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. Sp1- and Krüppel-like transcription factors

    Microsoft Academic Search

    Joanna Kaczynski; Tiffany Cook; Raul Urrutia

    2003-01-01

    SUMMARY: Sp1-like proteins and Krüppel-like factors (KLFs) are highly related zinc-finger proteins that are important components of the eukaryotic cellular transcriptional machinery. By regulating the expression of a large number of genes that have GC-rich promoters, Sp1-like\\/KLF transcription regulators may take part in virtually all facets of cellular function, including cell proliferation, apoptosis, differentiation, and neoplastic transformation. Individual members of

  3. Sp1 transcription factor: A long-standing target in cancer chemotherapy.

    PubMed

    Vizcaíno, Carolina; Mansilla, Sylvia; Portugal, José

    2015-08-01

    Sp1 (specificity protein 1) is a well-known member of a family of transcription factors that also includes Sp2, Sp3 and Sp4, which are implicated in an ample variety of essential biological processes and have been proven important in cell growth, differentiation, apoptosis and carcinogenesis. Sp1 activates the transcription of many cellular genes that contain putative CG-rich Sp-binding sites in their promoters. Sp1 and Sp3 proteins bind to similar, if not the same, DNA tracts and compete for binding, thus they can enhance or repress gene expression. Evidences exist that the Sp-family of proteins regulates the expression of genes that play pivotal roles in cell proliferation and metastasis of various tumors. In patients with a variety of cancers, high levels of Sp1 protein are considered a negative prognostic factor. A plethora of compounds can interfere with the trans-activating activities of Sp1 and other Sp proteins on gene expression. Several pathways are involved in the down-regulation of Sp proteins by compounds with different mechanisms of action, which include not only the direct interference with the binding of Sp proteins to their putative DNA binding sites, but also promoting the degradation of Sp protein factors. Down-regulation of Sp transcription factors and Sp1-regulated genes is drug-dependent and it is determined by the cell context. The acknowledgment that several of those compounds are safe enough might accelerate their introduction into clinical usage in patients with tumors that over-express Sp1. PMID:25960131

  4. Activation of human papillomavirus type 18 E6-E7 oncogene expression by transcription factor Sp1.

    PubMed Central

    Hoppe-Seyler, F; Butz, K

    1992-01-01

    The human papillomavirus 18 (HPV18) E6 and E7 proteins are considered to be primarily responsive for the transforming activity of the virus. In order to analyse the molecular mechanisms resulting in viral oncoprotein expression, it is necessary to identify the factors involved in the transcriptional regulation of the E6/E7 genes. Here we define by gel retardation experiments a sequence aberrant Sp1 binding site present in the promoter proximal part of the viral transcriptional control region (Upstream Regulatory Region, URR). Functional analyses employing transient reporter assays reveal that this Sp1 element is required for an efficient stimulation of the HPV18 E6/E7-promoter. Mutation of the Sp1 element in the natural context of the HPV18 URR leads to a strong decrease in the activity of the E6/E7-promoter in several cell lines. The magnitude of reduction varies between different cell types and is higher in cell lines of epithelial origin when compared with nonepithelial cells. Cotransfection assays using Sp1 expression vector systems further define the promoter proximal HPV18 Sp1 binding motif as a functional Sp1 element in vivo and show that its integrity is essential for the stimulation of the E6/E7-promoter by augmented levels of Sp1. These results indicate, that the cellular transcription factor Sp1 plays an important role for the stimulation of the E6/E7-promoter by the viral URR and represents a major determinant for the expression of HPV18 transforming genes E6 and E7. Images PMID:1336181

  5. 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

  6. 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.

  7. Transcription factor Sp3 antagonizes activation of the ornithine decarboxylase promoter by Sp1.

    PubMed Central

    Kumar, A P; Butler, A P

    1997-01-01

    Ornithine decarboxylase (ODC) expression is important for proliferation and is elevated in many tumor cells. We previously showed that Sp1 is a major positive regulator of ODC transcription. In this paper we have investigated transcriptional regulation of rat ODC by the closely related factor Sp3. While over-expression of Sp1 caused a dramatic activation of the ODC promoter, over-expression of Sp3 caused little or no activation in either Drosophila SL2 cells (lacking endogenous Sp1 or Sp3) or in H35 rat hepatoma cells. Furthermore, co-transfection studies demonstrated that Sp3 abolished trans -activation of the ODC promoter by Sp1. DNase I footprint studies and electrophoretic mobility shift assays demonstrated that both recombinant Sp1 and Sp3 bind specifically to several sites within the ODC promoter also protected by nuclear extracts, including overlapping GC and CT motifs located between -116 and -104. This CT element is a site of negative ODC regulation. Mutation of either element reduced binding, but mutation of both sites was required to eliminate binding of either Sp1 or Sp3. These results demonstrate that ODC is positively regulated by Sp1 and negatively regulated by Sp3, suggesting that the ratio of these transcription factors may be an important determinant of ODC expression during development or transformation. PMID:9115370

  8. Transforming Growth Factor ? Signaling Upregulates the Expression of Human GDP-Fucose Transporter by Activating Transcription Factor Sp1

    PubMed Central

    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

  9. Cytosine methylation does not affect binding of transcription factor Sp1

    SciTech Connect

    Harrington, M.A.; Jones, P.A. (Univ. of Southern California School of Medicine, Los Angeles (USA)); Imagawa, M.; Karin, M. (Univ. of California, San Diego, La Jolla (USA))

    1988-04-01

    DNA methylation may be a component of a multilevel control mechanism that regulates eukaryotic gene expression. The authors used synthetic oligonucleotides to investigate the effect of cytosine methylation on the binding of the transcription factor Sp1 to its target sequence (a G+C-rich sequence known as a GC box). Concatemers of double-stranded 14-mers containing a GC box successfully competed with the human metallothionein IIA promoter for binding to Sp1 in DNase I protection experiments. The presence of 5-methylcytosine in the CpG sequence of the GC box did not influence Sp1 binding. The result was confirmed using double-stranded 20-mers containing 16 base pairs of complementary sequence. Electrophoretic gel retardation analysis of annealed 28-mers containing a GC box incubated with an Sp1-containing HeLa cell nuclear extract demonstrated the formation of DNA-protein complexes; formation of these complexes was not inhibited when an oligomer without a GC box was used as a competitor. Once again, the presence of a 5-methylcytosine residue in the GC box did not influence the binding of the protein to DNA. The results therefore preclude a direct effect of cytosine methylation on Sp1-DNA interactions.

  10. Increased SP4 and SP1 transcription factor expression in the postmortem hippocampus of chronic schizophrenia.

    PubMed

    Pinacho, Raquel; Valdizán, Elsa M; Pilar-Cuellar, Fuencisla; Prades, Roger; Tarragó, Teresa; Haro, Josep Maria; Ferrer, Isidre; Ramos, Belén

    2014-11-01

    Altered levels of transcription factor specificity protein 4 (SP4) and 1 (SP1) in the cerebellum, prefrontal cortex and/or lymphocytes have been reported in severe psychiatric disorders, including early psychosis, bipolar disorder, and chronic schizophrenia subjects who have undergone long-term antipsychotic treatments. SP4 transgenic mice show altered hippocampal-dependent psychotic-like behaviours and altered development of hippocampal dentate gyrus. Moreover, NMDAR activity regulates SP4 function. The aim of this study was to investigate SP4 and SP1 expression levels in the hippocampus in schizophrenia, and the possible effect of antipsychotics and NMDAR blockade on SP protein levels in rodent hippocampus. We analysed SP4 and SP1 expression levels in the postmortem hippocampus of chronic schizophrenia (n = 14) and control (n = 11) subjects by immunoblot and quantitative RT-PCR. We tested the effect of NMDAR blockade on SP factors in the hippocampus of mouse treated with an acute dose of MK801. We also investigated the effect of subacute treatments with haloperidol and clozapine on SP protein levels in the rat hippocampus. We report that SP4 protein and both SP4 and SP1 mRNA expression levels are significantly increased in the hippocampus in chronic schizophrenia. Likewise, acute treatment with MK801 increased both SP4 and SP1 protein levels in mouse hippocampus. In contrast, subacute treatment with haloperidol and clozapine did not significantly alter SP protein levels in rat hippocampus. These results suggest that SP4 and SP1 upregulation may be part of the mechanisms deregulated downstream of glutamate signalling pathways in schizophrenia and might be contributing to the hippocampal-dependent cognitive deficits of the disorder. PMID:25175639

  11. 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

  12. Transcription Factors ETF, E2F, and SP-1 Are Involved in Cytokine-Independent Proliferation of Murine

    E-print Network

    Timmer, Jens

    Transcription Factors ETF, E2F, and SP-1 Are Involved in Cytokine-Independent Proliferation-regulated. The latter genes showed an overrepresen- tation of transcription factor binding sites (TFBS) for ETF (TEA hepatectomy con- tained overrepresented TFBS for ETF, E2F1, and SP-1 and displayed increased expression of E2F

  13. Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site

    PubMed Central

    2013-01-01

    Background Vascular Endothelial Growth Factor (VEGF) is regulated by a number of different factors, but the mechanism(s) behind androgen-mediated regulation of VEGF in prostate cancer are poorly understood. Results Three novel androgen receptor (AR) binding sites were discovered in the VEGF promoter and in vivo binding of AR to these sites was demonstrated by chromatin immunoprecipitation. Mutation of these sites attenuated activation of the VEGF promoter by the androgen analog, R1881 in prostate cancer cells. The transcription factors AR and Sp1 were shown to form a nuclear complex and both bound the VEGF core promoter in chromatin of hormone treated CWR22Rv1 prostate cancer cells. The importance of the Sp1 binding site in hormone mediated activation of VEGF expression was demonstrated by site directed mutagenesis. Mutation of a critical Sp1 binding site (Sp1.4) in the VEGF core promoter region prevented activation by androgen. Similarly, suppression of Sp1 binding by Mithramycin A treatment significantly reduced VEGF expression. Conclusions Our mechanistic study of androgen mediated induction of VEGF expression in prostate cancer cells revealed for the first time that this induction is mediated through the core promoter region and is dependent upon a critical Sp1 binding site. The importance of Sp1 binding suggests that therapy targeting the AR-Sp1 complex may dampen VEGF induced angiogenesis and, thereby, block prostate cancer progression, helping to maintain the indolent form of prostate cancer. PMID:23369005

  14. 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

  15. Regulation of transcription from the hepatitis B virus major surface antigen promoter by the Sp1 transcription factor.

    PubMed Central

    Raney, A K; Le, H B; McLachlan, A

    1992-01-01

    The DNA-binding proteins which recognize the regulatory sequence elements of the hepatitis B virus (HBV) major surface antigen promoter were examined by gel retardation analysis, using nuclear extracts from the human hepatoma cell line Huh7. Using this assay, we identified four regions (B, D, E, and F) of the promoter that interact with the same or similar transcription factor(s). In addition, the recognition sequence for the Sp1 transcription factor bound the same or similar transcription factor(s) present in Huh7 cell nuclear extracts, and this binding was inhibited by the four major surface antigen promoter elements, B, D, E, and F. Purified Sp1 transcription factor was shown to bind to three (B, D, and F) of the major surface antigen promoter regulatory sequence elements by DNase I footprinting. Using transient transfection assays with Drosophila Schneider line 2 cells, we found that transcription from the major surface antigen promoter was transactivated by exogenously expressed Sp1, whereas transcription from the other three HBV promoters was not. Deletion analysis of the major surface antigen promoter demonstrated that the promoter region between -35 and +157 was sufficient to confer Sp1 responsiveness. This promoter region includes one of the regulatory elements footprinted by the purified Sp1 transcription factor. The function of the B, D, E, and F promoter elements was further examined by using these binding sites cloned into a minimal promoter element. Each of these regulatory regions transactivated transcription from the minimal promoter element in response to exogenously expressed Sp1. This finding demonstrates that the HBV major surface antigen promoter contains four functional Sp1 binding sites which probably contribute to the level of expression from this promoter during viral infection. Images PMID:1331502

  16. Significant biological role of Sp1 transactivation in multiple myeloma

    PubMed Central

    Fulciniti, Mariateresa; Amin, Samir; Nanjappa, Puru; Rodig, Scott; Prabhala, Rao; Li, Cheng; Minvielle, Stephane; Tai, Yu-tzu; Tassone, Pierfrancesco; Avet-Loiseau, Herve; Hideshima, Teru; Anderson, Kenneth C.; Munshi, Nikhil C.

    2015-01-01

    Purpose The transcription factor Sp1 controls number of cellular processes by regulating the expression of critical cell cycle, differentiation and apoptosis-related genes containing proximal GC/GT-rich promoter elements. We here provide both experimental and clinical evidence that Sp1 plays an important regulatory role in MM cell growth and survival. Experimental design We have investigated the functional Sp1 activity in MM cells using a plasmid with renilla luciferase reporter gene driven by Sp1-responsive promoter. We have also used both SiRNA and ShRNA-mediated Sp1 knock-down to investigate the growth and survival effects of Sp1 on MM cells, and further investigated the anti-MM activity of Terameprocol (TMP), a small molecule which specifically competes with Sp1-DNA binding in vitro and in vivo. Results We have confirmed high Sp1 activity in MM cells which is further induced by adhesion to bone marrow stromal cells (BMSC). Sp1 knock down decreases MM cell proliferation and induces apoptosis. Sp1-DNA binding inhibition by TMP inhibits MM cell growth both in vitro and in vivo, inducing caspase 9-dependent apoptosis and overcoming the protective effects of BMSCs. Conclusions Our results demonstrate Sp1 as an important transcription factor in myeloma that can be therapeutically targeted for clinical application by TMP. PMID:21856768

  17. 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

  18. The transcription factor SP1 regulates centriole function and chromosomal stability through a functional interaction with the mammalian target of rapamycin/raptor complex.

    PubMed

    Astrinidis, Aristotelis; Kim, Jiyoon; Kelly, Crystal M; Olofsson, Beatrix A; Torabi, Behzad; Sorokina, Elena M; Azizkhan-Clifford, Jane

    2010-03-01

    Specificity protein 1 (SP1) is an essential transcription factor implicated in the regulation of genes that control multiple cellular processes, including cell cycle, apoptosis, and DNA damage. Very few nontranscriptional roles for SP1 have been reported thus far. Using confocal microscopy and centrosome fractionation, we identified SP1 as a centrosomal protein. Sp1-deficient mouse embryonic fibroblasts and cells depleted of SP1 by RNAi have increased centrosome number associated with centriole splitting, decreased microtubule nucleation, chromosome misalignment, formation of multipolar mitotic spindles and micronuclei, and increased incidence of aneuploidy. Using mass spectrometry, we identified P70S6K, an effector of the mTOR/raptor (mTORC1) kinase complex, as a novel interacting protein of SP1. We found that SP1-deficient cells have increased phosphorylation of the P70S6K effector ribosomal protein S6, suggesting that SP1 participates in the regulation of the mTORC1/P70S6K/S6 signaling pathway. We previously reported that aberrant mTORC1 activation leads to supernumerary centrosomes, a phenotype rescued by the mTORC1 inhibitor rapamycin. Similarly, treatment with rapamycin rescued the multiple centrosome phenotype of SP1-deficient cells. Taken together, these data strongly support the hypothesis that SP1 is involved in the control of centrosome number via regulation of the mTORC1 pathway, and predict that loss of SP1 function can lead to aberrant centriole splitting, deregulated mTORC1 signaling, and aneuploidy, thereby contributing to malignant transformation. PMID:20013896

  19. 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

  20. 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

  1. 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.

  2. Sequence-specific recognition of DNA by zinc-finger peptides derived from the transcription factor Sp1.

    PubMed Central

    Kriwacki, R W; Schultz, S C; Steitz, T A; Caradonna, J P

    1992-01-01

    We have overexpressed and purified two peptide fragments of Sp1 that contain the three "zinc-finger" domains necessary for specific Sp1 DNA binding. These peptides assume a stable, folded conformation in solution in the presence of Zn2+ as shown by DNA binding assays and NMR spectroscopy. Mobility-shift assays demonstrate that the Sp1 peptides recognize a number of different Sp1 DNA binding sites (GC boxes, with the core sequence GGGCGG). The dissociation constant for a 92-amino acid peptide binding to the GGGGCGGGGC sequence (Kd approximately 10 nM) and the relative affinities for several other DNA sequences definitively demonstrate Sp1-like binding properties. The thermodynamic binding site for Sp1-Zn92 has been mapped using the primer-extension/mobility-shift assay revealing that the 5' portion of the GC box DNA sequence (GGG GCG) contributes more strongly to the total binding energy than the 3' portion (GGGC). These findings are interpreted in the context of the Sp1 amino acid sequence in comparison with the structurally characterized Zif-268/DNA complex. A model is proposed that offers a structural explanation for the ability of Sp1 to recognize a diverse array of DNA sequences in terms of the individual (and different) DNA binding properties of each of the three zinc-finger domains. Images PMID:1329106

  3. Factors affecting mother-child play 

    E-print Network

    Welch, Jennifer Colleen

    1993-01-01

    FACTORS AFFECTING MOTHER-CHILD PLAY A Thesis by JENNIFER COLLEEN WELCH Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree MASTER OF SCIENCE August 1993 Major Subject...: Psychology FACTORS AFFECTING MOTHER-CHILD PLAY A Thesis by JENNIFER COLLEEN WELCH Submitted to Texas ASM University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved as to style and content bg: T' othy A. Cavell...

  4. Blocking Sp1 Transcription Factor Broadly Inhibits Extracellular Matrix Gene Expression In Vitro and In Vivo: Implications for the Treatment of Tissue Fibrosis

    Microsoft Academic Search

    Franck Verrecchia; Jérôme Rossert; Alain Mauviel

    2001-01-01

    Fibrosis is a consequence of injury characterized by accumulation of excess collagen and other extracellular matrix components, resulting in the destruction of normal tissue architecture and loss of function. Sp1 was originally described as a ubiquitous transcription factor. It is involved in the basal expression of extracellular matrix genes and may, therefore, be important in fibrotic processes. To evaluate the

  5. Induction of IL-6 gene expression in a CF bronchial epithelial cell line by Pseudomonas aeruginosa is dependent on transcription factors belonging to the Sp1 superfamily.

    PubMed

    Borgatti, Monica; Bezzerri, Valentino; Mancini, Irene; Nicolis, Elena; Dechecchi, Maria Cristina; Lampronti, Ilaria; Rizzotti, Paolo; Cabrini, Giulio; Gambari, Roberto

    2007-06-15

    Cystic fibrosis (CF) is a genetic disease characterized by chronic bacterial lung infection, most commonly sustained by Pseudomonas aeruginosa. Upon infection, elevated concentrations of pro-inflammatory cytokines (i.e. IL-6 and IL1beta) and chemokines (i.e. IL-8 and GROgamma) are found in the bronchoalveolar fluid of CF patients. We report in this paper that: (a) IL-8, IL-6, IL-1beta, ICAM-1, and GRO-gamma genes are upregulated following infection of CF bronchial epithelial IB3-1 cells with P. aeruginosa; (b) Sp1 transcription factor activity is induced following infection of the cystic fibrosis IB3-1 and CuFi-1 cell lines; (c) inhibition of Sp1 activity using transcription factor decoy molecules leads to inhibition of the expression of IL-6 gene. From the theoretical point of view, our results demonstrate that Sp1 transcription factor activity is induced following infection of CF cells with P. aeruginosa, and that this effect is important in the activation of IL-6 gene transcription. From the practical point of view, our data sustain the potential use of decoy molecules targeting the transcription factor Sp1 to control a relevant molecule involved in the inflammatory process associated with the cystic fibrosis airway pathology. PMID:17466942

  6. 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

  7. Triptolide-induced cell death in pancreatic cancer is mediated by O-GlcNAc modification of transcription factor Sp1.

    PubMed

    Banerjee, Sulagna; Sangwan, Veena; McGinn, Olivia; Chugh, Rohit; Dudeja, Vikas; Vickers, Selwyn M; Saluja, Ashok K

    2013-11-22

    Pancreatic cancer, the fourth most prevalent cancer-related cause of death in the United States, is a disease with a dismal survival rate of 5% 5 years after diagnosis. One of the survival proteins responsible for its extraordinary ability to evade cell death is HSP70. A naturally derived compound, triptolide, and its water-soluble prodrug, Minnelide, down-regulate the expression of this protein in pancreatic cancer cells, thereby causing cell death. However, the mechanism of action of triptolide has not been elucidated. Our study shows that triptolide-induced down-regulation of HSP70 expression is associated with a decrease in glycosylation of the transcription factor Sp1. We further show that triptolide inhibits glycosylation of Sp1, inhibiting the hexosamine biosynthesis pathway, particularly the enzyme O-GlcNAc transferase. Inhibition of O-GlcNAc transferase prevents nuclear localization of Sp1 and affects its DNA binding activity. This in turn down-regulates prosurvival pathways like NF-?B, leading to inhibition of HSF1 and HSP70 and eventually to cell death. In this study, we evaluated the mechanism by which triptolide affects glycosylation of Sp1, which in turn affects downstream pathways controlling survival of pancreatic cancer cells. PMID:24129563

  8. Altered Expression of NF-?B and SP1 after Exposure to Advanced Glycation End-Products and Effects of Neurotrophic Factors in AGEs Exposed Rat Retinas

    PubMed Central

    Yamamoto, Shuichi

    2015-01-01

    To determine the effect of advanced glycation end-products (AGEs) on neurite regeneration, and also to determine the regenerative effects of different neurotrophic factors (NTFs) on rat retinal explants, the retinas of SD rats were cultured in three-dimensional collagen gels and incubated in 6 types of media: (1) serum-free control culture media; (2) 100??g/mL AGEs-BSA media; (3) AGEs-BSA + 100?ng/mL neurotrophin-4 (NT-4) media; (4) AGEs-BSA + 100?ng/mL hepatocyte growth factor media; (5) AGEs-BSA + 100?ng/mL glial cell line-derived neurotrophic factor media; or (6) AGEs-BSA + 100?µM tauroursodeoxycholic acid media. After 7 days, the number of regenerating neurites was counted. The explants were immunostained for nuclear factor-?B (NF-?B) and specificity protein 1 (SP1). Statistical analyses were performed by one-way ANOVA. In retinas incubated with AGEs, the numbers of neurites were fewer than in control. All of the NTFs increased the number of neurites, and the increase was more significant in the NT-4 group. The number of NF-?B and SP1 immunopositive cells was higher in retinas exposed to AGEs than in control. All of the NTFs decreased the number of NF-?B immunopositive cells but did not significantly affect SP1 expression. These results demonstrate the potential of the NTFs as axoprotectants in AGEs exposed retinal neurons.

  9. Aristolochic acid I and ochratoxin A differentially regulate VEGF expression in porcine kidney epithelial cells—The involvement of SP-1 and HIFs transcription factors

    PubMed Central

    Stachurska, Anna; Kozakowska, Magdalena; Jozkowicz, Alicja; Dulak, Jozef; Loboda, Agnieszka

    2011-01-01

    Aristolochic acid I (AAI) and ochratoxin A (OTA) cause chronic kidney diseases. Recently, the contribution of hypoxic injuries and angiogenic disturbances to nephropathies has been suggested, but underlying mechanisms have not been fully clarified yet. In porcine kidney epithelial cell line, LLC-PK1 cells, treatment with non-toxic doses of AAI increased whereas with OTA decreased production of vascular endothelial growth factor (VEGF), the angiogenic factor with well-defined functions in kidney. Moreover, the activity of transcription factors regulating VEGF expression was differentially affected by examined compounds. Activity of hypoxia inducible factors (HIFs) and SP-1 was increased by AAI but diminished by OTA. Interestingly, AP-1 activity was inhibited while NF?B was not influenced by both toxins. Mithramycin A, a SP-1 inhibitor, as well as chetomin, an inhibitor of HIFs, reversed AAI-induced up-regulation of VEGF synthesis, indicating the importance of SP-1 and HIFs in this effect. Additionally, adenoviral overexpression of HIF-2? but not HIF-1? prevented OTA-diminished VEGF production suggesting the protective effect of this isoform towards the consequences exerted by OTA. These observations provide new insight into complex impact of AAI and OTA on angiogenic gene regulation. Additionally, it adds to our understanding of hypoxia influence on nephropathies pathology. PMID:21554934

  10. Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1.

    PubMed Central

    Su, K; Yang, X; Roos, M D; Paterson, A J; Kudlow, J E

    2000-01-01

    The transcription factor Sp1 was previously shown to undergo proteasome-dependent degradation when cells were glucose-starved and stimulated with the adenylate cyclase inducer, forskolin. However, the control of the Sp1 degradation process is largely unknown. Using in vitro and in vivo interaction studies, we show in the present study that Sp1 interacts with human Sug1 [hSug1, also known as p45 or thyroid-hormone-receptor interacting protein ('TRIP1')], an ATPase subunit of the 26 S proteasome and a putative transcriptional modulator. This interaction with Sp1 occurs through the C-terminus of hSug1, the region that contains the conserved ATPase domain in this protein. Both in vitro studies, in reconstituted degradation assays, and in vivo experiments, in which hSug1 is overexpressed in normal rat kidney cells, show that full-length hSug1 is able to stimulate the proteasome-dependent degradation of Sp1. However, hSug1 truncations that lack either the N- or C-terminal domain of hSug1 act as dominant negatives, inhibiting Sp1 degradation in vitro. Also, an ATPase mutant of hSug1, while still able to bind Sp1, acts as a dominant negative, blocking Sp1 degradation both in vitro and in vivo. These results demonstrate that hSug1 is involved in the degradation of Sp1 and that ATP hydrolysis by hSug1 is necessary for this process. Our findings indicate that hSug1 is an exchangeable proteasomal component that plays a critical regulatory role in the proteasome-dependent degradation of Sp1. However, hSug1 is not the factor limiting Sp1 degradation in the cells treated with glucosamine. This and other considerations suggest that hSug1 co-operation with other molecules is necessary to target Sp1 for proteasome degradation. PMID:10816420

  11. 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.

    -like Growth Factor-1 in Cardiac Muscle Cells Tao Li1 , Yung-Hsiang Chen1,2 , Tsun-Jui Liu1,2 , Jia Jia1) stimulation in cardiac muscle cells. The analysis showed that the Sp1 binding site is a likely target of IGF-1 and identified common promoter motifs that respond to IGF-1 stimulation in cardiac muscle cells. #12

  12. A Functional Common Polymorphism in a Sp1 Recognition Site of the Epidermal Growth Factor Receptor Gene Promoter

    Microsoft Academic Search

    Wanqing Liu; Federico Innocenti; Michael H. Wu; Apurva A. Desai; M. Eileen Dolan; Edwin H. Cook; Mark J. Ratain

    2005-01-01

    The epidermal growth factor receptor (EGFR) plays a prom- inent role in cell growth and development. Its regulation in humans is complex and incompletely understood. In this study, 12 new polymorphisms were discovered in the 5V-regulatory region of EGFR gene and 2 common single nucleotide polymorphisms (216G\\/T and 191C\\/A) were found in the essential promoter area, one of which is

  13. 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

  14. 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

  15. 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

  16. 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

  17. Expression of the rat liver carnitine palmitoyltransferase I (CPT-Ialpha) gene is regulated by Sp1 and nuclear factor Y: chromosomal localization and promoter characterization.

    PubMed Central

    Steffen, M L; Harrison, W R; Elder, F F; Cook, G A; Park, E A

    1999-01-01

    Carnitine palmitoyltransferase (CPT)-I catalyses the transfer of long-chain fatty acids from CoA to carnitine for translocation across the mitochondrial inner membrane. Expression of the 'liver' isoform of the CPT-I gene (CPT-Ialpha) is subject to developmental, hormonal and tissue-specific regulation. To understand the basis for control of CPT-Ialpha gene expression, we have characterized the proximal promoter of the CPT-Ialpha gene. Here, we report the sequence of 6839 base pairs of the promoter and the localization of the rat CPT-Ialpha gene to region q43 on chromosome 1. Our studies show that the first 200 base pairs of the promoter are sufficient to drive transcription of the CPT-Ialpha gene. Within this region are two sites that bind both Sp1 and Sp3 transcription factors. In addition, nuclear factor Y (NF-Y) binds the proximal promoter. Mutation at the Sp1 or NF-Y sites severely decreases transcription from the CPT-Ialpha promoter. Other protein binding sites were identified within the first 200 base pairs of the promoter by DNase I footprinting, and these elements contribute to CPT-Ialpha gene expression. Our studies demonstrate that CPT-Ialpha is a TATA-less gene which utilizes NF-Y and Sp proteins to drive basal expression. PMID:10333485

  18. Factors That Predict Digital Game Play

    Microsoft Academic Search

    Mary E. Green; Mary Nell McNeese

    2008-01-01

    This study examines gender, race, and the need for social gratification as significant predictors of the number of hours of weekday and weekend digital game play. Secondary analysis of data from the National Center for Education Statistics' Education Longitudinal Study of 2002 revealed that that Caucasian and Asian students were associated with diminished digital game play, whereas African Americans students

  19. Playing styles and possible causative factors in dogs' behaviour when playing with humans

    Microsoft Academic Search

    Lilla Toth; M arta Gacsi; Adam Miklosi

    Individual differences and causative factors could modify the behaviour of dogs in object related games played with a human partner. In a two-by-two within-subject design we observed 68 family dogs' behaviour when playing two different types of games (ball game and tugging) with two different play partners (owner or unfamiliar experimenter) in order to categorize each dog's playing style. In

  20. 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

  1. TWO PROMOTERS COORDINATE TRANSCRIPTION FROM THE HUMAN LHX3 GENE: REGULATION BY NUCLEAR FACTOR I AND SP1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The LHX3 transcription factor is required for pituitary and nervous system development in mammals. Mutations in the human gene are associated with hormone deficiency diseases. The gene generates two mRNAs, hLHX3a and hLHX3b, which encode three distinct proteins with different properties. Here, the c...

  2. Unique aspects of transcriptional regulation in neurons – nuances in NF?B and Sp1-related factors

    Microsoft Academic Search

    Xianrong R. Mao; Andrea M. Moerman-Herzog; Yuzhi Chen; Steven W. Barger

    2009-01-01

    The unique physiology and function of neurons create differences in their cellular physiology, including their regulation of gene expression. We began several years ago exploring the relationships between the NF?B transcription factor, neuronal survival, and glutamate receptor activation in telencephalic neurons. These studies led us to conclude that this population of cells is nearly incapable of activating the NF?B that

  3. Association Between COLIA1 Sp1 Alleles and Femoral Neck Geometry

    Microsoft Academic Search

    A. M. Qureshi; F. E. A. McGuigan; D. G. Seymour; J. D. Hutchison; D. M. Reid; S. H. Ralston

    2001-01-01

    Genetic factors play an important role in the pathogenesis of osteoporosis by affecting bone mineral density and other predictors of osteoporotic fracture risk such as ultrasound properties of bone and skeletal geometry. We previously identified a polymorphism of a Sp1 binding site in the Collagen Type 1 Alpha 1 gene (COLIA1) that has been associated with reduced BMD and an

  4. Demographic factors and playing variables in online computer gaming.

    PubMed

    Griffiths, Mark D; Davies, Mark N O; Chappell, Darren

    2004-08-01

    Despite the growing popularity of online game playing, there has been no primary survey of its players. Therefore, an online questionnaire survey was used to examine basic demographic factors of online computer game players who played the popular online game Everquest (i.e., gender, age, marital status, nationality, education level, occupation). The survey also examined playing frequency (i.e., amount of time spent playing the game a week), playing history (i.e., how long they had been playing the game, who they played the game with, whether they had ever gender swapped their game character), the favorite and least favorite aspects of playing the game, and what they sacrifice (if anything) to play the game. Results showed that 81% of online game players were male, and that the mean age of players was 27.9 years of age. For many players, the social aspects of the game were the most important factor in playing. A small minority of players appear to play excessively (over 80 h a week), and results suggest that a small minority sacrifice important activities in order to play (e.g., sleep, time with family and/or partner, work, or schooling). PMID:15331036

  5. Sp1-mediated transcriptional activation is repressed by Sp3.

    PubMed Central

    Hagen, G; Müller, S; Beato, M; Suske, G

    1994-01-01

    Sp1, Sp3 (SPR-2) and Sp4 (SPR-1) are human sequence-specific DNA binding proteins with very similar structural features. In this report, we have analyzed Sp3 in direct comparison with Sp1. We have raised antibodies against both Sp1 and Sp3, and show that Sp3 protein, like Sp1, is expressed in various cell lines. Co-transfection experiments in different mammalian cell lines reveal that in contrast to Sp1 and Sp4, Sp3 is not able to activate several Sp1 responsive promoters. In addition, Sp3 also fails to activate reporter constructs in Drosophila SL2 cells lacking endogenous Sp factors. Instead, we find that Sp3 represses Sp1-mediated activation in a linear dose-dependent manner. A mutant of Sp3 lacking the DNA binding domain does not affect activation by Sp1, suggesting that the inhibition is most likely due to the competition with Sp1 for their common binding sites. To determine if any structurally similar domain of Sp3 is able to replace partially homologous domains of Sp1, we have generated chimeric proteins and tested their activation characteristics in gene transfer experiments. It appears that neither the glutamine-rich domains A and B nor the D domain of Sp1 can be replaced by the homologous regions of Sp3. Our results suggest that Sp3 is an inhibitory member of the Sp family. Images PMID:8070411

  6. Role of transcription factor Sp1 in the 4-O-methylhonokiol-mediated apoptotic effect on oral squamous cancer cells and xenograft.

    PubMed

    Cho, Jin Hyoung; Lee, Ra Ham; Jeon, Young-Joo; Shin, Jae-Cheon; Park, Seon-Min; Choi, Nag-Jin; Seo, Kang Seok; Yoon, Goo; Cho, Seung-Sik; Kim, Ka Hwi; Cho, Jung Jae; Cho, Young Sik; Kim, Dae Hwan; Hong, Jin Tae; Lee, Tae-Hoon; Park, Hong Ju; Jung, Seunggon; Seo, Jae-Min; Chen, Hanyong; Dong, Zigang; Chae, Jung-Il; Shim, Jung-Hyun

    2015-07-01

    Recently, biphenolic components derived from the Magnolia family have been studied for anti-cancer, anti-stress, and anti-inflammatory pharmacological effects. However, the pharmacological mechanism of action of 4-O-methylhonokiol (MH) is not clear in oral cancer. The aim of this study was to investigate the role of MH in apoptosis and its molecular mechanism in oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, as well as tumor xenografts. Here, we demonstrated that MH decreased cell growth and induced apoptosis in HN22 and HSC4 cells through the regulation of specificity protein 1 (Sp1). We employed several experimental techniques such as MTS assay, DAPI staining, PI staining, Annexin-V/7-ADD staining, RT-PCR, western blot analysis, immunocytochemistry, immunohistochemistry, TUNEL assay and in vivo xenograft model analysis. MH inhibited Sp1 protein expression and reduced Sp1 protein levels via both proteasome-dependent protein degradation and inhibition of protein synthesis in HN22 and HSC4 cells; MH did not alter Sp1 mRNA levels. We found that MH directly binds Sp1 by Sepharose 4B pull-down assay and molecular modeling. In addition, treatment with MH or knocking down Sp1 expression suppressed oral cancer cell colony formation. Moreover, MH treatment effectively inhibited tumor growth and Sp1 levels in BALB/c nude mice bearing HN22 cell xenografts. These results indicated that MH inhibited cell growth, colony formation and also induced apoptosis via Sp1 suppression in OSCC cells and xenograft tumors. Thus, MH is a potent anti-cancer drug candidate for oral cancer. PMID:25982202

  7. O Glycosylation of an Sp1Derived Peptide Blocks Known Sp1 Protein Interactions

    Microsoft Academic Search

    MARK D. ROOS; KAIHONG SU; JOHN R. BAKER; JEFFREY E. KUDLOW

    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

  8. A critical role of Sp1- and Ets-related transcription factors in maintaining CTL-specific expression of the mouse perforin gene.

    PubMed

    Youn, B S; Kim, K K; Kwon, B S

    1996-10-15

    This study was designed to determine the potential cis-elements involved in transcriptional regulation of the mouse perforin gene. DNase I hypersensitive site (DHS) mapping revealed that the perforin locus contained six DHS within 7.0 kb of the 5' upstream sequence (-7.0 kb) and two DHS in intron 2. The six 5' upstream and one intronic DHS were detected in only perforin-expressing lymphocytes. Chloramphenicol acetyltransferase (CAT) activities directed by 5' upstream promoter were detected preferentially in perforin-expressing cell lines. A construct termed PFP5a containing -795 bp exhibited the highest CAT activity, and PFP9a20 containing only -73 bp also produced significantly high CAT activity in CTLL-R8 cells. The proximal region in PFP9a20 contained two potential Sp1 binding sites (GC box and GT box) and one Ets binding site (EBS). Electrophoretic mobility shift assay showed that each of the cis-elements bound specific protein factors. When single-point mutation was introduced to each GC box, EBS, and GT box in PFP9a20, at least 3-fold less CAT activity was observed in CTLL-R8 cells. To confirm the importance of the three cis-acting elements in the perforin gene expression, point mutation was introduced again to each proximal GC box, EBS, and GT box of PFP5a. The point mutations resulted in a 2.5- to 3-fold reduction of CAT activity. The results suggest that a combination of the three proximal cis-acting elements may constitute a minimal region responsible for CTL-specific expression of perforin. PMID:8871649

  9. Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors

    Microsoft Academic Search

    Debora N Mancini; Shiva M Singh; Trevor K Archer; David I Rodenhiser; DI Rodenhiser

    1999-01-01

    Tumour suppressor genes and growth regulatory genes are frequent targets for methylation defects that can result in aberrant expression and mutagenesis. We have established a methylation map of the promoter region of the neurofibromatosis (NF1) gene and demonstrated functional sensitivity for methylation at specific sites for the SP1 and CRE binding (CREB) proteins in the NF1 regulatory region. We evaluated

  10. Unusual Sp1-GC box interaction in a parvovirus promoter.

    PubMed Central

    Pitluk, Z W; Ward, D C

    1991-01-01

    The P4 promoter of the parvovirus minute virus of mice contains a single degenerate GC box sequence which binds the transcription factor Sp1 with high affinity. The two promoters of murine Sp1 were affinity purified, and their interactions with the P4 promoter were examined. Several unusual features were observed. Methylation interference experiments demonstrated that Sp1 makes contacts with both DNA strands, including the central guanine as well as an adenine residue on the cytidine-rich strand of the GC box. UV photocross-linking revealed that the 95- and the 105-kDa promoters cross-link exclusively to opposite strands of the GC box. These results suggest that the phosphorylation of the 95-kDa Sp1 promoter results in a change in the way Sp1 is positioned on the P4 GC box and identifies a high-affinity GC box motif. Images PMID:1942250

  11. Indole-3-carbinol and 3-3'-diindolylmethane antiproliferative signaling pathways control cell-cycle gene transcription in human breast cancer cells by regulating promoter-Sp1 transcription factor interactions.

