christian S.

    2013-01-01

    . Such groups are relevant to users who wish to conveniently explore several options before making a decision such as to purchase a specific product. Specifically, we demonstrate a practical proposal for finding top-k PoI groups in response to a query. We show how problem parameter settings can be mapped...

  15. Toleration, Groups, and Multiculturalism

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    have the ability to interfere with the group’s activities, an object of dislike or disapproval, an agent enjoying non-interference or a moral patient. This means that 'toleration of groups' can mean quite different things depending on the exact meaning of 'group' in relation to each component...

  16. Group B Strep Infection

    Science.gov (United States)

    ... IV) to kill the germs. If you take antibiotics while you’re in labor, the chances are very good that your baby won’t get this infection. What if my baby has group B strep? If your baby gets group B strep, he or she will be treated with IV antibiotics to kill the bacteria. Your baby will stay ...

  17. Group Process as Drama.

    Science.gov (United States)

    McLeod, John

    1984-01-01

    Suggests that drama, as well as training or therapy, may be employed as a useful research and practice paradigm in working with small groups. The implications of this view for group development as a whole, and for member and leader participation, are explored. (JAC)

  18. Group Work. Research Brief

    Science.gov (United States)

    Walker, Karen

    2010-01-01

    According to Johnson and Johnson, group work helps increase student retention and satisfaction, develops strong oral communication and social skills, as well as higher self-esteem (University of Minnesota, n.d.). Group work, when planned and implemented deliberately and thoughtfully helps students develop cognitive and leadership skills as well as…

  19. Physically detached 'compact groups'

    Science.gov (United States)

    Hernquist, Lars; Katz, Neal; Weinberg, David H.

    1995-01-01

    A small fraction of galaxies appear to reside in dense compact groups, whose inferred crossing times are much shorter than a Hubble time. These short crossing times have led to considerable disagreement among researchers attempting to deduce the dynamical state of these systems. In this paper, we suggest that many of the observed groups are not physically bound but are chance projections of galaxies well separated along the line of sight. Unlike earlier similar proposals, ours does not require that the galaxies in the compact group be members of a more diffuse, but physically bound entity. The probability of physically separated galaxies projecting into an apparent compact group is nonnegligible if most galaxies are distributed in thin filaments. We illustrate this general point with a specific example: a simulation of a cold dark matter universe, in which hydrodynamic effects are included to identify galaxies. The simulated galaxy distribution is filamentary and end-on views of these filaments produce apparent galaxy associations that have sizes and velocity dispersions similar to those of observed compact groups. The frequency of such projections is sufficient, in principle, to explain the observed space density of groups in the Hickson catalog. We discuss the implications of our proposal for the formation and evolution of groups and elliptical galaxies. The proposal can be tested by using redshift-independent distance estimators to measure the line-of-sight spatial extent of nearby compact groups.

  20. Introduction to quantum groups

    International Nuclear Information System (INIS)

    Sudbery, A.

    1996-01-01

    These pedagogical lectures contain some motivation for the study of quantum groups; a definition of ''quasi triangular Hopf algebra'' with explanations of all the concepts required to build it up; descriptions of quantised universal enveloping algebras and the quantum double; and an account of quantised function algebras and the action of quantum groups on quantum spaces. (author)

  1. Beam dynamics group summary

    International Nuclear Information System (INIS)

    Peggs, S.

    1994-01-01

    This paper summarizes the activities of the beam dynamics working group of the LHC Collective Effects Workshop that was held in Montreux in 1994. It reviews the presentations that were made to the group, the discussions that ensued, and the consensuses that evolved

  2. Our Deming Users' Group.

    Science.gov (United States)

    Dinklocker, Christina

    1992-01-01

    After training in the Total Quality Management concept, a suburban Ohio school district created a Deming Users' Group to link agencies, individuals, and ideas. The group has facilitated ongoing school/business collaboration, networking among individuals from diverse school systems, mentoring and cooperative learning activities, and resource…

  3. Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

    Science.gov (United States)

    Rhodes, Daniel R; Sanda, Martin G; Otte, Arie P; Chinnaiyan, Arul M; Rubin, Mark A

    2003-05-07

    Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). EZH2:ECAD status was statistically significantly associated

  4. Asymmetry within social groups

    DEFF Research Database (Denmark)

    Barker, Jessie; Loope, Kevin J.; Reeve, H. Kern

    2016-01-01

    Social animals vary in their ability to compete with group members over shared resources and also vary in their cooperative efforts to produce these resources. Competition among groups can promote within-group cooperation, but many existing models of intergroup cooperation do not explicitly account...... of two roles, with relative competitive efficiency and the number of individuals varying between roles. Players in each role make simultaneous, coevolving decisions. The model predicts that although intergroup competition increases cooperative contributions to group resources by both roles, contributions...... are predominantly from individuals in the less competitively efficient role, whereas individuals in the more competitively efficient role generally gain the larger share of these resources. When asymmetry in relative competitive efficiency is greater, a group's per capita cooperation (averaged across both roles...

  5. Supervision and group dynamics

    DEFF Research Database (Denmark)

    Hansen, Søren; Jensen, Lars Peter

    2004-01-01

     An important aspect of the problem based and project organized study at Aalborg University is the supervision of the project groups. At the basic education (first year) it is stated in the curriculum that part of the supervisors' job is to deal with group dynamics. This is due to the experience...... that many students are having difficulties with practical issues such as collaboration, communication, and project management. Most supervisors either ignore this demand, because they do not find it important or they find it frustrating, because they do not know, how to supervise group dynamics...... as well as at Aalborg University. The first visible result has been participating supervisors telling us that the course has inspired them to try supervising group dynamics in the future. This paper will explore some aspects of supervising group dynamics as well as, how to develop the Aalborg model...

  6. Summary of group discussions

    International Nuclear Information System (INIS)

    2009-01-01

    A key aspect of the workshop was the interaction and exchange of ideas and information among the 40 participants. To facilitate this activity the workshop participants were divided into five discussions groups. These groups reviewed selected subjects and reported back to the main body with summaries of their considerations. Over the 3 days the 5 discussion groups were requested to focus on the following subjects: the characteristics and capabilities of 'good' organisations; how to ensure sufficient resources; how to ensure competence within the organisation; how to demonstrate organisational suitability; the regulatory oversight processes - including their strengths and weaknesses. A list of the related questions that were provided to the discussion groups can be found in Appendix 3. Also included in Appendix 3 are copies of the slides the groups prepared that summarised their considerations

  7. Natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.

    1986-01-01

    A Natural Analogue Working Group was established by the Commission of the European Communities in 1985. The purpose of this group is to bring together modellers with earth scientists and others, so that maximum benefit can be obtained from natural analogue studies with a view to safe geological disposal of radioactive waste. The first meeting of this group was held in Brussels from November 5 to 7, 1985. The discussions mainly concerned the identification of the modellers' needs and of the earth scientists' capacity to provide for them. Following the debates, a written statement was produced by the Group; this document forms the core of the present Report. Notes and outlines of many of the presentations made are grouped in four appendixes. The valuable contribution of all those involved in the meeting is gratefully acknowledged

  8. Ordered groups and topology

    CERN Document Server

    Clay, Adam

    2016-01-01

    This book deals with the connections between topology and ordered groups. It begins with a self-contained introduction to orderable groups and from there explores the interactions between orderability and objects in low-dimensional topology, such as knot theory, braid groups, and 3-manifolds, as well as groups of homeomorphisms and other topological structures. The book also addresses recent applications of orderability in the studies of codimension-one foliations and Heegaard-Floer homology. The use of topological methods in proving algebraic results is another feature of the book. The book was written to serve both as a textbook for graduate students, containing many exercises, and as a reference for researchers in topology, algebra, and dynamical systems. A basic background in group theory and topology is the only prerequisite for the reader.

  9. Managing parental groups: personal impact of a group leadership course for child healthcare nurses.

    Science.gov (United States)

    Lefèvre, Åsa; Lundqvist, Pia; Drevenhorn, Eva; Hallström, Inger

    2017-02-01

    To investigate the experience and personal impact of a group leadership course for child healthcare nurses. During their child's first year, all parents in Sweden are invited to participate in parental groups within the child health service; however, only 49% choose to participate. Despite extensive experience, child healthcare nurses find managing parental groups challenging and express a need for training in group dynamics and group leadership. The study was designed as a controlled study with a pretest/post-test design where the participants form their own control group. A group leadership course was given to 56 child healthcare nurses and evaluated in a pre- and postintervention questionnaire, a course evaluation and an interview with the course leaders. The child healthcare nurses felt their group leadership skills were strengthened and the majority (96%) felt that the course had changed their way of leading parental groups. They felt that the group leader role had been clarified and that they had obtained several new tools to use in their groups. Clarifying the role of group leader and adding knowledge about group leadership and dynamics seems to have increased the self-confidence for child healthcare nurses in group leadership. Improved confidence in group management might motivate the child healthcare nurses to further develop parental groups to attract the parents who currently choose not to participate. © 2016 John Wiley & Sons Ltd.

  10. Inclusion, children's groups, music therapy

    DEFF Research Database (Denmark)

    Holck, Ulla; Jacobsen, Stine Lindahl

    2016-01-01

    portrayal of the qualities of musical interplay that promotes well-being in group settings and, thus, the inclusion of vulnerable students. Therefore, we open the chapter with a focus on musicality and on the importance of applying a musical approach in relation to the children.......Music has a rare ability to affect us directly. Pulse and rhythms make us move, and notes and harmonies inspire and express our inner emotions in a direct and immediate way that goes beyond what words or even other art forms can rarely achieve (Panksepp & Trevarthen, 2009). Music creates...... a delightful build-up of tension or soothes us, and its narrative character gives rise to mental imagery or memories. Music brings people together and helps build communities across languages and common divides. And – not least – music captures children’s immediate attention, so when the music starts, so do...

