Sample records for factor sp1 plays

  1. Interaction of Sp1 zinc finger with transport factor in the nuclear localization of transcription factor Sp1

    SciTech Connect

    Ito, Tatsuo [Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan)] [Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan); Kitamura, Haruka; Uwatoko, Chisana; Azumano, Makiko [Department of Molecular Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's University, Kodo, Kyotanabe City, Kyoto 610-0395 (Japan)] [Department of Molecular Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's University, Kodo, Kyotanabe City, Kyoto 610-0395 (Japan); Itoh, Kohji, E-mail: kitoh@ph.tokushima-u.ac.jp [Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan)] [Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan); Kuwahara, Jun, E-mail: jkuwahar@dwc.doshisha.ac.jp [Department of Molecular Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's University, Kodo, Kyotanabe City, Kyoto 610-0395 (Japan)] [Department of Molecular Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's University, Kodo, Kyotanabe City, Kyoto 610-0395 (Japan)

    2010-12-10

    Research highlights: {yields} Sp1 zinc fingers themselves interact with importin {alpha}. {yields} Sp1 zinc finger domains play an essential role as a nuclear localization signal. {yields} Sp1 can be transported into the nucleus in an importin-dependent manner. -- Abstract: Transcription factor Sp1 is localized in the nucleus and regulates the expression of many cellular genes, but the nuclear transport mechanism of Sp1 is not well understood. In this study, we revealed that GST-fused Sp1 protein bound to endogenous importin {alpha} in HeLa cells via the Sp1 zinc finger domains, which comprise the DNA binding domain of Sp1. It was found that the Sp1 zinc finger domains directly interacted with a wide range of importin {alpha} including the armadillo (arm) repeat domain and the C-terminal acidic domain. Furthermore, it turned out that all three zinc fingers of Sp1 are essential for binding to importin {alpha}. Taken together, these results suggest that the Sp1 zinc finger domains play an essential role as a NLS and Sp1 can be transported into the nucleus in an importin-dependent manner even though it possesses no classical NLSs.

  2. Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition

    PubMed Central

    Deniaud, Emmanuelle; Baguet, Joël; Chalard, Roxane; Blanquier, Bariza; Brinza, Lilia; Meunier, Julien; Michallet, Marie-Cécile; Laugraud, Aurélie; Ah-Soon, Claudette; Wierinckx, Anne; Castellazzi, Marc; Lachuer, Joël; Gautier, Christian

    2009-01-01

    Background The ubiquitous transcription factor Sp1 regulates the expression of a vast number of genes involved in many cellular functions ranging from differentiation to proliferation and apoptosis. Sp1 expression levels show a dramatic increase during transformation and this could play a critical role for tumour development or maintenance. Although Sp1 deregulation might be beneficial for tumour cells, its overexpression induces apoptosis of untransformed cells. Here we further characterised the functional and transcriptional responses of untransformed cells following Sp1 overexpression. Methodology and Principal Findings We made use of wild-type and DNA-binding-deficient Sp1 to demonstrate that the induction of apoptosis by Sp1 is dependent on its capacity to bind DNA. Genome-wide expression profiling identified genes involved in cancer, cell death and cell cycle as being enriched among differentially expressed genes following Sp1 overexpression. In silico search to determine the presence of Sp1 binding sites in the promoter region of modulated genes was conducted. Genes that contained Sp1 binding sites in their promoters were enriched among down-regulated genes. The endogenous sp1 gene is one of the most down-regulated suggesting a negative feedback loop induced by overexpressed Sp1. In contrast, genes containing Sp1 binding sites in their promoters were not enriched among up-regulated genes. These results suggest that the transcriptional response involves both direct Sp1-driven transcription and indirect mechanisms. Finally, we show that Sp1 overexpression led to a modified expression of G1/S transition regulatory genes such as the down-regulation of cyclin D2 and the up-regulation of cyclin G2 and cdkn2c/p18 expression. The biological significance of these modifications was confirmed by showing that the cells accumulated in the G1 phase of the cell cycle before the onset of apoptosis. Conclusion This study shows that the binding to DNA of overexpressed Sp1 induces an inhibition of cell cycle progression that precedes apoptosis and a transcriptional response targeting genes containing Sp1 binding sites in their promoter or not suggesting both direct Sp1-driven transcription and indirect mechanisms. PMID:19753117

  3. SP1 plays a pivotal role for basal activity of TIGAR promoter in liver cancer cell lines.

    PubMed

    Zou, Shubiao; Gu, Zhidong; Ni, Peihua; Liu, Xiangfan; Wang, Jiayi; Fan, Qishi

    2012-01-01

    TIGAR expression resulted in down-regulation of glycolysis, reduction of intracellular levels of reactive oxygen species, and protection from apoptosis. Despite biological importance, its promoter has not yet been characterized. In this study, we characterized that transcription factor SP1 plays a pivotal role for basal activity of TIGAR promoter. By 5'RACE, the transcription start site was identified locating at 134 bp upstream of the translation initiation site. Different portions of 5'-flanking and 5'-untranslated regions were fused to a luciferase reporter gene to create reporter plasmids, and constructs were transiently transfected into HepG2, Bel-7402, and Smmc-7721 cell lines for luciferase analysis. A minimal region -56/-4 bearing a SP1-binding site was characterized and plays a vital role. Data from electrophoretic mobility shift assay and chromatin immunoprecipitation showed that SP1 can interact with the SP1-binding site within TIGAR promoter in vitro and in vivo. Conclusively, SPl is indispensable for basal activity of TIGAR promoter. PMID:21761199

  4. Role of zinc finger structure in nuclear localization of transcription factor Sp1

    SciTech Connect

    Ito, Tatsuo; Azumano, Makiko [Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan); Uwatoko, Chisana [Faculty of Pharmaceutical Sciences, Doshisha Women's University, Kodo, Kyotanabe City, 610-0395 (Japan); Itoh, Kohji [Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan)], E-mail: kitoh@ph.tokushima-u.ac.jp; Kuwahara, Jun [Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical Sciences, University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505 (Japan); Faculty of Pharmaceutical Sciences, Doshisha Women's University, Kodo, Kyotanabe City, 610-0395 (Japan)], E-mail: jkuwahar@dwc.doshisha.ac.jp

    2009-02-27

    Transcription factor Sp1 is localized in the nucleus and regulates gene expression. Our previous study demonstrated that the carboxyl terminal region of Sp1 containing 3-zinc finger region as DNA binding domain can also serve as nuclear localization signal (NLS). However, the nuclear transport mechanism of Sp1 has not been well understood. In this study, we performed a gene expression study on mutant Sp1 genes causing a set of amino acid substitutions in zinc finger domains to elucidate nuclear import activity. Nuclear localization of the GFP-fused mutant Sp1 proteins bearing concomitant substitutions in the first and third zinc fingers was highly inhibited. These mutant Sp1 proteins had also lost the binding ability as to the GC box sequence. The results suggest that the overall tertiary structure formed by the three zinc fingers is essential for nuclear localization of Sp1 as well as dispersed basic amino acids within the zinc fingers region.

  5. Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1.

    PubMed Central

    Sif, S; Gilmore, T D

    1994-01-01

    We previously showed that v-Rel, the oncoprotein of the avian retrovirus Rev-T, can increase expression from promoters containing binding sites for the cellular transcription factor Sp1 in chicken embryo fibroblasts (S. Sif, A.J. Capobianco, and T.D. Gilmore, Oncogene 8:2501-2509, 1993). In those experiments, v-Rel appeared to increase the transactivating function of Sp1; that is, v-Rel stimulated transactivation by a GAL4-Sp1 protein that lacked the Sp1 DNA-binding domain. We have now shown that in vitro-synthesized v-Rel and GAL4-Sp1 form a complex that can be immunoprecipitated with either anti-Sp1 or anti-v-Rel antiserum. We have also shown that a glutathione S-transferase (GST)-Sp1 fusion protein can specifically interact with in vitro-translated v-Rel and with in vivo-synthesized v-Rel from transformed chicken spleen cells. In addition, we have found that the abilities of wild-type and two mutant forms of v-Rel to increase transactivation by Sp1 in vivo correlate with their abilities to interact with Sp1 in vitro. The sequences important for the interaction of v-Rel with Sp1 in vitro have been mapped to the first 147 amino acids of v-Rel. Other Rel proteins, such as c-Rel, RelA, p52, and p50, were also able to form a complex with Sp1 in vitro. These results suggest that v-Rel increases expression from Sp1 site-containing promoters by functionally interacting with Sp1 and that cellular Rel proteins and Sp1 are likely to interact to influence transcription from natural promoters. Images PMID:7933095

  6. Overexpression of the Transcription Factor Sp1 Activates the OAS-RNAse L-RIG-I Pathway

    PubMed Central

    Dupuis-Maurin, Valéryane; Brinza, Lilia; Baguet, Joël; Plantamura, Emilie; Schicklin, Stéphane; Chambion, Solène; Macari, Claire; Tomkowiak, Martine; Deniaud, Emmanuelle; Leverrier, Yann

    2015-01-01

    Deregulated expression of oncogenes or transcription factors such as specificity protein 1 (Sp1) is observed in many human cancers and plays a role in tumor maintenance. Paradoxically in untransformed cells, Sp1 overexpression induces late apoptosis but the early intrinsic response is poorly characterized. In the present work, we studied increased Sp1 level consequences in untransformed cells and showed that it turns on an early innate immune transcriptome. Sp1 overexpression does not activate known cellular stress pathways such as DNA damage response or endoplasmic reticulum stress, but induces the activation of the OAS-RNase L pathway and the generation of small self-RNAs, leading to the upregulation of genes of the antiviral RIG-I pathway at the transcriptional and translational levels. Finally, Sp1-induced intrinsic innate immune response leads to the production of the chemokine CXCL4 and to the recruitment of inflammatory cells in vitro and in vivo. Altogether our results showed that increased Sp1 level in untransformed cells constitutes a novel danger signal sensed by the OAS-RNase L axis leading to the activation of the RIG-I pathway. These results suggested that the OAS-RNase L-RIG-I pathway may be activated in sterile condition in absence of pathogen. PMID:25738304

  7. MPTP's Pathway of Toxicity Indicates Central Role of Transcription Factor SP1.

    PubMed

    Maertens, Alexandra; Luechtefeld, Thomas; Kleensang, Andre; Hartung, Thomas

    2015-05-01

    Deriving a Pathway of Toxicity from transcriptomic data remains a challenging task. We explore the use of weighted gene correlation network analysis (WGCNA) to extract an initial network from a small microarray study of MPTP toxicity in mice. Five modules were statistically significant; each module was analyzed for gene signatures in the Chemical and Genetic Perturbation subset of the Molecular Signatures Database as well as for over-represented transcription factor binding sites and WGCNA clustered probes by function and captured pathways relevant to neurodegenerative disorders. The resulting network was analyzed for transcription factor candidates, which were narrowed down via text-mining for relevance to the disease model, and then combined with the large-scale interaction FANTOM4 database to generate a genetic regulatory network. Modules were enriched for transcription factors relevant to Parkinson's disease. Transcription factors significantly improved the number of genes that could be connected in a given component. For each module, the transcription factor that had, by far, the highest number of interactions was SP1, and it also had substantial experimental evidence of interactions. This analysis both captures much of the known biology of MPTP toxicity and suggests several candidates for further study. Furthermore, the analysis strongly suggests that SP1 plays a central role in coordinating the cellular response to MPTP toxicity. PMID:25851821

  8. The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells

    SciTech Connect

    Zhang, Yingyi; Zhao, Yu; Li, Leilei; Shen, Yu; Cai, Xiaoli [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China)] [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)] [Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ye, Lihong, E-mail: yelihong@nankai.edu.cn [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China)] [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2013-05-03

    Highlights: •HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. •HBXIP serves as a coactivator of activating transcription factor Sp1. •HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. •HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-?B (NF-?B) in breast cancer cells. As an oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays crucial roles in carcinogenesis. In the present study, we found that both HBXIP and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP was able to increase transcriptional activity of NF-?B through PDGFB, suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was able to upregulate PDGFB at the levels of mRNA, protein and promoter in the cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through activating transcription factor Sp1. In function, HBXIP enhanced the proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote proliferation of breast cancer cells.

  9. A critical role of Sp1 transcription factor in regulating the human Ki67 gene expression

    Microsoft Academic Search

    Hui Tian; Guo-Wei Qian; Wang Li; Fei-Fei Chen; Jie-Hui Di; Bao-Fu Zhang; Dong-Sheng Pei; Ping Ma; Jun-Nian Zheng

    2011-01-01

    Ki-67 plays a crucial role in cell proliferation as well as maintenance or regulation of cell division. The mechanism governing\\u000a the Ki-67 gene expression remains unknown. Thus, we cloned the core promoter of the human Ki-67 gene and further investigated\\u000a its transcriptional regulation. The putative Sp1 binding sites were confirmed by electrophoretic mobility shift assay together\\u000a with an anti-Sp1 antibody-mediated

  10. Regulation of prion gene expression by transcription factors SP1 and metal transcription factor-1.

    PubMed

    Bellingham, Shayne A; Coleman, Louise A; Masters, Colin L; Camakaris, James; Hill, Andrew F

    2009-01-01

    Prion diseases are associated with the conformational conversion of the host-encoded cellular prion protein into an abnormal pathogenic isoform. Reduction in prion protein levels has potential as a therapeutic approach in treating these diseases. Key targets for this goal are factors that affect the regulation of the prion protein gene. Recent in vivo and in vitro studies have suggested a role for prion protein in copper homeostasis. Copper can also induce prion gene expression in rat neurons. However, the mechanism involved in this regulation remains to be determined. We hypothesized that transcription factors SP1 and metal transcription factor-1 (MTF-1) may be involved in copper-mediated regulation of human prion gene. To test the hypothesis, we utilized human fibroblasts that are deleted or overexpressing the Menkes protein (MNK), a major mammalian copper efflux protein. Menkes deletion fibroblasts have high intracellular copper, whereas Menkes overexpressed fibroblasts have severely depleted intracellular copper. We have utilized this system previously to demonstrate copper-dependent regulation of the Alzheimer amyloid precursor protein. Here we demonstrate that copper depletion in MNK overexpressed fibroblasts decreases cellular prion protein and PRNP gene levels. Conversely, expression of transcription factors SP1 and/or MTF-1 significantly increases prion protein levels and up-regulates prion gene expression in copper-replete MNK deletion cells. Furthermore, siRNA "knockdown" of SP1 or MTF-1 in MNK deletion cells decreases prion protein levels and down-regulates prion gene expression. These data support a novel mechanism whereby SP1 and MTF-1 act as copper-sensing transcriptional activators to regulate human prion gene expression and further support a role for the prion protein to function in copper homeostasis. Expression of the prion protein is a vital component for the propagation of prion diseases; thus SP1 and MTF-1 represent new targets in the development of key therapeutics toward modulating the expression of the cellular prion protein and ultimately the prevention of prion disease. PMID:18990686

  11. Transforming growth factor ? signaling upregulates the expression of human GDP-fucose transporter by activating transcription factor Sp1.

    PubMed

    Xu, Yu-Xin; Ma, Anna; Liu, Li

    2013-01-01

    GDP-fucose transporter plays a crucial role in fucosylation of glycoproteins by providing activated fucose donor, GDP-fucose, for fucosyltransferases in the lumen of the Golgi apparatus. Fucose-containing glycans are involved in many biological processes, which are essential for growth and development. Mutations in the GDP-fucose transporter gene cause leukocyte adhesion deficiency syndrome II, a disease characterized by slow growth, mental retardation and immunodeficiency. However, no information is available regarding its transcriptional regulation. Here, by using human cells, we show that TGF-?1 specifically induces the GDP-fucose transporter expression, but not other transporters tested such as CMP-sialic acid transporter, suggesting a diversity of regulatory pathways for the expression of these transporters. The regulatory elements that are responsive to the TGF-?1 stimulation are present in the region between bp -330 and -268 in the GDP-fucose transporter promoter. We found that this region contains two identical octamer GC-rich motifs (GGGGCGTG) that were demonstrated to be essential for the transporter expression. We also show that the transcription factor Sp1 specifically binds to the GC-rich motifs in vitro and Sp1 coupled with phospho-Smad2 is associated with the promoter region covering the Sp1-binding motifs in vivo using chromatin immunoprecipitation (ChIP) assays. In addition, we further confirmed that Sp1 is essential for the GDP-fucose transporter expression stimulated by TGF-?1 using a luciferase reporter system. These results highlight the role of TGF-? signaling in regulation of the GDP-fucose transporter expression via activating Sp1. This is the first transcriptional study for any nucleotide sugar transporters that have been identified so far. Notably, TGF-?1 receptor itself is known to be modified by fucosylation. Given the essential role of GDP-fucose transporter in fucosylation, the finding that TGF-?1 stimulates the expression of this transporter, suggests a possible intracellular link between the function of nucleotide sugar transporter and the TGF-? signaling pathway. PMID:24069312

  12. Sp1/Sp3 transcription factors regulate hallmarks of megakaryocyte maturation and platelet formation and function.

    PubMed

    Meinders, Marjolein; Kulu, Divine I; van de Werken, Harmen J G; Hoogenboezem, Mark; Janssen, Hans; Brouwer, Rutger W W; van Ijcken, Wilfred F J; Rijkers, Erik-Jan; Demmers, Jeroen A A; Krüger, Imme; van den Berg, Timo K; Suske, Guntram; Gutiérrez, Laura; Philipsen, Sjaak

    2015-03-19

    Sp1 and Sp3 belong to the specificity proteins (Sp)/Krüppel-like transcription factor family. They are closely related, ubiquitously expressed, and recognize G-rich DNA motifs. They are thought to regulate generic processes such as cell-cycle and growth control, metabolic pathways, and apoptosis. Ablation of Sp1 or Sp3 in mice is lethal, and combined haploinsufficiency results in hematopoietic defects during the fetal stages. Here, we show that in adult mice, conditional pan-hematopoietic (Mx1-Cre) ablation of either Sp1 or Sp3 has minimal impact on hematopoiesis, whereas the simultaneous loss of Sp1 and Sp3 results in severe macrothrombocytopenia. This occurs in a cell-autonomous manner as shown by megakaryocyte-specific (Pf4-Cre) double-knockout mice. We employed flow cytometry, cell culture, and electron microscopy and show that although megakaryocyte numbers are normal in bone marrow and spleen, they display a less compact demarcation membrane system and a striking inability to form proplatelets. Through megakaryocyte transcriptomics and platelet proteomics, we identified several cytoskeleton-related proteins and downstream effector kinases, including Mylk, that were downregulated upon Sp1/Sp3 depletion, providing an explanation for the observed defects in megakaryopoiesis. Supporting this notion, selective Mylk inhibition by ML7 affected proplatelet formation and stabilization and resulted in defective ITAM receptor-mediated platelet aggregation. PMID:25538045

  13. Measurement of the binding of transcription factor Sp1 to a single GC box recognition sequence.

    PubMed Central

    Letovsky, J; Dynan, W S

    1989-01-01

    The equilibrium constant was determined for the binding of the transcription factor Sp1 to a single consensus GC box DNA recognition site, (5'-GGGGCGGGGC-3'). For these experiments, single copies of the recognition site were synthesized and cloned in a standard plasmid background. Binding was measured either by a footprinting assay modified so that the binding reaction was at equilibrium, or by a gel mobility shift assay. The concentration of active Sp1 in the reactions and the dissociation constant were determined by computer-assisted fitting to theoretical curves. Values for the dissociation constant obtained in different experiments ranged from 4.1 X 10(-10) M to 5.3 X 10(-10) M. Several variants of the consensus recognition site were also tested. An A-substituted variant (5'-GGGGAGGGGC-3') and a T-substituted variant (5'-GGGGTGGGGC-3') were bound 3-fold and 6-fold more weakly than the consensus site, respectively. A G-substituted variant (5'-GGGGGGGGGC-3') was bound at least 30-fold more weakly than the consensus site. These findings help distinguish between alternative models for Sp1-DNA recognition. They are consistent with the presence of specific hydrogen-bond contacts between Sp1 and the central C-G base pair, but provide no particular evidence to support a model where local DNA structure is the dominant factor in the interaction. Images PMID:2717405

  14. Regulation of transcription of the RNA splicing factor hSlu7 by Elk-1 and Sp1 affects alternative splicing

    PubMed Central

    Alberstein, Moti; Amit, Maayan; Vaknin, Keren; O'Donnell, Amanda; Farhy, Chen; Lerenthal, Yaniv; Shomron, Noam; Shaham, Ohad; Sharrocks, Andrew D.; Ashery-Padan, Ruth; Ast, Gil

    2007-01-01

    Alternative splicing plays a major role in transcriptome diversity and plasticity, but it is largely unknown how tissue-specific and embryogenesis-specific alternative splicing is regulated. The highly conserved splicing factor Slu7 is involved in 3? splice site selection and also regulates alternative splicing. We show that Slu7 has a unique spatial pattern of expression among human and mouse embryonic and adult tissues. We identified several functional Ets binding sites and GC-boxes in the human Slu7 (hSlu7) promoter region. The Ets and GC-box binding transcription factors, Elk-1 and Sp1, respectively, exerted opposite effects on hSlu7 transcription: Sp1 protein enhances and Elk-1 protein represses transcription in a dose-dependent manner. Sp1 protein bound to the hSlu7 promoter in vivo, and depletion of Sp1 by RNA interference (RNAi) repressed hSlu7 expression. Elk-1 protein bound to the hSlu7 promoter in vivo, and depletion of Elk-1 by RNAi caused an increase in the endogenous level of hSlu7 mRNA. Further, depletion of either Sp1 or Elk-1 affected alternative splicing. Our results provide indications of a complex transcription regulation mechanism that controls the spatial and temporal expression of Slu7, presumably allowing regulation of tissue-specific alternative splicing events. PMID:17804646

  15. Molecular Characterisation, Evolution and Expression of Hypoxia-Inducible Factor in Aurelia sp.1

    PubMed Central

    Wang, Guoshan; Yu, Zhigang; Zhen, Yu; Mi, Tiezhu; Shi, Yan; Wang, Jianyan; Wang, Minxiao; Sun, Song

    2014-01-01

    The maintenance of physiological oxygen homeostasis is mediated by hypoxia-inducible factor (HIF), a key transcriptional factor of the PHD-HIF system in all metazoans. However, the molecular evolutionary origin of this central physiological regulatory system is not well characterized. As the earliest eumetazoans, Cnidarians can be served as an interesting model for exploring the HIF system from an evolutionary perspective. We identified the complete cDNA sequence of HIF-1? (ASHIF) from the Aurelia sp.1, and the predicted HIF-1? protein (pASHIF) was comprised of 674 amino acids originating from 2,025 bp nucleotides. A Pairwise comparison revealed that pASHIF not only possessed conserved basic helix-loop-helix (bHLH) and Per-Arnt-Sim (PAS) domains but also contained the oxygen dependent degradation (ODD) and the C-terminal transactivation domains (C-TAD), the key domains for hypoxia regulation. As indicated by sequence analysis, the ASHIF gene contains 8 exons interrupted by 7 introns. Western blot analysis indicated that pASHIF that existed in the polyps and medusa of Aurelia. sp.1 was more stable for a hypoxic response than normoxia. PMID:24926666

  16. Fluid shear stress-induced transcriptional activation of the vascular endothelial growth factor receptor-2 gene requires Sp1-dependent DNA binding.

    PubMed

    Urbich, Carmen; Stein, Monika; Reisinger, Kerstin; Kaufmann, Roland; Dimmeler, Stefanie; Gille, Jens

    2003-01-30

    Hemodynamic forces play a fundamental role in the regulation of endothelial cell survival. As signaling via the vascular endothelial growth factor (VEGF) receptor-2 pathway has been previously demonstrated to impact endothelial cell survival, we hypothesized that laminar shear stress may facilitate survival in part by inducing VEGF receptor-2 expression. This study shows a time- and dose-dependent upregulation of endothelial VEGF receptor-2 expression by fluid shear stress in microvascular and large-vessel derived endothelial cells. A functional analysis of the 5'-regulatory region of the VEGF receptor-2 promoter localized the shear stress-response element to a sequence between bp -60 and -37 that encompasses two adjacent consensus Sp1 transcription factor binding sites. Constitutive and shear stress-inducible Sp1-dependent complexes are bound to this element, indicating that fluid shear stress-induced transcriptional activation of the VEGF receptor-2 gene requires Sp1-dependent DNA binding. Together, these results suggest that biomechanical stimulation may lead to endothelial cell survival by upregulating VEGF receptor-2 expression. PMID:12560084

  17. An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways

    PubMed Central

    Hirose, Takashi; Horvitz, H. Robert

    2013-01-01

    During animal development, the proper regulation of apoptosis requires the precise spatial and temporal execution of cell-death programs, which can include both caspase-dependent and caspase-independent pathways1, 2. While the mechanisms of caspase-dependent and caspase-independent cell killing have been examined extensively, how these pathways are coordinated within a single cell that is fated to die is unknown. Here we show that the C. elegans Sp1 transcription factor SPTF-3 specifies the programmed cell deaths of at least two cells, the sisters of the pharyngeal M4 motor neuron and of the AQR sensory neuron, by transcriptionally activating both caspase-dependent and caspase-independent apoptotic pathways. SPTF-3 directly drives the transcription of the gene egl-1, which encodes a BH3-only protein that promotes apoptosis through the activation of the CED-3 caspase3. In addition, SPTF-3 directly drives the transcription of the AMPK-related gene pig-1, which encodes a protein kinase and functions in apoptosis of the M4 sister and AQR sister independently of the pathway that activates CED-34, 5. Thus, a single transcription factor controls two distinct cell-killing programs that act in parallel to drive apoptosis. Our findings reveal a bivalent regulatory node for caspase-dependent and caspase-independent pathways in the regulation of cell-type specific apoptosis. We propose that such nodes might act in a general mechanism for regulating cell-type specific apoptosis and could define therapeutic targets for diseases involving the dysregulation of apoptosis through multiple cell-killing mechanisms. PMID:23851392

  18. miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1

    PubMed Central

    Amodio, N; Di Martino, M T; Foresta, U; Leone, E; Lionetti, M; Leotta, M; Gullà, A M; Pitari, M R; Conforti, F; Rossi, M; Agosti, V; Fulciniti, M; Misso, G; Morabito, F; Ferrarini, M; Neri, A; Caraglia, M; Munshi, N C; Anderson, K C; Tagliaferri, P; Tassone, P

    2012-01-01

    MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells. PMID:23190608

  19. Hemoglobin switching in humans is accompanied by changes in the ratio of the transcription factors, GATA-1 and SP1.

    PubMed Central

    Bacon, E. R.; Dalyot, N.; Filon, D.; Schreiber, L.; Rachmilewitz, E. A.; Oppenheim, A.

    1995-01-01

    BACKGROUND: Understanding the mechanism of developmental regulation of hemoglobin switching has scientific as well as clinical relevance because of the influence of fetal hemoglobin (HbF) production in adulthood on the clinical manifestation of thalassemia and sickle cell anemia. We have previously found that the normal developmental patterns of globin gene expression are recapitulated in an experimental system of primary cultures that support differentiation of erythroid progenitors. We further found that high activities of the transcriptional activators, GATA-1 and SP1, are associated with normal adult erythroid differentiation. MATERIALS AND METHODS: In the present work, we have studied, the activities of GATA-1 and SP1 during differentiation of cultured erythroid progenitors derived from cord blood and from fetal livers, as well as from beta zero-thalassemia patients. RESULTS: The results showed high GATA-1 binding activity and very low SP1 activity in the fetal liver cultures. This pattern was in contrast to cultures derived from normal adult peripheral blood, in which both GATA-1 and SP1 activities were high. Cord blood cultures showed an additive combination of "adult" and "fetal" patterns. The progenitors derived from a beta zero-thalassemia patient with high HbF production showed "fetal" pattern. On the other hand, in cultures of 2 beta zero-thalassemia patients without high HbF, "adult" pattern was observed. CONCLUSIONS: In the present work, we show that human fetal and adult erythroid progenitors are distinct in their transcription factors, and that the commitment to fetal or adult program occurs at a very early differentiation stage. Our studies also demonstrate that under anemic stress, recruitment of fetal progenitors may occur in adulthood. Images FIG. 1 FIG. 2 FIG. 3 PMID:8529108

  20. Nerve Growth Factor Regulation of Cyclin D1 in PC12 Cells through a p21RAS Extracellular Signal-regulated Kinase Pathway Requires Cooperative Interactions between Sp1 and Nuclear Factor-?B

    PubMed Central

    Marampon, Francesco; Casimiro, Mathew C.; Fu, Maofu; Powell, Michael J.; Popov, Vladimir M.; Lindsay, Jaime; Zani, Bianca M.; Ciccarelli, Carmela; Watanabe, Genichi; Lee, Richard J.

    2008-01-01

    The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21RAS pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF induction of cyclin D1 involved cooperative interactions of extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase pathways downstream of p21RAS. NGF induced the cyclin D1 promoter via Sp1, nuclear factor-?B, and cAMP-response element/activated transcription factor sites. NGF induction via Sp1 involved the formation of a Sp1/p50/p107 complex. Cyclin D1 induction by NGF governs differentiation and neurite outgrowth in PC12 cells. PMID:18367547

  1. Play Deprivation: A Factor in Juvenile Violence.

    ERIC Educational Resources Information Center

    Frost, Joe; Jacobs, Paul J.

    1995-01-01

    Notes that the increasing number of violent crimes committed by children is a result of play deprivation. Discusses different forms of play and distinguishes between controlled and free play. Examines factors such as inadequate outdoor spaces, organized sports, and hi-tech entertainment which interfere with spontaneous play. Discusses the concept…

  2. CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1\\/Sp3 binding

    Microsoft Academic Search

    D. Li; L. Da; H. Tang; T. Li; M. Zhao

    2007-01-01

    Cell-death-inducing DFF45-like effector A (CIDE-A) belongs to a family of proapoptotic proteins, the expression of which is highly restricted in human tissues and cells. Here, the core region of the human CIDE-A promoter was characterized. Surprisingly, two Sp1\\/Sp3-binding sites, rather than tissue- specific transcription factors, were found to be required for the promoter activity. Although the ubiquitously expressed Sp1 and

  3. The Crz1/Sp1 Transcription Factor of Cryptococcus neoformans Is Activated by Calcineurin and Regulates Cell Wall Integrity

    PubMed Central

    Lev, Sophie; Desmarini, Desmarini; Chayakulkeeree, Methee; Sorrell, Tania C.; Djordjevic, Julianne T.

    2012-01-01

    Cryptococcus neoformans survives host temperature and regulates cell wall integrity via a calcium-dependent phosphatase, calcineurin. However, downstream effectors of C. neoformans calcineurin are largely unknown. In S. cerevisiae and other fungal species, a calcineurin-dependent transcription factor Crz1, translocates to nuclei upon activation and triggers expression of target genes. We now show that the C. neoformans Crz1 ortholog (Crz1/Sp1), previously identified as a protein kinase C target during starvation, is a bona fide target of calcineurin under non-starvation conditions, during cell wall stress and growth at high temperature. Both the calcineurin-defective mutant, ?cna1, and a CRZ1/SP1 mutant (?crz1) were susceptible to cell wall perturbing agents. Furthermore, expression of the chitin synthase encoding gene, CHS6, was reduced in both mutants. We tracked the subcellular localization of Crz1-GFP in WT C. neoformans and ?cna1 in response to different stimuli, in the presence and absence of the calcineurin inhibitor, FK506. Exposure to elevated temperature (30–37°C vs 25°C) and extracellular calcium caused calcineurin-dependent nuclear accumulation of Crz1-GFP. Unexpectedly, 1M salt and heat shock triggered calcineurin-independent Crz1-GFP sequestration within cytosolic and nuclear puncta. To our knowledge, punctate cytosolic distribution, as opposed to nuclear targeting, is a unique feature of C. neoformans Crz1. We conclude that Crz1 is selectively activated by calcium/calcineurin-dependent and independent signals depending on the environmental conditions. PMID:23251520

  4. The Crz1/Sp1 transcription factor of Cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity.

    PubMed

    Lev, Sophie; Desmarini, Desmarini; Chayakulkeeree, Methee; Sorrell, Tania C; Djordjevic, Julianne T

    2012-01-01

    Cryptococcus neoformans survives host temperature and regulates cell wall integrity via a calcium-dependent phosphatase, calcineurin. However, downstream effectors of C. neoformans calcineurin are largely unknown. In S. cerevisiae and other fungal species, a calcineurin-dependent transcription factor Crz1, translocates to nuclei upon activation and triggers expression of target genes. We now show that the C. neoformans Crz1 ortholog (Crz1/Sp1), previously identified as a protein kinase C target during starvation, is a bona fide target of calcineurin under non-starvation conditions, during cell wall stress and growth at high temperature. Both the calcineurin-defective mutant, ?cna1, and a CRZ1/SP1 mutant (?crz1) were susceptible to cell wall perturbing agents. Furthermore, expression of the chitin synthase encoding gene, CHS6, was reduced in both mutants. We tracked the subcellular localization of Crz1-GFP in WT C. neoformans and ?cna1 in response to different stimuli, in the presence and absence of the calcineurin inhibitor, FK506. Exposure to elevated temperature (30-37°C vs 25°C) and extracellular calcium caused calcineurin-dependent nuclear accumulation of Crz1-GFP. Unexpectedly, 1M salt and heat shock triggered calcineurin-independent Crz1-GFP sequestration within cytosolic and nuclear puncta. To our knowledge, punctate cytosolic distribution, as opposed to nuclear targeting, is a unique feature of C. neoformans Crz1. We conclude that Crz1 is selectively activated by calcium/calcineurin-dependent and independent signals depending on the environmental conditions. PMID:23251520

  5. Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21(Cip1) by modulating the transcription factor Sp1.

    PubMed

    Jin, Lin; Datta, Pran K

    2014-01-01

    We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21(Cip1). However, the functional mechanism of regulation of E-cadherin and p21(Cip1) by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21(Cip1) by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21(Cip1) promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21(Cip1) by >4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21(Cip1) by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21(Cip1) and to tumor progression. PMID:25483064

  6. Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK)

    PubMed Central

    Luo, Jingyan; Wang, Xiaoxiao; Xia, Zhibo; Yang, Lixuan; Ding, Zhiming; Chen, Shiyuan; Lai, Bingquan; Zhang, Nu

    2015-01-01

    Midkine (MDK) expression is associated with the proliferation of many cancers, including glioma. However, the upstream signaling that leads to MDK accumulation remains elusive. This study investigates the molecular mechanism that induces MDK overexpression in human glioma. The Repository for Molecular Brain Neoplasia Data was analyzed to identify potential MDK regulators. Expression of MDK and specificity protein 1 (SP1) was compared in glioma specimens. Chromatin immunoprecipitation assay was used to confirm the transcriptional regulation. MDK-force–expressed, SP1-silenced glioma cells were used to test rescue effects in vitro and in vivo. MDK and SP1 expression in gliomas was significantly higher than in adjacent tissues and was positively correlated in glioma clinical samples and cell lines. The promoter of the human MDK gene has a putative SP1 binding site. SP1 binds to the promoter of the MDK gene and directly regulates MDK expression. MDK or SP1 gene silencing inhibited the proliferation of glioma cells and reduced the tumor volume in nude mice. Overexpression of MDK in SP1-silenced cells could partially rescue the SP1 inhibition effects in vivo and in vitro. SP1 directly up-regulated the expression of MDK, and the SP1-MDK axis cooperated in glioma tumorigenesis. PMID:25428991

  7. Involvement of PKC{alpha} in insulin-induced PKC{delta} expression: Importance of SP-1 and NF{kappa}B transcription factors

    SciTech Connect

    Horovitz-Fried, Miriam [Faculty of Life Sciences, Department of Life Sciences, Bar-Ilan University, Ramat-Gan 52900 (Israel); Sampson, Sanford R. [Faculty of Life Sciences, Department of Life Sciences, Bar-Ilan University, Ramat-Gan 52900 (Israel)]. E-mail: sampsos@mail.biu.ac.il

    2007-01-05

    Protein kinase C delta (PKC{delta}) is a key molecule in insulin signaling essential for insulin-induced glucose transport in skeletal muscle. Recent studies in our laboratory have shown that insulin rapidly stimulates PKC{delta} activity and increases PKC{delta} protein and RNA levels, and that the SP-1 transcription factor is involved in insulin-induced transcription of the PKC{delta} gene. Activation of SP-1 involves serine phosphorylation and translocation to the nucleus. In this study we examined the possibility that PKC{alpha} might be involved in serine phosphorylation and activation of SP-1. We found that insulin rapidly phosphorylates and translocates SP-1. In the cytoplasm, SP-1 was constitutively associated with PKC{alpha}, and insulin stimulation caused these proteins to dissociate. In contrast, in the nucleus insulin induced an increase in association between PKC{alpha} and SP-1. PKC{alpha} inhibition blocked insulin-induced serine phosphorylation of SP-1 and its association with PKC{alpha} in the nucleus. Inhibition of PKC{alpha} also reduced the insulin-induced increase in PKC{delta} RNA and protein in the cytoplasmic and nuclear fractions. We also attempted to determine if another transcription factor might be involved in regulation of PKC{delta} expression. We earlier showed that insulin did not affect nuclear NF{kappa}B levels. Inhibition of NF{kappa}B, however, increased insulin-induced increase in PKC{delta} RNA and protein in the cytoplasmic and nuclear fractions. Surprisingly, this inhibition reduced the insulin-induced increase in cytoplasmic and nuclear PKC{alpha} RNA and protein. Inhibition of PKC{delta} reduced I{kappa}B{alpha} phosphorylation as well as NF{kappa}B activation. Thus, PKC{alpha} regulates insulin-induced PKC{delta} expression levels and this regulation involves activation of SP-1 and NF{kappa}B.

  8. Specificity protein 1 (Sp1)-dependent activation of the synapsin I gene (SYN1) is modulated by RE1-silencing transcription factor (REST) and 5'-cytosine-phosphoguanine (CpG) methylation.

    PubMed

    Paonessa, Francesco; Latifi, Shahrzad; Scarongella, Helena; Cesca, Fabrizia; Benfenati, Fabio

    2013-02-01

    The development and function of the nervous system are directly dependent on a well defined pattern of gene expression. Indeed, perturbation of transcriptional activity or epigenetic modifications of chromatin can dramatically influence neuronal phenotypes. The phosphoprotein synapsin I (Syn I) plays a crucial role during axonogenesis and synaptogenesis as well as in synaptic transmission and plasticity of mature neurons. Abnormalities in SYN1 gene expression have been linked to important neuropsychiatric disorders, such as epilepsy and autism. SYN1 gene transcription is suppressed in non-neural tissues by the RE1-silencing transcription factor (REST); however, the molecular mechanisms that allow the constitutive expression of this genetic region in neurons have not been clarified yet. Herein we demonstrate that a conserved region of human and mouse SYN1 promoters contains cis-sites for the transcriptional activator Sp1 in close proximity to REST binding motifs. Through a series of functional assays, we demonstrate a physical interaction of Sp1 on the SYN1 promoter and show that REST directly inhibits Sp1-mediated transcription, resulting in SYN1 down-regulation. Upon differentiation of neuroblastoma Neuro2a cells, we observe a decrease in endogenous REST and a higher stability of Sp1 on target GC boxes, resulting in an increase of SYN1 transcription. Moreover, methylation of Sp1 cis-sites in the SYN1 promoter region could provide an additional level of transcriptional regulation. Our results introduce Sp1 as a fundamental activator of basal SYN1 gene expression, whose activity is modulated by the neural master regulator REST and CpG methylation. PMID:23250796

  9. Regulation of human CETP gene expression: role of SP1 and SP3 transcription factors at promoter sites -690, -629, and -37

    Microsoft Academic Search

    Wilfried Le Goff; Laure Petit; M. John Chapman; Joëlle Thillet

    2003-01-01

    Cholesteryl ester transfer protein (CETP) is a key factor in plasma reverse cholesterol transport and is implicated in the pathophysiology of atherogenic dyslipidemia. Variations observed in plasma CETP mass and activity in both normolipi- demic and dyslipidemic individuals may reflect differences in CETP gene expression. We evaluated the respective roles of the Sp1 and Sp3 transcription factors on the promoter

  10. Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1

    SciTech Connect

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada)] [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada); Babiuk, Lorne A. [University of Alberta, Edmonton, Alberta (Canada)] [University of Alberta, Edmonton, Alberta (Canada); Liu, Qiang, E-mail: qiang.liu@usask.ca [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada)] [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada)

    2010-11-19

    Research highlights: {yields} A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. {yields} HCV-3a NS5A increases mature SREBP-1c protein level. {yields} HCV-3a NS5A activates SREBP-1c transcription. {yields} Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. {yields} Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

  11. Sp1 Transcription Factor and GATA1 cis-Acting Elements Modulate Testis-Specific Expression of Mouse Cyclin A1

    PubMed Central

    Panigrahi, Sunil K.; Vasileva, Ana; Wolgemuth, Debra J.

    2012-01-01

    Cyclin A1 is a male germ cell-specific cell cycle regulator that is essential for spermatogenesis. It is unique among the cyclins by virtue of its highly restricted expression in vivo, being present in pachytene and diplotene spermatocytes and not in earlier or later stages of spermatogenesis. To begin to understand the molecular mechanisms responsible for this narrow window of expression of the mouse cyclin A1 (Ccna1) gene, we carried out a detailed analysis of its promoter. We defined a 170-bp region within the promoter and showed that it is involved in repression of Ccna1 in cultured cells. Within this region we identified known cis-acting transcription factor binding sequences, including an Sp1-binding site and two GATA1-binding sites. Neither Sp1 nor GATA1 is expressed in pachytene spermatocytes and later stages of germ cell differentiation. Sp1 is readily detected at earlier stages of spermatogenesis. Site-directed mutagenesis demonstrated that neither factor alone was sufficient to significantly repress expression driven by the Ccna1 promoter, while concurrent binding of Sp1, and most likely GATA1 and possibly additional factors was inhibitory. Occupancy of Sp1 on the Ccna1 promoter and influence of GATA1-dependent cis-acting elements was confirmed by ChIP analysis in cell lines and most importantly, in spermatogonia. In contrast with many other testis-specific genes, the CpG island methylation status of the Ccna1 promoter was similar among various tissues examined, irrespective of whether Ccna1 was transcriptionally active, suggesting that this regulatory mechanism is not involved in the restricted expression of Ccna1. PMID:23112860

  12. Regulatory mechanism of PAC1 gene expression via Sp1 by nerve growth factor in PC12 cells.

    PubMed

    Miura, Ayako; Odahara, Naoko; Tominaga, Aiko; Inoue, Kazuhiko; Kambe, Yuki; Kurihara, Takashi; Miyata, Atsuro

    2012-06-12

    In addition to VPAC1 and VPAC2, PAC1 is involved in the pleiotropic action of pituitary adenylate cyclase activating polypeptide (PACAP) in the CNS. A luciferase reporter assay for the human PAC1 gene (-2160/+268) revealed that NGF treatment significantly augments the promoter activity of the PAC1 gene. Moreover, the Sp1 site at -282/-273 was shown to be essential for the NGF-augmented promoter activity of the PAC1 gene. Treatment with U0126, an MEK inhibitor, or Mithramycin A, an Sp1 inhibitor, significantly attenuated promoter activity. These results indicate that activation of Sp1 by the Ras/MAPK pathway might participate in neuron specific expression of the PAC1 gene. PMID:22609358

  13. The PP2A-A? gene is regulated by multiple transcriptional factors including Ets-1, SP1/SP3, and RXR?/?.

    PubMed

    Liu, J; Ji, W; Sun, S; Zhang, L; Chen, H-G; Mao, Y; Liu, L; Zhang, X; Gong, L; Deng, M; Chen, L; Han, W-J; Chen, P-C; Hu, W-F; Hu, X; Woodward, Z; Liu, W-B; Xiao, Y-M; Liang, S-P; Liu, Y; Liu, S-J; Li, D W-C

    2012-09-01

    Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65 kD scaffold A subunit, a 36 kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130 kDs. The scaffold subunits, PP2A-A?/?, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-A? and PP2A-A? lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-A? is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2? but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-A? gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXR?/?, are present in the proximal promoter of the mouse PP2A-A? gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXR?/? all bind to PP2A-A? gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXR?/? positively regulate the promoter of the PP2A-A? gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXR?/? and the luciferase reporter gene driven by PP2A-A? promoter further confirm their control over the PP2A-A? promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXR?/? can all bind to the PP2A-A? gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-A? gene. Moreover, our results provide important information explaining why PP2A-A? and PP2A-A? display distinct expression levels. PMID:22827437

  14. Hydroxyurea and interleukin-6 synergistically reactivate HIV-1 replication in a latently infected promonocytic cell line via SP1/SP3 transcription factors.

    PubMed

    Oguariri, Raphael M; Brann, Terrence W; Imamichi, Tomozumi

    2007-02-01

    The existence of viral latency limits the success of highly active antiretroviral therapy. With the therapeutic intention of reactivating latent virus to induce a cure, in this study we assessed the impact of cell synchronizers on HIV gene activation in latently infected U1 cells and investigated the molecular mechanisms responsible for such effect. Latently infected U1 cells were treated with 10 drugs including hydroxyurea (HU) and HIV-1 replication monitored using a p24 antigen capture assay. We found that HU was able to induce HIV-1 replication by 5-fold. HU has been used in the clinical treatment of HIV-1-infected patients in combination with didanosine; therefore, we investigated the impact of HU on HIV-1 activation in the presence of the proinflammatory cytokines, interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). IL-6 or TNF-alpha alone induced HIV replication by 18- and approximately 500-fold, respectively. Of interest, in the presence of HU, IL-6-mediated HIV-1 activation was enhanced by >90-fold, whereas TNF-alpha-mediated activation was inhibited by >30%. A reporter gene assay showed that HU and IL-6 synergized to activate HIV promoter activity via the Sp1 binding site. Electrophoretic mobility shift and supershift assays revealed increased binding of the Sp1 and Sp3 transcription factors to this region. Western blot analysis showed that HU and IL-6 co-stimulation resulted in increased levels of Sp1 and Sp3 proteins. In contrast, treatment with HU plus TNF-alpha down-regulated the expression of NF-kappaB. These findings suggest that Sp1/Sp3 is involved in controlling the HU/IL-6-induced reactivation of HIV-1 in latently infected cells. PMID:17150965

  15. B-Myb acts as a repressor of human COL1A1 collagen gene expression by interacting with Sp1 and CBF factors in scleroderma fibroblasts.

    PubMed Central

    Cicchillitti, Lucia; Jimenez, Sergio A; Sala, Arturo; Saitta, Biagio

    2004-01-01

    We investigated the role of B-Myb, a cell-cycle-regulated transcription factor, in the expression of the alpha1 (I) pro-collagen gene (COL1A1) in scleroderma fibroblasts. Scleroderma or SSc (systemic sclerosis) is a fibrotic disease characterized by excessive production of extracellular matrix components, especially type I collagen. Northern-blot analysis showed an inverse relationship between COL1A1 mRNA expression and that of B-Myb during exponential cell growth and during quiescence in human SSc fibroblasts. Overexpression of B-Myb in SSc fibroblasts was correlated with decreased COL1A1 mRNA expression. Transient transfections localized the down-regulatory effect of B-Myb to a region containing the proximal 174 bp of the COL1A1 promoter that does not contain B-Myb consensus binding sites. Gel-shift analysis, using nuclear extracts from normal and SSc fibroblasts transfected with B-Myb, showed no differences in DNA-protein complex formation when compared with the nuclear extracts from mock-transfected cells. However, we found that B-Myb decreases Sp1 (specificity protein 1) and CBF (CCAAT-binding factor) binding for their specific sites localized in the 174 bp COL1A1 proximal promoter. These results were also confirmed using B-Myb-immunodepleted nuclear extracts. Furthermore, immunoprecipitation assays using SSc nuclear extracts demonstrated a physical interaction of B-Myb with Sp1 and CBF transcription factors, and also an interaction between Sp1 and CBF. In addition, by employing full-length or deleted B-Myb cDNA construct, we found that B-Myb down-regulates the COL1A1 proximal promoter through its C-terminal domain. Thus these results suggest that B-Myb may be an important factor in the pathway(s) regulating collagen production in SSc fibroblasts. PMID:14613485

  16. Regulation of the Cyclin-dependent Kinase Inhibitor 1A Gene (CDKN1A) by the Repressor BOZF1 through Inhibition of p53 Acetylation and Transcription Factor Sp1 Binding*

    PubMed Central

    Kim, Min-Kyeong; Jeon, Bu-Nam; Koh, Dong-In; Kim, Kyung-Sup; Park, So-Yoon; Yun, Chae-Ok; Hur, Man-Wook

    2013-01-01

    The human POZ domain and Krüppel-like zinc finger (POK) family proteins play important roles in the regulation of apoptosis, cell proliferation, differentiation, development, oncogenesis, and tumor suppression. A novel POK family transcription factor, BTB/POZ and zinc finger domains factor on chromosome 1 (BOZF-1; also called ZBTB8A), contains a POZ domain and two C2H2-type Krüppel-like zinc fingers and is localized at nuclear speckles. Compared with paired normal tissues, BOZF1 expression is increased in cancer tissues of the prostate, breast, and cervix. BOZF1 repressed the transcription of p21WAF/CDKN1A by acting on the proximal promoter concentrated with Sp1-binding GC boxes. BOZF1 competed with Sp1 in binding to GC boxes 1–5/6 of the CDKN1A proximal promoter. In addition, BOZF1 interacted with p53 and decreased the acetylation of p53 by p300, which reduced the DNA binding activity of p53 at the far distal p53-binding element. BOZF1 blocked the two major molecular events that are important in both constitutive and inducible transcription activation of CDKN1A. BOZF1 is unique in that it bound to all the proximal GC boxes to repress transcription, and it inhibited p53 acetylation without affecting p53 stability. BOZF1 might be a novel proto-oncoprotein that stimulates cell proliferation. PMID:23329847

  17. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

    PubMed Central

    Miyata, Kohei; Yotsumoto, Fusanori; Nam, Sung Ouk; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Itamochi, Hiroaki; Kigawa, Junzo; Takada, Shuji; Asahara, Hiroshi; Kuroki, Masahide; Miyamoto, Shingo

    2014-01-01

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5?-deletion promoter constructs identified a GC-rich element between ?125 and ?178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells. PMID:25060396

  18. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma.

    PubMed

    Miyata, Kohei; Yotsumoto, Fusanori; Nam, Sung Ouk; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Itamochi, Hiroaki; Kigawa, Junzo; Takada, Shuji; Asahara, Hiroshi; Kuroki, Masahide; Miyamoto, Shingo

    2014-10-01

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF-targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5'-deletion promoter constructs identified a GC-rich element between -125 and -178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells. PMID:25060396

  19. EPAS-1 mediates SP-1-dependent FBI-1 expression and regulates tumor cell survival and proliferation.

    PubMed

    Wang, Xiaogang; Cao, Peng; Li, Zhiqing; Wu, Dongyang; Wang, Xi; Liang, Guobiao

    2014-01-01

    Factor binding IST-1 (FBI-1) plays an important role in oncogenic transformation and tumorigenesis. As FBI-1 is over-expressed in multiple human cancers, the regulation of itself would provide new effective options for cancer intervention. In this work, we aimed to study the role that EPAS-1 plays in regulating FBI-1. We use the fact that specificity protein-1 (SP-1) is one of the crucial transcription factors of FBI-1, and that SP-1 can interact with the endothelial pas domain protein-1 (EPAS-1) for the induction of hypoxia related genes. The study showed that EPAS-1 plays an indispensible role in SP-1 transcription factor-mediated FBI-1 induction, and participated in tumor cell survival and proliferation. Thus, EPAS-1 could be a novel target for cancer therapeutics. PMID:25192290

  20. EPAS-1 Mediates SP-1-Dependent FBI-1 Expression and Regulates Tumor Cell Survival and Proliferation

    PubMed Central

    Wang, Xiaogang; Cao, Peng; Li, Zhiqing; Wu, Dongyang; Wang, Xi; Liang, Guobiao

    2014-01-01

    Factor binding IST-1 (FBI-1) plays an important role in oncogenic transformation and tumorigenesis. As FBI-1 is over-expressed in multiple human cancers, the regulation of itself would provide new effective options for cancer intervention. In this work, we aimed to study the role that EPAS-1 plays in regulating FBI-1. We use the fact that specificity protein-1 (SP-1) is one of the crucial transcription factors of FBI-1, and that SP-1 can interact with the endothelial pas domain protein-1 (EPAS-1) for the induction of hypoxia related genes. The study showed that EPAS-1 plays an indispensible role in SP-1 transcription factor-mediated FBI-1 induction, and participated in tumor cell survival and proliferation. Thus, EPAS-1 could be a novel target for cancer therapeutics. PMID:25192290

  1. Fibroblast growth factor-2 up-regulates the expression of nestin through the Ras–Raf–ERK–Sp1 signaling axis in C6 glioma cells

    SciTech Connect

    Chang, Kai-Wei [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China)] [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China); Huang, Yuan-Li [Department of Biotechnology, College of Health Science, Asia University, Taichung 413, Taiwan (China)] [Department of Biotechnology, College of Health Science, Asia University, Taichung 413, Taiwan (China); Wong, Zong-Ruei; Su, Peng-Han [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China)] [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China); Huang, Bu-Miin [Department of Cell Biology and Anatomy, National Cheng-Kung University, Tainan 701, Taiwan (China)] [Department of Cell Biology and Anatomy, National Cheng-Kung University, Tainan 701, Taiwan (China); Ju, Tsai-Kai [Instrumentation Center, National Taiwan University, Taipei 106, Taiwan (China) [Instrumentation Center, National Taiwan University, Taipei 106, Taiwan (China); Technology Commons, College of Life Science, National Taiwan University, Taipei 106, Taiwan (China); Yang, Hsi-Yuan, E-mail: hyhy@ntu.edu.tw [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China)] [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China)

    2013-05-17

    Highlights: •Nestin expression in C6 glioma cells is induced by FGF-2. •Nestin expression is induced by FGF-2 via de novo RNA and protein synthesis. •The FGFR inhibitor SU5402 blocks the FGF-2-induced nestin expression. •The mRNA of FGFR1 and 3 are detected in C6 glioma cells. •Ras–Raf–ERK–Sp1 signaling pathway is responsibe for FGF-2-induced nestin expression. -- Abstract: Nestin is a 240-kDa intermediate filament protein expressed mainly in neural and myogenic stem cells. Although a substantial number of studies have focused on the expression of nestin during development of the central nervous system, little is known about the factors that induce and regulate its expression. Fibroblast growth factor-2 (FGF-2) is an effective mitogen and stimulates the proliferation and differentiation of a subset of nestin-expressing cells, including neural progenitor cells, glial precursor cells, and smooth muscle cells. To assess whether FGF-2 is a potent factor that induces the expression of nestin, C6 glioma cells were used. The results showed that nestin expression was up-regulated by FGF-2 via de novo RNA and protein synthesis. Our RT-PCR results showed that C6 glioma cells express FGFR1/3, and FGFRs is required for FGF-2-induced nestin expression. Further signaling analysis also revealed that FGF-2-induced nestin expression is mediated through FGFR–MAPK–ERK signaling axis and the transcriptional factor Sp1. These findings provide new insight into the regulation of nestin in glial system and enable the further studies on the function of nestin in glial cells.

  2. O glycosylation of an Sp1-derived peptide blocks known Sp1 protein interactions.

    PubMed Central

    Roos, M D; Su, K; Baker, J R; Kudlow, J E

    1997-01-01

    The O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins is dynamic and abundant in the nucleus and cytosol. Several transcription factors, including Sp1, have been shown to contain this modification; however, the functional role of O-GlcNAc in these proteins has not been determined. In this paper we describe the use of the previously characterized glutamine-rich transactivation domain of Sp1 (B-c) as a model to investigate the role of O-GlcNAc in Sp1's transcriptionally relevant protein-to-protein interactions with the TATA-binding-protein-associated factor (TAF110) and holo-Sp1. When the model Sp1 peptide was overexpressed in primate cells, this 97-amino-acid domain of Sp1 was found to contain a dominant O-GlcNAc residue at high stoichiometry, which allowed the mapping and mutagenesis of this glycosylation site. In vitro interaction studies between this segment of Sp1 and Drosophila TAF110 or holo-Sp1 indicate that the O-GlcNAc modification functions to inhibit the largely hydrophobic interactions between these proteins. In HeLa cells, the mutation at the mapped glycosylation site was permissive for transcriptional activation. We propose the hypothesis that the removal of O-GlcNAc from an interaction domain can be a signal for protein association. O-GlcNAc may thereby prevent untimely and ectopic interactions. PMID:9343410

  3. MicroRNA-124 Regulates Neuronal Differentiation of Mesenchymal Stem Cells by Targeting Sp1 mRNA.

    PubMed

    Mondanizadeh, Mahdieh; Arefian, Ehsan; Mosayebi, Ghasem; Saidijam, Massoud; Khansarinejad, Behzad; Hashemi, Seyed Mahmoud

    2015-06-01

    MicroRNAs play an important role in neuronal development and function. miR-124 is the most abundantly expressed miRNA in the nervous system. Several different mRNA targets have been proposed for miR-124, but the precise function of endogenous miR-124 and its mRNA targets remain to be further elucidated. Specificity protein 1 (Sp1) is a transcription factor that plays key roles in many cell processes including cell cycle. However, this transcription factor is nearly absent in differentiated neurons and a remarkable suppression of Sp1 expression was shown after neurogenesis. Since miR-124 is expressed abundantly in neurons and because Sp1 levels decrease during neurogenesis, it is possible that miR-124 could regulate the expression of Sp1 during neuronal development. Therefore, the aim of the present study was to evaluate the putative targeting of Sp1 by miR-124. Overexpression of miR-124 using a plasmid coding for pri-miR-124 in HEK293 cells decreased the expression of Sp1 mRNA. The results of dual-luciferase reporter assay demonstrated that miR-124 directly targeted the 3'-untranslated regions of Sp1 mRNA. To evaluate whether Sp1 expression was regulated by miR-124 during the process of neuronal differentiation, Adipose-derived mesenchymal stem cells (A-MSCs) were differentiated into neuron-like cells. The results of qPCR analysis showed that with the gradual increase of miR-124 expression during neurogenesis, the expression of Sp1 mRNA decreased accordingly. In summary, this study demonstrated for the first time that miR-124 is able to suppress Sp1 expression, which in turn affected the neuronal differentiation of mesenchymal stem cells. J. Cell. Biochem. 116: 943-953, 2015. © 2015 Wiley Periodicals, Inc. PMID:25559917

  4. Sox9/Sox6 and Sp1 are involved in the insulin-like growth factor-I-mediated upregulation of human type II collagen gene expression in articular chondrocytes.