    PubMed

    Firestone, Gary L; Bjeldanes, Leonard F

    2003-07-01

    Indole-3-carbinol (I3C), a compound that occurs naturally in Brassica vegetables such as cabbage and broccoli, can induce a G1 cell-cycle arrest of human MCF-7 breast cancer cells that is accompanied by the selective inhibition of cyclin-dependent kinase 6 (Cdk6) expression and stimulation of p21(Waf1/Cip1) gene expression. Construction and transfection of a series of promoter-reporter plasmids demonstrate that the indole-regulated changes in Cdk6 and p21(Waf1/Cip1) levels are due to specific effects on their corresponding promoters. Mutagenic analysis reveals that I3C signaling targets a composite transcriptional element in the Cdk6 promoter that requires both Sp1 and Ets transcription factors for transactivation function. Analysis of protein-DNA complexes formed with nuclear proteins isolated from I3C-treated and -untreated cells demonstrates that the Sp1 DNA element in the Cdk6 promoter interacts with an I3C-inhibited protein-protein complex that contains the Sp1 transcription factor. In indole-treated cells, a fraction of [(3)H]I3C was converted into its natural diindole product (3)H-labeled 3-3'-diindolylmethane ([(3)H]DIM), which accumulates in the nucleus; this suggests that DIM may have a role in the transcriptional activities of I3C. Mutagenic analysis of the p21(Waf1/Cip1) promoter reveals that in transfected breast cancer cells, DIM (as well as I3C) stimulates p21(Waf1/Cip1) transcription through an indole-responsive region of the promoter that contains multiple Sp1 consensus sequences. Furthermore, DIM treatment regulates the presence of a nuclear Sp1 DNA-binding activity. Our results demonstrate that both the Cdk6 and p21(Waf1/Cip1) promoters are newly defined downstream targets of the indole-signaling pathway, and that the observed transcriptional effects are due to a combination of the cellular activities of I3C and DIM. PMID:12840223

  12. Essential role of an activator protein-2 (AP-2)/specificity protein 1 (Sp1) cluster in the UVB-mediated induction of the human vascular endothelial growth factor in HaCaT keratinocytes.

    PubMed Central

    Brenneisen, Peter; Blaudschun, Ralf; Gille, Jens; Schneider, Lars; Hinrichs, Ralf; Wlaschek, Meinhard; Eming, Sabine; Scharffetter-Kochanek, Karin

    2003-01-01

    Chronic sun exposure of the skin has long been postulated to enhance cutaneous angiogenesis, resulting in highly vascularized skin cancers. As the UVB component of sunlight is a major contributor to photocarcinogenesis, we aimed to explore the effects of UVB radiation on vascular endothelial growth factor (VEGF) gene expression, using the immortalized keratinocyte cell line HaCaT as a model for transformed premalignant epithelial cells. In the present paper, we studied the molecular mechanism of UVB-induced VEGF providing a major angiogenic activity in tumour progression and invasion. After 12-24 h of UVB irradiation, a 2.4- to 2.7-fold increase in endogenous VEGF protein level was measured, correlating with an up to 2.5-fold induction of promoter-based reporter gene constructs of VEGF. Furthermore, we identified a GC-rich UVB-responsive region between -87 and -65 bp of the VEGF promoter. In electrophoretic mobility-shift assays, this region binds Sp1-dependent protein complexes constitutively and an additional UVB-inducible protein complex distinct from Sp1 protein. The transcription factor AP-2 (activator protein-2) was detected as a component of the UVB-inducible protein complex. The critical role of the AP-2/Sp1 (specificity protein 1) cluster was supported by demonstration of a significant reduction of UVB-mediated promoter activity upon deletion of this recognition site. The specificity of this region for UVB irradiation was demonstrated using PMA, which increased VEGF activity in HaCaT cells after transient transfection of the deleted promoter construct. In conclusion, our data clarified regulatory mechanisms of UVB-dependent VEGF stimulation which may be critical for angiogenic processes in the skin. PMID:12358602

  13. 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)

  14. Functional role of post-translational modifications of Sp1 in tumorigenesis

    PubMed Central

    2012-01-01

    Specific protein 1 (Sp1), the first transcription factor to be isolated, regulates the expression of numerous genes involved in cell proliferation, apoptosis, and differentiation. Recent studies found that an increase in Sp1 transcriptional activity is associated with the tumorigenesis. Moreover, post-translational modifications of Sp1, including glycosylation, phosphorylation, acetylation, sumoylation, ubiquitination, and methylation, regulate Sp1 transcriptional activity and modulate target gene expression by affecting its DNA binding activity, transactivation activity, or protein level. In addition, recent studies have investigated several compounds with anti-cancer activity that could inhibit Sp1 transcriptional activity. In this review, we describe the effect of various post-translational modifications on Sp1 transcriptional activity and discuss compounds that inhibit the activity of Sp1. PMID:23148884

  15. 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

  16. 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…

  17. Ets1 Stimulates Platelet-Derived Growth Factor A-Chain Gene Transcription and Vascular Smooth Muscle Cell Growth via Cooperative Interactions With Sp1

    Microsoft Academic Search

    Fernando S. Santiago; Levon M. Khachigian

    2010-01-01

    The platelet-derived growth factor (PDGF) family of ligands (composed of A-, B-, C-, and D-chains), potent mitogens, and chemoattractants for cells of mesenchymal origin has been implicated in numerous vascular pathologies involving smooth muscle cell (SMC) hyperplasia. Understanding the molecular mechanisms mediating PDGF transcription would provide new insights into strategies to control PDGF-dependent pathophysiologic processes. We demonstrated previously that PDGF-A

  18. Retinoic Acid and GM-CSF Coordinately Induce Retinal Dehydrogenase 2 (RALDH2) Expression through Cooperation between the RAR/RXR Complex and Sp1 in Dendritic Cells

    PubMed Central

    Ohoka, Yoshiharu; Yokota-Nakatsuma, Aya; Maeda, Naoko; Takeuchi, Hajime; Iwata, Makoto

    2014-01-01

    Retinoic acid (RA)-producing dendritic cells (DCs) play critical roles in gut immunity. Retinal dehydrogenase 2 (RALDH2) encoded by Aldh1a2 is a key enzyme for generating RA in DCs. Granulocyte–macrophage colony-stimulating factor (GM-CSF) potently induces RALDH2 expression in DCs in an RA-dependent manner, and RA alone weakly induces the expression. However, how GM-CSF and RA induce RALDH2 expression remains unclear. Here, we show that GM-CSF-induced activation of the transcription factor Sp1 and RA-dependent signaling via the RA receptor (RAR)/retinoid X receptor (RXR) complex contribute to Aldh1a2 expression. The RAR antagonist LE540 and the Sp1 inhibitor mithramycin A inhibited GM-CSF-induced Aldh1a2 expression in fms-related tyrosine kinase 3 ligand-generated bone marrow-derived DCs (BM-DCs). ERK and p38 MAPK inhibitors suppressed GM-CSF-induced nuclear translocation of Sp1 and Aldh1a2 expression. Sp1 and the RAR?/RXR? complex bound to GC-rich Sp1-binding sites and an RA response element (RARE) half-site, respectively, near the TATA box in the mouse Aldh1a2 promoter. The DNA sequences around these sites were highly conserved among different species. In the presence of RA, ectopic expression of RAR?/RXR? and Sp1 synergistically enhanced Aldh1a2 promoter-reporter activity. GM-CSF did not significantly induce Aldh1a2 expression in plasmacytoid DCs, peritoneal macrophages, or T cells, and the Aldh1a2 promoter in these cells was mostly unmethylated. These results suggest that GM-CSF/RA-induced RALDH2 expression in DCs requires cooperative binding of Sp1 and the RAR/RXR complex to the Aldh1a2 promoter, and can be regulated by a DNA methylation-independent mechanism. PMID:24788806

  19. 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

  20. 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.

  1. Sp1/Sp3 involved in activation of GATA-1 Cell Research | Vol 18 No 2 | February 2008

    E-print Network

    Tian, Weidong

    Sp1/Sp3 involved in activation of GATA-1 302 npg Cell Research | Vol 18 No 2 | February 2008 ORIGINAL ARTICLE Involvement of Sp1/Sp3 in the activation of the GATA-1 erythroid promoter in K562 cells August 2007; published online 15 January 2008 GATA-1 is a hematopoietic transcription factor

  2. 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

  3. Astaxanthin Suppresses MPP+-Induced Oxidative Damage in PC12 Cells through a Sp1/NR1 Signaling Pathway

    PubMed Central

    Ye, Qinyong; Zhang, Xiaodong; Huang, Bixia; Zhu, Yuangui; Chen, Xiaochun

    2013-01-01

    Objective: To investigate astaxanthin (ATX) neuroprotection, and its mechanism, on a 1-methyl-4-phenyl-pyridine ion (MPP+)-induced cell model of Parkinson’s disease. Methods: Mature, differentiated PC12 cells treated with MPP+ were used as an in vitro cell model. The MTT assay was used to investigate cell viability after ATX treatment, and western blot analysis was used to observe Sp1 (activated transcription factor 1) and NR1 (NMDA receptor subunit 1) protein expression, real-time PCR was used to monitor Sp1 and NR1 mRNA, and cell immunofluorescence was used to determine the location of Sp1 and NR1 protein and the nuclear translocation of Sp1. Results: PC12 cell viability was significantly reduced by MPP+ treatment. The expression of Sp1 and NR1 mRNA and protein were increased compared with the control (p < 0.01). Following co-treatment with ATX and MPP+, cell viability was significantly increased, and Sp1 and NR1 mRNA and protein were decreased, compared with the MPP+ groups (p < 0.01). In addition, mithracycin A protected PC12 cells from oxidative stress caused by MPP+ by specifically inhibiting the expression of Sp1. Moreover, cell immunofluorescence revealed that ATX could suppress Sp1 nuclear transfer. Conclusion: ATX inhibited oxidative stress induced by MPP+ in PC12 cells, via the SP1/NR1 signaling pathway. PMID:23538867

  4. 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.

  5. Winamp 1.92-SP1

    NSDL National Science Digital Library

    Winamp 1.92-SP1, created by Nullsoft, Inc., is a fast, easy-to-use, hi-fidelity music player for Windows 95/98/NT. The player supports numerous audio file formats, most notably MPEG Audio Layer 3 (MP3), which allows near CD-quality sound while compressing a four-minute song into approximately four megabytes. The player has an intuitive interface which includes an equalizer, multi-song programming, and other useful controls. MP3 is becoming widely used as a quality audio compression standard and Winamp is an excellent audio player for use with MP3 and other formats. Winamp is shareware for the Windows 95/98/NT platforms and may be used free of charge for fourteen days, after which time a $10 registration fee is required.

  6. Arabidopsis replication factor C subunit 1 plays an important role in embryogenesis.

    PubMed

    Xia, Shi-Tou; Xiao, Lang-Tao; Bi, Dong-Lin; Zhu, Zhao-Hai

    2007-06-01

    Replication factor C (RFC), consisting of one large subunit and four small subunits, is an important factor involved in DNA replication and repair mechanisms as well as cell proliferation. The subunit 1 of Arabidopsis RFC (AtRFC1) is a homologue of p140, the large subunit of human RFC. Three T-DNA insertion mutant lines of AtRFC1, i.e. rfc1-1, rfc1-2 and rfc1-3, with insertion mutations located in exons 16 and 19, and the promoter region respectively were verified. These mutations caused defects in embryogenesis and led to embryo and seed abortion. Transformation of wild type AtRFC1 gene into rfc1 mutant alleles reverted the mutant phenotypes, suggesting that AtRFC1 plays an important role in embryo development in Arabidopsis thaliana. PMID:17556804

  7. 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

  8. Inhibition of fatty acid synthase and Sp1 expression by 3,3'-diindolylmethane in human breast cancer cells.

    PubMed

    Saati, George E; Archer, Michael C

    2011-01-01

    The putative cancer preventive agent 3,3'-diindolylmethane (DIM) is formed in the acidic environment of the stomach following consumption of indole-3-carbinol (I3C), which is present in vegetables of the Brassica genus. We have recently shown that the transcription factor Sp1 is involved in the regulation of both proliferation and de novo lipogenesis in cancer cells. Here we show that DIM inhibits the proliferation of 3 human breast cancer cell lines, MCF-7, MDA-MB-231, and SKBr-3, and concomitantly inhibits the expression of Sp1 and fatty acid synthase (FAS). There were no DIM-related effects on the proliferation or expression of Sp1 or FAS in the nontumorigenic human breast epithelial cell line MCF-10A. These results suggest that inhibition of Sp1 and/or FAS expression could contribute to the anticancer properties of the dietary indoles. PMID:21767081

  9. Playing a Musical Instrument as a Protective Factor against Dementia and Cognitive Impairment: A Population-Based Twin Study.

    PubMed

    Balbag, M Alison; Pedersen, Nancy L; Gatz, Margaret

    2014-01-01

    Increasing evidence supports that playing a musical instrument may benefit cognitive development and health at young ages. Whether playing an instrument provides protection against dementia has not been established. In a population-based cotwin control study, we examined the association between playing a musical instrument and whether or not the twins developed dementia or cognitive impairment. Participation in playing an instrument was taken from informant-based reports of twins' leisure activities. Dementia diagnoses were based on a complete clinical workup using standard diagnostic criteria. Among 157 twin pairs discordant for dementia and cognitive impairment, 27 pairs were discordant for playing an instrument. Controlling for sex, education, and physical activity, playing a musical instrument was significantly associated with less likelihood of dementia and cognitive impairment (odds ratio [OR]?=?0.36 [95% confidence interval 0.13-0.99]). These findings support further consideration of music as a modifiable protective factor against dementia and cognitive impairment. PMID:25544932

  10. Playing a Musical Instrument as a Protective Factor against Dementia and Cognitive Impairment: A Population-Based Twin Study

    PubMed Central

    Pedersen, Nancy L.

    2014-01-01

    Increasing evidence supports that playing a musical instrument may benefit cognitive development and health at young ages. Whether playing an instrument provides protection against dementia has not been established. In a population-based cotwin control study, we examined the association between playing a musical instrument and whether or not the twins developed dementia or cognitive impairment. Participation in playing an instrument was taken from informant-based reports of twins' leisure activities. Dementia diagnoses were based on a complete clinical workup using standard diagnostic criteria. Among 157 twin pairs discordant for dementia and cognitive impairment, 27 pairs were discordant for playing an instrument. Controlling for sex, education, and physical activity, playing a musical instrument was significantly associated with less likelihood of dementia and cognitive impairment (odds ratio [OR]?=?0.36 [95% confidence interval 0.13–0.99]). These findings support further consideration of music as a modifiable protective factor against dementia and cognitive impairment. PMID:25544932

  11. Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation

    PubMed Central

    2010-01-01

    Background Neuropilin is a transmembrane receptor for vascular endothelial growth factor (VEGF) and is expressed in normal endothelial cells and upregulated in cancer cells. Neuropilin-1 (NRP-1) has been shown to promote tumour cell migration and survival in colon cancer in response to VEGF binding. The expression profiles of neuropilins, associated co-receptors and known ligands have been mapped in three colorectal cell lines: Caco-2, HCT116 & HT29. We have previously shown that butyrate, a naturally occurring histone deacetylase inhibitor (HDACi) produced by fermentation of fibre in the colon, causes apoptosis of colon cancer cell lines. Results Here we demonstrate that butyrate down-regulates NRP-1 and VEGF at the mRNA and protein level in colorectal cancer cell lines. NRP-1 is a known transcriptional target of Sp1, whose activity is regulated by acetylation. NRP-1 down-regulation by butyrate was associated with decreased binding affinity of Sp1 for canonical Sp-binding sites in the NRP-1 promoter. siRNA-mediated knock-down of Sp1 implied that Sp1 may have strong DNA binding activity but weak transactivation potential. Conclusion The downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre. PMID:20950431

  12. 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.

  13. Neuregulin-1 and Human Epidermal Growth Factor Receptors 2 and 3 Play a Role in Human Lung Development In Vitro

    Microsoft Academic Search

    Neil V. Patel; Michael J. Acarregui; Jeanne M. Snyder; Jonathan M. Klein; Mark X. Sliwkowski; Jeffrey A. Kern

    The human epidermal growth factor receptor (HER) family consists of four distinct receptors: HER1 (epidermal growth factor receptor), HER2, HER3, and HER4. Their specific activat- ing ligands are collectively known as neuregulins (NRG). We hypothesized that one member of the NRG family, NRG-1, and the HER family would play a role in fetal lung development. To test this hypothesis, we

  14. Transcription and RNA processing factors play complex roles in DT40 cells

    Microsoft Academic Search

    Stephanie Bush; James L. Manley

    Functional analysis of factors involved in transcription and RNA processing is difficult in vivo because of the importance of these processes to maintain cell viability. The ability to perform conditional knockouts and to generate stable transfectants in DT40 cells has facilitated the study of general transcription factors such as TATA binding proteins, essential splicing factors such as ASF\\/SF2 and crucial

  15. 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…

  16. Aggressive Play: Contributing Factors of Parental Roles on 3-6 YearOld Boys

    Microsoft Academic Search

    Maria McCusker; Stacy Van Doren

    This study assessed whether there is a correlation between parenting styles (permissive, authoritative, and authoritarian) and the level of aggressive acts and aggressive language in children's play. The participants were 31 parents and their preschool-age boys from a suburban Montessori School in Northwestern New Jersey. A parenting style survey from Active Parenting was used to assess the parent's discipline style.

  17. Tumor necrosis factor-alpha plays an important role in restenosis development

    Microsoft Academic Search

    Pascalle S. Monraats; Nuno M. M. Pires; Abbey Schepers; Willem R. P. Agema; Lianne S. M. Boesten; Vries de M. R; Aeilko H. Zwinderman; Moniek P. M. de Maat; Pieter A. F. M. Doevendans; Winter de R. J; R. A. Tio; J. Waltenberger; Hart't L. M; R. R. Frants; P. H. A. Quax; Vlijmen van B. J. M; L. M. Havekes; Laarse van der A; Wall van der E. E; J. W. Jukema

    2005-01-01

    Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNF, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER) project included 3104 patients who underwent a successful PCI. Systematic genotyping

  18. A review of platelet derived growth factor playing pivotal role in bone regeneration.

    PubMed

    Shah, Prasun; Keppler, Louise; Rutkowski, James

    2014-06-01

    This article is focused on the literature review and study of recent advances in the field of bone grafting, which involves platelet-derived growth factor (PDGF) as one of the facilitating factors in bone regeneration. This article includes a description of the mechanism of PDGF for use in surgeries where bone grafting is required, which promotes future application of PDGF for faster bone regeneration or inhibition of bone growth if required as in osteosarcoma. The important specific activities of PDGF include mitogenesis (increase in the cell populations of healing cells), angiogenesis (endothelial mitoses into functioning capillaries), and macrophage activation (debridement of the wound site and a second phase source of growth factors for continued repair and bone regeneration). Thus PDGF can be utilized in wound with bone defect to conceal the wound with repair of bony defect. PMID:24914921

  19. Factors influencing the degree and pattern of parental involvement in play therapy for sexually abused children.

    PubMed

    Hill, Andrew

    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 and pattern of parental involvement and to understand what effect these patterns of parental involvement were having on the process and outcomes of therapy. The study successfully identified a range of factors influencing the patterns of parental involvement, but more research will be needed to understand the effect on outcomes. PMID:19842540

  20. 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.

  1. Do Psychosexual Factors Play a Role in the Etiology of Provoked Vestibulodynia? A Critical Review

    Microsoft Academic Search

    Geneviève Desrochers; Sophie Bergeron; Tina Landry; Mélanie Jodoin

    2008-01-01

    The aim of this review was to critically examine published studies concerning the psychosexual aspects of provoked vestibulodynia. Despite the presence of several methodological limitations, some findings were consistently replicated. Overall, women with vestibulodynia demonstrate impaired sexual functioning, namely, lower levels of sexual desire, arousal, and frequency of intercourse. Childhood physical and sexual abuse represent potential risk factors for the

  2. Improved Adhesives Containing CNT\\/SP1 Nano Fillers

    Microsoft Academic Search

    A. Wolf; A. Buchman; A. Eitan; T. Fine; Y. Nevo; A. Heyman; O. Shoseyov

    2012-01-01

    Carbon nanotubes (CNT) have stimulated research due to their wide range of applications. However, their existence as aggregates and the difficulty in debundling and dispersion limits the improvement of properties when used as fillers. Many techniques have been employed to obtain such dispersions including mechanical, ultrasonic, and solution mixing, resulting in limited effect. Attaching a protein moiety such as SP1

  3. Nuclear receptor interaction protein, a coactivator of androgen receptors (AR), is regulated by AR and Sp1 to feed forward and activate its own gene expression through AR protein stability

    PubMed Central

    Chen, Pei-Hong; Tsao, Yeou-Ping; Wang, Chih-Chiang; Chen, Show-Li

    2008-01-01

    Previously, we found a novel gene, nuclear receptor interaction protein (NRIP), a transcription cofactor that can enhance an AR-driven PSA promoter activity in a ligand-dependent manner in prostate cancer cells. Here, we investigated NRIP regulation. We cloned a 413-bp fragment from the transcription initiation site of the NRIP gene that had strong promoter activity, was TATA-less and GC-rich, and, based on DNA sequences, contained one androgen response element (ARE) and three Sp1-binding sites (Sp1-1, Sp1-2, Sp1-3). Transient promoter luciferase assays, chromatin immunoprecipitation and small RNA interference analyses mapped ARE and Sp1-2-binding sites involved in NRIP promoter activation, implying that NRIP is a target gene for AR or Sp1. AR associates with the NRIP promoter through ARE and indirectly through Sp1-binding site via AR–Sp1 complex formation. Thus both ARE and Sp1-binding site within the NRIP promoter can respond to androgen induction. More intriguingly, NRIP plays a feed-forward role enhancing AR-driven NRIP promoter activity via NRIP forming a complex with AR to protect AR protein from proteasome degradation. This is the first demonstration that NRIP is a novel AR-target gene and that NRIP expression feeds forward and activates its own expression through AR protein stability. PMID:17984071

  4. The Cytotoxic Necrotizing Factor 1 from E. Coli: A Janus Toxin Playing with Cancer Regulators

    PubMed Central

    Fabbri, Alessia; Travaglione, Sara; Ballan, Giulia; Loizzo, Stefano; Fiorentini, Carla

    2013-01-01

    Certain strains of Escherichia coli have been indicated as a risk factor for colon cancer. E. coli is a normal inhabitant of the human intestine that becomes pathogenic, especially in extraintestinal sites, following the acquisition of virulence factors, including the protein toxin CNF1. This Rho GTPases-activating toxin induces dysfunctions in transformed epithelial cells, such as apoptosis counteraction, pro-inflammatory cytokines’ release, COX2 expression, NF-kB activation and boosted cellular motility. As cancer may arise when the same regulatory pathways are affected, it is conceivable to hypothesize that CNF1-producing E. coli infections can contribute to cancer development. This review focuses on those aspects of CNF1 related to transformation, with the aim of contributing to the identification of a new possible carcinogenic agent from the microbial world. PMID:23949007

  5. The cytotoxic necrotizing factor 1 from E. coli: a janus toxin playing with cancer regulators.

    PubMed

    Fabbri, Alessia; Travaglione, Sara; Ballan, Giulia; Loizzo, Stefano; Fiorentini, Carla

    2013-08-01

    Certain strains of Escherichia coli have been indicated as a risk factor for colon cancer. E. coli is a normal inhabitant of the human intestine that becomes pathogenic, especially in extraintestinal sites, following the acquisition of virulence factors, including the protein toxin CNF1. This Rho GTPases-activating toxin induces dysfunctions in transformed epithelial cells, such as apoptosis counteraction, pro-inflammatory cytokines' release, COX2 expression, NF-kB activation and boosted cellular motility. As cancer may arise when the same regulatory pathways are affected, it is conceivable to hypothesize that CNF1-producing E. coli infections can contribute to cancer development. This review focuses on those aspects of CNF1 related to transformation, with the aim of contributing to the identification of a new possible carcinogenic agent from the microbial world. PMID:23949007

  6. 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. PMID:25732926

  7. Basal Transcription Factor 3 Plays an Important Role in Seed Germination and Seedling Growth of Rice

    PubMed Central

    Wang, Wenyi; Xu, Mengyun; Wang, Ya

    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 (Osj10gBTF3Ri) transgenic lines. Seedling inhibition was more severe in the Osj10gBTF3Ri seedlings compared with their WT especially when treated with 100 or 200??M GA3; 50% reduction in shoots was observed in Osj10gBTF3Ri seedlings. The expression of Osj3g1BTF3, Osj3g2BTF3 and Osj10gBTF3 was primarily constitutive and generally modulated by NaCl, ABA, and GA3 stresses in both Osj10gBTF3Ri 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

  8. Transcription factor Krüppel-like factor 2 plays a vital role in endothelial colony forming cells differentiation

    PubMed Central

    Song, Yimeng; Li, Xiaoxia; Wang, Dawei; Fu, Chenglai; Zhu, Zhenjiu; Zou, Ming-Hui; Zhu, Yi

    2013-01-01

    Aims Endothelial colony forming cells (ECFCs) participate in post-natal vasculogenesis. We previously reported that vascular endothelial growth factor (VEGF) promotes human ECFC differentiation through AMP-activated protein kinase (AMPK) activation. However, the mechanisms underlying transcriptional regulation of ECFC differentiation still remain largely elusive. Here, we investigated the role of transcription factor Krüppel-like factor 2 (KLF2) in the regulation of ECFC function. Methods and results Human ECFCs were isolated from cord blood and cultured. Treatment with VEGF significantly increased endothelial markers in ECFCs and their capacity for migration and tube formation. The mRNA and protein levels of KLF2 were also significantly up-regulated. This up-regulation was abrogated by AMPK inhibition or by knockdown of KLF2 with siRNA. Furthermore, adenovirus-mediated overexpression of KLF2 promoted ECFC differentiation by enhancing expression of endothelial cell markers, reducing expression of progenitor cell markers, and increasing the capacity for tube formation in vitro, indicating the important role of KLF2 in ECFC-mediated angiogenesis. Histone deacetylase 5 (HDAC5) was phosphorylated by AMPK activity induced by VEGF and the AMPK agonist AICAR (5-amino-1-?-d-ribofuranosyl-imidazole-4-carboxamide). In vivo angiogenesis assay revealed that overexpression of KLF2 in bone-marrow-derived pro-angiogenic progenitor cells promoted vessel formation when the cells were implanted in C57BL/6 mice. Conclusion Up-regulation of KLF2 by AMPK activation constitutes a novel mechanism of ECFC differentiation, and may have therapeutic value in the treatment of ischaemic heart disease. PMID:23667185

  9. The Transcription Factor Bright Plays a Role in Marginal Zone B Lymphocyte Development and Autoantibody Production

    PubMed Central

    Oldham, Athenia L.; Miner, Cathrine A.; Wang, Hong-Cheng; Webb, Carol F.

    2011-01-01

    Previous data suggested that constitutive expression of the transcription factor Bright (B cell regulator of immunoglobulin heavy chain transcription), normally tightly regulated during B cell differentiation, was associated with autoantibody production. Here we show that constitutive Bright expression results in skewing of mature B lineage subpopulations toward marginal zone cells at the expense of the follicular subpopulation. C57Bl/6 transgenic mice constitutively expressing Bright in B lineage cells generated autoantibodies that were not the result of global increases in immunoglobulin or of breaches in key tolerance checkpoints typically defective in other autoimmune mouse models. Rather, autoimmunity correlated with increased numbers of marginal zone B cells and alterations in the phenotype and gene expression profiles of lymphocytes within the follicular B cell compartment. These data suggest a novel role for Bright in the normal development of mature B cell subsets and in autoantibody production. PMID:21963220

  10. SP1 is required for basal activation and chromatin accessibility of CD151 promoter in liver cancer cells

    Microsoft Academic Search

    Jiayi Wang; Xiangfan Liu; Peihua Ni; Zhidong Gu; Qishi Fan

    2010-01-01

    CD151 plays an important role in liver cancer metastasis. The mechanism on how CD151 is expressed remains unclear. Here we have identified SP1 is a protein functioning in constitutive activation of CD151. Applying a PCR-based chromatin accessibility assay, an open chromatin conformation was discovered localized around the transcription start site of the CD151 gene. Deletion constructs of the 5? flanking

  11. 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

  12. Game Playing Perfect Play

    E-print Network

    Hawick, Ken

    1 Game Playing #12;2 Outline · Perfect Play · Resource Limits · Alpha-Beta pruning · Games Blue, grand master #12;14 Alpha-Beta pruning Example MAX MIN A1 A2 A3 3 3 A11 A13 A12 3 12 8 X A23 A22 2 X X A31 A33 A32 14 Alpha-Beta · pruning

  13. Membrane Chaperone SecDF Plays a Role in the Secretion of Listeria monocytogenes Major Virulence Factors

    PubMed Central

    Burg-Golani, Tamar; Pozniak, Yair; Rabinovich, Lev; Sigal, Nadejda; Nir Paz, Ran

    2013-01-01

    Listeria monocytogenes is a Gram-positive human intracellular pathogen that infects diverse mammalian cells. Upon invasion, L. monocytogenes secretes multiple virulence factors that target host cellular processes and promote infection. It has been presumed, but was not empirically established, that the Sec translocation system is the primary mediator of this secretion. Here, we validate an important role for SecDF, a component of the Sec system, in the secretion of several critical L. monocytogenes virulence factors. A ?secDF mutant is demonstrated to exhibit impaired membrane translocation of listeriolysin O (LLO), PlcA, PlcB, and ActA, factors that mediate L. monocytogenes phagosomal escape and spread from cell to cell. This impaired translocation was monitored by accumulation of the factors on the bacterial membrane and by reduced activity upon secretion. This defect in secretion is shown to be associated with a severe intracellular growth defect of the ?secDF mutant in macrophages and a less virulent phenotype in mice, despite normal growth in laboratory medium. We further show that SecDF is upregulated when the bacteria reside in macrophage phagosomes and that it is necessary for efficient phagosomal escape. Taken together, these data support the premise that SecDF plays a role as a chaperone that facilitates the translocation of L. monocytogenes virulence factors during infection. PMID:24056100

  14. Specificity proteins Sp1 and Sp3 interact with the rat GTP Cyclohydrolase I proximal promoter to regulate transcription

    PubMed Central

    Chandran, Nitya Sarath; Vunnava, Prashanthi; Wu, Yanning; Kapatos, Gregory

    2008-01-01

    The role of the proximal promoter GC-box in regulating basal and cAMP-dependent GTP Cyclohydrolase I gene transcription was investigated using a variety of cell lines and techniques. These studies show that the GC-box is composed of a triad of cis-elements that in vitro bind specificity proteins Sp1 and Sp3. Sp1 and Sp3 were found associated with the native proximal promoter in PC12 cells but were not recruited to the promoter during cAMP-dependent transcription. Studies using Drosophila SL2 cells showed that Sp3 occupies two sites within the GC-box and enhances transcription when acting alone and synergistically when combined with nuclear factor-Y (NF-Y) and CCAAT/Enhancer-Binding Protein (C/EBP)?, cognate binding proteins for the adjacent cAMP response element (CRE) and CCAAT-box cAMP response elements. In contrast, Sp1 bound only one site within the GC-box and did not enhance transcription unless combined with NF-Y and C/EBP?. Studies in SL2 cells also showed that Sp1 and Sp3 do not co-occupy the GC-box, and accordingly Sp1 competes for Sp3 binding to repress Sp3-dependent transcription. In PC12 cells, complete mutation of the GC-box reduced basal but not cAMP-dependent transcription, resulting in an overall increase in the cAMP response and demonstrating that formation of this enhanceosome does not require Sp1 or Sp3. Experiments in which the GC-box was replaced with a Gal4 element and the promoter challenged with Gal4 fusion proteins support this conclusion and a role for Sp3 in maintaining high levels of basal transcription in PC12 cells. Equivalent amounts of Sp1 and Sp3 were found associated with the native proximal promoter in PC12 and Rat2 cells, which differ 10-fold in basal transcription. Similar levels of methylation of CpG dinucleotides located within the GC-box were also observed in these two cells lines. These results suggest that Sp1 and Sp3 bound to the GC-box might help to preserve an open chromatin configuration at the proximal promoter in cells which constitutively express low levels of GTP Cyclohydrolase I. PMID:18004997

  15. MPI Programming Environment for IBM SP1\\/SP2

    Microsoft Academic Search

    Hubertus Franke; Ching-farn Eric Wu; Michel Riviere; Pratap Pattnaik; Marc Snir

    1995-01-01

    In this paper we discuss an implementation of the MessagePassing Interface standard (MPI) for the IBMScalable Power PARALLEL 1 and 2 (SP1, SP2). Keyto a reliable and efficient implementation of a messagepassing library on these machines is the careful designof a UNIX-Socket like layer in the user space with controlledaccess to the communication adapters and withadequate recovery and flow control.

  16. COUP-TF Upregulates NGFI-A Gene Expression through an Sp1 Binding Site

    PubMed Central

    Pipaón, Carlos; Tsai, Sophia Y.; Tsai, Ming-Jer

    1999-01-01

    The formation of various tissues requires close communication between two groups of cells, epithelial and mesenchymal cells. COUP-TFs are transcription factors which have been shown to have functions in embryonic development. COUP-TFI is expressed mainly in the nervous system, and its targeted deletion leads to defects in the central and peripheral nervous systems. COUP-TFII is highly expressed in the mesenchymal component of the developing organs. A null mutation of COUP-TFII results in the malformation of the heart and blood vessels. From their expression pattern, we proposed that COUP-TFs regulate paracrine signals important for mesenchymal cell-epithelial cell interactions. In order to identify genes regulated by COUP-TF in this process, a rat urogenital mesenchymal cell line was stably transfected with a COUP-TFI expression vector. We found that NGFI-A, a gene with important functions in brain, organ, and vasculature development, has elevated mRNA and protein levels upon overexpression of COUP-TFI in these cells. A study of the promoter region of this gene identified a COUP-TF-responsive element between positions ?64 and ?46. Surprisingly, this region includes binding sites for members of the Sp1 family of transcription factors but no COUP-TF binding site. Mutations that abolish the Sp1 binding activity also impair the transactivation of the NGFI-A promoter by COUP-TF. Two regions of the COUP-TF molecule are shown to be important for NGFI-A activation: the DNA binding domain and the extreme C terminus of the putative ligand binding domain. The C-terminal region is likely to be important for interaction with coactivators. In fact, the coactivators p300 and steroid receptor activator 1 can enhance the transactivation of the NGFI-A promoter induced by COUP-TFI. Finally, we demonstrated that COUP-TF can directly interact with Sp1. Taken together, these results suggest that NGFI-A is a target gene for COUP-TFs and that the Sp1 family of transcription factors mediates its regulation by COUP-TFs. PMID:10082539

  17. 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

  18. Distributions centrales sur le produit semi-direct Sp(1)? H

    Microsoft Academic Search

    Raja Essoussi Mrad

    2001-01-01

    Let H be the field of quaternions, and Sp(1) the multiplicative group of quaternions of modulus 1. The group Sp(1) acts on H by left multiplication and we define the semi-direct product G=Sp(1)?H. We prove that the central distributions on G are of the form: S=C?1+?1?R, where C is a central distribution on Sp(1), R is a radial distribution on H,

  19. VaSP1, catalytically active serine proteinase from Vipera ammodytes ammodytes venom with unconventional active site triad.

    PubMed

    Kurtovi?, Tihana; Brgles, Marija; Leonardi, Adrijana; Lang Balija, Maja; Sajevic, Tamara; Križaj, Igor; Allmaier, Günter; Marchetti-Deschmann, Martina; Halassy, Beata

    2014-01-01

    VaSP1, a serine proteinase from Vipera ammodytes ammodytes venom, is a glycosylated monomer of 31.5 kDa, as determined by MALDI mass spectrometry, showing multiple isoelectric points between pH 6.5 and pH 8.5. Partial amino acid sequencing of VaSP1 by Edman degradation and MS/MS analysis identified sequences which allowed its classification among the so-called snake venom serine proteinase homologues, members of the peptidase S1 family, however being devoid of the canonical catalytic triad. Only few representatives of this group have been identified so far with just two of them characterised in detail at the protein level. Despite substitution of His57 with Arg, VaSP1 possesses proteolytic activity which can be inhibited by Pefabloc, benzamidine, Zn²? ions, DTT and trypsin inhibitor II, a Kunitz/BPTI group member. It hydrolyses N(?)-benzoyl-Phe-Val-Arg-p-NA, exhibiting Michaelis-Menten behaviour with K(m) = 48.2 ?M and V(m) = 0.019 nM s?¹. The pH for optimal activity on tested substrate is around 9.0. VaSP1 also cleaves insulin B-chain, digesting it at positions His¹?-Leu¹¹, Ala¹?-Leu¹? and Tyr¹?-Leu¹?. Furthermore, the novel serine proteinase is active towards wide array of proteins involved in haemostasis where its degradation of fibrinogen, fibrin, prothrombin, factor X and plasminogen in vivo probably results in depletion of coagulation factors in blood circulation. The possibility that VaSP1 possesses anticoagulant properties has been further indicated by its ability to prolong prothrombin time and activated partial thromboplastin time. PMID:24269689

  20. 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.