  11. Group prenatal care.

    Science.gov (United States)

    Mazzoni, Sara E; Carter, Ebony B

    2017-06-01

    Patients participating in group prenatal care gather together with women of similar gestational ages and 2 providers who cofacilitate an educational session after a brief medical assessment. The model was first described in the 1990s by a midwife for low-risk patients and is now practiced by midwives and physicians for both low-risk patients and some high-risk patients, such as those with diabetes. The majority of literature on group prenatal care uses CenteringPregnancy, the most popular model. The first randomized controlled trial of CenteringPregnancy showed that it reduced the risk of preterm birth in low-risk women. However, recent meta-analyses have shown similar rates of preterm birth, low birthweight, and neonatal intensive care unit admission between women participating in group prenatal care and individual prenatal care. There may be subgroups, such as African Americans, who benefit from this type of prenatal care with significantly lower rates of preterm birth. Group prenatal care seems to result in increased patient satisfaction and knowledge and use of postpartum family planning as well as improved weight gain parameters. The literature is inconclusive regarding breast-feeding, stress, depression, and positive health behaviors, although it is theorized that group prenatal care positively affects these outcomes. It is unclear whether group prenatal care results in cost savings, although it may in large-volume practices if each group consists of approximately 8-10 women. Group prenatal care requires a significant paradigm shift. It can be difficult to implement and sustain. More randomized trials are needed to ascertain the true benefits of the model, best practices for implementation, and subgroups who may benefit most from this innovative way to provide prenatal care. In short, group prenatal care is an innovative and promising model with comparable pregnancy outcomes to individual prenatal care in the general population and improved outcomes in some

  12. Effects of Expressive Writing on Psychological and Physical Health: The Moderating Role of Emotional Expressivity

    Science.gov (United States)

    Haltom, Kate E.; Mulvenna, Catherine M.; Lieberman, Matthew D.; Stanton, Annette L.

    2013-01-01

    The current study assessed main effects and moderators (including emotional expressiveness, emotional processing and ambivalence over emotional expression) of the effects of expressive writing in a sample of healthy adults. Young adult participants (N = 116) were randomly assigned to write for 20 minutes on four occasions about deepest thoughts and feelings regarding their most stressful/traumatic event in the past five years (expressive writing) or about a control topic (control). Dependent variables were indicators of anxiety, depression, and physical symptoms. No significant effects of writing condition were evident on anxiety, depressive symptoms, or physical symptoms. Emotional expressiveness emerged as a significant moderator of anxiety outcomes, however. Within the expressive writing group, participants high in expressiveness evidenced a significant reduction in anxiety at three-month follow-up, and participants low in expressiveness showed a significant increase in anxiety. Expressiveness did not predict change in anxiety in the control group. These findings on anxiety are consistent with the matching hypothesis, which suggests that matching a person’s naturally elected coping approach with an assigned intervention is beneficial. These findings also suggest that expressive writing about a stressful event may be contraindicated for individuals who do not typically express emotions. PMID:23742666

  13. The FORATOM Transport Working Group

    International Nuclear Information System (INIS)

    Lehmann, P.

    2000-01-01

    Based in Brussels, the European atomic forum FORATOM is the trade association of the European nuclear industry which was established in the early 1960s to promote nuclear power and to facilitate relations with the European institutions. One of the main mechanisms which FORATOM uses, in its dealings with the European Commission and other international organisations, is the involvement of several working groups bringing together groups of experts drawn from the industrial companies in order to identify the issues and to develop the widest possible common views on which the industry must express its representative, substantial and deliverable opinion. The Transport Working Group (TWG) has the objective of dealing with transport of radioactive material, especially nuclear materials. The TWG usually meets three times a year in Brussels or another selected location. It has strong links with the European Commission which are evidenced by the fact that it officially represents the European nuclear industry, with the status of observer, at the meetings of the Standing Working Group on Safe Transport of Radioactive Material which was set up in 1982, upon a request of the European Parliament, to advise the European Commission in the field of safe transport of radioactive materials. The Standing Working Group (SWG) assists the European Union's Member States in the revision process of IAEA recommendations and helps a correct and harmonious application of these recommendations within the European Union. In previous years, the Standing Working Group has proposed over 40 different studies, financed by the European Commission, on important transport issues. The FORATOM TWG encourages its member organisations to participate in studies proposed by the Commission and has been cooperating for many years with the Commission in the field of many studies aimed to improve the application of transport regulations. The need to maintain the safe and reliable operation of plants that generate

  14. Critical groups - basic concepts

    International Nuclear Information System (INIS)

    Carter, M.W.

    1992-01-01

    The potential exposure pathways from the land application site to man are presented. It is emphasised that the critical group is not necessary the population group closest to the source. It could be the group impact by the most significant pathways(s). Only by assessing the importance of each of these pathways and then combining them can a proper choice of critical group be made. It would be wrong to select a critical group on the basis that it seems the most probable one, before the pathways have been properly assessed. A calculation in Carter (1983) suggested that for the operating mine site, the annual doses to an Aboriginal person, a service worker and a local housewife, were all about the same and were in the range 0.1 to 0.2 mSv per year. Thus it may be that for the land application area, the critical group turns out to be non-Aboriginal rather than the expected Aboriginal group. 6 refs., 3 figs

  15. Efficient methods for overlapping group lasso.

    Science.gov (United States)

    Yuan, Lei; Liu, Jun; Ye, Jieping

    2013-09-01

    The group Lasso is an extension of the Lasso for feature selection on (predefined) nonoverlapping groups of features. The nonoverlapping group structure limits its applicability in practice. There have been several recent attempts to study a more general formulation where groups of features are given, potentially with overlaps between the groups. The resulting optimization is, however, much more challenging to solve due to the group overlaps. In this paper, we consider the efficient optimization of the overlapping group Lasso penalized problem. We reveal several key properties of the proximal operator associated with the overlapping group Lasso, and compute the proximal operator by solving the smooth and convex dual problem, which allows the use of the gradient descent type of algorithms for the optimization. Our methods and theoretical results are then generalized to tackle the general overlapping group Lasso formulation based on the l(q) norm. We further extend our algorithm to solve a nonconvex overlapping group Lasso formulation based on the capped norm regularization, which reduces the estimation bias introduced by the convex penalty. We have performed empirical evaluations using both a synthetic and the breast cancer gene expression dataset, which consists of 8,141 genes organized into (overlapping) gene sets. Experimental results show that the proposed algorithm is more efficient than existing state-of-the-art algorithms. Results also demonstrate the effectiveness of the nonconvex formulation for overlapping group Lasso.

  16. Affirmation, acknowledgment of in-group responsibility, group-based guilt, and support for reparative measures.

    Science.gov (United States)

    Cehajić-Clancy, Sabina; Effron, Daniel A; Halperin, Eran; Liberman, Varda; Ross, Lee D

    2011-08-01

    Three studies, 2 conducted in Israel and 1 conducted in Bosnia and Herzegovina, demonstrated that affirming a positive aspect of the self can increase one's willingness to acknowledge in-group responsibility for wrongdoing against others, express feelings of group-based guilt, and consequently provide greater support for reparation policies. By contrast, affirming one's group, although similarly boosting feelings of pride, failed to increase willingness to acknowledge and redress in-group wrongdoing. Studies 2 and 3 demonstrated the mediating role of group-based guilt. That is, increased acknowledgment of in-group responsibility for out-group victimization produced increased feelings of guilt, which in turn increased support for reparation policies to the victimized group. Theoretical and applied implications are discussed.

  17. After Effects expressions

    CERN Document Server

    Geduld, Marcus

    2013-01-01

    Put the power of Expressions to work in your animations with controls and efficiencies impossible to achieve with traditional keyframing techniques. No programming skills are required. Foundation concepts and skills orient the new designer and serve as a handy reference to the experienced one. Basics of creating expressions, variables, commands, and expression helpers precede the leap into javascript and math essentials for more advanced expressions that include randomness, physical simularions and 3D. Full color illustrations display the scripts and the resulti

  18. Groups - Modular Mathematics Series

    CERN Document Server

    Jordan, David

    1994-01-01

    This text provides an introduction to group theory with an emphasis on clear examples. The authors present groups as naturally occurring structures arising from symmetry in geometrical figures and other mathematical objects. Written in a 'user-friendly' style, where new ideas are always motivated before being fully introduced, the text will help readers to gain confidence and skill in handling group theory notation before progressing on to applying it in complex situations. An ideal companion to any first or second year course on the topic.

  19. Introduction to quantum groups

    CERN Document Server

    Chaichian, Masud

    1996-01-01

    In the past decade there has been an extemely rapid growth in the interest and development of quantum group theory.This book provides students and researchers with a practical introduction to the principal ideas of quantum groups theory and its applications to quantum mechanical and modern field theory problems. It begins with a review of, and introduction to, the mathematical aspects of quantum deformation of classical groups, Lie algebras and related objects (algebras of functions on spaces, differential and integral calculi). In the subsequent chapters the richness of mathematical structure

  20. Group key management

    Energy Technology Data Exchange (ETDEWEB)

    Dunigan, T.; Cao, C.

    1997-08-01

    This report describes an architecture and implementation for doing group key management over a data communications network. The architecture describes a protocol for establishing a shared encryption key among an authenticated and authorized collection of network entities. Group access requires one or more authorization certificates. The implementation includes a simple public key and certificate infrastructure. Multicast is used for some of the key management messages. An application programming interface multiplexes key management and user application messages. An implementation using the new IP security protocols is postulated. The architecture is compared with other group key management proposals, and the performance and the limitations of the implementation are described.

  1. Group therapy for adolescents

    Directory of Open Access Journals (Sweden)

    Nada Hribar

    2001-03-01

    Full Text Available The group included adolescents from secondary school and some students. The group had weekly sessions or twice on mounth. The adolescents had varied simptoms: depressive, anxiety, psychosomatic disorders, learning difficulties, cunduct problems. All of adolescents were common on many problems in social interactions. The goal of therapeutic work were: to increase assertiveness skills and to reduce the anxious in social situations. The adolescents in group raised a self-esteem and developed some assertiveness skills: eye contact" and effective communication skills, persistence, refusing and requesting, giving and receiving critism, etc. The methods of work and techniques were based on principles of cognitive-behaviour therapy.

  2. Matrix groups for undergraduates

    CERN Document Server

    Tapp, Kristopher

    2005-01-01

    Matrix groups touch an enormous spectrum of the mathematical arena. This textbook brings them into the undergraduate curriculum. It makes an excellent one-semester course for students familiar with linear and abstract algebra and prepares them for a graduate course on Lie groups. Matrix Groups for Undergraduates is concrete and example-driven, with geometric motivation and rigorous proofs. The story begins and ends with the rotations of a globe. In between, the author combines rigor and intuition to describe basic objects of Lie theory: Lie algebras, matrix exponentiation, Lie brackets, and maximal tori.

