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1

Targeting Sp1 transcription factors in prostate cancer therapy.  

PubMed

Transcription factors are proteins that regulate gene expression by binding to specific DNA sequences within gene promoter regions. Specificity protein (Sp) family transcription factors play a critical role in various cellular processes and have been shown to be associated with tumorigenesis. The Sp family consists of several members that contain a highly conserved DNA-binding domain composed of three zinc fingers at the C-terminus and serine/threonine- and glutamine-rich transactivation domains at the N-terminal. Sp1 is elevated in several cancers including prostate and is associated with the prognosis of patients. Sp1, Sp3, and Sp4 regulate a variety of cancer associated genes that are involved in cell cycle, proliferation, cell differentiation, and apoptosis. Studies have shown that in prostate cancer, Sp1 regulates important genes like androgen receptor, TGF-?, c-Met, fatty acid synthase, matrix metalloprotein (MT1-MMP), PSA, and ?-integrin. These results highlight the importance of Sp1 in prostate cancer and emphasize the potential therapeutic value of targeting Sp1. Several strategies, including the use of natural and synthetic compounds, have been used to inhibit Sp1 in prostate cancer. These include polyphenol quercetin, betulinic acid, acetyl-11-keto-beta-boswellic acid, tea phenols, isothiocyanates, thiazolidinediones, arsenic trioxide, and selenium. This review will describe the association of Sp proteins in prostate cancer with a special emphasis on some of the agents tested to target Sp proteins for the treatment of this malignancy. PMID:22022994

Sankpal, Umesh T; Goodison, Steven; Abdelrahim, Maen; Basha, Riyaz

2011-09-01

2

Elevated SP-1 Transcription Factor Expression and Activity Drives Basal and Hypoxia-induced Vascular Endothelial Growth Factor (VEGF) Expression in Non-Small Cell Lung Cancer  

PubMed Central

VEGF plays a central role in angiogenesis in cancer. Non-small cell lung cancer (NSCLC) tumors have increased microvascular density, localized hypoxia, and high VEGF expression levels; however, there is a lack of understanding of how oncogenic and tumor microenvironment changes such as hypoxia lead to greater VEGF expression in lung and other cancers. We show that NSCLC cells secreted higher levels of VEGF than normal airway epithelial cells. Actinomycin D inhibited all NSCLC VEGF secretion, and VEGF minimal promoter-luciferase reporter constructs were constitutively active until the last 85 base pairs before the transcription start site containing three SP-1 transcription factor-binding sites; mutation of these VEGF promoter SP-1-binding sites eliminated VEGF promoter activity. Furthermore, dominant negative SP-1, mithramycin A, and SP-1 shRNA decreased VEGF promoter activity, whereas overexpression of SP-1 increased VEGF promoter activity. Chromatin immunoprecipitation assays demonstrated SP-1, p300, and PCA/F histone acetyltransferase binding and histone H4 hyperacetylation at the VEGF promoter in NSCLC cells. Cultured NSCLC cells expressed higher levels of SP-1 protein than normal airway epithelial cells, and double-fluorescence immunohistochemistry showed a strong correlation between SP-1 and VEGF in human NSCLC tumors. In addition, hypoxia-driven VEGF expression in NSCLC cells was SP-1-dependent, with hypoxia increasing SP-1 activity and binding to the VEGF promoter. These studies are the first to demonstrate that overexpression of SP-1 plays a central role in hypoxia-induced VEGF secretion. PMID:22992725

Deacon, Karl; Onion, David; Kumari, Rajendra; Watson, Susan A.; Knox, Alan J.

2012-01-01

3

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

PubMed Central

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

Hoppe-Seyler, F; Butz, K

1992-01-01

4

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

5

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

6

Transcription Factor Sp1 Is Essential for Early Embryonic Development but Dispensable for Cell Growth and Differentiation  

Microsoft Academic Search

Transcription factor Sp1 has been implicated in the expression of many genes. Moreover, it has been suggested that Sp1 is linked to the maintenance of methylation-free CpG islands, the cell cycle, and the formation of active chromatin structures. We have inactivated the mouse Sp1 gene. Sp1?\\/? embryos are retarded in development, show a broad range of abnormalities, and die around

Marisol Marin; Alar Karis; Pim Visser; Frank Grosveld; Sjaak Philipsen

1997-01-01

7

Characterization of the rat mdr2 promoter and its regulation by the transcription factor Sp1.  

PubMed Central

The mdr2 gene encodes a P-glycoprotein that transports phospholipids across the canalicular membrane in hepatocytes. In this report we describe the isolation, sequencing and first functional characterization of the promoter of mdr2. Analysis of 1.6 kb of DNA upstream of the initiation of translation revealed that this sequence has a high GC content, lacks a TATA element and contains a number of putative transcription factor binding sites. We observed that transcription initiates at several sites between -290 and -463 and that this region was critical for promoter activity. Gel mobility shift assays indicated that Sp1 protein binds to a Sp1 consensus site located at -263. Co-expression of Sp1 protein with a reporter construct containing the -263 GC box demonstrated that Sp1 regulates transcription of this promoter. Expression of a non-functional Sp1 protein did not increase transcription from the mdr2 promoter. Mutation of the -263 GC box diminished the response of the promoter to Sp1 protein. Mutation of this site also decreased expression of this promoter in cells which normally express this gene. These data show that Spl has a role in the regulation of mdr2 expression. PMID:8774906

Brown, P C; Silverman, J A

1996-01-01

8

IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3.  

PubMed

IL-10 is an 18-kDa cytokine with a key role in homeostatic control of inflammatory and immune responses. We have investigated how transcription of the IL-10 gene is regulated, so as to be able to understand the circumstances of IL-10 expression in both health and disease. In the mouse, IL-10 gene expression is regulated by a TATA-type promoter with a critical cis-acting element containing GGA repeats located at -89 to -77. Its complementary sequence is similar to the cis-acting elements (TCC repeats) in the promoters of genes encoding epidermal growth factor receptor and CD58. All these elements comprise a common CCTCCT sequence with less conserved C + T-rich sequences. Eliminating this CCTCCT sequence results in a marked reduction in promoter activity, suggesting a necessary role in IL-10 gene expression. Despite its dissimilarity to the G + C-rich Sp1 consensus sequence (GC box), Sp1 and Sp3 transcription factors could be shown to bind to this motif. The requirement for Sp1 and Sp3 in transcription of IL-10 was confirmed using Drosophila SL2 cells, which lack endogenous Sp factors. These results suggest that the transcription of IL-10 is positively regulated by both Sp1 and Sp3. PMID:10861063

Tone, M; Powell, M J; Tone, Y; Thompson, S A; Waldmann, H

2000-07-01

9

Regulation of Neph3 gene in podocytes – key roles of transcription factors NF-?B and Sp1  

PubMed Central

Background Neph3 (filtrin) is expressed in the glomerular podocytes where it localizes at the specialized cell adhesion structures of the foot processes called slit diaphragms which form the outermost layer of the glomerular filtration barrier. Neph3 protein shows homology and structural similarity to Neph1, Neph2 and nephrin, which all are crucial for maintaining the normal glomerular ultrafiltration function. The exact function of Neph3 in the kidney is not known but we have previously shown that the level of Neph3 mRNA is decreased in proteinuric diseases. This suggests that Neph3 may play a role in the pathogenesis of kidney damage, and emphasizes the need to analyze the regulatory mechanisms of Neph3 gene. In this study we investigated the transcriptional regulation of Neph3 gene by identifying transcription factors that control Neph3 expression. Results We cloned and characterized approximately 5 kb fragment upstream of the Neph3 gene. Neph3 proximal promoter near the transcription start site was found to be devoid of TATA and CAAT boxes, but to contain a highly GC-rich area. Using promoter reporter gene constructs, we localized the main activating regulatory region of Neph3 gene in its proximal promoter region from -105 to -57. Within this region, putative transcription factor binding sites for NF-?B and Sp1 were found by computational analysis. Mutational screening indicated that NF-?B and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-?B and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-?B increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-?B and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-?B and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight into the molecular mechanisms that contribute to the expression of Neph3 gene. PMID:19703278

Ristola, Mervi; Arpiainen, Satu; Saleem, Moin A; Mathieson, Peter W; Welsh, Gavin I; Lehtonen, Sanna; Holthöfer, Harry

2009-01-01

10

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

11

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

PubMed Central

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

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

2014-01-01

12

Significant biological role of Sp1 transactivation in multiple myeloma  

PubMed Central

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

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

2015-01-01

13

Transcription Factors Sp1 and p73 Control the Expression of the Proapoptotic Protein NOXA in the Response of Testicular Embryonal Carcinoma Cells to Cisplatin*  

PubMed Central

Testicular germ cell tumors (TGCTs) are highly responsive to and curable by cisplatin-based chemotherapy even in advanced stages. We have studied the molecular mechanisms involved in the induction of apoptosis in response to cisplatin, and found that proapoptotic Noxa is transcriptionally up-regulated following cisplatin exposure, even in the absence of p53, in NTERA2 cisplatin-sensitive cells but not in 1411HP-resistant cells. Blockade of Noxa reduced the apoptotic response of embryonal carcinoma (EC) NTERA2 cells to cisplatin. A detailed analysis of the Noxa promoter revealed that p73 and Sp1-like factors, Sp1 and KLF6, played key roles in the transcriptional control of this gene. Overexpression of TAp73 induced Noxa whereas the dominant negative isoform ?Np73, reduced the levels of Noxa after cisplatin exposure in NTERA2 and 2102EP. Interestingly, down-regulation of Sp1 increased Noxa expression in response to cisplatin. However, blockade of KLF6 decreased cisplatin-induced up-regulation of Noxa in EC cell lines. In addition, tissue microarray analyses of TGCTs revealed that expression of Noxa correlates with good clinical prognosis in patients with embryonal carcinoma. Thus, our data show the transcriptional network that regulates Noxa in EC cells, which is key for their apoptotic response to cisplatin-based chemotherapy, and propose Noxa as a predictive factor of therapeutic response. PMID:22718761

Grande, Lara; Bretones, Gabriel; Rosa-Garrido, Manuel; Garrido-Martin, Eva M.; Hernandez, Teresa; Fraile, Susana; Botella, Luisa; de Alava, Enrique; Vidal, August; Garcia del Muro, Xavier; Villanueva, Alberto; Delgado, M. Dolores; Fernandez-Luna, Jose L.

2012-01-01

14

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

15

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

PubMed Central

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

Hirose, Takashi; Horvitz, H. Robert

2013-01-01

16

The FOXM1 transcription factor interacts with Sp1 to mediate EGF-dependent COX-2 expression in human glioma cells  

PubMed Central

Cyclooxygenase-2 (COX-2) is linked to worse prognosis in patients with malignant gliomas and other tumor types. Amplification/overexpression of epidermal growth factor receptor (EGFR) is commonly seen in these tumors. We have previously shown that EGFR signaling, through activation of p38-mitogen activated protein kinase (MAPK), protein kinase C-? (PKC-?), and Sp1, plays an important role in the regulation of COX-2 expression in glioma cells. Here, we report that the Src kinase also has a role in this signaling cascade upstream of p38-MAPK/PKC-?. In addition, more detailed analysis revealed the involvement of FOXM1, a member of the forkhead box family of transcriptional activators, in EGF-dependent COX-2 induction. FOXM1 protein levels increase after stimulation with EGF although its role in modulating COX-2 expression does not depend on this increase. While a conventional FOXM1 responsive element resides in a distal region (?2872/?2539 relative to the transcriptional start site) of the COX-2 promoter, this is not required for EGF-dependent induction of COX-2. Instead, FOXM1 is capable of interacting with Sp1 at the Sp1 binding site (?245/?240 relative to the start site) of the COX-2 promoter and appears to act in cooperation with Sp1 to mediate EGF-induced COX-2 expression. Definition of this novel interaction provides us with a clearer understanding of the mechanistic basis for the induction of COX-2 with EGF and guides our evaluation of potential newer therapeutic targets that have relevance in this disease. PMID:23635401

Xu, Kaiming; Shu, Hui-Kuo G.

2013-01-01

17

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

PubMed

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

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

2012-01-01

18

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

PubMed

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

Jin, Lin; Datta, Pran K

2014-10-17

19

Factors affecting mother-child play  

E-print Network

) Jennifer Colleen Welch, B. S. , Texas A&M University Chair of Advisory Committee: Dr. Timothy A. Cavell This study examined the effects of various maternal life stressors in relation to their effects on maternal directiveness during mother-child play...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...

Welch, Jennifer Colleen

1993-01-01

20

The Epstein-Barr virus immediate-early promoter BRLF1 can be activated by the cellular Sp1 transcription factor.  

PubMed Central

Disruption of viral latency in Epstein-Barr virus-infected cells is mediated through the activation of the BZLF1 (Z) immediate-early gene product. The Z protein can be derived from either of two promoters: the BZLF1 promoter, which directs transcription of a 1.0-kb mRNA encoding the Z gene product alone, or the upstream BRLF1 promoter, which directs transcription of a 2.8-kb bicistronic mRNA encoding the BRLF1 and BZLF1 immediate-early proteins. In this study we have examined the regulation of the BRLF1 promoter by viral and cellular factors. We found that the BRLF1 promoter is autoregulated by the BRLF1 transactivator through a nonbinding mechanism. We show that the BRLF1 (but not the BZLF1) promoter is highly responsive to the Sp1 transcription factor. Sp1 activation of the BRLF1 promoter is mediated through a consensus Sp1-binding site located from -39 to -44 (relative to the mRNA start site). We demonstrate that the BRLF1 promoter has high constitutive activity in C-33 cells (an epithelial cell line) and that the proximal Sp1-binding site is required for this activity. Despite the ubiquitous presence of Sp1 in many cell types, we found that the BRLF1 promoter has essentially no activity in lymphoid cell lines, suggesting that factors other than Sp1 may negatively regulate the BRLF1 promoter in these cells. Our findings demonstrate that the two potential promoters directing BZLF1 transcription are differentially regulated and that Sp1 can activate the BRLF1 promoter but not the BZLF1 promoter. Images PMID:1331521

Zalani, S; Holley-Guthrie, E A; Gutsch, D E; Kenney, S C

1992-01-01

21

The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity.  

PubMed Central

The von Hippel-Lindau tumor suppressor gene (VHL) has a critical role in the pathogenesis of clear-cell renal cell carcinoma (RCC), as VHL mutations have been found in both von Hippel-Lindau disease-associated and sporadic RCCs. Recent studies suggest that vascular endothelial growth factor (VEGF) mRNA is upregulated in RCC- and von Hippel-Lindau disease-associated tumors. We have therefore assessed the effect of the VHL gene product on VEGF expression. VEGF promoter-luciferase constructs were transiently cotransfected with a wild-type VHL (wt-VHL) vector in several cell lines, including 293 embryonic kidney and RCC cell lines. wt-VHL protein inhibited VEGF promoter activity in a dose-dependent manner up to 5- to 10-fold. Deletion analysis defined a 144-bp region of the VEGF promoter necessary for VHL repression. This VHL-responsive element is GC rich and specifically binds the transcription factor Sp1 in crude nuclear extracts. In Drosophila cells, cotransfected VHL represses Sp1-mediated activation but not basal activity of the VEGF promoter. We next demonstrated in coimmunoprecipitates that VHL and Sp1 were part of the same complex and, by using a glutathione-S-transferase-VHL fusion protein and purified Sp1, that VHL and Sp1 directly interact. Furthermore, endogenous VEGF mRNA levels were suppressed in permanent RCC cell lines expressing wt-VHL, and nuclear run-on studies indicated that VHL regulation of VEGF occurs at least partly at the transcriptional level. These observations support a new mechanism for VHL-mediated transcriptional repression via a direct inhibitory action on Sp1 and suggest that loss of Sp1 inhibition may be important in the pathogenesis of von Hippel-Lindau disease and RCC. PMID:9271438

Mukhopadhyay, D; Knebelmann, B; Cohen, H T; Ananth, S; Sukhatme, V P

1997-01-01

22

Sp1 Decoy Transfected to Carcinoma Cells Suppresses the Expression of Vascular Endothelial Growth Factor, Transforming Growth Factor b1, and Tissue Factor and Also Cell Growth and Invasion Activities  

Microsoft Academic Search

Vasculature development is thought to be an important aspect in the growth and metastasis of solid tumors. Among the angiogenic factors produced by tumor cells, vascular endothelial growth factor is considered to be the most potent and pathologically important. The synthesis of this growth factor has been shown to be modulated through Sp1 function following stimulation by tumor necrosis factor

Hiroaki Ishibashi; Kazunori Nakagawa; Mitsuho Onimaru; Emilio J Castellanous; Yasufumi Kaneda; Yutaka Nakashima; Kanemitsu Shirasuna; Katsuo Sueishi

2000-01-01

23

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

SciTech Connect

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

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

2010-11-19

24

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

Microsoft Academic Search

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

Franck Verrecchia; Jérôme Rossert; Alain Mauviel

2001-01-01

25

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

26

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, Garbiñe; Infante, Arantza; Schlangen, Karin; Aransay, Ana M.; Fullaondo, Ane; Soriano, Mario; García-Verdugo, José Manuel; Martín, Ángel G.

2012-01-01

27

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

PubMed Central

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

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

2014-01-01

28

Functional Interaction of Nuclear Factor Y and Sp1 Is Required for Activation of the Epstein-Barr Virus C Promoter  

PubMed Central

Two Epstein-Barr virus (EBV) latent cycle promoters, Wp and Cp, are activated sequentially during virus-induced transformation of primary B lymphocytes. Immediately postinfection, viral transcription initiates from Wp, leading to expression of EBV nuclear antigen 2 (EBNA2) and EBNA5. Within 36 h, there is a switch in promoter usage from Wp to the upstream Cp, which leads to expression of EBNA1 to EBNA6. EBNA2 appears to be required for the Wp-to-Cp switch, but the switching mechanism is not fully understood at the molecular level. In a previous investigation we showed that there is an EBNA2-independent activity of reporter constructs containing deletion fragments of Cp in B-lymphoid cell lines, and we demonstrated that Cp activity is highly dependent on several cellular transcription factors, including nuclear factor Y (NF-Y) and Sp1. In the present work, we analyzed the effect of NF-Y on Cp activity in greater detail. We demonstrate that (i) a dominant negative analogue of NF-Y abolishes Cp activity, (ii) NF-Y and Sp1 costimulate Cp, and (iii) the oriPI-EBNA1-induced transactivation of Cp requires concomitant expression of NF-Y and Sp1, although additional factors seem necessary for optimal activation. Furthermore, using the lymphoblastoid cell line EREB2-5, in which EBNA2 function is regulated by estrogen, we demonstrate that inactivation of EBNA2 results in decreased expression of NF-Y and down-regulation of Cp. On reconstitution of the EBNA2 function, the cells enter the cell cycle, NF-Y levels increase, and a concomitant Wp-to-Cp switch occurs. Taken together, our results suggest that NF-Y is essential for Cp activation and that up-regulation of NF-Y may contribute to a successful Wp-to-Cp switch during B-cell transformation. PMID:12502798

Boreström, Cecilia; Zetterberg, Henrik; Liff, Kristian; Rymo, Lars

2003-01-01

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

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

31

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

32

Xylosyltransferase-1 Expression Is Refractory to Inhibition by the Inflammatory Cytokines Tumor Necrosis Factor ? and IL-1? in Nucleus Pulposus Cells: Novel Regulation by AP-1, Sp1, and Sp3.  

PubMed

We investigated whether expression of xylosyltransferase-1 (XT-1), a key enzyme in glycosaminoglycan biosynthesis, is responsive to disk degeneration and to inhibition by the inflammatory cytokines tumor necrosis factor ? and IL-1? in nucleus pulposus (NP) cells. Analysis of human NP tissues showed that XT-1 expression is unaffected by degeneration severity; XT-1 and Jun, Fos, and Sp1 mRNA were positively correlated. Cytokines failed to inhibit XT-1 promoter activity and expression. However, cytokines decreased activity of XT-1 promoters containing deletion and mutation of the -730/-723 bp AP-1 motif, prompting us to investigate the role of AP-1 and Sp1/Sp3 in the regulation of XT-1 in healthy NP cells. Overexpression and suppression of AP-1 modulated XT-1 promoter activity. Likewise, treatment with the Sp1 inhibitors WP631 and mithramycin A or cotransfection with the plasmid DN-Sp1 decreased XT-1 promoter activity. Inhibitors of AP-1 and Sp1 and stable knockdown of Sp1 and Sp3 resulted in decreased XT-1 expression in NP cells. Genomic chromatin immunoprecipitation analysis showed AP-1 binding to motifs located at -730/-723 bp and -684/-677 bp and Sp1 binding to -227/-217 bp and -124/-114 bp in XT-1 promoter. These results suggest that XT-1 expression is refractory to the disease process and to inhibition by inflammatory cytokines and that signaling through AP-1, Sp1, and Sp3 is important in the maintenance of XT-1 levels in NP cells. PMID:25476526

Ye, Wei; Zhou, Jie; Markova, Dessislava Z; Tian, Ye; Li, Jun; Anderson, D Greg; Shapiro, Irving M; Risbud, Makarand V

2015-02-01

33

Three clustered Sp1 sites are required for efficient transcription of the TATA-less promoter of the gene for insulin-like growth factor-binding protein-2 from the rat.  

PubMed

Insulin-like growth factor-binding protein-2 (IGF-BP-2) transcription in rat liver varies with developmental age and fasting. To define the DNA elements required for efficient expression of the TATA-less rat IGFBP-2 gene, the native or mutated promoter was fused to a promoterless luciferase reporter gene and transfected into BRL-3A rat liver and 293 human embryonic kidney cell lines. Luciferase activity decreased approximately 25-fold with progressive 5' promoter deletions from nucleotide (nt) -581 to nt -189 (relative to ATG, +1). The smallest construct, however, still had > 21-fold greater luciferase activity than the promoterless construct. In DNase I foot-printing assays using native nt -276 to -36 promoter fragments or fragments containing block substitution mutations, BRL-3A nuclear extract and purified human transcription factor Sp1 protected a region from nt -234 to -215 containing one GC box and a broad region from nt -189 to -125 that contained three clustered but independent GC boxes. In gel retardation assays using an Sp1 oligonucleotide probe, BRL-3A extract formed two closely migrating complexes that were immunologically related to Sp1; Sp1 gave a single complex that co-migrated with the more retarded BRL-3A complex. Binding was competitively inhibited by oligonucleotides corresponding to each of the four GC boxes. The proximal three GC boxes were sufficient to allow trans-activation of the IGFBP-2 promoter by Sp1 in Drosophila SL2 cells. Independent block mutations indicated that all three of the GC boxes are required for promoter activity and are equally important. Thus, binding of Sp1 or Sp1-related proteins to three clustered GC boxes in the proximal IGFBP-2 promoter is essential for promoter activity. Multiple upstream regions also contribute to the full expression of the IGFBP-2 gene. PMID:7693708

Boisclair, Y R; Brown, A L; Casola, S; Rechler, M M

1993-11-25

34

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

35

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

36

Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1.  

PubMed Central

The constitutive androstane receptor (CAR) activates the expression of a reporter gene attached to the phenobarbital-response element (PBRE) of the cytochrome P450 2B1 (CYP2B1) gene in response to the barbiturate phenobarbital and the plant product picrotoxin. The xenobiotic-mediated increase in transactivation occurs in transfected primary hepatocytes and in liver transfected by biolistic-particle-mediated DNA transfer, but not in the transformed cell lines HepG2, CV-1 and HeLa, which support only constitutive activation of gene expression by CAR. Steroid co-activator 1 (SRC-1) enhances both constitutive and xenobiotic-induced CAR-mediated transactivation via the CYP2B1 PBRE in transfected primary hepatocytes. The nuclear receptor 1 (NR1) site of the PBRE is sufficient for CAR-mediated transactivation, but additional sequences within the PBRE, and hence the proteins that bind to them, are required for the interaction of CAR with SRC-1. The NR2 site of the PBRE binds proteins other than CAR, including an unidentified nuclear receptor heterodimerized with retinoid X receptor alpha. By binding to the proximal promoter of CYP2B1, the transcription factor Sp1 increases both basal transcription and xenobiotic-induced expression via the PBRE. Thus induction of CYP2B1 expression by xenobiotics is mediated by the nuclear receptor CAR and, for optimal expression, requires SRC-1 and Sp1. PMID:11256950

Muangmoonchai, R; Smirlis, D; Wong, S C; Edwards, M; Phillips, I R; Shephard, E A

2001-01-01

37

The Sp(1)-Kepler problems  

SciTech Connect

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

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

2009-07-15

38

Hydrogen Peroxide Decreases Endothelial Nitric Oxide Synthase Promoter Activity through the Inhibition of Sp1 Activity  

PubMed Central

We have previously shown that endothelial nitric oxide synthase (eNOS) promoter activity is decreased in endothelial cells in response to the addition of hydrogen peroxide (H2O2), and this involves, at least in part, the inhibition of AP-1 activity. Thus, the objective of this study was to determine if other cis-element(s) and transcription factor(s) are involved in the oxidant-mediated downregulation of eNOS. Our initial experiments indicated that although H2O2 treatment increased eNOS mRNA levels in ovine pulmonary arterial endothelial cells (OPAECs), there was a significant decrease in the promoter activity of an eNOS promoter construct containing 840?bp of upstream sequence. However, a truncated promoter construct that lacked the AP-1 element (650?bp) was also inhibited by H2O2. A similar effect was observed when the 650?bp human eNOS promoter construct was transfected into human PAECs. We also found that although exposure of the cells to PEG-catalase prevented the inhibitory effect on eNOS promoter activity, the hydroxyl radical scavenger, deferoxamine myslate, did not. Nor could we identify an increase in hydroxyl radical levels in cells exposed to H2O2. Exposure of PAECs caused a significant increase in labile zinc levels in response to H2O2. As the eNOS promoter has a cis-element for Sp1 binding, we evaluated the role of Sp1 in response to H2O2. As previously reported, mutation of the Sp1 consensus lead to the complete loss of eNOS promoter activity, confirming the key role of Sp1 in regulating basal eNOS promoter activity. In addition, we found, using electrophoretic mobility and supershift assays, that H2O2 decreased Sp1 binding. Finally, using chromatin immunoprecipitation analysis, we found a significant decrease in Sp1 binding to the eNOS promoter in vivo in response to treatment with H2O2. Together, these data suggest that the inhibition of Sp1 activity, possibly through loss of zinc in the protein, plays a role in the H2O2-induced inhibition of eNOS promoter activity. PMID:19105596

Kumar, Sanjiv; Sun, Xutong; Wiseman, Dean A.; Tian, Jing; Umapathy, Nagavedi S.; Verin, Alexander D.

2009-01-01

39

A Lipopolysaccharide-Specific Enhancer Complex Involving Ets, Elk-1, Sp1, and CREB Binding Protein and p300 Is Recruited to the Tumor Necrosis Factor Alpha Promoter In Vivo  

PubMed Central

The tumor necrosis factor alpha (TNF-?) gene is rapidly activated by lipopolysaccharide (LPS). Here, we show that extracellular signal-regulated kinase (ERK) kinase activity but not calcineurin phosphatase activity is required for LPS-stimulated TNF-? gene expression. In LPS-stimulated macrophages, the ERK substrates Ets and Elk-1 bind to the TNF-? promoter in vivo. Strikingly, Ets and Elk-1 bind to two TNF-? nuclear factor of activated T cells (NFAT)-binding sites, which are required for calcineurin and NFAT-dependent TNF-? gene expression in lymphocytes. The transcription factors ATF-2, c-jun, Egr-1, and Sp1 are also inducibly recruited to the TNF-? promoter in vivo, and the binding sites for each of these activators are required for LPS-stimulated TNF-? gene expression. Furthermore, assembly of the LPS-stimulated TNF-? enhancer complex is dependent upon the coactivator proteins CREB binding protein and p300. The finding that a distinct set of transcription factors associates with a fixed set of binding sites on the TNF-? promoter in response to LPS stimulation lends new insights into the mechanisms by which complex patterns of gene regulation are achieved. PMID:10913190

Tsai, Eunice Y.; Falvo, James V.; Tsytsykova, Alla V.; Barczak, Amy K.; Reimold, Andreas M.; Glimcher, Laurie H.; Fenton, Matthew J.; Gordon, David C.; Dunn, Ian F.; Goldfeld, Anne E.

