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1

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

SciTech Connect

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.

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

2

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

SciTech Connect

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

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

2009-02-27

3

The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System*  

PubMed Central

P2X7 receptors are involved not only in physiological functions but also in pathological brain processes. Although an increasing number of findings indicate that altered receptor expression has a causative role in neurodegenerative diseases and cancer, little is known about how expression of P2rx7 gene is controlled. Here we reported the first molecular and functional evidence that Specificity protein 1 (Sp1) transcription factor plays a pivotal role in the transcriptional regulation of P2X7 receptor. We delimited a minimal region in the murine P2rx7 promoter containing four SP1 sites, two of them being highly conserved in mammals. The functionality of these SP1 sites was confirmed by site-directed mutagenesis and Sp1 overexpression/down-regulation in neuroblastoma cells. Inhibition of Sp1-mediated transcriptional activation by mithramycin A reduced endogenous P2X7 receptor levels in primary cultures of cortical neurons and astrocytes. Using P2rx7-EGFP transgenic mice that express enhanced green fluorescent protein under the control of P2rx7 promoter, we found a high correlation between reporter expression and Sp1 levels in the brain, demonstrating that Sp1 is a key element in the transcriptional regulation of P2X7 receptor in the nervous system. Finally, we found that Sp1 mediates P2X7 receptor up-regulation in neuroblastoma cells cultured in the absence of serum, a condition that enhances chromatin accessibility and facilitates the exposure of SP1 binding sites. PMID:23139414

Garcia-Huerta, Paula; Diaz-Hernandez, Miguel; Delicado, Esmerilda G.; Pimentel-Santillana, Maria; Miras-Portugal, M? Teresa; Gomez-Villafuertes, Rosa

2012-01-01

4

The transcription factor Sp1 is responsible for aging-dependent altered nucleocytoplasmic trafficking.  

PubMed

Hyporesponsiveness to external signals, such as growth factors and apoptotic stimuli, is a cardinal feature of cellular senescence. We previously reported that an aging-dependent marked reduction in nucleocytoplasmic trafficking (NCT)-related genes could be responsible for this phenomenon. In searching for the mechanism, we identified the transcription factor, Sp1, as a common regulator of NCT genes, including various nucleoporins, importins, exportins, and Ran GTPase cycle-related genes. Sp1 knockdown led to a reduction of those genes in young human diploid fibroblast cells (HDF); Sp1 overexpression induced those genes in senescent cells. In addition, epidermal growth factor stimulation-induced p-ERK1/2 nuclear translocation and Elk-1 phosphorylation were severely impaired by Sp1 depletion in young HDFs; Sp1 overexpression restored the nuclear translocation of p-ERK1/2 in senescent HDFs. Furthermore, we observed that Sp1 protein levels were decreased in senescent cells, and H(2) O(2) treatment decreased Sp1 levels in a proteasome-dependent manner. In addition, O-GlcNAcylation of Sp1 was decreased in senescent cells as well as in H(2) O(2) -treated cells. Taken together, these results suggest that Sp1 could be a key regulator in the control of NCT genes and that reactive oxygen species-mediated alteration in Sp1 stability may be responsible for the generalized repression of those genes, leading to formation of the senescence-dependent functional nuclear barrier, resulting in subsequent hyporesponsiveness to external signals. PMID:23013401

Kim, Sung Y; Kang, Hyun T; Han, Jeong A; Park, Sang C

2012-12-01

5

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

SciTech Connect

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.

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

6

Negative Regulation of DsbA-L Gene Expression by the Transcription Factor Sp1.  

PubMed

Disulfide-bond A oxidoreductase-like protein (DsbA-L) possesses beneficial effects such as promoting adiponectin multimerization and stability, increasing insulin sensitivity, and enhancing energy metabolism. The expression level of DsbA-L is negatively correlated with obesity in mice and humans, but the underlying mechanisms remain unknown. To address this question, we generated reporter gene constructs containing the promoter sequence of the mouse DsbA-L gene. Deletion analysis showed that the proximal promoter of mouse DsbA-L is located between -186 and -34 bp relative to the transcription start site. In silico analysis identified a putative Sp1 transcription factor binding site in the first intron of the DsbA-L gene. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis indicated that Sp1 bound to this intron region in vitro and in intact cells. Overexpression of Sp1 or suppressing Sp1 expression by siRNA reduced or increased DsbA-L promoter activity, respectively. The binding activity of Sp1 was gradually decreased during 3T3-L1 cell differentiation and was significantly increased in adipose tissues of obese mice. Our results identify Sp1 as an inhibitor of DsbA-L gene transcription, and the Sp1-mediated inhibition of DsbA-L gene expression may provide a mechanism underlying obesity-induced adiponectin downregulation and insulin resistance. PMID:25024375

Fang, Qichen; Yang, Wenjing; Li, Huating; Hu, Wenxiu; Chen, Lihui; Jiang, Shan; Dong, Kun; Song, Qianqian; Wang, Chen; Chen, Shuo; Liu, Feng; Jia, Weiping

2014-12-01

7

C-terminal in Sp1-like artificial zinc-finger proteins plays crucial roles in determining their DNA binding affinity  

PubMed Central

Background It is well known that the C-terminal zinc-finger-3 in transcription factor Sp1 contributes more than the N-terminal zinc-finger-1 in determining Sp1’s DNA binding capacity. Sp1-like artificial poly-zinc-finger proteins (ZFPs) are powerful biotechnological tools for gene-specific recognization and manipulation. It is important to understand whether the C-terminal fingers in the Sp1-like artificial ZFPs remain crucial for their DNA binding ability. Recently, a set of p16 promoter-specific seven-ZFPs (7ZFPs) has been constructed to reactivate the expression of methylation-silenced p16. These 7ZFPs contain one N-terminal three-zinc-finger domain of Sp1 (3ZF), two Sp1-like two-zinc-finger domains derived from the Sp1 finger-2 and finger-3 (2ZF) in the middle and C-terminal regions. Results In the present study, sets of variants for several representative 7ZFPs with the p16-binding affinity were further constructed. This was accomplished through finger replacements and key amino acid mutations in the N-terminal fingers, C-terminal fingers, and linker peptide, respectively. Their p16-binding activity was analysed using gel mobility shift assays. Results showed that the motif replacement or a key amino acid mutation (S?>?R) at position +2 of the ?-helix in the C-terminal 2ZF domain completely abolished their p16-binding affinity. Deletion of three amino acids in a consensus linker (TGEKP?>?TG) between finger-7 and the 6 × Histidine-tag in the C-terminal also dramatically abolished their binding affinity. In contrast, the replacement of the finger-3 in the N-terminal 3ZF domain did not affect their binding affinity, but decreased their binding stability. Conclusions Altogether, the present study show that the C-terminal region may play crucial roles in determining the DNA binding affinity of Sp1-like artificial ZFPs. PMID:24289163

2013-01-01

8

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

E-print Network

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

Timmer, Jens

9

A crucial role for the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification  

PubMed Central

Mammalian development is regulated by the interplay of tissue-specific and ubiquitously expressed transcription factors, such as Sp1. Sp1 knockout mice die in utero with multiple phenotypic aberrations, but the underlying molecular mechanism of this differentiation failure has been elusive. Here, we have used conditional knockout mice as well as the differentiation of mouse ES cells as a model with which to address this issue. To this end, we examined differentiation potential, global gene expression patterns and Sp1 target regions in Sp1 wild-type and Sp1-deficient cells representing different stages of hematopoiesis. Sp1?/? cells progress through most embryonic stages of blood cell development but cannot complete terminal differentiation. This failure to fully differentiate is not seen when Sp1 is knocked out at later developmental stages. For most Sp1 target and non-target genes, gene expression is unaffected by Sp1 inactivation. However, Cdx genes and multiple Hox genes are stage-specific targets of Sp1 and are downregulated at an early stage. As a consequence, expression of genes involved in hematopoietic specification is progressively deregulated. Our work demonstrates that the early absence of active Sp1 sets a cascade in motion that culminates in a failure of terminal hematopoietic differentiation and emphasizes the role of ubiquitously expressed transcription factors for tissue-specific gene regulation. In addition, our global side-by-side analysis of the response of the transcriptional network to perturbation sheds a new light on the regulatory hierarchy of hematopoietic specification. PMID:24850855

Gilmour, Jane; Assi, Salam A.; Jaegle, Ulrike; Kulu, Divine; van de Werken, Harmen; Clarke, Deborah; Westhead, David R.; Philipsen, Sjaak; Bonifer, Constanze

2014-01-01

10

A crucial role for the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification.  

PubMed

Mammalian development is regulated by the interplay of tissue-specific and ubiquitously expressed transcription factors, such as Sp1. Sp1 knockout mice die in utero with multiple phenotypic aberrations, but the underlying molecular mechanism of this differentiation failure has been elusive. Here, we have used conditional knockout mice as well as the differentiation of mouse ES cells as a model with which to address this issue. To this end, we examined differentiation potential, global gene expression patterns and Sp1 target regions in Sp1 wild-type and Sp1-deficient cells representing different stages of hematopoiesis. Sp1(-/-) cells progress through most embryonic stages of blood cell development but cannot complete terminal differentiation. This failure to fully differentiate is not seen when Sp1 is knocked out at later developmental stages. For most Sp1 target and non-target genes, gene expression is unaffected by Sp1 inactivation. However, Cdx genes and multiple Hox genes are stage-specific targets of Sp1 and are downregulated at an early stage. As a consequence, expression of genes involved in hematopoietic specification is progressively deregulated. Our work demonstrates that the early absence of active Sp1 sets a cascade in motion that culminates in a failure of terminal hematopoietic differentiation and emphasizes the role of ubiquitously expressed transcription factors for tissue-specific gene regulation. In addition, our global side-by-side analysis of the response of the transcriptional network to perturbation sheds a new light on the regulatory hierarchy of hematopoietic specification. PMID:24850855

Gilmour, Jane; Assi, Salam A; Jaegle, Ulrike; Kulu, Divine; van de Werken, Harmen; Clarke, Deborah; Westhead, David R; Philipsen, Sjaak; Bonifer, Constanze

2014-06-01

11

Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1  

PubMed Central

PAX6 is a transcription factor that plays a major role in ocular morphogenesis. PAX6 is expressed in the eye, central nervous system and pancreas. Two alternative promoters, P0 and P1, which are differentially regulated during development, drive PAX6 transcription. We identified a 57 bp cis-regulatory element in exon 1 of the human PAX6 gene exon 1 enhancer (EIE). EIE enhances P1-driven PAX6 expression. Three regions in E1E (E1E-1, E1E-2 and E1E-3) have sequence similarities with binding sites of transcription factors ARP-1, Isl-1 and SEF, respectively. As shown by electrophoretic mobility shift assays, E1E-3, but not E1E-1 or E1E-2, bound to proteins in nuclear extracts of human glioma cells and transcription factor SEF bound to E1E-3. As shown by transient transfection experiments, deletion or site-specific mutations in E1E-3 dramatically decreased P1 promoter activity. Mutations in E1E-2, however, did not affect function of the P1 promoter. Co-transfection of SEF and PAX6 promoter–reporter constructs showed that SEF up-regulates PAX6 gene expression through the P1 promoter. Two Sp1 sites in the E1E region were also shown to be important by transient co-transfection assays. Data from immunoprecipitation and transient transfection assays demonstrated that SEF and Sp1 interacted in vitro and may act together in vivo to regulate PAX6 expression. PMID:11574690

Zheng, Jessica B.; Zhou, Yi-Hong; Maity, Tapati; Liao, Warren S.-L.; Saunders, Grady F.

2001-01-01

12

Transcriptional Regulation of the Novel Monoamine Oxidase Renalase: Crucial Roles of Transcription Factors Sp1, STAT3, and ZBP89.  

PubMed

Renalase, a novel monoamine oxidase, is emerging as an important regulator of cardiovascular, metabolic, and renal diseases. However, the mechanism of transcriptional regulation of this enzyme remains largely unknown. We undertook a systematic analysis of the renalase gene to identify regulatory promoter elements and transcription factors. Computational analysis coupled with transfection of human renalase promoter/luciferase reporter plasmids (5'-promoter-deletion constructs) into various cell types (HEK-293, IMR32, and HepG2) identified two crucial promoter domains at base pairs -485 to -399 and -252 to -150. Electrophoretic mobility shift assays using renalase promoter oligonucleotides with and without potential binding sites for transcription factors Sp1, STAT3, and ZBP89 displayed formation of specific complexes with HEK-293 nuclear proteins. Consistently, overexpression of Sp1, STAT3, and ZBP89 augmented renalase promoter activity; additionally, siRNA-mediated downregulation of Sp1, STAT3, and ZBP89 reduced the level of endogenous renalase transcription as well as the transfected renalase promoter activity. In addition, chromatin immunoprecipitation assays showed in vivo interactions of these transcription factors with renalase promoter. Interestingly, renalase promoter activity was augmented by nicotine and catecholamines; while Sp1 and STAT3 synergistically activated the nicotine-induced effect, Sp1 appeared to enhance epinephrine-evoked renalase transcription. Moreover, renalase transcript levels in mouse models of human essential hypertension were concomitantly associated with endogenous STAT3 and ZBP89 levels, suggesting crucial roles for these transcription factors in regulating renalase gene expression in cardiovascular pathological conditions. PMID:25295465

Sonawane, Parshuram J; Gupta, Vinayak; Sasi, Binu K; Kalyani, Ananthamohan; Natarajan, Bhargavi; Khan, Abrar A; Sahu, Bhavani S; Mahapatra, Nitish R

2014-11-11

13

Interaction of transcription factor Sp1 with the promoter of the gene for the multifunctional protein disulphide isomerase polypeptide.  

PubMed Central

Protein disulphide isomerase (PDI) is a unique polypeptide which resides in the lumen of the endoplasmic reticulum and also functions as the beta-subunit of prolyl 4-hydroxylase, as a cellular thyroid hormone-binding protein, as the smaller subunit of the microsomal triacylglycerol transfer protein complex, as a dehydroascorbate reductase and as a protein that binds various peptides in a specific manner. We have recently demonstrated that the promoter of the PDI gene contains six CCAAT boxes and other elements which are needed for efficient transcription. We now demonstrate that purified human recombinant transcription factor Sp1 interacts with two perfect GGGCGG sequences and three other GC-rich elements of the PDI promoter. Sp1 also appears to participate in the regulation of PDI gene expression, since overexpression of Sp1 stimulated PDI promoter activity in HeLa cells and mutations introduced into each of these Sp1-binding sites separately reduced the promoter strength, although even the largest decrease was only about 50%. These results support our view that expression of the gene for this polypeptide with multiple functions is secured by several regulatory elements, some of which are functionally redundant. Images Figure 2 PMID:8503862

Tasanen, K; Oikarinen, J; Kivirikko, K I; Pihlajaniemi, T

1993-01-01

14

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

PubMed Central

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

Amodio, N; Di Martino, M T; Foresta, U; Leone, E; Lionetti, M; Leotta, M; Gulla, 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

15

Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?  

PubMed Central

Background Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer. In the majority of thyroid cancers, however, iodide uptake is reduced, probably as a result of decreased NIS protein expression. Methods To identify the mechanisms that negatively affect NIS expression in thyroid tumors, we performed electrophoresis mobility shift assays and immunoblot analysis of nuclear protein extracts from normal and tumoral thyroid tissues from 14 unrelated patients. Results Two proteins closely related to the transcription factors AP2 and Sp1 were identified in the nuclear extracts. Expression of both AP2 and Sp1 in nuclear extracts from thyroid tumors was significantly higher than that observed in corresponding normal tissues. Conclusion These observations raise the possibility that NIS expression, and subsequently iodide transport, are reduced in thyroid tumors at least in part owing to alterations in the binding activity of AP2 and Sp1 transcription factors to NIS promoter. PMID:12475396

Chiefari, Eusebio; Brunetti, Antonio; Arturi, Franco; Bidart, Jean-Michel; Russo, Diego; Schlumberger, Martin; Filetti, Sebastiano

2002-01-01

16

Transcription factor Sp1 regulates T-type Ca(2+) channel CaV 3.1 gene expression.  

PubMed

Voltage-gated T-type Ca(2+) (CaV 3) channels mediate a number of physiological events in developing and mature cells, and are implicated in neurological and cardiovascular diseases. In mammals, there are three distinct T-channel genes (CACNA1G, CACNA1H, and CACNA1I) encoding proteins (CaV 3.1-CaV 3.3) that differ in their localization as well as in molecular, biophysical, and pharmacological properties. The CACNA1G is a large gene that contains 38 exons and is localized in chromosome 17q22. Only basic characteristics of the CACNA1G gene promoter region have been investigated classifying it as a TATA-less sequence containing several potential transcription factor-binding motifs. Here, we cloned and characterized a proximal promoter region and initiated the analysis of transcription factors that control CaV 3.1 channel expression using the murine Cacna1g gene as a model. We isolated a ?1.5?kb 5'-upstream region of Cacna1g and verified its transcriptional activity in the mouse neuroblastoma N1E-115 cell line. In silico analysis revealed that this region possesses a TATA-less minimal promoter that includes two potential transcription start sites and four binding sites for the transcription factor Sp1. The ability of one of these sites to interact with the transcription factor was confirmed by electrophoretic mobility shift assays. Consistent with this, Sp1 over-expression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents expressed in the N1E-115 cells. These results provide new insights into the molecular mechanisms that control CaV 3.1 channel expression. PMID:23868804

González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Felix, Ricardo

2014-05-01

17

A factor analysis of young children's play  

Microsoft Academic Search

The Play Rating Scale (PRS) was used to observe 2400 threeto five?year?old children's play behaviors. Factor analysis clearly identified two factors, the first dominated by communication of ideas through parallel play in the physical, manipulative and dramatic forms of educational play and the second by participation in physical and in communicative block play. Each scale was reliable and correlations among

Olivia N. Saracho

1993-01-01

18

Specificity Protein 1 (Sp1)-dependent Activation of the Synapsin I Gene (SYN1) Is Modulated by RE1-silencing Transcription Factor (REST) and 5?-Cytosine-Phosphoguanine (CpG) Methylation*  

PubMed Central

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

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

2013-01-01

19

Regulation of Transcription Factors and Repression of Sp1 by Prolactin Signaling Through the Short Isoform of Its Cognate Receptor  

PubMed Central

Prolactin (PRL) affects the development and function of the reproductive system by binding to two types of receptors, which differ by the size of their intracellular domain in rodents. Whereas the signaling pathway through the long form of the receptor (PRL-RL) is well characterized, signaling through the short form (PRL-RS) remains obscure. In this investigation, we examined transcription factors regulated by PRL in the ovary and decidua of mice expressing only PRL-RS in a PRL receptor null background. These mice provide a powerful in vivo model to study the selective signaling mechanism of PRL through PRL-RS independent of PRL-RL. We also examined the regulation of transcription factors in ovarian and uterine cell lines stably transfected with PRL-RS or PRL-RL. We focused our investigation on transcription factors similarly regulated in both these tissues and clearly established that signaling through PRL-RS does not activate the JaK/Stat in vivo but leads to severe down-regulation of Sp1 expression, DNA binding activity, and nuclear localization, events that appear to involve the calmodulin-dependent protein kinase pathway. Our in vivo and in culture data demonstrate that the PRL-RS activates a signaling pathway distinct from that of the PRL-RL. PMID:19342455

Devi, Y. Sangeeta; Shehu, Aurora; Stocco, Carlos; Halperin, Julia; Le, Jamie; Seibold, Anita M.; Lahav, Michal; Binart, Nadine; Gibori, Geula

2009-01-01

20

Sp1 Transcription Factor Interaction with Accumulated Prelamin A Impairs Adipose Lineage Differentiation in Human Mesenchymal Stem Cells: Essential Role of Sp1 in the Integrity of Lipid Vesicles  

PubMed Central

Lamin A (LMNA)-linked lipodystrophies may be either genetic (associated with LMNA mutations) or acquired (associated with the use of human immunodeficiency virus protease inhibitors [PIs]), and in both cases they share clinical features such as anomalous distribution of body fat or generalized loss of adipose tissue, metabolic alterations, and early cardiovascular complications. Both LMNA-linked lipodystrophies are characterized by the accumulation of the lamin A precursor prelamin A. The pathological mechanism by which prelamin A accumulation induces the lipodystrophy associated phenotypes remains unclear. Since the affected tissues in these disorders are of mesenchymal origin, we have generated an LMNA-linked experimental model using human mesenchymal stem cells treated with a PI, which recapitulates the phenotypes observed in patient biopsies. This model has been demonstrated to be a useful tool to unravel the pathological mechanism of the LMNA-linked lipodystrophies, providing an ideal system to identify potential targets to generate new therapies for drug discovery screening. We report for the first time that impaired adipogenesis is a consequence of the interaction between accumulated prelamin A and Sp1 transcription factor, sequestration of which results in altered extracellular matrix gene expression. In fact, our study shows a novel, essential, and finely tuned role for Sp1 in adipose lineage differentiation in human mesenchymal stem cells. These findings define a new physiological experimental model to elucidate the pathological mechanisms LMNA-linked lipodystrophies, creating new opportunities for research and treatment not only of LMNA-linked lipodystrophies but also of other adipogenesis-associated metabolic diseases. PMID:23197810

Ruiz de Eguino, Garbine; Infante, Arantza; Schlangen, Karin; Aransay, Ana M.; Fullaondo, Ane; Soriano, Mario; Garcia-Verdugo, Jose Manuel; Martin, Angel G.

2012-01-01

21

Factors affecting mother-child play  

E-print Network

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...

Welch, Jennifer Colleen

2012-06-07

22

Transcription factor-pathway co-expression analysis reveals cooperation between SP1 and ESR1 on dysregulating cell cycle arrest in non-hyperdiploid multiple myeloma  

PubMed Central

Multiple myeloma is a hematological cancer of plasma B-cells and remains incurable. Two major subtypes of myeloma, hyperdiploid (HMM) and non-hyperdiploid myeloma (NHMM), have distinct chromosomal alterations and different survival outcomes. Transcription factors (TrFs) have been implicated in myeloma oncogenesis but their dysregulation in myeloma subtypes are less studied. Here we develop a TrF-pathway co-expression analysis to identify altered co-expression between two sample types. We apply the method to the two myeloma subtypes and the cell cycle arrest pathway, which is significantly differentially expressed between the two subtypes. We find that TrFs MYC, NF-?B and HOXA9 have significantly lower co-expression with cell cycle arrest in HMM, co-occurring with their over-activation in HMM. In contrast, TrFs ESR1, SP1 and E2F1 have significantly lower co-expression with cell cycle arrest in NHMM. SP1 ChIP targets are enriched by cell cycle arrest genes. These results motivate a cooperation model of ESR1 and SP1 in regulating cell cycle arrest, and a hypothesis that their over-activation in NHMM disrupts proper regulation of cell cycle arrest. Co-targeting ESR1 and SP1 shows a synergistic effect on inhibiting myeloma proliferation in NHMM cell lines. Therefore, studying TrF-pathway co-expression dysregulation in human cancers facilitates forming novel hypotheses towards clinical utility. PMID:23925045

Wang, Xujun; Yan, Zhenyu; Fulciniti, Mariateresa; Li, Yingxiang; Gkotzamanidou, Maria; Amin, Samir B; Shah, Parantu K; Zhang, Yong

2014-01-01

23

A novel cis-acting element controlling the rat CYP2D5 gene and requiring cooperativity between C/EBP beta and an Sp1 factor.  

PubMed Central

The rat CYP2D5 gene encodes a cytochrome P450 and is expressed in liver cells. Its expression commences a few days after birth, and maximal mRNA levels are achieved when animals reach puberty. Transfection and DNA binding studies were performed to investigate the mechanism controlling developmentally programmed, liver-specific expression of CYP2D5. Transfection studies using a series of CYP2D5 upstream DNA chloramphenicol acetyltransferase gene fusion constructs identified a segment of DNA between nucleotides -55 and -156 that conferred transcriptional activity in HepG2 cells. Activity was markedly increased by cotransfection with a vector expressing C/EBP beta but was unaffected by vectors producing other liver-enriched transcription factors (C/EBP alpha, HNF-1 alpha, and DBP). DNase I footprinting revealed a region protected by both HepG2 and liver cell nuclear extracts between nucleotides -83 and -112. This region displayed some sequence similarity to the Sp1 consensus sequence and was able to bind the Sp1 protein, as assessed by a gel mobility shift assay. The role of Sp1 in CYP2D5 transcription was confirmed by trans activation of the 2D5-CAT construct in Drosophila melanogaster cells by using an Sp1 expression vector. C/EBP beta alone was unable to directly bind the -83 to -112 region of the promoter but was able to produce a ternary complex when combined with HepG2 nuclear extracts or recombinant human Sp1. C/EBP alpha was unable to substitute for C/EBP beta in forming this ternary complex. A poor C/EBP binding site is present adjacent to the Sp1 site, and mutagenesis of this site abolished formation of the ternary complex with the CYP2D5 regulatory region. These result establish that two transcription factors can work in conjunction, possibly by protein-protein interaction, to activate the CYP2D5 gene. Images PMID:8289814

Lee, Y H; Yano, M; Liu, S Y; Matsunaga, E; Johnson, P F; Gonzalez, F J

1994-01-01

24

Arsenic trioxide-mediated growth inhibition in gallbladder carcinoma cells via down-regulation of Cyclin D1 transcription mediated by Sp1 transcription factor  

SciTech Connect

Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of drug stimuli. Here, we demonstrated that arsenic trioxide inhibited the proliferation of gallbladder carcinoma in vivo and in vitro as well as the transcription of cell cycle-related protein Cyclin D1. And, Cyclin D1 overexpression inhibited the negative role of arsenic trioxide in cell cycle progression. We further explored the mechanisms by which arsenic trioxide affected Cyclin D1 transcription and found that the Sp1 transcription factor was down-regulated by arsenic trioxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggested that arsenic trioxide inhibited gallbladder carcinoma cell proliferation via down-regulation of Cyclin D1 transcription in a Sp1-dependent manner, which provided a new mechanism of arsenic trioxide-involved cell proliferation and may have important therapeutic implications in gallbladder carcinoma patients.

Ai, Zhilong [Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Lu, Weiqi [Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Ton, Saixiong [Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Liu, Houbao [Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Sou, Tao [Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shen, Zhenbin [Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Qin, Xinyu [Zhongshan Hospital, Fudan University, Shanghai 200032 (China)]. E-mail: smc_jjh@yahoo.com.cn

2007-08-31

25

Co-operative interactions between NFAT (nuclear factor of activated T cells) c1 and the zinc finger transcription factors Sp1/Sp3 and Egr-1 regulate MT1-MMP (membrane type 1 matrix metalloproteinase) transcription by glomerular mesangial cells.  

PubMed Central

The transition of normally quiescent glomerular MCs (mesangial cells) to a highly proliferative phenotype with characteristics of myofibroblasts is a process commonly observed in inflammatory diseases affecting the renal glomerulus, the ultimate result of which is glomerulosclerosis. Generation of proteolytically active MMP (matrix metalloproteinase)-2 by the membrane-associated membrane type 1 (MT1)-MMP is responsible for the transition of mesangial cells to the myofibroblast phenotype [Turck, Pollock, Lee, Marti and Lovett (1996) J. Biol. Chem. 271, 15074-15083]. In the present study, we show that the expression of MT1-MMP within the context of MCs is mediated by three discrete cis -acting elements: a proximal non-canonical Sp1 site that preferentially binds Sp1; an overlapping Sp1/Egr-1-binding site that preferentially binds Egr-1; and a more distal binding site for the NFAT (nuclear factor of activated T cells) that binds the NFAT c1 isoform present in MC nuclear extracts. Transfection with an NFAT c1 expression plasmid, or activation of calcineurin with a calcium ionophore, yielded major increases in NFAT c1 nuclear DNA-binding activity, MT1-MMP transcription and protein synthesis, which were additive with the lower levels of transactivation provided by the proximal Sp1 and the overlapping Sp1/Egr-1 sites. Specific binding of NFAT c1 to the MT1-MMP promoter was confirmed by chromatin immunoprecipitation studies, while MT1-MMP expression was suppressed by treatment with the calcineurin inhibitor, cyclosporin A. These studies are the first demonstration that a specific NFAT isoform enhances transcription of an MMP (MT1-MMP) that plays a major role in the proteolytic events that are a dominant feature of acute glomerular inflammation. Suppression of MT1-MMP by commonly used calcineurin inhibitors may play a role in the development of renal fibrosis following renal transplantation. PMID:14979875

Alfonso-Jaume, Maria Alejandra; Mahimkar, Rajeev; Lovett, David H

2004-01-01

26

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

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

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

1999-01-01

27

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

SciTech Connect

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

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

2013-05-17

28

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

PubMed

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

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

2014-01-01

29

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

PubMed Central

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

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

2014-01-01

30

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

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

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

31

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

PubMed Central

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

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

2002-01-01

32

Co-stimulation of the Bone-related Runx2 P1 Promoter in Mesenchymal Cells by SP1 and ETS Transcription Factors at Polymorphic Purine-rich DNA Sequences (Y-repeats)*S?  

PubMed Central

Transcriptional control of Runx2 gene expression through two alternative promoters (P1 and P2) is critical for the execution of its function as an osteogenic cell fate determining factor. In all vertebrates examined to date, the bone related P1 promoter contains a purine-rich region (-303 to -128 bp in the rat) that separates two regulatory domains. The length of this region differs dramatically between species even within the same order. Using deletion analysis, we show that part of this purine-rich region (-200 to -128) containing a duplicated element (Y-repeat) positively regulates Runx2 P1 transcription. Electrophoretic mobility assays and chromatin immunoprecipitations reveal that Y-repeat binds at least two different classes of transcription factors related to GC box binding proteins (e.g. SP1 and SP7/Osterix) and ETS-like factors (e.g. ETS1 and ELK1). Forced expression of SP1 increases Runx2 P1 promoter activity through the Y-repeats, and small interfering RNA depletion of SP1 decreases Runx2 expression. Similarly, exogenous expression of wild type ELK1, but not a defective mutant that cannot be phosphorylated, enhances Runx2 gene expression. SP1 is most abundant in proliferating cells, and ELK1 is most abundant in postconfluent cells; during MC3T3-E1 osteoblast differentiation, both proteins are transiently co-expressed when Runx2 expression is enhanced. Taken together, our data suggest that basal Runx2 gene transcription is regulated by dynamic interactions between SP1 and ETS-like factors during progression of osteogenesis. PMID:19017640

Zhang, Ying; Hassan, Mohammad Q.; Xie, Rong-Lin; Hawse, John R.; Spelsberg, Thomas C.; Montecino, Martin; Stein, Janet L.; Lian, Jane B.; van Wijnen, Andre J.; Stein, Gary S.

2009-01-01

33

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

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

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

2003-01-01

34

Estrogen blocks M-CSF gene expression and osteoclast formation by regulating phosphorylation of Egr-1 and its interaction with Sp-1.  

PubMed Central

Central to the pathogenesis of osteoporosis is the ability of estrogen deficiency to increase osteoclast formation by enhancing stromal cell production of the osteoclastogenic cytokine macrophage colony-stimulating factor (M-CSF). We report that stromal cells from ovariectomized mice exhibit increased casein kinase II-dependent phosphorylation of the nuclear protein Egr-1. Phosphorylated Egr-1 binds less avidly to the transcriptional activator Sp-1 and the resulting higher levels of free Sp-1 stimulate transactivation of the M-CSF gene. Estrogen replacement fails to block M-CSF mRNA expression and osteoclast formation in ovariectomized mice lacking Egr-1, confirming the critical role played by this transcription factor in mediating the antiosteoclastogenic effects of estrogen. Thus, by downregulating formation of a novel Egr-1/Sp-1 complex in stromal cells, estrogen deficiency results in enhanced levels of free Sp-1 and increased M-CSF gene expression and osteoclast formation. PMID:9819371

Srivastava, S; Weitzmann, M N; Kimble, R B; Rizzo, M; Zahner, M; Milbrandt, J; Ross, F P; Pacifici, R

1998-01-01

35

The Sp(1)-Kepler Problems  

E-print Network

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

Guowu Meng

2008-05-07

36

Play  

NASA Astrophysics Data System (ADS)

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

Harteveld, Casper

37

Nucleolin enhances internal ribosomal entry site (IRES)-mediated translation of Sp1 in tumorigenesis.  