    PubMed

    Renard, Emmanuelle; Porée, Benoît; Chadjichristos, Christos; Kypriotou, Magdalini; Maneix, Laure; Bigot, Nicolas; Legendre, Florence; Ollitrault, David; De Crombrugghe, Benoît; Malléin-Gérin, Frédéric; Moslemi, Safa; Demoor, Magali; Boumediene, Karim; Galéra, Philippe

    2012-06-01

    Type II collagen is a marker of articular cartilage encoded by the COL2A1 gene. The nature of the trans factors involved in the upregulation of this gene by insulin-like growth factor-I (IGF-I) remains unclear. We found that IGF-I increased type II collagen synthesis by a transcriptional control mechanism involving a 715-bp region within the COL2A1 first-intron specific enhancer. The overproduction of L-Sox5/Sox6/Sox9 and Sp1 and decoy experiments targeting these factors demonstrated their action in concert in IGF-I trans-activation. These results were supported by the data obtained in knockdown experiments in which siRNA against Sox9/Sox6 and Sp1 prevented the IGF-I-induced increase in collagen II production. Indeed, each of these trans-activators increased the expression of others. IGF-I increased the binding of Sox9 and Sp1/Sp3 to their cis elements in the enhancer, and we provide the first evidence of Sox9 interaction with the promoter by chromatin immunoprecipitation. Interactions with COL2A1 were also observed for Sp1, p300/CBP, and Tip60. Finally, a physical interaction between Sox9, p300, Sp3, and Sp1 was detected. These data demonstrate the role of Sox9, Sp1/Sp3, and euchromatin-associated factors (p300, Tip60) in the IGF-I-induced upregulation of COL2A1, indicating possible use of this growth factor in articular cartilage engineering applications to promote repair in patients with degenerative diseases, such as osteoarthritis. PMID:22215151

  5. Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line.

    PubMed Central

    Takahashi, Shigeru; Matsuura, Naomi; Kurokawa, Takako; Takahashi, Yuji; Miura, Takashi

    2002-01-01

    We reported previously that the 5'-flanking region (nucleotides -1976 to -1655) of the human haem oxygenase-1 ( hHO-1 ) gene enhances hHO-1 promoter activity in human hepatoma HepG2 cells, but not in HeLa cells [Takahashi, Takahashi, Ito, Nagano, Shibahara and Miura (1999) Biochim. Biophys. Acta 1447, 231-235]. To define more precisely the regulatory elements involved, in the present study we have functionally dissected this region and localized the enhancer to a 50 bp fragment (-1793 to -1744). Site-direct mutagenesis analysis revealed that two regions were responsible for this enhancer activity, i.e. a hepatocyte nuclear factor-4 (HNF-4) homologous region and a GC box motif homologous region. Mutation in either region alone moderately decreased enhancer activity. However, mutations in both regions reduced promoter activity to the basal level. Electrophoretic mobility-shift assays demonstrated that the P5-2 fragment (-1793 to -1744) interacted with at least two nuclear factors, i.e. HNF-4 and Sp1/Sp3. Co-transfection experiments using Drosophila SL2 cells revealed that HNF-4 and Sp1/Sp3 synergistically stimulated the enhancer activity of the P5-2 fragment. These results indicate that co-operation of HNF-4 with Sp1 or Sp3 leads to the activation of hHO-1 gene expression in hepatoma cells. PMID:12133007

  6. Involvement of specific proteins (Sp1/Sp3) and nuclear factor Y in basal transcription of the distal promoter of the rat pyruvate carboxylase gene in {beta}-cells

    SciTech Connect

    Sunyakumthorn, Piyanate [Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Boonsaen, Thirajit [Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Boonsaeng, Vichai [Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Wallace, John C. [School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Jitrapakdee, Sarawut [Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand)]. E-mail: scsji@mahidol.ac.th

    2005-04-01

    Pyruvate carboxylase plays diverse roles in different biosynthetic pathways, including glucose-induced insulin secretion in pancreatic {beta}-cells. We have localized the control region of the P2 promoter by generating a series of 5'-nested deletion constructs, and both 25- and 9-bp internal deletion constructs, as well as by performing site-directed mutagenesis. Transient transfections of these constructs into INS-1 cells identified a CCAAT box and a GC box that are located at -65/-61 and -48/-41, respectively, as the important determinants. Disruption of the GC box resulted in a 4-fold reduction of the reporter activity, while disruption of the proximal CCAAT box (-65/-61) but not the distal CCAAT box (-95/-91) increased the reporter activity by 3-fold. Simultaneous disruptions of both the GC box and the CCAAT box reduced the reporter activity to a level that was close to that of the single GC box mutation. Electrophoretic mobility shift assays (EMSAs) and supershift EMSAs using nuclear extract from INS-1 cells demonstrated that Sp1 and Sp3 bind a GC box while the nuclear factor Y was shown to bind the proximal but not the distal CCAAT box.

  7. Antifibrotic effect of synthetic Smad/Sp1 chimeric decoy oligodeoxynucleotide through the regulation of epithelial mesenchymal transition in unilateral ureteral obstruction model of mice.

    PubMed

    Sung, Woo Jung; Kim, Kyung-Hyun; Kim, Yong-Jin; Chang, Young-Chae; Lee, In Hee; Park, Kwan-Kyu

    2013-10-01

    Renal tubulointerstitial fibrosis is considered to be a common final pathway related to the progressive loss of renal function in chronic kidney disease. It is characterized by the excessive accumulation of extracellular matrix through the pivotal role of epithelial-mesenchymal transition. Transforming growth factor-?1 is postulated to play a central role in renal fibrosis via a downstream pathway such as Smad. Specificity protein 1 (Sp1), which is another transcription factor, is also involved in the basal expression of extracellular matrix. In this study, we investigate the effect of Smad decoy oligodeoxynucleotides (ODN) and Sp1 decoy ODN in unilateral ureteral obstruction induced renal fibrosis in mice. Furthermore, the effectiveness of the newly designed chimeric decoy ODN, which contains both Smad and Sp1 binding sequences in one decoy molecule (Smad/Sp1 chi decoy ODN), was demonstrated. The expression of fibrosis and inflammatory related cytokines and products of fibrosis were ameliorated in the Smad, Sp1 and chimeric decoy ODN treated groups compared with the scrambled decoy ODN treated group. Epithelial-mesenchymal transition was suppressed by the Smad, Sp1 and Smad/Sp1 chi decoy ODN. Immunohistochemistry and Western-blot analysis revealed that Smad/Sp1 chi decoy ODN showed a more significant inhibitory effect on fibrosis and EMT compared with Smad and Sp1 decoy ODNs. These results support the efficacy of Smad/Sp1 chi decoy compared with a single Smad or Sp1 decoy ODNs in preventing renal fibrosis induced by unilateral ureteral obstruction. PMID:23791891

  8. Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

    Microsoft Academic Search

    Günter Finkenzeller; Angelica Sparacio; Antje Technau; Dieter Marmé; Gerhard Siemeister

    1997-01-01

    Stimulation of NIH3T3 cells with platelet-derived growth factor (PDGF)-BB enhances expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of tumor angiogenesis. Here, we identified cis-acting VEGF promoter elements and trans-acting factors which are involved in PDGF-stimulated VEGF expression. By 5?-deletion and transient transfection analysis, a G+C-rich region at ?85 to ?50 of the

  9. Isolation and characterization of the 5´-upstream region of the human voltage-gated Ca(2+) channel ? 2?-1 auxiliary subunit gene: promoter analysis and regulation by transcription factor Sp1.

    PubMed

    Martínez-Hernández, Elizabeth; González-Ramírez, Ricardo; Sandoval, Alejandro; Cisneros, Bulmaro; Delgado-Lezama, Rodolfo; Felix, Ricardo

    2013-06-01

    The ?2? proteins are auxiliary subunits of high-voltage-activated Ca(2+) channels associated with alterations of surface expression, kinetics, and voltage-dependent properties of the channel complex. Four mammalian genes and several splice ?2? subunit variants have been cloned and described, though very little information concerning the transcriptional mechanisms that regulate their expression is available. Here, we report the identification and characterization of the human ?2?-1 subunit gene promoter and its regulation by specific transcription factor 1 (Sp1). Transient transfection of human neuroblastoma SH-SY5Y cells with a promoter/luciferase reporter construct revealed a ~1.5 kb 5´-UTR fragment of the CACNA2D1 gene that produced high levels of luciferase activity. Deletional analysis of this sequence showed that the minimal promoter was located within a 413-bp region (nt -326 to +98) with respect to the transcription start site. In this region, no canonical TATA box was present, but a high GC content and five potential Sp1 binding sites were found. The ability of two of these sites to interact with the transcription factor was confirmed by electrophoretic mobility shift assays. Likewise, Sp1 overexpression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of ?2? protein expressed in the SH-SY5Y cells, as well as reduced the amplitude of whole-cell patch clamp Ca(2+) currents in dorsal root ganglion neurons. This study thus represents the first identification of the transcriptional control region in the gene encoding the Ca(2+) channel ?2?-1 auxiliary subunit. PMID:23242029

  10. Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1.

    PubMed

    Yu, Hoi-Tin; Chan, William Wai-Lun; Chai, Ka-Ho; Lee, Chris Wing-Cheung; Chang, Raymond Chuen-Chung; Yu, Man-Shan; McLoughlin, Declan M; Miller, Christopher C J; Lau, Kwok-Fai

    2010-03-01

    FE65 is a neuronal-enriched adaptor protein that binds to the Alzheimer's disease amyloid precursor protein (APP). FE65 forms a transcriptionally active complex with the APP intracellular domain (AICD). The precise gene targets for this complex are unclear but several Alzheimer's disease-linked genes have been proposed. Additionally, evidence suggests that FE65 influences APP metabolism. The mechanism by which FE65 expression is regulated is as yet unknown. To gain insight into the regulatory mechanism, we cloned a 1.6 kb fragment upstream of the human FE65 gene and found that it possesses particularly strong promoter activity in neurones. To delineate essential regions in the human FE65 promoter, a series of deletion mutants were generated. The minimal FE65 promoter was located between -100 and +5, which contains a functional Sp1 site. Overexpression of the transcription factor Sp1 potentiates the FE65 promoter activity. Conversely, suppression of the FE65 promoter was observed in cells either treated with an Sp1 inhibitor or in which Sp1 was knocked down. Furthermore, reduced levels of Sp1 resulted in downregulation of endogenous FE65 mRNA and protein. These findings reveal that Sp1 plays a crucial role in transcriptional control of the human FE65 gene. PMID:20091743

  11. E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout Sp1 recognition sequence.

    PubMed

    Peralta-Zaragoza, Oscar; Bermúdez-Morales, Víctor; Gutiérrez-Xicotencatl, Lourdes; Alcocer-González, Juan; Recillas-Targa, Félix; Madrid-Marina, Vicente

    2006-01-01

    Human Papillomavirus (HPV) infection is the main etiologic agent of cervical cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An association between TGF-beta1 gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta1 expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta1 core promoter that is responsible for trans-activation and that corresponds to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sp1e recognition site abolished the trans-activation caused by E6 and E7. These results suggest a physical interaction and functional cooperation between viral oncoproteins and cellular regulatory elements of the TGF-beta1 promoter, and may explain the contribution of HPV-16 to TGF-beta1 gene expression in cervical cancer. PMID:16987065

  12. Play

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    Designing a game with a serious purpose involves considering the worlds of Reality and Meaning yet it is undeniably impossible to create a game without a third world, one that is specifically concerned with what makes a game a game: the play elements. This third world, the world of people like designers and artists, and disciplines as computer science and game design, I call the world of Play and this level is devoted to it. The level starts off with some of the misperceptions people have of play. Unlike some may think, we play all the time, even when we grow old—this was also very noticeable in designing the game Levee Patroller as the team exhibited very playful behavior at many occasions. From there, I go into the aspects that characterize this world. The first concerns the goal of the game. This relates to the objectives people have to achieve within the game. This is constituted by the second aspect: the gameplay. Taking actions and facing challenges is subsequently constituted by a gameworld, which concerns the third aspect. And all of it is not possible without the fourth and final aspect, the type of technology that creates and facilitates the game. The four aspects together make up a “game concept” and from this world such a concept can be judged on the basis of three closely interrelated criteria: engagement, immersion, and fun.

  13. Transcription Factor Sp1 Mediates Cell-Specific trans-Activation of the Human Cytomegalovirus DNA Polymerase Gene Promoter by Immediate-Early Protein IE86 in Glioblastoma U373MG Cells

    PubMed Central

    Wu, Jun; O’Neill, Joseph; Barbosa, Miguel S.

    1998-01-01

    Human cytomegalovirus (HCMV) gene expression is highly cell and tissue specific. Cell factor-mediated regulatory interactions are involved in regulating the restricted expression of the HCMV major immediate-early (IE) gene (J. F. Baskar, P. P. Smith, G. Nilaver, R. A. Jupp, S. Hoffmann, N. J. Peffer, D. J. Tenney, A. M. Colberg-Poley, P. Ghazal, and J. A. Nelson, 70:3207–3213, 1996). To gain an understanding of HCMV early gene activation, we studied the effect of each of the three major IE proteins, IE72, IE86, and IE55, on the HCMV DNA polymerase gene (pol; UL54) promoter. In transient-expression assays, the IE86 protein alone was able to transactivate the pol promoter, but IE72 and IE55 were not, in permissive U373MG cells. However, we were unable to detect IE86-mediated transactivation in nonpermissive HeLa or C33-A cells. Using electrophoretic mobility shift assays (EMSAs), we found that expression of the IE86 protein in U373MG cells resulted in specific binding of a DNA complex to an inverted-repeat element, IR1, of the pol promoter. Antibody supershifting and EMSA-Western blotting experiments further showed that IE86 and the cellular transcription factor Sp1 were components of the IR1 DNA-binding complex. Furthermore, we found that binding of DNA by Sp1 was dramatically increased in the presence of IE86. Interestingly, this IE86-induced DNA-binding activity of Sp1 was inhibited by a repressor activity presented in HeLa cells. In summary, our study suggests that a viral regulatory protein can modulate the DNA binding activity of a cellular transcription factor, resulting in cell-specific transactivation of viral genes. PMID:9420220

  14. Sp1 and SF1 Interact and Cooperate in the Regulation of Human Steroidogenic Acute Regulatory Protein Gene Expression

    Microsoft Academic Search

    TERUO SUGAWARA; MASAKI SAITO; SEIICHIRO FUJIMOTO

    2000-01-01

    Steroidogenic acute regulatory (StAR) protein plays a critical role in the movement of cholesterol from the outer to the inner mitochon- drial membrane. Steroidogenic factor 1 (SF-1) controls basal and cAMP-stimulated transcription of the StAR gene. The 1.3-kb StAR promoter has three SF-1 binding sites, and two consensus transcrip- tion factor Sp1 binding sequences near the two most distal SF-1

  15. The Sp(1)-Kepler Problems

    E-print Network

    Guowu Meng

    2010-03-05

    Let $n\\ge 2$ be a positive integer. To each irreducible representation $\\sigma$ of $\\mathrm{Sp}(1)$, an $\\mathrm{Sp}(1)$-Kepler problem in dimension $(4n-3)$ is constructed and analyzed. This system is super integrable and when $n=2$ it is equivalent to a generalized MICZ-Kepler problem in dimension five. The dynamical symmetry group of this system is $\\widetilde {\\mathrm O}^*(4n)$ with the Hilbert space of bound states ${\\mathscr H}(\\sigma)$ being the unitary highest weight representation of $\\widetilde {\\mathrm {O}^*}(4n)$ with highest weight $$(\\underbrace{-1, ..., -1}_{2n-1}, -(1+\\bar\\sigma)),$$ which occurs at the right-most nontrivial reduction point in the Enright-Howe-Wallach classification diagram for the unitary highest weight modules. Here $\\bar\\sigma$ is the highest weight of $\\sigma$. Furthermore, it is shown that the correspondence $\\sigma\\leftrightarrow \\mathscr H(\\sigma)$ is the theta-correspondence for dual pair $(\\mathrm{Sp}(1), \\mathrm{O}^*(4n))\\subseteq\\mathrm{Sp}_{8n}(\\mathbb R)$.

  16. The Sp(1)-Kepler problems

    SciTech Connect

    Meng Guowu [Department of Mathematics, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)

    2009-07-15

    Let n{>=}2 be a positive integer. To each irreducible representation {sigma} of Sp(1), an Sp(1)-Kepler problem in dimension (4n-3) is constructed and analyzed. This system is superintegrable, and when n=2 it is equivalent to a generalized MICZ-Kepler problem in dimension of 5. The dynamical symmetry group of this system is O-tilde*(4n) with the Hilbert space of bound states H({sigma}) being the unitary highest weight representation of O*-tilde(4n) with highest weight, (-1,{center_dot}{center_dot}{center_dot},-1,-(1+{sigma})), which occurs at the rightmost nontrivial reduction point in the Enright-Howe-Wallach classification diagram for the unitary highest weight modules. Here {sigma} is the highest weight of {sigma}. Furthermore, it is shown that the correspondence {sigma}{r_reversible}H({sigma}) is the theta-correspondence for dual pair (Sp(1),O*(4n))subset Sp(8n,R)

  17. Using DNA Microarray to Identify Sp1 as a Transcriptional Regulatory Element of Insulin-like Growth Factor-1 in Cardiac Muscle Cells

    E-print Network

    Kibler, Dennis F.

    in the promoter region. Insulin-like growth factor 1 (IGF-1) modulates myocardial gene expression and regulates-like Growth Factor-1 in Cardiac Muscle Cells Tao Li1 , Yung-Hsiang Chen1,2 , Tsun-Jui Liu1,2 , Jia Jia1 Chemistry, Physiology and Biophysics, Center for Cardiovascular Hormone Research, University of California

  18. Arf Induction by Tgf? Is Influenced by Sp1 and C/ebp? in Opposing Directions

    PubMed Central

    Zheng, Yanbin; Devitt, Caitlin; Liu, Jing; Iqbal, Nida; Skapek, Stephen X.

    2013-01-01

    Recent studies show that Arf, a bona fide tumor suppressor, also plays an essential role during mouse eye development. Tgf? is required for Arf promoter activation in developing mouse eyes, and its capacity to induce Arf depends on Smads 2/3 as well as p38 Mapk. Substantial delay between activation of these pathways and increased Arf transcription imply that changes in the binding of additional transcription factors help orchestrate changes in Arf expression. Focusing on proteins with putative DNA binding elements near the mouse Arf transcription start, we now show that Tgf? induction of this gene correlated with decreased expression and DNA binding of C/ebp? to the proximal Arf promoter. Ectopic expression of C/ebp? in mouse embryo fibroblasts (MEFs) blocked Arf induction by Tgf?. Although basal levels of Arf mRNA were increased by C/ebp? loss in MEFs and in the developing eye, Tgf? was still able to increase Arf, indicating that derepression was not the sole factor. Chromatin immunoprecipitation (ChIP) assay showed increased Sp1 binding to the Arf promotor at 24 and 48 hours after Tgf? treatment, at which time points Arf expression was significantly induced by Tgf?. Chemical inhibition of Sp1 and its knockdown by RNA interference blocked Arf induction by Tgf? in MEFs. In summary, our results indicate that C/ebp? and Sp1 are negative and positive Arf regulators that are influenced by Tgf?. PMID:23940569

  19. Specificity protein 1 (Sp1) maintains basal epithelial expression of the miR-200 family: implications for epithelial-mesenchymal transition.

    PubMed

    Kolesnikoff, Natasha; Attema, Joanne L; Roslan, Suraya; Bert, Andrew G; Schwarz, Quenten P; Gregory, Philip A; Goodall, Gregory J

    2014-04-18

    Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelial state with their expression lost in cells undergoing EMT. EMT can be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200 expression via a self-reinforcing double negative feedback loop to promote the mesenchymal state. However, it remains unclear what factors drive and maintain epithelial-specific expression of miR-200 in the absence of EMT-inducing factors. Here, we show that the transcription factor Specificity Protein 1 (Sp1) binds to the miR-200b?200a?429 proximal promoter and activates miR-200 expression in epithelial cells. In mesenchymal cells, Sp1 expression is maintained, but its ability to activate the miR-200 promoter is perturbed by ZEB-mediated repression. Reduction of Sp1 expression caused changes in EMT-associated markers in epithelial cells. Furthermore, we observed co-expression of Sp1 and miR-200 during mouse embryonic development wherein miR-200 expression was only lost in regions with high ZEB expression. Together, these findings indicate that miR-200 family members require Sp1 to drive basal expression and to maintain an epithelial state. PMID:24627491

  20. Transcriptional regulation of the human manganese superoxide dismutase gene: the role of specificity protein 1 (Sp1) and activating protein-2 (AP-2).

    PubMed Central

    Xu, Yong; Porntadavity, Sureerut; St Clair, Daret K

    2002-01-01

    Manganese superoxide dismutase (MnSOD) plays an important role in regulating cellular redox conditions. Expression of MnSOD has been shown to protect against damage by oxidative stress and to suppress the malignant phenotype of human cancer cells. We have previously cloned the human MnSOD (SOD2) gene and analysed its 5' proximal promoter, which has been characterized by a lack of a TATA or CAAT box and the presence of multiple GC boxes. To define further the molecular mechanisms for the regulation of MnSOD expression, multiple transcription factor-binding motifs containing overlapping specificity protein 1 (Sp1)- and activator protein (AP)-2-binding sites were identified by DNase I footprinting analysis. Functional studies in three cell lines with different levels of Sp1 and AP-2 proteins suggested that the cellular levels of these proteins may differentially regulate transcription via GC-binding motifs in the human SOD2 promoter. Co-transfection of an Sp1 expression vector resulted in an increase in the transcription of the promoter-driven reporter gene. In contrast, co-transfection of the AP-2 expression vector caused a decrease in transcription. Direct mutagenesis analysis of Sp1- and AP-2-binding sites showed that Sp1 is essential for transcription of the human SOD2 gene, whereas AP-2 plays a negative role in the transcription. Immunoprecipitation of Sp1 and AP-2 proteins demonstrated that Sp1 interacts with AP-2 in vivo. Two-hybrid analysis revealed that interaction between Sp1 and AP-2 plays both a positive and negative role in the transcription of the reporter gene in vivo. Taken together, our data indicate that AP-2 down-regulates transcription of the human SOD2 gene via its interaction with Sp1 within the promoter region. These findings, coupled with our previous observation that several cancer cell lines have mutations in the promoter region of the human MnSOD gene, which lead to an increase in an AP-2-binding site and a decrease in the promoter activity, signal the importance of understanding the promoter structure and the regulation of the human SOD2 gene by Sp1 and AP-2. PMID:11853549

  1. Video Game Playing and Gambling in Adolescents: Common Risk Factors

    ERIC Educational Resources Information Center

    Wood, Richard T. A.; Gupta, Rina; Griffiths, Mark

    2004-01-01

    Video games and gambling often contain very similar elements with both providing intermittent rewards and elements of randomness. Furthermore, at a psychological and behavioral level, slot machine gambling, video lottery terminal (VLT) gambling and video game playing share many of the same features. Despite the similarities between video game…

  2. Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT).

    PubMed

    Kyo, S; Takakura, M; Taira, T; Kanaya, T; Itoh, H; Yutsudo, M; Ariga, H; Inoue, M

    2000-02-01

    Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. The human telomerase catalytic subunit (hTERT) is a rate limiting determinant of the enzymatic activity of human telomerase. In the previous study, we identified the proximal 181 bp core promoter responsible for transcriptional activity of the hTERT gene. To identify the regulatory factors of transcription, transient expression assays were performed using hTERT promoter reporter plasmids. Serial deletion assays of the core promoter revealed that the 5'-region containing the E-box, which binds Myc/Max, as well as the 3'-region containing the GC-box, which binds Sp1, are essential for transactivation. The mutations introduced in the E-box or GC-box significantly decreased transcriptional activity of the promoter. Overexpression of Myc/Max or Sp1 led to significant activation of transcription in a cell type-specific manner, while Mad/Max introduction repressed it. However, the effects of Myc/Max on transactivation were marginal when Sp1 sites were mutated. Western blot analysis using various cell lines revealed a positive correlation between c-Myc and Sp1 expression and transcriptional activity of hTERT. Using fibroblast lineages in different stages of transformation, we found that c-Myc and Sp1 were induced to a dramatic extent when cells overcame replicative senescence and obtained immortal characteristics, in association with telomerase activation. These findings suggest that c-Myc and Sp1 cooperatively function as the major determinants of hTERT expression, and that the switching functions of Myc/Max and Mad/Max might also play roles in telomerase regulation. PMID:10637317

  3. Inhibition of Sp1 Functions by Its Sequestration into PML Nuclear Bodies

    PubMed Central

    Li, June; Zou, Wen-Xin; Chang, Kun-Sang

    2014-01-01

    Promyelocytic leukemia nuclear bodies (PML NBs) are comprised of PML and a striking variety of its associated proteins. Various cellular functions have been attributed to PML NBs, including the regulation of gene expression. We report here that induced expression of PML recruits Sp1 into PML NBs, leading to the reduction of Sp1 transactivation function. Specifically, Chromatin immunoprecipitation (ChIP) assay demonstrated that induced expression of PML significantly diminishes the amount of Sp1 binding to its target gene promoter, immunofluorescence staining showed dramatic increase in the co-localization between PML and Sp1 upon induction of PML expression, moreover, PML and Sp1 co-fractionated in the core nuclear matrix. Our study further showed that PML promotes SUMOylation of Sp1 in a RING-motif-dependent manner, SUMOylation of Sp1 facilitates physical interaction between Sp1 and PML and recruitment of Sp1 into the PML NBs, the SUMO binding motif of PML was also important for its interaction with Sp1. The results of this study demonstrate a novel mechanism by which PML regulates gene expression through sequestration of the transcription factor into PML NBs. PMID:24728382

  4. Characterization of the human topoisomerase IIbeta (TOP2B) promoter activity: essential roles of the nuclear factor-Y (NF-Y)- and specificity protein-1 (Sp1)-binding sites.

    PubMed Central

    Lok, Chun-Nam; Lang, Alexander J; Mirski, Shelagh E L; Cole, Susan P C

    2002-01-01

    Eukaryotic topoisomerase II (topo II) catalyses topological genomic changes essential for chromosome segregation, chromatin reorganization, DNA replication and transcription. Mammalian topo II exists as two isoforms, designated alpha and beta. Human topo IIalpha is an important cancer drug target, and an established determinant of drug sensitivity and resistance. Human topo IIbeta is also the target of anticancer drugs but its role in drug resistance is less clear. The two human topo II proteins are encoded by the TOP2A and TOP2B genes, respectively, which despite their highly conserved structural organization, are subject to distinctly different modes of regulation. In the present study, we have cloned and characterized the human TOP2B promoter containing a 1.3 kb fragment of the 5'-flanking and untranslated region (-1067 to +193). We found that the promoter activity of this TOP2B fragment was constant throughout the cell cycle, in contrast to the activity of the proximal promoter of TOP2A which was low in resting cells and enhanced during proliferation. Analyses of 5'-serially and internally deleted luciferase reporter constructs revealed that 80% of the TOP2B promoter activity could be attributed to the region between -533 and -481. Mutational analyses of putative regulatory elements indicated that two inverted CCAAT boxes (ICBs) within this region were essential for TOP2B promoter activity and gel mobility-shift assays indicated these sites bound the transcription factor nuclear factor-Y (NF-Y). Co-transfection experiments using a dominant-negative form of subunit A of NF-Y suggested that TOP2B promoter activity required direct interaction of NF-Y with the ICBs. In addition, a specificity protein-1 (Sp1)-binding GC box located just upstream of the ICBs was shown to contribute to TOP2B promoter activity in a synergistic manner with the ICBs. Our results suggest that the binding sites for NF-Y and Sp1 are critical for TOP2B transcription. PMID:12197834

  5. Sumoylation differentially regulates Sp1 to control cell differentiation.

    PubMed

    Gong, Lili; Ji, Wei-Ke; Hu, Xiao-Hui; Hu, Wen-Feng; Tang, Xiang-Cheng; Huang, Zhao-Xia; Li, Ling; Liu, Mugen; Xiang, Shi-Hua; Wu, Erxi; Woodward, Zachary; Liu, Yi-Zhi; Nguyen, Quan Dong; Li, David Wan-Cheng

    2014-04-15

    The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 (Sp1), a major transcription factor that controls expression of lens-specific genes such as ?-crystallins, was positively regulated by SUMO1 but negatively regulated by SUMO2. SUMO2 was found to inhibit Sp1 functions through several mechanisms: sumoylating it at K683 to attenuate DNA binding, and at K16 to increase its turnover. SUMO2 also interfered with the interaction between Sp1 and the coactivator, p300, and recruited a repressor, Sp3 to ?-crystallin gene promoters, to negatively regulate their expression. Thus, stable SUMO1, but diminishing SUMO2/3, during lens development is necessary for normal lens differentiation. In support of this conclusion, SUMO1 and Sp1 formed complexes during early and later stages of lens development. In contrast, an interaction between SUMO2/3 and Sp1 was detected only during the initial lens vesicle stage. Together, our results establish distinct roles of different SUMO isoforms and demonstrate for the first time, to our knowledge, that Sp1 acts as a major transcription factor target for SUMO control of cell differentiation. PMID:24706897

  6. Expression of alpha V integrin is modulated by Epstein-Barr virus nuclear antigen 3C and the metastasis suppressor Nm23-H1 through interaction with the GATA-1 and Sp1 transcription factors

    SciTech Connect

    Choudhuri, Tathagata [Department of Microbiology and The Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States); Verma, Subhash C. [Department of Microbiology and The Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States); Lan, Ke [Department of Microbiology and The Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States); Robertson, Erle S. [Department of Microbiology and The Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States)]. E-mail: erle@mail.med.upenn.edu

    2006-07-20

    Epstein-Barr virus (EBV) is a lymphotrophic herpesvirus infecting most of the world's population. It is associated with a number of human lymphoid and epithelial tumors and lymphoproliferative diseases in immunocompromised patients. A subset of latent EBV antigens is required for immortalization of primary B-lymphocytes. The metastatic suppressor Nm23-H1 which is downregulated in human invasive breast carcinoma reduces the migration and metastatic activity of breast carcinoma cells when expressed from a heterologous promoter. Interestingly, the EBV nuclear antigen 3C (EBNA3C) reverses these activities of Nm23-H1. The alpha V integrins recognize a variety of ligands for signaling and are involved in cell migration and proliferation and also serve as major receptors for extracellular-matrix-mediated cell adhesion and migration. The goal of this study was to determine if Nm23-H1 and EBNA3C can modulate alpha V integrin expression and downstream activities. The results of our studies indicate that Nm23-H1 downregulates alpha V intregrin expression in a dose responsive manner. In contrast, EBNA3C can upregulate alpha V integrin expression. Furthermore, the study showed that the association of the Sp1 and GATA transcription factors with Nm23-H1 is required for modulation of the alpha V integrin activity. Thus, these results suggest a direct correlation between the alpha V integrin expression and the interaction of Nm23-H1 with EBNA3C.

  7. Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells.

    PubMed

    Cui, Jiajun; Meng, Xianfeng; Gao, Xudong; Tan, Guangxuan

    2010-03-01

    Pokemon, which stands for POK erythroid myeloid ontogenic factor, can regulate expression of many genes and plays an important role in tumorigenesis. Curcumin, a natural and non-toxic yellow compound, has capacity for antioxidant, free radical scavenger, anti-inflammatory properties. Recent studies shows it is a potential inhibitor of cell proliferation in a variety of tumour cells. To investigate whether curcumin can regulate the expression of Pokemon, a series of experiments were carried out. Transient transfection experiments demonstrated that curcumin could decrease the activity of the Pokemon promoter. Western blot analysis suggested that curcumin could significantly decrease the expression of the Pokemon. Overexpression of Sp1 could enhance the activity of the Pokemon promoter, whereas knockdown of Sp1 could decrease its activity. More important, we also found that curcumin could decrease the expression of the Pokemon by suppressing the stimulation of the Sp1 protein. Therefore, curcumin is a potential reagent for tumour therapy which may target Pokemon. PMID:19444642

  8. Association of p107 with Sp1: Genetically Separable Regions of p107 Are Involved in Regulation of E2F- and Sp1Dependent Transcription

    Microsoft Academic Search

    PRAN K. DATTA; PRADIP RAYCHAUDHURI; ANDSRILATA BAGCHI

    1995-01-01

    The retinoblastoma-related protein p107 has been shown to be a regulator of the transcription factor E2F. p107 associates with E2F via its pocket region and represses E2F-dependent transcription. In this study, we provide evidence for a novel interaction between p107 and the transcription factor Sp1. We show that p107 can be found endogenously associated with Sp1 in the extracts of

  9. Sp1 Facilitates DNA Double-Strand Break Repair through a Nontranscriptional Mechanism

    PubMed Central

    Beishline, Kate; Kelly, Crystal M.; Olofsson, Beatrix A.; Koduri, Sravanthi; Emrich, Jacqueline; Greenberg, Roger A.

    2012-01-01

    Sp1 is a ubiquitously expressed transcription factor that is phosphorylated by ataxia telangiectasia mutated kinase (ATM) in response to ionizing radiation and H2O2. Here, we show by indirect immunofluorescence that Sp1 phosphorylated on serine 101 (pSp1) localizes to ionizing radiation-induced foci with phosphorylated histone variant ?H2Ax and members of the MRN (Mre11, Rad50, and Nbs1) complex. More precise analysis of occupancy of DNA double-strand breaks (DSBs) by chromatin immunoprecipitation (ChIP) shows that Sp1, like Nbs1, resides within 200 bp of DSBs. Using laser microirradiation of cells, we demonstrate that pSp1 is present at DNA DSBs by 7.5 min after induction of damage and remains at the break site for at least 8 h. Depletion of Sp1 inhibits repair of site-specific DNA breaks, and the N-terminal 182-amino-acid peptide, which contains targets of ATM kinase but lacks the zinc finger DNA binding domain, is phosphorylated, localizes to DSBs, and rescues the repair defect resulting from Sp1 depletion. Together, these data demonstrate that Sp1 is rapidly recruited to the region immediately adjacent to sites of DNA DSBs and is required for DSB repair, through a mechanism independent of its sequence-directed transcriptional effects. PMID:22826432

  10. GATA4 regulates ANF expression synergistically with Sp1 in a cardiac hypertrophy model

    PubMed Central

    Hu, Xiaoqing; Li, Tao; Zhang, Chenguang; Liu, Yinan; Xu, Ming; Wang, Weiping; Jia, Zhuqing; Ma, Kangtao; Zhang, Youyi; Zhou, Chunyan

    2011-01-01

    Abstract Cardiac hypertrophy in response to multiple stimuli has important physiological and pathological significances. GATA4 serves as a nuclear integrator of several signalling pathways during cardiac hypertrophy. Sp1 and Sp3 are also reported to be involved in this process. However, the mechanism by which GATA4 acts as a mediator, integrating these ubiquitously expressed transcriptional factors, is poorly understood. We found that the expression of GATA4 and Sp1 was up-regulated in the myocardium of a pressure overload hypertrophy rat model, as well in phenylephrine-induced (PE-induced) hypertrophic growth of neonatal cardiomyocytes. GST pull-down assays demonstrated that GATA4 could interact with Sp1 in vitro. Therefore, we proposed that GATA4 cooperates with Sp1 in regulating ANF expression, as its reactivation is closely linked with hypertrophy. Further studies demonstrated that GATA4 could activate the ANF promoter synergistically with Sp1 through direct interaction. In contrast, Sp3 exhibited antagonistic function, and overexpression of Sp3 repressed the transcriptional synergy between Sp1 and GATA4. We also found that Sp1 alone could activate the ANF promoter in cardiomyocytes, whereas Sp3 exerted negative effects on ANF expression. Bioinformatics analysis revealed novel Sp-binding sites on the ANF promoter. The recruitment of GATA4 and Sp1 on the ANF promoter was enhanced during phenylephrine-mediated hypertrophy, whereas the recruitment of Sp3 was reduced. The phosphorylation of GATA4 by ERK1/2 kinase could enhance the affinity between GATA4 and Sp1. Thus, our findings revealed the critical interaction of GATA4 and Sp1 in modulating ANF expression, indicating their involvement in cardiac hypertrophy. PMID:20874724

  11. Is video-game playing a risk factor for pathological gambling in Australian adolescents?

    PubMed

    Delfabbro, Paul; King, Daniel; Lambos, Chrisi; Puglies, Stan

    2009-09-01

    Very little research has been conducted to examine the relationship between video-game playing and gambling in adolescence. In this study, 2,669 adolescents aged 13-17 years were surveyed to obtained details of their involvement in gambling and video-game playing as well as a measure of pathological gambling (the DSM-IV-J). The results showed that, the frequency of video game playing was significantly related to pathological gambling, but that the effect size was very small and largely accounted for by the greater popularity of both activities amongst boys. There was some evidence for stronger associations between technologically similar activities, namely arcade video games and an interest in gaming machines, but other factors discussed in the paper may also account for this association. In summary, the findings suggested that playing video-games is unlikely to be a significant risk factor for pathological gambling during adolescence. PMID:19578983

  12. Non-redundant selector and growth-promoting functions of two sister genes, buttonhead and Sp1, in Drosophila leg development.

    PubMed

    Estella, Carlos; Mann, Richard S

    2010-06-01

    The radically distinct morphologies of arthropod and tetrapod legs argue that these appendages do not share a common evolutionary origin. Yet, despite dramatic differences in morphology, it has been known for some time that transcription factors encoded by the Distalless (Dll)/Dlx gene family play a critical role in the development of both structures. Here we show that a second transcription factor family encoded by the Sp8 gene family, previously implicated in vertebrate limb development, also plays an early and fundamental role in arthropod leg development. By simultaneously removing the function of two Sp8 orthologs, buttonhead (btd) and Sp1, during Drosophila embryogenesis, we find that adult leg development is completely abolished. Remarkably, in the absence of these factors, transformations from ventral to dorsal appendage identities are observed, suggesting that adult dorsal fates become derepressed when ventral fates are eliminated. Further, we show that Sp1 plays a much more important role in ventral appendage specification than btd and that Sp1 lies genetically upstream of Dll. In addition to these selector-like gene functions, Sp1 and btd are also required during larval stages for the growth of the leg. Vertebrate Sp8 can rescue many of the functions of the Drosophila genes, arguing that these activities have been conserved, despite more than 500 million years of independent evolution. These observations suggest that an ancient Sp8/Dlx gene cassette was used in an early metazoan for primitive limb-like outgrowths and that this cassette was co-opted multiple times for appendage formation in multiple animal phyla. PMID:20585625

  13. Modifying factors in sports-related concussion: dangerous style of play.

    PubMed

    Diamond, Alex B; Solomon, Gary S

    2014-09-01

    In its third iteration, the Concussion in Sport Group identified 10 modifying factors that were presumed clinically to influence the investigation and management of concussions in sports. "Dangerous style of play" was delineated as one of these factors, most likely based on clinical lore. These modifying factors were retained in a more recent Concussion in Sport Group statement. To date, there has been no concerted effort to support or refute the inclusion of this constellation of behaviors as a modifying factor in sports-related concussion. This article reviews and summarizes the limited evidence related to a dangerous style of play in sports-related concussion, offers a preliminary assessment of its relevance as a modifying factor, and provides additional information on other aspects of player, coach, and governing body behavior and their potential effect(s) on reducing concussive injuries. PMID:25295762

  14. Down-regulation of Sp1 suppresses cell proliferation, clonogenicity and the expressions of stem cell markers in nasopharyngeal carcinoma

    PubMed Central

    2014-01-01

    Background Transcription factor Sp1 is multifaceted, with the ability to function as an oncogene or a tumor suppressor, depending on the cellular context. We previously reported that Sp1 is required for the transcriptional activation of the key oncogenes in nasopharyngeal carcinoma (NPC), including B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1) and centromere protein H (CENPH), but the role of Sp1 and its underlying mechanisms in NPC remained largely unexplored. The objective of this study was to investigate the cellular function of Sp1 and to verify the clinical significance of Sp1 as a potential therapeutic target in NPC. Methods The levels of Sp1 in the normal primary nasopharyngeal epithelial cells (NPECs) and NPC cell lines were analyzed by Quantitative Real-time RT-PCR (qRT-PCR) and Western blot. The location and expression of Sp1 in the NPC tissues were detected by immunohistochemistry staining (IHC). The effect of Sp1 knockdown on the cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype in NPC cells were evaluated by MTT, flow cytometry, clonogenicity analysis and sphere formation assay. Results The mRNA and protein levels of Sp1 were elevated in NPC cell lines than in the normal primary NPECs. Higher expression of Sp1 was found in NPC tissues with advanced clinical stage (P?=?0.00036). Either inhibition of Sp1 activity by mithramycin A, the FDA-approved chemotherapeutic anticancer drug or Sp1 silencing by two distinct siRNA against Sp1 suppressed the growth of NPC cells. Mechanism analysis revealed that Sp1 silencing may suppress cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype through inducing the expression of p27 and p21, and impairing the expressions of the critical stem cell transcription factors (SCTFs), including Bmi1, c-Myc and KLF4 in NPC cells. Conclusions Sp1 was enriched in advanced NPC tissues and silencing of Sp1 significantly inhibited cell proliferation, clonogenicity, anchorage-independent growth and the stem-cell like phenotype of NPC cells, suggesting Sp1 may serve as an appealing drug target for NPC. PMID:25099028

  15. Functional Analyses of Natural Variation in Sp1 Binding Sites of a TATA-Less Promoter

    Microsoft Academic Search

    Jeff A. Segal; J. Lynn Barnett; Douglas L. Crawford

    1999-01-01

    .   Within the lactate dehydrogenase-B (LdhB) proximal promoter is a region with multiple in vivo footprinted sites that resembles the binding site for the transcription\\u000a factor SP1. Like many sequences that regulate transcription rate, these Sp1 binding sites are well conserved among species\\u000a of the teleost fish Fundulus. The only exception is in the northern population of F. heteroclitus, where

  16. Factors affecting return to play after anterior cruciate ligament reconstruction: a review of the current literature.

    PubMed

    Bauer, Matthew; Feeley, Brian T; Wawrzyniak, John R; Pinkowsky, Gregory; Gallo, Robert A

    2014-11-01

    Anterior cruciate ligament reconstruction has been reported to produce normal or near-normal knee results in > 90% of patients. A recent meta-analysis suggested that, despite normal or near-normal knees, many athletes do not return to sports. Rates and timing of return to competitive athletics are quite variable depending on the graft type, the age of the patient, the sport, and the level of play. Even when athletes do return to play, often they do not return to their previous level. Graft failure, subjective physical factors, and psychological factors, including fear of reinjury and lack of motivation, appear to play a large role in patients' ability to return to sporting activities. PMID:25419890

  17. Contributing factors, prevention, and management of playing-related musculoskeletal disorders among flute players internationally.

    PubMed

    Lonsdale, Karen; Laakso, E-Liisa; Tomlinson, Vanessa

    2014-09-01

    Major studies have shown that flutists report playing-related pain in the neck, middle/upper back, shoulders, wrists, and hands. The current survey was designed to establish the injury concerns of flute players and teachers of all backgrounds, as well as their knowledge and awareness of injury prevention and management. Questions addressed a range of issues including education, history of injuries, preventative and management strategies, lifestyle factors, and teaching methods. At the time of the survey, 26.7% of all respondents were suffering from flute playing-related discomfort or pain; 49.7% had experienced flute playing-related discomfort or pain that was severe enough to distract while performing; and 25.8% had taken an extended period of time off playing because of discomfort or pain. Consistent with earlier studies, the most common pain sites were the fingers, hands, arms, neck, middle/upper back, and shoulders. Further research is needed to establish possible links between sex, instrument types, and ergonomic set up. Further investigation is recommended to ascertain whether certain types of physical training, education, and practice approaches may be more suitable than current methods. A longitudinal study researching the relationship between early education, playing position, ergonomic set-up, and prevalence of injury is recommended. PMID:25194113

  18. A GT box element is essential for basal and cyclic adenosine 3',5'-monophosphate regulation of the human surfactant protein A2 gene in alveolar type II cells: evidence for the binding of lung nuclear factors distinct from Sp1.

    PubMed

    Young, P P; Mendelson, C R

    1997-07-01

    The gene encoding surfactant protein-A (SP-A) is developmentally regulated in type II cells of the fetal lung. In humans there are two SP-A genes, SP-A1 and SP-A2. The SP-A2 gene is more highly regulated by cAMP and during fetal development than SP-A1. In earlier studies we determined that 296 bp of sequence flanking the 5'-end of the SP-A2 gene is sufficient to mediate high basal and cAMP-inducible reporter gene expression in primary cultures of transfected type II cells, suggesting that this region contains important cis-acting elements involved in tissue-specific and hormonal regulation of SP-A2 promoter activity. We also observed that mutagenesis of a cAMP response element (CRE)-like sequence at -242 bp (CRE(SP-A2)) greatly reduced basal and cAMP-stimulated expression in transfected type II cells. In the present study, we identified a GT box (GGGGTGGGG) at -61 bp of SP-A2 5'-flanking sequence that is highly conserved among the SP-A genes of different species. In type II cell transfection studies, we found that mutagenesis of the GT box of SP-A2 markedly reduced basal and abolished cAMP-induced reporter gene expression. Thus, CRE(SP-A2) and the GT box cooperatively interact to mediate basal and cAMP induction of SP-A2 promoter activity in type II cells. By electrophoretic mobility shift assays (EMSA), it was observed that nuclear proteins isolated from primary cultures of type II cells bound the GT box as five specific complexes. By contrast, nuclear proteins isolated from lung fibroblasts displayed notably reduced binding activity. Competition and supershift EMSA indicate that the ubiquitously expressed transcription factor Sp1, a GC box-binding protein of approximately 100 kDa, is a component of the complex of proteins that bind the GT box of SP-A2. The finding that only two of the five GT box-binding complexes were supershifted by incubation with Sp1 antibody suggests that a factor(s) in type II cell nuclear extracts that is distinct from Sp1 also interacts with the GT box. By UV cross-linking and SDS-PAGE/EMSA analysis, we have identified a approximately 55-kDa GT box-binding factor in type II cell nuclear proteins that preferentially binds the GT box of SP-A2 over the consensus Sp1 GC box sequence. This 55-kDa factor was able to bind the GT box independently of Sp1. PMID:9212056

  19. Zac1, an Sp1-like protein, regulates human p21{sup WAF1/Cip1} gene expression in HeLa cells

    SciTech Connect

    Liu, Pei-Yao [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China)] [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Hsieh, Tsai-Yuan [Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China)] [Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Liu, Shu-Ting; Chang, Yung-Lung [Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC (China)] [Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Lin, Wei-Shiang [Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China)] [Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Wang, Wei-Ming, E-mail: ades0431@ms38.hinet.net [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China) [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Huang, Shih-Ming, E-mail: shihming@ndmctsgh.edu.tw [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China) [Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC (China)

    2011-12-10

    Zac1 functions as both a transcription factor and a transcriptional cofactor for p53, nuclear receptors (NRs) and NR coactivators. Zac1 might also act as a transcriptional repressor via the recruitment of histone deacetylase 1 (HDAC1). The ability of Zac1 to interact directly with GC-specific elements indicates that Zac1 possibly binds to Sp1-responsive elements. In the present study, our data show that Zac1 is able to interact directly with the Sp1-responsive element in the p21{sup WAF1/Cip1} gene promoter and enhance the transactivation activity of Sp1 through direct physical interaction. Our data further demonstrate that Zac1 might enhance Sp1-specific promoter activity by interacting with the Sp1-responsive element, affecting the transactivation activity of Sp1 via a protein-protein interaction, or competing the HDAC1 protein away from the pre-existing Sp1/HDAC1 complex. Finally, the synergistic regulation of p21{sup WAF1/Cip1} gene expression by Zac1 and Sp1 is mediated by endogenous p53 protein and p53-responsive elements in HeLa cells. Our work suggests that Zac1 might serve as an Sp1-like protein that directly interacts with the Sp1-responsive element to oligomerize with and/or to coactivate Sp1.

  20. Does hepatocyte growth factor/c-Met signal play synergetic role in lung cancer?

    PubMed Central

    Wang, Xiangdong; Li, Ka; Chen, Hong; Wang, Diane; Zhang, Yong; Bai, Chunxue

    2010-01-01

    Abstract There is growing evidence that the signal pathway between hepatocyte growth factor (HGF) and its receptor c-Met plays an important role in the development of lung cancer, although the specificity of such role is to be clarified. It seems clear that the HGF/c-Met signal contributes to the metastasis of cancer cells to the lung by stimulating the hyperproduction and overactivation of cytokines and enzymes, e.g. HGF, vascular endothelial growth factor and matrix metalloproteases. The HGF/c-Met signal may act as the candidate responsible for the development of epidermal growth factor receptor (EGFR) kinase inhibitor resistance. Experimental evidence showed that the combination of both EGFR and c-Met inhibitors had synergetic or additive therapeutic effects on lung cancer. Although the mechanism of interaction between HGF/c-Met and transforming growth factor-a/EGFR remains unclear, the cross-talk and balance between those two signal pathways are critical and necessary in the development of new therapies for lung cancer. PMID:20178463

  1. OBIF, an osteoblast induction factor, plays an essential role in bone formation in association with osteoblastogenesis.

    PubMed

    Mizuhashi, Koji; Kanamoto, Takashi; Ito, Masako; Moriishi, Takeshi; Muranishi, Yuki; Omori, Yoshihiro; Terada, Koji; Komori, Toshihisa; Furukawa, Takahisa

    2012-05-01

    In vertebrate bone formation, the functional mechanisms of transcription factors in osteoblastic differentiation have been relatively well elucidated; however, the exact roles of cell-extrinsic molecules are less clear. We previously identified human and mouse Obif, an osteoblast induction factor, also known as Tmem119, which encodes a single transmembrane protein. OBIF is predominantly expressed in osteoblasts in mouse. While exogenous Obif expression stimulated osteoblastic differentiation, knockdown of Obif inhibits the osteoblastic differentiation of pre-osteoblastic MC3T3-E1 cells. In order to investigate an in vivo role of OBIF in bone formation, we generated Obif-deficient mice by targeted gene disruption. Analyses of micro-computed tomography (mCT) revealed that Obif(-/-) mice exhibit significantly reduced cortical thickness in the mid-shaft of the femur at postnatal day 14 (P14). Furthermore, progressive bone hypoplasia is observed after 8 weeks. The expression levels of osteoblast marker genes, Collagen 1a1, Osteopontin, Runx2, and Osterix, in the calvaria were decreased in Obif(-/-) mice at P4. These data indicate that Obif plays an essential role in bone formation through regulating osteoblastogenesis. PMID:22416756

  2. RhoA signaling via serum response factor plays an obligatory role in myogenic differentiation.

    PubMed

    Wei, L; Zhou, W; Croissant, J D; Johansen, F E; Prywes, R; Balasubramanyam, A; Schwartz, R J

    1998-11-13

    Serum response factor (SRF) plays a central role during myogenesis, being required for the expression of striated alpha-actin genes. As shown here, the small GTPase RhoA-dependent activation of SRF results in the expression of muscle-specific genes, thereby promoting myogenic differentiation in myoblast cell lines. Co-expression of activated V14-RhoA and SRF results in an approximately 10-fold activation of the skeletal alpha-actin promoter in replicating myoblasts, while SRFpm1, a dominant negative SRF mutant, blocks RhoA dependent skeletal alpha-actin promoter activity. Serum withdrawal further potentiates RhoA- and SRF-mediated activation of alpha-actin promoter to about 30-fold in differentiated myotubes. In addition, the proximal SRE1 in the skeletal alpha-actin promoter is sufficient to mediate RhoA signaling via SRF. Furthermore, SRFpm1 and to a lesser extent dominant negative N19-RhoA inhibit myoblast fusion, postreplicative myogenic differentiation, and expression of direct SRF targets such as skeletal alpha-actin and indirect targets such as myogenin and alpha-myosin heavy chain. Moreover, RhoA also stimulates the autoregulatable murine SRF gene promoter in myoblasts, and the expression level of SRF is reduced in myoblasts overexpressing N19-RhoA. Our study supports the concept that RhoA signaling via SRF serves as an obligatory muscle differentiation regulatory pathway. PMID:9804789

  3. Surgical site infections associated with methicillin-resistant Staphylococcus aureus: do postoperative factors play a role?

    PubMed

    Manian, Farrin A; Meyer, P Lynn; Setzer, Janice; Senkel, Diane

    2003-04-01

    Patients with surgical site infections (SSIs) who underwent surgery during the period of September 1997 through December 1999 and January through July 2001 were retrospectively studied to compare patients infected with methicillin-resistant Staphylococcus aureus (MRSA) with those infected with organisms other than MRSA. Of patients with SSI who had known culture results, 77 (28.5%) of 270 had cultures that yielded MRSA. On univariate analysis, age of >or=70 years, duration of surgery of >or=4 h, duration of postoperative antibiotic treatment of >1 day, and discharge to a long-term care facility (LTCF) were significantly associated with MRSA SSI (P<.05 for all). On multivariate analysis, only discharge to an LTCF (odds ratio [OR], 2.3; P=.04) and duration of postoperative antibiotic treatment of >1 day (OR, 2.0; P=.03) were significantly associated with MRSA SSI; there was also a trend toward MRSA SSI being associated with use of a surgical drain for >1 day (P=.078). Postoperative factors may play a more important role in the causation of MRSA SSI than has previously been appreciated. PMID:12652387

  4. The Arabidopsis MYB96 transcription factor plays a role in seed dormancy.

    PubMed

    Lee, Hong Gil; Lee, Kyounghee; Seo, Pil Joon

    2015-03-01

    Seed dormancy facilitates to endure environmental disadvantages by confining embryonic growth until the seeds encounter favorable environmental conditions for germination. Abscisic acid (ABA) and gibberellic acid (GA) play a pivotal role in the determination of the seed dormancy state. ABA establishes seed dormancy, while GA triggers seed germination. Here, we demonstrate that MYB96 contributes to the fine-tuning of seed dormancy regulation through the coordination of ABA and GA metabolism. The MYB96-deficient myb96-1 seeds germinated earlier than wild-type seeds, whereas delayed germination was observed in the activation-tagging myb96-1D seeds. The differences in germination rate disappeared after stratification or after-ripening. The MYB96 transcription factor positively regulates ABA biosynthesis genes 9-CIS-EPOXYCAROTENOID DIOXYGENASE 2 (NCED2), NCED5, NCED6, and NCED9, and also affects GA biosynthetic genes GA3ox1 and GA20ox1. Notably, MYB96 directly binds to the promoters of NCED2 and NCED6, primarily modulating ABA biosynthesis, which subsequently influences GA metabolism. In agreement with this, hyperdormancy of myb96-1D seeds was recovered by an ABA biosynthesis inhibitor fluridone, while hypodormancy of myb96-1 seeds was suppressed by a GA biosynthesis inhibitor paclobutrazol (PAC). Taken together, the metabolic balance of ABA and GA underlies MYB96 control of primary seed dormancy. PMID:25616734

  5. Ring-Sp1 decoy oligonucleotide effectively suppresses extracellular matrix gene expression and fibrosis of rat kidney induced by unilateral ureteral obstruction.