  3. Effects of Different Types of Electroacupuncture on Expression of High Mobility Group Box Pro-tein-1 and Interleukin-10 in Hippocampus of APP/PS1 Mice%不同电针法对APP/PS1小鼠海马高迁移率族蛋白B1和白细胞介素-10表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵江豪; 姚海江; 王远征; 卢梦晗; 李昱颉; 宋萌; 杨利娟; 刘俊彤; 李志刚

    2018-01-01

    目的 观察"通督启神"法脉冲电针与音乐电针对APP/PS1模型小鼠空间学习记忆能力及海马内炎症介质表达的影响.方法 APP/PS1双转基因雄性小鼠32只随机分为模型组(n=8)、药物组(n=8)、脉冲电针组(n=8)和音乐电针组(n=8),相同月龄C57BL/6雄性小鼠作为正常对照组(n=8).脉冲电针组与音乐电针组以各自电针仪电针百会、印堂,留针20 min,取针后点刺人中.药物组予盐酸多奈哌齐0.92 mg/kg灌胃.正常对照组、模型组与药物组以相同方法抓取束缚20 min.治疗15 d后,行Morris水迷宫测试,免疫组化观察海马高迁移率族蛋白B1(HMGB1)与白细胞介素-10(IL-10)表达,Western blotting检测海马HMGB1与IL-10的表达.结果 两个电针组从训练第4天起,逃避潜伏较模型组缩短(P0.05);海马HMGB1的表达降低(P0.05).结论 "通督启神"法脉冲电针与音乐电针均能改善APP/PS1小鼠学习记忆功能,音乐电针在抑制炎性因子表达、促进抗炎因子表达方面可能优于脉冲电针.%Objective To compare the effect of impulse electroacupuncture (impulse-EA) and music electroacupuncture (music-EA) for Tongdu Qishen on spatial learning and memory, and expression of cytokine in the hippocampus of APP/PS1 mice. Methods A total of 32 APP/PS1 double transgenic male mice were randomly divided into model group (n=8), drug group (n=8), impulse-EA group (n=8) and music-EA group (n=8), the same background and age male C57BL/6 mice were observed as normal group (n=8). The impulse-EA group and music-EA group accepted EA at Baihui (GV20) and Yintang (GV29), connected with their own electroacupuncture stimulators, for 20 minuts, then, they were pricked Renzhong (GV26) for a while. The drug group accepted donepezil hydrochloride 0.92 mg/kg intra-gastrically. The normal group, model group and drug group were grabbed and bounded in the same way. After 15 days of treatment, they were assessed with Morris water maze. The expression of

  4. Expressiveness in musical performance: Pedagogic aspect

    Directory of Open Access Journals (Sweden)

    Jović Natalija R.

    2016-01-01

    Full Text Available The subject of our research relates to pedagogic aspects of expressive vocal-instrumental musical performance. We intended to examine: (1 how undergraduate students see/conceptualize and evaluate expressiveness in musical performance; (2 whether and how they were trained in the skill of expressive musical performance during their musical training; (3 whether and in which way they rehearse the expressive component of musical performance and interpretation and (4 whether there are any differences regarding gender, age, instrument, department, year of study and years of instrument playing in relation to the group of dependant variables related to expressiveness, tuition and practice. The sample for the research included 82 students of instrumental and theory departments at the Faculty of Music in Belgrade. Psychological and pedagogical aspects of musical expressiveness during vocal-instrumental performance were analyzed. The results show that students highly evaluate expressiveness but its place is secondary compared to mastering technical and tonal requirements. Statistically significant differences were shown regarding gender, age and departments. It can be concluded that there is a potential for the development and enhancement of expressiveness of students if we abandon the traditional view that expressiveness is linked exclusively to talent. The findings indicate that pedagogical work should be directed towards finding purposeful strategies for training individual expressiveness.

  5. The motivation to express prejudice.

    Science.gov (United States)

    Forscher, Patrick S; Cox, William T L; Graetz, Nicholas; Devine, Patricia G

    2015-11-01

    Contemporary prejudice research focuses primarily on people who are motivated to respond without prejudice and the ways in which unintentional bias can cause these people to act in a manner inconsistent with this motivation. However, some real-world phenomena (e.g., hate speech, hate crimes) and experimental findings (e.g., Plant & Devine, 2001, 2009) suggest that some prejudice is intentional. These phenomena and findings are difficult to explain solely from the motivations to respond without prejudice. We argue that some people are motivated to express prejudice, and we develop the Motivation to Express Prejudice Scale (MP) to measure this motivation. In 7 studies involving more than 6,000 participants, we demonstrate that, across scale versions targeted at Black people and gay men, the MP has good reliability and convergent, discriminant, and predictive validity. In normative climates that prohibit prejudice, the internal and external motivations to express prejudice are functionally nonindependent, but they become more independent when normative climates permit more prejudice toward a target group. People high in the motivation to express prejudice are relatively likely to resist pressure to support programs promoting intergroup contact and to vote for political candidates who support oppressive policies. The motivation to express prejudice predicted these outcomes even when controlling for attitudes and the motivations to respond without prejudice. This work encourages contemporary prejudice researchers to give greater consideration to the intentional aspects of negative intergroup behavior and to broaden the range of phenomena, target groups, and samples that they study. (c) 2015 APA, all rights reserved).

  6. UnitedHealth Group

    Science.gov (United States)

    UnitedHealth Group provides accessible and affordable services, improved quality of care, coordinated health care efforts, and a supportive environment for shared decision making between patients and their physicians.

  7. Homogeneous group, research, institution

    Directory of Open Access Journals (Sweden)

    Francesca Natascia Vasta

    2014-09-01

    Full Text Available The work outlines the complex connection among empiric research, therapeutic programs and host institution. It is considered the current research state in Italy. Italian research field is analyzed and critic data are outlined: lack of results regarding both the therapeutic processes and the effectiveness of eating disorders group analytic treatment. The work investigates on an eating disorders homogeneous group, led into an eating disorder outpatient service. First we present the methodological steps the research is based on including the strong connection among theory and clinical tools. Secondly clinical tools are described and the results commented. Finally, our results suggest the necessity of validating some more specifical hypothesis: verifying the relationship between clinical improvement (sense of exclusion and painful emotions reduction and specific group therapeutic processes; verifying the relationship between depressive feelings, relapses and transition trough a more differentiated groupal field.Keywords: Homogeneous group; Eating disorders; Institutional field; Therapeutic outcome

  8. Color transparency study group

    International Nuclear Information System (INIS)

    Appel, J.A.; Pordes, S.; Botts, J.; Bunce, G.; Farrar, G.

    1990-01-01

    The group studied the relatively new notion of color transparency, discussed present experimental evidence for the effect, and explored several ideas for future experiments. This write-up summarizes these discussions. 11 refs., 1 fig

  9. Generalized quantum groups

    International Nuclear Information System (INIS)

    Leivo, H.P.

    1992-01-01

    The algebraic approach to quantum groups is generalized to include what may be called an anyonic symmetry, reflecting the appearance of phases more general than ±1 under transposition. (author). 6 refs

  10. Groups – Additive Notation

    Directory of Open Access Journals (Sweden)

    Coghetto Roland

    2015-06-01

    Full Text Available We translate the articles covering group theory already available in the Mizar Mathematical Library from multiplicative into additive notation. We adapt the works of Wojciech A. Trybulec [41, 42, 43] and Artur Korniłowicz [25].

  11. Groups – Additive Notation

    OpenAIRE

    Coghetto Roland

    2015-01-01

    We translate the articles covering group theory already available in the Mizar Mathematical Library from multiplicative into additive notation. We adapt the works of Wojciech A. Trybulec [41, 42, 43] and Artur Korniłowicz [25].

  12. Creativity and group innovation

    NARCIS (Netherlands)

    Nijstad, B.A.; de Dreu, C.K.W.

    2002-01-01

    Comments on M. West's article regarding the validity of an integrative model of creativity and innovation implementation in work groups. Variables affecting the level of team innovation; Relationship between predictors and team innovation; Promotion of constructive conflict.

  13. Truck shovel users group

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, J. [Surface Mining Association for Research and Technology, AB (Canada)

    2008-07-01

    The Truck Shovel Users Group (TSUG) was developed as part of the Surface Mining Association for Research and Technology (SMART), an association of companies that meet to coordinate technology developments for the mining industry. The TSUG meet regularly to discuss equipment upgrades, maintenance planning systems, and repair techniques. The group strives to maximize the value of its assets through increased safety, equipment performance and productivity. This presentation provided administrative details about the TSUG including contact details and admission costs. It was concluded that members of the group must be employed by companies that use heavy mining equipment, and must also be willing to host meetings, make presentations, and support the common goals of the group. tabs., figs.

  14. The theory of groups

    CERN Document Server

    Hall, Marshall

    2018-01-01

    This 1959 text offers an unsurpassed resource for learning and reviewing the basics of a fundamental and ever-expanding area. "This remarkable book undoubtedly will become a standard text on group theory." - American Scientist.

  15. Radiation Protection Group

    CERN Document Server

    2006-01-01

    The Radioactive Waste Section of the Radiation Protection Group wishes to inform you that the Radioactive Waste Treatment Centre will be closed on the afternoon of Tuesday 19 December 2006. Thank-you for your understanding.

  16. The Military Cooperation Group

    National Research Council Canada - National Science Library

    Renzi, Jr, Alfred E

    2006-01-01

    .... This thesis will describe a structure to assist with both those needs. The premise is that an expanded and improved network of US Military Groups is the weapon of choice for the war on terror, and beyond...

  17. Introduction to group theory

    Directory of Open Access Journals (Sweden)

    Canals B.

    2012-03-01

    Full Text Available This chapter is a concise mathematical introduction into the algebra of groups. It is build up in the way that definitions are followed by propositions and proofs. The concepts and the terminology introduced here will serve as a basis for the following chapters that deal with group theory in the stricter sense and its application to problems in physics. The mathematical prerequisites are at the bachelor level.1

  18. Groups, rings, modules

    CERN Document Server

    Auslander, Maurice

    2014-01-01

    This classic monograph is geared toward advanced undergraduates and graduate students. The treatment presupposes some familiarity with sets, groups, rings, and vector spaces. The four-part approach begins with examinations of sets and maps, monoids and groups, categories, and rings. The second part explores unique factorization domains, general module theory, semisimple rings and modules, and Artinian rings. Part three's topics include localization and tensor products, principal ideal domains, and applications of fundamental theorem. The fourth and final part covers algebraic field extensions

  19. Focus Group Guide

    Science.gov (United States)

    2017-07-01

    home for the arrival of school- aged children. TIP: Do not conduct focus groups in a command conference room in the command group area. Doing so...organizational effectiveness and equal opportunity/equal employment opportunity/fair treatment and sexual assault and response factors (which are listed on the... Sexual Harassment (C) Sex Harassment Retaliation (D) Discrimination - Sex (E) Discrimination - Race (F) Discrimination - Disability (G

  20. Choice Shifts in Groups

    OpenAIRE

    Kfir Eliaz; Debraj Ray

    2004-01-01

    The phenomenon of "choice shifts" in group decision-making is fairly ubiquitous in the social psychology literature. Faced with a choice between a ``safe" and ``risky" decision, group members appear to move to one extreme or the other, relative to the choices each member might have made on her own. Both risky and cautious shifts have been identified in different situations. This paper demonstrates that from an individual decision-making perspective, choice shifts may be viewed as a systematic...