2000-01-01

40

Sp1/3 and NF-1 mediate basal transcription of the human P2X1 gene in megakaryoblastic MEG-01 cells  

PubMed Central

Background P2X1 receptors play an important role in platelet function as they can induce shape change, granule centralization and are also involved in thrombus formation. As platelets have no nuclei, the level of P2X1 expression depends on transcriptional regulation in megakaryocytes, the platelet precursor cell. Since nothing is known about the molecular mechanisms regulating megakaryocytic P2X1 expression, this study aimed to identify and functionally characterize the P2X1 core promoter utilized in the human megakaryoblastic cell line MEG-01. Results In order to identify cis-acting elements involved in the transcriptional regulation of P2X1 expression, the ability of 4.7 kb P2X1 upstream sequence to drive luciferase reporter gene expression was tested. Low promoter activity was detected in proliferating MEG-01 cells. This activity increased 20-fold after phorbol-12-myristate-13-acetate (PMA) induced differentiation. A transcription start site was detected 365 bp upstream of the start codon by primer extension. Deletion analysis of reporter constructs indicated a core promoter located within the region -68 to +149 bp that contained two Sp1 sites (named Sp1a and Sp1b) and an NF-1 site. Individual mutations of Sp1b or NF-1 binding sites severely reduced promoter activity whereas triple mutation of Sp1a, Sp1b and NF-1 sites completely abolished promoter activity in both untreated and PMA treated cells. Sp1/3 and NF-1 proteins were shown to bind their respective sites by EMSA and interaction of Sp1/3, NF-1 and TFIIB with the endogenous P2X1 core promoter in MEG-01 cells was demonstrated by chromatin immunoprecipitation. Alignment of P2X1 genes from human, chimp, rat, mouse and dog revealed consensus Sp1a, Sp1b and NF-1 binding sites in equivalent positions thereby demonstrating evolutionary conservation of these functionally important sites. Conclusion This study has identified and characterized the P2X1 promoter utilized in MEG-01 cells and shown that binding of Sp1/3 and NF-1 to elements in the direct vicinity of the transcription start site is essential for basal transcription. Targeting the function of these transcription factors in megakaryocytes may therefore provide a basis for the future therapeutic manipulation of platelet P2X1 function. PMID:16529657

Zhao, Jiangqin; Ennion, Steven J

2006-01-01

41

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

PubMed Central

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

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

2014-01-01

42

An Alu element in the myeloperoxidase promoter contains a composite SP1-thyroid hormone-retinoic acid response element.  

PubMed

An Alu element preceding the myeloperoxidase gene (MPO) contains four hexamer motifs related to the consensus recognition sequence for nuclear hormone receptors (AGGTCA), arranged as direct repeats with spacing of 2, 4, and 2 nucleotides (DR-2-4-2). Gel shift experiments and transient transfection assays demonstrate that these sequences include binding sites for retinoic acid and thyroid hormone receptors and function in vivo to activate transcription of a chloramphenicol acetyltransferase reporter gene. The first DR-2 elements of the series do not bind known receptors but do bind the SP1 transcription factor. Two alleles of the MPO gene exist that differ at one position within this element, resulting in one allele with and one without a strong SP1 binding site. The element with the SP1 site activates transcription by 25-fold in transient transfection assays, while the alternative allele confers severalfold less transcriptional activity. Most cases of acute myelocytic leukemia are homozygous for the allele with the SP1 binding site, suggesting this element plays an important role in regulating the MPO gene in myeloid leukemias. This MPO-Alu is a representative of an Alu subclass numbering approximately 400,000 copies, suggesting many genes may be regulated by such elements. PMID:8662930

Piedrafita, F J; Molander, R B; Vansant, G; Orlova, E A; Pfahl, M; Reynolds, W F

1996-06-14

43

Postirradiation examination results from SP1  

Microsoft Academic Search

This paper describes the postirradiation examination results from several of the fuel pins irradiated in the SP-1 test. The SP-1 test is the first of two tests irradiated in EBR-II to be examined. These tests are designed to provide a direct comparison of the performance potential of UOâ and UN fuel pins under conditions anticipated for the SP-100 reactor. In

R. A. Karnesky; R. E. Mason

1986-01-01

44

O-Linked N-Acetylglucosaminylation of Sp1 Inhibits the Human Immunodeficiency Virus Type 1 Promoter?  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) gene expression and replication are regulated by the promoter/enhancer located in the U3 region of the proviral 5? long terminal repeat (LTR). The binding of cellular transcription factors to specific regulatory sites in the 5? LTR is a key event in the replication cycle of HIV-1. Since transcriptional activity is regulated by the posttranslational modification of transcription factors with the monosaccharide O-linked N-acetyl-d-glucosamine (O-GlcNAc), we evaluated whether increased O-GlcNAcylation affects HIV-1 transcription. In the present study we demonstrate that treatment of HIV-1-infected lymphocytes with the O-GlcNAcylation-enhancing agent glucosamine (GlcN) repressed viral transcription in a dose-dependent manner. Overexpression of O-GlcNAc transferase (OGT), the sole known enzyme catalyzing the addition of O-GlcNAc to proteins, specifically inhibited the activity of the HIV-1 LTR promoter in different T-cell lines and in primary CD4+ T lymphocytes. Inhibition of HIV-1 LTR activity in infected T cells was most efficient (>95%) when OGT was recombinantly overexpressed prior to infection. O-GlcNAcylation of the transcription factor Sp1 and the presence of Sp1-binding sites in the LTR were found to be crucial for this inhibitory effect. From this study, we conclude that O-GlcNAcylation of Sp1 inhibits the activity of the HIV-1 LTR promoter. Modulation of Sp1 O-GlcNAcylation may play a role in the regulation of HIV-1 latency and activation and links viral replication to the glucose metabolism of the host cell. Hence, the establishment of a metabolic treatment might supplement the repertoire of antiretroviral therapies against AIDS. PMID:19193796

Jochmann, Ramona; Thurau, Mathias; Jung, Susan; Hofmann, Christian; Naschberger, Elisabeth; Kremmer, Elisabeth; Harrer, Thomas; Miller, Matthew; Schaft, Niels; Stürzl, Michael

2009-01-01

45

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

46

Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors  

PubMed Central

Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

2014-01-01

47

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

PubMed

In recent years there have been rapid developments in the use of growth factors for accelerated healing of injury. Growth factors have been used in maxillo-facial and plastic surgery with success and the technology is now being developed for orthopaedics and sports medicine applications. Growth factors mediate the biological processes necessary for repair of soft tissues such as muscle, tendon and ligament following acute traumatic or overuse injury, and animal studies have demonstrated clear benefits in terms of accelerated healing. There are various ways of delivering higher doses of growth factors to injured tissue, but each has in common a reliance on release of growth factors from blood platelets. Platelets contain growth factors in their alpha-granules (insulin-like growth factor-1, basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, vascular endothelial growth factor, transforming growth factor-beta(1)) and these are released upon injection at the site of an injury. Three commonly utilised techniques are known as platelet-rich plasma, autologous blood injections and autologous conditioned serum. Each of these techniques has been studied clinically in humans to a very limited degree so far, but results are promising in terms of earlier return to play following muscle and particularly tendon injury. The use of growth factors in sports medicine is restricted under the terms of the World Anti-Doping Agency (WADA) anti-doping code, particularly because of concerns regarding the insulin-like growth factor-1 content of such preparations, and the potential for abuse as performance-enhancing agents. The basic science and clinical trials related to the technology are reviewed, and the use of such agents in relation to the WADA code is discussed. PMID:17984193

Creaney, L; Hamilton, B

2008-05-01

48

Spider egg case core fibers: trimeric complexes assembled from TuSp1, ECP-1, and ECP-2.  

PubMed

Spider silk proteins are well-known for their extraordinary mechanical properties, displaying remarkable strength and toughness. In this study, matrix-assisted laser desorption ionization (MALDI) tandem time-of-flight (TOF) mass spectrometry (MS/MS) and reverse genetics were used to isolate a new cDNA sequence that encodes for a protein assembled into egg case silk from the black widow spider, Latrodectus hesperus. Analysis of the primary sequence of this protein reveals approximately 52% identity to the egg case protein 1 (ECP-1) fibroin-like family member. On the basis of the similarity in the primary sequence and expression pattern, we have named this factor egg case protein 2 (ECP-2). Alignments of ECP-1 and ECP-2 demonstrate highly conserved N termini, with 16 Cys residues found within the first 153 amino acids. Traditional ensemble repeats found within reported fibroins were poorly represented in the primary sequence of ECP-2, but scattered blocks of polyalanine were present, along with a C terminus rich in GA repeats. Reverse transcription quantitative PCR analysis showed that ECP-2 is predominantly expressed in the tubuliform gland. Relative to ECP-1, ECP-2 mRNA levels were determined to be >2-fold higher. MALDI MS/MS analysis of peptide fragments generated from the large-diameter core fiber after enzymatic digestion and acid hydrolysis demonstrated the presence of a fiber that is trimeric in nature, containing tubuliform spidroin 1 (TuSp1), ECP-1, and ECP-2. We also report an additional primary sequence for TuSp1, demonstrating that TuSp1 contains two Cys residues within a nonrepetitive N-terminal region. In combination with the distinctive protein architectures of ECP-1 and ECP-2, along with their co-localization with TuSp1 in the core fiber, our findings suggest that ECP-1 and ECP-2 play important structural roles in the egg case silk fiber. PMID:16533031

Hu, Xiaoyi; Kohler, Kristin; Falick, Arnold M; Moore, Anne M F; Jones, Patrick R; Vierra, Craig

2006-03-21

49

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

50

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

51

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

52

MYD88-independent growth and survival effects of Sp1 transactivation in Waldenstrom macroglobulinemia.  

PubMed

Sp1 transcription factor controls a pleiotropic group of genes and its aberrant activation has been reported in a number of malignancies, including multiple myeloma. In this study, we investigate and report its aberrant activation in Waldenström macroglobulinemia (WM). Both loss of and gain of Sp1 function studies have highlighted a potential oncogenic role of Sp1 in WM. We have further investigated the effect of a small molecule inhibitor, terameprocol (TMP), targeting Sp1 activity in WM. Treatment with TMP inhibited the growth and survival and impaired nuclear factor-?B and signal transducer and activator of transcription activity in WM cells. We next investigated and observed that TMP treatment induced further inhibition of WM cells in MYD88 knockdown WM cells. Moreover, we observed that Bruton's tyrosine kinase, a downstream target of MYD88 signaling pathway, is transcriptionally regulated by Sp1 in WM cells. The combined use of TMP with Bruton's tyrosine kinase or interleukin-1 receptor-associated kinase 1 and 4 inhibitors resulted in a significant and synergistic dose-dependent antiproliferative effect in MYD88-L265P-expressing WM cells. In summary, these results demonstrate Sp1 as an important transcription factor that regulates proliferation and survival of WM cells independent of MYD88 pathway activation, and provide preclinical rationale for clinical development of TMP in WM alone or in combination with inhibitors of MYD88 pathway. PMID:24622324

Fulciniti, Mariateresa; Amodio, Nicola; Bandi, Rajya Lakshmi; Munshi, Mansa; Yang, Guang; Xu, Lian; Hunter, Zachary; Tassone, Pierfrancesco; Anderson, Kenneth C; Treon, Steven P; Munshi, Nikhil C

2014-04-24

53

Abstract--Distribution factors play a key role in many system security analysis and market applications. The injection shift  

E-print Network

1 Abstract-- Distribution factors play a key role in many system security analysis and market of the other distribution factors. The line outage distribution factors (LODFs) may be computed using the ISFs distribution factors, line outage distribution factors, multiple-line outages, system security. I. INTRODUCTION

54

MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1  

PubMed Central

Background MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined. Methods Metastasis-associated tumor gene family 2 (MTA2) and transcription factor specificity protein 1 (Sp1) expression were detected in 127 gastric cancer samples by immunohistochemistry staining. SGC-7901 and AGS gastric cancer cell lines transfected by MTA2 shRNA was used for biological function investigation. Binding and regulation activities of Sp1 on MTA2 promoter were investigated by chromatin immunoprecipitation and luciferase reporter gene. Results The expression rate of MTA2 in gastric cancer tissues was 55.9% (71/127), and its expression was closely related to the depth of tumor invasion, lymph nodes metastasis, and TNM staging. MTA2 knockdown in human SGC-7901 and AGS gastric cancer cells significantly inhibited migration and invasion in vitro, and disrupted structure of cytoskeleton. MTA2 knockdown also attenuated xenografts growth and lung metastasis in nude mice model. MTA2 expression was positively correlated with transcription factor Sp1 in gastric cancer tissues (r?=?0.326, P?Sp1 bound to human MTA2 gene promoter at region from -1043 bp to -843 bp. Transcriptional activity of MTA2 promoter could be enhanced by Sp1 overexpression. Conclusions MTA2 knockdown impairs invasion and metastasis of gastric cancer cells, and attenuates xenografts growth in vivo. Sp1 regulates MTA2 expression at transcriptional level. PMID:24010737

2013-01-01

55

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

PubMed

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

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

2007-06-01

56

The Transcription Factor NFATp Plays a Key Role in Susceptibility to TB in Mice  

PubMed Central

In T cells, the transcription factor nuclear factor of activated T cells p (NFATp) is a key regulator of the cytokine genes tumor necrosis factor (TNF) and interferon-? (IFN-?). Here, we show that NFATp-deficient (NFATp?/?) mice have a dramatic and highly significant increase in mortality after Mycobacterium tuberculosis (MTb) infection as compared to mortality of control animals after MTb infection. Animals deficient in NFATp have significantly impaired levels of TNF and IFN-? transcription and protein expression in naïve or total CD4+ T cells, but display wild-type levels of TNF mRNA or protein from MTb-stimulated dendritic cells (DC). The rapid mortality and disease severity observed in MTb-infected NFATp?/? mice is associated with dysregulated production of TNF and IFN-? in the lungs, as well as with increased levels of TNF, in their serum. Furthermore, global blocking of TNF production by injection of a TNF neutralizaing agent at 6 weeks, but not 12 weeks, post-MTb-infection further decreased the survival rate of both wild-type and NFATp?/? mice, indicating an early role for TNF derived from cells from the monocyte lineage in containment of infection. These results thus demonstrate that NFATp plays a critical role in immune containment of TB disease in vivo, through the NFATp-dependent expression of TNF and IFN-? in T cells. PMID:22844476

Falvo, James V.; Goldfeld, Anne E.

2012-01-01

57

Transcriptional Activation of REST by Sp1 in Huntington's Disease Models  

PubMed Central

In Huntington's disease (HD), mutant huntingtin (mHtt) disrupts the normal transcriptional program of disease neurons by altering the function of several gene expression regulators such as Sp1. REST (Repressor Element-1 Silencing Transcription Factor), a key regulator of neuronal differentiation, is also aberrantly activated in HD by a mechanism that remains unclear. Here, we show that the level of REST mRNA is increased in HD mice and in NG108 cells differentiated into neuronal-like cells and expressing a toxic mHtt fragment. Using luciferase reporter gene assay, we delimited the REST promoter regions essential for mHtt-mediated REST upregulation and found that they contain Sp factor binding sites. We provide evidence that Sp1 and Sp3 bind REST promoter and interplay to fine-tune REST transcription. In undifferentiated NG108 cells, Sp1 and Sp3 have antagonistic effect, Sp1 acting as an activator and Sp3 as a repressor. Upon neuronal differentiation, we show that the amount and ratio of Sp1/Sp3 proteins decline, as does REST expression, and that the transcriptional role of Sp3 shifts toward a weak activator. Therefore, our results provide new molecular information to the transcriptional regulation of REST during neuronal differentiation. Importantly, specific knockdown of Sp1 abolishes REST upregulation in NG108 neuronal-like cells expressing mHtt. Our data together with earlier reports suggest that mHtt triggers a pathogenic cascade involving Sp1 activation, which leads to REST upregulation and repression of neuronal genes. PMID:21179468

Ravache, Myriam; Weber, Chantal; Mérienne, Karine; Trottier, Yvon

2010-01-01

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

Epidermal Growth Factor Receptor Plays a Significant Role in Hepatocyte Growth Factor Mediated Biological Responses in Mammary Epithelial Cells  

PubMed Central

Breast cancers often have deregulated hepatocyte growth factor (HGF) and c-Met signaling that results in increased tumor growth and invasion. Elucidating the mechanism responsible for HGF/c-Met action in breast cancer progression has been difficult as c-Met communicates with a number of secondary receptors that can lead to various pathological outcomes. Understanding how these secondary receptors facilitate HGF/c-Met cellular responses will aid in the development of better therapeutic treatment options for breast cancer patients with elevated HGF signaling. In the present study it was shown that the epidermal growth factor receptor (EGFR) plays a significant role in HGF/c-Met mediated biological activities indicative of advanced tumor pathology, including enhanced proliferation and invasion. The clinically relevant EGFR inhibitor gefitinib was used to determine the role of EGFR in HGF-induced proliferation and motility in several mammary carcinoma cells including PyVmT, MDA-MB-231 and 4T1. Our analyses indicated that EGFR inhibition significantly blocked HGF activation of c-Met and EGFR and that inhibition of these pathways mitigated HGF induced proliferation and motility. The data indicate that this inhibition was not through a direct effect of gefitinib on c-Met, but that EGFR is necessary for c-Met activation in the assays performed. These results provide a novel mechanism of action for EGFR as a mediator of HGF signaling thereby linking EGFR to the oncogenic potential of c-Met in mammary carcinomas cells. PMID:17495520

Bonine-Summers, Alyssa R.; Aakre, Mary E.; Brown, Kimberly A.; Arteaga, Carlos L.; Pietenpol, Jennifer A.; Moses, Harold L.; Cheng, Nikki

2012-01-01

60

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

PubMed

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

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

2014-01-01

61

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

PubMed Central

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

Pedersen, Nancy L.

2014-01-01

62

The ULT trxG factors play a role in arabidopsis fertilization.  

PubMed

Trithorax group (trxG) and Polycomb group (PcG) proteins are epigenetic modifiers that play key roles in eukaryotic development by promoting active or repressive gene expression states, respectively. Although PcG proteins have well-defined roles in controlling developmental transitions, cell fate decisions and cellular differentiation in plants, relatively little is known about the functions of plant trxG factors. We recently determined the biological roles for the ULT1 and ULT2 trxG genes during Arabidopsis vegetative and reproductive development. Our study revealed that ULT1 and ULT2 genes have overlapping activities in regulating Arabidopsis shoot and floral stem cell activity, and that they have a redundant function in establishing the apical-basal polarity axis of the gynoecium. Here we present data that ult1 and ult1 ult2 siliques contain a significant proportion of aborted ovules, supporting an additional role for ULT1 in Arabidopsis fertility. Our results add to the number of plant developmental processes that are regulated by trxG activity. PMID:25531183

Monfared, Mona M; Fletcher, Jennifer C

2014-12-01

63

Identification of Poly(ADP-Ribose) Polymerase-1 as a Cell Cycle Regulator through Modulating Sp1 Mediated Transcription in Human Hepatoma Cells  

PubMed Central

The transcription factor Sp1 is implicated in the activation of G0/G1 phase genes. Modulation of Sp1 transcription activities may affect G1-S checkpoint, resulting in changes in cell proliferation. In this study, our results demonstrated that activated poly(ADP-ribose) polymerase 1 (PARP-1) promoted cell proliferation by inhibiting Sp1 signaling pathway. Cell proliferation and cell cycle assays demonstrated that PARP inhibitors or PARP-1 siRNA treatment significantly inhibited proliferation of hepatoma cells and induced G0/G1 cell cycle arrest in hepatoma cells, while overexpression of PARP-1 or PARP-1 activator treatment promoted cell cycle progression. Simultaneously, inhibition of PARP-1 enhanced the expression of Sp1-mediated checkpoint proteins, such as p21 and p27. In this study, we also showed that Sp1 was poly(ADP-ribosyl)ated by PARP-1 in hepatoma cells. Poly(ADP-ribosyl)ation suppressed Sp1 mediated transcription through preventing Sp1 binding to the Sp1 response element present in the promoters of target genes. Taken together, these data indicated that PARP-1 inhibition attenuated the poly(ADP-ribosyl)ation of Sp1 and significantly increased the expression of Sp1 target genes, resulting in G0/G1 cell cycle arrest and the decreased proliferative ability of the hepatoma cells. PMID:24367566

Du, Meng; Kang, Xiang; Luo, Xi; Gao, Lu; Wang, Cheng; Zhang, Yanqing; Zhang, Chun; Tong, Qiangsong; Huang, Kai; Zhang, Fengxiao; Huang, Dan

2013-01-01

64

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

65

Sp1 and Egr1 regulate transcription of the Dmrt1 gene in Sertoli cells.  

PubMed

Dmrt1 is a recently described gene that is specifically expressed in the gonads and is required for postnatal testis differentiation. Here, we describe the transcriptional mechanisms regulating the Dmrt1 proximal promoter in testicular Sertoli cells. A genomic clone containing exon 1 of the rat Dmrt1 gene and more than 9 kilobases of 5' flanking sequence was isolated and characterized. Several prominent transcriptional start sites were identified, with the major site located 102 bases from the translational start. The Dmrt1 5' flanking region from -5000 to +74 was transcriptionally active in primary Sertoli cells, and deletion analysis of this fragment identified 2 major regions needed for full Dmrt1 promoter function. These regions were located between -3200 and -2000 base pairs (bp) and downstream of -150 bp relative to the major transcriptional start site. DNase I footprint analysis of the region downstream of -150 bp revealed 3 regions that are bound by proteins from Sertoli cell nuclear extracts. Site-directed mutagenesis of these regions identified 2 elements that activate the Dmrt1 promoter and 2 that repress it. The positive elements bind the transcription factors Sp1, Sp3, and Egr1, suggesting that these transcription factors play a critical role in Dmrt1 regulation in the testis. PMID:11870074

Lei, Ning; Heckert, Leslie L

2002-03-01

66

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

67

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

Microsoft Academic Search

The alternative sigma factor (RpoE) is involved in the response to extracytoplasmic stress and plays a role in the virulence of a variety of different bacteria. To assess the role of in Vibrio cholerae pathogenesis, a rpoE mutant was constructed and analyzed using the infant mouse model. The results here show that contributes significantly to the virulence of V. cholerae.

Gabriela Kovacikova; Karen Skorupski

2002-01-01

68

Central role of Sp1-regulated CD39 in hypoxia/ischemia protection  

PubMed Central

Hypoxia is common to several inflammatory diseases, where multiple cell types release adenine-nucleotides (particularly adenosine triphosphate/adenosine diphosphate). Adenosine triphosphate/adenosine diphosphate is metabolized to adenosine through a 2-step enzymatic reaction initiated by CD39 (ectonucleoside-triphosphate-diphosphohydrolase-1). Thus, extracellular adenosine becomes available to regulate multiple inflammatory endpoints. Here, we hypothesized that hypoxia transcriptionally up-regulates CD39 expression. Initial studies revealed hypoxia-dependent increases in CD39 mRNA and immunoreactivity on endothelia. Examination of the human CD39 gene promoter identified a region important in hypoxia inducibility. Multiple levels of analysis, including site-directed mutagenesis, chromatin immunoprecipitation, and inhibition by antisense, revealed a critical role for transcription-factor Sp1 in hypoxia-induction of CD39. Using a combination of cd39?/? mice and Sp1 small interfering RNA in in vivo cardiac ischemia models revealed Sp1-mediated induction of cardiac CD39 during myocardial ischemia. In summary, these results identify a novel Sp1-dependent regulatory pathway for CD39 and indicate the likelihood that CD39 is central to protective responses to hypoxia/ischemia. PMID:18812468

Köhler, David; Eckle, Tobias; Kong, Tianqing; Robson, Simon C.

2009-01-01

69

Users guide for the ANL IBM SP1  

SciTech Connect

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

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

1994-10-01

70

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.

71

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

PubMed Central

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

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

2013-01-01

72

Hepatocyte growth factor plays a dual role in regulating skeletal muscle satellite cell proliferation and differentiation  

Microsoft Academic Search

The role of hepatocyte growth factor (HGF) and its receptor, c-met, in proliferation and differentiation of satellite cells was studied in primary cultures of chicken skeletal muscle satellite cells and a myogenic C2 cell line. HGF mRNA was expressed mainly in the myotubes of both cultures. The addition of conditioned medium derived from those cultures had a scattering effect on

Ronit Gal-Levi; Yael Leshem; Shunsuke Aoki; Toshikazu Nakamura; Orna Halevy

1998-01-01

73

Do psychosexual factors play a role in the etiology of provoked vestibulodynia? A critical review.  

PubMed

The aim of this review was to critically examine published studies concerning the psychosexual aspects of provoked vestibulodynia. Despite the presence of several methodological limitations, some findings were consistently replicated. Overall, women with vestibulodynia demonstrate impaired sexual functioning, namely, lower levels of sexual desire, arousal, and frequency of intercourse. Childhood physical and sexual abuse represent potential risk factors for the development of this condition. Additionally, specific psychological states such as anxiety, fear of pain, hypervigilance, catastrophizing, and depression, are more frequently reported by these women. More rigorous studies are needed to establish which psychosexual variables may exacerbate and/or maintain vestibulodynia. PMID:18398760

Desrochers, Geneviève; Bergeron, Sophie; Landry, Tina; Jodoin, Mélanie

2008-01-01

74

Suppression of survivin promoter activity by YM155 involves disruption of Sp1-DNA interaction in the survivin core promoter  

PubMed Central

YM155, a novel survivin suppressant, shows potent antitumor activity against various human cancers and is currently in phase II clinical trials. In this study, we investigated whether YM155 selectively inhibits survivin transcription. We hypothesize that inhibition of survivin transcription plays a role in YM155-mediated survivin inhibition. We found that YM155 inhibited survivin promoter activity, while it showed minimal inhibitory effect on four control gene promoters in transfection and luciferase activity assay experiments, indicating its selectivity. Transfection of various survivin promoter-luciferase constructs followed by luciferase assays revealed that the survivin core promoter (269 bp) plays a major role in YM155-mediated inhibitory effects. However, flow cytometry analysis indicated that inhibition of survivin promoter activity by YM155 is cell cycle-independent without G1 cell arrests. Electrophoretic mobility shift assays (EMSA) identified that YM155 abrogates nuclear proteins binding to the region of -149 to -71, in which Sp1 is a major candidate, and that YM155 treatment induces Sp1 re-subcellular localization without inhibiting its expression. Forced expression of Sp1 neutralized YM155-mediated downregulation of survivin promoter activity. Consistently, mutation of the identified Sp1 sites in the oligonucleotide probe diminished DNA-protein interactions in EMSA experiments, and mutation of the Sp1 sites in the survivin promoter-luciferase construct diminished survivin promoter activity. These findings indicate that YM155 inhibition of survivin expression is at least in part through its inhibition of survivin transcription by disruption of Sp1 interaction with the region of -149 to -71 in the survivin core promoter. PMID:22773958

Cheng, Qiuying; Ling, Xiang; Haller, Andrew; Nakahara, Takahito; Yamanaka, Kentaro; Kita, Aya; Koutoku, Hiroshi; Takeuchi, Masahiro; Brattain, Michael G; Li, Fengzhi

2012-01-01

75

Hypoxia-inducible factor 2? plays a critical role in the formation of alveoli and surfactant.  

PubMed

Alveolarization of the developing lung is an important step toward the switch from intrauterine life to breathing oxygen-rich air after birth. The distal airways structurally change to minimize the gas exchange path, and Type II pneumocytes increase the production of surfactants, which are required to reduce surface tension at the air-liquid interface in the alveolus. Hypoxia-inducible factor 2? (Hif2?) is an oxygen-regulated transcription factor expressed in endothelial and Type II cells, and its expression increases toward the end of gestation. We investigated the role of Hif2? in Type II cells by conditionally expressing an oxygen-insensitive mutant of Hif2? in airway epithelial cells during development. Newborn mice expressing the mutant Hif2? were born alive but quickly succumbed to respiratory distress. Subsequent analysis of the lungs revealed dilated alveoli covered with enlarged, aberrant Type II cells and a diminished number of Type I cells. The Type II cells accumulated glycogen in part by increased glucose uptake via the up-regulation of the glucose transporter 1. Furthermore, the cells lacked two crucial enzymes involved in the metabolism of glycogen into surfactant lipids, lysophosphatidylcholine acyltransferase and ATP-binding cassette sub-family A member 3. We conclude that Hif2? is a key regulator in alveolar maturation and the production of phospholipids by Type II cells. PMID:22298531

Huang, Yadi; Kempen, Marjon Buscop-van; Munck, Anne Boerema-de; Swagemakers, Sigrid; Driegen, Siska; Mahavadi, Poornima; Meijer, Dies; van Ijcken, Wilfred; van der Spek, Peter; Grosveld, Frank; Günther, Andreas; Tibboel, Dick; Rottier, Robbert J

2012-02-01

76

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

PubMed Central

BTF3 has been recognized to be involved in plant growth and development. But its function remains mostly unknown during seed germination and seedling stage. Here, we have analyzed OsBTF3-related sequences in Oryza sativa L. subspecies, japonica, which resembles with the conserved domain of a nascent polypeptide associated complex (NAC) with different homologs of OsBTF3 and human BTF3. Inhibition of Osj10gBTF3 has led to considerable morphological changes during seed germination and seedling growth. Germination percentage was not influenced by the application of GA3, ABA, and NaCl but all concentrations caused wild-type (WT) seeds to germinate more rapidly than the RNAi (Osj10gBTF3Ri) transgenic lines. Seedling inhibition was more severe in the Osj10gBTF3Ri seedlings compared with their WT especially when treated with 100 or 200??M GA3; 50% reduction in shoots was observed in Osj10gBTF3Ri seedlings. The expression of Osj3g1BTF3, Osj3g2BTF3 and Osj10gBTF3 was primarily constitutive and generally modulated by NaCl, ABA, and GA3 stresses in both Osj10gBTF3Ri lines and WT at the early seedling stage, suggesting that Osj3g1BTF3 and Osj10gBTF3 are much similar but different from Osj3g2BTF3 in biological function. These results show that OsBTF3 plays an important role in seed germination and seedling growth gives a new perception demonstrating that more multifaceted regulatory functions are linked with BTF3 in plants. PMID:24971328

Wang, Wenyi; Xu, Mengyun; Wang, Ya

2014-01-01

77

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

PubMed Central

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

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

2014-01-01

78

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

PubMed

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

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

2014-12-16

79

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

PubMed

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

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

2015-01-01

80

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

PubMed Central

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

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

2013-01-01

81

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

82

Structural and functional characterization of the human and mouse fibulin-1 gene promoters: role of Sp1 and Sp3.  

