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Sample records for factors sp1 sp3

  1. Accessible chromatin structure permits factors Sp1 and Sp3 to regulate human TGFBI gene expression.

    Science.gov (United States)

    Lee, Jong-Joo; Park, Keunhee; Shin, Myeong Heon; Yang, Wook-Jin; Song, Min-Ji; Park, Joo-Hong; Yong, Tai-Soon; Kim, Eung Kweon; Kim, Hyoung-Pyo

    2011-06-03

    Transforming growth factor beta 1-induced (TGFBI) protein is an extracellular matrix (ECM) protein that is associated with other ECM proteins and functions as a ligand for various types of integrins. In this study, we investigated how human TGFBI expression is regulated in lung and breast cancer cells. We observed that the TGFBI promoter in A549 and MBA-MD-231 cells, which constitutively express TGFBI, existed in an open chromatin conformation associated with transcriptionally permissive histone modifications. Moreover, we found that TGFBI expression required Sp1 transcription elements that can bind transcription factors Sp1 and Sp3 in vitro. Occupancy of the TGFBI promoter by Sp1 and Sp3 in vivo was only observed in TGFBI-expressing cells, indicating that open chromatin conformation might facilitate the binding of Sp1 and Sp3 to the TGFBI promoter region. TGFBI promoter activity was impaired when Sp1 elements were mutated, but was increased when Sp1 or Sp3 factors was overexpressed. Furthermore, Sp1 inhibition in vivo by mithramycin A, as well as knockdown of Sp1 and/or Sp3 expression by short interfering RNA, significantly reduced TGFBI mRNA and protein levels. Thus, our data demonstrated that the expression of TGFBI is well correlated with chromatin conformation at the TGFBI promoter, and that factors Sp1 and Sp3 are the primary determinants for the control of constitutive expression of TGFBI gene. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. An Sp1/Sp3 binding polymorphism confers methylation protection.

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    Yanis A Boumber

    2008-08-01

    Full Text Available Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001. Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001. The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and approximately 2-3-fold lower levels of methylation by bisulfite sequencing (P<0.001, suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state.

  3. Dual functions of transcription factors, transforming growth factor-beta-inducible early gene (TIEG)2 and Sp3, are mediated by CACCC element and Sp1 sites of human monoamine oxidase (MAO) B gene.

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    Ou, Xiao-Ming; Chen, Kevin; Shih, Jean C

    2004-05-14

    Monoamine oxidases (MAO) A and B catalyze the oxidative deamination of many biogenic and dietary amines. Abnormal expression of MAO has been implicated in several psychiatric and neurodegenerative disorders. Human MAO B core promoter (-246 to -99 region) consists of CACCC element flanked by two clusters of overlapping Sp1 sites. Here, we show that cotransfection with transforming growth factor (TGF)-beta-inducible early gene (TIEG)2 increased MAO B gene expression at promoter, mRNA, protein, and catalytic activity levels in both SH-SY5Y and HepG2 cells. Mutation of the CACCC element increased the MAO B promoter activity, and cotransfection with TIEG2 further increased the promoter activity, suggesting that CACCC was a repressor element. This increase was reduced when the proximal Sp1 overlapping sites was mutated. Similar interactions were found with Sp3. These results showed that TIEG2 and Sp3 were repressors at the CACCC element but were activators at proximal Sp1 overlapping sites of MAO B. Gel-shift and chromatin immunoprecipitation assays showed that TIEG2 and Sp3 bound directly to CACCC element and the proximal Sp1 sites in both synthetic oligonucleotides and natural MAO B core promoter. TIEG2 had a higher affinity to Sp1 sites than CACCC element, whereas Sp3 had an equal affinity to both elements. Thus, TIEG2 was an activator, but Sp3 had no effect on MAO B gene expression. This study provides new insights into MAO B gene expression and illustrates the complexity of gene regulation.

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

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

    2002-11-01

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

  5. The interferon-γ-mediated inhibition of lipoprotein lipase gene transcription in macrophages involves casein kinase 2- and phosphoinositide-3-kinase-mediated regulation of transcription factors Sp1 and Sp3

    OpenAIRE

    2008-01-01

    The mechanisms underlying transcriptional inhibition by interferon-γ (IFN-γ) are poorly understood despite the existence of a large number of genes that are regulated in this manner and the key role of this cytokine in inflammatory disorders such as atherosclerosis. We have previously identified a novel mechanism for transcriptional inhibition by IFN-γ that involves a reduction in the binding of transcription factors Sp1 and Sp3 to regulatory sequences in the lipoprotein lipase (LPL) gene. In...