  1. Group Capability Model

    Science.gov (United States)

    Olejarski, Michael; Appleton, Amy; Deltorchio, Stephen

    2009-01-01

    The Group Capability Model (GCM) is a software tool that allows an organization, from first line management to senior executive, to monitor and track the health (capability) of various groups in performing their contractual obligations. GCM calculates a Group Capability Index (GCI) by comparing actual head counts, certifications, and/or skills within a group. The model can also be used to simulate the effects of employee usage, training, and attrition on the GCI. A universal tool and common method was required due to the high risk of losing skills necessary to complete the Space Shuttle Program and meet the needs of the Constellation Program. During this transition from one space vehicle to another, the uncertainty among the critical skilled workforce is high and attrition has the potential to be unmanageable. GCM allows managers to establish requirements for their group in the form of head counts, certification requirements, or skills requirements. GCM then calculates a Group Capability Index (GCI), where a score of 1 indicates that the group is at the appropriate level; anything less than 1 indicates a potential for improvement. This shows the health of a group, both currently and over time. GCM accepts as input head count, certification needs, critical needs, competency needs, and competency critical needs. In addition, team members are categorized by years of experience, percentage of contribution, ex-members and their skills, availability, function, and in-work requirements. Outputs are several reports, including actual vs. required head count, actual vs. required certificates, CGI change over time (by month), and more. The program stores historical data for summary and historical reporting, which is done via an Excel spreadsheet that is color-coded to show health statistics at a glance. GCM has provided the Shuttle Ground Processing team with a quantifiable, repeatable approach to assessing and managing the skills in their organization. They now have a common

  2. Parton Distributions Working Group

    International Nuclear Information System (INIS)

    Barbaro, L. de; Keller, S. A.; Kuhlmann, S.; Schellman, H.; Tung, W.-K.

    2000-01-01

    This report summarizes the activities of the Parton Distributions Working Group of the QCD and Weak Boson Physics workshop held in preparation for Run II at the Fermilab Tevatron. The main focus of this working group was to investigate the different issues associated with the development of quantitative tools to estimate parton distribution functions uncertainties. In the conclusion, the authors introduce a Manifesto that describes an optimal method for reporting data

  3. Renormalization Group Theory

    International Nuclear Information System (INIS)

    Stephens, C. R.

    2006-01-01

    In this article I give a brief account of the development of research in the Renormalization Group in Mexico, paying particular attention to novel conceptual and technical developments associated with the tool itself, rather than applications of standard Renormalization Group techniques. Some highlights include the development of new methods for understanding and analysing two extreme regimes of great interest in quantum field theory -- the ''high temperature'' regime and the Regge regime

  4. Independents' group posts loss

    International Nuclear Information System (INIS)

    Sanders, V.; Price, R.B.

    1992-01-01

    Low oil gas prices and special charges caused the group of 50 U.S. independent producers Oil and Gas Journal tracks to post a combined loss in first half 1992. The group logged a net loss of $53 million in the first half compared with net earnings of $354 million in first half 1991, when higher oil prices during the Persian Gulf crisis buoyed earnings in spite of crude oil and natural gas production declines. The combined loss in the first half follows a 45% drop in the group's earnings in 1991 and compares with the OGJ group of integrated oil companies whose first half 1992 income fell 47% from the prior year. Special charges, generally related to asset writedowns, accounted for most of the almost $560 million in losses posted by about the third of the group. Nerco Oil and Gas Inc., Vancouver, Wash., alone accounted for almost half that total with charges related to an asset writedown of $238 million in the first quarter. Despite the poor first half performance, the outlook is bright for sharply improved group earnings in the second half, assuming reasonably healthy oil and gas prices and increased production resulting from acquisitions and in response to those prices

  5. Exploration of Support Behavior in Counseling Groups with Counseling Trainees

    Science.gov (United States)

    Harel, Yoni; Shechtman, Zipora; Cutrona, Carolyn

    2012-01-01

    The study explores the types of support expressed in counseling groups attended by trainee counselors. Support is a crucial factor in human life in general, and in groups in particular, yet little is known about the type of support presented in counseling groups. Type of support was categorized by means of the Social Support Behavior Code (SSBC;…

  6. A Community Art Therapy Group for Adults with Chronic Pain

    Science.gov (United States)

    O'Neill, Aimee; Moss, Hilary

    2015-01-01

    This paper describes a community art therapy group for people living with chronic pain. Nine adults were offered 12 weekly group art therapy sessions that included art therapy activities such as guided imagery focusing on body scans followed by art responses and artistic expressions of the pain experience. This pilot group art therapy program is…

  7. Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials

    International Nuclear Information System (INIS)

    Fountzilas, George; Tsolaki, Eleftheria; Televantou, Despina; Timotheadou, Eleni; Koutras, Angelos; Klouvas, George; Samantas, Epaminontas; Pisanidis, Nikolaos; Karanikiotis, Charisios; Sfakianaki, Ioanna; Pavlidis, Nicholas; Dafni, Urania; Gogas, Helen; Linardou, Helena; Kalogeras, Konstantine T; Pectasides, Dimitrios; Dimopoulos, Meletios A; Bobos, Mattheos; Kotoula, Vassiliki; Batistatou, Anna; Xanthakis, Ioannis; Papadimitriou, Christos; Kostopoulos, Ioannis; Koletsa, Triantafillia

    2013-01-01

    The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy. Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients with high-risk operable breast cancer, enrolled in two consecutive phase III trials, were assessed in a central laboratory by fluorescence in situ hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe). Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >2.2 and ≥2.0, respectively, or gene copy number higher than 6. Additionally, HER2, TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry (IHC) and patients were classified according to their IHC phenotype. Treatment consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy and radiation, as indicated. HER2 amplification was found in 23.7% of the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55), respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2 amplification). Adjusting for treatment groups in the Cox model, HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with time to relapse or time to death. HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with outcome in high-risk breast cancer patients treated with anthracycline-based adjuvant chemotherapy. Australian New Zealand Clinical

  8. Changes in platelet functional parameters and CD62 P expression ...

    African Journals Online (AJOL)

    EB

    Objective: To investigate the changes in platelet functional parameters and CD62 P expression in liver cirrhosis as a possible .... bleeding and non-bleeding group with hepatic cirrhosis (±s). Group ... the body's coagulate function requirement.

  9. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R

    2013-01-01

    showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction...... previous reports, Neuroglobin over expression is not global but confined to a few well-defined brain regions, and only in neurons. This study confirms previous reports showing a correlation between reduced infarct volume and elevated Neuroglobin levels, but underlines the need to study the likely...

  10. Assessment of Group Preferences and Group Uncertainty for Decision Making

    Science.gov (United States)

    1976-06-01

    the individ- uals. decision making , group judgments should be preferred to individual judgments if obtaining group judgments costs more. -26- -YI IV... decision making group . IV. A. 3. Aggregation using conjugate distribution. Arvther procedure for combining indivi(jai probability judgments into a group...statisticized group group decision making group judgment subjective probability Delphi method expected utility nominal group 20. ABSTRACT (Continue on

  11. Cyclic Soft Groups and Their Applications on Groups

    Directory of Open Access Journals (Sweden)

    Hacı Aktaş

    2014-01-01

    Full Text Available In crisp environment the notions of order of group and cyclic group are well known due to many applications. In this paper, we introduce order of the soft groups, power of the soft sets, power of the soft groups, and cyclic soft group on a group. We also investigate the relationship between cyclic soft groups and classical groups.

  12. Coordinating Group report

    International Nuclear Information System (INIS)

    1994-01-01

    In December 1992, western governors and four federal agencies established a Federal Advisory Committee to Develop On-site Innovative Technologies for Environmental Restoration and Waste Management (the DOIT Committee). The purpose of the Committee is to advise the federal government on ways to improve waste cleanup technology development and the cleanup of federal sites in the West. The Committee directed in January 1993 that information be collected from a wide range of potential stakeholders and that innovative technology candidate projects be identified, organized, set in motion, and evaluated to test new partnerships, regulatory approaches, and technologies which will lead to improve site cleanup. Five working groups were organized, one to develop broad project selection and evaluation criteria and four to focus on specific contaminant problems. A Coordinating Group comprised of working group spokesmen and federal and state representatives, was set up to plan and organize the routine functioning of these working groups. The working groups were charged with defining particular contaminant problems; identifying shortcomings in technology development, stakeholder involvement, regulatory review, and commercialization which impede the resolution of these problems; and identifying candidate sites or technologies which could serve as regional innovative demonstration projects to test new approaches to overcome the shortcomings. This report from the Coordinating Group to the DOIT Committee highlights the key findings and opportunities uncovered by these fact-finding working groups. It provides a basis from which recommendations from the DOIT Committee to the federal government can be made. It also includes observations from two public roundtables, one on commercialization and another on regulatory and institutional barriers impeding technology development and cleanup

  13. Quantum group and Manin plane related to a coloured braid group representation

    International Nuclear Information System (INIS)

    Basu Mallick, B.

    1993-07-01

    By considering 'coloured' braid group representation we have obtained a quantum group, which reduces to the standards GL q (2) and GL pq (2) cases at some particular limits of the 'colour' parameters. In spite of quite complicated nature, all of these new quantum group relations can be expressed neatly in the Heisenberg-Weyl form, for a nontrivial choice of the basis elements. Furthermore, it is possible to associate invariant Manin planes, parametrized by the 'colour' variables, with such quantum group structure. (author). 26 refs

  14. The Effects of Group Members' Personalities on a Test Taker's L2 Group Oral Discussion Test Scores

    Science.gov (United States)

    Ockey, Gary J.

    2009-01-01

    The second language group oral is a test of second language speaking proficiency, in which a group of three or more English language learners discuss an assigned topic without interaction with interlocutors. Concerns expressed about the extent to which test takers' personal characteristics affect the scores of others in the group have limited its…

  15. Allele specific expression and methylation in the bumblebee, Bombus terrestris

    Directory of Open Access Journals (Sweden)

    Zoë Lonsdale

    2017-09-01

    Full Text Available The social hymenoptera are emerging as models for epigenetics. DNA methylation, the addition of a methyl group, is a common epigenetic marker. In mammals and flowering plants methylation affects allele specific expression. There is contradictory evidence for the role of methylation on allele specific expression in social insects. The aim of this paper is to investigate allele specific expression and monoallelic methylation in the bumblebee, Bombus terrestris. We found nineteen genes that were both monoallelically methylated and monoallelically expressed in a single bee. Fourteen of these genes express the hypermethylated allele, while the other five express the hypomethylated allele. We also searched for allele specific expression in twenty-nine published RNA-seq libraries. We found 555 loci with allele-specific expression. We discuss our results with reference to the functional role of methylation in gene expression in insects and in the as yet unquantified role of genetic cis effects in insect allele specific methylation and expression.