PubMed

Our previous study indicated that specificity protein-1 (Sp1) is accumulated during hypoxia in an internal ribosomal entry site (IRES)-dependent manner. Herein, we found that the Sp1 was induced strongly at the protein level, but not in the mRNA level, in lung tumor tissue, indicating that translational regulation might contribute to the Sp1 accumulation during tumorigenesis. A further study showed that the translation of Sp1 was dramatically induced through an IRES-dependent pathway. RNA immunoprecipitation analysis of proteins bound to the 5'-untranslated region (5'-UTR) of Sp1 identified interacting protein - nucleolin. Knockdown of nucleolin significantly inhibited IRES-mediated translation of Sp1, suggesting that nucleolin positively facilitates Sp1 IRES activation. Further analysis of the interaction between nucleolin and the 5'-UTR of Sp1 mRNA revealed that the GAR domain was important for IRES-mediated translation of Sp1. Moreover, gefitinib, and LY294002 and MK2206 compounds inhibited IRES-mediated Sp1 translation, implying that activation of the epithelial growth factor receptor (EGFR) pathway via Akt activation triggers the IRES pathway. In conclusion, EGFR activation-mediated nucleolin phosphorylated at Thr641 and Thr707 was recruited to the 5'-UTR of Sp1 as an IRES trans-acting factor to modulate Sp1 translation during lung cancer formation. PMID:25173817

Hung, Chia-Yang; Yang, Wen-Bin; Wang, Shao-An; Hsu, Tsung-I; Chang, Wen-Chang; Hung, Jan-Jong

2014-12-01

38

Sp1 and CTF\\/NF1 Transcription Factors Are Involved in the Basal Expression of the Hmgi-c Proximal Promoter  

Microsoft Academic Search

HMGI-C is a nuclear architectural factor which is expressed during embryogenesis but not in adult tissues while it becomes re-expressed following neoplastic transformation. In this paper we identify the promoter region of the mouse Hmgi-c gene and by stepwise deletion of the 5? sequences we map the promoter activity of the most abundant transcript to a very short fragment containing

Alessandra Rustighi; Fiamma Mantovani; Alfredo Fusco; Vincenzo Giancotti; Guidalberto Manfioletti

1999-01-01

39

HDAC4 inhibits the transcriptional activation of mda-7/IL-24 induced by Sp1  

PubMed Central

Melanoma differentiation-associated gene/interleukin-24 (mda-7/IL-24) is a cytokine that can activate monocytes and T helper 2 cells. The expression of mda-7/IL-24 gradually fades with the progression of melanoma, and it is undetectable at the metastatic stage. Ectopic expression of mda-7/IL-24 selectively suppresses growth and induces apoptosis in cancer cells with little harm to normal cells. However, the transcriptional regulation of the mda-7/IL-24 gene has not been extensively studied. In this study, we show that the expression of mda-7/IL-24 was upregulated by the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate (NaBu), whereas it was downregulated by HDAC4. We also found that the histone acetylation level and the binding of the transcriptional factor Sp1 to the mad-7 promoter were reduced upon HDAC4 treatment. Moreover, the HDAC inhibitor TSA induced histone hyperacetylation and stimulated Sp1 binding to the mda-7/IL-24 promoter, which in turn enhanced the expression of mda-7/IL-24. Therefore, we conclude that histone acetylation modification plays an important role in the regulation of mda-7/IL-24 and that the transcription factor Sp1 participates in this process. PMID:20383178

Pan, Lina; Pan, Hong; Jiang, Hao; Du, Juan; Wang, Xiuli; Huang, Baiqu; Lu, Jun

2010-01-01

40

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

PubMed Central

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

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

2013-01-01

41

Arf induction by Tgf? is influenced by Sp1 and C/ebp? in opposing directions.  

PubMed

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

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

2013-01-01

42

The Play Factor: Effect of Social Skills Group Play Therapy on Adolescent African-American Males  

ERIC Educational Resources Information Center

The purpose of this study was to examine the effectiveness of Social Skills Group Play Therapy on remedying the social skills deficits of adolescent African-American males. Additionally, the study investigated whether age and grade level impacted the outcome of the intervention. The participants were adolescent African-American males ages 10 to…

Earls, Melissa K.

2009-01-01

43

Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer.  

PubMed

Colorectal cancer (CRC) is a serious public health problem that results due to changes of diet and various environmental stress factors in the world. Curcumin is a traditional medicine used for treatment of a wide variety of tumors. However, antimetastasis mechanism of curcumin on CRC has not yet been completely investigated. Here, we explored the underlying molecular mechanisms of curcumin on metastasis of CRC cells in vitro and in vivo. Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo. We found that curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells. Moreover, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT. These results suggest that curcumin executes its antimetastasis function through downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in CRC cells. PMID:23970932

Chen, Chun-Chieh; Sureshbabul, Munisamy; Chen, Huei-Wen; Lin, Yu-Shuang; Lee, Jen-Yi; Hong, Qi-Sheng; Yang, Ya-Chien; Yu, Sung-Liang

2013-01-01

44

Video Game Playing and Gambling in Adolescents: Common Risk Factors  

Microsoft Academic Search

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 playing and gambling there have been very few studies that have

Richard T. A. Wood; Rina Gupta; Jeffrey L. Derevensky; Mark Griffiths

2004-01-01

45

Sp1 and Sp3 mediate basal and serum-induced expression of human CENP-W.  

PubMed

Cancer-upregulated gene 2 (CUG2), which was named since it was originally identified as a putative oncogene up-regulated in various human cancers, was recently renamed CENP-W based on the new findings that it is a component of the centromeric complex playing a crucial role in the assembly of functional kinetochore complex during mitosis. To understand the transcriptional regulation of CENP-W, we analyzed its TATA-less promoter and identified a GC-rich putative Sp1 binding site located at -46 to -36 that was critical in CENP-W expression. Competitive electrophoretic gel mobility shift assay using mutated oligos and supershift assays with Sp1 and Sp3 antibodies demonstrated that both proteins specifically bound to this promoter region. Moreover, we found that CENP-W was highly induced by serum stimulation followed by serum deprivation, with Sp1 and Sp3 transcription factors involved in this transactivation. Taken together, our results suggest that Sp1 together with Sp3 may function as the main regulator of the basal and serum-induced transcription of CENP-W. PMID:20180024

Kim, Hyejin; Lee, Sunhee; Park, Byoungwoo; Che, Lihua; Lee, Soojin

2010-10-01

46

Video Game Playing and Gambling in Adolescents: Common Risk Factors  

ERIC Educational Resources Information Center

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…

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

2004-01-01

47

Factors Influencing Learning through Play in ICT Settings  

ERIC Educational Resources Information Center

Using a mixed method approach of questionnaires, observations and field notes, the authors have studied a number of settings during the past two years which have focussed on the development of ICT capability through play. Some of these have involved children identified as disaffected or disadvantaged, whilst others have involved initial teacher…

Kennewell, Steve; Morgan, Alex

2006-01-01

48

A Factor Analysis of Pre-school Children's Play Strategies and Cognitive Style.  

ERIC Educational Resources Information Center

Explores children's play as social behavior in relation to cognitive style and identifies the social factors underlying both young children's play and cognitive style. Indicates that field-dependent children participated more in social play activities, while field-independent children engaged in more nonsocial play activities. Discusses the…

Saracho, Olivia N.

1999-01-01

49

Factors associated with symbolic play development in preschoolers with hearing impairments and language processing delays  

Microsoft Academic Search

A child's ability to play is dependent on various factors, both internal and environmental. This study examines the relationships between symbolic play development in children, language development in children, parental role behaviors and parenting stress. This project is specifically concerned with the development of play in relation to these other factors in a population of hearing impaired and language processing

Jennifer A Maltz

2003-01-01

50

JMJD2A-dependent silencing of Sp1 in advanced breast cancer promotes metastasis by downregulation of DIRAS3.  

PubMed

Specificity protein 1(Sp1) is a ubiquitous transcription factor and is highly expressed in breast cancer. However, its expression pattern and role in breast cancer progression remain unclear. The purpose of this study is to examine the expression pattern of Sp1 and determine its role in breast cancer progression. Immunohistochemistry (IHC) was performed on breast cancer tissues to reveal the expression pattern of Sp1. Spearman rank correlation was used for clinical statistics. Gene and protein expressions were monitored by IHC analysis, quantitative polymerase chain reaction, and Western blot. Wound-healing and Transwell assays were conducted to assess the role of Sp1 in breast cancer. Co-immunoprecipitation, deletion mutagenesis, chromatin immunoprecipitation, and dual luciferase reporter gene assays were used for investigation of the regulatory network. Sp1 expression was downregulated in late stage breast cancer and in highly invasive breast cancer cell lines. Expression of Sp1 was negatively correlated with TNM staging (P = 0.002) and metastasis status (P = 0.023). Overexpression of Sp1 inhibited breast cancer cell migratory and invasive abilities, whereas knockdown of GTP-binding RAS-like 3 (DIRAS3, also known as ARHI, NOEY2) attenuated the inhibitory effects. Moreover, re-expression of DIRAS3 abolished Sp1 knockdown-mediated cell migration and invasion. Jumonji domain containing 2A (JMJD2A) inhibited Sp1 autoregulation and explains Sp1 expression pattern in breast cancer. Sp1 negatively regulated breast cancer metastasis by transcriptional activation of DIRAS3. Inhibition of Sp1 autoregulation by JMJD2A contributed to Sp1 expression pattern in breast cancer. Our findings provided evidence that targeted therapy against Sp1 might be useful in early stage breast cancer. However, in late stages, development of Sp1 activator may be more promising for breast cancer treatments. PMID:25193278

Li, Liliang; Gao, Pan; Li, Yuhua; Shen, Yiwen; Xie, Jianhui; Sun, Daming; Xue, Aimin; Zhao, Ziqin; Xu, Zude; Zhang, Mingchang; Li, Beixu; Jiang, Jieqing

2014-10-01

51

Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1) promoter and its regulation by Sp1  

PubMed Central

Background Activin receptor-like kinase 1 (ALK1) is a Transforming Growth Factor-? (TGF-?) receptor type I, mainly expressed in endothelial cells that plays a pivotal role in vascular remodelling and angiogenesis. Mutations in the ALK1 gene (ACVRL1) give rise to Hereditary Haemorrhagic Telangiectasia, a dominant autosomal vascular dysplasia caused by a haploinsufficiency mechanism. In spite of its patho-physiological relevance, little is known about the transcriptional regulation of ACVRL1. Here, we have studied the different origins of ACVRL1 transcription, we have analyzed in silico its 5'-proximal promoter sequence and we have characterized the role of Sp1 in the transcriptional regulation of ACVRL1. Results We have performed a 5'Rapid Amplification of cDNA Ends (5'RACE) of ACVRL1 transcripts, finding two new transcriptional origins, upstream of the one previously described, that give rise to a new exon undiscovered to date. The 5'-proximal promoter region of ACVRL1 (-1,035/+210) was analyzed in silico, finding that it lacks TATA/CAAT boxes, but contains a remarkably high number of GC-rich Sp1 consensus sites. In cells lacking Sp1, ACVRL1 promoter reporters did not present any significant transcriptional activity, whereas increasing concentrations of Sp1 triggered a dose-dependent stimulation of its transcription. Moreover, silencing Sp1 in HEK293T cells resulted in a marked decrease of ACVRL1 transcriptional activity. Chromatin immunoprecipitation assays demonstrated multiple Sp1 binding sites along the proximal promoter region of ACVRL1 in endothelial cells. Furthermore, demethylation of CpG islands, led to an increase in ACVRL1 transcription, whereas in vitro hypermethylation resulted in the abolishment of Sp1-dependent transcriptional activation of ACVRL1. Conclusions Our results describe two new transcriptional start sites in ACVRL1 gene, and indicate that Sp1 is a key regulator of ACVRL1 transcription, providing new insights into the molecular mechanisms that contribute to the expression of ACVRL1 gene. Moreover, our data show that the methylation status of CpG islands markedly modulates the Sp1 regulation of ACVRL1 gene transcriptional activity. PMID:20587022

2010-01-01

52

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

PubMed Central

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

2014-01-01

53

Young Mothers' Play with Their Toddlers: Individual Variability as a Function of Psychosocial Factors  

ERIC Educational Resources Information Center

There is no one style of parenting which characterizes young mothers as a group. In addition, life circumstances play an important role in shaping maternal behaviour. The aim of this study was to identify patterns of maternal play behaviour and contextual (social and personal) factors associated with these different patterns. In this study, 107…

Driscoll, Joan Riley; Easterbrooks, M. Ann

2007-01-01

54

HSF1 and Sp1 regulate FUT4 gene expression and cell proliferation in breast cancer cells.  

PubMed

Lewis Y (LeY) is a carbohydrate tumor-associated antigen. The majority of cancer cells derived from epithelial tissues express LeY type difucosylated oligosaccharides. Fucosyltransferase IV (FUT4) is an essential enzyme that catalyzes the synthesis of LeY oligosaccharides. In a previous study we reported that FUT4 is associated with cell proliferation; however, despite the important role of FUT4 in cancer proliferation and apoptosis, little is known about the mechanisms underlying the regulation of FUT4 transcription. In the current study we investigated the regulation of FUT4 transcription in human breast cancer. We compared the regulation of human FUT4 gene transcription in human breast cancer cells (MCF-7 and MDA-MB-231) using promoter/luciferase analyses. Using a series of promoter deletion constructs, we identified a potential regulatory site located between 0.8 and 1.6 kb of the FUT4 promoter. As shown by EMSA and ChIP analyses, heat-shock factor 1 (HSF1) and Sp1are required for FUT4 promoter activity. In addition, we explored the role of HSF1 and Sp1 on cell proliferation, and found that the ERK1/2 MAPK and PI3K/Akt signaling pathways regulate the expression of FUT4, which play a role in cell proliferation via HSF1 and Sp1. These results suggest that FUT4 is a target gene for HSF1 and Sp1 that is required for cell cycle progression in breast cancer epithelial cells. PMID:23959823

Yang, Xuesong; Wang, Jiao; Liu, Shuiai; Yan, Qiu

2014-01-01

55

Expression Patterns of SP1 and SP3 During Mouse Spermatogenesis  

PubMed Central

Because of their prominent roles in regulation of gene expression, it is important to understand how levels of Krüpple-like transcription factors SP1 and SP3 change in germ cells during spermatogenesis. Using immunological techniques we found that both factors decreased sharply during meiosis. SP3 declined during the leptotene to pachytene transition while SP1 fell somewhat later, as spermatocytes progressed beyond early pachytene. SP3 reappeared for a period in round spermatids. For Sp1 it is known that the transition to pachytene is accompanied by loss of the normal 8.2 kb mRNA and appearance of a prevalent 8.8 kb variant, which has not been well characterized. We have now shown that this pachytene-specific transcript contains a long, unspliced sequence from the first intron and that this sequence inhibits expression of a reporter, probably due to its many short open reading frames. A second testis-specific Sp1 transcript in spermatids of 2.4 kb has also been reported previously. Like the 8.8 kb variant, it is also translationally compromised. We have confirmed by Northern blotting that the 8.8, 8.2 and 2.4 kb variants account for the major testis Sp1 transcripts. Thus the unexpected decline of SP1 protein in the face of continuing Sp1 transcription is explained in large part by poor translation of both novel testis transcripts. As part of this work we also identified five additional minor Sp1 cap sites by 5? RACE, including a trans-spliced RNA originating from the Glcci1 gene. PMID:18417714

Ma, Wenli; Horvath, Gary C.; Kistler, Malathi K.; Kistler, W. Stephen

2008-01-01

56

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

PubMed Central

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

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

2013-01-01

57

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

PubMed

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

Diamond, Alex B; Solomon, Gary S

2014-09-01

58

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.

59

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

PubMed

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

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

2014-11-01

60

Risk Factors in Adolescence: The Case of Gambling, Videogame Playing, and the Internet  

Microsoft Academic Search

It has been noted that adolescents may be more susceptible to pathological gambling. Not only is it usually illegal, but it appears to be related to high levels of problem gambling and other delinquent activities such as illicit drug taking and alcohol abuse. This paper examines risk factors not only in adolescent gambling but also in videogame playing (which shares

Mark Griffiths; Richard T. A. Wood

2000-01-01

61

Involvement of Sp1 and microsatellite repressor sequences in the transcriptional control of the human CD30 gene.  

PubMed

CD30, as a member of the tumor necrosis factor (TNF) receptor family, is expressed on the surface of activated lymphoid cells. CD30 overexpression is a characteristic of lymphoproliferative diseases such as Hodgkin's/non-Hodgkin's lymphomas, embryonal carcinoma, and a number of Th2-associated diseases. The CD30 gene has been mapped to a region of the murine genome that is involved in susceptibility to systemic lupus erythematosus. Functionally, CD30 may play a role in the deletion of autoreactive T cells. We were interested in determining the molecular nature of CD30 overexpression. Sequence comparison has revealed significant identity between the TATA-less human and murine CD30 promoters; they share a number of common consensus binding motifs. Transfection assays identified three regions of transcriptional importance; the region between position -1.2 kb and -336 bp, containing a CCAT microsatellite sequence, a conserved Sp1 site at positions -43 to -38, and a downstream promoter element (DPE) at positions +24 to +29. EMSA and DNase I footprinting showed specific DNA-protein interactions of the CD30 promoter with the Sp1 site and the CCAT repeat region. The DPE element was shown to be essential for start site selection. We conclude that the conserved Sp1 site at -43 to -38 is associated with maximum reporter gene activity, the DPE element is required for start site selection, and the CCAT tetranucleotide repeats act to repress transcription. We also have shown that the microsatellite is multiallelic, when we screened a random healthy population. Further studies are required to determine whether microsatellite instability in the repressor predisposes susceptible individuals to CD30 overexpression. PMID:10793083

Croager, E J; Gout, A M; Abraham, L J

2000-05-01

62

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

PubMed

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

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

2014-09-01

63

Heat stress protection in Aspen sp1 transgenic Arabidopsis thaliana.  

PubMed

It is known that the stable protein 1 (SP1) detected in aspen plants remains soluble upon boiling and that sp1 expression in transgenic aspen is resistant to salt stress. Presently, we analyzed the effect of expression of SP1 in Arabidopsis thaliana plants and their response to high temperature stress. After 45 degrees C for 16 h, relative to wild type plants, sp1 transgenic plants exhibited stronger growth and were better in several physiological properties including chlorophyll, chlorophyll fluorescence, water content, proline content, and malondialdehyde content. These preliminarily results suggest that the over-expression of SP1 may notably enhance heat-tolerant level of transgenic A. thaliana plants. PMID:18510869

Zhu, Bo; Xiong, Ai-Sheng; Peng, Ri-He; Xu, Jing; Zhou, Jun; Xu, Jin-Tao; Jin, Xiao-Fen; Zhang, Yang; Hou, Xi-Lin; Yao, Quan-Hong

2008-05-31

64

PPARbeta/delta regulates the human SIRT1 gene transcription via Sp1.  

PubMed

NAD-dependent deacetylase SIRT1 is known to be activated by caloric restriction and is related to longevity. A natural polyphenolic compound resveratrol is also shown to increases SIRT1 activity and extends lifespan. However, the transcriptional regulation of SIRT1 gene has not completely examined in the context of metabolism. Thus, in this study, we characterized the 5' -flanking region of human SIRT1 gene. We first found that representative metabolic hormones and related factors (glucocorticoid, glucagon/cAMP, and insulin) did not show significant effect on SIRT1 gene transcription. PPARalpha and PPARgamma1 without/with their specific ligands did not have significant effect as well. In contrast, expression of PPARbeta/delta (PPARdelta markedly increased the 5' -promoter activity of SIRT1 gene, which was further amplified by the addition of GW501516, a selective PPARdelta agonist. Deletion/mutation mapping analyses failed to identify PPAR binding element but revealed the presence of canonical Sp1 binding site, which was conserved among species. The Sp1 site is functional, because Sp1 overexpresson significantly enhanced SIRT1 promoter activity, and the binding of Sp1 to the element was confirmed by EMSA and ChIP assays. Interestingly, specific Sp1 antagonist mithramycin completely abolished the PPARdelta-mediated induction of SIRT1 gene transcription. Altogether, our data suggest the predominant role of PPARdelta in the transcriptional regulation of SIRT1 gene. Furthermore, the effects of PPARdelta seem to be mediated by Sp1. We assume that, in vivo, starvation increases lipolysis-derived free fatty acid and activates PPARdelta and the resultant increase in SIRT1 expression, in addition to the activation by NAD and AMPK, facilitates the deacetylation of a variety of proteins involved in mitochondrial beta-oxidation pathway and cell survival. PMID:20160399

Okazaki, Mizuho; Iwasaki, Yasumasa; Nishiyama, Mitsuru; Taguchi, Takafumi; Tsugita, Makoto; Nakayama, Shuichi; Kambayashi, Machiko; Hashimoto, Kozo; Terada, Yoshio

2010-01-01

65

Kr?ppel-Like Factor KLF8 Plays a Critical Role in Adipocyte Differentiation  

PubMed Central

KLF8 (Krüppel-like factor 8) is a zinc-finger transcription factor known to play an essential role in the regulation of the cell cycle, apoptosis, and differentiation. However, its physiological roles and functions in adipogenesis remain unclear. In the present study, we show that KLF8 acts as a key regulator controlling adipocyte differentiation. In 3T3-L1 preadipocytes, we found that KLF8 expression was induced during differentiation, which was followed by expression of peroxisome proliferator-activated receptor ? (PPAR?) and CCAAT/enhancer-binding protein ? (C/EBP?). Adipocyte differentiation was significantly attenuated by the addition of siRNA against KLF8, whereas overexpression of KLF8 resulted in enhanced differentiation. Furthermore, luciferase reporter assays demonstrated that overexpression of KLF8 induced PPAR?2 and C/EBP? promoter activity, suggesting that KLF8 is an upstream regulator of PPAR? and C/EBP?. The KLF8 binding sites were localized by site mutation analysis to ?191 region in C/EBP? promoter and ?303 region in PPAR? promoter, respectively. Taken together, these data reveal that KLF8 is a key component of the transcription factor network that controls terminal differentiation during adipogenesis. PMID:23285057

Lee, Yoo Jeong; Lee, Min-Young; Choi, Hyeonjin; Lee, Hyemin; Kim, Jae-woo

2012-01-01

66

The Factors of Design on Playing Equipment in Young Children Schools by Viewpoint of Young Children Behavioral Development  

ERIC Educational Resources Information Center

The main purpose of this study was to explore the care-givers of preschool education institutions whose cognition on playing equipment functions, conditions of both setting and using, and the main factors which should beware of design. Besides, not only constructed the factors of design, but also provided suggestions about setting and designing of…

Kuo, Chuen-tzay

2009-01-01

67

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

Microsoft Academic Search

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

Paul Delfabbro; Daniel King; Chrisi Lambos; Stan Puglies

2009-01-01

68

The Effectiveness of Child-Centered Play Therapy on Developmental and Diagnostic Factors in Children Who Are Homeless  

Microsoft Academic Search

Children who are homeless have numerous emotional, social, behavioral, and developmental challenges. This pilot research study examined the effectiveness of child-centered play therapy on developmental and diagnostic factors in 36 elementary schoolchildren who are homeless. Results indicate statistically significant improvement in 1 of 2 developmental strands and 1 of 3 diagnostic profiles as measured by the Boxall Profile. Specifically, children

Jennifer Baggerly; William W. Jenkins

2009-01-01

69

Children's play after anaesthesia and surgery: background factors and associations to behaviour during anaesthetic induction.  

PubMed

Children can experience anaesthetic induction as fearful and frightening and this can lead to postoperative behaviour changes and symptoms of high anxiety. A fearful experience can also lead to avoidant reactions due to raised negative emotions in situations similar to that, which evoked the fear. To analyse children's reactions after anaesthesia to anaesthetic play equipment, 49 children (three-six years old) were video-filmed during play with anaesthetic equipment 14 days after anaesthesia and surgery. The risk that the child avoided playing with anaesthetic equipment was increased if the child took the premedication unwillingly and if the child was younger. The risk for not telling about the experience was increased if the child took the premedication unwillingly and if the child showed signs of shyness. The risk for telling mostly unspecific memories increased if the child was younger and if the child showed signs of shyness. Avoidant reactions could bee seen in 50 percent of the children. It is important to be aware of the characteristics of a vulnerable child (age, shyness) and to meet the child without raising negative emotions in any part of the anaesthetic process, in order to avoid negative reactions in future encounters. PMID:20212059

Proczkowska-Björklund, Marie; Gustafsson, Per A; Svedin, Carl Göran

2010-06-01

70

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

Microsoft Academic Search

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

Andrew Hill

2009-01-01

71

Inherited Factors Play an Important Role in Breast Cancer Progression According to New Study in Mice  

Cancer.gov

New research in mice and five independent collections of human breast tumors has enabled NCI scientists to confirm that genes for factors contributing to susceptibility for breast cancer metastasis can be inherited. The new findings support earlier results from the same laboratory.

72

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

SciTech Connect

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

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

2008-03-01

73

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

Microsoft Academic Search

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

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

2002-01-01

74

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

PubMed

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

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

2014-01-01

75

Mineralocorticoid receptor interaction with SP1 generates a new response element for pathophysiologically relevant gene expression.  

PubMed

The mineralocorticoid receptor (MR) is a ligand-induced transcription factor belonging to the steroid receptor family and involved in water-electrolyte homeostasis, blood pressure regulation, inflammation and fibrosis in the renocardiovascular system. The MR shares a common hormone-response-element with the glucocorticoid receptor but nevertheless elicits MR-specific effects including enhanced epidermal growth factor receptor (EGFR) expression via unknown mechanisms. The EGFR is a receptor tyrosine kinase that leads to activation of MAP kinases, but that can also function as a signal transducer for other signaling pathways. In the present study, we mechanistically investigate the interaction between a newly discovered MR- but not glucocorticoid receptor- responsive-element (=MRE1) of the EGFR promoter, specificity protein 1 (SP1) and MR to gain general insights into MR-specificity. Biological relevance of the interaction for EGFR expression and consequently for different signaling pathways in general is demonstrated in human, rat and murine vascular smooth muscle cells and cells of EGFR knockout mice. A genome-wide promoter search for identical binding regions followed by quantitative PCR validation suggests that the identified MR-SP1-MRE1 interaction might be applicable to other genes. Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes. PMID:23821666

Meinel, Sandra; Ruhs, Stefanie; Schumann, Katja; Strätz, Nicole; Trenkmann, Kay; Schreier, Barbara; Grosse, Ivo; Keilwagen, Jens; Gekle, Michael; Grossmann, Claudia

2013-09-01

76

Which factors play a role in clinical decision-making in subfertility?  

PubMed

Sixteen vignettes of subfertile couples were constructed by varying fertility history, post-coital test, sperm motility, FSH concentration and Chlamydia antibody titre (CAT). Thirty-five gynaecologists estimated probabilities of treatment-independent pregnancy, intrauterine insemination (IUI) and IVF. Thereafter, they chose IUI, IVF or no treatment. The relative contribution of each factor to probability estimates and to subsequent treatment decisions was calculated. Duration of subfertility and maternal age were the most important contributors for gynaecologists' estimates of treatment-independent pregnancy [relative contribution (RC) 41, 26%]. Maternal age and FSH concentration were the most important contributors in the estimates for IUI (RC: 51, 25%) and for IVF (RC: 64, 31%). The decision to start IVF was mainly determined by maternal age, duration of subfertility, FSH concentration and CAT. The relative contribution of maternal age and duration of subfertility was in concordance with existing prediction models, whereas previous pregnancy and FSH concentration were under- and overestimated respectively. In conclusion, maternal age, duration of subfertility and FSH concentration are the main factors in clinical decision-making in subfertility. Gynaecologists overestimate the importance of FSH concentration, but underestimate that of a previous pregnancy, as compared with their importance reported in prediction models and guidelines. PMID:16740221

van der Steeg, Jan W; Steures, Pieternel; Eijkemans, Marinus J C; Habbema, J Dik F; Bossuyt, Patrick M M; Hompes, Peter G A; van der Veen, Fulco; Mol, Ben W J

2006-04-01

77

Prefoldin Plays a Role as a Clearance Factor in Preventing Proteasome Inhibitor-induced Protein Aggregation*  

PubMed Central

Prefoldin is a molecular chaperone composed of six subunits, PFD1–6, and prevents misfolding of newly synthesized nascent polypeptides. Although it is predicted that prefoldin, like other chaperones, modulates protein aggregation, the precise function of prefoldin against protein aggregation under physiological conditions has never been elucidated. In this study, we first established an anti-prefoldin monoclonal antibody that recognizes the prefoldin complex but not its subunits. Using this antibody, it was found that prefoldin was localized in the cytoplasm with dots in co-localization with polyubiquitinated proteins and that the number and strength of dots were increased in cells that had been treated with lactacystin, a proteasome inhibitor, and thapsigargin, an inducer of endoplasmic reticulum stress. Knockdown of prefoldin increased the level of SDS-insoluble ubiquitinated protein and reduced cell viability in lactacystin and thapsigargin-treated cells. Opposite results were obtained in prefoldin-overexpressed cells. It has been reported that mice harboring a missense mutation L110R of MM-1?/PFD5 exhibit neurodegeneration in the cerebellum. Although the prefoldin complex containing L110R MM-1? was properly formed in vitro and in cells derived from L110R MM-1? mice, the levels of ubiquitinated proteins and cytotoxicity were higher in L110R MM-1? cells than in wild-type cells under normal conditions and were increased by lactacystin and thapsigargin treatment, and growth of L110R MM-1? cells was attenuated. Furthermore, the polyubiquitinated protein aggregation level was increased in the brains of L110R MM-1? mice. These results suggest that prefoldin plays a role in quality control against protein aggregation and that dysfunction of prefoldin is one of the causes of neurodegenerative diseases. PMID:23946485

Abe, Akira; Takahashi-Niki, Kazuko; Takekoshi, Yuka; Shimizu, Takashi; Kitaura, Hirotake; Maita, Hiroshi; Iguchi-Ariga, Sanae M. M.; Ariga, Hiroyoshi

2013-01-01

78

Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor.  

PubMed

The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers. Cetuximab is an anti-EGFR antibody that has been approved for use in oncology. Previously we investigated mechanisms of resistance to cetuximab using a model derived from the non-small cell lung cancer line NCI-H226. We demonstrated that cetuximab-resistant clones (Ctx(R)) had increased nuclear localization of the EGFR. This process was mediated by Src family kinases (SFKs), and nuclear EGFR had a role in resistance to cetuximab. To better understand SFK-mediated nuclear translocation of EGFR, we investigated which SFK member(s) controlled this process as well as the EGFR tyrosine residues that are involved. Analyses of mRNA and protein expression indicated upregulation of the SFK members Yes (v-Yes-1 yamaguchi sarcoma viral oncogene) and Lyn (v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog) in all Ctx(R) clones. Further, immunoprecipitation analysis revealed that EGFR interacts with Yes and Lyn in Ctx(R) clones, but not in cetuximab-sensitive (Ctx(S)) parental cells. Using RNAi interference, we found that knockdown of either Yes or Lyn led to loss of EGFR translocation to the nucleus. Conversely, overexpression of Yes or Lyn in low nuclear EGFR-expressing Ctx(S) parental cells led to increased nuclear EGFR. Chromatin immunoprecipitation (ChIP) assays confirmed nuclear EGFR complexes associated with the promoter of the known EGFR target genes B-Myb and iNOS. Further, all Ctx(R) clones exhibited upregulation of B-Myb and iNOS at the mRNA and protein levels. siRNAs directed at Yes or Lyn led to decreased binding of EGFR complexes to the B-Myb and iNOS promoters based on ChIP analyses. SFKs have been shown to phosphorylate EGFR on tyrosines 845 and 1101 (Y845 and Y1101), and mutation of Y1101, but not Y845, impaired nuclear entry of the EGFR. Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR nuclear translocation in this model of cetuximab resistance. PMID:22430206

Iida, M; Brand, T M; Campbell, D A; Li, C; Wheeler, D L

2013-02-01

79

Membrane chaperone SecDF plays a role in the secretion of Listeria monocytogenes major virulence factors.  