  6. Predictive value of Sp1/Sp3/FLIP signature for prostate cancer recurrence.

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    Roble G Bedolla

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

  7. The lung enriched transcription factor TTF-1 and the ubiquitously expressed proteins Sp1 and Sp3 interact with elements located in the minimal promoter of the rat Clara cell secretory protein gene.

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    Toonen, R F; Gowan, S; Bingle, C D

    1996-01-01

    The mechanisms that direct expression of the Clara cell secretory protein (CCSP) gene to the bronchiolar epithelial cells of the lung remain to be elucidated. Previous studies have identified a number of proteins which bind to a functionally important region (Region 1) located -132 to -76 bp from the transcription start site in the rat CCSP gene. Subsequently we have shown that while Region 1 is an important positive regulator of CCSP gene expression, sequences 3' of this region (-75 to +38) are sufficient to confer tissue-specific expression of a reporter gene. In the present study we have used transient transfections with a deletion series of CCSP-CAT reporter plasmids (where CAT is chloramphenicol acetyltransferase) and gel mobility shift assays with a series of overlapping oligonucleotides covering the whole minimal promoter region to study protein-DNA interactions within this region. These studies have identified a conserved functional binding site for the lung and thyroid enriched homeodomain transcription factor TTF-1, located between positions -51 and -42 from the transcription start site. CCSP-CAT chimaeric reporters containing this region are specifically activated by TTF-1 in co-transfection assays, and nuclear extracts from cells which express TTF-1 bind to this region, as does in vitro translated rat TTF-1. Three additional conserved regions were identified, and in further gel mobility shift studies with an oligonucleotide spanning the conserved region immediately 5' to the TTF-1 site we identified a binding site for the ubiquitously expressed zinc-finger-containing proteins Sp1 and Sp3. These studies suggest that cell-type-restricted and ubiquitous nuclear proteins may play a combined role in the regulation of the CCSP gene within the bronchiolar epithelium by interacting with the minimal promoter region. PMID:8687389

  8. A novel SP1/SP3 dependent intronic enhancer governing transcription of the UCP3 gene in brown adipocytes.

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    Christoph Hoffmann

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

  9. Human Telomerase Reverse Transcriptase (hTERT) Transcription Requires Sp1/Sp3 Binding to the Promoter and a Permissive Chromatin Environment.

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    Cheng, De; Zhao, Yuanjun; Wang, Shuwen; Jia, Wenwen; Kang, Jiuhong; Zhu, Jiyue

    2015-12-11

    The transcription of human telomerase gene hTERT is regulated by transcription factors (TFs), including Sp1 family proteins, and its chromatin environment. To understand its regulation in a relevant chromatin context, we employed bacterial artificial chromosome reporters containing 160 kb of human genomic sequence containing the hTERT gene. Upon chromosomal integration, the bacterial artificial chromosomes recapitulated endogenous hTERT expression, contrary to transient reporters. Sp1/Sp3 expression did not correlate with hTERT promoter activity, and these TFs bound to the hTERT promoters in both telomerase-positive and telomerase-negative cells. Mutation of the proximal GC-box resulted in a dramatic decrease of hTERT promoter activity, and mutations of all five GC-boxes eliminated its transcriptional activity. Neither mutations of GC-boxes nor knockdown of endogenous Sp1 impacted promoter binding by other TFs, including E-box-binding proteins, and histone acetylation and trimethylation of histone H3K9 at the hTERT promoter in telomerase-positive and -negative cells. The result indicated that promoter binding by Sp1/Sp3 was essential, but not a limiting step, for hTERT transcription. hTERT transcription required a permissive chromatin environment. Importantly, our data also revealed different functions of GC-boxes and E-boxes in hTERT regulation; although GC-boxes were essential for promoter activity, factors bound to the E-boxes functioned to de-repress hTERT promoter.

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

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    Li, Dong; Da, Liang; Tang, Hong; Li, Tsaiping; Zhao, Mujun

    2008-01-01

    Cell-death-inducing DFF45-like effector A (CIDE-A) belongs to a family of proapoptotic proteins, the expression of which is highly restricted in human tissues and cells. Here, the core region of the human CIDE-A promoter was characterized. Surprisingly, two Sp1/Sp3-binding sites, rather than tissue-specific transcription factors, were found to be required for the promoter activity. Although the ubiquitously expressed Sp1 and Sp3 were crucial, they alone could not adequately regulate the specific expression of CIDE-A. We found that the expression of CIDE-A was further regulated by CpG methylation of the promoter region. By performing bisulfite sequencing, we observed dense CpG methylation of the promoter region in tissues and cells with low or no expression of CIDE-A but not in tissues with high level of CIDE-A expression. In vitro methylation of this region showed significantly reduced transcriptional activity. Treatment of CIDE-A-negative cells with 5-aza-2'-deoxycytidine demethylated the CpG sites; this opened the closed chromatin conformation and markedly enhanced the binding affinity of Sp1/Sp3 to the promoter in vivo, thereby restoring CIDE-A expression. These data indicated that CpG methylation plays a crucial role in establishing and maintaining tissue- and cell-specific transcription of the CIDE-A gene through the regulation of Sp1/Sp3 binding.