    PubMed

    Chae, Y-M; Park, K-K; Lee, I-K; Kim, J-K; Kim, C-H; Chang, Y-C

    2006-03-01

    Tubulointerstitial fibrosis is the consequence of an injury characterized by the accumulation of excess collagen and other extracellular matrix components, resulting in the destruction of the normal kidney architecture and subsequent loss of function. A transcription factor Sp1, originally described as a ubiquitous transcription factor, is involved in the basal expression of extracellular matrix genes and may, therefore, be important in fibrotic processes. Here, we report on the design of a ring-Sp1 decoy oligonucleotide, containing the consensus Sp1 binding sequence in a single decoy molecule without an open end, to create a novel therapeutic strategy for fibrosis. The ring-Sp1 decoy oligonucleotide is highly resistant to degradation by nucleases or serum compared to the conventional phosphorothioated double-stranded Sp1 decoy oligonucleotide, and effectively suppressed the expression of transforming growth factor-beta1 and fibronectin, the binding of Sp1 to the promoter region of these genes, and proliferation in response to serum in normal rat kidney fibroblasts. Moreover, treatment with the ring-Sp1 decoy in vivo significantly attenuates extracellular matrix gene expression in the rat kidney in which a unilateral ureteral obstruction had been induced. These results suggest that the ring-Sp1 decoy oligonucleotide represents promising therapeutic alternative to the conventional treatment of fibrotic disorders. PMID:16341057

  6. Structural basis for Ufm1 processing by UfSP1.

    PubMed

    Ha, Byung Hak; Ahn, Hee-Chul; Kang, Sung Hwan; Tanaka, Keiji; Chung, Chin Ha; Kim, Eunice Eun Kyeong

    2008-05-23

    Ubiquitin-fold modifier 1 (Ufm1) is a newly identified ubiquitin-like protein. Like ubiquitin and other ubiquitin-like proteins, Ufm1 is synthesized as a precursor that needs to be processed to expose the conserved C-terminal glycine prior to its conjugation to target proteins. Two novel proteases, named UfSP1 and UfSP2, have been shown to be responsible for the release of Ufm1 from Ufm1-conjugated cellular proteins as well as for the processing of its precursor. They show no sequence homology with known proteases. Here, we describe the 1.7A resolution crystal structure of mouse UfSP1, consisting of 217 amino acids. The structure reveals that it is a novel cysteine protease having a papain-like fold, with Cys(53), Asp(175), and His(177) that form a catalytic triad, and Tyr(41) that participates in the formation of the oxyanion hole. This differs from the canonical catalytic triad of papain-like proteases in that the aspartate and the histidine residues are from the "Asp-Pro-His" box. The Asp-Pro-His configuration seen in UfSP1, together with Atg4B and M48(USP), seem to form a new subfamily of the cysteine protease superfamily. The mutagenesis study of the active site residues confirms structural basis for catalysis. The interaction between UfSP1 and Ufm1 appears quite substantial, since the K(D) value was estimated to be 1.6 mum by the isothermal titration calorimetry analysis. Furthermore, the NMR data shows that the loop between beta3 and alpha2 in addition to the C-terminal region of Ufm1 plays a role in binding to UfSP1. PMID:18321862

  7. Gata4 and Sp1 regulate expression of the erythropoietin receptor in cardiomyocytes

    PubMed Central

    von Salisch, Sandy; Klar, Martin; Thurisch, Boris; Bungert, Jörg; Dame, Christof

    2011-01-01

    Abstract Experimental studies indicate significant cardioprotective effects of recombinant erythropoietin (Epo) by binding to the Epo receptor (EpoR) and by inducing various molecular mechanisms, including activation of Gata4, a transcription factor that induces anti-apoptotic genes. However, specific molecular mechanisms of EpoR regulation in cardiomyocytes are unknown. We identified a 774 bp regulatory domain in the EpoR 5? flanking region by reporter gene assays in murine HL-1 cardiomyocytes. The binding sites for Gata and Sp transcription factors both significantly contributed to EpoR promoter activity. DNA-binding studies (EMSA and ChIP assays) identified Gata4 and Sp1 as EpoR promoter-binding proteins in HL1 cardiomyocytes. Although Sp1 alone stimulates EpoR only slightly, forced expression of Gata4 significantly induced EpoR mRNA expression. In addition, knockdown of Gata4 (but also of Sp1) resulted in a significant decrease of EpoR transcript levels in HL-1 cardiomyocytes. Cumulative in vitro data suggest that function of the Sp1 site is essential for the Gata4-mediated transcription. In vivo, analysis of transgenic mice expressing an inducible small-hairpin RNA against Gata4 confirmed suppression of EpoR expression in the heart. Treating mice with high-dose doxorubicin not only resulted in Gata4 protein depletion, but also down-regulated EpoR, followed by up-regulation of EpoR transcripts when Gata4 levels recovered. In conclusion, we identified Gata4 as novel regulator of EpoR transcription in cardiomyocytes. In models of cardiac injury, down-regulation of Gata4 or Sp1 may limit the accessibility of the EpoR for binding of erythropoiesis-stimulating agents (ESA). Thereby our data underline the essential role of Gata4 in mediating cardioprotective effects. PMID:21029371

  8. Is Video-Game Playing a Risk Factor for Pathological Gambling in Australian Adolescents?

    Microsoft Academic Search

    Paul Delfabbro; Daniel King; Chrisi Lambos; Stan Puglies

    2009-01-01

    Very little research has been conducted to examine the relationship between video-game playing and gambling in adolescence.\\u000a In this study, 2,669 adolescents aged 13–17 years were surveyed to obtained details of their involvement in gambling and video-game\\u000a playing as well as a measure of pathological gambling (the DSM-IV-J). The results showed that, the frequency of video game\\u000a playing was significantly related

  9. Users guide for the ANL IBM SP1

    SciTech Connect

    Gropp, W.; Lusk, E.; Pieper, S.C.

    1994-10-01

    This guide presents the features of the IBM SP1 installed in the Mathematics and Computer Science Division at Argonne National Laboratory. The guide describes the available hardware and software, access policies, and hints for using the system productively.

  10. Growth factor delivery methods in the management of sports injuries: the state of play

    Microsoft Academic Search

    L Creaney

    2008-01-01

    In recent years there have been rapid developments in the use of growth factors for accelerated healing of injury. Growth factors have been used in maxillo-facial and plastic surgery with success and the technology is now being developed for orthopaedics and sports medicine applications. Growth factors mediate the biological processes necessary for repair of soft tissues such as muscle, tendon

  11. Factors Related to Play Therapists' Social Justice Advocacy Attitudes

    ERIC Educational Resources Information Center

    Parikh, Sejal B.; Ceballos, Peggy; Post, Phyllis

    2013-01-01

    The authors used a correlational research design to examine how belief in a just world, political ideology, socioeconomic status of family of origin, and percentage of racial minority clients were related to social justice advocacy attitudes among play therapists. A multiple regression was used to analyze the data. Results indicated that belief in…

  12. Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases its DNA-binding activity during mitosis.

    PubMed

    Yang, Hang-Che; Chuang, Jian-Ying; Jeng, Wen-Yih; Liu, Chia-I; Wang, Andrew H-J; Lu, Pei-Jung; Chang, Wen-Chang; Hung, Jan-Jong

    2014-12-16

    We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not sufficient for the inhibition of its DNA-binding activity during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro motif of Sp1 to modulate the interaction between phospho-Sp1 and CDK1, thereby facilitating CDK1-mediated phosphorylation of Sp1 at Ser720, Thr723 and Thr737 during mitosis. Loss of the C-terminal end of Sp1 (amino acids 741-785) significantly increased Sp1 phosphorylation, implying that the C-terminus inhibits CDK1-mediated Sp1 phosphorylation. Binding analysis of Sp1 peptides to Pin1 by isothermal titration calorimetry indicated that Pin1 interacts with Thr739(p)-Sp1 peptide but not with Thr739-Sp1 peptide. X-ray crystallography data showed that the Thr739(p)-Sp1 peptide occupies the active site of Pin1. Increased Sp1 phosphorylation by CDK1 during mitosis not only stabilized Sp1 levels by decreasing interaction with ubiquitin E3-ligase RNF4 but also caused Sp1 to move out of the chromosomes completely by decreasing its DNA-binding activity, thereby facilitating cell cycle progression. Thus, Pin1-mediated conformational changes in the C-terminal region of Sp1 are critical for increased CDK1-mediated Sp1 phosphorylation to facilitate cell cycle progression during mitosis. PMID:25398907

  13. Ischemia/reperfusion-induced upregulation of TIGAR in brain is mediated by SP1 and modulated by ROS and hormones involved in glucose metabolism.

    PubMed

    Sun, Meiling; Li, Mei; Huang, Qiao; Han, Feng; Gu, Jin-Hua; Xie, Jiaming; Han, Rong; Qin, Zheng-Hong; Zhou, Zhipeng

    2015-01-01

    We previously found that TIGAR (TP53-induced glycolysis and apoptosis regulator) was upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. The present study sought to investigate the regulatory mechanisms of TIGAR upregulation in animal and cellular models of stroke. The animal and cellular models of ischemia/reperfusion were produced by transient middle cerebral artery occlusion and reperfusion (tMCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R), respectively. The expression of TIGAR protein in cortical tissues and hippocampal neuronal cell line HT22 cells or primary neurons was determined. Glucose, hormones and hydrogen peroxide (H2O2) were administered to mice via injection into the tail vein or lateral ventricle or directly added into cell culture medium. In mice subjected to tMCAO/R, the blood glucose level rapidly increased, peaking at 0.5?h and then declined. TIGAR protein was also significantly increased and then declined with a delayed time-course. The increase in TIGAR protein was blunted when blood glucose levels were controlled with insulin. However, administering glucose solution to mice or adding glucose to cell culture medium had no effect on TIGAR protein levels. In contrast adrenaline, hydrocortisone, glucagon and H2O2 significantly increased TIGAR protein expression, whereas insulin inhibited TIGAR expression. The transcription factor SP1 was induced by ischemia/reperfusion ahead of TIGAR upregulation. Inhibiting SP1 with mithramycin A or silencing SP1 with siRNA blocked the ischemia-induced TIGAR upregulation. These results suggest that ROS and hormones regulating blood glucose metabolism play a role in ischemia/reperfusion-induced TIGAR upregulation. PMID:25445985

  14. Factors Influencing the Degree and Pattern of Parental Involvement in Play Therapy for Sexually Abused Children

    Microsoft Academic Search

    Andrew Hill

    2009-01-01

    Although much has been written about the role of therapists in children's recovery from child sexual abuse, relatively little attention has been paid to the role of nonoffending parents. This study investigated the work of a team of therapists who sometimes included such parents in therapy sessions with children. The study sought to understand what factors were influencing the degree

  15. PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1

    SciTech Connect

    Rankin, Sherri L.; Guy, Clifford S. [Division of Biomedical Sciences - M5352, Memorial University of Newfoundland, Faculty of Medicine, 300 Prince Philip Drive, St. John's, NL, A1B 3V6 (Canada); Mearow, Karen M. [Division of Biomedical Sciences - M5352, Memorial University of Newfoundland, Faculty of Medicine, 300 Prince Philip Drive, St. John's, NL, A1B 3V6 (Canada)], E-mail: kmearow@mun.ca

    2009-02-13

    p75NTR is expressed throughout the nervous system and its dysregulation is associated with pathological conditions. We have recently demonstrated a signalling cascade initiated by laminin (LN), which upregulates PTEN and downregulates p75NTR. Here we investigate the mechanism by which PTEN modulates p75NTR. Studies using PTEN mutants show that its protein phosphatase activity directly modulates p75NTR protein expression. Nuclear relocalization of PTEN subsequent to LN stimulation suggests transcriptional control of p75NTR expression, which was confirmed following EMSA and ChIP analysis of Sp1 transcription factor binding activity. LN and PTEN independently decrease the DNA-binding ability of PTEN to the p75NTR promoter. Sp1 regulation of p75NTR occurs via dephosphorylation of Sp1, thus reducing p75NTR transcription and protein expression. This mechanism represents a novel regulatory pathway which controls the expression level of a receptor with broad implications not only for the development of the nervous system but also for progression of pathological conditions.

  16. Unusual angiogenic factor plays a role in lizard pregnancy but is not unique to viviparity.

    PubMed

    Whittington, Camilla M; Grau, Georges E; Murphy, Christopher R; Thompson, Michael B

    2015-03-01

    Angiogenesis (blood vessel growth), a key process of mammalian pregnancy, facilitates gas exchange and nutrient transport between the mother and the embryo and is regulated by a suite of growth factors. Vascular endothelial growth factor (VEGF) is crucial to this process in pregnant mammals and potentially pregnant squamates (lizards and snakes), as we investigate here. VEGF111 , an unusual and potent angiogenic splice variant of VEGF, increases its expression during pregnancy in the uterus of a viviparous lizard, in parallel with similar increases in uterine angiogenesis during gestation. However, we also find that VEGF111 is expressed in oviparous skinks, and is not ubiquitous among viviparous skinks. Thus, different mechanisms of uterine angiogenesis during pregnancy may evolve concurrent with viviparity in different lizard lineages. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 152-158, 2015. © 2015 Wiley Periodicals, Inc. PMID:25732926

  17. Mathematics performance and the role played by affective and background factors peter grootenboer and brian hemmings

    NASA Astrophysics Data System (ADS)

    Grootenboer, Peter; Hemmings, Brian

    2007-12-01

    In this article, we report on a study examining those factors which contribute to the mathematics performance of a sample of children aged between 8 and 13 years. The study was designed specifically to consider the potency of a number of mathematical affective factors, as well as background characteristics (viz., gender, ethnicity, and socioeconomic status), on children's mathematics performance. Data were collected by surveying the children and drawing on performance ratings from their teachers. A correlation analysis revealed that the relationships between the respective dispositional and background variables with mathematics performance were significant and in the direction as predicted. Moreover, the findings from a logistic regression showed that a combination of these variables was able to appropriately classify students who either were below-average or above-average mathematics performers. We pay particular attention to the influence of certain dispositions with respect to mathematics performance and conclude by detailing the implications of the study for teachers and researchers.

  18. Nuclear factor of activated T-cells (NFAT) plays a role in SV40 infection

    SciTech Connect

    Manley, Kate [Graduate Program in Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912 (United States); O'Hara, Bethany A. [Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912 (United States); Atwood, Walter J. [Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912 (United States)], E-mail: Walter_Atwood@Brown.edu

    2008-03-01

    Recent evidence highlighted a role for the transcription factor, nuclear factor of activated T-cells (NFAT), in the transcription of the human polyomavirus JCV. Here we show that NFAT is also important in the transcriptional control of the related polyomavirus, Simian Virus 40 (SV40). Inhibition of NFAT activity reduced SV40 infection of Vero, 293A, and HeLa cells, and this block occurred at the stage of viral transcription. Both NFAT3 and NFAT4 bound to the SV40 promoter through {kappa}B sites located within the 72 bp repeated enhancer region. In Vero cells, NFAT was involved in late transcription, but in HeLa and 293A cells both early and late viral transcription required NFAT activity. SV40 large T-Ag was found to increase NFAT activity and provided a positive feedback loop to transactivate the SV40 promoter.

  19. Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium

    Microsoft Academic Search

    Heidrun Koebernick; Leander Grode; John R. David; Wolfgang Rohde; Michael S. Rolph; Hans-Willi Mittrücker; Stefan H. E. Kaufmann

    2002-01-01

    The cytokine macrophage migration inhibitory factor (MIF) exerts a multitude of biological functions. Notably, it induces inflammation at the interface between the immune system and the hypothalamus-pituitary-adrenal stress axis. The role of MIF in infectious diseases is not understood completely. Here, we show that MIF-deficient (MIF\\/) knockout mice fail to control an infection with wild-type Salmonella typhimurium. Increased susceptibility was

  20. The p65 Subunit of NF-?B Inhibits COL1A1 Gene Transcription in Human Dermal and Scleroderma Fibroblasts through Its Recruitment on Promoter by Protein Interaction with Transcriptional Activators (c-Krox, Sp1, and Sp3)*

    PubMed Central

    Beauchef, Gallic; Bigot, Nicolas; Kypriotou, Magdalini; Renard, Emmanuelle; Porée, Benoît; Widom, Russell; Dompmartin-Blanchere, Anne; Oddos, Thierry; Maquart, François-Xavier; Demoor, Magali; Boumediene, Karim; Galera, Philippe

    2012-01-01

    Transcriptional mechanisms regulating type I collagen genes expression in physiopathological situations are not completely known. In this study, we have investigated the role of nuclear factor-?B (NF-?B) transcription factor on type I collagen expression in adult normal human (ANF) and scleroderma (SF) fibroblasts. We demonstrated that NF-?B, a master transcription factor playing a major role in immune response/apoptosis, down-regulates COL1A1 expression by a transcriptional control involving the ?112/?61 bp sequence. This 51-bp region mediates the action of two zinc fingers, Sp1 (specific protein-1) and Sp3, acting as trans-activators of type I collagen expression in ANF and SF. Knockdown of each one of these trans factors by siRNA confirmed the trans-activating effect of Sp1/Sp3 and the p65 subunit of NF-?B trans-inhibiting effect on COL1A1 expression. Despite no existing ?B consensus sequence in the COL1A1 promoter, we found that Sp1/Sp3/c-Krox and NF-?B bind and/or are recruited on the proximal promoter in chromatin immunoprecipitation (ChIP) assays. Attempts to elucidate whether interactions between Sp1/Sp3/c-Krox and p65 are necessary to mediate the NF-?B inhibitory effect on COL1A1 in ANF and SF were carried out; in this regard, immunoprecipitation assays revealed that they interact, and this was validated by re-ChIP. Finally, the knockdown of Sp1/Sp3/c-Krox prevents the p65 inhibitory effect on COL1A1 transcription in ANF, whereas only the siRNAs targeting Sp3 and c-Krox provoked the same effect in SF, suggesting that particular interactions are characteristic of the scleroderma phenotype. In conclusion, our findings highlight a new mechanism for COL1A1 transcriptional regulation by NF-?B, and these data could allow the development of new antifibrotic strategies. PMID:22139845

  1. Basal transcription factor 3 plays an important role in seed germination and seedling growth of rice.

    PubMed

    Wang, Wenyi; Xu, Mengyun; Wang, Ya; Jamil, Muhammad

    2014-01-01

    BTF3 has been recognized to be involved in plant growth and development. But its function remains mostly unknown during seed germination and seedling stage. Here, we have analyzed OsBTF3-related sequences in Oryza sativa L. subspecies, japonica, which resembles with the conserved domain of a nascent polypeptide associated complex (NAC) with different homologs of OsBTF3 and human BTF3. Inhibition of Osj10gBTF3 has led to considerable morphological changes during seed germination and seedling growth. Germination percentage was not influenced by the application of GA3, ABA, and NaCl but all concentrations caused wild-type (WT) seeds to germinate more rapidly than the RNAi (Osj10gBTF3 (Ri)) transgenic lines. Seedling inhibition was more severe in the Osj10gBTF3 (Ri) seedlings compared with their WT especially when treated with 100 or 200??M GA3; 50% reduction in shoots was observed in Osj10gBTF3 (Ri) seedlings. The expression of Osj3g1BTF3, Osj3g2BTF3 and Osj10gBTF3 was primarily constitutive and generally modulated by NaCl, ABA, and GA3 stresses in both Osj10gBTF3 (Ri) lines and WT at the early seedling stage, suggesting that Osj3g1BTF3 and Osj10gBTF3 are much similar but different from Osj3g2BTF3 in biological function. These results show that OsBTF3 plays an important role in seed germination and seedling growth gives a new perception demonstrating that more multifaceted regulatory functions are linked with BTF3 in plants. PMID:24971328

  2. The mouse vitamin D receptor is mainly expressed through an Sp1-driven promoter in vivo.

    PubMed

    Jehan, F; DeLuca, H F

    2000-05-15

    The availability of the mouse vitamin D receptor (mVDR) gene has allowed a characterization of a TATA-less promoter containing a cluster of four Sp1 sites named Sp1-1, Sp1-2, Sp1-3, and Sp1-4 (F. Jehan and H. F. DeLuca, 1997, Proc. Natl. Acad. Sci. USA 94, 10138-10143). By means of primer extension analysis, S1 nuclease mapping and ribonuclease protection assay, the start site has been deduced, as has the existence of other minor transcription start sites. Initiation of transcription at the major site is located 4 bp upstream of the 5' end of the mVDR cDNA sequence and very close to the putative Sp1 sites. A second minor promoter might exist between exon 1 and exon 2 of the mVDR gene. The nucleotide sequence of the Sp1 region is well conserved between the mouse, the human, and the chicken VDR genes, suggesting an important role for these Sp1 sites. Gel shift analysis of the four Sp1 sites of the mVDR promoter has confirmed specific binding complexes to Sp1-1, Sp1-2, and Sp1-4 (Sp1-3 rather binds an unknown complex that is unable to bind the canonical Sp1 GGGGCGGGGC). Deletion or mutation of all the Sp1 sites eliminates promoter activity. However, mutation or deletion of individual Sp1 sites did not dramatically change the promoter activity, except for mutation of Sp1-3 that increases promoter activity. We, therefore, conclude that the mVDR promoter is controlled by the Sp1 sites and is the main VDR promoter in intestine and kidney. PMID:10845704

  3. ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine receptor gene.

    PubMed

    Yang, Y; Hwang, C K; Junn, E; Lee, G; Mouradian, M M

    2000-12-01

    The human D(1A) dopamine receptor is transcribed from a tissue-specific regulated gene under the control of two promoters. An activator region (AR1) located between nucleotides -1154 and -1136 (relative to the first ATG) enhances transcription from the upstream promoter that is active in the brain. In this investigation, we sought to identify the nuclear factors that regulate the D(1A) gene through their binding to AR1 using yeast one-hybrid screening. Sp3 and Zic2 were among the positive clones isolated. Although Sp1 was not isolated from this screening and purified Sp1 alone does not bind to AR1 in gel shift experiments, this general transcription factor binds to AR1 in the presence of D(1A) expressing NS20Y nuclear extract and activates the D(1A) promoter. Thus, Sp1 appears to require an unknown factor(s) or post-translational modification to interact with AR1. On the other hand, Zic2 and Sp3 inhibit Sp1-induced activation of the D(1A) gene in an AR1-dependent manner. Zic2 and D(1A) genes have reciprocal brain regional distributions; Zic2 is expressed primarily in the cerebellum, and D(1A) is highly expressed in corpus striatum. These observations collectively suggest that one of the physiologic functions of Zic2 is repression of D(1A) gene transcription and that the intracellular balance among Sp1, Sp3 and Zic2 is important for regulating the tissue-specific expression of this dopamine receptor. PMID:10984499

  4. The ‘Perfect Storm’ and Acute Coronary Syndrome Onset: Do Psychosocial Factors Play a Role?

    PubMed Central

    Burg, Matthew M.; Edmondson, Donald; Shimbo, Daichi; Shaffer, Jonathan; Kronish, Ian M.; Whang, William; Alcántara, Carmela; Schwartz, Joseph E.; Muntner, Paul; Davidson, Karina W.

    2013-01-01

    The revolution in cardiac care over the past two decades, characterized by emergent revascularization, drug eluting stents, anti-platelet medications, and advanced imaging has had little impact on overall ACS recurrence, or ACS prevention. The “Perfect Storm” refers to a confluence of events and processes, including atherosclerotic plaque, coronary flow dynamics, hemostatic and fibrinolytic function, metabolic and inflammatory conditions, neurohormonal dysregulation, and environmental events that give rise to, and result in an ACS event. In this article we illustrate the limits of the traditional main effect research model, giving a brief description of the current state of knowledge regarding the development of atherosclerotic plaque and the rupturing of these plaques that defines an ACS event. We then apply the Perfect Storm conceptualization to describe a program of research concerning a psychosocial vulnerability factor that contributes to increased risk of recurrent ACS and early mortality, and that has defied our efforts to identify underlying pathophysiology and successfully mount efforts to fully mitigate this risk. PMID:23621970

  5. Eukaryotic initiation factor 5A plays an essential role in luteinizing hormone receptor regulation.

    PubMed

    Menon, Bindu; Gulappa, Thippeswamy; Menon, K M J

    2014-11-01

    Down-regulation of LH receptor (LHR) in the ovary by its ligand is mediated by a specific RNA-binding protein, designated LH receptor mRNA-binding protein (LRBP), through translational suppression and mRNA degradation. Using yeast 2-hybrid screens, we previously identified eukaryotic initiation factor 5A (eIF5A) as one of the proteins that interacts with LRBP during LHR mRNA down-regulation. The present study examined the role of eIF5A and its hypusination in the context of LHR mRNA down-regulation. The association of eIF5A with LRBP or LHR mRNA was determined using immunoprecipitation and RNA immunoprecipitation assays. The results showed that the association of eIF5A with the LHR mRNA-LRBP complex increased significantly during down-regulation. Furthermore, gel fractionation and the hypusination activity assay both showed increased hypusination of eIF5A during LHR mRNA down-regulation. Abolishment of hypusination by pretreatment with the chemical inhibitor GC7 prevented the association of eIF5A with LHR mRNA and LRBP. Inhibition of hypusination also reduced the extent of ligand-induced down-regulation of LHR mRNA as well as the expression of functional LHRs assessed by real-time PCR and (125)I-human chorionic gonadotropin (hCG) binding assays, respectively. The loss of human chorionic gonadotropin-mediated downstream signaling during LHR down-regulation was also restored by inhibition of hypusination of eIF5A. Thus, the present study, for the first time, reveals the crucial role of eIF5A and its hypusination in the regulation of LHR expression in the ovary. PMID:25216047

  6. Binding of SP1 to the immediate-early protein-responsive element of the human cytomegalovirus DNA polymerase promoter.

    PubMed Central

    Luu, P; Flores, O

    1997-01-01

    Human cytomegalovirus (HCMV), a member of the herpesvirus family of DNA viruses, encodes two major immediate-early (IE) transcription factors, IE72 and IE86, that are important for regulated expression of the viral genome. The purpose of this study was to identify the host cellular components required for regulation of the HCMV DNA polymerase promoter (UL54) by HCMV IE proteins. Extensive mutagenesis defined a DNA element located between -54 and -43 relative to the transcription start site that was required for both basal transcriptional activity and transactivation by viral IE proteins. A single copy of the UL54 -54/-43 sequence enhanced the responsiveness of a heterologous minimal promoter to HCMV IE proteins. Fractionation of extracts prepared from uninfected cells led to the isolation of two cellular proteins with apparent molecular masses of 95 and 105 kDa that bound specifically to the UL54 -54/-43 element. Biochemical and immunochemical analyses identified this protein as the transcription factor SP1. Although initial inspection of the UL54 -54/-43 sequence did not predict an SP1 binding site, subsequent analyses indicated that it is indeed a nonconsensus GC box. We propose that SP1 is required to direct basal levels of promoter activity and that SP1-regulated transcription complexes allow the entry of HCMV IE proteins into the transcription cycle. PMID:9261391

  7. A formal anthropological view of motivation models of problematic MMO play: achievement, social, and immersion factors in the context of culture.

    PubMed

    Snodgrass, Jeffrey G; Dengah, H J Francois; Lacy, Michael G; Fagan, Jesse

    2013-04-01

    Yee (2006) found three motivational factors-achievement, social, and immersion-underlying play in massively multiplayer online role-playing games ("MMORPGs" or "MMOs" for short). Subsequent work has suggested that these factors foster problematic or addictive forms of play in online worlds. In the current study, we used an online survey of respondents (N?=?252), constructed and also interpreted in reference to ethnography and interviews, to examine problematic play in the World of Warcraft (WoW; Blizzard Entertainment, 2004-2013). We relied on tools from psychological anthropology to reconceptualize each of Yee's three motivational factors in order to test for the possible role of culture in problematic MMO play: (a) For achievement, we examined how "cultural consonance" with normative understandings of success might structure problematic forms of play; (b) for social, we analyzed the possibility that developing overvalued virtual relationships that are cutoff from offline social interactions might further exacerbate problematic play; and (c) in relation to immersion, we examined how "dissociative" blurring of actual- and virtual-world identities and experiences might contribute to problematic patterns. Our results confirmed that compared to Yee's original motivational factors, these culturally sensitive measures better predict problematic forms of play, pointing to the important role of sociocultural factors in structuring online play. PMID:23690445

  8. Scaffolding, Analysis and Materials: Contributing Factors in an Unexpected Finding of Advanced Infant/Toddler Pretend Play?

    ERIC Educational Resources Information Center

    Morrissey, Anne-Marie

    2014-01-01

    As part of a longitudinal study, infant/toddler pretend play development and maternal play modelling were investigated in dyadic context. A total of 21 children were videotaped in monthly play sessions with their mothers, from age 8 to 17 months. Child and mother pretend play frequencies and levels were measured using Brown's Pretend Play

  9. Sp1 and CREB regulate basal transcription of the human SNF2L gene

    SciTech Connect

    Xia Yu; Jiang Baichun; Zou Yongxin; Gao Guimin; Shang Linshan; Chen Bingxi; Liu Qiji [Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Gong Yaoqin [Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China)], E-mail: yxg8@sdu.edu.cn

    2008-04-04

    Imitation Switch (ISWI) is a member of the SWI2/SNF2 superfamily of ATP-dependent chromatin remodelers, which are involved in multiple nuclear functions, including transcriptional regulation, replication, and chromatin assembly. Mammalian genomes encode two ISWI orthologs, SNF2H and SNF2L. In order to clarify the molecular mechanisms governing the expression of human SNF2L gene, we functionally examined the transcriptional regulation of human SNF2L promoter. Reporter gene assays demonstrated that the minimal SNF2L promoter was located between positions -152 to -86 relative to the transcription start site. In this region we have identified a cAMP-response element (CRE) located at -99 to -92 and a Sp1-binding site at -145 to -135 that play a critical role in regulating basal activity of human SNF2L gene, which were proven by deletion and mutation of specific binding sites, EMSA, and down-regulating Sp1 and CREB via RNAi. This study provides the first insight into the mechanisms that control basal expression of human SNF2L gene.

  10. Methylation of Adjacent CpG Sites Affects Sp1/Sp3 Binding and Activity in the p21Cip1 Promoter

    PubMed Central

    Zhu, Wei-Guo; Srinivasan, Kanur; Dai, Zunyan; Duan, Wenrui; Druhan, Lawrence J.; Ding, Haiming; Yee, Lisa; Villalona-Calero, Miguel A.; Plass, Christoph; Otterson, Gregory A.

    2003-01-01

    DNA methylation in the promoter of certain genes is associated with transcriptional silencing. Methylation affects gene expression directly by interfering with transcription factor binding and/or indirectly by recruiting histone deacetylases through methyl-DNA-binding proteins. In this study, we demonstrate that the human lung cancer cell line H719 lacks p53-dependent and -independent p21Cip1 expression. p53 response to treatment with gamma irradiation or etoposide is lost due to a mutation at codon 242 of p53 (C?W). Treatment with depsipeptide, an inhibitor of histone deacetylase, was unable to induce p53-independent p21Cip1 expression because the promoter of p21Cip1 in these cells is hypermethylated. By analyzing luciferase activity of transfected p21Cip1 promoter vectors, we demonstrate that depsipeptide functions on Sp1-binding sites to induce p21Cip1 expression. We hypothesize that hypermethylation may interfere with Sp1/Sp3 binding. By using an electrophoretic mobility shift assay, we show that, although methylation within the consensus Sp1-binding site did not reduce Sp1/Sp3 binding, methylation outside of the consensus Sp1 element induced a significant decrease in Sp1/Sp3 binding. Depsipeptide induced p21Cip1 expression was reconstituted when cells were pretreated with 5-aza-2?-deoxycytidine. Our data suggest, for the first time, that hypermethylation around the consensus Sp1-binding sites may directly reduce Sp1/Sp3 binding, therefore leading to a reduced p21Cip1 expression in response to depsipeptide treatment. PMID:12773551

  11. Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells.

    PubMed

    Sasaki, Haruka; Kurotaki, Daisuke; Osato, Naoki; Sato, Hideaki; Sasaki, Izumi; Koizumi, Shin-ichi; Wang, Hongsheng; Kaneda, Chika; Nishiyama, Akira; Kaisho, Tsuneyasu; Aburatani, Hiroyuki; Morse, Herbert C; Ozato, Keiko; Tamura, Tomohiko

    2015-01-01

    Basophils and mast cells play critical roles in host defense against pathogens and allergic disorders. However, the molecular mechanism by which these cells are generated is not completely understood. Here we demonstrate that interferon regulatory factor-8 (IRF8), a transcription factor essential for the development of several myeloid lineages, also regulates basophil and mast cell development. Irf8(-/-) mice displayed a severe reduction in basophil counts, which was accounted for by the absence of pre-basophil and mast cell progenitors (pre-BMPs). Although Irf8(-/-) mice retained peripheral tissue mast cells, remaining progenitors from Irf8(-/-) mice including granulocyte progenitors (GPs) were unable to efficiently generate either basophils or mast cells, indicating that IRF8 also contributes to the development of mast cells. IRF8 appeared to function at the GP stage, because IRF8 was expressed in GPs, but not in basophils, mast cells, and basophil/mast cell-restricted progenitor cells. Furthermore, we demonstrate that GATA2, a transcription factor known to promote basophil and mast cell differentiation, acts downstream of IRF8. These results shed light on the pathways and mechanism underlying the development of basophils and mast cells. PMID:25398936

  12. Transforming growth factor-beta in the red nucleus plays antinociceptive effect under physiological and pathological pain conditions.

    PubMed

    Wang, J; Yu, J; Ding, C-P; Han, S-P; Zeng, X-Y; Wang, J-Y

    2015-04-16

    Previous studies have demonstrated that the red nucleus (RN) participates in the modulation of neuropathic pain and plays both a facilitated role by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-?) and interleukin-1? (IL-1?), and an inhibitory role through the anti-inflammatory cytokine IL-10. In this study, we sought to investigate the expressions and roles of transforming growth factor-beta (TGF-?), a potent anti-inflammatory cytokine, as well as its type 1 receptor (TGF-?-R1) in the RN in normal and neuropathic pain rats. Immunohistochemistry showed that TGF-? and TGF-?-R1 were constitutively expressed in the RN of normal rats, and co-localized with neurons and all three glial cell types, astrocytes, microglia and oligodendrocytes. Following spared nerve injury (SNI), the expression levels of TGF-? and TGF-?-R1 were significantly down-regulated in the RN contralateral (but not ipsilateral) to the nerve injury side of rats at one week and reached the lowest level at two weeks after SNI, and both of them were co-localized with neurons and oligodendrocytes but not with astrocytes and microglia. Microinjection of different doses of anti-TGF-? antibody (250, 125, 50ng) into the unilateral RN of normal rats dose-dependently decreased the mechanical withdrawal threshold of contralateral (but not ipsilateral) hind paw and induced significant mechanical hypersensitivity, which was similar to mechanical allodynia induced by peripheral nerve injury. In contrast, microinjection of different doses of recombinant rat TGF-?1 (500, 250, 100ng) into the RN contralateral to the nerve injury side of SNI rats dose-dependently increased the paw withdrawal threshold and significantly alleviated mechanical allodynia induced by SNI. These results suggest that TGF-? in the RN participates in nociceptive processing and plays antinociceptive effects under normal physiological condition and in the development of neuropathic pain induced by SNI. PMID:25662509

  13. Hypermethylation of Sp1 binding site suppresses hypothalamic POMC in neonates and may contribute to metabolic disorders in adults: impact of maternal dietary CLAs.

    PubMed

    Zhang, Xiaomei; Yang, Ran; Jia, Yan; Cai, Demin; Zhou, Bo; Qu, Xiaoli; Han, Huihua; Xu, Liang; Wang, Linfeng; Yao, Yanan; Yang, Guoqing

    2014-05-01

    Epigenetic regulation of neuropeptide genes associated with central appetite control plays an important part in the development of nutritional programming. While proopiomelanocortin (POMC) is critical in appetite control, the molecular mechanism of methylation-related regulation of POMC remains unclear. Based on the report that the proximal specificity protein 1 (Sp1) binding site in POMC promoter is crucial for the leptin-mediated activation of POMC, the methylation of this site was investigated in this study in both cultured cells and postnatal mice reared by the dams with dietary supplementation of conjugated linoleic acids (CLAs). The change of milk composition made the offspring undergo the increase of food intake, suppression of POMC, attenuation of Sp1-promoter interaction, and the hypermethylation of cytosine guanine (CpG) dinucleotides at -100 and -103 within the Sp1 binding site of POMC promoter, which may be associated with the decrease of hypothalamic Sp1 and/or plasma S-adenosylhomocystein. In cultured cells, the methylation of the -100 CpG dinucleotides of the POMC promoter blocked both the formation of Sp1-promoter complex and the leptin-induced activation of POMC. In addition, a catch-up growth and adult metabolic changes like adult hyperglycemia and insulin resistance were observed in these postnatal pups, suggesting that this CLA-mediated hypermethylation may contribute, at least in part, to the metabolic disorders. PMID:24379351

  14. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice

    PubMed Central

    Zhang, Xiuqi; Garcia, Oscar A.; Wang, Rebecca F.; Stevenson, Mary C.; Threadgill, David W.; Russell, William E.

    2014-01-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies. PMID:24407590

  15. Transcription Factor ?B Plays an Important Role in the Production of Extracellular Membrane-Derived Vesicles in Listeria monocytogenes

    PubMed Central

    Lee, Jung Hwa; Choi, Chi-Won; Lee, Taewon; Kim, Seung Il; Lee, Je-Chul; Shin, Ji-Hyun

    2013-01-01

    Gram-negative bacteria produce extracellular outer membrane vesicles (OMVs) that interact with host cells. Unlike Gram-negative bacteria, less is known about the production and role of extracellular membrane vesicles (MVs) in Gram-positive bacteria. The food-borne pathogen Listeria monocytogenes can survive under extreme environmental and energy stress conditions and the transcription factor ?B is involved in this survival ability. Here, we first determined the production of MVs from L. monocytogenes and evaluated whether general stress transcription factor ?B affected production of MVs in L. monocytogenes. L. monocytogenes secreted MVs during in vitro broth culture. The wild-type strain actively produced MVs approximately nine times more and also produced more intact shapes of MVs than those of the isogenic ?sigB mutant. A proteomic analysis showed that 130 and 89 MV proteins were identified in the wild-type and ?sigB mutant strains, respectively. Wild-type strain-derived MVs contained proteins regulated by ?B such as transporters (OpuCA and OpuCC), stress response (Kat), metabolism (LacD), translation (InfC), and cell division protein (FtsZ). Gene Ontology (GO) enrichment analysis showed that wild-type-derived MV proteins corresponded to several GO terms, including response to stress (heat, acid, and bile resistance) and extracellular polysaccharide biosynthetic process, but not the ?sigB mutant. Internalin B (InlB) was almost three times more contained in MVs derived from the wild-type strain than in MVs derived from the ?sigB mutant. Taken together, these results suggest that ?B plays a pivotal role in the production of MVs and protein profiles contained in MVs. L. monocytogenes MVs may contribute to host infection and survival ability under various stressful conditions. PMID:23977379

  16. ALK5 and ALK1 play antagonistic roles in transforming growth factor ?-induced podosome formation in aortic endothelial cells.

    PubMed

    Curado, Filipa; Spuul, Pirjo; Egaña, Isabel; Rottiers, Patricia; Daubon, Thomas; Veillat, Véronique; Duhamel, Paul; Leclercq, Anne; Gontier, Etienne; Génot, Elisabeth

    2014-12-01

    Transforming growth factor ? (TGF-?) and related cytokines play a central role in the vascular system. In vitro, TGF-? induces aortic endothelial cells to assemble subcellular actin-rich structures specialized for matrix degradation called podosomes. To explore further this TGF-?-specific response and determine in which context podosomes form, ALK5 and ALK1 TGF-? receptor signaling pathways were investigated in bovine aortic endothelial cells. We report that TGF-? drives podosome formation through ALK5 and the downstream effectors Smad2 and Smad3. Concurrent TGF-?-induced ALK1 signaling mitigates ALK5 responses through Smad1. ALK1 signaling induced by BMP9 also antagonizes TGF-?-induced podosome formation, but this occurs through both Smad1 and Smad5. Whereas ALK1 neutralization brings ALK5 signals to full potency for TGF-?-induced podosome formation, ALK1 depletion leads to cell disturbances not compatible with podosome assembly. Thus, ALK1 possesses passive and active modalities. Altogether, our results reveal specific features of ALK1 and ALK5 signaling with potential clinical implications. PMID:25266657

  17. New Play.

    ERIC Educational Resources Information Center

    Lersten, Kenneth C.

    There have been many theories and hypotheses about play, one of which is the equation of play with "transcendence." Play may have the ingredients to allow us to transcend and, for a moment, remythologize life. There have been recent authors who have given play the status of theology, indicating that play contains elements also found in religion.…

  18. Sp1-like proteins function in the transcription of human ferredoxin genes

    Microsoft Academic Search

    Jing-Ruey Yeh; Li-Chung Hsu; Bon-chu Chung

    2000-01-01

    We characterized a regulatory element located in the ?76 to ?62 region of the human ferredoxin gene. This region bound to Sp1-like proteins with low affinity, as shown using electrophoretic mobility shift, competition, antibody binding, and Southwestern experiments. The similarity of the regulatory element to Sp1 extends beyond its DNA-binding domain, as cloned Sp1 functioned equally well when fused to

  19. Sp1Like Proteins Function in the Transcription of Human Ferredoxin Genes

    Microsoft Academic Search

    Jing-Ruey Yeh; Li-Chung Hsu; Bon-chu Chung

    2000-01-01

    We characterized a regulatory element located in the –76 to –62 region of the human ferredoxin gene. This region bound to Sp1-like proteins with low affinity, as shown using electrophoretic mobility shift, competition, antibody binding, and Southwestern experiments. The similarity of the regulatory element to Sp1 extends beyond its DNA-binding domain, as cloned Sp1 functioned equally well when fused to

  20. Language Play.

    ERIC Educational Resources Information Center

    Schwartz, Judy I.

    This paper discusses kinds and characteristics of language play, explores the relationship of such play to wider domains of language and play, and speculates on the possible contributions of language play for language mastery and cognitive development. Jump rope chants and ritual insults ("Off my case, potato face") and other expressive language…

  1. Cyclin A regulates a cell-cycle-dependent expression of CKAP2 through phosphorylation of Sp1

    SciTech Connect

    Kang, Du-Seock [Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon 440-746 (Korea, Republic of)] [Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon 440-746 (Korea, Republic of); Hong, Kyeong-Man [Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769 (Korea, Republic of)] [Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769 (Korea, Republic of); Park, Joobae [Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon 440-746 (Korea, Republic of)] [Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon 440-746 (Korea, Republic of); Bae, Chang-Dae, E-mail: cdbae@skku.edu [Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon 440-746 (Korea, Republic of)] [Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon 440-746 (Korea, Republic of)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer We identified a GC box and a CHR element in human CKAP2 minimal promoter. Black-Right-Pointing-Pointer The CHR element repressed the CKAP2 minimal promoter activity at the G1/S phase. Black-Right-Pointing-Pointer The GC box was essential for the basic promoter activity of human CKAP2. Black-Right-Pointing-Pointer The GC box was also essential for the cyclic expression of human CKAP2. Black-Right-Pointing-Pointer The phosphorylation of Sp1, mediated by Cyclin A, underlies the cyclic expression. -- Abstract: CKAP2 plays crucial roles in proper chromosome segregation and maintaining genomic stability. CKAP2 protein showed cell-cycle-dependent expression, which reached a maximum level at the G2/M phase and disappeared at the onset of G1 phase. To elucidate the mechanisms underlying cell cycle-dependent expression of CKAP2, we cloned and analyzed the human CKAP2 promoter. The upstream 115-bp region from the transcription start site was sufficient for minimal CKAP2 promoter activity. We identified 2 regulatory sequences; a CHR (-110 to -104 bp) and a GC box (-41 to -32 bp). We confirmed Sp1 bound to the GC box using a supershift assay and a ChIP assay. Mutation in the GC box resulted in a near complete loss of CKAP2 promoter activity while mutation in the CHR decreased the promoter activity by 50%. The CHR mutation showed enhanced activity at the G1/S phase, but still retained cyclic activity. The Chromatin IP revealed that the amount of Sp1 bound to the GC box gradually increased and reached a maximum level at the G2/M phase. The amount of Sp1 bound to the GC box was greatly reduced when Cyclin A was depleted, which was restored by adding Cyclin A/Cdk2 complex back into the nuclear extracts. Together, we concluded that the GC box was responsible for the cyclic activity of human CKAP2 promoter through the phosphorylation of Sp1, possibly by Cyclin A/Cdk complex.

  2. Alu elements contain many binding sites for transcription factors and may play a role in regulation of developmental processes

    PubMed Central

    Polak, Paz; Domany, Eytan

    2006-01-01

    Background The human genome contains over one million Alu repeat elements whose distribution is not uniform. While metabolism-related genes were shown to be enriched with Alu, in structural genes Alu elements are under-represented. Such observations led researchers to suggest that Alu elements were involved in gene regulation and were selected to be present in some genes and absent from others. This hypothesis is gaining strength due to findings that indicate involvement of Alu elements in a variety of functions; for example, Alu sequences were found to contain several functional transcription factor (TF) binding sites (BSs). We performed a search for new putative BSs on Alu elements, using a database of Position Specific Score Matrices (PSSMs). We searched consensus Alu sequences as well as specific Alu elements that appear on the 5 Kbp regions upstream to the transcription start site (TSS) of about 14000 genes. Results We found that the upstream regions of the TSS are enriched with Alu elements, and the Alu consensus sequences contain dozens of putative BSs for TFs. Hence several TFs have Alu-associated BSs upstream of the TSS of many genes. For several TFs most of the putative BSs reside on Alu; a few of these were previously found and their association with Alu was also reported. In four cases the fact that the identified BSs resided on Alu went unnoticed, and we report this association for the first time. We found dozens of new putative BSs. Interestingly, many of the corresponding TFs are associated with early markers of development, even though the upstream regions of development-related genes are Alu-poor, compared with translational and protein biosynthesis related genes, which are Alu-rich. Finally, we found a correlation between the mouse B1 and human Alu densities within the corresponding upstream regions of orthologous genes. Conclusion We propose that evolution used transposable elements to insert TF binding motifs into promoter regions. We observed enrichment of biosynthesis genes with Alu-associated BSs of developmental TFs. Since development and cell proliferation (of which biosynthesis is an essential component) were proposed to be opposing processes, these TFs possibly play inhibitory roles, suppressing proliferation during differentiation. PMID:16740159

  3. Sequence analysis and expression of Met-rich storage protein SP-1 of Hyphantria cunea.

    PubMed

    Mi, C H; Hwan, H I; Hwa, C D; Jae, S S

    1998-04-30

    We isolated and sequenced a cDNA clone corresponding to the 2.5 kb storage protein (SP-1) from fall webworm, Hyphantria cunea. The SP-1 gene encoded a pre-protein of 753 amino acids, including a signal peptide of 15 amino acids. The deduced amino acid sequence of SP-1 contained one potential N-glycosylation site, and the calculated isoelectric point and molecular weight of secreted SP-1 were pI = 8.38 and 86.8 kDa, respectively. A Northern blot of mRNA from various developmental stages revealed that the SP-1 mRNA in fat body appears in early last instar larvae and accumulates to a maximum level at the end of last instar larvae. The persistence of SP-1 transcript through the early pupal stage suggests that its mRNA might be stable or expressed during the pupal stage. SP-1 transcription was also found in the ovary as well as testis. This local expression of SP-1 in both reproductive organs seems to allow the insect to keep its reproductive activity under a nutritional stress. PMID:9638655

  4. Genome Sequence of the Microsporidian Species Nematocida sp1 Strain ERTm6 (ATCC PRA-372)

    PubMed Central

    Bakowski, Malina A.; Priest, Margaret; Young, Sarah

    2014-01-01

    Microsporidia comprise a phylum of obligate intracellular pathogens related to fungi. Microsporidia Nematocida sp1 strain ERTm6 was isolated from wild-caught Caenorhabditis briggsae and causes a lethal intestinal infection in Caenorhabditis nematodes. We report the genome sequence of N. sp1 ERTm6, which will facilitate study of the Nematocida genus and other Microsporidia. PMID:25237020

  5. Genome Sequence of the Microsporidian Species Nematocida sp1 Strain ERTm6 (ATCC PRA-372).

    PubMed

    Bakowski, Malina A; Priest, Margaret; Young, Sarah; Cuomo, Christina A; Troemel, Emily R

    2014-01-01

    Microsporidia comprise a phylum of obligate intracellular pathogens related to fungi. Microsporidia Nematocida sp1 strain ERTm6 was isolated from wild-caught Caenorhabditis briggsae and causes a lethal intestinal infection in Caenorhabditis nematodes. We report the genome sequence of N. sp1 ERTm6, which will facilitate study of the Nematocida genus and other Microsporidia. PMID:25237020

  6. Why people continue to play online games: in search of critical design factors to increase customer loyalty to online contents.

    PubMed

    Choi, Dongseong; Kim, Jinwoo

    2004-02-01

    As people increasingly play online games, numerous new features have been proposed to increase players' log-on time at online gaming sites. However, few studies have investigated why people continue to play certain online games or which design features are most closely related to the amount of time spent by players at particular online gaming sites. This study proposes a theoretical model using the concepts of customer loyalty, flow, personal interaction, and social interaction to explain why people continue to play online network games. The study then conducts a large-scale survey to validate the model. Finally, it analyzes current online games to identify design features that are closely related to the theoretical concepts. The results indicate that people continue to play online games if they have optimal experiences while playing the games. This optimal experience can be attained if the player has effective personal interaction with the system or pleasant social interactions with other people connected to the Internet. Personal interaction can be facilitated by providing appropriate goals, operators and feedback; social interaction can be facilitated through appropriate communication places and tools. This paper ends with the implications of applying the study results to other domains such as e-commerce and cyber communities. PMID:15006164

  7. City Play.

    ERIC Educational Resources Information Center

    Dargan, Amanda; Zeitlin, Steve

    2000-01-01

    Today, fewer city blocks preserve the confidence of lifestyle and urban geography that sustain traditional games and outdoor play. Large groups of children choosing sides and organizing Red Rover games are no longer commonplace. Teachers must encourage free play; urban planners must build cities that are safe play havens. (MLH)

  8. Interplay Between Egr-1 and Sp1 Critical for 13-cis Retinoic Acid Mediated Transcriptional Repression of Angiotensin Type 1A Receptor

    PubMed Central

    Snyder, Russell; Thekkumkara, Thomas

    2013-01-01

    Recently, we have demonstrated that 13-cis retinoic acid (13cRA) down-regulates rat angiotensin type 1A receptor (AT1AR) gene transcription through a MAP Kinase (ERK1/2) dependent mechanism in rat liver epithelial and aortic smooth muscle cells. However, the exact mechanism remained unknown. In this study, we determined the signaling intermediates activated by ERK1/2 involved in 13cRA mediated AT1AR down-regulation. Serially deleted rat AT1AR promoter CAT constructs indicate fragments containing a region ?2541 and ?1836 bp upstream of the 5 prime possess an Sp1 consensus sequence (5?-TGGGGCGGGGCGGGG-3?) have reduced CAT activity. Mobility shift analysis using untreated nuclear extracts in the presence of mithramycin A suggest the trans-acting factor binding to this cis-acting element is Sp1. 13cRA significantly reduced specific binding without any change in Sp1 protein expression. Studies showed 13cRA maximally phosphorylates and tranlocates to the nucleus ERK1/2 within 5–10 minutes, activating Egr-1 mRNA expression at 20 minutes followed by de novo protein synthesis, leading to an Egr-1/Sp1 interaction. siRNA silencing of Egr-1 restored AT1AR mRNA and protein expression in 13cRA treated cells, and Sp1 silencing results in complete loss of AT1AR expression. Our study suggests that 13cRA mediated activation of ERK1/2, through Egr-1, is capable of disrupting Sp1, the requisite transactivator for AT1AR expression, providing a novel paradigm in AT1AR gene transcription. PMID:23475749

  9. The Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*

    PubMed Central

    Yao, Chen; Yao, Gang-Qing; Sun, Ben-hua; Zhang, Changqing; Tommasini, Steven M.; Insogna, Karl

    2014-01-01

    Colony-stimulating factor 1 (CSF1) is known to promote osteoclast progenitor survival, but its roles in osteoclast differentiation and mature osteoclast function are less well understood. In a microarray screen, Jun dimerization protein 2 (JDP2) was identified as significantly induced by CSF1. Recent reports indicate that JDP2 is required for normal osteoclastogenesis and skeletal metabolism. Because there are no reports on the transcriptional regulation of this gene, the DNA sequence from ?2612 to +682 bp (relative to the transcription start site) of the JDP2 gene was cloned, and promoter activity was analyzed. The T box-binding element (TBE) between ?191 and ?141 bp was identified as the cis-element responsible for CSF1-dependent JDP2 expression. Using degenerate PCR, Tbx3 was identified as the major isoform binding the TBE. Overexpression of Tbx3 induced JDP2 promoter activity, whereas suppressing Tbx3 expression substantially attenuated CSF1-induced transcription. Suppressing Tbx3 in osteoclast precursors reduced JDP2 expression and significantly impaired RANKL/CSF1-induced osteoclastogenesis. A MEK1/2-specific inhibitor was found to block CSF1-induced JDP2 expression. Consistent with these data, JDP2?/? mice were found to have increased bone mass. In summary, CSF1 up-regulates JDP2 expression by inducing Tbx3 binding to the JDP2 promoter. The downstream signaling cascade from activated c-Fms involves the MEK1/2-ERK1/2 pathway. Tbx3 plays an important role in osteoclastogenesis at least in part by regulating CSF1-dependent expression of JDP2. PMID:24394418

  10. Factoring

    NSDL National Science Digital Library

    Mr Clark

    2012-10-31

    Test your factoring skills Factors and Multiples Jeopardy How much do you know about factoring and multiples? Play Jeopardy and find out! Prime Factoring Turkey Shoot Blast these turkeys using your factoring skills. Help the Professor Super save the planet by "cooking" the Giant Frozen Turkeys of Destruction. Math Lines 12 X-Factor Shoot the ball at the other factors to get a product of 12. You can also ...

  11. miR-365, a Novel Negative Regulator of Interleukin-6 Gene Expression, Is Cooperatively Regulated by Sp1 and NF-?B*

    PubMed Central

    Xu, Zheng; Xiao, Shao-Bo; Xu, Peng; Xie, Qian; Cao, Lu; Wang, Dang; Luo, Rui; Zhong, Yao; Chen, Huan-Chun; Fang, Liu-Rong

    2011-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a central role in host defense. IL-6 expression can be regulated at both a transcriptional and a post-transcriptional level. We used a combination of bioinformatics and experimental techniques to demonstrate that the miR-365 is a direct negative regulator of IL-6. Overexpression of miR-365 mimics decreased activity of a luciferase reporter containing the IL-6 3?-UTR and led to repression of IL-6 protein. In contrast, ectopic expression of a miR-365 inhibitor elevated IL-6 expression. The negative regulation of miR-365 was strictly dependent on a microRNA binding element in the 3?-UTR of IL-6 mRNA. Deletion mutant analysis of the miR-365 promoter showed that two transcription factors, Sp1 and NF-?B, are essential for the transcriptional regulation of miR-365. We also demonstrate that the MAPK/ERK pathway contributes to the regulation of miR-365. Furthermore, miR-365 exhibited a greater negative regulatory effect on IL-6 than hsa-let-7a, a previously identified microRNA negatively regulating IL-6. Taken together, our results show that miR-365 is a novel negative regulator of IL-6. PMID:21518763

  12. An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation.

    PubMed Central

    Perkins, N D; Agranoff, A B; Pascal, E; Nabel, G J

    1994-01-01

    Induction of human immunodeficiency virus type 1 (HIV-1) gene expression in stimulated T cells has been attributed to the activation of the transcription factor NF-kappa B. The twice-repeated kappa B sites within the HIV-1 long terminal repeat are in close proximity to three binding sites for Sp1. We have previously shown that a cooperative interaction of NF-kappa B with Sp1 is required for the efficient stimulation of HIV-1 transcription. In this report, we define the domains of each protein responsible for this effect. Although the transactivation domains seemed likely to mediate this interaction, we find, surprisingly, that this interaction occurs through the putative DNA-binding domains of both proteins. Sp1 specifically interacted with the amino-terminal region of RelA(p65). Similarly, RelA bound directly to the zinc finger region of Sp1. This interaction was specific and resulted in cooperative DNA binding to the kappa B and Sp1 sites in the HIV-1 long terminal repeat. Furthermore, the amino-terminal region of RelA did not associate with several other transcription factors, including MyoD, E12, or Kox15, another zinc finger protein. These findings suggest that the juxtaposition of DNA-binding sites promotes a specific protein interaction between the DNA-binding regions of these transcription factors. This interaction is required for HIV transcriptional activation and may provide a mechanism to allow for selective activation of kappa B-regulated genes. Images PMID:7935378

  13. Shadow Play

    ERIC Educational Resources Information Center

    Trundle, Kathy Cabe; Hilson, Margilee P.

    2012-01-01

    A bunny rabbit playfully hops across the wall. Then hands realign and fingers shift to make a hawk soar toward the ceiling. Most children have enjoyed the delightful experience of playing with shadow puppets. The authors build on this natural curiosity to help students link shadows to complex astronomical concepts such as seasons. The…

  14. Play and Positive Group Dynamics

    ERIC Educational Resources Information Center

    Thompson, Pam; White, Samantha

    2010-01-01

    Play is an important part of a child's life and essential to learning and development (Vygotsky, 1978). It is vital that students participate in play and that play be conducted in a restorative manner. Play allows a variety of group dynamics to emerge. Irvin Yalom (1995) identifies 11 curative factors of the group experience. These factors include…

  15. U(3)_C \\times Sp(1)_L \\times U(1)_L \\times U(1)_R

    E-print Network

    Luis Alfredo Anchordoqui

    2011-10-20

    We outline the basic setting of the U(3)_C \\times Sp(1)_L \\times U(1)_L \\times U(1)_R gauge theory and review the associated phenomenological aspects related to experimental searches for new physics at hadron colliders.