PubMed Central

Fibulin-1 is a multifunctional extracellular protein involved in diverse biological processes including cardiovascular development, haemostasis and cancer. To investigate the transcriptional regulation of the gene encoding fibulin-1 we cloned and analysed about 4.0 kb of the 5'-flanking regions of both the human and mouse fibulin-1 genes. The human and mouse fibulin-1 promoters share little sequence similarity except for a short region of approx. 150-170 bp immediately upstream of the translation start site. The conserved region contains a TATA-like sequence (ATAATT) and multiple consensus binding sites for Sp1 and activator protein 2 (AP-2). That the short conserved region in each gene confers basal promoter activity is demonstrated by transient transfections of promoter deletion constructs for both the human and mouse genes into cells that express fibulin-1 constitutively. Co-transfections of promoter constructs with expression plasmids for Sp1, Sp3 and Sp4 into Drosophila SL2 cells indicate that Sp1 and Sp3 are essential for transcriptional activation and that these two factors act synergistically. Electrophoretic mobility-shift assays show that Sp1 and Sp3, but not AP-2, bind to the basal promoter of the human fibulin-1 gene. The results demonstrate the functional importance of Sp1 and Sp3 in regulating the expression of the fibulin-1 gene. PMID:11829738

Castoldi, Mirco; Chu, Mon-Li

2002-01-01

83

A hypermorphic SP1-binding CD24 variant associates with risk and progression of multiple sclerosis  

PubMed Central

A large number of risk alleles have been identified for multiple sclerosis (MS). However, how genetic variations may affect pathogenesis remains largely unknown for most risk alleles. Through direct sequencing of CD24 promoter region, we identified a cluster of 7 new single nucleotide polymorphisms in the CD24 promoter. A hypermorphic haplotype consisting of 3 SNPs was identified through association studies consisting of 935 control and 764 MS patients (P=0.001, odds ratio 1.3). The variant is also associated with more rapid progression of MS (P=0.016, log rank test). In cells that are heterozygous for the risk allele, chromatin immunoprecipitation revealed that risk allele specifically bind to a transcription factor SP1, which is selectively required for the hypermorphic promoter activity of the variant. In MS patients, the CD24 transcript levels associate with the SP1-binding variant in a dose-dependent manner (P=7x10-4). Our data revealed a potential role for SP1-mediated transcriptional regulation in MS pathogenesis. PMID:22937211

Wang, Lizhong; Liu, Runhua; Li, Dongling; Lin, Shili; Fang, Xianfeng; Backer, Grant; Kain, Mandy; Rammoham, Kottil; Zheng, Pan; Liu, Yang

2012-01-01

84

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

PubMed

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

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

2015-01-01

85

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

PubMed Central

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

Gu, Bo; Eick, Dirk; Bensaude, Olivier

2013-01-01

86

Phosphorylated Sp1 is the regulator of DNA-PKcs and DNA ligase IV transcription of daunorubicin-resistant leukemia cell lines.  

PubMed

Multidrug resistance (MDR) is a serious problem faced in the treatment of malignant tumors. In this study, we characterized the expression of non-homologous DNA end joining (NHEJ) components, a major DNA double strand break (DSB) repair mechanism in mammals, in K562 cell and its daunorubicin (DNR)-resistant subclone (K562/DNR). K562/DNR overexpressed major enzymes of NHEJ, DNA-PKcs and DNA ligase IV, and K562/DNR repaired DSB more rapidly than K562 after DNA damage by neocarzinostatin (MDR1-independent radiation-mimetic). Overexpressed DNA-PKcs and DNA ligase IV were also observed in DNR-resistant HL60 (HL60/DNR) cells as compared with parental HL60 cells. Expression level of DNA-PKcs mRNA paralleled its protein level, and the promoter activity of DNA-PKcs of K562/DNR was higher than that of K562, and the 5'-region between -49bp and the first exon was important for its activity. Because this region is GC-rich, we tried to suppress Sp1 family transcription factor using mithramycin A (MMA), a specific Sp1 family inhibitor, and siRNAs for Sp1 and Sp3. Both MMA and siRNAs suppressed DNA-PKcs expression. Higher serine-phosphorylated Sp1 but not total Sp1 of both K562/DNR and HL60/DNR was observed compared with their parental K562 and HL60 cells. DNA ligase IV expression of K562/DNR was also suppressed significantly with Sp1 family protein inhibition. EMSA and ChIP assay confirmed higher binding of Sp1 and Sp3 with DNA-PKcs 5'-promoter region of DNA-PKcs of K562/DNR than that of K562. Thus, the Sp1 family transcription factor affects important NHEJ component expressions in anti-cancer drug-resistant malignant cells, leading to the more aggressive MDR phenotype. PMID:24530422

Nishida, Yayoi; Mizutani, Naoki; Inoue, Minami; Omori, Yukari; Tamiya-Koizumi, Keiko; Takagi, Akira; Kojima, Tetsuhito; Suzuki, Motoshi; Nozawa, Yoshinori; Minami, Yosuke; Ohnishi, Kazunori; Naoe, Tomoki; Murate, Takashi

2014-01-01

87

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

PubMed Central

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

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

1999-01-01

88

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

PubMed Central

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

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

2013-01-01

89

A microfluidic-FCS platform for investigation on the dissociation of Sp1-DNA complex by doxorubicin  

PubMed Central

The transcription factor (TF) Sp1 is a well-known RNA polymerase II transcription activator that binds to GC-rich recognition sites in a number of essential cellular and viral promoters. In addition, direct interference of Sp1 binding to DNA cognate sites using DNA-interacting compounds may provide promising therapies for suppression of cancer progression and viral replication. In this study, we present a rapid, sensitive and cost-effective evaluation of a GC intercalative drug, doxorubicin (DOX), in dissociating the Sp1–DNA complex using fluorescence correlation spectroscopy (FCS) in a microfluidic system. FCS allows assay miniaturization without compromising sensitivity, making it an ideal analytical method for integration of binding assays into high-throughput, microfluidic platforms. A polydimethylsiloxane (PDMS)-based microfluidic chip with a mixing network is used to achieve specific drug concentrations for drug titration experiments. Using FCS measurements, the IC50 of DOX on the dissociation of Sp1–DNA complex is estimated to be 0.55 ?M, which is comparable to that measured by the electrophoretic mobility shift assay (EMSA). However, completion of one drug titration experiment on the proposed microfluidic-FCS platform is accomplished using only picograms of protein and DNA samples and less than 1 h total assay time, demonstrating vast improvements over traditional ensemble techniques. PMID:17108358

Yeh, Hsin-Chih; Puleo, Christopher M.; Lim, Teck Chuan; Ho, Yi-Ping; Giza, Paul E.; Huang, Ru Chih C.; Wang, Tza-Huei

2006-01-01

90

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.

91

Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk  

PubMed Central

The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of ovarian cancer. We found no association between variation in IGF1, IGFBP1 or IGFBP3 and risk of invasive disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at P<0.05 and followed-up one of the associated SNPs. We conducted genotyping in 3216 additional non-Hispanic white cases and 5382 additional controls and were able to independently replicate our initial findings. In the combined set of studies, rs4320932 was associated with a 13% decreased risk of ovarian cancer per copy of the minor allele carried (95% confidence interval 0.81–0.93, P-trend=7.4 × 10?5). No heterogeneity of effect across study centers was observed (phet=0.25). IGF2 is emerging as an important gene for ovarian cancer; additional genotyping is warranted to further confirm these associations with IGF2 and to narrow down the region harboring the causal SNP. PMID:21422097

Pearce, Celeste Leigh; Doherty, Jennifer A.; Van Den Berg, David J.; Moysich, Kirsten; Hsu, Chris; Cushing-Haugen, Kara L.; Conti, David V.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Pharoah, Paul D.P.; Song, Honglin; Kjaer, Susanne K.; Hogdall, Estrid; Hogdall, Claus; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Gronwald, Jacek; Medrek, Krzysztof; Jakubowska, Anna; Lubinski, Jan; Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M.; Berchuck, Andrew; Schildkraut, Joellen M.; Iversen, Edwin S.; Moorman, Patricia G.; Edlund, Christopher K.; Stram, Daniel O.; Pike, Malcolm C.; Ness, Roberta B.; Rossing, Mary Anne; Wu, Anna H.

2011-01-01

92

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

PubMed

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

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

2014-12-01

93

TNF receptor associated factor 3 plays a key role in development and function of invariant natural killer T cells  

PubMed Central

TCR signaling is a prerequisite for early stage development of invariant natural killer T (iNKT) cells, whereas IL-15 signaling is required for expansion and maturation at later stages. In this study, we show that TNF receptor associated factor 3 (TRAF3) plays a critical role in the transition between these two distinct signaling pathways and developmental stages. TRAF3-deficient iNKT cells in CD4CreTRAF3flox/flox (T-TRAF3?/?) mice exhibit defective up-regulation of T-bet and CD122, two critical molecules for IL-15 signaling, and as a consequence, IL-15–mediated iNKT cell proliferation and survival are impaired. Consistently, development of iNKT cells in T-TRAF3?/? mice shows a major defect at developmental stages 2 and 3, but not stages 0 and 1. We further demonstrated that defective T-bet up-regulation occurring during the stage 1 to stage 2 transition results from reduced TCR signaling in TRAF3?/? iNKT cells. In addition, mature TRAF3?/? iNKT cells displayed defective cytokine responses upon TCR stimulation. Collectively, our results reveal that by modulating the relative strength of TCR signaling, TRAF3 is an important regulator of iNKT cell development and functions. PMID:23650438

Yi, Zuoan; Stunz, Laura L.

2013-01-01

94

Adjacent proline residues in the inhibitory domain of the Oct-2 transcription factor play distinct functional roles.  

PubMed Central

A 40 amino acid region of Oct-2 from amino acids 142 to 181 functions as an active repressor domain capable of inhibiting both basal activity and activation of promoters containing a TATA box, but not of those that contain an initiator element. Based on our observation that the equivalent region of the closely related Oct-1 factor does not act as an inhibitory domain, we have mutated specific residues in the Oct-2 domain in an attempt to probe their importance in repressor domain function. Although mutations of several residues have no or minimal effect, mutation of proline 175 to arginine abolishes the ability to inhibit both basal and activated transcription. In contrast, mutation of proline 174 to arginine confers upon the domain the ability to repress activation of an initiator-containing promoter by acidic activation domains, and also suppresses the effect of the proline 175 mutation. Hence, adjacent proline residues play key roles in the functioning of the inhibitory domain and in limiting its specificity to TATA-box-containing promoters. PMID:9580701

Liu, Y Z; Lee, I K; Locke, I; Dawson, S J; Latchman, D S

1998-01-01

95

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

96

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

97

Nicotiana benthamiana protein, NbPCIP1, interacting with Potato virus X coat protein plays a role as susceptible factor for viral infection  

Microsoft Academic Search

The interactions of viral coat protein (CP) and host factors play an important role in viral replication and\\/or host defense mechanism. In this study, we constructed Nicotiana benthamiana cDNA library to find host factors interacting with Potato virus X (PVX) CP. Using yeast two-hybrid assay, we screened 3.3×106 independent yeast transformants from N. benthamiana cDNA library and identified six positive

Mi-Ri Park; Sang-Ho Park; Sang-Yun Cho; Kook-Hyung Kim

2009-01-01

98

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

PubMed

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

Choi, Dongseong; Kim, Jinwoo

2004-02-01

99

DNA methylation and Sp1 binding determine the tissue-specific transcriptional activity of the mouse Abcc6 promoter  

PubMed Central

Summary The gene encoding the ABCC6 protein, an ABC transporter of the multidrug resistance-associated protein (MRP), is mainly expressed in liver and kidney. Mutations in ABCC6 are responsible for the development of the pseudoxanthoma elasticum (PXE) phenotype. PXE is a recessive disease characterized by the calcification of elastic fibers resulting in dermal, vascular and ocular clinical manifestations. The physiological function of ABCC6 and the rodent orthologs Abcc6 is unknown and their precise relationship to elastic fibers is only a matter of speculation. Despite several studies focused on the transcriptional regulation of ABCC6/Abcc6, the molecular signals conferring the tissue-specificity to the ABCC6/Abcc6 expression are not well defined. In this report, we determined the level of the mouse Abcc6 promoter methylation in tissues with low level of expression (tail extremity and skin), intermediate (kidney) and high level of expression (liver). We observed that high and moderate levels of methylation correlated with low levels of Abcc6 expression. Moreover, we determined that CpG methylation of the Abcc6 proximal promoter region was interfering with the binding of the Sp1 transcription factor thereby inhibiting Sp1-dependent transactivation. Thus, our data provides the first direct evidence that an epigenetic mechanism regulates the binding of the transcription factor Sp1 to the proximal promoter and participates in the tissue-specific expression control of the mouse Abcc6 gene. PMID:17214963

Douet, Vanessa; Heller, Matthew B.; Le Saux, Olivier

2007-01-01

100

Radioimmunoassay of serum SP 1 and HPL in normal and abnormal pregnancies  

Microsoft Academic Search

Zusammenfassung Zur Bestimmung des schwangerschaftsspezifischen ?1-Glykoproteins (SP 1) wurde ein Radioimmunoassay entwickelt. Die Normalbereiche für SP 1 und das humane Plazenta-Laktogen (HPL) in der zweiten Schwangerschaftshälfte bestimmten wir aus 372 Serumproben von 40 ungestörten Schwangerschaftsverläufen. Der Median von SP 1 stieg von 40 ?g\\/ml in der 22. SSW auf 168 ?g\\/ml in der 36. SSW kontinuierlich an und blieb danach

M. Pluta; W. qHardt; K. Schmidt-Gollwitzer; M. Schmidt-Gollwitzer

1979-01-01

101

Playing Shakespeare.  

ERIC Educational Resources Information Center

Describes a yearlong project at 12 Catholic middle schools in the Diocese of Arlington, Virginia, to incorporate the plays of William Shakespeare into the curriculum. Teachers attended university lectures and directed students in performances of the plays. Concludes that Shakespeare can be understood and enjoyed by middle school students. (BCY)

Bashian, Kathleen Ryniker

1993-01-01

102

Playing war  

Microsoft Academic Search

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

Ian Graham Ronald Shaw

2010-01-01

103

Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1.  

PubMed

7,8-Dihydroxyflavone (7,8-DHF) is a member of the flavonoid family and has recently been identified as a brain-derived neurotrophic factor mimetic that selectively activates tropomyosin-receptor kinase B with high affinity. The antioxidant and anticancer effects of 7,8-DHF have been reported. However, the pharmacological mechanisms of 7,8-DHF in oral cancer are unclear. Thus, we investigated the mechanisms of the antiproliferative action of 7,8-DHF on HN22 and HSC4 oral squamous cell carcinoma cell lines. We demonstrated that 7,8-DHF decreased cell growth and induced apoptosis in the HN22 and HSC4 cells through regulation of specificity protein 1 (Sp1) using the MTS assay, DAPI staining, Annexin V, propidium iodide staining, reverse transcription-polymerase chain reaction, immunocytochemistry, pull-down assay and western blot analysis. The results showed that the Sp1 protein bound with 7,8-DHF in the HN22 and HSC4 cells. Taken together, the results suggest that 7,8-DHF could modulate Sp1 transactivation and induce apoptotic cell death by regulating the cell cycle and suppressing antiapoptotic proteins. Furthermore, 7,8-DHF may be valuable for cancer prevention and better clinical outcomes. PMID:25434704

Lee, Ra Ham; Shin, Jae-Cheon; Kim, Ka-Hwi; Choi, Yung Hyun; Chae, Jung-Il; Shim, Jung-Hyun

2015-02-01

104

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 ...

Mr Clark

2012-10-31

105

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

SciTech Connect

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

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

2012-04-20

106

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

PubMed Central

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

Lim, Siew Pheng; Garzino-Demo, Alfredo

2000-01-01

107

Play & Play Grounds. A Report.  

ERIC Educational Resources Information Center

Using camera and tape recorder, a photographer and an early childhood specialist explored as a team the universe of children's outdoor play, seeking worthy and innovative ideas and stressing urban playground problems and solutions. The resulting photographs and text focus on (1) the characteristics of play, (2) the nature of playgrounds, and (3)…

Stone, Jeannette Galambos

108

Nuclear Respiratory Factor 1 Plays an Essential Role in Transcriptional Initiation from the Hepatitis B Virus X Gene Promoter  

Microsoft Academic Search

The X gene of hepatitis B virus (HBV) is one of the major factors in HBV-induced hepatocarcinogenesis and is essential for the establishment of productive HBV replication in vivo. Recent studies have shown that the X gene product targets mitochondria and induces calcium flux, thereby activating Ca-dependent signal trans- duction pathways. However, regulatory mechanisms of X gene expression have remained

Yumiko Tokusumi; Sharleen Zhou; Shinako Takada

2004-01-01

109

The Role Played by the Interaction between Genetic Factors and Attachment in the Stress Response in Infancy  

ERIC Educational Resources Information Center

Background: The importance of understanding which environmental and biological factors are involved in determining individual differences in physiological response to stress is widely recognized, given the impact that stress has on physical and mental health. Methods: The child-mother attachment relationship and some genetic polymorphisms…

Frigerio, Alessandra; Ceppi, Elisa; Rusconi, Marianna; Giorda, Roberto; Raggi, Maria Elisabetta; Fearon, Pasco

2009-01-01

110

Immunosuppression by human placenta lactogen (HPL) and the pregnancy-specific ? 1 -glycoprotein (SP1)  

Microsoft Academic Search

The in vitro effect of human placenta lactogen (HPL) and the gravidity-specificß1-Glycoprotein (SP-1) on the lymphocyte transformation was investigated in 20 healthy women. It was shown that simultaneous incubation of the lymphocytes with HPL or SP-1 together with PHA has no influence on the incorporation rate of H3-Thymidine.

C. Cerni; G. Tatra; H. Bohn

1977-01-01

111

Concentrations of placental proteins (HPL and SP1) in maternal serum throughout normal pregnancy  

Microsoft Academic Search

Summary Throughout 65 normal singleton pregnancies 332 blood samples were obtained and analyzed for pregnancy-specific ?1 glycoprotein (SP1) and human placental lactogen (HPL). The measurement of SP1 in maternal serum was made using radial immunodiffusion, that of HPL by using radioimmunoassay. There was wide variation in the number and timing of blood samples obtained from patients, and therefore the results

M. P. Baur; O. Bellmann; J. Tebbe; N. Lang

1982-01-01

112

The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway  

PubMed Central

Background The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA transcriptional activator were generated and characterized. Results Transcriptional profiling experiments revealed that overexpression of ORCA2 results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of ORCA2 significantly affects the levels of several TIA metabolites. ORCA2 overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors. Conclusions Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude. PMID:24099172

2013-01-01

113

Targeting of the HIV-1 long terminal repeat with chromomycin potentiates the inhibitory effects of a triplex-forming oligonucleotide on Sp1-DNA interactions and in vitro transcription.  

PubMed Central

We have studied the effects of chromomycin and of a triple-helix-forming oligonucleotide (TFO) that recognizes Sp1 binding sites on protein-DNA interactions and HIV-1 transcription. Molecular interactions between chromomycin, the Sp1 TFO and target DNA sequences were studied by gel retardation, triplex affinity capture using streptavidin-coated magnetic beads and biosensor technology. We also determined whether chromomycin and a TFO recognizing the Sp1 binding sites of the HIV-1 long terminal repeat (LTR) inhibit the activity of restriction enzyme HaeIII, which recognizes a sequence (5'-GGCC-3') located within these Sp1 binding sites. The effects of chromomycin and the TFO on the interaction between nuclear proteins or purified Sp1 and a double-stranded oligonucleotide containing the Sp1 binding sites of the HIV-1 LTR were studied by gel retardation. The effects of both chromomycin and TFO on transcription were studied by using an HIV-1 LTR-directed in vitro transcription system. Our results indicate that low concentrations of chromomycin potentiate the effects of the Sp1 TFO in inhibiting protein-DNA interactions and HIV-1-LTR-directed transcription. In addition, low concentrations of chromomycin do not affect binding of the TFO to target DNA molecules. The results presented here support the hypothesis that both DNA binding drugs and TFOs can be considered as sequence-selective modifiers of DNA-protein interactions, possibly leading to specific alterations of biological functions. In particular, the combined use of chromomycin and TFOs recognizing Sp1 binding sites could be employed in order to abolish the biological functions of promoters (such as the HIV-1 LTR) whose activity is potentiated by interactions with the promoter-specific transcription factor Sp1. PMID:9307046

Bianchi, N; Rutigliano, C; Passadore, M; Tomassetti, M; Pippo, L; Mischiati, C; Feriotto, G; Gambari, R

1997-01-01

114

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

Microsoft Academic Search

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

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

2003-01-01

115

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

NASA Astrophysics Data System (ADS)

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

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

2012-03-01

116

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

PubMed Central

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

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

2013-01-01

117

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

PubMed

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

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

2013-01-01

118

Characterization of an Essential Orc2p-Associated Factor That Plays a Role in DNA Replication  

Microsoft Academic Search

TheSaccharomyces cerevisiaeOrc2 protein is a subunit of the origin recognition complex, ORC, which binds in a sequence-specific manner to yeast origins of DNA replication. With screens for orc2-1 synthetic lethal mutations and Orc2p two-hybrid interactors, a novel Orc2p-associated factor (Oaf1p) was identified.OAF1is essential,itsgeneproductislocalizedtothenucleus,andanoaf1temperature-sensitivemutantarrestsaslarge budded cells with a single nucleus. The mutantoaf1-2, isolated in the synthetic lethal screen, loses plasmids containing

CHRISTOPHER F. J. HARDY

1996-01-01

119

A hexamerin protein, AgSP-1, is associated with diapause in the boll weevil(1).  

PubMed

The objective of this research was to identify a reliable biochemical indicator for diapause (dormancy) in the boll weevil, Anthonomus grandis. Hemolymph polypeptides from reproductive and diapausing weevils were compared using denaturing sodium dodecyl sulpfate (SDS)-polyacrylamide gel electrophoresis (PAGE). A 77-kDa protein, which proved to be a hexamerin (AgSP-1), strongly correlated with morphological diapause characters in both male and female adult weevils. N-terminal sequence analysis identified the first 25 amino acids of the mature protein and was used to develop an antibody to AgSP-1. Anti-AgSP-1 reacted only with hemolymph from diapausing weevils of both sexes but not with hemolymph from reproductive weevils. Also, the yolk protein, vitellogenin (VG), inversely correlated with AgSP-1. When hemolymph VG was high, AgSP-1 was absent or barely perceptible.Juvenile hormone regulates VG synthesis in most insect species. Juvenile hormone is reported to stimulate reproductive maturation in the boll weevil (Physiological Entomology 22 (1997) 261) and to be absent during diapause (Physiological Entomology 22 (1997a) 269). Therefore, the juvenile hormone (JH) mimic, methoprene, was used to assess the role of JH activity in the boll weevil for terminating diapause, stimulating reproductive maturation and possibly influencing AgSP-1 titers. Application of methoprene was not effective in activating reproductive development. Hemolymph from methoprene-treated, females contained VG and AgSP-1 titers that were similar to acetone-treated and untreated control weevils.Using a genomic DNA library and 3' RACE, two clones were isolated that yielded the complete sequence of AgSP-1 as well as a portion of the 5' untranslated region. Northern blot analysis confirmed the presence of a 2.5 kB transcript for AgSP-1 in the fat body of diapausing weevils. AgSP-1 was also present in the fat body of reproductive weevils, but to a lesser extent. No sex-related differences in gene expression were observed; diapausing weevils of both sexes showed similar levels of AgSP-1 expression. An inverse correlation was observed between the VG transcript and AgSP-1 mRNA. VG was highly expressed in the fat body of reproductive females and only slightly expressed in tissue from diapausing females. Our data suggests that AgSP-1 is a diapause-specific protein in adult weevils and that JH, alone, is not effective in terminating diapause. PMID:12770051

Lewis, D K.; Spurgeon, D; Sappington, T W.; Keeley, L L.

2002-09-01

120

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

PubMed Central

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

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

2013-01-01

121

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.

122

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

123

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

124

[What factors play a role in a listener's feelings evoked by irony?: the effect of listeners' personality traits and relationship with the speaker].  

PubMed

This research investigated what factors play a role in a listener's feelings evoked by irony. In Experiment 1, participants imagined their best friend or an acquaintance as the speaker, and rated how they felt when apparent ironical utterances were made. The effects of the listener's empathy and conversational indirectness were examined. In Experiment 2, participants rated how they felt when apparent ironical utterances or literal utterances were made. The effects of the listeners' self-esteem and attitude toward humor were examined. The results showed that cognitions about joking relationships and the listener's attitude toward humor played an important role in the listener's feelings evoked by irony, whereas the listeners' self-esteem and their interpretation of conversational indirectness affected their perception of irony. Irony evoked positive feelings when the joke or the humor of irony was evaluated as positive politeness by the listener due to the listener's attitude toward humor or a joking relationship with the speaker. PMID:22117301

Akimoto, Yoritaka; Miyazawa, Shiho

2011-10-01

125

CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation.  

PubMed

Arterial thrombosis is an important complication of diabetes and cancer, being an important target for therapeutic intervention. Crataeva tapia bark lectin (CrataBL) has been previously shown to have hypoglycemiant effect and also to induce cancer cell apoptosis. It also showed inhibitory activity against Factor Xa (Kiapp=8.6 ?m). In the present study, we evaluated the anti-thrombotic properties of CrataBL in arterial thrombosis model. CrataBL prolongs the activated partial thromboplastin time on human and mouse plasma, and it impairs the heparin-induced potentiation of antithrombin III and heparin-induced platelet activation in the presence of low-dose ADP. It is likely that the dense track of positive charge on CrataBL surface competes with the heparin ability to bind to antithrombin III and to stimulate platelets. In the photochemically induced thrombosis model in mice, in the groups treated with 1.25, 5.0, or 10 mg/kg CrataBL, prior to the thrombus induction, the time of total artery occlusion was prolonged by 33.38%, 65%, and 66.11%, respectively, relative to the time of the control group. In contrast to heparin, the bleeding time in CrataBL-treated mice was no longer than in the control. In conclusion, CrataBL was effective in blocking coagulation and arterial thrombus formation, without increasing bleeding time. PMID:25153385

Salu, Bruno R; Ferreira, Rodrigo S; Brito, Marlon V; Ottaiano, Tatiana F; Cruz, José Walber M C; Silva, Mariana Cristina C; Correia, Maria Tereza S; Paiva, Patrícia M G; Maffei, Francisco Humberto A; Oliva, Maria Luiza Vilela

2014-09-01

126

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

127

Macrophage migration arrest due to a winning balance of Rac2/Sp1 repression over ?-catenin-induced PLD expression  

PubMed Central

Monocytes and neutrophils infiltrate into tissues during inflammation and stay for extended periods of time until the initial insult is resolved or sometimes remain even longer in the case of chronic inflammation. The mechanism as to why phagocytes become immobilized after the initial cell migration event is not understood completely. Here, we show that overexpression or hyperactivation of Rac2 decreases sustained chemotactic responses of macrophages to MCP-1/CCL2. The resulting leukocyte arrest is not caused by a diminished availability of the cytokine receptor CCR2 that remains intact during MCP-1 stimulation. We show a novel mechanism that links the Rac2-dependent arrest of chemotaxis to decreased expression of PLD2 through the transcription regulator Sp1. Prolonged Rac2 activity leads to nuclear overactivation of Sp1, which acts as a repressor for PLD2. Also, another signaling component plays a regulatory role: ?-catenin. Although early times of stimulation (?20 min) with MCP-1/CCL2 resulted in activation of ?-catenin with a positive effect on PLD2, after ?3 h of stimulation, the levels of ?-catenin were reduced and not able to prevent the negative effect of Rac2 on PLD2 activity. This is a novel molecular mechanism underlying immobilization of monocyte/macrophage migration that is important for the physiological maintenance of leukocytes at the site of inflammation. If this immobilization is prolonged enough, it could lead to chronic inflammation. PMID:23898047

Speranza, Francis J.; Mahankali, Madhu; Gomez-Cambronero, Julian

2013-01-01

128

The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-?-induced bone resorption lacunae on mouse calvariae  

Microsoft Academic Search

Tumor necrosis factor (TNF)-? exerts its biological function via TNF type 1 and type 2 receptors (TNFR1 and TNFR2). We have\\u000a previously reported that bone resorption induced by lipopolysaccharide (LPS) in TNFR2-deficient mice is accelerated compared\\u000a to that in wild-type (WT) mice. Although these results suggested that TNFR2 might have a protective role in bone resorption,\\u000a we could not exclude

Kenichi NaganoNeil; Neil Alles; Anower Hussain Mian; Asako Shimoda; Nobuyuki Morimoto; Yukihiko Tamura; Hitoyata Shimokawa; Kazunari Akiyoshi; Keiichi Ohya; Kazuhiro Aoki

129

Fortran vs. C++: Electrostatic Plasma PIC Simulation on the Intel Paragon & IBM SP1 \\Lambday  

E-print Network

Fortran vs. C++: Electrostatic Plasma PIC Simulation on the Intel Paragon & IBM SP1 \\Lambday be introduced by extreme heat, pressure or electric 1 #12; 2 Norton et al. discharges. The free electrons can

Bystroff, Chris

130

Immunohistochemical location of HPL, SP1 and ?-HCG in normal placentas of varying gestational age  

Microsoft Academic Search

Summary Sixty-four placentas at various gestational ages were examined by immunohistochemical stains for HPL, SP1 and ?-HCG according to a modified PAP method (Sternberger 1970). Syncytiotrophoblast cell layer was identified as the main site of synthesis. Extravillous immunohistochemical reactions for HPL and SP1 (but not for ?-HCG) were found in X-cells of the basal plate and in the intervillous trophoblast

T. Beck; G. Schweikhart; E. Stolz

1986-01-01

131

CRiSP1 Passage: Columbia River Salmon Passage Model and Data  

NSDL National Science Digital Library

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

132

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

133

CO Induces Nrf2-Dependent Heme Oxygenase-1 Transcription by Cooperating with Sp1 and c-Jun in Rat Brain Astrocytes.  