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

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

    2003-01-01

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

  12. Sp3 controls fibroblast growth factor receptor 4 gene activity during myogenic differentiation.

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    Cavanaugh, Eric; DiMario, Joseph X

    2017-03-27

    Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling is a critical component in the regulation of myoblast proliferation and differentiation. The transient FGFR4 gene expression during the transition from proliferating myoblasts to differentiated myotubes indicates that FGFR4 regulates this critical phase of myogenesis. The Specificity Protein (SP) family of transcription factors controls FGFR family member gene activity. We sought to determine if members of the Sp family regulate mouse FGFR4 gene activity during myogenic differentiation. RT-PCR and western blot analysis of FGFR4 mRNA and protein revealed transient expression over 72h, with peak expression between 24 and 36h after addition of differentiation medium to C2C12 myogenic cultures. Sp3 also displayed a transient expression pattern with peak expression occurring after 6h of differentiation. We cloned a 1527bp fragment of the mouse FGFR4 promoter into a luciferase reporter. This FGFR4 promoter contains eight putative Sp binding sites and directed luciferase gene activity comparable to native FGFR4 expression. Overexpression of Sp1 and Sp3 showed that Sp1 repressed FGFR4 gene activity, and Sp3 activated FGFR4 gene activity during myogenic differentiation. Mutational analyses of multiple Sp binding sites within the FGFR4 promoter revealed that three of these sites were transcriptionally active. Electromobility shift assays and chromatin immunoprecipitation of the area containing the activator sites showed that Sp3 bound to this promoter location.

  13. Identification of Sp1 as a Transcription Activator to Regulate Fibroblast Growth Factor 21 Gene Expression

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    Shuqin Chen

    2017-01-01

    Full Text Available Fibroblast growth factor 21 (FGF21 is a metabolic hormone with multiple beneficial effects on lipid and glucose homeostasis. Previous study demonstrated that FGF21 might be one of the Sp1 target genes. However, the transcriptional role of Sp1 on FGF21 in adipose tissue and liver has not been reported. In this study, we found that the proximal promoter of mouse FGF21 is located between −63 and −20 containing two putative Sp1-binding sites. Sp1 is a mammalian transcription factor involved in the regulation of many genes during physiological and pathological processes. Our study showed that overexpression of Sp1 or suppressing Sp1 expression resulted in increased or reduced FGF21 promoter activity, respectively. Mutation analysis demonstrated that the Sp1-binding site located between −46 and −38 plays a primary role in transcription of FGF21. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis indicated that Sp1 specifically bound to this region. Furthermore, the binding activity of Sp1 was significantly increased in adipose tissues of HFD-induced obese mouse and liver of DEN-treated mouse. Thus, our results demonstrate that Sp1 positively regulates the basal transcription of FGF21 in the liver and adipose tissue and contributes to the obesity-induced FGF21 upregulation in mouse adipose tissue and hepatic FGF21 upregulation in hepatocarcinogenesis.

  14. Overexpression of transcription factor Sp1 leads to gene expression perturbations and cell cycle inhibition.

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    Emmanuelle Deniaud

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

  15. ESTROGEN REGULATION OF LRP16 GENE EXPRESSION INVOLVES SP1 TRANSCRIPTION FACTOR

    Institute of Scientific and Technical Information of China (English)

    SI Yi-ling; HAN Wei-dong; ZhAO Ya-li; LI Qi; HAO Hao-jie; SONG Hai-jing; MU Yi-ming; YU Li

    2006-01-01

    Objective: To investigate the role of Sp1 as transcription factor required for transactivation of LRP16 gene by estrogen. Methods: Specific antibodies of Erα and Sp1 were used to precipitate the target DNA/protein complexes of MCF-7 cells at different time points after estrogen treatment (Chromatin immunoprecipitation assay), the promoter region of LRP16 gene was amplified by semi-nested polymerase chain reaction (snPCR). Small interfering RNA (siRNA) against Sp1 was transiently cotransfected with LRP16-Luc (containing the region from -213bp to -126bp of LRP16 gene promoter) in MCF-7 cells. The luciferase activities were measured by dual-luciferase assay. Results: The results of chromatin immunoprecipitation assay showed that Sp1 protein directly bound to the -213bp to -126bp region of LRP16 gene, and Erα could enhance the affinity of Sp1 to DNA. Sp1-siRNA specifically decreased the transactivation of LRP16-Luc by 17β-estradiol to 70-80%. Conclusion: The estrogen-induced transactivation of the human LRP16 gene was mediated by Sp1 protein. Moreover, the interactions of ER(/Sp1 functional complex with LRP16 promoter DNA were required for enhanced LRP16 gene transactivation.