  1. CTD serine-2 plays a critical role in splicing and termination factor recruitment to RNA polymerase II in vivo

    PubMed Central

    Gu, Bo; Eick, Dirk; Bensaude, Olivier

    2013-01-01

    Co-transcriptional pre-mRNA processing relies on reversible phosphorylation of the carboxyl-terminal domain (CTD) of Rpb1, the largest subunit of RNA polymerase II (RNAP II). In this study, we replaced in live cells the endogenous Rpb1 by S2A Rpb1, where the second serines (Ser2) in the CTD heptapeptide repeats were switched to alanines, to prevent phosphorylation. Although slower, S2A RNAP II was able to transcribe. However, it failed to recruit splicing components such as U2AF65 and U2 snRNA to transcription sites, although the recruitment of U1 snRNA was not affected. As a consequence, co-transcriptional splicing was impaired. Interestingly, the magnitude of the S2A RNAP II splicing defect was promoter dependent. In addition, S2A RNAP II showed an impaired recruitment of the cleavage factor PCF11 to pre-mRNA and a defect in 3?-end RNA cleavage. These results suggest that CTD Ser2 plays critical roles in co-transcriptional pre-mRNA maturation in vivo: It likely recruits U2AF65 to ensure an efficient co-transcriptional splicing and facilitates the recruitment of pre-mRNA 3?-end processing factors to enhance 3?-end cleavage. PMID:23275552

  2. Inhibition of Fatty Acid Synthase and Sp1 Expression by 3,3?-Diindolylmethane in Human Breast Cancer Cells

    Microsoft Academic Search

    George E. Saati; Michael C. Archer

    2011-01-01

    The putative cancer preventive agent 3,3?-diindolylmethane (DIM) is formed in the acidic environment of the stomach following consumption of indole-3-carbinol (I3C), which is present in vegetables of the Brassica genus. We have recently shown that the transcription factor Sp1 is involved in the regulation of both proliferation and de novo lipogenesis in cancer cells. Here we show that DIM inhibits

  3. 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

  4. GCDCA down-regulates gene expression by increasing Sp1 binding to the NOS-3 promoter in an oxidative stress dependent manner.

    PubMed

    González-Rubio, Sandra; López-Sánchez, Laura; Muñoz-Castañeda, Juan; Linares, Clara I; Aguilar-Melero, Patricia; Rodríguez-Perálvarez, Manuel; Sánchez-Sánchez, Rafael; Fernández-Álvarez, Ana; Casado, Marta; Montero-Álvarez, Jose L; Rodríguez-Ariza, Antonio; Muntané, Jordi; de la Mata, Manuel; Ferrín, Gustavo

    2015-07-01

    During the course of cholestatic liver diseases, the toxic effect of bile acids accumulation has been related to the decreased expression of endothelial nitric oxide synthase (NOS-3) and cellular oxidative stress increase. In the present study, we have investigated the relationship between these two biological events. In the human hepatocarcinoma cell line HepG2, cytotoxic response to GCDCA was characterized by the reduced activity of the respiratory complexes II+III, the increased expression and activation of the transcription factor Sp1, and a higher binding capacity of this at positions -1386, -632 and -104 of the NOS-3 promoter (pNOS-3). This was associated with a decreased promoter activity and a consequent reduction of NOS-3 expression. The use of antioxidants in GCDCA-treated cells caused a lower activation of Sp1 and the recovery of the pNOS-3 activity and NOS-3 expression and activity. Similarly, the specific inhibition of Sp1 resulted in the improvement of NOS-3 expression. Both, antioxidant treatment and Sp1 inhibition were associated with the reduction of cell death-related parameters. Bile duct ligation in rats confirmed in vitro results concerning the activation of Sp1 and the reduction of NOS-3 expression. Our results provide direct evidence for the involvement of Sp1 in the regulation of NOS-3 expression during cholestasis. Thus, the identification of Sp1 as a potential negative regulator of NOS-3 expression represents a new mechanism by which the accumulation of bile acids causes a cytotoxic effect through the oxidative stress increase, and provides a new potential target in cholestatic liver diseases. PMID:25931146

  5. The Alternative Sigma Factor ?E Plays an Important Role in Intestinal Survival and Virulence in Vibrio cholerae

    PubMed Central

    Kovacikova, Gabriela; Skorupski, Karen

    2002-01-01

    The alternative sigma factor ?? (RpoE) is involved in the response to extracytoplasmic stress and plays a role in the virulence of a variety of different bacteria. To assess the role of ?? in Vibrio cholerae pathogenesis, a ?rpoE mutant was constructed and analyzed using the infant mouse model. The results here show that ?? contributes significantly to the virulence of V. cholerae. The ?rpoE mutant was highly attenuated with a 50% lethal dose more than 3 logs higher than that for the parental strain, and its ability to colonize the intestine was reduced approximately 30-fold. A time course of infection revealed that the number of CFU of the ?rpoE mutant was approximately 1 log lower than that of the parental strain by 12 h postinoculation and decreased further by 24 h. The defect in virulence in the ?rpoE mutant thus appears to be a diminished ability to survive within the intestinal environment. The results here also show that ?? is not required for growth and survival of V. cholerae in vitro at high temperatures but is required under other stressful conditions, such as in the presence of 3% ethanol. As in Escherichia coli, the expression of rpoE in V. cholerae is dependent upon two promoters located upstream of the gene, P1 and P2. P1 appears to be ?70 dependent, whereas the downstream promoter, P2, is positively autoregulated by ??. PMID:12228259

  6. ALK5 and ALK1 Play Antagonistic Roles in Transforming Growth Factor ?-Induced Podosome Formation in Aortic Endothelial Cells

    PubMed Central

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

    2014-01-01

    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

  7. Transcriptional regulation of cell-specific expression of the human cystathionine beta -synthase gene by differential binding of Sp1/Sp3 to the -1b promoter.

    PubMed

    Ge, Y; Matherly, L H; Taub, J W

    2001-11-23

    Cystathionine beta-synthase (CBS) catalyzes the condensation of serine and homocysteine to form cystathionine, an intermediate step in the synthesis of cysteine. We previously characterized the CBS -1b minimal promoter (-3792 to -3667) and found that Sp1/Sp3, nuclear factor Y, and USF-1 were involved in the regulation of basal promoter activity (Ge, Y., Konrad, M. A., Matherly, L. H., Taub, J. W. (2001) Biochem. J. 357, 97-105). In this study, the critical cis-elements and transcription factors in the CBS -1b upstream region (-4046 to -3792) were examined in HT1080 and HepG2 cells, which differ approximately 10-fold in levels of CBS transcripts transcribed from the CBS -1b promoter. In DNase I footprint and gel shift analyses and transient transfections of mutant CBS -1b promoter constructs into HT1080 and HepG2 cells, transcriptionally important roles for Sp1/Sp3 binding to three GC boxes and one GT box and for binding of myeloid zinc finger 1-like proteins to two myeloid zinc finger 1 elements were indicated. In gel shift assays, very low levels of Sp1/Sp3 DNA-protein complexes were detected in HT1080 cells compared with HepG2 cells despite comparable levels of nuclear factor Y and USF-1 binding and similar levels of Sp1 and Sp3 proteins on Western blots. Mixing of HT1080 and HepG2 nuclear extracts resulted in no difference in total Sp factor binding in gel shift assays, thus excluding a role for an unknown activator or inhibitor in the disparate Sp1/Sp3 binding between the lines. Increased Sp1/Sp3 binding in gel shift assays was observed upon treatment of HT1080 nuclear extracts with protein kinase A, and decreased Sp1/Sp3 binding resulted from treatment of HepG2 nuclear extracts with calf alkaline phosphatase, suggesting a role for changes in Sp1/Sp3 phosphorylation in transcription factor binding and transactivation of the CBS -1b promoter. Characterization of CBS promoter structure and function should clarify the molecular bases for variations in CBS gene expression in genetic diseases and the relationship between CBS and Down syndrome. PMID:11562358

  8. Sp1, a new biomarker that identifies a subset of aggressive pancreatic ductal adenocarcinoma.

    PubMed

    Jiang, Naomi Y; Woda, Bruce A; Banner, Barbara F; Whalen, Giles F; Dresser, Karen A; Lu, Di

    2008-07-01

    Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Sp1 is a sequence-specific DNA binding protein that is important in the transcription of a number of regulatory genes involved in cancer cell growth, differentiation, and metastasis. In this study, we investigated Sp1 expression in pancreatic ductal adenocarcinoma and its association with clinical outcome. We studied 42 patients with primary pancreatic adenocarcinoma. The expression of Sp1 in pancreatic adenocarcinoma was evaluated by immunohistochemical staining. All 42 patients had clinical follow-up information and were evaluated for survival. Sp1 protein was aberrantly overexpressed in a subset of primary pancreatic adenocarcinoma. These tumors all developed metastasis, whereas none of the primary tumors without lymph node metastasis showed Sp1 overexpression. Statistically, Sp1 overexpression was associated with higher stage, higher grade, and lymph node metastasis (P < 0.001, P = 0.036, and P < 0.0001, respectively). Additionally, patients of this subset had a much shorter overall survival than patients without Sp1 overexpression, as evidenced by Kaplan-Meier plots and the log-rank test (P = 0.002). The 5-year overall survival rate was 19% in patients with Sp1 overexpression, compared with 55% in patients without Sp1 overexpression. The median survival was only 13 months for patients with Sp1 overexpression, compared with 65 months for patients without Sp1 overexpression. In conclusion, Sp1 is a new biomarker that identifies a subset of pancreatic ductal adenocarcinoma with aggressive clinical behavior. It can be used at initial diagnosis of pancreatic adenocarcinoma to identify patients with an increased probability of cancer metastasis and much shortened overall survival. PMID:18628415

  9. Socially-induced brain ‘fertilization’: play promotes brain derived neurotrophic factor transcription in the amygdala and dorsolateral frontal cortex in juvenile rats

    Microsoft Academic Search

    Nakia S. Gordon; Sharon Burke; Huda Akil; Stanley J. Watson; Jaak Panksepp

    2003-01-01

    Rough and tumble (R&T) play is assumed to have beneficial effects in developing organisms. To evaluate this idea, brain derived neurotrophic factor (BDNF) gene expression was evaluated in 32-day-old juvenile rats that were allowed to play for 30 min prior to sacrifice. In situ hybridization for BDNF mRNA revealed that the amygdala and dorsolateral frontal cortex had significantly elevated BDNF

  10. Domain analysis for estrogen receptor/Sp1-mediated transactivation and detection of estrogen receptor/Sp1 protein interactions in living cells 

    E-print Network

    Kim, KyoungHyun

    2005-11-01

    Estrogen Receptor ? (ER?)/Sp1 activation of GC-rich gene promoters in breast cancer cells is dependent, in part, on the activation function 1 (AF1) of ER?. This study investigates contributions of the DNA binding domain ...

  11. Downregulation of Sp1 is involved in ?-lapachone-induced cell cycle arrest and apoptosis in oral squamous cell carcinoma.

    PubMed

    Jeon, Young-Joo; Bang, Woong; Shin, Jae-Cheon; Park, Seon-Min; Cho, Jung-Jae; Choi, Yung Hyun; Seo, Kang Seok; Choi, Nag-Jin; Shim, Jung-Hyun; Chae, Jung-Il

    2015-06-01

    ?-lapachone (?-lap) is a naturally occurring quinone obtained from the bark of lapacho tree (Tabebuia avellanedae) with anti-proliferative properties against various cancers. The present study investigated the cell proliferation and apoptosis effect of ?-lap on two oral squamous cell carcinoma lines (OSCCs). We carried out a series of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl-2H-tetrazolium (MTS) assays, 4',6-diamidino-2-phenylindole (DAPI) staining, cell cycle analysis, and western blot analysis to characterize ?-lap and its underlying signaling pathway. We demonstrated that ?-lap-treated cells significantly reduced cell proliferation but increased DNA condensation and increased sub-G1 population in OSCCs. Particularly, ?-lap suppresses activation of transcription factor specificity protein 1 (Sp1) followed by apoptosis in a concentration-dependent manner in OSCCs. Furthermore, ?-lap modulated protein expression levels of cell cycle regulatory proteins and apoptosis-related proteins that are known as Sp1 target genes, resulting in apoptosis. Our results collectively indicated that ?-lap was able to modulate Sp1 transactivation and induce apoptosis through the regulation of cell cycle and apoptosis-related proteins. Therefore, ?-lap may be used in cancer prevention and therapies to improve clinical outcome as an anticancer drug candidate. PMID:25891355

  12. 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.

  13. The Human Immunodeficiency Virus Type 1 Tat Protein Up-Regulates the Promoter Activity of the Beta-Chemokine Monocyte Chemoattractant Protein 1 in the Human Astrocytoma Cell Line U-87 MG: Role of SP-1, AP-1, and NF-?B Consensus Sites

    PubMed Central

    Lim, Siew Pheng; Garzino-Demo, Alfredo

    2000-01-01

    It has been shown that the human immunodeficiency virus type 1 (HIV-1) Tat protein can specifically enhance expression and release of monocyte chemoattractant protein 1 (MCP-1) from human astrocytes. In this study, we show evidence that Tat-induced MCP-1 expression is mediated at the transcriptional level. Transient transfection of an expression construct encoding the full-length Tat into the human glioblastoma-astrocytoma cell line U-87 MG enhances reporter gene activity from cotransfected deletion constructs of the MCP-1 promoter. HIV-1 Tat exerts its effect through a minimal construct containing 213 nucleotides upstream of the translational start site. Site-directed mutagenesis studies indicate that an SP1 site (located between nucleotides ?123 and ?115) is critical for both constitutive and Tat-enhanced expression of the human MCP-1 promoter, as mutation of this SP1 site significantly diminished reporter gene expression in both instances. Gel retardation experiments further demonstrate that Tat strongly enhances the binding of SP1 protein to its DNA element on the MCP-1 promoter. Moreover, we also observe an increase in the binding activities of transcriptional factors AP1 and NF-?B to the MCP-1 promoter following Tat treatment. Mutagenesis studies show that an upstream AP1 site and an adjacent NF-?B site (located at ?128 to ?122 and ?150 to ?137, respectively) play a role in Tat-mediated transactivation. In contrast, a further upstream AP1 site (?156 to ?150) does not appear to be crucial for promoter activity. We postulate that a Tat-mediated increase in SP1 binding activities augments the binding of AP1 and NF-?B, leading to synergistic activation of the MCP-1 promoter. PMID:10644332

  14. 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

  15. The morphology and kinematics of the Fine Ring Nebula, planetary nebula Sp 1, and the shaping influence of its binary central star

    NASA Astrophysics Data System (ADS)

    Jones, D.; Mitchell, D. L.; Lloyd, M.; Pollacco, D.; O'Brien, T. J.; Meaburn, J.; Vaytet, N. M. H.

    2012-03-01

    We present the first detailed spatiokinematical analysis and modelling of the planetary nebula Shapley 1 (Sp 1), which is known to contain a close-binary central star system. Close-binary central stars have been identified as a likely source of shaping in planetary nebulae, but with little observational support to date. Deep narrow-band imaging in the light of [O III] ?5007 Å suggests the presence of a large bow shock to the west of the nebula, indicating that it is undergoing the first stages of an interaction with the interstellar medium. Further narrow-band imaging in the light of H?+ [N II] ?6584 Å combined with long-slit observations of the H? emission have been used to develop a spatiokinematical model of Sp 1. The model clearly reveals Sp 1 to be a bipolar, axisymmetric structure viewed almost pole-on. The symmetry axis of the model nebula is within a few degrees of perpendicular to the orbital plane of the central binary system - strong evidence that the central close-binary system has played an important role in shaping the nebula. Sp 1 is one of the very few nebulae to have this link, between nebular symmetry axis and binary plane, shown observationally. Based on the observations made with European Southern Observatory telescopes at the La Silla or Paranal Observatories under programme IDs 74.D-0373 and 55.D-0550.

  16. 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 ...

  17. 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…

  18. 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…

  19. Playing war

    Microsoft Academic Search

    Ian Graham Ronald Shaw

    2010-01-01

    This paper argues that war video games are transitional spaces that connect players to the ‘war on terror’. It explores the pervasive influence of militarism in video games and how the US Army is enlisting play as an active force in blurring the distinctions between civilian and soldier. The paper begins by theorizing what exactly it means to ‘play’, and

  20. Answering patient questions about the role lifestyle factors play in cancer onset and recurrence: what do health care professionals say?

    PubMed

    Miles, Anne; Simon, Alice; Wardle, Jane

    2010-03-01

    This qualitative study examined how cancer specialists answer patient questions about what might have caused their cancer. Findings showed that while they were often candid about the role of smoking and drinking in cancer onset and that of diet in cancer recurrence, body weight and exercise were rarely mentioned. Any reluctance to discuss the role of lifestyle factors in cancer onset and recurrence arose from a desire to minimize patient distress, limitations in specialists' knowledge of the causes of cancer and perceived inadequacy of the available causal explanations when risk factors are multiple and probabilistic. PMID:20207672

  1. Structural features, antioxidant and immunological activity of a new polysaccharide (SP1) from sisal residue.

    PubMed

    Zhang, Xuehong; Liu, Lina; Lin, Cuiwu

    2013-08-01

    A new water-soluble polysaccharide (SP1) with molecular weight of 9192Da was isolated from the residue after extracting fiber from sisal leaf and its structure was investigated. Monosaccharide composition analysis showed that SP1 was composed of Rha, GalA, Gal, Ara and Glc in a molar ratio of 1.82:1.69:1.00:0.23:0.15. The structure analysis indicated that the SP1 was comprised of a backbone of alternating 1,2-linked-?-l-Rhap and 1,4-linked-?-d-GalpA units, and the neutral polysaccharide side chains composed of Galp, Ara and Glcp residues were attached to the O-4 position of 1,2-linked-?-l-Rhap residues. SP1 could stimulate ConA-induced T lymphocyte proliferation and had noticeable DPPH radical-scavenging ability. PMID:23624283

  2. MPI on IBM SP1\\/SP2: current status and future directions

    Microsoft Academic Search

    Hubertus Franke; Peter Hochschild; P. Pattnik J. Prost; Jean-Pierre Prost; Marc Snir

    1994-01-01

    A complete prototype implementation of MPI on the IBM Scalable Power PARALLEL 1 and 2 (SP1, SP2) is discussed. This implementation achieves essentially the same performance as the native EUI library, although MPI is much larger. The paper describes the implementation of EUI on SP1\\/SP2, and the modifications required to to implement MPI, initial performance measurements, and directions for future

  3. 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).

  4. The study of capacity fading processes of Li-ion batteries: major factors that play a role

    Microsoft Academic Search

    B Markovsky; A Rodkin; Y. S Cohen; O Palchik; E Levi; D Aurbach; H.-J Kim; M Schmidt

    2003-01-01

    In this work, we studied the impact of some factors on the behavior of practical electrodes of Li-ion batteries. These included elevated temperatures (45–80°C), prolonged storage of Li-ion cells, and additives in the electrolyte solution. The Li-ion battery systems studied included negative electrodes (anodes) comprising of mesocarbon microbeads (MCMB) and mesocarbon fibers (MCF), and LixCoO2 positive electrodes (cathodes) in an

  5. Hypoxia inducible factor 3? plays a critical role in alveolarization and distal epithelial cell differentiation during mouse lung development.

    PubMed

    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

  6. Characterization of an essential Orc2p-associated factor that plays a role in DNA replication.

    PubMed Central

    Hardy, C F

    1996-01-01

    The Saccharomyces cerevisiae Orc2 protein is a subunit of the origin recognition complex, ORC, which binds in a sequence-specific manner to yeast origins of DNA replication. With screens for orc2-1 synthetic lethal mutations and Orc2p two-hybrid interactors, a novel Orc2p-associated factor (Oaf1p) was identified. OAF1 is essential, its gene product is localized to the nucleus, and an oaf1 temperature-sensitive mutant arrests as large budded cells with a single nucleus. The mutant oaf1-2, isolated in the synthetic lethal screen, loses plasmids containing a single origin of DNA replication at a high rate, but it maintains plasmids carrying multiple potential origins of DNA replication. In addition, the OAF1 gene product tagged with the hemagglutinin antigen epitope binds to a DNA affinity column containing covalently linked tandem repeats of an essential origin element. These results suggest a role for OAFI in the initiation of DNA replication. Mutant alleles of cdc7 and cdc14 were also isolated in the orc2-1 synthetic lethal screen. Cdc7p, like Oaf1p, also interacts with Orc2p in two-hybrid assays. PMID:8657159

  7. The chromatin-remodeling factor AtINO80 plays crucial roles in genome stability maintenance and in plant development.

    PubMed

    Zhang, Chi; Cao, Lin; Rong, Liang; An, Zengxuan; Zhou, Wangbin; Ma, Jinbiao; Shen, Wen-Hui; Zhu, Yan; Dong, Aiwu

    2015-05-01

    INO80 is a conserved chromatin-remodeling factor in eukaryotes. While a previous study reported that the Arabidopsis thaliana INO80 (AtINO80) is required for somatic homologous recombination (HR), the role of AtINO80 in plant growth and development remains obscure. Here, we identified and characterized two independent atino80 mutant alleles, atino80-5 and atino80-6, which display similar and pleiotropic phenotypes, including smaller plant and organ size, and late flowering. Under standard growth conditions, atino80-5 showed decreased HR; however, after genotoxic treatment, HR in the mutant increased, accompanied by more DNA double-strand breaks and stronger cellular responses. Transcription analysis showed that many developmental and environmental responsive genes are overrepresented in the perturbed genes in atino80-5. These genes significantly overlapped with the category of H2A.Z body-enriched genes. AtINO80 also interacts with H2A.Z, and facilitates the enrichment of H2A.Z at the ends of the key flowering repressor genes FLC and MAF4/5. Our characterization of the atino80-5 and atino80-6 mutants confirms and extends the previous AtINO80 study, and provides perspectives for linking studies of epigenetic mechanisms involved in plant chromatin stability with plant response to developmental and environmental cues. PMID:25832737

  8. 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…

  9. Play School

    ERIC Educational Resources Information Center

    Rich, Jennifer L.

    2004-01-01

    This article describes Fifth Dimension, an after-school program which mixes play and computer games to improve the education and social skills of mostly poor, disadvantaged kids. Although Fifth Dimension seems tailor-made for a poor, rural community, its roots are urban. The after-school program was founded by a group of researchers in San Diego…

  10. 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…

  11. Transforming growth factor beta (TGF?) plays a crucial role in prolonging allograft survival in an allodepletion ("pruning") skin transplant model.

    PubMed

    Watson, Debbie; Zhang, Geoff Yu; Hu, Min; Wang, Yuan-Min; Fletcher, Jeffery; Sartor, Mary; Alexander, Stephen I

    2014-05-01

    Adoptive cell therapies involving cell manipulation to achieve tolerance are increasingly being studied in animal models and in human trials. We have demonstrated that the specific removal of allo-stimulated dividing cells (or "pruning") promotes long-term allograft survival across a major MHC mismatch in transplant models including skin, heart and islet transplants. In this study, we examine the role of transforming growth factor beta (TGF?), an important regulatory cytokine, on allograft survival in our allodepletion or "pruning" skin transplant model. Increased proliferation of CD4(+) T cells was observed following allo-stimulation of BALB/c spleen cells (labeled with CFSE) in the presence of the regulatory cytokines TGF? and (interleukin-2) IL-2 in a mixed lymphocyte culture (MLC). Expression of the regulatory gene forkhead box-3 (FoxP3) was increased in both the allo-stimulated non-dividing (ND) (CFSE(high)) and dividing (D) (CFSE(low)) CD4(+) T cell populations, with the highest expression found in the D CD4(+) T cell population. Mice reconstituted with allo-stimulated ND CD4(+) T cells following TGF?/IL-2 stimulation showed prolonged allograft survival, similar to previous data. Significantly, TGF?/IL-2 stimulation prevented acute rejection of allografts across a major MHC mismatch in the presence of highly activated allo-stimulated D CD4(+) T cells. Blockade of TGF? promoted rejection of allografts even following depletion of allo-stimulated D CD4(+) T cells. These studies support a crucial role for TGF? in the survival of allografts and shows that regulatory cytokines TGF?/IL2 can delay the rejection of allografts, even in the presence of highly activated alloreactive T cells. PMID:24746800

  12. Protein kinase CK2/PTEN pathway plays a key role in platelet-activating factor-mediated murine anaphylactic shock.

    PubMed

    Kang, Nam-In; Yoon, Ha-Yong; Kim, Han-A; Kim, Kyoung-Jin; Han, Myung-Kwan; Lee, Young-Rae; Hwang, Pyoung-Han; Soh, Byoung-Yul; Shin, Sook-Jeong; Im, Suhn-Young; Lee, Hern-Ku

    2011-06-01

    Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate. In this study, we examined the possible involvement of PTEN in PAF-mediated anaphylactic shock. Induction of anaphylaxis or PAF injection resulted in a rapid decrease in PTEN activity, followed by increases in PI3K activity and phosphorylation of Akt and eNOS. Systemic administration of adenoviruses carrying PTEN cDNA (adenoviral PTEN), but not the control AdLacZ, not only attenuated anaphylactic symptoms, but also reversed anaphylaxis- or PAF-induced changes in PTEN and PI3K activities, as well as phosphorylation of Akt and eNOS. We found that the decreased PTEN activity was associated with PTEN phosphorylation, the latter effect being prevented by the protein kinase CK2 inhibitor, DMAT. DMAT also inhibited anaphylactic symptoms as well as the anaphylaxis- or PAF-mediated PTEN/PI3K/Akt/eNOS signaling cascade. CK2 activity was increased by PAF. The present data provide, as the key mechanism underlying anaphylactic shock, PAF triggers the upstream pathway CK2/PTEN, which ultimately leads to the activation of PI3K/Akt/eNOS. Therefore, CK2/PTEN may be a potent target in the control of anaphylaxis and other many PAF-mediated pathologic conditions. PMID:21531890

  13. The Sigma Factor AlgU Plays a Key Role in Formation of Robust Biofilms by Nonmucoid Pseudomonas aeruginosa?

    PubMed Central

    Bazire, Alexis; Shioya, Kouki; Soum-Soutéra, Emmanuelle; Bouffartigues, Emeline; Ryder, Cynthia; Guentas-Dombrowsky, Linda; Hémery, Gaëlle; Linossier, Isabelle; Chevalier, Sylvie; Wozniak, Daniel J.; Lesouhaitier, Olivier; Dufour, Alain

    2010-01-01

    The extracytoplasmic function sigma factor AlgU of Pseudomonas aeruginosa is responsible for alginate overproduction, leading to mucoidy and chronic infections of cystic fibrosis patients. We investigated here the role of AlgU in the formation of nonmucoid biofilms. The algU mutant of P. aeruginosa PAO1 (PAOU) showed a dramatic impairment in biofilm formation under dynamic conditions. PAOU was defective both in cell attachment to glass and in development of robust, shear-resistant biofilms. This was explained by an impaired production of extracellular matrix, specifically of the exopolysaccharide Psl, as revealed by microscopy and enzyme-linked immunosorbent assay. Complementing the algU mutation with a plasmid-borne algU gene restored wild-type phenotypes. Compared with that in PAO1, expression of the psl operon was reduced in the PAOU strain, and the biofilm formation ability of this strain was partially restored by inducing the transcription of the psl operon. Furthermore, expression of the lectin-encoding lecA and lecB genes was reduced in the PAOU strain. In agreement with the requirement of LecB for type IV pilus biogenesis, PAOU displayed impaired twitching motility. Collectively, these genetic downregulation events explain the biofilm formation defect of the PAOU mutant. Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes, but AlgU is involved in the expression of the ppyR gene, whose product was reported to positively control psl expression. Expressing the ppyR gene in PAOU partially restored the formation of robust biofilms. PMID:20348252

  14. Histone deacetylase 3 represses p15{sup INK4b} and p21{sup WAF1/cip1} transcription by interacting with Sp1

    SciTech Connect

    Huang Weifeng [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Tan Dapeng [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Wang Xiuli [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Han Songyan [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Tan Jiang [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Zhao Yanmei [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Lu Jun [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China)]. E-mail: ycsuo@nenu.edu.cn; Huang Baiqu [Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China)

    2006-01-06

    Histone deacetylase 3 (HDAC3) has been implicated to play roles in governing cell proliferation. Here we demonstrated that the overexpression of HDAC3 repressed transcription of p15{sup INK4b} and p21{sup WAF1/cip1} genes in 293T cells, and that the recruitment of HDAC3 to the promoter regions of these genes was critical to this repression. We also showed that HDAC3 repressed GAL4-Sp1 transcriptional activity, and that Sp1 was co-immunoprecipitated with FLAG-tagged HDAC3. We conclude that HDAC3 can repress p15{sup INK4b} and p21{sup WAF1/cip1} transcription by interacting with Sp1. Furthermore, knockdown of HDAC3 by RNAi up-regulated the transcriptional expression of p15{sup INK4b}, but not that of p21{sup WAF1/cip1}, implicating the different roles of HDAC3 in repression of p15{sup INK4b} and p21{sup WAF1/cip1} transcription. Data from this study indicate that the inhibition of p15{sup INK4b} and p21{sup WAF1/cip1} may be one of the mechanisms by which HDAC3 participates in cell cycle regulation and oncogenesis.

  15. 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.

  16. Up-regulation of type II collagen gene by 17?-estradiol in articular chondrocytes involves Sp1/3, Sox-9, and estrogen receptor ?

    PubMed

    Maneix, Laure; Servent, Aurélie; Porée, Benoît; Ollitrault, David; Branly, Thomas; Bigot, Nicolas; Boujrad, Noureddine; Flouriot, Gilles; Demoor, Magali; Boumediene, Karim; Moslemi, Safa; Galéra, Philippe

    2014-08-01

    The existence of a link between estrogen deprivation and osteoarthritis (OA) in postmenopausal women suggests that 17?-estradiol (17?-E2) may be a modulator of cartilage homeostasis. Here, we demonstrate that 17?-E2 stimulates, via its receptor human estrogen receptor ? 66 (hER?66), type II collagen expression in differentiated and dedifferentiated (reflecting the OA phenotype) articular chondrocytes. Transactivation of type II collagen gene (COL2A1) by ligand-independent transactivation domain (AF-1) of hER?66 was mediated by "GC" binding sites of the -266/-63-bp promoter, through physical interactions between ER?, Sp1/Sp3, Sox9, and p300, as demonstrated in chromatin immunoprecipitation (ChIP) and Re-Chromatin Immuno-Precipitation (Re-ChIP) assays in primary and dedifferentiated cells. 17?-E2 and hER?66 increased the DNA-binding activities of Sp1/Sp3 and Sox-9 to both COL2A1 promoter and enhancer regions. Besides, Sp1, Sp3, and Sox-9 small interfering RNAs (siRNAs) prevented hER?66-induced transactivation of COL2A1, suggesting that these factors and their respective cis-regions are required for hER?66-mediated COL2A1 up-regulation. Our results highlight the genomic pathway by which 17?-E2 and hER?66 modulate Sp1/Sp3 heteromer binding activity and simultaneously participate in the recruitment of the essential factors Sox-9 and p300 involved respectively in the chondrocyte-differentiated status and COL2A1 transcriptional activation. These novel findings could therefore be attractive for tissue engineering of cartilage in OA, by the fact that 17?-E2 could promote chondrocyte redifferentiation. PMID:25081415

  17. Cloning and Characterization of the Human Trefoil Factor 3 Gene Promoter

    PubMed Central

    Zhou, Yifang; Mao, Xuefei; Deng, Xiangdong

    2014-01-01

    Human trefoil factor 3 (hTFF3) is a small-molecule peptide with potential medicinal value. Its main pharmacological function is to alleviate gastrointestinal mucosal injuries caused by various factors and promote the repair of damaged mucosa. However, how its transcription is regulated is not yet known. The aim of this study was to clone the hTFF3 gene promoter region, identify the core promoter and any transcription factors that bind to the promoter, and begin to clarify the regulation of its expression. The 5? flanking sequence of the hTFF3 gene was cloned from human whole blood genomic DNA by PCR. Truncated promoter fragments with different were cloned and inserted into the pGL3-Basic vector to determine the position of the core hTFF3 promoter. Transcription element maintaining basic transcriptional activity was assessed by mutation techniques. Protein-DNA interactions were analyzed by chromatin immunoprecipitation (ChIP). RNA interference and gene over-expression were performed to assay the effect of transcription factor on the hTFF3 expression. The results showed that approximately 1,826 bp of the fragment upstream of hTFF3 was successfully amplified, and its core promoter region was determined to be from ?300 bp to ?280 bp through analysis of truncated mutants. Mutation analysis confirmed that the sequence required to maintain basic transcriptional activity was accurately positioned from ?300 bp to ?296 bp. Bioinformatic analysis indicated that this area contained a Sp1 binding site. Sp1 binding to the hTFF3 promoter was confirmed by ChIP experiments. Sp1 over-expression and interference experiments showed that Sp1 enhanced the transcriptional activity of the hTFF3 promoter and increased hTFF3 expression. This study demonstrated that Sp1 plays an important role in maintaining the transcription of hTFF3. PMID:24743382

  18. Arabidopsis transcription factor genes NF-YA1, 5, 6, and 9 play redundant roles in male gametogenesis, embryogenesis, and seed development.

    PubMed

    Mu, Jinye; Tan, Helin; Hong, Sulei; Liang, Yan; Zuo, Jianru

    2013-01-01

    Nuclear factor Y (NF-Y) is a highly conserved transcription factor presented in all eukaryotic organisms, and is a heterotrimer consisting of three subunits: NF-YA, NF-YB, and NF-YC. In Arabidopsis, these three subunits are encoded by multigene families. The best-studied member of the NF-Y transcription factors is LEAFY COTYLEDON1 (LEC1), a NF-YB family member, which plays a critical role in embryogenesis and seed maturation. However, the function of most NF-Y genes remains elusive. Here, we report the characterization of four genes in the NF-YA family. We found that a gain-of-function mutant of NF-YA1 showed defects in male gametogenesis and embryogenesis. Consistently, overexpression of NF-YA1, 5, 6, and 9 affects male gametogenesis, embryogenesis, seed morphology, and seed germination, with a stronger phenotype when overexpressing NF-YA1 and NF-YA9. Moreover, overexpression of these NF-YA genes also causes hypersensitivity to abscisic acid (ABA) during seed germination, retarded seedling growth, and late flowering at different degrees. Intriguingly, overexpression of NF-YA1, 5, 6, and 9 is sufficient to induce the formation of somatic embryos from the vegetative tissues. However, single or double mutants of these NF-YA genes do not have detectable phenotype. Collectively, these results provide evidence that NF-YA1, 5, 6, and 9 play redundant roles in male gametophyte development, embryogenesis, seed development, and post-germinative growth. PMID:22933713

  19. Early experiences with the IBM SP1 and the high-performance switch

    SciTech Connect

    Gropp, W. [ed.

    1993-11-01

    The IBM SP1 is IBM`s newest parallel distributed-memory computer. As part of a joint project with IBM, Argonne took delivery of an early system in order to evaluate the software environment and to begin porting programming packages and applications to this machine. This report discusses the results of those efforts once the high-performance switch was installed. An earlier report (ANL/MCS-TM-177) emphasized software usability and the initial ports to the SP1. This report contains performance results and discusses some applications and tools not covered in TM 177.

  20. 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

  1. Autophagosomal I?B? Degradation Plays a Role in the Long Term Control of Tumor Necrosis Factor-?-induced Nuclear Factor-?B (NF-?B) Activity*

    PubMed Central

    Colleran, Amy; Ryan, Aideen; O'Gorman, Angela; Mureau, Coralie; Liptrot, Catherine; Dockery, Peter; Fearnhead, Howard; Egan, Laurence J.

    2011-01-01

    Transcription factor NF-?B is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of NF-?B is well understood, but little is known about the mechanisms of its long term activation. We studied the effect of a single application of TNF-? on NF-?B activity for up to 48 h in intestinal epithelial cells. Results show that NF-?B remained persistently activated up to 48 h after TNF-? and that the long term activation of NF-?B was accompanied by a biphasic degradation of I?B?. The first phase of I?B? degradation was proteasome-dependent, but the second was not. Further investigation showed that TNF-? stimulated formation of autophagosomes in intestinal epithelial cells and that I?B? co-localized with autophagosomal vesicles. Pharmacological or genetic blockade of autophagosome formation or the inhibition of lysosomal proteases decreased TNF-?-induced degradation of I?B? and lowered NF-?B target gene expression. Together, these findings indicate a role of autophagy in the control of long term NF-?B activity. Because abnormalities in autophagy have been linked to ineffective innate immunity, we propose that alterations in NF-?B may mediate this effect. PMID:21454695

  2. NtbZIP60, an endoplasmic reticulum-localized transcription factor, plays a role in the defense response against bacterial pathogens in Nicotiana tabacum.

    PubMed

    Tateda, Chika; Ozaki, Rei; Onodera, Yu; Takahashi, Yoshihiro; Yamaguchi, Koji; Berberich, Thomas; Koizumi, Nozomu; Kusano, Tomonobu

    2008-11-01

    A spermine-based signal transduction pathway plays a defensive role against incompatible pathogens. We identified a novel spermine-responsive cDNA from Nicotiana tabacum that encodes a basic region/leucine zipper protein with a putative transmembrane domain. Identity to Arabidopsis thaliana AtbZIP60 was sufficiently high to name the novel cDNA NtbZIP60. Expression analysis revealed that NtbZIP60 is a component of the spermine-signal pathway, and is also involved in the unfolded protein response (UPR), as demonstrated for AtbZIP60. The gene product, NtbZIP60, localizes to the endoplasmic reticulum (ER) in plant cells; once the putative transmembrane domain is eliminated from the intact protein, it targets the nucleus. The putative processed form of NtbZIP60 transactivates target genes through binding to plant-specific UPR cis-elements. Expression of NbbZIP60, an NtbZIP60 ortholog in Nicotiana benthamiana, was significantly up-regulated at 6 h and later time points upon infection with the non-host pathogen Pseudomonas cichorii, while it was unaffected by infection with the compatible pathogen Pseudomonas syringae pv. tabaci. Furthermore, NbbZIP60-silenced N. benthamiana plants allowed higher multiplication of P. cichorii compared to the control plants. Taken together, the results suggest that this ER-localized transcription factor is involved in the spermine-signal transduction pathway and plays an important role in plant innate immunity. PMID:18758894

  3. 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.

  4. Involvement of the GC-rich sequence and specific proteins (Sp1/Sp3) in the basal transcription activity of neurogranin gene

    SciTech Connect

    Gui Jingang [Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543 (Singapore); Song Yan [Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543 (Singapore); Han, N.-L.R. [Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543 (Singapore); Zhou Shufeng [Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543 (Singapore); Sheu, F.-S. [Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543 (Singapore) and University Scholars Program, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260 (Singapore)]. E-mail: dbssfs@nus.edu.sg

    2006-06-23

    Neurogranin (Ng), a neuronal protein implicated in learning and memory, contains a TATA-less promoter. Analysis of 5'-deletion mutations and site-directed mutations of the mouse Ng promoter revealed that a 258 bp 5'-flanking sequence (+3 to +260) conferred the basal transcription activity, and that the GC-rich sequence (+22 to +33) served as an important determinant of the promoter activity. Transient transfection of the Sp1 expression plasmid transactivated the reporter activity in neuroblastoma N2A cells while knocking down of endogenous Sp1 expression resulted in a 2.5-fold reduction of the reporter activity in HEK 293 cells. Exogenous expression of Sp3 in HEK 293 cells, however, repressed the reporter activity by 50%. Nevertheless, by gel shift assays, Sp1 and Sp3 were not found to be responsible for the protein-DNA complexes formed by the GC-rich sequence. Moreover, a nuclear factor from the mouse brain tissues was discovered to bind to multiple AT-rich regions in Ng promoter.