PubMed

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

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

2013-12-01

80

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

PubMed Central

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

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

2013-01-01

81

Cigarette Smoke Induces MUC5AC Protein Expression through the Activation of Sp1*  

PubMed Central

Cigarette smoke (CS) exposure is associated with increased mucus production and chronic obstructive pulmonary disease (COPD). MUC5AC is the major inducible mucus gene in the airway. The purpose of this investigation was to elucidate the mechanisms of CS-induced activation of MUC5AC gene transcription. We observed that the region ?3724/?3224 of the MUC5AC promoter is critical for CS-induced gene transcriptional activity and that this region contains two Sp1 binding sites. Using a lung-relevant model, we observed that CS increased nuclear Sp1 protein expression. Consequently, CS exposure resulted in enhanced Sp1-DNA binding activity and Sp1 trans-activation. Co-transfection of the MUC5AC-luc reporter with Sp1 expression plasmids resulted in significantly increased MUC5AC-luc activity, whereas co-treatment with mithramycin A, a Sp1 inhibitor, abolished CS-induced MUC5AC promoter activity. Using mobility shift assay and chromatin immunoprecipitation, we demonstrated that two Sp1 binding sites in the MUC5AC promoter are functional and responsive to CS exposure. A mutation of either Sp1 binding site in the MUC5AC promoter significantly decreased CS-induced promoter activity. Together, these data indicate that CS induces MUC5AC gene transcription predominantly through increased Sp1 nuclear protein levels and increased Sp1 binding to its promoter region. PMID:22700966

Di, Y. Peter; Zhao, Jinming; Harper, Richart

2012-01-01

82

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

PubMed

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

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

2014-05-01

83

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

ERIC Educational Resources Information Center

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

Morrissey, Anne-Marie

2014-01-01

84

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

PubMed

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

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

2013-04-01

85

Evidence that the Elongation Factor TFIIS Plays a Role in Transcription Initiation at GAL1 in Saccharomyces cerevisiae  

PubMed Central

TFIIS is a transcription elongation factor that has been extensively studied biochemically. Although the in vitro mechanisms by which TFIIS stimulates RNA transcript cleavage and polymerase read-through have been well characterized, its in vivo roles remain unclear. To better understand TFIIS function in vivo, we have examined its role during Gal4-mediated activation of the Saccharomyces cerevisiae GAL1 gene. Surprisingly, TFIIS is strongly associated with the GAL1 upstream activating sequence. In addition, TFIIS recruitment to Gal4-binding sites is dependent on Gal4, SAGA, and Mediator but not on RNA polymerase II (Pol II). The association of TFIIS is also necessary for the optimal recruitment of TATA-binding protein and Pol II to the GAL1 promoter. These results provide strong evidence that TFIIS plays an important role in the initiation of transcription at GAL1 in addition to its well-characterized roles in transcription elongation. PMID:15767671

Prather, Donald M.; Larschan, Erica; Winston, Fred

2005-01-01

86

A Novel SP1/SP3 Dependent Intronic Enhancer Governing Transcription of the UCP3 Gene in Brown Adipocytes  

PubMed Central

Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein implicated in lipid handling and metabolism of reactive oxygen species. Its transcription is mainly regulated by peroxisome proliferator-activated receptors (PPAR), a family of nuclear hormone receptors. Employing bandshift assays, RNA interference and reporter gene assays we examine an intronic region in the UCP3 gene harboring a cis-element essential for expression in brown adipocytes. We demonstrate binding of SP1 and SP3 to this element which is adjacent to a direct repeat 1 element mediating activation of UCP3 expression by PPAR? agonists. Transactivation mediated by these elements is interdependent and indispensable for UCP3 expression. Systematic deletion uncovered a third binding element, a putative NF1 site, in close proximity to the SP1/3 and PPAR? binding elements. Data mining demonstrated binding of MyoD and Myogenin to this third element in C2C12 cells, and, furthermore, revealed recruitment of p300. Taken together, this intronic region is the main enhancer driving UCP3 expression with SP1/3 and PPAR? as the core factors required for expression. PMID:24391766

Hoffmann, Christoph; Zimmermann, Anika; Hinney, Anke; Volckmar, Anna-Lena; Jarrett, Harry W.; Fromme, Tobias; Klingenspor, Martin

2013-01-01

87

The inhibitory effect of chimeric decoy oligodeoxynucleotide against NF-?B and Sp1 in renal interstitial fibrosis.  

PubMed

The pathophysiology of chronic renal disease is characterized by a progressive loss of renal function and deposition of the extracellular matrix, leading to widespread tissue fibrosis. Much of the matrix in chronic renal disease is synthesized by interstitial myofibroblasts, recruited from resident fibroblasts and circulating precursors. These changes are believed to be derived from epithelial-mesenchymal transition (EMT) of tubuloepithelial cells. To develop a novel therapeutic approach for treating renal fibrosis, we examined the simultaneous inhibition of the transcription factors NF-?B and Sp1 in a mouse model of unilateral ureteral obstruction (UUO). To simultaneously inhibit both NF-?B and Sp1, we developed chimeric (Chi) decoy oligodeoxynucleotide (ODN) which contained binding sequences for both NF-?B and Sp1 in a single decoy molecule to enhance the effective use of decoy ODN strategy. Chi decoy ODN significantly attenuated tubulointerstitial fibrosis in a mouse model of UUO compared to scrambled decoy ODN, as demonstrated by the reduced interstitial volume, macrophage infiltration, and fibrosis-related gene expression. Interestingly, Chi decoy ODN also regulated EMT-related gene expression, leading to the inhibition of renal fibrotic changes in vivo and in vitro. The present study demonstrates the feasibility of Chi decoy ODN treatment for preventing renal fibrosis and EMT processes. This strategy might be useful to improve the clinical outcome after chronic renal disease. PMID:23114611

Kim, Kyung-Hyun; Park, Ji-Hyun; Lee, Woo-Ram; Park, Jae-Shin; Kim, Hyun-Chul; Park, Kwan-Kyu

2013-05-01

88

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

PubMed Central

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

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

2014-01-01

89

New Play.  

ERIC Educational Resources Information Center

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

Lersten, Kenneth C.

90

Translational and transcriptional control of Sp1 against ischaemia through a hydrogen peroxide-activated internal ribosomal entry site pathway  

PubMed Central

The exact mechanism underlying increases in Sp1 and the physiological consequences thereafter remains unknown. In rat primary cortical neurons, oxygen-glucose deprivation (OGD) causes an increase in H2O2 as well as Sp1 in early ischaemia but apparently does not change mRNA level or Sp1 stability. We hereby identified a longer 5?-UTR in Sp1 mRNA that contains an internal ribosome entry site (IRES) that regulates rapid and efficient translation of existing mRNAs. By using polysomal fragmentation and bicistronic luciferase assays, we found that H2O2 activates IRES-dependent translation. Thus, H2O2 or tempol, a superoxide dismutase-mimetic, increases Sp1 levels in OGD-treated neurons. Further, early-expressed Sp1 binds to Sp1 promoter to cause a late rise in Sp1 in a feed-forward manner. Short hairpin RNA against Sp1 exacerbates OGD-induced apoptosis in primary neurons. While Sp1 levels increase in the cortex in a rat model of stroke, inhibition of Sp1 binding leads to enhanced apoptosis and cortical injury. These results demonstrate that neurons can use H2O2 as a signalling molecule to quickly induce Sp1 translation through an IRES-dependent translation pathway that, in cooperation with a late rise in Sp1 via feed-forward transcriptional activation, protects neurons against ischaemic damage. PMID:21441538

Yeh, Shiu Hwa; Yang, Wen Bin; Gean, Po Wu; Hsu, Chung Yi; Tseng, Joseph T.; Su, Tsung Ping; Chang, Wen Chang; Hung, Jan Jong

2011-01-01

91

Translational and transcriptional control of Sp1 against ischaemia through a hydrogen peroxide-activated internal ribosomal entry site pathway.  

PubMed

The exact mechanism underlying increases in Sp1 and the physiological consequences thereafter remains unknown. In rat primary cortical neurons, oxygen-glucose deprivation (OGD) causes an increase in H(2)O(2) as well as Sp1 in early ischaemia but apparently does not change mRNA level or Sp1 stability. We hereby identified a longer 5'-UTR in Sp1 mRNA that contains an internal ribosome entry site (IRES) that regulates rapid and efficient translation of existing mRNAs. By using polysomal fragmentation and bicistronic luciferase assays, we found that H(2)O(2) activates IRES-dependent translation. Thus, H(2)O(2) or tempol, a superoxide dismutase-mimetic, increases Sp1 levels in OGD-treated neurons. Further, early-expressed Sp1 binds to Sp1 promoter to cause a late rise in Sp1 in a feed-forward manner. Short hairpin RNA against Sp1 exacerbates OGD-induced apoptosis in primary neurons. While Sp1 levels increase in the cortex in a rat model of stroke, inhibition of Sp1 binding leads to enhanced apoptosis and cortical injury. These results demonstrate that neurons can use H(2)O(2) as a signalling molecule to quickly induce Sp1 translation through an IRES-dependent translation pathway that, in cooperation with a late rise in Sp1 via feed-forward transcriptional activation, protects neurons against ischaemic damage. PMID:21441538

Yeh, Shiu Hwa; Yang, Wen Bin; Gean, Po Wu; Hsu, Chung Yi; Tseng, Joseph T; Su, Tsung Ping; Chang, Wen Chang; Hung, Jan Jong

2011-07-01

92

Sex Disparities in the Quality of Diabetes Care: Biological and Cultural Factors May Play a Different Role for Different Outcomes  

PubMed Central

OBJECTIVE To investigate the quality of type 2 diabetes care according to sex. RESEARCH DESIGN AND METHODS Clinical data collected during the year 2009 were extracted from electronic medical records; quality-of-care indicators were evaluated. Multilevel logistic regression analysis was applied to estimate the likelihood of women versus men to be monitored for selected parameters, to reach clinical outcomes, and to be treated with specific classes of drugs. The intercenter variability in the proportion of men and women achieving the targets was also investigated. RESULTS Overall, 415,294 patients from 236 diabetes outpatient centers were evaluated, of whom 188,125 (45.3%) were women and 227,169 (54.7%) were men. Women were 14% more likely than men to have HbA1c >9.0% in spite of insulin treatment (odds ratio 1.14 [95% CI 1.10–1.17]), 42% more likely to have LDL cholesterol (LDL-C) ?130 mg/dL (1.42 [1.38–1.46]) in spite of lipid-lowering treatment, and 50% more likely to have BMI ?30 kg/m2 (1.50 [1.50–1.54]). Women were less likely to be monitored for foot and eye complications. In 99% of centers, the percentage of men reaching the LDL-C target was higher than in women, the proportion of patients reaching the HbA1c target was in favor of men in 80% of the centers, and no differences emerged for blood pressure. CONCLUSIONS Women show a poorer quality of diabetes care than men. The attainment of the LDL-C target seems to be mainly related to pathophysiological factors, whereas patient and physician attitudes can play an important role in other process measures and outcomes. PMID:23835692

Rossi, Maria Chiara; Cristofaro, Maria Rosaria; Gentile, Sandro; Lucisano, Giuseppe; Manicardi, Valeria; Mulas, Maria Franca; Napoli, Angela; Nicolucci, Antonio; Pellegrini, Fabio; Suraci, Concetta; Giorda, Carlo

2013-01-01

93

Language Play.  

ERIC Educational Resources Information Center

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

Schwartz, Judy I.

94

Why Play?  

ERIC Educational Resources Information Center

Discusses the importance of pretend play for various aspects of children's development and the difficulty for adults, especially Montessorians, in understanding such play. Presents views of leading play researchers and theorists regarding role of play in distinguishing fantasy from reality, in acting as a springboard to representational thought,…

Torrence, Martha

2001-01-01

95

ER?-dependent effects on uterine endothelial cells are cell specific and mediated via Sp1  

PubMed Central

STUDY QUESTION What are the in vitro effects of estrogen receptor ? (ER?) activation on the function of endothelial cells (ECs) from different vascular beds: human endometrial ECs (HEECs; endometrium), uterine myometrial microvascular ECs (UtMVECs; myometrium) and human umbilical vein ECs (HUVECs)? SUMMARY ANSWER Studies conducted in vitro demonstrate that the ER? agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) has EC type-specific effects on patterns of gene expression and network formation. Identification of a key role for the transcription factor Sp1 in ER?-dependent signaling in uterine ECs offers new insights into cell-specific molecular mechanisms of estrogen action in the human uterus. WHAT IS KNOWN ALREADY Estrogens, acting via ERs (ER? and ER?), have important, body-wide impacts on the vasculature. The human uterus is an estrogen target organ, the endometrial lining of which exhibits physiological, cyclical angiogenesis. In fixed tissue sections, human endometrial ECs are immunopositive for ER?. STUDY DESIGN, SIZE, DURATION Cells were treated with a vehicle control or the ER? agonist, DPN, for 2 h or 24 h (n = 5) followed by gene expression analysis. Functional assays were analyzed after a 16 h incubation with ligand (n = 5). PARTICIPANT/MATERIALS, SETTING, METHODS Analysis of DPN-treated ECs using Taqman gene array cards focused on genes involved in angiogenesis and inflammation identified cell type-specific ER?-dependent changes in gene expression, with validation using qPCR and immunohistochemistry. Molecular mechanisms involved in ER? signaling were investigated using bioinformatics, reporter assays, immunoprecipitation, siRNA and a specific inhibitor blocking Sp1-binding sites. The endometrium and myometrium from women with regular menses were used to validate the protein expression of candidate genes. MAIN RESULTS AND THE ROLE OF CHANCE HEECs and UtMVECs were ER?+/ER??. Treatment of ECs with DPN had opposite effects on network formation: a decrease in network formation in HEECs (P ? 0.001) but an increase in UtMVECs (P ? 0.05). Genomic analysis identified opposite changes in ER? target gene expression with only three common transcripts (HEY1, ICAM1, CASP1) in all three ECs; a unique profile was observed for each. An important role for Sp1 was identified, consistent with the regulation of ER? target genes via association with the transcription factor (‘tethered’ mechanism). LIMITATIONS, REASONS FOR CAUTION The study was mainly carried out in vitro using ECs of which one type was immortalized. Although the analysis of the protein expression of candidate genes was carried out using intact tissue samples from patients, investigations into in vivo angiogenesis were not carried out. WIDER IMPLICATIONS OF THE FINDINGS These results have implications for our understanding of the mechanisms responsible for ER?-dependent changes in EC gene expression in hormone-dependent disorders. STUDY FUNDING/COMPETEING INTEREST(S) The study was funded by a Medical Research Council Programme Grant. E.G. is the recipient of an MRC Career Development Fellowship. The authors have nothing to disclose. PMID:23756706

Greaves, Erin; Collins, Frances; Critchley, Hilary O.D.; Saunders, Philippa T.K.

2013-01-01

96

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

PubMed

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

Zhang, Xuehong; Liu, Lina; Lin, Cuiwu

2013-08-01

97

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

E-print Network

of ER? on activation of ER?/Sp1. 17Beta-estradiol (E2) and the antiestrogens 4-hydroxytamoxifen and ICI 182,780 induced reporter gene activity in MCF-7 and MDA-MB-231 cells cotransfected with human or mouse ER? (hER? or MOR), but not ER? and GC...

Kim, KyoungHyun

2005-11-01

98

JWA suppresses tumor angiogenesis via Sp1-activated matrix metalloproteinase-2 and its prognostic significance in human gastric cancer.  

PubMed

JWA, a multifunctional microtubule-binding protein, plays an important role in regulating tumor metastasis via inhibition of matrix metalloproteinase-2 (MMP-2). Recent investigations suggest that MMP-2 is an angiogenesis-associated molecule. In this study, we provide novel evidence that JWA inhibits tumor angiogenesis in gastric cancer (GC). In two independent retrospective GC cohorts, we found that the expression of JWA was downregulated and that of MMP-2 was upregulated in GC tissues compared with the same in normal gastric mucosa. For patients treated with surgery alone, a strong and independent negative prognostic value was shown for low JWA and high MMP-2 expressions separately, which was even stronger when combined (hazard ratio = 7.75, P < 0.001, in the training cohort; hazard ratio = 2.31, P < 0.001, in the validation cohort). Moreover, we found that loss of JWA expression was strongly correlated with increased GC angiogenesis. In vitro, JWA inhibited MMP-2 at both messenger RNA and protein levels by modulating Sp1 activity. Knockdown of endogenous JWA resulted in enhanced human umbilical vein endothelial cell tube formation and MMP-2 expression. Furthermore, JWA was found to inhibit Sp1 activity via an ubiquitin-proteasome-dependent mechanism and to downregulate the expression of the proangiogenic MMP-2. Our findings imply that JWA and MMP-2 may serve as promising prognostic markers in resectable GC, with JWA as a useful biomarker of angiogenesis in GC and a potential therapeutic target by MMP-2 modulation. PMID:24072772

Chen, Yansu; Huang, Yefei; Huang, Yulin; Xia, Xiaowei; Zhang, Jianbing; Zhou, Yan; Tan, Yongfei; He, Song; Qiang, Fulin; Li, Aiping; Re, Oluf Dimitri; Li, Gang; Zhou, Jianwei

2014-02-01

99

CLONING OF THE HUMAN ACTIVATED LEUKOCYTE CELL ADHESION MOLECULE PROMOTER AND IDENTIFICATION OF ITS TISSUE-INDEPENDENT TRANSCRIPTIONAL ACTIVATION BY Sp1  

PubMed Central

Activated leukocyte cell adhesion molecule (ALCAM) belongs to the immunoglobulin cell adhesion molecule super family. ALCAM is implicated in tumor progression, inflammation, and the differentiation of hematopoietic stem cells. Hitherto, the identity of regulatory DNA elements and cognate transcription factors responsible for ALCAM gene expression remained unknown. In this report, the human ALCAM promoter was cloned and its transcriptional mechanisms elucidated. The promoter is TATA-less and contains multiple GC-boxes. A proximal 650-bp promoter fragment conferred tissue-independent activation, whereas two contiguous regions upstream of this region negatively influenced promoter activity in a tissue-specific manner. The positive regulatory promoter region was mapped to a core 50 base pair sequence containing a conical Sp1 element. Mutation analysis revealed that this element alone or in tandem with elements immediately upstream was required for maximal promoter activity. Chromatin analysis revealed that Sp1 binds exclusively to the canonical binding sequence in vivo, but not to DNA sequence immediately upstream. Finally, we showed that over-expression of Sp1 significantly increased the basal promoter activity. Thus, Sp1 activated the ALCAM promoter in most cells. These findings have important ramifications for unraveling the roles of ALCAM in inflammation and tumorigenesis. PMID:22941204

TAN, FANG; MBUNKUI, FLAUBERT; OFORI-ACQUAH, SOLOMON F.

2013-01-01

100

Play Therapy  

PubMed Central

Play therapy is a treatment modality in which the therapist engages in play with the child. Its use has been documented in a variety of settings and with a variety of diagnoses. Treating within the context of play brings the therapist and the therapy to the level of the child. By way of an introduction to this approach, a case is presented of a six-year-old boy with oppositional defiant disorder. The presentation focuses on the events and interactions of a typical session with an established patient. The primary issues of the session are aggression, self worth, and self efficacy. These themes manifest themselves through the content of the child’s play and narration of his actions. The therapist then reflects these back to the child while gently encouraging the child toward more positive play. Though the example is one of nondirective play therapy, a wide range of variation exists under the heading of play therapy. PMID:19724720

Lawver, Timothy; Blankenship, Kelly

2008-01-01

101

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

SciTech Connect

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.

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

102

Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma.  

PubMed

Licochalcone A (LCA), a chalconoid derived from root of Glycyrrhiza inflata, has been known to possess a wide range of biological functions such as antitumor, anti-angiogenesis, antiparasitic, anti-oxidant, antibacterial and anti-inflammatory effects. However, the anticancer effects of LCA on oral squamous cell carcinoma (OSCC) have not been reported. Our data showed that LCA inhibited OSCC cell (HN22 and HSC4) growth in a concentration- and time-dependent manner. Mechanistically, it was mediated via downregulation of specificity protein 1 (Sp1) expression and subsequent regulation of Sp1 downstream proteins such as p27, p21, cyclin D1, Mcl-1 and survivin. Here, we found that LCA caused apoptotic cell death in HSC4 and HN22 cells, as characterized by sub-G1 population, nuclear condensation, Annexin V staining, and multi-caspase activity and apoptotic regulatory proteins such as Bax, Bid, Bcl(-xl), caspase-3 and PARP. Consequently, this study strongly suggests that LCA induces apoptotic cell death of OSCC cells via downregulation of Sp1 expression, prompting its potential use for the treatment of human OSCC. PMID:24858379

Cho, Jung Jae; Chae, Jung-Il; Yoon, Goo; Kim, Ka Hwi; Cho, Jin Hyoung; Cho, Seung-Sik; Cho, Young Sik; Shim, Jung-Hyun

2014-08-01

103

Why Play?  

ERIC Educational Resources Information Center

This paper draws together briefly theories and knowledge from research in morphology and cognitive psychology, as well as some hypothetical information from traditional psychiatry, to show the ramifications of play in children's development. Play is defined as any of a wide variety of behaviors through which an individual attempts to discover what…

Weininger, O.

104

Playing as \\  

Microsoft Academic Search

Playing as an evil character is an option available in a number of video games. Both single player games and MMOs support this choice. What motivations, then, do players have for taking this option? This research project includes a study of fifteen individuals who have played as both good and evil characters in either single player games or MMOs. Their

105

Shadow Play  

ERIC Educational Resources Information Center

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…

Trundle, Kathy Cabe; Hilson, Margilee P.

2012-01-01

106

Factoring  

NSDL National Science Digital Library

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 ...

Clark, Mr

2012-10-31

107

Parallel spatial direct numerical simulation of boundary-layer flow transition on IBM SP1  

SciTech Connect

The spatially evolving disturbances that are associated with laminar-to-turbulent transition in three-dimensional boundary-layer flows are computed with the PSDNS code on an IBM SP1 parallel supercomputer. By remapping the distributed data structure during the course of the calculation, optimized serial library routines can be utilized that substantially increase the computational performance. Although the remapping incurs a high communication penalty, the parallel efficiency of the code remains above 40 percent for all performed calculations. By using appropriate compile options and optimized library routines, the serial code achieves 52-56 Mflops on a single node of the SP1 (45 percent of theoretical peak performance). The actual performance of the PSDNS code on the SP1 is evaluated with a ``real world`` simulation that consists of 1.7 million grid points. Comparisons to the Cray Y/MP and Cray C-90 are made for this large scale simulation.

Hanebutte, U.R. [Argonne National Lab., IL (United States); Joslin, R.D. [National Aeronautics and Space Administration, Hampton, VA (United States). Langley Research Center; Zubair, M. [International Business Machines Corp., Yorktown Heights, NY (United States). Thomas J. Watson Research Center

1995-07-01

108

GATA-6 mediates transcriptional activation of aquaporin-5 through interactions with Sp1  

PubMed Central

We investigated mechanisms underlying GATA-6-mediated transcriptional activation of the alveolar epithelial type I cell-enriched gene aquaporin-5 (AQP5). GATA-6 expression increases in alveolar epithelial cells in primary culture, concurrent with upregulation of AQP5 and transition to a type I cell-like phenotype. Cotransfections in MLE-15 and NIH 3T3 cells demonstrated trans-activation by GATA-6 of a rat 1,716-bp-AQP5-luciferase (?1716-AQP5-Luc) reporter. Electrophoretic mobility shift assay and chromatin immunoprecipitation identified an interaction between GATA-6 and putative binding sites in the AQP5 promoter. However, mutation of these sites did not reduce GATA-6-mediated activation, implicating mechanisms in addition to direct binding of GATA-6 to DNA. A 5?-deletion construct, ?358-AQP5-Luc, that does not encompass GATA motifs was still activated by GATA-6 by as much as 50% relative to ?1716-AQP5-Luc. Internal deletion of the ?358/?173 GC-rich domain, which includes several putative Sp1 consensus sites, reduced trans-activation by ?60%, suggesting importance of this region for GATA-mediated activity. ?358-AQP5-Luc was similarly activated by both GATA-6 and a GATA DNA-binding defective mutant, whereas cotransfections in Schneider S2 cells demonstrated dose-dependent trans-activation of ?358-AQP5-Luc by Sp1. Activation of ?358-AQP5-Luc by GATA-6 was dramatically reduced by Sp1 small-interfering RNA, and ?358-AQP5-Luc was activated synergistically by GATA-6 and Sp1 in NIH 3T3 cells. Furthermore, association between endogenous GATA-6 and Sp1 was demonstrated by coimmunoprecipitation. These results suggest that transcriptional activation of AQP5 by GATA-6 is mediated at least in part through cooperative interactions with Sp1 occurring at the proximal promoter. PMID:18768929

Zhou, Beiyun; Francis, Tricia A.; Yang, Hui; Tseng, Wanru; Zhong, Qian; Frenkel, Baruch; Morrisey, Edward. E.; Ann, David. K.; Minoo, Parviz; Crandall, Edward D.; Borok, Zea

2008-01-01

109

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

SciTech Connect

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.

Gropp, W. [ed.

1993-11-01

110

Profiling and comparing transcription factors activated in non-metastatic and metastatic nasopharyngeal carcinoma cells.  

PubMed

Transcription factors (TFs) are modulators of gene expression that are critically important in the establishment and progression of human cancers. In the current study, the activity profiles of TFs in a normal nasopharyngeal epithelial cell line and in nasopharyngeal carcinoma (NPC) cell lines were studied using oligonucleotide array-based TF assays. Compared to the normal epithelial cell line NP69, nine TFs in the non-metastatic NPC cell line (6-10B) and eight TFs in a metastatic NPC cell line (5-8F) were upregulated. Among upregulated TFs, Sp1, AP2, and ATF/CREB families exhibited relatively high activities in NPC cell lines. Transcription levels of Sp1, ATF-1, ATF-2, AP2alpha, AP2gamma, and CREB1 were higher in 5-8F cells than in 6-10B cells. In addition, higher expression of the Sp1 target genes MMP-9 and VEGF was observed in 5-8F cells. Sp1 silencing reduced VEGF and MMP-9 expression. Inhibition of Sp1 expression and activity in 5-8F cells by mithramycin resulted in downregulated expression and secretion of MMP-9 and VEGF, concomitant with inhibition of cell migration and invasion. These results suggest that dynamic changes in TF activities occur in NPC cells and that these changes may play important roles in regulating the expression of genes associated with the development and progression of NPC. PMID:19911387

Su, Bo; Xiang, Bo; Wang, Li; Cao, Li; Xiao, Lan; Li, Xiaoling; Li, Xiayu; Wu, Minghua; Li, Guiyuan

2010-01-01

111

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

SciTech Connect

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.

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

112

Play and Positive Group Dynamics  

ERIC Educational Resources Information Center

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…

Thompson, Pam; White, Samantha

2010-01-01

113

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

E-print Network

of the prasinophyte alga Micromonas pusilla by phycodnavirus MpV SP1. Under a light­dark regimen, viral genomes accumu for nearly half of global annual primary production through their oxygenic photosynthesis (Falkowski, lysis accelerates the release of dissolved organic matter (DOM) from cells into the water (Gobler et al

Lawrence, J.E.

114

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

PubMed Central

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

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

2012-01-01

115

Receptors for tumor necrosis factor-alpha play a protective role against obesity and alter adipose tissue macrophage status.  

PubMed

TNF-alpha signals through two receptors, TNFR1 and TNFR2. Our goals were: 1) determine the role of TNFRs in obesity and metabolic disease and 2) investigate whether TNFRs contribute to the link between obesity and adipose tissue macrophage infiltration and polarization. R1(-/-)R2(-/-) (RKO) and wild-type (WT) mice were fed standard chow or a high-fat/high-sucrose diet (HFHS) over 14 wk. Body composition, food intake, and energy expenditure were measured. Oral glucose tolerance and insulin sensitivity tests assessed glucose homeostasis. Adipose tissue and systemic inflammatory status were evaluated by quantifying plasma adipokine levels and macrophage-specific gene expression in fat. RKO mice were heavier (10%) and fatter (18%) than WT controls at 4 wk of age and were 26% heavier and 50% fatter than WT after 14 wk of HFHS diet feeding. Age- and diet-adjusted 24-h oxygen consumption, activity, and respiratory exchange ratio were significantly reduced in RKO mice. Obese RKO mice were markedly insulin resistant, suggesting that intact TNFR signaling is not required for the effect of obesity to impair glucose metabolism. Adipose tissue from HFHS-fed RKO mice exhibited increased macrophage infiltration, but compared with WT mice, macrophage phenotypic markers featured a predominance of antiinflammatory M2 over proinflammatory M1 cells. TNFRs play a physiological role to limit body weight and adiposity by modestly increasing metabolic rate and fatty acid oxidation, and they are required for obesity-induced activation of adipose tissue macrophages. Despite these effects, TNFRs are not required for obesity-induced insulin resistance. PMID:19477937

Pamir, Nathalie; McMillen, Timothy S; Kaiyala, Karl J; Schwartz, Michael W; LeBoeuf, Renée C

2009-09-01

116

Receptors for Tumor Necrosis Factor-? Play a Protective Role against Obesity and Alter Adipose Tissue Macrophage Status  

PubMed Central

TNF-? signals through two receptors, TNFR1 and TNFR2. Our goals were: 1) determine the role of TNFRs in obesity and metabolic disease and 2) investigate whether TNFRs contribute to the link between obesity and adipose tissue macrophage infiltration and polarization. R1?/?R2?/? (RKO) and wild-type (WT) mice were fed standard chow or a high-fat/high-sucrose diet (HFHS) over 14 wk. Body composition, food intake, and energy expenditure were measured. Oral glucose tolerance and insulin sensitivity tests assessed glucose homeostasis. Adipose tissue and systemic inflammatory status were evaluated by quantifying plasma adipokine levels and macrophage-specific gene expression in fat. RKO mice were heavier (10%) and fatter (18%) than WT controls at 4 wk of age and were 26% heavier and 50% fatter than WT after 14 wk of HFHS diet feeding. Age- and diet-adjusted 24-h oxygen consumption, activity, and respiratory exchange ratio were significantly reduced in RKO mice. Obese RKO mice were markedly insulin resistant, suggesting that intact TNFR signaling is not required for the effect of obesity to impair glucose metabolism. Adipose tissue from HFHS-fed RKO mice exhibited increased macrophage infiltration, but compared with WT mice, macrophage phenotypic markers featured a predominance of antiinflammatory M2 over proinflammatory M1 cells. TNFRs play a physiological role to limit body weight and adiposity by modestly increasing metabolic rate and fatty acid oxidation, and they are required for obesity-induced activation of adipose tissue macrophages. Despite these effects, TNFRs are not required for obesity-induced insulin resistance. PMID:19477937

Pamir, Nathalie; McMillen, Timothy S.; Kaiyala, Karl J.; Schwartz, Michael W.; LeBoeuf, Renee C.

2009-01-01

117

Playing Teacher.  

ERIC Educational Resources Information Center

The acceptance of animation technologies is increasing. Video games, such as Sony PlayStation (SONY, 2002), have become part of the culture for young people from kindergarten through undergraduate school. Animation technologies have been implemented into educational systems in the form of animated pedagogical agents (Johnson, 2000). The research…

Gilbert, Juan E.

118

Clay Play  

ERIC Educational Resources Information Center

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…

Rogers, Liz; Steffan, Dana

2009-01-01

119

Sweet Play  

ERIC Educational Resources Information Center

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…

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

2010-01-01

120

The role played by environmental factors in the integration of a transfer station in a municipal solid waste management system.  

PubMed

Transfer stations are an integral part of present-day municipal solid waste management systems. The main criteria used to decide on the location of a transfer station has traditionally been the minimization of transport costs, since it is cheaper to transport great amounts of waste over long distances in large loads than in small ones. In this study, we are going to consider the environmental factor in order to compare the feasibility of using a transfer station integrated within a waste management system. Applying the Life Cycle Assessment technique will enable us to obtain an objective parameter that quantifies the environmental impact of transportation and of operating a transfer station. Taking the current rates of solid wastes generation in the Plana region of Castellón (Spain) as our starting point, in this study we compare the environmental costs involved in the process of taking municipal wastes directly to the nearest waste treatment facility, with those involved in a waste management system integrating a transfer station. Comparing these two cases, an average reduction of 16.8% in the environmental impact can be obtained when a transfer station is incorporated in the waste management system. PMID:16765037

Bovea, M D; Powell, J C; Gallardo, A; Capuz-Rizo, S F

2007-01-01

121

Alterations in the Sp1 binding and Fmr-1 gene expression in the cortex of the brain during maturation and aging of mouse.  