  16. Dual role of Sp3 transcription factor as an inducer of apoptosis and a marker of tumour aggressiveness.

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    Khadija Essafi-Benkhadir

    Full Text Available BACKGROUND: The ambiguous role of transcription factor Sp3 for tumour progression is still debated since it was described as a transcriptional repressor or activator. Here we tried to decipher the molecular mechanisms implicated in Sp3 accumulation observed in aggressive tumours. METHODOLOGY: We generated normal and tumour cell lines conditionally expressing Sp3. Cell growth was analyzed in vitro and after inoculation in nude mice. Apoptosis was assessed by pan- caspase activity assays, by counting fragmented nuclei and by determination of caspase 9 cleavage. Gene expression was determined by quantitative PCR. Cleavage by different caspases was performed after in vitro translation of the Sp3 cDNA in the presence of [S(35] labelled methionine. Different tumour cell lines and head and neck tumour samples were tested for the presence of Sp3 by western blots. Correlation between Sp3 expression and overall survival has been statistically determined. PRINCIPAL FINDINGS: Conditional over-expression of Sp3 induces apoptosis and modifies expression of genes implicated in the regulation of cell cycle and pro and anti apoptotic genes. Sp3 over-expression strongly reduces the development of tumours in nude mice confirming its pro-apoptotic potential in vivo. However, cells can survive to apoptosis through selective Sp3 cleavage by caspase. Sp3 induction in established tumours resulted in transient regression then progression. Progression coincides with re-accumulation of the full length form of Sp3. Sp3 is over-expressed in tumour cell lines of different origins. The presence of high levels of the full-length form of Sp3 indicates a poor prognosis for overall survival of patients with head and neck tumours. CONCLUSIONS: Full length Sp3 accumulation highlights bypass of tumour cell apoptotic capacities and is indicative of head and neck tumours aggressiveness.

  17. Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation.

    NARCIS (Netherlands)

    M. Marin; A. Karis (Alar); P. Visser (Pim); F.G. Grosveld (Frank); J.N.J. Philipsen (Sjaak)

    1997-01-01

    textabstractTranscription 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. S

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

    NARCIS (Netherlands)

    J. Gilmour (Jane); S.A. Assi (Salam); U. Jaegle (Ulrike); D.I. Kulu (Divine); H.J.G. van de Werken (Harmen); D. Clarke (Deborah); P. Westhead (Paul); J.N.J. Philipsen (Sjaak); C. Bonifer (Constanze)

    2014-01-01

    textabstractMammalian 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 elusi

  19. Molecular characterisation, evolution and expression of hypoxia-inducible factor in Aurelia sp.1.

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

    2014-01-01

    The maintenance of physiological oxygen homeostasis is mediated by hypoxia-inducible factor (HIF), a key transcriptional factor of the PHD-HIF system in all metazoans. However, the molecular evolutionary origin of this central physiological regulatory system is not well characterized. As the earliest eumetazoans, Cnidarians can be served as an interesting model for exploring the HIF system from an evolutionary perspective. We identified the complete cDNA sequence of HIF-1α (ASHIF) from the Aurelia sp.1, and the predicted HIF-1α 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.

  20. O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities.

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    Ha, Changhoon; Lim, Kihong

    2015-11-13

    The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome.

  1. The specificity protein factor Sp1 mediates transcriptional regulation of P2X7 receptors in the nervous system.

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    García-Huerta, Paula; Díaz-Hernandez, Miguel; Delicado, Esmerilda G; Pimentel-Santillana, María; Miras-Portugal, M Teresa; Gómez-Villafuertes, Rosa

    2012-12-28

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

  2. HBXIP up-regulates ACSL1 through activating transcriptional factor Sp1 in breast cancer.

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    Wang, Yue; Cai, Xiaoli; Zhang, Shuqin; Cui, Ming; Liu, Fabao; Sun, Baodi; Zhang, Weiying; Zhang, Xiaodong; Ye, Lihong