  5. Resource dynamics during infection of Micromonas pusilla by virus MpV-Sp1

    E-print Network

    Lawrence, J.E.

    of the prasinophyte alga Micromonas pusilla by phycodnavirus MpV SP1. Under a light­dark regimen, viral genomes accumu and was stalled in darkness, meanwhile viral genome replication proceeded slowly in the dark. Viral exploi- tation and Raven, 1997; Field et al., 1998). Removal of phytoplankton cells from marine trophic webs can occur

  6. 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

  7. Prostaglandin E2 and Transforming Growth Factor-? Play a Critical Role in Suppression of Allergic Airway Inflammation by Adipose-Derived Stem Cells

    PubMed Central

    Park, Mi-Kyung; Park, Hye-Kyung; Yu, Hak-Sun; Roh, Hwan-Jung

    2015-01-01

    Background The role of soluble factors in the suppression of allergic airway inflammation by adipose-derived stem cells (ASCs) remains to be elucidated. Moreover, the major soluble factors responsible for the immunomodulatory effects of ASCs in allergic airway diseases have not been well documented. We evaluated the effects of ASCs on allergic inflammation in asthmatic mice treated with a prostaglandin E2 (PGE2) inhibitor or transforming growth factor-? (TGF-?) neutralizing antibodies. Methods and Findings Asthmatic mice were injected intraperitoneally with a PGE2 inhibitor or TGF-? neutralizing antibodies at approximately the same time as ASCs injection and were compared with non-treated controls. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF), eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13, and enhanced the Th1 cytokine (Interferon-?) and regulatory cytokines (IL-10 and TGF-?) in the BALF and lung draining lymph nodes (LLNs). ASCs engraftment caused significant increases in the regulatory T cell (Treg) and IL-10+ T cell populations in LLNs. However, blocking PGE2 or TGF-? eliminated the immunosuppressive effect of ASCs in allergic airway inflammation. Conclusions ASCs are capable of secreting PGE2 and TGF-?, which may play a role in inducing Treg expansion. Furthermore, treatment with a PGE2 inhibitor or TGF-? neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-? are the major soluble factors responsible for suppressing allergic airway inflammation. PMID:26176545

  8. 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 ...

  9. IFN regulatory factor-1 plays a central role in the regulation of the expression of class I and II MHC genes in vivo.

    PubMed

    Hobart, M; Ramassar, V; Goes, N; Urmson, J; Halloran, P F

    1997-05-01

    Transcription factor interferon regulatory factor-1 (IRF-1) is implicated in regulating class I MHC expression in vitro. We investigated the in vivo relationship between IRF-1 and MHC expression in kidney and other nonlymphoid organs, assessing MHC expression in mice with disrupted IRF-1 genes (IRF-1 KO) compared with mice with intact IRF-1 genes (WT). In kidneys of IRF-1 KO mice, basal class I expression was decreased, particularly on arterial endothelium, but basal class II expression was unchanged. The induction of both class I and class II expression by injected rIFN-gamma was reduced in IRF-1 KOs, compared with WT mice. Similarly, stimuli that induce endogenous IFN-gamma production (LPS or oxazolone) massively increased MHC expression in kidneys of WT mice, with little increase in IRF-1 KO mice. Impaired class II induction by rIFN-gamma in IRF-1 KO mice probably reflects the role of IRF-1 in regulating class II transactivator (CIITA) expression: rIFN-gamma induced CIITA mRNA less in kidneys of IRF-1 KO mice than in WT mice. In organs of WT mice, IRF-1 mRNA was expressed in the basal state, and rIFN-gamma treatment increased IRF-1 mRNA before the induction of class I or CIITA mRNA. Treatment of WT mice with cycloheximide plus rIFN-gamma superinduced IRF-1 mRNA expression, but partially inhibited CIITA mRNA expression, indicating that IRF-1 mRNA induction is not dependent on new protein synthesis, unlike CIITA. Thus, in vivo, IRF-1 plays a major role in basal and induced class I expression and in induction of class II by IFN-gamma, probably via CIITA induction. PMID:9126988

  10. 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

  11. Analysis of a new type of major ampullate spider silk gene, MaSp1s.

    PubMed

    Han, Leng; Zhang, Lei; Zhao, Tianfu; Wang, Yujun; Nakagaki, Masao

    2013-05-01

    Spider dragline silk, which is secreted from the major ampullate silk glands, is a unique fibrous protein with a combination of tensile strength and elasticity. Here, we describe a new short type of dragline silk gene, Cyrtophora moluccensis MaSp1s. The full-length gene is only 1320 base pairs (bp), which encodes 439 amino acids that includes the intact non-repetitive N-terminal (149 residues), C-terminal (98 residues) and so-called repetitive regions (192 residues); the deduced molecular weight is approximately 40 kDa. The sequence analysis demonstrated that the two termini are highly homologous to the other characterized dragline silk genes but that the so-called repetitive region is different. Our results suggest that MaSp1s is a possible new characteristic dragline gene; the discovery of this gene should enhance our understanding of the major ampullate spider silk genes. PMID:23403024

  12. Overexpression of HDAC1 induces cellular senescence by Sp1/PP2A/pRb pathway

    SciTech Connect

    Chuang, Jian-Ying [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China)] [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China); Hung, Jan-Jong, E-mail: petehung@mail.ncku.edu.tw [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China) [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China); Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 701, Taiwan (China)

    2011-04-15

    Highlights: {yields} Overexpression of HDAC1 induces Sp1 deacetylation and raises Sp1/p300 complex formation to bind to PP2Ac promoter. {yields} Overexpression of HDAC1 strongly inhibits the phosphorylation of pRb through up-regulation of PP2A. {yields} Overexpressed HDAC1 restrains cell proliferaction and induces cell senescence though a novel Sp1/PP2A/pRb pathway. -- Abstract: Senescence is associated with decreased activities of DNA replication, protein synthesis, and cellular division, which can result in deterioration of cellular functions. Herein, we report that the growth and division of tumor cells were significantly repressed by overexpression of histone deacetylase (HDAC) 1 with the Tet-off induced system or transient transfection. In addition, HDAC1 overexpression led to senescence through both an accumulation of hypophosphorylated active retinoblastoma protein (pRb) and an increase in the protein level of protein phosphatase 2A catalytic subunit (PP2Ac). HDAC1 overexpression also increased the level of Sp1 deacetylation and elevated the interaction between Sp1 and p300, and subsequently that Sp1/p300 complex bound to the promoter of PP2Ac, thus leading to induction of PP2Ac expression. Similar results were obtained in the HDAC1-Tet-off stable clone. Taken together, these results indicate that HDAC1 overexpression restrained cell proliferation and induced premature senescence in cervical cancer cells through a novel Sp1/PP2A/pRb pathway.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. The human immunodeficiency virus-1 Tat protein increases cell proliferation, alters sensitivity to zinc chelator-induced apoptosis, and changes Sp1 DNA binding in HeLa cells.

    PubMed

    Seve, M; Favier, A; Osman, M; Hernandez, D; Vaitaitis, G; Flores, N C; McCord, J M; Flores, S C

    1999-01-15

    The HIV-1 transcriptional regulatory protein Tat is a pleiotropic factor that represses expression of the human Mn-superoxide dismutase. Tat increases oxidative stress, as shown by decreased glutathione and NADPH levels. These redox changes enhance proliferation and apoptosis and alter the activity of zinc thiolate-containing proteins such as Sp1. Cells stably producing the Tat protein have an increased proliferation rate, which can be inhibited by pretreatment with the antioxidant mercaptopropionylglycine. Conversely, cells exposed to low concentrations of the oxidant paraquat are stimulated to divide. Intermediate and higher paraquat levels result in increased apoptosis or necrosis, respectively, suggesting that the physiological end point depends on the dose of oxidant used. Furthermore, treatment with the zinc chelator (N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) sensitizes HeLa-tat cells to apoptosis. In these cells, binding of the zinc-containing factor Sp1 to its DNA sequence is higher than in parental cells. Normal DNA binding is partially restored by pretreatment with a compound that mimics superoxide dismutase activity. Interestingly, Sp1-DNA interactions decrease more rapidly in the HeLa-tat cells after TPEN treatment. HeLa cell extracts incubated in the presence of purified Tat protein have increased Sp1 binding, consistent with the results observed in Tat-transfected cells. These results suggest that the Tat protein, via direct or indirect mechanisms, increases proliferation, sensitizes cells to apoptosis, and changes the conformation of Sp1, affecting its ability to bind to its cognate DNA sequence and to retain its zinc. PMID:9882443

  19. Why Swedish people play online poker and factors that can increase or decrease trust in poker Web sites: A qualitative investigation

    Microsoft Academic Search

    Richard T. A. Wood; Mark D. Griffiths

    2008-01-01

    Three face-to-face focus groups that included 24 online poker players were conducted in Stockholm to investigate their motivations for playing online poker and issues relating to their trust of poker Web sites. Casual players played because they liked the convenience, the ease of learning, the low stake size, the relief from boredom, and the social interactions. \\

  20. Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1.

    PubMed

    Han, Song-Iee; Tsunekage, Yukino; Kataoka, Kohsuke

    2015-08-15

    Haploinsufficiency of the Gata3 gene, which encodes a zinc-finger transcription factor, is associated with the disorder hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome in humans. However, the roles of Gata3 in transcriptional regulation in the parathyroid glands are not well-understood. In this study, we show that Gata3 activates transcription of parathyroid hormone (PTH), which is secreted from parathyroid glands and is critical for regulating serum calcium and phosphate homeostasis. Gata3 interacted with Gcm2 and MafB, two known transcriptional regulators of parathyroid development, and synergistically stimulated the PTH promoter. An SP1-binding element (GC box) located within the PTH-promoter proximal region was critical for activating transcription by Gata3. In addition, the ubiquitous transcription factor SP1 also interacted with Gata3 as well as MafB and Gcm2, and HDR syndrome-associated Gata3 mutants were defective in activating the PTH promoter. These results suggest that Gata3 is a critical regulator of PTH gene expression. PMID:25917456

  1. 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

  2. ?-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

  3. ?-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

  4. Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette smoke-induced chronic obstructive pulmonary diseases via the suppression of Erk-Sp1 signaling.

    PubMed

    Shin, In-Sik; Shin, Na-Rae; Park, Ji-Won; Jeon, Chan-Mi; Hong, Ju-Mi; Kwon, Ok-Kyoung; Kim, Joong-Sun; Lee, In-Chul; Kim, Jong-Choon; Oh, Sei-Ryang; Ahn, Kyung-Seop

    2015-01-01

    The incidence of chronic obstructive pulmonary disease (COPD) has substantially increased in recent decade. Cigarette smoke (CS) is the most important risk factor in the development of COPD. In this study, we investigated the effects of melatonin on the development of COPD using a CS and lipopolysaccharide (LPS)-induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid carcinoma cell. On day 4, the mice were treated intranasally with LPS. The mice were exposed to CS for 1 hr per day (8 cigarettes per day) from day 1 to day 7. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 hr before CS exposure. Melatonin markedly decreased the neutrophil count in the BALF, with reduction in the proinflammatory mediators and MUC5AC. Melatonin inhibited Erk phosphorylation and Sp1 expression induced by CS and LPS treatment. Additionally, melatonin decreased airway inflammation with a reduction in myeloperoxidase expression in lung tissue. In in vitro experiments, melatonin suppressed the elevated expression of proinflammatory mediators induced by CSC treatment. Melatonin reduced Erk phosphorylation and Sp1 expression in CSC-stimulated H292 cells. In addition, cotreatment of melatonin and Erk inhibitors significantly limited the proinflammatory mediators with greater reductions in Erk phosphorylation and Sp1 expression than that observed in H292 cells treated with Erk inhibitor alone. Taken together, melatonin effectively inhibited the neutrophil airway inflammation induced by CS and LPS treatment, which was closely related to downregulation of Erk phosphorylation. These findings suggest that melatonin has a therapeutic potential for the treatment of COPD. PMID:25388990

  5. Evidence that Spt2\\/Sin1, an HMG-Like Factor, Plays Roles in Transcription Elongation, Chromatin Structure, and Genome Stability in Saccharomyces cerevisiae

    Microsoft Academic Search

    Amine Nourani; Francois Robert; Fred Winston

    2006-01-01

    Spt2\\/Sin1 is a DNA binding protein with HMG-like domains that has been suggested to play a role in chromatin-mediated transcription in Saccharomyces cerevisiae. Previous studies have suggested models in which Spt2 plays an inhibitory role in the initiation of transcription of certain genes. In this work, we have taken several approaches to study Spt2 in greater detail. Our results have

  6. ERK-dependent activation of Sp1 is required for low-power laser irradiation-induced vascular endothelial cell proliferation

    NASA Astrophysics Data System (ADS)

    Feng, Jie; Xing, Da

    2012-12-01

    Here, we report that low-power laser irradiation (LPLI) activates ERK/Sp1 pathway to upregulate VEGF expression and promote vascular endothelial cell proliferation. We demonstrate for the first time that LPLI enhances DNA-binding activity and transactivation activity of Sp1 on VEGF promoter. Additionally, ERK translocates from cytoplasm to nucleus following LPLI. Moreover, activated ERK phosphorylates Sp1 and results in increased EKR-Sp1 interaction. Selective inhibition of Sp1 or ERK suppresses the effect of LPLI on the promotion of cell cycle progression and proliferation. These findings provide a novel link between LPLI and angiogenesis, supplying potential therapy strategies for angiogenesis with LPLI.

  7. The Nuclear Factor Y subunits NF-YB2 and NF-YB3 play additive roles in the promotion of flowering by inductive long-day photoperiods in Arabidopsis

    Microsoft Academic Search

    Roderick W. Kumimoto; Luc Adam; Graham J. Hymus; Peter P. Repetti; T. Lynne Reuber; Colleen M. Marion; Frederick D. Hempel; Oliver J. Ratcliffe

    2008-01-01

    Accumulating evidence supports a role for members of the plant Nuclear Factor Y (NF-Y) family of CCAAT-box binding transcription\\u000a factors in the regulation of flowering time. In this study we have used a genetic approach to show that the homologous proteins\\u000a NF-YB3 and NF-YB2 have comparable activities and play additive roles in the promotion of flowering, specifically under inductive\\u000a photoperiodic

  8. The Human Immunodeficiency Virus1 Tat Protein Increases Cell Proliferation, Alters Sensitivity to Zinc Chelator-Induced Apoptosis, and Changes Sp1 DNA Binding in HeLa Cells

    Microsoft Academic Search

    Michel Seve; Alain Favier; Mireille Osman; Daniel Hernandez; Gisela Vaitaitis; Natalia C. Flores; Joe M. McCord; Sonia C. Flores

    1999-01-01

    The HIV-1 transcriptional regulatory protein Tat is a pleiotropic factor that represses expression of the human Mn-superoxide dismutase. Tat increases oxidative stress, as shown by decreased glutathione and NADPH levels. These redox changes enhance proliferation and apoptosis and alter the activity of zinc thiolate-containing proteins such as Sp1. Cells stably producing the Tat protein have an increased proliferation rate, which

  9. 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

  10. Vygotsky on play: child's play or more

    E-print Network

    Wagner, Carol Anne

    2000-01-01

    The thesis examines L. S. Vygotsky's theory of play, its relationship to his theory of the Zone of Proximal Development (ZPD), and how they relate to cognitive development in children. Specifically considered is the influence of play...

  11. 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…

  12. Estrogen Receptor beta binds Sp1 and recruits a Corepressor Complex to the Estrogen Receptor alpha Gene Promoter

    PubMed Central

    Bartella, V; Rizza, P; Barone, I; Zito, D; Giordano, F; Giordano, C; Catalano, S; Mauro, L; Sisci, D; Panno, ML; Fuqua, SA; Andò, Sebastiano

    2015-01-01

    Human estrogen receptors (ERs) alpha and beta are crucially involved in the regulation of mammary growth and development. Normal breast tissues display a prevalently expression of ER beta than ER alpha, which drastically increases during breast tumorogenesis. So, it is reasonable to assume how a dysregulation of the two estrogen receptor subtypes may induce breast cancer development. However, the molecular mechanism underlying the opposite role played by the two estrogen receptors on tumor cell growth remains to be elucidated. In the present study, we have demonstrated that ER beta overexpression in breast cancer cells decreases cell proliferation and down-regulates ER alpha mRNA and protein content along with a concomitant repression of estrogen-regulated genes. Transient transfection experiments, using a vector containing the human ER alpha promoter region, showed that elevated levels of the ER beta down-regulated basal ER alpha promoter activity. Furthermore, side-directed mutagenesis and deletion analysis have revealed that the proximal GC-rich motifs at ?223 and ?214 is crucial for the ER beta-induced ER alpha down-regulation in breast cancer cells. This occurred through ER beta-Sp1 protein-protein interaction within the ER alpha promoter region and the recruitment of a corepressor complex containing NCoR/SMRT (nuclear receptor corepressor/silencing mediator of retinoic acid and thyroid hormone receptor), accompanied by hypoacetylation of histone H4 and displacement of RNA polymerase II. Silencing of NCoR gene expression by RNA interference reversed the down-regulatory effect of ER beta on ER alpha gene expression and cell proliferation. Our results provide evidence for a novel mechanism by which overexpression of ER beta through NCoR is able to down regulate ER alpha gene expression, thus inhibiting ER alpha’s driving role on breast cancer cell growth. PMID:22622808

  13. 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

  14. Isolation and partial characterization of ?SP-1, a Salmonella specific lytic phage from intestinal content of broiler chicken.

    PubMed

    Augustine, Jeena; Louis, Linda; Varghese, Siju M; Bhat, Sarita G; Kishore, Archana

    2013-02-01

    Salmonella enterica subsp. enterica serovar Enteritidis is a major causative agent of gastroenteritis with contaminated eggs and chicken meat being the major source of infection. Phages are seriously being considered as a safe and cheaper alternative to antibiotics. The intestinal content of chicken was used as source for isolating phages. Phage designated as ?SP-1 was selected for the study. Transmission electron microscopy (TEM) of phage ?SP-1 revealed that it belonged to family Podoviridae. The optimal multiplicity of infection (MOI) was 5 phages/cell. Latent and rise period were calculated to be 30 and 55 minutes respectively, while burst size was 44 phages/bacterial cell. The genome size of ?SP-1 was estimated to be 86?kb from pulsed-field gel electrophoresis analysis (PFGE). The effect of different physical and chemical parameters like temperature, pH, salinity and CaCl? were analyzed to optimize the conditions for large scale production of phages and to check the viability of ?SP-1 under different physiochemical conditions. A temperature of 40?°C, pH 8 and 0.25?M NaCl were found to be optimum for phage adsorption and it was able to survive up to a temperature of 50?°C for 3?min. Capability to survive under hostile environmental conditions, absence of virulence genes in genome and genus specificity suggest suitability of ?SP-1 to be used as a biocontrol agent. PMID:22733367

  15. miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6.

    PubMed

    Zhu, Xiaolan; Li, Yuefeng; Xie, Chanjuan; Yin, Xinming; Liu, Yueqin; Cao, Yuan; Fang, Yue; Lin, Xin; Xu, Yao; Xu, Wenlin; Shen, Huiling; Wen, Jian

    2014-09-15

    Multidrug resistance (MDR) remains a major obstacle to effective chemotherapy treatment in ovarian cancer. In our study, paclitaxel-resistant ovarian cancer patients and cell lines had decreased miR-145 levels and expressed high levels of Sp1 and Cdk6. Introducing miR-145 into SKOV3/PTX and A2780/PTX cells led to a reduction in Cdk6 and Sp1 along with downregulation of P-gp and pRb. These changes resulted in increased accumulation of antineoplastic drugs and G1 cell cycle arrest, which rendered the cells more sensitive to paclitaxel in vitro and in vivo. These effects could be reversed by reintroducing Sp1 or Cdk6 into cells expressing high levels of miR-145, resulting in restoration of P-gp and pRb levels. Furthermore, we confirmed that both Cdk6 and Sp1 are targets of miR-145. Intriguingly, demethylation with 5-aza-dC led to reactivation of miR-145 expression in drug-resistant ovarian cancer cell lines, which also resulted in increased sensitivity to paclitaxel. Collectively, these findings begin to elucidate the role of miR-145 as an important regulator of chemoresistance in ovarian cancer by controlling both Cdk6 and Sp1. PMID:24510775

  16. The Developmentally Regulated Expression of Serum Response Factor Plays a Key Role in the Control of Smooth Muscle-Specific Genes

    Microsoft Academic Search

    Curtis L. Browning; Donald E. Culberson; Ileana V. Aragon; Rebecca A. Fillmore; Jeffrey D. Croissant; Robert J. Schwartz; Warren E. Zimmer

    1998-01-01

    Serum response factor (SRF) is a MADS box transcription factor that has been shown to be important in the regulation of a variety of muscle-specific genes. We have previously shown SRF to be a major component of multiplecis\\/transinteractions found along the smooth muscle ?-actin (SMGA) promoter. In the studies reported here, we have further characterized the role of SRF in

  17. The Denial of Play.

    ERIC Educational Resources Information Center

    Sutton-Smith, Brian

    Well meaning parents and teachers often use children's play for the purposes of literacy and socialization. Yet, these attempts may deny play to children by subordinating play to some other concept. Evidence shows that even when parents play with their very young children they generally play games like shopping, cooking, and eating; whereas when…

  18. Children's Play and Television.

    ERIC Educational Resources Information Center

    Powell, Mark

    2001-01-01

    Discusses adverse effects of FCC deregulation of children's television programming on children's play behavior. Discusses the difference between play and imitation, the role of high quality dramatic play in healthy child development, the popularity of war play, and use of toys to increase dramatic play. Considers ways to help children gain control…

  19. ATP-sensitive potassium channels expressed by human monocytes play a role in stasis-induced thrombogenesis via tissue factor pathway

    Microsoft Academic Search

    Diethart Schmid; Dawid L. Staudacher; Rodolpho Bueno; Paul G. Spieckermann; Thomas Moeslinger

    2007-01-01

    Blood stasis is one of the key risk factors in deep vein thrombosis. Localized blood oxygen and glucose depletion are main characteristics observed during stasis. However, the causal chain leading to clot formation is still obscure. According to our hypothesis, energy depletion causes opening of K(ATP) channels present on monocytes, facilitating influx of calcium and triggering tissue factor-(TF)-dependent procoagulatory activity

  20. Nitric oxide inhibits endothelial IL-1[beta]-induced ICAM-1 gene expression at the transcriptional level decreasing Sp1 and AP-1 activity.

    PubMed Central

    Berendji-Grün, D.; Kolb-Bachofen, V.; Kröncke, K. D.

    2001-01-01

    BACKGROUND: Nitric oxide (NO) has frequently been shown to inhibit leukocyte adherence to activated endothelium thus displaying anti-adhesive and immunosuppressive activities. A molecular mechanism contributing to this effect is described. MATERIALS AND METHODS: Primary murine aortic endothelial cells were activated with interleukin (IL)-1beta to express intercellular adhesion molecule-1 (ICAM-1) mRNA in the presence or absence of the physiological spontaneous NO-donor S-nitrosocysteine. Subsequently, semiquantitative RT-PCR and gel shift assays with nuclear extracts were performed to analyse the effects of NO on ICAM-1 mRNA expression and on the activity of transcription factors involved in ICAM-1 transcription. In addition, luciferase reporter gene activity of cytokine-activated cells transiently transfected with an ICAM-1 promoter-luciferase construct and cultured in the presence of the slow-releasing NO-donor DETA/NO was determined. RESULTS: NO at subtoxic concentrations decreases IL-1beta-induced endothelial ICAM-1 mRNA expression. This inhibition occurs at the transcriptional level, as NO affects IL-1b-induced ICAM-1 promoter activity in transiently transfected cells. Using gel-shift assays and double-stranded oligonucleotide consensus sequences of the known transcription factor binding sites of the ICAM-1 promoter, Sp1 and AP-1 were identified as transcriptional activators of IL-1beta-driven ICAM-1 expression. The DNA binding of both of these transcription factors to specific binding sites of the ICAM-1 promoter was decreased in MAEC exposed to NO. CONCLUSIONS: Our studies indicate that the anti-adhesive effect of NO concentrations equivalent to high-output NO synthesis is mediated, at least in part, by inhibition of ICAM-1 expression via a concerted action of NO on the redox-sensitive transcriptional activators Sp1 and AP-1. This molecular mechanism may contribute to the anti-inflammatory actions of NO synthesized by the inducible NO synthase. PMID:11788788

  1. NtbZIP60, an endoplasmic reticulum-localized transcription factor, plays a role in the defense response against bacterial pathogens in Nicotiana tabacum

    Microsoft Academic Search

    Chika Tateda; Rei Ozaki; Yu Onodera; Yoshihiro Takahashi; Koji Yamaguchi; Thomas Berberich; Nozomu Koizumi; Tomonobu Kusano

    2008-01-01

    A spermine-based signal transduction pathway plays a defensive role against incompatible pathogens. We identified a novel\\u000a spermine-responsive cDNA from Nicotiana tabacum that encodes a basic region\\/leucine zipper protein with a putative transmembrane domain. Identity to Arabidopsis thaliana\\u000a AtbZIP60 was sufficiently high to name the novel cDNA NtbZIP60. Expression analysis revealed that NtbZIP60 is a component of the spermine-signal pathway, and

  2. Sp1 phosphorylation by cyclin-dependent kinase 1/cyclin B1 represses its DNA-binding activity during mitosis in cancer cells.

    PubMed

    Chuang, J-Y; Wang, S-A; Yang, W-B; Yang, H-C; Hung, C-Y; Su, T-P; Chang, W-C; Hung, J-J

    2012-11-22

    Sp1 is important for the transcription of many genes. Our previous studies have shown that Sp1 is degraded in normal cell, but it is preserved in cancer cells during mitosis and exists a priori in the daughter cells, ready to engage in gene transcription and thereby contributes to the proliferation and survival of cancer cells. The mechanism by which Sp1 is preserved in cancer cells during mitosis remains unknown. In this study, we observed that Sp1 strongly colocalized with cyclin-dependent kinase 1 (CDK1)/cyclin B1 during mitosis. Moreover, we showed that Sp1 is a novel mitotic substrate of CDK1/cyclin B1 and is phosphorylated by it at Thr 739 before the onset of mitosis. Phospho-Sp1 reduced its DNA-binding ability and facilitated the chromatin condensation process during mitosis. Mutation of Thr739 to alanine resulted in Sp1 remaining in the chromosomes, delayed cell-cycle progression, and eventually led to apoptosis. Screening of Sp1-associated proteins during mitosis by using liquid chromatography/mass spectrometry indicated the tethering of Sp1 to myosin/F-actin. Furthermore, phospho-Sp1 and myosin/F-actin appeared to exist as a congregated ring at the periphery of the chromosome. However, at the end of mitosis and the beginning of interphase, Sp1 was dephosphorylated by PP2A and returned to the chromatin. These results indicate that cancer cells use CDK1 and PP2A to regulate the movement of Sp1 in and out of the chromosomes during cell-cycle progression, which may benefit cancer-cell proliferation. PMID:22266860

  3. MiR-324-5p Suppresses Hepatocellular Carcinoma Cell Invasion by Counteracting ECM Degradation through Post-Transcriptionally Downregulating ETS1 and SP1

    PubMed Central

    Yang, Xuewei; Liang, Huihong; Jiang, Xiaofeng; Zhang, Dawei; Xue, Ping; Chen, De; Shao, Zili

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the common malignancies, which is highly metastatic and the third common cause of cancer deaths in the world. The invasion and metastasis of cancer cells is a multistep and complex process which is mainly initiated by extracellular matrix (ECM) degradation. Aberrant expression of microRNA has been investigated in HCC and shown to play essential roles during HCC progression. In the present study, we found that microRNA-324-5p (miR-324-5p) was downregulated in both HCC cell lines and tissues. Ectopic miR-324-5p led to the reduction of HCC cells invasive and metastatic capacity, whereas inhibition of miR-324-5p promoted the invasion of HCC cells. Matrix metalloproteinase 2 (MMP2) and MMP9, the major regulators of ECM degradation, were found to be downregulated by ectopic miR-324-5p, while upregulated by miR-324-5p inhibitor. E26 transformation-specific 1 (ETS1) and Specificity protein 1 (SP1), both of which could modulate MMP2 and MMP9 expression and activity, were presented as the direct targets of and downregulated by miR-324-5p. Downregulation of ETS1 and SP1 mediated the inhibitory function of miR-324-5p on HCC migration and invasion. Our study demonstrates that miR-324-5p suppresses hepatocellular carcinoma cell invasion and might provide new clues to invasive HCC therapy. PMID:26177288

  4. A clip domain serine proteinase plays a role in antibacterial defense but is not required for prophenoloxidase activation in shrimp.

    PubMed

    Amparyup, Piti; Wiriyaukaradecha, Kriangpol; Charoensapsri, Walaiporn; Tassanakajon, Anchalee

    2010-02-01

    The clip domain serine proteinases (clip-SPs) play critical roles in the signaling processes during embryonic development and in the innate immunity of invertebrates. In the present study, we identified a homolog of the clip-SP, designated as PmClipSP1, by searching the Penaeus monodon EST database (http://pmonodon.biotec.or.th), and using RACE-PCR to obtain the complete gene which contained a 1101bp open reading frame encoding 366 amino acids with a 25 amino acid signal peptide. The deduced PmClipSP1 protein sequence, which shares a predicted structural similarity to the clip-SPs of other arthropod species, appears to possess a clip domain at the N-terminus and an enzymatically active serine proteinase domain at the C-terminus. Tissue distribution analyses revealed that, at the transcript level, PmClipSP1 is mainly expressed in shrimp hemocytes, whilst temporal gene expression analyses showed that the hemocyte PmClipSP1 transcript levels were upregulated at 3h and downregulated at 6-48h following systemic Vibrio harveyi infection. RNAi-mediated silencing of the PmClipSP1 gene, by injection of double-stranded RNA (dsRNA) corresponding to the PmClipSP1 gene into shrimp, significantly reduced PmClipSP1 transcript levels, but neither significantly altered the other clip-SP and clip-SPH transcript levels nor reduced the total phenoloxidase (PO) enzyme activity in shrimp hemocytes, compared to the levels seen in the GFP dsRNA control, suggesting that PmClipSP1 is not involved in the proPO system. However, suppression of the PmClipSP1 gene led to a significant increase in the number of viable bacteria in the hemolymph (approximately 2.4-fold) and in the mortality rate (59%) of shrimp systemically infected with V. harveyi. These findings suggest that PmClipSP1 plays a role in the antibacterial defense mechanism of P. monodon shrimp. PMID:19751760

  5. A critical Sp1 element in the rhesus rhadinovirus (RRV) Rta promoter confers high-level activity that correlates with cellular permissivity for viral replication

    PubMed Central

    DeMaster, Laura K.; Rose, Timothy M.

    2013-01-01

    KSHV establishes characteristic latent infections in vitro, while RRV, a related macaque rhadinovirus, establishes characteristic permissive infections with virus replication. We identified cells that are not permissive for RRV replication and recapitulate the latent KSHV infection and reactivation processes. The RRV replication and transactivator (Rta) promoter was characterized in permissive and non-permissive cells and compared to the KSHV Rta promoter. Both promoters contained a critical Sp1 element, had equivalent activities in different cell types, and were inhibited by LANA. RRV and KSHV infections were non-permissive in cells with low Rta promoter activity. While RRV infections were permissive in cells with high basal promoter activity, KSHV infections remained non-permissive. Our studies suggest that RRV lacks the Rta-inducible LANA promoter that is responsible for LANA inhibition of the KSHV Rta promoter and induction of latency during KSHV infection. Instead, the outcome of RRV infection is determined by host factors, such as Spl. PMID:24314650

  6. Vascular endothelial growth factor plays a critical role in the formation of the pre-metastatic niche via prostaglandin E2.

    PubMed

    Liu, Shili; Jiang, Man; Zhao, Qiang; Li, Shancheng; Peng, Yanping; Zhang, Pengfei; Han, Mingyong

    2014-12-01

    Factors secreted by primary tumors can alter the microenvironment at distant organ sites, generating pre-metastatic niches for subsequent metastatic cancer cell colonization. Breast cancer cells have a propensity to home preferentially to the lung, but the underlying molecular mechanisms whereby primary breast carcinoma-derived factors affect the pre-metastatic lung environment before the arrival of the tumor cells are poorly understood. In this study, 4T1 mammary carcinoma cells were subcutaneously injected into the mammary glands of mice, resulting in the induction of inflammation, increased total vessel density and recruitment of bone marrow-derived cells (BMDCs) in pre-metastatic lungs. Subsequent examination revealed that the sites of inflammatory cell clusters in the lungs were tumor metastasis sites. Moreover, vascular endothelial growth factor (VEGF) induced prostaglandin E2 (PGE2) production in mouse pulmonary microvascular endothelial cells (MPVECs) and enhanced the adhesion of 4T1 cells. Treatment with the cyclooxygenase-2 inhibitor celecoxib significantly reduced 4T1 cell adhesion to MPVECs, and also reduced cancer metastasis and the inflammatory response. These results suggest that VEGF may be an underlying carcinoma-derived factor responsible for formation of the pre-metastatic niche in the lung of 4T1 cell-bearing mice. This study, therefore, demonstrated that primary tumors can alter the lung microenvironment during the pre-metastatic phase by triggering an in?ammatory response and PGE2 production. Primary tumor-derived VEGF might thus be a crucial factor responsible for the formation of the pre-metastatic niche by inducing PGE2 production. PMID:25333935

  7. 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…

  8. 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

  9. 55-kd Tumor Necrosis Factor Receptor Is Expressed by Human Keratinocytes and Plays a Pivotal Role in Regulation of Human Keratinocyte ICAM-1 Expression

    Microsoft Academic Search

    Uwe Trefzer; Manfred Brockhaus; Hansruedi Loetscher; Frauke Parlow; Alexander Kapp; Erwin Schöpf; Jean Krutmann

    1991-01-01

    Tumor necrosis factor ? (TNF?) is a potent modulator of human keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression. TNF? is known to exert its biologic effects by binding to specific cell-surface receptors. Two distinct TNF binding molecules, the 55-kd and the 75-kd TNF receptor (TNFR) recently have been found to be expressed by human cells. These two receptor types are independently

  10. 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

  11. 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) ...

  12. 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

  13. Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site.

    PubMed

    Coric, Pascale; Turcaud, Serge; Souquet, Florence; Briant, Laurence; Gay, Bernard; Royer, Jacques; Chazal, Nathalie; Bouaziz, Serge

    2013-04-01

    Bevirimat (2), the first-in-class HIV-1 maturation inhibitor, shows a low efficacy due essentially to the natural polymorphism of its target, the CA-SP1 junction. Moreover, its low hydrosolubility makes it difficult to study its interaction with the CA-SP1 junction. We have synthesized new derivatives of bevirimat by adding different hydrophilic substituents at the C-28 position to improve their hydrosolubility and perform the structural study of a complex by NMR. Synthesis of the new derivatives, the effect of substituents at the C-28 position and their hydrosolubility are discussed. The ability of these molecules to inhibit viral infection and their cytotoxicity is assessed. Compared to the well-known bevirimat (2), one of our compounds (16) shows a higher hydrosolubility associated with a 2.5 fold increase in activity, a higher selectivity index and a better antiviral profile. Moreover, for the first time a direct interaction between a derivative of bevirimat (16) and the domain CA-SP1-NC is shown by NMR. Information from this study should allow us to decipher the mechanism by which bevirimat inhibits HIV-1 maturation and how the natural polymorphism of the spacer peptide SP1 triggers resistance to inhibitors. PMID:23399723

  14. Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication in Saccharomyces cerevisiae.

    PubMed Central

    Zhu, Wenge; Rainville, Irene R; Ding, Min; Bolus, Margaret; Heintz, Nicholas H; Pederson, David S

    2002-01-01

    Clf1p is an essential, highly conserved protein in S. cerevisiae that has been implicated in pre-mRNA splicing. Clf1p's ortholog in Drosophila, Crn, is required for normal cell proliferation. Cells depleted of Clf1p arrest primarily with large buds, a single nucleus, a 2C DNA content, and a short, intact mitotic spindle. We isolated temperature-sensitive clf1 mutants that exhibit similar mitotic defects when released to the restrictive temperature from an early S-phase block. While these mutants also accumulate unspliced pre-mRNA at the restrictive temperature, the mitotic arrest does not appear to result from a failure to splice tubulin pre-mRNA. Moreover, the same mutants exhibit a delayed entry into S phase when released to the restrictive temperature from a G1 phase block. This delay could not be suppressed by disruption of the S-phase CDK inhibitor SIC1, suggesting that Clf1p is involved in DNA replication. Consistent with this possibility, we find that Clf1p (but not the mutant clf1p) interacts with the DNA replication initiation protein Orc2p in two-hybrid and co-immunoprecipitation assays, that Clf1p preferentially associates with origins of DNA replication, and that this association is Orc2p dependent. These observations suggest that Clf1p plays a direct role in the initiation of DNA replication. PMID:11973290

  15. Activation of heat shock factor 1 plays a role in pyrrolidine dithiocarbamate-mediated expression of the co-chaperone BAG3.