  16. Linear algebraic groups

    CERN Document Server

    Springer, T A

    1998-01-01

    "[The first] ten chapters...are an efficient, accessible, and self-contained introduction to affine algebraic groups over an algebraically closed field. The author includes exercises and the book is certainly usable by graduate students as a text or for self-study...the author [has a] student-friendly style… [The following] seven chapters... would also be a good introduction to rationality issues for algebraic groups. A number of results from the literature…appear for the first time in a text." –Mathematical Reviews (Review of the Second Edition) "This book is a completely new version of the first edition. The aim of the old book was to present the theory of linear algebraic groups over an algebraically closed field. Reading that book, many people entered the research field of linear algebraic groups. The present book has a wider scope. Its aim is to treat the theory of linear algebraic groups over arbitrary fields. Again, the author keeps the treatment of prerequisites self-contained. The material of t...

  17. Summary report: injection group

    International Nuclear Information System (INIS)

    Simpson, J.; Ankenbrandt, C.; Brown, B.

    1984-01-01

    The injector group attempted to define and address several problem areas related to the SSC injector as defined in the Reference Design Study (RDS). It also considered the topic of machine utilization, particularly the question of test beam requirements. Details of the work are given in individually contributed papers, but the general concerns and consensus of the group are presented within this note. The group recognized that the injector as outlined in the RDS was developed primarily for costing estimates. As such, it was not necessarily well optimized from the standpoint of insuring the required beam properties for the SSC. On the other hand, considering the extraordinary short time in which the RDS was prepared, it is an impressive document and a good basis from which to work. Because the documented SSC performance goals are ambitious, the group sought an injector solution which would more likely guarantee that SSC performance not be limited by its injectors. As will be seen, this leads to a somewhat different solution than that described in the RDS. Furthermore, it is the consensus of the group that the new, conservative approach represents only a modest cost increase of the overall project well worth the confidence gained and the risks avoided

  18. Matrix groups for undergraduates

    CERN Document Server

    Tapp, Kristopher

    2016-01-01

    Matrix groups touch an enormous spectrum of the mathematical arena. This textbook brings them into the undergraduate curriculum. It makes an excellent one-semester course for students familiar with linear and abstract algebra and prepares them for a graduate course on Lie groups. Matrix Groups for Undergraduates is concrete and example-driven, with geometric motivation and rigorous proofs. The story begins and ends with the rotations of a globe. In between, the author combines rigor and intuition to describe the basic objects of Lie theory: Lie algebras, matrix exponentiation, Lie brackets, maximal tori, homogeneous spaces, and roots. This second edition includes two new chapters that allow for an easier transition to the general theory of Lie groups. From reviews of the First Edition: This book could be used as an excellent textbook for a one semester course at university and it will prepare students for a graduate course on Lie groups, Lie algebras, etc. … The book combines an intuitive style of writing w...

  19. Frailty Across Age Groups.

    Science.gov (United States)

    Pérez-Zepeda, M U; Ávila-Funes, J A; Gutiérrez-Robledo, L M; García-Peña, C

    2016-01-01

    The implementation of an aging biomarker into clinical practice is under debate. The Frailty Index is a model of deficit accumulation and has shown to accurately capture frailty in older adults, thus bridging biological with clinical practice. To describe the association of socio-demographic characteristics and the Frailty Index in different age groups (from 20 to over one hundred years) in a representative sample of Mexican subjects. Cross-sectional analysis. Nationwide and population-representative survey. Adults 20-years and older interviewed during the last Mexican National Health and Nutrition Survey (2012). A 30-item Frailty Index following standard construction was developed. Multi-level regression models were performed to test the associations of the Frailty Index with multiple socio-demographic characteristics across age groups. A total of 29,504 subjects was analyzed. The 30-item Frailty Index showed the highest scores in the older age groups, especially in women. No sociodemographic variable was associated with the Frailty Index in all the studied age groups. However, employment, economic income, and smoking status were more consistently found across age groups. To our knowledge, this is the first report describing the Frailty Index in a representative large sample of a Latin American country. Increasing age and gender were closely associated with a higher score.

  20. Illinois Wind Workers Group

    Energy Technology Data Exchange (ETDEWEB)

    David G. Loomis

    2012-05-28

    The Illinois Wind Working Group (IWWG) was founded in 2006 with about 15 members. It has grown to over 200 members today representing all aspects of the wind industry across the State of Illinois. In 2008, the IWWG developed a strategic plan to give direction to the group and its activities. The strategic plan identifies ways to address critical market barriers to the further penetration of wind. The key to addressing these market barriers is public education and outreach. Since Illinois has a restructured electricity market, utilities no longer have a strong control over the addition of new capacity within the state. Instead, market acceptance depends on willing landowners to lease land and willing county officials to site wind farms. Many times these groups are uninformed about the benefits of wind energy and unfamiliar with the process. Therefore, many of the project objectives focus on conferences, forum, databases and research that will allow these stakeholders to make well-educated decisions.

  1. Focus group discussions

    CERN Document Server

    Hennink, Monique M

    2014-01-01

    The Understanding Research series focuses on the process of writing up social research. The series is broken down into three categories: Understanding Statistics, Understanding Measurement, and Understanding Qualitative Research. The books provide researchers with guides to understanding, writing, and evaluating social research. Each volume demonstrates how research should be represented, including how to write up the methodology as well as the research findings. Each volume also reviews how to appropriately evaluate published research. Focus Group Discussions addresses the challenges associated with conducting and writing focus group research. It provides detailed guidance on the practical and theoretical considerations in conducting focus group discussions including: designing the discussion guide, recruiting participants, training a field team, moderating techniques and ethical considerations. Monique Hennink describes how a methodology section is read and evaluated by others, such as journal reviewers or ...

  2. Bell, group and tangle

    International Nuclear Information System (INIS)

    Solomon, A. I.

    2010-01-01

    The 'Bell' of the title refers to bipartite Bell states, and their extensions to, for example, tripartite systems. The 'Group' of the title is the Braid Group in its various representations; while 'Tangle' refers to the property of entanglement which is present in both of these scenarios. The objective of this note is to explore the relation between Quantum Entanglement and Topological Links, and to show that the use of the language of entanglement in both cases is more than one of linguistic analogy.

  3. A Quantum Groups Primer

    Science.gov (United States)

    Majid, Shahn

    2002-05-01

    Here is a self-contained introduction to quantum groups as algebraic objects. Based on the author's lecture notes for the Part III pure mathematics course at Cambridge University, the book is suitable as a primary text for graduate courses in quantum groups or supplementary reading for modern courses in advanced algebra. The material assumes knowledge of basic and linear algebra. Some familiarity with semisimple Lie algebras would also be helpful. The volume is a primer for mathematicians but it will also be useful for mathematical physicists.

  4. MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer.

    Science.gov (United States)

    Momose, Kota; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2017-07-01

    Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD-L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair-deficient tumors are associated with improved survival, although they are not sensitive to 5-fluorouracil-based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5-year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (PMLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD-L1 expression.

  5. Introduction to quantum groups

    International Nuclear Information System (INIS)

    Monteiro, Marco A.R.

    1994-01-01

    An elementary introduction to quantum groups is presented. The example of Universal Enveloping Algebra of deformed SU(2) is analysed in detail. It is also discussed systems made up of bosonic q-oscillators at finite temperature within the formalism of Thermo-Field Dynamics. (author). 39 refs

  6. Lectures on Lie groups

    CERN Document Server

    Hsiang, Wu-Yi

    2017-01-01

    This volume consists of nine lectures on selected topics of Lie group theory. We provide the readers a concise introduction as well as a comprehensive 'tour of revisiting' the remarkable achievements of S Lie, W Killing, É Cartan and H Weyl on structural and classification theory of semi-simple Lie groups, Lie algebras and their representations; and also the wonderful duet of Cartans' theory on Lie groups and symmetric spaces.With the benefit of retrospective hindsight, mainly inspired by the outstanding contribution of H Weyl in the special case of compact connected Lie groups, we develop the above theory via a route quite different from the original methods engaged by most other books.We begin our revisiting with the compact theory which is much simpler than that of the general semi-simple Lie theory; mainly due to the well fittings between the Frobenius-Schur character theory and the maximal tori theorem of É Cartan together with Weyl's reduction (cf. Lectures 1-4). It is a wonderful reality of the Lie t...

  7. Gluten Intolerance Group

    Science.gov (United States)

    ... Intolerance Group (GIG), the industry leader in the certification of gluten-free products and food services, announced today that a wide ... of gluten-free products. One of the top certification programs in the world, GFCO inspects products and manufacturing facilities for gluten, in an effort ...

  8. With the Radiobiology Group

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    The Radiobiology Group carries out experiments to study the effect of radiation on living cells. The photo shows the apparatus for growing broad beans which have been irradiated by 250 GeV protons. The roots are immersed in a tank of running water (CERN Weekly Bulletin 26 January 1981 and Annual Report 1980 p. 160). Karen Panman, Marilena Streit-Bianchi, Roger Paris.

  9. Group control of elevators

    Energy Technology Data Exchange (ETDEWEB)

    Umeda, Yasukazu; Hikita, Shiro; Tuji, Sintaro (Mitsubishi Electric Corp., Tokyo (Japan))

    1988-09-05

    Items to be evaluated in the group control of elevators, and a typical control system are described. A new system in which the fuzzy rule base is employed is introduced together with the configuration. The items to be evaluated are waiting time, riding time, accuracy of forecasting, energy saving, and ease of usage. The everage waiting time of less than 20 seconds with less than 3% waiting rate of more than 60 seconds is accepted as a satisfactory service condition. There are many conflicting matters in group-controlling, and the study for the controlling must deal with the optimization of multi-purpose problems. The standards for group-control evaluation differ according to building structures and the tastes of users, and an important problem is where to give emphasis of the evaluation. The TRAFFIC PATTERN LEARNING METHOD has been applied in the system for careful control to accommodate the traffic. No specific function is provided for the evaluation, but the call allocation is made by fuzzy rule-base. The configuration of a new group-control system is introduced. 7 references, 7 figures, 1 table.

  10. Functional Group Analysis.

    Science.gov (United States)

    Smith, Walter T., Jr.; Patterson, John M.