  16. CRiSP1 Passage: Columbia River Salmon Passage Model and Data

    NSDL National Science Digital Library

    The CRiSP1 Passage Columbia River Salmon Passage Model, developed by researchers at the University of Washington, "predicts downstream migration and survival of individual stocks of wild and hatchery spawned juvenile fish from the tributaries and dams of the Columbia and Snake rivers to the estuary." At the site, viewers may download the CRiSP1 Passage model (v1.6.0) in addition to PATH Spring and Fall Chinook Data Files (self-extracting files).

  17. Sp1 and TAFII130 Transcriptional Activity Disrupted in Early Huntington's Disease

    Microsoft Academic Search

    Anthone W. Dunah; Hyunkyung Jeong; April Griffin; Yong-Man Kim; David G. Standaert; Steven M. Hersch; M. Maral Mouradian; Anne B. Young; Naoko Tanese; Dimitri Krainc

    2002-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis. Here, we report that huntingtin interacts with the transcriptional activator Sp1 and coactivator TAFII130. Coexpression of Sp1 and TAFII130 in cultured striatal cells from wild-type and HD transgenic mice reverses the transcriptional inhibition

  18. Relationship between parents' report rate of twin language and factors related to linguistic development: older sibling, nonverbal play and preschool attendance.

    PubMed

    Hayashi, Chisato; Hayakawa, Kazuo; Tsuboi, Chika; Oda, Keiko; Amau, Yukiko; Kobayashi, Yoko; Kato, Kenji

    2006-02-01

    The definition and nature of twin language has been a focus of recent studies concerned with the phenomenon. There has been a call for a tighter definition and understanding of the meaning of twin language (Thorpe et al., 2001). This article sought to identify social factors associated with the parent report of twin language and thus provide further understanding of the phenomenon. Data from 583 mothers of twins aged 25 to 59 months were analyzed using multiple logistic regression. Factors included in the modeling of parent-report twin language included social experience factors such as presence of siblings, attendance at preschool education and reports of nonverbal play. It was found that twin pairs who didn't have an older sibling, who showed frequent nonverbal play and who didn't attend preschool were more likely to have a twin language. Moreover, in the group not having an older sibling, the influence of whether twins attended preschool or not was strong and the odds ratio was 0.589 (95% confidence intervals 0.360-0.963). The findings suggest that social experience factors are important predictors of the parent reporting of twin language. PMID:16611482

  19. Hypoxia Inducible Factor 3? Plays a Critical Role in Alveolarization and Distal Epithelial Cell Differentiation during Mouse Lung Development

    PubMed Central

    Huang, Yadi; Kapere Ochieng, Joshua; Kempen, Marjon Buscop-van; Munck, Anne Boerema-de; Swagemakers, Sigrid; van IJcken, Wilfred; Grosveld, Frank; Tibboel, Dick; Rottier, Robbert J.

    2013-01-01

    Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF). HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIF?, and a constitutively expressed subunit, HIF1?. HIF1? and HIF2?, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIF? gene, HIF3?, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3?, NEPAS and IPAS. HIF3? gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS) or weak transcriptional activators (HIF3?/NEPAS). Previously, we and others have shown the importance of the Hif1? and Hif2? factors in lung development, and here we investigated the role of Hif3? during pulmonary development. Therefore, HIF3? was conditionally expressed in airway epithelial cells during gestation and although HIF3? transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3? expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3? expression, the level of Hif2? was reduced, but that of Hif1? was not affected. Two regulatory genes, Rar?, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3? expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3? binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3? affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel function of Hif3? beyond the hypoxia response. PMID:23451260

  20. Inheritance and memory of stress-induced epigenome change: roles played by the ATF-2 family of transcription factors

    PubMed Central

    Seong, Ki-Hyeon; Maekawa, Toshio; Ishii, Shunsuke

    2012-01-01

    Data on the inheritance-of-stress effect have been accumulating and some mechanistic insights, such as epigenetic regulation, have also been suggested. In particular, the modern view of Lamarckian inheritance appears to be affected by the finding that stress-induced epigenetic changes can be inherited. This review summarizes the current data on the inheritance of stress effect and possible mechanisms involved in this process. In particular, we focus on the stress-induced epigenetic changes mediated by the ATF-2 family of transcription factors. PMID:22380515

  1. Spatial Factors Play a Major Role as Determinants of Endemic Ground Beetle Beta Diversity of Madeira Island Laurisilva

    PubMed Central

    Boieiro, Mário; Carvalho, José C.; Cardoso, Pedro; Aguiar, Carlos A. S.; Rego, Carla; de Faria e Silva, Israel; Amorim, Isabel R.; Pereira, Fernando; Azevedo, Eduardo B.; Borges, Paulo A. V.; Serrano, Artur R. M.

    2013-01-01

    The development in recent years of new beta diversity analytical approaches highlighted valuable information on the different processes structuring ecological communities. A crucial development for the understanding of beta diversity patterns was also its differentiation in two components: species turnover and richness differences. In this study, we evaluate beta diversity patterns of ground beetles from 26 sites in Madeira Island distributed throughout Laurisilva – a relict forest restricted to the Macaronesian archipelagos. We assess how the two components of ground beetle beta diversity (?repl – species turnover and ?rich - species richness differences) relate with differences in climate, geography, landscape composition matrix, woody plant species richness and soil characteristics and the relative importance of the effects of these variables at different spatial scales. We sampled 1025 specimens from 31 species, most of which are endemic to Madeira Island. A spatially explicit analysis was used to evaluate the contribution of pure environmental, pure spatial and environmental spatially structured effects on variation in ground beetle species richness and composition. Variation partitioning showed that 31.9% of species turnover (?repl) and 40.7% of species richness variation (?rich) could be explained by the environmental and spatial variables. However, different environmental variables controlled the two types of beta diversity: ?repl was influenced by climate, disturbance and soil organic matter content whilst ?rich was controlled by altitude and slope. Furthermore, spatial variables, represented through Moran’s eigenvector maps, played a significant role in explaining both ?repl and ?rich, suggesting that both dispersal ability and Madeira Island complex orography are crucial for the understanding of beta diversity patterns in this group of beetles. PMID:23724065

  2. Physician perspectives and compliance with patient advance directives: the role external factors play on physician decision making

    PubMed Central

    2012-01-01

    Background Following passage of the Patient Self Determination Act in 1990, health care institutions that receive Medicare and Medicaid funding are required to inform patients of their right to make their health care preferences known through execution of a living will and/or to appoint a surrogate-decision maker. We evaluated the impact of external factors and perceived patient preferences on physicians’ decisions to honor or forgo previously established advance directives (ADs). In addition, physician views regarding legal risk, patients’ ability to comprehend complexities involved with their care, and impact of medical costs related to end-of-life care decisions were explored. Methods Attendees of two Mayo Clinic continuing medical education courses were surveyed. Three scenarios based in part on previously court-litigated matters assessed impact of external factors and perceived patient preferences on physician compliance with patient-articulated wishes regarding resuscitation. General questions measured respondents’ perception of legal risk, concerns over patient knowledge of idiosyncrasies involved with their care, and impact medical costs may have on compliance with patient preferences. Responses indicating strength of agreement or disagreement with statements were treated as ordinal data and analyzed using the Cochran Armitage trend test. Results Three hundred eighty-eight of 951 surveys were completed (41% response rate). Eighty percent reported they were likely to honor a patient’s AD despite its 5 year age. Fewer than half (41%) would honor the AD of a patient in ventricular fibrillation who had expressed a desire to “pass away in peace.” Few (17%) would forgo an AD following a family’s request for continued resuscitative treatment. A majority (52%) considered risk of liability to be lower when maintaining someone alive against their wishes than mistakenly failing to provide resuscitative efforts. A large percentage (74%) disagreed that patients could not appreciate complexities surrounding their care while 69% agreed that costs should never impact a physician’s decision as to whether to comply with a patient’s AD. Conclusions Our findings highlight the impact, albeit small, external factors have on physician AD compliance. Most respondents based their decision on the clinical situation at hand and interpretation of the patient’s initial wishes and preferences expressed by the AD. PMID:23171364

  3. Zinc Finger Independent Genome-Wide Binding of Sp2 Potentiates Recruitment of Histone-Fold Protein Nf-y Distinguishing It from Sp1 and Sp3.

    PubMed

    Völkel, Sara; Stielow, Bastian; Finkernagel, Florian; Stiewe, Thorsten; Nist, Andrea; Suske, Guntram

    2015-02-01

    Transcription factors are grouped into families based on sequence similarity within functional domains, particularly DNA-binding domains. The Specificity proteins Sp1, Sp2 and Sp3 are paradigmatic of closely related transcription factors. They share amino-terminal glutamine-rich regions and a conserved carboxy-terminal zinc finger domain that can bind to GC rich motifs in vitro. All three Sp proteins are ubiquitously expressed; yet they carry out unique functions in vivo raising the question of how specificity is achieved. Crucially, it is unknown whether they bind to distinct genomic sites and, if so, how binding site selection is accomplished. In this study, we have examined the genomic binding patterns of Sp1, Sp2 and Sp3 in mouse embryonic fibroblasts by ChIP-seq. Sp1 and Sp3 essentially occupy the same promoters and localize to GC boxes. The genomic binding pattern of Sp2 is different; Sp2 primarily localizes at CCAAT motifs. Consistently, re-expression of Sp2 and Sp3 mutants in corresponding knockout MEFs revealed strikingly different modes of genomic binding site selection. Most significantly, while the zinc fingers dictate genomic binding of Sp3, they are completely dispensable for binding of Sp2. Instead, the glutamine-rich amino-terminal region is sufficient for recruitment of Sp2 to its target promoters in vivo. We have identified the trimeric histone-fold CCAAT box binding transcription factor Nf-y as the major partner for Sp2-chromatin interaction. Nf-y is critical for recruitment of Sp2 to co-occupied regulatory elements. Equally, Sp2 potentiates binding of Nf-y to shared sites indicating the existence of an extensive Sp2-Nf-y interaction network. Our results unveil strikingly different recruitment mechanisms of Sp1/Sp2/Sp3 transcription factor members uncovering an unexpected layer of complexity in their binding to chromatin in vivo. PMID:25793500

  4. Zinc Finger Independent Genome-Wide Binding of Sp2 Potentiates Recruitment of Histone-Fold Protein Nf-y Distinguishing It from Sp1 and Sp3

    PubMed Central

    Finkernagel, Florian; Stiewe, Thorsten; Nist, Andrea; Suske, Guntram

    2015-01-01

    Transcription factors are grouped into families based on sequence similarity within functional domains, particularly DNA-binding domains. The Specificity proteins Sp1, Sp2 and Sp3 are paradigmatic of closely related transcription factors. They share amino-terminal glutamine-rich regions and a conserved carboxy-terminal zinc finger domain that can bind to GC rich motifs in vitro. All three Sp proteins are ubiquitously expressed; yet they carry out unique functions in vivo raising the question of how specificity is achieved. Crucially, it is unknown whether they bind to distinct genomic sites and, if so, how binding site selection is accomplished. In this study, we have examined the genomic binding patterns of Sp1, Sp2 and Sp3 in mouse embryonic fibroblasts by ChIP-seq. Sp1 and Sp3 essentially occupy the same promoters and localize to GC boxes. The genomic binding pattern of Sp2 is different; Sp2 primarily localizes at CCAAT motifs. Consistently, re-expression of Sp2 and Sp3 mutants in corresponding knockout MEFs revealed strikingly different modes of genomic binding site selection. Most significantly, while the zinc fingers dictate genomic binding of Sp3, they are completely dispensable for binding of Sp2. Instead, the glutamine-rich amino-terminal region is sufficient for recruitment of Sp2 to its target promoters in vivo. We have identified the trimeric histone-fold CCAAT box binding transcription factor Nf-y as the major partner for Sp2-chromatin interaction. Nf-y is critical for recruitment of Sp2 to co-occupied regulatory elements. Equally, Sp2 potentiates binding of Nf-y to shared sites indicating the existence of an extensive Sp2-Nf-y interaction network. Our results unveil strikingly different recruitment mechanisms of Sp1/Sp2/Sp3 transcription factor members uncovering an unexpected layer of complexity in their binding to chromatin in vivo. PMID:25793500

  5. Predictive Value of Sp1/Sp3/FLIP Signature for Prostate Cancer Recurrence

    PubMed Central

    Bedolla, Roble G.; Gong, Jingjing; Prihoda, Thomas J.; Yeh, I-Tien; Thompson, Ian M.; Ghosh, Rita; Kumar, Addanki P.

    2012-01-01

    Prediction of prostate cancer prognosis is challenging and predictive biomarkers of recurrence remain elusive. Although prostate specific antigen (PSA) has high sensitivity (90%) at a PSA level of 4.0 ng/mL, its low specificity leads to many false positive results and considerable overtreatment of patients and its performance at lower ranges is poor. Given the histopathological and molecular heterogeneity of prostate cancer, we propose that a panel of markers will be a better tool than a single marker. We tested a panel of markers composed of the anti-apoptotic protein FLIP and its transcriptional regulators Sp1 and Sp3 using prostate tissues from 64 patients with recurrent and non-recurrent cancer who underwent radical prostatectomy as primary treatment for prostate cancer and were followed with PSA measurements for at least 5 years. Immunohistochemical staining for Sp1, Sp3, and FLIP was performed on these tissues and scored based on the proportion and intensity of staining. The predictive value of the FLIP/Sp1/Sp3 signature for clinical outcome (recurrence vs. non-recurrence) was explored with logistic regression, and combinations of FLIP/Sp1/Sp3 and Gleason score were analyzed with a stepwise (backward and forward) logistic model. The discrimination of the markers was identified by sensitivity-specificity analysis and the diagnostic value of FLIP/Sp1/Sp3 was determined using area under the curve (AUC) for receiver operator characteristic curves. The AUCs for FLIP, Sp1, Sp3, and Gleason score for predicting PSA failure and non-failure were 0.71, 0.66, 0.68, and 0.76, respectively. However, this increased to 0.93 when combined. Thus, the “biomarker signature” of FLIP/Sp1/Sp3 combined with Gleason score predicted disease recurrence and stratified patients who are likely to benefit from more aggressive treatment. PMID:23028678

  6. Clay Play

    ERIC Educational Resources Information Center

    Rogers, Liz; Steffan, Dana

    2009-01-01

    This article describes how to use clay as a potential material for young children to explore. As teachers, the authors find that their dialogue about the potential of clay as a learning medium raises many questions: (1) What makes clay so enticing? (2) Why are teachers noticing different play and conversation around the clay table as compared to…

  7. Sweet Play

    ERIC Educational Resources Information Center

    Leung, Shuk-kwan S.; Lo, Jane-Jane

    2010-01-01

    This article features Sweet play math, a "math by the month" activity that involves decorating and making sugar cubes. Teachers may want to substitute straws, paper squares, alphabet blocks, or such commercially made manipulatives as Unifix[R] cubes for the real sweets. Given no allergy concerns, teachers and students alike would enjoy some sweet…

  8. The transcription factor Pap1/Caf3 plays a central role in the determination of caffeine resistance in Schizosaccharomyces pombe.

    PubMed

    Benko, Z; Fenyvesvolgyi, C; Pesti, M; Sipiczki, M

    2004-03-01

    We previously identified four nuclear genes (caf1+-caf4+) in Schizosaccharomyces pombe, mutations in which confer resistance to caffeine and brefeldin A. caf1+, caf2+ and caf4+ were sequenced and found to be identical to the multidrug-resistance/stress-response genes hba1, crm1 and trr1, respectively. Here we show that caf3 is allelic to pap1, which encodes an AP-1-like transcription factor. The allele associated with caffeine resistance, caf3-89, contains a single-nucleotide exchange that results in a Leu-->Ser exchange in the NES (nuclear export signal) domain of the gene product. Due to this alteration, the modified protein can not be exported from the nucleus back into the cytoplasm, and thus accumulates in the nucleus. The activity of pap1/caf3 is shown to be necessary for manifestation of the caffeine resistance caused by mutations in the genes hba1/caf1 and crm1/caf2. We also cloned two genes that confer caffeine resistance when carried on a multicopy plasmid. One of them turned out to be a truncated allele of pad1/bfr2/sks1, which codes for a subunit of the 26 S proteosome. The putative product of the other gene, designated caf5, has a structure highly similar to that of MFS permeases. It contains two groups of six transmembrane spanning domains each, with the conserved motifs WRW, PET and GAIGGPVLGP in the fifth and sixth domains. These results are all consistent with our earlier hypothesis, which suggested that the caf genes are functionally interlinked in a complex detoxification mechanism. caf5 and pad1 may also encode parts of this mechanism. PMID:14758541

  9. Sp1-mediated microRNA-182 expression regulates lung cancer progression

    PubMed Central

    Yang, Wen-Bin; Chen, Ping-Hsin; Hsu, Tsung-I; Fu, Tzu-Fun; Su, Wu-Chou; Liaw, Hungjiun; Chang, Wen-Chang; Hung, Jan-Jong

    2014-01-01

    Our recent study indicated that overexpression of Sp1 enhances the proliferation of lung cancer cells, while represses metastasis. In this study, we found that the transcriptional activity of FOXO3 was increased, but its protein levels decreased following Sp1 expression. Sp1 increased expression of miR-182, which was then recruited to the 3'-untranslated region of FOXO3 mRNA to silence its translational activity. Knockdown of miR-182 inhibited lung cancer cells growth, but enhanced the invasive and migratory abilities of these cells through increased N-cadherin expression. Repression of FOXO3 expression in the miR-182 knockdown cells partially reversed this effect, suggesting that miR-182 promotes cancer cell growth and inhibits cancer metastatic activity by regulating the expression of FOXO3. The expression of several cancer metastasis-related genes such as ADAM9, CDH9 and CD44 was increased following miR-182 knockdown. In conclusion, in the early stages of lung cancer progression, Sp1 stimulates miR-182 expression, which in turn decreases FOXO3 expression. This stimulates proliferation and tumor growth. In the late stages, Sp1 and miR-182 decline, thus increasing FOXO3 expression, which leads to lung metastasis. PMID:24519909

  10. Activation of PPAR{gamma} negatively regulates O-GlcNAcylation of Sp1

    SciTech Connect

    Chung, Sung Soo; Kim, Ji Hyun; Park, Ho Seon; Choi, Hye Hun; Lee, Kyeong Won; Cho, Young Min; Lee, Hong Kyu [Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Park, Kyong Soo [Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of)], E-mail: kspark@snu.ac.kr

    2008-08-08

    O-GlcNAcylation is a kind of post-translational modification and many nuclear and cytoplasmic proteins are O-GlcNAcylated. In this study, we demonstrated that thiazolidinediones (TZDs), which are used as insulin sensitizer, specifically inhibited the O-GlcNAcylation of Sp1 but did not affect the O-GlcNAcylation of the total proteins in cell culture systems and mouse models. This effect was mediated by peroxisome proliferator activated receptor {gamma} (PPAR{gamma}) activation and probably by synthesis of a specific protein induced by PPAR{gamma} activation. In addition, we demonstrated that the O-GlcNAcylation sites in the zinc-finger domain were involved in the transcriptional activation of Sp1 and that rosiglitazone, a member of TZDs, affected Sp1 transcriptional activity partially by regulating the O-GlcNAcylation level of these sites. Considering the role of hexosamine biosynthesis pathway in hyperglycemia-induced insulin resistance and Sp1 in the hyperglycemia-induced gene expression, the regulation of Sp1 O-GlcNAcylation by TZDs may help to explain the function of TZDs as a treatment for insulin resistance and diabetes.

  11. Transcriptional Activation of the cAMP-responsive Modulator Promoter in Human T Cells Is Regulated by Protein Phosphatase 2A-mediated Dephosphorylation of SP-1 and Reflects Disease Activity in Patients with Systemic Lupus Erythematosus*

    PubMed Central

    Juang, Yuang-Taung; Rauen, Thomas; Wang, Ying; Ichinose, Kunihiro; Benedyk, Konrad; Tenbrock, Klaus; Tsokos, George C.

    2011-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous abnormalities recorded at the cellular, molecular, and genetic level. Expression of the basic leucine zipper transcription factor cAMP-responsive element modulator (CREM)? was reported to be abnormally increased in T cells from SLE patients. CREM? suppresses IL-2 and T cell receptor ? chain gene transcription by direct binding to the respective promoters. Here, we show that increased CREM expression is the result of enhanced promoter activity. DNA binding analyses reveal direct binding of transcription factor specificity protein-1 (SP-1) to the CREM promoter resulting in enhanced transcriptional activity and increased CREM expression. Protein phosphatase 2A is known to activate SP-1 through dephosphorylation at its serine residue 59. Our results show that nuclei from SLE T cells contain lower levels of Ser59-phosphorylated SP-1 protein and a stronger SP-1 binding to the CREM promoter. We conclude that protein phosphatase 2A accounts for enhanced SP-1 dephosphorylation at Ser59 in SLE T cells. More importantly, CREM promoter activity mirrors reliably disease activity in SLE patients, underscoring its potential role as a biomarker for the prediction of flares in SLE patients. PMID:21097497

  12. Thrombin induces Sp1-mediated antiviral effects in cytomegalovirus-infected human retinal pigment epithelial cells.

    PubMed

    Scholz, Martin; Vogel, Jens-Uwe; Höver, Gerold; Prösch, Susanna; Kotchetkov, Ruslan; Cinatl, Jaroslav; Koch, Frank; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2004-11-01

    Human cytomegalovirus (HCMV) retinitis causing retinal detachment and destruction of the blood-retina barrier is closely related to retinal hemorrhage/coagulation. However, the effects of procoagulants on HCMV (re)activation in retinal cells have not been investigated yet. Therefore, we studied whether thrombin modulates the expression of HCMV immediate early (IE) and late (L) genes in cultured human retinal pigment epithelial cells (RPE). Thrombin specifically stimulated the protease-activated receptor-1 (PAR-1) on RPE and, surprisingly, inhibited basal and 12,0-tetradecanoylphorbol 13-acetate-stimulated HCMV IE gene expression in infected RPE. On the other hand, HCMV strongly induced Sp1 DNA binding activity, which was prevented by thrombin/PAR1-mediated Sp1 hyperphosphorylation. Our data suggest that thrombin/PAR-1 may inhibit Sp1-dependent HCMV replication, which might be an important regulatory mechanism for HCMV persistence and replication in RPE. PMID:13680213

  13. Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

    PubMed Central

    2011-01-01

    Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

  14. Maximizing Chemical Diversity of Fungal Metabolites: Biogenetically Related Heptaketides of the Endolichenic Fungus Corynespora sp.1

    E-print Network

    Arnold, A. Elizabeth

    of the Endolichenic Fungus Corynespora sp.1 E. M. Kithsiri Wijeratne, Bharat P. Bashyal, Malkanthi K. Gunatilaka,§ A of the endolichenic fungus Corynespora sp. BA-10763, its metabolite profiles under several culture conditions were and a fungus of marine origin.10 Recent success in maximizing chemical diversity of metabolites of plant

  15. Sp1 modification of human endothelial nitric oxide synthase promoter increases the hypoxia-stimulated activity.

    PubMed

    Yang, Yunhua; Liu, Song; Fan, Zhenhua; Li, Zhuo; Liu, Jing; Xing, Feiyue

    2014-05-01

    Human endothelial nitric oxide synthase (eNOS) gene has a TATA-less weak promoter with a low activity. The aim of this study was to increase eNOS promoter activity by modification. Human eNOS promoter was modified by inserting a Sp1 element at a -74 bp site and function of the modified promoter was investigated via a hypoxia model induced by cobalt chloride in human umbilical vein endothelial cells. The results demonstrated that the Sp1-modified promoter resulted in a significant increase of normalized luciferase activity in the presence of hypoxia. There was a correlation between the transcriptional activity of the Sp1-modified promoter and the level of eNOS expression with enhancement of nitric oxide production. Together, these data indicate that human eNOS promoter activity is increased by inserting Sp1 binding site into the GC-rich region of the promoter in response to hypoxia, suggesting that this provides an approach to ameliorate microcirculation barrier of some cardiovascular disease and to study its mechanistic process. PMID:24681424

  16. Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca{sup 2+} influx

    SciTech Connect

    Moon, Dong-Oh [Department of Biology Education, Daegu University, Gyungsan, Gyeongbuk 712–714 (Korea, Republic of)] [Department of Biology Education, Daegu University, Gyungsan, Gyeongbuk 712–714 (Korea, Republic of); Kang, Chang-Hee; Kang, Sang-Hyuck [Department of Marine Life Sciences, Jeju National University, Jeju 690–756 (Korea, Republic of)] [Department of Marine Life Sciences, Jeju National University, Jeju 690–756 (Korea, Republic of); Choi, Yung-Hyun [Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614–054 (Korea, Republic of)] [Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614–054 (Korea, Republic of); Hyun, Jin-Won; Chang, Weon-Young; Kang, Hee-Kyoung; Koh, Young-Sang; Maeng, Young-Hee; Kim, Young-Ree [School of Medicine, Jeju National University, Jeju-si 690–756 (Korea, Republic of)] [School of Medicine, Jeju National University, Jeju-si 690–756 (Korea, Republic of); Kim, Gi-Young, E-mail: immunkim@jejunu.ac.kr [Department of Marine Life Sciences, Jeju National University, Jeju 690–756 (Korea, Republic of)] [Department of Marine Life Sciences, Jeju National University, Jeju 690–756 (Korea, Republic of)

    2012-02-15

    Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation. Highlights: ? Capsaicin sensitizes TRAIL-induced apoptosis through activation of caspases. ? Capsaicin induces expression of DR5 through Sp1 activation. ? Capsaicin activates calcium signaling pathway.

  17. CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383.

    PubMed

    Reynard, Louise N; Bui, Catherine; Syddall, Catherine M; Loughlin, John

    2014-08-01

    GDF5 encodes an extracellular signalling molecule that is essential for normal skeletal development. The rs144383 C to T SNP located in the 5'UTR of this gene is functional and has a pleiotropic effect on the musculoskeletal system, being a risk factor for knee-osteoarthritis (OA), congenital hip dysplasia, lumbar disc degeneration and Achilles tendon pathology. rs143383 exerts a joint-wide effect on GDF5 expression, with expression of the OA-associated T allele being significantly reduced relative to the C allele, termed allelic expression imbalance. We have previously reported that the GDF5 locus is subject to DNA methylation and that allelic imbalance of rs143383 is mediated by SP1, SP3 and DEAF1 transcriptional repressors. In this study, we have assayed GDF5 methylation in normal and osteoarthritic cartilage, and investigated the effect of methylation on the allelic imbalance of rs143383. We observed demethylation of the GDF5 5'UTR in OA knee cartilage relative to both OA (p = 0.009) and non-OA (p = 0.001) hip cartilage, with the most significant demethylation observed at the highly conserved +37 CpG site located 4 bp upstream of rs143383. Methylation modulates the level and direction of allelic imbalance of rs143383, with methylation of the +37 CpG dinucleotide within the SP1/SP3 binding site having an allele-specific effect on SP1 and SP3 binding. Furthermore, methylation attenuated the repressive effects of SP1, SP3 and DEAF1 on GDF5 promoter activity. This data suggest that the differential methylation of the +37 CpG site between osteoarthritic hip and knee cartilage may be responsible for the knee-specific effect of rs143383 on OA susceptibility. PMID:24861163

  18. Filamin B plays a key role in vascular endothelial growth factor-induced endothelial cell motility through its interaction with Rac-1 and Vav-2.

    PubMed

    Del Valle-Pérez, Beatriz; Martínez, Vanesa Gabriela; Lacasa-Salavert, Cristina; Figueras, Agnès; Shapiro, Sandor S; Takafuta, Toshiro; Casanovas, Oriol; Capellà, Gabriel; Ventura, Francesc; Viñals, Francesc

    2010-04-01

    Actin-binding proteins filamin A (FLNA) and B (FLNB) are expressed in endothelial cells and play an essential role during vascular development. In order to investigate their role in adult endothelial cell function, we initially confirmed their expression pattern in different adult mouse tissues and cultured cell lines and found that FLNB expression is concentrated mainly in endothelial cells, whereas FLNA is more ubiquitously expressed. Functionally, small interfering RNA knockdown of endogenous FLNB in human umbilical vein endothelial cells inhibited vascular endothelial growth factor (VEGF)-induced in vitro angiogenesis by decreasing endothelial cell migration capacity, whereas FLNA ablation did not alter these parameters. Moreover, FLNB-depleted cells increased their substrate adhesion with more focal adhesions. The molecular mechanism underlying this effect implicates modulation of small GTP-binding protein Rac-1 localization and activity, with altered activation of its downstream effectors p21 protein Cdc42/Rac-activated kinase (PAK)-4/5/6 and its activating guanine nucleotide exchange factor Vav-2. Moreover, our results suggest the existence of a signaling complex, including FLNB, Rac-1, and Vav-2, under basal conditions that would further interact with VEGFR2 and integrin alphavbeta5 after VEGF stimulation. In conclusion, our results reveal a crucial role for FLNB in endothelial cell migration and in the angiogenic process in adult endothelial cells. PMID:20110358

  19. Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: Possible reaction of cadmium with the zinc finger domain of Sp1

    SciTech Connect

    Kothinti, Rajendra K.; Blodgett, Amy B.; Petering, David H. [Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201 (United States); Tabatabai, Niloofar M., E-mail: ntabatab@mcw.ed [Kidney Disease Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

    2010-05-01

    Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose transporters, SGLT1 and SGLT2 and that Sp1 from Cd-exposed cells displayed reduced binding to the GC boxes of the mouse SGLT1 promoter in vitro. Here, we identified a GC box upstream of mouse SGLT2 gene. ChIP assays on PMKC revealed that exposure to 5 muM Cd abolished Sp1 binding to SGLT1 GC box while it decreased Sp1 binding to SGLT2 GC sequence by 30% in vivo. The in vitro DNA binding assay, EMSA, demonstrated that binding of Sp1 from Cd (7.5 muM)-treated PMKC to the SGLT2 GC probe was 86% lower than in untreated cells. Sp1 is a zinc finger protein. Compared to PMKC exposed to 5 muM Cd alone, inclusion of 5 muM Zn restored SGLT1 and 2 mRNA levels by 15% and 30%, respectively. Cd (10 muM) decreased the binding of recombinant Sp1 (rhSp1) to SGLT1 and SGLT2 GC probes to 12% and 8% of untreated controls. Cd exerted no effect on GC-bound rhSp1. Co-treatment with Cd and Zn showed that added Zn significantly restored rhSp1 binding to the SGLT1 and SGLT2. Addition of Zn post Cd treatment was not stimulatory. We conclude that Cd can replace Zn in Sp1 DNA binding domain to reduce its binding to GC sites in mouse SGLT1 and SGLT2 promoters.

  20. Playing It Safe.

    ERIC Educational Resources Information Center

    O'Neill, Steve

    2000-01-01

    Provides tips on how to avoid accidents and injuries on school playgrounds. Tips include removing of old, dangerous equipment; relocating play areas to safer ground; choosing the right surface; factoring in long-term costs for replenishing and redistributing loose materials; and considering Americans with Disabilities Act issues. (GR)

  1. Sp1 mediates repression of the resistin gene by PPAR{gamma} agonists in 3T3-L1 adipocytes

    SciTech Connect

    Chung, S.S. [Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul (Korea, Republic of); Choi, H.H. [Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul (Korea, Republic of); Cho, Y.M. [Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Internal Medicine, Seoul National University, College of Medicine, Seoul (Korea, Republic of); Lee, H.K. [Department of Internal Medicine, Seoul National University, College of Medicine, Seoul (Korea, Republic of); Park, K.S. [Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul (Korea, Republic of) and Department of Internal Medicine, Seoul National University, College of Medicine, Seoul (Korea, Republic of)]. E-mail: kspark@snu.ac.kr

    2006-09-15

    Resistin is an adipokine related to obesity and insulin resistance. Expression of the resistin gene is repressed by the treatment of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists, thiazolidinediones (TZDs). In this study, we investigated the mechanism by which TZDs inhibit the resistin gene expression. Resistin gene expression was decreased by TZD in fully differentiated 3T3-L1 adipocytes, which was abolished after treatment of cycloheximide (a protein synthesis inhibitor). TZD could not repress the expression of the resistin gene in the presence of mithramycin A (an Sp1 binding inhibitor). Sp1 binding site of the resistin promoter (-122/-114 bp) was necessary for the repression. Further investigation of the effect of TZDs on the modification of Sp1 showed that the level of O-glycosylation of Sp1 was decreased in this process. These results suggest that PPAR{gamma} activation represses the expression of the resistin gene by modulating Sp1 activity.

  2. Hypoxia-Inducible Factors Modulate the Stemness and Malignancy of Colon Cancer Cells by Playing Opposite Roles in Canonical Wnt Signaling

    PubMed Central

    Santoyo-Ramos, Paula; Likhatcheva, María; García-Zepeda, Eduardo A.; Castañeda-Patlán, M. Cristina; Robles-Flores, Martha

    2014-01-01

    This study examined the role played by hypoxia-inducible factors (HIFs) in malignant phenotype maintenance and canonical Wnt signaling. Under normoxia, we determined that both HIF-1? and HIF-2? are expressed in human colon cancer cells but not in their non-malignant counterparts. The stable knockdown of HIF-1? or HIF-2? expression induced negative effects on the malignant phenotype of colon cancer cells, with lactate production, the rate of apoptosis, migration, CXCR4-mediated chemotaxis, and tumorigenic activity all being significantly affected by HIF knockdown and with HIF-1? depletion exerting greater effects. Knockdown of these two HIF transcripts induced different and even opposite effects on ?-catenin transcriptional activity in colon cancer cells with different genetic Wnt signaling pathways. In SW480 cells, HIF-2? knockdown did not affect ?-catenin levels, increasing the transcriptional activity of ?-catenin by inducing its nuclear accumulation, whereas HIF-1? silencing negatively affected the stability and transcriptional activity of ?-catenin, inducing its exit from the nuclei and its recruitment to the cell membrane by E-cadherin. In addition, although HIF-1? depletion induced a reversal of the epithelial-to-mesenchymal transition (EMT), HIF-2? silencing altered the expression of the stem cell markers CD44, Oct4, and CD24 and of the differentiation marker CK20 in the opposite direction as HIF-1? silencing. Remarkably, HIF-2? knockdown also enhanced ?-catenin transcriptional activity under hypoxia in cells that displayed normal Wnt signaling, suggesting that the gene negatively modulates canonical Wnt signaling in colon cancer cells. Taken together, our results indicate that HIFs play opposing roles in canonical Wnt signaling and are essential for the stemness and malignancy maintenance of colon cancer cells. PMID:25396735

  3. An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways

    E-print Network

    Hirose, Takashi

    During animal development, the proper regulation of apoptosis requires the precise spatial and temporal execution of cell-death programs, which can include both caspase-dependent and caspase-independent pathways. Although ...

  4. Core Binding Factor Beta Plays a Critical Role by Facilitating the Assembly of the Vif-Cullin 5 E3 Ubiquitin Ligase

    PubMed Central

    Fribourgh, Jennifer L.; Nguyen, Henry C.; Wolfe, Leslie S.; DeWitt, David C.; Zhang, Wenyan; Yu, Xiao-Fang; Rhoades, Elizabeth

    2014-01-01

    ABSTRACT The HIV-1 virion infectivity factor (Vif) targets the cellular cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) for degradation via the host ubiquitin-proteasome pathway. Vif recruits a cellular E3 ubiquitin ligase to polyubiquitinate A3G/F. The activity of Vif critically depends on the cellular core binding factor beta (CBF?). In this study, we investigated the Vif-CBF? interaction and the role of CBF? in the E3 ligase assembly. Vif-CBF? interaction requires an extensive region of Vif spanning most of its amino terminus and zinc finger region, and cullin 5 (Cul5) binding enhances the stability of the Vif-CBF? interaction. Our results further demonstrate that CBF? plays a critical role in facilitating Cul5 binding to the Vif/elongin B/elongin C complex. Vif, with or without bound substrate, is unable to bind Cul5 in the absence of CBF?. These studies support the notion that CBF? serves as a molecular chaperone to facilitate Vif-E3 ligase assembly. IMPORTANCE The host antiviral restriction factors A3G/F inhibit viral replication. The HIV-1 protein Vif targets A3G/F for degradation. This immune evasion activity of Vif is dependent on the cellular factor CBF?. Multiple regions of Vif are known to be important for Vif function, but the mechanisms are unclear. The studies described here provide important information about the Vif-CBF? interaction interface and the function of CBF? in E3 ligase assembly. In particular, our comprehensive Vif-CBF? interface mapping results help to delineate the role of various Vif regions, determining if they are important for binding CBF? or A3G/F. Furthermore, our studies reveal an important potential mechanism of CBF? that has not been shown before. Our results suggest that CBF? may serve as a molecular chaperone to enable Vif to adopt an appropriate conformation for interaction with the Cul5-based E3 ligase. This study advances our understanding of how CBF? facilitates the Vif-mediated degradation of APOBEC3 proteins. PMID:24390320

  5. The Theobroma cacao B3 domain transcription factor TcLEC2 plays a duel role in control of embryo development and maturation

    PubMed Central

    2014-01-01

    Background The Arabidopsis thaliana LEC2 gene encodes a B3 domain transcription factor, which plays critical roles during both zygotic and somatic embryogenesis. LEC2 exerts significant impacts on determining embryogenic potential and various metabolic processes through a complicated genetic regulatory network. Results An ortholog of the Arabidopsis Leafy Cotyledon 2 gene (AtLEC2) was characterized in Theobroma cacao (TcLEC2). TcLEC2 encodes a B3 domain transcription factor preferentially expressed during early and late zygotic embryo development. The expression of TcLEC2 was higher in dedifferentiated cells competent for somatic embryogenesis (embryogenic calli), compared to non-embryogenic calli. Transient overexpression of TcLEC2 in immature zygotic embryos resulted in changes in gene expression profiles and fatty acid composition. Ectopic expression of TcLEC2 in cacao leaves changed the expression levels of several seed related genes. The overexpression of TcLEC2 in cacao explants greatly increased the frequency of regeneration of stably transformed somatic embryos. TcLEC2 overexpressing cotyledon explants exhibited a very high level of embryogenic competency and when cultured on hormone free medium, exhibited an iterative embryogenic chain-reaction. Conclusions Our study revealed essential roles of TcLEC2 during both zygotic and somatic embryo development. Collectively, our evidence supports the conclusion that TcLEC2 is a functional ortholog of AtLEC2 and that it is involved in similar genetic regulatory networks during cacao somatic embryogenesis. To our knowledge, this is the first detailed report of the functional analysis of a LEC2 ortholog in a species other then Arabidopsis. TcLEC2 could potentially be used as a biomarker for the improvement of the SE process and screen for elite varieties in cacao germplasm. PMID:24758406

  6. Activation of PPAR? negatively regulates O-GlcNAcylation of Sp1

    Microsoft Academic Search

    Sung Soo Chung; Ji Hyun Kim; Ho Seon Park; Hye Hun Choi; Kyeong Won Lee; Young Min Cho; Hong Kyu Lee; Kyong Soo Park

    2008-01-01

    O-GlcNAcylation is a kind of post-translational modification and many nuclear and cytoplasmic proteins are O-GlcNAcylated. In this study, we demonstrated that thiazolidinediones (TZDs), which are used as insulin sensitizer, specifically inhibited the O-GlcNAcylation of Sp1 but did not affect the O-GlcNAcylation of the total proteins in cell culture systems and mouse models. This effect was mediated by peroxisome proliferator activated

  7. Development of the rhopalial nervous system in Aurelia sp.1 (Cnidaria, Scyphozoa)

    Microsoft Academic Search

    Nagayasu Nakanishi; Volker Hartenstein; David K. Jacobs

    2009-01-01

    We examined the development of the nervous system in the rhopalium, a medusa-specific sensory structure, in Aurelia sp.1 (Cnidaria, Scyphozoa) using confocal microscopy. The rhopalial nervous system appears primarily ectodermal and contains\\u000a neurons immunoreactive to antibodies against tyrosinated tubulin, taurine, GLWamide, and FMRFamide. The rhopalial nervous\\u000a system develops in an ordered manner: the presumptive gravity-sensing organ, consisting of the lithocyst

  8. Macrophage migration inhibitory factor plays a permissive role in the maintenance of cardiac contractile function under starvation through regulation of autophagy

    PubMed Central

    Xu, Xihui; Pacheco, Benjamin D.; Leng, Lin; Bucala, Richard; Ren, Jun

    2013-01-01

    Aims The cytokine macrophage migration inhibitory factor (MIF) protects the heart through AMPK activation. Autophagy, a conserved pathway for bulk degradation of intracellular proteins and organelles, helps preserve and recycle energy and nutrients for cells to survive under starvation. This study was designed to examine the role of MIF in cardiac homeostasis and autophagy regulation following an acute starvation challenge. Methods and results Wild-type (WT) and MIF knockout mice were starved for 48 h. Echocardiographic data revealed little effect of starvation on cardiac geometry, contractile and intracellular Ca2+ properties. MIF deficiency unmasked an increase in left ventricular end-systolic diameter, a drop in fractional shortening associated with cardiomyocyte contractile and intracellular Ca2+ anomalies following starvation. Interestingly, the unfavourable effect of MIF deficiency was associated with interruption of starvation-induced autophagy. Furthermore, restoration of autophagy using rapamycin partially protected against starvation-induced cardiomyocyte contractile defects. In our in vitro model of starvation, neonatal mouse cardiomyocytes from WT and MIF?/? mice and H9C2 cells were treated with serum free-glucose free DMEM for 2 h. MIF depletion dramatically attenuated starvation-induced autophagic vacuole formation in neonatal mouse cardiomyocytes and exacerbated starvation-induced cell death in H9C2 cells. Conclusion In summary, these results indicate that MIF plays a permissive role in the maintenance of cardiac contractile function under starvation by regulation of autophagy. PMID:23674514

  9. Integrated high-throughput analysis identifies Sp1 as a crucial determinant of p53-mediated apoptosis

    PubMed Central

    Li, H; Zhang, Y; Ströse, A; Tedesco, D; Gurova, K; Selivanova, G

    2014-01-01

    The restoration of p53 tumor suppressor function is a promising therapeutic strategy to combat cancer. However, the biological outcomes of p53 activation, ranging from the promotion of growth arrest to the induction of cell death, are hard to predict, which limits the clinical application of p53-based therapies. In the present study, we performed an integrated analysis of genome-wide short hairpin RNA screen and gene expression data and uncovered a previously unrecognized role of Sp1 as a central modulator of the transcriptional response induced by p53 that leads to robust induction of apoptosis. Sp1 is indispensable for the pro-apoptotic transcriptional repression by p53, but not for the induction of pro-apoptotic genes. Furthermore, the p53-dependent pro-apoptotic transcriptional repression required the co-binding of Sp1 to p53 target genes. Our results also highlight that Sp1 shares with p53 a common regulator, MDM2, which targets Sp1 for proteasomal degradation. This uncovers a new mechanism of the tight control of apoptosis in cells. Our study advances the understanding of the molecular basis of p53-mediated apoptosis and implicates Sp1 as one of its key modulators. We found that small molecules reactivating p53 can differentially modulate Sp1, thus providing insights into how to manipulate p53 response in a controlled way. PMID:24971482

  10. Sp1 Sites in the Noncoding Control Region of BK Polyomavirus Are Key Regulators of Bidirectional Viral Early and Late Gene Expression

    PubMed Central

    Bethge, Tobias; Hachemi, Helen A.; Manzetti, Julia; Gosert, Rainer; Schaffner, Walter

    2015-01-01

    ABSTRACT In kidney transplant patients with BK polyomavirus (BKPyV) nephropathy, viral variants arise bearing rearranged noncoding control regions (rr-NCCRs) that increase viral early gene expression, replicative fitness, and cytopathology. rr-NCCRs result from various deletions and duplications of archetype NCCR (ww-NCCR) sequences, which alter transcription factor binding sites (TFBS). However, the role of specific TFBS is unclear. We inactivated 28 TFBS in the archetype NCCR by selective point mutations and examined viral gene expression in bidirectional reporter constructs. Compared to the archetype, group 1 mutations increased viral early gene expression similar to rr-NCCR and resulted from inactivating one Sp1 or one Ets1 TFBS near the late transcription start site (TSS). Group 2 mutations conferred intermediate early gene activation and affected NF1, YY1, and p53 sites between early and late TSS. Group 3 mutations decreased early and late gene expression and included two other Sp1 sites near the early TSS. Recombinant viruses bearing group 1 NCCRs showed increased replication in human renal epithelial cells similar to clinical rr-NCCR variants. Group 2 and 3 viruses showed intermediate or no replication, respectively. A literature search revealed unnoticed group 1 mutations in BKPyV nephropathy, hemorrhagic cystitis, and disseminated disease. IMPORTANCE The NCCRs of polyomaviruses mediate silent persistence of the viral genome as well as the appropriately timed (re)activation of the viral life cycle. This study indicates that the basal BKPyV NCCR is critically controlled by a hierarchy of single TFBS in the archetype NCCR that direct, modulate, and execute the bidirectional early and late viral gene expression. The results provide new insights into how BKPyV NCCR functions as a viral sensor of host cell signals and shed new light on how transcription factors like Sp1 control bidirectional viral gene expression and contribute to replication and pathology. PMID:25589646

  11. Proto-oncogene FBI-1 represses transcription of p21CIP1 by inhibition of transcription activation by p53 and Sp1.

    PubMed

    Choi, Won-Il; Jeon, Bu-Nam; Yun, Chae-Ok; Kim, Pyung-Hwan; Kim, Sung-Eun; Choi, Kang-Yell; Kim, Se Hoon; Hur, Man-Wook

    2009-05-01

    Aberrant transcriptional repression through chromatin remodeling and histone deacetylation has been postulated as the driving force for tumorigenesis. FBI-1 (formerly called Pokemon) is a member of the POK family of transcriptional repressors. Recently, FBI-1 was characterized as a critical oncogenic factor that specifically represses transcription of the tumor suppressor gene ARF, potentially leading indirectly to p53 inactivation. Our investigations on transcriptional repression of the p53 pathway revealed that FBI-1 represses transcription of ARF, Hdm2 (human analogue of mouse double minute oncogene), and p21CIP1 (hereafter indicated as p21) but not of p53. FBI-1 showed a more potent repressive effect on p21 than on p53. Our data suggested that FBI-1 is a master controller of the ARF-Hdm2-p53-p21 pathway, ultimately impinging on cell cycle arrest factor p21, by inhibiting upstream regulators at the transcriptional and protein levels. FBI-1 acted as a competitive transcriptional repressor of p53 and Sp1 and was shown to bind the proximal Sp1-3 GC-box and the distal p53-responsive elements of p21. Repression involved direct binding competition of FBI-1 with Sp1 and p53. FBI-1 also interacted with corepressors, such as mSin3A, NCoR, and SMRT, thereby deacetylating Ac-H3 and Ac-H4 histones at the promoter. FBI-1 caused cellular transformation, promoted cell cycle proliferation, and significantly increased the number of cells in S phase. FBI-1 is aberrantly overexpressed in many human solid tumors, particularly in adenocarcinomas and squamous carcinomas. The role of FBI-1 as a master controller of the p53 pathway therefore makes it an attractive therapeutic target. PMID:19244234

  12. The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites.

    PubMed Central

    Lin, J X; Leonard, W J

    1997-01-01

    The interleukin-2 IL-2 receptor beta-chain (IL-2Rbeta) is an essential component of the receptors for IL-2 and IL-15. Although IL-2Rbeta is constitutively expressed by lymphocytes, its expression can be further induced by a number of stimuli, including phorbol 12-myristate 13-acetate (PMA). We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2Rbeta promoter. Both Sp1 and Sp3 bound to the 5' portion of this region, whereas a PMA-inducible factor (PIF) mainly bound to its 3' portion and bound to the Sp binding motifs as well. In Jurkat T cells, induction of PIF DNA binding activity was rapidly induced, required de novo protein synthesis, and was sustained at a high level for at least 23 h. Interestingly, PIF was constitutively activated in human T-cell leukemia virus type 1-transformed MT-2 cells. In this paper, we demonstrate that PIF is Egr-1 based on its recognition by anti-Egr-1 antisera in gel mobility shift assays, even though the IL-2Rbeta DNA binding motif differed substantially from the canonical Egr-1 binding site. In addition, Egr-1 bound to the Sp binding site. In Jurkat cells, both sites were required for maximal IL-2Rbeta promoter activity, and in HeLaS3 cells, transfection of Egr-1 could drive activity of a reporter construct containing both sites. Moreover, Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation. Thus, Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2Rbeta promoter activity. PMID:9199305

  13. Characterization of a family of cysteine rich proteins and development of a MaSp1 derived miniature fibroin

    NASA Astrophysics Data System (ADS)

    Chuang, Tyler Casey

    Spider silk displays a unique balance of high tensile strength and extensibility, making it one of the toughest materials on the planet. Dragline silk, also known as the lifeline of the spider, represents one of the best studied fiber types and many labs are attempting to produce synthetic dragline silk fibers for commercial applications. In these studies, we develop a minifibroin for expression studies in bacteria. Using recombinant DNA methodology and protein expression studies, we develop a natural minifibroin that contains the highly conserved N- and C-terminal domains, along with several internal block repeats of MaSp1. We also characterize a family of small cysteine-rich proteins (CRPs) and demonstrate that these factors are present within the spinning dope of the major ampullate gland using MS analysis. Biochemical studies and characterization of one of the family members, CRP1, demonstrate that this factor can self-polymerize into higher molecular weight complexes under oxidizing conditions, but can be converted into a monomeric species under reducing conditions. Self-polymerization of CRP1 is also shown to be independent of pH and salt concentration, two important chemical cues that help fibroin aggregation. Overall, our data demonstrate that the polymerization state of CRP1 is dependent upon redox state, suggesting that the redox environment during fiber extrusion may help regulate the oligomerization of CRP molecules during dragline silk production.

  14. Inhibition of Transcription Factor Specificity Protein 1 Alters the Gene Expression Profile of Keratinocytes Leading to Upregulation of Kallikrein-Related Peptidases and Thymic Stromal Lymphopoietin

    Microsoft Academic Search

    Lianghua Bin; Byung E Kim; Clifton F Hall; Sonia M Leach; Donald Y M Leung

    2011-01-01

    Transcription factor specificity protein 1 (Sp1) is involved in diverse cellular functions. We recently found that Sp1 was significantly decreased in skin biopsy samples obtained from patients with atopic dermatitis (AD) and had an even greater reduction in AD patients with a history of eczema herpeticum. In the current study, we sought to better understand the role of Sp1 in

  15. Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter[S

    PubMed Central

    Jeon, Bu-Nam; Kim, Yeon-Sook; Choi, Won-Il; Koh, Dong-In; Kim, Min-Kyeong; Yoon, Jae-Hyeon; Kim, Min-Young; Hur, Benjamin; Paik, Philip Dong-Hyun; Hur, Man-Wook

    2012-01-01

    Kr-pok (kidney cancer-related POZ domain and Krüppel-like protein) is a new proto-oncogenic POZ-domain transcription factor. Fatty acid synthase gene (FASN) encodes one of the key enzymes in fatty acids synthesis and is the only enzyme that synthesizes fatty acids in cancer cells. Sp1 and SREBP-1c are the two major transcription activators of FASN. We investigated whether Kr-pok modulates transcription of the FASN. FASN expression is significantly decreased in Kr-pok knockout murine embryonic fibroblasts. Coimmunoprecipitation, GST fusion protein pull-down, and immunocytochemistry assays show that the zinc-finger domain of Kr-pok interacts directly with the bZIP DNA binding domain of SREBP-1. Electrophoretic mobility shift assay, oligonucleotide pull-down, and chromatin immunoprecipitation assays showed that Kr-pok changes the transcription factor binding dynamics of Sp1 and SREBP-1c to the SRE/E-box elements of the proximal promoter. We found that Kr-pok expression increased during 3T3-L1 preadipocyte differentiation and that FASN expression is decreased by the knockdown of Kr-pok. Kr-pok facilitates the SREBP-1c-mediated preadipocyte differentiation and/or fatty acid synthesis. Kr-pok may act as an important regulator of fatty acid synthesis and may induce rapid cancer cell proliferation by increasing palmitate synthesis. PMID:22331133

  16. ?-elemene inhibited expression of DNA methyltransferase 1 through activation of ERK1/2 and AMPK? signalling pathways in human lung cancer cells: the role of Sp1

    PubMed Central

    Zhao, ShunYu; Wu, Jingjing; Zheng, Fang; Tang, Qing; Yang, LiJun; Li, Liuning; Wu, WanYin; Hann, Swei Sunny

    2015-01-01

    ?-elemene, a compound derived from Rhizoma zedoariae, is a promising new plant-derived drug with broad-spectrum anticancer activity. However, the underlying mechanism by which this agent inhibits human lung cancer cell growth has not been well elucidated. In this study, we showed that ?-elemene inhibits human non-small cell lung carcinoma (NSCLC) cell growth, and increased phosphorylation of ERK1/2, Akt and AMPK?. Moreover, ?-elemene inhibited expression of DNA methyltransferase 1 (DNMT1), which was not observed in the presence of the specific inhibitors of ERK (PD98059) or AMPK (compound C). Overexpression of DNMT1 reversed the effect of ?-elemene on cell growth. Interestingly, metformin not only reversed the effect of ?-elemene on phosphorylation of Akt but also strengthened the ?-elemene-reduced DNMT1. In addition, ?-elemene suppressed Sp1 protein expression, which was eliminated by either ERK1/2 or AMPK inhibitor. Conversely, overexpression of Sp1 antagonized the effect of ?-elemene on DNMT1 protein expression and cell growth. Taken together, our results show that ?-elemene inhibits NSCLC cell growth viaERK1/2- and AMPK?-mediated inhibition of transcription factor Sp1, followed by reduction in DNMT1 protein expression. Metformin augments the effect of ?-elemene by blockade of Akt signalling and additively inhibition of DNMT1 protein expression. The reciprocal ERK1/2 and AMPK? signalling pathways contribute to the overall responses of ?-elemene. This study reveals a potential novel mechanism by which ?-elemene inhibits growth of NSCLC cells. PMID:25598321

  17. ?-elemene inhibited expression of DNA methyltransferase 1 through activation of ERK1/2 and AMPK? signalling pathways in human lung cancer cells: the role of Sp1.

    PubMed

    Zhao, ShunYu; Wu, Jingjing; Zheng, Fang; Tang, Qing; Yang, LiJun; Li, Liuning; Wu, WanYin; Hann, Swei Sunny

    2015-03-01

    ?-elemene, a compound derived from Rhizoma zedoariae, is a promising new plant-derived drug with broad-spectrum anticancer activity. However, the underlying mechanism by which this agent inhibits human lung cancer cell growth has not been well elucidated. In this study, we showed that ?-elemene inhibits human non-small cell lung carcinoma (NSCLC) cell growth, and increased phosphorylation of ERK1/2, Akt and AMPK?. Moreover, ?-elemene inhibited expression of DNA methyltransferase 1 (DNMT1), which was not observed in the presence of the specific inhibitors of ERK (PD98059) or AMPK (compound C). Overexpression of DNMT1 reversed the effect of ?-elemene on cell growth. Interestingly, metformin not only reversed the effect of ?-elemene on phosphorylation of Akt but also strengthened the ?-elemene-reduced DNMT1. In addition, ?-elemene suppressed Sp1 protein expression, which was eliminated by either ERK1/2 or AMPK inhibitor. Conversely, overexpression of Sp1 antagonized the effect of ?-elemene on DNMT1 protein expression and cell growth. Taken together, our results show that ?-elemene inhibits NSCLC cell growth via ERK1/2- and AMPK?-mediated inhibition of transcription factor Sp1, followed by reduction in DNMT1 protein expression. Metformin augments the effect of ?-elemene by blockade of Akt signalling and additively inhibition of DNMT1 protein expression. The reciprocal ERK1/2 and AMPK? signalling pathways contribute to the overall responses of ?-elemene. This study reveals a potential novel mechanism by which ?-elemene inhibits growth of NSCLC cells. PMID:25598321

  18. Control of vulval competence and centering in the nematode Oscheius sp. 1 CEW1.

    PubMed Central

    Louvet-Vallée, Sophie; Kolotuev, Irina; Podbilewicz, Benjamin; Félix, Marie-Anne

    2003-01-01

    To compare vulva development mechanisms in the nematode Oscheius sp. 1 to those known in Caenorhabditis elegans, we performed a genetic screen for vulva mutants in Oscheius sp. 1 CEW1. Here we present one large category of mutations that we call cov, which affect the specification of the Pn.p ventral epidermal cells along the antero-posterior axis. The Pn.p cells are numbered from 1 to 12 from anterior to posterior. In wild-type Oscheius sp. 1 CEW1, the P(4-8).p cells are competent to form the vulva and the progeny of P(5-7).p actually form the vulva, with the descendants of P6.p adopting a central vulval fate. Among the 17 mutations (defining 13 genes) that we characterize here, group 1 mutations completely or partially abolish P(4-8).p competence, and this correlates with early fusion of the Pn.p cells to the epidermal syncytium. In this group, we found a putative null mutation in the lin-39 HOM-C homolog, the associated phenotype of which could be weakly mimicked by injection of a morpholino against Osp1-lin-39 in the mother's germ line. Using cell ablation in a partially penetrant competence mutant, we show that vulval competence is partially controlled by a gonadal signal. Most other mutants found in the screen display phenotypes unknown in C. elegans. Group 2 mutants show a partial penetrance of Pn.p competence loss and an abnormal centering of the vulva on P5.p, suggesting that these two processes are coregulated by the same pathway in Oscheius sp. 1. Group 3 mutants display an enlarged competence group that includes P3.p, thus demonstrating the existence of a specific mechanism inhibiting P3.p competence. Group 4 mutants display an abnormal centering of the vulval pattern on P7.p and suggest that a specific mechanism centers the vulval pattern on a single Pn.p cell. PMID:12586702

  19. Fatty Acid Desaturation and Elongation Reactions of Trichoderma sp. 1OH2-3

    Microsoft Academic Search

    Akinori Ando; Jun Ogawa; Shigenobu Kishino; Taiyo Ito; Norifumi Shirasaka; Eiji Sakuradani; Kenzo Yokozeki; Sakayu Shimizu

    2009-01-01

    The fatty acid desaturation and elongation reactions catalyzed by Trichoderma sp. 1-OH-2-3 were investigated. This strain converted palmitic acid (16:0) mainly to stearic acid (18:0), and further to\\u000a oleic acid (c9-18:1), linoleic acid (c9,c12-18:2), and ?-linolenic acid (c9,c12,c15-18:3) through elongation, and ?9, ?12, and ?15 desaturation reactions, respectively. Palmitoleic acid (c9-16:1) and cis-9,cis-12-hexadecadienoic acid were also produced from 16:0 by

  20. Learning Through Play

    MedlinePLUS

    ... Offer play opportunities that encourage turn taking and problem solving. Consider family routines and priorities when recommending play strategies. Observe, identify, and develop play strategies that promote ...