    PubMed

    Song, Shaoming; Kole, Sutapa; Precht, Patricia; Pazin, Michael J; Bernier, Michel

    2010-11-01

    Adaptive responses to physical and inflammatory stressors are mediated by transcription factors and molecular chaperones. The transcription factor heat shock factor 1 (HSF1) has been implicated in extending lifespan in part by increasing expression of heat shock response genes. Pyrrolidine dithiocarbamate (PDTC) is a small thiol compound that exerts in vivo and in vitro anti-inflammatory properties through mechanisms that remain unclear. Here we report that PDTC induced the release of monomeric HSF1 from the molecular chaperone heat shock protein 90 (Hsp90), with concomitant increase in HSF1 trimer formation, translocation to the nucleus, and binding to promoter of target genes in human HepG2 cells. siRNA-mediated silencing of HSF1 blocked BAG3 gene expression by PDTC. The protein levels of the co-chaperone BAG3 and its interaction partner Hsp72 were stimulated by PDTC in a dose-dependent fashion, peaking at 6h. Inhibition of Hsp90 function by geldanamycin derivatives and novobiocin elicited a pattern of HSF1 activation and BAG3 expression that was similar to PDTC. Chromatin immunoprecipitation studies showed that PDTC and the inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin enhanced the binding of HSF1 to the promoter of several target genes, including BAG3, HSPA1A, HSPA1B, FKBP4, STIP1 and UBB. Cell treatment with PDTC increased significantly the level of Hsp90? thiol oxidation, a posttranslational modification known to inhibit its chaperone function. These results unravel a previously unrecognized mechanism by which PDTC and related compounds could confer cellular protection against inflammation through HSF1-induced expression of heat shock response genes. PMID:20692357

  16. Activation of heat shock factor 1 plays a role in pyrrolidine dithiocarbamate-mediated expression of the co-chaperone BAG3

    PubMed Central

    Song, Shaoming; Kole, Sutapa; Precht, Patricia; Pazin, Michael J.; Bernier, Michel

    2010-01-01

    Adaptive responses to physical and inflammatory stressors are mediated by transcription factors and molecular chaperones. The transcription factor heat shock factor 1 (HSF1) has been implicated in extending lifespan in part by increasing expression of heat shock response genes. Pyrrolidine dithiocarbamate (PDTC) is a small thiol compound that exerts in vivo and in vitro anti-inflammatory properties through mechanisms that remain unclear. Here we report that PDTC induced the release of monomeric HSF1 from the molecular chaperone heat shock protein 90 (Hsp90), with concomitant increase in HSF1 trimer formation, translocation to the nucleus, and binding to promoter of target genes in human HepG2 cells. siRNA-mediated silencing of HSF1 blocked BAG3 gene expression by PDTC. The protein levels of the co-chaperone BAG3 and its interaction partner Hsp72 were stimulated by PDTC in a dose-dependent fashion, peaking at 6 hours. Inhibition of Hsp90 function by geldanamycin derivatives and novobiocin elicited a pattern of HSF1 activation and BAG3 expression that was similar to PDTC. Chromatin immunoprecipitation studies showed that PDTC and the inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin enhanced the binding of HSF1 to the promoter of several target genes, including BAG3, HSPA1A, HSPA1B, FKBP4, STIP1 and UBB. Cell treatment with PDTC increased significantly the level of Hsp90? thiol oxidation, a posttranslational modification known to inhibit its chaperone function. These results unravel a previously unrecognized mechanism by which PDTC and related compounds could confer cellular protection against inflammation through HSF1-induced expression of heat shock response genes. PMID:20692357

  17. 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

  18. Histone deacetylase inhibitors modulate the transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-a gene: interactive roles of modified histones, histone acetyltransferase, p300, AND Sp1.

    PubMed

    Kumar, Prerna; Tripathi, Satyabha; Pandey, Kailash N

    2014-03-01

    Atrial natriuretic peptide (ANP) binds guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) and produces the intracellular second messenger, cGMP, which regulates cardiovascular homeostasis. We sought to determine the function of histone deacetylases (HDACs) in regulating Npr1 (coding for GC-A/NPRA) gene transcription, using primary mouse mesangial cells treated with class-specific HDAC inhibitors (HDACi). Trichostatin A, a pan inhibitor, and mocetinostat (MGCD0103), a class I HDAC inhibitor, significantly enhanced Npr1 promoter activity (by 8- and 10-fold, respectively), mRNA levels (4- and 5.3-fold, respectively), and NPRA protein (2.7- and 3.5-fold, respectively). However, MC1568 (class II HDAC inhibitor) had no discernible effect. Overexpression of HDAC1 and HDAC2 significantly attenuated Npr1 promoter activity, whereas HDAC3 and HDAC8 had no effect. HDACi-treated cultured cells in vitro and intact animals in vivo showed significantly reduced binding of HDAC1 and -2 and increased accumulation of acetylated H3-K9/14 and H4-K12 at the Npr1 promoter. Deletional analyses of the Npr1 promoter along with ectopic overexpression and inhibition of Sp1 confirmed that HDACi-induced Npr1 gene transcription is accomplished by Sp1 activation. Furthermore, HDACi attenuated the interaction of Sp1 with HDAC1/2 and promoted Sp1 association with p300 and p300/cAMP-binding protein-associated factor; it also promoted the recruitment of p300 and p300/cAMP-binding protein-associated factor to the Npr1 promoter. Our results demonstrate that trichostatin A and MGCD0103 enhanced Npr1 gene expression through inhibition of HDAC1/2 and increased both acetylation of histones (H3-K9/14, H4-K12) and Sp1 by p300, and their recruitment to Npr1 promoter. Our findings define a novel epigenetic regulatory mechanism that governs Npr1 gene transcription. PMID:24451378

  19. 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)

  20. 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 ...

  1. Adlerian Play Therapy.

    ERIC Educational Resources Information Center

    Kottman, Terry; Warlick, Jayne

    1990-01-01

    Describes Adlerian method of play therapy. Claims Adlerian therapy represents an integration of the concepts and techniques of individual psychology into a method of using play to help troubled children. (Author/ABL)

  2. 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 ...

  3. 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 ...

  4. Promoting Early Play

    Microsoft Academic Search

    I. A. van Berckelaer-Onnes

    2003-01-01

    Early forms of play involving the exploration of objects is repetitive and limited in scope in children with autism, consistent with a weak drive towards central coherence. The importance is stressed of early manipulative and relational play for the development of meaningful perceptual representations and the subsequent development of functional and symbolic play. It is argued that intervention designed to

  5. Playful "Moments" in Psychotherapy

    ERIC Educational Resources Information Center

    Terr, Lenore C.; Deeney, John M.; Drell, Martin; Dodson, Jerry W.; Gaensbauer, Theodore J.; Massie, Henry; Minde, Klaus; Stewart, George; Teal, Stewart; Winters, Nancy C.

    2006-01-01

    This article demonstrates how taking the time out to play, commenting pungently on play, serving up surprise and adventure, and developing mutually understood codes or inside jokes help the psychiatrist to turn a child around. In this article, the authors categorized what principles of treatment their 10 vignettes about playfulness illustrated,…

  6. Play, Policy & Practice.

    ERIC Educational Resources Information Center

    Klugman, Edgar, Ed.

    In 1992, the U.S.-Israel Binational Science Foundation (BSF), in conjunction with Wheelock College (Boston), sponsored its second workshop on children's play, entitled "Play and Cognitive Ability: The Cultural Context." This volume reflects the presentations and discussions held at the workshop, offering perspectives on children's play that, taken…

  7. A Conserved Loop in the Catalytic Domain of Eukaryotic Elongation Factor 2 Kinase Plays a Key Role in Its Substrate Specificity

    PubMed Central

    Moore, Claire E.; Regufe da Mota, Sergio; Mikolajek, Halina

    2014-01-01

    Eukaryotic elongation factor 2 kinase (eEF2K) is the best-characterized member of the ?-kinase family. Within this group, only eEF2K and myosin heavy chain kinases (MHCKs) have known substrates. Here we have studied the roles of specific residues, selected on the basis of structural data for MHCK A and TRPM7, in the function of eEF2K. Our data provide the first information regarding the basis of the substrate specificity of ?-kinases, in particular the roles of residues in the so-called N/D loop, which appears to occupy a position in the structure of ?-kinases similar to that of the activation loop in other kinases. Several mutations in the EEF2K gene occur in tumors, one of which (Arg303Cys) is at a highly conserved residue in the N/D loop. This mutation greatly enhances eEF2K activity and may be cytoprotective. Our data support the concept that the major autophosphorylation site (Thr348 in eEF2K) docks into a binding pocket to help create the kinase-competent conformation. This is similar to the situation for MHCK A and is consistent with this being a common feature of ?-kinases. PMID:24732796

  8. Vygotsky on play: child's play or more 

    E-print Network

    Wagner, Carol Anne

    2000-01-01

    on this development and of the ZPD as it is related to a child's play. Vygotsky's life and the sociocultural atmosphere in which his theories were developed are briefly examined and an overview of Vygotskian theories, including identified themes and major processes...

  9. Inter-Play

    NSDL National Science Digital Library

    Inter-Play is a Web-based, multilingual index to plays published as part of collections, anthologies, or periodicals, and compiles many citations to plays not indexed by standard print indexes. Inter-Play contains about 16,130 bibliographic citations and spans in date from the late nineteenth century to the present. Although the index is multilingual, the search interface is in English. Users may search the index by author or title only. Inter-Play is updated frequently by its co-editors: Robert Westover and Janet Wright, humanities librarians at Portland State University.

  10. [Alpha-fetoprotein, HPL, ostriol and SP1 concentrations in prostaglandin-induced mid-trimester abortions (author's transl)].

    PubMed

    Cornely, M; Schumann, K; Völker, W; Weitzel, H

    1978-06-01

    Maternal serum concentrations of AFP, HPL, SP1 and Estriol were measured in the course of prostaglandin-induced abortions. Termination of pregnancy between the 13th and 25th week of pregnancy was done for medical reasons. Patients were treated with PGE2, PGF2alpha and with 16-phenoxy-PGE2-methansulfonamid, respectively. Prostaglandins were administered systemically, i. e. intravenously. Current measurement of HPL and AFP-concentrations showed a contrary sense. These changes of concentrations were related to fetal death and membrane rupture in some cases as is demonstrated in four diagrams. Typical and sharply decreasing values of Estriol followed fetal death in patients with intact pregnancies before. As for an anencephalic fetus, AFP-concentrations increased slightly too, HPL values decreased like in other abortions. Only minimal changes of SP1 concentrations were found generally in all patients and during abortion time. PMID:78872

  11. Apolipoprotein E4 Is Deficient in Inducing Macrophage ABCA1 Expression and Stimulating the Sp1 Signaling Pathway

    PubMed Central

    Okoro, Emmanuel Ugochukwu; Zhao, Yanfeng; Guo, ZhongMao; Zhou, Lichun; Lin, Xinghua; Yang, Hong

    2012-01-01

    ATP binding cassette A1 (ABCA1) is a membrane protein that promotes cellular cholesterol efflux. Using RAW 264.7 macrophages, we studied the relative effects of apolipoprotein (apo) E3 and apoE4 on ABCA1 and on the signaling pathway that regulates its expression. Both lipid-associated and lipid-free apoE4 forms induced ?30% lower levels of ABCA1 protein and mRNA than apoE3 forms. Phosphorylated levels of phosphoinositol 3-kinase (PI3K), protein kinase C? (PKC?) and specificity protein 1 (Sp1) were also lower when treated with apoE4 compared to apoE3. The reduced ability of apoE4 to induce ABCA1 expression, PKC? and Sp1 phosphorylation were confirmed in human THP-1 monocytes/macrophages. Sequential phosphorylation of PI3K, PKC? and Sp1 has been suggested as a mechanism for upregulation of ABCA1 expression. Both apoE3 and apoE4 reduced total cholesterol and cholesterol esters in lipid-laden RAW 264.7 cells, and induced apoAI-mediated cholesterol efflux. However, the cholesterol esters and cholesterol efflux in apoE4-treated cells were ?50% and ?24% lower, respectively, compared to apoE3-treated cells. Accumulation of cholesterol esters in macrophages is a mechanism for foam cell formation. Thus the reduced ability of apoE4 to activate the PI3K-PKC?-Sp1 signaling pathway and induce ABCA1 expression likely impairs cholesterol ester removal, and increases foam cell formation. PMID:22984509

  12. Large-Scale Evidence for the Effect of the COLIA1 Sp1 Polymorphism on Osteoporosis Outcomes: The GENOMOS Study

    Microsoft Academic Search

    Stuart H. Ralston; André G. Uitterlinden; Maria Luisa Brandi; Susana Balcells; Bente L. Langdahl; Paul Lips; Roman Lorenc; Barbara Obermayer-Pietsch; Serena Scollen; Mariona Bustamante; Lise Bjerre Husted; Alisoun H. Carey; Adolfo Diez-Perez; Alison M. Dunning; Alberto Falchetti; Elzbieta Karczmarewicz; Marcin Kruk; Joyce B. J. van Meurs; Jon Mangion; Fiona E. A. McGuigan; Leonardo Mellibovsky; Francesca del Monte; Huibert A. P. Pols; Jonathan Reeve; David M. Reid; Wilfried Renner; Fernando Rivadeneira; Natasja M. van Schoor; Rachael E. Sherlock

    2006-01-01

    BackgroundOsteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G\\/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been

  13. The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage site in immature Gag particles

    PubMed Central

    2011-01-01

    Background Bevirimat, the prototype Human Immunodeficiency Virus type 1 (HIV-1) maturation inhibitor, is highly potent in cell culture and efficacious in HIV-1 infected patients. In contrast to inhibitors that target the active site of the viral protease, bevirimat specifically inhibits a single cleavage event, the final processing step for the Gag precursor where p25 (CA-SP1) is cleaved to p24 (CA) and SP1. Results In this study, photoaffinity analogs of bevirimat and mass spectrometry were employed to map the binding site of bevirimat to Gag within immature virus-like particles. Bevirimat analogs were found to crosslink to sequences overlapping, or proximal to, the CA-SP1 cleavage site, consistent with previous biochemical data on the effect of bevirimat on Gag processing and with genetic data from resistance mutations, in a region predicted by NMR and mutational studies to have ?-helical character. Unexpectedly, a second region of interaction was found within the Major Homology Region (MHR). Extensive prior genetic evidence suggests that the MHR is critical for virus assembly. Conclusions This is the first demonstration of a direct interaction between the maturation inhibitor, bevirimat, and its target, Gag. Information gained from this study sheds light on the mechanisms by which the virus develops resistance to this class of drug and may aid in the design of next-generation maturation inhibitors. PMID:22151792

  14. Why People Play.

    ERIC Educational Resources Information Center

    Ellis, M. J.

    A critical analysis is made of the content and assumptions of the many theories or explanations for play behavior. The seven chapters of the book are as follows. Chapter One, A Purview of the Problems, is a brief overview of the problems inherent in attempting to manage play, and the arguments for and against. The second chapter, Definitions of…

  15. 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.

  16. Clinical Intuition at Play

    ERIC Educational Resources Information Center

    Marks-Tarlow, Terry

    2014-01-01

    A clinical psychologist and consulting psychotherapist discusses how elements of play, inherent in the intuition required in analysis, can provide a cornerstone for serious therapeutic work. She argues that many aspects of play--its key roles in human development, individual growth, and personal creativity, among others--can help therapists and…

  17. 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…

  18. Transcription Factor IID Recruitment and Sp1 Activation DUAL FUNCTION OF TAF1 IN CYCLIN D1 TRANSCRIPTION*

    E-print Network

    Wang, Edith

    10.1074/jbc.M300412200 Traci L. Hilton and Edith H. Wang§ From the University of Washington the model that TAF1 carries out two independent functions at the cy- clin D1 promoter. Understanding of transcription. In support of this model, the deregulated expression of cyclins A and D1 has been found

  19. NO PLAY: A MEANS OF CONFLICT RESOLUTION

    Microsoft Academic Search

    RALPH R. MILLER

    1967-01-01

    IN AN ITERATIVE, INDIVIDUALISTICALLY MOTIVATED PRISONER’S DILEMMA TYPE GAME PLAYED FOR MONETARY REINFORCERS, A NO-PLAY OPTION WAS FOUND TO SIGNIFICANTLY INCREASE THE PROBABILITY OF RESOLVING THE CONFLICT. BY MANIPULATING MATRIX VALUES, 3 POSSIBLE FUNCTIONS OF THE NO-PLAY OPTION WERE FACTORED OUT AND EXAMINED: WITHDRAWAL, INITIATION OF A CHANGE IN STRATEGY, AND THREAT AND PUNISHMENT. WITHDRAWAL WAS INFREQUENTLY FOUND TO BE

  20. Play the Tuberculosis Game

    MedlinePLUS

    ... Malaria MRI Nerve Signaling Pavlov's Dog Split Brain Experiments The Cell and its Organelles The Genetic Code ... Life and Work Teachers' Questionnaire Tuberculosis Play Tuberculosis Experiments & Discoveries About the game Discover and experience some ...

  1. 1H, 13C and 15N NMR assignments of the aciniform spidroin (AcSp1) repetitive domain of Argiope trifasciata wrapping silk.

    PubMed

    Xu, Lingling; Tremblay, Marie-Laurence; Meng, Qing; Liu, Xiang-Qin; Rainey, Jan K

    2012-10-01

    Spider silk is one of nature's most remarkable biomaterials due to extraordinary strength and toughness not found in today's synthetic materials. Of the seven types of silk, wrapping silk (AcSp1) is the most extensible of the types of silks and has no sequence similarity to the other types. Here we report the chemical shifts for the AcSp1 199 amino acid protein repeat unit and its anticipated secondary structure based on secondary chemical shifts. PMID:21989955

  2. Nuclear-factor-{kappa}B (NF-{kappa}B) and radical oxygen species play contrary roles in transforming growth factor-{beta}1 (TGF-{beta}1)-induced apoptosis in hepatocellular carcinoma (HCC) cells

    SciTech Connect

    Wang Fang [Department of Pharmacology and Toxicology, Indiana University Purdue University Indianapolis, 1044 W. Walnut St., Indianapolis, IN 46224 (United States)], E-mail: wang44@iupui.edu; Kaur, Swayamjot [Cancer Institute of New Jersey, New Brunswick, NJ 08903-2681 (United States); Cavin, Lakita G.; Arsura, Marcello [Department of Pharmacology, University of Tennessee Cancer Institute (UTCI), University of Tennessee Health Science Center (UTHSC), College of Medicine, Memphis, TN 38163 (United States)

    2008-12-26

    Nuclear-Factor-{kappa}B (NF-{kappa}{beta} can counteract transforming growth factor-{beta}1 (TGF-{beta}1)-induced apoptosis in malignant hepatocytes through up-regulation of its downstream genes, such as X-linked inhibitor of apoptosis protein (XIAP). Reports have demonstrated that TGF-{beta}1 can induce oxidative stress, and c-Jun N-terminal Kinase1 (JNK1) is indispensable for TGF-{beta}1-induced apoptosis pathway, but the relationship between radical oxygen species (ROS) and the activation of JNKs is still unclear. In the present study, we found that ROS can induce JNK activation in TGF-{beta}1 mediated apoptosis in hepatocytes. The inhibitors of hydrogen peroxide and superoxide, which were produced by mitochondria under stress, could inhibit the phosphorylation of c-Jun in XIAP knockdown cells. In conclusion, it is the first time to show that both NF-{kappa}B and antioxidants can counteract TGF-{beta}1-induced apoptosis in hepatic cell death through JNK1 pathway.

  3. Induction of truncated form of tenascin-X (XB-S) through dissociation of HDAC1 from SP-1/HDAC1 complex in response to hypoxic conditions

    SciTech Connect

    Kato, Akari; Endo, Toshiya; Abiko, Shun; Ariga, Hiroyoshi [Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812 (Japan); Matsumoto, Ken-ichi [Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812 (Japan)], E-mail: kematsum@pharm.hokudai.ac.jp

    2008-08-15

    ABSTRACT: XB-S is an amino-terminal truncated protein of tenascin-X (TNX) in humans. The levels of the XB-S transcript, but not those of TNX transcripts, were increased upon hypoxia. We identified a critical hypoxia-responsive element (HRE) localized to a GT-rich element positioned from - 1410 to - 1368 in the XB-S promoter. Using an electrophoretic mobility shift assay (EMSA), we found that the HRE forms a DNA-protein complex with Sp1 and that GG positioned in - 1379 and - 1378 is essential for the binding of the nuclear complex. Transfection experiments in SL2 cells, an Sp1-deficient model system, with an Sp1 expression vector demonstrated that the region from - 1380 to - 1371, an HRE, is sufficient for efficient activation of the XB-S promoter upon hypoxia. The EMSA and a chromatin immunoprecipitation (ChIP) assay showed that Sp1 together with the transcriptional repressor histone deacetylase 1 (HDAC1) binds to the HRE of the XB-S promoter under normoxia and that hypoxia causes dissociation of HDAC1 from the Sp1/HDAC1 complex. The HRE promoter activity was induced in the presence of a histone deacetylase inhibitor, trichostatin A, even under normoxia. Our results indicate that the hypoxia-induced activation of the XB-S promoter is regulated through dissociation of HDAC1 from an Sp1-binding HRE site.

  4. Zinc binding ligands and cellular zinc trafficking: apo-metallothionein, glutathione, TPEN, proteomic zinc, and Zn-Sp1.

    PubMed

    Rana, Ujala; Kothinti, Rajendra; Meeusen, Jeffrey; Tabatabai, Niloofar M; Krezoski, Susan; Petering, David H

    2008-03-01

    Many cell types contain metal-ion unsaturated metallothionein (MT). Considering the Zn(2+) binding affinity of metallothionein, the existence of this species in the intracellular environment constitutes a substantial "thermodynamic sink". Indeed, the mM concentration of glutathione may be thought of in the same way. In order to understand how apo-MT and the rest of the Zn-proteome manage to co-exist, experiments examined the in vitro reactivity of Zn-proteome with apo-MT, glutathione (GSH), and a series of common Zn(2+) chelating agents including N,N,N',N'-(2-pyridylethyl)ethylenediammine (TPEN), EDTA, and [(2,2'-oxyproplylene-dinitrilo]tetraacetic acid (EGTA). Less than 10% of Zn-proteome from U87mg cells reacted with apo-MT or GSH. In contrast, each of the synthetic chelators was 2-3 times more reactive. TPEN, a cell permeant reagent, also reacted rapidly with both Zn-proteome and Zn-MT in LLC-PK(1) cells. Taking a specific zinc finger protein for further study, apo-MT, GSH, and TPEN inhibited the binding of Zn(3)-Sp1 with its cognate DNA site (GC-1) in the sodium-glucose co-transporter promoter of mouse kidney. In contrast, preformation of Zn(3)-Sp1-(GC-1) prevented reaction with apo-MT and GSH; TPEN remained active but at a higher concentration. Whereas, Zn(3)-Sp1 is active in cells containing apo-MT and GSH, exposure of LLC-PK(1) cells to TPEN for 24h largely inactivated its DNA binding activity. The results help to rationalize the steady state presence of cellular apo-MT in the midst of the many, diverse members of the Zn-proteome. They also show that TPEN is a robust intracellular chelator of proteomic Zn(2+). PMID:18171589

  5. Electrostatic charges instigate 'concertina-like' mechanisms of molecular toughening in MaSp1 (spider silk) proteins.

    PubMed

    Pahlevan, Mahdi; Toivakka, Martti; Alam, Parvez

    2014-08-01

    According to a recent article authored by Ortega-Jimenez and Dudley [1], the capture success of spiders is in part due to electrostatic charges on the surfaces of insects that macroscopically deform the spider web and increase the chances of insect-web contact. In this brief communication, we further show that electrostatic charges instigate a molecular 'concertina-like' mechanism of deformation in MaSp1 protein, which effectively begins the toughening-up of dragline silk threads prior to insect-web contact. PMID:24907767

  6. Pathways to Play: Developing Play Skills in Young Children.

    ERIC Educational Resources Information Center

    Heidemann, Sandra; Hewitt, Deborah

    Play skills are vital to a child's overall healthy development. However, the training many caregivers receive may not include extensive information on play skills. This book presents a play checklist to help caregivers observe children's play skills, pinpoint play skills on which children need to work, and plan goals for improving those play

  7. Play Dough Planets

    NSDL National Science Digital Library

    2012-08-03

    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.

  8. Autophagosomal IkappaB alpha degradation plays a role in the long term control of tumor necrosis factor-alpha-induced nuclear factor-kappaB (NF-kappaB) activity.

    PubMed

    Colleran, Amy; Ryan, Aideen; O'Gorman, Angela; Mureau, Coralie; Liptrot, Catherine; Dockery, Peter; Fearnhead, Howard; Egan, Laurence J

    2011-07-01

    Transcription factor NF-?B is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of NF-?B is well understood, but little is known about the mechanisms of its long term activation. We studied the effect of a single application of TNF-? on NF-?B activity for up to 48 h in intestinal epithelial cells. Results show that NF-?B remained persistently activated up to 48 h after TNF-? and that the long term activation of NF-?B was accompanied by a biphasic degradation of I?B?. The first phase of I?B? degradation was proteasome-dependent, but the second was not. Further investigation showed that TNF-? stimulated formation of autophagosomes in intestinal epithelial cells and that I?B? co-localized with autophagosomal vesicles. Pharmacological or genetic blockade of autophagosome formation or the inhibition of lysosomal proteases decreased TNF-?-induced degradation of I?B? and lowered NF-?B target gene expression. Together, these findings indicate a role of autophagy in the control of long term NF-?B activity. Because abnormalities in autophagy have been linked to ineffective innate immunity, we propose that alterations in NF-?B may mediate this effect. PMID:21454695

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

    PubMed Central

    Rawat, Suman R.; Männistö, Minna K.; Starovoytov, Valentin; Goodwin, Lynne; Nolan, Matt; Hauser, Lauren; Land, Miriam; Davenport, Karen Walston; Woyke, Tanja; Häggblom, Max M.

    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. PMID:23450133

  10. Bioactive metabolites produced by Penicillium sp. 1 and sp. 2, two endophytes associated with Alibertia macrophylla (Rubiaceae).

    PubMed

    Oliveira, Camila M; Silva, Geraldo H; Regasini, Luis O; Zanardi, Lisinéia M; Evangelista, Alana H; Young, Maria C M; Bolzani, Vanderlan S; Araujo, Angela R

    2009-01-01

    In the course of our continuous search for bioactive metabolites from endophytic fungi living in plants from the Brazilian flora, leaves of Alibertia macrophylla (Rubiaceae) were submitted to isolation of endophytes, and two species of Penicillium were isolated. The acetonitrile fraction obtained in corn from a culture of Penicillium sp. 1 afforded orcinol (1). On the other hand, Penicillium sp. 1 cultivated in potato-dextrose-broth furnished two different compounds, cyclo-(L-Pro-L-Val) (2) and uracil (3). The chromatographic fractionation of the acetonitrile fraction obtained from Penicillium sp. 2 led to three dihydroisocoumarins, 4-hydroxymellein (4), 8-methoxymellein (5) and 5-hydroxymellein (6). Compounds 5 and 6 were obtained from the Penicillium genus for the first time. Additionally, metabolites 1-6 were evaluated for their antifungal and acetylcholinesterase (AChE) inhibitory activities. The most active compounds 1 and 4 exhibited detection limits of 5.00 and 10.0 microg against Cladosporium cladosporioides and C. sphaerospermum, respectively. Compound 2 showed a detection limit of 10.0 microg, displaying potent AChE inhibitory activity. PMID:20158153

  11. 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…

  12. "Playing" with Science

    ERIC Educational Resources Information Center

    Allen, Dave

    2012-01-01

    When faced with a multitude of tasks, any opportunity to "kill two birds with one stone" is welcome. Drama has always excited the author: as a child performing in plays, later as a student and now as a teacher directing performances and improvising within lessons. The author was lucky enough to have inspirational teachers during his primary and…

  13. Learn to Play Chess!

    NSDL National Science Digital Library

    2013-01-01

    This tutorial uses video and interactives to teach the basic moves and other features of the game of chess. The site offers other opportunities to learn and play chess online against other registered opponents. If under 13 yers of age, a learner must have a parent or coach register first and then create learner accounts.

  14. 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.)

  15. The BpeAB-OprB Efflux Pump of Burkholderia pseudomallei 1026b Does Not Play a Role in Quorum Sensing, Virulence Factor Production, or Extrusion of Aminoglycosides but Is a Broad-Spectrum Drug Efflux System ?

    PubMed Central

    Mima, Takehiko; Schweizer, Herbert P.

    2010-01-01

    Most Burkholderia pseudomallei strains are intrinsically aminoglycoside resistant, mainly due to AmrAB-OprA-mediated efflux. Rare naturally occurring or genetically engineered mutants lacking this pump are aminoglycoside susceptible despite the fact that they also encode and express BpeAB-OprB, which was reported to mediate efflux of aminoglycosides in the Singapore strain KHW. To reassess the role of BpeAB-OprB in B. pseudomallei aminoglycoside resistance, we used mutants overexpressing or lacking this pump in either AmrAB-OprA-proficient or -deficient strain 1026b backgrounds. Our data show that BpeAB-OprB does not mediate efflux of aminoglycosides but is a multidrug efflux system which extrudes macrolides, fluoroquinolones, tetracyclines, acriflavine, and, to a lesser extent, chloramphenicol. Phylogenetically, BpeAB-OprB is closely related to Pseudomonas aeruginosa MexAB-OprM, which has a similar substrate spectrum. AmrAB-OprA is most closely related to MexXY, the only P. aeruginosa efflux pump known to extrude aminoglycosides. Since BpeAB-OprB in strain KHW was also implicated in playing a major role in export of acylated homoserine lactone (AHL) quorum-sensing molecules and in expression of diverse virulence factors, we explored whether this was also true in the strain 1026b background. The results showed that BpeAB-OprB was not required for AHL export, and mutants lacking this efflux system exhibited normal swimming motility and siderophore production, which were severely impaired in KHW bpeAB-oprB mutants. Biofilm formation was impaired in 1026b ?(amrRAB-oprA) and ?(amrRAB-oprA) ?(bpeAB-oprB) mutants. At present, we do not know why our BpeAB-OprB susceptibility and virulence factor expression results with 1026b and its derivatives are different from those previously published for Singapore strain KHW. PMID:20498323

  16. 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.…

  17. Play It Safe

    NSDL National Science Digital Library

    2012-06-26

    This fast-paced strategy game combines probability and mathematical reasoning, and helps hone memory and mental math skills. Players turn over cards until they get a total as close as possible to 40. They need to decide when to get out of the game, since they don't want to go over 40--so they need to pay careful attention to which cards have already been played. Available as a web page or downloadable pdf. Also available in Spanish.

  18. Play: Working Partner of Growth.

    ERIC Educational Resources Information Center

    McKee, Judy Spitler, Ed.

    This volume is a collection of nine papers focusing on different aspects of play. The first section, "Play, Growth, Development, and Learning," contains discussions dealing with make-believe play and learning; an all-in-fun approach to thinking, playing, and language learning for young children; and ways children learn through play. The second…

  19. Correlations between the Vega 2 plasma wave (APV-N) and dust (SP-1) observations at Comet Halley

    SciTech Connect

    Oberc, P.; Parzydlo, W.; Vaisberg, O.L. (Centrum Badan Kosmicznych, Warsaw (Poland) Institut Kosmicheskikh Issledovanii, Moscow (USSR))

    1990-07-01

    The Comet Halley outer coma's 0.03-25 Hz low-sensitivity electric field waveforms are presently studied, in conjunction with simultaneous observations of dust particle mass spectra, in order to ascertain effective regions for the generation of impulses in various amplitude ranges by particle impacts from particular mass channels. The areas for production of positive impulses by particles of mass magnitudes of orders 10 to the -17th to the -16th, 10 to the -16th to the -15th, and 10 to the -15th to the -14th g, were respectively equal to about 2.5, 6.3, and 4.0 units of the SP-1 sensor's 81 sq cm area. An adequate correspondence is obtained between experimental results and interpretation if the impact ionization yield is rather high, while the dust-induced plasma's expansion velocity is several times smaller than appears in the extant literature. 21 refs.

  20. 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 ...

  1. Baroreceptor Reflex Role Play

    NSDL National Science Digital Library

    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.

  2. Therapeutic effects of the Sp1 inhibitor mithramycin A in glioblastoma

    Microsoft Academic Search

    Janina Seznec; Björn Silkenstedt; Ulrike Naumann

    2011-01-01

    Mithramycin A (MitA) is a chemotherapeutic compound which has been used in the therapy of several types of cancer. For experimental\\u000a cancer it has been shown that MitA mediates the expression of genes involved in tumor progression such as genes involved in\\u000a immunosurveillance, cell motility or cell death. MitA works synergistically with Apo2L\\/tumor necrosis factor-related apoptosis-inducing\\u000a ligand (TRAIL), and with antiangiogenic

  3. 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

  4. Factorize

    NSDL National Science Digital Library

    2010-01-01

    In this activity, students find factor pairs for a given number and then create a rectangle with those dimensions on a coordinate plane. This activity allows students to explore factorizations of numbers and how they relate to rectangles with that number as an area. This activity includes supplemental materials, including background information about the topics covered, a description of how to use the application, and exploration questions for use with the java applet.

  5. 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

  6. Additive Effect of Sp1 and Sp3 in Regulation of the ED-L1E Promoter of the EBV LMP 1 Gene in Human Epithelial Cells

    Microsoft Academic Search

    Chi-Neu Tsai; Chiu-Mei Lee; Chih-Kai Chien; Szu-Cheng Kuo; Yu-Sun Chang

    1999-01-01

    The ED-L1E promoter of the LMP 1 gene is a GC box-containing promoter. To test if Sp1\\/Sp3 are important for modulating ED-L1E promoter activity through the GC box, site-specific mutation and deletion constructs carrying a reporter gene were transfected into NPCTW076 and C33A cells. Results showed that deletion or mutation of the GC box abolished ED-L1E activity. Association of Sp1\\/Sp3

  7. 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)

  8. 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

  9. Therapeutic effects of the Sp1 inhibitor mithramycin A in glioblastoma.

    PubMed

    Seznec, Janina; Silkenstedt, Björn; Naumann, Ulrike

    2011-02-01

    Mithramycin A (MitA) is a chemotherapeutic compound which has been used in the therapy of several types of cancer. For experimental cancer it has been shown that MitA mediates the expression of genes involved in tumor progression such as genes involved in immunosurveillance, cell motility or cell death. MitA works synergistically with Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and with antiangiogenic agents. We were therefore interested in analyzing whether MitA might be a suitable agent for glioma therapy. We demonstrate herein that the cell death sensitizing effects of MitA are cell line specific, independent of the endogenous status of the tumor suppressor p53 as well as of the endogenous expression of X-linked inhibitor of apoptosis (XIAP) or basal sensitivity towards death ligand-induced cell death. In glioma cells, MitA reduced the secretion and activity of the migration-involved matrix metalloproteinases (MMP), diminished vascular endothelial growth factor (VEGF), and increased recepteur d'origine nantais (RON) kinase messenger RNA (mRNA), paralleled by a significant reduction of glioma cell migration. In contrast to other cancer types, in glioma cells MitA did not alter the expression of the immunorelevant genes major histocompatibility complex I class related (MIC)-A, MIC-B or UL16 binding proteins (ULBP). We conclude that, whereas MitA-mediated reduction of XIAP expression and sensitization to Apo2L/TRAIL are cell line specific, its antimigratory effects are more general and might be the result of altered expression of MMP, VEGF, and/or RON kinase. Therefore, MitA might be a potential agent to reduce glioma cell migration. PMID:20556479

  10. 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.

  11. 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…

  12. 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…

  13. 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…

  14. 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.

  15. Mass spectrum and spatial distribution of dust in the head of Comet Halley according to measurements made with SP1 instrument on VEGA 1 and 2

    Microsoft Academic Search

    O. L. Vaisberg; V. N. Smirnov; L. S. Gorn; M. V. Iovlev

    1987-01-01

    Measurements made with the SP-1 instrument indicate that the mass spectrum of dust particles in the Comet Halley head increases with decreasing mass in the mass range from 10 to the -14th to 10 to the -16th g. The dust coma is made up of several shells with different characteristics, indicating the existence of different types of particles. The observation

  16. Unbiased Mapping of Transcription Factor Binding Sites along Human Chromosomes 21 and 22 Points to Widespread Regulation of Noncoding RNAs

    Microsoft Academic Search

    Simon Cawley; Stefan Bekiranov; Huck H. Ng; Philipp Kapranov; Edward A. Sekinger; Dione Kampa; Antonio Piccolboni; Victor Sementchenko; Jill Cheng; Alan J. Williams; Raymond Wheeler; Brant Wong; Jorg Drenkow; Mark Yamanaka; Sandeep Patel; Shane Brubaker; Hari Tammana; Gregg Helt; Kevin Struhl; Thomas R Gingeras

    2004-01-01

    Using high-density oligonucleotide arrays representing essentially all nonrepetitive sequences on human chromosomes 21 and 22, we map the binding sites in vivo for three DNA binding transcription factors, Sp1, cMyc, and p53, in an unbiased manner. This mapping reveals an unexpectedly large number of transcription factor binding site (TFBS) regions, with a minimal estimate of 12,000 for Sp1, 25,000 for

  17. Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription FactorsD?

    PubMed Central

    Liu, Fang; Pore, Nabendu; Kim, Mijin; Voong, K. Ranh; Dowling, Melissa; Maity, Amit; Kao, Gary D.

    2006-01-01

    Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression, including expression of HDAC4, a class II HDAC implicated in the modulation of cellular differentiation and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were all readily repressed by mithramycin, suggesting regulation by GC-rich DNA sequences. We validated consensus binding sites for Sp1/Sp3 transcription factors in the HDAC4 promoter through truncation studies and targeted mutagenesis. Specific and functional binding by Sp1/Sp3 at these sites was confirmed with chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA). Cotransfection of either Sp1 or Sp3 with a reporter driven by the HDAC4 promoter led to high activities in SL2 insect cells (which lack endogenous Sp1/Sp3). In human cells, restored expression of Sp1 and Sp3 up-regulated HDAC4 protein levels, whereas levels were decreased by RNA-interference-mediated knockdown of either protein. Finally, variable levels of Sp1 were in concordance with that of HDAC4 in a number of human tissues and cancer cell lines. These studies together characterize for the first time the activity of the HDAC4 promoter, through which Sp1 and Sp3 modulates expression of HDAC4 and which may contribute to tissue or cell-line-specific expression of HDAC4. PMID:16280357

  18. Problematic Game Play: The Diagnostic Value of Playing Motives, Passion, and Playing Time in Men

    PubMed Central

    Kneer, Julia; Rieger, Diana

    2015-01-01

    Internet gaming disorder is currently listed in the DSM—not in order to diagnose such a disorder but to encourage research to investigate this phenomenon. Even whether it is still questionable if Internet Gaming Disorder exists and can be judged as a form of addiction, problematic game play is already very well researched to cause problems in daily life. Approaches trying to predict problematic tendencies in digital game play have mainly focused on playing time as a diagnostic criterion. However, motives to engage in digital game play and obsessive passion for game play have also been found to predict problematic game play but have not yet been investigated together. The present study aims at (1) analyzing if obsessive passion can be distinguished from problematic game play as separate concepts, and (2) testing motives of game play, passion, and playing time for their predictive values for problematic tendencies. We found (N = 99 males, Age: M = 22.80, SD = 3.81) that obsessive passion can be conceptually separated from problematic game play. In addition, the results suggest that compared to solely playing time immersion as playing motive and obsessive passion have added predictive value for problematic game play. The implications focus on broadening the criteria in order to diagnose problematic playing. PMID:25942516

  19. A 1.2 kb deletion in the 5' region of the beta-amylase gene is responsible for the lack of beta-amylase activity in soybean cultivar Altona sp 1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have identified near-isogenic soybean lines, one containing normal beta-amylase activity (Altona Sp 1b) and the other with undetectable beta-amylase activity (Altona sp 1). The molecular basis for the absence of beta-amylase activity in the mutant has not been investigated. In thi...