PubMed

Upregulation of heme oxygenase 1 (HO-1) by carbon monoxide (CO) delivered by CO-releasing molecules (CORMs) may be utilized as a therapeutic intervention for neurodegenerative diseases. This study was to delineate the two putative anti-oxidant response elements (AREs) in modulating HO-1 gene by participating with its promoter elements in rat brain astrocytes (RBA-1). CORM-2-induced HO-1 expression was mediated through superoxide, p38 mitogen-activated protein kinase(MAPK), extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), protein tyrosine kinase 2 (Pyk2), platelet-derived growth factor receptor (PDGFR), and phosphatidylinositol 3'-kinase (PI3K/Akt), revealed by the pharmacological inhibitors or knockdown of these signaling molecules. CORM-2-enhanced HO-1 promoter activity was inhibited by co-transfection with small interfering RNA (siRNA) of c-Jun, specificity protein 1 (Sp1), or nuclear factor-erythroid 2-related factor 2 (Nrf2). Immunoprecipitation assay showed that CORM-2 increased the association of nuclear Nrf2 with Sp1 and c-Jun. Furthermore, chromatin immunoprecipitation (ChIP) assay confirmed that Nrf2, Sp1, and c-Jun are associated with the proximal ARE binding site on HO-1 promoter, suggesting that Nrf2/Sp1/c-Jun cooperations are key transcription factors modulating HO-1 expression. Mechanistically, CORM-2-induced ARE promoter activity was reduced by the inhibitors of reactive oxygen species (ROS), p38 MAPK, Pyk2, MAPK/ERK kinases 1 and 2 (MEK1/2), PDGFR, and PI3K/Akt or the siRNAs of c-Jun, SP1, and Nrf2. These findings suggested that CORM-2 increases formation of c-Jun, Sp1, and Nrf2 complex and binding with ARE1 binding site, which is mediated through both ROS/p38 MAPK and Pyk2-dependent PDGFR/PI3K/Akt/Erk1/2 pathways, resulting in HO-1 expression in RBA-1 cells. PMID:25148934

Chi, Pei-Ling; Lin, Chih-Chung; Chen, Yu-Wen; Hsiao, Li-Der; Yang, Chuen-Mao

2014-08-23

134

A regulatory loop involving miR-22, Sp1, and c-Myc modulates CD147 expression in breast cancer invasion and metastasis.  

PubMed

Breast cancer is the most common cancer in women for which the metastatic process is still poorly understood. CD147 is upregulated in breast cancer and has been associated with tumor progression, but little is known about its regulatory mechanisms. In this study, we demonstrated that CD147 was overexpressed in breast cancer tissues and cell lines, and the high expression correlated with tumor invasion and metastasis. We also found that the transcription factors Sp1 and c-Myc could bind to the CD147 promoter and enhance its expression. The CD147 mRNA has a 748-bp 3'-untranslated region (UTR) with many miRNA target sites, suggesting possible regulation by miRNAs. We discovered that miR-22 repressed CD147 expression by directly targeting the CD147 3'UTR. We also determined that miR-22 could indirectly participate in CD147 modulation by downregulating Sp1 expression. miR-22 could form an autoregulatory loop with Sp1, which repressed miR-22 transcription by binding to the miR-22 promoter. Together with the c-Myc-mediated inhibition of miR-22 expression, our investigation identified a miR-22/Sp1/c-Myc network that regulates CD147 gene transcription. In addition, miR-22 overexpression suppressed breast cancer cell invasion, metastasis, and proliferation by targeting CD147 in vitro and in vivo. Furthermore, we found that miR-22 was significantly downregulated in breast cancer tissues and that its expression was inversely correlated with the tumor-node-metastasis stage and lymphatic metastasis in patients. Our study provides the first evidence that an miR-22/Sp1/c-Myc network regulates CD147 upregulation in breast cancer and that miR-22 represses breast cancer invasive and metastatic capacities. PMID:24906624

Kong, Ling-Min; Liao, Cheng-Gong; Zhang, Yang; Xu, Jing; Li, Yu; Huang, Wan; Zhang, Yi; Bian, Huijie; Chen, Zhi-Nan

2014-07-15

135

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

136

Association of the Collagen Type 1 (COL1A 1) Sp1 Binding Site Polymorphism to Femoral Neck Bone Mineral Density and Wrist Fracture in 1044 Elderly Swedish Women  

Microsoft Academic Search

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population

P. Gerdhem; H. Brändström; F. Stiger; K. Obrant; H. Melhus; Ö. Ljunggren; A. Kindmark; K. Åkesson

2004-01-01

137

Characterization of the human activator protein-2gamma (AP-2gamma) gene: control of expression by Sp1/Sp3 in breast tumour cells.  

PubMed Central

The activator protein-2 (AP-2) family of DNA-binding transcription factors are developmentally regulated and also play a role in human neoplasia. In particular, the AP-2gamma protein has been shown to be overexpressed in a high percentage of breast tumours. In the present study, we report the complete sequence determination of the human TFAP2C gene encoding the AP-2gamma transcription factor plus the mapping of the transcription start site used in breast tumour-derived cells. The 5'-end of the gene lies within a CpG island and transcription is initiated at a single site within a classical initiator motif. We have gone on to investigate why some breast tumour-derived cell lines readily express AP-2gamma, whereas others do not, and show that the proximal promoter (+191 to -312) is differentially active in the two cell phenotypes. DNase footprinting led to the identification of three Sp1/Sp3-binding sites within this region, two of which are absolutely required both for promoter function and cell-type-specific activity. By Western blotting a panel of expressing and non-expressing breast tumour lines we show that the latter have higher levels of Sp3. Furthermore, increasing Sp3 levels in AP-2gamma-expressing cells led to the repression of AP-2gamma promoter activity, particularly when Sp3 inhibitory function was maximized through sumoylation. We propose that differences in the level and activity of Sp3 between breast tumour lines can determine the expression level of their AP-2gamma gene. PMID:12733991

Hasleton, Mark D; Ibbitt, J Claire; Hurst, Helen C

2003-01-01

138

Polymorphism at the Sp 1 Binding Site in the Collagen Type I ? 1 Gene Does Not Predict Bone Mineral Density in Postmenopausal Women in Sweden  

Microsoft Academic Search

.   Polymorphisms at the binding site of the Sp 1 transcription factor of the collagen type I ?1 gene have recently been suggested\\u000a to be an important marker for low bone mineral density (BMD) and vertebral fracture in a population of predominantly postmenopausal\\u000a British women. We examined whether the unfavorable ``s'' allele was associated with low BMD in 64 patients

M. Lidén; B. Wilén; S. Ljunghall; H. Melhus

1998-01-01

139

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

PubMed

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

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

2008-11-01

140

The transcription factor PHR1 plays a key role in the regulation of sulfate shoot-to-root flux upon phosphate starvation in Arabidopsis  

PubMed Central

Background Sulfate and phosphate are both vital macronutrients required for plant growth and development. Despite evidence for interaction between sulfate and phosphate homeostasis, no transcriptional factor has yet been identified in higher plants that affects, at the gene expression and physiological levels, the response to both elements. This work was aimed at examining whether PHR1, a transcription factor previously shown to participate in the regulation of genes involved in phosphate homeostasis, also contributed to the regulation and activity of genes involved in sulfate inter-organ transport. Results Among the genes implicated in sulfate transport in Arabidopsis thaliana, SULTR1;3 and SULTR3;4 showed up-regulation of transcripts in plants grown under phosphate-deficient conditions. The promoter of SULTR1;3 contains a motif that is potentially recognizable by PHR1. Using the phr1 mutant, we showed that SULTR1;3 up-regulation following phosphate deficiency was dependent on PHR1. Furthermore, transcript up-regulation was found in phosphate-deficient shoots of the phr1 mutant for SULTR2;1 and SULTR3;4, indicating that PHR1 played both a positive and negative role on the expression of genes encoding sulfate transporters. Importantly, both phr1 and sultr1;3 mutants displayed a reduction in their sulfate shoot-to-root transfer capacity compared to wild-type plants under phosphate-deficient conditions. Conclusions This study reveals that PHR1 plays an important role in sulfate inter-organ transport, in particular on the regulation of the SULTR1;3 gene and its impact on shoot-to-root sulfate transport in phosphate-deficient plants. PHR1 thus contributes to the homeostasis of both sulfate and phosphate in plants under phosphate deficiency. Such a function is also conserved in Chlamydomonas reinhardtii via the PHR1 ortholog PSR1. PMID:21261953

2011-01-01

141

Macrophage migration inhibitory factor (MIF) plays a critical role in pathogenesis of ultraviolet-B (UVB) -induced nonmelanoma skin cancer (NMSC).  

PubMed

Mounting evidence suggests that macrophage migration inhibitory factor (MIF) may serve as an important link between chronic inflammation and cancer development. The proinflammatory and proangiogenic activities of MIF position it as a potentially important player in the development and progression of nonmelanoma skin cancer (NMSC). To assess the role of MIF in the development and progression of NMSC, we exposed MIF(-/-) BALB/c mice to acute and chronic ultraviolet B (UVB) irradiation. Our studies demonstrate that MIF(-/-) BALB/c mice have a significantly diminished acute inflammatory response to UVB exposure compared to wild-type mice, as measured by myeloperoxidase activity, dermal neutrophil infiltration, and edematous response. Relative to wild-type mice, MIF(-/-) mice also show significantly lower vascular endothelial growth factor (VEGF) concentrations in whole skin and significantly lower 8-oxo-dG adduct concentrations in epidermal DNA following UVB exposure. Furthermore, MIF(-/-) mice showed significant increases in p53 activity, epidermal thickness, and epidermal cell proliferation following acute UVB insult. In response to chronic UVB exposure, MIF(-/-) mice showed a 45% reduction in tumor incidence, significantly less angiogenesis, and delayed tumor progression when compared to their wild-type counterparts. These data indicate that MIF plays an important role in UVB-induced NMSC development and progression. PMID:18952710

Martin, Jason; Duncan, F Jason; Keiser, Tracy; Shin, Samuel; Kusewitt, Donna F; Oberyszyn, Tatiana; Satoskar, Abhay R; VanBuskirk, Anne M

2009-03-01

142

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

PubMed

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

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

2010-04-01

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

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

PubMed

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

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

2014-08-01

145

Identification of a novel enhancer that binds Sp1 and contributes to induction of cold-inducible RNA-binding protein (cirp) expression in mammalian cells  

PubMed Central

Background There are a growing number of reports on the sub-physiological temperature culturing of mammalian cells for increased recombinant protein yields. However, the effect varies and the reasons for the enhancement are not fully elucidated. Expression of cold-inducible RNA-binding protein (cirp, also called cirbp or hnRNP A18) is known to be induced in response to mild, but not severe, hypothermia in mammalian cells. To clarify the molecular mechanism underlying the induction and to exploit this to improve the productivity of recombinant proteins, we tried to identify the regulatory sequence(s) in the 5? flanking region of the mouse cirp gene. Results By transiently transfecting HEK293 cells with plasmids expressing chloramphenicol acetyltransferase as a reporter, we found that the cirp 5? flanking region octanucleotide 5?-TCCCCGCC-3? is a mild-cold responsive element (MCRE). When 3 copies of MCRE were placed upstream of the CMV promoter and used in transient transfection, reporter gene expression was increased 3- to 7-fold at 32°C relative to 37°C in various cell lines including HEK293, U-2 OS, NIH/3T3, BALB/3T3 and CHO-K1 cells. In stable transfectants, MCRE also enhanced the reporter gene expression at 32°C, although more copy numbers of MCRE were necessary. Sp1 transcription factor bound to MCRE in vitro. Immunohistochemistry and chromatin immunoprecipitation assays demonstrated that more Sp1, but not Sp3, was localized in the nucleus to bind to the cirp regulatory region containing MCRE at 32°C than 37°C. Overexpression of Sp1 protein increased the expression of endogenous Cirp as well as a reporter gene driven by the 5? flanking region of the cirp gene, and down-regulation of Sp1 had the opposite effect. Mutations within the MCRE sequence in the 5? flanking region abolished the effects of Sp1 on the reporter gene expression both at 37°C and 32°C. Conclusions Cold-induced, as well as constitutive, expression of cirp is dependent, at least partly, on MCRE and Sp1. The present novel enhancer permits conditional high-level gene expression at moderately low culture temperatures and could be utilized to increase the yield of recombinant proteins in mammalian cells. PMID:23046908

2012-01-01

146

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

147

Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶  

PubMed Central

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

2013-01-01

148

Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis.  

PubMed

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of TLRs mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. In this article, we show that activation of TLR2, TLR3, and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture in a mouse model, augmented cfB levels in the serum, peritoneal cavity, and major organs including the kidney and heart. Cecal ligation and puncture also led to the alternative pathway activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum alternative pathway via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 upregulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production, and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M; Wu, Xiaobo; Atkinson, John P; Chao, Wei

2013-12-01

149

Cell growth defect factor1/chaperone-like protein of POR1 plays a role in stabilization of light-dependent protochlorophyllide oxidoreductase in Nicotiana benthamiana and Arabidopsis.  

PubMed

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

2013-10-01

150

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

151

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

SciTech Connect

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

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

2006-06-23

152

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

153

Performance of NAS parallel application-benchmarks on IBM SP1  

Microsoft Academic Search

We present the performance of three application benchmarks (BT, LU, and SP) from the NAS Parallel Benchmark suite on the IBM scalable POWERparallel 1 (SP1) system. We present performance results on both Class A and Class B problem sets. We compare the performance of two communication protocols, MPL and MPL\\/p, and also present results on a cluster of workstations called

Vijay K. Naik

1994-01-01

154

Scalability study of parallel spatial direct numerical simulation code on IBM SP1 parallel supercomputer  

NASA Technical Reports Server (NTRS)

The implementation and the performance of a parallel spatial direct numerical simulation (PSDNS) code are reported for the IBM SP1 supercomputer. The spatially evolving disturbances that are associated with laminar-to-turbulent in three-dimensional boundary-layer flows are computed with the PS-DNS code. 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% 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% of theoretical peak performance). The actual performance of the PSDNS code on the SP1 is evaluated with a 'real world' simulation that consists of 1.7 million grid points. One time step of this simulation is calculated on eight nodes of the SP1 in the same time as required by a Cray Y/MP for the same simulation. The scalability information provides estimated computational costs that match the actual costs relative to changes in the number of grid points.

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

1994-01-01

155

Posttranslational, reversible O-glycosylation is stimulated by high glucose and mediates plasminogen activator inhibitor-1 gene expression and Sp1 transcriptional activity in glomerular mesangial cells.  

PubMed

Metabolic flux through the hexosamine biosynthetic pathway (HBP) is increased in the presence of high glucose (HG) and potentially stimulates the expression of genes associated with the development of diabetic nephropathy. A number of synthetic processes are coupled to the HBP, including enzymatic intracellular O-glycosylation (O-GlcNAcylation), the addition of single O-linked N-acetylglucosamine monosaccharides to serine or threonine residues. Despite much data linking flow through the HBP and gene expression, the exact contribution of O-GlcNAcylation to HG-stimulated gene expression remains unclear. In glomerular mesangial cells, HG-stimulated plasminogen activator inhibitor-1 (PAI-1) gene expression requires the HBP and the transcription factor, Sp1. In this study, the specific role of O-GlcNAcylation in HG-induced PAI-1 expression was tested by limiting this modification with a dominant-negative O-linked N-acetylglucosamine transferase, by overexpression of neutral beta-N-acetylglucosaminidase, and by knockdown of O-linked beta-N-acetylglucosamine transferase expression by RNA interference. Decreasing O-GlcNAcylation by these means inhibited the ability of HG to increase endogenous PAI-1 mRNA and protein levels, the activity of a PAI-1 promoter-luciferase reporter gene, and Sp1 transcriptional activation. Conversely, treatment with the beta-N-acetylglucosaminidase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate, in the presence of normal glucose increased Sp1 O-GlcNAcylation and PAI-1 mRNA and protein levels. These findings demonstrate for the first time that among the pathways served by the HBP, O-GlcNAcylation, is obligatory for HG-induced PAI-1 gene expression and Sp1 transcriptional activation in mesangial cells. PMID:16365142

Goldberg, Howard J; Whiteside, Catharine I; Hart, Gerald W; Fantus, I George

2006-01-01

156

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

PubMed

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

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

2014-08-01

157

Resistin promotes the expression of vascular endothelial growth factor in ovary carcinoma cells.  

PubMed

Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is associated with obesity, insulin resistance and inflammation. Recently, resistin has been postulated to play a role in angiogenesis. Here, we investigated the hypothesis that resistin regulates ovary carcinoma production of vascular endothelial growth factor (VEGF) and the angiogenic processes. We found that in human ovarian epithelial carcinoma cells (HO-8910), resistin (10-150 ng/mL) enhanced both VEGF protein and mRNA expression in a time- and concentration-dependent manner, as well as promoter activity. Furthermore, resistin enhanced DNA-binding activity of Sp1 with VEGF promoter in a PI3K/Akt-dependent manner. PI3K/Akt activated by resistin led to increasing interaction with Sp1, triggering a progressive phosphorylation of Sp1 on Thr453 and Thr739, resulting in the upregulation of VEGF expression. In an in vitro angiogenesis system for endothelial cells (EA.hy926) co-cultured with HO-8910 cells, we observed that the addition of resistin stimulated endothelial cell tube formation, which could be abolished by VEGF neutralizing antibody. Our findings suggest that the PI3K/Akt-Sp1 pathway is involved in resistin-induced VEGF expression in HO-8910 cells and indicates that antiangiogenesis therapy may be beneficial treatment against ovarian epithelial carcinoma, especially in obese patients. PMID:23652833

Pang, Li; Zhang, Yi; Yu, Yu; Zhang, Shulan

2013-01-01

158

The Extracytoplasmic Function Sigma Factor SigV Plays a Key Role in the Original Model of Lysozyme Resistance and Virulence of Enterococcus faecalis  

PubMed Central

Background Enterococcus faecalis is one of the leading agents of nosocomial infections. To cause diseases, pathogens or opportunistic bacteria have to adapt and survive to the defense systems encountered in the host. One of the most important compounds of the host innate defense response against invading microorganisms is lysozyme. It is found in a wide variety of body fluids, as well as in cells of the innate immune system. Lysozyme could act either as a muramidase and/or as a cationic antimicrobial peptide. Like Staphylococcus aureus, E. faecalis is one of the few bacteria that are completely lysozyme resistant. Results This study revealed that oatA (O-acetyl transferase) and dlt (D-Alanylation of lipoteicoic acids) genes contribute only partly to the lysozyme resistance of E. faecalis and that a specific transcriptional regulator, the extracytoplasmic function SigV sigma factor plays a key role in this event. Indeed, the sigV single mutant is as sensitive as the oatA/dltA double mutant, and the sigV/oatA/dltA triple mutant displays the highest level of lysozyme sensitivity suggesting synergistic effects of these genes. In S. aureus, mutation of both oatA and dlt genes abolishes completely the lysozyme resistance, whereas this is not the case in E. faecalis. Interestingly SigV does not control neither oatA nor dlt genes. Moreover, the sigV mutants clearly showed a reduced capacity to colonize host tissues, as they are significantly less recovered than the parental JH2-2 strain from organs of mice subjected to intravenous or urinary tract infections. Conclusions This work led to the discovery of an original model of lysozyme resistance mechanism which is obviously more complex than those described for other Gram positive pathogens. Moreover, our data provide evidences for a direct link between lysozyme resistance and virulence of E. faecalis. PMID:20300180

Le Jeune, André; Torelli, Riccardo; Sanguinetti, Maurizio; Giard, Jean-Christophe; Hartke, Axel; Auffray, Yanick; Benachour, Abdellah

2010-01-01

159

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

160

Transcriptional regulation of the Alström syndrome gene ALMS1 by members of the RFX family and Sp1  

PubMed Central

Mutations in the human gene ALMS1 cause Alström syndrome, a disorder characterised by neurosensory degeneration, metabolic defects and cardiomyopathy. ALMS1 encodes a centrosomal protein implicated in the assembly and maintenance of primary cilia. Expression of ALMS1 varies between tissues and recent data suggest that its transcription is modulated during adipogenesis and growth arrest. However the ALMS1 promoter has not been defined. This study focused on identifying and characterising the ALMS1 proximal promoter, initially by using 5' RACE to map transcription start sites. Luciferase reporter assay and EMSA data strongly suggest that ALMS1 transcription is regulated by the ubiquitous factor Sp1. In addition, reporter assay, EMSA, chromatin immunoprecipitation and RNA interference data indicate that ALMS1 transcription is regulated by regulatory factor X (RFX) proteins. These transcription factors are cell-type restricted in their expression profile and known to regulate genes of the ciliogenic pathway. We show binding of RFX proteins to an evolutionarily conserved X-box in the ALMS1 proximal promoter and present evidence that these proteins are responsible for ALMS1 transcription during growth arrest induced by low serum conditions. In summary, this work provides the first data on transcription factors regulating general and context-specific transcription of the disease-associated gene ALMS1. PMID:20381594

Purvis, Tracey L.; Hearn, Tom; Spalluto, Cosma; Knorz, Victoria J.; Hanley, Karen Piper; Sanchez-Elsner, Tilman; Hanley, Neil A.; Wilson, David I.

2010-01-01

161

HIF-1? depletion results in SP1-mediated cell cycle disruption and alters the cellular response to chemotherapeutic drugs.  

PubMed

Hypoxia inducible factor (HIF) is the major transcription factor involved in the regulation of the cellular response to hypoxia, or low oxygen tensions. Even though HIF-1 function is mostly studied following hypoxic stress, well oxygenated areas of several diseased tissues have detectable levels of this transcription factor. Therefore, it is surprising how little is known about the function of HIF in normoxia. This study seeks to fill this gap. Using transient HIF-1? knockdown, as well as, stable cell lines generated using short hairpin RNAs (shRNA), we have further characterized the role of HIF-1? in normoxia. Our data reveals that knockdown of HIF-1? results in a significant increase in cells in the G1 phase of the cell cycle. We find that HIF-1? depletion increases the protein and mRNA of both p21 and p27. p21 is induced via, at least in part, p53-independent but SP1-dependent mechanisms. Interestingly, HIF-1? knockdown also alters the cellular response to chemotherapeutic agents. These data have important implications in not only for the further understanding of HIF-1?, a major transcription factor, but also for the use of HIF-targeted and combination therapies in cancer treatment. PMID:21412054

Culver, Carolyn; Melvin, Andrew; Mudie, Sharon; Rocha, Sonia

2011-04-15

162

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

163

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

164

Dephosphorylation of Sp1 at Ser-59 by protein phosphatase 2A (PP2A) is required for induction of CYP1A1 transcription after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin or omeprazole.  

PubMed

The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole (OP). Activated AhR can induce CYP1A1 transcription by binding to the xenobiotic responsive element (XRE). However, the mechanism of activation of the CYP1A1 promoter region is poorly understood. Previous reports showed that Sp1 could bind to a GC-rich region near the CYP1A1 promoter. This study sought to clarify the function of Sp1 in CYP1A1 transcription. Phosphorylation of Sp1 at Ser-59 (pSer-59) was previously reported to be closely related to transcriptional regulation. We used a site-specific phospho-antibody to show that treatment with TCDD or OP drastically reduced the level of pSer-59 in Sp1 from HepG2 cells. This reduction was too much, we hypothesized that the reduced phosphorylation level resulted from activation of phosphatase activity. Given that pSer-59 is dephosphorylated by PP2A, we examined the effect of a PP2A inhibitor, okadaic acid (OA), on pSer-59 and transcription of CYP1A1. The results showed that OA blocked dephosphorylation of Ser-59 and drastically inhibited transcription of CYP1A1. Similar results were obtained after knockdown of PP2A. Treatment with OA had no effect on the expression of AhR, its nuclear translocation, or its ability to bind to the XRE. Furthermore, dephosphorylation of Sp1 at Ser-59 was not affected by knockdown of AhR. These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription. This signaling pathway was independent of the AhR-mediated pathway. PMID:24382322

Shimoyama, Shuji; Kasai, Shuya; Kahn-Perlès, Brigitte; Kikuchi, Hideaki

2014-02-01

165

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

166

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

PubMed

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

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

2013-05-01

167

Complete genome sequence of Kosakonia sacchari type strain SP1T  

PubMed Central

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 SP1T (=CGMCC1.12102T=LMG 26783T) 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 SP1T 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

2014-01-01

168

Defect mapping accuracy of KLA-Tencor Surfscan 6200, 6400, and SP1  

Microsoft Academic Search

KLA-Tencor Surfscan 6200, 6400, and SP1, are most widely used for product qualification, monitoring of manufacturing tools, and defect root cause analyses on unpatterned semiconductor wafers. In addition to the defect number and size, these instruments provides x\\/y coordinates of surface defects (defect mapping). These defect maps are needed for map-to-map comparison to determine adders from a particular process and

Po-Fu Huang; Yuri S. Uritsky; C. R. Brundle

2001-01-01

169

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

SciTech Connect

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

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

2011-04-15

170

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

171

Des Regles et du Jeu. Complementarite des facteurs genetiques et epigenetiques dans le developpement cerebral (Of Rules and of Play. The Complementary Nature of Genetic and Epigenetic Factors in Brain Development).  