    1984-01-01

    Literature on analytical methods related to the functional groups of 17 chemical compounds is reviewed. These compounds include acids, acid azides, alcohols, aldehydes, ketones, amino acids, aromatic hydrocarbons, carbodiimides, carbohydrates, ethers, nitro compounds, nitrosamines, organometallic compounds, peroxides, phenols, silicon compounds,…

  11. Moral motivation within groups

    NARCIS (Netherlands)

    Lee, Romy van der

    2013-01-01

    Morality is of particular importance to people: People want to be considered moral and want to belong to moral groups. Consequently, morality judgments have the potential to motivate individuals to behave in ways that are considered to be ‘good’. In the current dissertation, I examined the impact of

  12. Smoot Group Cosmology

    Science.gov (United States)

    the Universe About Cosmology Planck Satellite Launched Cosmology Videos Professor George Smoot's group conducts research on the early universe (cosmology) using the Cosmic Microwave Background radiation (CMB science goals regarding cosmology. George Smoot named Director of Korean Cosmology Institute The GRB

  13. Groups and Symmetry

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 10. Groups and Symmetry: A Guide to Discovering Mathematics. Geetha Venkataraman. Book Review Volume 4 Issue 10 October 1999 pp 91-92. Fulltext. Click here to view fulltext PDF. Permanent link:

  14. Public interest group involvement

    International Nuclear Information System (INIS)

    Shelley, P.

    1986-01-01

    Including public interest groups in the siting process for nuclear waste disposal facilities is of great importance. Controversial sitings often result in litigation, but involving public interest groups early in the process will lessen the change of this. They act as surrogates for the general public and should be considered as members of the team. It is important to remember though, that all public interest groups are different. In choosing public panels such as public advisory committees, members should not be chosen on the basis of some quota. Opposition groups should not be excluded. Also, it is important to put the right person in charge of the committee. The goal of public involvement is to identify the conflicts. This must be done during the decision process, because conflicts must be known before they can be eliminated. Regarding litigation, it is important to ease through and around legal battles. If the siting process has integrity and a good faith effort has been shown, the court should uphold the effort. In addition, it is important to be negotiable and to eliminate shortcuts

  15. Leukosis/Sarcoma Group

    Science.gov (United States)

    The leukosis/sarcoma (L/S) group of diseases designates a variety of transmissible benign and malignant neoplasms of chickens caused by members that belong to the family Retroviridae. Because the expansion of the literature on this disease, it is no longer feasible to cite all relevant publications ...

  16. Working Group Report: Neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    de Gouvea, A.; Pitts, K.; Scholberg, K.; Zeller, G. P. [et al.

    2013-10-16

    This document represents the response of the Intensity Frontier Neutrino Working Group to the Snowmass charge. We summarize the current status of neutrino physics and identify many exciting future opportunities for studying the properties of neutrinos and for addressing important physics and astrophysics questions with neutrinos.

  17. Group: radiation dosimetry

    International Nuclear Information System (INIS)

    Caldas, L.V.E.

    1990-01-01

    The main activities of the radiation dosimetry group is described, including the calibration of instruments, sources and radioactive solutions and the determination of neutron flux; development, production and market dosimetric materials; development radiation sensor make the control of radiation dose received by IPEN workers; development new techniques for monitoring, etc. (C.G.C.)

  18. Categorization by Groups

    NARCIS (Netherlands)

    R.W. Hamilton (Rebecca); S. Puntoni (Stefano); N.T. Tavassoli (Nader)

    2006-01-01

    textabstractCategorization is a core psychological process central to consumer and managerial decision-making. While a substantial amount of research has been conducted to examine individual categorization behaviors, relatively little is known about the group categorization process. In two

  19. Gamma gamma technology group

    Indian Academy of Sciences (India)

    The purpose of the meeting was to form a group of people who ... able by looking at the energy deposited at the face of the final dipole, 4.5 m from ... A F Zarnecki has made a good start on background studies, V Telnov has proposed.

  20. Group theory in physics

    CERN Document Server

    Cornwell, J F

    1989-01-01

    Recent devopments, particularly in high-energy physics, have projected group theory and symmetry consideration into a central position in theoretical physics. These developments have taken physicists increasingly deeper into the fascinating world of pure mathematics. This work presents important mathematical developments of the last fifteen years in a form that is easy to comprehend and appreciate.

  1. Anaphylaxis vulnerable groups

    African Journals Online (AJOL)

    Ehab

    Age groups vulnerable to serious attacks of anaphylaxis include infants, teenagers, pregnant women, and the elderly. Concomitant diseases, such as severe or uncontrolled asthma, cardiovascular disease, mastocytosis or clonal mast cell disorders and the concurrent use of some medications such as beta adrenergic ...

  2. Special Interest Groups.

    Science.gov (United States)

    Degi, Bruce J.

    1999-01-01

    Offers a reflection on the shootings at Columbine High School in Littleton, Colorado, on April 20, 1999. Notes how every special-interest group has used the tragedy to support its own point of view, and concludes that teachers have become bystanders in the education of America's children. (SR)

  3. Ignalina Safety Analysis Group

    International Nuclear Information System (INIS)

    Ushpuras, E.

    1995-01-01

    The article describes the fields of activities of Ignalina NPP Safety Analysis Group (ISAG) in the Lithuanian Energy Institute and overview the main achievements gained since the group establishment in 1992. The group is working under the following guidelines: in-depth analysis of the fundamental physical processes of RBMK-1500 reactors; collection, systematization and verification of the design and operational data; simulation and analysis of potential accident consequences; analysis of thermohydraulic and neutronic characteristics of the plant; provision of technical and scientific consultations to VATESI, Governmental authorities, and also international institutions, participating in various projects aiming at Ignalina NPP safety enhancement. The ISAG is performing broad scientific co-operation programs with both Eastern and Western scientific groups, supplying engineering assistance for Ignalina NPP. ISAG is also participating in the joint Lithuanian - Swedish - Russian project - Barselina, the first Probabilistic Safety Assessment (PSA) study of Ignalina NPP. The work is underway together with Maryland University (USA) for assessment of the accident confinement system for a range of breaks in the primary circuit. At present the ISAG personnel is also involved in the project under the grant from the Nuclear Safety Account, administered by the European Bank for reconstruction and development for the preparation and review of an in-depth safety assessment of the Ignalina plant

  4. Gartner Group reports

    CERN Document Server

    Gartner Group. Stamford, CT

    Gartner Group is the one of the leading independent providers of research and analysis material for IT professionals. Their reports provide in-depth analysis of dominant trends, companies and products. CERN has obtained a licence making these reports available online to anyone within CERN. The database contains not only current reports, updated monthly, but also some going back over a year.

  5. Lattices in group manifolds

    International Nuclear Information System (INIS)

    Lisboa, P.; Michael, C.

    1982-01-01

    We address the question of designing optimum discrete sets of points to represent numerically a continuous group manifold. We consider subsets which are extensions of the regular discrete subgroups. Applications to Monte Carlo simulation of SU(2) and SU(3) gauge theory are discussed. (orig.)

  6. Teaching Badminton to Groups.

    Science.gov (United States)

    Nelson, Jonathan E.

    1980-01-01

    Numerous ideas for teaching badminton to large groups are presented. The focus is on drills and techniques for off the court instructional stations. Instead of having students waiting their turn to play, more students can participate actively as they rotate from one station to another. (JN)

  7. Regular Expression Pocket Reference

    CERN Document Server

    Stubblebine, Tony

    2007-01-01

    This handy little book offers programmers a complete overview of the syntax and semantics of regular expressions that are at the heart of every text-processing application. Ideal as a quick reference, Regular Expression Pocket Reference covers the regular expression APIs for Perl 5.8, Ruby (including some upcoming 1.9 features), Java, PHP, .NET and C#, Python, vi, JavaScript, and the PCRE regular expression libraries. This concise and easy-to-use reference puts a very powerful tool for manipulating text and data right at your fingertips. Composed of a mixture of symbols and text, regular exp

  8. Regular expressions cookbook

    CERN Document Server

    Goyvaerts, Jan

    2009-01-01

    This cookbook provides more than 100 recipes to help you crunch data and manipulate text with regular expressions. Every programmer can find uses for regular expressions, but their power doesn't come worry-free. Even seasoned users often suffer from poor performance, false positives, false negatives, or perplexing bugs. Regular Expressions Cookbook offers step-by-step instructions for some of the most common tasks involving this tool, with recipes for C#, Java, JavaScript, Perl, PHP, Python, Ruby, and VB.NET. With this book, you will: Understand the basics of regular expressions through a

  9. Group representations, error bases and quantum codes

    Energy Technology Data Exchange (ETDEWEB)

    Knill, E

    1996-01-01

    This report continues the discussion of unitary error bases and quantum codes. Nice error bases are characterized in terms of the existence of certain characters in a group. A general construction for error bases which are non-abelian over the center is given. The method for obtaining codes due to Calderbank et al. is generalized and expressed purely in representation theoretic terms. The significance of the inertia subgroup both for constructing codes and obtaining the set of transversally implementable operations is demonstrated.

  10. Group leaders optimization algorithm

    Science.gov (United States)

    Daskin, Anmer; Kais, Sabre

    2011-03-01

    We present a new global optimization algorithm in which the influence of the leaders in social groups is used as an inspiration for the evolutionary technique which is designed into a group architecture. To demonstrate the efficiency of the method, a standard suite of single and multi-dimensional optimization functions along with the energies and the geometric structures of Lennard-Jones clusters are given as well as the application of the algorithm on quantum circuit design problems. We show that as an improvement over previous methods, the algorithm scales as N 2.5 for the Lennard-Jones clusters of N-particles. In addition, an efficient circuit design is shown for a two-qubit Grover search algorithm which is a quantum algorithm providing quadratic speedup over the classical counterpart.

  11. Communication from ST Group

    CERN Document Server

    TS Department

    2008-01-01

    Please note that owing the preparations for the Open Days, the FM Group will not able to handle specific requests for waste collection from 2nd to 6th of April, nor removal or PC transport requests between the 31 March and 11 April. We kindly ask you to plan the collection of all types of waste and any urgent transport of office furniture or PCs before 31 March. Waste collection requests must be made by contacting FM Support on 77777 or at the e-mail address mailto:Fm.Support@cern.ch; removal of office furniture or PC transport requests must be made using the EDH ‘Transport request’ form (select "Removals" or "PC transport" from the drop-down menu). For any question concerning the sorting of waste, please consult the following web site: http://dechets-waste.web.cern.ch/dechets-waste/ Thank you for your understanding and collaboration. TS/FM Group

  12. Mindfulness for group facilitation

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Krohn, Simon

    2014-01-01

    In this paper, we argue that mindfulness techniques can be used for enhancing the outcome of group performance. The word mindfulness has different connotations in the academic literature. Broadly speaking there is ‘mindfulness without meditation’ or ‘Western’ mindfulness which involves active...... thinking and ‘Eastern’ mindfulness which refers to an open, accepting state of mind, as intended with Buddhist-inspired techniques such as meditation. In this paper, we are interested in the latter type of mindfulness and demonstrate how Eastern mindfulness techniques can be used as a tool for facilitation....... A brief introduction to the physiology and philosophy of Eastern mindfulness constitutes the basis for the arguments of the effect of mindfulness techniques. The use of mindfulness techniques for group facilitation is novel as it changes the focus from individuals’ mindfulness practice...