  20. The Values of Outdoor Play

    ERIC Educational Resources Information Center

    Elkind, David

    2006-01-01

    This article describes outdoor play as a solid foundation and a central vehicle of knowledge about the real world. Outdoor play is important to all age levels, but particularly in early childhood and the elementary years. Children's outdoor play is not a luxury. It is critical in children's ability to learn about the world, others, and themselves.…

  1. 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…

  2. 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…

  3. Play Therapy in School Counseling

    ERIC Educational Resources Information Center

    Trice-Black, Shannon; Bailey, Carrie Lynn; Kiper Riechel, Morgan E.

    2013-01-01

    Play therapy is an empirically supported intervention used to address a number of developmental issues faced in childhood. Through the natural language of play, children and adolescents communicate feelings, thoughts, and experiences. Schools provide an ideal setting for play therapy in many ways; however, several challenges exist in implementing…

  4. Visible Thought in Dramatic Play

    ERIC Educational Resources Information Center

    Hatcher, Beth; Petty, Karen

    2004-01-01

    In this article, the authors help teachers see below the surface so that play can be used to help children's learning and communication. A closer and deeper look at play can reveal children's learning of concept development, communication, budding social relationships, and very specific literacy skills. The authors state, that viewing play not…

  5. Piaget, Play and Cognition, Revisited.

    ERIC Educational Resources Information Center

    Sutton-Smith, Brian

    Piaget's early contribution to theorizing about play is discussed critically with reference to three major interrelated problems. These are: (1) that despite their equipotentiality in Piaget's theory of intelligence, imitation and play are not conceptualized as making an equal contribution to cognition, play taking a subordinate role; (2) that…

  6. Intentionality, social play, and definition

    Microsoft Academic Search

    Colin Allen; Marc Bekoff

    1994-01-01

    Social play is naturally characterized in intentional terms. An evolutionary account of social play could help scientists to understand the evolution of cognition and intentionality. Alexander Rosenberg (1990) has argued that if play is characterized intentionally or functionally, it is not a behavioral phenotype suitable for evolutionary explanation. If he is right, his arguments would threaten many projects in cognitive

  7. Studying infant and toddler play.

    PubMed

    Marino, B L

    1991-02-01

    The play of infants and toddlers is a rich and flexible research modality. Play assessment can be an outcome measure of cognition or social ability, or it can be measured in conjunction with related constructs such as language to give a broad view of early development. Play can also be an effective intervention in studies of cognition, language, motor, or social development. This article offers strategies for the researcher who is interested in infant and toddler play. Emphasis is placed on environmental variables that the researcher manipulates to optimize the child's performance. Play measures are briefly addressed. PMID:1990120

  8. Thinking about Children's Play: Play Is Not Work, Nor Is Work Play.

    ERIC Educational Resources Information Center

    Elkind, David

    2001-01-01

    Addresses the concept of "play as a child's work," from the viewpoints of Montessori, Freud, and Piaget. Contends that children's play: (1) like adult play, may be individual or social; (2) has immediate value for the child as a way of expressing feelings; and (3) is a healthy counterpoise to work. (SD)

  9. The Influence of Play Material on Discourse During Play

    Microsoft Academic Search

    Elizabeth I. Burroughs; Sharon E. Murray

    1992-01-01

    The present study examined the effect that selected play materials have on certain aspects of children's conversational behavior. Thirty-six children, ranging in age from 48-59 months, served as subjects within eighteen same-sex dyads. Each dyad engaged in three separate ten-minute play sessions. The dyads played with a different material during each of the three sessions. The materials used were Playdoh,

  10. 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

  11. Susceptibility to Osteoporotic Fracture is Determined by Allelic Variation at the Sp1 Site, Rather than Other Polymorphic Sites at the COL1A1 Locus

    Microsoft Academic Search

    F. E. A. McGuigan; D. M. Reid; S. H. Ralston

    2000-01-01

    :   Previous studies have identified an association between osteoporotic fracture and a polymorphism affecting a Sp1 binding\\u000a site in the first intron of the collagen type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this association\\u000a is direct or the result of linkage disequilibrium with other polymorphisms situated nearby. In this study we analyzed the\\u000a relationship between

  12. 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…

  13. Partners in Play: An Adlerian Approach to Play Therapy.

    ERIC Educational Resources Information Center

    Kottman, Terry

    In response to increasing concern about the mental health of young children, the field of play therapy is expanding rapidly. This book explains the principles of Adlerian therapy and offers step-by-step instructions on how to integrate these concepts and techniques into the practice of play therapy. Ideas are presented on how to build an…

  14. Let's Play: Teaching Play Skills to Young Children with Autism

    ERIC Educational Resources Information Center

    Boutot, E. Amanda; Guenther, Tracee; Crozier, Shannon

    2005-01-01

    Watch any young child and you will likely see him or her engaged in some form of play. Play is an integral part of early childhood development in which typically developing children learn social and language skills, as well as appropriate behaviors, problem solving, and a variety of other cognitive skills. By its very definition, autism is a…

  15. Integrating play in neurodevelopmental treatment.

    PubMed

    Anderson, J; Hinojosa, J; Strauch, C

    1987-07-01

    This article presents one perspective on the integration of play activities within a neurodevelopmental frame of reference. Based on the premise that activities are characteristic of occupational therapy intervention, issues related to combining play activities with neurodevelopmental principles are discussed. Clinical examples are also provided to illustrate the value of integrating play activities within the occupational therapy treatment of the child with cerebral palsy. PMID:3688158

  16. Symbolic play and language development.

    PubMed

    Orr, Edna; Geva, Ronny

    2015-02-01

    Symbolic play and language are known to be highly interrelated, but the developmental process involved in this relationship is not clear. Three hypothetical paths were postulated to explore how play and language drive each other: (1) direct paths, whereby initiation of basic forms in symbolic action or babbling, will be directly related to all later emerging language and motor outputs; (2) an indirect interactive path, whereby basic forms in symbolic action will be associated with more complex forms in symbolic play, as well as with babbling, and babbling mediates the relationship between symbolic play and speech; and (3) a dual path, whereby basic forms in symbolic play will be associated with basic forms of language, and complex forms of symbolic play will be associated with complex forms of language. We micro-coded 288 symbolic vignettes gathered during a yearlong prospective bi-weekly examination (N=14; from 6 to 18 months of age). Results showed that the age of initiation of single-object symbolic play correlates strongly with the age of initiation of later-emerging symbolic and vocal outputs; its frequency at initiation is correlated with frequency at initiation of babbling, later-emerging speech, and multi-object play in initiation. Results support the notion that a single-object play relates to the development of other symbolic forms via a direct relationship and an indirect relationship, rather than a dual-path hypothesis. PMID:25658200

  17. Development of a real-time PCR assay (SYBR Green I) for rapid identification and quantification of scyphomedusae Aurelia sp.1 planulae

    NASA Astrophysics Data System (ADS)

    Wang, Jianyan; Zhen, Yu; Mi, Tiezhu; Yu, Zhigang; Wang, Guoshan

    2015-04-01

    The complicated life cycle of Aurelia spp., comprising benthic asexually-reproducing polyps and sexually-reproducing medusae, makes it hard for researchers to identify and track them, especially for early stage individuals, such as planulae. To solve this problem, we developed a real-time PCR assay (SYBR Green I) to identify planulae in both cultured and natural seawater samples. Species-specific primers targeting Aurelia sp.1 mitochondrial 16S rDNA (mt 16S rDNA) regions were designed. Using a calibration curve constructed with plasmids containing the Aurelia sp.1 mt 16S rDNA fragment and a standard curve for planulae, the absolute number of mt 16S rDNA copies per planula was determined and from that the total number of planulae per sample was estimated. For the field samples, a 100-fold dilution of the sample DNA combined with a final concentration of 0.2 ?g/?L BSA in the PCR reaction mixture was used to remove real-time PCR inhibitors. Samples collected in Jiaozhou Bay from July to September 2012 were subsequently analyzed using this assay. Peak Aurelia sp.1 planula abundance occurred in July 2012 at stations near Hongdao Island and Qingdao offshore; abundances were very low in August and September. The real-time PCR assay (SYBR Green I) developed here negates the need for traditional microscopic identification, which is laborious and time-consuming, and can detect and quantify jellyfish planulae in field plankton samples rapidly and specifically.

  18. Playful biometrics: controversial technology through the lens of play.

    PubMed

    Ellerbrok, Ariane

    2011-01-01

    This article considers the role of play in the context of technological emergence and expansion, particularly as it relates to recently emerging surveillance technologies. As a case study, I consider the trajectory of automated face recognition—a biometric technology of numerous applications, from its more controversial manifestations under the rubric of national security to a clearly emerging orientation toward play. This shift toward “playful” biometrics—or from a technology traditionally coded as “hard” to one now increasingly coded as “soft”—is critical insofar as it renders problematic the traditional modes of critique that have, up until this point, challenged the expansion of biometric systems into increasingly ubiquitous realms of everyday life. In response to this dynamic, I propose theorizing the expansion of face recognition specifically in relation to “play,” a step that allows us to broaden the critical space around newly emerging playful biometrics, as well as playful surveillance more generally. In addition, play may also have relevance for theorizing other forms of controversial technology, particularly given its potential role in processes of obfuscation, normalization, and marginalization. PMID:22175066

  19. Playground Play: Educational and Inclusive

    ERIC Educational Resources Information Center

    Moore, Lisa

    2011-01-01

    It is easy to understand that fun is one of the key ingredients to any playground activity. But what one may not realize is that play systems--including slides, tunnels, activity panels, and more--encourage a lot more than just fun: there is learning at work in playground play, as well as the opportunity to include children of all abilities in…

  20. Revisiting the Landscape of Play.

    ERIC Educational Resources Information Center

    Veale, Ann

    2001-01-01

    Examines the traditional place of play in contemporary early childhood programs in light of new directions in theory and curriculum, the push for educational outcomes, and perceived pressures of the global market economy. Maintains that a new focus on teaching through play may provide a way to reconcile demand for outcomes with a concern for…

  1. Neuroscience, Play, and Child Development.

    ERIC Educational Resources Information Center

    Frost, Joe L.

    This paper presents a brief overview of the array of neuroscience research as it applies to play and child development. The paper discusses research showing the importance of play for brain growth and child development, and recommends that families, schools and other social and corporate institutions rearrange their attitudes and priorities about…

  2. Game Playing: The Next Moves

    Microsoft Academic Search

    Susan L. Epstein

    1999-01-01

    Computer programs now play many board games as well or better than the most expert humans. Human players, however, learn, plan, allocate resources, and integrate mul- tiple streams of knowledge. This paper highlights recent achievements in game playing, describes some cogni- tively-oriented work, and poses three related challenge problems for the AI community.

  3. Making Play Work for Education

    ERIC Educational Resources Information Center

    Weisberg, Deena Skolnick; Kittredge, Audrey K.; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick; Klahr, David

    2015-01-01

    Children, especially in the preschool years, learn a tremendous amount through play. Research on guided play demonstrates how schools can couple a curriculum-centered preschool program with a developmentally appropriate pedagogical approach to classroom teaching. However, to fully test this claim, we need a clear definition of the term…

  4. 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…

  5. 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:…

  6. 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…

  7. 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…

  8. 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.

  9. 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…

  10. 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…

  11. 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.

  12. The Many Faces of Play.

    ERIC Educational Resources Information Center

    Werth, Louise H.

    1984-01-01

    Presents descriptions of play reflecting recent theories, including the psychoanalytic works of Freud, Erikson, and Peller; Piaget's developmental theory (with discussion of Sutton-Smith); and the views of Smilansky and Parten. (AS)

  13. 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.

  14. Play for Children in Hospital

    ERIC Educational Resources Information Center

    Hardgrove, Carol; And Others

    1976-01-01

    Contains six short articles on therapeutic play. Each article is an edited version of a paper delivered at the XIV World Congress of Pediatrics in Buenos Aires on the subject of children in the hospital. (JMB)

  15. A tale of three fingers: the family of mammalian Sp/XKLF transcription factors.

    PubMed Central

    Philipsen, S; Suske, G

    1999-01-01

    One of the most common regulatory elements is the GC box and the related GT/CACC box, which are widely distributed in promoters, enhancers and locus control regions of housekeeping as well as tissue-specific genes. For long it was generally thought that Sp1 is the major factor acting through these motifs. Recent discoveries have shown that Sp1 is only one of many transcription factors binding and acting through these elements. Sp1 simply represents the first identified and cloned protein of a family of transcription factors characterised by a highly conserved DNA-binding domain consisting of three zinc fingers. Currently this new family of transcription factors has at least 16 different mammalian members. Here, we will summarise and discuss recent advances that have been directed towards understanding the biological role of these proteins. PMID:10454592

  16. 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

  17. 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

  18. 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

  19. 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

  20. "Playing God" and germline intervention.

    PubMed

    Peters, T

    1995-08-01

    The phrase "playing God" so popular with journalists takes on a serious meaning in the debate over germline genetic intervention. While guarding against the dangers of human pride implied in the phrase "playing God," special attention is given here to the Christian concept of the human being as created in the divine image, the imago dei. Human beings are dubbed "created co-creators." In this light ethical arguments proscribing germline intervention are examined and refuted, leaving the door open for creative responsibility on the part of the present generation for our future progeny. PMID:8568437

  1. Rollovers during play: Complementary perspectives.

    PubMed

    Smuts, Barbara; Bauer, Erika; Ward, Camille

    2015-07-01

    In this commentary, we compare and contrast Norman et al.s' findings on rollovers during dog play (Norman et al., 2015; the "target article") with our work on dog play fighting (Bauer and Smuts, 2007; Ward et al., 2008). We first review our major findings and then correct some errors in the target article's descriptions of our work. We then further explore the concept of "defensive" rollovers proposed in the target article. We conclude that a combination of the target article's approach and ours should inform future investigations of dog rollovers. PMID:25907148

  2. Kindergarten Play: The Foundation of Reading.

    ERIC Educational Resources Information Center

    Gentile, Lance M.; Hoot, James L.

    1983-01-01

    Discusses the critical relationships among play, learning to read, and early reading achievement. Gives examples of kindergarten play activities that nurture the ability to read, including painting, playing with lettered blocks, movement activities, sociodramatic play, and field trips. (FL)

  3. Building Curriculum during Block Play

    ERIC Educational Resources Information Center

    Andrews, Nicole

    2015-01-01

    Blocks are not just for play! In this article, Nicole Andrews describes observing the interactions of three young boys enthusiastically engaged in the kindergarten block center of their classroom, using blocks in a building project that displayed their ability to use critical thinking skills, physics exploration, and the development of language…

  4. Integrating Time, Place, and Play

    ERIC Educational Resources Information Center

    Gallavan, Nancy P.

    2004-01-01

    "Time, Place, and Play," is a short phrase, but is summarizes three very big concepts--history, geography, and culture--that are part of the elementary social studies curriculum. This article relates the story of how twenty-five elementary and middle school teachers, meeting over several weeks in a university class, designed a unit of study on the…

  5. 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)

  6. The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription.

    PubMed

    Fernández-Guizán, Azahara; Mansilla, Sylvia; Barceló, Francisca; Vizcaíno, Carolina; Núñez, Luz-Elena; Morís, Francisco; González, Segundo; Portugal, José

    2014-08-01

    DIG-MSK (demycarosyl-3D-?-D-digitoxosyl-mithramycin SK) is a recently isolated compound of the mithramycin family of antitumor antibiotics, which includes mithramycin A (MTA) and mithramycin SK (MSK). Here, we present evidence that the binding of DIG-MSK to DNA shares the general features of other mithramycins such as the preference for C/G-rich tracts, but there are some differences in the strength of binding and the DNA sequence preferentially recognized by DIG-MSK. We aimed at gaining further insights into the DIG-MSK mechanism of action by direct comparison with the effects of the parental MTA. Similar to MTA, MSK and DIG-MSK accumulated rapidly in A2780, IGROV1 and OVCAR3 human ovarian cancer cell lines, and DIG-MSK was a potent inhibitor of both basal and induced expression of an Sp1-driven luciferase vector. This inhibitory activity was confirmed for the endogenous Sp1 gene and a set of Sp-responsive genes, and compared to that of MTA and MSK. Furthermore, DIG-MSK was stronger than MTA as inhibitor of Sp3-driven transcription and endogenous Sp3 gene expression. Differences in the effects of MTA, MSK and DIG-MSK on gene expression may have a large influence on their biological activities. PMID:24907531

  7. Serine proteases SP1 and SP13 mediate the melanization response of Asian corn borer, Ostrinia furnacalis, against entomopathogenic fungus Beauveria bassiana.

    PubMed

    Chu, Yuan; Liu, Yang; Shen, Dongxu; Hong, Fang; Wang, Guirong; An, Chunju

    2015-06-01

    Exposure to entomopathogenic fungi is one approach for insect pest control. Little is known about the immune interactions between fungus and its insect host. Melanization is a prominent immune response in insects in defending against pathogens such as bacteria and fungi. Clip domain serine proteases in insect plasma have been implicated in the activation of prophenoloxidase, a key enzyme in the melanization. The relationship between host melanization and the infection by a fungus needs to be established. We report here that the injection of entomopathogenic fungus Beauveria bassiana induced both melanin synthesis and phenoloxidase activity in its host insect, the Asian corn borer, Ostrinia furnacalis (Guenée). qRT-PCR analysis showed several distinct patterns of expression of 13 clip-domain serine proteases in response to the challenge of fungi, with seven increased, two decreased, and four unchanged. Of special interest among these clip-domain serine protease genes are SP1 and SP13, the orthologs of Manduca sexta HP6 and PAP1 which are involved in the prophenoloxidase activation pathway. Recombinant O. furnacalis SP1 was found to activate proSP13 and induce the phenoloxidase activity in corn borer plasma. Additionally, SP13 was determined to directly cleave prophenoloxidase and therefore act as the prophenoloxidase activating protease. Our work thus reveals a biochemical mechanism in the melanization in corn borer associated with the challenge by B. bassiana injection. These insights could provide valuable information for better understanding the immune responses of Asian corn borer against B. bassiana. PMID:25900291

  8. 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.

  9. 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…

  10. Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPK? and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun.

    PubMed

    Tang, Qing; Zhao, Shunyu; Wu, Jingjing; Zheng, Fang; Yang, LiJun; Hu, JingHeng; Hann, Swei Sunny

    2015-07-01

    Despite the anti-cancer effect of emodin observed in several cancers, the underlying molecular mechanism remains to be elucidated. In this study, we showed that emodin-inhibited NSCLC cell growth and increased phosphorylation of AMPK? and ERK1/2. In addition, emodin-inhibited ILK protein expression. The overexpression of ILK reversed the effect of emodin on cell growth inhibition. Furthermore, the blockade of AMPK by compound C abrogated, while metformin, an activator of AMPK, strengthened the effect of emodin on the inhibition of ILK expression. Interestingly, the inhibitor of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK1/2 (PD98059) attenuated emodin-induced phosphorylation of AMPK?. Moreover, emodin reduced the protein expression of Sp1 and AP-1 subunit c-Jun. Exogenous expression of Sp1 and c-Jun diminished emodin-reduced ILK protein expression. Emodin suppressed ILK promoter activity, which was not observed in cells overexpression of Sp1 and treated with compound C. Intriguingly, exogenous expression of c-Jun overcame the emodin-inhibited Sp1 protein expression. Collectively, our results demonstrate that emodin inhibits ILK expression through AMPK?-mediated reduction of Sp1 and c-Jun. Metformin enhances the effects of emodin. Exogenous expression of Sp1 and c-Jun resists emodin-inhibited ILK promoter activity and protein expression. In addition, the overexpression of c-Jun diminishes emodin-induced AMPK? signaling. Thus, the crosstalk of AMPK? and MEK/ERK1/2 signaling and the reciprocal interaction between Sp1 and c-Jun proteins contribute to the overall responses of emodin. This novel signaling axis may be a therapeutic potential for prevention and treatment of NSCLC. PMID:25889897

  11. Encouraging children's development through play.

    PubMed

    Randall, P

    1994-04-01

    Play is a major part of a young child's education. Children deprived of play experiences can develop learning and other problems from which they may take years to recover. Parents should be encouraged to buy toys which are right for their child's stages of development. "Educational toys" can be useful in stimulating particular aspects of development, eg hand-eye co-ordination, manual dexterity, association of cause and effect. A good variety of toys is important. Children become more quickly bored than adults because their attention span is shorter. A good principle is to buy toys that are challenging without being too difficult, However, children also need time to relax with older, more familiar toys and easily completed activities. PMID:8688616

  12. Play and the arousal hypothesis 

    E-print Network

    Oberdieck, Fernando Guillermo

    1974-01-01

    were injected with a . 1M caffeine solution. Subjects were tested every other day for a total of twelve test sessions, The hypothesis was not supported. Aroused subjects played with test objects significantly more (p&. 05) than non-aroused subjects... of 12 test sessions. The sequence of testing subjects within each group was randomly determined each day. 13 Ten minutes prior to testing, experimental subjet ts received o 10 mg/kg subcutaneous injection with a . lit solution of caffeine (Eastman...

  13. Taxi! Role-Play Two

    Microsoft Academic Search

    James Clawson; Gerry Yemen

    Sold as a set, this role-playing series encourages students to clarify different points of view when in leadership roles (UVA-OB-0921, 0922, and 0923). Before seeking solutions, students must get a clear, comprehensive picture of the problems at hand. Using the "want-got-gap" model works well. The material affords students an opportunity to develop persuasion techniques. The exercise involves three roles: 1)

  14. Taxi! Role-Play One

    Microsoft Academic Search

    James Clawson; Gerry Yemen

    Sold as a set, this role-playing series encourages students to clarify different points of view when in leadership roles (UVA-OB-0921, 0922, and 0923). Before seeking solutions, students must get a clear, comprehensive picture of the problems at hand. Using the "want-got-gap" model works well. The material affords students an opportunity to develop persuasion techniques. The exercise involves three roles: 1)

  15. Taxi! Role-Play Three

    Microsoft Academic Search

    James Clawson; Gerry Yemen

    Sold as a set, this role-playing series encourages students to clarify different points of view when in leadership roles (UVA-OB-0921, 0922, and 0923). Before seeking solutions, students must get a clear, comprehensive picture of the problems at hand. Using the "want-got-gap" model works well. The material affords students an opportunity to develop persuasion techniques. The exercise involves three roles: 1)

  16. 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.

  17. Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes

    Microsoft Academic Search

    Francesca Orso; Davide Corà; Benedetta Ubezio; Paolo Provero; Michele Caselle; Daniela Taverna

    2010-01-01

    BACKGROUND: Different approaches have been developed to dissect the interplay between transcription factors (TFs) and their cis-acting sequences on DNA in order to identify TF target genes. Here we used a combination of computational and experimental approaches to identify novel direct targets of TFAP2A, a key TF for a variety of physiological and pathological cellular processes. Gene expression profiles of

  18. Supporting Free Play in Ubiquitous Computer Games

    Microsoft Academic Search

    Regan L. Mandryk; Kori M. Inkpen

    2001-01-01

    Children's imaginations allow them to experience creative and exciting play activities. These types of experiences fall under the category of free play, a type of play activity that is essential to children's development. Traditionally, computer supported cooperative play (CSCP) has been limited by the constraints of technology. The structured, static nature of computer interaction does not support children's free play

  19. Play for All. [CD-ROM].

    ERIC Educational Resources Information Center

    Moore, Robin C.; Goltsman, Susan M.

    A CD-ROM provides a tour of some of the world's greatest play environments, presenting 94 photographic images that illustrate the key concepts and recommendations from Play For All guidelines. It is organized into 10 categories covering a range of play area settings, including play equipment, sand settings, water settings, play props, and animal…

  20. 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…

  1. Play Therapy: The Art of the Relationship.

    ERIC Educational Resources Information Center

    Landreth, Garry L.

    Play therapy, described as a dynamic approach to counseling with children which allows the therapist to fully experience the child's world, is discussed in this book. These topics are presented: (1) the meaning of play, including functions of play and symbolic play; (2) history and development of play therapy, including psychoanalytic, release,…

  2. SP1-mediated microRNA-520d-5p suppresses tumor growth and metastasis in colorectal cancer by targeting CTHRC1

    PubMed Central

    Yan, Li; Yu, Jiang; Tan, Fei; Ye, Geng-Tai; Shen, Zhi-Yong; Liu, Hao; Zhang, Yan; Wang, Jie-Fu; Zhu, Xian-Jun; Li, Guo-Xin

    2015-01-01

    Recent evidence suggests that miR-520 family has an important role in regulating tumorigenesis and development of various types of solid cancers. However, as one of the most common cancers in the world, there is little known about the underlying regulatory mechanisms of miR-520 in colorectal cancer (CRC). In the present study, we investigated the expression of microRNA-520d-5p (miR-520d-5p) in CRC specimens and then explored its potential role and mechanism in CRC progression. We found that miR-520d-5p was markedly down-regulated in CRC clinical specimens compared with adjacent normal tissues by real-time PCR. Dual-luciferase assays confirmed that miR-520d-5p directly targeting CTHRC1 and SP1 transactivate miR-520d-5p by binding to its upstream promoter region. The biological functional experiments showed that ectopic re-expression of miR-520d-5p suppressed CRC cell proliferation, migration and invasion, whereas the inhibition of miR-520d-5p displayed an inverse effect in vitro and in vivo. Western blot shown that miR-520d-5p abrogated the epithelial-mesenchymal transition by inactivating the phosphorylation of Erk1/2. In conclusion, our findings indicate that miR-520d-5p is significantly down-expressed and involved in CRC progression and metastasis by targeting CTHRC1 and regulated by SP1, which provide new support for miR-520d-5p maybe as a novel anti-onco molecular target for the treatment of CRC in the future.

  3. 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…

  4. 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.

  5. Chin force in violin playing.

    PubMed

    Obata, Satoshi; Kinoshita, Hiroshi

    2012-06-01

    Force generated between the left mandible of violinists and the chinrest of the violin was examined using a force-sensing chinrest developed in this study. A strain-gauge force sensor was built, and it was fixed between the violin's top plate and a chin cup. Fifteen professional/amateur violinists held the violin statically, played musical scales with different sound properties and sounding techniques, as well as an excerpt from a Max Bruch concerto. Peak and mean forces were evaluated for each task. In a separate experiment, lateral movement of the lower teeth due to different levels of voluntary chin force exertion was measured. Static holding forces observed were 15 and 22 N with and without the help of the left hand, respectively. Peak force increased from 16 N at soft dynamics to 20 N at strong dynamics during scales. The force further increased to 29 N with the use of vibrato technique and 35 N during shifts. Tempo and hand position did not affect the force. Playing a Bruch concerto induced a mean peak force of 52 N, ranging from 31 to 82 N among the violinists. The developed force-sensing chinrest could accurately record the generated chin force. Typical chin force to stabilize the violin during ordinary musical performance was less than 30 N, but it could momentarily exceed 50 N when technically demanding musical pieces were performed. The lateral shift of the mandible was fairly small (<0.4 mm) even with high chin-force exertion, possibly due to clenching of the molars. PMID:21952980

  6. Sound Spectra and Technique in Trumpet Playing

    NASA Astrophysics Data System (ADS)

    McLean, James; Ball, Stephen; Kruger, Johnathan

    2004-03-01

    To a surprising degree, the connections between the methodology of trumpet playing and the quality of the sounds produced are poorly understood. One especially notable example is the force with which the instrument is pressed against the lips, especially for higher pitches. Different players, even at the same level of expertise, will use forces that differ by as much as a factor of 3 or 4. There is little consensus as to whether or how this is important. We have modified a trumpet to allow dynamic measurement of both the magnitude of this force, and the asymmetry with which it is applied. This trumpet is being used to monitor the force applied by players from beginners to experts, while simultaneously monitoring the sound spectrum, facial expressions, and intra-oral pressure. We will present our findings on the correlations between these different parameters.

  7. Toward a Nonverbal Syntax of Play Therapy

    Microsoft Academic Search

    Saralea E. Chazan

    2001-01-01

    Play therapy receives an innovative, theoretical underpinning for in-depth intervention with children. It is suggested that a new instrument to measure a child's play activity would enhance the understanding of young patients. Interestingly, the word cluster is employed here also to describe categories and components in a child's play. Long clinical experience has shown that nonverbal communication while playing presents

  8. 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

  9. Active Gaming: The Future of Play?

    ERIC Educational Resources Information Center

    Witherspoon, Lisa; Manning, John P.

    2012-01-01

    The authors examine technology-driven games--especially active gaming--as an evolving form of children's play. They offer an overview of play and its developmental benefits, describe the literature on the emergence of technology-driven play, and reflect on the diminishment of physical play in contemporary culture. They suggest that active gaming,…

  10. 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…

  11. 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…

  12. Strategies for Family Facilitation of Play Dates

    ERIC Educational Resources Information Center

    Chambers, Cynthia R.; Horn, Eva M.

    2010-01-01

    Play dates can serve several functions for young children, including children with social difficulties, such as developmental delays, behavioral disorders, autism spectrum disorders, and shyness. Play dates provide children with additional opportunities to be around peers and to practice skills associated with peer play interactions. Play dates…

  13. 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…

  14. Two-Character Plays for Student Actors: A Collection of 15 One-Act Plays.

    ERIC Educational Resources Information Center

    Mauro, Robert

    Designed for workshop or classroom use, this collection of short plays for two actors is a source of material for auditions and readings and a valuable training tool for acting classes. The collection contains plays for men only, plays for women only, plays for men and women, plays with a wide variety of roles, plays of comedy and serious drama,…

  15. 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.

  16. Problems with a Play Paradigm: A Reply to Dansky.

    ERIC Educational Resources Information Center

    Simon, Tony; Smith, Peter K.

    1986-01-01

    In answer to points raised by Dansky (1985) about specific inferences from Simon and Smith's study (1985) and broader issues about a single-session paradigm used in play and problem solving studies, Simon and Smith argue that their study adequately demonstrated how methodological factors in paradigm can swamp the effects of any treatment…

  17. Cultural Diversity and Play from an Ecological Perspective.

    ERIC Educational Resources Information Center

    Rettig, Michael A.

    2002-01-01

    Explores factors to consider when implementing cultural awareness activities with young children in schools. Discusses considerations regarding children's awareness of differences and ways in which we can be similar to and different from each other. Play is discussed as a vehicle through which children can learn about others in a natural context.…

  18. Sp1 Mediates a Therapeutic Role of MiR-7a/b in Angiotensin II-Induced Cardiac Fibrosis via Mechanism Involving the TGF-? and MAPKs Pathways in Cardiac Fibroblasts

    PubMed Central

    Li, Rui; Xiao, Jie; Qing, Xiaoteng; Xing, Junhui; Xia, Yanfei; Qi, Jia; Liu, Xiaojun; Zhang, Sen; Sheng, Xi; Zhang, Xinyu; Ji, Xiaoping

    2015-01-01

    MicroRNA-7a/b (miR-7a/b) protects cardiac myocytes from apoptosis during ischemia/reperfusion injury; however, its role in angiotensin II (ANG II)-stimulated cardiac fibroblasts (CFs) remains unknown. Therefore, the present study investigated the anti-fibrotic mechanism of miR-7a/b in ANG II-treated CFs. ANG II stimulated the expression of specific protein 1 (Sp1) and collagen I in a dose- and time-dependent manner, and the overexpression of miR-7a/b significantly down-regulated the expression of Sp1 and collagen I stimulated by ANG II (100 nM) for 24 h. miR-7a/b overexpression effectively inhibited MMP-2 expression/activity and MMP-9 expression, as well as CF proliferation and migration. In addition, miR-7a/b also repressed the activation of TGF-?, ERK, JNK and p38 by ANG II. The inhibition of Sp1 binding activity by mithramycin prevented collagen I overproduction; however, miR-7a/b down-regulation reversed this effect. Further studies revealed that Sp1 also mediated miR-7a/b-regulated MMP expression and CF migration, as well as TGF-? and ERK activation. In conclusion, miR-7a/b has an anti-fibrotic role in ANG II-treated CFs that is mediated by Sp1 mechanism involving the TGF-? and MAPKs pathways. PMID:25923922

  19. SP Transcription Factor Paralogs and DNA-Binding Sites Coevolve and Adaptively Converge in Mammals and Birds

    PubMed Central

    Yokoyama, Ken Daigoro; Pollock, David D.

    2012-01-01

    Functional modification of regulatory proteins can affect hundreds of genes throughout the genome, and is therefore thought to be almost universally deleterious. This belief, however, has recently been challenged. A potential example comes from transcription factor SP1, for which statistical evidence indicates that motif preferences were altered in eutherian mammals. Here, we set out to discover possible structural and theoretical explanations, evaluate the role of selection in SP1 evolution, and discover effects on coregulatory proteins. We show that SP1 motif preferences were convergently altered in birds as well as mammals, inducing coevolutionary changes in over 800 regulatory regions. Structural and phylogenic evidence implicates a single causative amino acid replacement at the same SP1 position along both lineages. Furthermore, paralogs SP3 and SP4, which coregulate SP1 target genes through competitive binding to the same sites, have accumulated convergent replacements at the homologous position multiple times during eutherian and bird evolution, presumably to preserve competitive binding. To determine plausibility, we developed and implemented a simple model of transcription factor and binding site coevolution. This model predicts that, in contrast to prevailing beliefs, even small selective benefits per locus can drive concurrent fixation of transcription factor and binding site mutants under a broad range of conditions. Novel binding sites tend to arise de novo, rather than by mutation from ancestral sites, a prediction substantiated by SP1-binding site alignments. Thus, multiple lines of evidence indicate that selection has driven convergent evolution of transcription factors along with their binding sites and coregulatory proteins. PMID:23019068

  20. Play Therapy Summer 2014 Seminar Series LSUHSC Play Therapy Clinic $50/Seminar for Professionals & $45/Seminar for Students (with ID)

    E-print Network

    be discussed. Seminar # 3: July 11th (9:30-12:30pm) Presented by Dr. Erin Dugan Advanced Skills and Dimensions Series Registration Form _____ June 6th _____ June 20th _____ July 11th _____ July 18th TOTAL of the basic principles, objectives, goals, therapeutic factors, tenets and dimensions of play therapy

  1. Terameprocol (tetra-O-methyl nordihydroguaiaretic acid), an inhibitor of Sp1-mediated survivin transcription, induces radiosensitization in non-small cell lung carcinoma

    PubMed Central

    Sun, Yunguang; Giacalone, Nicholas J.; Lu, Bo

    2010-01-01

    Introduction Survivin, an inhibitor of apoptosis protein (IAP) and key regulator of mitosis, is up-regulated in a variety of cancers and is often associated with a worse prognosis. Terameprocol down-regulates the Sp1-mediated transcription of survivin and Cdk1, which is important for cell cycle progression, as well as many other proteins. Survivin inhibition has previously been shown to result in the induction of apoptosis and radiosensitization. Methods This study examined the effects of terameprocol administration on survivin transcription and expression in HCC2429 and H460 lung cancer cells. We also examined the combined effects of radiation and terameprocol on apoptosis and radiosensitivity. Results Using immunoblot analysis and luciferase assays, we confirmed that terameprocol decreases survivin transcription and protein expression. Ultimately, however, decreases in survivin expression failed to correlate with an increase in apoptosis. Nonetheless, clonogenic assay revealed that terameprocol induces increased radiosensitization in HCC2429 (DER = 1.26, p = 0.019) and H460 (DER = 1.18, p = 0.001) cells. Additionally, the data show no effect of terameprocol on cell cycle in either HCC2429 or H460 cells. Conclusions Terameprocol significantly enhances the sensitivity of non-small cell lung carcinoma cell lines to radiation therapy, although the mechanism of action remains unclear. Further study is warranted to assess the potential of terameprocol as an agent that may enhance the therapeutic ratio of radiotherapy in lung cancer. PMID:21107289

  2. Continuity and Change in Play Styles as a Function of Sex of Child

    Microsoft Academic Search

    Beverly I. Fagot

    1981-01-01

    To look at continuity and change in play, children were observed in a natural setting using an observation schedule which allowed for coding the children's behavior and reactions to that behavior by others in the environment. The behavior scores were factor analyzed with six factors (play styles) resulting. The present paper discusses a group of sixty-seven boys and girls who

  3. Playing the Day Away: The Importance of Constructive Play in Early Childhood Settings.

    ERIC Educational Resources Information Center

    Oliver, Susan J.; Klugman, Edgar

    2002-01-01

    Discusses the importance of play for the development of young children. Defines constructive play and identifies the benefits of play for children. Describes the current play landscape as characterized by increasing "screen time," limited outdoor play time, increased violence exposure, overscheduling, and overfacilitating. Emphasizes that the…

  4. DEMOGRAPHIC WHO PLAYS COMPUTER AND VIDEO GAMES?

    E-print Network

    Marketplace Netflix partnership BBC iPlayer PS3 PlayTV etc. #12;CONNECTED GAMING #12;22 | 57 NEXT GENERATIONGAMING TRENDS #12;DEMOGRAPHIC SHIFTS #12;3 | 57 WHO PLAYS COMPUTER AND VIDEO GAMES? Source: ESA "Essential Facts", 2008 65% OF AMERICAN HOUSEHOLDS PLAY COMPUTER VIDEO GAMES #12;4 | 57 COMING UP NEXT Image

  5. 27 CFR 9.168 - Fair Play.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Fair Play. 9.168 Section 9.168 Alcohol...American Viticultural Areas § 9.168 Fair Play. (a) Name. The name of the viticultural...area described in this section is “Fair Play.” (b) Approved maps. The...