  1. Achromobacter denitrificans strain SP1 efficiently remediates di(2-ethylhexyl)phthalate.

    PubMed

    Pradeep, S; Josh, M K Sarath; Binod, P; Devi, R Sudha; Balachandran, S; Anderson, Robin C; Benjamin, Sailas

    2015-02-01

    This study describes how Achromobacter denitrificans strain SP1, a novel isolate from heavily plastics-contaminated sewage sludge efficiently consumed the hazardous plasticizer, di(2-ethylhexyl)phthalate (DEHP) as carbon source supplemented in a simple basal salt medium (BSM). Response surface methodology was employed for the statistical optimization of the process parameters such as temperature (32°C), agitation (200 rpm), DEHP concentration (10 mM), time (72 h) and pH (8.0). At these optimized conditions, experimentally observed DEHP degradation was 63%, while the predicted value was 59.2%; and the correlation coefficient between them was 0.998, i.e., highly significant and fit to the predicted model. Employing GC-MS analysis, the degradation pathway was partially deduced with intermediates such as mono(2-ethylhexyl)phthalate and 2-ethyl hexanol. Briefly, this first report describes A. denitrificans strain SP1 as a highly efficient bacterium for completely remediating the hazardous DEHP (10 mM) in 96 h in BSM (50% consumed in 60 h), which offers great potentials for efficiently cleaning the DEHP-contaminated environments such as soil, sediments and water upon its deployment. PMID:25463861

  2. Scalability of Parallel Spatial Direct Numerical Simulations on Intel Hypercube and IBM SP1 and SP2

    NASA Technical Reports Server (NTRS)

    Joslin, Ronald D.; Hanebutte, Ulf R.; Zubair, Mohammad

    1995-01-01

    The implementation and performance of a parallel spatial direct numerical simulation (PSDNS) approach on the Intel iPSC/860 hypercube and IBM SP1 and SP2 parallel computers is documented. Spatially evolving disturbances associated with the laminar-to-turbulent transition in boundary-layer flows are computed with the PSDNS code. The feasibility of using the PSDNS to perform transition studies on these computers is examined. The results indicate that PSDNS approach can effectively be parallelized on a distributed-memory parallel machine by remapping the distributed data structure during the course of the calculation. Scalability information is provided to estimate computational costs to match the actual costs relative to changes in the number of grid points. By increasing the number of processors, slower than linear speedups are achieved with optimized (machine-dependent library) routines. This slower than linear speedup results because the computational cost is dominated by FFT routine, which yields less than ideal speedups. By using appropriate compile options and optimized library routines on the SP1, the serial code achieves 52-56 M ops on a single node of the SP1 (45 percent of theoretical peak performance). The actual performance of the PSDNS code on the SP1 is evaluated with a "real world" simulation that consists of 1.7 million grid points. One time step of this simulation is calculated on eight nodes of the SP1 in the same time as required by a Cray Y/MP supercomputer. For the same simulation, 32-nodes of the SP1 and SP2 are required to reach the performance of a Cray C-90. A 32 node SP1 (SP2) configuration is 2.9 (4.6) times faster than a Cray Y/MP for this simulation, while the hypercube is roughly 2 times slower than the Y/MP for this application. KEY WORDS: Spatial direct numerical simulations; incompressible viscous flows; spectral methods; finite differences; parallel computing.

  3. Play therapy: a review

    Microsoft Academic Search

    Maggie L. Porter; Peggy Jessee

    2009-01-01

    This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing effective techniques, limit setting and how to deal

  4. Play Therapy: A Review

    ERIC Educational Resources Information Center

    Porter, Maggie L.; Hernandez-Reif, Maria; Jessee, Peggy

    2009-01-01

    This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing…

  5. Learning to play: Playing to learn

    Microsoft Academic Search

    Pauline Davey Zeece; Susan K. Graul

    1990-01-01

    Have you ever heard comments such as “In this program we focus on learning —not playing” or “Is this a day care program where children learn or play?” At a time when the importance of early life experiences has gained public attention, there is the temptation to overlook or at least misunderstand the value and importance of play.

  6. All the World's a Stage? Consequences of a Role-Playing Pedagogy on Psychological Factors and Writing and Rhetorical Skill in College Undergraduates

    ERIC Educational Resources Information Center

    Stroessner, Steven J.; Beckerman, Laurie Susser; Whittaker, Alexis

    2009-01-01

    Reacting to the Past is a pedagogy involving collaborative role playing in history-based games over a semester. This article presents results from a systematic assessment of this novel pedagogy conducted in 3 phases following student focus group interviews. Interviews indicated that the method was generally popular compared with traditional…

  7. Why do adult dogs 'play'?

    PubMed

    Bradshaw, John W S; Pullen, Anne J; Rooney, Nicola J

    2015-01-01

    Among the Carnivora, play behaviour is usually made up of motor patterns characteristic of predatory, agonistic and courtship behaviour. Domestic dogs are unusual in that play is routinely performed by adults, both socially, with conspecifics and with humans, and also asocially, with objects. This enhanced playfulness is commonly thought to be a side effect of paedomorphosis, the perpetuation of juvenile traits into adulthood, but here we suggest that the functions of the different types of play are sufficiently distinct that they are unlikely to have arisen through a single evolutionary mechanism. Solitary play with objects appears to be derived from predatory behaviour: preferred toys are those that can be dismembered, and a complex habituation-like feedback system inhibits play with objects that are resistant to alteration. Intraspecific social play is structurally different from interspecific play and may therefore be motivationally distinct and serve different goals; for example, dogs often compete over objects when playing with other dogs, but are usually more cooperative when the play partner is human. The majority of dogs do not seem to regard competitive games played with a human partner as "dominance" contests: rather, winning possession of objects during games appears to be simply rewarding. Play may be an important factor in sociality, since dogs are capable of extracting social information not only from games in which they participate, but also from games that they observe between third parties. We suggest that the domestic dog's characteristic playfulness in social contexts is an adaptive trait, selected during domestication to facilitate both training for specific purposes, and the formation of emotionally-based bonds between dog and owner. Play frequency and form may therefore be an indicator of the quality of dog-owner relationships. PMID:25251020

  8. Trends in youth's videogame playing, overall computer use, and communication technology use: The impact of self-esteem and the Big Five personality factors

    Microsoft Academic Search

    Edward A. Witt; Adam J. Massman; Linda A. Jackson

    2011-01-01

    The objective of the current research is to model trends in video game playing, overall computer use, and communication technology use in a longitudinal sample of youths, aged 11–16 over a 3-year interval. In addition, individual difference characteristics that may be predictive of these trends were included, namely, socio-demographic characteristics (gender, ethnicity, and parental income) and personality characteristics (self-esteem, the

  9. Dissimilatory Metal Reduction by the Facultative Anaerobe Pantoea agglomerans SP1

    PubMed Central

    Francis, Chris A.; Obraztsova, Anna Y.; Tebo, Bradley M.

    2000-01-01

    Anaerobic enrichments with acetate as the electron donor and Fe(III) as the terminal electron acceptor were obtained from sediments of Salt Pond, a coastal marine basin near Woods Hole, Mass. A pure culture of a facultatively anaerobic Fe(III) reducer was isolated, and 16S rRNA analysis demonstrated that this organism was most closely related to Pantoea (formerly Enterobacter) agglomerans, a member of the family Enterobacteriaceae within the gamma subdivision of the Proteobacteria. This organism, designated strain SP1, can grow by coupling the oxidation of acetate or H2 to the reduction of a variety of electron acceptors, including Fe(III), Mn(IV), Cr(VI), and the humic substance analog 2,6-anthraquinone disulfonate, but not sulfate. To our knowledge, this is the first mesophilic facultative anaerobe reported to couple acetate oxidation to dissimilatory metal reduction. PMID:10653716

  10. Biocontrol of Salmonella Enteritidis in spiked chicken cuts by lytic bacteriophages ?SP-1 and ?SP-3.

    PubMed

    Augustine, Jeena; Bhat, Sarita G

    2015-04-01

    The ability of host specific bacteriophages ?SP-1 and ?SP-3 to lyse Salmonella in artificially contaminated cuts of pressure cooked chicken meat was evaluated at different temperatures -4?°C, room temperature (28?±?0.5 °C) and 37?°C applying low and high multiplicity of infection (MOI). Bacteriophages were able to significantly reduce the bacterial counts at all the temperatures studied. At 4?°C, individual application of ? SP-1and ? SP-3 resulted in significant drop in bacterial counts (log10 2.46 and 2.1?CFU/ml, respectively) at high MOI and (log10 0.98 and 0.52?CFU/ml, respectively) at low MOI, when compared to the untreated control on day 3. Similarly at room temperature the drop was log10 3.99 and 3.46?CFU/ml at high MOI and log10 2.51 and 2.3?CFU/ml at low MOI. At 37?°C the drop was log10 1.98 and 2.38 at high MOI and at low MOI it was log10 1.52 and 1.98?CFU/ml. Increased efficiency was observed when phages where applied as cocktail at high MOI as the bacterial counts at the end of day 3 dropped by log10 3.52?CFU/ml at 37?°C and to beyond detectable level at 4?°C and room temperature. The average reduction of bacterial load in the same group was -4?°C (79%), room temperature (92%) and 37?°C (78%). PMID:25588852

  11. Examining Resource and Protective Factors in the Adjustment of Latino Youth in Low Income Families: What Role Does Maternal Acculturation Play?

    Microsoft Academic Search

    Alexandra Loukas; Marie-Anne Suizzo; Hazel M. Prelow

    2007-01-01

    This longitudinal study examined whether the risk and positive factors contributing to the delinquent behaviors and internalizing\\u000a problems of 454 Latino adolescents varied across maternal linguistic acculturation and adolescent gender. Although the level\\u000a of cumulative risk to which the 10-to-14-year old adolescents were exposed did not vary by maternal linguistic acculturation,\\u000a the factors contributing to their subsequent adjustment 16 months

  12. The Interactomes of Influenza Virus NS1 and NS2 Proteins Identify New Host Factors and Provide Insights for ADAR1 Playing a Supportive Role in Virus Replication

    PubMed Central

    de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

    2013-01-01

    Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution. PMID:23853584

  13. Examining Resource and Protective Factors in the Adjustment of Latino Youth in Low Income Families: What Role Does Maternal Acculturation Play?

    ERIC Educational Resources Information Center

    Loukas, Alexandra; Suizzo, Marie-Anne; Prelow, Hazel M.

    2007-01-01

    This longitudinal study examined whether the risk and positive factors contributing to the delinquent behaviors and internalizing problems of 454 Latino adolescents varied across maternal linguistic acculturation and adolescent gender. Although the level of cumulative risk to which the 10-to-14-year old adolescents were exposed did not vary by…

  14. Activation of TGF-?1 Promoter by Hepatitis C Virus-Induced AP-1 and Sp1: Role of TGF-?1 in Hepatic Stellate Cell Activation and Invasion

    PubMed Central

    Presser, Lance D.; McRae, Steven; Waris, Gulam

    2013-01-01

    Our previous studies have shown the induction and maturation of transforming growth factor-beta 1 (TGF-?1) in HCV-infected human hepatoma cells. In this study, we have investigated the molecular mechanism of TGF-?1 gene expression in response to HCV infection. We demonstrate that HCV-induced transcription factors AP-1, Sp1, NF-?B and STAT-3 are involved in TGF-?1 gene expression. Using chromatin immunoprecipitation (ChIP) assay, we further show that AP-1 and Sp1 interact with TGF-b1 promoter in vivo in HCV-infected cells. In addition, we demonstrate that HCV-induced TGF-?1 gene expression is mediated by the activation of cellular kinases such as p38 MAPK, Src, JNK, and MEK1/2. Next, we determined the role of secreted bioactive TGF-?1 in human hepatic stellate cells (HSCs) activation and invasion. Using siRNA approach, we show that HCV-induced bioactive TGF-?1 is critical for the induction of alpha smooth muscle actin (?-SMA) and type 1 collagen, the markers of HSCs activation and proliferation. We further demonstrate the potential role of HCV-induced bioactive TGF-?1 in HSCs invasion/cell migration using a transwell Boyden chamber. Our results also suggest the role of HCV-induced TGF-?1 in HCV replication and release. Collectively, these observations provide insight into the mechanism of TGF-?1 promoter activation, as well as HSCs activation and invasion, which likely manifests in liver fibrosis associated with HCV infection. PMID:23437118

  15. The Play of Psychotherapy

    ERIC Educational Resources Information Center

    Marks-Tarlow, Terry

    2012-01-01

    The author reviews the role of play within psychotherapy. She does not discuss the formal play therapy especially popular for young children, nor play from the Jungian perspective that encourages the use of the sand tray with adults. Instead, she focuses on the informal use of play during psychotherapy as it is orchestrated intuitively. Because…

  16. CHI3L1 plays a role in cancer through enhanced production of pro-inflammatory/pro-tumorigenic and angiogenic factors

    PubMed Central

    Libreros, Stephania; Garcia-Areas, Ramon

    2014-01-01

    Elevated serum levels of a glycoprotein known as chitinase-3-like protein 1 (CHI3L1) have been correlated with poor prognosis and shorter survival of patients with cancer and inflammatory diseases. The biological and physiological functions of CHI3L1 in cancer have not yet been completely elucidated. In this review, we describe the role of CHI3L1 in inducing pro-inflammatory/pro-tumorigenic and angiogenic factors that could promote tumor growth and metastasis. PMID:24222276

  17. The Arabidopsis homologs of CCR4-associated factor 1 show mRNA deadenylation activity and play a role in plant defence responses

    Microsoft Academic Search

    Wenxing Liang; Changbao Li; Fang Liu; Hongling Jiang; Shuyu Li; Jiaqiang Sun; Xiaoyan Wu; Chuanyou Li

    2009-01-01

    Messenger RNA (mRNA) turnover in eukaryotic cells begins with shortening of the poly (A) tail at the 3? end, a process called deadenylation. In yeast, the deadenylation reaction is predominantly mediated by CCR4 and CCR4-associated factor 1 (CAF1), two components of the well-characterised protein complex named CCR4-NOT. We report here that AtCAF1a and AtCAF1b, putative Arabidopsis homologs of the yeast

  18. Socioeconomic factors play a more important role in childhood vaccination coverage than parental perceptions: a cross-sectional study in Greece

    Microsoft Academic Search

    K. Danis; T. Georgakopoulou; T. Stavrou; D. Laggas; T. Panagiotopoulos

    2010-01-01

    To identify predictive factors of complete and age-appropriate vaccination status in Greece, we conducted a cross-sectional study, using stratified cluster sampling, among children attending the first year of the Greek Grammar school (about 6 years of age) and their parents\\/guardians. Almost 88% (N=3878) of pupils in the selected clusters (school classrooms) provided their vaccination booklet and their parents\\/guardians completed a

  19. Two Distinct Signaling Pathways Downstream of Janus Kinase 2 Play Redundant Roles for Antiapoptotic Activity of Granulocyte-Macrophage Colony-stimulating Factor

    Microsoft Academic Search

    Rui Liu; Tohru Itoh; Ken-ichi Arai; Sumiko Watanabe

    Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces proliferation and sustains the viability of the mouse interleukin-3-dependent cell line BA\\/F3 expressing the hGM- CSF receptor. Analysis of the antiapoptosis activity of GM-CSF receptor bc mutants showed that box1 but not the C-terminal region containing tyrosine residues is essential for GM-CSF-depen- dent antiapoptotic activity. Because bc mutants, which activate Janus kinase 2 but

  20. Understanding Playful Pedagogies, Play Narratives and Play Spaces

    ERIC Educational Resources Information Center

    Goouch, Kathy

    2008-01-01

    This paper is a tentative attempt to unwrap and understand one aspect of playful practice and the influences which determine its existence in early years settings. "Storying" events, those occasions when teachers and children together "make up" stories or parts of stories, develop roles or co-construct fantasies, occur moment by moment in some…

  1. Quantitative Analysis of Estrogen Receptor Expression Shows SP1 antibody is more sensitive than 1D5

    PubMed Central

    Welsh, Allison W.; Harigopal, Malini; Wimberly, Hallie; Prasad, Manju; Rimm, David L.

    2012-01-01

    Studies comparing rabbit monoclonal SP1 antibody to 1D5 for ER immunohistochemical (IHC) testing show conflicting results. Here we use a standardized quantitative immunofluorescent (QIF) ER assay to determine the level and significance of discordance between antibodies. Both antibodies are assessed by QIF on our Index TMA of cell lines and case controls, followed by QIF and IHC on two retrospective cohorts from Yale. On the Index TMA, SP1 displayed stronger signal-to-noise than 1D5. On the patient cohorts, the range of discrepancy between the two antibodies is 8% to 16.9%, with the majority of discrepant cases being SP1-positive/1D5-negative. Kaplan Meier analysis of the discrepant cases shows outcome comparable to double positive cases, suggesting that SP1 is more sensitive than 1D5. A series of cases with high levels of ER-beta shows that neither antibody cross-reacts, suggesting equivalent specificity. Future efforts are needed to determine if response to endocrine therapies show superiority of either antibody as a companion diagnostic test. PMID:22820659

  2. Achromobactor denitrificans SP1 produces pharmaceutically active 25C prodigiosin upon utilizing hazardous di(2-ethylhexyl)phthalate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Achromobacter denitrificans SP1 isolated from soil sludge heavily contaminated with plastic waste produced a novel pharmaceutically-active 25C prodigiosin analog during growth in a simple mineral salt medium supplemented with hazardous di(2-ethylhexyl)phthalate (DEHP) blended PVC plastics (in situ) ...

  3. CORRELATION OF MRI GRADING OF BONE STRESS INJURIES WITH CLINICAL RISK FACTORS AND RETURN TO PLAY: A 5-YEAR PROSPECTIVE STUDY IN COLLEGIATE TRACK AND FIELD ATHLETES

    PubMed Central

    Nattiv, Aurelia; Kennedy, Gannon; Barrack, Michelle T.; Abdelkerim, Ashraf; Goolsby, Marci A.; Arends, Julie C.; Seeger, Leanne L.

    2015-01-01

    Background Bone stress injuries are common in track and field athletes. Knowledge of risk factors and correlation of these to magnetic resonance imaging (MRI) grading could be helpful in determining recovery time. Purpose To examine the relationships between MRI grading of bone stress injury with clinical risk factors and time to return to sport in collegiate track and field athletes. Study Design Prospective cohort over 5 years. Methods Two hundred and eleven male and female collegiate track and field and cross-country athletes were followed prospectively through their competitive seasons. All athletes had a pre-participation history, physical exam, and anthropometric measurements obtained annually. An additional questionnaire was completed regarding nutritional behaviors, menstrual patterns and prior injuries, as well as a 3-day diet record. Dual energy X-ray absorptiometry was obtained at baseline and each year of participation in the study. Athletes with clinical evidence of bone stress injuries had plain radiographs. If radiographs were negative, MRI was obtained. Bone stress injuries were evaluated by two independent radiologists utilizing an MRI grading system. MRI grading and risk factors were evaluated to identify predictors of time to return to sport. Results Thirty-four (12 males, 22 females) of the 211 collegiate athletes sustained 61 bone stress injuries during the 5-year study period. The average prospective assessment for participants was 2.1 years. MRI grade and total body bone mineral density (BMD) emerged as significant and independent predictors of time to return to sport in the multiple regression model. Specifically, the higher the MRI grade, the longer the recovery time (p<0.002). Location of bone injury at predominantly trabecular sites of the femoral neck, pubic bone and sacrum (p<0.001), and lower total body BMD (p<0.029) independently predicted prolonged time to return to sport. Conclusions Higher MRI grade, lower BMD, and skeletal sites of predominant trabecular bone structure were independently associated with delayed recovery of bone stress injuries in track and field athletes. Knowledge of these risk factors, as well as nutritional and menstrual factors, can be clinically useful in determining time to return to sport. PMID:23825184

  4. Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors.

    PubMed

    Jeon, Bu-Nam; Yoo, Jung-Yoon; Choi, Won-Il; Lee, Choong-Eun; Yoon, Ho-Geun; Hur, Man-Wook

    2008-11-28

    FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp -308 to -188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp -65 to -56) and GC-box 2 (bp -18 to -9), the latter of which is also bound by FBI-1. We found that FRE3 (bp -244 to -236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression. PMID:18801742

  5. Epigenetic repression of LEDGF during UVB exposure by recruitment of SUV39H1 and HDAC1 to the Sp1-responsive elements within LEDGF promoter CpG island

    PubMed Central

    Bhargavan, Biju; Chhunchha, Bhavana; Fatma, Nigar; Kubo, Eri; Kumar, Anil; Singh, Dhirendra P.

    2013-01-01

    Expression level of lens epithelial derived growth factor (LEDGF) is vital for LEDGF-mediated cell survival and cytoprotection against proapoptotic stimuli. We previously demonstrated that LEDGF is transcriptionally regulated by Sp1-responsive elements within a CpG island in the LEDGF promoter. Herein, we report on the existence of epigenetic signaling involved in the repression of LEDGF transcription in lens epithelial cells (LECs) facing UVB. UVB exposure led to histone H3 dimethylation and deacetylation at its CpG island, where a histone deacetylase/histone methylase (HDAC1/SUV39H1) complex was recruited. Exposure of LECs to UVB stress altered LEDGF protein and mRNA expression as well as promoter activity, while failing to methylate the CpG island. These events were correlated with increased reactive oxygen species (ROS) and increased cell death. LEDGF promoter activity and expression remained unaltered after 5-Aza treatment, but were relieved with tricostatin A, an inhibitor of HDACs. Expression analysis disclosed that UVB radiation altered the global expression levels of acetylated histone proteins, diminished total histone acetyltransferase (HAT) activity and increased HDAC activity and HDAC1 expression. In silico analysis of LEDGF proximal promoter and ChIP analyses disclosed HDAC1/SUV39H1 complex anchored to the -170/-10 nt promoter regions at Sp1-responsive elements and also attenuated Sp1 binding, resulting in HDAC1- and SUV39H1-dependent deacetylation and dimethylation of H3 at K9. Acetylation of H3K9 was essential for LEDGF active transcription, while enrichment of H3K9me2 at Sp1-responsive elements within CpGs (-170/-10) by UVB radiation repressed LEDGF transcription. Our study may contribute to understanding diseases associated with LEDGF aberrant expression due to specific epigenetic modifications, including blinding disorders. PMID:23386123

  6. Ets and GATA Transcription Factors Play a Critical Role in PMA-Mediated Repression of the ck? Promoter via the Protein Kinase C Signaling Pathway

    PubMed Central

    Kuan, Chee Sian; Yee, Yoke Hiang; See Too, Wei Cun; Few, Ling Ling

    2014-01-01

    Background Choline kinase is the most upstream enzyme in the CDP-choline pathway. It catalyzes the phosphorylation of choline to phosphorylcholine in the presence of ATP and Mg2+ during the biosynthesis of phosphatidylcholine, the major phospholipid in eukaryotic cell membranes. In humans, choline kinase (CK) is encoded by two separate genes, ck? and ck?, which produce three isoforms, CK?1, CK?2, and CK?. Previous studies have associated ck? with muscle development; however, the molecular mechanism underlying the transcriptional regulation of ck? has never been elucidated. Methodology/Principal Findings In this report, the distal promoter region of the ck? gene was characterized. Mutational analysis of the promoter sequence and electrophoretic mobility shift assays (EMSA) showed that Ets and GATA transcription factors were essential for the repression of ck? promoter activity. Supershift and chromatin immunoprecipitation (ChIP) assays further identified that GATA3 but not GATA2 was bound to the GATA site of ck? promoter. In addition, phorbol-12-myristate-13-acetate (PMA) decreased ck? promoter activity through Ets and GATA elements. PMA also decreased the ck? mRNA and protein levels about 12 hours after the promoter activity was down-regulated. EMSA further revealed that PMA treatment increased the binding of both Ets and GATA transcription factors to their respective DNA elements. The PMA-mediated repressive effect was abolished by chronic PMA treatment and by treatment with the PKC inhibitor PKC412, but not the PKC inhibitor Go 6983, suggesting PKC? or PKC? as the PKC isozyme involved in the PMA-mediated repression of ck? promoter. Further confirmation by using PKC isozyme specific inhibitors identified PKC? as the isozyme that mediated the PMA repression of ck? promoter. Conclusion/Significance These results demonstrate the participation of the PKC signaling pathway in the regulation of ck? gene transcription by Ets and GATA transcription factors. PMID:25490397

  7. 14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1

    Microsoft Academic Search

    Hye-Young Hong; Woo-Kwang Jeon; Eun-Jin Bae; Shin-Tae Kim; Ho-Jae Lee; Seong-Jin Kim; Byung-Chul Kim

    2010-01-01

    The expression of 14-3-3 proteins is dysregulated in various types of cancer. This study was undertaken to investigate the\\u000a effects of 14-3-3 ? and 14-3-3 ? on cell growth inhibition mediated by transforming growth factor-beta 1 (TGF-?1). Mouse mammary\\u000a epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-?1-mediated growth\\u000a inhibition displayed increased expression

  8. Risk analysis of prospects vs. plays: The play`s the thing!

    SciTech Connect

    Rose, P.R. [Telegraph Exploration, Inc., Austin, TX (United States)

    1996-09-01

    The most difficult and crucial decision in petroleum exploration is not which prospect to drill, but rather, which new play to enter. Such a decision, whether ultimately profitable or not, commits the Organization to years of involvement, expenditures of $millions, and hundreds of man-years of effort. Even though uncertainties and risks are high, organizations commonly make the new-play decision in a disjointed, non-analytic, even superficial way. The economic consequences of a bad play choice can be disastrous. Using established principles of prospect risk analysis, modern petroleum exploration organizations routinely assign economic value to individual prospects, but they actually operate via exploration programs in plays and trends. Accordingly, the prospect is the economic unit of exploration, whereas the play is the operational unit. Plays can be successfully analyzed as full-cycle economic risk ventures, however, using many principles of prospect risk analysis. Economic measures such as Expected Present Value, DCFROR, etc. apply equally to plays or prospects. The predicted field-size distribution of the play is analogous to the forecast prospect reserves distribution. Economic truncation applies to both. Variance of play reserves is usually much greater than for prospect reserves. Geologic chance factors such as P{sub reservoir}, P{sub generation}, etc., must be distinguished as independent or shared among prospects in the play, so they should be defined so as to apply as well to the play as to its constituent prospects. They are analogous to multiple objectives on a prospect, and are handled different in reforming the risk analysis.

  9. Socioeconomic factors play a more important role in childhood vaccination coverage than parental perceptions: a cross-sectional study in Greece.

    PubMed

    Danis, K; Georgakopoulou, T; Stavrou, T; Laggas, D; Panagiotopoulos, T

    2010-02-17

    To identify predictive factors of complete and age-appropriate vaccination status in Greece, we conducted a cross-sectional study, using stratified cluster sampling, among children attending the first year of the Greek Grammar school (about 6 years of age) and their parents/guardians. Almost 88% (N=3878) of pupils in the selected clusters (school classrooms) provided their vaccination booklet and their parents/guardians completed a questionnaire regarding beliefs and attitudes towards immunization. Belonging to a minority group, having other siblings and perceiving long distance to immunization site as a barrier were independent predictors of both incomplete and delayed vaccination status in the final logistic regression model. Maternal age >or=30 years and the perception that natural disease is preferable to vaccination were associated with complete vaccination, whereas paternal education of high school or higher was the other independent determinant of age-appropriate immunization. Socioeconomic factors rather than parental beliefs and attitudes towards immunization explained underimmunization. Further interventions are warranted to enhance vaccine coverage in high-risk groups identified in this study. PMID:20006570

  10. Cellular prion protein accelerates colorectal cancer metastasis via the Fyn-SP1-SATB1 axis.

    PubMed

    Wang, Qianwei; Qian, Jianming; Wang, Fangrui; Ma, Zhenyu

    2012-12-01

    The cellular prion protein (PrPc) is a glycoprotein anchored by glycosylphosphatidylinositol to the cell surface and is abundantly expressed in various tissues. The putative roles of PrPc are thought to be related to cell signaling, survival, and differentiation and cancer progression. In this study, we demonstrated that the expression of PrPc correlates with a more aggressive and histologically unfavorable disease in colorectal carcinomas. Moreover, we found that PrPc mediates the process of epithelial-mesenchymal transition and, thereby, promotes CRC metastasis. Transcriptome profiling of PrPc-depleted cells revealed downregulation of the special AT-rich sequence-binding protein-1 (SATB1). PrPc is demonstrated to be involved in regulating SATB1 expression via the Fyn-SP1 pathway. Since SATB1 has been previously proposed as a key protein that controls tumor development and progression, knockdown of PrPc resulted in a reduced metastatic capacity in CRC cells, as well as a reduction in distant metastases in vivo. In conclusion, our data characterize a novel molecular mechanism that links PrPc expression to the regulation of CRC metastasis. Targeting PrPc will, therefore, be a promising strategy to overcome the metastatic advantage in colorectal tumors. PMID:22972305

  11. ERK5 regulates muscle cell fusion through Klf transcription factors.

    PubMed

    Sunadome, Kazunori; Yamamoto, Takuya; Ebisuya, Miki; Kondoh, Kunio; Sehara-Fujisawa, Atsuko; Nishida, Eisuke

    2011-02-15

    In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here, we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, MEF2, and their target genes. Promoter analysis coupled to microarray assay reveals that Klf-binding motifs are highly enriched in the promoter regions of ERK5-dependent upregulated genes. Remarkably, Klf2 and Klf4 expression are also upregulated during differentiation in an ERK5-dependent manner, and knockdown of Klf2 or Klf4 specifically suppresses muscle cell fusion. Moreover, we show that Sp1 transcription factor links ERK5 to Klf2/4, and that nephronectin, a Klf transcriptional target, is involved in muscle cell fusion. Therefore, an ERK5/Sp1/Klf module plays a key role in the fusion process during skeletal muscle differentiation. PMID:21316587

  12. Architecture that affords play

    E-print Network

    Fallon, Paul Eric

    1981-01-01

    Play is a form of behavior common to all people. A person's propensity to play depends not only on his physiological and emotional state, but also on his surroundings. This thesis investigates environmental qualities ...

  13. Role-Playing Mitosis.

    ERIC Educational Resources Information Center

    Wyn, Mark A.; Stegink, Steven J.

    2000-01-01

    Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)

  14. Play the Electrocardiogram Game

    MedlinePLUS

    ... and Work Teachers' Questionnaire Electrocardiogram Play the ECG Game About the game ECG is used for diagnosing heart conditions by ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  15. Play the MRI Game

    MedlinePLUS

    ... Teachers' Questionnaire MRI Play MRI the Magnetic Miracle Game About the game In the MRI imaging technique, strong magnets and ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  16. Play the Tuberculosis Game

    MedlinePLUS

    ... Questionnaire Tuberculosis Play Tuberculosis Experiments & Discoveries About the game Discover and experience some of the classic methods ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  17. Romantic / classical Science play

    E-print Network

    /modernity Sex Time dilation and length contraction Historical Galileo/fictional Galileo (interpretation'd like: Art history [play with images] Workshops [Field trip] Galileo plays Things we need: Galileo

  18. The Arabidopsis gene SIGMA FACTOR-BINDING PROTEIN 1 plays a role in the salicylate- and jasmonate-mediated defence responses

    PubMed Central

    XIE, Y.-D.; LI, W.; GUO, D.; DONG, J.; ZHANG, Q.; FU, Y.; REN, D.; PENG, M.; XIA, Y.

    2011-01-01

    The chloroplast-localized SIB1 protein was previously identified by its interaction with SIGMA FACTOR 1 (SIG1), a component of the RNA polymerase machinery responsible for transcription of plastid genes. The physiological function of SIB1 is little known. We found that expression of SIB1 is induced by infection with Pseudomonas syringae, suggesting its possible involvement in the defence response. The sib1 loss-of-function mutation compromises induction of some defence-related genes triggered by pathogen infection and the treatments with salicylic acid (SA) and jasmonic acid (JA), two key signalling molecules in the defence response. Conversely, constitutive over-expression of SIB1 causes the plants to hyper-activate defence-related genes following pathogen infection or the SA and JA treatments, leading to enhanced resistance to infection by P. syringae. SIB1 is a member of the large plant-specific VQ motif-containing protein family, and might act as a link to connect defence signalling with chloroplast function. PMID:20040062

  19. Play Is the Way

    ERIC Educational Resources Information Center

    Gross, Steve; Sanderson, Rebecca Cornelli

    2012-01-01

    Historically, play has been viewed as a frivolous break from important endeavors like working and learning when, in fact, a child's ability to fully and freely engage in play is essential to their learning, productivity, and overall development. A natural drive to play is universal across all young mammals. Children from every society on earth…

  20. The Excellence of Play.

    ERIC Educational Resources Information Center

    Moyles, Janet R., Ed.

    Recognizing that for young children, play is a tool for learning, this book compiles contributions by different authors, reflecting both up-to-date research and current classroom practice as they relate to children's play. Part 1 of the book explores the value of play as a cross-cultural concept as well as one rooted in the Western world. Gender…

  1. The Pedagogy of Play

    ERIC Educational Resources Information Center

    Giesbrecht, Sheila

    2012-01-01

    Play is important. Environmental educators Sobel and Louv write about the relationship between children and outside play and suggest that early transcendental experiences within nature allow children to develop empathetic orientations towards the natural world. Children who play out-of-doors develop an appreciation for the environment and…

  2. The Power of Play

    Microsoft Academic Search

    Hae-Jin Mun

    2009-01-01

    Based on child psychologist, Dr. David Elkind’s intellectual\\/ motivational theory of play development, the presenter will be discussing the efficacy and the necessity of play and ways to integrate play into the classroom. Physiological, developmental and psychological education has extended our view of what contributes to learning and what is necessary to create a positive learning environment.

  3. Play the Mosquito Game

    MedlinePLUS

    ... and Work Teachers' Questionnaire Malaria Play the Mosquito Game Play the Parasite Game About the games Malaria is one of the world's most common ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  4. The Importance of Play.

    ERIC Educational Resources Information Center

    Sher, Allen

    Play is the spontaneous or organized recreational activity of children; it is at the heart of the preschool curriculum. Play aids in the development of physical, intellectual, and social skills. Children's play progresses through three developmental stages: solitary, parallel, and social. Preschool teachers should arrange for four kinds of…

  5. Dramatic Play and Print.

    ERIC Educational Resources Information Center

    Einarsdottir, Johanna

    1996-01-01

    Discusses a project that examined literacy development within the context of play in two Reykjavik preschool classrooms. Suggests that preschool teachers should enrich dramatic play with literacy props and print materials. Indicates that incorporating print materials in dramatic play provides a natural extension of children's preschool work and…

  6. The Arabidopsis homologs of CCR4-associated factor 1 show mRNA deadenylation activity and play a role in plant defence responses.

    PubMed

    Liang, Wenxing; Li, Changbao; Liu, Fang; Jiang, Hongling; Li, Shuyu; Sun, Jiaqiang; Wu, Xiaoyan; Li, Chuanyou

    2009-03-01

    Messenger RNA (mRNA) turnover in eukaryotic cells begins with shortening of the poly (A) tail at the 3' end, a process called deadenylation. In yeast, the deadenylation reaction is predominantly mediated by CCR4 and CCR4-associated factor 1 (CAF1), two components of the well-characterised protein complex named CCR4-NOT. We report here that AtCAF1a and AtCAF1b, putative Arabidopsis homologs of the yeast CAF1 gene, partially complement the growth defect of the yeast caf1 mutant in the presence of caffeine or at high temperatures. The expression of AtCAF1a and AtCAF1b is induced by multiple stress-related hormones and stimuli. Both AtCAF1a and AtCAF1b show deadenylation activity in vitro and point mutations in the predicted active sites disrupt this activity. T-DNA insertion mutants disrupting the expression of AtCAF1a and/or AtCAF1b are defective in deadenylation of stress-related mRNAs, indicating that the two AtCAF1 proteins are involved in regulated mRNA deadenylation in vivo. Interestingly, the single and double mutants of AtCAF1a and AtCAF1b show reduced expression of pathogenesis-related (PR) genes PR1 and PR2 and are more susceptible to Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection, whereas transgenic plants over-expressing AtCAF1a show elevated expression of PR1 and PR2 and increased resistance to the same pathogen. Our results suggest roles of the AtCAF1 proteins in regulated mRNA deadenylation and defence responses to pathogen infections. PMID:19065152

  7. African oil plays

    SciTech Connect

    Clifford, A.J. (BHP Petroleum, Melbourne, Victoria (Australia))

    1989-09-01

    The vast continent of Africa hosts over eight sedimentary basins, covering approximately half its total area. Of these basins, only 82% have entered a mature exploration phase, 9% have had little or no exploration at all. Since oil was first discovered in Africa during the mid-1950s, old play concepts continue to bear fruit, for example in Egypt and Nigeria, while new play concepts promise to become more important, such as in Algeria, Angola, Chad, Egypt, Gabon, and Sudan. The most exciting developments of recent years in African oil exploration are: (1) the Gamba/Dentale play, onshore Gabon; (2) the Pinda play, offshore Angola; (3) the Lucula/Toca play, offshore Cabinda; (4) the Metlaoui play, offshore Libya/Tunisia; (5) the mid-Cretaceous sand play, Chad/Sudan; and (6) the TAG-I/F6 play, onshore Algeria. Examples of these plays are illustrated along with some of the more traditional oil plays. Where are the future oil plays likely to develop No doubt, the Saharan basins of Algeria and Libya will feature strongly, also the presalt of Equatorial West Africa, the Central African Rift System and, more speculatively, offshore Ethiopia and Namibia, and onshore Madagascar, Mozambique, and Tanzania.

  8. The Play Activity Questionnaire: A parent report measure of children's play preferences

    Microsoft Academic Search

    Jo-Anne K. Finegan; G. Alison Niccols; James E. Zacher; Jane E. Hood

    1991-01-01

    Three studies describe the development and validation of the Play Activity Questionnaire (PQ), a parent report measure of children's play preferences. In Study 1, the 15-item PQ was completed by parents of 239 6- to 8-year-old children, and exploratory factor analysis revealed four play factors: Active and Adventurous, Athletic, Rough-and-Tumble, and Quiet. In Study 2, the factor structure was replicated

  9. Factorize

    NSDL National Science Digital Library

    Visualize factors through building rectangular areas on a grid. First enter all the factorizations of a number, then draw each factor set as an area on the grid. Factorize is one of the Interactivate assessment explorers.

  10. kids: Play music

    E-print Network

    Trainor, Laurel J.

    print kids: Play music by Tina Barseghian that kids who have learned how to play an instrument perform better in tests associated with literacy little Beethoven. Read the next secret to raising smart kids. Go back to the Big Story: 7 secrets

  11. Theories of Play.

    ERIC Educational Resources Information Center

    Peller, Lili E.

    1996-01-01

    Discusses several theories of play advanced before the development of psychoanalysis, including the theories of surplus energy, recreation, and practice. Examines the psychoanalytical view advanced by Freud and others, which focuses on the emotional release of play and its role in discovery and learning. (MDM)

  12. The Fear of Play

    ERIC Educational Resources Information Center

    Almon, Joan

    2009-01-01

    Real play--play that is initiated and directed by children and that bubbles up from within the child rather than being imposed by adults--has largely disappeared from the landscape of childhood in the United States. There are many reasons for this, such as the long hours spent in front of screens each day or in activities organized by adults. In…

  13. Play and Digital Media

    ERIC Educational Resources Information Center

    Johnson, James E.; Christie, James F.

    2009-01-01

    This article examines how play is affected by computers and digital toys. Research indicates that when computer software targeted at children is problem-solving oriented and open-ended, children tend to engage in creative play and interact with peers in a positive manner. On the other hand, drill-and-practice programs can be quite boring and limit…

  14. Return to Play

    ERIC Educational Resources Information Center

    Mangan, Marianne

    2013-01-01

    Call it physical activity, call it games, or call it play. Whatever its name, it's a place we all need to return to. In the physical education, recreation, and dance professions, we need to redesign programs to address the need for and want of play that is inherent in all of us.

  15. An Invitation to Play.

    ERIC Educational Resources Information Center

    Lange, Jenny; Zieher, Connie

    The manual is intended to provide suggestions for play to parents of young children with exceptional educational needs. Nineteen types of activities are described and pictured, including make believe with boxes, dress-up activities, kitchen play, bubbles, small motor activities using beans and buttons, use of throw-away materials, painting,…

  16. Let's Just Play

    ERIC Educational Resources Information Center

    Schmidt, Janet

    2003-01-01

    Children have a right to play. The idea is so simple it seems self-evident. But a stroll through any toy superstore, or any half-hour of so-called "children's" programming on commercial TV, makes it clear that violence, not play, dominates what's being sold. In this article, the author discusses how teachers and parents share the responsibility in…

  17. Factors affecting mother-child play

    E-print Network

    Welch, Jennifer Colleen

    1993-01-01

    INTRODUCTION Parent training has been utilized clinically for over 25 years in the treatment of children with a wide range of problems. Some of these problems include emotional and behavioral difficulties, medical disorders, physical and/or mental...

  18. Regulation of renin enhancer activity by nuclear factor I and Sp1/Sp3 , Sean T. Glenna

    E-print Network

    Gronostajski, Richard M.

    in kidney tumor-derived As4.1 cells, which express high levels of renin mRNA, is dependent on a proximal, including submandibular gland, adrenal gland, testes, ovary, anterior prostate, placenta and fetal have been identified in Ren-1c using a kidney tumor-derived As4.1 cell line, which was developed from

  19. Art and Play:

    E-print Network

    Marcel Duchamp; Er Calder; Jean Tinguely; Claes Oldenburg Elizabeth Murray; Caroline Rutledge Armijo

    “The idea—demystifying art, making it more accessible—appealed to me. It’s great for kids to get the feeling art is about play and you can play with it.”1 Elizabeth Murray Often, we find ourselves alone, busy working on a project. It could stem from an idea inspired by reading a favorite book, watching a movie, eating in a new restaurant, or visiting an amusement

  20. Characterization of a marine-isolated mercury-resistant Pseudomonas putida strain SP1 and its potential application in marine mercury reduction.

    PubMed

    Zhang, Weiwei; Chen, Lingxin; Liu, Dongyan

    2012-02-01

    The Pseudomonas putida strain SP1 was isolated from marine environment and was found to be resistant to 280 ?M HgCl?. SP1 was also highly resistant to other metals, including CdCl?, CoCl?, CrCl?, CuCl?, PbCl?, and ZnSO?, and the antibiotics ampicillin (Ap), kanamycin (Kn), chloramphenicol (Cm), and tetracycline (Tc). mer operon, possessed by most mercury-resistant bacteria, and other diverse types of resistant determinants were all located on the bacterial chromosome. Cold vapor atomic absorption spectrometry and a volatilization test indicated that the isolated P. putida SP1 was able to volatilize almost 100% of the total mercury it was exposed to and could potentially be used for bioremediation in marine environments. The optimal pH for the growth of P. putida SP1 in the presence of HgCl? and the removal of HgCl? by P. putida SP1 was between 8.0 and 9.0, whereas the optimal pH for the expression of merA, the mercuric reductase enzyme in mer operon that reduces reactive Hg²? to volatile and relatively inert monoatomic Hg? vapor, was around 5.0. LD?? of P. putida SP1 to flounder and turbot was 1.5?×?10? CFU. Biofilm developed by P. putida SP1 was 1- to 3-fold lower than biofilm developed by an aquatic pathogen Pseudomonas fluorescens TSS. The results of this study indicate that P. putida SP1 is a low virulence strain that can potentially be applied in the bioremediation of HgCl? contamination over a broad range of pH. PMID:21751007

  1. Looking into Children's Play Communities

    ERIC Educational Resources Information Center

    Mabry, Mark; Fucigna, Carolee

    2009-01-01

    Play, particularly children's sociodramatic play, is the cornerstone of early childhood classrooms in the United States. Early childhood educators learn and expound mantras of "the value of play," "play-based programs," "children learning through play," and "play as child's work." They strive to promote the importance of making a place for play in…

  2. Inhibition of transcription factor specificity protein 1 alters the gene expression profile of keratinocytes leading to upregulation of kallikrein-related peptidases and thymic stromal lymphopoietin.

    PubMed

    Bin, Lianghua; Kim, Byung E; Hall, Clifton F; Leach, Sonia M; Leung, Donald Y M

    2011-11-01

    Transcription factor specificity protein 1 (Sp1) is involved in diverse cellular functions. We recently found that Sp1 was significantly decreased in skin biopsy samples obtained from patients with atopic dermatitis (AD) and had an even greater reduction in AD patients with a history of eczema herpeticum. In the current study, we sought to better understand the role of Sp1 in skin biological processes by using a small-interfering RNA (siRNA) technique to knock down Sp1 gene expression in normal human keratinocytes (NHKs) and investigated the genome-wide gene expression profiling of Sp1-silenced NHKs. The gene arrays revealed that 53 genes had greater than 3-fold changes in the expression in Sp1-silenced NHKs as compared with scrambled siRNA-silenced cells. Strikingly, six kallikrein (KLK)-related peptidase genes, namely KLK5, KLK6, KLK7, KLK8, KLK10, and KLK12, were upregulated in NHKs following Sp1 silencing. Functionally, protease activity was significantly enhanced in Sp1-silenced keratinocytes as compared with scrambled siRNA-silenced keratinocytes. Moreover, thymic stromal lymphopoietin (TSLP), an epithelial-derived T(H)2-promoting cytokine, was induced in Sp1-silenced keratinocytes because of elevated KLK activity. These results indicate that Sp1 expression deficiency leads to abnormally increased KLK protease activity in keratinocytes and may contribute to T(H)2 immune responses in the skin by inducing TSLP. PMID:21753780

  3. Play down protein to play up metabolism?

    PubMed Central

    Müller, Timo D.; Tschöp, Matthias H.

    2014-01-01

    Who among us hasn’t fantasized about a diet that allows ingestion of a surfeit of calories that are burned off effortlessly by ramping up energy expenditure? In this issue of the JCI, research led by Christopher Morrison suggests that this dream may become a reality; however, a complete understanding of the molecular interface that connects nutrient choices with our cellular metabolism will be required. Laeger et al. show that the expression and secretion of the weight-reducing hormone fibroblast growth factor 21 (FGF21) is regulated by dietary proteins and not, as has been heretofore assumed, simply triggered by reduced caloric intake. This study not only sheds new light on the role of FGF21 in systems metabolism, but also on the ways our bodies cope with the ever-changing availability of different dietary macronutrients. PMID:25133420

  4. Play down protein to play up metabolism?

    PubMed

    Müller, Timo D; Tschöp, Matthias H

    2014-09-01

    Who among us hasn't fantasized about a diet that allows ingestion of a surfeit of calories that are burned off effortlessly by ramping up energy expenditure? In this issue of the JCI, research led by Christopher Morrison suggests that this dream may become a reality; however, a complete understanding of the molecular interface that connects nutrient choices with our cellular metabolism will be required. Laeger et al. show that the expression and secretion of the weight-reducing hormone fibroblast growth factor 21 (FGF21) is regulated by dietary proteins and not, as has been heretofore assumed, simply triggered by reduced caloric intake. This study not only sheds new light on the role of FGF21 in systems metabolism, but also on the ways our bodies cope with the ever-changing availability of different dietary macronutrients. PMID:25133420

  5. MicroRNA-29b Regulates Ethanol-induced Neuronal Apoptosis in the Developing Cerebellum through SP1/RAX/PKR Cascade*

    PubMed Central

    Qi, Yuanlin; Zhang, Mingfang; Li, Hui; Frank, Jacqueline A.; Dai, Lu; Liu, Huijuan; Chen, Gang

    2014-01-01

    Neuronal loss is a prominent etiological factor for fetal alcohol spectrum disorders. The cerebellum is one of the areas in the developing central nervous system that is most sensitive to ethanol, especially during the temporal window of ethanol vulnerability. MicroRNAs are small, non-coding RNAs capable of regulating diverse cellular functions including apoptosis. Ethanol exposure has been shown to interfere with the expression of microRNAs. However, the role of microRNAs in ethanol neurotoxicity is still not clear. In the present study, we identified a particular microRNA, miR-29b, as a novel target of ethanol in the developing cerebellar granule neurons. We discovered that ethanol exposure suppressed miR-29b and induced neuronal apoptosis. Overexpression of miR-29b rendered neurons protection against ethanol-induced apoptosis. Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade. More importantly, the expression of miR-29b is developmentally regulated, which may account for, at least partially, the temporal window of ethanol sensitivity in the developing cerebellum. PMID:24554719

  6. Serum Starvation-Induced Voltage-Gated Potassium Channel Kv7.5 Expression and Its Regulation by Sp1 in Canine Osteosarcoma Cells

    PubMed Central

    Lee, Bo Hyung; Ryu, Pan Dong; Lee, So Yeong

    2014-01-01

    The KCNQ gene family, whose members encode Kv7 channels, belongs to the voltage-gated potassium (Kv) channel group. The roles of this gene family have been widely investigated in nerve and muscle cells. In the present study, we investigated several characteristics of Kv7.5, which is strongly expressed in the canine osteosarcoma cell line, CCL-183. Serum starvation upregulated Kv7.5 expression, and the Kv7 channel opener, flupirtine, attenuated cell proliferation by arresting cells in the G0/G1 phase. We also showed that Kv7.5 knockdown helps CCL-183 cells to proliferate. In an effort to find an endogenous regulator of Kv7.5, we used mithramycin A to reduce the level of the transcription factor Sp1, and it strongly inhibited the induction of Kv7.5 in CCL-183 cells. These results suggest that the activation of Kv7.5 by flupirtine may exert an anti-proliferative effect in canine osteosarcoma. Therefore, Kv7.5 is a possible molecular target for canine osteosarcoma therapy. PMID:24434641

  7. MicroRNA-29b regulates ethanol-induced neuronal apoptosis in the developing cerebellum through SP1/RAX/PKR cascade.

    PubMed

    Qi, Yuanlin; Zhang, Mingfang; Li, Hui; Frank, Jacqueline A; Dai, Lu; Liu, Huijuan; Chen, Gang

    2014-04-01

    Neuronal loss is a prominent etiological factor for fetal alcohol spectrum disorders. The cerebellum is one of the areas in the developing central nervous system that is most sensitive to ethanol, especially during the temporal window of ethanol vulnerability. MicroRNAs are small, non-coding RNAs capable of regulating diverse cellular functions including apoptosis. Ethanol exposure has been shown to interfere with the expression of microRNAs. However, the role of microRNAs in ethanol neurotoxicity is still not clear. In the present study, we identified a particular microRNA, miR-29b, as a novel target of ethanol in the developing cerebellar granule neurons. We discovered that ethanol exposure suppressed miR-29b and induced neuronal apoptosis. Overexpression of miR-29b rendered neurons protection against ethanol-induced apoptosis. Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade. More importantly, the expression of miR-29b is developmentally regulated, which may account for, at least partially, the temporal window of ethanol sensitivity in the developing cerebellum. PMID:24554719

  8. P300 plays a role in p16(INK4a) expression and cell cycle arrest.

    PubMed

    Wang, X; Pan, L; Feng, Y; Wang, Y; Han, Q; Han, L; Han, S; Guo, J; Huang, B; Lu, J

    2008-03-20

    As a cyclin-dependent kinase inhibitor, p16(INK4a) plays a key role in cell cycle progression and cellular differentiation, and its expression is frequently altered in human cancers through epigenetically mediated transcriptional silencing. In this report, we demonstrate that p300 was able to induce cell cycle arrest, and this process was reversed by p16(INK4a) silencing by RNA interference in HeLa cells. We also show that p300 was involved in activation of p16(INK4a) expression in 293T cells. Specifically, p300 cooperated with Sp1 to stimulate both p16(INK4a) promoter activity and mRNA expression. Co-immunoprecipitation and mammalian two-hybrid assays revealed that p300 and Sp1 formed a complex through interaction between the Q domain of p300 and the N-terminal domain of Sp1. The chromatin immunoprecipitation assays verified that p300 was recruited to p16(INK4a) promoter, and the histone acetyltransferase domain of p300 participated in p16(INK4a) activation through inducing hyperacetylation of histone H4 at p16(INK4a) gene. These data suggest that p300 plays a critical role in transcriptional regulation of p16(INK4a) and in cell cycle arrest. PMID:17906698

  9. Play Dough Planets

    NSDL National Science Digital Library

    This is a lesson about planet sizes. Learners will demonstrate the size (volume) differences between Earth, Earth’s Moon, and Mars. An extension to estimate the distance between the Earth and the Moon, and the Earth and Mars, using the scale of the play dough planets' sizes is provided. Advance preparation of the play dough (recipie provided) is required. This is lesson 3 of 16 in the MarsBots learning module. It was adapted from 3-D Model of the Earth and Moon, an activity in The Universe at Your Fingertips.

  10. Complete genome sequence of Terriglobus saanensis type strain SP1PR4T, an Acidobacteria from tundra soil

    SciTech Connect

    Rawat, Suman R. [Rutgers University; Mannisto, Minna [Finnish Forest Research Institute, Parkano, Finland; Starovoytov, Valentin [Rutgers University; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Hauser, Loren John [ORNL; Land, Miriam L [ORNL; Davenport, Karen W. [Los Alamos National Laboratory (LANL); Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Haggblom, Max [Rutgers University

    2012-01-01

    Terriglobus saanensis SP1PR4T is a novel species of the genus Terriglobus. T. saanensis is of ecological interest because it is a representative of the phylum Acidobacteria, which are dominant members of bacterial soil microbiota in Arctic ecosystems. T. saanensis is a cold-adapted acidophile and a versatile heterotroph utilizing a suite of simple sugars and complex polysaccharides. The genome contained an abundance of genes assigned to metabolism and transport of carbohydrates including gene modules encoding for carbohydrate-active enzyme (CAZyme) family involved in breakdown, utilization and biosynthesis of diverse structural and storage polysaccharides. T. saanensis SP1PR4T represents the first member of genus Terriglobus with a completed genome sequence, consisting of a single replicon of 5,095,226 base pairs (bp), 54 RNA genes and 4,279 protein-coding genes. We infer that the physiology and metabolic potential of T. saanensis is adapted to allow for resilience to the nutrient-deficient conditions and fluctuating temperatures of Arctic tundra soils.

  11. bHLH-PAS family transcription factor methoprene-tolerant plays a key role in JH action in preventing the premature development of adult structures during larval-pupal metamorphosis

    PubMed Central

    Parthasarathy, R.; Tan, Anjiang; Palli, Subba R.