  13. Working group 4: Terrestrial

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    A working group at a Canada/USA symposium on climate change and the Arctic identified major concerns and issues related to terrestrial resources. The group examined the need for, and the means of, involving resource managers and users at local and territorial levels in the process of identifying and examining the impacts and consequences of climatic change. Climatic change will be important to the Arctic because of the magnitude of the change projected for northern latitudes; the apparent sensitivity of its terrestrial ecosystems, natural resources, and human support systems; and the dependence of the social, cultural, and economic welfare of Arctic communities, businesses, and industries on the health and quality of their environment. Impacts of climatic change on the physical, biological, and associated socio-economic environment are outlined. Gaps in knowledge needed to quantify these impacts are listed along with their relationships with resource management. Finally, potential actions for response and adaptation are presented

  14. Duality and quantum groups

    International Nuclear Information System (INIS)

    Alvarez-Gaume, L.; Gomez, C.; Sierra, G.

    1990-01-01

    We show that the duality properties of Rational Conformal Field Theories follow from the defining relations and the representation theory of quantum groups. The fusion and braiding matrices are q-analogues of the 6j-symbols and the modular transformation matrices are obtained from the properties of the co-multiplication. We study in detail the Wess-Zumino-Witten models and the rational gaussian models as examples, but carry out the arguments in general. We point out the connections with the Chern-Simons approach. We give general arguments of why the general solution to the polynomial equations of Moore and Seiberg describing the duality properties of Rational Conformal Field Theories defines a Quantum Group acting on the space of conformal blocks. A direct connection between Rational Theories and knot invariants is also presented along the lines of Jones' original work. (orig.)

  15. The Areva Group

    International Nuclear Information System (INIS)

    2004-08-01

    This document provides information on the Areva Group, a world nuclear industry leader, offering solutions for nuclear power generation, electricity transmission and distribution and interconnect systems to the telecommunications, computer and automotive markets. It presents successively the front end division including the group business lines involved in producing nuclear fuel for electric power generation (uranium mining, concentration, conversion and enrichment and nuclear fuel fabrication); the reactors and services division which designs and builds PWR, BWR and research reactors; the back end division which encompasses the management of the fuel that has been used in nuclear power plants; the transmission and distribution division which provides products, systems and services to the medium and high voltage energy markets; the connectors division which designs and manufactures electrical, electronic and optical connectors, flexible micro circuitry and interconnection systems. Areva is implemented in Europe, north and south america, africa and asia-pacific. (A.L.B.)

  16. The Ombudperson Initiative Group

    CERN Multimedia

    Laura Stewart

    Following many discussions that took place at some of the ATLAS Women's Network lunch gatherings, a few ATLAS women joined forces with similarly concerned CERN staff women to form a small group last Fall to discuss the need for a CERN-wide Ombudsperson. This has since evolved into the Ombudsperson Initiative Group (OIG) currently composed of the following members: Barbro Asman, Stockholm University; Pierre Charrue, CERN AB; Anna Cook, CERN IT; Catherine Delamare, CERN and IT Ombudsperson; Paula Eerola, Lund University; Pauline Gagnon, Indiana University; Eugenia Hatziangeli, CERN AB; Doreen Klem, CERN IT; Bertrand Nicquevert, CERN TS and Laura Stewart, CERN AT. On June 12, members of the OIG met with representatives of Human Resources (HR) and the Equal Opportunity Advisory Panel (EOAP) to discuss the proposal drafted by the OIG. The meeting was very positive. Everybody agreed that the current procedures at CERN applicable in the event of conflict required a thorough review, and that a professionnally trai...

  17. Metrically universal abelian groups

    Czech Academy of Sciences Publication Activity Database

    Doucha, Michal

    2017-01-01

    Roč. 369, č. 8 (2017), s. 5981-5998 ISSN 0002-9947 R&D Projects: GA AV ČR IAA100190902 Institutional support: RVO:67985840 Keywords : Abelian group Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 1.426, year: 2016 http://www.ams.org/journals/tran/2017-369-08/S0002-9947-2017-07059-8/

  18. Storage ring group summary

    International Nuclear Information System (INIS)

    King, N.M.

    1980-01-01

    The Storage Ring Group set out to identify and pursue salient problems in accelerator physics for heavy ion fusion, divorced from any particular reference design concept. However, it became apparent that some basic parameter framework was required to correlate the different study topics. As the Workshop progressed, ring parameters were modified and updated. Consequently, the accompanying papers on individual topics will be found to refer to slightly varied parameters, according to the stage at which the different problems were tackled

  19. MAGIC user's group software

    International Nuclear Information System (INIS)

    Warren, G.; Ludeking, L.; McDonald, J.; Nguyen, K.; Goplen, B.

    1990-01-01

    The MAGIC User's Group has been established to facilitate the use of electromagnetic particle-in-cell software by universities, government agencies, and industrial firms. The software consists of a series of independent executables that are capable of inter-communication. MAGIC, SOS, μ SOS are used to perform electromagnetic simulations while POSTER is used to provide post-processing capabilities. Each is described in the paper. Use of the codes for Klystrode simulation is discussed

  20. Multibunch working group

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    The goal of this working group was to foment discussions about the use and limitations of multi-bunch, representatives from most operating or in-project synchrotron radiation sources (ALS, SPEAR, BESSY-2, SPRING-8, ANKA, DELTA, PEP-2, DIAMOND, ESRF...) have presented their experience. The discussions have been led around 3 topics: 1) resistive wall instabilities and ion instabilities, 2) higher harmonic cavities, and 3) multibunch feedback systems.

  1. Group 4. Containment

    International Nuclear Information System (INIS)

    McCauley, V.S.; Keiser, J.R.

    1992-01-01

    This paper summarizes the findings of the Containment Working Group which met at the Workshop on Radioactive, Hazardous, and/or Mixed Waste Sludge Management. The Containment Working Group (CWG) examined the problems associated with providing adequate containment of waste forms from both short- and long-term storage. By its nature, containment encompasses a wide variety of waste forms, storage conditions, container types, containment schemes, and handling activities. A containment system can be anything from a 55-gal drum to a 100-ft-long underground vault. Because of the diverse nature of containment systems, the CWG chose to focus its limited time on broad issues that are applicable to the design of any containment system, rather than attempting to address problems specific to a particular containment system or waste-form type. Four major issues were identified by the CWG. They relate to: (1) service conditions and required system performance; (2) ultimate disposition; (3) cost and schedule; and (4) acceptance criteria, including quality assurance/quality control (QA/QC) concerns. All of the issues raised by the group are similar in that they all help to define containment system requirements

  2. Enhancer of zeste homolog 2 as an independent prognostic marker for cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shuling Chen

    Full Text Available Novel biomarkers are of particular interest for predicting cancer prognosis. This study aimed to explore the associations between enhancer of zeste homolog 2 (EZH2 and patient survival in various cancers.Relevant literature was retrieved from PubMed and Web of Science databases. Pooled hazard ratios (HRs, odds ratios (ORs, and 95% confidence intervals (CIs were calculated.Forty-nine studies (8,050 patients were included. High EZH2 expression was significantly associated with shorter overall (hazard ratio [HR] 1.74, 95% CI: 1.46-2.07, disease-free (HR 1.59, 95% CI: 1.27-1.99, metastasis-free (HR 2.19, 95% CI: 1.38-3.47, progression-free (HR 2.53, 95% CI: 1.52-4.21, cancer-specific (HR 3.13, 95% CI: 1.70-5.74, and disease-specific (HR 2.29, 95% CI: 1.56-3.35 survival, but not recurrence-free survival (HR 1.38, 95% CI: 0.93-2.06. Moreover, EZH2 expression significantly correlated with distant metastasis (OR 3.25, 95% CI: 1.07-9.87 in esophageal carcinoma; differentiation (OR 3.00, 95% CI: 1.37-6.55 in non-small cell lung cancer; TNM stage (OR 3.18, 95% CI: 2.49-4.08 in renal cell carcinoma; and histological grade (OR 4.50, 95% CI: 3.33-6.09, estrogen receptor status (OR 0.15, 95% CI: 0.11-0.20 and progesterone receptor status (OR 0.30, 95% CI: 0.23-0.39 in breast cancer.Our results suggested that EZH2 might be an independent prognostic factor for multiple survival measures in different cancers.

  3. Epigenetic remodeling and modification to preserve skeletogenesis in vivo.

    Science.gov (United States)

    Godfrey, Tanner C; Wildman, Benjamin J; Javed, Amjad; Lengner, Christopher J; Hassan, Mohammad Quamarul

    2018-12-01

    Current studies offer little insight on how epigenetic remodeling of bone-specific chromatin maintains bone mass in vivo. Understanding this gap and precise mechanism is pivotal for future therapeutic innovation to prevent bone loss. Recently, we found that low bone mass is associated with decreased H3K27 acetylation (activating histone modification) of bone specific gene promoters. Here, we aim to elucidate the epigenetic mechanisms by which a miRNA cluster controls bone synthesis and homeostasis by regulating chromatin accessibility and H3K27 acetylation. In order to decipher the epigenetic axis that regulates osteogenesis, we studied a drug inducible anti-miR-23a cluster (miR-23a Cl ZIP ) knockdown mouse model. MiR-23a cluster knockdown (heterozygous) mice developed high bone mass. These mice displayed increased expression of Runx2 and Baf45a, essential factors for skeletogenesis; and decreased expression of Ezh2, a chromatin repressor indispensable for skeletogenesis. ChIP assays using miR-23a Cl knockdown calvarial cells revealed a BAF45A-EZH2 epigenetic antagonistic mechanism that maintains bone formation. Together, our findings support that the miR-23a Cl connection with tissue-specific RUNX2-BAF45A-EZH2 function is a novel molecular epigenetic axis through which a miRNA cluster orchestrates chromatin modification to elicit major effects on osteogenesis in vivo.

  4. miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes.