  6. Young Children's Literacy-Related Play

    ERIC Educational Resources Information Center

    Saracho, Olivia N.; Spodek, Bernard

    2006-01-01

    Studies indicate that young children's literacy learning can be promoted in a play setting. Literacy interactions, strategies, and activities in the children's play environment can facilitate their acquisition of literacy. In literacy-related play experiences, children select and utilize their abilities that are essential for literacy learning in…

  7. Choosing a Play for Your Amateur Group.

    ERIC Educational Resources Information Center

    Butler, Ivan

    This play-choosing guide is designed to help amateur theatrical companies in matching the casting, staging, costuming, and financial resources at their disposal with the corresponding requirements of about a hundred full-length plays. The plays have been divided into three categories: farces and comedies, drama, and thrillers and mysteries, and…

  8. Children in Play, Story, and School.

    ERIC Educational Resources Information Center

    Goncu, Artin, Ed.; Klein, Elisa L.

    In honor of the contributions of Greta G. Fein to the fields of developmental psychology and early childhood education, a community of scholars prepared this volume to explore how social play arises, social play's developmental and educational significance, and the ways in which social play can be promoted in early childhood settings. In addition,…

  9. Master Players: Learning from Children at Play.

    ERIC Educational Resources Information Center

    Reynolds, Gretchen; Jones, Elizabeth

    Developed as a companion volume to "The Play's the Thing," this book defines and analyzes the concept of master player based on videotaped observations of preschool children at play. An in-depth discussion reveals the multi-faceted nature of play, individual differences in both teachers' and children's styles, and the complexity of intervention…

  10. Evaluation of vision training using 3D play game

    NASA Astrophysics Data System (ADS)

    Kim, Jung-Ho; Kwon, Soon-Chul; Son, Kwang-Chul; Lee, Seung-Hyun

    2015-03-01

    The present study aimed to examine the effect of the vision training, which is a benefit of watching 3D video images (3D video shooting game in this study), focusing on its accommodative facility and vergence facility. Both facilities, which are the scales used to measure human visual performance, are very important factors for man in leading comfortable and easy life. This study was conducted on 30 participants in their 20s through 30s (19 males and 11 females at 24.53 ± 2.94 years), who can watch 3D video images and play 3D game. Their accommodative and vergence facility were measured before and after they watched 2D and 3D game. It turned out that their accommodative facility improved after they played both 2D and 3D games and more improved right after they played 3D game than 2D game. Likewise, their vergence facility was proved to improve after they played both 2D and 3D games and more improved soon after they played 3D game than 2D game. In addition, it was demonstrated that their accommodative facility improved to greater extent than their vergence facility. While studies have been so far conducted on the adverse effects of 3D contents, from the perspective of human factor, on the imbalance of visual accommodation and convergence, the present study is expected to broaden the applicable scope of 3D contents by utilizing the visual benefit of 3D contents for vision training.

  11. Emotionality and intentionality in bonobo playful communication.

    PubMed

    Demuru, Elisa; Ferrari, Pier F; Palagi, Elisabetta

    2015-01-01

    Great apes show very complex systems for communicating emotions and intentions. Whereas gestures are intentional signals, facial expressions can disclose both emotions and intentions. The playful context is a good field to explore the possible dichotomy between intentionally and emotionally driven signals as it has been suggested that one of its functions is to learn producing and decoding communicative patterns. To understand how signals are produced during play and how they are modified in the course of ontogeny, we investigated the use of playful facial expressions and gestures in bonobos (Pan paniscus), a tolerant species showing a high propensity to play even as adults. Our results showed that the use of play faces and gestures is strongly influenced by the characteristics of the play session. Both play faces and gestures were more often performed when social play involved physical contact and when the receiver was visually attending, thus suggesting that both signals can be strategically employed when communicating becomes more urgent. Compared to play faces, gestures were more frequent during dyadic than polyadic sessions, when a unique receiver was involved. Being gestures not context specific, they are probably used more selectively by the sender. On the contrary, play faces are context specific and transmit an unequivocal positive message that cannot be misconceived. These features legitimize a broad use of playful facial expressions, independently of the number of playmates. The similarities and differences in the production of these signals are probably linked to the different degree of emotionality and intentionality characterizing them. PMID:25204682

  12. Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promoter.

    PubMed

    Liu, A; Prenger, M S; Norton, D D; Mei, L; Kusiak, J W; Bai, G

    2001-11-30

    We reported previously that nerve growth factor (NGF) up-regulates activity of the N-methyl-D-aspartate receptor 1 (NR1) promoter. We have explored the pathways and nuclear targets of NGF signaling in regulating the NR1 promoter. PD98059 and wortmannin, but not rapamycin, significantly attenuated NGF-induced transcriptional activity from an NR1 promoter-luciferase construct. Coexpressing constitutively active forms of Ras, Raf, or MAPK/ERK kinase 1 (MEK1) increased promoter activity dramatically. The MEK1-induced increase was largely prevented by mutations of the tandem GC boxes in the promoter. Promoter activity was also increased significantly by coexpressed GC box-binding proteins (Sp1, 3, or 4) in nonstimulated PC12 cells. Either an extracellular signal-regulated kinase-1 (ERK1)- or Sp1-specific antibody coprecipitated Sp1 with ERKs, and the coprecipitation was enhanced significantly by NGF treatment of PC12 cells. ERK2 also incorporated radioactivity of [gamma(32)P]ATP into recombinant Sp1. However, ERK2-treated Sp1 and PC12 nuclear extracts or nuclear extracts from NGF-treated cells exhibited reduced binding to the promoter or a consensus GC box. Our results suggest that NGF utilizes both the Ras/ERK and phosphatidylinositol 3-kinase pathways to up-regulate NR1 promoter activity and that Sp1 is a novel substrate of NGF-activated ERKs. NGF-increased NR1 promoter activity may involve a complicated mechanism of Sp1 phosphorylation and possible transcription factor exchange. PMID:11571288

  13. 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

  14. Exploring Young Children's Literacy Development Through Play

    Microsoft Academic Search

    Olivia N. Saracho

    2001-01-01

    An exploratory study was conducted to determine the effects of literacy?enriched play centers and the emergent literacy behaviors of five?year?old kindergarten children. This study focused on play activities that promote reading and writing that can be integrated in play centers in the early childhood curriculum. Qualitative analysis of the data indicated that a language or literacy component can be integrated

  15. Play in the Context of the Family

    Microsoft Academic Search

    Julia B. Levine

    1988-01-01

    Symbolic play has been traditionally studied as a behavior emitted by the child, reflecting his or her developmental level and affective concerns. In this article, symbolic play between parent(s) and child is considered as a relational dialogue with significance for both the parent-child relationship and family adaptation. A review of previous research on parent-child play (which has almost exclusively focused

  16. Mammalian play: training for the unexpected.

    PubMed

    Spinka, M; Newberry, R C; Bekoff, M

    2001-06-01

    In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling kinematic, structural, motivational, emotional, cognitive, social, ontogenetic, and phylogenetic aspects of play. It may also account for a diversity of individual methods for coping with unexpected misfortunes. PMID:11409050

  17. A functional YY1 binding site is necessary and sufficient to activate Surf-1 promoter activity in response to serum growth factors.

    PubMed Central

    Cole, E G; Gaston, K

    1997-01-01

    The human Surf-1 and Surf-2 housekeeping genes are divergently transcribed and share a bi-directional, TATA-less promoter. Housekeeping promoters typically contain complex arrays of transcription factor binding sites and several studies have suggested that many of these sites might be functionally redundant. The Surf-1/Surf-2 promoter region contains four factor binding sites; members of the ETS family of transcription factors bind to two of these sites whilst YY1 binds to a third site immediately downstream of the major Surf-1 transcription start point. Here we show that Sp1 binds to the fourth transcription factor binding site. Although YY1 and Sp1 have previously been shown to interact both in vitro and in vivo, these proteins function independently at the Surf-1/Surf-2 promoter. The binding of Sp1 alone is sufficient to bring about full promoter activity in the Surf-2 direction. In contrast, both Sp1 and ETS proteins are required to bring about full promoter activity in the Surf-1 direction. The YY1 binding site is not required for basal transcription in either direction. The YY1 binding site is, however, both necessary and sufficient to confer growth factor inducibility on transcription in the Surf-1 direction. Our data suggest that functionally redundant transcription factor binding sites might not be a general feature of housekeeping promoters. PMID:9278494

  18. Metamorphosis: Play, Spirituality and the Animal

    ERIC Educational Resources Information Center

    Bone, Jane

    2010-01-01

    Animal- and bird-becoming is an aspect of play as metamorphosis connected to spirituality in early childhood settings. The reconceptualisation of play presented here is supported by research that explored the spiritual experiences of young children in different early childhood contexts. Qualitative case study research carried out in Aotearoa New…

  19. Adapting personal music for synesthetic game play

    Microsoft Academic Search

    Sam Rossoff; George Tzanetakis; Bruce Gooch

    2010-01-01

    Music can significantly effect game play and help players understand underlying patterns in the game, or the effects of their actions on the characters. Conversely, inappropriate music can have a negative effect on players by creating additional difficulties. While game makers recognize the effects of music on game play, solutions that provide users with a choice in personal music are

  20. 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…

  1. ARTS & SCIENCES New Play Design Lab

    E-print Network

    Gilchrist, James F.

    COLLEGE OF ARTS & SCIENCES New Play Design Lab A Critical Conversation Transfer of Volatiles, New Direction THE ARTS Mile-High Artwork ... New Play Design Lab ... Mapping Shadow and Light Shaping the Modern Presidency scotch roman The magazine of Lehigh University's College of Arts

  2. 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…

  3. Role-Playing in Counselor Student Development

    ERIC Educational Resources Information Center

    Osborn, Debra; Costas, Lisa

    2013-01-01

    This study examined how role-plays impacted 27 counseling students' overall skills as measured by instructor ratings and self-ratings during practice triads in a microskills course. A Mann-Whitney U nonparametric test revealed no significant difference for scripted versus personal concerns role-plays. Students indicated a strong belief that…

  4. Play as a Pathway of Behavior

    ERIC Educational Resources Information Center

    Henricks, Thomas S.

    2011-01-01

    Seeking to understand play as part of a more general theory of human relationships, the author defines play as one of four fundamental categories of behavior, the others being work, ritual, and communitas. He discusses how each of these behaviors is organized as a "pathway" that offers distinctive opportunities for experiencing life and for…

  5. Development of intelligent play practice for trampolines

    Microsoft Academic Search

    Helle Skovbjerg Karoff; Lars Elbæk; Sigrid Rytz Hansen

    2012-01-01

    This paper addresses the use of technology as an add-on to traditional and well-known dynamics of play. By introducing the process of development simulated by the interactive trampoline, this paper seeks to emphasize the relationship between physical activity, safety and sociality as important issues for future development of interactive design for play practices.

  6. Sack Racers at Day of Play

    NASA Technical Reports Server (NTRS)

    2005-01-01

    From left, Mallory Doody, 5, Natalie Cambre, 3, Madison Doody, 7, and Anna Cambre, 6, get ready to compete in a sack race. 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.

  7. Listening to Boys and Girls During Play.

    ERIC Educational Resources Information Center

    Liss, Marsha B.; And Others

    To examine the nature of sex differences in children's speech during play, 10 boys and 10 girls in kindergarten were videotaped continuously during 10 minute dyadic play sessions involving non-sex-typed toys. Each child participated twice -- once with a same-sex peer and once with an opposite-sex peer. The videotapes were coded according to whom…

  8. 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

  9. 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…

  10. End-User Learning through Application Play.

    ERIC Educational Resources Information Center

    Belanger, France; Van Slyke, Craig

    2000-01-01

    "Play" with computer applications is form of self-directed, experiential learning. This learning results in improved mental models of applications; application use for work tasks further refines the models. Application play may benefit organizations that invest considerable resources in technology training. (SK)

  11. Play Therapy for Children with Disabilities.

    ERIC Educational Resources Information Center

    Carmichael, Karla D.

    Play therapy can be used to help children with disabilities to develop a sense of strength and competency. Play therapy literature concerning children with disabilities is divided into two distinct approaches: (1) the "I am" attribute which deals with emotional adjustment and helps the child to develop positive self-esteem, personal competency,…

  12. Girls' Physically Active Play and Parental Behavior.

    ERIC Educational Resources Information Center

    Tauber, Margaret A.

    Sex differences in children's physical activity levels, and associations between girls' activity level, childrearing characteristics and parent-child play behavior were investigated in a quasi-naturalistic situation. As part of a longitudinal project, 144 third grade children were videotaped in a 1-hour play session with one of their parents. A…

  13. Children's Gendered Drawings of Play Behaviours

    ERIC Educational Resources Information Center

    Akseer, Tabasum; Lao, Mary Grace; Bosacki, Sandra

    2012-01-01

    According to child psychologists, vital links exist between children's drawings and their emotional, social, and cognitive development. Previous research has explored the important relations between drawings and play in educational settings. Given the vast research that explores the ambiguous topic of children's play, according to Richer (1990),…

  14. 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…

  15. 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…

  16. Epidermal growth factor (EGF) receptor gene transcription

    SciTech Connect

    Kageyama, R.; Merlino, G.T.; Pastan, I.

    1988-05-05

    The authors have studied in vitro transcription of the human epidermal growth factor (EGF) receptor proto-oncogene using nuclear extracts of A431 human epidermoid carcinoma cells, which overproduce the EGF receptor. With the in vitro system we found that Sp1 and other trans-acting factors bound to the EGF receptor promoter regions and are required for maximal expression. Fractionation showed that a DEAE-Sepharose fraction (BA) contained a novel factor, which specifically stimulated EGF receptor transcription 5- to 10-fold. The molecular mass of the native form of the factor is about 270-kDa based on its migration on Sephacryl S-300. This factor may activate transcription of the proto-oncogene through a weak or indirect interaction with the DNA template.

  17. Sequence-structure correlations in silk: Poly-Ala repeat of N. clavipes MaSp1 is naturally optimized at a critical length scale.

    PubMed

    Bratzel, Graham; Buehler, Markus J

    2012-03-01

    Spider silk is a self-assembling biopolymer that outperforms many known materials in terms of its mechanical performance despite being constructed from simple and inferior building blocks. While experimental studies have shown that the molecular structure of silk has a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies in particular under variations of genetic sequences have been reported. Here we report atomistic-level structures of the MaSp1 protein from the Nephila Clavipes spider dragline silk sequence, obtained using an in silico approach based on replica exchange molecular dynamics (REMD) and explicit water molecular dynamics. We apply this method to study the effects of a systematic variation of the poly-alanine repeat lengths, a parameter controlled by the genetic makeup of silk, on the resulting molecular structure of silk at the nanoscale. Confirming earlier experimental and computational work, a structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly ?-sheet crystal domains while disorderly regions are formed by glycine-rich repeats that consist of 3(10)-helix type structures and ?-turns. Our predictions are directly validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots combined with an analysis of the secondary structure content. The key result of our study is our finding of a strong dependence of the resulting silk nanostructure depending on the poly-alanine length. We observe that the wildtype poly-alanine repeat length of six residues defines a critical minimum length that consistently results in clearly defined ?-sheet nanocrystals. For poly-alanine lengths below six, the ?-sheet nanocrystals are not well-defined or not visible at all, while for poly-alanine lengths at and above six, the characteristic nanocomposite structure of silk emerges with no significant improvement of the quality of the ?-sheet nanocrystal geometry. We present a simple biophysical model that explains these computational observations based on the mechanistic insight gained from the molecular simulations. Our findings set the stage for understanding how variations in the spidroin sequence can be used to engineer the structure and thereby functional properties of this biological superfiber, and present a design strategy for the genetic optimization of spidroins for enhanced mechanical properties. The approach used here may also find application in the design of other self-assembled molecular structures and fibers and in particular biologically inspired or completely synthetic systems. PMID:22340682

  18. Factor Track

    NSDL National Science Digital Library

    This problem helps learners improve their knowledge of factors, especially those in the usual multiplication tables, and encourages the problem solving strategy of trial and error. The goal of the game is to go around the track in as few moves as possible, keeping to the rules that a player can move any number of spaces which is a factor of the number the player is on, except 1. There is a "training" track to play on initially to see the rules in action and then a more complicated track for players to use. The Teachers' Notes page offers suggestions for implementation, key discussion questions, ideas for extension and support.

  19. Gut-Enriched Kruppel-Like Factor Interaction with Smad3 Inhibits Myofibroblast Differentiation

    Microsoft Academic Search

    Biao Hu; Zhe Wu; Tianju Liu; Matthew R. Ullenbruch; Hong Jin; Sem H. Phan

    2006-01-01

    Gut-enriched Kruppel-like factor (GKLF) has been reported to par- tially inhibit -smooth muscle actin (-SMA) gene transcription by competing for binding to the TGF- control element (TCE) with known activators such as Sp1 and other Kruppel-like factors. This incomplete inhibition via the TCE suggests an additional mecha- nism, which was evaluated in this study. The results showed that an -SMA

  20. 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…

  1. 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

  2. Nystulian Play Therapy: Applications of Adlerian Psychology.

    ERIC Educational Resources Information Center

    Nystul, Michael S.

    1980-01-01

    Nystulian Play Therapy is based on Adlerian strategies. Encouragement of and respect for the child are emphasized. Teacher and parent education are important parts of a comprehensive approach to affective positive change in the child. (JAC)

  3. Back to Sleep, Tummy to Play

    MedlinePLUS

    ... Español Text Size Email Print Share 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 ...

  4. When Girls versus Boys Play Alone: Nonsocial Play and Adjustment in Kindergarten.

    ERIC Educational Resources Information Center

    Coplan, Robert J.; Gavinski-Molina, Marie-Helene; Lagace-Seguin, Daniel G.; Wichmann, Cherami

    2001-01-01

    Examined relations between different forms of children's nonsocial play behaviors and adjustment in kindergarten. Results from regression analyses revealed that different types of nonsocial play were differentially associated with child characteristics and indices of adjustment. For some forms of nonsocial play, the nature of these associations…

  5. 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,…

  6. "Good-Fit" Teacher-Child Play Interactions and the Subsequent Autonomous Play of Preschool Children

    ERIC Educational Resources Information Center

    Trawick-Smith, Jeffrey; Dziurgot, Traci

    2011-01-01

    The purpose of this study was to test a model of adult-child play interactions in preschool classrooms, based on the work of Vygotsky and neo-Vygotskian scholars. The model predicts that adults will tailor the play support they provide to the immediate needs of individual children, and that this will lead to subsequent independent play. Classroom…

  7. Including Children with Autism in Social and Imaginary Play with Typical Peers: Integrated Play Groups Model

    ERIC Educational Resources Information Center

    Wolfberg, Pamela; Bottema-Beutel, Kristen; DeWitt, Mila

    2012-01-01

    Peer-play experiences are a vital part of children's socialization, development, and culture. Children with autism face distinct challenges in social and imaginary play, which place them at high risk for being excluded by peers. Without explicit support, they are likely to remain isolated from peers and the consistent interactive play that…

  8. Helping Parents Stay Confident in Their Own Playful Instincts: In a World of Professional Play Specialists

    ERIC Educational Resources Information Center

    Oliver, Susan J.; Klugman, Edgar

    2006-01-01

    This article provides an insight into the world of professional play specialists and provides suggestions to parents on how to be more confident about their role in play. Play need not be work for moms and dads, but it should be a family priority that they enjoy and about which the feel just great when they have devoted time and energy to do it.…

  9. 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…

  10. Differences in Practitioners' Understanding of Play and How This Influences Pedagogy and Children's Perceptions of Play

    ERIC Educational Resources Information Center

    McInnes, Karen; Howard, Justine; Miles, Gareth; Crowley, Kevin

    2011-01-01

    This paper presents research that examines the links between practitioners' understanding of play and its relationship to learning, their pedagogic interactions with children and children's own perceptions of their play. Previous research has shown a mismatch between practitioners' understanding of play and their practice. This research identifies…

  11. 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…

  12. 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…

  13. Categorising Risky Play--How Can We Identify Risk-Taking in Children's Play?

    ERIC Educational Resources Information Center

    Sandseter, Ellen Beate Hansen

    2007-01-01

    There is a growing debate on the balance between making sure our children are safe versus letting the children play in physically and emotionally stimulating and challenging environments. The focus is now on children's right to do risky play. There are no studies categorising risky play. The present study has aimed to do this. Qualitative…

  14. Joint pretend play originates in imitation and creativity Three examples of children's own play

    Microsoft Academic Search

    Monika Riihel

    In this paper I focus on small groups of children as organised by adults in day care situations. Two of the examples are from the video-report Playing Researchers (Riihel‰ 2000) and children are creating play together when getting acquainted with water and fire. The third example is a study on self-organising collaboration between children playing with chairs. The situations which

  15. 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

  16. Safe Active Play: A Guide to Avoiding Play Area Hazards. [Videotape.

    ERIC Educational Resources Information Center

    1997

    Active play provides healthy exercise and allows children to test their skills against challenges in their environment, but when play results in even minor injury, it may be taking place in a hazardous setting. This video is designed to teach caregivers, child care program staff and recreation officials how to create safe play environments. Based…

  17. "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…

  18. 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…

  19. Gamification: Playful TeachingGamification: Playful Teaching for Generation-X/-Y/-Z/...

    E-print Network

    Iosup, Alexandru

    Gamification: Playful TeachingGamification: Playful Teaching for Generation-X/-Y/-Z/... Alexandru Curiosity* 4TUD Onderwijsdag/EducationDay'13 * "A Magical New Adventure" #12;Gamification* in Higher it if it ain't broken? = A play in 7 acts, 3 set pieces, and 75 minutes 3. What is Gamification? Any other

  20. '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.

  1. 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.

  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. Position Statement on Active Outdoor Play

    PubMed Central

    Tremblay, Mark S.; Gray, Casey; Babcock, Shawna; Barnes, Joel; Costas Bradstreet, Christa; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William; Power, Marlene; Sandseter, Ellen Beate Hansen; Simon, Brenda; Brussoni, Mariana

    2015-01-01

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3–12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N = 9) and cross-sectorial individuals/organizations (N = 17), and an extensive stakeholder consultation process (N = 1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: “Access to active play in nature and outdoors—with its risks— is essential for healthy child development. We recommend increasing children’s opportunities for self-directed play outdoors in all settings—at home, at school, in child care, the community and nature.” The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development. PMID:26062040

  4. Mobile Play: Blogging, Tagging, and Messaging Eric Paulos

    E-print Network

    Paulos, Eric

    Mobile Play: Blogging, Tagging, and Messaging Eric Paulos Intel Research 2150 Shattuck Avenue #1300 elements will be examined: blogging, tagging, and message play. Keywords Play, blogging, tagging, messaging

  5. South Africa's AIDS play provokes controversy.

    PubMed

    Lee, N

    1996-03-01

    The European Union (EU) has earmarked a total of 40 million rand (US$12 million) to foster AIDS awareness in South Africa. 14.27 million rand, approximately US$3.45 million, has been allocated by the Department of Health to fund "Sarafina 2," a controversial musical show about AIDS awareness written by Mbongeni Ngema. The allocation of such a large portion of EU funding to this one play has been strongly criticized. The funds could have instead been used to provide essential services. In response, the Department of Health claims that the money had not been subjected to the usual checking processes because the amount had been specifically dedicated to the production of the play. The EU ambassador, however, has reportedly stated that the play was never discussed and was not part of their program. The director of the AIDS directorate was out of the country when Ngema's tender for the play was accepted last August, and it was not until November that she learned about her department's sponsoring of the play. The health department has now forbade its employees from discussing the matter with the media. Minister of Health Nkosazana Zuma should expect a tough time when she goes before Manto Tshabalala's parliamentary portfolio committee on health which has been charged with investigating the matter. The committee will also review some of the accounting related to this issue. PMID:8596329

  6. 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.

  7. Atlas of major Appalachian basin gas plays

    SciTech Connect

    Aminian, K.; Avary, K.L.; Baranoski, M.T.; Flaherty, K.; Humphreys, M.; Smosna, R.A.

    1995-06-01

    This regional study of gas reservoirs in the Appalachian basin has four main objectives: to organize all of the -as reservoirs in the Appalachian basin into unique plays based on common age, lithology, trap type and other geologic similarities; to write, illustrate and publish an atlas of major gas plays; to prepare and submit a digital data base of geologic, engineering and reservoir parameters for each gas field; and technology transfer to the oil and gas industry during the preparation of the atlas and data base.

  8. 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.

  9. Considerations for return-to-play and retirement decisions after concussion.

    PubMed

    Cantu, Robert C; Register-Mihalik, Johna K

    2011-10-01

    Return-to-play and retirement decisions after concussion are often difficult and complex. The complexity of these decisions may be influenced by many factors, including the number, proximity, and severity of previous concussions; gender; age; sport played; exposure to head impacts; and predisposing or pre-existing conditions. These circumstances and conditions can confound the decisions concerning return to play and retirement. Clinicians should carefully weigh how these circumstances and conditions influence quality of life and how they interact with the effects of concussion. Furthermore, clinicians should consider past and potential exposures to both subconcussive and concussive impacts during the athlete's lifetime when deliberating a return to play or retirement. The purpose of this overview is to highlight and discuss these issues as they factor into the return-to-play and retirement decisions after a concussive injury in an effort to provide clinicians with evidence-based information that can be used in the decision-making process. PMID:22035687

  10. Psychological needs, purpose in life, and problem video game playing among Chinese young adults.

    PubMed

    Wu, Anise M S; Lei, Lamis L M; Ku, Lisbeth

    2013-01-01

    The negative impacts of excessive and problematic video game playing on both children and adults are attracting increasing concern. Based on self-determination theory (SDT; Ryan & Deci, 2000), this study hypothesized that the three basic psychological needs of autonomy, competence, and relatedness are positively associated with purpose in life, which in turn acts as a protective factor against problem video game playing among Chinese young adult players. Through a questionnaire survey with a sample of 165 Chinese adults aged between 18 and 30 years (mean age?=?22.7 years), we found that perceived autonomy, competence, relatedness, and purpose in life were all negatively correlated with problem game playing. The demographic and psychological factors explained 38% of the variances of problem game playing. Specifically, gender, perceived relatedness, and purpose in life emerged as the three most salient predictors of problem game playing among the Chinese young adults. The mediating role of purpose in life was evidenced and it was found that purpose in life mediated the influences of the psychological needs proposed by SDT on problem game playing. Moreover, young men were significantly more susceptible to problem game playing than their female counterparts. To conclude, psychological needs and purpose in life influenced Chinese young adults' vulnerability to problem game playing directly or indirectly. Intervention programs that encourage social involvement and voluntary work, as well as counseling service that helps clients to search for life purpose, are suggested for intervening in problem game playing among Chinese young adults. PMID:22506646

  11. 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

  12. Tigers are something else: A case for family play

    Microsoft Academic Search

    Dean M. Busby; Alison C. Lufkin

    1992-01-01

    This paper is an attempt to bridge the two worlds of family therapy and filial play therapy, introducing the complementary idea of play in therapy. Family play therapy challenges the idea that play is only useful in the treatment of children. Clinical examples are given and uses of play are discussed, including evaluation, play as a therapeutic tool, and the

  13. The benefits of playing video games.

    PubMed

    Granic, Isabela; Lobel, Adam; Engels, Rutger C M E

    2014-01-01

    Video games are a ubiquitous part of almost all children's and adolescents' lives, with 97% playing for at least one hour per day in the United States. The vast majority of research by psychologists on the effects of "gaming" has been on its negative impact: the potential harm related to violence, addiction, and depression. We recognize the value of that research; however, we argue that a more balanced perspective is needed, one that considers not only the possible negative effects but also the benefits of playing these games. Considering these potential benefits is important, in part, because the nature of these games has changed dramatically in the last decade, becoming increasingly complex, diverse, realistic, and social in nature. A small but significant body of research has begun to emerge, mostly in the last five years, documenting these benefits. In this article, we summarize the research on the positive effects of playing video games, focusing on four main domains: cognitive, motivational, emotional, and social. By integrating insights from developmental, positive, and social psychology, as well as media psychology, we propose some candidate mechanisms by which playing video games may foster real-world psychosocial benefits. Our aim is to provide strong enough evidence and a theoretical rationale to inspire new programs of research on the largely unexplored mental health benefits of gaming. Finally, we end with a call to intervention researchers and practitioners to test the positive uses of video games, and we suggest several promising directions for doing so. PMID:24295515

  14. Block Play: Practical Suggestions for Common Dilemmas

    ERIC Educational Resources Information Center

    Tunks, Karyn Wellhousen

    2009-01-01

    Learning materials and teaching methods used in early childhood classrooms have fluctuated greatly over the past century. However, one learning tool has stood the test of time: Wood building blocks, often called unit blocks, continue to be a source of pleasure and learning for young children at play. Wood blocks have the unique capacity to engage…

  15. Smart Playing Cards: A Ubiquitous Computing Game

    Microsoft Academic Search

    Kay Römer; Svetlana Domnitcheva

    2002-01-01

    We present the ‘Smart Playing Cards’ application, a ubiquitous computing game that augments a classical card game with information technological functionality by attaching RFID tags to the cards. We also mention requirements that such an application makes on a supporting software infrastructure for ubiquitous computing.

  16. Sound Spectra and Technique in Trumpet Playing

    Microsoft Academic Search

    James McLean; Stephen Ball; Johnathan Kruger

    2004-01-01

    To a surprising degree, the connections between the methodology of trumpet playing and the quality of the sounds produced are poorly understood. One especially notable example is the force with which the instrument is pressed against the lips, especially for higher pitches. Different players, even at the same level of expertise, will use forces that differ by as much as

  17. Problem Solvers: Solutions--Playing Basketball

    ERIC Educational Resources Information Center

    Smith, Jeffrey

    2014-01-01

    In this article, fourth grade Upper Allen Elementary School (Mechanicsburg, Pennsylvania) teacher Jeffrey Smith describes his exploration of the Playing Basketball activity. Herein he describes how he found the problem to be an effective way to review concepts associated with the measurement of elapsed time with his students. Additionally, it…

  18. A Century of Plays by American Women.

    ERIC Educational Resources Information Center

    France, Rachel, Ed.

    Chosen for their literary quality and because they reflect the historical periods in which they were written, the 23 one-act dramas in this anthology represent the work of American female playwrights. The plays range from the realistic dramas produced in the "Little Theatres" of New York City at the turn of the century to current off-Broadway…

  19. Preadolescent Girls' and Boys' Virtual MUD Play

    ERIC Educational Resources Information Center

    Calvert, Sandra L.; Strouse, Gabrielle A.; Strong, Bonnie L.; Huffaker, David A.; Lai, Sean

    2009-01-01

    Same and opposite-sex pairs of preadolescents interacted twice in a MUD, a virtual domain where they created characters known as avatars and socially interacted with one another. Boys interacted primarily through rapid scene shifts and playful exchanges; girls interacted with one another through written dialogue. Opposite-sex pairs lagged behind…

  20. At Play in Fields of Ideas

    ERIC Educational Resources Information Center

    Schofield, Andrew; Rogers, Theresa

    2004-01-01

    The authors have come to believe, based on several years of collaborative work in an alternative literacy program, that developing the multiple literacies of struggling youth requires a curricular playfulness with students' ideas, biographies, and imaginations across genres and media. Social literacy and multiliteracy theories are powerful and…

  1. Gender, Play, Language, and Creativity in Preschoolers

    ERIC Educational Resources Information Center

    Holmes, Robyn M.; Romeo, Lynn

    2013-01-01

    This study explored the effects of a child's gender and school setting on preschoolers' language abilities (receptive vocabulary), creativity, and social play. The participants were primarily European-American children who spoke English as a primary language (nine children were bilingual), and were from middle income socioeconomic…

  2. Instrument Records And Plays Back Acceleration Signals

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J.

    1994-01-01

    Small, battery-powered, hand-held instrument feeds power to accelerometer and records time-varying component of output for 15 seconds in analog form. No power needed to maintain content of memory; memory chip removed after recording and stored indefinitely. Recorded signal plays back at any time up to several years later. Principal advantages: compactness, portability, and low cost.

  3. Jumping Rope at Day of Play

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Sarah Dastugue, 11, leaps in the air as Libby Knox, 9, swings a jump rope. The children were participants in Nickelodeon's Worldwide Day of Play celebration at Stennis Space Center (SSC) on Oct. 1. On the day of the event, children all over the world participate in physical activities as part of the celebration.

  4. SpaceWire Plug and Play Updates

    NASA Technical Reports Server (NTRS)

    Rakow, Glenn

    2007-01-01

    This viewgraph presentation reviews the work of the SpaceWire Plug N Play Workgroup. (SpW PnP WG). The chief product of SpW PnP WG will be to develop specification of necessary hardware features required in support upper layer (software) PnP implementations.

  5. To Play Words Based on Video Identifying

    Microsoft Academic Search

    Yingjie Li

    2010-01-01

    Games are interesting and they provide the ability to critical thinking and problem solving skills. But the negative impacts of playing games are obvious. Efforts have made to plus the educational contents into games. But plainness decreases the games' amusement. A game frame for words learning is proposed. The contesting rules of volleyball sport like and video analysis techniques are

  6. Using Minecraft for Instruction and Creative Play

    E-print Network

    LaViola Jr., Joseph J.

    Using Minecraft for Instruction and Creative Play Abstract Inline with the BSCS 5E instructional in a heavily modified Minecraft game server. We currently are developing games around kinematics, Boolean logic; Constructivism; Minecraft ACM Classification Keywords K.3.0. Computers and Education: General Introduction

  7. Using Role Play To Develop Cultural Competence.

    ERIC Educational Resources Information Center

    Shearer, Ruth; Davidhizar, Ruth

    2003-01-01

    Role playing is a useful method for teaching cultural competence in nurse-patient situations. Successful implementation depends on identification of objectives and grading criteria, adequate time, guidelines for role specifications, monitoring of the process, delineation of the relationship to theory, and facilitation of constructive analysis.…

  8. Playing with Words. Spotlight: Language Arts.

    ERIC Educational Resources Information Center

    Wolf, Aline D.

    2001-01-01

    Presents ways adults in Montessori 6-to-9 classrooms can help students expand their vocabularies. Suggestions for building vocabulary and understanding include using Command Cards to teach a variety of verbs, providing opportunities to play with words and memorize poetry, and making classical literature available. Maintains that lack of concern…

  9. A Simulation of Coevolution Using Playing Cards

    ERIC Educational Resources Information Center

    Tatina, Robert

    2007-01-01

    In this article, the author describes a simulation of a coevolutionary "arms race" and introduce a way of teaching it that lets students use the theory of natural selection to explain the outcomes of the simulation. The simulation uses the numerical cards from an UNO[R] playing card deck to represent the speeds of individuals in populations of…

  10. THE RELATIONSHIP BETWEEN BETTING AND LOTTERY PLAY

    Microsoft Academic Search

    DAVID FORREST; O. DAVID GULLEY; ROBERT SIMMONS

    2010-01-01

    We apply a novel daily time series data set of daily turnover from one of Britain’s leading bookmakers to analyze potential substitution between lottery play and bookmaker betting. We find some evidence that bettors do substitute away from horse race, soccer and numbers betting when the effective price of lottery tickets is unusually low, that is, when there is a

  11. 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…

  12. A Role-Play Rorschach Procedure

    ERIC Educational Resources Information Center

    Bricklin, Barry

    1975-01-01

    Three subjects were used in a role playing study based on the subject's own Rorschach responses. The results proved to be valuable as an aspect of therapeutic involvement. Results also help to expand and clarify the psychological meaning of Rorschach images. (Author/DEP)

  13. Expert Behavior in Children's Video Game Play.

    ERIC Educational Resources Information Center

    VanDeventer, Stephanie S.; White, James A.

    2002-01-01

    Investigates the display of expert behavior by seven outstanding video game-playing children ages 10 and 11. Analyzes observation and debriefing transcripts for evidence of self-monitoring, pattern recognition, principled decision making, qualitative thinking, and superior memory, and discusses implications for educators regarding the development…

  14. The Communication Game: Dump and Play

    ERIC Educational Resources Information Center

    Muma, John R.

    1975-01-01

    The author identifies two operations, "dump" and "play", that take place in human communication and analyzes the communication efforts of young children (prior to age 8) in terms of the limitations in cognitive development that govern their communication. (Author/LS)

  15. Gaming: Eat Breakfast, Drink Milk, Play Xbox

    ERIC Educational Resources Information Center

    O'Hanlon, Charlene

    2007-01-01

    Plagued by one of the most overweight populaces in the country, the state of West Virginia was looking for a solution to its obesity problem that would appeal to the school-age crowd. It turned to Linda Carson, a professor at West Virginia University's School of Physical Education. Carson recalled witnessing kids lining up in an arcade to play a…

  16. Geriatrix: A Role-Playing Game.

    ERIC Educational Resources Information Center

    Hoffman, Stephanie B.; And Others

    1985-01-01

    To sensitize medical students to the complexities of geriatric patient care, the geriatrics faculty of Upstate Medical Center's Clinical Campus developed Geriatrix, a role-playing game. Students attempt to win points in a board game containing Fact, Concept, and Crisis Squares. Crises promote exposure to ethical dilemmas and invite intense debate…

  17. Role-Play in the Science Classroom

    ERIC Educational Resources Information Center

    Worch, Eric A.; Scheuermann, Amy M.; Haney, Jodi J.