PubMed

Fragile X mental retardation protein (FMRP) has been implicated in learning, memory and cognition, therefore, information on alterations in FMRP expression during maturation and aging may provide a clue towards understanding mechanisms of age-dependent cognitive changes in the brain. In the present paper, we have studied Fmr-1 gene expression and its correlation with interaction of a tans-acting factor Sp1with Fmr-1 promoter in the cerebral cortex of female mice at post natal period during maturation and aging. Our data reveal that level of Fmr-1 transcript in the cerebral cortex is significantly up regulated at day 7 after birth compared to day 0 (the day of birth) and is gradually down regulated from day 15 onward to old age. The pattern of Fmr-1 transcript levels corresponds with the level of FMRP, however, its level is significantly up regulated in old age compared to adult mice. Our EMSA data revealed the formation of a single complex as a result of binding of Sp1with Fmr-1 promoter sequence. Its intensity gradually decreased from the day 0 (day of birth) till day 15, remained unaltered in young, significantly decreased in adult and significantly increased in old age. Our data suggests that age-dependent alteration in the Fmr-1 gene expression is associated with Sp1 interaction with Fmr-1 promoter which in turn might be related with cognitive development during brain maturation and aging. PMID:25015265

Gaur, Pankaj; Prasad, S

2014-10-01

122

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

SciTech Connect

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.

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

123

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

PubMed

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

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

2014-05-01

124

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

PubMed

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

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

125

p53 cooperates with Sp1 to regulate breed-dependent expression of glucocorticoid receptor in the liver of preweaning piglets.  

PubMed

Previous studies indicate that Chinese indigenous pig breeds demonstrate distinct pattern of glucocorticoid receptor (GR) expression, which is associated with their unique growth and metabolic phenotypes. Here we sought to unravel the transcriptional mechanisms underlying the breed-specific hepatic GR expression in preweaning Chinese Erhualian (EHL) and Western Large White (LW) piglets. Total GR mRNA and the predominant GR mRNA variant 1-9/10 were expressed significantly higher in EHL compared with LW piglets (P<0.01), which was associated with more enriched histone H3 acetylation on 1-9/10 promoter (P<0.05). Nuclear content of transcription factor specificity protein 1 (Sp1) was significantly lower in EHL piglets, yet its binding to GR 1-9/10 promoter was significantly higher in EHL piglets, as revealed by chromatin immunoprecipitation assays. Although p53 binding to GR promoter 1-9/10 did not differ between breeds, expression of p53 mRNA and protein, as well as its binding to Sp1, were significantly higher in EHL piglets. Moreover, p53 activator doxorubicin significantly enhanced GR 1-9/10 promoter activity in HepG2 cells at 100 nM, which was associated with significantly higher protein content of p53 and GR. Sp1 inhibitor, mithramycin A, significantly inhibited (P<0.05) the basal activity of GR promoter 1-9/10 and completely blocked doxorubicin -induced activation of GR promoter 1-9/10. These data indicate that higher hepatic GR expression in EHL piglets attributes mainly to the enhanced transcription of GR promoter 1-9/10, which is achieved from breed-specific interaction of p53 and Sp1 on porcine GR 1-9/10 promoter. PMID:23950944

Zou, Huafeng; Jiang, Zheng; Li, Runsheng; Jia, Yimin; Yang, Xiaojing; Ni, Yingdong; Zhao, Ruqian

2013-01-01

126

Intervention in genotoxic stress-induced senescence by cordycepin through activation of eIF2? and suppression of Sp1.  

PubMed

In this study, we show that cordycepin (3'-deoxyadenosine), a major nucleoside isolated from Cordyceps species, attenuates genotoxic stress-induced senescence. Etoposide- or doxorubicin-treated cells exhibited senescent morphology, growth arrest, and positive staining for senescence-associated ?-galactosidase. The induction of the senescent phenotype was inhibited by the treatment of cordycepin. This suppression was correlated with blunted activation of the p16(INK4a) and p21(WAF1/CIP1) gene promoters, as well as a decreased level of p21 (WAF1/CIP1) mRNA. Other adenosine-related substances including ATP, ADP, and adenosine did not mimic the suppressive effect of cordycepin. The antisenescence effect of cordycepin was mediated by activation of eukaryotic translation initiation factor 2? (eIF2?) because (1) cordycepin induced phosphorylation of eIF2?, (2) selective activation of eIF2? mimicked the suppressive effect of cordycepin on senescence, and (3) functional knockdown of eIF2? reversed the effect of cordycepin. Unexpectedly, induction of p53 by etoposide was not inhibited by cordycepin, whereas (1) expression of Sp1 (required for the induction of p21(WAF1/CIP1) and activation of p16(INK4a) by genotoxic stress) was attenuated by cordycepin, (2) DNA binding activity of Sp1 was also inhibited, and (3) selective inhibition of Sp1 reproduced the suppressive effect of cordycepin on senescence. These results suggest that cordycepin interferes with senescence signaling via activation of eIF2? and suppression of Sp1 without affecting the level of p53. PMID:23690541

Gu, Liubao; Johno, Hisashi; Nakajima, Shotaro; Yoshitomi, Tatsuya; Takahashi, Shuhei; Kitamura, Masanori

2013-08-01

127

Involvement of insulin-like growth factor-I in psoriasis as a paracrine growth factor: dermal fibroblasts play a regulatory role in developing psoriatic lesions  

Microsoft Academic Search

\\u000a Abstract To investigate the contribution of dermal fibroblasts to the development of psoriasis, we examined the expression of mRNA\\u000a for insulin-like growth factor-I (IGF-I) and its regulator IGF-I binding proteins (IGFBPs) in psoriatic fibroblasts by RT-PCR.\\u000a We also studied the effect of inflammatory cytokines including interferon gamma (IFN-?), tumor necrosis factor alfa (TNF-?),\\u000a and IFN-? on the expression of IGF-I

H. Miura; S. Sano; M. Higashiyama; K. Yoshikawa; S. Itami

2000-01-01

128

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

SciTech Connect

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

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

2010-05-01

129

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

SciTech Connect

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

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

2006-09-15

130

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

E-print Network

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 ...

Hirose, Takashi

131

Evidence for Physical Interaction Between the Zinc-Finger Transcription Factors YY1 and Sp1  

Microsoft Academic Search

Two promoter elements are important for basal-level transcription, the TATA motif typically located 30 nucleotides upstream of the transcription initiation site and the initiator (Inr) element encompassing the start site. The mechanism of how Inr elements work is poorly understood, partly because very few proteins that bind to Inr elements have been identified and isolated. The recently cloned YY1 is

Jeng-Shin Lee; Katherine M. Galvin; Yang Shi

1993-01-01

132

LETTER doi:10.1038/nature12329 An Sp1 transcription factor coordinates caspase-  

E-print Network

sister cell dies by apoptosis soon after its generation (Fig. 1a)6,7 . We constructed a Pceh-28::gfp reporter transgene that expresses green fluorescent protein (GFP) spe- cifically in the M4 neuron of wild of mapping and transformation-rescue studies, are alleles of the genes sptf-3 and pig-1, respectively (Fig. 1

Horvitz, H. Robert

133

The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements.  

PubMed Central

We report that thyroid hormone (T3) receptor (T3R) can activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). Purified chick T3R-alpha 1 (cT3R-alpha 1) binds as monomers and homodimers to a region in the LTR (nucleotides -104 to -75 [-104/-75]) which contains two tandem NF-kappa B binding sites and to a region (-80/-45) which contains three Sp1 binding sites. In contrast, human retinoic acid receptor alpha (RAR-alpha) and mouse retinoid X receptor beta (RXR-beta) do not bind to these elements. However, RXR-beta binds to these elements as heterodimers with cT3R-alpha 1 and to a lesser extent with RAR-alpha. Gel mobility shift assays also revealed that purified NF-kappa B p50/65 or p50/50 can bind to one but not both NF-kappa B sites simultaneously. Although the binding sites for p50/65, p50/50, and T3R, or Sp1 and T3R, overlap, their binding is mutually exclusive, and with the inclusion of RXR-beta, the major complex is the RXR-beta-cT3R-alpha 1 heterodimer. The NF-kappa B region of the LTR and the NF-kappa B elements from the kappa light chain enhancer both function as T3 response elements (TREs) when linked to a heterologous promoter. The TREs in the HIV-1 NF-kappa B sites appear to be organized as a direct repeat with an 8- or 10-bp gap between the half-sites. Mutations within the NF-kappa B motifs which eliminate binding of cT3R-alpha 1 also abolish stimulation by T3, indicating that cT3R-alpha 1 binding to the Sp1 region does not independently mediate activation by T3. The Sp1 region, however, is converted to a functionally strong TRE by the viral tat factor. These studies indicate that the HIV-1 LTR contains both tat-dependent and tat-independent TREs and reveal the potential for T3R to modulate other genes containing NF-kappa B- and Sp1-like elements. Furthermore, they indicate the importance of other transcription factors in determining whether certain T3R DNA binding sequences can function as an active TRE. Images PMID:8393143

Desai-Yajnik, V; Samuels, H H

1993-01-01

134

Characterization of SP1, a stress-responsive, boiling-soluble, homo-oligomeric protein from aspen.  

PubMed

sp1 cDNA was isolated from aspen (Populus tremula) plants by immunoscreening an expression library using polyclonal antibodies against BspA protein. BspA, which is a boiling-stable protein, accumulates in aspen plants in response to water stress and abscisic acid application (Pelah et al., 1995). The sp1 cDNA was found to encode a 12.4-kD generally hydrophilic protein with a hydrophobic C terminus, which is different from the BspA protein and was termed SP1 (stable protein 1). Northern-blot analysis revealed that sp1 encodes a small mRNA (about 0.6 kb) that is expressed in aspen plants under non-stress conditions and is accumulated after salt, cold, heat, and desiccation stress, and during the recovery from stress. The SP1 detected in plants remained soluble upon boiling, migrated both as a 12.4-kD band and a much higher mass of 116 kD on a 17% (w/v) Tricine-sodium dodecyl sulfate-polyacrylamide gel. Comparative protease digestion patterns, amino acid analyses, and the N-terminal sequences of the 12.4- and 116-kD proteins revealed that SP1 is homo-oligomeric. Furthermore, gel filtration chromatography analysis indicated that SP1 exists in aspen plants as a complex, composed of 12 subunits of 12.4 kD. A large number of sequences deduced from expressed sequence tags and genomic sequences of other organisms with unknown function show high homology to SP1. Thus, SP1 may represent a new protein family. Here, we present the first report on this putative protein family: the cloning, isolation, and characterization of SP1, a stress-responsive, boiling-soluble, oligomeric protein. PMID:12376651

Wang, Wang-Xia; Pelah, Dan; Alergand, Tal; Shoseyov, Oded; Altman, Arie

2002-10-01

135

Complete genome sequence of Kosakonia sacchari type strain SP1(T.).  

PubMed

Kosakonia sacchari sp. nov. is a new species within the new genus Kosakonia, which was included in the genus Enterobacter. K sacchari is a nitrogen-fixing bacterium named for its association with sugarcane (Saccharum officinarum L.). K sacchari bacteria are Gram-negative, aerobic, non-spore-forming, motile rods. Strain SP1(T) (=CGMCC1.12102(T)=LMG 26783(T)) is the type strain of the K sacchari sp. nov and is able to colonize and fix N2 in association with sugarcane plants, thus promoting plant growth. Here we summarize the features of strain SP1(T) and describe its complete genome sequence. The genome contains a single chromosome and no plasmids, 4,902,024 nucleotides with 53.7% GC content, 4,460 protein-coding genes and 105 RNA genes including 22 rRNA genes, 82 tRNA genes, and 1 ncRNA gene. PMID:25197499

Chen, Mingyue; Zhu, Bo; Lin, Li; Yang, Litao; Li, Yangrui; An, Qianli

2014-06-15

136

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

Microsoft Academic Search

Summary Viruses infecting marine phytoplankton drive phy- toplankton diversity, terminate blooms and shuttle genetic material. Assessments of the scale of viral impacts on trophic networks are, however, speculative. We investigated fluxes of DNA between host and virus during infection of the prasinophyte alga Micromonas pusilla by phycodnavirus MpV SP1. Under a light-dark regimen, viral genomes accumu- lated to a transient

Christopher M. Brown; Douglas A. Campbell; Janice E. Lawrence

2007-01-01

137

DsbA Plays a Critical and Multifaceted Role in the Production of Secreted Virulence Factors by the Phytopathogen Erwinia carotovora subsp. atroseptica*S?  

PubMed Central

Erwinia carotovora subsp. atroseptica is an enterobacterial phytopathogen causing economically significant soft rot disease. Pathogenesis is mediated by multiple secreted virulence factors, many of which are secreted by the type II (Out) secretion system. DsbA catalyzes the introduction of disulfide bonds into periplasmic and secreted proteins. In this study, the extracellular proteome (secretome) of wild type E. carotovora subsp. atroseptica SCRI1043, and dsbA and out mutants, was analyzed by spectral counting mass spectrometry. This revealed that dsbA inactivation had a huge impact on the secretome and identified diverse DsbA- and Out-dependent secreted proteins, representing known, predicted, and novel candidate virulence factors. Further characterization of the dsbA mutant showed that secreted enzyme activities, motility, production of the quorumsensing signal, and virulence were absent or substantially reduced. The impact of DsbA on secreted virulence factor production was mediated at multiple levels, including impacting on the Out secretion system and the virulence gene regulatory network. Transcriptome analyses revealed that the abundance of a broad, but defined, set of transcripts, including many virulence factors, was altered in the dsbA mutant, identifying a new virulence regulon responsive to extracytoplasmic conditions. In conclusion, DsbA plays a crucial, multifaceted role in the pathogenesis of E. carotovora subsp. atroseptica. PMID:18562317

Coulthurst, Sarah J.; Lilley, Kathryn S.; Hedley, Peter E.; Liu, Hui; Toth, Ian K.; Salmond, George P. C.

2008-01-01

138

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

PubMed Central

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

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

2014-01-01

139

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

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

2011-01-01

140

Cloning and Characterization of the Human Trefoil Factor 3 Gene Promoter  

PubMed Central

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

Zhou, Yifang; Mao, Xuefei; Deng, Xiangdong

2014-01-01

141

Propensity for HBZ-SP1 isoform of HTLV-I to inhibit c-Jun activity correlates with sequestration of c-Jun into nuclear bodies rather than inhibition of its DNA-binding activity  

SciTech Connect

HTLV-I bZIP factor (HBZ) contains a C-terminal zipper domain involved in its interaction with c-Jun. This interaction leads to a reduction of c-Jun DNA-binding activity and prevents the protein from activating transcription of AP-1-dependent promoters. However, it remained unclear whether the negative effect of HBZ-SP1 was due to its weak DNA-binding activity or to its capacity to target cellular factors to transcriptionally-inactive nuclear bodies. To answer this question, we produced a mutant in which specific residues present in the modulatory and DNA-binding domain of HBZ-SP1 were substituted for the corresponding c-Fos amino acids to improve the DNA-binding activity of the c-Jun/HBZ-SP1 heterodimer. The stability of the mutant, its interaction with c-Jun, DNA-binding activity of the resulting heterodimer, and its effect on the c-Jun activity were tested. In conclusion, we demonstrate that the repression of c-Jun activity in vivo is mainly due to the HBZ-SP1-mediated sequestration of c-Jun to the HBZ-NBs.

Clerc, Isabelle, E-mail: isabelle.clerc@univ-montp1.f [Universite Montpellier 1, Centre d'etudes d'agents Pathogenes et Biotechnologies pour la Sante (CPBS) (France); CNRS, UM5236, CPBS, F-34965 Montpellier (France); Universite Montpellier 2, CPBS, F-34095 Montpellier (France); Hivin, Patrick, E-mail: patrick.hivin@cea.f [Universite Montpellier 1, Centre d'etudes d'agents Pathogenes et Biotechnologies pour la Sante (CPBS) (France); CNRS, UM5236, CPBS, F-34965 Montpellier (France); Universite Montpellier 2, CPBS, F-34095 Montpellier (France); Rubbo, Pierre-Alain, E-mail: p.rubbo@hotmail.co [Universite Montpellier 1, Centre d'etudes d'agents Pathogenes et Biotechnologies pour la Sante (CPBS) (France); CNRS, UM5236, CPBS, F-34965 Montpellier (France); Universite Montpellier 2, CPBS, F-34095 Montpellier (France); Lemasson, Isabelle, E-mail: LEMASSONI@ecu.ed [East Carolina University, Department of Microbiology and Immunology, North Carolina (United States); Barbeau, Benoit, E-mail: barbeau.benoit@uqam.c [Universite du Quebec a Montreal, Departement des sciences biologiques, Montreal (Canada); Mesnard, Jean-Michel, E-mail: jean-michel.mesnard@univ-montp1.f [Universite Montpellier 1, Centre d'etudes d'agents Pathogenes et Biotechnologies pour la Sante (CPBS) (France); CNRS, UM5236, CPBS, F-34965 Montpellier (France); Universite Montpellier 2, CPBS, F-34095 Montpellier (France)

2009-09-01

142

Quotients of AdSp+1×Sq: Causally well-behaved spaces and black holes  

NASA Astrophysics Data System (ADS)

Starting from the recent classification of quotients of Freund-Rubin backgrounds in string theory of the type AdSp+1×Sq by one-parameter subgroups of isometries, we investigate the physical interpretation of the associated quotients by discrete cyclic subgroups. We establish which quotients have well-behaved causal structures, and of those containing closed timelike curves, which have interpretations as black holes. We explain the relation to previous investigations of quotients of asymptotically flat spacetimes and plane waves, of black holes in AdS spacetimes, and of Gödel-type universes.

Figueroa-O'Farrill, José; Madden, Owen; Ross, Simon F.; Simón, Joan

2004-06-01

143

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

PubMed Central

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

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

2014-01-01

144

The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation  

PubMed Central

Background The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC). Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous studies. Therefore, HCC cells were subjected to treatment with resveratrol and then analyzed to determine the effects of resveratrol on the migration and invasion. Methodology and Principal Findings Modified Boyden chamber assays revealed that resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM. The results of casein zymography and western blotting revealed that the activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol. Western blot analysis also showed that resveratrol inhibits phosphorylation of JNK1/2. Tests of the mRNA level, real-time PCR, and promoter assays evaluated the inhibitory effects of resveratrol on u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay showed that reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol. Conclusions Resveratrol inhibits u-PA expression and the metastasis of HCC cells and is a powerful chemopreventive agent. The inhibitory effects were associated with the downregulation of the transcription factors of SP-1 signaling pathways. PMID:23437203

Yeh, Chao-Bin; Hsieh, Ming-Ju; Lin, Chiao-Wen; Chiou, Hui-Ling; Lin, Pen-Yuan; Chen, Tzy-Yen; Yang, Shun-Fa

2013-01-01

145

Mithramycin Is a Gene-Selective Sp1 Inhibitor That Identifies a Biological Intersection between Cancer and Neurodegeneration  

PubMed Central

Oncogenic transformation of postmitotic neurons triggers cell death, but the identity of genes critical for degeneration remain unclear. The antitumor antibiotic mithramycin prolongs survival of mouse models of Huntington’s disease in vivo and inhibits oxidative stress-induced death in cortical neurons in vitro. We had correlated protection by mithramycin with its ability to bind to GC-rich DNA and globally displace Sp1 family transcription factors. To understand how antitumor drugs prevent neurodegeneration, here we use structure-activity relationships of mithramycin analogs to discover that selective DNA-binding inhibition of the drug is necessary for its neuroprotective effect. We identify several genes (Myc, c-Src, Hif1?, and p21waf1/cip1) involved in neoplastic transformation, whose altered expression correlates with protective doses of mithramycin or its analogs. Most interestingly, inhibition of one these genes, Myc, is neuroprotective, whereas forced expression of Myc induces Rattus norvegicus neuronal cell death. These results support a model in which cancer cell transformation shares key genetic components with neurodegeneration. PMID:21543616

Sleiman, Sama F.; Langley, Brett C.; Basso, Manuela; Berlin, Jill; Xia, Li; Payappilly, Jimmy B.; Kharel, Madan K.; Guo, Hengchang; Marsh, J. Lawrence; Thompson, Leslie Michels; Mahishi, Lata; Ahuja, Preeti; MacLellan, W. Robb; Geschwind, Daniel H.; Coppola, Giovanni; Rohr, Jurgen; Ratan, Rajiv R.

2013-01-01

146

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

NASA Astrophysics Data System (ADS)

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.

Feng, Jie; Xing, Da

2012-12-01

147

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

PubMed Central

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

2014-01-01

148

The Arabidopsis thaliana GRF-INTERACTING FACTOR gene family plays an essential role in control of male and female reproductive development.  

PubMed

Reproductive success of angiosperms relies on the precise development of the gynoecium and the anther, because their primary function is to bear and to nurture the embryo sac/female gametophyte and pollen, in which the egg and sperm cells, respectively, are generated. It has been known that the GRF-INTERACTING FACTOR (GIF) transcription co-activator family of Arabidopsis thaliana (Arabidopsis) consists of three members and acts as a positive regulator of cell proliferation. Here, we demonstrate that GIF proteins also play an essential role in development of reproductive organs and generation of the gamete cells. The gif1 gif2 gif3 triple mutant, but not the single or double mutants, failed to establish normal carpel margin meristem (CMM) and its derivative tissues, such as the ovule and the septum, resulting in a split gynoecium and no observable embryo sac. The gif triple mutant also displayed severe structural and functional defects in the anther, producing neither microsporangium nor pollen grains. Therefore, we propose that the GIF family of Arabidopsis is a novel and essential component required for the cell specification maintenance during reproductive organ development and, ultimately, for the reproductive competence. PMID:24355747

Lee, Byung Ha; Wynn, April N; Franks, Robert G; Hwang, Yong-sic; Lim, Jun; Kim, Jeong Hoe

2014-02-01

149

Dissimilatory Metal Reduction by the Facultative Anaerobe Pantoea agglomerans SP1  

PubMed Central

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

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

2000-01-01

150

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

PubMed

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

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

2013-02-01

151

Basal expression of the human MAPEG members microsomal glutathione transferase 1 and prostaglandin E synthase genes is mediated by Sp1 and Sp3.  

PubMed

Microsomal glutathione transferase (MGST1) and prostaglandin E synthase (PGES) are both members of the MAPEG (Membrane Associated Proteins involved in Eicosanoid and Glutathione metabolism) superfamily. In humans, their organ distribution is quite distinct with the former being widely and constitutively expressed whereas PGES is largely inducible. In order to study the basal expression of these genes, we characterized the promoter regions and identified the elements and the transcription factors required using in vitro assays, including reporter analysis of deletion and mutant clones and EMSA. The results indicate that Sp1 is the protein mediating the basal transcription of MGST1. It appears that both the Sp1 and Sp3 proteins are important for the basal expression of PGES. In addition, mutational analysis of two Barbie-box elements in the PGES promoter showed that these were not involved in the down-regulation of PGES by phenobarbital (PB). These results provide the first description of the basal regulation of these genes in humans. PMID:12818425

Ekström, Lena; Lyrenäs, Louise; Jakobsson, Per-Johan; Morgenstern, Ralf; Kelner, Michael J

2003-06-19

152

Receptor Activator of NF-?B (RANK) Cytoplasmic IVVY535–538 Motif Plays an Essential Role in Tumor Necrosis Factor-? (TNF)-mediated Osteoclastogenesis*  

PubMed Central

Tumor necrosis factor-? (TNF) enhances osteoclast formation and activity leading to bone loss in various pathological conditions, but its precise role in osteoclastogenesis remains controversial. Although several groups showed that TNF can promote osteoclastogenesis independently of the receptor activator of NF-?B (RANK) ligand (RANKL), others demonstrated that TNF-mediated osteoclastogenesis needs permissive levels of RANKL. Here, we independently reveal that although TNF cannot stimulate osteoclastogenesis on bone slices, it can induce the formation of functional osteoclasts on bone slices in the presence of permissive levels of RANKL or from bone marrow macrophages (BMMs) pretreated by RANKL. TNF can still promote the formation of functional osteoclasts 2 days after transient RANKL pretreatment. These data have confirmed that TNF-mediated osteoclastogenesis requires priming of BMMs by RANKL. Moreover, we investigated the molecular mechanism underlying the dependence of TNF-mediated osteoclastogenesis on RANKL. RANK, the receptor for RANKL, contains an IVVY535–538 motif that has been shown to play a vital role in osteoclastogenesis by committing BMMs to the osteoclast lineage. We show that TNF-induced osteoclastogenesis depends on RANKL to commit BMMs to the osteoclast lineage and RANKL regulates the lineage commitment through the IVVY motif. Mechanistically, the IVVY motif controls the lineage commitment by reprogramming osteoclast genes into an inducible state in which they can be activated by TNF. Our findings not only provide important mechanistic insights into the action of RANKL in TNF-mediated osteoclastogenesis but also establish that the IVVY motif may serve as an attractive therapeutic target for bone loss in various bone disorders. PMID:20870724

Jules, Joel; Shi, Zhenqi; Liu, Jianzhong; Xu, Duorong; Wang, Shunqing; Feng, Xu

2010-01-01

153

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

Microsoft Academic Search

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

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

2011-01-01

154

A Content Analysis of Interviews with Players of Massively Multiplayer Online Role-Play Games (MMORPGs): Motivating Factors and the Impact on Relationships  

Microsoft Academic Search

This paper explores the intrapersonal and interpersonal motivations involved in the playing of MMORPGs, and the impacts of\\u000a gaming on online and offline relationships. Twenty-one participants completed an online synchronous interview in which they\\u000a discussed their personal experiences of playing MMORPGs. An online survey was then developed to further explore the findings\\u000a of the interviews and this was completed by

Jacqui Taylor; James Taylor

2009-01-01

155

Esculetin (6,7-dihydroxycoumarin): A potential cancer chemopreventive agent through suppression of Sp1 in oral squamous cancer cells.  

PubMed

Esculetin (6,7-dihydroxycoumarin), a coumarin compound, is known to inhibit proliferation and induce apoptosis in several types of human cancer cells and is regarded as a promising chemotherapeutic agent. The purpose of the present study was to investigate the anti-proliferative effects of esculetin on two oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, through regulation of specificity protein 1 (Sp1). We examined the apoptotic effects of esculetin were measured by MTS assay, DAPI staining, Annexin V, PI staining, RT-PCR, western blot analysis and immunocytochemistry in HN22 and HSC4 cells. Taken together, the results of the present study indicate that esculetin had anti-proliferative effect on the growth of OSCC cells (HN22 and HSC4) in a dose- and time-dependent manner. The treatment of HN22 and HSC4 cells with esculetin led to a significant reduction in growth and induced apoptosis, followed by the regulation of Sp1 and Sp1 regulatory protein. This indicates that esculetin inhibited cell growth and induced apoptosis by suppressing Sp1 in HN22 and HSC4 cells, suggesting it to be a potent anticancer drug candidate for oral cancer. PMID:25310400

Cho, Jin Hyoung; Shin, Jae-Cheon; Cho, Jung-Jae; Choi, Yung Hyun; Shim, Jung-Hyun; Chae, Jung-Il

2015-01-01

156

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

E-print Network

that is essential for the terminal maturation of proerythroblasts, megakaryocytic cells and mast cells is restricted to erythroid cells, megakaryocytes, eosinophils and mast cells, as well as to Sertoli cellsSp1/Sp3 involved in activation of GATA-1 302 npg Cell Research | Vol 18 No 2 | February 2008

Tian, Weidong

157

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

PubMed Central

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

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

2012-01-01

158

Characteristics of risky play  

Microsoft Academic Search

This paper explores what makes children's risky play risky. Risky play can generally be defined as thrilling and exciting forms of play that involve a risk of physical injury. Few, if any, studies have been conducted to explore what identifies play activity as risky. The present study aims to determine what characteristics to judge risky play by. Risky play in

Ellen Beate Hansen Sandseter

2009-01-01

159

Play Therapy: A Review  

ERIC Educational Resources Information Center

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…

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

2009-01-01

160

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

Microsoft Academic Search

Reacting to the Past is a pedagogy involving collaborative role playing in history-based games over a semester. This article presents results from a systematic assessment of this novel pedagogy conducted in 3 phases following student focus group interviews. Interviews indicated that the method was generally popular compared with traditional pedagogies, although several concerns about the course were raised. Quasi-experimental procedures

Steven J. Stroessner; Laurie Susser Beckerman; Alexis Whittaker

2009-01-01

161

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

ERIC Educational Resources Information Center

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

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

2009-01-01

162

Musical Instrument Choice and Playing History in Post-Secondary Level Music Students: Some Descriptive Data, Some Causes and Some Background Factors  

ERIC Educational Resources Information Center

Why do musicians specialize in the specific instruments that they do? Research has shown effects of such factors as the perceived masculinity/femininity of instruments and musician's personality but there are little background data on other factors. The present study had two major aims. The first aim was to gather some useful background data on…

Chen, Simy Meng-Yu; Howard, Robert W.

2004-01-01

163

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

PubMed Central

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

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

2013-01-01

164

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

Microsoft Academic Search

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

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

2011-01-01

165

Children's Play and Television.  

ERIC Educational Resources Information Center

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…

Powell, Mark

2001-01-01

166

Role Played by Hypothalamic Nuclear Factor B in Alcohol-Mediated Activation of the Rat Hypothalamic-Pituitary-Adrenal Axis  

Microsoft Academic Search

The DNA binding protein nuclear factor-B (NF-B) is a tran- scription factor translocated from the cytosol to the nucleus in response to stressors. Here we determined whether the known ability of alcohol to activate the hypothalamic-pitu- itary axis was mediated by NF-B, tested the hypothesis that this phenomenon was accompanied by increased hypotha- lamic NF-B transcripts, and investigated some of

Soon Lee; Catherine Rivier

2005-01-01

167

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

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

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

2014-03-01

168

War, Conflict and Play. Debating Play  

ERIC Educational Resources Information Center

Young refugees from many parts of the world are increasingly present in UK early years settings. This book explores the crucial importance of play for young refugee children's development. It considers the implications of war and conflict on young children and notes how opportunities for play are denied. It provides a framework for early years…

Hyder, Tina

2004-01-01

169

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

PubMed

Three studies describe the development and validation of the Play Activity Questionnaire (PQ), a parent report measure of children's play preferences. In Study 1, the 15-item PQ was completed by parents of 239 6- to 8-year-old children, and exploratory factor analysis revealed four play factors: Active and Adventurous, Athletic, Rough-and-Tumble, and Quiet. In Study 2, the factor structure was replicated with PQ data on 203 children of a broader age range (4 to 12 years). The play factors accounted for 65.7% of the variance. Boys' scores exceeded girls' scores on the Athletic and Rough-and-Tumble play factors. Girls' scores exceeded boys' scores on the Quiet play factor. Sex differences were not observed on the Active and Adventurous play factor. Interparent agreement was moderately high, and PQ factor scores were unrelated to social class or nationality. Individual factor scores showed moderate to high stability over 5 months. Validity of the play factors was examined in Study 3 by relating factor scores to measures of activity level, aggression, and sex-typed play. Play factor scores were associated with several of these measures, suggesting that the PQ is a valid measure of children's play behavior with potential applications in the fields of developmental psychopathology and psychoneuroendocrinology, and in studies of normal play and sex-role development. PMID:1953330

Finegan, J A; Niccols, G A; Zacher, J E; Hood, J E

1991-08-01

170

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

PubMed Central

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

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

2012-01-01

171

Cilostazol inhibits insulin-stimulated expression of sterol regulatory binding protein-1c via inhibition of LXR and Sp1.  