    Science.gov (United States)

    Luo, Chonglin; Tetteh, Paul W; Merz, Patrick R; Dickes, Elke; Abukiwan, Alia; Hotz-Wagenblatt, Agnes; Holland-Cunz, Stefan; Sinnberg, Tobias; Schittek, Birgit; Schadendorf, Dirk; Diederichs, Sven; Eichmüller, Stefan B

    2013-03-01

    MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes (c-Met and YB1) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box-binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that miR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF.

  5. Darwin and Emotion Expression

    Science.gov (United States)

    Hess, Ursula; Thibault, Pascal

    2009-01-01

    In his book "The Expression of the Emotions in Man and Animals," Charles Darwin (1872/1965) defended the argument that emotion expressions are evolved and adaptive (at least at some point in the past) and serve an important communicative function. The ideas he developed in his book had an important impact on the field and spawned rich domains of…

  6. Freedom of Expression.

    Science.gov (United States)

    Update on Law-Related Education, 1988

    1988-01-01

    Presents an activity which uses hypothetical situations to explore the proper boundaries of freedom of expression and the role of the U.S. Supreme Court in interpreting its limits. Appropriate for grades 4-12, the lesson includes such topics as the "clear and present danger" clause, student expression, obscenity, and defamation. (GEA)

  7. The analytic renormalization group

    Directory of Open Access Journals (Sweden)

    Frank Ferrari

    2016-08-01

    Full Text Available Finite temperature Euclidean two-point functions in quantum mechanics or quantum field theory are characterized by a discrete set of Fourier coefficients Gk, k∈Z, associated with the Matsubara frequencies νk=2πk/β. We show that analyticity implies that the coefficients Gk must satisfy an infinite number of model-independent linear equations that we write down explicitly. In particular, we construct “Analytic Renormalization Group” linear maps Aμ which, for any choice of cut-off μ, allow to express the low energy Fourier coefficients for |νk|<μ (with the possible exception of the zero mode G0, together with the real-time correlators and spectral functions, in terms of the high energy Fourier coefficients for |νk|≥μ. Operating a simple numerical algorithm, we show that the exact universal linear constraints on Gk can be used to systematically improve any random approximate data set obtained, for example, from Monte-Carlo simulations. Our results are illustrated on several explicit examples.

  8. Technology working group

    International Nuclear Information System (INIS)

    Tsujikura, Y.

    2000-01-01

    The workshop of 26-27 june 2000, on nuclear power Plant LIfe Management (PLIM), also included working groups in which major issues facing PLIM activities for nuclear power plants were identified and discussed. The first group was on Technology. Utilities should consider required provisions capacity by properly maintaining and preserving the existing power plants to the extent practicable and taking into account growing demand, limits of energy conservation, and difficulties in finding new power plant sites. Generally, the extension of the life of nuclear power plant (e.g. from 40 years to 60 years) is an attractive option for utilities, as the marginal cost of most existing nuclear power plants is lower than that of almost all other power sources. It is also an attractive option for environmental protection. Consequently, PLIM has become an important issue in the context of the regulatory reform of the electricity markets. Therefore, the three main objectives of the Technology working group are: 1) Documenting how the safety of nuclear power plants being operated for the long-term has been confirmed, and suggesting ways of sharing this information. 2) Addressing development of advanced maintenance technologies necessary over the plant lifetime, and clarifying their technical challenges. 3) Suggesting potential areas of research and development that might, be necessary. Some potential examples of such research include: - improving the effectiveness of maintenance methods to assure detection of incipient faults; - providing cost effective preventive maintenance programmes; - furnishing systematic, cost-effective refurbishment programmes framed to be consistent with efforts to extend the time between re-fuelling; - developing a methodology that moves routine maintenance on-line without compromising safety. (author)

  9. Notes on quantum groups

    International Nuclear Information System (INIS)

    Pressley, A.; Chari, V.; Tata Inst. of Fundamental Research, Bombay

    1990-01-01

    The authors presents an introduction to quantum groups defined as a deformation of the universal enveloping algebra of a Lie algebra. After the description of Hopf algebras with some examples the approach of Drinfel'd and Jimbo is described, where the quantization of a Lie algebra represents a Hopf algebra, defined over the algebra of formal power series in an indetermined h. The authors show that this approach arises from a r-matrix, which satisfies the classical Yang-Baxter equation. As example quantum sl 2 is considered. Furthermore the approaches of Manin and Woroniwicz and the R-matrix approach are described. (HSI)

  10. Unilever Group : equity valuation

    OpenAIRE

    Pires, Susana Sofia Castelo

    2014-01-01

    The following dissertation has the purpose to value the Unilever Group, but more specifically Unilever N.V. being publicly traded in the Amsterdam Exchange Index. Unilever is seen as a global player and one of most successful and competitive fast-moving consumer goods companies. In order to valuate Unilever’s equity, a Discounted Cash Flow (DCF) approach is first carried out, since it is believed to be the most reliable methodology. The value estimated was €36.39, advising one to buy its s...

  11. Statistical Group Comparison

    CERN Document Server

    Liao, Tim Futing

    2011-01-01

    An incomparably useful examination of statistical methods for comparisonThe nature of doing science, be it natural or social, inevitably calls for comparison. Statistical methods are at the heart of such comparison, for they not only help us gain understanding of the world around us but often define how our research is to be carried out. The need to compare between groups is best exemplified by experiments, which have clearly defined statistical methods. However, true experiments are not always possible. What complicates the matter more is a great deal of diversity in factors that are not inde

  12. Renormalization Group Functional Equations

    CERN Document Server

    Curtright, Thomas L

    2011-01-01

    Functional conjugation methods are used to analyze the global structure of various renormalization group trajectories. With minimal assumptions, the methods produce continuous flows from step-scaling {\\sigma} functions, and lead to exact functional relations for the local flow {\\beta} functions, whose solutions may have novel, exotic features, including multiple branches. As a result, fixed points of {\\sigma} are sometimes not true fixed points under continuous changes in scale, and zeroes of {\\beta} do not necessarily signal fixed points of the flow, but instead may only indicate turning points of the trajectories.

  13. Grouping Notes Through Nodes

    DEFF Research Database (Denmark)

    Dove, Graham; Abildgaard, Sille Julie Jøhnk; Biskjær, Michael Mose

    , both individually and when grouped, and their role in categorisation in semantic long-term memory. To do this, we adopt a multimodal analytical approach focusing on interaction between humans, and between humans and artefacts, alongside language. We discuss in detail examples of four different...... externalisation functions served by Post-ItTM notes, and show how these functions are present in complex overlapping combinations rather than being discrete. We then show how the temporal development of Post-ItTM note interactions supports categorisation qualities of semantic long-term memory....

  14. Grouping Notes Through Nodes

    DEFF Research Database (Denmark)

    Dove, Graham; Abildgaard, Sille Julie; Biskjær, Michael Mose

    2017-01-01

    , both individually and when grouped, and their role in categorisation in semantic long-term memory. To do this, we adopt a multimodal analytical approach focusing on interaction between humans, and between humans and artefacts, alongside language. We discuss in detail examples of four different...... externalisation functions served by Post-ItTM notes, and show how these functions are present in complex overlapping combinations rather than being discrete. We then show how the temporal development of Post-ItTM note interactions supports categorisation qualities of semantic long-term memory....

  15. Groups and symmetry

    CERN Document Server

    Farmer, David W

    1995-01-01

    In most mathematics textbooks, the most exciting part of mathematics-the process of invention and discovery-is completely hidden from the reader. The aim of Groups and Symmetry is to change all that. By means of a series of carefully selected tasks, this book leads readers to discover some real mathematics. There are no formulas to memorize; no procedures to follow. The book is a guide: Its job is to start you in the right direction and to bring you back if you stray too far. Discovery is left to you. Suitable for a one-semester course at the beginning undergraduate level, there are no prerequ

  16. Theory and modeling group

    Science.gov (United States)

    Holman, Gordon D.

    1989-01-01

    The primary purpose of the Theory and Modeling Group meeting was to identify scientists engaged or interested in theoretical work pertinent to the Max '91 program, and to encourage theorists to pursue modeling which is directly relevant to data which can be expected to result from the program. A list of participants and their institutions is presented. Two solar flare paradigms were discussed during the meeting -- the importance of magnetic reconnection in flares and the applicability of numerical simulation results to solar flare studies.

  17. The OMERACT Ultrasound Group

    DEFF Research Database (Denmark)

    Terslev, Lene; Iagnocco, Annamaria; Bruyn, George A W

    2017-01-01

    OBJECTIVE: To provide an update from the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group on the progress for defining ultrasound (US) minimal disease activity threshold at joint level in rheumatoid arthritis (RA) and for standardization of US application in juvenile idiopathic......) and power Doppler (PD). Synovial effusion (SE) was scored a binary variable. For JIA, a Delphi approach and subsequent validation in static images and patient-based exercises were used to developed preliminary definitions for synovitis and a scoring system. RESULTS: For minimal disease activity, 7% HC had...

  18. A village group, Trashibiola

    OpenAIRE

    Thomson, John, 1837-1921, photographer

    2003-01-01

    158 x 111 mm. Woodburytype. A view showing a group of villagers seated in a paved courtyard in front of a stonewalled house (the principal house in the village). The village is near the town of Paphos. The photograph appears in Thomson's 'Through Cyprus with the camera, in the autumn of 1878' (vol.2, London: Sampson Low, Marston, Searle, and Rivington, 1879). Thomson states that the purpose of the gathering was twofold: to welcome strangers to the village and to discuss a point of law c...

  19. Bevalac computer support group

    International Nuclear Information System (INIS)

    McParland, C.; Bronson, M.

    1985-01-01

    During the past year, a group was created and placed under the leadership of Charles McParland. This is an expansion of previous Bevalac software efforts and has responsibilities in three major hardware and software areas. The first area is the support of the existing data acquisition/analysis VAX 11/780s at the Bevalac. The second area is the continued support of present data acquisition programs. The third principal area of effort is the development of new data acquisition systems to meet the increasing needs of the Bevalac experimental program

  20. Social group utility maximization

    CERN Document Server

    Gong, Xiaowen; Yang, Lei; Zhang, Junshan

    2014-01-01

    This SpringerBrief explains how to leverage mobile users' social relationships to improve the interactions of mobile devices in mobile networks. It develops a social group utility maximization (SGUM) framework that captures diverse social ties of mobile users and diverse physical coupling of mobile devices. Key topics include random access control, power control, spectrum access, and location privacy.This brief also investigates SGUM-based power control game and random access control game, for which it establishes the socially-aware Nash equilibrium (SNE). It then examines the critical SGUM-b