    2017-03-11

    The oncoprotein hepatitis B X-interacting protein (HBXIP) results in the dysregulation of lipid metabolism to enhance the development of breast cancer. Acyl-CoA synthetase long-chain family member 1 (ACSL1) is required for thioesterification of long-chain fatty acids into their acyl-CoA derivatives. In this study, we present a hypothesis that HBXIP might be involved in the regulation of ACSL1 in breast cancer. Interestingly, we found that the overexpression of HBXIP was able to up-regulate ACSL1 at the levels of mRNA and protein in a dose-dependent manner in breast cancer cells. Conversely, silencing of HBXIP led to the opposite results. Mechanistically, HBXIP as a coactivator interacted with transcriptional factor Sp1 through binding to the promoter of ACSL1 by ChIP assays analysis, leading to the transcription of ACSL1 in breast cancer cells. Immunohistochemistry staining revealed that the positive rate of ACSL1 was 71.4% (35/49) in clinical breast cancer tissues, HBXIP 79.6% (39/49), in which the positive rate of ACSL1 was 76.9% (30/39) in the HBXIP-positive specimens. But, few positive rate of ACSL1 10% (1/10) was observed in normal breast tissues. The mRNA levels of ACSL1 were significantly higher in clinical breast cancer tissues than those in their corresponding peritumor tissues. The mRNA levels of ACSL1 were positively associated with those of HBXIP in clinical breast cancer tissues. Thus, we conclude that the oncoprotein HBXIP is able to up-regulate ACSL1 through activating the transcriptional factor Sp1 in breast cancer.

  3. Overexpression of the transcription factor Sp1 activates the OAS-RNAse L-RIG-I pathway.

    Directory of Open Access Journals (Sweden)

    Valéryane Dupuis-Maurin

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

  4. Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites.

    Science.gov (United States)

    Xiong, S; Chirala, S S; Wakil, S J

    2000-04-11

    To understand cholesterol-mediated regulation of human fatty acid synthase promoter I, we tested various 5'-deletion constructs of promoter I-luciferase reporter gene constructs in HepG2 cells. The reporter gene constructs that contained only the Sp-1-binding site (nucleotides -82 to -74) and the two tandem sterol regulatory elements (SREs; nucleotides -63 to -46) did not respond to cholesterol. Only the reporter gene constructs containing a nuclear factor-Y (NF-Y) sequence, the CCAAT sequence (nucleotides -90 to -86), an Sp-1 sequence, and the two tandem SREs responded to cholesterol. The NF-Y-binding site, therefore, is essential for cholesterol response. Mutating the SREs or the NF-Y site and inserting 4 bp between the Sp-1- and NF-Y-binding sites both resulted in a minimal cholesterol response of the reporter genes. Electrophoretic mobility-shift assays using anti-SRE-binding protein (SREBP) and anti-NF-Ya antibodies confirmed that these SREs and the NF-Y site bind the respective factors. We also identified a second Sp-1 site located between nucleotides -40 and -30 that can substitute for the mutated Sp-1 site located between nucleotides -82 and -74. The reporter gene expression of the wild-type promoter and the Sp-1 site (nucleotides -82 to -74) mutant promoter was similar when SREBP1a [the N-terminal domain of SREBP (amino acids 1-520)] was constitutively overexpressed, suggesting that Sp-1 recruits SREBP to the SREs. Under the same conditions, an NF-Y site mutation resulted in significant loss of reporter gene expression, suggesting that NF-Y is required to activate the cholesterol response.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-03

    Highlights: •HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. •HBXIP serves as a coactivator of activating transcription factor Sp1. •HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. •HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-κB (NF-κB) 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-κB 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.

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

    Science.gov (United States)

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

    2013-01-01

    GDP-fucose transporter plays a crucial role in fucosylation of glycoproteins by providing activated fucose donor, GDP-fucose, for fucosyltransferases in the lumen of the Golgi apparatus. Fucose-containing glycans are involved in many biological processes, which are essential for growth and development. Mutations in the GDP-fucose transporter gene cause leukocyte adhesion deficiency syndrome II, a disease characterized by slow growth, mental retardation and immunodeficiency. However, no information is available regarding its transcriptional regulation. Here, by using human cells, we show that TGF-β1 specifically induces the GDP-fucose transporter expression, but not other transporters tested such as CMP-sialic acid transporter, suggesting a diversity of regulatory pathways for the expression of these transporters. The regulatory elements that are responsive to the TGF-β1 stimulation are present in the region between bp -330 and -268 in the GDP-fucose transporter promoter. We found that this region contains two identical octamer GC-rich motifs (GGGGCGTG) that were demonstrated to be essential for the transporter expression. We also show that the transcription factor Sp1 specifically binds to the GC-rich motifs in vitro and Sp1 coupled with phospho-Smad2 is associated with the promoter region covering the Sp1-binding motifs in vivo using chromatin immunoprecipitation (ChIP) assays. In addition, we further confirmed that Sp1 is essential for the GDP-fucose transporter expression stimulated by TGF-β1 using a luciferase reporter system. These results highlight the role of TGF-β signaling in regulation of the GDP-fucose transporter expression via activating Sp1. This is the first transcriptional study for any nucleotide sugar transporters that have been identified so far. Notably, TGF-β1 receptor itself is known to be modified by fucosylation. Given the essential role of GDP-fucose transporter in fucosylation, the finding that TGF-β1 stimulates the expression of