PubMed

Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolic syndrome. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver. Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1). Cilostazol is an antiplatelet agent that prevents atherosclerosis and decreases serum triglyceride levels. However, little is known about the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1c transcription in the liver. The effects of cilostazol on the expression of SREBP-1c and its target genes in response to insulin or an LXR agonist (T0901317) were examined using real-time RT-PCR and western blot analysis on cultured hepatocytes. To investigate the effect of cilostazol on SREBP-1c at the transcriptional level, transient transfection reporter assays and electrophoretic mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin-induced and LXR-agonist-induced expression of SREBP-1c and its downstream targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes. Cilostazol also inhibited activation of the SREBP-1c promoter by insulin, T0901317 and Sp1 in a luciferase reporter assay. EMSA analysis showed that cilostazol inhibits SREBP-1c expression by repressing the binding of LXR and Sp1 to the promoter region. These results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via the inhibition of LXR and Sp1 activity and that cilostazol is a negative regulator of hepatic lipogenesis. PMID:24458133

Jung, Yun-A; Kim, Hee Kyoung; Bae, Kwi-Hyun; Seo, Hye-Young; Kim, Hye-Soon; Jang, Byoung Kuk; Jung, Gwon-Soo; Lee, In-Kyu; Kim, Mi-Kyung; Park, Keun-Gyu

2014-01-01

172

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

PubMed

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

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

2014-12-01

173

The Play of Psychotherapy  

ERIC Educational Resources Information Center

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…

Marks-Tarlow, Terry

2012-01-01

174

Children's Empowerment in Play  

ERIC Educational Resources Information Center

This article examines the level of empowerment and autonomy children can create in their play experiences. It examines the play discourses that children build and maintain and considers the importance of play contexts in supporting children's emotional and social development. These aspects of play are often unseen or misunderstood by the adult…

Canning, Natalie

2007-01-01

175

Understanding Playful Pedagogies, Play Narratives and Play Spaces  

ERIC Educational Resources Information Center

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

Goouch, Kathy

2008-01-01

176

Vygotsky on play: child's play or more  

E-print Network

: Educational Psychology VYGOTSKY ON PLAY: CHILD'S PLAY OR MORE A Thesis by CAROL ANNE WAGNER Submitted to the Office of Graduate Studies of Texas ASM University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved... as to style and content by: Stephanie L. Knight (Chair of Committee) Michael 3. sh (Member) ohn 3. McD rmott (Memb 3ames M. Rosenheim (Member) D I . Palmer (He of D partment) May 2000 Major Subject: Educational Psychology ABSTRACT Vygotsky...

Wagner, Carol Anne

2012-06-07

177

Play: early and eternal.  

PubMed Central

A systematic 12-week investigation of development of play behavior was conducted with eight socially reared rhesus monkey infants. A new, basic and primary play form termed self-motion play or peragration was identified and examined. This behavior follows a human model which includes a wide range of pleasurable activities involving motion of the body through space, e.g., rocking, swinging, running, leaping, and water or snow skiing. It can be argued that self-motion play is the initial primate play form and because of its persistence constitutes a reinforcing agent for maintaining many complex patterns and even pastimes. Monkey self-motion play in the present study was divided into five separate patterns in order to compare the relative importance of social and individual peragration play, the role of apparatus and the overall developmental relationships between the different individual and social self-motion play patterns. The data showed that from 90 to 180 days of age self-motion play was independent of other forms of play, that individual self-motion play appeared earlier and with significantly greater increases in frequency than did social self-motion play, and that apparatus was a necessary component for significant increases in social self-motion play. Other findings were that self-motion play existed independent of locomotion and, though initiated by exploration, was separate from it. Therapeutic implications of self-motion play were discussed. Images PMID:1057178

Mears, C E; Harlow, H F

1975-01-01

178

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

E-print Network

homologous NFI genes (NFI- A, -B, -C and -X) in vertebrates and multiple alternatively spliced isoforms from developing intrarenal arteries [3,4]. As the renal arterial tree develops, renin is expressed in the newly forming arterial branches. Subsequently, renin expression is progressively restricted to smaller arteries

Gronostajski, Richard M.

179

TGF? signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1.  

PubMed

Research on myelination has focused on identifying molecules capable of inducing oligodendrocyte (OL) differentiation in an effort to develop strategies that promote functional myelin regeneration in demyelinating disorders. Here, we show that transforming growth factor ? (TGF?) signaling is crucial for allowing oligodendrocyte progenitor (OP) cell cycle withdrawal, and therefore, for oligodendrogenesis and postnatal CNS myelination. Enhanced oligodendrogenesis and subcortical white matter (SCWM) myelination was detected after TGF? gain of function, while TGF? receptor II (TGF?-RII) deletion in OPs prevents their development into mature myelinating OLs, leading to SCWM hypomyelination in mice. TGF? signaling modulates OP cell cycle withdrawal and differentiation through the transcriptional modulation of c-myc and p21 gene expression, mediated by the interaction of SMAD3/4 with Sp1 and FoxO1 transcription factors. Our study is the first to demonstrate an autonomous and crucial role of TGF? signaling in OL development and CNS myelination, and may provide new avenues in the treatment of demyelinating diseases. PMID:24899714

Palazuelos, Javier; Klingener, Michael; Aguirre, Adan

2014-06-01

180

Role-Playing Mitosis.  

ERIC Educational Resources Information Center

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)

Wyn, Mark A.; Stegink, Steven J.

2000-01-01

181

The concept of play  

Microsoft Academic Search

Recent criticisms of the concept of play do not go far enough. After noting the possible roles of generalization, thresholds and learning in play activities, it is suggested that the facts subsummed under the term \\

Harold Schlosberg

1947-01-01

182

Architecture that affords play  

E-print Network

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 ...

Fallon, Paul Eric

1981-01-01

183

Playing With Fire?  

MedlinePLUS

... Main Page The Pink Locker Society Playing With Fire? KidsHealth > Kids > Staying Safe > Playing It Safe Outdoors ... night, or a professional fireworks display. Continue Why Fire Fascinates Fire is a tool and a fascinating ...

184

The Pedagogy of Play  

ERIC Educational Resources Information Center

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

Giesbrecht, Sheila

2012-01-01

185

The Power of Play  

Microsoft Academic Search

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

Hae-Jin Mun

2009-01-01

186

Play, Policy & Practice.  

ERIC Educational Resources Information Center

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…

Klugman, Edgar, Ed.

187

Literacy through Play.  

ERIC Educational Resources Information Center

When young children play in a purposefully designed, literacy-rich environment, teachers can discover and capitalize on teachable moments. This book discusses how children develop literacy and how early childhood teachers use play and other child-centered experiences to facilitate literacy development. Chapter 1, "Play and Developmentally…

Owocki, Gretchen

188

The play of change  

Microsoft Academic Search

Purpose – Two claims are made about play that bears on managing change in organizations. First, play is a creative dynamic of human community; and in particular, it is the form taken by love at the boundary of fantasy and reality. Second, play is known, not by analysis via the mind and reason, but by intuition via the body and

Lloyd Sandelands

2010-01-01

189

Outdoor Creative Play Areas.  

ERIC Educational Resources Information Center

Guidelines are given for the development of outdoor play areas on school sites to provide children with natural areas and simple facilities for creative play. Site selection, analysis, and development are discussed. Natural, topographical features of the environment and natural play equipment are suggested. Illustrations are also presented to aid…

Miller, Peggy L.

190

Girls@Play  

Microsoft Academic Search

This paper reports on findings from a three-year, Canadian federally funded research project entitled “Education, Gender and Gaming” in which we documented the play practices of girls and boys playing console-based games. We show, in particular, how many of the presumptions and assumptions about “girls playing games” simply do not hold over time, or given a particular context. We therefore

Jennifer Jenson; Suzanne de Castell

2011-01-01

191

Play Is the Way  

ERIC Educational Resources Information Center

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

Gross, Steve; Sanderson, Rebecca Cornelli

2012-01-01

192

Nuclear factor-?B plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells  

PubMed Central

Since more than 75% of breast cancers overexpress estrogen receptors (ER), endocrine therapy targeting ER has significantly improved the survival rate. Nonetheless, breast cancer still afflicts women worldwide and the major problem behind it is resistance to endocrine therapy. We have previously shown the involvement of nuclear factor-?B (NF-?B) in neoplastic proliferation of human breast cancer cells; however, the association with the transformation of ER-positive cells remains unclear. In the current study, we focused on roles of NF-?B in the hormone dependency of breast cancers by means of ER-positive MCF-7 cells. Blocking of NF-?B signals in ER-negative cells stopped proliferation by downregulation of D-type cyclins. In contrast, the MCF-7 cells were resistant to NF-?B inhibition. Under estrogen-free conditions, the ER levels were reduced when compared with the original MCF-7 cells and the established cell subline exhibited tamoxifen resistance. Additionally, NF-?B participated in cell growth instead of the estrogen-ER axis in the subline and consequently, interfering with the NF-?B signals induced additive anticancer effects with tamoxifen. MMP-9 production responsible for cell migration, as well as the cell expansion in vivo, were suppressed by NF-?B inhibition. Therefore, we suggest that NF-?B is a master switch in both ER-positive and ER-negative breast cancers. PMID:24531845

Oida, Kumiko; Matsuda, Akira; Jung, Kyungsook; Xia, Yan; Jang, Hyosun; Amagai, Yosuke; Ahn, Ginnae; Nishikawa, Sho; Ishizaka, Saori; Jensen-Jarolim, Erika; Matsuda, Hiroshi; Tanaka, Akane

2014-01-01

193

Nuclear factor-?B plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells.  

PubMed

Since more than 75% of breast cancers overexpress estrogen receptors (ER), endocrine therapy targeting ER has significantly improved the survival rate. Nonetheless, breast cancer still afflicts women worldwide and the major problem behind it is resistance to endocrine therapy. We have previously shown the involvement of nuclear factor-?B (NF-?B) in neoplastic proliferation of human breast cancer cells; however, the association with the transformation of ER-positive cells remains unclear. In the current study, we focused on roles of NF-?B in the hormone dependency of breast cancers by means of ER-positive MCF-7 cells. Blocking of NF-?B signals in ER-negative cells stopped proliferation by downregulation of D-type cyclins. In contrast, the MCF-7 cells were resistant to NF-?B inhibition. Under estrogen-free conditions, the ER levels were reduced when compared with the original MCF-7 cells and the established cell subline exhibited tamoxifen resistance. Additionally, NF-?B participated in cell growth instead of the estrogen-ER axis in the subline and consequently, interfering with the NF-?B signals induced additive anticancer effects with tamoxifen. MMP-9 production responsible for cell migration, as well as the cell expansion in vivo, were suppressed by NF-?B inhibition. Therefore, we suggest that NF-?B is a master switch in both ER-positive and ER-negative breast cancers. PMID:24531845

Oida, Kumiko; Matsuda, Akira; Jung, Kyungsook; Xia, Yan; Jang, Hyosun; Amagai, Yosuke; Ahn, Ginnae; Nishikawa, Sho; Ishizaka, Saori; Jensen-Jarolim, Erika; Matsuda, Hiroshi; Tanaka, Akane

2014-01-01

194

Intestinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors  

PubMed Central

AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction, and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic rats. METHODS: Male Wister rats were fed with a diet containing maize flour, lard, cholesterol, and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide (NO) production inhibitor, N?-nitro-L-arginine methyl ester (L-NAME) intraperitoneally, and an iNOS inhibitor, aminoguanidine hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk, or a HO-1 inhibitor, zinc protoporphyrin (ZnPP) intraperitoneally 12 h prior to killing. Blood, liver and lung tissues were sampled. RESULTS: Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1 ± 1.1 (count/filed) at the 4th wk to 14.5 ± 2.4 (count/filed) at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide (LPS) (0.31 ± 0.08 EU/mL vs control 0.09 ± 0.03 EU/mL), alanine transferase (ALT, 219.1 ± 17.4 U/L vs control 5.9 ± 2.2 U/L) and portal vein pressure. Compared with normal control animals, the number of total cells in bronchoalveolar lavage fluid (BALF) of the cirrhotic rats at the 8th wk was not changed, but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold, protein expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) started to increase significantly at the 4th wk, and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS. NO2-/NO3- was also increased, which was correlated to the increase of iNOS (r = 0.7699, P < 0.0001) and eNOS (r = 0.5829, P < 0.002). mRNA expression of eNOS and iNOS was highly consistent with their protein expression. CONCLUSION: Progression and severity of HPS as indicated by both increased pulmonary capillaries and histological changes are closely associated with LPS levels and progression of hepatic dysfunction as indicated by increased levels of ALT and portal vein pressure. Intestinal endotoxemia plays a central role in the development of HPS in the cirrhotic rat model by inducing NO and/or CO. PMID:18081228

Zhang, Hui-Ying; Han, De-Wu; Su, Ai-Rong; Zhang, Li-Tong; Zhao, Zhong-Fu; Ji, Jing-Quan; Li, Bao-Hong; Ji, Cheng

2007-01-01

195

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.

196

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

PubMed

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

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

2012-10-01

197

Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice.  

PubMed

Although somatic mutations and overexpression of the tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) are strongly associated with bladder cancer, evidence for their functional involvement in the pathogenesis remains elusive. Previously we showed that activation of Fgfr3 alone is not sufficient to initiate urothelial tumourigenesis in mice. Here we hypothesize that cooperating mutations are required for Fgfr3-dependent tumourigenesis in the urothelium and analyse a mouse model in which an inhibitor of Pi3k-Akt signalling, Pten, is deleted in concert with Fgfr3 activation (UroIICreFgfr3(+/) (K644E) Pten(flox) (/flox)). Two main phenotypical characteristics were observed in the urothelium: increased urothelial thickness and abnormal cellular histopathology, including vacuolization, condensed cellular appearance, enlargement of cells and nuclei, and loss of polarity. These changes were not observed when either mutation was present individually. Expression patterns of known urothelial proteins indicated the abnormal cellular differentiation. Furthermore, quantitative analysis showed that Fgfr3 and Pten mutations cooperatively caused cellular enlargement, while Pten contributed to increased cell proliferation. Finally, FGFR3 overexpression was analysed along the level of phosphorylated mTOR in 66 T1 urothelial tumours in tissue microarray, which supported the occurrence of functional association of these two signalling pathways in urothelial pathogenesis. Taken together, this study provides evidence supporting a functional role of FGFR3 in the process of pathogenesis in urothelial neoplasms. Given the wide availability of inhibitors specific to FGF signalling pathways, our model may open the avenue for FGFR3-targeted translation in urothelial disease. PMID:24519156

Foth, Mona; Ahmad, Imran; van Rhijn, Bas W G; van der Kwast, Theodorus; Bergman, Andre M; King, Louise; Ridgway, Rachel; Leung, Hing Y; Fraser, Sioban; Sansom, Owen J; Iwata, Tomoko

2014-06-01

198

African oil plays  

SciTech Connect

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

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

1989-09-01

199

A single polymorphism in HIV-1 subtype C SP1 is sufficient to confer natural resistance to the maturation inhibitor bevirimat.  

PubMed

3-O-(3',3'-Dimethylsuccinyl) betulinic acid (DSB), also known as PA-457, bevirimat (BVM), or MPC-4326, is a novel HIV-1 maturation inhibitor. Unlike protease inhibitors, BVM blocks the cleavage of the Gag capsid precursor (CA-SP1) to mature capsid (CA) protein, resulting in the release of immature, noninfectious viral particles. Despite the novel mechanism of action and initial progress made in small-scale clinical trials, further development of bevirimat has encountered unexpected challenges, because patients whose viruses contain genetic polymorphisms in the Gag SP1 (positions 6 to 8) protein do not generally respond well to BVM treatment. To better define the role of amino acid residues in the HIV-1 Gag SP1 protein that are involved in natural polymorphisms to confer resistance to the HIV-1 maturation inhibitor BVM, a series of Gag SP1 chimeras involving BVM-sensitive (subtype B) and BVM-resistant (subtype C) viruses was generated and characterized for sensitivity to BVM. We show that SP1 residue 7 of the Gag protein is a primary determinant of SP1 polymorphism-associated drug resistance to BVM. PMID:21502630

Lu, Wuxun; Salzwedel, Karl; Wang, Dan; Chakravarty, Suvobrata; Freed, Eric O; Wild, Carl T; Li, Feng

2011-07-01

200

A Single Polymorphism in HIV-1 Subtype C SP1 Is Sufficient To Confer Natural Resistance to the Maturation Inhibitor Bevirimat ?  

PubMed Central

3-O-(3?,3?-Dimethylsuccinyl) betulinic acid (DSB), also known as PA-457, bevirimat (BVM), or MPC-4326, is a novel HIV-1 maturation inhibitor. Unlike protease inhibitors, BVM blocks the cleavage of the Gag capsid precursor (CA-SP1) to mature capsid (CA) protein, resulting in the release of immature, noninfectious viral particles. Despite the novel mechanism of action and initial progress made in small-scale clinical trials, further development of bevirimat has encountered unexpected challenges, because patients whose viruses contain genetic polymorphisms in the Gag SP1 (positions 6 to 8) protein do not generally respond well to BVM treatment. To better define the role of amino acid residues in the HIV-1 Gag SP1 protein that are involved in natural polymorphisms to confer resistance to the HIV-1 maturation inhibitor BVM, a series of Gag SP1 chimeras involving BVM-sensitive (subtype B) and BVM-resistant (subtype C) viruses was generated and characterized for sensitivity to BVM. We show that SP1 residue 7 of the Gag protein is a primary determinant of SP1 polymorphism-associated drug resistance to BVM. PMID:21502630

Lu, Wuxun; Salzwedel, Karl; Wang, Dan; Chakravarty, Suvobrata; Freed, Eric O.; Wild, Carl T.; Li, Feng

2011-01-01

201

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

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.

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

202

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

SciTech Connect

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.

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

2012-01-01

203

Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1.  

PubMed Central

The activities of certain nuclear regulatory proteins are modified by high concentrations of S-nitrosothiols associated with nitrosative stress. In the present study, we have studied the effect of physiological (low microM) concentrations of the endogenous S-nitrosothiol, GSNO (S-nitrosoglutathione), on the activities of nuclear regulatory proteins Sp3 and Sp1 (specificity proteins 3 and 1). Low concentrations of GSNO increased Sp3 binding, as well as Sp3-dependent transcription of the cystic fibrosis transmembrane conductance regulatory gene, cftr. However, higher GSNO levels prevented Sp3 binding, augmented Sp1 binding and prevented both cftr transcription and CFTR (cystic fibrosis transmembrane conductance regulator) expression. We conclude that low concentrations of GSNO favour Sp3 binding to 'housekeeping' genes such as cftr, whereas nitrosative stress-associated GSNO concentrations shut off Sp3-dependent transcription, possibly to redirect cellular resources. Since low micromolar concentrations of GSNO also increase the maturation and activity of a clinically common CFTR mutant, whereas higher concentrations have the opposite effect, these observations may have implications for dosing of S-nitrosylating agents used in cystic fibrosis clinical trials. PMID:14766015

Zaman, Khalequz; Palmer, Lisa A; Doctor, Allan; Hunt, John F; Gaston, Benjamin

2004-01-01

204

Apoptotic sensitivity of colon cancer cells to histone deacetylase inhibitors is mediated by an Sp1/Sp3-activated transcriptional program involving immediate-early gene induction.  

PubMed

Histone deacetylase inhibitors (HDACi) induce growth arrest and apoptosis in colon cancer cells and are being considered for colon cancer therapy. The underlying mechanism of action of these effects is poorly defined with both transcription-dependent and -independent mechanisms implicated. We screened a panel of 30 colon cancer cell lines for sensitivity to HDACi-induced apoptosis and correlated the differences with gene expression patterns induced by HDACi in the five most sensitive and resistant lines. A robust and reproducible transcriptional response involving coordinate induction of multiple immediate-early (fos, jun, egr1, egr3, atf3, arc, nr4a1) and stress response genes (Ndrg4, Mt1B, Mt1E, Mt1F, Mt1H) was selectively induced in HDACi sensitive cells. Notably, a significant percentage of these genes were basally repressed in colon tumors. Bioinformatics analysis revealed that the promoter regions of the HDACi-induced genes were enriched for KLF4/Sp1/Sp3 transcription factor binding sites. Altering KLF4 levels failed to modulate apoptosis or transcriptional responses to HDACi treatment. In contrast, HDACi preferentially stimulated the activity of Spl/Sp3 and blocking their action attenuated both the transcriptional and apoptotic responses to HDACi treatment. Our findings link HDACi-induced apoptosis to activation of a Spl/Sp3-mediated response that involves derepression of a transcriptional network basally repressed in colon cancer. PMID:20068171

Wilson, Andrew J; Chueh, Anderly C; Tögel, Lars; Corner, Georgia A; Ahmed, Naseem; Goel, Sanjay; Byun, Do-Sun; Nasser, Shannon; Houston, Michele A; Jhawer, Minaxi; Smartt, Helena J M; Murray, Lucas B; Nicholas, Courtney; Heerdt, Barbara G; Arango, Diego; Augenlicht, Leonard H; Mariadason, John M

2010-01-15

205

The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways.  

PubMed

Despite the importance of multiple tetraspanin proteins in cancer invasion and metastasis, little is known about the role and significance of tetraspanin CD81 in these processes. In the present study, we examined CD81 effects on melanoma cell invasiveness and metastasis. Transfection of CD81 into melanoma cells lacking endogenous CD81 expression significantly enhanced the migrating, invasive, and metastatic abilities of melanoma cells. Interestingly, membrane type 1 matrix metalloproteinase (MT1-MMP) expression was found in CD81-expressing melanoma cells but not in CD81-deficient cells. siRNA knockdown of CD81 in melanoma cells with endogenous CD81 demonstrated decreased MT1-MMP levels and cell motility. Notably, CD81-induced cell migration was abrogated by antibody blocking and siRNA knockdown of MT1-MMP, indicating that MT1-MMP is responsible for CD81-stimulated melanoma cell migration. Promoter analysis revealed an essential role of the Sp1 transcription factor in CD81-induced MT1-MMP transcription. We also demonstrate that the Sp1-activating Akt pathway is involved in adhesion-dependent CD81 signaling to induce MT1-MMP expression and cell motility. Importantly, human skin cancer tissue specimens displayed a positive correlation of CD81 with MT1-MMP expression levels and a close association of CD81 with malignant melanomas. Taken together, these results strongly suggest that CD81 stimulates melanoma cell motility by inducing MT1-MMP expression through the Akt-dependent Sp1 activation signaling pathway, leading to increased melanoma invasion and metastasis. PMID:24733393

Hong, In-Kee; Byun, Hee-Jung; Lee, Jaeseob; Jin, Young-June; Wang, Sun-Ju; Jeoung, Doo-Il; Kim, Young-Myeong; Lee, Hansoo

2014-05-30

206

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

Microsoft Academic Search

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

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

1991-01-01

207

Distinct contributions of model MaSp1 and MaSp2 like peptides to the mechanical properties of synthetic major ampullate silk fibers as revealed in silico  

PubMed Central

All characterized major ampullate silks from orb-web weaving spiders are composites of primarily two different proteins: MaSp1 and MaSp2. The conserved association of MaSp1 and MaSp2 in these spider species, the highly conserved amino acid motifs, and variable ratios of MaSp1 to MaSp2 demonstrate the importance of both MaSp1 and MaSp2 to the strength and elasticity of the fiber. Computer simulated mechanical tests predicted differing roles for MaSp1 and MaSp2 in the mechanical properties of the fibers. Recombinant MaSp1 and MaSp2 proteins were blended and spun into fibers mimicking the computer-simulated conditions. Mechanical testing verified the differing roles of MaSp1 and MaSp2. PMID:20657704

Brooks, Amanda E; Nelson, Shane R; Jones, Justin A; Koenig, Courtney; Hinman, Michael; Stricker, Shane; Lewis, Randolph V

2008-01-01

208

Play and Digital Media  

ERIC Educational Resources Information Center

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…

Johnson, James E.; Christie, James F.

2009-01-01

209

Play, Toys and Television.  

ERIC Educational Resources Information Center

In Western societies, television has transformed the life, culture, and points of reference of the child. Its particular sphere of influence is the child's play culture. This play culture is not hermetic: it is very oriented toward manipulation; has a symbolic role as a representational medium; evolves along with the child; has a certain amount of…

Brougere, Gilles

210

Playing with Autistic Children.  

ERIC Educational Resources Information Center

The paper looks at the development of a play group for autistic children with descriptions of the autistic population, the daily program, the program's philosophy, the play group model, and actual lessons. Children, who ranged in age from 5 to 9 years, often chose activities which were self-stimulating and/or repetitive. The daily program included…

Casner, Mary W.; Marks, Susan F.

211

The Fear of Play  

ERIC Educational Resources Information Center

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

Almon, Joan

2009-01-01

212

Let's Just Play  

ERIC Educational Resources Information Center

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

Schmidt, Janet

2003-01-01

213

Return to Play  

ERIC Educational Resources Information Center

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.

Mangan, Marianne

2013-01-01

214

Role Playing and Skits  

ERIC Educational Resources Information Center

Explores non-scripted role playing, dialogue role playing, sociodrama, and skits as variations of simulation techniques. Provides step-by-step guidelines for conducting such sessions. Successful Meetings, Bill Communications, Inc., 1422 Chestnut Street, Philadelphia, Pa. 19102. Subscription Rates: yearly (US, Canada, Mexico) $14.00; elsewhere,…

Letwin, Robert, Ed.

1975-01-01

215

Narrative, Play, and Development.  

ERIC Educational Resources Information Center

Reviews Josephs's (1998) article connecting play as a discourse in metaphorical transformations with narrative and identity development, focusing on using narrative as a discourse of accounting for self and others in space and time and the role of self-thematization, death, and play in development. Concludes that Josephs advocates the cancellation…

Bamberg, Michael

1998-01-01

216

The Play's the Thing  

ERIC Educational Resources Information Center

The modern special education theater in the United States has hosted many plays, none with a larger or more diverse cast than the learning disabilities (LD) play. During the prologue, the children with LD were waiting in the wings, not yet identified as LD but there, nonetheless. With the advent of compulsory education in this country, awareness…

Bateman, Barbara

2005-01-01

217

Hyperosmolarity-induced up-regulation of claudin-4 mediated by NADPH oxidase-dependent H2O2 production and Sp1/c-Jun cooperation.  

PubMed

Claudin-4 is exclusively localized in the tight collecting ducts in the renal tubule. We examined what molecular mechanism is involved in the regulation of claudin-4 expression. In Madin-Darby canine kidney cells, hyperosmolarity increased the expression level of claudin-4 and the production of reactive oxygen species, which were inhibited by diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, and manganese (III) tetrakis (4-benzoic acid)porphyrin (MnTBAP), a scavenger of H2O2. Both hyperosmolarity and H2O2 increased p-ERK1/2 and p-JNK, which were inhibited by U0126, a MEK inhibitor, and SP600125, a JNK inhibitor, respectively. Immunoprecipitation assay showed that hyperosmolarity increased the association of nuclear Sp1 with c-Jun, which was inhibited by U0126 and SP600125. In mouse inner medullary collecting duct cells and rat kidney slices, hyperosmolarity increased the expression level of claudin-4, which was inhibited by DPI, MnTBAP, U0126, and SP600125. Hyperosmolarity increased luciferase reporter activity of claudin-4, which was inhibited by U0126, SP600125, Sp1 siRNA, and c-Jun siRNA. The activity was inhibited by the mutation in the Sp1 binding site. Chromatin immunoprecipitation assay and avidin-biotin conjugated DNA assay showed that Sp1 and c-Jun are associated with the Sp1 binding site. These results suggest that hyperosmolarity increases nuclear Sp1/c-Jun complex and the association of the complex with the Sp1 binding site, resulting in the segment-specific expression of claudin-4 in the kidney. PMID:23816505

Ikari, Akira; Atomi, Kosuke; Yamazaki, Yasuhiro; Sakai, Hideki; Hayashi, Hisayoshi; Yamaguchi, Masahiko; Sugatani, Junko

2013-12-01

218

microRNA-128 plays a critical role in human non-small cell lung cancer tumourigenesis, angiogenesis and lymphangiogenesis by directly targeting vascular endothelial growth factor-C.  

PubMed

Recent studies have indicated that microRNAs (miRNAs) are important gene regulators that play critical roles in biological processes and function as either tumour suppressors or oncogenes. Therefore, the expression levels of miRNAs can be important and reliable biomarkers for cancer detection and prognostic prediction, and potentially serve as targets for cancer therapy. In this study, we showed that the expression level of miR-128 was significantly downregulated in non-small cell lung cancer (NSCLC) tissues and cancer cells, and was significantly correlated with NSCLC differentiation, pathological stage and lymph node metastasis. Ectopic miR-128 overexpression significantly suppressed in vitro proliferation, colony formation, immigration and invasion, and induced G1 arrest and apoptosis of NSCLC cells. Interestingly, ectopic miR-128 overexpression could significantly inhibit vascular endothelial growth factor (VEGF)-C expression and reduce the activity of a luciferase reporter containing the VEGF-C 3'-untranslated region. In addition, overexpression of miR-128 in NSCLC cells and human umbilical vein endothelial cells (HUVECs) cells led to decreased expression of VEGF-A, vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3, critical factors responsible for cancer angiogenesis and lymphangiogenesis, and subsequently decreased phosphorylation of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (AKT) and p38 signalling pathways. Furthermore, in vivo restoration of miR-128 significantly suppressed tumourigenicity of A549 cells in nude mice and inhibited both angiogenesis and lymphangiogenesis of tumour xenografts. These findings suggest that miR-128 could play a role in NSCLC tumourigenesis at least in part by modulation of angiogenesis and lymphangiogenesis through targeting VEGF-C, and could simultaneously block ERK, AKT and p38 signalling pathways. Therapeutic strategies to restore miR-128 in NSCLC could be useful to inhibit tumour progression. PMID:25001183

Hu, Jing; Cheng, Yongxia; Li, Yuezhen; Jin, Zaishun; Pan, Yanming; Liu, Guibo; Fu, Songbin; Zhang, Yafang; Feng, Kejian; Feng, Yukuan

2014-09-01

219

Evidence That Spt10 and Spt21 of Saccharomyces cerevisiae Play Distinct Roles in Vivo and Functionally Interact With MCB-Binding Factor, SCB-Binding Factor and Snf1  

Microsoft Academic Search

Mutations in SPT10 and SPT21 of Saccharomyces cerevisiae have been previously shown to cause two prominent mutant phenotypes: (1) defects in transcription of particular histone genes and (2) suppression of Ty and -insertion mutations (Spt phenotype). The requirement for Spt10 and Spt21 for transcription of particular histone genes suggested that they may interact with two factors previously shown to be

David Hess; Fred Winston

2005-01-01

220

Phylogenetic placement of the spider genus Nephila (Araneae: Araneoidea) inferred from rRNA and MaSp1 gene sequences.  

PubMed

The family status of the genus Nephila, which belongs to Tetragnathidae currently but Araneidae formerly, was reexamined based on molecular phylogenetic analyses. In the present study, 12S and 18S rRNA gene fragments of eight species of spiders were amplified and sequenced. In addition, 3'-end partial cDNA of major ampullate spidroin-1 (MaSp1) gene of Argiope amoena was cloned and sequenced, and the 3'-end non-repetitive region's cDNA sequence of MaSp1 gene and the predicted amino acid sequence of C-terminal non-repetitive region of MaSp1 were aligned with some previously known sequences. The resulting phylogeny showed that Araneidae and Tetragnathidae are not a sister group in the superfamily Araneoidea, and the genus Nephila is closer to the genera of the family Araneidae rather than to those of Tetragnathidae. We suggest that the genus Nephila should be transferred back to Araneidae. Or the subfamily Nephilinae might be elevated to family level after it was redefined and redelimited. Furthermore, the study showed that 3'-end non-repetitive region's cDNA sequence of MaSp1 gene and C-terminal non-repetitive region's amino acid sequence of MaSp1 are useful molecular markers for phylogenetic analysis of spiders. PMID:15056930

Pan, Hong-Chun; Zhou, Kai-Ya; Song, Da-Xiang; Qiu, Yang

2004-03-01

221

Plays in Performance  

E-print Network

, subjective perspective. Characterizations are vivid and striking. The protagonist, Sonny, is mercurial, manic-depressive, on the edge of suicide, grasping for order and meaning, deriving black humor from desperation and despair. The parents, played...

Editors

1988-04-01

222

Play in orphanages  

Microsoft Academic Search

Objectives: This paper attempts to validate the programme of structured play lasting 90 minutes a day, for use in orphanages, to check\\u000a if it can be replicated in other orphanages, with similar results.Methods : A 2-week workshop on the structured play scheme was conducted at the Missionaries of Charity Orphanage in Delhi, the venue\\u000a of the original project. 15 MOC

Vikas Taneja; R. S. Beri; J. M. Puliye

2004-01-01

223

Play and Digital Media  

Microsoft Academic Search

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 children's initiative and decision-making. Digital toys with

James E. Johnson; James F. Christie

2009-01-01

224

Increased expression of colonic Wnt9A through Sp1-mediated transcriptional effects involving arylsulfatase B, chondroitin 4-sulfate, and galectin-3.  