    2009-01-01

    The activity shared here is an animal role-playing lesson developed, field-tested, and refined for "Nature's Neighborhood", a newly designed children's education facility at the Toledo Zoo. The activity is targeted at students in kindergarten through second grade, but it can be adapted for use in grades three and four as well. Through students'…

  18. World History Plays, Puzzles and Activities.

    ERIC Educational Resources Information Center

    Stevens, Lawrence

    This instructional resource, for grades 7-10, includes a collection of 10 plays with related learning activities. Units of study include: (1) "Alexander the Great and the Greeks"; (2) "The Black Death and the End of the Middle Ages"; (3) "Robert Clive and Imperialism"; (4) "Christopher Columbus and the Age of Exploration"; (5) "Fall of the…

  19. A Child's Power in Game-Play

    ERIC Educational Resources Information Center

    McLeod, Julie; Lin, Lin

    2010-01-01

    This paper is the first of its series that studies the power children have in game-play and examines its implications for teaching and learning. As a start, the paper describes a framework of power based on a synthesis of various types of power underlined in literature. The paper then looks into the power issue through observation and interviews…

  20. Playing with Triangulations Oswin Aichholzer1

    E-print Network

    Demaine, Erik

    . A triangulation of S is a simplicial decomposition of its convex hull having S as vertex set. #12;2 Oswin games played on planar triangulations. We introduce three broad categories of such games: constructing, transforming, and marking triangulations. In various situations, we develop polynomial-time algorithms

  1. Putting Play Back into the Playground

    ERIC Educational Resources Information Center

    Couper, Llyween

    2011-01-01

    During 2008 and 2009, a group of nine Resource Teachers: Learning and Behaviour (RTLB) from Canterbury met as a Community of Practice to investigate the way that play in the school playground contributes to the social competence of students. While the original concern was around the needs of students who were unable to manage their behaviour in…

  2. 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…

  3. Structure and promoter activity of the human glia maturation factor-gamma gene: a TATA-less, GC-rich and bidirectional promoter

    Microsoft Academic Search

    Yoko Kawai; Kiyofumi Asai; Yutaka Miura; Yuichiro Inoue; Manami Yamamoto; Akihiko Moriyama; Naoki Yamamoto; Taiji Kato

    2003-01-01

    Human glia maturation factor-gamma (hGMFG) was recently identified as a gene that is homologous to glia maturation factor-beta (GMFB). In this study, we determined the organization of the 9.5-kb hGMFG gene and characterized its promoter activity. The 5?-flanking region of the first exon has putative elements for binding transcription factors Sp-1, GATA-1, AML-1a, Lyf-1 and Ets-1, but there were no

  4. Comparative studies on discrete and concatemeric DNA-sepharose columns for purification of transcription factors.

    PubMed

    Gadgil, H; Taylor, W L; Jarrett, H W

    2001-05-11

    Concatemers, tandem copies of DNA elements ligated together, are widely used for the DNA affinity chromatography of transcription factors. Purification of different transcription factors using discrete, concatemeric and T18:A18 tailed DNA affinity columns was studied. Columns having a discrete DNA sequence bound by cytidylic-adenylic-adenylic-thymidylic oligonucleotide (CAAT) enhancer binding protein (C/EBP) yields significantly more green fluorescent protein-C/EBP (GFP-C/EBP) fusion protein than a concatemeric DNA column made from five tandem repeats of the same DNA sequence. For lac repressor protein, the concatemeric and T18:A18 tailed columns show greater retention times than a discrete, untailed DNA affinity column. It was observed that the T18:A18 tailed column gives better resolution than either the discrete or concatemeric columns, of mixtures containing both lac repressor and GFP-C/EBP. Discrete concatemeric and T18:A18 tail columns all bound the Sp1 transcription factor and showed similar retention. The T18:A18 tailed column gives higher yield for Sp1 than the other columns. Our study shows concatemeric columns do not have any distinct advantage for the three different transcription factors we studied including Sp1, the original justification for the concatemeric approach. PMID:11403491

  5. CANNABINOID AND OPIOID MODULATION OF SOCIAL PLAY BEHAVIOR IN ADOLESCENT RATS: DIFFERENTIAL BEHAVIORAL MECHANISMS

    PubMed Central

    Trezza, Viviana; Vanderschuren, Louk J.M.J.

    2008-01-01

    We have recently shown that the pharmacological mechanisms through which cannabinoid and opioid drugs influence social play behavior in adolescent rats can be partially dissociated. Here, we characterize the effects of the direct cannabinoid agonist WIN55,212-2, the indirect cannabinoid agonist URB597 and the opioid agonist morphine on social play at the behavioral level. By treating either one or both partners of the test dyad, we show that these drugs differentially affect play solicitation and play responsiveness. By testing these drugs in animals which were either familiar or unfamiliar to the test cage, we show that environmental factors differentially modulate the effects of cannabinoid and opioid drugs on social play. These results support and extend our previous findings suggesting that, although cannabinoid and opioid systems interact in the modulation of social play behavior in adolescent rats, they do so through partially dissociable behavioral and pharmacological mechanisms. PMID:18434104

  6. The relationship between COLI A1 polymorphisms (Sp 1) and COLI A2 polymorphisms (Eco R1 and Puv II) with bone mineral density in Chinese men and women.

    PubMed

    Lau, E M C; Choy, D T K; Li, M; Woo, J; Chung, T; Sham, A

    2004-08-01

    Polymerase chain reaction was used to amplify across variable restriction sites of the COLI A1 and COLI A2 genes that encode the alpha 1 and 2 subunits of type I collagen. The relationship between these polymorphisms and bone mineral density (BMD) was studied in 683 Chinese men and women. In 100 men and women, COLI A1 Sp1 polymorphism was not found, which was consistent with other previous studies in Asian populations. However a statistically significant relationship was observed between COLI A2 Eco R1 and Puv II genotypes among the Chinese men studied. The mean BMD was consistently lower in men of the EE and PP genotype (P < 0.05 by analysis of variance [ANOVA]) than in men of the ee and pp genotypes. However, no association between BMD and the Eco R1 or Puv II genotypes was observed in Chinese women (P > 0.05 by ANOVA). We conclude that the COLI Al Sp1 binding site is absent in Hong Kong Chinese, whereas the COLI A2 Eco R1 and Puv II genetic polymorphisms may be associated with the BMD of elderly Chinese men. PMID:15085313

  7. Parenting Talent: A Qualitative Investigation of the Roles Parents Play in Talent Development

    ERIC Educational Resources Information Center

    Witte, Amanda L.; Kiewra, Kenneth A.; Kasson, Sarah C.; Perry, Kyle R.

    2015-01-01

    Previous research has linked talent development to four factors--early experience, coaching, practice, and motivation. In addition to these factors, contemporary talent experts suggest that parents play a critical role in talent development. The purpose of the present study was to uncover parents' in-time perspectives on the talent development…

  8. Block Play: It's Not Just for Boys Anymore--Strategies for Encouraging Girls' Block Play

    ERIC Educational Resources Information Center

    Tokarz, Barb

    2008-01-01

    While block play is essential for both boys' and girls' social, cognitive, language, and motor development, girls do not engage in block play as frequently as boys. This situation can be attributed to the socialization process--children learn societal expectations for behavior and materials for both boys and girls--lack of experience for girls…

  9. Watching the Children Watching "Play School": Indicators of Engagement, Play and Learning

    ERIC Educational Resources Information Center

    Harrison, Cathie

    2012-01-01

    This paper provides an overview of one aspect of a research project to investigate the contribution of the television program "Play School" to the health and wellbeing of young Australian children. The research question for this aspect of the study was: How do young children respond to the various elements and segments of "Play School" when viewed…

  10. Mystery Plays: 8 Plays for the Classroom Based on Stories by Famous Writers.

    ERIC Educational Resources Information Center

    Conklin, Tom, Ed.

    Intended for teachers of grades 4-8, this book presents eight plays based on classic mysteries by famous writers such as Sir Arthur Conan Doyle, Nathaniel Hawthorne, Ellery Queen, Dashiell Hammett, and O. Henry. The excitement of mystery stories offers a great way to introduce young people to the pleasures of reading. The plays in the book have…

  11. Teachers and Parents Play to Learn: Play-Based Instruction in Computer Technology

    ERIC Educational Resources Information Center

    Parker, Denise

    2010-01-01

    Play is so important that it is declared as one of the human rights by the United Nations. Although it is focused on children, play does "not" stop there. In the 1990s the author designed and facilitated a blended curriculum for a Head Start Program. The instructional goal was to introduce and get the children to effectively and independently use…

  12. Home Video Games: Children and Parents Learn to Play and Play to Learn.

    ERIC Educational Resources Information Center

    Mitchell, Edna

    Twenty families in the San Francisco Bay area (California) with new Atari home video game sets were studied from February through June 1981 to obtain data on how the game-playing affected family interaction. Records of play were kept for one week each month and each family member was interviewed at the beginning and the end of the study. It was…

  13. Grammar J, as in Jazzing Around: The Roles "Play" Plays in Style.

    ERIC Educational Resources Information Center

    Ostrom, Hans

    This paper asks what role "play" plays in writing and how it can help a writer, whatever dread, boredom, skill, or ethnicity he/she brings to writing. Some of the ideas in the paper come from Africa, courtesy of Robert Farris Thompson. In his "philosophy of discourse" discussed in the paper, Thompson speaks of the "big picture," a culture's deep…

  14. Play on: Retrospective Reports of the Persistence of Pretend Play into Middle Childhood

    ERIC Educational Resources Information Center

    Smith, Eric D.; Lillard, Angeline S.

    2012-01-01

    Piaget (1962) asserted that children stop engaging in pretend play when they enter the concrete operational stage because they become able to accommodate reality and no longer need to assimilate it to their wishes. Consistent also with the views of Vygotsky, discussion of pretend play in developmental psychology is typically confined to early…

  15. "We Should Be Playing, Not Talking": Play, Self-Agency and Moving towards Depressive Moments

    ERIC Educational Resources Information Center

    Poynton, Margaret

    2012-01-01

    This paper describes the use of play in the psychotherapy of a latency child from a severely traumatised background. It considers the meaning of play in relation to the role of the psychotherapist and to psychotherapeutic technique and explores its functions in terms of the child's development. The paper documents the psychotherapist's learning…

  16. Playing with Others: Head Start Children's Peer Play and Relations with Kindergarten School Competence

    PubMed Central

    Eggum-Wilkens, Natalie D.; Fabes, Richard A.; Castle, Sherri; Zhang, Linlin; Hanish, Laura D.; Martin, Carol Lynn

    2014-01-01

    Time-sampled observations of Head Start preschoolers' (N = 264; 51.5% boys; 76% Mexican American; M = 53.11 and SD = 6.15 months of age) peer play in the classroom were gathered during fall and spring semesters. One year later, kindergarten teachers rated these children's school competence. Latent growth models indicated that, on average, children's peer play was moderately frequent and increased over time during preschool. Children with higher initial levels or with higher slopes of peer play in Head Start had higher levels of kindergarten school competence. Results suggest that Head Start children's engagement with peers may foster development of skills that help their transition into formal schooling. These findings highlight the importance of peer play, and suggest that peer play in Head Start classrooms contributes to children's adaptation to the demands of formal schooling. PMID:24882941

  17. Vitiligo – Exogenous Factors

    Microsoft Academic Search

    Hagit Matz; Ethel Tur

    2004-01-01

    Vitiligo is an acquired depigmentary disorder of the skin that results from the selective destruction of melanocytes. The etiology of vitiligo is poorly understood. There appears to be a genetic predisposition, but additional factors are probably involved. The purpose of this article is to outline the factors that might play a role in the development of vitiligo. These include trauma

  18. Exploring the enjoyment of playing browser games.

    PubMed

    Klimmt, Christoph; Schmid, Hannah; Orthmann, Julia

    2009-04-01

    Browser games--mostly persistent game worlds that can be used without client software and monetary cost with a Web browser--belong to the understudied digital game types, although they attract large player communities and motivate sustained play. The present work reports findings from an online survey of 8,203 players of a German strategy browser game ("Travian"). Results suggest that multiplayer browser games are enjoyed primarily because of the social relationships involved in game play and the specific time and flexibility characteristics ("easy-in, easy-out"). Competition, in contrast, seems to be less important for browser gamers than for users of other game types. Findings are discussed in terms of video game enjoyment and game addiction. PMID:19260776

  19. Institutional games played by confined juveniles.

    PubMed

    Bartollas, C; Sieverdes, C M

    1983-01-01

    This study examined the games played by 561 juvenile offenders confined in six coeducational correctional facilities in one state. The types of games these residents used against staff and peers within the confines of the institution varied considerably. The study documented nineteen games used by males and females, twelve to deal with staff and seven to deal with peers. The games were defined as therapeutic games, material games, psychological games, and physical games. Peer-oriented games included attention-seeking activities and a variety of dominance games. Additionally, these games were described and tabulated according to the sex and race of the residents. The conclusion was that game-playing behavior was no less frequent in coeducational institutions than it was in single-sex institutions. PMID:6650271

  20. Play-wrestlers and their injuries.

    PubMed

    McCarthy, T; Crushell, E; Synnott, K; Kiely, P; McCormack, D

    2005-03-01

    Television (TV) broadcast wrestling series have become very popular amongst Irish children in recent years. Over a four-month study period, 2.3% of injuries seen at a busy paediatric fracture clinic were attributable to play-wrestling. The mean age was 9.5 years (range 4-15 years). All of the children had been role-playing wrestlers and imitating wrestling "moves" seen on TV. None had formal training in wrestling or martial arts. The commonest injury was fracture of the distal radius (7/13). One child required general anaesthetic for manipulation of a dorsally displaced fracture of radius. All other injuries were treated conservatively and resolved without sequelae. PMID:15869066

  1. A New Family of Predicted Krüppel-Like Factor Genes and Pseudogenes in Placental Mammals

    PubMed Central

    Pei, Jimin; Grishin, Nick V.

    2013-01-01

    Krüppel-like factors (KLF) and specificity proteins (SP) constitute a family of zinc-finger-containing transcription factors that play important roles in a wide range of processes including differentiation and development of various tissues. The human genome possesses 17 KLF genes (KLF1–KLF17) and nine SP genes (SP1–SP9) with diverse functions. We used sequence similarity searches and gene synteny analysis to identify a new putative KLF gene/pseudogene named KLF18 that is present in most of the placental mammals with sequenced genomes. KLF18 is a chromosomal neighbor of the KLF17 gene and is likely a product of its duplication. Phylogenetic analyses revealed that mammalian predicted KLF18 proteins and KLF17 proteins experienced elevated rates of evolution and are grouped with KLF1/KLF2/KLF4 and non-mammalian KLF17. Predicted KLF18 proteins maintain conserved features in the zinc fingers of the SP/KLF family, while possessing repeats of a unique sequence motif in their N-terminal regions. No expression data have been reported for KLF18, suggesting that it either has highly restricted expression patterns and specialized functions, or could have become a pseudogene in extant placental mammals. Besides KLF18 genes/pseudogenes, we identified several KLF18-like genes such as Zfp352, Zfp352-like, and Zfp353 in the genomes of mouse and rat. These KLF18-like genes do not possess introns inside their coding regions, and gene expression data indicate that some of them may function in early embryonic development. They represent further expansions of KLF members in the murine lineage, most likely resulted from several events of retrotransposition and local gene duplication starting from an ancient spliced mRNA of KLF18. PMID:24244731

  2. Model area describes NW Pennsylvania's Medina play

    SciTech Connect

    Pees, S.T.

    1983-05-23

    The Medina Group sandstones of the Lower Silurian area comprise the currently most active drilling objective for gas in northwestern Pennsylvania. A model area of 186 sq. miles in the midst of the Medina play is the subject of this article. Medina gas qualifies for 107 gas prices due to the official FERC tight sand classification of the pay zones. The Medina Group sandstones have wide distribution in the region and appear to be gas-bearing throughout most of their areal extent.

  3. Experts at PlayUnderstanding Skilled Expertise

    Microsoft Academic Search

    Stuart Reeves; Barry Brown; Eric Laurier

    2009-01-01

    Developing from David Sudnow's accounts of expertise, this article examines the gameplay of Counter-Strike, a popular online game. Although Counter-Strike at first may seem an unsophisticated pursuit, players display remarkable dexterity developed through many hours of play. Through participating in the game and analyzing videos of gameplay, we examine Counter-Strike as an example of expert technology use. As players move

  4. Teaching mothers to use non-directive play skills 

    E-print Network

    Constantin, Lisette Patrice

    1992-01-01

    . Timothy A. Cavell Parent training programs have become a common approach for treating families with emotionally and behaviorally disturbed children. A component common to most programs is non-directive, parent-child play. Although non-directive play...'s Play Ratings of Child's Play Ratings of Joint Play Child Compliance Parent Perceptions of Play Mother's Attributions Consumer Satisfaction Ratings 19 19 20 21 21 21 23 23 CONCLUSION and DISCUSSION REFERENCES APPENDIX A APPENDIX B...

  5. Science Concepts Young Children Learn through Water Play

    ERIC Educational Resources Information Center

    Gross, Carol M.

    2012-01-01

    Water is fascinating, fun, and multifaceted. Children can play with it endlessly. But play, for play's sake, is not water's only value (Crosser, 1994, Tovey, 1993). Indeed, water play is a compelling focus of study for young children (Chalufour & Worth, 2005). The concepts that young children learn from water play are essential for early childhood…

  6. Play and Learning--Inseparable Dimensions in Preschool Practice

    ERIC Educational Resources Information Center

    Samuelsson, Ingrid Pramling; Johansson, Eva

    2006-01-01

    This article is a theoretical discussion on the dimensions of learning in play and the dimensions of play in learning, using the playful interaction between children and teachers as a starting point. From an empirical study observations of two situations were chosen, one from a mealtime and one of children's play, both typical examples of playful

  7. Understanding the Importance of Play in Physical Education

    ERIC Educational Resources Information Center

    Clements, Rhonda

    2005-01-01

    While most child development experts acknowledge there is no universally agreed upon definition of children's play, there is general agreement that a lack of play, commonly known as "play deprivation" in play theories and research, can greatly stifle the child's normal healthy development. Therefore, the need for daily play experiences and daily…

  8. Teaching about the French Revolution--A Play.

    ERIC Educational Resources Information Center

    Pezone, Michael

    2002-01-01

    Presents a play about the French Revolution, discussing how the play was used within a global history course. States that students read the play, work in groups to rewrite the play, and perform their version of the play. Includes key questions that are asked of the students. (CMK)

  9. Plato and Play: Taking Education Seriously in Ancient Greece

    ERIC Educational Resources Information Center

    D'Angour, Armand

    2013-01-01

    In this article, the author outlines Plato's notions of play in ancient Greek culture and shows how the philosopher's views on play can be best appreciated against the background of shifting meanings and evaluations of play in classical Greece. Play--in various forms such as word play, ritual, and music--proved central to the development…

  10. Levels of Social Play: Observing and Recording Preschoolers.

    ERIC Educational Resources Information Center

    Barbakoff, Sondra; Yo, Yang Pei

    Noting that observing preschool children at play allows teachers to understand how individual children develop their social skills, this article describes different levels of social play and shows how teachers may use a running record and check list to assess such play. Children are described as engaging in onlooker play, solitary play, parallel…

  11. A longitudinal study of children’s outside play using family environment and perceived physical environment as predictors

    PubMed Central

    2014-01-01

    Background A natural and cheap way of increasing children’s physical activity is stimulating unstructured outside play. Purpose This study examined whether characteristics of the family and perceived physical environment were associated with the duration of children’s outside play. Methods Parents participating in the “Be Active, Eat Right” cluster RCT control group (N?=?2007) provided information on potential predictors of outside play (i.e. family and perceived physical environment) of their 5-year-old child by questionnaire. Child outside play was assessed by parental reports both at five and seven years. Linear regression analyses, adjusted for seasonality, were performed to evaluate associations between potential predictors and child outside play. Linear mixed models were fitted to evaluate the relationship between potential predictors and the development of outside play over two years, with season entered as a random factor. Results Family environment was the strongest construct predicting child outside play, while parent perceived physical environment had no significant association with child outside play. Parental habit strength and the presence of rules were the strongest predictors of increased outside play. Parent perceived difficulty in improving child outside play was the strongest predictor of decreased outside play. Conclusion Family environment predicted child outside play and not perceived physical environment. Parental rules and habit strength regarding improving outside play were associated with an improvement of child’s engagement in outside play. PMID:24934086

  12. Pervasive computing in play-based occupational therapy for children

    E-print Network

    Chi, Pei-Yu

    Embedding digital technology into playful activity can make play-based occupational therapy more effective. This study proposes two play-based activities to improve children's eating and tooth-brushing behavior.

  13. Synthesis of a trisaccharide repeat of the zwitterionic Sp1 capsular polysaccharide utilizing 2-Azido-4-benzylamino-4N,3-O-carbonyl-2,4,6-trideoxy-d-galactopyranosyl trichloroacetimidate.

    PubMed

    Iynkkaran, Ithayavani; Bundle, David R

    2013-08-30

    2-Azido-4-benzylamino-4N,3-O-carbonyl-2,4,6-trideoxy-d-galactopyranosyl trichloroacetimidate 2 conveniently prepared in six steps from 6-deoxy-d-glucal glycosylated a selectively protected ?1,3 linked methyl galabioside to afford the trisaccharide skeleton of a repeating unit of the Sp1 zwitterionic capsular polysaccharide. Lithium hydroxide hydrolysis of the 3,4-cyclic carbamate permitted the creation of a 2-acetamido-4-amino-2,4,6-trideoxygalactose residue. Selective cleavage of p-methoxybenzyl ethers by trifluoroacetic acid gave a selectively deprotected trisaccharide with two hydroxymethyl groups that were oxidized by the TEMPO reagent to afford access to trisaccharide glycoside 1 containing 2-acetamido-4-amino-2,4,6-trideoxygalactose and two galacturonic acid residues. PMID:23746649

  14. Understanding Positive Play: An Exploration of Playing Experiences and Responsible Gambling Practices.

    PubMed

    Wood, Richard T A; Griffiths, Mark D

    2014-09-01

    This study is one of the first to explore in detail the behaviors, attitudes and motivations of players that show no signs of at-risk or problem gambling behavior (so-called 'positive players'). Via an online survey, 1484 positive players were compared with 209 problem players identified using the Lie/Bet screen. The study identified two distinct groups of positive players defined according to their motivations to play and their engagement with responsible gambling (RG) practices. Those positive players that played most frequently employed the most personal RG strategies. Reasons that positive players gave for gambling were focused on leisure (e.g., playing for fun, being entertained, and/or winning a prize). By contrast, problem gamblers were much more focused upon modifying mood states (e.g., excitement, relaxation, depression and playing when bored or upset). The present study also suggests that online gambling is not, by default, inherently riskier than gambling in more traditional ways, as online gambling was the most popular media by which positive players gambled. Furthermore, most positive players reported that it was easier to stick to their limits when playing the National Lottery online compared to traditional retail purchasing of tickets. Problem players were significantly more likely than positive players to gamble with family and friends, suggesting that, contrary to a popular RG message, social play may not be inherently safer than gambling alone. It is proposed that players (generally) may identify more with the term 'positive play' than the term 'RG' which is frequently interpreted as being aimed at people with gambling problems, rather than all players. PMID:25209455

  15. Play and flow: Implications for online learning

    Microsoft Academic Search

    Steven Pace

    2007-01-01

    Many of the diverse pleasures that people experience during recreational computing activities can be synthesised into a single concept known as flow. Flow is a state of intense mental focus that occurs when a person's perceptual and cognitive systems are challenged at near capacity without being exceeded. It typically results in feelings of enjoyment and reduced awareness of factors that

  16. Epigenetic Modifications of Keap1 Regulate Its Interaction With the Protective Factor Nrf2 in the Development of Diabetic Retinopathy

    PubMed Central

    Mishra, Manish; Zhong, Qing; Kowluru, Renu A.

    2014-01-01

    Purpose. Diabetes induces oxidative imbalance in the retina and impairs Nrf2-mediated antioxidant response, and elevates Keap1, the cytoplasmic repressor of Nrf2. The goal of this study was to understand the role of epigenetic modifications at Keap1 promoter in regulation of Nrf2 function. Methods. The effect of high glucose on the binding of transcriptional factor Sp1 at Keap1 promoter and histone methylation status of the promoter was investigated in retinal endothelial cells. Role of histone methylation was confirmed in cells transfected with siRNA of methyltransferase enzyme Set7/9 (SetD7). In vitro results were confirmed in the retina from streptozotocin-induced diabetic rats. The role of epigenetic modifications of Keap1 promoter in the metabolic memory was examined in rats maintained in poor control for 3 months followed by good control for 3 months. Results. Hyperglycemia increased the binding of Sp1 at Keap1 promoter, and enriched H3K4me1 and activated SetD7. SetD7-siRNA prevented increase in Sp1 binding at Keap1 promoter and Keap1 expression, and ameliorated decrease in Nrf2-regulated antioxidant genes. Cessation of hyperglycemia failed to attenuate increased binding of Sp1 at Keap1, and the promoter continued to be methylated with increased expression of Keap1 and decreased expression of Nrf2-regulated genes. Conclusions. Epigenetic modifications at Keap1 promoter by SetD7 facilitate its binding with Sp1, increasing its expression. Keap1 restrains Nrf2 in the cytosol, impairing its transcriptional activity. Reversal of hyperglycemia fails to provide any benefit to epigenetic modifications of Keap1 promoter, suggesting their role in both the development of diabetic retinopathy and the metabolic memory phenomenon. PMID:25301875

  17. Imperial boyhood: piracy and the play ethic.

    PubMed

    Deane, Bradley

    2011-01-01

    Representations of perpetual boyhood came to fascinate the late Victorians, partly because such images could naturalize a new spirit of imperial aggression and new policies of preserving power. This article traces the emergence of this fantasy through a series of stories about the relationship of the boy and the pirate, figures whose opposition in mid-Victorian literature was used to articulate the moral legitimacy of colonialism, but who became doubles rather than antitheses in later novels, such as R.L. Stevenson's "Treasure Island" and Joseph Conrad's "Lord Jim." Masculine worth needed no longer to be measured by reference to transcendent, universal laws, but by a morally flexible ethic of competitive play, one that bound together boyishness and piracy in a satisfying game of international adventure. PMID:22355829

  18. New plays spur West Canada action

    SciTech Connect

    Not Available

    1980-02-25

    Industry spokesmen forecast an increase of 10-15% in Western Canada drilling activity during 1980 with well completions reaching 8000-8200 for the year. Well completions in Western Canada in 1979 totaled 7239, compared with 6792 in 1978. Areas of greatest activity during 1980 will include the Elmworth-Deep basin gas area stretching from northwestern Alberta into northeastern British Columbia; the West Pembina oil play, where first discoveries were announced in 1977; continuing emphasis on deep gas tests in the Foothills region by majors; and shallow gas and deeper oil exploration and development drilling in the Medicine Hat region and Suffield Block in southeastern Alberta. The Canadian Association of Oilwell Drilling Contractors expects the drilling-rig inventory to reach 520 rigs during 1980, with almost full utilization during the winter drilling season.

  19. In Play We Trust. Rapid Facial Mimicry Predicts the Duration of Playful Interactions in Geladas

    PubMed Central

    Mancini, Giada; Ferrari, Pier Francesco; Palagi, Elisabetta

    2013-01-01

    The primate play-face is homologous to the human facial display accompanying laughter. Through facial mimicry, the play-face evokes in the perceiver a similar positive emotional state. This sensorimotor and emotional sharing can be adaptive, as it allows individuals to fine-tune their own motor sequences accordingly thus increasing cooperation in play. It has been recently demonstrated that, not only humans and apes, but also geladas are able to mimic others' facial expressions. Here, we describe two forms of facial mimicry in Theropithecus gelada: rapid (RFM, within 1.0 s) and delayed (DFM, within 5.0 s). Play interactions characterized by the presence of RFM were longer than those with DFM thus suggesting that RFM is a good indicator of the quality of communicative exchanges and behavioral coordination. These findings agree with the proposal of a mirror mechanism operating during perception and imitation of facial expressions. In an evolutionary perspective, our findings suggest that RFM not only was already present in the common ancestor of cercopitecoids and hominoids, but also that there is a relationship between RFM and length and quality of playful interactions. PMID:23785501

  20. Does urokinase play a role in renal stone formation?

    PubMed

    du Toit, P J; Van Aswegen, C H; Steinmann, C M; Klue, L; Du Plessis, D J

    1997-07-01

    Renal stone formation is a complex multifactorial disease, and it is believed that the initial step in the pathogenesis of urolithiasis must be the precipitation of an organic matrix of mucoproteins followed by precipitation of minerals onto this matrix. An important factor in this process may be the activity and/or concentration of the urinary enzyme, urokinase, which would affect the level of urinary mucoproteins such as uromucoid. In support of this hypothesis, ELISA studies were conducted to investigate the urokinase concentrations in urine obtained from males (22-60 years) with and without renal stones. These results showed a significant decrease in urinary urokinase concentration of renal stone patients which, once again, underlines the possible involvement of urokinase in renal stone formation. Therefore, it seems logical to conclude that urokinase may play an integral role in this multifactorial disease. PMID:9247909

  1. English soccer teams' aggressive behavior when playing away from home.

    PubMed

    Thomas, Sion; Reeves, Colin; Smith, Andrew

    2006-04-01

    Speculation about key factors affecting home advantage still exists. The present study investigated aggressive behavior amongst English Football Premiership (soccer) players and its relation to home advantage. The frequency of aggressive behaviour, identified by the award of a penalty or disciplinary card (yellow for caution or red for dismissal) was analysed over 2000-2003. Chi-square analyses assessed whether a greater frequency of aggressive behavior was performed by teams away from home. In decided matches, teams playing away received significantly more cautions (yellow cards) than home teams. A further analysis of tied matches indicated that away teams received significantly more cautions (yellow cards) than home teams. No significant differences between home and away teams were found for dismissals and penalties awarded. Reasons for these findings are considered. PMID:16826650

  2. The Development of Play in Infants, Toddlers, and Young Children.

    ERIC Educational Resources Information Center

    Casby, Michael W.

    2003-01-01

    The first of two articles on play reviews the development of play in typically developing infants, toddlers, and young children, including Piaget's observations on the development of play; developmental play research following Piaget (research by Lunzer, Sinclair, Lezine, Lowe, Rosenblatt, Uzgiris and Hunt, Fenson and others, Watson and Fischer,…

  3. An Investigation of the Status of Outdoor Play

    ERIC Educational Resources Information Center

    Clements, Rhonda

    2004-01-01

    This study discusses the extent to which children in the USA today participate in active, outdoor play, compared with the previous generation. Eight hundred and thirty mothers nationwide were surveyed regarding their active, outdoor play experiences as children, as well as their children's play experiences today. The mother's play

  4. Needed: Playleaders--The Adult's Role in Children's Play.

    ERIC Educational Resources Information Center

    Benson, Tammy R.

    Research on play and its positive effect on children's development is abundant. Adults can ensure that children receive the full benefits of play by becoming effective playleaders and by guiding children through enriching play experiences. Adults need to let children know that play is an important part of their educational experience. This can be…

  5. Learning through Play: Portraits, Photoshop, and Visual Literacy Practices

    ERIC Educational Resources Information Center

    Honeyford, Michelle A.; Boyd, Karen

    2015-01-01

    Play has a significant role in language and literacy learning. However, even when valued in schools, opportunities for play are limited beyond early childhood education. This study of an after-school program for adolescents looks closely at several forms of play that students engaged in to produce self-portraits. The study suggests that play and…

  6. Children's Expressions of Exhilaration and Fear in Risky Play

    ERIC Educational Resources Information Center

    Sandseter, Ellen Beate Hansen

    2009-01-01

    Children naturally seek and conduct exciting forms of play that involve a risk of physical injury (risky play). Even though several prior studies give descriptions of risky play, none of them deeply explore children's expressions of how they experience different kinds of risky play. This study aims to do that. The results from video observations…

  7. Play-Based Interventions. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2012

    2012-01-01

    "Play-based interventions" are practices designed to improve socio-emotional, physical, language, and cognitive development through guided interactive play. During play sessions, an interventionist uses strategies including modeling, verbal redirection, reinforcement, and indirect instruction to sustain and encourage child play activities. Through…

  8. Coping with Ninja Turtle Play in My Kindergarten Classroom.

    ERIC Educational Resources Information Center

    Gronlund, Gaye

    1992-01-01

    Describes one teacher's efforts to understand children's aggressive play by reading literature that suggests children use play to construct meaning, viewing the Ninja Turtle cartoon show, and interviewing children about their superhero play. Male and female roles in play, aggression and violence, and television commercialism are discussed. (LB)

  9. Sex and Violence: Words at Play in the Shakespeare Classroom

    ERIC Educational Resources Information Center

    Paquette, Maryellen G.

    2007-01-01

    Maryellen G. Paquette reveals the excitement and learning that can occur when high school students are presented with multiple opportunities to play. Activities that employ playful language and the whole body allow students to embody, name, and identify with complicated emotions and situations in Shakespeare's plays. In addition, play can be…

  10. Playing to learn: case-injected genetic algorithms for learning to play computer games

    Microsoft Academic Search

    Sushil J. Louis; Chris Miles

    2005-01-01

    We use case-injected genetic algorithms (CIGARs) to learn to competently play computer strategy games. CIGARs periodically inject individuals that were successful in past games into the population of the GA working on the current game, biasing search toward known successful strategies. Computer strategy games are fundamentally resource allocation games characterized by complex long-term dynamics and by imperfect knowledge of the

  11. Does Play Matter to Parents? Taiwanese Parents' Perceptions of Child's Play

    ERIC Educational Resources Information Center

    Lin, Yen-Chun; Yawkey, Thomas D.

    2013-01-01

    The main purpose of this study was to gain an understanding of Taiwanese parents' perceptions of child's play. Data were collected via parent questionnaires. To ensure greater variability in parents' backgrounds, kindergartens with families from different social backgrounds were recruited. A total sample of 142 parents with…

  12. Playing with violence: Gamers’ social construction of violent video game play as tolerable deviance

    Microsoft Academic Search

    Fern M. Delamere; Susan M. Shaw

    2006-01-01

    Relatively little research has focused on leisure pastimes that include violence. The current study explores one increasingly popular leisure activity: violent video games. Regardless of the simulated violence and socially anomic behaviour in games, they have become a socially accepted leisure activity. That is, whereas there is a degree of social concern, unease, and sometimes disdain about violent game play,

  13. The Need for Play & Play-Like Activities in the Junior Classroom.

    ERIC Educational Resources Information Center

    Silver, Allan

    1992-01-01

    Draws from personal experiences in teaching a fourth-grade class in Canada to highlight the benefits for students of incorporating into the curriculum such playlike activities as shaping plasticine models, painting, cutting and pasting, and playing games. Identifies skills reinforced by particular activities and the benefits of the activities to…

  14. "Play and Culture Studies, Vol. 2: Play Contexts Revisited," by Stuart Reifel, Ed. Book Review.

    ERIC Educational Resources Information Center

    Bergen, Doris

    2000-01-01

    Notes that variety and difference in writing styles, methodology, and theoretical perspectives are both the greatest strength and greatest limitation of this book containing articles on child, adult, and animal play written by authors from education, psychology, anthropology, and sociology. Suggests that readers can gain theoretical and…

  15. The Transfer of Learning from Play Practices to Game Play in Young Adult Soccer Players

    ERIC Educational Resources Information Center

    Holt, Josh E.; Ward, Phillip; Wallhead, Tristan L.

    2006-01-01

    Background: Physical educators and coaches face an ongoing problem of presenting fun and enjoyable practices that also provide efficient learning of technical and tactical sports skills. Effective instruction also promotes the transfer of learning from practice tasks to the real game. Play Practice (PP) describes a structure for teaching sports…

  16. Energy Expenditure during Physically Interactive Video Game Playing in Male College Students with Different Playing Experience

    ERIC Educational Resources Information Center

    Sell, Katie; Lillie, Tia; Taylor, Julie

    2008-01-01

    Objective: Researchers have yet to explore the effect of physically interactive video game playing on energy expenditure, despite its potential for meeting current minimal daily activity and energy expenditure recommendations. Participants and Methods: Nineteen male college students-12 experienced "Dance Dance Revolution" (DDR) players and 7…

  17. A Staged Reading of the Play: And the Sun Stood Still: A Play about Nicolaus Copernicus

    NASA Astrophysics Data System (ADS)

    Sobel, Dava

    2013-04-01

    The aging Copernicus has shelved his wild idea of a Sun-centered cosmos, choosing instead to make peace with his bishop and concentrate on his private affairs. But a young stranger overturns those intentions when he arrives uninvited at Copernicus's door and pushes him to publish the dangerous theory.[4pt] Discussion of the play with the playwright after the staged reading.

  18. Multiple sclerosis: does Nogo play a role?

    PubMed

    Lee, Jae Young; Petratos, Steven

    2013-08-01

    Over the past decade, there has been substantial interest in the role of the integral myelin protein, Nogo-A, from fundamental neurobiological to clinical perspectives. It is now a well-known inhibitor of neurite outgrowth through its cognate receptor, Nogo receptor 1 (NgR1). Nogo-A can only signal through NgR1 upon heteromeric collaboration with p75(NTR), TROY, and LINGO-1 to induce axonal retraction. Both Nogo-A and NgR1 are expressed in multiple sclerosis (MS) lesions, suggesting that Nogo signaling may play a pivotal role in disease progression. There are several approaches targeting Nogo signaling in animal models of MS, and these therapeutic effects are currently in debate. One of the points of contention arises from the localization of the aforementioned signaling molecules, considering that MS and its animal models of disease are governed by inflammatory infiltration of the central nervous system. Furthermore, an impressive list of ligands for NgR1 continues to be compiled, possibly leading to disparities in the results obtained from the various animal models. In this review, we systematically dissect the complexities of Nogo signaling, which may be relevant in the future directions of neuroprotective therapies for MS. PMID:23423307

  19. PDZ Domain Proteins: Plug and Play!

    NSDL National Science Digital Library

    Claire Nourry (Marseille; Laboratory of Molecular Pharmacology REV)

    2003-04-22

    PDZ domains (an acronym from PSD-95, Dlg, and ZO-1) are protein modules found in many cytoplasmic proteins (more than 400 in humans); they are discussed in this STKE Review. They are associated with a wide range of other protein-protein interaction domains (for example, WW, PTB, LRR, SH3) or with domains that exhibit particular enzymatic activities (such as guanosine triphosphatases, serine-threonine kinases, phosphatases), and they participate in various intracellular protein networks. PDZ domains bind to very diverse carboxyl-termini of protein partners in a specific (and sometimes reversible) manner, which enables the formation of supramolecular networks. Scaffolding of proteins by PDZ domain proteins usually occurs at specific sites within the cell (such as the plasma membrane or the Golgi apparatus) and is frequently involved in localizing proteins to specialized subcellular compartments of polarized cells, such as the presynaptic terminals and postsynaptic densities of neurons and the basolateral or apical membranes of epithelial cells. Genetic models in invertebrates and vertebrates that are now available for some PDZ proteins illuminate the large set of biological processes in which this protein family is involved, from the establishment and maintenance of the cytoarchitecture to signaling events. Accordingly, defects of PDZ proteins that play a central role in tissue homeostasis result in pathological conditions including cancer and developmental abnormalities. The simplicity of PDZ domain interactions has enabled the design of pharmacological inhibitors of potential therapeutic interest.

  20. College Coursework on Children's Play and Future Early Childhood Educators' Intended Practices: The Mediating Influence of Perceptions of Play

    ERIC Educational Resources Information Center

    Jung, Eunjoo; Jin, Bora

    2015-01-01

    Research on the role of play coursework in future professionals' integration of play in education is essential in the colleges where future professionals are trained. However, the literature on this topic is very thin. It remains unclear whether college coursework on children's play is related to students' intentions to integrate play in early…