  7. Repression of Human T-lymphotropic virus type 1 Long Terminal Repeat sense transcription by Sp1 recruitment to novel Sp1 binding sites

    Science.gov (United States)

    Fauquenoy, Sylvain; Robette, Gwenaëlle; Kula, Anna; Vanhulle, Caroline; Bouchat, Sophie; Delacourt, Nadège; Rodari, Anthony; Marban, Céline; Schwartz, Christian; Burny, Arsène; Rohr, Olivier; Van Driessche, Benoit; Van Lint, Carine

    2017-01-01

    Human T-lymphotropic Virus type 1 (HTLV-1) infection is characterized by viral latency in the majority of infected cells and by the absence of viremia. These features are thought to be due to the repression of viral sense transcription in vivo. Here, our in silico analysis of the HTLV-1 Long Terminal Repeat (LTR) promoter nucleotide sequence revealed, in addition to the four Sp1 binding sites previously identified, the presence of two additional potential Sp1 sites within the R region. We demonstrated that the Sp1 and Sp3 transcription factors bound in vitro to these two sites and compared the binding affinity for Sp1 of all six different HTLV-1 Sp1 sites. By chromatin immunoprecipitation experiments, we showed Sp1 recruitment in vivo to the newly identified Sp1 sites. We demonstrated in the nucleosomal context of an episomal reporter vector that the Sp1 sites interfered with both the sense and antisense LTR promoter activities. Interestingly, the Sp1 sites exhibited together a repressor effect on the LTR sense transcriptional activity but had no effect on the LTR antisense activity. Thus, our results demonstrate the presence of two new functional Sp1 binding sites in the HTLV-1 LTR, which act as negative cis-regulatory elements of sense viral transcription. PMID:28256531

  8. Critical analysis of the potential for the therapeutic targeting of the Sp1 transcription factor in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jutooru I

    2014-06-01

    . This review summarizes the role of Sp1 in pancreatic cancer and delineates the mechanisms of action of various drugs that downregulate expression of Sp1 and other Sp transcription factors.Keywords: Sp transcription factors, microRNAs, ZBTB repressors, ROS

  9. REDOX-SENSITIVE TRANSCRIPTION FACTORS EGR-1 AND SP1 IN THE PATHOGENESIS OF EXPERIMENTAL GASTRIC ULCER.

    Science.gov (United States)

    Beregovyi, S M; Chervinska, T M; Dranitsina, A S; Szabo, S; Tolstanova, G M

    2015-01-01

    Changes in redox status of gastric mucosa cells are the main pathogenic factor of gastric erosion and gastric ulcer development. Pro-oxidants can affect cell transcription activity via changes in redox-sensitive transcription factors. Egr-1 and Sp-1 may regulate the transcription of genes that are associated with the pathogenesis of gastric ulcer (growthfactors, cell cycle regulators, etc.). The aim of the present study was to reveal the possible involvement of zinc-finger transcriptionfactors Egr-1 & Sp-1 in the molecular mechanisms underlying gastric lesions caused by aspirin administration and stress. Gastric ulcer was induced in male rats (180-220 g) by immobilization stress combined with water-immersion (IMO-WI) or aspirin gavage (10 mg/100 g). The rats were euthanized 20 min, 1 hour, or 3 hours following the ulcerogenic factor exposure. Protein expression was determined by Western blot analysis and RT-PCR; levels of SH-groups of proteins were determined by method of Ellman et al. Development of gastric ulcer lesions was associated with twofold (P gastric mucosa. These changes were accompanied by significant (P gastric ulcer models, and the changes in IMO-WI were more profound. Increased levels of Egr-1 were associated with the decrease in SpI protein levels. We showed for the first time the competitive interaction between redox-sensitive transcription factors Egr-1 and Sp1 in the early phases of gastric ulcer development, which might facilitate inducible transcriptional activity of Egr-1 at the expense of reduction in Sp1 activity.

  10. Unique aspects of transcriptional regulation in neurons – nuances in NFκB and Sp1-related factors

    Directory of Open Access Journals (Sweden)

    Chen Yuzhi

    2009-05-01

    Full Text Available Abstract The unique physiology and function of neurons create differences in their cellular physiology, including their regulation of gene expression. We began several years ago exploring the relationships between the NFκB transcription factor, neuronal survival, and glutamate receptor activation in telencephalic neurons. These studies led us to conclude that this population of cells is nearly incapable of activating the NFκB that is nonetheless expressed at reasonable levels. A subset of the κB cis elements are instead bound by members of the Sp1 family in neurons. Also surprising was our discovery that Sp1 itself, typically described as ubiquitous, is severely restricted in expression within forebrain neurons; Sp4 seems to be substituted during neuronal differentiation. These findings and their implications for neuronal differentiation – as well as potential dedifferentiation during degenerative processes – are discussed here.