    2008-01-01

    The biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect’s life. However, the molecular actions of these hormones are not well understood. Recent studies in the red flour beetle, Tribolium castaneum, demonstrated the utility of this insect as a model system to study JH action. These studies confirmed that the bHLH-PAS family transcription factor, methoprene-tolerant (TcMet,) plays a key role in JH action during larval stages. In this study, we investigated the role of TcMet in JH action during larval-pupal metamorphosis. The phenotypes of TcMet RNAi insects shared similarity with the phenotypes of some allatectomized lepidopteran larvae that were attempting to undergo precocious larval-pupal metamorphosis. Knocking-down TcMet during the final instar also disrupted larval-pupal ecdysis, resulting in the development of adultoid underneath the larval skin. However, the loss of TcMet did not completely block remodeling of internal tissues such as midgut. T. castaneum larvae injected with TcMet dsRNA demonstrated a resistance to a JH analog (JHA), hydroprene, irrespective of time and route of application. Knocking-down TcMet also caused down regulation of JH-response genes, JHE and Kr-h1 suggesting that TcMet might be involved in the expression of these genes. Based on the phenotype, gene expression, and JHA action studies in TcMet RNAi insects, this study concludes that Met plays a key role in JH action for preventing the premature development of adult structures during larval-pupal metamorphosis. PMID:18450431

  12. Integrated Play Groups

    ERIC Educational Resources Information Center

    Glovak, Sandra

    2007-01-01

    As an occupational therapist running social play groups with sensory integration for children on the autism spectrum, the author frequently doubted the wisdom of combining several children on the spectrum into a group. In fact, as the owner of a clinic she said, "No more!" The groups seemed like a waste of parents' time and money, and she refused…

  13. A manipulator plays Jenga

    Microsoft Academic Search

    Torsten Kroger; Bernd Finkemeyer; Simon Winkelbach; Lars-Oliver Eble; Sven Molkenstruck; FRIEDRICH M. WAHL

    2008-01-01

    This article describes an overview of a prototypical manipulation control system, which is able to play Jenga. The implementation of the Jenga game has been chosen to verify the integration of existing concepts such as force\\/torque control, distance control, real-time behavior of distributed control systems, sensor data fusion, online trajectory computation, and visual servoing in one exhibit. This exhibit has

  14. The Paradoxes of Play.

    ERIC Educational Resources Information Center

    Rokosz, Francis M.

    1988-01-01

    The article makes a case against the structuring of intramural sports programs on the basis of the varsity athletics model, arguing that the latter model's components of competition and aggression mar the former's intrinsic rewards of play, creativity, and enhanced human relationships. (CB)

  15. Playing with danger.

    PubMed

    Pearce, Lynne

    Young people who sit still for hours playing computer games can double their risk of potentially fatal blood clots. The charity Lifeblood is alerting nurses to 'e-thrombosis'. It is calling on them to ensure young people are aware of the risks of prolonged immobility and the need to take regular breaks from gaming or using a computer. PMID:23061127

  16. Leveling the Playing Field

    ERIC Educational Resources Information Center

    Brighouse, Harry

    2006-01-01

    This article comments on Fullinwider and Lichtenberg's "Leveling the Playing Field". It reviews their central claims and comments on both their arguments and their reform proposals, and suggests alternative, bolder, egalitarian proposals which involve a higher degree of effective privatization than theirs. (Contains 1 note.)

  17. Play's Importance in School

    ERIC Educational Resources Information Center

    Sandberg, Anette; Heden, Rebecca

    2011-01-01

    The purpose of this study is to contribute knowledge on and gain an understanding of elementary school teachers' perspectives on the function of play in children's learning processes. The study is qualitative with a hermeneutical approach and has George Herbert Mead as a theoretical frame of reference. Interviews have been carried out with seven…

  18. One Play a Day

    ERIC Educational Resources Information Center

    Blankenship, Mark

    2007-01-01

    Undergraduate theater students rarely get the chance to work on a major world premiere, but this year hundreds of them will. Currently, more than 70 colleges and universities are participating in "365 Days/365 Plays," an ambitious project from Pulitzer Prize-winning playwright Suzan-Lori Parks. Every week, as they mount their portion of this epic…

  19. Abstraction through Game Play

    ERIC Educational Resources Information Center

    Avraamidou, Antri; Monaghan, John; Walker, Aisha

    2012-01-01

    This paper examines the computer game play of an 11-year-old boy. In the course of building a virtual house he developed and used, without assistance, an artefact and an accompanying strategy to ensure that his house was symmetric. We argue that the creation and use of this artefact-strategy is a mathematical abstraction. The discussion…

  20. Play and Culture. Beginnings Workshop.

    ERIC Educational Resources Information Center

    Cronin, Sharon; Jones, Elizabeth; Evans, Kathleen; Jarman, Cheryl Greer; Cooper, Renatta M.; Reynolds, Gretchen

    1999-01-01

    Presents five articles on the interactions of play and culture in early childhood education. The workshop titles are: "Play and Cultural Differences" (Cronin and Jones); "Play in a Classroom of Iu-Mien Children: (Evans); "The Culture of Play: A Personal Perspective" (Jarman); "'But They're Only Playing': Interpreting Play to Parents" (Cooper); and…

  1. Development through Work and Play.

    ERIC Educational Resources Information Center

    Hartung, Paul J.

    2002-01-01

    Five proposals are made for incorporating a work-play perspective in career development research: (1) fuse work and play conceptually over the life course; (2) imbue developmental career theory with a work-play fusion; (3) study work and play across the life span; (4) investigate work and play within the life space; and (5) consider a work-play

  2. Role of the intronic enhancer in tumor necrosis factor-mediated induction of manganous superoxide dismutase.

    PubMed

    Guo, Zhu; Boekhoudt, Gunther H; Boss, Jeremy M

    2003-06-27

    Manganous superoxide dismutase (Mn-SOD), a tumor necrosis factor (TNF)-inducible gene product, plays an important role in removing superoxide anions produced inside mitochondria. Two regulatory regions, the proximal promoter region (PPR), which is upstream from the transcription initiation site, and the TNF-responsive element (TNFRE), which is inside intron 2, are responsible for Mn-SOD expression. To understand how each of these regions contributes to the transcription of Mn-SOD, quantitative reverse transcription-PCR, chromatin immunoprecipitations, and in vivo nuclease sensitivity assays were performed on the murine Mn-SOD gene. These assays demonstrate that Sp1 and nuclear factor (NF)-kappaB p65 are required for Mn-SOD induction by TNF. Sp1 bound the PPR constitutively, whereas NF-kappaB p65 and C/EBP-beta bound the TNFRE only after TNF treatment. Binding of C/EBP-beta to the TNFRE was dependent on the presence of NF-kappaB p65. The chromatin structure within the TNFRE became more accessible to nuclease digestion after TNF treatment. This accessibility required Sp1 and NF-kappaB p65. Treatment of cells with an inhibitor of histone deacetylation, or transient transfection with coactivator-expressing plasmids, enhanced the expression of Mn-SOD. NF-kappaB p65 binding was required for acetylation of histones H3 and H4 at the PPR and the TNFRE. Together, these data suggest communication between the PPR and the TNFRE which involves chromatin remodeling and histone acetylation during the induction process of Mn-SOD in response to TNF. PMID:12684509

  3. Eat Smart. Play Hard.

    NSDL National Science Digital Library

    The Food and Nutrition Service of the US Department of Agriculture offers online educational material as part of "Eat Smart. Play Hard." -- a public information campaign designed to promote healthy living in American children. While the site and its materials are geared for use by state and local program coordinators, anyone is welcome to download the available information and activity sheets. Click on Cool Stuff for Kids for nutrition-related puzzles and games. Parents Place offers informational brochures and an educational bookmark.

  4. Trefoil Factor 1 is involved in gastric cell copper homeostasis.

    PubMed

    Esposito, Roberta; Montefusco, Sandro; Ferro, Piera; Monti, Maria Chiara; Baldantoni, Daniela; Tosco, Alessandra; Marzullo, Liberato

    2015-02-01

    Trefoil Factor 1 belongs to a group of small secreted proteins (the Trefoil Factor Family proteins), that are localized within the mucous granules and are expressed and secreted by epithelial cells that line mucous membranes. Trefoil factors are mainly expressed in the gastrointestinal tract, where they normally contribute to maintain the integrity of the mucosa. We recently demonstrated a selective binding ability of Trefoil Factor 1 for copper ions, through its carboxy-terminal tail, and we also observed that copper levels influence the equilibrium between the monomeric and homodimeric forms of Trefoil Factor 1, thus modulating its biological activity. Here we report that transcriptional regulation of Trefoil Factor 1 is also affected by copper levels, through the modulated binding of the copper-sensing transcription factor Sp1 onto the responsive elements present in the regulatory region of the gene. In addition we demonstrate that copper overload causes an accumulation of the trefoil protein in the Trans-Golgi Network and that Trefoil Factor 1 levels can influence copper excretion and copper related toxicity. These findings suggest that the protein might play a role in the overall complex mechanisms of copper homeostasis in the gastrointestinal tissues. PMID:25486181

  5. Play in Practice: Case Studies in Young Children's Play.

    ERIC Educational Resources Information Center

    Brown, Cheryl Render, Ed.; Marchant, Catherine, Ed.

    This book uses a collection of stories, or "cases," as a basis for reflection, discussion, and learning about the many roles "play" has in children's lives. Each of the 12 cases addresses an issue of play from one of three categories--the role of adults in play, the cultural meanings of play, and the issues related to play in special settings.…

  6. Cell Growth Defect Factor1/CHAPERONE-LIKE PROTEIN OF POR1 Plays a Role in Stabilization of Light-Dependent Protochlorophyllide Oxidoreductase in Nicotiana benthamiana and Arabidopsis[C][W

    PubMed Central

    Lee, Jae-Yong; Lee, Ho-Seok; Song, Ji-Young; Jung, Young Jun; Reinbothe, Steffen; Park, Youn-Il; Lee, Sang Yeol; Pai, Hyun-Sook

    2013-01-01

    Angiosperms require light for chlorophyll biosynthesis because one reaction in the pathway, the reduction of protochlorophyllide (Pchlide) to chlorophyllide, is catalyzed by the light-dependent protochlorophyllide oxidoreductase (POR). Here, we report that Cell growth defect factor1 (Cdf1), renamed here as CHAPERONE-LIKE PROTEIN OF POR1 (CPP1), an essential protein for chloroplast development, plays a role in the regulation of POR stability and function. Cdf1/CPP1 contains a J-like domain and three transmembrane domains, is localized in the thylakoid and envelope membranes, and interacts with POR isoforms in chloroplasts. CPP1 can stabilize POR proteins with its holdase chaperone activity. CPP1 deficiency results in diminished POR protein accumulation and defective chlorophyll synthesis, leading to photobleaching and growth inhibition of plants under light conditions. CPP1 depletion also causes reduced POR accumulation in etioplasts of dark-grown plants and as a result impairs the formation of prolamellar bodies, which subsequently affects chloroplast biogenesis upon illumination. Furthermore, in cyanobacteria, the CPP1 homolog critically regulates POR accumulation and chlorophyll synthesis under high-light conditions, in which the dark-operative Pchlide oxidoreductase is repressed by its oxygen sensitivity. These findings and the ubiquitous presence of CPP1 in oxygenic photosynthetic organisms suggest the conserved nature of CPP1 function in the regulation of POR. PMID:24151298

  7. Sp1 trans-activates and is required for maximal aldosterone induction of the ?ENaC gene in collecting duct cells

    PubMed Central

    Yu, Zhiyuan; Kong, Qun

    2013-01-01

    The epithelial Na+ channel (ENaC) in the distal nephron constitutes the rate-limiting step for renal sodium reabsorption. Aldosterone increases tubular sodium absorption in large part by increasing ?ENaC transcription in collecting duct principal cells. We previously reported that Af9 binds to +78/+92 of ?ENaC and recruits Dot1a to repress basal and aldosterone-sensitive ?ENaC transcription in mouse inner medullary collecting duct (mIMCD)3 cells. Despite this epigenetic repression, basal ?ENaC transcription is still evident and physiologically necessary, indicating basal operation of positive regulators. In the present study, we identified Sp1 as one such regulator. Gel shift and antibody competition assays using a +208/+240 probe revealed DNA-Sp1-containing complexes in mIMCD3 cells. Mutation of the +222/+229 element abrogated Sp1 binding in vitro and in promoter-reporter constructs stably expressed in mIMCD3 cells. Compared with the wild-type promoter, an ?ENaC promoter-luciferase construct with +222/+229 mutations exhibited much lower activity and impaired trans-activation in Sp1 overexpression experiments. Conversely, Sp1 knockdown inhibited endogenous ?ENaC mRNA and the activity of the wild-type ?ENaC promoter but not the mutated construct. Aldosterone triggered Sp1 recruitment to the ?ENaC promoter, which was required for maximal induction of ?ENaC promoter activity and was blocked by spironolactone. Sequential chromatin immunoprecipitation assays and functional tests of +78/+92 and +222/+229 ?ENaC promoter mutants indicated that while Sp1, Dot1a, and Af9 co-occupy the ?ENaC promoter, the Sp1 effects are functionally independent from Dot1a and Af9. In summary, Sp1 binding to a cis-element at +222/+229 represents the first identified constitutive driver of ?ENaC transcription, and it contributes to maximal aldosterone trans-activation of ?ENaC. PMID:23804453

  8. Factorize

    NSDL National Science Digital Library

    2000-01-01

    This interactive applet allows a student to visually explore the concept of factors by creating different rectangular arrays for a number. The user constructs the array by clicking and dragging on a grid. The length and width of the array are factors of the number. A student can elect an option of a randomly selected number or the student selects his own number between 2 and 50. Exploration questions are included to promote student discovery of mathematical concepts with factors.

  9. Playing with Poetry

    NSDL National Science Digital Library

    Mrs. Payne

    2010-06-04

    The third grade core states that we should read and write poems as part of our language arts instruction. Come play with words as we explore some published poetry and write our own! We'll even publish your finished work in class. Use these activities below as your homework for the week as we study poetry in class each day. Remember: Whenever you're working on the internet, make sure you have a grown-up's permission and that they approve of each website you go on. Monday's Homework: Pick three poems to read from this website,Poems for Kids, and read ...

  10. Baroreceptor Reflex Role Play

    NSDL National Science Digital Library

    Marlene Y. MacLeish

    2012-06-26

    In this activity about the baroreceptor reflex (BR) arc (page 123 of the PDF), learners discover the importance of maintaining adequate arterial blood pressure through a role playing exercise. This activity will model how the brain processes information and sends out signals to the heart and arteries. Learners can also consider how this affects astronauts in the microgravity environment of space. The lesson guide, part of NASA's "The Brain in Space: A Teacher's Guide with Activities for Neuroscience," includes background information and evaluation strategies. Note: this activity requires 9 learners per group.

  11. Playing Connect Three

    NSDL National Science Digital Library

    This activity promotes students to explore and analyze the number of different ways of achieving each of the specific outcomes when adding and subtracting positive and negative integers while playing the game, "Connect Three." By answering key questions, the players work out a strategy for improving their chances of winning the game. The Teachers' Notes page offers suggestions for implementation, discussion questions, ideas for support, extension and answers to questions are provided. A pdf of the game board and a spreadsheet to simulate tossing the dice are linked.

  12. Farm Hall: The Play

    NASA Astrophysics Data System (ADS)

    Cassidy, David C.

    2013-03-01

    It's July 1945. Germany is in defeat and the atomic bombs are on their way to Japan. Under the direction of Samuel Goudsmit, the Allies are holding some of the top German nuclear scientists--among them Heisenberg, Hahn, and Gerlach--captive in Farm Hall, an English country manor near Cambridge, England. As secret microphones record their conversations, the scientists are unaware of why they are being held or for how long. Thinking themselves far ahead of the Allies, how will they react to the news of the atomic bombs? How will these famous scientists explain to themselves and to the world their failure to achieve even a chain reaction? How will they come to terms with the horror of the Third Reich, their work for such a regime, and their behavior during that period? This one-act play is based upon the transcripts of their conversations as well as the author's historical work on the subject.[4pt] Discussion of the play with the playwright follows after the staged reading.

  13. Ancient properties of spider silks revealed by the complete gene sequence of the prey-wrapping silk protein (AcSp1).

    PubMed

    Ayoub, Nadia A; Garb, Jessica E; Kuelbs, Amanda; Hayashi, Cheryl Y

    2013-03-01

    Spider silk fibers have impressive mechanical properties and are primarily composed of highly repetitive structural proteins (termed spidroins) encoded by a single gene family. Most characterized spidroin genes are incompletely known because of their extreme size (typically >9 kb) and repetitiveness, limiting understanding of the evolutionary processes that gave rise to their unusual gene architectures. The only complete spidroin genes characterized thus far form the dragline in the Western black widow, Latrodectus hesperus. Here, we describe the first complete gene sequence encoding the aciniform spidroin AcSp1, the primary component of spider prey-wrapping fibers. L. hesperus AcSp1 contains a single enormous (?19 kb) exon. The AcSp1 repeat sequence is exceptionally conserved between two widow species (?94% identity) and between widows and distantly related orb-weavers (?30% identity), consistent with a history of strong purifying selection on its amino acid sequence. Furthermore, the 16 repeats (each 371-375 amino acids long) found in black widow AcSp1 are, on average, >99% identical at the nucleotide level. A combination of stabilizing selection on amino acid sequence, selection on silent sites, and intragenic recombination likely explains the extreme homogenization of AcSp1 repeats. In addition, phylogenetic analyses of spidroin paralogs support a gene duplication event occurring concomitantly with specialization of the aciniform glands and the tubuliform glands, which synthesize egg-case silk. With repeats that are dramatically different in length and amino acid composition from dragline spidroins, our L. hesperus AcSp1 expands the knowledge base for developing silk-based biomimetic technologies. PMID:23155003

  14. Playing My Heart Out: Original Play as Adventure.

    ERIC Educational Resources Information Center

    Donaldson, O. Fred

    1999-01-01

    "Original" play denotes play that is pre-cultural--before conceptualizations and learned responses. Four anecdotes about play with an infant with Down's syndrome, a child with leukemia, a lioness, and a dying woman illustrate the connections between beings and between the ordinary and the sacred during trusting, fearless, playful encounters. (SV)

  15. Playing Together Beats Playing Apart, Especially for Girls

    Microsoft Academic Search

    Kori Inkpen; Kellogg S. Booth; Maria Klawe; Rena Upitis

    1995-01-01

    This paper describes follow-on studies focusing on how gender and grouping affects performance and attitudes of children playing a puzzle solving game called The Incredible Machine (TIM). We found that children playing together on one machine solved significantly more puzzles than children playing alone on one machine. Female\\/Female pairs playing together on one machine, on average, completed significantly more puzzles

  16. Who played the Raptors?

    NSDL National Science Digital Library

    National Council of Teachers of Mathematics (NCTM)

    2002-01-01

    In this online activity, students analyze predictions made by sportswriters about which basketball teams will win to determine which teams are playing each other. The Getting Started link describes how to set up a table to organize the given information. The activity is one of 80 mathematical challenges featured on the Figure This! web site, where real-world uses of mathematics are emphasized. The solution illustrates and explains three different ways to successfully organize information, including using a Venn diagram. The related questions challenge students to use logic and organizational skills to analyze data in a pet survey and to draw a conclusion from information about automobile preferences. Background information about famous names in the field of logic and a list of literary books containing logic puzzles are included. Copyright 2005 Eisenhower National Clearinghouse

  17. Factors

    NSDL National Science Digital Library

    2011-05-24

    This lesson is designed to develop students' abilities to find factors of whole numbers. The lesson also introduces prime numbers. This lesson provides links to discussions and activities related to factors as well as suggested ways to integrate them into the lesson. Finally, the lesson provides links to follow-up lessons designed for use in succession with the current one. Note, reading level is not indicated because the lesson does not include student reading material.

  18. Factoring

    NSDL National Science Digital Library

    Mrs. Taylor

    2010-10-19

    In this lesson we will explore prime numbers and factors A prime number has only two factors, 1 and itself. The Greek scholar, Eratosthenes of Cyrene lived from approximately 275 to 195 BC. He is know for being the first to have computed the size of the Earth and served as the director of the famous library in

  19. Combinatorial action of transcription factors orchestrates cell cycle-dependent expression of the ribosomal protein genes and ribosome biogenesis.

    PubMed

    Nosrati, Nagisa; Kapoor, Neetu R; Kumar, Vijay

    2014-05-01

    Nucleolar assembly begins at the early G1 phase of the cell cycle and is a hub of ribosomal DNA transcription and rRNA biosynthesis. The newly-formed rRNAs together with ribosomal proteins (RPs) constitute the building block of the ribosomal machinery. Although RPs play a major role in protein biosynthesis, their own regulation and expression is rather poorly understood. In the present study, we investigated the regulation of RP genes RPS27a, RPS24, RPS6, RPL9 and RPL4 in synchronized mammalian cell culture. Quantitative RT-PCR analysis indicated their expression during the mid to late G1 phase, whereas the rRNA genes were expressed during the early G1 phase of the cell cycle. The promoter reporter analysis of the RPS27a gene revealed that it could be synergistically stimulated by the transcription factors specificity protein 1 (Sp1) and cAMP response element-binding protein (CREB). However, E2F transcription factor 1 (E2F1) appeared to negatively regulate gene expression. Chromatin immunoprecipitation studies confirmed the promoter occupancy of Sp1, CREB and E2F1. Although Sp1 and CREB binding enhanced the promoter occupancy of histone acetyltransferases PCAF, p300 and CREB binding protein, E2F1 facilitated the recruitment of histone deacetylases. Both acetylation (histone H4 pan-acetyl, histone H3 acetyl Lys 14) and methylation (histone H3 trimethyl Lys 9) marks were observed in the RPS27a promoter region, suggesting their important regulatory role in gene expression. Because the promoter regions of most RP genes are well conserved, we propose that their orchestrated regulation and synthesis during the cell cycle facilitates ribosome biogenesis. PMID:24646001

  20. Play Therapy in Elementary Schools

    ERIC Educational Resources Information Center

    Landreth, Garry L.; Ray, Dee C.; Bratton, Sue C.

    2009-01-01

    Because the child's world is a world of action and activity, play therapy provides the psychologist in elementary-school settings with an opportunity to enter the child's world. In the play therapy relationship, toys are like the child's words and play is the child's language. Therefore, children play out their problems, experiences, concerns, and…

  1. Playful Learning and Montessori Education

    ERIC Educational Resources Information Center

    Lillard, Angeline S.

    2013-01-01

    Although Montessori education is often considered a form of playful learning, Maria Montessori herself spoke negatively about a major component of playful learning--pretend play, or fantasy--for young children. In this essay, the author discusses this apparent contradiction: how and why Montessori education includes elements of playful learning…

  2. Music Learning and Child's Play.

    ERIC Educational Resources Information Center

    Littleton, Danette

    1998-01-01

    Reviews various studies on childs play and its relation to young childrens development in music learning processes and explores the role that cognitive and social play categories have in studying childrens play with music. Provides strategies for initiating music-play opportunities in a preschool classroom. (CMK)

  3. Playing with molecules.

    PubMed

    Toon, Adam

    2011-12-01

    Recent philosophy of science has seen a number of attempts to understand scientific models by looking to theories of fiction. In previous work, I have offered an account of models that draws on Kendall Walton's 'make-believe' theory of art. According to this account, models function as 'props' in games of make-believe, like children's dolls or toy trucks. In this paper, I assess the make-believe view through an empirical study of molecular models. I suggest that the view gains support when we look at the way that these models are used and the attitude that users take towards them. Users' interaction with molecular models suggests that they do imagine the models to be molecules, in much the same way that children imagine a doll to be a baby. Furthermore, I argue, users of molecular models imagine themselves viewing and manipulating molecules, just as children playing with a doll might imagine themselves looking at a baby or feeding it. Recognising this 'participation' in modelling, I suggest, points towards a new account of how models are used to learn about the world, and helps us to understand the value that scientists sometimes place on three-dimensional, physical models over other forms of representation. PMID:22332319

  4. Rough and Tumble Play 101

    ERIC Educational Resources Information Center

    Carlson, Frances

    2009-01-01

    Many people fear that play-fighting or rough and tumble play is the same as real fighting. There is also a fear that this rough play will become real fighting if allowed to continue. Most of all, parents and teachers fear that during the course of rough and tumble play a child may be hurt. To provide for and allow children to play rough without…

  5. Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters

    NASA Technical Reports Server (NTRS)

    Stains, Joseph P.; Lecanda, Fernando; Screen, Joanne; Towler, Dwight A.; Civitelli, Roberto

    2003-01-01

    Loss-of-function mutations of gap junction proteins, connexins, represent a mechanism of disease in a variety of tissues. We have shown that recessive (gene deletion) or dominant (connexin45 overexpression) disruption of connexin43 function results in osteoblast dysfunction and abnormal expression of osteoblast genes, including down-regulation of osteocalcin transcription. To elucidate the molecular mechanisms of gap junction-sensitive transcriptional regulation, we systematically analyzed the rat osteocalcin promoter for sensitivity to gap junctional intercellular communication. We identified an Sp1/Sp3 containing complex that assembles on a minimal element in the -70 to -57 region of the osteocalcin promoter in a gap junction-dependent manner. This CT-rich connexin-response element is necessary and sufficient to confer gap junction sensitivity to the osteocalcin proximal promoter. Repression of osteocalcin transcription occurs as a result of displacement of the stimulatory Sp1 by the inhibitory Sp3 on the promoter when gap junctional communication is perturbed. Modulation of Sp1/Sp3 recruitment also occurs on the collagen Ialpha1 promoter and translates into gap junction-sensitive transcriptional control of collagen Ialpha1 gene expression. Thus, regulation of Sp1/Sp3 recruitment to the promoter may represent a potential general mechanism for transcriptional control of target genes by signals passing through gap junctions.

  6. Playing with Switches, Birth through Two. Let's Play! Project.

    ERIC Educational Resources Information Center

    State Univ. of New York, Buffalo. Center for Assistive Technology.

    This guide to playing with switches for parents and early intervention personnel was developed by the "Let's Play! Project," a 3-year federally supported project that worked to promote play in infants and toddlers with disabilities through the use of assistive technology. Switches are used with electronic toys to help young children easily…

  7. The Significance of Play and the Environment around Play

    ERIC Educational Resources Information Center

    Vickerius, Maria; Sandberg, Anette

    2006-01-01

    The purpose of this study is to increase the knowledge and understanding of play and its significance, to illuminate play and its significance to the individual and the social interplay, and also to compare the environment around play today with adult memories of environments in childhood. The purpose of the study is also that the result and the…

  8. PlayPals: Tangible Interfaces for Remote Communication and Play

    E-print Network

    Ishii, Hiroshi

    of wireless figurines with their electronic accessories that provide children with a playful way to communicate between remote locations. PlayPals is designed for children aged 5-8 to share multimedia Play, Toys, Children. ACM Classification Keywords H5.m. Information interfaces and presentation

  9. Achromobacter denitrificans SP1 produces pharmaceutically active 25C prodigiosin upon utilizing hazardous di(2-ethylhexyl)phthalate.

    PubMed

    Pradeep, S; Sarath Josh, M K; Balachandran, S; Sudha Devi, R; Sadasivam, R; Thirugnanam, P E; Doble, Mukesh; Anderson, Robin C; Benjamin, Sailas

    2014-11-01

    This first report describes the purification and identification of an orange-red pigment produced by Achromobacter denitrificans strain SP1 (isolated from sewage sludge heavily contaminated with plastics) during its growth in a simple basal salt medium supplemented with the hazardous di(2-ethylhexyl)phthalate (DEHP) blended in PVC blood bag (in situ) or free DEHP (ex situ) as carbon source. The cell-bound pigment was elucidated, characterized at molecular level, and described as an unusual 25C prodigiosin analog for the first time. At laboratory conditions (in flasks), the dry cell mass was 75.2mg/g blood bag, which upon extraction yielded 7.1mg prodigiosin; at this stage the pH of the medium was dropped from 7.2 to 3.5. Considering its pharmaceutical importance, taking 10 known prodigiosins as controls, this 25C prodigiosin was subjected to molecular docking studies, showed comparable and promising binding efficiencies with the crucial molecular human targets like cycloxygenase-2, ZAP-70 kinase and Jak-3 kinase. PMID:25201292

  10. Playing Safe: Eliminating Hazards on Children's Playgrounds.

    ERIC Educational Resources Information Center

    Wallach, Frances

    1992-01-01

    Discusses typical playground hazards, environmental factors affecting safety in play areas, playground safety guidelines and standards established by the Consumer Product Safety Commission and the American Society of Testing Materials, and playground surfacing and equipment. Offers suggestions for reducing the number and severity of playground…

  11. Motivations for Play in Online Games

    Microsoft Academic Search

    Nick Yee

    2006-01-01

    An empirical model of player motivations in online games provides the foundation to under- stand and assess how players differ from one another and how motivations of play relate to age, gender, usage patterns, and in-game behaviors. In the current study, a factor analytic ap- proach was used to create an empirical model of player motivations. The analysis revealed 10

  12. Childhood play experiences of women in traditional and nontraditional professions

    Microsoft Academic Search

    Patricia Boyne Coats; Steven J. Overman

    1992-01-01

    One hundred ten women in both traditional and nontraditional professions were compared on childhood play and related socialization experiences. The purpose of the study was to investigate the effects that different play experiences had on career choices of professional women. A survey questionnaire on play experiences and related factors was administered to the subjects. Chi Squares and t-tests for differences

  13. Medical Play for Young Children.

    ERIC Educational Resources Information Center

    Jessee, Peggy O.; Wilson, Heidi; Morgan, Dee

    2000-01-01

    Discusses young children's emotional responses during medical examinations and procedures, developmental changes in how they conceptualize illness causation, and the role of play to reduce stress. Describes how teachers can best facilitate structured dramatic medical play therapeutically. (KB)

  14. Safety Play Surfaces Buying Guide.

    ERIC Educational Resources Information Center

    Morris, Susan

    1990-01-01

    Describes standards for playing surfaces and characteristics of play surfaces made of organic loose material, inorganic loose material, and compact materials. Necessary site preparation is discussed. An extensive, annotated list of manufacturers of surfaces is included. (DR)

  15. Melanoma upregulates ICAM-1 expression on endothelial cells through engagement of tumor CD44 with endothelial E-selectin and activation of a PKC?-p38-SP-1 pathway.

    PubMed

    Zhang, Pu; Goodrich, Chris; Fu, Changliang; Dong, Cheng

    2014-11-01

    Cancer metastasis involves multistep adhesive interactions between tumor cells (TCs) and endothelial cells (ECs), but the molecular mechanisms of intercellular communication in the tumor microenvironment remain elusive. Using static and flow coculture systems in conjunction with flow cytometry, we discovered that certain receptors on the ECs are upregulated on melanoma cell adhesion. Direct contact but not separate coculture between human umbilical endothelial cells (HUVECs) and a human melanoma cell line (Lu1205) increased intercellular adhesion molecule 1 (ICAM-1) and E-selectin expression on HUVECs by 3- and 1.5-fold, respectively, compared with HUVECs alone. The nonmetastatic cell line WM35 failed to promote ICAM-1 expression changes in HUVECs on contact. Enzyme-linked immunosorbent assay (ELISA) revealed that EC-TC contact has a synergistic effect on the expression of the cytokines interleukin (IL)-8, IL-6, and growth-related oncogene ? (Gro-?). By using E-selectin cross-linking and beads coated with CD44 immunopurified from Lu1205 cells, we showed that CD44/selectin ligation was responsible for the ICAM-1 up-regulation on HUVECs. Protein kinase C? (PKC-?) activation was found to be the downstream target of the CD44/selectin-initiated signaling, as ICAM-1 elevation was inhibited by siRNA targeting PKC? or a dominant negative form of PKC? (PKC? DN). Western blot analysis and electrophoretic mobility shift assays (EMSAs) showed that TC-EC contact mediated p38 phosphorylation and binding of the transcription factor SP-1 to its regulation site. In conclusion, CD44/selectin binding signals ICAM-1 up-regulation on the EC surface through a PKC?-p38-SP-1 pathway, which further enhances melanoma cell adhesion to ECs during metastasis. PMID:25138157

  16. Meanings of Play among Children

    ERIC Educational Resources Information Center

    Glenn, Nicole M.; Knight, Camilla J.; Holt, Nicholas L.; Spence, John C.

    2013-01-01

    The purpose of this study was to examine meanings of play among children. Thirty-eight students aged 7-9 years from a suburban public school in Western Canada participated in focus groups. Data analysis revealed participants saw almost anything as an opportunity for play and would play almost anywhere with anyone. However, they perceived parents…

  17. Play Therapy: Basics and Beyond.

    ERIC Educational Resources Information Center

    Kottman, Terry

    This book provides an atheoretical orientation to basic concepts involved in play therapy and an introduction to different skills used in play therapy. The demand for mental professionals and school counselors who have training and expertise in using play as a therapeutic tool when working with children has increased tremendously. In response to…

  18. Preschoolers' Thinking during Block Play

    ERIC Educational Resources Information Center

    Piccolo, Diana L.; Test, Joan

    2010-01-01

    Children build foundations for mathematical thinking in early play and exploration. During the preschool years, children enjoy exploring mathematical concepts--such as patterns, shape, spatial relationships, and measurement--leading them to spontaneously engage in mathematical thinking during play. Block play is one common example that engages…

  19. Playing Othello Using Monte Carlo

    Microsoft Academic Search

    J. a. m. Nijssen

    Abstract This paper deals with the construction of an AI player to play the game Othello. A lot of tech- niques are already known to let AI players play the game Othello. Some of these techniques even allow current AI players to beat even the best human,Othello players. These players use very complicated deterministic algorithms to play the game. We

  20. The Biology of Human Play.

    ERIC Educational Resources Information Center

    Byers, John A.

    1998-01-01

    Maintains that the "getting into shape" hypothesis of explaining the inverted-U distribution of exercise play across age is likely incorrect. Argues that the biological study of human physical activity play, as recommended by Pellegrini and Smith (1998), will reveal whether physical activity play represents an example of performance-dependent…

  1. Play in Evolution and Development

    ERIC Educational Resources Information Center

    Pellegrini, Anthony D.; Dupuis, Danielle; Smith, Peter K.

    2007-01-01

    In this paper we examine the role of play in human ontogeny and phylogeny, following Surplus Resource Theory. We consider how juveniles use play to sample their environment in order to develop adaptive behaviors. We speculate about how innovative behaviors developed in play in response to environmental novelty may influence subsequent evolutionary…

  2. Solar Power at Play

    NASA Astrophysics Data System (ADS)

    2007-03-01

    For the very first time, astronomers have witnessed the speeding up of an asteroid's rotation, and have shown that it is due to a theoretical effect predicted but never seen before. The international team of scientists used an armada of telescopes to discover that the asteroid's rotation period currently decreases by 1 millisecond every year, as a consequence of the heating of the asteroid's surface by the Sun. Eventually it may spin faster than any known asteroid in the solar system and even break apart. ESO PR Photo 11a/07 ESO PR Photo 11a/07 Asteroid 2000 PH5 "The Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect is believed to alter the way small bodies in the Solar System rotate," said Stephen Lowry (Queens University Belfast, UK), lead-author of one of the two companion papers in which this work is reported [1, 2]. "The warming caused by sunlight hitting the surfaces of asteroids and meteoroids leads to a gentle recoil effect as the heat is released," he added. "By analogy, if one were to shine light on a propeller over a long enough period, it would start spinning." Although this is an almost immeasurably weak force, its effect over millions of years is far from negligible. Astronomers believe the YORP effect may be responsible for spinning some asteroids up so fast that they break apart, perhaps leading to the formation of double asteroids. Others may be slowed down so that they take many days to complete a full turn. The YORP effect also plays an important role in changing the orbits of asteroids between Mars and Jupiter, including their delivery to planet-crossing orbits, such as those of near-Earth asteroids. Despite its importance, the effect has never been seen acting on a solar system body, until now. Using extensive optical and radar imaging from powerful Earth-based observatories, astronomers have directly observed the YORP effect in action on a small near-Earth asteroid, known as (54509) 2000 PH5. Shortly after its discovery in 2000, it was realised that asteroid 2000 PH5 would be the ideal candidate for such a YORP detection. With a diameter of just 114 metres, it is relatively small and so more susceptible to the effect. Also, it rotates very fast, with one 'day' on the asteroid lasting just over 12 Earth minutes, implying that the YORP effect may have been acting on it for some time. With this in mind, the team of astronomers undertook a long term monitoring campaign of the asteroid with the aim of detecting any tiny changes in its rotation speed. Over a 4-year time span, Stephen Lowry, Alan Fitzsimmons and colleagues took images of the asteroid at a range of telescope sites including ESO's 8.2-m Very Large Telescope array and 3.5-m New Technology Telescope in Chile, the 3.5-m telescope at Calar Alto, Spain, along with a suite of other telescopes from the Czech Republic, the Canary Islands, Hawaii, Spain and Chile. With these facilities the astronomers measured the slight brightness variations as the asteroid rotated. ESO PR Photo 11b/07 ESO PR Photo 11b/07 Radar Images of 2000 PH5 Over the same time period, the radar team led by Patrick Taylor and Jean-Luc Margot of Cornell University employed the unique capabilities of the Arecibo Observatory in Puerto Rico and the Goldstone radar facility in California to observe the asteroid by 'bouncing' a radar pulse off the asteroid and analysing its echo. "With this technique we can reconstruct a 3-D model of the asteroid's shape, with the necessary detail to allow a comparison between the observations and theory," said Taylor. After careful analysis of the optical data, the asteroid's spin rate was seen to steadily increase with time, at a rate that can be explained by the YORP theory. Critically, the effect was observed year after year, for more than 4 years. Furthermore, this number was elegantly supported via analysis of the combined radar and optical data, as it was required that the asteroid is increasing its spin rate at exactly this rate in order for a satisfactory 3-D shape model to be determined. ESO PR Video

  3. Parental assessment of peer play: Development and validation of the parent version of the Penn Interactive Peer Play Scale

    Microsoft Academic Search

    John Fantuzzo; Julia Mendez; Erin Tighe

    1998-01-01

    The purpose of this investigation was to evaluate the construct validity of the parent version of the Penn Interactive Peer Play Scale (PIPPS) and to compare it with the teacher version. PIPPS were collected on 297 urban Head Start children. The Parent PIPPS replicated the three-factor solution found with the teacher version, supporting the following constructs of peer play: Play

  4. The Influence of Play Context and Adult Attitudes on Young Children's Physical Risk-Taking during Outdoor Play

    ERIC Educational Resources Information Center

    Little, Helen; Wyver, Shirley; Gibson, Frances

    2011-01-01

    Many children naturally seek challenging physically active play which may involve injury-risk. Prior studies have attempted to describe the characteristics of risky play but to date none have considered factors that impact on opportunities for risky play or the likely resultant outcomes. Using semi-structured interviews and naturalistic…

  5. Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells

    Microsoft Academic Search

    Jiajun Cui; Xianfeng Meng; Xudong Gao; Guangxuan Tan

    2010-01-01

    Pokemon, which stands for POK erythroid myeloid ontogenic factor, can regulate expression of many genes and plays an important\\u000a role in tumorigenesis. Curcumin, a natural and non-toxic yellow compound, has capacity for antioxidant, free radical scavenger,\\u000a anti-inflammatory properties. Recent studies shows it is a potential inhibitor of cell proliferation in a variety of tumour\\u000a cells. To investigate whether curcumin can

  6. Genome-Wide Occupancy of SREBP1 and Its Partners NFY and SP1 Reveals Novel Functional Roles and Combinatorial Regulation of Distinct Classes of Genes

    Microsoft Academic Search

    Brian D. Reed; Alexandra E. Charos; Anna M. Szekely; Sherman M. Weissman; Michael Snyder

    2008-01-01

    The sterol regulatory element-binding protein (SREBP) family member SREBP1 is a critical transcriptional regulator of cholesterol and fatty acid metabolism and has been implicated in insulin resistance, diabetes, and other diet-related diseases. We globally identified the promoters occupied by SREBP1 and its binding partners NFY and SP1 in a human hepatocyte cell line using chromatin immunoprecipitation combined with genome tiling

  7. Understanding Young Children's Learning through Play: Building Playful Pedagogies

    ERIC Educational Resources Information Center

    Broadhead, Pat; Burt, Andy

    2011-01-01

    This timely and accessible text introduces, theorises and practically applies two important concepts which now underpin early years practice: those of "playful learning" and "playful pedagogies". Pat Broadhead and Andy Burt draw upon filmed material, conversations with children, reflection, observation, and parental and staff interviews, in their…

  8. Playing with the Multiple Intelligences: How Play Helps Them Grow

    ERIC Educational Resources Information Center

    Eberle, Scott G.

    2011-01-01

    Howard Gardner first posited a list of "multiple intelligences" as a liberating alternative to the assumptions underlying traditional IQ testing in his widely read study "Frames of Mind" (1983). Play has appeared only in passing in Gardner's thinking about intelligence, however, even though play instructs and trains the verbal, interpersonal,…

  9. The Influence of Play Material on Discourse during Play.

    ERIC Educational Resources Information Center

    Burroughs, Elizabeth I.; Murray, Sharon E.

    1992-01-01

    Evaluation of the conversational behavior of 36 children (ages 48-59 months) playing in dyads with 3 different materials (modeling dough, a farm set, and animal puppets) found that each toy elicited the same amount of talking, though there were differences in discourse structure attributable to play materials. (DB)

  10. Plays in Performance and Review

    E-print Network

    1983-04-01

    SPRING 1983 95 Plays in Performance and Review Tres Marías y una Rosa at the University of Texas Tres Marías y una Rosa was recently performed by the students of Miriam Balboa Echeverría's Spanish Play Production class at the University of Texas... at Austin. The theater class, which Echeverría has taught each spring since 1978, previously has performed such plays as Arrabal's Cementerio de auto móviles, Calderón's Casa con dos puertas, mala es de guardar and Vargas Llosa's La señorita de Tacna...

  11. Interferon-? induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells.

    PubMed

    Zhang, Jiarong; Li, Shuangdi; Yan, Qin; Chen, Xiaoyue; Yang, Yixia; Liu, Xuelian; Wan, Xiaoping

    2013-01-01

    Infection by human papillomavirus (HPV) can cause cervical intraepithelial neoplasia (CIN) and cancer. Down-regulation of E6 and E7 expression may be responsible for the positive clinical outcomes observed with IFN treatment, but the molecular basis has not been well determined. As miRNAs play an important role in HPV induced cervical carcinogenesis, we hypothesize that IFN-? can regulate the expressions of specific miRNAs in cervical cancer cells, and that these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic potential. In this study, we found that miR-129-5p to be a candidate IFN-? inducible miRNA. MiR-129-5p levels gradually decrease with the development of cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela cells. This study is the first report of a cellular miRNA with anti-HPV activity and provides new insights into regulatory mechanisms between the HPV and the IFN system in host cells at the miRNA level. PMID:24358111

  12. Social Studies "Play" in Kindergarten.

    ERIC Educational Resources Information Center

    Labbo, Linda D.

    1998-01-01

    Believes structured playtime that occurs in a well-designed play center can provide rich opportunities for young children to construct knowledge related to both social studies and literacy. Expounds how elementary teachers can create an integrated play center by collaborating with their students on the design, implementation, and response to the…

  13. Sand and Water Table Play

    ERIC Educational Resources Information Center

    Wallace, Ann H.; White, Mary J.; Stone, Ryan

    2010-01-01

    The authors observed preschoolers engaged at the sand and water table to determine if math could be found within their play. Wanting to understand how children interact with provided materials and what kinds of math ideas they explore during these interactions, the authors offer practical examples of how such play can promote mathematical…

  14. Invention at Play. Educators' Manual.

    ERIC Educational Resources Information Center

    Judd, Michael; Lacasse, Jane; Smith, Monica; Reilly, Katie

    A Smithsonian exhibition was developed that looked at invention in an innovative way. It aimed to encourage visitors to make connections between their own lives and abilities and those of inventors. The role of play in the invention process was examined. Play is a universal and familiar activity and can help people find the link between their own…

  15. Principles of Play for Soccer

    ERIC Educational Resources Information Center

    Ouellette, John

    2004-01-01

    Soccer coaches must understand the principles of play if they want to succeed. The principles of play are the rules of action that support the basic objectives of soccer and the foundation of a soccer coaching strategy. They serve as a set of permanent criteria that coaches can use to evaluate the efforts of their team. In this article, the author…

  16. The Play of Socratic Dialogue

    ERIC Educational Resources Information Center

    Smith, Richard

    2011-01-01

    Proponents of philosophy for children generally see themselves as heirs to the "Socratic" tradition. They often claim too that children's aptitude for play leads them naturally to play with abstract, philosophical ideas. However in Plato's dialogues we find in the mouth of "Socrates" many warnings against philosophising with the young. Those…

  17. Puzzle Play Improves Math Skills

    NSDL National Science Digital Library

    2012-02-16

    This brief press release from the National Science Foundation summarizes the results of a University of Chicago study linking puzzle play with math skills. The study found that puzzle play proved to be a significant predictor of spatial skills. The study also found gender differences in child/parent interactions and in acquired skills.

  18. Niger Delta play types, Nigeria

    SciTech Connect

    Akinpelu, A.O. [Chevron Nigeria Limited, Lagos (Nigeria)

    1995-08-01

    Exploration databases can be more valuable when sorted by play type. Play specific databases provide a system to organize E & P data used in evaluating the range of values of parameters for reserve estimation and risk assessment. It is important both in focusing the knowledge base and in orienting research effort. A play in this context is any unique combination of trap, reservoir and source properties with the right dynamics of migration and preservation that results in hydrocarbon accumulation. This definitions helps us to discriminate the subtle differences found with these accumulation settings. About 20 play types were identified around the Niger Delta oil province in Nigeria. These are grouped into three parts: (1) The proven plays-constituting the bulk of exploration prospects in Nigeria today. (2) The unproven or semi-proven plays usually with some successes recorded in a few tries but where knowledge is still inadequate. (3) The unproven or analogous play concept. These are untested but geologically sound ideas which may or may not have been tried elsewhere. With classification and sub grouping of these play types into specific databases, intrinsic attributes and uniqueness of each of them with respect to the four major risk elements and the eight parameters for reserve estimation can be better understood.

  19. Critical Play Radical Game Design

    E-print Network

    , as in casual games, or in more comprehensive games both on- and offline, such as the multiplayer PC game WorldCritical Play Radical Game Design Mary Flanagan The MIT Press Cambridge, Massachusetts London Cataloging-in-Publication Data Flanagan, Mary, 1969­ Critical play : radical game design / Mary Flanagan. p

  20. Transmedia Play: Literacy across Media

    ERIC Educational Resources Information Center

    Alper, Meryl; Herr-Stephenson, Rebecca

    2013-01-01

    Transmedia play is a new way to understand how children develop critical media literacy and new media literacies through their interactions with contemporary media that links stories and structures across platforms. This essay highlights five characteristics of transmedia play that make it particularly useful for learning:…

  1. Empowering Groups that Enable Play

    ERIC Educational Resources Information Center

    Wilson, David Sloan; Marshall, Danielle; Iserhott, Hindi

    2011-01-01

    Creating play environments for children usually requires groups of adults working together. An extensive scientific literature describes how groups function to achieve shared goals in general terms, and groups attempting to empower play may find this literature useful. Design principles for managing natural resources, identified by Elinor Ostrom…

  2. The Social Competence of Play.

    ERIC Educational Resources Information Center

    Fein, Greta G.

    This is a study of how young children gain social competence through pretend play or role playing. Subjects were 38 Caucasian children (19 females, 19 males) who were observed at four ages: 12, 18, 24 and 30 months. The same set of toys, which included a doll, a saucepan, doll bottles, coffee mug, teacup, teaspoon, doll crib, blanket, toy phone…

  3. Including "Everyone" in Outdoor Play.

    ERIC Educational Resources Information Center

    Flynn, Lynda L.; Kieff, Judith

    2002-01-01

    Presents guidelines for outdoor play that are important when young children have special needs. Details a decision-making process for planning adaptations and practical strategies for making adaptations and interventions to enhance outdoor play for children with special needs. Lists adaptations for a child who is blind, is deaf, has physical…

  4. Play Therapy with Special Populations.

    ERIC Educational Resources Information Center

    Carmichael, Karla D.

    This paper notes that therapists often feel unqualified to deal with special populations of children because of a lack of understanding of the universalness of play therapy. Suggestions are offered for beginning play therapists who may work with a number of special populations of children. It is recommended that the social learning approach to…

  5. MAJOR OIL PLAYS IN UTAH AND VICINITY

    SciTech Connect

    Thomas C. Chidsey, Jr.

    2003-04-01

    Utah oil fields have produced a total of 1.2 billion barrels (191 million m{sup 3}). However, the 15 million barrels (2.4 million m{sup 3}) of production in 2000 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play; locations of major oil pipelines; descriptions of reservoir outcrop analogs; and identification and discussion of land use constraints. All play maps, reports, databases, and so forth, produced for the project will be published in interactive, menu-driven digital (web-based and compact disc) and hard-copy formats. This report covers research activities for the second quarter of the first project year (October 1 through December 31, 2002). This work included (1) gathering field and pipeline data to produce a digital oil and gas field and pipeline map, and (2) Uinta Basin well database compilation. The oil and gas field map will help to delineate the various oil plays to be described later in the project. The map will also identify CO{sub 2} resources, and will be useful in the planning and economic evaluation of best practices using CO{sub 2} to flood mature oil reservoirs. The play descriptions will be enhanced with the updated oil and gas pipeline map. It can be used to plan economic evaluation of exploration activities and field development, particularly if H{sub 2}S is produced or CO{sub 2} in needed for best practices. Well databases developed for the project will better define the limits of oil plays in the Uinta Basin and evaluate shows for potential new plays in the basin. Technology transfer activities consisted of a technical presentation to the Utah Stake Holder Board Members belonging to the Uinta Basin Oil and Gas Collaborative Group. The project home page was updated on the Utah Geological Survey Internet web site.

  6. Elementary GLOBE: Earth System Play

    NSDL National Science Digital Library

    2008-12-01

    The class will brainstorm, write, create, and produce a play in which they represent how all the Earth systems are interconnected. This play can be based on the Elementary GLOBE book "All About Earth: Our World on Stage" or on other student-generated topics representing interconnections of the Earth systems. The purpose of the play is to serve as a performance assessment providing students with the opportunity to display what they have learned about the Earth as a system in a creative manner. Through this activity, students will demonstrate their knowledge of how the hydrosphere, atmosphere, geosphere and biosphere interact.

  7. Genome-wide analysis of murine bone marrow-derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells

    PubMed Central

    MIERZEJEWSKA, KATARZYNA; HEO, JINBEOM; KANG, JEONG WOOK; KANG, HYUNSOOK; RATAJCZAK, JANINA; RATAJCZAK, MARIUSZ Z.; KUCIA, MAGDA; SHIN, DONG-MYUNG

    2013-01-01

    It has been postulated that the most primitive population of stem cells, Oct4+Sca-1+Lin?CD45? very small embryonic-like stem cells (VSELs), differentiate into tissue-committed stem cells in adult mice. However, Oct4+ VSELs remain quiescent in adult tissues and do not form teratomas. In thi study, we report the characteristics of the VSEL transcriptome by gene set enrichment analysis employing a microarray database established from 20 murine bone marrow-derived, FACS-sorted VSELs in comparison with hematopoietic stem cells and embryonic stem cells. In the Oct4+ VSELs, we observed the upregulation of tissue-specific gene sets and a gene set encoding the complement-coagulation cascade. By contrast, in the VSELs, we observed the downregulation of genes involved in the UV radiation response, mRNA processing and mitogenic growth factor signaling [e.g., insulin-like growth factor-1 (IGF-1) and neurotrophic tyrosine kinase receptor A (TRKA), as well as the ERK and PI3K pathways]. Employing leading-edge subset analysis and real-time PCR assays, we observed that several genes, such as growth factor receptor-bound protein 2 (GRB2), son of sevenless homolog 1 (SOS1), SHC (Src homology 2 domain containing) transforming protein 1 (SHC1), mitogen-activated protein kinase kinase 1 (MAP2K1), v-akt murine thymoma viral oncogene homolog 3 (AKT3), ELK1, ribosomal protein S6 kinase, 90kDa, polypeptide 3 (RPS6KA3), glycogen synthase kinase 3? (GSK3?) and casein kinase 2, alpha 1 polypeptide (CSNK2A1), which are involved in mitogenic growth factor signaling pathways, were commonly downregulated in the VSELs. Notably, this repression was reversed in the VSELs co-cultured over a C2C12 supportive cell-line, whereby they are induced to form VSEL-derived spheres (VSEL-DSs); thus, they are enriched, forming more differentiated stem cells. Therefore, we suggest that the repression of mitogenic growth factor signaling (e.g., through the IGF-1 receptor) may prevent uncontrolled Oct4+ VSEL proliferation and teratoma formation. Thus, restoring the responsiveness to mitogenic growth factors may be a crucial step in employing these cells in regenerative medicine. PMID:23708325

  8. Analytical Chemistry Role Playing Experiments

    NSDL National Science Digital Library

    2011-04-14

    This page features a number of laboratory experiments (available for download in PDF format) which allow students the opportunity to role play in groups to solve problems. Experiments involve titrations, gravimetry, atomic absorption, chromatography.

  9. Design guidance for play spaces

    E-print Network

    , the woodland site and the play location (which may relate to its geography, geology, history or natural history of plastic or powder coated steel. ­ Do not fall into the trap of going immediately to a supplier

  10. The Play Dough Evaluation Project

    NSDL National Science Digital Library

    Mary Heckscher

    2006-02-01

    Fourth-grade students gain a deeper understanding of the meaning of "properties" by evaluating and comparing play doughs. Students also hone their observation and reporting skills and enrich their vocabulary, integrating language arts into this activity.

  11. Src-family kinases play an essential role in differentiation signaling downstream of macrophage colony-stimulating factor receptors mediating persistent phosphorylation of phospholipase C-?2 and MAP kinases ERK1 and ERK2

    Microsoft Academic Search

    C Bourgin-Hierle; S Gobert-Gosse; J Thérier; M-F Grasset; G Mouchiroud

    2008-01-01

    Macrophage colony-stimulating factor (M-CSF) has been found to be involved in multiple developmental processes, especially production of cells belonging to the mononuclear phagocyte system. The decision of myeloid progenitor cells to commit to differentiation depends on activation levels of the mitogen-activated protein kinases (MAPK), ERK1 and ERK2. Using the murine myeloid progenitor cell line FD-Fms, we show here that persistent

  12. Three Plays of Egon Wolff.

    E-print Network

    Peden, Margaret S.

    1969-10-01

    real situation. . . ." Wolff is obviously primarily concerned with the expression of ideas, although he specifically decries plays that "are like intellectual hothouses in which ideas struggle in vain to reach the air." Mansión de lechuzas develops.... This theme is, of course, inextricably linked with the second, the destruction of the old by the new. There is an almost text-book progres sion of treatment of this theme in the three plays discussed. In Mansión . . . the entrance of "that outside...

  13. Play by Playbook: The Collected Zebracon Plays 

    E-print Network

    Smith, Paula

    1995-01-01

    : Ruth Kurz Rooster, Coronor: Edith Crowe Princess: Connie Faddis I've been writing or helping with fannish plays since 1976. In 1981, Kendra Hunter phoned me and said that forZebraCon 2, there should be a Starsky & Hutch play. "And we thinkyou should... an all-singing, all-dancing version of, say, Graven Images ... hmm..." Kendra was also responsible for us doing the "kiss in the alley" in stop-start freeze-frame mode. I have never heard an audience bellylaugh like that before. Or since. _7_ Graven...

  14. Play and culture: a study of English and Asian children

    Microsoft Academic Search

    Elizabeth Child

    1983-01-01

    The investigation described in this paper examines the relevance of social factors to variations in preschool children's play behaviour. The research was carried out by direct observation in three virtually identical playbuses (obsolete buses converted to mobile play-centres) which catered for children below school age in different areas of Birmingham where the population was made up of a variety of

  15. Evidence for cooperative mineralization of diuron by Arthrobacter sp. BS2 and Achromobacter sp. SP1 isolated from a mixed culture enriched from diuron exposed environments.

    PubMed

    Devers-Lamrani, Marion; Pesce, Stéphane; Rouard, Nadine; Martin-Laurent, Fabrice

    2014-12-01

    Diuron was found to be mineralized in buffer strip soil (BS) and in the sediments (SED) of the Morcille river in the Beaujolais vineyard repeatedly treated with this herbicide. Enrichment cultures from BS and SED samples led to the isolation of three bacterial strains transforming diuron to 3,4-dichloroaniline (3,4-DCA) its aniline derivative. 16S rRNA sequencing revealed that they belonged to the genus Arthrobacter (99% of similarity to Arthrobacter globiformis strain K01-01) and were designated as Arthrobacter sp. BS1, BS2 and SED1. Diuron-degrading potential characterized by sequencing of the puhA gene, characterizing the diuron-degradaing potential, revealed 99% similarity to A. globiformis strain D47 puhA gene isolated a decade ago in the UK. These isolates were also able to use chlorotoluron for their growth. Although able to degrade linuron and monolinuron to related aniline derivatives they were not growing on them. Enrichment cultures led to the isolation of a strain from the sediments entirely degrading 3,4-DCA. 16S rRNA sequence analysis showed that it was affiliated to the genus Achromobacter (99% of similarity to Achromobacter sp. CH1) and was designated as Achromobacter sp. SP1. The dcaQ gene encoding enzyme responsible for the transformation of 3,4-DCA to chlorocatechol was found in SP1 with 99% similarity to that of Comamonas testosteroni WDL7. This isolate also used for its growth a range of anilines (3-chloro-4-methyl-aniline, 4-isopropylaniline, 4-chloroaniline, 3-chloroaniline, 4-bromoaniline). The mixed culture composed of BS2 and SP1 strains entirely mineralizes (14)C-diuron to (14)CO2. Diuron-mineralization observed in the enrichment culture could result from the metabolic cooperation between these two populations. PMID:25061887

  16. Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma

    PubMed Central

    Kong, Ling-Min; Liao, Cheng-Gong; Chen, Liang; Yang, Hu-Shan; Zhang, Si-He; Zhang, Zheng; Bian, Hui-Jie; Xing, Jin-Liang; Chen, Zhi-Nan

    2011-01-01

    Abstract CD147 is a transmembrane glycoprotein overexpressed in human hepatocellular carcinoma (HCC) which could promote HCC progression and metastasis. Promoter methylation is one of the most important processes in gene regulation. In this study, we aim to investigate CD147 promoter methylation status and the correlation with clinicopathological features and prognosis in HCC. CD147 promoter methylation statuses and expression levels in normal and HCC cell lines and 54 paired HCC and adjacent non-tumour (ANT) tissues were, respectively, examined by bisulphite genomic sequencing, methylation-specific PCR, real-time RT-PCR, Western blot and immunohistochemistry. The correlations of promoter methylation statuses with CD147 expression level and the clinicopathological features were statistically analysed in HCC patients. Significantly higher expression of CD147 and significantly lower promoter methylation level were observed in HCC cell lines compared to normal cell lines and tissues control. In vivo and in vitro analysis indicated that demethylation with 5-Aza-2?-deoxycytidine led to increased CD147 expression through enhancing Sp1 binding affinity, and methylation with methyltransferase reduced CD147 transcriptional activity through interfering Sp1 binding. CD147 promoter methylation level in HCC tissues (22.22%) was lower than that in ANT tissues (46.30%; P < 0.05). Within HCC tissues, a significant inverse correlation was observed between CD147 expression and methylation level (r=?0.615). Moreover, HCC patients with unmethylated CD147 promoter had a significantly higher recurrence rate (88.1%versus 58.3%; P < 0.05) and death rate (83.3%versus 50.0%; P < 0.05) than patients with methylated CD147 promoter. In conclusions, promoter hypomethylation up-regulates CD147 expression primarily through increasing Sp1 binding and associates with poor prognosis in HCC patients. PMID:20629990

  17. MiR-200b expression in breast cancer: a prognostic marker and act on cell proliferation and apoptosis by targeting Sp1.