PubMed

In cultured human colonic epithelial cells and mouse colonic tissue, exposure to the common food additive carrageenan leads to inflammation, activation of Wnt signaling, increased Wnt9A expression, and decline in the activity of the enzyme arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase). In this study, the novel transcriptional mechanism by which carrageenan and decline in ARSB increase Wnt9A expression in NCM460 and HT-29 human colonic epithelial cells and in mouse colon is presented. Increased expression of Wnt9A has been associated with multiple malignancies, including colon carcinoma, and with ectodermal and mesoendodermal morphogenesis. When ARSB activity was reduced by siRNA or by exposure to carrageenan (1 ?g/ml for 24 h), degradation of chondroitin 4-sulfate (C4S) was inhibited, leading to accumulation of more highly sulfated C4S, which binds less galectin-3, a ?-galactoside-binding protein. Nuclear galectin-3 increased and mediated increased binding of Sp1 to the Sp1 consensus sequence in the Wnt9A promoter, shown by oligonucleotide-binding assay and by chromatin immunoprecipitation assay. When galectin-3 was silenced, the increases in Sp1 binding to the Wnt9A promoter and in Wnt9A expression, which followed carrageenan or ARSB silencing, were inhibited. Mithramycin A, a specific inhibitor of Sp1 oligonucleotide binding, and Sp1 siRNA blocked the carrageenan- and ARSB siRNA-induced increases in Wnt9A expression. These studies reveal how carrageenan exposure can lead to transcriptional events in colonic epithelial cells through decline in arylsulfatase B activity, with subsequent impact on C4S, galectin-3, Sp1, and Wnt9A and can exert significant effects on Wnt-initiated signaling and related vital cell processes. PMID:24778176

Bhattacharyya, Sumit; Feferman, Leo; Tobacman, Joanne K

2014-06-20

225

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

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.

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

226

Play Dough Planets  

NSDL National Science Digital Library

This is a lesson about planet sizes. Learners will demonstrate the size (volume) differences between Earth, Earthâs 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.

227

Pathways to Play: Developing Play Skills in Young Children.  

ERIC Educational Resources Information Center

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

Heidemann, Sandra; Hewitt, Deborah

228

Time perspective as a predictor of massive multiplayer online role-playing game playing.  

PubMed

This article focuses on the relationship between the time perspective (TP) personality trait and massive multiplayer online role-playing game (MMORPG) playing. We investigate the question of frequency of playing. The TP was measured with Zimbardo's TP Inventory (ZTPI), which includes five factors-past negative, past positive, present hedonistic, present fatalistic, and future. The study used data from 154 MMORPG players. We demonstrated that TP partially explained differences within a group of players with respect to the frequency of playing. Significant positive correlations were found between present factors and the amount of time spent playing MMORPGs, and significant negative correlation was found between the future factor and the time spent playing MMORPGs. Our study also revealed the influence of future-present balance on playing time. Players who scored lower in future-present balance variables (their present score was relatively high compared with their future score) reported higher values in playing time. In contrast to referential studies on TP and drug abuse and gambling, present fatalistic TP was demonstrated to be a stronger predictor of extensive playing than present hedonistic TP, which opened the question of motivation for playing. The advantage of our study compared with other personality-based studies lies in the fact that TP is a stable but malleable personality trait with a direct link to playing behavior. Therefore, TP is a promising conceptual resource for excessive playing therapy. PMID:22032796

Lukavska, Katerina

2012-01-01

229

Learn to Play Chess!  

NSDL National Science Digital Library

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.

2013-01-01

230

Statistics at Play  

ERIC Educational Resources Information Center

An exciting event had occurred for the grade 3 classes at Woodlands State School. A new play space designated for the older grades had now been opened to the third graders. In sharing their excitement over this "real treat, real privilege," the teachers invited the children to find out more about playgrounds and, in particular, their new…

English, Lyn D.

2014-01-01

231

Play's Importance in School  

ERIC Educational Resources Information Center

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

Sandberg, Anette; Heden, Rebecca

2011-01-01

232

"Playing" with Science  

ERIC Educational Resources Information Center

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…

Allen, Dave

2012-01-01

233

Abstraction through Game Play  

ERIC Educational Resources Information Center

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

Avraamidou, Antri; Monaghan, John; Walker, Aisha

2012-01-01

234

Romantic / classical Science play  

E-print Network

Romantic / classical Science play Space/time [Brechtian theater] Epic theater Didactic Alienation) Iteration Fractals Free research/authority Argument from authority Logical fallacy Basic postulates Prose vs. verse Meter Alien anthropology Props and staging Believing game They Say / I Say Illusion #12;Things we

235

One Play a Day  

ERIC Educational Resources Information Center

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…

Blankenship, Mark

2007-01-01

236

Bicentennial Plays and Programs.  

ERIC Educational Resources Information Center

This book contains royalty-free material on bicentennial themes for presentation by schools and amateur groups. The first section, Plays and Pageants, contains "Our Great Declaration,""A Star for Old Glory,""Sing, America, Sing,""Washington Marches On,""When Freedom Was News," and "A Dish of Green Peas." The second section, Playlets and…

Fisher, Aileen

237

E-Play  

Microsoft Academic Search

E-Play is an electronic entertainer, pacifier, and communicator that meets needs of very small children, from infancy to preschool, is robust and simple to control, and is activated by touch only. Children choose activities by touching a picture, thus it is a natural design for use with kids having no computer experience. We have explored two types of contents -

Claudia V. Goldman; Scott Kirkpatricki

2002-01-01

238

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

PubMed Central

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

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

2008-01-01

239

Development through Work and Play.  

ERIC Educational Resources Information Center

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

Hartung, Paul J.

2002-01-01

240

Play and Culture. Beginnings Workshop.  

ERIC Educational Resources Information Center

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

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

1999-01-01

241

HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism.  

PubMed

Cancer cells have complex, unique characteristics that distinguish them from normal cells, such as increased growth rates and evasion of anti-proliferative signals. Global inhibition of class I and II histone deacetylases (HDACs) stops cancer cell proliferation in vitro and has proven effective against cancer in clinical trials, at least in part, through transcriptional reactivation of the p21(WAF1/Cip1)gene. The HDACs that regulate p21(WAF1/Cip1) are not fully identified. Using small interfering RNAs, we found that HDAC4 participates in the repression of p21(WAF1/Cip1) through Sp1/Sp3-, but not p53-binding sites. HDAC4 interacts with Sp1, binds and reduces histone H3 acetylation at the Sp1/Sp3 binding site-rich p21(WAF1/Cip1) proximal promoter, suggesting a key role for Sp1 in HDAC4-mediated repression of p21(WAF1/Cip1). Induction of p21(WAF1/Cip1) mediated by silencing of HDAC4 arrested cancer cell growth in vitro and inhibited tumor growth in an in vivo human glioblastoma model. Thus, HDAC4 could be a useful target for new anti-cancer therapies based on selective inhibition of specific HDACs. PMID:18850004

Mottet, D; Pirotte, S; Lamour, V; Hagedorn, M; Javerzat, S; Bikfalvi, A; Bellahcène, A; Verdin, E; Castronovo, V

2009-01-15

242

Enhanced dissolution rate of felodipine using spherical agglomeration with Inutec SP1 by quasi emulsion solvent diffusion method.  

PubMed

Felodipine is a second generation calcium channel blocker widely used as antihypertensive and antianginal drug which belongs to BCS class II category. Hence, its low water solubility limits the pharmacological effect. The aim of this study was to improve the dissolution rate of felodipine using spherical agglomeration technique with acetone, water and dichloromethane as good solvent, poor solvent and bridging liquid, respectively. The quasi emulsion solvent diffusion technique was used as a method for spherical agglomeration. Inutec SP1 was used as an emulsion stabilizer and as hydrophilic polymer in agglomeration process. The FTIR and DSC results showed no change in the drug after crystallization process. PXRD studies showed sharp peaks in the diffractograms of spherical agglomerates with minor reduction in height of the peaks. The particle size of spherical agglomerates (FI-2) was about 134.33 ± 13.57 µm, n=3 and the dissolution efficiency of felodipine up to 120 min increased to about 4-fold in phosphate buffer containing 1.8% Tween 80 (pH 6.8). Spherical agglomerates showed enhanced solubility compared to untreated powder possibly due to the partial conversion to amorphous form. PMID:21589802

Tapas, A R; Kawtikwar, P S; Sakarkar, D M

2009-07-01

243

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

PubMed

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

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

2014-11-01

244

Play It Safe  

NSDL National Science Digital Library

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.

Terc

2010-01-01

245

Methylation-enhanced binding of Sp1 to the stage selector element of the human gamma-globin gene promoter may regulate development specificity of expression.  

PubMed Central

The human gamma-globin gene promoter contains a stage selector element (SSE) responsible for preferential interaction of the promoter with a powerful erythroid-specific enhancer in the fetal developmental stage (S.M. Jane, P.A. Ney, E.F. Vanin, D.L. Gumucio, and A.W. Nienhuis. EMBO J. 11:2691-2699, 1992). The element binds two proteins, the ubiquitous activator Sp1 and a protein previously known as -50 gamma and now named the stage selector protein (SSP). Binding of the second protein correlates with SSE activity in transient-transfection assays. We now report that a de novo binding site for the SSP is created by the -202(C-->G) mutation that causes hereditary persistence of fetal hemoglobin (HPFH). This site functions in an analogous manner to the SSE in hybrid beta-promoter/reporter gene constructs transfected into K562 cells. In contrast, the wild-type -202 sequence, which fails to bind the SSP, is incapable of activating the beta-gene promoter. Both the -50 and -202 HPFH sites for SSP binding overlap a consensus sequence for the transcriptional regulator Sp1. In addition, both sites contain CpG dinucleotides that are contact bases for SSP. Since the gamma promoter is known to be hypomethylated in fetal cells but fully methylated at CpG residues in adult erythroid cells, we examined the effects of this DNA modification on protein binding to the two regions. Gel mobility shift assays with nuclear extract from K562 cells (which contain both Sp1 and SSP) demonstrate preferential binding of SSP to the SSE and HPFH sites under conditions in which probe was limiting. Methylation of the CpG residues reverses this preference only in the SSE site, with a marked increase in the binding of Sp1 at the expense of the SSP. Purified Sp1 binds with 10-fold higher affinity to the methylated than to the nonmethylated -50 probe but with the same affinity to the -202 HPFH probe. The methylation-induced preferential binding of Sp1 to the SSE at the expense of SSP may be part of the mechanism by which the gamma genes are repressed in normal adult erythroid cells. In cells containing the -202 HPFH mutation, the inability of Sp1 to displace SSP in the methylated state may explain the persistence of gamma-promoter activity and gamma-gene expression observed in adults with this mutation. Images PMID:7684493

Jane, S M; Gumucio, D L; Ney, P A; Cunningham, J M; Nienhuis, A W

1993-01-01

246

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

ERIC Educational Resources Information Center

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.…

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

247

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

PubMed Central

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

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

2013-01-01

248

Disease Role Play  

NSDL National Science Digital Library

Students in collaborative groups will develop an action plan to address a new disease. This activity provides 3 roles for student participation: scientist, public health official and community leader. Each group member will be required to remain within the parameters described by the scenario during the role play. For example, the scientists will be given a data sheet the they will need to interpret. This group member will be the only one with knowledge of the disease. Only this person will act as a disease expert. Once the groups have an opportunity to read their scenarios and prepare for a committee meeting, they will meet and devise an action plan.

BEGIN:VCARD VERSION:2.1 FN:Chris Kuka N:Kuka;Chris ORG:Bend Senior High School REV:2005-04-12 END:VCARD

1994-07-30

249

Baroreceptor Reflex Role Play  

NSDL National Science Digital Library

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.

Macleish, Marlene Y.; Mclean, Bernice R.

2012-06-26

250

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

E-print Network

Play Therapy Summer 2014 Seminar Series LSUHSC Play Therapy Clinic $50/Seminar for Professionals@lsuhsc.edu Seminar #1: June 6th (10:15am-1:15pm) Presented by: Dr. Erin Dugan Introduction to Play Therapy & Basic of the basic principles, objectives, goals, therapeutic factors, tenets and dimensions of play therapy

251

Play at Home, Play in the Classroom: Parent/Professional Partnerships in Supporting Child Play.  

ERIC Educational Resources Information Center

Discussion of the role of play in development of young children with disabilities considers the different forms of play as the child develops, the social nature of play, contexts and play materials, and the value of including play goals and strategies in the individualized family service plan or individual education program developed cooperatively…

Buchanan, Michelle; Cooney, Margaret

2000-01-01

252

Who played the Raptors?  

NSDL National Science Digital Library

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

National Council of Teachers of Mathematics (NCTM)

2002-01-01

253

Differential utilization of the promoter of peripheral-type benzodiazepine receptor by steroidogenic versus nonsteroidogenic cell lines and the role of Sp1 and Sp3 in the regulation of basal activity.  

PubMed

The peripheral-type benzodiazepine receptor (PBR) is involved in many cellular functions, including steroidogenesis, oxidative processes, cellular proliferation, and apoptosis. Secretory and glandular tissues, especially steroid hormone-producing cells, are particularly rich in PBR. To understand the mechanisms of PBR expression and regulation, we established an mRNA expression profile in mouse tissues and cell lines and subsequently mapped the transcription start site and characterized the promoter of the gene. Our findings indicate that PBR tissue mRNA levels are relatively high in kidney, spleen, muscle, lung, adrenal gland, thymus, and stomach; are intermediate in pancreas, uterus, prostate, heart, and testis; and are low in brain and liver. Relatively high levels of PBR mRNA were also observed in the steroid-synthesizing MA-10 mouse Leydig tumor cells compared with adrenocortical Y1 mouse cells and nonsteroidogenic NIH-3T3 mouse fibroblasts, although PBR protein levels were much higher in both steroidogenic cells compared with fibroblasts. Transcription was initiated primarily at an adenine nucleotide 61 nucleotides upstream of the translation start site, but internal initiation was also observed. A 2.7-kb fragment of the mouse PBR promoter was cloned and sequenced. Sequence analysis revealed the absence of TATA or CCAAT boxes, but the presence of many putative transcription factor-binding sites, including Sp1/Sp3, AP2, Ik2, AP1, SOX, GATA, and SRY. Functional characterization revealed that two Sp1/Sp3 sites in the proximal promoter are important for basal activity in all cell lines tested and that the steroidogenic MA-10 and Y1 cells use different areas of the promoter compared with nonsteroidogenic NIH-3T3 cells. PMID:14630713

Giatzakis, Christoforos; Papadopoulos, Vassilios

2004-03-01

254

Child's Play: Revisiting Play in Early Childhood Settings.  

ERIC Educational Resources Information Center

Noting that play is an essential aspect of learning for young children, this book presents a collection of articles on children's play in Australia. Part 1, "Play, Development, and Learning," contains the following chapters: (1) "The Role of Play in Development and Learning" (Ann Glover); (2) "Stop, Look, and Listen: Adopting an Investigative…

Dau, Elizabeth, Ed.; Jones, Elizabeth, Ed.

255

Literacy Play: Is It Really Play Anymore? Issues in Education.  

ERIC Educational Resources Information Center

Raises concerns about whether literacy-enriched play in early childhood settings is really play. Presents a vignette to illustrate how a teacher can model literacy unobtrusively, thereby enhancing literacy, but unwittingly draw children away from meaningful play activities. Differentiates the cognitive processes involved in play and literacy…

Trawick-Smith, Jeffrey; Picard, Theresa

2003-01-01

256

Play Therapist's Perspectives on Culturally Sensitive Play Therapy  

Microsoft Academic Search

The Association for Play Therapy (2009) promotes play therapists’ awareness of personal cultural identity, obtaining continuous cultural knowledge, and displaying culturally appropriate practices. Play therapy research includes studies on working with specific culturally diverse populations. Founding play therapists, such as Virginia Axline, have made suggestions for toys that should be included in the therapist’s playroom. This exploratory survey inquired about

Krystal M Vaughn

2012-01-01

257

Playing My Heart Out: Original Play as Adventure.  

ERIC Educational Resources Information Center

"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)

Donaldson, O. Fred

1999-01-01

258

Play in evolution and development  

Microsoft Academic Search

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

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

2007-01-01

259

PLAY IN THE UNIVERSITY CLASSROOM  

Microsoft Academic Search

The use of play is suggested as a bona fide teaching adjunct because play inherently increases pleasure in experimentation and risk with new ideas and skills. Play introduces opportunities for trial-and-error learning in addition to the more traditional inductive and deductive learning modes of academia. Moreover, momentary playfulness in classroom interactions facilitates the transition from one class period to another;

Henry W Maier

1980-01-01

260

Children's play - a forgotten right  

Microsoft Academic Search

Play - the forgotten right describes the important and often overlooked role of play in children's learning. It describes the characteristics of a good play space and points to the inadequate in provision for children's play in Europe (and virtually all other societies). It also discusses the impact on children (and on their later development as adults) of deprived or

Bob Hughes

1990-01-01

261

Music Learning and Child's Play.  

ERIC Educational Resources Information Center

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

Littleton, Danette

1998-01-01

262

Enhanced Reality Live Role Playing  

Microsoft Academic Search

Live role-playing is a form of improvisational theatre played for the experience of the performers and without an audience. These games form a challenging application domain for ubiquitous technology. We discuss the design options for enhanced reality live role-playing and the role of technology in live role-playing games.

Jonas Söderberg; Annika Waern; Karl-Petter Åkessson; Staffan Björk; Jennica Falk

263

Playing with molecules.  

PubMed

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

Toon, Adam

2011-12-01

264

A small-molecule metastasis inhibitor, norcantharidin, downregulates matrix metalloproteinase-9 expression by inhibiting Sp1 transcriptional activity in colorectal cancer cells.  

PubMed

Norcantharidin (NCTD) is a small-molecule metastasis inhibitor without renal toxicity derived from a renal toxic compound cantharidin, which is found in blister beetles (Mylabris phalerata Pall.), commonly used in traditional Chinese medicine. The anti-metastatic capacity of NCTD is apparently through the downexpression of matrix metalloproteinase-9 (MMP-9) activity. The aim of this study was to clarify the transcriptional regulation of MMP-9 gene by NCTD in colorectal cancer CT-26 cells. NCTD not only downregulated MMP-9 mRNA and protein expression, but also inhibited gelatinase activity in a concentration- and time-dependent manner. In CT26 cells with transfection of cis-element reporter plasmids, NCTD treatment decreased reporter luciferase activity from a Sp1 construct, augmented with a NF-kappaB construct, but this did not occur with an AP-1 construct. Further transfecting with constructs containing wild-type or various mutant MMP-9 promoters in CT26 cells indicated that Sp1, but not the others, was required for NCTD-inhibition of MMP-9 promoter transactivation. More evidence by electrophoretic mobility shift assay demonstrated that NCTD inhibited the DNA-binding activity of Sp1. In addition, the increase effect of NF-kappaB-luciferase activity by NCTD may include the upexpression of nuclear STAT1 and result in competitive suppression of NF-kappaB-binding activity in MMP-9 promoter. In conclusion, the metastasis inhibitor NCTD downregulates MMP-9 expression by inhibiting Sp1 transcriptional activity in colorectal cancer CT26 cells. PMID:19616522

Chen, Yu-Jen; Chang, Wei-Min; Liu, Yi-Wen; Lee, Chia-Yun; Jang, Yi-Hua; Kuo, Cheng-Deng; Liao, Hui-Fen

2009-10-30

265

Rough and Tumble Play 101  

ERIC Educational Resources Information Center

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…

Carlson, Frances

2009-01-01

266

Designing playful interactions for social interaction and physical play  

Microsoft Academic Search

This paper describes three design values that we apply for designing playful interactions. Interactive play objects can stimulate\\u000a social interaction and physical play by providing motivating feedback to players’ behavior; they can allow players to create\\u000a their own game goals and rules in an open-ended play context and support social player interaction patterns. This design approach\\u000a is illustrated by six

Tilde Bekker; Janienke Sturm; Berry Eggen

2010-01-01

267

PlayPals: Tangible Interfaces for Remote Communication and Play  

E-print Network

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

Ishii, Hiroshi

268

Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation.  

PubMed Central

The endothelial cell-specific mitogen vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) represents a central regulator of cutaneous angiogenesis. Increased VPF/VEGF expression has recently been reported in psoriatic skin and healing wounds, both conditions in which transforming growth factor-alpha (TGF alpha) and its ligand, the epidermal growth factor receptor, are markedly up-regulated. Since TGF alpha strongly induces VPF/VEGF synthesis in keratinocytes, TGF alpha-mediated VPF/VEGF expression is likely to play a significant role in the initiation and maintenance of increased vascular hyperpermeability and hyperproliferation in skin biology. The objectives of the present studies were to determine the molecular mechanisms responsible for TGF alpha-induced transcriptional activation of the VPF/VEGF gene. We have identified a GC-rich TGF alpha-responsive region between -88 bp and -65 bp of the VPF/VEGF promoter that is necessary for constitutive and TGF alpha-inducible transcriptional activation. In electrophoretic mobility shift assays, this region binds Sp1-dependent protein complexes constitutively and an additional TGF alpha-inducible protein complex that is distinct from Sp1 protein. Both AP-2 and Egr-1 transcription factors were detected as components of the TGF alpha-inducible protein complex in supershift EMSA studies. In co-transfection studies, an AP-2 but not an Egr-1 expression vector activated VPF/VEGF transcription, thus indicating that AP-2 protein is functionally important in TGF alpha-induced VPF/VEGF gene expression. By clarifying regulatory mechanisms that are critical for angiogenic processes in the skin, these studies may form the basis for new therapeutic strategies to modulate VPF/VEGF expression in cutaneous inflammation and wound healing. PMID:9049304

Gille, J; Swerlick, R A; Caughman, S W

1997-01-01

269

Medical Play for Young Children.  

ERIC Educational Resources Information Center

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

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

2000-01-01

270

Healthy Post-Play Snacks  

MedlinePLUS

... Friendly Worksites Program Requirements Fit-Friendly Resources Healthy Post-Play Snacks Updated:Nov 12,2013 As nearly ... sure kids have access to healthier foods—including post-play snacks. All too often, kids are rewarded ...

271

Motivations for Play in Online Games  

Microsoft Academic Search

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

Nick Yee

2006-01-01

272

Solar Power at Play  

NASA Astrophysics Data System (ADS)

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

2007-03-01

273

Play Therapy: Basics and Beyond.  

ERIC Educational Resources Information Center

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

Kottman, Terry

274

Preschoolers' Thinking during Block Play  

ERIC Educational Resources Information Center

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…

Piccolo, Diana L.; Test, Joan

2010-01-01

275

The Importance of Being Playful.  

ERIC Educational Resources Information Center

Recent research provides evidence of the strong connections between quality of play in preschool years and children's readiness for school instruction. Mature play, characterized by imaginary situations, multiple roles, clearly defined rules, flexible themes, language development, length of play, helps students' cognitive development. (Contains 12…

Bodrova, Elena; Leong, Deborah J.

2003-01-01

276

Meanings of Play among Children  

ERIC Educational Resources Information Center

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…

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

2013-01-01

277

Play Therapy in School Counseling  

ERIC Educational Resources Information Center

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…

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

2013-01-01

278

Playing Othello Using Monte Carlo  

Microsoft Academic Search

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

J. a. m. Nijssen

279

Pretend Play and Creative Processes  

ERIC Educational Resources Information Center

The authors contend that many cognitive abilities and affective processes important in creativity also occur in pretend play and that pretend play in childhood affects the development of creativity in adulthood. They discuss a variety of theories and observations that attempt to explain the importance of pretend play to creativity. They argue that…

Russ, Sandra W.; Wallace, Claire E.

2013-01-01

280

Piaget, Play and Cognition, Revisited.  

ERIC Educational Resources Information Center

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…

Sutton-Smith, Brian

281

Play in Evolution and Development  

ERIC Educational Resources Information Center

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

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

2007-01-01

282

Reflections on Research and Practice in Outdoor Play Environments.  

ERIC Educational Resources Information Center

Cites research which suggests that U.S. playgrounds are hazardous and developmentally sterile. Factors that affect the relationship of playgrounds to child development include (1) the developmental appropriateness of playground environments; (2) gender differences in outdoor play; (3) well-equipped play environments; (4) the use of portable play

Frost, Joe L.

1992-01-01

283

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

ERIC Educational Resources Information Center

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…

Little, Helen; Wyver, Shirley; Gibson, Frances

2011-01-01

284

On knowing it's only play: The role of play signals in play fighting  

Microsoft Academic Search

Play fighting in many species contains behavioral elements of direct aggression; that is, those behavior patterns that are used to threaten and contact opponents. Although many investigators have alleged that there are play signals that can be used to unambiguously distinguish playful from nonplayful aggression, the existence of such signals is mainly anecdotal and correlational. For most species, such signals

Sergio M. Pellis; Vivien C. Pellis

1996-01-01

285

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

PubMed

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

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

2014-10-01

286

Transforming growth factor beta-activated kinase 1 (TAK1) kinase adaptor, TAK1-binding protein 2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in tumor necrosis factor signaling pathway.  

PubMed

Transforming growth factor beta-activated kinase 1 (TAK1) kinase is an indispensable signaling intermediate in tumor necrosis factor (TNF), interleukin 1, and Toll-like receptor signaling pathways. TAK1-binding protein 2 (TAB2) and its closely related protein, TAB3, are binding partners of TAK1 and have previously been identified as adaptors of TAK1 that recruit TAK1 to a TNF receptor signaling complex. TAB2 and TAB3 redundantly mediate activation of TAK1. In this study, we investigated the role of TAB2 by analyzing fibroblasts having targeted deletion of the tab2 gene. In TAB2-deficient fibroblasts, TAK1 was associated with TAB3 and was activated following TNF stimulation. However, TAB2-deficient fibroblasts displayed a significantly prolonged activation of TAK1 compared with wild type control cells. This suggests that TAB2 mediates deactivation of TAK1. We found that a TAK1-negative regulator, protein phosphatase 6 (PP6), was recruited to the TAK1 complex in wild type but not in TAB2-deficient fibroblasts. Furthermore, we demonstrated that both PP6 and TAB2 interacted with the polyubiquitin chains and this interaction mediated the assembly with TAK1. Our results indicate that TAB2 not only activates TAK1 but also plays an essential role in the deactivation of TAK1 by recruiting PP6 through a polyubiquitin chain-dependent mechanism. PMID:19955178

Broglie, Peter; Matsumoto, Kunihiro; Akira, Shizuo; Brautigan, David L; Ninomiya-Tsuji, Jun

2010-01-22

287

Well Played: The Origins and Future of Playfulness  

ERIC Educational Resources Information Center

In this article, the author synthesizes research from several disciplines to shed light on play's central role in healthy development. Gordon builds on research in attachment theory that correlates secure attachment in infancy with adult well-being to demonstrate how playfulness might be a lifelong outcome of secure attachment and a primary…

Gordon, Gwen

2014-01-01

288

Playing with toys: Towards autonomous robot manipulation for therapeutic play  

Microsoft Academic Search

When young children play, they often manipulate toys that have been specifically designed to accommodate and stimulate their perceptual-motor skills. Robotic playmates capable of physically manipulating toys have the potential to engage children in therapeutic play and augment the beneficial interactions provided by overtaxed care givers and costly therapists. To date, assistive robots for children have almost exclusively focused on

Alexander J. B. Trevor; Hae Won Park; Ayanna M. Howard; Charles C. Kemp

2009-01-01

289

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

ERIC Educational Resources Information Center

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…

Broadhead, Pat; Burt, Andy

2011-01-01

290

Play and the Peer Culture: Play Styles and Object Use.  

ERIC Educational Resources Information Center

Findings suggested that: (1) peer culture is not a unitary whole but rather a differentiated social system comprised of various groups and different types of players; (2) objects play an important role in peer culture as entry vehicles and social markers; and (3) play periods are social arenas in which the dynamics of the peer culture are enacted.…

Elgas, Peggy M.; And Others

1988-01-01

291

The Influence of Play Material on Discourse during Play.  

ERIC Educational Resources Information Center

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

Burroughs, Elizabeth I.; Murray, Sharon E.

1992-01-01

292

Social play among preschool children  

Microsoft Academic Search

Observations of the spontaneous play of nursery school children by the one-minute sampling method indicated that preschool children most frequently play in groups of two, the size of play groups increases with age, two-thirds of the two-child groups are unisexual, the majority of the child's favorite playmates are of the same sex, the I Q has little influence on the

M. B. Parten

1933-01-01

293

Molecular and functional characterization of the promoter region of the mouse LDH/C gene: enhancer-assisted, Sp1-mediated transcriptional activation.  

PubMed

Molecular and functional studies of the LDH/C 5' upstream promoter elements were undertaken to elucidate the molecular mechanisms involved in temporal activation of LDH/C gene expression in differentiating germ cells. Ligation mediated-PCR (LM-PCR) gene walking techniques were exploited to isolate a 2.1 kb fragment of the mouse LDH/C 5' promoter region. DNA sequence analysis of this isolated genomic fragment indicated that the mouse LDH/C promoter contained TATA and CCAT boxes as well as a GC-box (Sp1-binding site) situated upstream from the transcription start site. PCR-based in vivo DNase I footprinting analysis of a 600 bp fragment of the proximal LDH/C promoter region (-524/+38) in isolated mouse pachytene spermatocytes identified a single footprint over the GC-box motif. Three DNase I hypersensitive sites were also detectable in vivo, in a region containing (CT)n(GA)n repeats upstream from the CCAT box domain. Functional characterization of the promoter region was carried out in a rat C6 glioma cell line and an SV40 transformed germ cell line (GC-1 spg) using wild-type and mutated LDH/C promoter CAT reporter constructs. These studies provide experimental evidence suggesting that transcriptional activation of the LDH/C promoter is regulated by enhancer-mediated coactivation of the Sp1 proteins bound to the GC-box motif footprinted in vivo in pachytene spermatocytes. PMID:9153323

Yang, J; Thomas, K

1997-06-01

294

Lottery play and problem gambling  

Microsoft Academic Search

This study sought to determine if lottery play along with other possible causes engenders problem gambling. Problem gambling was defined as a progression and measured by three scales: Gambling behavior, loss of control over gambling and gambling consequences. Possible causes of problem gambling included lottery play, personality traits, exposure to gambling, leisure pursuits, marital status, residence, and other background characteristics

Joseph Hraba; Waiman Mok; David Huff

1990-01-01

295

Sand and Water Table Play  

ERIC Educational Resources Information Center

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…

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

2010-01-01

296

Neuroscience, Play, and Child Development.  

ERIC Educational Resources Information Center

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…

Frost, Joe L.

297

Shale Play Industry Transportation Challenges,  

E-print Network

in excess of 50 MMT/Yr. · Life of current Shale Oil & Gas explora-on trendShale Play Industry Transportation Challenges, Changes, and Opportunities of Transporta-on (in associa-on with Minnesota DOT) #12;#12;Shale Play Industry

Minnesota, University of

298

Consistency and Cautious Fictitious Play  

Microsoft Academic Search

We study a variation of fictitious play, in which the probability of each action is an exponential function of that action's utility against the historical frequency of opponents' play. Regardless of the opponents' strategies, the utility received by an agent using this rule is nearly the best that could be achieved against the historical frequency. Such rules are approximately optimal

Drew Fudenberg; David K. Levine

1994-01-01

299

Play Therapy with Special Populations.  

ERIC Educational Resources Information Center

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

Carmichael, Karla D.

300

Puzzle Play Improves Math Skills  

NSDL National Science Digital Library

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

2012-02-16

301

The Social Competence of Play.  

ERIC Educational Resources Information Center

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…

Fein, Greta G.

302

Playground Play: Educational and Inclusive  

ERIC Educational Resources Information Center

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…

Moore, Lisa

2011-01-01

303

A Place for Block Play.  

ERIC Educational Resources Information Center

Discusses the importance of block play--including its contributions to perceptual, fine motor, and cognitive development--and components of a good preschool block play area. Recommends unit blocks complemented by stacking blocks, toys, beads, cubes, and Brio wooden toys. Makes recommendations for space, size, locations and connections to other…

Moore, Gary T.