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

    Directory of Open Access Journals (Sweden)

    Schlumberger Martin

    2002-12-01

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

  12. Inhibition of the transcription factor Sp1 suppresses colon cancer stem cell growth and induces apoptosis in vitro and in nude mouse xenografts.

    Science.gov (United States)

    Zhao, Yingying; Zhang, Wenjing; Guo, Zheng; Ma, Feng; Wu, Yao; Bai, Yang; Gong, Wei; Chen, Ye; Cheng, Tianming; Zhi, Fachao; Zhang, Yali; Wang, Jide; Jiang, Bo

    2013-10-01

    The transcription factor specificity protein 1 (Sp1) plays a role in the development and progression of various types of human cancers, while cancer stem cells (CSCs) are important in cancer cell self-renewal, resistance to chemotherapy and metastatic potential. This study investigated the role of Sp1 in colon CSC growth and apoptosis. Colon CSCs were successfully enriched using special culture medium and identified by typical CSC gene expression. In a quiescent state, these CSCs formed spheres with slow proliferation; overexpressed Sp1, CD44, CD166 and CD133 proteins; upregulated mesenchymal markers; and a downregulated epithelial marker were noted. In ex vivo experiments, the Sp1 protein was expressed in 74.8% of colon cancer tissues, whereas it was expressed only in 42.2% of the distant normal colon mucosae. Furthermore, inhibition of SP1 expression using Sp1 siRNA or mithramycin A (MIT) led to marked suppression of CSC growth and induced apoptosis. In addition, the percentage of CD44+/CD166+ cells was significantly downregulated both in vivo and in vitro following Sp1 inhibition. In conclusion, Sp1 suppression attenuated the characteristics of colon CSCs. Thus, Sp1 inhibition may be potentially useful for the future development of a novel therapeutic strategy to control colon cancer.

  13. Regulation of Neph3 gene in podocytes - key roles of transcription factors NF-kappaB and Sp1

    LENUS (Irish Health Repository)

    Ristola, Mervi

    2009-08-24

    Abstract 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-κB and Sp1 were found by computational analysis. Mutational screening indicated that NF-κB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-κB and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-κB increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-κB and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-κB and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight

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

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada); Babiuk, Lorne A. [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)

    2010-11-19

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

  15. Differential control of Notch1 gene transcription by Klf4 and Sp3 transcription factors in normal versus cancer-derived keratinocytes.

    Directory of Open Access Journals (Sweden)

    Chiara Lambertini

    Full Text Available In specific cell types like keratinocytes, Notch signaling plays an important pro-differentiation and tumor suppressing function, with down-modulation of the Notch1 gene being associated with cancer development. Besides being controlled by p53, little else is known on regulation of Notch1 gene expression in this context. We report here that transcription of this gene is driven by a TATA-less "sharp peak" promoter and that the minimal functional region of this promoter, which extends from the -342 bp position to the initiation codon, is differentially active in normal versus cancer cells. This GC rich region lacks p53 binding sites, but binds Klf4 and Sp3. This finding is likely to be of biological significance, as Klf4 and, to a lesser extent, Sp3 are up-regulated in a number of cancer cells where Notch1 expression is down-modulated, and Klf4 over-expression in normal cells is sufficient to down-modulate Notch1 gene transcription. The combined knock-down of Klf4 and Sp3 was necessary for the reverse effect of increasing Notch1 transcription, consistent with the two factors exerting an overlapping repressor function through their binding to the Notch1 promoter.

  16. Antitumorigenic effect of atmospheric-pressure dielectric barrier discharge on human colorectal cancer cells via regulation of Sp1 transcription factor

    Science.gov (United States)

    Han, Duksun; Cho, Jin Hyoung; Lee, Ra Ham; Bang, Woong; Park, Kyungho; Kim, Minseok S.; Shim, Jung-Hyun; Chae, Jung-Il; Moon, Se Youn