    PubMed

    Yao, YaSai; Hu, Jian; Shen, Zan; Yao, RuYong; Liu, ShiHai; Li, Yong; Cong, Hui; Wang, XinGang; Qiu, WenSheng; Yue, Lu

    2015-04-01

    MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells. In the present study, we investigated the roles and mechanisms of miR-200b in human breast cancer (BC). MiR-200b expression was carried out by qRT-PCR in human BC cell lines and clinical samples and the prognostic potential of miR-200b expression was further evaluated. In vitro, effects of miR-200b on BC cell proliferation, apoptosis and cell cycle distribution were tested by CCK-8 kit, flow cytometric analysis respectively. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-200b after the preliminary screening by employing open access software. We found that miR-200b was significantly down-regulated in both BC tissues and cell lines. The low expression of miR-200b was correlated with late TNM stage, negative oestrogen receptor and positive HER-2 status. Multivariate analysis showed that miR-200b expression was an independent prognostic predictor for BC patients. Integrated analysis identified Sp1 as a direct and functional target of miR-200b. Knockdown of Sp1 inhibited cell proliferation, induce apoptosis and act on cell cycle resembling that of miR-200b high expression. Our data demonstrates that miR-200b has potential to serve as prognostic biomarker and tumour suppressor for BC patients. As a direct and functional target of miR-200b, Sp1 and miR-200b both could be an exciting target for BC treatment strategy. PMID:25639535

  18. MiR-200b expression in breast cancer: a prognostic marker and act on cell proliferation and apoptosis by targeting Sp1

    PubMed Central

    Yao, YaSai; Hu, Jian; Shen, Zan; Yao, RuYong; Liu, ShiHai; Li, Yong; Cong, Hui; Wang, XinGang; Qiu, WenSheng; Yue, Lu

    2015-01-01

    MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells. In the present study, we investigated the roles and mechanisms of miR-200b in human breast cancer (BC). MiR-200b expression was carried out by qRT-PCR in human BC cell lines and clinical samples and the prognostic potential of miR-200b expression was further evaluated. In vitro, effects of miR-200b on BC cell proliferation, apoptosis and cell cycle distribution were tested by CCK-8 kit, flow cytometric analysis respectively. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-200b after the preliminary screening by employing open access software. We found that miR-200b was significantly down-regulated in both BC tissues and cell lines. The low expression of miR-200b was correlated with late TNM stage, negative oestrogen receptor and positive HER-2 status. Multivariate analysis showed that miR-200b expression was an independent prognostic predictor for BC patients. Integrated analysis identified Sp1 as a direct and functional target of miR-200b. Knockdown of Sp1 inhibited cell proliferation, induce apoptosis and act on cell cycle resembling that of miR-200b high expression. Our data demonstrates that miR-200b has potential to serve as prognostic biomarker and tumour suppressor for BC patients. As a direct and functional target of miR-200b, Sp1 and miR-200b both could be an exciting target for BC treatment strategy. PMID:25639535

  19. Induction of p53-independent apoptosis by a novel synthetic hexahydrocannabinol analog is mediated via Sp1-dependent NSAID-activated gene-1 in colon cancer cells.

    PubMed

    Thapa, Dinesh; Babu, Dinesh; Park, Min-A; Kwak, Mi-Kyoung; Lee, Yong-Rok; Kim, Jeong Min; Kwon, Taeg Kyu; Kim, Jung-Ae

    2010-07-01

    Nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) has received greater attention as a novel molecular target for anti-cancer therapeutics in recent years. We identified a novel synthetic hexahydrocannabinol analog, LYR-8 [(1-((9S)-1-hydroxy-6,6,9-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-2-yl)ethanone)], as a potent NAG-1 and apoptosis inducer in a panel of human cancer cells. LYR-8 did not possess any affinity for cannabinoid receptor CB(1) or CB(2), which eliminates the concern about potential psychoactive side effects. LYR-8 dramatically induced NAG-1 expression and apoptosis in HCT116 (wild-type p53) and HT29 (mutant p53) colon cancer cells. The NAG-1 expression by LYR-8 was not blocked by pifithrin-alpha, a specific p53 inhibitor, which was different from doxorubicin that induced p53-dependent NAG-1 transcriptional activity. The induction of NAG-1 promoter activity by LYR-8 was strongly correlated with increased Sp1 activation as noted in various luc-promoter activities. Furthermore, pretreatment with the specific Sp1 inhibitor mithramycin A completely reversed the LYR-8-induced NAG-1 expression in both HCT116 and HT29 cells. Knockdown of NAG-1 using siRNA significantly reversed LYR-8-induced cell death in both wild-type and mutant p53-expressing colon cancer cells. Furthermore, sensitization with NAG-1 inducer sulindac sulfide synergized LYR-8-induced cell death in both colon cancer cells. These results suggest that induction of NAG-1 via Sp1 activation is a promising therapeutic approach in cancer treatment, and that a novel compound like LYR-8 could be a potent chemotherapeutic agent for colon cancers including p53-mutated cancer. PMID:20230799

  20. The influence of play context and adult attitudes on young children's physical risk?taking during outdoor play

    Microsoft Academic Search

    Helen Little; Shirley Wyver; Frances Gibson

    2011-01-01

    Many children naturally seek challenging physically active play which may involve injury?risk. Prior studies have attempted to describe the characteristics of risky play but to date none have considered factors that impact on opportunities for risky play or the likely resultant outcomes. Using semi?structured interviews and naturalistic observations, this study aimed to investigate adult attitudes towards risk?taking and whether children's

  1. Glucosamine-induced Sp1 O-GlcNAcylation ameliorates hypoxia-induced SGLT dysfunction in primary cultured renal proximal tubule cells.

    PubMed

    Suh, Han Na; Lee, Yu Jin; Kim, Mi Ok; Ryu, Jung Min; Han, Ho Jae

    2014-10-01

    The aim of this study is to determine whether GlcN could recover the endoplasmic reticulum (ER) stress-induced dysfunction of Na(+) /glucose cotransporter (SGLT) in renal proximal tubule cells (PTCs) under hypoxia. With the rabbit model, the renal ischemia induced tubulointerstitial abnormalities and decreased SGLTs expression in tubular brush-border, which were recovered by GlcN. Thus, the protective mechanism of GlcN against renal ischemia was being examined by using PTCs. Hypoxia decreased the level of protein O-GlcNAc and the expression of O-GlcNAc transferase (OGT) while increased O-GlcNAcase (OGA) and these were reversed by GlcN. Hypoxia also decreased the expression of SGLTs (SGLT1 and 2) and [(14) C]-?-methyl-D-glucopyranoside (?-MG) uptake which were recovered by GlcN and PUGNAc (OGA inhibitor). Hypoxia enhanced reactive oxygen species (ROS) and then ER stress proteins, glucose-regulated protein 78 (GRP78), and C/EBP-homologous protein (CHOP). However, the expression of GRP78 increased till 6?h and then decreased whereas CHOP increased gradually. Moreover, decreased GRP78 and increased CHOP were reversed by NAC (antioxidant) and GlcN. GlcN ameliorated hypoxia-induced decrease of O-GlcNAc modification of Sp1 but OGT or Sp1 siRNAs blocked the recovery effect of GlcN on SGLT expression and ?-MG uptake. In addition, hypoxia-decreased GRP78 and HIF-1? expression was reversed by GlcN but OGT siRNA or Sp1 siRNA ameliorated the effect of GlcN. When PTCs were transfected with GRP78 siRNA or HIF-1? siRNA, SGLT expression and ?-MG uptake was decreased. Taken together, these data suggest that GlcN-induced O-GlcNAc modified Sp1 with stimulating GRP78 and HIF-1? activity ameliorate hypoxia-induced SGLT dysfunction in renal PTCs. J. Cell. Physiol. 229: 1557-1568, 2014. © 2014 Wiley Periodicals, Inc. PMID:24591095

  2. PinX1, a Telomere Repeat-binding Factor 1 (TRF1)-interacting Protein, Maintains Telomere Integrity by Modulating TRF1 Homeostasis, the Process in Which Human Telomerase Reverse Transcriptase (hTERT) Plays Dual Roles*

    PubMed Central

    Yoo, Jeong Eun; Park, Young Nyun; Oh, Bong-Kyeong

    2014-01-01

    TRF1, a telomere-binding protein, is important for telomere protection and homeostasis. PinX1 interacts with TRF1, but the physiological consequences of their interaction in telomere protection are not yet understood. Here we investigated PinX1 function on TRF1 stability in HeLa cells. PinX1 overexpression stabilized TRF1, but PinX1 depletion by siRNA led to TRF1 degradation, TRF1 ubiquitination, and less TRF1 telomere association. The depletion also induced DNA damage responses at telomeres and chromosome instability. These telomere dysfunctional phenotypes were in fact due to TRF1 deficiency. We also report that hTERT, a catalytic component of telomerase, plays dual roles in the TRF1 steady state pathway. PinX1-mediated TRF1 stability was not observed in hTERT-negative immortal cells, but was pronounced when hTERT was ectopically expressed in the cells, suggesting that hTERT may be needed in the PinX1-mediated TRF1 stability pathway. Interestingly, the knockdown of both PinX1 and hTERT in HeLa cells stabilized TRF1, suppressed DNA damage response activation, and restored chromosome stability. In summary, our findings suggested that PinX1 may maintain telomere integrity by regulating TRF1 stability and that hTERT may act as both a positive and a negative regulator of TRF1 homeostasis in a PinX1-dependent manner. PMID:24415760

  3. MAJOR PLAYS IN UTAH AND VICINITY

    SciTech Connect

    Craig D. Morgan; Thomas C. Chidsey

    2003-11-01

    Utah oil fields have produced over 1.2 billion barrels (191 million m{sup 3}). However, the 13.7 million barrels (2.2 million m{sup 3}) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil-producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play; locations of major oil pipelines; descriptions of reservoir outcrop analogs; and identification and discussion of land-use constraints. All play maps, reports, databases, and so forth, produced for the project will be published in interactive, menu-driven digital (web-based and compact disc) and hard-copy formats. This report covers research activities for the first quarter of the second project year (July 1 through September 30, 2003). This work included (1) describing the Conventional Southern Uinta Basin Play, subplays, and outcrop reservoir analogs of the Uinta Green River Conventional Oil and Gas Assessment Unit (Eocene Green River Formation), and (2) technology transfer activities. The Conventional Oil and Gas Assessment Unit can be divided into plays having a dominantly southern sediment source (Conventional Southern Uinta Basin Play) and plays having a dominantly northern sediment source (Conventional Northern Uinta Basin Play). The Conventional Southern Uinta Basin Play is divided into six subplays: (1) conventional Uteland Butte interval, (2) conventional Castle Peak interval, (3) conventional Travis interval, (4) conventional Monument Butte interval, (5) conventional Beluga interval, and (6) conventional Duchesne interval fractured shale/marlstone. We are currently conducting basin-wide correlations to define the limits of the six subplays. Production-scale outcrop analogs provide an excellent view, often in three dimensions, of reservoir-facies characteristics and boundaries contributing to the overall heterogeneity of reservoir rocks. They can be used as a ''template'' for evaluation of data from conventional core, geophysical and petrophysical logs, and seismic surveys. Outcrop analogs for each subplay except the Travis interval are found in Indian and Nine Mile Canyons. During this quarter, the project team members submitted an abstract to the American Association of Petroleum Geologists for presentation at the 2004 annual national convention in Dallas, Texas. The project home page was updated on the Utah Geological Survey Internet web site.

  4. Purposeful Play in Rural Venezuela

    ERIC Educational Resources Information Center

    Chesterfield, Ray

    1977-01-01

    Describes how children in rural Venezuela are trained in agricultural skills by the extended family. The highly organized training encourages play and exploration as important elements in familiarzing children with implements and methods of food production. It is suggested that rural school planners draw ideas from the rural family's educative…

  5. ENGINEERING PLAY: CHILDREN'S SOFTWARE AND

    E-print Network

    Ito, Mimi

    from the children's software industry. Drawing from this material, this study describes "learning to learning and hacker subcultures, and becomes a tool for children to create their own virtual worldsENGINEERING PLAY: CHILDREN'S SOFTWARE AND THE PRODUCTIONS OF EVERYDAY LIFE A DISSERTATION SUBMITTED

  6. Interpretive Reproduction in Children's Play

    ERIC Educational Resources Information Center

    Corsaro, William A.

    2012-01-01

    The author looks at children's play from the perspective of interpretive reproduction, emphasizing the way children create their own unique peer cultures, which he defines as a set of routines, artifacts, values, and concerns that children engage in with their playmates. The article focuses on two types of routines in the peer culture of preschool…

  7. Playing Interactivity in Public Space

    Microsoft Academic Search

    2010-01-01

    Digital interactive art provokes active inputs from the audience along with enjoyable and curious experiences, which alter the way audiences perceive and experience art. Through interactivity, outcomes become discernable and manifest upon diverse multimedia interfaces. This process is referred to as “play” - the action and outcome are often deemed major elements of this process. The purpose of this study

  8. Fort Play Children Recreate Recess

    ERIC Educational Resources Information Center

    Powell, Mark

    2007-01-01

    Recess beckons well before it actually arrives. Its allure can be heard in children's lunchtime conversations as they discuss imaginary roles, plans, alliances and teams, with an obvious appetite for play and its unbounded possibility. For some children, recess provides the most important reasons to come to school. In team sports, games of chase…

  9. Percolating the Power of Play

    Microsoft Academic Search

    Sarah Faye Cohen; Timothy Miner; Laurent Nishikawa

    2007-01-01

    At a campus that percolates the power and promise of play, the Champlain College Library asked students from our Electronic Game Design Program and the Emergent Media Center to create a game to comple- ment our Information Literacy (IL) program. Little did we know that this collaboration would lead us to question and re-envision what we mean by informa- tion

  10. Outdoor Play: Occupation in Context

    Microsoft Academic Search

    Linn Wakeford; Roger Ideishi; Judith Olson; Petra Kern

    2006-01-01

    Research indicates that playgrounds and other outdoor environments offer children important opportunities for play, learning and social participation that differ from those offered by indoor environments (DeBord, Hestenes, Moore, Cosco, & McGinnis, 2002; Nabors, Willoughby, & McManamin, 2001). In addition, inclusion, group membership and meaningful participation are all challenges presented when the playground environment anc activities do not match the

  11. Obama Plays Cheerleader for STEM

    ERIC Educational Resources Information Center

    Robelen, Erik W.

    2010-01-01

    Amid a struggling economy, a raft of foreign-policy headaches, and the tail end of a heated campaign season, President Barack Obama carved out time in his schedule last month to watch students in the State Dining Room demonstrate a solar-powered model car, a water-purification system, and a soccer-playing robot. The science fair was the fifth…

  12. Sculpting Cells with Play Doh.

    ERIC Educational Resources Information Center

    Way, Virginia A.

    1982-01-01

    Suggests using Play Doh to mold models of the nucleus, mitochondria, and inner cellular structures. Students can conceptualize the cell's structures as three-dimensional even though they appear two-dimensional under a microscope. Includes instructions for preparing homemade dough. (Author/JN)

  13. Playing Piano across the Curriculum.

    ERIC Educational Resources Information Center

    Hamel, Barbara L.

    2000-01-01

    Contends that the amount of piano study required of music education majors to pass the piano proficiency examination is insufficient. States that keyboarding across the curriculum will enable music education majors to become proficient in playing the piano. Offers suggestions for including the keyboard within other courses. (CMK)

  14. Human cytomegalovirus hyperimmune globulin not only neutralizes HCMV infectivity, but also inhibits HCMV-induced intracellular NF-kappaB, Sp1, and PI3-K signaling pathways.

    PubMed

    Andreoni, Kenneth A; Wang, Xin; Huang, Shu-Mei; Huang, Eng-Shang

    2002-05-01

    Inhibition of virus-induced intracellular signaling pathways and viral infectivity are our ultimate goals in the development of effective antiviral agents to control human cytomegalovirus (HCMV) infections. The HCMV hyperimmune globulin may meet such criteria. In a human embryonic lung (HEL) fibroblast culture model, pretreatment of Towne strain HCMV with HCMV hyperimmune globulin was shown to inhibit viral infectivity successfully, as measured by a standard plaque assay. The extracellular viral titers and extracellular viral DNA, as measured by plaque assay and PCR, respectively, were also decreased. In addition, the HCMV hyperimmune globulin prevented HCMV from inducing the intracellular activation of NF-kappaB, Sp-1, and PI3-K signaling pathways. The PI3-K pathway was examined by following phosphorylation (activation) of two of its downstream kinases, Akt and p70S6K. HCMV hyperimmune globulin also prevented the production of immediate early, early, and late viral proteins. These studies show that HCMV hyperimmune globulin neutralization of HCMV prevents the earliest known events observed after viral envelope glycoproteins bind their cell membrane receptors, i.e., NF-kappaB, Sp-1 and PI3-K activation. This suggests that HCMV hyperimmune globulin not only can inhibit viral infectivity, but can also prevent the abnormal cellular signaling that may induce unwanted cellular proliferation or cytokine synthesis. PMID:11920815

  15. Preferential binding of anti-cancer drug adriamycin to the Sp1 binding site in c-met promoter region: A spectroscopic and molecular modeling study

    NASA Astrophysics Data System (ADS)

    Singhal, Garima; Rajeswari, Moganty R.

    2009-02-01

    The c-met gene encodes a transmembrane glycoprotein receptor with tyrosine kinase activity and overexpression of MET receptor is found in a number of common human malignancies. Regulation of c-met oncogene expression in general can be controlled by several DNA binding anti-cancer drugs. Interaction of adriamycin with a short oligonucleotide (24RY), which is part of the positive regulatory element (-233 to -68) in c-met gene was studied using UV-Vis absorption and fluorescence spectroscopy, UV-thermal melting, and molecular modeling. Strong binding of adriamycin to 24RY (overall binding constant K, 1- 3 × 10 5 M -1) is thermodynamically favored and is accompanied by the following: a marked increase in the melting temperature of 24RY by +15 °C and ˜60% decrease in absorption at 480 nm, ˜80% quenching of fluorescence at 555 nm along with a blue shift of the ?emimax to 522 nm of adriamycin. Present data reveals that adriamycin binds to ˜ 5 bp (GCGGG) of the Sp1 binding site in 24RY and thus competes with Sp1 binding to the promoter site which results in down-regulation of kinase. Therefore, targeting c-met is a promising approach as it is an attractive novel oncogene for cancer therapeutics.

  16. Processing of SP1 precursor in a cell-free system from poly(A+) mRNA of human placenta.

    PubMed

    Bocco, J L; Panzetta, G M; Flury, A; Patrito, L C

    1988-01-01

    Cell-free translation of polyadenylated mRNA from human term placenta in a wheat germ extract, after immunoprecipitation with antibodies directed against purified pregnant serum SP1, yielded a single polypeptide of 31 kDa. Addition of dog pancreatic microsomal vesicles to the translation system resulted in the appearance of two polypeptides, one of them of 46 kDa and the other of 28 kDa. Both polypeptides were protected from limited proteolysis and when the assay was performed with lytic detergent concentrations in addition to proteases, this protection was abolished indicating that the polypeptides were segregated into the microsomal vesicles. The cleavage of a signal peptide of 3 kDa from the 31 kDa primary translation product gives rise to 28 kDa and accounts for the slight increase in electrophoretic mobility. The treatment of the immunoprecipitated products with Endoglycosidase H and alpha-mannosidase, suggested that only the 46 kDa polypeptide is a glycoprotein. From the results obtained we conclude that SP1 is synthesized and processed to a glycoprotein of 46 kDa which would be a protomeric form of the oligomers reported in pregnant serum by other authors. PMID:3262195

  17. Extraversion and Computer Game Play: Who Plays What Games?

    Microsoft Academic Search

    Xiaowen Fang; Miaoqi Zhu

    \\u000a In the last two years, our research group has been conducting online surveys on enjoyment of computer game play and player\\u000a personalities. From the preliminary data we collected as of now, we observed positive relationship between the personality\\u000a trait, extraversion, and players’ choice of games. This paper presents a research project that attempts to explore this relationship\\u000a and investigate the

  18. Using the Method of Ethology To Study Australian Preschool Children's Play and Social Behaviour.

    ERIC Educational Resources Information Center

    Rolfe, Sharne A.; Crossley, Stella A.

    1997-01-01

    Evaluated the ethological approach in studying children's interactions and play in an Australian preschool. Factor analysis yielded a gender-linked factor loading on looking and playing house, a physical activity factor, and a sociability factor. Findings suggest that though time consuming and labor-intensive, this approach can provide unique…

  19. Symbolic Play in Preschool and Primary Settings.

    ERIC Educational Resources Information Center

    Nourot, Patricia Moninghan; Van Hoorn, Judith L.

    1991-01-01

    A review of research on children's symbolic play discusses ways for teachers to (1) defend the inclusion of play in the curriculum; (2) understand and respect differences in the ways children play; and (3) facilitate play in the classroom. Discusses the complexity of play and the controversy about play as part of the curriculum. (GLR)

  20. Molecular mechanism for cooperation between Sp1 and steroidogenic factor-1 (SF1) to regulate bovine CYP11A gene expression

    Microsoft Academic Search

    Zheng Liu; Evan R. Simpson

    1999-01-01

    Bovine cholesterol side-chain cleavage cytochrome P450 (P450scc; product of the CYP11A gene) gene expression is regulated by gonadotropins via cAMP in the ovary, and by ACTH via cAMP in adrenal cortical cells. Previously, we characterized response elements located at ?57\\/?32 and at ?111\\/?101 bp in the 5?-flanking region of the bovine CYP11A gene required for cAMP-stimulated transcription in both mouse

  1. Playing Games with Quantum Mechanics

    E-print Network

    Simon J. D. Phoenix; Faisal Shah Khan

    2012-02-22

    We present a perspective on quantum games that focuses on the physical aspects of the quantities that are used to implement a game. If a game is to be played, it has to be played with objects and actions that have some physical existence. We call such games playable. By focusing on the notion of playability for games we can more clearly see the distinction between classical and quantum games and tackle the thorny issue of what it means to quantize a game. The approach we take can more properly be thought of as gaming the quantum rather than quantizing a game and we find that in this perspective we can think of a complete quantum game, for a given set of preferences, as representing a single family of quantum games with many different playable versions. The versions of Quantum Prisoners Dilemma presented in the literature can therefore be thought of specific instances of the single family of Quantum Prisoner's Dilemma with respect to a particular measurement. The conditions for equilibrium are given for playable quantum games both in terms of expected outcomes and a geometric approach. We discuss how any quantum game can be simulated with a classical game played with classical coins as far as the strategy selections and expected outcomes are concerned.

  2. Subtypes of Nonsocial Play and Psychosocial Adjustment in Malaysian Preschool Children

    ERIC Educational Resources Information Center

    Choo, Mei Sze; Xu, Yiyuan; Haron, P. Fatimah

    2012-01-01

    This study examined subtypes of nonsocial play and their relation to psychosocial adjustment in Malaysian preschool children (N = 141, 72 boys, M age = 4.65 years). Confirmatory factor analyses revealed that a three-factor model that distinguished social reticence, solitary-active play, and solitary-passive play fit the data reasonably well, and…

  3. MAJOR OIL PLAYS IN UTAH AND VICINITY

    SciTech Connect

    Thomas C. Chidsey Jr; Craig D. Morgan; Roger L. Bon

    2003-07-01

    Utah oil fields have produced over 1.2 billion barrels (191 million m{sup 3}). However, the 13.7 million barrels (2.2 million m{sup 3}) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play; locations of major oil pipelines; descriptions of reservoir outcrop analogs; and identification and discussion of land use constraints. All play maps, reports, databases, and so forth, produced for the project will be published in interactive, menu-driven digital (web-based and compact disc) and hard-copy formats. This report covers research activities for the third quarter of the first project year (January 1 through March 31, 2003). This work included gathering field data and analyzing best practices in the eastern Uinta Basin, Utah, and the Colorado portion of the Paradox Basin. Best practices used in oil fields of the eastern Uinta Basin consist of conversion of all geophysical well logs into digital form, running small fracture treatments, fingerprinting oil samples from each producing zone, running spinner surveys biannually, mapping each producing zone, and drilling on 80-acre (32 ha) spacing. These practices ensure that induced fractures do not extend vertically out of the intended zone, determine the percentage each zone contributes to the overall production of the well, identify areas that may be by-passed by a waterflood, and prevent rapid water breakthrough. In the eastern Paradox Basin, Colorado, optimal drilling, development, and production practices consist of increasing the mud weight during drilling operations before penetrating the overpressured Desert Creek zone; centralizing treatment facilities; and mixing produced water from pumping oil wells with non-reservoir water and injecting the mixture into the reservoir downdip to reduce salt precipitation, dispose of produced water, and maintain reservoir pressure to create a low-cost waterflood. During this quarter, technology transfer activities consisted of technical presentations to members of the Technical Advisory Board in Colorado and the Colorado Geological Survey. The project home page was updated on the Utah Geological Survey Internet web site.

  4. Caring About Kids: The Importance of Play.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHHS), Rockville, MD. Div. of Scientific and Public Information.

    In several brief sections, this pamphlet defines play, discusses how play helps a child develop, and how play changes as a child grows older, indicates the role of toys and certain play activities in promoting sex stereotypes, and identifies the role of fantasy and imagination in children's play. A discussion of the role of parents in fostering…

  5. [Gymnophallus rebecqui n. sp. (syn. Parvatrema sp. 1, J. Rebecq, 1964) (Digenea: Gymnophallidae), an intestinal parasite of ducks from Camargue (France)].

    PubMed

    Bartoli, P

    1983-01-01

    Gymnophallus rebecqui n. sp. replace Parvatrema sp. 1 J. Rebecq, 1964. Metacercariae are described. They occur free in the extrapallial space of Cerastoderma glaucum and Abra ovata, at the central part of the valves. Pallial epithelium hypertrophy is induced by metacercariae and damages are produced at the inner face of the shell of Abra ovata. Adults have been reared in laboratory hosts (Aythya ferina, A. fuligula, Anas platyrhynchos, Tadorna tadorna and Larus argentatus michaellis). Natural adults have been discovered in the anterior and median gut of Aythya ferina, A. fuligula and Anas clypeata. Adults are described and compared with other related Gymnophallid species. This new species is not a member of Parvatrema but belongs to Gymnophallus genera. PMID:6614742

  6. Excessive computer game playing among Norwegian adults: self-reported consequences of playing and association with mental health problems.

    PubMed

    Wenzel, H G; Bakken, I J; Johansson, A; Götestam, K G; Øren, Anita

    2009-12-01

    Computer games are the most advanced form of gaming. For most people, the playing is an uncomplicated leisure activity; however, for a minority the gaming becomes excessive and is associated with negative consequences. The aim of the present study was to investigate computer game-playing behaviour in the general adult Norwegian population, and to explore mental health problems and self-reported consequences of playing. The survey includes 3,405 adults 16 to 74 years old (Norway 2007, response rate 35.3%). Overall, 65.5% of the respondents reported having ever played computer games (16-29 years, 93.9%; 30-39 years, 85.0%; 40-59 years, 56.2%; 60-74 years, 25.7%). Among 2,170 players, 89.8% reported playing less than 1 hr. as a daily average over the last month, 5.0% played 1-2 hr. daily, 3.1% played 2-4 hr. daily, and 2.2% reported playing > 4 hr. daily. The strongest risk factor for playing > 4 hr. daily was being an online player, followed by male gender, and single marital status. Reported negative consequences of computer game playing increased strongly with average daily playing time. Furthermore, prevalence of self-reported sleeping problems, depression, suicide ideations, anxiety, obsessions/ compulsions, and alcohol/substance abuse increased with increasing playing time. This study showed that adult populations should also be included in research on computer game-playing behaviour and its consequences. PMID:20229923

  7. Superhero Play: What's a Teacher to Do?

    ERIC Educational Resources Information Center

    Bauer, Karen L.; Dettore, Ernest

    1997-01-01

    Examines the appeal of superheroes to children and adults' beliefs about superhero play, and suggests some potential benefits of such play. Offers examples of ways to successfully incorporate superhero play into an early childhood classroom. (Author/KB)

  8. The Various Texts of Tennessee Williams's Plays.

    ERIC Educational Resources Information Center

    Gunn, Drewey Wayne

    1978-01-01

    Presents a list of the various texts of Williams's plays which were published prior to 1977, including plays produced but not yet published. Notes the existence of unpublished versions of printed plays when such were used for a production. (JMF)

  9. The Wade Factor: Marketing? A Team Sport Worth Playing

    ERIC Educational Resources Information Center

    Perna, Mark C.

    2005-01-01

    Customer service people are the first line of marketing, sales and revenue growth. Give them the proper training and understanding to enthusiastically lead all potential students or customers through the information-gathering and sign-up process. It does not matter how many calls schools receives through a well-planned marketing campaign if the…

  10. [The "familiarity" variable in maternal role playing in preschool children].

    PubMed

    Gourdon, B; Laflaquière, A; Barré, I

    1994-01-01

    The present investigation was effected in the context of several other studies involving mother role playing with dolls in children of both sexes aged 2 to 6. Previous studies had shown an interaction between several variables: sex of the child and of the doll, absence of toys representing maternal activities, naked or clothed dolls, playing in couples of same sex or different sexes. The present study involves a new factor: degree of familiarity between children. Three variables can be distinguished in the analysis of couples of friends: (1) exploratory activities of the body of the dolls: smaller children (boys and girls) explore the body for itself whereas older girls do it while assuming a maternal role and older boys take distance from this activity. (2) Involvement in mother role playing: girls are more involved than boys, older children have richer activities than the younger. (3) Choice of activity (mother role playing or other). Observation of activities in non-friends couples emphasize two factors. The first is the same as in couples of friends (exploration of the body of the dolls), the second being the emotional tone of play sessions. Children of both sexes are diversely tolerant of the non-friends situation. This has an important impact on the quality of playing and therefore on representations of playing and on identification behaviors. Analysis of this last factor in the context of the other findings on mother role playing suggests an evolution of mother role playing behaviors and leads to reformulate the parameters involved in the construction of representations of parental roles. PMID:7972535

  11. Identification of a DNA structural motif that includes the binding sites for Sp1, p53 and GA-binding protein.

    PubMed Central

    MacLeod, M C

    1993-01-01

    We have analyzed predicted helical twist angles in the 21-bp repeat region of the SV40 genome, using a semi-empirical model previously shown to accurately predict backbone conformations. Unexpectedly, the pattern of twist angles characteristic of the six GC-boxes is repeated an additional five times at positions that are regularly interspersed with the six GC-box sequences. These patterns of helical twist angles are associated with a second, imperfectly-repeated sequence motif, the TR-box 5'-RRNTRGG. Unrelated DNA sequences that interact with trans-acting factors (p53 and GABP) exhibit similar twist angle patterns, due to elements of the general form 5'-RRRYRRR that occur as interspersed arrays with a spacing of 10-11 bp and an offset of 4-6 bp. Arrays of these elements, which we call pyrimidine sandwich elements (PSEs), may play an important role in the interaction of trans-acting factors with DNA control regions. In 13 human proto-oncogenes analyzed, we identified 31 PSE arrays, 11 of which were in the 5'-flanking regions of the genes. The most extensive array was found in the promoter region of the K-ras gene. Extending over 80 bp of DNA, it contained 16 PSEs that showed an average deviation from the SV40 criterion pattern of angles of only 1.2 degrees. PMID:8385318

  12. MAJOR OIL PLAYS IN UTAH AND VICINITY

    SciTech Connect

    Thomas C. Chidsey, Jr.

    2003-01-01

    Utah oil fields have produced a total of 1.2 billion barrels (191 million m{sup 3}). However, the 15 million barrels (2.4 million m{sup 3}) of production in 2000 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play; locations of major oil pipelines; descriptions of reservoir outcrop analogs; and identification and discussion of land use constraints. All play maps, reports, databases, and so forth, produced for the project will be published in interactive, menu-driven digital (web-based and compact disc) and hard-copy formats. This report covers research activities for the first quarter of the first project year (July 1 through September 30, 2002). This work included producing general descriptions of Utah's major petroleum provinces, gathering field data, and analyzing best practices in the Utah Wyoming thrust belt. Major Utah oil reservoirs and/or source rocks are found in Devonian through Permian, Jurassic, Cretaceous, and Tertiary rocks. Stratigraphic traps include carbonate buildups and fluvial-deltaic pinchouts, and structural traps include basement-involved and detached faulted anticlines. Best practices used in Utah's oil fields consist of waterflood, carbon-dioxide flood, gas-injection, and horizontal drilling programs. Nitrogen injection and horizontal drilling programs have been successfully employed to enhance oil production from the Jurassic Nugget Sandstone (the major thrust belt oil-producing reservoir) in Wyoming's Painter Reservoir and Ryckman Creek fields. At Painter Reservoir field a tertiary, miscible nitrogen-injection program is being conducted to raise the reservoir pressure to miscible conditions. Supplemented with water injection, the ultimate recovery will be 113 million bbls (18 million m{sup 3}) of oil (a 68 percent recovery factor over a 60-year period). The Nugget reservoir has significant heterogeneity due to both depositional facies and structural effects. These characteristics create ideal targets for horizontal wells and horizontal laterals drilled from existing vertical wells. Horizontal drilling programs were conducted in both Painter Reservoir and Ryckman Creek fields to encounter potential undrained compartments and increase the overall field recovery by 0.5 to 1.5 percent per horizontal wellbore. Technology transfer activities consisted of exhibiting a booth display of project materials at the Rocky Mountain Section meeting of the American Association of Petroleum Geologists, a technical presentation to the Wyoming State Geological Survey, and two publications. A project home page was set up on the Utah Geological Survey Internet web site.

  13. Hand kinematics of piano playing

    PubMed Central

    Flanders, Martha; Soechting, John F.

    2011-01-01

    Dexterous use of the hand represents a sophisticated sensorimotor function. In behaviors such as playing the piano, it can involve strong temporal and spatial constraints. The purpose of this study was to determine fundamental patterns of covariation of motion across joints and digits of the human hand. Joint motion was recorded while 5 expert pianists played 30 excerpts from musical pieces, which featured ?50 different tone sequences and fingering. Principal component analysis and cluster analysis using an expectation-maximization algorithm revealed that joint velocities could be categorized into several patterns, which help to simplify the description of the movements of the multiple degrees of freedom of the hand. For the thumb keystroke, two distinct patterns of joint movement covariation emerged and they depended on the spatiotemporal patterns of the task. For example, the thumb-under maneuver was clearly separated into two clusters based on the direction of hand translation along the keyboard. While the pattern of the thumb joint velocities differed between these clusters, the motions at the metacarpo-phalangeal and proximal-phalangeal joints of the four fingers were more consistent. For a keystroke executed with one of the fingers, there were three distinct patterns of joint rotations, across which motion at the striking finger was fairly consistent, but motion of the other fingers was more variable. Furthermore, the amount of movement spillover of the striking finger to the adjacent fingers was small irrespective of the finger used for the keystroke. These findings describe an unparalleled amount of independent motion of the fingers. PMID:21880938

  14. Hand kinematics of piano playing.

    PubMed

    Furuya, Shinichi; Flanders, Martha; Soechting, John F

    2011-12-01

    Dexterous use of the hand represents a sophisticated sensorimotor function. In behaviors such as playing the piano, it can involve strong temporal and spatial constraints. The purpose of this study was to determine fundamental patterns of covariation of motion across joints and digits of the human hand. Joint motion was recorded while 5 expert pianists played 30 excerpts from musical pieces, which featured ?50 different tone sequences and fingering. Principal component analysis and cluster analysis using an expectation-maximization algorithm revealed that joint velocities could be categorized into several patterns, which help to simplify the description of the movements of the multiple degrees of freedom of the hand. For the thumb keystroke, two distinct patterns of joint movement covariation emerged and they depended on the spatiotemporal patterns of the task. For example, the thumb-under maneuver was clearly separated into two clusters based on the direction of hand translation along the keyboard. While the pattern of the thumb joint velocities differed between these clusters, the motions at the metacarpo-phalangeal and proximal-phalangeal joints of the four fingers were more consistent. For a keystroke executed with one of the fingers, there were three distinct patterns of joint rotations, across which motion at the striking finger was fairly consistent, but motion of the other fingers was more variable. Furthermore, the amount of movement spillover of the striking finger to the adjacent fingers was small irrespective of the finger used for the keystroke. These findings describe an unparalleled amount of independent motion of the fingers. PMID:21880938

  15. Return to play after thyroiditis in a football athlete.

    PubMed

    Eken, Joshua L; Smoot, M Kyle

    2013-09-01

    A collegiate football athlete presented to his athletic trainer with acute chest pain during practice. Subsequent workup revealed that the patient was in the hyperthyroid state of subacute thyroiditis. There are no published case reports or existing guidelines to guide clinicians on making the decision of when it is safe to return to play after hyperthyroid crisis. Return to play in cases of subacute thyroiditis should include resolution of symptoms, trending of thyroid function tests to euthyroid state, consideration of cardiovascular factors, and a graded return to play. PMID:23624573

  16. The psychophysiology of flow during piano playing.

    PubMed

    de Manzano, Orjan; Theorell, Töres; Harmat, László; Ullén, Fredrik

    2010-06-01

    Expert performance is commonly accompanied by a subjective state of optimal experience called flow. Previous research has shown positive correlations between flow and quality of performance and suggests that flow may function as a reward signal that promotes practice. Here, piano playing was used as a flow-inducing behavior in order to analyze the relationship between subjective flow reports and psychophysiological measures. Professional classical pianists were asked to play a musical piece and then rate state flow. The performance was repeated five times in order to induce a variation in flow, keeping other factors constant, while recording the arterial pulse pressure waveform, respiration, head movements, and activity from the corrugator supercilii and zygomaticus major facial muscles. A significant relation was found between flow and heart period, blood pressure, heart rate variability, activity of the zygomaticus major muscle, and respiratory depth. These findings are discussed in relation to current models of emotion, attention, and expertise, and flow is proposed to be a state of effortless attention, which arises through an interaction between positive affect and high attention. PMID:20515220

  17. Major Oil Plays in Utah and Vicinity

    SciTech Connect

    Thomas C. Chidsey; Craig D. Morgan; Kevin McClure; Douglas A. Sprinkel; Roger L. Bon; Hellmut H. Doelling

    2003-12-31

    Utah oil fields have produced over 1.2 billion barrels (191 million m{sup 3}). However, the 13.7 million barrels (2.2 million m{sup 3}) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil-producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; locations of major oil pipelines; identification and discussion of land-use constraints; descriptions of reservoir outcrop analogs; and summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play. This report covers research activities for the sixth quarter of the project (October 1 through December 31, 2003). This work included describing outcrop analogs for the Jurassic Twin Creek Limestone and Mississippian Leadville Limestone, major oil producers in the thrust belt and Paradox Basin, respectively, and analyzing best practices used in the southern Green River Formation play of the Uinta Basin. Production-scale outcrop analogs provide an excellent view of reservoir petrophysics, facies characteristics, and boundaries contributing to the overall heterogeneity of reservoir rocks. They can be used as a ''template'' for evaluation of data from conventional core, geophysical and petrophysical logs, and seismic surveys. In the Utah/Wyoming thrust belt province, the Jurassic Twin Creek Limestone produces from subsidiary closures along major ramp anticlines where the low-porosity limestone beds are extensively fractured and sealed by overlying argillaceous and non-fractured units. The best outcrop analogs for Twin Creek reservoirs are found at Devils Slide and near the town of Peoa, Utah, where fractures in dense, homogeneous non-porous limestone beds are in contact with the basal siltstone units (containing sealed fractures) of the overlying units. The shallow marine, Mississippian Leadville Limestone is a major oil and gas reservoir in the Paradox Basin of Utah and Colorado. Hydrocarbons are produced from basement-involved, northwest-trending structural traps with closure on both anticlines and faults. Excellent outcrops of Leadville-equivalent rocks are found along the south flank of the Uinta Mountains, Utah. For example, like the Leadville, the Mississippian Madison Limestone contains zones of solution breccia, fractures, and facies variations. When combined with subsurface geological and production data, these outcrop analogs can improve (1) development drilling and production strategies such as horizontal drilling, (2) reservoir-simulation models, (3) reserve calculations, and (4) design and implementation of secondary/tertiary oil recovery programs and other best practices used in the oil fields of Utah and vicinity. In the southern Green River Formation play of the Uinta Basin, optimal drilling, development, and production practices consist of: (1) owning drilling rigs and frac holding tanks; (2) perforating sandstone beds with more than 8 percent neutron porosity and stimulate with separate fracture treatments; (3) placing completed wells on primary production using artificial lift; (4) converting wells relatively soon to secondary waterflooding maintaining reservoir pressure above the bubble point to maximize oil recovery; (5) developing waterflood units using an alternating injector--producer pattern on 40-acre (16-ha) spacing; and (6) recompleting producing wells by perforating all beds that are productive in the waterflood unit. As part of technology transfer activities during this quarter, an abstract describing outcrop reservoir analogs was accepted by the American Assoc

  18. Parent-Child Play: Descriptions and Implications.

    ERIC Educational Resources Information Center

    MacDonald, Kevin, Ed.

    This volume provides the latest research and theory in the area of children's play with their parents. It includes discussions of the basic processes involved in parent-child play, parent-child play in atypical populations of children, and parent-child play from a cross-cultural perspective. Fifteen chapters follow the introduction, "Parents and…

  19. Reconceptualizing Play: Aesthetic Self-Definitions

    ERIC Educational Resources Information Center

    Guss, Faith

    2005-01-01

    This article aims to trouble the identity of children's dramatic play(ing). It contains two interweaving threads of discourse. In one thread lies a discussion of how children can trouble and extend their own identities through the aesthetic form-languages and conventions they employ and deploy in their dramatic playing/pretend playing.…

  20. Pretend Play in the Early Childhood Classroom

    ERIC Educational Resources Information Center

    McEntire, Nancy

    2009-01-01

    This article presents and summarizes recent resources related to pretend play in the early childhood classroom. These include "Contemporary Perspectives on Play in Early Childhood Education" by Olivia N. Sarachoe and Bernard Spodek; "Dramatic Play: Bring It Back" by Tammy Benson; and "The Importance of Being Playful" by Elena Bodrova and Deborah…

  1. Conceptualizing the Play Policies in Preschool Curriculums

    ERIC Educational Resources Information Center

    Sener, Tulin

    2013-01-01

    This research attempted to describe the play policies in preschool institutions in Ankara, Turkey. The aim of this study is to determine the approaches of the preschools to the children's play. "Play Policy Questionnaire" administered to all directors and teachers of 20 public preschools and 20 private preschools. Play policy of…

  2. Introduction to Plays, English: 5112.44.

    ERIC Educational Resources Information Center

    Ozan, Ruth S.

    Several plays are studied to introduce students to theatrical terms and to the elements of a play in this quinmester course for Dade County High Schools. Several approaches to the study of the play are suggested such as individual and a large group production of a play, the use of a unified theme such as Youth vs. Tradition, or the line of…

  3. Turkish Adaptation of Test of Pretended Play

    ERIC Educational Resources Information Center

    Aydin, Aydan

    2012-01-01

    The objective of present research is to conduct validity and reliability analysis of the verbal section of Test of Pretended Play that will measure pretended play behaviors of pre-school age children (3-6 years of age). Test of Pretended Play was first developed by Vicky Lewis and Jill Boucher in 1997. This test aimed to measure pretended play

  4. Superman Comes to Preschool: Superhero TV Play.

    ERIC Educational Resources Information Center

    Ritchie, Kathleen E.; Johnson, Zita M.

    Systematic efforts at the Arizona State Child Study Laboratory were successful in replacing children's undesirable superhero play with other types of sociodramatic play. Teachers found superhero play undesirable because it was aggressive and noisy and was accompanied by an increase in random activity. Observations indicated that superhero play had…

  5. Superhero Play: What's a Teacher to Do?

    Microsoft Academic Search

    Karen L. Bauer; Ernest Dettore

    1997-01-01

    The dilemma over whether or not teachers should allow superhero play in their classroom continues. This article examines adults' beliefs about superhero play and suggests some potential benefits of such play. The authors offer examples of ways they have incorporated superhero play in their classroom.

  6. Teatro! Hispanic Plays for Young People.

    ERIC Educational Resources Information Center

    Vigil, Angel

    This collection of 14 folk drama scripts is drawn from the Hispanic culture and traditions of the American Southwest and designed for use in educational settings. The plays are short, simple, and easy to produce. A single play can fill a class period, while several plays grouped together would make a school assembly. Six plays, intended for grades…

  7. Heuristic Evaluation Functions for General Game Playing

    Microsoft Academic Search

    James Clune

    2007-01-01

    A general game playing program plays games that it has not previously encountered. A game manager pro- gram sends the game playing programs a description of a game's rules and objectives in a well-defined game description language. A central challenge in creating effective general game playing programs is that of con- structing heuristic evaluation functions from game de- scriptions. This

  8. Monitored Play Therapy: Conceptual and Methodological Issues.

    ERIC Educational Resources Information Center

    Golden, Bobbie

    There are many unanswered questions about play therapy. Monitored play therapy is an attempt to discover answers to these questions. The main emphasis is on quantitative recording and analysis of the process and outcome of play therapy. However, because of its newness, monitored play therapy also has some weaknesses. The main strong point is the…

  9. PLAY THERAPY WITH MULTIPLE PERSONALITY DISORDER CLIENTS

    Microsoft Academic Search

    Jeffrey Wm. Klein; Garry L. Landreth

    1993-01-01

    The use of play therapy with child alters of adults who have multiple personality disorders is explored. Various approaches to play therapy that are used with children may also be effectively used with child alters. Play may be used to help sublimate expressions of anger, recover dissociated memories, and increase communication and cooperation among alter personalities. Play therapy offers distinct

  10. Play and Social Interaction in Middle Childhood

    ERIC Educational Resources Information Center

    Bergen, Doris; Fromberg, Doris Pronin

    2009-01-01

    This article discusses traditional and contemporary definitions of middle childhood play, the value of such play for children's development and learning, the implications of home, school, and societal practices that have resulted in changing the play scenario of middle childhood, and suggestions for assuring that play's value will be maintained…

  11. Transforming Play: An Analysis of First-, Third-, and Fifth-Graders' Play.

    ERIC Educational Resources Information Center

    Bagley, Donna M.; Chaille, Christine

    1996-01-01

    Compared children's play with transformational objects (vehicles that change to robots) to play with representational objects (cars and figures). Found that those playing with transformers engaged in more parallel play and manipulative activity, while those with representational objects displayed more social play and more symbolic play. Found no…

  12. MAJOR OIL PLAYS IN UTAH AND VICINITY

    SciTech Connect

    Thomas C. Chidsey; Craig D. Morgan; Kevin McClure; Grant C. Willis

    2003-09-01

    Utah oil fields have produced over 1.2 billion barrels (191 million m{sup 3}). However, the 13.7 million barrels (2.2 million m{sup 3}) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil-producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play; locations of major oil pipelines; descriptions of reservoir outcrop analogs; and identification and discussion of land use constraints. All play maps, reports, databases, and so forth, produced for the project will be published in interactive, menu-driven digital (web-based and compact disc) and hard-copy formats. This report covers research activities for the fourth quarter of the first project year (April 1 through June 30, 2003). This work included describing outcrop analogs to the Jurassic Nugget Sandstone and Pennsylvanian Paradox Formation, the major oil producers in the thrust belt and Paradox Basin, respectively. Production-scale outcrop analogs provide an excellent view, often in three dimensions, of reservoir-facies characteristics and boundaries contributing to the overall heterogeneity of reservoir rocks. They can be used as a ''template'' for evaluation of data from conventional core, geophysical and petrophysical logs, and seismic surveys. The Nugget Sandstone was deposited in an extensive dune field that extended from Wyoming to Arizona. Outcrop analogs are found in the stratigraphically equivalent Navajo Sandstone of southern Utah which displays large-scale dunal cross-strata with excellent reservoir properties and interdunal features such as oases, wadi, and playa lithofacies with poor reservoir properties. Hydrocarbons in the Paradox Formation are stratigraphically trapped in carbonate buildups (or phylloid-algal mounds). Similar carbonate buildups are exposed in the Paradox along the San Juan River of southeastern Utah. Reservoir-quality porosity may develop in the types of facies associated with buildups such as troughs, detrital wedges, and fans, identified from these outcrops. When combined with subsurface geological and production data, these outcrop analogs can improve (1) development drilling and production strategies such as horizontal drilling, (2) reservoir-simulation models, (3) reserve calculations, and (4) design and implementation of secondary/tertiary oil recovery programs and other best practices used in the oil fields of Utah and vicinity. During this quarter, technology transfer activities consisted of exhibiting the project plans, objectives, and products at a booth at the 2003 annual convention of the American Association of Petroleum Geologists. The project home page was updated on the Utah Geological Survey Internet web site.

  13. CD109 Plays a Role in Osteoclastogenesis

    PubMed Central

    Jiang, Hongwei; Tenenbaum, Howard; Glogauer, Michael

    2013-01-01

    Osteoclasts are large multinucleated cells that arise from the fusion of cells from the monocyte/macrophage lineage. Osteoclastogenesis is mediated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) and involves a complex multistep process that requires numerous other elements, many of which remain undefined. The primary aim of this project was to identify novel factors which regulate osteoclastogenesis. To carry out this investigation, microarray analysis was performed comparing two pre-osteoclast cell lines generated from RAW264.7 macrophages: one that has the capacity to fuse forming large multinucleated cells and one that does not fuse. It was found that CD109 was up-regulated by>17-fold in the osteoclast forming cell line when compared to the cell line that does not fuse, at day 2 of the differentiation process. Results obtained with microarray were confirmed by RT-qPCR and Western blot analyses in the two cell lines, in the parental RAW264.7 cell line, as well as primary murine monocytes from bone marrow. A significant increase of CD109 mRNA and protein expression during osteoclastogenesis occurred in all tested cell types. In order to characterize the role of CD109 in osteoclastogenesis, CD109 stable knockdown cell lines were established and fusion of osteoclast precursors into osteoclasts was assessed. It was found that CD109 knockdown cell lines were less capable of forming large multinucleated osteoclasts. It has been shown here that CD109 is expressed in monocytes undergoing RANKL-induced osteoclastogenesis. Moreover, when CD109 expression is suppressed in vitro, osteoclast formation decreases. This suggests that CD109 might be an important regulator of osteoclastogenesis. Further research is needed in order to characterize the role played by CD109 in regulation of osteoclast differentiation. PMID:23593435

  14. Factor Game

    NSDL National Science Digital Library

    Adapted with permission from "Prime Time: Factors and Multiples," Connected Mathematics Project, G. Lappan, J. Fey, W. Fitzgerald, S. Friel and E. Phillips

    2000-01-01

    This is an interactive applet game exercises a student's factoring ability. A student can play against the computer or against a friend on grids containing the numbers 1-30, 1-49, or 1-100. Each player in turn chooses a number from the board, and then the opponent claims all of its remaining proper factors. A player's score is the sum of all the numbers and factors she/he has chosen. When there are no numbers remaining with unclaimed factors, the game ends and the player with the greater total is the winner.

  15. Major Oil Plays In Utah And Vicinity

    SciTech Connect

    Thomas Chidsey

    2007-12-31

    Utah oil fields have produced over 1.33 billion barrels (211 million m{sup 3}) of oil and hold 256 million barrels (40.7 million m{sup 3}) of proved reserves. The 13.7 million barrels (2.2 million m3) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. However, in late 2005 oil production increased, due, in part, to the discovery of Covenant field in the central Utah Navajo Sandstone thrust belt ('Hingeline') play, and to increased development drilling in the central Uinta Basin, reversing the decline that began in the mid-1980s. The Utah Geological Survey believes providing play portfolios for the major oil-producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming can continue this new upward production trend. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios include descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; locations of major oil pipelines; identification and discussion of land-use constraints; descriptions of reservoir outcrop analogs; and summaries of the state-of-the-art drilling, completion, and secondary/tertiary recovery techniques for each play. The most prolific oil reservoir in the Utah/Wyoming thrust belt province is the eolian, Jurassic Nugget Sandstone, having produced over 288 million barrels (46 million m{sup 3}) of oil and 5.1 trillion cubic feet (145 billion m{sup 3}) of gas. Traps form on discrete subsidiary closures along major ramp anticlines where the depositionally heterogeneous Nugget is also extensively fractured. Hydrocarbons in Nugget reservoirs were generated from subthrust Cretaceous source rocks. The seals for the producing horizons are overlying argillaceous and gypsiferous beds in the Jurassic Twin Creek Limestone, or a low-permeability zone at the top of the Nugget. The Nugget Sandstone thrust belt play is divided into three subplays: (1) Absaroka thrust - Mesozoic-cored shallow structures, (2) Absaroka thrust - Mesozoic-cored deep structures, and (3) Absaroka thrust - Paleozoic-cored shallow structures. Both of the Mesozoic-cored structures subplays represent a linear, hanging wall, ramp anticline parallel to the leading edge of the Absaroka thrust. Fields in the shallow Mesozoic subplay produce crude oil and associated gas; fields in the deep subplay produce retrograde condensate. The Paleozoic-cored structures subplay is located immediately west of the Mesozoic-cored structures subplays. It represents a very continuous and linear, hanging wall, ramp anticline where the Nugget is truncated against a thrust splay. Fields in this subplay produce nonassociated gas and condensate. Traps in these subplays consist of long, narrow, doubly plunging anticlines. Prospective drilling targets are delineated using high-quality, two-dimensional and three-dimensional seismic data, forward modeling/visualization tools, and other state-of-the-art techniques. Future Nugget Sandstone exploration could focus on more structurally complex and subtle, thrust-related traps. Nugget structures may be present beneath the leading edge of the Hogsback thrust and North Flank fault of the Uinta uplift. The Jurassic Twin Creek Limestone play in the Utah/Wyoming thrust belt province has produced over 15 million barrels (2.4 million m{sup 3}) of oil and 93 billion cubic feet (2.6 billion m{sup 3}) of gas. Traps form on discrete subsidiary closures along major ramp anticlines where the low-porosity Twin Creek is extensively fractured. Hydrocarbons in Twin Creek reservoirs were generated from subthrust Cretaceous source rocks. The seals for the producing horizons are overlying argillaceous and clastic beds, and non-fractured units within the Twin Creek. The Twin Creek Limestone thrust belt play is divided into two subplays: (1) Absaroka thrust-Mesozoic-cored structures and (2) A

  16. A Simple Intelligent Agent for Playing Abalone Game: ABLA

    Microsoft Academic Search

    Ender Ozcan; Berk Hulagu

    Forming winning strategies for board games requires good heuristics and fast search algorithms on game trees. High branching factors and the need for looking deeper in game trees are overwhelming, even for today's high performance PC's. Therefore, better game-plays are only available with better algorithms and heuristics for an ordinary player, not with faster machines. Abalone is a recent two-person

  17. The Impact of Pretend Play on Children's Development: A Review of the Evidence

    ERIC Educational Resources Information Center

    Lillard, Angeline S.; Lerner, Matthew D.; Hopkins, Emily J.; Dore, Rebecca A.; Smith, Eric D.; Palmquist, Carolyn M.

    2013-01-01

    Pretend play has been claimed to be crucial to children's healthy development. Here we examine evidence for this position versus 2 alternatives: Pretend play is 1 of many routes to positive developments (equifinality), and pretend play is an epiphenomenon of other factors that drive development. Evidence from several domains is considered. For…

  18. Factor Dazzle

    NSDL National Science Digital Library

    2011-01-01

    This interactive online game helps students develop fluency with identifying factors while fostering strategic thinking. A student can play against the computer or against a friend on a 6 by 6 grid containing the numbers 1-36. Each player in turn chooses a number from the board, and then the opponent claims all of its remaining proper factors. A player's score is the sum of all the numbers and factors she/he has chosen. When there are no numbers remaining with unclaimed factors, the game ends and the player with the greater total is the winner. This game is part of NCTM's Calculation Nation project (cataloged separately). Users may login as a guest and play against the computer, or register (free) to challenge other players online.