ERIC Educational Resources Information Center

Discusses the importance of genetic and epigenetic factors in the development of the nervous system and the performances it conditions. From the perspective of rules, play, and relaxation of rules, learning and education are not considered as a kind of conditioning but as providing a content in which the cumulative expression of potential can take…

Lambert, Jean-Francois

1997-01-01

172

Retinoic Acid (RA) Regulates 17?-Hydroxysteroid Dehydrogenase Type 2 Expression in Endometrium: Interaction of RA Receptors with Specificity Protein (SP) 1/SP3 for Estradiol Metabolism  

PubMed Central

Context: The enzyme 17?-hydroxysteroid dehydrogenase type 2 (HSD17B2) exerts a local antiestrogenic effect by metabolizing biologically active estradiol to inactive estrone in endometrial epithelial cells. Retinoic acid (RA) induces HSD17B2 expression, but the underlying mechanism is not known. Objective: Our objective was to elucidate the molecular mechanisms responsible for HSD17B2 expression in human endometrial cells. Method: Human endometrial Ishikawa and RL95–2 cell lines were cultured in the presence or absence of RA to analyze endogenous HSD17B2 expression, transcription factor complex formation, and promoter activity. Results: RA induced HSD17B2 mRNA levels in a dose- and time-dependent manner in endometrial cells. The RA antagonist ANG11273 abolished RA-induced HSD17B2 expression. Small interfering RNA ablation of RA receptor (RAR)? or retinoid X receptor (RXR)? completely blocked RA-induced HSD17B2 gene expression. Analysis of serial deletion and site-directed mutants of the HSD17B2 promoter fused to a reporter gene indicated that RA induction requires a cis-regulatory sequence that binds the specificity protein (SP) class of transcription factors. Chromatin-immunoprecipitation-PCR and gel-shift assays showed that RAR?/RXR? and SP1/SP3 interact with this HSD17B2 promoter sequence. Small interfering RNA ablation of SP1 and SP3 expression markedly decreased HSD17B2 basal expression and blocked RA-induced expression. Finally, immunoprecipitationimmunoblotting demonstrated RA-induced interactions between RAR?/RXR? and SP1/SP3 in intact endometrial cells. Conclusions: In endometrial epithelial cells, RA stimulates formation of a multimeric complex comprised of RAR?/RXR? tethered to transcription factors SP1 and SP3 on the HSD17B2 promoter. Assembly of this transcriptional complex is necessary for RA induction of HSD17B2 expression and may be an important mechanism for local estradiol inactivation in the endometrium. PMID:18270252

Cheng, You-Hong; Yin, Ping; Xue, Qing; Yilmaz, Bertan; Dawson, Marcia I.; Bulun, Serdar E.

2008-01-01

173

Multiple recombining loci encode MaSp1, the primary constituent of dragline silk, in widow spiders (Latrodectus: Theridiidae).  

PubMed

Spiders spin a functionally diverse array of silk fibers, each composed of one or more unique proteins. Most of these proteins, in turn, are encoded by members of a single gene family thought to have arisen through duplication and divergence of an ancestral silk gene. Because of its remarkable mechanical properties, orb weaver dragline silk, a composite of 2 proteins (MaSp1 and MaSp2), is the best studied. Here, we demonstrate that multiple loci encode MaSp1 in widow spiders (Latrodectus). Because these copies may be the result of more recent duplication events than those leading to the currently recognized silk gene paralogs, they offer insight into the early evolutionary fate of silk gene duplicates. In addition to 3 presumed functional MaSp1 loci in Latrodectus hesperus (Western black widow) and Latrodectus geometricus (brown widow) genomes, we find a MaSp1 pseudogene in L. hesperus, demonstrating the potential for unrecognized extinction of silk gene paralogs. We also document recombination events among L. hesperus MaSp1 loci and between Latrodectus MaSp1 loci and MaSp2. This result supports the hypothesis that concerted evolution occurs not only within an individual silk gene but also among silk gene paralogs. One of the L. geometricus MaSp1 copies encodes a protein that has diverged in amino acid composition and potentially converged on the secondary structure of MaSp2. Based on the presence of multiple MaSp1 loci and the phylogenetic distribution of MaSp1 versus MaSp2, we propose that MaSp2 is derived from an ancestral MaSp1 duplicate. Finally, divergence has occurred in the upstream flanking sequences of the L. hesperus MaSp1 loci, the region most likely to contain regulatory motifs, providing ample opportunity for differential expression. However, the benefits associated with increased protein production may be the primary mechanism maintaining multiple functional MaSp1 copies in widow genomes. PMID:18048404

Ayoub, Nadia A; Hayashi, Cheryl Y

2008-02-01

174

Why do adult dogs 'play'?  

PubMed

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

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

2015-01-01

175

The transcription factor PHR1 plays a key role in the regulation of sulfate shoot-to-root flux upon phosphate starvation in Arabidopsis  

Microsoft Academic Search

BACKGROUND: Sulfate and phosphate are both vital macronutrients required for plant growth and development. Despite evidence for interaction between sulfate and phosphate homeostasis, no transcriptional factor has yet been identified in higher plants that affects, at the gene expression and physiological levels, the response to both elements. This work was aimed at examining whether PHR1, a transcription factor previously shown

Hatem Rouached; David Secco; Bulak Arpat; Yves Poirier

2011-01-01

176

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

177

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

178

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

179

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

PubMed

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

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

2015-01-01

180

Play through the Profiles: Profiles through Play.  

ERIC Educational Resources Information Center

Recognizing the perceived conflict between a belief in the value of play to early childhood development and a commitment to an early childhood pedagogical framework, this book attempts to validate play as a fundamental component of learning and an avenue through which learning outcomes can be identified and confirmed. The book is designed to…

Fleer, Marilyn, Ed.

181

COL1A1 Sp1 variation and bone phenotypes in an Italian population  

PubMed Central

Summary Background Osteoporosis is the most common metabolic bone disorder of the elderly, affecting the normal bone turnover with an increased bone resorption and subsequent higher risk of fragility fractures. Collagen type 1 is the most represented protein in bone matrix. A genetic variation (Sp1) in intron 1 of COL1A1 gene has been associated to modulation of expression of the alpha 1 chain of collagen type 1 and it is considered a candidate polymorphism for predisposition to osteoporosis status and fragility fractures. Association studies, in ethnically different populations, are needed to strongly confirm the role of this polymorphism in bone metabolism. Materials and methods We enrolled over 2,000 Italian individuals and studied their bone mineral density (BMD) and fractures in relation to age, sex and body mass index (BMI). Moreover, we analyzed the distribution of Sp1 polymorphism in these individuals and associated it to normal bone status, osteopenic condition or osteoporosis diagnosis, BMD and the presence of low-trauma fractures. Results The most rare ss genotype showed a trend for osteoporosis diagnosis with respect to both normal and osteopenic status. The same genotype resulted to be associated to lower values of BMD both at spine and femur sites. No association was found with fractures. Discussion In conclusion the presence of the homozygote ss genotype seemed to predispose to osteoporosis diagnosis and to be more frequent in subjects with lower spine and femur BMD values. PMID:24133532

Marini, Francesca; Parri, Simone; Masi, Laura; Ciuffi, Simone; Guazzini, Andrea; Fabbri, Sergio; Luzi, Ettore; Cianferotti, Luisella; Brandi, Maria Luisa

2013-01-01

182

Playfulness and creativity.  

PubMed

Playful play is undoubtedly fun. Even so, many people think, incorrectly, that as they get older, they are no longer capable of such frivolous activity. They should heed George Bernard Shaw's advice: "We don't stop playing because we grow old, we grow old because we stop playing." The motivation to be playful comes from within. No external bribes are needed. In fact attempting to encourage such activity with food or money is likely to be counterproductive. PMID:25562292

Bateson, Patrick

2015-01-01

183

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

NASA Technical Reports Server (NTRS)

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

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

1995-01-01

184

Estrogen receptor beta binds Sp1 and recruits a corepressor complex to the estrogen receptor alpha gene promoter.  

PubMed

Human estrogen receptors alpha and beta are crucially involved in the regulation of mammary growth and development. Normal breast tissues display a relative higher expression of ER beta than ER alpha, which drastically changes during breast tumorogenesis. Thus, it is reasonable to suggest that a dysregulation of the two estrogen receptor subtypes may induce breast cancer development. However, the molecular mechanisms underlying the potential opposing roles played by the two estrogen receptors on tumor cell growth remain to be elucidated. In the present study, we have demonstrated that ER beta overexpression in breast cancer cells decreases cell proliferation and down-regulates ER alpha mRNA and protein content, along with a concomitant repression of estrogen-regulated genes. Transient transfection experiments, using a vector containing the human ER alpha promoter region, showed that elevated levels of ER beta down-regulated basal ER alpha promoter activity. Furthermore, site-directed mutagenesis and deletion analysis revealed that the proximal GC-rich motifs at -223 and -214 are critical for the ER beta-induced ER alpha down-regulation in breast cancer cells. This occurred through ER beta-Sp1 protein-protein interactions within the ER alpha promoter region and the recruitment of a corepressor complex containing the nuclear receptor corepressor NCoR, accompanied by hypoacetylation of histone H4 and displacement of RNA-polymerase II. Silencing of NCoR gene expression by RNA interference reversed the down-regulatory effects of ER beta on ER alpha gene expression and cell proliferation. Our results provide evidence for a novel mechanism by which overexpression of ER beta through NCoR is able to down regulate ER alpha gene expression, thus blocking ER alpha's driving role on breast cancer cell growth. PMID:22622808

Bartella, V; Rizza, P; Barone, I; Zito, D; Giordano, F; Giordano, C; Catalano, S; Mauro, L; Sisci, D; Panno, M L; Fuqua, S A W; Andò, S

2012-07-01

185

The tumor suppressor gene KCTD11REN is regulated by Sp1 and methylation and its expression is reduced in tumors.  

PubMed

A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 (HIC1) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11REN (KCTD11). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells. PMID:20591193

Mancarelli, M Michela; Zazzeroni, Francesca; Ciccocioppo, Lucia; Capece, Daria; Po, Agnese; Murgo, Simona; Di Camillo, Raffaello; Rinaldi, Christian; Ferretti, Elisabetta; Gulino, Alberto; Alesse, Edoardo

2010-01-01

186

The tumor suppressor gene KCTD11REN is regulated by Sp1 and methylation and its expression is reduced in tumors  

PubMed Central

A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 (HIC1) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11REN (KCTD11). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells. PMID:20591193

2010-01-01

187

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

Microsoft Academic Search

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

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

2009-01-01

188

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

PubMed Central

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

Libreros, Stephania; Garcia-Areas, Ramon

2014-01-01

189

Identification of the Cytoplasmic Regions of Fibroblast Growth Factor (FGF) Receptor 1 Which Play Important Roles in Induction of Neurite Outgrowth in PC12 Cells by FGF1  

Microsoft Academic Search

Fibroblast growth factor 1 (FGF-1) induces neurite outgrowth in PC12 cells. Recently, we have shown that the FGF receptor 1 (FGFR-1) is much more potent than FGFR-3 in induction of neurite outgrowth. To identify the cytoplasmic regions of FGFR-1 that are responsible for the induction of neurite outgrowth in PC12 cells, we took advantage of this difference and prepared receptor

HSIEN-YI LIN; JINGSONG XU; IRENE ISCHENKO; DAVID M. ORNITZ; SIMON HALEGOUA; MICHAEL J. HAYMAN

1998-01-01

190

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

PubMed

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

Libreros, Stephania; Garcia-Areas, Ramon; Iragavarapu-Charyulu, Vijaya

2013-12-01

191

Increased Growth Factors Play a Role in Wound Healing Promoted by Noninvasive Oxygen-Ozone Therapy in Diabetic Patients with Foot Ulcers  

PubMed Central

Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-? (TGF-?), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%, P < 0.05). The wound size reduction was significantly more in ozone group than in control group (P < 0.001). After treatment, the expressions of VEGF, TGF-?, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-?, and PDGF at early stage of the treatment. (Clinical trial registry number is ChiCTR-TRC-14004415). PMID:25089169

Zhang, Jing; Guan, Meiping; Xie, Cuihua; Luo, Xiangrong; Zhang, Qian; Xue, Yaoming

2014-01-01

192

Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers.  

PubMed

Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-? (TGF-?), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%, P < 0.05). The wound size reduction was significantly more in ozone group than in control group (P < 0.001). After treatment, the expressions of VEGF, TGF-?, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-?, and PDGF at early stage of the treatment. (Clinical trial registry number is ChiCTR-TRC-14004415). PMID:25089169

Zhang, Jing; Guan, Meiping; Xie, Cuihua; Luo, Xiangrong; Zhang, Qian; Xue, Yaoming

2014-01-01

193

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

PubMed Central

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

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

2014-01-01

194

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

Microsoft Academic Search

Background  Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess\\u000a different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics\\u000a in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation.\\u000a \\u000a \\u000a \\u000a \\u000a Results  A microarray experiment was conducted using

Daofeng Li; Yunqin Zhang; Xiaona Hu; Xiaoye Shen; Lei Ma; Zhen Su; Tao Wang; Jiangli Dong

2011-01-01

195

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

PubMed

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

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

2014-09-15

196

Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells  

PubMed Central

The major structural elements of retroviruses are contained in a single polyprotein, Gag, which in human immunodeficiency virus type 1 (HIV-1) comprises the MA, CA, spacer peptide 1 (SP1), NC, SP2, and p6 polypeptides. In the immature HIV-1 virion, the domains of Gag are arranged radially with the N-terminal MA domain at the membrane and C-terminal NC-SP2-p6 region nearest to the center. Here, we report the three-dimensional structures of individual immature HIV-1 virions, as obtained by electron cryotomography. The concentric shells of the Gag polyprotein are clearly visible, and radial projections of the different Gag layers reveal patches of hexagonal order within the CA and SP1 shells. Averaging well-ordered unit cells leads to a model in which each CA hexamer is stabilized by a bundle of six SP1 helices. This model suggests why the SP1 spacer is essential for assembly of the Gag lattice and how cleavage between SP1 and CA acts as a structural switch controlling maturation. PMID:17396149

Wright, Elizabeth R; Schooler, Jordan B; Ding, H Jane; Kieffer, Collin; Fillmore, Christopher; Sundquist, Wesley I; Jensen, Grant J

2007-01-01

197

Play the Electrocardiogram Game  

MedlinePLUS

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

198

Play the Tuberculosis Game  

MedlinePLUS

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

199

Play the MRI Game  

MedlinePLUS

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

200

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

201

NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells  

PubMed Central

The phenotype of NFATc2?/? c3?/? (double knockout [DKO]) mice implies a disturbed regulation of T cell responses, evidenced by massive lymphadenopathy, splenomegaly, and autoaggressive phenomena. The population of CD4+ CD25+ T cells from DKO mice lacks regulatory capacity, except a small subpopulation that highly expresses glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR) and CD25. However, neither wild-type nor DKO CD4+ CD25+ regulatory T cells (T reg cells) are able to suppress proliferation of DKO CD4+ CD25? T helper cells. Therefore, combined NFATc2/c3 deficiency is compatible with the development of CD4+ CD25+ T reg cells but renders conventional CD4+ T cells unresponsive to suppression, underlining the importance of NFAT proteins for sustaining T cell homeostasis. PMID:15657288

Bopp, Tobias; Palmetshofer, Alois; Serfling, Edgar; Heib, Valeska; Schmitt, Steffen; Richter, Christoph; Klein, Matthias; Schild, Hansjörg; Schmitt, Edgar; Stassen, Michael

2005-01-01

202

The Excellence of Play.  

ERIC Educational Resources Information Center

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

Moyles, Janet R., Ed.

203

Play the Mosquito Game  

MedlinePLUS

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

204

Dramatic Play and Print.  

ERIC Educational Resources Information Center

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

Einarsdottir, Johanna

1996-01-01

205

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

206

Playful Teaching Practices  

ERIC Educational Resources Information Center

In physical education, playful teaching practices are essential to relationship building and creating "connections" for successful group dynamics. Perhaps most importantly, playful teachers develop positive attitudes in their students and help students understand that learning can be fun and joyful. Playful teaching practices also greatly enhance…

Michaelis, Bill

2005-01-01

207

Vygotsky on play: child's play or more  

E-print Network

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

Wagner, Carol Anne

2000-01-01

208

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

PubMed Central

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

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

2011-01-01

209

A conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase plays a key role in its substrate specificity.  

PubMed

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

Moore, Claire E; Regufe da Mota, Sergio; Mikolajek, Halina; Proud, Christopher G

2014-06-01

210

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

PubMed Central

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

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

2014-01-01

211

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.

212

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

213

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

PubMed

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

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

2009-03-01

214

Repression of the Luteinizing Hormone Receptor Gene Promoter by Cross Talk among EAR3\\/COUP-TFI, Sp1\\/Sp3, and TFIIB  

Microsoft Academic Search

Transcription of luteinizing hormone receptor (LHR) gene is activated by Sp1\\/Sp3 at two Sp1 sites and is repressed by nuclear orphan receptors EAR2 and EAR3 through a direct-repeat (DR) motif. To elucidate the mechanism of the orphan receptor-mediated gene repression, we explored the functional connection between the orphan receptors and Sp1\\/Sp3 complex, and its impact on the basal transcription machinery.

Ying Zhang; Maria L. Dufau

2003-01-01

215

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

PubMed Central

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

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

2013-01-01

216

Intergenerational learning through play  

Microsoft Academic Search

Play is universal. No matter who you are or where you live, play is a way to learn about yourself and the world around you.\\u000a Shared play experiences are a good way to build mutually beneficial relationships among younger and older generations, and\\u000a these interactions contribute to cognitive growth, improved social skills, physical development and emotional well-being.\\u000a This article outlines

Lindsay Davis; Elizabeth Larkin; Stephen B. Graves

2002-01-01

217

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

218

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

219

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

220

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

221

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

222

Family Play Therapy.  

ERIC Educational Resources Information Center

This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

Ariel, Shlomo

223

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

224

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

225

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

226

A Single-Base Substitution in the Proximal Sp1 Site of the Human Low Density Lipoprotein Receptor Promoter as a Cause of Heterozygous Familial Hypercholesterolemia  

Microsoft Academic Search

We have identified a Finnish family with a typical phenotype of heterozygous familial hypercholesterolemia (FH) due to a single-base substitution in the proximal Sp1 binding site of the low density lipoprotein (LDL) receptor gene promoter. The mutation, a C --> T substitution at nucleotide -43, cosegregated with the FH phenotype in six available family members and abolished binding of Sp1

Ulla-Maija Koivisto; Jorma J. Palvimo; Olli A. Janne; Kimmo Kontula

1994-01-01

227

Down-regulation of hTERT expression plays an important role in 15-deoxy-Delta12,14-prostaglandin J2-induced apoptosis in cancer cells.  

PubMed

The cyclopentenone prostaglandin 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) has been shown to possess antineoplastic activity in human cancers of various origins. However, the mechanism of the antineoplastic activity of 15d-PGJ2 remains to be completely elucidated. It has been reported that inhibiting the expression of human telomerase reverse transcriptase (hTERT), a major determinant of telomerase activity, induces rapid apoptosis in cancer cells. In this study, we investigated the effect of 15d-PGJ2 on hTERT expression. Treatment with 30 microM 15d-PGJ2 for 72 h induced apoptosis in the colon cancer cells LS180. 15d-PGJ2 treatment decreased hTERT protein expression in a dose-dependent manner. Down-regulation of hTERT expression by hTERT-specific small inhibitory RNA induced apoptosis. These results indicate that the down-regulation of hTERT expression by 15d-PGJ2 plays an important role in its proapoptotic properties. Since 15d-PGJ2 reduced hTERT mRNA expression, we examined the effect of 15d-PGJ2 on the DNA-binding activity of c-Myc, specificity protein 1 (Sp1) and estrogen receptor (ER) to the hTERT gene promoter using an electrophoretic mobility shift assay. 15d-PGJ2 attenuated the DNA-binding of all three transcriptional factors. Further, we observed that 15d-PGJ2 inhibited the DNA binding of these factors by different mechanisms; suppressed c-Myc mRNA expression, enhanced Sp1 protein degradation via the ubiquitin-proteasome pathway and inhibited ERbeta phosphorylation at serine residues. We conclude that hTERT down-regulation by 15d-PGJ2 plays an important role in its proapoptotic properties. Furthermore, 15d-PGJ2 inhibits the transcriptional activity of c-Myc, Sp1 and ER by three different mechanisms and results in the transcriptional repression of the hTERT gene. PMID:19360348

Moriai, Mikako; Tsuji, Naoki; Kobayashi, Daisuke; Kuribayashi, Kageaki; Watanabe, Naoki

2009-05-01

228

Romantic / classical Science play  

E-print Network

Romantic / classical Science play Space/time [Brechtian theater] Epic theater Didactic Alienation/modernity Sex Time dilation and length contraction Historical Galileo/fictional Galileo (interpretation Shakespeare Brecht Einstein Stoppard Films Pictures Music Graphs #12;

229

Fair play in contests  

Microsoft Academic Search

The aim of this paper is to incorporate fair play norms into the analysis of contests where players have the ability to cheat\\u000a in order to improve their chances of winning. We propose a utility function integrating fair play norms and apply it to a\\u000a stylized model of rank-order tournament with cheating. We study how the set of equilibria is

Nicolas Eber

2011-01-01

230

An Sp1 Response Element in the Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50 Promoter Mediates Lytic Cycle Induction by Butyrate  

PubMed Central

Kaposi's sarcoma-associated herpesvirus (KSHV) can be driven into the lytic cycle in vitro by phorbol esters and sodium butyrate. This report begins to analyze the process by which butyrate activates the promoter of KSHV open reading frame 50 (ORF50), the key viral regulator of the KSHV latency to lytic cycle switch. A short fragment of the promoter, 134 nucleotides upstream of the translational start of ORF50, retained basal uninduced activity and conferred maximal responsiveness to sodium butyrate. The butyrate response element was mapped to a consensus Sp1-binding site. By means of electrophoretic mobility shift assays, both Sp1 and Sp3 were shown to form complexes in vitro with the ORF50 promoter at the Sp1 site. Butyrate induced the formation of a group of novel complexes, including several Sp3-containing complexes, one Sp1-containing complex, and several other complexes that were not identified with antibodies to Sp1 or Sp3. Formation of all butyrate-induced DNA-protein complexes was mediated by the consensus Sp1 site. In insect and mammalian cell lines, Sp1 significantly activated the ORF50 promoter linked to luciferase. Chromatin immunoprecipitation experiments in a PEL cell line showed that butyrate induced Sp1, CBP, and p300 binding to the ORF50 promoter in vivo in an on-off manner. The results suggest that induction of the KSHV lytic cycle by butyrate is mediated through interactions at the Sp1/Sp3 site located 103 to 112 nucleotides upstream of the translational initiation of ORF50 presumably by enhancing the binding of Sp1 to this site. PMID:15650166

Ye, Jianjiang; Shedd, Duane; Miller, George

2005-01-01

231

Krüppel-like Factor 4 activates HBG gene expression in primary erythroid cells  

PubMed Central

Summary The SP1/Krüppel-like Factor (SP1/KLF) family of transcription factors plays a role in diverse cellular processes, including proliferation, differentiation and control of gene transcription. The discovery of KLF1 (EKLF), a key regulator of HBB (?-globin) gene expression, expanded our understanding of the role of KLFs in erythropoiesis. In this study, we investigated a mechanism of HBG (?-globin) regulation by KLF4. siRNA-mediated gene silencing and enforced expression of KLF4 in K562 cells substantiated the ability of KLF4 to positively regulate endogenous HBG gene transcription. The physiological significance of this finding was confirmed in primary erythroid cells, where KLF4 knockdown at day 11 significantly attenuated HBG mRNA levels and enforced expression at day 28 stimulated the silenced HBG genes. In vitro binding characterization using the ?-CACCC and ?-CACCC probes demonstrated KLF4 preferentially binds the endogenous ?-CACCC, while CREB binding protein (CREBBP) binding was not selective. Co-immunoprecipitation studies confirmed protein-protein interaction between KLF4 and CREBBP. Furthermore, sequential chromatin immunoprecipitation assays showed co-localization of both factors in the ?-CACCC region. Subsequent luciferase reporter studies demonstrated that KLF4 trans-activated HBG promoter activity and that CREBBP enforced expression resulted in gene repression. Our data supports a model of antagonistic interaction of KLF4/CREBBP trans-factors in HBG regulation. PMID:21539536

Kalra, Inderdeep S.; Alam, Md M.; Choudhary, Pankaj K.; Pace, Betty S.

2014-01-01

232

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

PubMed Central

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

2011-01-01

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

Learning by Writing Plays.  

ERIC Educational Resources Information Center

Describes Ellen Norman Melamed's Playwriting Project, a 15-session classroom program that requires each participating student to write and design a play, to do at least one revision of each stage of his/her work, and to submit a critical assessment of the experience at the end of the term. (PRA)

Chansky, Dorothy

1990-01-01

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

Integrated Play Groups  

ERIC Educational Resources Information Center

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

Glovak, Sandra

2007-01-01

237

Beginning to Play  

ERIC Educational Resources Information Center

This book focuses on the need to equip practitioners to meet the play needs of children in today's early years settings. With babies and very young children increasingly being cared for in out-of-home care settings, it is essential for early years practitioners to be responsive and reflective to ensure that these young children's needs are met in…

Forbes, Ruth

2004-01-01

238

"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

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

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

241

TGF? Signaling Regulates the Timing of CNS Myelination by Modulating Oligodendrocyte Progenitor Cell Cycle Exit through SMAD3/4/FoxO1/Sp1  

PubMed Central

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

2014-01-01

242

Characterization of human deoxyribonuclease I gene (DNASE1) promoters reveals the utilization of two transcription-starting exons and the involvement of Sp1 in its transcriptional regulation.  

PubMed

Levels of deoxyribonuclease I (DNase I) activity in vivo have been shown to be altered by physiological and/or pathological processes. However, no information is available on the regulation of DNase I gene (DNASE1) expression in vivo or in vitro. We first mapped the transcription start sites of DNASE1 in human pancreas and in the DNase I-producing human pancreatic cancer cell line QGP-1, and revealed a novel site approximately 12 kb upstream of exon 1, which was previously believed to be the single transcription-starting exon. This initiation site marks an alternative starting exon, designated 1a. Exons 1 and 1a were used simultaneously as transcription-starting exons in pancreas and QGP-1 cells. Promoter assay, EMSA and chromatin immunoprecipitation analysis with QGP-1 cells showed the promoter region of exon 1a in which the Sp1 transcription factor is specifically involved in promoter activity. This is the first to be identified as a transcription factor responsible for gene expression of vertebrate DNase I genes. Furthermore, RT-PCR analysis indicated alternative splicing of human DNASE1 pre-mRNA in pancreas and QGP-1 cells. Only two transcripts among eight alternative splicing products identified can be translated to produce intact DNase I protein. These results suggest that human DNASE1 expression is regulated through the use of alternative promoter and alternative splicing. PMID:16771825

Kominato, Yoshihiko; Ueki, Misuzu; Iida, Reiko; Kawai, Yasuyuki; Nakajima, Tamiko; Makita, Chikako; Itoi, Masako; Tajima, Yutaka; Kishi, Koichiro; Yasuda, Toshihiro

2006-07-01

243

Why Play Logical Games?  

Microsoft Academic Search

Game semantics has almost achieved the status of a paradigm in computer science but philosophers are slow to take notice.\\u000a One reason for this might be the lack of a convincing philosophical account of logical games, what it means to play them,\\u000a for the proponent to win, etc., pointedly raised by Wilfrid Hodges as the ‘Dawkins question’. In this paper,

Mathieu Marion

244

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

E-print Network

, liver tissue of mice challenged with CCl4 displayed hepatocytes with intense p-ERK1/2 staining hepatec- tomy (PHx) or hepatotoxic chemicals (e.g., CCl4) induces a complex regeneration process restoring

Timmer, Jens

245

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

E-print Network

in kidney tumor-derived As4.1 cells, which express high levels of renin mRNA, is dependent on a proximal have been identified in Ren-1c using a kidney tumor-derived As4.1 cell line, which was developed from,13]. In the mouse kidney, these renin genes are approx- imately equivalently expressed [7]. However, they are dif

Gronostajski, Richard M.

246

Laboratory and in situ investigations of factors affecting the growth and survivorship of the Scyphozoan jellyfish Aurelia sp1  

E-print Network

air saturated waters (Kideys and Romanova, 2001). Other hypoxicair saturated controls and in the Experiment 1 low-oxygen treatment and less than 1 ephyrae day -1 in hypoxicair-saturated controls are statistically distinct from those of the low oxygen treatment in Experiment 1 and both of the hypoxic

Cawood, Alison Michelle

2012-01-01

247

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.

Chris Kuka (Bend Senior High School REV)

1994-07-30

248

Playing with Poetry  

NSDL National Science Digital Library

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

Payne, Mrs.

2010-06-04

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.

Marlene Y. MacLeish

2012-06-26

250

Play Theories: A Contemporary Review.  

ERIC Educational Resources Information Center

Reviews two sets of play theories, classical and modern, noting that the reason and purpose for play are explained by classical theories; the role of play in child development, determined by modern theories. States that process of play has dual functions of personal expression and social adaptation. Examines the relationship between play and…

Mellou, Eleni

1994-01-01

251

Farm Hall: The Play  

NASA Astrophysics Data System (ADS)

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

Cassidy, David C.

2013-03-01

252

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

PubMed

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

Pahlevan, Mahdi; Toivakka, Martti; Alam, Parvez

2014-08-01

253

Overexpression of PGC?1? enhances cell proliferation and tumorigenesis of HEK293 cells through the upregulation of Sp1 and Acyl-CoA binding protein.  