1997-01-01

304

Outdoor Play: Combating Sedentary Lifestyles  

ERIC Educational Resources Information Center

Increasingly sedentary lifestyles are contributing to overweight and other health concerns as children spend less and less time outside engaged in active play. Outdoor play provides important opportunities to explore the natural world, interact with peers, engage in vigorous physical activity, and learn about our environment. However, outdoor…

Thigpen, Betsy

2007-01-01

305

The Play of Socratic Dialogue  

ERIC Educational Resources Information Center

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…

Smith, Richard

2011-01-01

306

Empowering Groups that Enable Play  

ERIC Educational Resources Information Center

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…

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

2011-01-01

307

Nutrient regulation of gene expression by the sterol regulatory element binding proteins: Increased recruitment of gene-specific coregulatory factors and selective hyperacetylation of histone H3 in vivo  

PubMed Central

We have evaluated the mechanism for sterol-regulated gene expression by the sterol regulatory element binding proteins (SREBPs) in intact cells. We show that activation of SREBPs by sterol depletion results in the increased binding of Sp1 to a site adjacent to SREBP in the promoter for the low density lipoprotein (LDL) receptor gene in vivo. Similarly, sterol depletion resulted in the increased recruitment of two distinct SREBP coregulatory factors, NF-Y and CREB, to the promoter for hydroxymethyl glutaryl CoA reductase, another key gene of intracellular cholesterol homeostasis. Furthermore, increased acetylation of histone H3 but not H4 was also detected in chromatin from both promoters on SREBP activation. Thus, SREBP activation results in the similar selective recruitment of different coregulatory generic transcription factors to two separate cholesterol-regulated promoters. These studies demonstrate the utility of the chromatin immunoprecipitation technique for analyzing the differential action of low-abundance transcription factors in fundamental regulatory events in intact cells. Our results also provide key in vivo support for the mechanism proposed from cell-free experiments, where SREBP increased the binding of Sp1 to the LDL receptor promoter. Finally, our findings also indicate that subtle differences in the pattern of core histone acetylation play a role in selective gene activation. PMID:10841543

Bennett, Mary K.; Osborne, Timothy F.

2000-01-01

308

DOI:10.2298/ABS1002199M INVOLVEMENT OF UBIQUITOUS AND TALE TRANSCRIPTION FACTORS, AS WELL AS LIGANDED RXR?, IN THE REGULATION OF HUMAN SOX2 GENE EXPRESSION IN THE NT2/D1  

E-print Network

Abstract- SOX2 is a key transcription factor in embryonic development representing a universal marker of pluripotent stem cells. Based on the functional redundancy and overlapping expression patterns of SOXB1 subgroup members during development, the goal of this study has been to analyze if some aspects of regulation of expression are preserved between human SOX2 and SOX3 genes. Thus, we have tested several transcription factors previously demonstrated to play roles in controlling SOX3 gene activity for potential participation in the regulation of SOX2 gene expression in NT2/D1 cells. Here we report on the activation of SOX2 expression by ubiquitous transcription factors (NF-Y, Sp1 and MAZ), TALE family members (Pbx1 and Meis1), as well as liganded RXR?. Elucidating components involved in the regulation of SOX gene expression represent a valuable contribution in unraveling the regulatory networks operating in pluripotent embryonic cells.

Embryonal Carcinoma; Cell Line; Milena Milivojevi?; Gordana Nik?evi?; Nataša Kova?evi?-gruji?i?; A. Krsti?; Marija Mojsin; Danijela Drakuli?; Milena Stevanovi?

309

Analysing playing using the note-time playing path.  

PubMed

This article introduces a new method of data analysis that represents the playing of written music as a graph. The method, inspired by Miklaszewski, charts low-level note timings from a sound recording of a single-line instrument using high-precision audio-to-MIDI conversion software. Note onset times of pitch sequences are then plotted against the score-predicted timings to produce a Note-Time Playing Path (NTPP). The score-predicted onset time of each sequentially performed note (horizontal axis) unfolds in performed time down the page (vertical axis). NTPPs provide a visualisation that shows (1) tempo variations, (2) repetitive practice behaviours, (3) segmenting of material, (4) precise note time positions, and (5) time spent on playing or not playing. The NTPP can provide significant new insights into behaviour and cognition of music performance and may also be used to complement established traditional approaches such as think-alouds, interviews, and video coding. PMID:21287106

de Graaff, Deborah L E; Schubert, Emery

2011-03-01

310

Game Experience May Vary: Understanding Play  

Microsoft Academic Search

Why do we call it game research and not play research? For the last decade of videogame studies, most of the attention has\\u000a been paid to games as formal entities. At first, games seem easier to understand: they generally have clear rules and goals.\\u000a They would be perfect machineries with formal mechanics if it was not for one factor: humans

Gonzalo Frasca

2009-01-01

311

Inhibitory mechanism of vascular endothelial growth factor (VEGF) by bucillamine.  

PubMed

1. Vascular endothelial growth factor (VEGF) plays an important role in the neovascularization of ischaemic retinal diseases such as proliferative diabetic retinopathy. We determined that bucillamine, an anti-rheumatic drug, inhibits the VEGF production induced by hypoxia in bovine retinal microcapillary endothelial cells (BREC). To further clarify the inhibitory mechanism, we investigated the possible mechanism by which bucillamine exerts this inhibitory effect. 2. Bucillamine (100 micro M) decreased the hypoxia-induced increase of VEGF mRNA by 54.5% (P<0.001). Bucillamine (100 micro M) reduced the hypoxia-induced VEGF content in culture media by 29.0% (P<0.001), while monosulfydryl drugs, N-acetylcysteine and D-penicillamine, did not. 3. Bucillamine (100 micro M) did not affect VEGF mRNA half-life (hypoxia, 4.3 h; hypoxia+bucillamine, 3.9 h; normoxia, 2.7 h; normoxia+bucillamine, 2.7 h). 4. Reporter gene studies revealed that bucillamine reduced transcriptional activity in the 5'-flanking region of the VEGF gene by 74.0%. Hypoxia stimulated binding activity of BREC nuclear protein to a hypoxia responsive element (HRE), which was decreased by bucillamine. 5. Bucillamine inhibited hypoxic-induction of HIF-1alpha mRNA by 73.1% (P<0.001). Bucillamine also inhibited spontaneous VEGF mRNA expression by 26.6%. Furthermore, it inhibited activity of VEGF promoter and decreased binding activity to Sp1 and HRE, but did not alter AP1 and AP2 activity in normoxia. 6. These data suggest that bucillamine inhibits hypoxic induction of VEGF through inhibition of HIF-1 induction and binding activity in BREC. Bucillamine also inhibits the spontaneous expression of VEGF mRNA by its effect on Sp1 and HRE binding. PMID:12411422

Koyama, Shinji; Takagi, Hitoshi; Otani, Atsushi; Oh, Hideyasu; Nishimura, Kazuo; Honda, Yoshihito

2002-11-01

312

MAJOR OIL PLAYS IN UTAH AND VICINITY  

SciTech Connect

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.

Thomas C. Chidsey, Jr.

2003-04-01

313

Focused Play Therapy and Non-Directive Play Therapy  

Microsoft Academic Search

There are two schools of thought for providing play therapy to children: non-directive and focused. This paper reviews the rationale for both non-directive and focused approaches to play therapy. The authors discuss why nonduective therapy alone may be ineffective in treating sexually abused children and abuse-reactive children. A prescriptive approach is proposed that combines the rapport building component of nondirecdve

Lucinda A. Rasmussen; Carolyn Cunningham

1995-01-01

314

Elementary GLOBE: Earth System Play  

NSDL National Science Digital Library

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

2008-12-01

315

The Plays of William Shakespeare  

NSDL National Science Digital Library

This e-text site offers the complete plays of William Shakespeare with introductions, concordances, a character guide, and well-known quotations for each play. The online concordance allows users to instantly search for all occurences of any particular word or phrase in each play -- a useful means of examining motifs and themes. The extensive, searchable glossary is also helpful for looking up unfamiliar Elizabethan vocabulary, and an online forum allows users to share their thoughts on the Bard with other readers. According to the site, an e-text of the Sonnets is forthcoming.

316

The Play Dough Evaluation Project  

NSDL National Science Digital Library

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

Heckscher, Mary

2006-02-01

317

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

PubMed

It has been postulated that the most primitive population of stem cells, Oct4(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs), differentiate into tissue-committed stem cells in adult mice. However, Oct4(+) VSELs remain quiescent in adult tissues and do not form teratomas. In thi study, we report the characteristics of the VSEL transcriptome by gene set enrichment analysis employing a microarray database established from 20 murine bone marrow-derived, FACS-sorted VSELs in comparison with hematopoietic stem cells and embryonic stem cells. In the Oct4(+) VSELs, we observed the upregulation of tissue-specific gene sets and a gene set encoding the complement-coagulation cascade. By contrast, in the VSELs, we observed the downregulation of genes involved in the UV radiation response, mRNA processing and mitogenic growth factor signaling [e.g., insulin-like growth factor?1 (IGF-1) and neurotrophic tyrosine kinase receptor A (TRKA), as well as the ERK and PI3K pathways]. Employing leading-edge subset analysis and real-time PCR assays, we observed that several genes, such as growth factor receptor-bound protein 2 (Grb2), son of sevenless homolog 1 (Sos1), SHC (Src homology 2 domain containing) transforming protein 1 (Shc1), mitogen-activated protein kinase kinase 1 (Map2k1), v-akt murine thymoma viral oncogene homolog 3 (Akt3), Elk1, ribosomal protein S6 kinase, 90 kDa, polypeptide 3 (Rps6kA3), glycogen synthase kinase 3? (Gsk3?) and casein kinase 2, alpha 1 polypeptide (Csnk2A1), which are involved in mitogenic growth factor signaling pathways, were commonly downregulated in the VSELs. Notably, this repression was reversed in the VSELs co-cultured over a C2C12 supportive cell-line, whereby they are induced to form VSEL-derived spheres (VSEL-DSs); thus, they are enriched, forming more differentiated stem cells. Therefore, we suggest that the repression of mitogenic growth factor signaling (e.g., through the IGF-1 receptor) may prevent uncontrolled Oct4(+) VSEL proliferation and teratoma formation. Thus, restoring the responsiveness to mitogenic growth factors may be a crucial step in employing these cells in regenerative medicine. PMID:23708325

Mierzejewska, Katarzyna; Heo, Jinbeom; Kang, Jeong Wook; Kang, Hyunsook; Ratajczak, Janina; Ratajczak, Mariusz Z; Kucia, Magda; Shin, Dong-Myung

2013-08-01

318

Play Fighting and Real Fighting  

Microsoft Academic Search

Rough-and-tumble play (R&T) is a distinctive form of behaviour, prominent in children. It has been studied by a variety of\\u000a methods which complement each other in interesting ways.\\u000a \\u000a Although superficially similar to real fighting, play fighting is distinct from it, and there are recognised cues which can\\u000a be used in telling these two behaviours apart. These have been discerned by

Peter K. Smith

319

Stromal Cell-Derived FactorPlays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury  

Microsoft Academic Search

Background—After myocardial infarction (MI), bone marrow-derived cells (BMDCs) are found within the myocardium. The mechanisms determining BMDC recruitment to the heart remain unclear. We investigated the role of stromal cell-derived factor-1 (SDF-1) in this process. Methods and Results—MI produced in mice by coronary ligation induced SDF-1 mRNA and protein expression in the infarct and border zone and decreased serum SDF-1

J. Dawn Abbott; Yan Huang; Dingang Liu; Reed Hickey; Diane S. Krause; Frank J. Giordano

2004-01-01

320

[Gymnophallus rebecqui n. sp. (syn. Parvatrema sp. 1, J. Rebecq, 1964) (Digenea: Gymnophallidae), an intestinal parasite of ducks from Camargue (France)].  

PubMed

Gymnophallus rebecqui n. sp. replace Parvatrema sp. 1 J. Rebecq, 1964. Metacercariae are described. They occur free in the extrapallial space of Cerastoderma glaucum and Abra ovata, at the central part of the valves. Pallial epithelium hypertrophy is induced by metacercariae and damages are produced at the inner face of the shell of Abra ovata. Adults have been reared in laboratory hosts (Aythya ferina, A. fuligula, Anas platyrhynchos, Tadorna tadorna and Larus argentatus michaellis). Natural adults have been discovered in the anterior and median gut of Aythya ferina, A. fuligula and Anas clypeata. Adults are described and compared with other related Gymnophallid species. This new species is not a member of Parvatrema but belongs to Gymnophallus genera. PMID:6614742

Bartoli, P

1983-01-01

321

The potent enhancer activity of the polycythemic strain of spleen focus-forming virus in hematopoietic cells is governed by a binding site for Sp1 in the upstream control region and by a unique enhancer core motif, creating an exclusive target for PEBP/CBF.  

PubMed Central

The polycythemic strain of the spleen focus-forming virus (SFFVp) contains the most potent murine retroviral enhancer configuration known so far for gene expression in myeloerythroid hematopoietic cells. In the present study, we mapped two crucial elements responsible for the high activity of the SFFVp enhancer to an altered upstream control region (UCR) containing a GC-rich motif (5'-GGGCGGG-3') and to a unique enhancer core (5'-TGCGGTC-3'). Acquisition of these motifs accounts for half of the activity of the complete retroviral enhancer in hematopoietic cells, irrespective of the developmental stage or lineage. Furthermore, the UCR motif contains the major determinant for the enhancer activity of SFFVp in embryonic stem (ES) cells. Using electrophoretic mobility shift assays, we show that the UCR of SFFVp, but not of Friend murine leukemia virus, is targeted by the ubiquitous transcriptional activator, Sp1. The core motif of SFFVp creates a specific and high-affinity target for polyomavirus enhancer binding protein/core binding factor (PEBP/CBF) and excludes access of CAAT/enhancer binding protein. Cotransfection experiments with ES cells imply that PEBP/CBF cooperates with the neighboring element, LVb (the only conserved Ets consensus in the SFFVp enhancer), and that the Sp1 motif in the UCR stimulates transactivation through the Ets-PEBP interaction. Putative secondary structures of the retroviral enhancers are proposed based on these data. PMID:9261349

Baum, C; Itoh, K; Meyer, J; Laker, C; Ito, Y; Ostertag, W

1997-01-01

322

Playing in a Virtual World: Exploration and Aspects of Play  

E-print Network

My research is concerned with ‘explorable virtual worlds’, usually those that are ‘artworks’, dealing with aesthetic and affective domains. Whilst developing theoretical enquiries I have come across a number of issues of terminology and word use. Particularly problematic are terms such as ‘game’, ‘games’, and ‘play’. This paper is a broad survey of some of those issues and key theorists in the field. 1.

Alison Gazzard

323

Guided Play: Where Curricular Goals Meet a Playful Pedagogy  

ERIC Educational Resources Information Center

Decades of research demonstrate that a strong curricular approach to preschool education is important for later developmental outcomes. Although these findings have often been used to support the implementation of educational programs based on direct instruction, we argue that "guided play" approaches can be equally effective at delivering content…

Weisberg, Deena Skolnick; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick

2013-01-01

324

Gay Youth at a Social Gathering: Play and Identity Development.  

ERIC Educational Resources Information Center

Being gay or lesbian has been associated with many risk factors for youth, including the risk of rejection by family and peers. A limited study concerning gay youth at play and the significance of play in identity development of gay youth is reported here. The report has two purposes: to describe the social activities at a gathering specifically…

Reed, Donald B.; Geddes, Jackie

325

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

Microsoft Academic Search

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

Helen Little; Shirley Wyver; Frances Gibson

2011-01-01

326

Science Adventures in Children's Play.  

ERIC Educational Resources Information Center

The stated purpose of this pamphlet is to suggest simple, natural, interesting experiences in children's play that have science implications. It tells how the teacher may capitalize on the innate curiosity of children by incorporating science discovery in daily classroom experiences. This how-to-do-it manual directs map-making and activities for…

Rieger, Edythe

327

ENGINEERING PLAY: CHILDREN'S SOFTWARE AND  

E-print Network

distributed interactions between children, technology, designers, programmers, marketers, parents" as children mobilize technologies in relation to adults at moments of play. In addition, these genres contestations in the US over children's culture, education, and technology. #12;v To Momoko Ito (1939-1995) #12

Ito, Mimi

328

Sculpting Cells with Play Doh.  

ERIC Educational Resources Information Center

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)

Way, Virginia A.

1982-01-01

329

Interpretive Reproduction in Children's Play  

ERIC Educational Resources Information Center

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

Corsaro, William A.

2012-01-01

330

Financial Aid's New Playing Field.  

ERIC Educational Resources Information Center

The decline of aid-blind college admissions, therefore of a "level playing field," complicates both admissions and financial aid processes. Institutions will have to revise recruitment procedures to bring in the best students. Financial aid will be one element in those procedures, depending on the relative wealth of the institution. (MSE)

Chace, William M.

1994-01-01

331

Obama Plays Cheerleader for STEM  

ERIC Educational Resources Information Center

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

Robelen, Erik W.

2010-01-01

332

Playful Learning and Creative Societies  

E-print Network

and complexity of our transactions and interactions) has accentuated the need for creativity in all aspects's children prepare for life in a society in which creativity and innovation are more important than ever that children develop and refine their imagination, curiosity, and creativity. As children playfully explore

Resnick, Mitchel

333

It's Time for Creative Play.  

ERIC Educational Resources Information Center

Playgrounds should be diverse and flexible so that children have many different opportunities for natural, creative play. Equipment should encourage group activities, challenge children at different levels of development, and enhance physical fitness. Such playgrounds could receive enthusiastic public support. (PP)

Beckwith, Jay

1982-01-01

334

Playing safe in coordination games  

Microsoft Academic Search

This paper presents results from a series of experiments designed to test the impact on subject behavior of changes in the risk dominance and payoff dominance characteristics of two player coordination games. The main finding is that changes in risk dominance significantly affect play of the subjects, whereas changes in the level of payoff dominance do not. Observed history of

David Schmidt; Robert Shupp; James M. Walker; Elinor Ostrom

2003-01-01

335

Extraversion and Computer Game Play: Who Plays What Games?  

Microsoft Academic Search

\\u000a In the last two years, our research group has been conducting online surveys on enjoyment of computer game play and player\\u000a personalities. From the preliminary data we collected as of now, we observed positive relationship between the personality\\u000a trait, extraversion, and players’ choice of games. This paper presents a research project that attempts to explore this relationship\\u000a and investigate the

Xiaowen Fang; Miaoqi Zhu

336

Playing Games with Quantum Mechanics  

E-print Network

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.

Simon J. D. Phoenix; Faisal Shah Khan

2012-02-21

337

Synthetic playing surfaces and athlete health.  

PubMed

Synthetic playing surfaces have evolved considerably since their introduction in the 1960s. Today, third-generation turf is routinely installed in professional, collegiate, and community settings. Proponents of artificial surfaces tout their versatility and durability in a variety of climates. However, the health and injury ramifications have yet to be clearly defined. Musculoskeletal injury is largely affected by the shoe-playing surface interface. However, conclusive statements cannot be made regarding the risk of certain shoe-playing surface combinations because of the variety of additional factors, such as weather conditions, shoe wear, and field wear. Historically, clinical studies have indicated that higher injury rates occur on artificial turf than on natural surfaces. This conclusion is backed by robust biomechanical data that suggest that torque and strain may be greater on artificial surfaces than on natural grass. Recent data on professional athletes suggest that elite athletes may sustain injuries at increased rates on the newer surfaces. However, these surfaces remain attractive to athletes and administrators alike because of their durability, relative ease of maintenance, and multiuse potential. PMID:23637148

Drakos, Mark C; Taylor, Samuel A; Fabricant, Peter D; Haleem, Amgad M

2013-05-01

338

Assessing Different Aspects of Pretend Play within a Play Setting: Towards a Standardized Assessment of Pretend Play in Young Children  

ERIC Educational Resources Information Center

The present study suggests a method with which to assess the interrelations between different types of pretend play. In contrast to standard methods in this area, the various types of pretend play were measured within an interactive play scenario. The pretend play tasks were included in a semi-structured play sequence and presented to young…

Frahsek, Stefanie; Mack, Wolfgang; Mack, Christina; Pfalz-Blezinger, Charlotte; Knopf, Monika

2010-01-01

339

The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter  

PubMed Central

Human differentially expressed in chondrocytes (DEC), mouse stimulated with retinoic acid and rat split and hairy related proteins constitute a structurally distinct class of the basic helix-loop-helix proteins. DEC1is abundantly expressed in tumors and protects against apoptosis induced by serum starvation. In this study, we report that DEC1 antiapoptosis is achieved by inducing survivin, an antiapoptotic protein. In paired tumor–normal tissues, survivin and DEC1 exhibited a paralleled expression pattern. Tetracycline-induced expression of DEC1 in stable lines proportionally increased the expression of survivin. In reporter assays, DEC1 transactivated the survivin promoter but repressed the DEC2 promoter. In contrast to the repression, the activation was delayed and varied depending on serum concentrations and cycle blockers. Studies with reporter mutants located, in the survivin promoter, two Sp1 sites that supported DEC1 transactivation. Electrophoretic mobility shift assay and chromatin immunoprecipitation detected the presence of DEC1 in the survivin promoter. These findings establish that the survivin gene is a transcription target of DEC1, and induction of survivin is at least in part responsible for DEC1 antiapoptosis. PMID:16462771

Li, Y; Xie, M; Yang, J; Yang, D; Deng, R; Wan, Y; Yan, B

2014-01-01

340

Subtypes of Nonsocial Play and Psychosocial Adjustment in Malaysian Preschool Children  

ERIC Educational Resources Information Center

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…

Choo, Mei Sze; Xu, Yiyuan; Haron, P. Fatimah

2012-01-01

341

Prechool Teachers' Play Experiences Then and Now.  

ERIC Educational Resources Information Center

Many preschool teachers recognize the importance of play for children's development and learning and emphasize play in their classrooms. This paper explores how they remember their own childhood play and how they perceive children's play today. Twenty Swedish preschool teachers were interviewed regarding their views of play. Two characteristic…

Sandberg, Anette; Samuelsson, Ingrid Pramling

342

Supporting Free Play in Ubiquitous Computer Games  

Microsoft Academic Search

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

Regan L. Mandryk; Kori M. Inkpen

2001-01-01

343

Play Therapy: Voice of a Silent Scream  

ERIC Educational Resources Information Center

Play Therapy is based upon the fact that play is the child's natural medium of self-expression. It is an opportunity that is given to the child to "play out" his/her feelings and problems just as, in certain types of adult therapy, an individual "talks out" his difficulties. Children use play to express feelings and thoughts. Play emerges from the…

Rakesh, Annuradha; H, Uma; Srinath, Shoba

2010-01-01

344

Mae west and the ‘queer plays  

Microsoft Academic Search

The article explores the history of three of the plays Mae West wrote and staged on Broadway between 1926 and 1928. Sex, in which West played a prostitute, offered the ‘fallen woman' a happy ending; The Drag and The Pleasure Man, plays about homosexuality, were staged with gay actors playing themselves. All three plays were closed by the police. Although

Lillian Schlissel

2002-01-01

345

Imagination: The Connection between Writing and Play.  

ERIC Educational Resources Information Center

Educational psychologists and researchers attest to the importance of play in learning, but studies indicate that children are playing less, and often less effectively, justifying the need for play within the school curriculum. The area of language arts is a natural place for imaginative play. One elementary school project incorporated playing,…

Mills, Beth Solow

346

Beginnings Workshop. The Value of Play.  

ERIC Educational Resources Information Center

Presents four articles exploring children's play: (1) "Play, Policy, and Practice: The Essential Connections" (Edgar Klugman, Sandra Waite-Stupiansky); (2) "What's New in Play Research?" (Doris Pronin Fromberg), including play processes and implications for practitioners; (3) "Observing Children's Play" (Margaret Cooney), describing benefits of…

Klugman, Edgar; And Others

1997-01-01

347

Frame Play in Early Childhood Education.  

ERIC Educational Resources Information Center

Describes frame play as a type of play in which children and teacher jointly plan the theme, roles, and actions and produce an extended imaginary play situation that can be repeated. Presents other types of play and discusses teachers' role in supporting theme development, resource organization, and environment transformation. Analyzes frame play

Brostrom, Stig

1998-01-01

348

Superhero Play: What's a Teacher to Do?  

ERIC Educational Resources Information Center

Examines the appeal of superheroes to children and adults' beliefs about superhero play, and suggests some potential benefits of such play. Offers examples of ways to successfully incorporate superhero play into an early childhood classroom. (Author/KB)

Bauer, Karen L.; Dettore, Ernest

1997-01-01

349

Playing the game: psychological factors in surviving cancer.  

PubMed

Cancer is a threat that can rob a person of their physical and mental wellbeing. While cancer awareness has ventured to the forefront of social consciousness, led by surges from Lance Armstrong and other celebrities affected by cancer, the medical world continually remains foiled in terms of regulating the many confounding variables that spawn cancer: toxins, pollutants, poor diet, etc. Yet there is a hope: one variable thought to affect cancer prognosis may be distinctly tractable: positive mental attitude (PMA). Principles of PMA that are readily utilized in the science of sports psychology to spur athletes to victory may be productively applied to the hospital arena. The parallels between sports and medicine are abundant, and can be utilized by the cancer patient to help secure victory. This paper describes the steps to victory, along with stratagems and concepts on how to keep the "opponent"--cancer--from gaining any further advantage. PMID:19637498

Rom, Stephen A; Miller, Laurence; Peluso, Jennifer

2009-01-01

350

Classroom Contextual Effects on Children's Play  

Microsoft Academic Search

Examined the effects of age, sex, and context of preschool classrooms on children's play. In Study 1, observed 3-, 4-, and 5-year-olds playing in art, blocks, and replica play areas in their age-graded classrooms. Results suggested that children's play was related to Age × Play Area interactions. These relations were not independent of children's sex-related self-selection into the play areas

A. D. Pellegrini; Jane C. Perlmutter

1989-01-01

351

Excessive computer game playing among Norwegian adults: self-reported consequences of playing and association with mental health problems.  

PubMed

Computer games are the most advanced form of gaming. For most people, the playing is an uncomplicated leisure activity; however, for a minority the gaming becomes excessive and is associated with negative consequences. The aim of the present study was to investigate computer game-playing behaviour in the general adult Norwegian population, and to explore mental health problems and self-reported consequences of playing. The survey includes 3,405 adults 16 to 74 years old (Norway 2007, response rate 35.3%). Overall, 65.5% of the respondents reported having ever played computer games (16-29 years, 93.9%; 30-39 years, 85.0%; 40-59 years, 56.2%; 60-74 years, 25.7%). Among 2,170 players, 89.8% reported playing less than 1 hr. as a daily average over the last month, 5.0% played 1-2 hr. daily, 3.1% played 2-4 hr. daily, and 2.2% reported playing > 4 hr. daily. The strongest risk factor for playing > 4 hr. daily was being an online player, followed by male gender, and single marital status. Reported negative consequences of computer game playing increased strongly with average daily playing time. Furthermore, prevalence of self-reported sleeping problems, depression, suicide ideations, anxiety, obsessions/ compulsions, and alcohol/substance abuse increased with increasing playing time. This study showed that adult populations should also be included in research on computer game-playing behaviour and its consequences. PMID:20229923

Wenzel, H G; Bakken, I J; Johansson, A; Götestam, K G; Øren, Anita

2009-12-01

352

Chin force in violin playing.  

PubMed

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

Obata, Satoshi; Kinoshita, Hiroshi

2012-06-01

353

All About Play Your child's most interactive activity of the day is perhaps during play time. Every child enjoys play  

E-print Network

or "imaginary" play. -Example: Playing with dolls, playing dress-up, pretending to be a fireman, having a tea pretend play. Whether it is taking a doll to the store or dressing up as his/her favorite character together. For example, you can take a toy doll and rock it in your arms and say "Shhh" in order to tell

O'Toole, Alice J.

354

Early Play Arousal, Sex-Typed Play, and Activity Level as Precursors to Later Rough-and-Tumble Play.  

ERIC Educational Resources Information Center

The extent of father's participation in rough-and-tumble (R&T) play with their children when the children were 18 months old, and children's early preferences for play sex-typed as boys' play, were related to levels of children's R&T play in first grade. (MDM)

McBride-Chang, Catherine; Jacklin, Carol Nagy

1993-01-01

355

MAJOR OIL PLAYS IN UTAH AND VICINITY  

SciTech Connect

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.

Thomas C. Chidsey, Jr.

2003-01-01

356

Histone Deacetylase 1/Sp1/MicroRNA-200b Signaling Accounts for Maintenance of Cancer Stem-Like Cells in Human Lung Adenocarcinoma  

PubMed Central

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

Pan, Ban-Zhou; De, Wei; Wang, Rui; Chen, Long-Bang

2014-01-01

357

Superman Comes to Preschool: Superhero TV Play.  

ERIC Educational Resources Information Center

Systematic efforts at the Arizona State Child Study Laboratory were successful in replacing children's undesirable superhero play with other types of sociodramatic play. Teachers found superhero play undesirable because it was aggressive and noisy and was accompanied by an increase in random activity. Observations indicated that superhero play had…

Ritchie, Kathleen E.; Johnson, Zita M.

358

Preschool Teachers' Views of Active Play  

ERIC Educational Resources Information Center

This study surveyed 98 teachers of 4-year-olds about dramatic play in their classrooms and about their attitudes and practices about rough-and-tumble play. Gender differences emerged in the nature of dramatic play reported and in the ways in which teachers interacted with children engaged in different forms of dramatic play. Teachers also reported…

Logue, Mary Ellin; Harvey, Hattie

2010-01-01

359

Pretend Play in the Early Childhood Classroom  

ERIC Educational Resources Information Center

This article presents and summarizes recent resources related to pretend play in the early childhood classroom. These include "Contemporary Perspectives on Play in Early Childhood Education" by Olivia N. Sarachoe and Bernard Spodek; "Dramatic Play: Bring It Back" by Tammy Benson; and "The Importance of Being Playful" by Elena Bodrova and Deborah…

McEntire, Nancy

2009-01-01

360

Superhero Play: What's a Teacher to Do?  

Microsoft Academic Search

The dilemma over whether or not teachers should allow superhero play in their classroom continues. This article examines adults' beliefs about superhero play and suggests some potential benefits of such play. The authors offer examples of ways they have incorporated superhero play in their classroom.

Karen L. Bauer; Ernest Dettore

1997-01-01

361

Conceptualizing the Play Policies in Preschool Curriculums  

ERIC Educational Resources Information Center

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…

Sener, Tulin

2013-01-01

362

Teatro! Hispanic Plays for Young People.  

ERIC Educational Resources Information Center

This collection of 14 folk drama scripts is drawn from the Hispanic culture and traditions of the American Southwest and designed for use in educational settings. The plays are short, simple, and easy to produce. A single play can fill a class period, while several plays grouped together would make a school assembly. Six plays, intended for grades…

Vigil, Angel

363

Parent-Child Play: Descriptions and Implications.  

ERIC Educational Resources Information Center

This volume provides the latest research and theory in the area of children's play with their parents. It includes discussions of the basic processes involved in parent-child play, parent-child play in atypical populations of children, and parent-child play from a cross-cultural perspective. Fifteen chapters follow the introduction, "Parents and…

MacDonald, Kevin, Ed.

364

Active Gaming: The Future of Play?  

ERIC Educational Resources Information Center

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,…

Witherspoon, Lisa; Manning, John P.

2012-01-01

365

Children, Play, and Development. Fourth Edition  

ERIC Educational Resources Information Center

Children, Play, and Development, Fourth Edition, discusses the relationship of play to the physical, social, intellectual, and emotional growth of the child. Author Fergus P. Hughes focuses on the historical, sociocultural, and ethological context of play; the role of development in play; and the wide range of theories that provide a framework for…

Hughes, Fergus P.

2010-01-01

366

Developing scenarios for robot assisted play  

Microsoft Academic Search

This paper describes the user-centred development of play scenarios for robot assisted play, as part of the IROMEC project that develops a novel robotic toy for children with special needs. The project investigates how robotic toys can become social mediators, encouraging children with special needs to discover a range of play styles, from solitary to collaborative play (with peers, carers\\/teachers,

Ben Robins; Ester Ferrari; Kerstin Dautenhahn

2008-01-01

367

Children's Spontaneous Play in Writer's Workshop  

ERIC Educational Resources Information Center

Research on the relationship between literacy and play has a rich history. Yet few studies have examined children's use of spontaneous play during literacy events as children are learning to read and write. This case study examines the use of play and the quality of playfulness in a kindergarten/first grade multiage classroom during Writer's…

Lysaker, Judith T.; Wheat, Jennifer; Benson, Emily

2010-01-01

368

Play in Cultural Contexts = Mang Kultuurikontekstis.  

ERIC Educational Resources Information Center

This volume compiles articles based on the presentations delivered at two conferences. The conferences presented a multidisciplinary overview of research on children's play in different cultural contexts. The articles are grouped under six subheadings: play in the family context, play in the zone of proximal development, play in the kindergarten,…

Saar, Aino, Ed.; Hakkarainen, Pentti, Ed.