  19. Play the Immune System Defender Game

    MedlinePLUS

    ... Questionnaire The Immune System Play the Immune System Game About the game Granulocytes, macrophages and dendritic cells are immune cells ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  20. The Early Years: Inquiry at Play

    NSDL National Science Digital Library

    Peggy Ashbrook

    2010-09-01

    Play and science inquiry are essential parts of early childhood programs. Imaginative play, unscripted yet guided by children's own rules, allows students to use their imagination and develop self-regulation, symbolic thinking, memory, language, and socia

  1. Back to Sleep, Tummy to Play

    MedlinePLUS

    ... Tummy to Play Ages & Stages Listen Back to Sleep, Tummy to Play Article Body What Are The 2 Most Important Things To Remember About Safe Sleep Practices? Healthy babies are safest when sleeping on ...

  2. Making Theater: Developing Plays with Young People.

    ERIC Educational Resources Information Center

    Kohl, Herbert R.

    Intended for teachers who have no particular experience or training in teaching theater, but who have a love of theater and enjoy a good play, this book discusses making theater with children. It explores improvisation, reading and acting with scripts, adapting plays for young actors, and writing plays. The examples presented in the text are…

  3. Playworkers: Creating Opportunities for Children's Play.

    ERIC Educational Resources Information Center

    Clements, Rhonda

    2000-01-01

    Describes the role of playworkers, nonformal educators who facilitate children's opportunities for unstructured and structured play experiences in a variety of settings. Identifies six issues confronting society today and indicates how playworkers can help address each: increased urbanization, inappropriate play objects, lack of physical play,…

  4. Play Therapy in Political Theory: Machiavelli's Mandragola.

    ERIC Educational Resources Information Center

    Lukes, Timothy J.

    1981-01-01

    Suggests that having political science college students perform in class Machiavelli's play "Mandragola" is an excellent way to expand student's appreciation of Machiavelli. Article provides a synopsis of the play, discusses Machiavelli's intent, examines the meaning of the play, and presents classroom logistics. (RM)

  5. New directions in play: consensus or collision?

    Microsoft Academic Search

    Elizabeth Wood

    2007-01-01

    The aims of this article are to explore contemporary challenges to developing play in early childhood settings, and to identify areas of consensus and collision in policy and practice. Contemporary research highlights the effectiveness of mixed pedagogical approaches, including child- and adult-initiated play. Whilst early childhood specialists recognise these approaches as central to high-quality curricula in early childhood settings, play

  6. Language Play in Child Second Language Acquisition.

    ERIC Educational Resources Information Center

    Peck, Sabrina

    Play sessions of two Mexican children (one five and one eight years old) with English-speaking friends were recorded and the use of language play was examined. Language play is viewed as a non-literal, rule-bound use of language that children engage in for its own sake, either cooperatively or competitively. Practice opportunities and children's…

  7. Superheroes: An Opportunity for Prosocial Play

    ERIC Educational Resources Information Center

    De-Souza, Desalyn; Radell, Jacqueline

    2011-01-01

    Superhero play has long been thought of as violent, aggressive, and disruptive. Some argue that aggressive play should not be allowed because it exposes children to inappropriate concepts and attitudes and sends the message that the use of aggression can achieve a desired goal. However, educators know that pretend play is an avenue for healthy…

  8. Empirically Based Play Interventions for Children

    ERIC Educational Resources Information Center

    Reddy, Linda A., Ed.; Files-Hall, Tara M., Ed.; Schaefer, Charles E., Ed.

    2005-01-01

    "Empirically Based Play Interventions for Children" is a compilation of innovative, well-designed play interventions, presented for the first time in one text. Play therapy is the oldest and most popular form of child therapy in clinical practice and is widely considered by practitioners to be uniquely responsive to children's developmental needs.…

  9. Playing Pylos with an autonomous robot

    Microsoft Academic Search

    Oswin Aichholzer; Daniel Detassis; Thomas Hackl; Gerald Steinbauer; Johannes Thonhauser

    2010-01-01

    In this paper, Pylos playing autonomous robot is discussed. This robot is combined with optimal game winning strategies. This results in an artificial companion which plays the board game Pylos in a fully interactive manner and up to the highest possible level. In the long term this could lead to interesting competitions between various autonomous robots playing several board games

  10. A Review of Research on Play.

    ERIC Educational Resources Information Center

    Fromberg, Doris Pronin

    Uninformed of the power of play as an educational tool, many people view play as a waste of time and call for a return to teaching basic academic skills during the period of early childhood. This chapter demonstrates that play is a major vehicle for learning, focusing on the dynamics of sociodramatic interaction that are integral to understanding…

  11. Play under Siege: A Historical Overview

    ERIC Educational Resources Information Center

    Zigler, Edward F.; Bishop-Josef, Sandra J.

    2009-01-01

    In this updated version of their chapter from "Children's Play: The Roots of Reading" (published by ZERO TO THREE in 2004), the authors describe the recent attack on play, in both early childhood and elementary education. They provide a historical overview of the contentious relationship between play and cognitive development. The authors stress…

  12. Introduction to Artificial Intelligence Game Playing

    E-print Network

    Qu, Rong

    Introduction to Artificial Intelligence (G51IAI) Dr Rong Qu Game Playing Garry Kasparov and Deep Blue. © 1997, GM Gabriel Schwartzman's Chess Camera, courtesy IBM. #12;G51IAI - Game Playing Game (1912-1954) Chess playing program Within 10 years a computer will be a chess champion Herbert Simon

  13. The Play Professional in the United Kingdom

    ERIC Educational Resources Information Center

    Millbank, Anna-Marie

    2005-01-01

    Playwork is a respected field of study composed of experts who have studied the theories and practices of play for the purposes of training other individuals in best practices to better facilitate children's play. The profession is founded on the belief that play is an essential childhood element and the right of every child. In this article, the…

  14. Gender Differences in Students' Mathematics Game Playing

    ERIC Educational Resources Information Center

    Lowrie, Tom; Jorgensen, Robyn

    2011-01-01

    The investigation monitored the digital game-playing behaviours of 428 primary-aged students (aged 10-12 years). Chi-square analysis revealed that boys tend to spend more time playing digital games than girls while boys and girls play quite different game genres. Subsequent analysis revealed statistically significant gender differences in terms of…

  15. Doing Reality with Play: Play as a Children's Resource in Organizing Everyday Life in Daycare Centres.

    ERIC Educational Resources Information Center

    Strandell, Harriet

    1997-01-01

    Presents results from ethnographic study on children's everyday life in Finnish daycare centers. Raises question of the relationship between play and real life, and analyzes play and playfulness as communicative resources used by children in creating everyday routines. Argues play is not a separate children's world; by using play, children also…

  16. Play and Mate Preference: Testing the Signal Theory of Adult Playfulness

    ERIC Educational Resources Information Center

    Chick, Garry; Yarnal, Careen; Purrington, Andrew

    2012-01-01

    The overwhelming majority of play research concerns juveniles. However, a full understanding of the phenomenon requires knowledge of play and playfulness across the life spans of those animals, including humans, who play in adulthood. The authors investigate a theory of play based on Darwin's concept of sexual selection that may account for the…

  17. Methylation of human papillomavirus Type 16 CpG sites at E2-binding site 1 (E2BS1), E2BS2, and the Sp1-binding site in cervical cancer samples as determined by high-resolution melting analysis-PCR.

    PubMed

    Jacquin, Elise; Baraquin, Alice; Ramanah, Rajeev; Carcopino, Xavier; Morel, Adrien; Valmary-Degano, Séverine; Bravo, Ignacio G; de Sanjosé, Silvia; Riethmuller, Didier; Mougin, Christiane; Prétet, Jean-Luc

    2013-10-01

    High-risk (HR) human papillomavirus (HPV)-associated carcinogenesis is driven mainly by the overexpression of E7 and E6 oncoproteins following viral DNA integration and the concomitant loss of the E2 open reading frame (ORF). However, the integration of HR-HPV DNA is not systematically observed in cervical cancers. The E2 protein acts as a transcription factor that governs viral oncogene expression. The methylation of CpGs in the E2-binding sites (E2BSs) in the viral long control region abrogates E2 binding, thus impairing the E2-mediated regulation of E7/E6 transcription. Here, high-resolution melting (HRM)-PCR was developed to quantitatively analyze the methylation statuses of E2BS1, E2BS2, and the specificity protein 1 (Sp1)-binding site in 119 HPV16-positive cervical smears. This is a rapid assay that is suitable for the analysis of cervical samples. The proportion of cancer samples with methylated E2BS1, E2BS2, and Sp1-binding site CpGs was 47%, whereas the vast majority of samples diagnosed as being within normal limits, low-grade squamous intraepithelial lesions (LSIL), or high-grade squamous intraepithelial lesions (HSIL) harbored unmethylated CpGs. Methylation levels varied widely, since some cancer samples harbored up to 60% of methylated HPV16 genomes. A pyrosequencing approach was used as a confirmation test and highlighted that quantitative measurement of methylation can be achieved by HRM-PCR. Its prognostic value deserves to be investigated alone or in association with other biomarkers. The reliability of this single-tube assay offers great opportunities for the investigation of HPV16 methylation in other HPV-related cancers, such as head and neck cancers, which are a major public health burden. PMID:23863566

  18. [Emotion regulatory processes in evoked play narratives].

    PubMed

    Lemche, Erwin; Lennertz, Ilka; Orthmann, Claudia; Ari, Alkim; Grote, Katja; Häfker, Jessika; Klann-Delius, Gisela

    2003-03-01

    Evoked play narratives have been demonstrated to provide a novel window towards internal emotion regulation and mental representations. The present study evaluates covariations between emotion themes and mother-child interaction, as well as child behavior problems. An exploratory study in non-referred children in the 3-6 age span utilizing the MacArthur-method was conducted by taking emotional, conflictive and moral themes as indices of emotion-regulatory processes. Emotion themes were linked to external measures of dyadic Emotional Availability, interparental relationship quality, and behavior problems employing the 4/18 version of the Child Behavior Checklist. Mental representations were aggregated using the Person Representation Coding System. Of a principal components analysis with subsequent varimax-rotation for narrative content codes resulted four emotion theme composites: social conflicting, a prosocial aggregate, an antisocial aggregate, and a composite conflict solving/-understanding. The 4-factor solution displayed meaningful correlation patterns with the mental representations of self and parents, as well as with most of the external measures. Although subsequent studies ought to be methodologically improved both in design and sample size, the results of the present investigation give rise to the assumption that future efforts of validating emotion-regulatory processes with more established outside measures are likely to be successful. PMID:12693352

  19. Histone Deacetylase 1/Sp1/MicroRNA-200b Signaling Accounts for Maintenance of Cancer Stem-Like Cells in Human Lung Adenocarcinoma

    PubMed Central

    Pan, Ban-Zhou; De, Wei; Wang, Rui; Chen, Long-Bang

    2014-01-01

    The presence of cancer stem-like cells (CSCs) is one of the mechanisms responsible for chemoresistance that has been a major hindrance towards lung adenocarcinoma (LAD) treatment. Recently, we have identified microRNA (miR)-200b as a key regulator of chemoresistance in human docetaxel-resistant LAD cells. However, whether miR-200b has effects on regulating CSCs remains largely unclear and needs to be further elucidated. Here, we showed that miR-200b was significantly downregulated in CD133+/CD326+ cells that exhibited properties of CSCs derived from docetaxel-resistant LAD cells. Also, restoration of miR-200b could inhibit maintenance and reverse chemoresistance of CSCs. Furthermore, suppressor of zeste-12 (Suz-12) was identified as a direct and functional target of miR-200b, and silencing of Suz-12 phenocopied the effects of miR-200b on CSCs. Additionally, overexpression of histone deacetylase (HDAC) 1 was identified as a pivotal mechanism responsible for miR-200b repression in CSCs through a specificity protein (Sp) 1-dependent mechanism, and restoration of miR-200b by HDAC1 repression significantly suppressed CSCs formation and reversed chemoresistance of CSCs by regulating Suz-12-E-cadherin signaling. Also, downregulation of HDAC1 or upregulation of miR-200b reduced the in vivo tumorigenicity of CSCs. Finally, Suz-12 was inversely correlated with miR-200b, positively correlated with HDAC1 and up-regulated in docetaxel-resistant LAD tissues compared with docetaxel-sensitive tissues. Taken together, the HDAC1/miR-200b/Suz-12-E-cadherin signaling might account for maintenance of CSCs and formation of chemoresistant phenotype in docetaxel-resistant LAD cells. PMID:25279705

  20. Production of extracellular polymeric substances (EPS) by Serratia sp.1 using wastewater sludge as raw material and flocculation activity of the EPS produced.

    PubMed

    Bezawada, J; Hoang, N V; More, T T; Yan, S; Tyagi, N; Tyagi, R D; Surampalli, R Y

    2013-10-15

    Growth profile and extracellular polymeric substances (EPS) production of Serratia sp.1 was studied in shake flask fermentation for 72 h using wastewater sludge as raw material. Maximum cell concentration of 6.7 × 10(9) cfu/mL was obtained at 48 h fermentation time. EPS dry weight, flocculation activity and dewaterability of different EPS (tightly bound or TB-EPS, loosely bound or LB-EPS and broth-EPS or B-EPS) were also measured. The highest concentration of LB-EPS (2.45 g/L) and TB-EPS (0.99 g/L) were attained at 48 h of fermentation. Maximum flocculation activity and dewaterability (?CST) of TB-EPS (76.4%, 14.5s and 76.5%, 15.5s), LB-EPS (67.8%, 8.1s and 64.7%, 7.6s) and broth EPS (61%, 6.1s and 70.4%, 6.8s) were obtained at 36 and 48 h of growth. Higher flocculation activity and dewaterability were achieved with TB-EPS than with the two other EPS. Characterization of TB-EPS and LB-EPS was done in terms of their protein and carbohydrate content. Protein content was much higher in TB-EPS where as carbohydrate content was only slightly higher in TB-EPS than LB-EPS. Morphology of the Serratia strain after fermentation in sludge and TSB was observed under a scanning electron microscope and the cell size was found to be bigger in the sludge medium than the TSB medium. PMID:23722177

  1. Comparative analysis of nuclear ribosomal DNA from the moon jelly Aurelia sp.1 (Cnidaria: Scyphozoa) with characterizations of the 18S, 28S genes, and the intergenic spacer (IGS)

    Microsoft Academic Search

    Jang-Seu Ki; Il-Chan Kim; Jae-Seong Lee

    Nuclear ribosomal DNAs (rDNA) constitute a multi-gene family with tandemly arranged units linked by an intergenic spacer (IGS).\\u000a Here we present the complete DNA sequence (7,731 bp) of a single repeat unit of an rDNA sequence from the moon jelly Aurelia sp.1 (Cnidaria: Scypozoa). The tandemly repeated rDNA units consisted of coding and non- coding regions, whose arrangement\\u000a was 18S

  2. Chinese and German teachers' conceptions of play and learning and children's play behaviour

    Microsoft Academic Search

    Shu-Chen Wu; Nirmala Rao

    2011-01-01

    Commonalities and distinctions in Hong Kong-Chinese and German kindergarten teachers' conceptions of play and learning were examined. Six video clips of play episodes reflecting common play behavior and themes were selected from observations made during free play in two kindergartens in Hong Kong and two in Germany. Ten Chinese and seven German teachers viewed clips of children in their own

  3. Playing with Mathematics: Play in Early Childhood as a Context for Mathematical Learning

    ERIC Educational Resources Information Center

    Mathematics Education Research Group of Australasia, 2010

    2010-01-01

    Play is an essential part of young children's lives. This symposium highlights the integral role of play in young children's mathematics learning and examines the teacher's role in facilitating and extending this. Papers examine key tenets of play, contributing to theoretical understandings and presenting data on teacher's perceptions of play and…

  4. Playful Bottle:Playful Bottle: a Mobile Social Persuasion System to

    E-print Network

    Chu, Hao-hua

    Playful Bottle:Playful Bottle: a Mobile Social Persuasion System to Motivate HealthyWater Intake on information from sensing part to give suggestion to user 3 #12;Motivation ­ Playful BottleMotivation Playful Bottle Healthy Drinking Behavior [target behavior] People (office workers [target users]) forget

  5. Picture Me Playing: Increasing Pretend Play Dialogue of Children with Autism Spectrum Disorders

    Microsoft Academic Search

    Linda C. MurdockJan; Jan Q. Hobbs

    2011-01-01

    This study examined the effectiveness of the Picture Me Playing intervention for increasing the play dialogue of preschool\\u000a children with ASD during pretend play opportunities with typical peers. Picture Me Playing is a pictorially enhanced, script\\u000a based intervention targeting character role play through a narrative vignette. A single-treatment counterbalanced design was\\u000a utilized to contrast the performance of intervention and comparison

  6. Playful expressions of one-year-old chimpanzee infants in social and solitary play contexts

    PubMed Central

    Ross, Kirsty M.; Bard, Kim A.; Matsuzawa, Tetsuro

    2014-01-01

    Knowledge of the context and development of playful expressions in chimpanzees is limited because research has tended to focus on social play, on older subjects, and on the communicative signaling function of expressions. Here we explore the rate of playful facial and body expressions in solitary and social play, changes from 12- to 15-months of age, and the extent to which social partners match expressions, which may illuminate a route through which context influences expression. Naturalistic observations of seven chimpanzee infants (Pan troglodytes) were conducted at Chester Zoo, UK (n = 4), and Primate Research Institute, Japan (n = 3), and at two ages, 12 months and 15 months. No group or age differences were found in the rate of infant playful expressions. However, modalities of playful expression varied with type of play: in social play, the rate of play faces was high, whereas in solitary play, the rate of body expressions was high. Among the most frequent types of play, mild contact social play had the highest rates of play faces and multi-modal expressions (often play faces with hitting). Social partners matched both infant play faces and infant body expressions, but play faces were matched at a significantly higher rate that increased with age. Matched expression rates were highest when playing with peers despite infant expressiveness being highest when playing with older chimpanzees. Given that playful expressions emerge early in life and continue to occur in solitary contexts through the second year of life, we suggest that the play face and certain body behaviors are emotional expressions of joy, and that such expressions develop additional social functions through interactions with peers and older social partners. PMID:25104942

  7. A Kruppel-like factor KLF15 contributes fasting-induced transcriptional activation of mitochondrial acetyl-CoA synthetase gene AceCS2.

    PubMed

    Yamamoto, Joji; Ikeda, Yukio; Iguchi, Haruhisa; Fujino, Takahiro; Tanaka, Toshiya; Asaba, Hiroshi; Iwasaki, Satoshi; Ioka, Ryoichi X; Kaneko, Izumi W; Magoori, Kenta; Takahashi, Sadao; Mori, Toshiyuki; Sakaue, Hiroshi; Kodama, Tatsuhiko; Yanagisawa, Masashi; Yamamoto, Tokuo T; Ito, Sadayoshi; Sakai, Juro

    2004-04-23

    Acetyl-CoA synthetase 2 (AceCS2) produces acetyl-CoA for oxidation through the citric acid cycle in the mitochondrial matrix. AceCS2 is highly expressed in the skeletal muscle and is robustly induced by fasting. Quantification of AceCS2 transcripts both in C2C12 and human myotubes indicated that fasting-induced AceCS2 gene expression appears to be independent on insulin action. Characterization of 5'-flanking region of the mouse AceCS2 gene demonstrates that Krüppel-like factor 15 (KLF15) plays a key role in the trans-activation of the AceCS2 gene. Deletion and mutation analyses of AceCS2 promoter region revealed that the most proximal KLF site is a curtail site for the trans-activation of the AceCS2 gene by KLF15. Using Sp-null Drosophila SL2 cells, we showed that the combination of KLF15 and Sp1 resulted in a synergistic activation of the AceCS2 promoter. Mutation analyses of three GC-boxes in the AceCS2 promoter indicated that the GC-box, located 8 bases downstream of the most proximal KLF15 site, is the most important GC-box in the synergistic trans-activation of the AceCS2 gene by KLF15 and Sp1. GST pull-down assays showed that KLF15 interacts with Sp1 in vitro. Quantification of various KLF transcripts revealed that 48 h fasting robustly induced the KLF15 transcripts in the skeletal muscle. Together with the trans-activation of the AceCS2 promoter, it is suggested that fasting-induced AceCS2 expression is largely contributed by KLF15. Furthermore, KLF15 overexpression induced the levels of AceCS2 transcripts both in myoblasts and in myotubes, indicating that AceCS2 gene expression in vivo is indeed induced by KLF15. PMID:14960588

  8. Shaping Cooperative Cross-Sex Play

    ERIC Educational Resources Information Center

    Serbin, Lisa A.; And Others

    1977-01-01

    Contingent praise by classroom teachers was used to cue and reinforce cross-sex cooperative play in 2 nursery school classes of 4-year-old children. Results suggested that previous learning and/or current classroom contingencies may reinforce same-sex playmate choices when teachers do not deliberately reinforce play between boys and girls. (JMB)

  9. Playing by Ear: Foundation or Frill?

    ERIC Educational Resources Information Center

    Woody, Robert H.

    2012-01-01

    Many people divide musicians into two types: those who can read music and those who play by ear. Formal music education tends to place great emphasis on producing musically literate performers but devotes much less attention to teaching students to make music without notation. Some would suggest that playing by ear is a specialized skill that is…

  10. Habit tic deformity secondary to guitar playing.

    PubMed

    Wu, Jashin J

    2009-01-01

    A 29-year-old man exhibited linear ridges of the right thumbnail that had been present for ten years. After he stopped playing the guitar for three months, the proximal portion of the abnormality cleared. Nail changes similar to the habit tic deformity may be produced by guitar playing. PMID:19379660

  11. Enhancing Dramatic Play with Prop Boxes.

    ERIC Educational Resources Information Center

    Myhre, Susan M.

    1997-01-01

    Notes that dramatic play is an important outlet for toddlers and small children, and that prop boxes allow children to know their world, role play, and enhance their imaginations. Provides lists for 20 different prop boxes, and information on getting started, collecting, organizing, and using prop boxes. (SD)

  12. Agentive and Communitarian Play in Early Childhood

    ERIC Educational Resources Information Center

    Dmytro, Dana; Kubiliene, Neringa; Cameron, Catherine Ann

    2014-01-01

    Play has long been recognised as a vehicle by which significant developmental advances occur during early childhood. Children use play to explore their relationships, their psychosocial skills, and their environment, and through their experiences, they begin to adopt specific capacities and values that have an impact on future socio-emotional and…

  13. Role-Playing Methods in the Classroom.

    ERIC Educational Resources Information Center

    Chesler, Mark; Fox, Robert

    This book, one of three Teacher Resource Booklets on Classroom Social Relations and Learning developed at the Center for Research on Utilization of Scientific Knowledge at the University of Michigan, discusses the theoretical background of role playing and gives a step-by-step discussion of how to use role playing in the classroom. There are…

  14. Creative and Constructive Play with Light

    E-print Network

    in or swallow up ray- a narrow beam of light reflects- stops light wave and changes direction, bounces back for key vocabulary. Teach sign language for key vocabulary. #12;9/19/12 3 Overview of Light Play light using an interactive computer program to enhance children's light play through shadows, mixing

  15. Get Moving! Active Play Indoors and Outdoors

    NSDL National Science Digital Library

    2014-04-30

    In this activity, learners explore the importance of active play. Parts A and B of this experience provide learners with a variety of active play options for indoors and outdoors that promote physical fitness. This activity is featured on pp. 20-21 of the "Health House: Food, Fitness, & Fun 24/7!" unit of study for K-2 learners.

  16. Preschool Children's Outdoor Play Area Preferences

    ERIC Educational Resources Information Center

    Holmes, Robyn M.; Procaccino, Jill K.

    2009-01-01

    This study explores preschool children's outdoor play preferences. The sample was 40 (20 male, 20 female) primarily European-American three and four year olds. Data were collected via naturalistic observation and analyzed using repeated measures ANOVAs and MANOVAs. The independent variable was sex of child; dependent variable was play space…

  17. Contemporary Play Therapy: Theory, Research, and Practice

    ERIC Educational Resources Information Center

    Schaefer, Charles E., Ed.; Gerard Kaduson, Heidi, Ed.

    2006-01-01

    This highly practical book presents current developments in play therapy, including innovative applications for particular problems and populations. Contributors first discuss the latest ideas and techniques emerging from object-relations, experiential, dynamic, and narrative perspectives. Next, research evaluating the effectiveness of play

  18. Executive Functions Development and Playing Games

    ERIC Educational Resources Information Center

    Petty, Ana Lucia; de Souza, Maria Thereza C. Coelho

    2012-01-01

    The aim of this paper is to discuss executive functions and playing games, considering Piaget's work (1967) and the neuropsychological framework (Barkley, 1997, 2000; Cypel, 2007). Two questions guide the discussion: What are the intersections between playing games and the development of executive functions? Can we stimulate children with learning…

  19. Helping Young Children See Math in Play

    ERIC Educational Resources Information Center

    Parks, Amy Noelle; Blom, Diana Chang

    2013-01-01

    The purpose of this article is to provide strategies for recognizing meaningful mathematics in common play contexts in early childhood classrooms and to offer suggestions for how teachers might intervene in these moments to help children attend to the mathematical ideas embedded in their play. In particular, the author's focus on the concepts…

  20. Play Therapy: Basics and Beyond. Second Edition

    ERIC Educational Resources Information Center

    Kottman, Terry

    2011-01-01

    Written for use in play therapy and child counseling courses, this extraordinarily practical text provides a detailed examination of basic and advanced play therapy concepts and skills and guidance on when and how to use them. Kottman's multitheoretical approach and wealth of explicit techniques are also helpful for clinicians who want to gain…

  1. New Directions in Play: Consensus or Collision?

    ERIC Educational Resources Information Center

    Wood, Elizabeth

    2007-01-01

    The aims of this article are to explore contemporary challenges to developing play in early childhood settings, and to identify areas of consensus and collision in policy and practice. Contemporary research highlights the effectiveness of mixed pedagogical approaches, including child- and adult-initiated play. Whilst early childhood specialists…

  2. Drawings as Spaces for Intellectual Play

    ERIC Educational Resources Information Center

    Wood, Elizabeth; Hall, Emese

    2011-01-01

    The aims of this article are to explore the links between drawing and playing and to conceptualise drawings as spaces for intellectual play. The empirical research that supports this position is based on an interpretivist study involving 14 children aged four-six in a primary school in England. Over a one-year period, 882 drawings were collected…

  3. It's Time to Stop Defending Play

    ERIC Educational Resources Information Center

    Burton, Rosemary

    2011-01-01

    Children learn through play. Talk to early childhood educators and they will say this is the core of what they know about how children learn best. Talk to many parents and they say that allowing children to simply play all day is not teaching kids anything. This is the signature argument that has defined the early childhood field. The author…

  4. Restaurant Role-Play in Psychology

    ERIC Educational Resources Information Center

    Borya, Anthony

    2013-01-01

    Research methods is perceived as a technical and difficult topic by some students. Using role-play to teach it can make it more accessible, meaningful and engaging. Role-playing the familiar roles of customer and waiting staff at a restaurant and discussing the variables that may affect the size of tips can help students to learn some of the key…

  5. Play and the Acquisition of Symbols.

    ERIC Educational Resources Information Center

    Fein, Greta G.

    This paper examines the interrelationship between children's acquisition and use of symbols and the development of imaginative play. The paper focuses on the use of pretend play as an expression of the child's capacity for symbolic functioning and as an index of intellectual development. The first section of the paper reviews developmental changes…

  6. Eventful Play: Preschooler's Scripts for Pretense.

    ERIC Educational Resources Information Center

    Seidman, Susan

    Two studies were conducted to analyze script and event structures of preschool children's dialogues during play. To identify scripts in discourse data, the following procedural guidelines were developed and followed: (1) identify exchanges of continuous discourse, (2) delineate all conversational episodes, (3) select all episodes with pretend play

  7. Mindbrain and Play-Literacy Connections

    ERIC Educational Resources Information Center

    Roskos, Kathleen A.; Christie, James F.

    2011-01-01

    Research on the relationship between play and early literacy flourished in the 1990s but slowed to a trickle at the start of the new millennium. As we see it, play-literacy research is stuck in a theoretical and methodological rut. Two promising conceptual frameworks--connectionist and dynamic systems theories--can supply the thrust needed to get…

  8. Governing Early Childhood Education through Play

    Microsoft Academic Search

    JO AILWOOD

    2003-01-01

    Play serves as a significant nodal point in the discursive relations of early childhood education. The aim of this article is to ask how play has come to appear so necessary to early childhood educational settings and how this perceived necessity governs the behaviour of both adults and young children. To do this the author make use of concepts provided

  9. Playing with Technology: Is It All Bad?

    ERIC Educational Resources Information Center

    Slutsky, Ruslan; Slutsky, Mindy; DeShelter, Lori M.

    2014-01-01

    Technology now plays a very large role in the way children of all ages play. Children want access to technology, so parents and teachers must determine the best ways to present it to them. Computers are a popular form of technology for children as young as age three. With that in mind, computer games should be problem-solving oriented and…

  10. Mathematical Learning in a Context of Play

    ERIC Educational Resources Information Center

    Edo, Meque; Planas, Nuria; Badillo, Edelmira

    2009-01-01

    In this article we analyse a didactical situation centred on the creation and use of a symbolic play environment in a class of pupils aged five and six years-old. The main source of data for this paper comes from an experimentation planned in relation to the following research question: does symbolic play in simulated contexts help pupils to…

  11. The Excellence of Play. Second Edition

    ERIC Educational Resources Information Center

    Moyles, Janet, Ed.

    2005-01-01

    This second edition of "The Excellence of Play" encapsulates all of the many changes that have taken place in early childhood in the last decade. It examines the vital importance of play as a tool for learning and teaching for children and practitioners, supporting all those who work in early childhood education and care in developing and…

  12. LOOKING AT PLAY IN OCTOPUS VULGARIS

    Microsoft Academic Search

    M. Kuba; D. V. Meisel; R. A. Byrne; U. Griebel; J. A. Mather

    Prior to the demonstration of play behavior in turtles and birds it was thought to be limited to mammals. To more effectively understand the context facilitating playful behavior and its subsequent evolution as a prominent, perhaps even critical, trait in animal life it is necessary to investigate it in different phyla. Aristoteles and Plinius were the first to describe a

  13. Gender-Typed Play and Amniotic Testosterone

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

    2005-01-01

    Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

  14. Teaching teachers to play and teach games

    Microsoft Academic Search

    Steven Wright; Michael McNeill; Joan Fry; John Wang

    2005-01-01

    This study was designed to determine the extent to which a technical and a tactical approach to teaching a basketball unit to physical education teacher education (PETE) students would each affect their games playing abilities, perceived ability to teach, and approach preference for teaching the game. Pre- and post-unit data were collected through videotape of half-court games play, questionnaire and

  15. Interactive Play and Learning for Children

    E-print Network

    Cheok, Adrian

    2008-01-01

    One of the most socially and culturally beneficial uses of human computer interaction research is enhancing play and learning for children. It is very important to understand the needs of children and craft visionary ...

  16. Wood Play Structures Are a Joint Effort.

    ERIC Educational Resources Information Center

    Anthony, Margaret

    1987-01-01

    Outlines how an elementary school in Storrs, Connecticut, developed and built its own wooden play structure for the playground. Discusses safety, liability, and risks involved when playground equipment is built by volunteers. (MD)

  17. Aguas!: An Introduction to Hispanic Plays.

    ERIC Educational Resources Information Center

    Saldana, Johnny

    1996-01-01

    Notes that the number of Hispanic children in schools is growing. Presents an annotated bibliography of 46 Hispanic plays, sources of information, and organizations dealing with Hispanic themes and ideas. (PA)

  18. Rac GTPases play multiple roles in erythropoiesis

    E-print Network

    Ji, Peng

    The four members of the Rac family of GTPases –Rac1, Rac2, Rac3 and RhoG – are members of the Rho superfamily that regulates the organization, dynamics, and function of the actin cytoskeleton. Rac GTPases play significant ...

  19. Playing games with UML tools Perdita Stevens

    E-print Network

    Stevens, Perdita

    FMCO 2002 Playing games with UML tools Perdita Stevens incorporating early joint work with Jennifer interfaces in arbitrary contexts ­ that was a pipe dream. Instead we can aim for appropriate libraries

  20. Playing violent video games increases intergroup bias.

    PubMed

    Greitemeyer, Tobias

    2014-01-01

    Previous research has shown how, why, and for whom violent video game play is related to aggression and aggression-related variables. In contrast, less is known about whether some individuals are more likely than others to be the target of increased aggression after violent video game play. The present research examined the idea that the effects of violent video game play are stronger when the target is a member of an outgroup rather than an ingroup. In fact, a correlational study revealed that violent video game exposure was positively related to ethnocentrism. This relation remained significant when controlling for trait aggression. Providing causal evidence, an experimental study showed that playing a violent video game increased aggressive behavior, and that this effect was more pronounced when the target was an outgroup rather than an ingroup member. Possible mediating mechanisms are discussed. PMID:24085715

  1. Laser Toys: Not Always Child's Play

    MedlinePLUS

    ... mail this page Home For Consumers Consumer Updates Laser Toys: Not Always Child's Play Search the Consumer ... an open room. back to top FDA Regulates Lasers A laser creates a powerful, targeted beam of ...

  2. Stop Playing Favorites with the Tax Code

    E-print Network

    Taylor, Lori L.

    particularly harmful form of playing favorites with the tax code by encouraging vertical integration and discouraging reliance upon outside small businesses. Eliminating sales tax exemptions and exclusions would go a long way toward solving budget problems...

  3. 'Dora' & Kids at Day of Play

    NASA Technical Reports Server (NTRS)

    2005-01-01

    From left, Cobie Smith, 5, and Tatume Smith, also 5, have their picture taken with 'Dora the Explorer.' The children were participants in Nickelodeon's Worldwide Day of Play celebration at Stennis Space Center (SSC) on Oct. 1. The Worldwide Day of Play is sponsored annually by Nickelodeon television network to encourage children to be physically active. Approximately 150 children participated in the event at SSC.

  4. Dead Zone - Background and Role Play

    NSDL National Science Digital Library

    In this exercise from ATEEC, students will complete a critical thinking activity on hypoxia and the Mississippi River watershed. The activity requires role playing "a public meeting to discuss the Integrated Assessment of Hypoxia in the Northern Gulf of Mexico, along with the recommendations for future action contained in the report and in the action plan." This document lists resources required for the activity, goals, six stakeholders for the students to role play, and additional resources.

  5. Gender Differences in Cognitive Load and Competition Anxiety Affect 6th Grade Students' Attitude toward Playing and Intention to Play at a Sequential or Synchronous Game

    ERIC Educational Resources Information Center

    Hwang, Ming-Yueh; Hong, Jon-Chao; Cheng, Hao-Yueh; Peng, Yu-Chi; Wu, Nien-Chen

    2013-01-01

    Do girls have more competition anxiety and exogenous cognitive load than equally able boys during the playing of stressful competitive on-line games? This question led to the adoption of a technology acceptance model to compare the influence factors of competitors in sequential and synchronous games. Confirmatory factor analysis of the data on 220…

  6. Neural contributions to flow experience during video game playing.

    PubMed

    Klasen, Martin; Weber, René; Kircher, Tilo T J; Mathiak, Krystyna A; Mathiak, Klaus

    2012-04-01

    Video games are an exciting part of new media. Although game play has been intensively studied, the underlying neurobiology is still poorly understood. Flow theory is a well-established model developed to describe subjective game experience. In 13 healthy male subjects, we acquired fMRI data during free play of a video game and analyzed brain activity based on the game content. In accordance with flow theory, we extracted the following factors from the game content: (i) balance between ability and challenge; (ii) concentration and focus; (iii) direct feedback of action results; (iv) clear goals; and (v) control over the situation/activity. We suggest that flow is characterized by specific neural activation patterns and that the latter can be assessed-at least partially-by content factors contributing to the emergence of flow. Each of the content factors was characterized by specific and distinguishable brain activation patterns, encompassing reward-related midbrain structures, as well as cognitive and sensorimotor networks. The activation of sensory and motor networks in the conjunction analyses underpinned the central role of simulation for flow experience. Flow factors can be validated with functional brain imaging which can improve the understanding of human emotions and motivational processes during media entertainment. PMID:21596764

  7. Neural contributions to flow experience during video game playing

    PubMed Central

    Weber, René; Kircher, Tilo T. J.; Mathiak, Krystyna A.; Mathiak, Klaus

    2012-01-01

    Video games are an exciting part of new media. Although game play has been intensively studied, the underlying neurobiology is still poorly understood. Flow theory is a well-established model developed to describe subjective game experience. In 13 healthy male subjects, we acquired fMRI data during free play of a video game and analyzed brain activity based on the game content. In accordance with flow theory, we extracted the following factors from the game content: (i) balance between ability and challenge; (ii) concentration and focus; (iii) direct feedback of action results; (iv) clear goals; and (v) control over the situation/activity. We suggest that flow is characterized by specific neural activation patterns and that the latter can be assessed—at least partially—by content factors contributing to the emergence of flow. Each of the content factors was characterized by specific and distinguishable brain activation patterns, encompassing reward-related midbrain structures, as well as cognitive and sensorimotor networks. The activation of sensory and motor networks in the conjunction analyses underpinned the central role of simulation for flow experience. Flow factors can be validated with functional brain imaging which can improve the understanding of human emotions and motivational processes during media entertainment. PMID:21596764

  8. The Play's the Thing: Showing Middle School Students How to Read a Play, "The Monkey's Paw."

    ERIC Educational Resources Information Center

    Blake, Robert W.

    Intended for middle school teachers interested in helping students (especially those with no experience attending theater) learn how to read and see a play by themselves, this paper provides a lesson plan based on W. W. Jacobs's dramatic play, "The Monkey's Paw." After furnishing a rationale for reading this particular play, the paper discusses…

  9. "Prey Play": Learning about Predators and Prey through an Interactive, Role-Play Game

    ERIC Educational Resources Information Center

    Deaton, Cynthia C. M.; Dodd, Kristen; Drennon, Katherine; Nagle, Jack

    2012-01-01

    "Prey Play" is an interactive role-play activity that provides fifth-grade students with opportunities to examine predator-prey interactions. This four-part, role-play activity allows students to take on the role of a predator and prey as they reflect on the behaviors animals exhibit as they collect food and interact with one another, as well as…

  10. Aggressive Outcomes and Videogame Play: The Role of Length of Play and the Mechanisms at Work

    Microsoft Academic Search

    Marina Krcmar; Kenneth Lachlan

    2009-01-01

    Recent meta-analytic findings (Sherry, 2007) suggest that the effect of violent video games on aggression tends to decrease the longer participants play. Therefore, it is likely that different mechanisms may be at work depending on the length of play. In this study, we employed a 4 (length of game play) × 2 (sex) design to examine the effect of length

  11. HRP-2 plays the yoyo: From human to humanoid yoyo playing using optimal control

    Microsoft Academic Search

    Katja Mombaur; Manish N. Sreenivasa

    2010-01-01

    Yoyo playing may seem easy for a human, but it is a challenging problem for a humanoid robot. This paper presents an approach to generate yoyo motions for the humanoid robot, HRP-2, based on motion recorded from human yoyo playing, dynamical models and numerical optimal control techniques. We recorded vertical yoyo playing of 4 subjects measuring yoyo height and rotation

  12. The Elements of Play: Toward a Philosophy and a Definition of Play

    ERIC Educational Resources Information Center

    Eberle, Scott G.

    2014-01-01

    Scholars conventionally find play difficult to define because the concept is complex and ambiguous. The author proffers a definition of play that takes into consideration its dynamic character, posits six basic elements of play (anticipation, surprise, pleasure, understanding, strength, and poise), and explores some of their emotional, physical,…

  13. Play as Self-Realization: Toward a General Theory of Play

    ERIC Educational Resources Information Center

    Henricks, Thomas S.

    2014-01-01

    In a wide-ranging essay that reviews the major theories of plays and relates them to significant notions of the self, the author addresses the question of why we play. He does so to argue that play is a biologically driven project of self-understanding and self-realization, one that humans--although they also share the experience with other…

  14. The "State of Play" in Australia: Early Childhood Educators and Play-Based Learning

    ERIC Educational Resources Information Center

    Sumsion, Jennifer; Grieshaber, Sue; McArdle, Felicity; Shield, Paul

    2014-01-01

    This article provides an overview of the Education Meets Play study that will investigate early childhood educators' use of play-based learning, now mandatory under the "National Quality Standard". By building on what can be gleaned about educators' approaches to play-based learning prior to the implementation of the…

  15. Learning to play, playing to learn : A case study of a ludic learning space

    Microsoft Academic Search

    Alice Y. Kolb; David A. Kolb

    2010-01-01

    Purpose – The purpose of this paper is to propose an experiential learning framework for understanding how play can potentially create a unique ludic learning space conducive to deep learning. Design\\/methodology\\/approach – The framework is developed by integrating two perspectives. First, from multidisciplinary theories of play to uncover the underlying play principles that contribute to the emergence of the ludic

  16. When play is a family business: adult play, hierarchy, and possible stress reduction in common marmosets.

    PubMed

    Norscia, Ivan; Palagi, Elisabetta

    2011-04-01

    Easy to recognize but not easy to define, animal play is a baffling behavior because it has no obvious immediate benefits for the performers. However, the absence of immediate advantages, if true, would leave adult play (costly but maintained by evolution, spanning lemurs to Homo sapiens) unexplained. Although a commonly held view maintains that play is limited by stress, an emergent hypothesis states that play can regulate stress in the short term. Here we explored this hypothesis in a captive family group of New World monkeys, Callithrix jacchus (common marmoset). We observed six subjects and gathered data on aggressive, play, and scratching behavior via focal (6 h/individual) and all occurrences sampling (115 h). We found that play levels were highest during pre-feeding, the period of maximum anxiety due to the forthcoming competition over food. Scratching (the most reliable indicator of stress in primates) and play showed opposite trends along hierarchy, with dominants scratching more and playing less than subordinates. Finally, scratching decreased after play, whereas play appeared to be unrelated to previous scratching events, symptoms of a potential stressful state. In conclusion, both play timing and hierarchical distribution indicate that play limits stress, more than vice versa, at least in the short term. PMID:21107884

  17. Playing with Technology: Mother-Toddler Interaction Scores Lower during Play with Electronic Toys

    ERIC Educational Resources Information Center

    Wooldridge, Michaela B.; Shapka, Jennifer

    2012-01-01

    To investigate play with electronic toys (battery-operated or digital), 25 mother-toddler (16-24 months old) dyads were videotaped in their homes playing with sets of age-appropriate electronic and non-electronic toys for approximately 10 min each. Parent-child interactions were coded from recorded segments of both of the play conditions using the…

  18. Can I Play with You? The Intersection of Play and Writing in a Kindergarten Classroom

    ERIC Educational Resources Information Center

    Yoon, Haeny S.

    2014-01-01

    Play is well documented as a purposeful, authentic way for children to engage in literacy practices. Although the benefits of play are widely agreed upon, there is some debate regarding its place in school. In fact, play is often marginalized in place of "back to the basics" language instruction. For kindergartners, this means word…

  19. What Play Therapists Do within the Therapeutic Relationship of Humanistic/Non-Directive Play Therapy

    ERIC Educational Resources Information Center

    Robinson, Sally

    2011-01-01

    Play therapists are increasingly being employed in schools, yet there is confusion among many health, education and social care practitioners about the role of play therapists. This paper explains how play therapists position themselves and what they do through an examination of the therapeutic relationship between the therapist and child. It…

  20. How Do Playful People Play? Gendered and Racial Leisure Perspectives, Motives, and Preferences of College Students

    Microsoft Academic Search

    Lynn A. Barnett

    2011-01-01

    Playfulness is an aspect of personality that predisposes individuals to reframe boring situations into more amusing ones for themselves. This study extends knowledge about the playfulness construct by contrasting college students who were high or low in playfulness relative to the activity preferences they make, the motives they have, and their perspectives on their leisure time. Significant differences were found

  1. Factor X deficiency

    Microsoft Academic Search

    James Uprichard; David J. Perry

    2002-01-01

    Factor X is one of the vitamin K-dependent serine proteases. It plays a crucial role in the coagulation cascade, as the first enzyme in the common pathway of thrombus formation. The gene for factor X maps to the long arm of chromosome 13, approximately 2.8 kb downstream of the factor VII gene. The gene consists of eight exons, each of

  2. Play Therapy for Bereaved Children: Adapting Strategies to Community, School, and Home Settings

    ERIC Educational Resources Information Center

    Webb, Nancy Boyd

    2011-01-01

    Play therapy is a highly adaptable treatment method that can be modified according to children's ages, circumstances, and settings in which counseling occurs. Play therapy may be used in schools, community settings, and homes to help children following the death of a significant other. After reviewing basic developmental factors that affect…

  3. Watch me Playing, I am a Professional: a First Study on Video Game Live Streaming

    E-print Network

    California at Santa Barbara, University of

    Factors, Measurement Keywords E-sport, Twitch.tv, Video game, StarCraft II, Social com- munity, PopularityWatch me Playing, I am a Professional: a First Study on Video Game Live Streaming Mehdi Kaytoue because we stop playing...". Enjoying video games at a professional level is not a young boy dream anymore

  4. COLLEGE MEN'S PSYCHOLOGICAL AND PHYSIOLOGICAL RESPONSES ASSOCIATED WITH VIOLENT VIDEO GAME PLAY

    Microsoft Academic Search

    CECIL LAMONTE POWELL

    Research suggests that playing violent video games increases the likelihood of aggression. However, less clear is how individual characteristics influence the mechanisms that lead to aggression. Using Anderson and Bushman's (2002) General Aggression Model as a framework, the present study examined the independent and joint effects of individual differences and situational factors on affective and physiological reactivity to playing a

  5. An understanding of Japanese children's perceptions of fun, barriers, and facilitators of active free play.

    PubMed

    Lee, Yinghua; Takenaka, Koji; Kanosue, Kazuyuki

    2014-01-31

    Physical activity contributes to children's physical and mental well-being. Research suggests that active free play helps to maintain and increase physical activity in children and also contributes to social and emotional well-being. To date, these studies have focused on Western countries. Thus, this study was conducted to gain insights into the factors of perceptions of fun, barriers, and facilitators affecting active free play from the perspective of Japanese children using focus group interviews. In Japan, 12 focus groups were conducted with 60 children aged 9-11 years. Children's perceptions of fun in active free play were categorized into socializing, achievement, emotions, and freedom. Additionally, active boys' groups were interested in free play and adventure play; girls' groups were interested in free play with less physical movement and challenges; inactive boys' groups were interested in relaxing and competitive play with bodily contact. However, children mentioned that busy schedules, weather, and health-related factors acted as main barriers. Lastly, children noted facilitators include setting schedules, having access to equipment and playgrounds, and holding special events. The findings provide insights into active free play-related factors for active and inactive Japanese children and also clarify the differences between Japanese and Western children. Such findings will contribute to designing interventions to increase active free play. PMID:24486818

  6. Bluetooth as a Playful Public Art Interface

    NASA Astrophysics Data System (ADS)

    Stukoff, Maria N.

    This chapter investigates how the application of emergent communication technologies assisted in the design of playful art experience in a public place. Every Passing Moment (EPM), was a mobile public artwork that tracked and recorded any discoverable Bluetooth device to automatically seed a flower in a virtual garden projected onto an urban screen. The EPM was the first public art work to run blu_box, a custom-designed Bluetooth system for mobile telephony. The aim of blu_box was to build a system that supported playful interactions between the public and an urban screen, openly accessible to anyone with a Bluetooth-enabled mobile phone. This participatory engagement was observed in EPM on three levels, namely; unconscious, conscious, and dynamic play. Furthermore, this chapter highlights how sound and face-to-face communication proved imperative in the play dynamics of EPM. In conclusion, this chapter proposes ways in which the use of emergent communication technologies in public places, especially when interfaced with urban screening platforms, can construct playful city spaces for the public at large.

  7. Specificity Protein 1 Transcription Factor Regulates Human ARTS Promoter Activity through Multiple Binding Sites

    PubMed Central

    Chen, Jinling; Zhu, Dandan; Sun, Xiaolei; Wang, Jianxin; Feng, Jinrong; Song, Ke; Duan, Yinong

    2015-01-01

    Apoptosis-related protein in the TGF-? signaling pathway (ARTS) is an unusual mitochondrial Septin-like protein which functions as a tumor suppressor. There are various splice variants derived from the human Septin4 gene, one of which is ARTS, also known as Septin4_i2. Unlike other Septin4 members, ARTS can induce apoptosis in many cells, however, the underlying molecular mechanism for the transcriptional regulation of ARTS has yet to be deciphered. In this study, we attempted to analyze the promoter region of ARTS in cultured HEK-293T and LX-2 cells with the purpose of elucidating the underlying transcriptional mechanisms driving ARTS expression. We effectively demonstrated that the -824 to -5 bp region of the ARTS promoter was essential for ARTS transcription and identified four putative specificity protein 1 (Sp1) binding sites within this core promoter region. ChIP analysis showed that Sp1 protein could bind to two of these sites (-735/-718 and -173/-157) and mutation of each Sp1 binding site led to a significant decrease in ARTS promoter activity. In conclusion, all the results indicated that the Sp1 transcription factor could contribute to ARTS gene transcription. The underlying molecular events of the specific promoter of ARTS could also be used to explain why ARTS is selectively silenced during some human diseases. This would provide basis for further study on the function of ARTS on cell apoptosis. PMID:25790304

  8. Cracking Bank PINs by Playing Mastermind

    NASA Astrophysics Data System (ADS)

    Focardi, Riccardo; Luccio, Flaminia L.

    The bank director was pretty upset noticing Joe, the system administrator, spending his spare time playing Mastermind, an old useless game of the 70ies. He had fought the instinct of telling him how to better spend his life, just limiting to look at him in disgust long enough to be certain to be noticed. No wonder when the next day the director fell on his chair astonished while reading, on the newspaper, about a huge digital fraud on the ATMs of his bank, with millions of Euros stolen by a team of hackers all around the world. The article mentioned how the hackers had 'played with the bank computers just like playing Mastermind', being able to disclose thousands of user PINs during the one-hour lunch break. That precise moment, a second before falling senseless, he understood the subtle smile on Joe's face the day before, while training at his preferred game, Mastermind.

  9. On the significance of adult play: what does social play tell us about adult horse welfare?

    NASA Astrophysics Data System (ADS)

    Hausberger, Martine; Fureix, Carole; Bourjade, Marie; Wessel-Robert, Sabine; Richard-Yris, Marie-Annick

    2012-04-01

    Play remains a mystery and adult play even more so. More typical of young stages in healthy individuals, it occurs rarely at adult stages but then more often in captive/domestic animals, which can imply spatial, social and/or feeding deprivations or restrictions that are challenging to welfare, than in animals living in natural conditions. Here, we tested the hypothesis that adult play may reflect altered welfare states and chronic stress in horses, in which, as in several species, play rarely occurs at adult stages in natural conditions. We observed the behaviour (in particular, social play) of riding school horses during occasional outings in a paddock and measured several stress indicators when these horses were in their individual home boxes. Our results revealed that (1) the number of horses and rates of adult play appeared very high compared to field report data and (2) most stress indicators measured differed between `players' and `non-players', revealing that most `playful' animals were suffering from more chronic stress than `non-playful' horses. Frequency of play behaviour correlated with a score of chronic stress. This first discovery of a relationship between adult play and altered welfare opens new lines of research that certainly deserves comparative studies in a variety of species.

  10. Circuit Bending with Play-Doh

    NSDL National Science Digital Library

    Science Museum of Minnesota

    2012-06-26

    Break open that used musical toy and squish some Play-Doh over the circuit boards, and you will hear some weird and distorted sounds the manufacturer never intended! In this activity learners experiment with the strange conductive properties of Play-Doh in order to safely short-circuit a musical toy. This is an entertaining activity about basic circuitry, sounds, and short circuiting or "circuit bending" battery powered musical toys. Note: often it is difficult to unscrew the musical toys open, and the insides are delicate. So consider this when turning this into a group activity.

  11. To Play Trail and Go Ape!

    E-print Network

    B e d g e b u r y F o r e s t To Play Trail and Go Ape! National Cycle Network Route 18Enntrance oA21 Overflow Car Park TTo V enenen du u b e ucat y r forest o theTTo deB and Go Ape! oTTo d e B and Go Ape! railTo Play g d 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 A B C D E F G H I J

  12. The Relationship Between Smile Type and Play Type During Parent–Infant Play

    Microsoft Academic Search

    K. Laurie Dickson; Heather Walker; Alan Fogel

    1997-01-01

    This study examined the relationship between smile type and play type during parent–infant interactions in the home. Thirty-six mother–infant and father–infant dyads were videotaped playing for 10 min. Smile type (basic, Duchenne, and duplay smiles) and play type (object, physical, vocal, and book reading) were coded. Results of loglinear analysis indicated that different types of smiles occur during different types

  13. The relationship between smile type and play type during parent-infant play

    Microsoft Academic Search

    K. Laurie Dickson; Heather Walker; Alan Fogel

    1997-01-01

    This study examined the relationship between smile type and play type during parent-infant interac- tions in the home. Thirty-six mother-infant and father-infant dyads were videotaped playing for 10 min. Smile type (basic, Duchenne, and duplay smiles) and play type (object, physical, vocal, and book reading) were coded. Results of loglinear analysis indicated that different types of smiles occur during different

  14. Home video game playing in schoolchildren: a study of incidence and patterns of play

    Microsoft Academic Search

    Carol A. Phillips; Susan Rolls; Andrew Rouse; Mark D. Griffiths

    1995-01-01

    The recent increase in the home video games market has resulted in the ready availability of such games. This study attempted to quantify the extent of home video game playing in a typical population of 11-16-year-olds (429 males and 387 females). Of the children questioned 77.2% played video games. The most common pattern of play was daily with most of

  15. Assembling and Dissembling: Policy as Productive Play

    ERIC Educational Resources Information Center

    Koyama, Jill P.; Varenne, Herve

    2012-01-01

    In this piece, the authors examine educational policy by focusing on the ways in which actors "play" or selectively follow, negotiate, and appropriate cultural instructions and rules. They outline a framework that situates assemblage, a notion utilized in actor-network theory, within the critical cultural study of policy. Treating policy…

  16. Children's Thinking Styles, Play, and Academic Performance

    ERIC Educational Resources Information Center

    Holmes, Robyn M.; Liden, Sharon; Shin, Lisa

    2013-01-01

    Based on the study of seventy-four middle school children of mostly Filipino and part Hawaiian heritages, this article explores the relationships of children's thinking styles, play preferences, and school performance. Using the Group Embedded Figures Test, the Articulation of the Body Scale, and written responses to three questions, the authors…

  17. Benefit Concert: Brian Ganz Plays Chopin

    E-print Network

    von der Heydt, Rüdiger

    "West"; the Harlem Renaissance; Southern women writers; and courses in American Sign LanguageOdyssey Benefit Concert: Brian Ganz Plays Chopin Ori Soltes on Golden Age Cities Local and Regional with tried and true favorites. To begin with, we are proud to feature a special-event benefit concert

  18. How to Build & Play a Theremin

    NSDL National Science Digital Library

    Keppinger, Mark

    Learn how to build a theremin in this free online video guide to electronic musical instruments, including the history of theremins, playing tips, and how to build your own. The theremin is one of the earliest fully electronic musical instruments, and is named after its inventor Leon Theremin. Designed to be played without being touched, the instrument consists of circuitry including two antennas that the user moves their hands around to play. The instrument was originally used to research proximity sensors in Russia. The inventor of the synthesizer, Robert Moog, attributes his success to his interest in the theremin. With the invention of other, simpler to play electrical instruments, the theremin did not experience commercial success. Amongst electrical enthusiasts however, it has stayed popular over the years. In this series of expert video clips, learn more about the theremin. Our expert goes into detail about what makes up the complicated workings of the theremin including the coils and other components. Get a full history on the musical instrument and learn about the many uses of a theremin. What makes a theremin sound so special? Get answers to this question and many more in our expert instructional videos.

  19. Block Talk: Spatial Language during Block Play

    ERIC Educational Resources Information Center

    Ferrara, Katrina; Hirsh-Pasek, Kathy; Newcombe, Nora S.; Golinkoff, Roberta Michnick; Lam, Wendy Shallcross

    2011-01-01

    Spatial skills are a central component of intellect and show marked individual differences. There is evidence that variations in the spatial language young children hear, which directs their attention to important aspects of the spatial environment, may be one of the mechanisms that contributes to these differences. To investigate how play affects…

  20. Rethinking Role Play in the Reception Class

    ERIC Educational Resources Information Center

    Rogers, Sue; Evans, Julie

    2007-01-01

    Background: In 2000 the so-called "Reception" class was re-conceived (in curricular terms, at least) as the second and final year of the Foundation Stage, a distinctive educational phase for children aged 3 until entry to key stage 1 at 5 or 6 years old. The "Curriculum guidance for the Foundation Stage" endorses a play-based, informal curriculum…