PubMed

Peroxisome proliferator-activated receptor ? coactivator-1? (PGC?1?), a coactivator interacting with multiple transcription factors, regulates several metabolic processes. Although recent studies have focused on the role of PGC?1? in cancer, the underlying molecular mechanism has not been clarified. Therefore, we evaluated the role of PGC?1? in cell proliferation and tumorigenesis using human embryonic kidney (HEK)293 cells and colorectal cancer cells. We established stable HEK293 cell lines expressing PGC?1? and examined cell proliferation, anchorage-independent growth, and oncogenic potential compared to parental HEK293 cells. To identify the molecular PGC?1? targets for increased cell proliferation and tumorigenesis, the GeneFishing™ DEG (differentially expressed genes) screening system was used. Western blot analysis and immunofluorescence staining were performed for a regulated gene product to confirm the results. Forced expression of PGC?1? in HEK293 cells promoted cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC?1? showed enhanced tumor formation when subcutaneously injected into the bilateral flanks of immunodeficient mice. The results of the GeneFishing DEG screening system identified one upregulated gene (Acyl-CoA binding protein; ACBP). Real-time RT-PCR, western blot analysis, and immunofluorescence staining showed that ACBP was markedly increased in HEK293 cells stably overexpressing PGC?1? (PGC?1?-HEK293 cells) compared to those expressing an empty vector. In PGC?1?, ACBP, and specificity protein 1 (Sp1) siRNA knockdown experiments in PGC?1?-HEK293 and SNU-C4 cells, we also observed inhibition of cell proliferation, reduced expression of antioxidant enzymes, and increased H2O2-induced reactive oxygen species production and apoptosis. These findings suggest that PGC?1? may promote cell proliferation and tumorigenesis through upregulation of ACBP. We provide evidence that increased Sp1 expression might contribute to enhanced ACBP expression by PGC?1?. The current results also suggest that PGC?1?, whose expression is related to enhanced cell proliferation and tumorigenesis, may be a good candidate molecular target for cancer therapy. PMID:25585584

Shin, Sung-Won; Yun, Seong-Hoon; Park, Eun-Seon; Jeong, Jin-Sook; Kwak, Jong-Young; Park, Joo-In

2015-03-01

254

Child's Play: A Multidisciplinary Perspective  

Microsoft Academic Search

Competition obscures the realities and significance of play, in particular, the bodily play originating in infancy and typical\\u000a of young children. A multidisciplinary perspective on child's play elucidates the nature of child's play and validates the\\u000a distinction between competition and play. The article begins with a consideration of ethological research on play in young\\u000a human and nonhuman animals, proceeds to

Maxine Sheets-Johnstone

2003-01-01

255

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

PubMed Central

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

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

2014-01-01

256

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

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

Factorize  

NSDL National Science Digital Library

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

2000-01-01

259

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

260

Egr-1 regulates the transcription of NGX6 gene through a Sp1/Egr-1 overlapping site in the promoter  

PubMed Central

Background As a novel candidate metastasis suppressor gene, Nasopharyngeal carcinoma-associated gene 6 (NGX6) is involved in cellular growth, cell cycle progression and tumor angiogenesis. Previous studies have shown that NGX6 gene is down-regulated in colorectal cancer (CRC). However, little is known about its transcriptional regulation. Results We defined the minimal promoter of NGX6 gene in a 186-bp region (from-86 to +100) through mutation construct methods and luciferase assays. Results from Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) revealed that Early growth response gene 1 (Egr-1) binds to the Sp1/Egr-1 overlapping site of NGX6 minimal promoter. Overexpression of Egr-1 increased the promoter activity and mRNA level of NGX6 gene; while knock-down of endogenous Egr-1 decreased mRNA expression of NGX6 gene. Conclusion These results demonstrate that Egr-1 regulates NGX6 gene transcription through an overlapping Sp1/Egr-1 binding site as a positive regulator of NGX6 gene. PMID:25029911

2014-01-01

261

Asbestos in play sand  

SciTech Connect

A letter in the New England Journal of Medicine (Oct. 2 issue) stated that a carbonate sand marketed in New Jersey was contaminated with 2 to 4 percent tremolite asbestos. The authors were called on by one of the federal agencies to repeat the analysis of this sand, specifically for its asbestos content. The sand was pulverized and immersed in oils with known refractive indexes, and the predominant amphibole was characterized by polarized light microscopy. The optical characteristics were noted, and the indexes of refraction were measured and found to be consistent with tremolite. On the basis of optical characterization, the authors concluded that all the tremolite visualized with light microscopy consisted of large, single cleavage fragments and was not asbestiform. They used the technique of x-ray diffraction, as did the author of the original report, which showed the presence of an amphibole mineral (probably tremolite) in the carbonate sand. The technique was not used, and cannot be used, to distinguish between the tremolite habits (asbestiform or nonasbestiform). An acid-insoluble residue, recovered from the carbonate sand, was examined by analytic electron microscopy. The tremolite grains were observed to consist of single untwinned, crystalline fragments. Few defects were noted. Selected area electron diffraction nets were indicative of fragments lying near or at the common amphibole cleavage plane. These characteristics are consistent with cleavage fragments and not asbestos. Aspect ratios reflected short particles (less than 5.1). On the basis of their examination of the carbonate play sand, they conclude that it did not contain tremolite asbestos.

Langer, A.M.; Nolan, R.P.

1987-04-02

262

Inhibitory effect of acetyl-11-keto-beta-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells.  

PubMed

Androgen receptor (AR)-mediated signaling is crucial for the development and progression of prostate cancer (PCa). Naturally occurring phytochemicals that target the AR signaling offer significant protection against this disease. Acetyl-11-keto-beta-boswellic acid (AKBA), a compound isolated from the gum-resin of Boswellia carterii, caused G1-phase cell cycle arrest with an induction of p21(WAF1/CIP1), and a reduction of cyclin D1 as well in prostate cancer cells. AKBA-mediated cellular proliferation inhibition was associated with a decrease of AR expression at mRNA and protein levels. Furthermore, the functional biomarkers used in evaluation of AR transactivity showed suppressions of prostate-specific antigen promoter-dependent and androgen responsive element-dependent luciferase activities. Additionally, down-regulation of an AR short promoter mainly containing a Sp1 binding site suggested the essential role of Sp1 for the reduction of AR expression in cells exposed to AKBA. Interruption effect of AKBA on Sp1 binding activity but not Sp1 protein levels was further confirmed by EMSA and transient transfection with a luciferase reporter driven by three copies of the Sp1 binding site of the AR promoter. Therefore, anti-AR properties ascribed to AKBA suggested that AKBA-containing drugs could be used for the development of novel therapeutic chemicals. PMID:18430409

Yuan, Hui-Qing; Kong, Feng; Wang, Xiao-Ling; Young, Charles Y F; Hu, Xiao-Yan; Lou, Hong-Xiang

2008-06-01

263

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

264

TAF1 Histone Acetyltransferase Activity in Sp1 Activation of the Cyclin D1 Promoter  

Microsoft Academic Search

A missense mutation within the histone acetyltransferase (HAT) domain of the TATA binding protein- associated factor TAF1 induces ts13 cells to undergo a late G1 arrest and decreases cyclin D1 transcription. We have found that TAF1 mutants (844-850 and 848-850, from which amino acids 844 through 850 and 848 through 850 have been deleted, respectively) deficient in HAT activity are

Traci L. Hilton; Yun Li; Elizabeth L. Dunphy; Edith H. Wang

2005-01-01

265

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

266

NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene.  

PubMed

Expression of the human monocyte chemoattractant protein-1 (hMCP-1) is ubiquitous in various cell types and is increased by a wide variety of stimuli. We initially found that the effects of various stimuli, including IL-1 beta, TNF-alpha, and 2-O-tetradecanoylphorbol 13-acetate, on the expression of hMCP-1 mRNA were quite different among A172 glioblastoma cells, HT1080 fibrosarcoma cells, and SKLMS1 leiomyosarcoma cells. These findings suggested that hMCP-1 expression is regulated both in a stimulus-specific and a tissue-specific manner. To elucidate the mechanism underlying this stimulus-specific and tissue-specific regulation, we isolated a hMCP-1 5'-flanking genomic DNA fragment and sequenced it extensively up to bp 3011 upstream from the transcriptional start site. Among many putative cis-elements, we identified two cis-elements critical for the transcription of the hMCP-1 gene. The first element is a remote kappa B binding site located far upstream between bp -2612 and -2603 that was important for IL-1 beta-, TNF-alpha-, and 2-O-tetradecanoylphorbol 13-acetate-induced enhancer activity. Mutation at the kappa B consensus site resulted in a complete loss of these stimulus-induced enhancer activities. The second element is a GC box located between bp -64 and -59 that was important for the maintenance of basal transcriptional activity. Overexpression of rSp1 resulted in increased hMCP-1 transcriptional activity, possibly suggesting the role of Sp1 in controlling basal hMCP-1 transcription via this GC box. These results together indicate that hMCP-1 expression is controlled by at least two distinct regulatory elements: a kappa B site and a GC box that seem to be associated with stimulus-specific and tissue-specific regulation, respectively. PMID:8051410

Ueda, A; Okuda, K; Ohno, S; Shirai, A; Igarashi, T; Matsunaga, K; Fukushima, J; Kawamoto, S; Ishigatsubo, Y; Okubo, T

1994-09-01

267

Mathematical Adventures in Role Play  

ERIC Educational Resources Information Center

The provision of role play is vital in every early years setting. It provides opportunities for the development of all areas of learning. With careful thought and planning, all role play situations can provide children with mathematical adventures. Many examples of good quality role play had been observed in a variety of settings throughout…

Tyce, Constance

2002-01-01

268

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

269

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

270

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

271

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

PubMed

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

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

2013-03-01

272

Ancient Properties of Spider Silks Revealed by the Complete Gene Sequence of the Prey-Wrapping Silk Protein (AcSp1)  

PubMed Central

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

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

2013-01-01

273

Cooperation of E2F-p130 and Sp1-pRb Complexes in Repression of the Chinese Hamster dhfr Gene  

PubMed Central

In mammalian cells reiterated binding sites for Sp1 and two overlapping and inverted E2F sites at the transcription start site regulate the dhfr promoter during the cell growth cycle. Here we have examined the contributions of the dhfr Sp1 and E2F sites in the repression of dhfr gene expression. In serum-starved cells or during serum stimulation, the Chinese hamster dhfr gene was not derepressed by trichostatin A (TSA), an inhibitor of histone deacetylases (HDAC). Immunoprecipitation experiments showed that HDAC1 and hypophosphorylated retinoblastoma protein (pRb) are associated with Sp1 in serum-starved CHOC400 cells. In transfection experiments, reporter plasmids containing the reiterated dhfr Sp1 sites were stimulated 10-fold by TSA, while a promoter containing four dhfr E2F sites and a TATA box was responsive to E2F but was completely unaffected by TSA. HDAC1 did not coprecipitate with p130-E2F DNA binding complexes, the predominant E2F binding activity in cell extracts after serum starvation, suggesting that p130 imposes a TSA-insensitive state on the dhfr promoter. In support of this notion, recruitment of GAL4-p130 to a dihydrofolate reductase-GAL4 reporter rendered the promoter insensitive to TSA, while repression by GAL4-pRb was sensitive to TSA. Upon phosphorylation of pRb and p130 after serum stimulation, the Sp1-pRb and p130-E2F interactions were lost while the Sp1-HDAC1 interaction persisted into S phase. Together these studies suggest a dynamic model for the cooperation of pRb and p130 in repression of dhfr gene expression during withdrawal from the cell cycle. We propose that, during initial phases of cell cycle withdrawal, the binding of dephosphorylated pRb to Sp1-HDAC1 complexes and complexes of E2F-1 -to -3 with DP results in transient, HDAC-dependent suppression of dhfr transcription. Upon withdrawal of cells into G0, recruitment of p130 to E2F-4–DP-1 complexes at the transcription start site results in a TSA-insensitive complex that cooperates with Sp1-HDAC-pRb complexes to stably repress dhfr promoter activity in quiescent cells. PMID:11158299

Chang, Young-Chae; Illenye, Sharon; Heintz, Nicholas H.

2001-01-01

274

Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells.  

PubMed

Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcription factor, such as Survivin and Cdk1. In the present study we evaluated the gene expression of Survivin, its spliced variants and Cdk1 in GBM samples and cell lines. Moreover, we investigated the effects of M4N combined or not with TMZ and/or radiation on GBM primary cultures and cell lines. qRT-PCR assays were performed to determine the Survivin-spliced variants and Cdk1 gene mRNA expression in GBM tumor samples and cell lines. Cell proliferation was measured by XTT assay and cell cycle and apoptosis were determined by flow cytometry. Drug combination analyses using different schedules of administration (simultaneous and sequential) were performed on GBM cell lines and primary cultures based on the Chou-Talalay method. For clonogenic survival, doses of 2, 4, and 6 Gy of gamma radiation. were used. All Survivin-spliced variants and the Cdk1 gene were expressed in GBM samples (n?=?16) and cell lines (n?=?6), except the Survivin-2B variant that was only expressed in GBM cell lines. M4N treatment down regulated the expression of Cdk1, Survivin and the Survivin-?Ex3 variant, while the Survivin-2B variant was up-regulated. M4N decreased the cell proliferation separately and synergistically with TMZ, and enhanced the effects of radiation, mainly when associated with TMZ. M4N also induced apoptotic cell death, decreased the mitotic index and arrested the cell cycle mainly in the G2/M phase. Our results suggest a potential clinical application of M4N in combination with TMZ and radiation for GB treatment. PMID:23299390

Castro-Gamero, Angel Mauricio; Borges, Kleiton Silva; Moreno, Daniel Antunes; Suazo, Veridiana Kill; Fujinami, Mayara Missono; de Paula Gomes Queiroz, Rosane; de Oliveira, Harley Francisco; Carlotti, Carlos Gilberto; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga

2013-08-01

275

The oncoprotein hepatitis B X-interacting protein promotes the migration of ovarian cancer cells through the upregulation of S-phase kinase-associated protein 2 by Sp1.  

PubMed

Hepatitis B X-interacting protein (HBXIP) is a novel oncoprotein. We have previously reported that HBXIP promotes the proliferation and migration of breast cancer cells. S-phase kinase-associated protein 2 (Skp2) is another oncoprotein which is important for migration. In this study, we investigated whether Skp2 is involved in the migration enhanced by HBXIP in ovarian cancer. The expression of HBXIP and Skp2 in ovarian cancer tissues was examined by immunohistochemistry using tissue microarrays. The role of HBXIP and Skp2 in the migration of ovarian cancer cells was investigated by wound-healing assay and Transwell migration assay. The effect of HBXIP on Skp2 was assessed by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, luciferase reporter gene assays and chromatin immunoprecipitation in ovarian cancer cells (SKOV3 and CAOV3). We found that both HBXIP and Skp2 were highly expressed in ovarian cancer tissues. We observed that the overexpression of HBXIP enhanced the migration of ovarian cancer cells, while Skp2 siRNAs decreased the cell migration enhanced by HBXIP. The HBXIP siRNAs inhibited ovarian cancer cell migration and Skp2 rescued the migration inhibition induced by HBXIP siRNA. HBXIP could upregulate Skp2 at the levels of mRNA and protein in ovarian cancer cells. Moreover, HBXIP increased the activity of Skp2 promoter via binding to the transcription factor Sp1. HBXIP is highly expressed in ovarian cancer tissues. HBXIP enhances the migration of ovarian cancer cells. HBXIP was able to stimulate the activity of Skp2 promoter via transcription factor Sp1 thus promoting the migration of ovarian cancer cells. PMID:24788380

Xu, Fuqiang; Zhu, Xiaoming; Han, Tao; You, Xiaona; Liu, Fabao; Ye, Lihong; Zhang, Xiaodong; Wang, Xiaohong; Yao, Yuanqing

2014-07-01

276

Behavioral approaches to promoting play.  

PubMed

A variety of techniques grounded in behavioral psychology, and more specifically in applied behavior analysis, have been established to increase and improve play skills in children with autistic spectrum disorders. This article introduces a set of efficacious methods, which range from highly structured techniques to more naturalistic strategies. It focuses on object play as other authors in the issue discuss social play in greater depth. Behavioral techniques that are reviewed include: discrete trial training, use of stereotyped behaviors to increase play skills, pivotal response training, reciprocal imitation training, differential reinforcement of appropriate behavior, in vivo modeling and play scripts, and video modeling. A discussion of expanding behavior techniques to teach more complex play as well as training in varied environments is also presented. References are provided to allow the reader to obtain more in-depth information about each technique. PMID:14678679

Stahmer, Aubyn C; Ingersoll, Brooke; Carter, Cynthia

2003-12-01

277

The Importance of Play: Why Children Need to Play  

ERIC Educational Resources Information Center

In this article, the authors discuss the important role of dramatic ("pretend") play in early childhood with increasing emphasis at school on developing academic skills in children at younger and younger ages. Play is especially beneficial to children's learning when it reaches a certain degree of sophistication. In other words, "unproductive"…

Bodrova, Elena; Leong, Deborah J.

2005-01-01

278

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

279

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

280

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

NASA Technical Reports Server (NTRS)

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

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

2003-01-01

281

Licochalcone A induces apoptosis in malignant pleural mesothelioma through downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic pathway.  

PubMed

Licochalcone A (LCA) is a natural product derived from the roots of Glycyrrhiza inflata exhibiting a wide range of bioactivities such as antitumor, anti-oxidant and anti-bacterial effects. Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer with a poor prognosis because of its rapid progression. However, LCA has not been investigated concerning its effects on MPM. Preliminarily, we observed that LCA negatively modulated not only cell growth, but also specificity protein 1 (Sp1) expression in MSTO-211H and H28 cell lines. It was found that IC50 values of LCA for growth inhibition of MSTO-211H and H28 cells were approximately 26 and 30 µM, respectively. Consistent with downregulation of Sp1, expression of Sp1 regulatory proteins such as Cyclin D1, Mcl-1 and Survivin was substantially diminished. Mechanistically, LCA triggered the mitochondrial apoptotic pathway by affecting the ratio of mitochondrial proapoptotic Bax to anti-apoptotic Bcl-xL. Bid induced loss of mitochondrial membrane potential, eventually leading to multi-caspase activation and increased sub-G1 population. Moreover, nuclear staining with DAPI highlighted nuclear condensation and fragmentation of apoptotic features. Flow cytometry analyses after staining cells with Annexin V and propiodium iodide corroborated LCA-mediated apoptotic cell death of MPM cells. In conclusion, these results present that LCA may be a potential bioactive material to control human MPM cells by apoptosis via the downregulation of Sp1. PMID:25586190

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

2015-03-01

282

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.

283

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

284

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

285

CALMING PLAY FOR HEALTHY MINDS  

E-print Network

Managing stress 13 14 15 #12;MENTAL REST Also involves: Personal time Relaxation CALMING PLAY FOR MENTAL REST- YOGA CALMING PLAY FOR MENTAL REST- PEACEFUL SPACES 16 17 18 #12;BOOKS ABOUT MENTAL REST ENGAGING volunteering: · Teaching yoga · Conversing about feelings during circle time 19 20 21 #12;ENGAGING

286

Playing To Get Smart. Viewpoint.  

ERIC Educational Resources Information Center

Asserts that it is through play with materials and relationships, invention of classification systems, and solving problems in dialogue with others that young children develop the basic skills they will need to become effective contributors to the health of a changing world. Offers suggestions for teaching children play skills by providing…

Jones, Elizabeth

2003-01-01

287

Behavioral Approaches to Promoting Play.  

ERIC Educational Resources Information Center

This article introduces methods for increasing and improving play skills in children with autistic spectrum disorders. Behavioral techniques that are reviewed include discrete trial training, use of stereotyped behaviors to increase play skills, pivotal response training, reciprocal imitation training, differential reinforcement of appropriate…

Stahmer, Aubyn C.; Ingersoll, Brooke; Carter, Cynthia

2003-01-01

288

Behavioral Approaches to Promoting Play  

Microsoft Academic Search

A variety of techniques grounded in behavioral psychology, and more specifically in applied behavior analysis, have been established to increase and improve play skills in children with autistic spectrum disorders. This article introduces a set of efficacious methods, which range from highly structured techniques to more naturalistic strategies. It focuses on object play as other authors in the issue discuss

Aubyn C. Stahmer; Brooke Ingersoll; Cynthia Carter

2003-01-01

289

Playing the Game of School.  

ERIC Educational Resources Information Center

Ways to succeed in school and advice on reading books and textbooks are covered in four essays. The analogy of playing the "game of school" and preparing for and playing a sport is developed by Charles I. Brown in two essays. Study activities that are designed to be done before, during, and after class are suggested to help the student maximize…

Brown, Charles I.; And Others

290

Fifteen effective play therapy techniques  

Microsoft Academic Search

A plethora of innovative play therapy techniques have been developed in recent years to implement the therapeutic powers of play. The purpose of this article is to concisely describe 15 techniques that are effective, enjoyable, inexpensive, and easy to implement. Included in the description of each technique are the therapeutic rationale, materials needed, step-by-step implementation guide, and applications. The techniques

Tara M. Hall; Heidi Gerard Kaduson; Charles E. Schaefer

2002-01-01

291

Niger Delta play types, Nigeria  

SciTech Connect

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

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

1995-08-01

292

Inhibition of bladder cancer invasion by Sp1-mediated BTG2 expression via inhibition of DNA methyltransferase 1.  

PubMed

Significantly lower endogenous expression of B-cell translocation gene 2 (BTG2) was observed in human muscle-invasive bladder cancers (MIBC) than matched normal tissues and non-muscle invasive bladder cancers (NMIBC). BTG2 expression was inversely correlated with increased expression of the DNA methyltransferases DNMT1 and DNMT3a in MIBC, but not NMIBC, suggesting a potential role for BTG2 expression in muscle invasion of bladder cancer. Over 90% of tumor tissues revealed strong methylation at CpG islands of the BTG2 gene, compared with no methylation in the normal tissues, implying epigenetic regulation of BTG2 expression in bladder carcinogenesis. By using EJ bladder cancer cells and the demethylating agent decitabine, transcription of BTG2 was shown to be up-regulated by inhibiting DNMT1 expression via modification at CpG islands. DNMT1 binding to the BTG2 gene further regulated BTG2 expression by chromatin remodeling, such as H3K9 dimethylation and H3K4 trimethylation, and Sp1 activation. Induced BTG2 expression significantly reduced EJ cell tumorigenesis and invasiveness together with induction of G2 /M arrest. These results demonstrate an important role for the BTG2(/TIS21/PC3) gene in the progression of bladder cancers, and suggest that BTG2(/TIS21/PC3) is a promising epigenetic target for prevention of muscle invasion in human bladder cancers. PMID:25284287

Devanand, Preethi; Kim, Sun Il; Choi, Yong Won; Sheen, Seung Soo; Yim, Hyunee; Ryu, Min Sook; Kim, Se Joong; Kim, Wun-Jae; Lim, In Kyoung

2014-12-01

293

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

294

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

295

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.

296

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

297

Analytical Chemistry Role Playing Experiments  

NSDL National Science Digital Library

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

2011-04-14

298

Playing in the Gutters: Enhancing Children's Cognitive and Social Play.  

ERIC Educational Resources Information Center

Adding plastic gutters to the nursery school's sand area began as a science curriculum enhancement and evolved into a whole curriculum that stimulated cognitive exploration, cooperative dramatic play, language enhancement, and general fun. The children manipulated the gutters and materials such as sand, water, buckets, and tennis balls in a…

Dinwiddie, Sue A.

1993-01-01

299

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

300

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

301

Value of Five Tumor Markers (AFP, CEA, hCG, hPL and SP1) in Diagnosis and Staging of Testicular Germ Cell Tumors  

Microsoft Academic Search

Serum levels of AFP, CEA, hCG, hPL and SP1 were measured by specific radioimmunoassays in 111 patients with testicular germ cell tumors. Seminomas, mature teratomas and ‘pure type’ embryonal carcinomas, as well as the latter two types of tumor with seminomatous admixture, do not produce markers unless in advanced stages when they may do so (small amounts of hCG, hPL

Janusz J. Szymendera; Józef Zborzil; Ludwika Sikorowa; Andrzej Gadek

1981-01-01

302

Structural and electronic properties of new 1D and 2D carbon allotropes with mixed sp1 - sp3 hybridization types  

NASA Astrophysics Data System (ADS)

New 1D and 2D highly porous carbon allotropes are designed, which combine the atoms in sp1 and sp3 hybridization. The structural motifs of suggested compounds can emerge from the same polyyne building blocks as for experimentally fabricated expanded cubane. The structural, electronic properties and relative stability of proposed 1D and 2D carbon allotropes have been examined and discussed through the calculations on the basis of the density functional theory.

Enyashin, A. N.; Ivanovskii, A. L.

2014-08-01

303

"Cum play" among gay men.  

PubMed

The exchange of semen, often referred to as "cum play," has featured in gay literature and may be a unique aspect of many gay men's sexual behavior. We investigated the prevalence of "cum play" and its context among 1153 HIV-negative and 147 HIV-positive Australian gay men in an online survey. Receptive cum play (partner ejaculating or rubbing his semen over participant's anus, or participant using partner's semen as lubricant) was reported by one in six HIV-negative and one quarter of HIV-positive men on the same occasion of protected anal intercourse with a casual partner (PAIC). HIV-negative men who engaged in receptive cum play during PAIC often believed that their partner was HIV seroconcordant and tended to trust that partner. They were also generally more optimistic about the likelihood of HIV transmission, and they often only used condoms at their partners' instigation. Cum play was not uncommon and highlights the narrowness (or danger) of focusing on condom use without considering the implications of broader sexual practices and their meaning for sexual health promotion. "Safe sex" for some gay and bisexual men does not necessarily mean consistent commitment to condom use or to avoiding semen exchange. Many feel confident in their knowledge of their partner's HIV serostatus and only use condoms with these partners at their partner's request. Their commitment to safe sex may not necessarily be compromised by their practice of cum play, but the extent to which this could represent a risk for HIV transmission depends on the reliability of their assessment of their partners' HIV serostatus. PMID:23519589

Prestage, Garrett; Hurley, Michael; Brown, Graham

2013-10-01

304

Membrane-Type 1 Matrix Metalloproteinase Is Regulated by Sp1 through the Differential Activation of AKT, JNK, and ERK Pathways in Human Prostate Tumor Cells1  

PubMed Central

We and other investigators have previously shown that membrane-type 1 matrix metalloproteinase (MT1-MMP) is overexpressed in invasive prostate cancer cells. However, the mechanism for this expression is not known. Here, we show that MT1-MMP is minimally expressed in nonmalignant primary prostate cells, moderately expressed in DU-145 cells, and highly expressed in invasive PC-3 and PC-3N cells. Using human MT1-MMP promoter reporter plasmids and mobility shift assays, we show that Sp1 regulates MT1-MMP expression in DU-145, PC-3, and PC-3N cells and in PC3-N cells using chromatin immunoprecipitation analysis and silencing RNA. Investigation of signaling pathway showed that DU-145 cells express constitutively phosphorylated extracellular stress-regulated kinase (ERK), whereas PC-3 and PC-3N cells express constitutively phosphorylated AKT/PKB and c-Jun NH2 terminal kinase (JNK). We show that MT1-MMP and Sp1 levels are decreased in PC-3 and PC-3N cells when phosphatidylinositol-3 kinase and JNK are inhibited, and that MT1-MMP levels are decreased in DU-145 cells when MEK is inhibited. Transient transfection of PC-3 and PC-3N cells with a dominant-negative JNK or p85, and of DU-145 cells with a dominant negative ERK, reduces MT1-MMP promoter activity. These results indicate differential signaling control of Sp1-mediated transcriptional regulation of MT1-MMP in prostate cancer cell lines. PMID:17534446

Sroka, Isis C; Nagle, Raymond B; Bowden, G Tim

2007-01-01

305

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

306

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

307

Intensity of tennis match play  

Microsoft Academic Search

This review focuses on the characteristics of tennis players during match play and provides a greater insight into the energy demands of tennis. A tennis match often lasts longer than an hour and in some cases more than five hours. During a match there is a combination of periods of maximal or near maximal work and longer periods of moderate

J Fernandez; A Mendez-Villanueva; B M Pluim

2006-01-01

308

Teaching Shakespeare Through Play Production.  

ERIC Educational Resources Information Center

A performance-oriented approach to teaching William Shakespeare's literature has been found to be effective and enthusiastically received by college students. Ten years of teaching Shakespeare through full play production has shown that the rewards, eloquently expressed in the testimony of students, more than compensate for extra work required of…

Stodder, Joseph H.

1995-01-01

309

Teaching Technical Skills through Play.  

ERIC Educational Resources Information Center

The value of light-hearted play in teaching technical recreational sport skills is immense. Children as well as adults can learn more quickly and completely with a games-oriented approach. Often without realizing the hidden goal of excellent skiing or paddling, participants respond to intriguing tasks in a game, immerse themselves in good…

Gullion, Laurie

310

Purposeful Play in Rural Venezuela  

ERIC Educational Resources Information Center

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

Chesterfield, Ray

1977-01-01

311

AN EVALUATION OF THE PLAY \\  

Microsoft Academic Search

The purpose of this study is to reveal the impact of Purlie Victorious on the American theatrical and social scene when first produced at the Cort Theatre in New York City, September through May 1961. The resulting theatrical reviews and the public reaction to this dramatic comedy established it as one of the first successfully produced plays by an American

VON HUGO WASHINGTON

1979-01-01

312

Fort Play Children Recreate Recess  

ERIC Educational Resources Information Center

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

Powell, Mark

2007-01-01

313

Play Chinese Games. 1987, Revised.  