1998-01-01

369

Strategies for Family Facilitation of Play Dates  

ERIC Educational Resources Information Center

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…

Chambers, Cynthia R.; Horn, Eva M.

2010-01-01

370

Are medical treatments for individuals and groups like single-play and multiple-play gambles?  

E-print Network

versus groups; medical treatment decisions; multiple-play; repeated- play; aggregation #12;Manuscript-play decisions than when making single-play decisions. Samuelson (1963) initiated this literatureAre medical treatments for individuals and groups like single-play and multiple-play gambles

371

Transforming Play: An Analysis of First-, Third-, and Fifth-Graders' Play.  

ERIC Educational Resources Information Center

Compared children's play with transformational objects (vehicles that change to robots) to play with representational objects (cars and figures). Found that those playing with transformers engaged in more parallel play and manipulative activity, while those with representational objects displayed more social play and more symbolic play. Found no…

Bagley, Donna M.; Chaille, Christine

1996-01-01

372

The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid  

Microsoft Academic Search

BACKGROUND: Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB) specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction

Jing Zhou; Chin Ho Chen; Christopher Aiken

2004-01-01

373

Major Oil Plays In Utah And Vicinity  

SciTech Connect

Utah oil fields have produced over 1.33 billion barrels (211 million m{sup 3}) of oil and hold 256 million barrels (40.7 million m{sup 3}) of proved reserves. The 13.7 million barrels (2.2 million m3) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. However, in late 2005 oil production increased, due, in part, to the discovery of Covenant field in the central Utah Navajo Sandstone thrust belt ('Hingeline') play, and to increased development drilling in the central Uinta Basin, reversing the decline that began in the mid-1980s. The Utah Geological Survey believes providing play portfolios for the major oil-producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming can continue this new upward production trend. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios include descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; locations of major oil pipelines; identification and discussion of land-use constraints; descriptions of reservoir outcrop analogs; and summaries of the state-of-the-art drilling, completion, and secondary/tertiary recovery techniques for each play. The most prolific oil reservoir in the Utah/Wyoming thrust belt province is the eolian, Jurassic Nugget Sandstone, having produced over 288 million barrels (46 million m{sup 3}) of oil and 5.1 trillion cubic feet (145 billion m{sup 3}) of gas. Traps form on discrete subsidiary closures along major ramp anticlines where the depositionally heterogeneous Nugget is also extensively fractured. Hydrocarbons in Nugget reservoirs were generated from subthrust Cretaceous source rocks. The seals for the producing horizons are overlying argillaceous and gypsiferous beds in the Jurassic Twin Creek Limestone, or a low-permeability zone at the top of the Nugget. The Nugget Sandstone thrust belt play is divided into three subplays: (1) Absaroka thrust - Mesozoic-cored shallow structures, (2) Absaroka thrust - Mesozoic-cored deep structures, and (3) Absaroka thrust - Paleozoic-cored shallow structures. Both of the Mesozoic-cored structures subplays represent a linear, hanging wall, ramp anticline parallel to the leading edge of the Absaroka thrust. Fields in the shallow Mesozoic subplay produce crude oil and associated gas; fields in the deep subplay produce retrograde condensate. The Paleozoic-cored structures subplay is located immediately west of the Mesozoic-cored structures subplays. It represents a very continuous and linear, hanging wall, ramp anticline where the Nugget is truncated against a thrust splay. Fields in this subplay produce nonassociated gas and condensate. Traps in these subplays consist of long, narrow, doubly plunging anticlines. Prospective drilling targets are delineated using high-quality, two-dimensional and three-dimensional seismic data, forward modeling/visualization tools, and other state-of-the-art techniques. Future Nugget Sandstone exploration could focus on more structurally complex and subtle, thrust-related traps. Nugget structures may be present beneath the leading edge of the Hogsback thrust and North Flank fault of the Uinta uplift. The Jurassic Twin Creek Limestone play in the Utah/Wyoming thrust belt province has produced over 15 million barrels (2.4 million m{sup 3}) of oil and 93 billion cubic feet (2.6 billion m{sup 3}) of gas. Traps form on discrete subsidiary closures along major ramp anticlines where the low-porosity Twin Creek is extensively fractured. Hydrocarbons in Twin Creek reservoirs were generated from subthrust Cretaceous source rocks. The seals for the producing horizons are overlying argillaceous and clastic beds, and non-fractured units within the Twin Creek. The Twin Creek Limestone thrust belt play is divided into two subplays: (1) Absaroka thrust-Mesozoic-cored structures and (2) A

Thomas Chidsey

2007-12-31

374

Development of the children's active play imagery questionnaire.  

PubMed

The purpose of the current study was to develop an instrument, the Children's Active Play Imagery Questionnaire (CAPIQ), to assess imagery use during children's (7-14 years) active play. Phase 1 involved an assessment of content validity using experts (N = 7), while Phase 2 assessed the factorial validity of the CAPIQ using a sample of children (N = 302). Phase 3 contributed to the factorial validity of the CAPIQ by utilising confirmatory factor analysis among an independent sample of children (N = 252). The final version of the CAPIQ consists of 11 items across three factors: fun, social and capability. Further use of the CAPIQ will aid in identifying types of imagery used among children (7-14 years) in their active play, which may contribute to physical activity interventions. PMID:24410533

Cooke, Lisa; Munroe-Chandler, Krista; Hall, Craig; Tobin, Danielle; Guerrero, Michelle

2014-01-01

375

Imaginary Play Companions: Characteristics and Functions.  

ERIC Educational Resources Information Center

Investigates some of the following characteristics associated with young children playing with imaginary play companions (IPCs): intelligence, parental and socioeconomic and educational background, family size, and birth order. Compares these children to those without IPCs. (HOD)

Kalyan-Masih, V.

1986-01-01

376

The Early Years: Inquiry at Play  

NSDL National Science Digital Library

Play and science inquiry are essential parts of early childhood programs. Imaginative play, unscripted yet guided by children's own rules, allows students to use their imagination and develop self-regulation, symbolic thinking, memory, language, and socia

Ashbrook, Peggy

2010-09-01

377

Optimization of Baseball Swing Parameters For Three Levels of Play  

Microsoft Academic Search

Hitting homeruns in baseball is a key factor to the sport: it provides a guaranteed run for the team, excitement for the fans, and bragging rights for the individual. This investigation adapts Hubbard i et al's work to examine the optimal swing parameters resulting in maximum range at three different levels of play: Little League, high school, and college. The

Annie Chase

378

Fantasy Play of Preschoolers as a Function of Toy Structures.  

ERIC Educational Resources Information Center

Two studies are presented which investigate the influence of various toy structures on the frequency of individual fantasy play forms in 3- to 6-year-old children. In the first study, the effects of high-realistic/high-complexity and low-realistic/low-complexity toy structures were compared. There were significant main effects for the factor toy…

Einsiedler, Wolfgang

379

Interfaces for Physical Play - Issues and various solutions  

Microsoft Academic Search

Gaming is a large industry which has very much been developed around and is dominated by stationary play interfaces, where the player doesn't have to move more than their arms and maybe legs. This has inherent issues and can be seen as a contributing factor to obesity, creating a generation gap between young and old and poor links between the

Ben Dick

380

Preschool Teachers' Views of Active Play  

Microsoft Academic Search

This study surveyed 98 teachers of 4-year-olds about dramatic play in their classrooms and about their attitudes and practices about rough-and-tumble play. Gender differences emerged in the nature of dramatic play reported and in the ways in which teachers interacted with children engaged in different forms of dramatic play. Teachers also reported their coursework in early childhood education as the

Mary Ellin Logue; Hattie Harvey

2009-01-01

381

Growing as One Plays with a Balloon  

ERIC Educational Resources Information Center

In this article, the author recounts her experience with Tracy, who was playing with a balloon outside her office when she was five years old, and gives an up-to-date story of Tracy since 1985, 1990, and 2006. In reflecting on Tracy's play, the author realizes that Tracy is helping her see clearly what play is really all about, that in playing to…

Torbert, Marianne

2006-01-01

382

Physical Development: Taking Time for Physical Play  

ERIC Educational Resources Information Center

This article discusses children's physical development through physical play. Here, the author gives ways to incorporate opportunities for physical play. For infants, time for play may have to revolve around nap schedules. This may mean allowing for different wake-sleep cycles for different infants. Teachers can divide the infants into groups so…

Strickland, Eric

2004-01-01

383

Who Plays, and Why, in Picture Books.  

ERIC Educational Resources Information Center

Describes the findings of a content analysis of 64 picture books on play themes for elementary school children. The books were analyzed to determine who was playing (sex of child or adult; ethnic group membership) and why (play for fun, for social benefits, or for self-enhancement). (SS)

McVaigh, Betty Lee; Johnson, Mary Frances K.

1979-01-01

384

Happy Festivus! Parody as playful consumer resistance  

Microsoft Academic Search

Drawing upon literary theory, play and consumer resistance literature, we conceptualize consumer parodic resistance – a resistant form of play that critically refunctions dominant consumption discourses and marketplace ideologies. We explore parodic resistance empirically by analyzing Festivus, a parody of Christmas. Festivus is found to be primarily constructed as a playful rejection of the established grand narratives and conventions of

Ilona Mikkonen; Domen Bajde

2012-01-01

385

Play, Dreams and Imitation in Robota  

Microsoft Academic Search

Imitation, play and dreams are as many means for the child to develop her\\/his understanding of the world and of its social rules. What if we were to have a robot we could play with? What if we could through play and daily interactions, as we do with our children, be a m odel for it and teach it (what?)

Aude Billard

386

Young Children's Literacy-Related Play  

ERIC Educational Resources Information Center

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…

Saracho, Olivia N.; Spodek, Bernard

2006-01-01

387

Preschool Children's Cognitive Styles and Play Behaviors.  

ERIC Educational Resources Information Center

Tested 2,400 three- to five-year olds for cognitive style and observed their play behaviors. Repeated measures multivariate analysis indicated that field-independent children engaged in more play than did field-dependent children. Significant interaction was found for age, cognitive style, and play behaviors. Older field-independent children…

Saracho, Olivia N.

1996-01-01

388

Exploring Young Children's Literacy Development through Play.  

ERIC Educational Resources Information Center

This exploratory study examined effects of literacy- enriched play centers and the emergent literacy of 5-year-old kindergartners. Qualitative analysis indicated that a language or literacy component can be integrated into kindergartners' play activities. Play activities promoted the invented symbols and messages in children's writing. Teachers…

Saracho, Olivia N.

2001-01-01

389

Superheroes: An Opportunity for Prosocial Play  

ERIC Educational Resources Information Center

Superhero play has long been thought of as violent, aggressive, and disruptive. Some argue that aggressive play should not be allowed because it exposes children to inappropriate concepts and attitudes and sends the message that the use of aggression can achieve a desired goal. However, educators know that pretend play is an avenue for healthy…

De-Souza, Desalyn; Radell, Jacqueline

2011-01-01

390

Documenting Children's Play Stories to Enhance Learning  

ERIC Educational Resources Information Center

Play episodes are common occurrences in many preschool classrooms. Observation of this type of play can provide teacher with valuable insights into children's development, skills, and interest. How might the teachers use this "play story" to extend and enhance the children's learning particularly literacy learning, in meaningful ways? This article…

Reifel, Stuart; Nicholson, Shelley

2008-01-01

391

Pretend Play of Children with Cerebral Palsy  

ERIC Educational Resources Information Center

Background and Purpose: Evaluate self-initiated pretend play of children with cerebral palsy. Method: Twenty preschool children participated in the study. Pretend play ability was measured by using the child-initiated pretend play assessment culturally adapted to Brazil. Results: There were significant negative correlations between the children's…

Pfeifer, Luzia Iara; Pacciulio, Amanda Mota; dos Santos, Camila Abrao; dos Santos, Jair Licio; Stagnitti, Karen Ellen

2011-01-01

392

Young Children's Playfully Complex Communication: Distributed Imagination  

ERIC Educational Resources Information Center

This paper draws on research exploring young children's playful and humorous communication. It explores how playful activity mediates and connects children in complex activity systems where imagination, cognition, and consciousness become distributed across individuals. Children's playfulness is mediated and distributed via artefacts (tools, signs…

Alcock, Sophie

2010-01-01

393

Play Therapy for Severe Psychological Trauma. [Videotape  

ERIC Educational Resources Information Center

In this 36-minute educational video, a play and family therapist elucidates the nature of trauma, how to recognize it clinically, and how to manage its powerful effects upon children's development with the use of specific play materials and techniques. With a reenacted clinical interview, footage from an actual play therapy session, and a detailed…

Gil, Eliana

394

The Play Professional in the United Kingdom  

ERIC Educational Resources Information Center

Playwork is a respected field of study composed of experts who have studied the theories and practices of play for the purposes of training other individuals in best practices to better facilitate children's play. The profession is founded on the belief that play is an essential childhood element and the right of every child. In this article, the…

Millbank, Anna-Marie

2005-01-01

395

New directions in play: consensus or collision?  

Microsoft Academic Search

The aims of this article are to explore contemporary challenges to developing play in early childhood settings, and to identify areas of consensus and collision in policy and practice. Contemporary research highlights the effectiveness of mixed pedagogical approaches, including child- and adult-initiated play. Whilst early childhood specialists recognise these approaches as central to high-quality curricula in early childhood settings, play

Elizabeth Wood

2007-01-01

396

27 CFR 9.168 - Fair Play.  

...2014-04-01 2014-04-01 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...

2014-04-01

397

27 CFR 9.168 - Fair Play.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 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...

2011-04-01

398

27 CFR 9.168 - Fair Play.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 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...

2012-04-01

399

27 CFR 9.168 - Fair Play.  

Code of Federal Regulations, 2010 CFR

...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...

2010-04-01

400

27 CFR 9.168 - Fair Play.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 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...

2013-04-01

401

A Review of Research on Play.  

ERIC Educational Resources Information Center

Uninformed of the power of play as an educational tool, many people view play as a waste of time and call for a return to teaching basic academic skills during the period of early childhood. This chapter demonstrates that play is a major vehicle for learning, focusing on the dynamics of sociodramatic interaction that are integral to understanding…

Fromberg, Doris Pronin

402

Short-Term Play Therapy for Children.  

ERIC Educational Resources Information Center

Play therapy offers a powerful means of helping children resolve a wide range of psychological difficulties, and many play approaches are ideally suited to short-term work. This book brings together leading play therapists to share their expertise on facilitating children's healing in a shorter time frame. The book provides knowledge and skills…

Kaduson, Heidi Gerard, Ed.; Schaefer, Charles E., Ed.

403

Montessori and Play: Theory vs. Practice.  

ERIC Educational Resources Information Center

Surveyed Montessori preprimary teachers concerning attitudes toward pretend play in the classroom. Found mixed feelings among teachers toward pretend play. By a margin of 2 to 1, teachers were dissatisfied with the training they had received regarding the role of children's play in Montessori settings. (KB)

Torrence, Martha

2001-01-01

404

Children's Play: The Roots of Reading  

ERIC Educational Resources Information Center

Extensive empirical research has documented the value of play for both cognitive and social development. In this collection, leading experts in play research, child development, and early childhood education examine recent policy decisions and demonstrate the importance of play in helping children learn basic literacy skills, social awareness,…

Zigler, Edward F., Ed.; Zigler, Dorothy G., Ed.; Bishop-Josef, Sandra J., Ed.

2004-01-01

405

Language Play in Child Second Language Acquisition.  

ERIC Educational Resources Information Center

Play sessions of two Mexican children (one five and one eight years old) with English-speaking friends were recorded and the use of language play was examined. Language play is viewed as a non-literal, rule-bound use of language that children engage in for its own sake, either cooperatively or competitively. Practice opportunities and children's…

Peck, Sabrina

406

Play Therapy Practices among Elementary School Counselors  

ERIC Educational Resources Information Center

When elementary school counselors have a solid developmental understanding of children, play therapy might be one counseling intervention that they use with their students. Landreth (2002) has promoted the use of play therapy in schools by explaining that its objective is to help children get ready to profit from what teachers have to offer. Play

Ray, Dee C.; Armstrong, Stephen A.; Warren, E. Scott; Balkin, Richard S.

2005-01-01

407

Playfulness-based design in educational games: a perspective on an evolutionary contest game  

Microsoft Academic Search

Playfulness steering is an emerging approach in educational game design and play. The integration of arithmetical computation, game strategy, and teamwork into one game allows players to interactively “steer” the playfulness and enhance learning. In this paper an evolutionary contest game was designed and implemented to examine the influencial factors. Using action research, focus groups and hermeneutic methods, this study

Jon-Chao Hong; Ming-Yueh Hwang; Chin-Hsieh Lu; Ching-Ling Cheng; Yu-Chen Lee; Chan-Li Lin

2009-01-01

408

The Impact of Pretend Play on Children's Development: A Review of the Evidence  

ERIC Educational Resources Information Center

Pretend play has been claimed to be crucial to children's healthy development. Here we examine evidence for this position versus 2 alternatives: Pretend play is 1 of many routes to positive developments (equifinality), and pretend play is an epiphenomenon of other factors that drive development. Evidence from several domains is considered. For…

Lillard, Angeline S.; Lerner, Matthew D.; Hopkins, Emily J.; Dore, Rebecca A.; Smith, Eric D.; Palmquist, Carolyn M.

2013-01-01

409

Opponent Modeling and Spatial Similarity to Retrieve and Reuse Superior Plays.  

National Technical Information Service (NTIS)

Plays are sequences of actions to be undertaken by a collection of agents, or teammates. The success of a play depends on a number of factors including, perhaps most importantly, the opponent's play. In this paper, we present an approach for online oppone...

D. W. Aha, G. Sukthankar, K. Laviers, M. Klenk, M. Molineaux

2009-01-01

410

Picture Me Playing: Increasing Pretend Play Dialogue of Children with Autism Spectrum Disorders  

ERIC Educational Resources Information Center

This study examined the effectiveness of the Picture Me Playing intervention for increasing the play dialogue of preschool children with ASD during pretend play opportunities with typical peers. Picture Me Playing is a pictorially enhanced, script based intervention targeting character role play through a narrative vignette. A single-treatment…

Murdock, Linda C.; Hobbs, Jan Q.

2011-01-01

411

Play and Mate Preference: Testing the Signal Theory of Adult Playfulness  

ERIC Educational Resources Information Center

The overwhelming majority of play research concerns juveniles. However, a full understanding of the phenomenon requires knowledge of play and playfulness across the life spans of those animals, including humans, who play in adulthood. The authors investigate a theory of play based on Darwin's concept of sexual selection that may account for the…

Chick, Garry; Yarnal, Careen; Purrington, Andrew

2012-01-01

412

Effect of Background Music Tempo and Playing Method on Shopping Website Browsing  

Microsoft Academic Search

\\u000a Background music is one of the critical factors that affect browsers’ behavior on shopping website. This study adopted a laboratory\\u000a experiment to explore the effects of background music tempo and playing method on cognitive response in an online store. The\\u000a independent variables were background music tempo (fast vs. slow) and playing method of music (playing the same music continuously,\\u000a re-playing

Chien-Jung Lai; Ya-Ling Wu; Ming-Yuan Hsieh; Chang-Yung Kung; Yu-Hua Lin

413

Play at the Art Table: A Study of Children's Play Behaviors while Drawing.  

ERIC Educational Resources Information Center

This descriptive study examined children's drawings and related language episodes to differentiate drawings exhibiting play from those exhibiting exploratory behavior. Drawings categorized as play were further analyzed to identify constructive and imaginary play. The play theory used as the basis of the study proposes that exploration and…

Escobedo, Theresa H.

414

Playing with Mathematics: Play in Early Childhood as a Context for Mathematical Learning  

ERIC Educational Resources Information Center

Play is an essential part of young children's lives. This symposium highlights the integral role of play in young children's mathematics learning and examines the teacher's role in facilitating and extending this. Papers examine key tenets of play, contributing to theoretical understandings and presenting data on teacher's perceptions of play and…

Mathematics Education Research Group of Australasia, 2010

2010-01-01

415

Social Coordination during Pretend Play: Comparisons with Nonpretend Play and Effects on Expressive Content.  

ERIC Educational Resources Information Center

Examined the role of pretend play interactions in stimulating social and emotional competence by comparing the quality of pretend and nonpretend social play. Found that pretend play involved more complex, mutually responsive, and emotionally invested social interaction than nonpretend play. Expression of psychosocial issues within pretense was…

Lorimier, Sylvie de; And Others

1995-01-01

416

Human Immunodeficiency Virus Type 1 Resistance to the Small Molecule Maturation Inhibitor 3-O-(3',3'-Dimethylsuccinyl)-Betulinic Acid Is Conferred by a Variety of Single Amino Acid Substitutions at the CA-SP1 Cleavage Site in Gag  

Microsoft Academic Search

The compound 3-O-(3,3-dimethylsuccinyl)-betulinic acid (DSB) potently and specifically inhibits human immunodeficiency virus type 1 (HIV-1) replication by delaying the cleavage of the CA-SP1 junction in Gag, leading to impaired maturation of the viral core. In this study, we investigated HIV-1 resistance to DSB by analyzing HIV-1 mutants encoding a variety of individual amino acid substitutions in the CA-SP1 cleavage site.

Jing Zhou; Chin Ho Chen; Christopher Aiken

2006-01-01

417

Mammalian play: training for the unexpected.  

PubMed

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

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

2001-06-01

418

Playful expressions of one-year-old chimpanzee infants in social and solitary play contexts  

PubMed Central

Knowledge of the context and development of playful expressions in chimpanzees is limited because research has tended to focus on social play, on older subjects, and on the communicative signaling function of expressions. Here we explore the rate of playful facial and body expressions in solitary and social play, changes from 12- to 15-months of age, and the extent to which social partners match expressions, which may illuminate a route through which context influences expression. Naturalistic observations of seven chimpanzee infants (Pan troglodytes) were conducted at Chester Zoo, UK (n = 4), and Primate Research Institute, Japan (n = 3), and at two ages, 12 months and 15 months. No group or age differences were found in the rate of infant playful expressions. However, modalities of playful expression varied with type of play: in social play, the rate of play faces was high, whereas in solitary play, the rate of body expressions was high. Among the most frequent types of play, mild contact social play had the highest rates of play faces and multi-modal expressions (often play faces with hitting). Social partners matched both infant play faces and infant body expressions, but play faces were matched at a significantly higher rate that increased with age. Matched expression rates were highest when playing with peers despite infant expressiveness being highest when playing with older chimpanzees. Given that playful expressions emerge early in life and continue to occur in solitary contexts through the second year of life, we suggest that the play face and certain body behaviors are emotional expressions of joy, and that such expressions develop additional social functions through interactions with peers and older social partners. PMID:25104942

Ross, Kirsty M.; Bard, Kim A.; Matsuzawa, Tetsuro

2014-01-01

419

The Processes of Monitored Play-Therapy.  

ERIC Educational Resources Information Center

This paper describes the processes of Monitored Play-Therapy, a method which seeks to measure the changes which may take place over a number of play therapy sessions. The laboratory is in use at Georgia State College in Atlanta and is designed for boys seven through twelve years of age. The Monitored Playroom Laboratory consists of a control booth…

Rogers, Mary Brown

420

Child's Play: A Work-Family Issue.  

ERIC Educational Resources Information Center

Many parents find that the daily stress of coping with the demanding realities of their work lives leaves them with little personal and family time; playing with their children may therefore fall to the bottom of the "to-do list." One of the tasks of early childhood professionals thus becomes helping parents understand the nature and value of play

Kuchner, Joan F.

421

Adapting personal music for synesthetic game play  

Microsoft Academic Search

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

Sam Rossoff; George Tzanetakis; Bruce Gooch

2010-01-01

422

“Work” versus “play” and early childhood care  

Microsoft Academic Search

The ancient dispute over the appropriate role of work versus play in the lives of the young rests on assumptions of children's original nature. Those committed to an innate goodness position have been strong advocates of freedom and play; while those distrusting children's natural instincts have pressed for social control and disciplined work. This paper scans the historical antagonism and

Joan F. Goodman

1994-01-01

423

Gender-Typed Play and Amniotic Testosterone  

Microsoft Academic Search

Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of 53 children (31 boys and 22 girls). A strong

Rebecca Christine Knickmeyer; Sally Wheelwright; Kevin Taylor; Peter Raggatt; Gerald Hackett; Simon Baron-Cohen

2005-01-01

424

Gender-Typed Play and Amniotic Testosterone  

ERIC Educational Resources Information Center

Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

2005-01-01

425

Girls' Physically Active Play and Parental Behavior.  

ERIC Educational Resources Information Center

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…

Tauber, Margaret A.

426

Mathematical Learning in a Context of Play  

ERIC Educational Resources Information Center

In this article we analyse a didactical situation centred on the creation and use of a symbolic play environment in a class of pupils aged five and six years-old. The main source of data for this paper comes from an experimentation planned in relation to the following research question: does symbolic play in simulated contexts help pupils to…

Edo, Meque; Planas, Nuria; Badillo, Edelmira

2009-01-01

427

Helping Young Children See Math in Play  

ERIC Educational Resources Information Center

The purpose of this article is to provide strategies for recognizing meaningful mathematics in common play contexts in early childhood classrooms and to offer suggestions for how teachers might intervene in these moments to help children attend to the mathematical ideas embedded in their play. In particular, the author's focus on the concepts…

Parks, Amy Noelle; Blom, Diana Chang

2013-01-01

428

Back to Sleep, Tummy to Play  

MedlinePLUS

... will enjoy tummy time and begin to enjoy play in this position. Doesn’t Sleeping On Her Back ... fun themselves. Back To Sleep and Tummy To Play Follow these easy steps to create a safe sleep environment in your home, family child care home, or child ...

429

Competitive Sports: Helping Kids Play it Cool  

MedlinePLUS

... Sometimes kids don't want to play a sport but don't know how to tell their parents. So ask if your child really wants to play or is just doing it to please you or someone else. Remember, while things like college scholarships are a nice reward for hard work, they ...

430

Personality and enjoyment of computer game play  

Microsoft Academic Search

This paper introduces a research framework of game play based on a review of media enjoyment theories, personality theories, effects of computer game play, and technology acceptance model. The proposed framework suggests that an appropriate fit between characteristics of the player and gaming technology will result in greater enjoyment while social influence may moderate effects of the fit. An empirical

Xiaowen Fang; Fan Zhao

2010-01-01

431

Sack Racers at Day of Play  

NASA Technical Reports Server (NTRS)

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.

2005-01-01

432

Selecting major Appalachian basin gas plays  

SciTech Connect

Under a cooperative agreement with the Morgantown Energy Technology Center (METC) the Appalachian Oil and Natural Gas Research Consortium (AONGRC) is preparing a geologic atlas of the major gas plays in the Appalachian basin, and compiling a database for all fields in each geologic play. the first obligation under this agreement was to prepare a topical report that identifies the major gas plays, briefly describes each play, and explains how the plays were selected. Four main objectives have been defined for this initial task: assign each gas reservoir to a geologic play, based on age, trap type, degree of structural control, and depositional environment; organize all plays into geologically-similar groups based on the main criteria that defines each play; prepare a topical report for METC; and transfer this technology to industry through posters and talks at regional geological and engineering meetings including the Appalachian Petroleum Geology Symposium, Northeastern Section meeting of the Geological Society of America, the METC Gas Contractors Review meeting, the Kentucky Oil and Gas Association, and the Appalachian Energy Group.

Patchen, D.G.; Nuttall, B.C.; Baranoski, M.T.; Harper, J.A.; Schwietering, J.F.; Van Tyne, A.; Aminian, K.; Smosna, R.A.

1992-06-01

433

Selecting major Appalachian basin gas plays  

SciTech Connect

Under a cooperative agreement with the Morgantown Energy Technology Center (METC) the Appalachian Oil and Natural Gas Research Consortium (AONGRC) is preparing a geologic atlas of the major gas plays in the Appalachian basin, and compiling a database for all fields in each geologic play. the first obligation under this agreement was to prepare a topical report that identifies the major gas plays, briefly describes each play, and explains how the plays were selected. Four main objectives have been defined for this initial task: assign each gas reservoir to a geologic play, based on age, trap type, degree of structural control, and depositional environment; organize all plays into geologically-similar groups based on the main criteria that defines each play; prepare a topical report for METC; and transfer this technology to industry through posters and talks at regional geological and engineering meetings including the Appalachian Petroleum Geology Symposium, Northeastern Section meeting of the Geological Society of America, the METC Gas Contractors Review meeting, the Kentucky Oil and Gas Association, and the Appalachian Energy Group.

Patchen, D.G.; Nuttall, B.C.; Baranoski, M.T.; Harper, J.A.; Schwietering, J.F.; Van Tyne, A.; Aminian, K.; Smosna, R.A.

1992-01-01

434

Role-Playing in Counselor Student Development  

ERIC Educational Resources Information Center

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…

Osborn, Debra; Costas, Lisa

2013-01-01

435

Shaping Cooperative Cross-Sex Play  

ERIC Educational Resources Information Center

Contingent praise by classroom teachers was used to cue and reinforce cross-sex cooperative play in 2 nursery school classes of 4-year-old children. Results suggested that previous learning and/or current classroom contingencies may reinforce same-sex playmate choices when teachers do not deliberately reinforce play between boys and girls. (JMB)

Serbin, Lisa A.; And Others

1977-01-01

436

Play system for therapy for the elderly  

Microsoft Academic Search

Growth of the elderly population and a shortage of therapists indicates the value of using computer systems for therapy. This paper describes a system that integrates entertainment and therapy: a Play System for therapy for the elderly. A specially designed game platform enables diagnosis and treatment of cognitive problems through game playing. The system is supervised by professional trainer who

Rina Zviel-Girshin; Arie Reichman; Inbal Abraham; Lior Hammer; Asaf Shema; Alon Kimhi

2011-01-01

437

Drawings as Spaces for Intellectual Play  

ERIC Educational Resources Information Center

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…

Wood, Elizabeth; Hall, Emese

2011-01-01

438

Work and Play: Are They Really Opposites?  

ERIC Educational Resources Information Center

Noting that current discussion of the best way to accomplish the goal of "No Child Left Behind" has focused on the value of play versus a structured program for early education, this paper uses science education as a model for examining how children learn and the problems arising when artificial lines are drawn between work and play. The paper…

Rosberg, Merilee A.

439

Feature Construction for Game Playing1  

Microsoft Academic Search

To build an evaluation function for game-playing, one needs to construct informative features that enable accurate relative assessment of a game state. This chapter describes the feature construction problem, and suggests directions for dealing with shortcomings in the present state of the art. An essential ingredient of a good game-playing program is the ability to approximate well the relative utility

Paul E. Utgoff

2001-01-01

440

Playing video games: learning and information literacy  

Microsoft Academic Search

Purpose – This paper aims to identify what motivates young people to play video games, and the extent to which video games are perceived as facilitating learning and information literacy. Design\\/methodology\\/approach – The study adopted a qualitative approach, interviewing a convenience sample of 28 young people who enjoy playing video games. They were aged between 12 and 19, and all

Sabina Gumulak; Sheila Webber

2011-01-01

441

Playing by Ear: Foundation or Frill?  

ERIC Educational Resources Information Center

Many people divide musicians into two types: those who can read music and those who play by ear. Formal music education tends to place great emphasis on producing musically literate performers but devotes much less attention to teaching students to make music without notation. Some would suggest that playing by ear is a specialized skill that is…

Woody, Robert H.

2012-01-01

442

Mindbrain and Play-Literacy Connections  

ERIC Educational Resources Information Center

Research on the relationship between play and early literacy flourished in the 1990s but slowed to a trickle at the start of the new millennium. As we see it, play-literacy research is stuck in a theoretical and methodological rut. Two promising conceptual frameworks--connectionist and dynamic systems theories--can supply the thrust needed to get…

Roskos, Kathleen A.; Christie, James F.

2011-01-01

443

The Theatre Student: Producing Plays for Children.  

ERIC Educational Resources Information Center

This book was written to clarify the role that theatre plays in the life of children. Its contents include a prologue, eleven chapters, and an epilogue. In the prologue, the truly educated person is described as one who has learned to make controlled use of all his capacities. Participation in role-playing experiences, such as involvement with the…

Johnson, Richard C.

444

Governing Early Childhood Education through Play  

Microsoft Academic Search

Play serves as a significant nodal point in the discursive relations of early childhood education. The aim of this article is to ask how play has come to appear so necessary to early childhood educational settings and how this perceived necessity governs the behaviour of both adults and young children. To do this the author make use of concepts provided

JO AILWOOD

2003-01-01