ERIC Educational Resources Information Center

This document, designed to introduce all ages to a selection of popular Chinese games, describes these games and provides instructions and materials for making the items needed to play most of them. Section 1 suggests class activities that can be related to some of the games. Section 2 presents instructions for the physical or outdoor games of:…

White, Caryn

314

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

315

The Role-Playing Journal.  

ERIC Educational Resources Information Center

Advocates asking business communications students to compose entries into role-playing journals as a means of practicing the concepts of audience analysis and appropriateness of language to speaker and context. Describes the assignment, the way it can be analyzed, and the benefits of the approach. (HB)

Loughman, Thomas P.

1994-01-01

316

Regulation of Na(+)/K(+)-ATPase by neuron-specific transcription factor Sp4: implication in the tight coupling of energy production, neuronal activity and energy consumption in neurons.  

PubMed

A major source of energy demand in neurons is the Na(+)/K(+)-ATPase pump that restores the ionic gradient across the plasma membrane subsequent to depolarizing neuronal activity. The energy comes primarily from mitochondrial oxidative metabolism, of which cytochrome c oxidase (COX) is a key enzyme. Recently, we found that all 13 subunits of COX are regulated by specificity (Sp) factors, and that the neuron-specific Sp4, but not Sp1 or Sp3, regulates the expression of key glutamatergic receptor subunits as well. The present study sought to test our hypothesis that Sp4 also regulates Na(+)/K(+)-ATPase subunit genes in neurons. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutational analysis, over-expression, and RNA interference studies, we found that Sp4, with minor contributions from Sp1 and Sp3, functionally regulate the Atp1a1, Atp1a3, and Atp1b1 subunit genes of Na(+)/K(+)-ATPase in neurons. Transcripts of all three genes were up-regulated by depolarizing KCl stimulation and down-regulated by the impulse blocker tetrodotoxin (TTX), indicating that their expression was activity-dependent. Silencing of Sp4 blocked the up-regulation of these genes induced by KCl, whereas over-expression of Sp4 rescued them from TTX-induced suppression. The effect of silencing or over-expressing Sp4 on primary neurons was much greater than those of Sp1 or Sp3. The binding sites of Sp factors on these genes are conserved among mice, rats and humans. Thus, Sp4 plays an important role in the transcriptional coupling of energy generation and energy consumption in neurons. PMID:24219545

Johar, Kaid; Priya, Anusha; Wong-Riley, Margaret T T

2014-02-01

317

Regulation of Na+/K+-ATPase by neuron-specific transcription factor Sp4: implication in the tight coupling of energy production, neuronal activity and energy consumption in neurons  

PubMed Central

A major source of energy demand in neurons is the Na+/K+-ATPase pump that restores the ionic gradient across the plasma membrane subsequent to depolarizing neuronal activity. The energy comes primarily from mitochondrial oxidative metabolism, of which cytochrome c oxidase (COX) is a key enzyme. Recently, we found that all 13 subunits of COX are regulated by specificity (Sp) factors, and that the neuron-specific Sp4, but not Sp1 or Sp3, regulates the expression of key glutamatergic receptor subunits as well. The present study sought to test our hypothesis that Sp4 also regulates Na+/K+-ATPase subunit genes in neurons. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutational analysis, over-expression, and RNA interference studies, we found that Sp4, with minor contributions from Sp1 and Sp3, functionally regulate the Atp1a1, Atp1a3, and Atp1b1 subunit genes of Na+/K+-ATPase in neurons. Transcripts of all three genes were up-regulated by depolarizing KCl stimulation and down-regulated by the impulse blocker tetrodotoxin (TTX), indicating that their expression was activity-dependent. Silencing of Sp4 blocked the up-regulation of these genes induced by KCl, whereas over-expression of Sp4 rescued them from TTX-induced suppression. The effect of silencing or over-expressing Sp4 on primary neurons was much greater than those of Sp1 or Sp3. The binding sites of Sp factors on these genes are conserved among mice, rats and humans. Thus, Sp4 plays an important role in the transcriptional coupling of energy generation and energy consumption in neurons. PMID:24219545

Johar, Kaid; Priya, Anusha; Wong-Riley, Margaret T. T.

2014-01-01

318

Src-family kinases play an essential role in differentiation signaling downstream of macrophage colony-stimulating factor receptors mediating persistent phosphorylation of phospholipase C-gamma2 and MAP kinases ERK1 and ERK2.  

PubMed

Macrophage colony-stimulating factor (M-CSF) has been found to be involved in multiple developmental processes, especially production of cells belonging to the mononuclear phagocyte system. The decision of myeloid progenitor cells to commit to differentiation depends on activation levels of the mitogen-activated protein kinases (MAPK), ERK1 and ERK2. Using the murine myeloid progenitor cell line FD-Fms, we show here that persistent activity of Src-family kinases (SFK) is necessary for FD-Fms cell differentiation to macrophages in response to M-CSF. Chemical inhibition of SFK blocked FD-Fms cell differentiation while it caused strong inhibition of the late phosphorylation of phospholipase C (PLC)-gamma2 and MAPK. The PLC inhibitor U73122, previously shown to block M-CSF-induced differentiation, strongly decreased long-term MAPK phosphorylation. Interestingly, inhibiting SFK with SU6656 or the MAPK kinases MEK with U0126 significantly impaired development of mononuclear phagocytes in cultures of mouse bone marrow cells stimulated with M-CSF. Collectively, results support a model in which SFK are required for sustained PLC activity and MAPK activation above threshold required for commitment of myeloid progenitors to macrophage differentiation. PMID:17972959

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

2008-01-01

319

Combined transcriptome, genetic diversity and metabolite profiling in tomato fruit reveals that the ethylene response factor SlERF6 plays an important role in ripening and carotenoid accumulation.  

PubMed

Solanum lycopersicum (tomato) and its wild relatives harbor genetic diversity that yields heritable variation in fruit chemistry that could be exploited to identify genes regulating their synthesis and accumulation. Carotenoids, for example, are essential in plant and animal nutrition, and are the visual indicators of ripening for many fruits, including tomato. Whereas carotenoid synthesis is well characterized, factors regulating flux through the pathway are poorly understood at the molecular level. To exploit the impact of tomato genetic diversity on carotenoids, Solanum pennellii introgression lines were used as a source of defined natural variation and as a resource for the identification of candidate regulatory genes. Ripe fruits were analyzed for numerous fruit metabolites and transcriptome profiles generated using a 12,000 unigene oligoarray. Correlation analysis between carotenoid content and gene expression profiles revealed 953 carotenoid-correlated genes. To narrow the pool, subnetwork analysis of carotenoid-correlated transcription revealed 38 candidates. One candidate for impact on trans-lycopene and ?-carotene accumulation was functionally charaterized, SlERF6, revealing that it indeed influences carotenoid biosynthesis and additional ripening phenotypes. Reduced expression of SlERF6 by RNAi enhanced both carotenoid and ethylene levels during fruit ripening, demonstrating an important role for SlERF6 in ripening, integrating the ethylene and carotenoid synthesis pathways. PMID:22111515

Lee, Je Min; Joung, Je-Gun; McQuinn, Ryan; Chung, Mi-Young; Fei, Zhangjun; Tieman, Denise; Klee, Harry; Giovannoni, James

2012-04-01

320

Infantile experience and play motivation  

Microsoft Academic Search

Fully-fledged affective systems in mature animals are in part the result of the impact of infantile experience on brain development. The present experimental series examines whether tactile stimulation in infancy (early handling) influences rough-and-tumble play (R&T) throughout the juvenile period, using a testing regime of 17 days divided into five parts where handled (H) and nonhandled (NH) Wistar rats are

Raúl Aguilar

2010-01-01

321

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

322

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

PubMed Central

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

Philipsen, S; Suske, G

1999-01-01

323

MAJOR OIL PLAYS IN UTAH AND VICINITY  

SciTech Connect

Utah oil fields have produced over 1.2 billion barrels (191 million m{sup 3}). However, the 13.7 million barrels (2.2 million m{sup 3}) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play; locations of major oil pipelines; descriptions of reservoir outcrop analogs; and identification and discussion of land use constraints. All play maps, reports, databases, and so forth, produced for the project will be published in interactive, menu-driven digital (web-based and compact disc) and hard-copy formats. This report covers research activities for the third quarter of the first project year (January 1 through March 31, 2003). This work included gathering field data and analyzing best practices in the eastern Uinta Basin, Utah, and the Colorado portion of the Paradox Basin. Best practices used in oil fields of the eastern Uinta Basin consist of conversion of all geophysical well logs into digital form, running small fracture treatments, fingerprinting oil samples from each producing zone, running spinner surveys biannually, mapping each producing zone, and drilling on 80-acre (32 ha) spacing. These practices ensure that induced fractures do not extend vertically out of the intended zone, determine the percentage each zone contributes to the overall production of the well, identify areas that may be by-passed by a waterflood, and prevent rapid water breakthrough. In the eastern Paradox Basin, Colorado, optimal drilling, development, and production practices consist of increasing the mud weight during drilling operations before penetrating the overpressured Desert Creek zone; centralizing treatment facilities; and mixing produced water from pumping oil wells with non-reservoir water and injecting the mixture into the reservoir downdip to reduce salt precipitation, dispose of produced water, and maintain reservoir pressure to create a low-cost waterflood. During this quarter, technology transfer activities consisted of technical presentations to members of the Technical Advisory Board in Colorado and the Colorado Geological Survey. The project home page was updated on the Utah Geological Survey Internet web site.

Thomas C. Chidsey Jr; Craig D. Morgan; Roger L. Bon

2003-07-01

324

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

325

Play: A Fundamental Equalizer for ESL Children.  

ERIC Educational Resources Information Center

Investigated the effects of play on English-as-a-Second-Language (ESL) children as part of a study on the use of play in upper elementary school children. Results found that play significantly facilitated communication and socialization while nurturing independence and self-esteem. The paper rationalizes the use of play, defines play, and…

Silver, Allan

1999-01-01

326

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

PubMed

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

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

2014-12-01

327

The Various Texts of Tennessee Williams's Plays.  

ERIC Educational Resources Information Center

Presents a list of the various texts of Williams's plays which were published prior to 1977, including plays produced but not yet published. Notes the existence of unpublished versions of printed plays when such were used for a production. (JMF)

Gunn, Drewey Wayne

1978-01-01

328

The Wade Factor: Marketing? A Team Sport Worth Playing  

ERIC Educational Resources Information Center

Customer service people are the first line of marketing, sales and revenue growth. Give them the proper training and understanding to enthusiastically lead all potential students or customers through the information-gathering and sign-up process. It does not matter how many calls schools receives through a well-planned marketing campaign if the…

Perna, Mark C.

2005-01-01

329

Teachers Critique the Curriculum: Frame Factors at Play  

ERIC Educational Resources Information Center

This paper is the collaborative effort of students in a course called EDL 646: Curriculum for Teaching, a professional course for graduate students in education, composed mostly of teachers in public schools engaged in various master's degree programs. One goal of the course is to introduce students to the task of curriculum analysis. Here, the…

Poetter, Thomas S.

2007-01-01

330

Hand kinematics of piano playing  

PubMed Central

Dexterous use of the hand represents a sophisticated sensorimotor function. In behaviors such as playing the piano, it can involve strong temporal and spatial constraints. The purpose of this study was to determine fundamental patterns of covariation of motion across joints and digits of the human hand. Joint motion was recorded while 5 expert pianists played 30 excerpts from musical pieces, which featured ?50 different tone sequences and fingering. Principal component analysis and cluster analysis using an expectation-maximization algorithm revealed that joint velocities could be categorized into several patterns, which help to simplify the description of the movements of the multiple degrees of freedom of the hand. For the thumb keystroke, two distinct patterns of joint movement covariation emerged and they depended on the spatiotemporal patterns of the task. For example, the thumb-under maneuver was clearly separated into two clusters based on the direction of hand translation along the keyboard. While the pattern of the thumb joint velocities differed between these clusters, the motions at the metacarpo-phalangeal and proximal-phalangeal joints of the four fingers were more consistent. For a keystroke executed with one of the fingers, there were three distinct patterns of joint rotations, across which motion at the striking finger was fairly consistent, but motion of the other fingers was more variable. Furthermore, the amount of movement spillover of the striking finger to the adjacent fingers was small irrespective of the finger used for the keystroke. These findings describe an unparalleled amount of independent motion of the fingers. PMID:21880938

Flanders, Martha; Soechting, John F.

2011-01-01

331

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

332

Major Oil Plays in Utah and Vicinity  

SciTech Connect

Utah oil fields have produced over 1.2 billion barrels (191 million m{sup 3}). However, the 13.7 million barrels (2.2 million m{sup 3}) of production in 2002 was the lowest level in over 40 years and continued the steady decline that began in the mid-1980s. The Utah Geological Survey believes this trend can be reversed by providing play portfolios for the major oil-producing provinces (Paradox Basin, Uinta Basin, and thrust belt) in Utah and adjacent areas in Colorado and Wyoming. Oil plays are geographic areas with petroleum potential caused by favorable combinations of source rock, migration paths, reservoir rock characteristics, and other factors. The play portfolios will include: descriptions and maps of the major oil plays by reservoir; production and reservoir data; case-study field evaluations; locations of major oil pipelines; identification and discussion of land-use constraints; descriptions of reservoir outcrop analogs; and summaries of the state-of-the-art drilling, completion, and secondary/tertiary techniques for each play. This report covers research activities for the sixth quarter of the project (October 1 through December 31, 2003). This work included describing outcrop analogs for the Jurassic Twin Creek Limestone and Mississippian Leadville Limestone, major oil producers in the thrust belt and Paradox Basin, respectively, and analyzing best practices used in the southern Green River Formation play of the Uinta Basin. Production-scale outcrop analogs provide an excellent view of reservoir petrophysics, facies characteristics, and boundaries contributing to the overall heterogeneity of reservoir rocks. They can be used as a ''template'' for evaluation of data from conventional core, geophysical and petrophysical logs, and seismic surveys. In the Utah/Wyoming thrust belt province, the Jurassic Twin Creek Limestone produces from subsidiary closures along major ramp anticlines where the low-porosity limestone beds are extensively fractured and sealed by overlying argillaceous and non-fractured units. The best outcrop analogs for Twin Creek reservoirs are found at Devils Slide and near the town of Peoa, Utah, where fractures in dense, homogeneous non-porous limestone beds are in contact with the basal siltstone units (containing sealed fractures) of the overlying units. The shallow marine, Mississippian Leadville Limestone is a major oil and gas reservoir in the Paradox Basin of Utah and Colorado. Hydrocarbons are produced from basement-involved, northwest-trending structural traps with closure on both anticlines and faults. Excellent outcrops of Leadville-equivalent rocks are found along the south flank of the Uinta Mountains, Utah. For example, like the Leadville, the Mississippian Madison Limestone contains zones of solution breccia, fractures, and facies variations. When combined with subsurface geological and production data, these outcrop analogs can improve (1) development drilling and production strategies such as horizontal drilling, (2) reservoir-simulation models, (3) reserve calculations, and (4) design and implementation of secondary/tertiary oil recovery programs and other best practices used in the oil fields of Utah and vicinity. In the southern Green River Formation play of the Uinta Basin, optimal drilling, development, and production practices consist of: (1) owning drilling rigs and frac holding tanks; (2) perforating sandstone beds with more than 8 percent neutron porosity and stimulate with separate fracture treatments; (3) placing completed wells on primary production using artificial lift; (4) converting wells relatively soon to secondary waterflooding maintaining reservoir pressure above the bubble point to maximize oil recovery; (5) developing waterflood units using an alternating injector--producer pattern on 40-acre (16-ha) spacing; and (6) recompleting producing wells by perforating all beds that are productive in the waterflood unit. As part of technology transfer activities during this quarter, an abstract describing outcrop reservoir analogs was accepted by the American Assoc

Thomas C. Chidsey; Craig D. Morgan; Kevin McClure; Douglas A. Sprinkel; Roger L. Bon; Hellmut H. Doelling

2003-12-31

333

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

NASA Astrophysics Data System (ADS)

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

Singhal, Garima; Rajeswari, Moganty R.

2009-02-01

334

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.

335

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

336

PLAY THERAPY WITH MULTIPLE PERSONALITY DISORDER CLIENTS  

Microsoft Academic Search

The use of play therapy with child alters of adults who have multiple personality disorders is explored. Various approaches to play therapy that are used with children may also be effectively used with child alters. Play may be used to help sublimate expressions of anger, recover dissociated memories, and increase communication and cooperation among alter personalities. Play therapy offers distinct

Jeffrey Wm. Klein; Garry L. Landreth

1993-01-01

337

Turkish Adaptation of Test of Pretended Play  

ERIC Educational Resources Information Center

The objective of present research is to conduct validity and reliability analysis of the verbal section of Test of Pretended Play that will measure pretended play behaviors of pre-school age children (3-6 years of age). Test of Pretended Play was first developed by Vicky Lewis and Jill Boucher in 1997. This test aimed to measure pretended play

Aydin, Aydan

2012-01-01

338

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

339

Free Play in the Early Childhood Classroom.  

ERIC Educational Resources Information Center

Examines the contributions of free play, the role of the teacher in planning and promoting free play, and the experiential background of children that promotes play activities. Discusses the importance of providing a variety of play materials, and lists the criteria for selecting equipment. (RS)

Brown, David L.; Briggs, L. D.

1989-01-01

340

Toward a Nonverbal Syntax of Play Therapy  

Microsoft Academic Search

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

Saralea E. Chazan

2001-01-01

341

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

342

Transcriptional autorepression of Msx1 gene is mediated by interactions of Msx1 protein with a multi-protein transcriptional complex containing TATA-binding protein, Sp1 and cAMP-response-element-binding protein-binding protein (CBP/p300).  

PubMed Central

The TATA-less murine Msx1 promoter contains two Msx1-binding motifs, located at -568 to -573 and +25 to +30, and is subject to potent autorepression [Takahashi, Guron, Shetty, Matsui and Raghow (1997) J. Biol. Chem. 272, 22667-22678]. To investigate the molecular mechanism by which Msx1 represses the activity of its own promoter, we transfected C2C12 myoblasts with Msx1-promoter-luciferase constructs and assessed reporter gene activity, with and without the exogenous expression of Msx1. We demonstrate that Msx1-mediated autorepression remained unaffected, regardless of the presence or absence of the Msx1 recognition motifs on the promoter. Furthermore, graded exogenous expression of TATA-binding protein (TBP), Sp1 or cAMP-response-element-binding protein-binding protein (CBP/p300) could counteract the autoinhibitory activity of Msx1. Finally, we demonstrate that Msx1 protein can be immunoprecipitated in a multiprotein complex containing TBP, Sp1 and CBP/p300. We hypothesize that the interaction of Msx1 protein with one or more ubiquitous or tissue-restricted transcription factors mediates transcriptional autorepression of the Msx1 gene. PMID:10215616

Shetty, S; Takahashi, T; Matsui, H; Ayengar, R; Raghow, R

1999-01-01

343

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

344

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

345

When does playing hard to get increase romantic attraction?  

PubMed

Folk wisdom suggests playing hard to get is an effective strategy in romantic attraction. However, prior research has yielded little support for this belief. This article seeks to reconcile these contrasting views by investigating how 2 hitherto unconsidered factors, (a) the asymmetry between wanting (motivational) and liking (affective) responses and (b) the degree of psychological commitment, can determine the efficacy of playing hard to get. We propose that person B playing hard to get with person A will simultaneously increase A's wanting but decrease A's liking of B. However, such a result will only occur if A is psychologically committed to pursuing further relations with B; otherwise, playing hard to get will decrease both wanting and liking. Two studies confirm these propositions. We discuss implications for interpersonal attraction and the interplay between emotion and motivation in determining preferences. PMID:23668234

Dai, Xianchi; Dong, Ping; Jia, Jayson S

2014-04-01

346

[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

347

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

348

Play the Immune System Defender Game  

MedlinePLUS

... Questionnaire The Immune System Play the Immune System Game About the game Granulocytes, macrophages and dendritic cells are immune cells ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

349

Gender differences in students’ mathematics game playing  

Microsoft Academic Search

The investigation monitored the digital game-playing behaviours of 428 primary-aged students (aged 10–12 years). Chi-square analysis revealed that boys tend to spend more time playing digital games than girls while boys and girls play quite different game genres. Subsequent analysis revealed statistically significant gender differences in terms of the types of mathematics-rich games students prefer to play. Girls preferred to

Tom Lowrie; Robyn Jorgensen

2011-01-01

350

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

351

Physical Activity Play: Consensus and Debate.  

ERIC Educational Resources Information Center

Considers areas of consensus from commentaries, including the value of an evolutionary perspective and the utility of exploring variations in physical activity play. Examines areas of debate, including the nonplay-play distinction, functions of rough-and-tumble play, and the opportunities of juveniles for exercise training. Calls for more directed…

Pelligrini, A. D.; Smith, Peter K.

1998-01-01

352

Commentary: At Play in the Public Area.  

ERIC Educational Resources Information Center

Notes the omission of a historical perspective in the research papers in this special issue on prosocial and aggressive play. Maintains that the past several hundred years can be characterized as a time of domesticating children's play, and that more research on rough-and-tumble play is needed. (LB)

Sutton-Smith, Brian

1992-01-01

353

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

354

Gender Differences in Students' Mathematics Game Playing  

ERIC Educational Resources Information Center

The investigation monitored the digital game-playing behaviours of 428 primary-aged students (aged 10-12 years). Chi-square analysis revealed that boys tend to spend more time playing digital games than girls while boys and girls play quite different game genres. Subsequent analysis revealed statistically significant gender differences in terms of…

Lowrie, Tom; Jorgensen, Robyn

2011-01-01

355

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

356

Playing Computer Games Versus Better Learning.  

ERIC Educational Resources Information Center

This study investigated whether kindergarten students who played Sony Play Station (Lightspan) computer games learned better than peers who did not play such games. Participants were 47 African-American kindergartners from two classes of an urban school in the Northeast. A pretest and posttest with control group design was used in the study. The…

Din, Feng S.; Caleo, Josephine

357

Making Theater: Developing Plays with Young People.  

ERIC Educational Resources Information Center

Intended for teachers who have no particular experience or training in teaching theater, but who have a love of theater and enjoy a good play, this book discusses making theater with children. It explores improvisation, reading and acting with scripts, adapting plays for young actors, and writing plays. The examples presented in the text are…

Kohl, Herbert R.

358

Empirically Based Play Interventions for Children  

ERIC Educational Resources Information Center

"Empirically Based Play Interventions for Children" is a compilation of innovative, well-designed play interventions, presented for the first time in one text. Play therapy is the oldest and most popular form of child therapy in clinical practice and is widely considered by practitioners to be uniquely responsive to children's developmental needs.…

Reddy, Linda A., Ed.; Files-Hall, Tara M., Ed.; Schaefer, Charles E., Ed.

2005-01-01

359

The Nature of Play: A Motivational Taxonomy.  

ERIC Educational Resources Information Center

To examine the concept of play, a taxonomy of five categories of play was devised and four studies were conducted in an attempt to distinguish among these categories on a motivational and emotional basis. Play is defined as an autotelic, self-rewarding activity. In each of the four studies, undergraduates (total N=520) read a scenario representing…

Day, Hy I.; Fountain, Angela

360

Dimensions of Play: Reflections and Directions.  

ERIC Educational Resources Information Center

For many children, societal changes have restricted the opportunities for and the right to play. Adults deal with these violations of children's right to play by trying to correct problems, preventing future problems, or by denying that problems can or could exist. In order to meet the challenge of preserving children's play rights, we need to be…

Jambor, Tom

361

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

362

Children in Play, Story, and School.  

ERIC Educational Resources Information Center

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

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

363

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

364

Contrived Role Playing and Attitude Change.  

ERIC Educational Resources Information Center

This study asked whether structured role playing and attendant experiences in extracurricular play productions were predictably associated with attitude changes in high school students. The major hypothesis was that students who participated in plays would become more open-minded and flexible and would show greater change toward more positive…

Schwartz, Henrietta S.

365

Currently in press, Games and Culture Journal The Promise of Play: A New Approach towards Productive Play  

E-print Network

identity, contingency, productive play, China. INTRODUCTION In the early 1970s, cultural theorist and media critic Raymond Williams identified electronic media such as television as crucial factors in the production and re- production of social and cultural identity. He argued that media are sites of collective

Dourish,Paul

366

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

367

Factor Game  

NSDL National Science Digital Library

This is an interactive applet game exercises a student's factoring ability. A student can play against the computer or against a friend on grids containing the numbers 1-30, 1-49, or 1-100. Each player in turn chooses a number from the board, and then the opponent claims all of its remaining proper factors. A player's score is the sum of all the numbers and factors she/he has chosen. When there are no numbers remaining with unclaimed factors, the game ends and the player with the greater total is the winner.

Adapted with permission from "Prime Time: Factors and Multiples," Connected Mathematics Project, G. Lappan, J. Fey, W. Fitzgerald, S. Friel and E. Phillips

2000-01-01

368

Emotionality and intentionality in bonobo playful communication.  

PubMed

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

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

2015-01-01

369

Factor Dazzle  

NSDL National Science Digital Library

This interactive online game helps students develop fluency with identifying factors while fostering strategic thinking. A student can play against the computer or against a friend on a 6 by 6 grid containing the numbers 1-36. Each player in turn chooses a number from the board, and then the opponent claims all of its remaining proper factors. A player's score is the sum of all the numbers and factors she/he has chosen. When there are no numbers remaining with unclaimed factors, the game ends and the player with the greater total is the winner. This game is part of NCTM's Calculation Nation project (cataloged separately). Users may login as a guest and play against the computer, or register (free) to challenge other players online.

2011-01-01

370

Keys to Creating Safe Play Areas on Farms  

MedlinePLUS

... Sliding Play – slides, chutes, sledding. Swinging Play - swings, tire swings, rings. Quality play equipment does not have ... Sliding Play – slides, chutes, sledding. Swinging Play - swings, tire swings, rings. Quality play equipment does not have ...

371

Antioxidant treatment induces transcription and expression of transforming growth factor beta in cultured renal proximal tubular cells.  

PubMed

Transforming growth factor beta (TGF-beta) plays an important role in the development of tubulointerstitial fibrosis in chronic renal disease. We were interested whether interference with oxygen radicals may modulate TGF-beta expression. Unexpectedly, we discovered that diphenylene iodine (DIP), an inhibitor of NADP(H) oxidase, induces a robust increase in TGF-beta transcript expression in cultured mouse proximal tubular cells (MCT cells). A similar increase was seen with EUK-8, a synthetic salen-manganese complex with high oxyradical scavenger activities. This induction of TGF-beta1 mRNA was paralleled by increasing protein expression. Transient transfection of MCT cells with a reporter construct in which murine TGF-beta1 enhancer/promoter elements were cloned in front of the luciferase gene, revealed that DIP, EUK-8, and Tiron all stimulated transcription of the TGF-beta1 gene whereas exogenous H2O2 suppressed transcription. Antisense oligonucleotides against p22phox, but not sense oligonucleotides, also increased transcriptional activity of TGF-beta1. Mutagenesis of Sp1 binding sites in the mouse TGF-beta1 enhancer/promoter abolished the stimulatory effect of the antioxidants. Gel shift experiments revealed that DIP as well as EUK-8 activated binding of nuclear proteins to Sp1 consensus sequence. Our data provide evidence that TGF-beta1 transcription is negatively regulated in MCT cells under basal conditions by NADP(H) oxidase-mediated oxygen radicals. Thus, antioxidant therapy may increase local synthesis of TGF-beta1 in the tubulointerstitium. PMID:11163763

Wolf, G; Hannken, T; Schroeder, R; Zahner, G; Ziyadeh, F N; Stahl, R A

2001-01-19

372

Play as a Window on Child Development: The Relationship between Play and Other Developmental Domains.  

ERIC Educational Resources Information Center

Two studies examined relationships between play and other developmental domains. Found that play was correlated with adaptive and fine motor skills at 12 months and with language at 20 months. Between 14-36 months, play was correlated with all Mullen Scale of Early Learning subtests. Language expressive and visual expressive scales predicted play

Eisert, Debra; Lamorey, Suzanne

1996-01-01

373

Physical Activity Play: The Nature and Function of a Neglected Aspect of Play.  

ERIC Educational Resources Information Center

Considers the nature and developmental functions of physical activity play. Distinguishes three kinds of physical activity play with consecutive age peaks: rhythmic stereotypies, exercise play, and rough-and-tumble play. Considers gender differences and function in terms of immediate and deferred consequences in physical, cognitive, and social…

Pellegrini, A. D.; Smith, Peter K.

1998-01-01

374

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

375

Chinese and German Teachers' Conceptions of Play and Learning and Children's Play Behaviour  

ERIC Educational Resources Information Center

Commonalities and distinctions in Hong Kong-Chinese and German kindergarten teachers' conceptions of play and learning were examined. Six video clips of play episodes reflecting common play behavior and themes were selected from observations made during free play in two kindergartens in Hong Kong and two in Germany. Ten Chinese and seven German…

Wu, Shu-Chen; Rao, Nirmala

2011-01-01

376

Transcription factors for dental stem cell differentiation.  

PubMed

Dental stem cells are excellent for oral and craniofacial tissue engineering. A profound knowledge about molecular processes in dental stem cells is necessary to create treatment approaches in oral medicine. Transcription factors regulate gene expression and provide decisive information for cellular functions. In recent years, the authors have investigated transcriptomes in dental stem cells before and after osteogenic differentiation. The present paper reports on the potential role of selected transcription factors, including ZBTB16, TP53, and SP1, in dental stem cell differentiation. This review discusses putative molecular processes in dental stem cells and summarizes the current knowledge. PMID:24278957

Viale-Bouroncle, Sandra; Felthaus, Oliver; Schmalz, Gottfried; Reichert, Torsten E; Morsczeck, Christian

2013-01-01

377

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

Microsoft Academic Search

This study examined the effectiveness of the Picture Me Playing intervention for increasing the play dialogue of preschool\\u000a children with ASD during pretend play opportunities with typical peers. Picture Me Playing is a pictorially enhanced, script\\u000a based intervention targeting character role play through a narrative vignette. A single-treatment counterbalanced design was\\u000a utilized to contrast the performance of intervention and comparison

Linda C. MurdockJan; Jan Q. Hobbs

2011-01-01

378

Role-Playing Methods in the Classroom.  

ERIC Educational Resources Information Center

This book, one of three Teacher Resource Booklets on Classroom Social Relations and Learning developed at the Center for Research on Utilization of Scientific Knowledge at the University of Michigan, discusses the theoretical background of role playing and gives a step-by-step discussion of how to use role playing in the classroom. There are…

Chesler, Mark; Fox, Robert

379

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

380

Drawings as spaces for intellectual play  

Microsoft Academic Search

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 from home and school contexts,

Elizabeth Wood; Emese Hall

2011-01-01

381

Play Therapy Behaviors of Sexually Abused Children.  

ERIC Educational Resources Information Center

The purpose of this study was to identify play therapy behaviors of sexually abused children. Surveys were sent to members of the Association for Play Therapy, of which 249 respondents, who worked with 16 or more sexually abused children, were used. Results indicate that there are identifiable and highly interrelated PTBs of sexually abused…

Homeyer, Linda E.; Landreth, Garry L.

382

The Excellence of Play. Second Edition  

ERIC Educational Resources Information Center

This second edition of "The Excellence of Play" encapsulates all of the many changes that have taken place in early childhood in the last decade. It examines the vital importance of play as a tool for learning and teaching for children and practitioners, supporting all those who work in early childhood education and care in developing and…

Moyles, Janet, Ed.

2005-01-01

383

The Thing's the Play: Doing "Hamlet."  

ERIC Educational Resources Information Center

Argues for the use of film in the teaching of William Shakespeare's "Hamlet" because the play was meant to be seen and heard and not just read. Outlines a method of teaching the play by which students select a scene and perform it. Gives an example of a successful student performance. (HB)

Sowder, Wilbur H., Jr.

1993-01-01

384

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

385

Restaurant Role-Play in Psychology  

ERIC Educational Resources Information Center

Research methods is perceived as a technical and difficult topic by some students. Using role-play to teach it can make it more accessible, meaningful and engaging. Role-playing the familiar roles of customer and waiting staff at a restaurant and discussing the variables that may affect the size of tips can help students to learn some of the key…

Borya, Anthony

2013-01-01

386

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.

387

Habit tic deformity secondary to guitar playing.  

PubMed

A 29-year-old man exhibited linear ridges of the right thumbnail that had been present for ten years. After he stopped playing the guitar for three months, the proximal portion of the abnormality cleared. Nail changes similar to the habit tic deformity may be produced by guitar playing. PMID:19379660

Wu, Jashin J

2009-01-01

388

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

389

Play Therapy: Basics and Beyond. Second Edition  

ERIC Educational Resources Information Center

Written for use in play therapy and child counseling courses, this extraordinarily practical text provides a detailed examination of basic and advanced play therapy concepts and skills and guidance on when and how to use them. Kottman's multitheoretical approach and wealth of explicit techniques are also helpful for clinicians who want to gain…

Kottman, Terry

2011-01-01

390

Playing with Technology: Is It All Bad?  

ERIC Educational Resources Information Center

Technology now plays a very large role in the way children of all ages play. Children want access to technology, so parents and teachers must determine the best ways to present it to them. Computers are a popular form of technology for children as young as age three. With that in mind, computer games should be problem-solving oriented and…

Slutsky, Ruslan; Slutsky, Mindy; DeShelter, Lori M.

2014-01-01

391

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

392

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

393

Triiodothyronine Represses MUC5AC Expression by Antagonizing Sp1 Binding to Its Promoter in Human Bronchial Epithelial HBE16 Cells  

PubMed Central

Mucus hypersecretion is a distinguished feature of chronic inflammatory airway diseases. Interestingly, in this condition thyroid function is impaired with decreased level of triiodothyronine (T3), indicating potential link between low level of T3 and mucus hypersecretion. But the underlying mechanisms are poorly understood. In this study we aimed to elucidate the effect of T3 on MUC5AC secretion in human bronchial epithelial HBE16 cells and further investigate how T3 regulates MUC5AC gene expression at transcriptional level. By RT-PCR and ELISA we showed that T3 inhibited MUC5AC mRNA expression and protein secretion in HBE16 cells. Furthermore, luciferase assay and site-directed mutagenesis analysis demonstrated that T3 repressed MUC5AC expression at transcriptional level and the mechanism might partly lie in the specific inhibition of Sp1 binding to the promoter. Our results suggest that decreased T3 level leads to the release of repression of MUC5AC expression and thus contributes to mucus hypersecretion. PMID:22500101

Wang, Xiaolong; Li, Qi; Zhou, Xiangdong; Kolosov, Victor P.; Perelman, Juliy M.

2012-01-01

394

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

PubMed Central

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

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

2010-01-01

395

Laser Toys: Not Always Child's Play  

MedlinePLUS

... toy laser products. According to Dan Hewett, health promotion officer at FDA's Center for Devices and Radiological ... is engaged in other activity (such as playing sports). Look for a statement that it complies with ...

396

Can Kids with Asthma Play Sports?  

MedlinePLUS

... than develop stronger lungs . They've played professional football and basketball, and they've even won medals ... flare-ups , and so are sports like baseball, football, and gymnastics. In some sports, you need to ...

397

Rac GTPases play multiple roles in erythropoiesis  

E-print Network

The four members of the Rac family of GTPases –Rac1, Rac2, Rac3 and RhoG – are members of the Rho superfamily that regulates the organization, dynamics, and function of the actin cytoskeleton. Rac GTPases play significant ...

Ji, Peng

398

Playing violent video games increases intergroup bias.  

PubMed

Previous research has shown how, why, and for whom violent video game play is related to aggression and aggression-related variables. In contrast, less is known about whether some individuals are more likely than others to be the target of increased aggression after violent video game play. The present research examined the idea that the effects of violent video game play are stronger when the target is a member of an outgroup rather than an ingroup. In fact, a correlational study revealed that violent video game exposure was positively related to ethnocentrism. This relation remained significant when controlling for trait aggression. Providing causal evidence, an experimental study showed that playing a violent video game increased aggressive behavior, and that this effect was more pronounced when the target was an outgroup rather than an ingroup member. Possible mediating mechanisms are discussed. PMID:24085715

Greitemeyer, Tobias

2014-01-01

399

Aguas!: An Introduction to Hispanic Plays.  

ERIC Educational Resources Information Center

Notes that the number of Hispanic children in schools is growing. Presents an annotated bibliography of 46 Hispanic plays, sources of information, and organizations dealing with Hispanic themes and ideas. (PA)

Saldana, Johnny

1996-01-01

400

Videogame Editions for Play and Study  

E-print Network

We discuss four types of access to videogames that are analogous to the use of different sorts of editions in literary scholarship: (1) the use of hardware to play games on platforms compatible with the original ones, (2) ...

Fernández-Vara, Clara

2014-06-05

401

Preadolescent girls' and boys' virtual MUD play  

Microsoft Academic Search

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

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

2009-01-01

402

Dead Zone - Background and Role Play  

NSDL National Science Digital Library

In this exercise from ATEEC, students will complete a critical thinking activity on hypoxia and the Mississippi River watershed. The activity requires role playing "a public meeting to discuss the Integrated Assessment of Hypoxia in the Northern Gulf of Mexico, along with the recommendations for future action contained in the report and in the action plan." This document lists resources required for the activity, goals, six stakeholders for the students to role play, and additional resources.

403

The Elements of Play: Toward a Philosophy and a Definition of Play  

ERIC Educational Resources Information Center

Scholars conventionally find play difficult to define because the concept is complex and ambiguous. The author proffers a definition of play that takes into consideration its dynamic character, posits six basic elements of play (anticipation, surprise, pleasure, understanding, strength, and poise), and explores some of their emotional, physical,…

Eberle, Scott G.

2014-01-01

404

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

ERIC Educational Resources Information Center

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

Sandseter, Ellen Beate Hansen

2007-01-01

405

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

ERIC Educational Resources Information Center

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

1997

406

"Prey Play": Learning about Predators and Prey through an Interactive, Role-Play Game  

ERIC Educational Resources Information Center

"Prey Play" is an interactive role-play activity that provides fifth-grade students with opportunities to examine predator-prey interactions. This four-part, role-play activity allows students to take on the role of a predator and prey as they reflect on the behaviors animals exhibit as they collect food and interact with one another, as well as…

Deaton, Cynthia C. M.; Dodd, Kristen; Drennon, Katherine; Nagle, Jack

2012-01-01

407

Assessing Preschool Children's Pretend Play: Preliminary Validation of the Affect in Play Scale-Preschool Version  

ERIC Educational Resources Information Center

Research Findings: A description of the development and preliminary validation of the Affect in Play Scale-Preschool version (APS-P) is presented by demonstrating associations among preschool children's play, creativity, and daily behavior using multiple methodologies. Thirty-three preschool-age children completed a standardized 5-minute play task…

Kaugars, Astrida Seja; Russ, Sandra W.

2009-01-01

408

The "State of Play" in Australia: Early Childhood Educators and Play-Based Learning  

ERIC Educational Resources Information Center

This article provides an overview of the Education Meets Play study that will investigate early childhood educators' use of play-based learning, now mandatory under the "National Quality Standard". By building on what can be gleaned about educators' approaches to play-based learning prior to the implementation of the…

Sumsion, Jennifer; Grieshaber, Sue; McArdle, Felicity; Shield, Paul

2014-01-01

409

Play as Self-Realization: Toward a General Theory of Play  

ERIC Educational Resources Information Center

In a wide-ranging essay that reviews the major theories of plays and relates them to significant notions of the self, the author addresses the question of why we play. He does so to argue that play is a biologically driven project of self-understanding and self-realization, one that humans--although they also share the experience with other…

Henricks, Thomas S.

2014-01-01

410

Neural contributions to flow experience during video game playing  

PubMed Central

Video games are an exciting part of new media. Although game play has been intensively studied, the underlying neurobiology is still poorly understood. Flow theory is a well-established model developed to describe subjective game experience. In 13 healthy male subjects, we acquired fMRI data during free play of a video game and analyzed brain activity based on the game content. In accordance with flow theory, we extracted the following factors from the game content: (i) balance between ability and challenge; (ii) concentration and focus; (iii) direct feedback of action results; (iv) clear goals; and (v) control over the situation/activity. We suggest that flow is characterized by specific neural activation patterns and that the latter can be assessed—at least partially—by content factors contributing to the emergence of flow. Each of the content factors was characterized by specific and distinguishable brain activation patterns, encompassing reward-related midbrain structures, as well as cognitive and sensorimotor networks. The activation of sensory and motor networks in the conjunction analyses underpinned the central role of simulation for flow experience. Flow factors can be validated with functional brain imaging which can improve the understanding of human emotions and motivational processes during media entertainment. PMID:21596764

Weber, René; Kircher, Tilo T. J.; Mathiak, Krystyna A.; Mathiak, Klaus

2012-01-01

411

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

412

Syntenin increases the invasiveness of small cell lung cancer cells by activating p38, AKT, focal adhesion kinase and SP1  

PubMed Central

Syntenin is a PDZ domain-containing adaptor protein that has been recently shown to regulate migration and invasion in several tumors. Small cell lung cancer (SCLC) is notorious for its invasiveness and strong potential for metastasis. We therefore studied the influence of syntenin on the invasiveness of SCLC. Immunohistochemistry in tumor tissues showed that syntenin was more frequently expressed in small cell carcinomas than other neuroendocrine tumors, such as carcinoids and neuroblastomas, suggesting that syntenin expression may be related to more aggressive forms of neuroendocrine tumors. In SCLC patients, syntenin overexpression in tumor cells was significantly associated with more extensive and advanced disease at the time of diagnosis (P=0.029). Overexpression of syntenin in SCLC cells that were intrinsically syntenin-low increased the invasiveness of cells and led to the induction of extracellular matrix (ECM)-degrading membrane type 1-matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase 2 (MMP2). In contrast, suppression of syntenin in syntenin-high cells was associated with the downregulation of MT1-MMP. Contrary to the results of previous studies using malignant melanomas and breast carcinomas, signaling cascades were shown to be further transduced through p38 MAPK and PI3K/AKT, with activation of SP1 rather than NF-?B, under circumstances not involving ECM interaction. In addition, the upstream molecule focal adhesion kinase was induced by syntenin activation, in spite of the absence of ECM interaction. These results suggest that syntenin might contribute to the invasiveness of SCLC and could be utilized as a new therapeutic target for controlling invasion and metastasis in SCLC. PMID:24722482

Kim, Wook Youn; Jang, Ji-young; Jeon, Yoon Kyung; Chung, Doo Hyun; Kim, Young Goo; Kim, Chul-Woo

2014-01-01

413

Gender Differences in Cognitive Load and Competition Anxiety Affect 6th Grade Students' Attitude toward Playing and Intention to Play at a Sequential or Synchronous Game  

ERIC Educational Resources Information Center

Do girls have more competition anxiety and exogenous cognitive load than equally able boys during the playing of stressful competitive on-line games? This question led to the adoption of a technology acceptance model to compare the influence factors of competitors in sequential and synchronous games. Confirmatory factor analysis of the data on 220…

Hwang, Ming-Yueh; Hong, Jon-Chao; Cheng, Hao-Yueh; Peng, Yu-Chi; Wu, Nien-Chen

2013-01-01

414

Technical demands of soccer match play in the English championship.  

PubMed

The aim of this study was to investigate the effect of match play on the performance of technical actions in professional soccer players. Using computerized notational analysis, technical performance was quantified for the outfield players of one team during the 2010/2011 English Championship season. This retrospective study evaluated temporal patterns in the performance of players who completed more than 10 games (n = 10). Total possessions and number of ball distributions were lower in the second versus the first half of match play (10 ± 7%, p = 0.010 and 11 ± 8% p = 0.009, respectively). Analysis across 15-minute intervals revealed reductions during the last 15-minutes of match play in the total number of possessions (0:00-14:59 minutes: 11.8 ± 1.9 vs. 75:00-89:59 minutes: 9.5 ± 1.7, p < 0.05) and distributions (0:00-14:59 minutes: 10.9 ± 2.3 vs. 75:00-89:59 minutes: 8.7 ± 2.1, p < 0.05). The number of touches taken per possession, number of challenges, percentage of challenges won, length of forward distributions and percentage success of distributions were all similar between halves and across 15-minute intervals. These results demonstrate that match-specific factors reduced total possessions and number of passes in the second half of match play. Coaching staff could use this information to inform team tactics and technical training sessions. PMID:23287830

Russell, Mark; Rees, Gethin; Kingsley, Michael I C

2013-10-01

415

Rules Made to Be Broken: Literacy and Play in a Fourth-Grade Setting.  

ERIC Educational Resources Information Center

A microanalysis of play in a fourth-grade classroom highlights its governing patterns and rules in play in which literacy is a factor. Social rituals of children are products of interaction and observation of the adult culture. They are a window into how schools and culture inform each other. (SLD)

Power, Brenda Miller

1992-01-01

416

Play Therapy for Bereaved Children: Adapting Strategies to Community, School, and Home Settings  

ERIC Educational Resources Information Center

Play therapy is a highly adaptable treatment method that can be modified according to children's ages, circumstances, and settings in which counseling occurs. Play therapy may be used in schools, community settings, and homes to help children following the death of a significant other. After reviewing basic developmental factors that affect…

Webb, Nancy Boyd

2011-01-01

417

An understanding of Japanese children's perceptions of fun, barriers, and facilitators of active free play.  

PubMed

Physical activity contributes to children's physical and mental well-being. Research suggests that active free play helps to maintain and increase physical activity in children and also contributes to social and emotional well-being. To date, these studies have focused on Western countries. Thus, this study was conducted to gain insights into the factors of perceptions of fun, barriers, and facilitators affecting active free play from the perspective of Japanese children using focus group interviews. In Japan, 12 focus groups were conducted with 60 children aged 9-11 years. Children's perceptions of fun in active free play were categorized into socializing, achievement, emotions, and freedom. Additionally, active boys' groups were interested in free play and adventure play; girls' groups were interested in free play with less physical movement and challenges; inactive boys' groups were interested in relaxing and competitive play with bodily contact. However, children mentioned that busy schedules, weather, and health-related factors acted as main barriers. Lastly, children noted facilitators include setting schedules, having access to equipment and playgrounds, and holding special events. The findings provide insights into active free play-related factors for active and inactive Japanese children and also clarify the differences between Japanese and Western children. Such findings will contribute to designing interventions to increase active free play. PMID:24486818

Lee, Yinghua; Takenaka, Koji; Kanosue, Kazuyuki

2014-01-31

418

Motion Fields to Predict Play Evolution in Dynamic Sport Scenes Kihwan Kim1  

E-print Network

actions and in- teractions are complex as they are driven by many factors, such as the short-term goals Gretsky, the legendary hockey player, "A good hockey player plays where the puck is. A great hockey player

Haro, Antonio

419

What Role Do Epigenetics and Developmental Epigenetics Play in Health and Disease?  

MedlinePLUS

... Clinical Trials Resources and Publications What role do epigenetics & developmental epigenetics play in health & disease? Skip sharing on social media links Share this: Page Content Epigenetic factors (also known as epigenetic marks) control many ...

420

Oxidative Stress Induces Premature Senescence by Stimulating Caveolin-1 Gene Transcription through p38 Mitogen-Activated Protein Kinase/Sp1–Mediated Activation of Two GC-Rich Promoter Elements  

PubMed Central

Cellular senescence is believed to represent a natural tumor suppressor mechanism. We have previously shown that up-regulation of caveolin-1 was required for oxidative stress–induced premature senescence in fibroblasts. However, the molecular mechanisms underlying caveolin-1 up-regulation in senescent cells remain unknown. Here, we show that subcytotoxic oxidative stress generated by hydrogen peroxide application promotes premature senescence and stimulates the activity of a (?1,296) caveolin-1 promoter reporter gene construct in fibroblasts. Functional deletion analysis mapped the oxidative stress response elements of the mouse caveolin-1 promoter to the sequences ?244/?222 and ?124/?101. The hydrogen peroxide–mediated activation of both Cav-1 (?244/?222) and Cav-1 (?124/?101) was prevented by the antioxidant quercetin. Combination of electrophoretic mobility shift studies, chromatin immunoprecipitation analysis, Sp1 overexpression experiments, as well as promoter mutagenesis identifies enhanced Sp1 binding to two GC-boxes at ?238/?231 and ?118/?106 as the core mechanism of oxidative stress–triggered caveolin-1 transactivation. In addition, signaling studies show p38 mitogen-activated protein kinase (MAPK) as the upstream regulator of Sp1-mediated activation of the caveolin-1 promoter following oxidative stress. Inhibition of p38 MAPK prevents the oxidant-induced Sp1-mediated up-regulation of caveolin-1 protein expression and development of premature senescence. Finally, we show that oxidative stress induces p38-mediated up-regulation of caveolin-1 and premature senescence in normal human mammary epithelial cells but not in MCF-7 breast cancer cells, which do not express caveolin-1 and undergo apoptosis. This study delineates for the first time the molecular mechanisms that modulate caveolin-1 gene transcription upon oxidative stress and brings new insights into the redox control of cellular senescence in both normal and cancer cells. PMID:17108117

Dasari, Arvind; Bartholomew, Janine N.; Volonte, Daniela; Galbiati, Ferruccio

2015-01-01

421

Comparative analysis of nuclear ribosomal DNA from the moon jelly Aurelia sp.1 (Cnidaria: Scyphozoa) with characterizations of the 18S, 28S genes, and the intergenic spacer (IGS)  

Microsoft Academic Search

Nuclear ribosomal DNAs (rDNA) constitute a multi-gene family with tandemly arranged units linked by an intergenic spacer (IGS).\\u000a Here we present the complete DNA sequence (7,731 bp) of a single repeat unit of an rDNA sequence from the moon jelly Aurelia sp.1 (Cnidaria: Scypozoa). The tandemly repeated rDNA units consisted of coding and non- coding regions, whose arrangement\\u000a was 18S

Jang-Seu Ki; Il-Chan Kim; Jae-Seong Lee

422

Evaluation of Five Tumor Markers (AFP, CEA, hCG, hPL and SP1) in Monitoring Therapy and Follow-up of Patients with Testicular Germ Cell Tumors  

Microsoft Academic Search

61 patients with seminoma and 113 with nonseminomatous germ cell tumors of the testis were treated according to the histology, stage of disease, and serum levels of tumor markers (CEA, AFP, hCG, hPL and SP1). 33 were stage I, 63 stage II, and 78 stage III patients. Most patients with seminoma, mature teratoma, immature teratoma, and ‘pure type’ embryonal carcinoma,

Janusz J. Szymendera; Józef Zborzil; Ludwika Sikorowa

1983-01-01

423

Cracking Bank PINs by Playing Mastermind  

NASA Astrophysics Data System (ADS)

The bank director was pretty upset noticing Joe, the system administrator, spending his spare time playing Mastermind, an old useless game of the 70ies. He had fought the instinct of telling him how to better spend his life, just limiting to look at him in disgust long enough to be certain to be noticed. No wonder when the next day the director fell on his chair astonished while reading, on the newspaper, about a huge digital fraud on the ATMs of his bank, with millions of Euros stolen by a team of hackers all around the world. The article mentioned how the hackers had 'played with the bank computers just like playing Mastermind', being able to disclose thousands of user PINs during the one-hour lunch break. That precise moment, a second before falling senseless, he understood the subtle smile on Joe's face the day before, while training at his preferred game, Mastermind.

Focardi, Riccardo; Luccio, Flaminia L.

424

Circuit Bending with Play-Doh  

NSDL National Science Digital Library

Break open that used musical toy and squish some Play-Doh over the circuit boards, and you will hear some weird and distorted sounds the manufacturer never intended! In this activity learners experiment with the strange conductive properties of Play-Doh in order to safely short-circuit a musical toy. This is an entertaining activity about basic circuitry, sounds, and short circuiting or "circuit bending" battery powered musical toys. Note: often it is difficult to unscrew the musical toys open, and the insides are delicate. So consider this when turning this into a group activity.

Minnesota, Science M.

2012-06-26

425

Changes in the Expression of Transcription Factors Involved in Modulating the Expression of EPO-R in Activated Human CD4-Positive Lymphocytes.  

PubMed

We have recently described the presence of the erythropoietin receptor (EPO-R) on CD4(+) lymphocytes and demonstrated that its expression increases during their activation, reaching a level reported to be typical for erythroid progenitors. This observation suggests that EPO-R expression is modulated during lymphocyte activation, which may be important for the cells' function. Here we investigated whether the expression of GATA1, GATA3 and Sp1 transcription factors is correlated with the expression of EPO-R in human CD4(+) lymphocytes stimulated with monoclonal anti-CD3 antibody. The expression of GATA1, GATA3 and Sp1 transcription factors in CD4(+) cells was estimated before and after stimulation with anti-CD3 antibody by Western Blot and flow cytometry. The expression of EPO-R was measured using real-time PCR and flow cytometry. There was no change in the expression of GATA1 and GATA3 in CD4(+) lymphocytes after stimulation with anti-CD3 antibody. However, stimulation resulted in the significantly increased expression of the Sp1 factor. CD4(+) lymphocytes stimulated with anti-CD3 antibody exhibited an increase in both the expression level of EPOR gene and the number of EPO-R molecules on the cells' surface, the latter being significantly correlated with the increased expression of Sp1. Sp1 is noted to be the single transcription factor among the ones studied whose level changes as a result of CD4(+) lymphocyte stimulation. It seems that Sp1 may significantly affect the number of EPO-R molecules present on the surface of activated CD4(+) lymphocytes. PMID:23577103

Lisowska, Katarzyna A; Frackowiak, Joanna E; Mikosik, Anna; Witkowski, Jacek M

2013-01-01

426

Changes in the Expression of Transcription Factors Involved in Modulating the Expression of EPO-R in Activated Human CD4-Positive Lymphocytes  

PubMed Central

We have recently described the presence of the erythropoietin receptor (EPO-R) on CD4+ lymphocytes and demonstrated that its expression increases during their activation, reaching a level reported to be typical for erythroid progenitors. This observation suggests that EPO-R expression is modulated during lymphocyte activation, which may be important for the cells’ function. Here we investigated whether the expression of GATA1, GATA3 and Sp1 transcription factors is correlated with the expression of EPO-R in human CD4+ lymphocytes stimulated with monoclonal anti-CD3 antibody. The expression of GATA1, GATA3 and Sp1 transcription factors in CD4+ cells was estimated before and after stimulation with anti-CD3 antibody by Western Blot and flow cytometry. The expression of EPO-R was measured using real-time PCR and flow cytometry. There was no change in the expression of GATA1 and GATA3 in CD4+ lymphocytes after stimulation with anti-CD3 antibody. However, stimulation resulted in the significantly increased expression of the Sp1 factor. CD4+ lymphocytes stimulated with anti-CD3 antibody exhibited an increase in both the expression level of EPOR gene and the number of EPO-R molecules on the cells’ surface, the latter being significantly correlated with the increased expression of Sp1. Sp1 is noted to be the single transcription factor among the ones studied whose level changes as a result of CD4+ lymphocyte stimulation. It seems that Sp1 may significantly affect the number of EPO-R molecules present on the surface of activated CD4+ lymphocytes. PMID:23577103

Lisowska, Katarzyna A.; Frackowiak, Joanna E.; Mikosik, Anna; Witkowski, Jacek M.

2013-01-01

427

Home video game playing in schoolchildren: a study of incidence and patterns of play  

Microsoft Academic Search

The recent increase in the home video games market has resulted in the ready availability of such games. This study attempted to quantify the extent of home video game playing in a typical population of 11-16-year-olds (429 males and 387 females). Of the children questioned 77.2% played video games. The most common pattern of play was daily with most of

Carol A. Phillips; Susan Rolls; Andrew Rouse; Mark D. Griffiths

1995-01-01

428

Observing Play Activity: The Children’s Developmental Play Instrument (CDPI) with Reliability Studies  

Microsoft Academic Search

The Children’s Developmental Play Instrument is a multidimensional tool intended for use in observing the play activity of\\u000a mainstream children. The instrument consists of scales to segment a child’s activity and to analyze the child’s play activity\\u000a into Affective, Cognitive, Narrative and Developmental Components. Subsequently, the Functional Analysis is used to rate the\\u000a Engagement of the child, the Use of

Saralea E. Chazan

2009-01-01

429

Playing with Liquid Foams: Learning Physical Chemistry  

ERIC Educational Resources Information Center

Who has never played with soap bubbles? They are so beautiful and amazing, they have a perfect spherical shape and surprising tints. Foams are structures of bubbles of an incredible complexity and they are a perfect system to stimulate students' interest in the chemistry and physics of surface phenomena. In this article I propose a simple…

Ritacco, Hernan

2008-01-01

430

World History Plays, Puzzles and Activities.  

ERIC Educational Resources Information Center

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

Stevens, Lawrence

431

Assembling and Dissembling: Policy as Productive Play  

ERIC Educational Resources Information Center

In this piece, the authors examine educational policy by focusing on the ways in which actors "play" or selectively follow, negotiate, and appropriate cultural instructions and rules. They outline a framework that situates assemblage, a notion utilized in actor-network theory, within the critical cultural study of policy. Treating policy…

Koyama, Jill P.; Varenne, Herve

2012-01-01