    2017-02-01

    Human colorectal cancer cell lines (HT29 and HCT116) were exposed to dielectric barrier discharge (DBD) plasma at atmospheric pressure to investigate the anticancer capacity of the plasma. The dose- and time-dependent effects of DBDP on cell viability, regulation of transcription factor Sp1, cell-cycle analysis, and colony formation were investigated by means of MTS assay, DAPI staining, propidium iodide staining, annexin V-FITC staining, Western blot analysis, RT-PCR analysis, fluorescence microscopy, and anchorage-independent cell transformation assay. By increasing the duration of plasma dose times, significant reductions in the levels of both Sp1 protein and Sp1 mRNA were observed in both cell lines. Also, expression of negative regulators related to the cell cycle (such as p53, p21, and p27) was increased and of the positive regulator cyclin D1 was decreased, indicating that the plasma treatment led to apoptosis and cell-cycle arrest. In addition, the sizes and quantities of colony formation were significantly suppressed even though two cancer promoters, such as TPA and epidermal growth factor, accompanied the plasma treatment. Thus, plasma treatment inhibited cell viability and colony formation by suppressing Sp1, which induced apoptosis and cell-cycle arrest in these two human colorectal cancer cell lines.

  17. Mechanism of regulation of FGFR4 gene expression by transcription factor Sp1 in human infant rhabdomyosarcomas%转录因子Sp1调节儿童横纹肌肉瘤成纤维细胞生长因子基因表达的机制

    Institute of Scientific and Technical Information of China (English)

    于顺江; 陈力; 陈怡东; 王京

    2011-01-01

    Objective To investigate the role of transcription factor Sp1 in the fibroblast growth factor receptor 4 (FGFR4) expression regulation and to obtain insight into the regulatory mechanisms goveming FGFR4 gene regulation and overexpression in human infant rhabdomyosarcomas. Methods By using a series of cellular and molecular biology methods like transfection, Northern blotting, Western blotting etc., the mRNA and protein expression of FGFR4 was detected. The regulatory effects of Sp1 on the FGFR4 expression in the human rhabdomyosarcoma-derived cells were analyzed. Results Sp1 could be express highly in the human rhabdomyosarcoma-derived cells, and its binding to FGFR4 promoter could upregulate the FGFR4 expression, which was influenced by the methylation of FGFR4 promoter. Conclusion Sp1 induces the expression of FGFR4 in human infant rhabdomyosarcomas by directly binding of Sp1 with DNA cis elements in FGFR4 gene promoter region.%目的 探讨转录因子Sp1调节儿童横纹肌肉瘤成纤维细胞生长因子受体4(FGFR4)基因表达的作用及其调节的分子机制.方法 应用细胞及分子生物学技术如细胞转染、RNA和蛋白质印迹等方法检测2种不同横纹肌肉瘤细胞株中的FGFR4 mRNA和蛋白的表达,观察Sp1对FG-FR4表达的调节作用,探讨Sp1凋节FGFR4基因表达的机制.结果 Sp1在儿童横纹肌肉瘤中可高度表达,Sp1与FGFR4启动区结合并上调了FGFR4的表达.Sp1的这一调节作用不受FGFR4启动区甲基化作用的影响.结论 Sp1促进FGFR4在儿童横纹肌肉瘤细胞中的表达,该作用可能是通过Sp1与FGFR4启动区的顺式元件直接结合而实现的.

  18. Role of transcription factor Sp1 in the quercetin-mediated inhibitory effect on human malignant pleural mesothelioma.

    Science.gov (United States)

    Chae, Jung-Il; Cho, Jin Hyoung; Lee, Kyung-Ae; Choi, Nag-Jin; Seo, Kang Seok; Kim, Sang-Bum; Lee, Sang-Han; Shim, Jung-Hyun

    2012-10-01

    Quercetin (Qu) is found in plants, including red onions and in the skins of red apples, and induces the apoptosis of certain malignant cells. However, no report has been issued on the apoptotic effect of Qu on human malignant pleural mesothelioma. In the present study, it was found that MSTO-211H mesothelioma cell viability was reduced and apoptotic cell death was increased by Qu (20-80 µM), which was found to have an IC₅₀ of 58 µM. In addition, Qu increased the sub-G₁ cell population, and was found to interact with specificity protein 1 (Sp1) and significantly suppressed its expression at the protein and mRNA levels. Furthermore, Qu modulated the levels of Sp1 regulatory genes, such as cyclin D1, myeloid cell leukemia (Mcl)-1 and survivin in MSTO-211H cells. Apoptotic signaling cascades were activated by the cleavage of Bid, caspase-3 and PARP, and by the downregulation of Bcl-xL and the upregulation of Bax in MSTO-211H cells. Our results strongly suggest that Sp1 be considered as a novel molecular target of Qu in human malignant pleural mesothelioma.

  19. Starvation after Cobalt-60 γ-Ray Radiation Enhances Metastasis in U251 Glioma Cells by Regulating the Transcription Factor SP1.

    Science.gov (United States)

    Zhao, Tuo; Wang, Hailong; Ma, Hong; Wang, Hao; Chen, Bo; Deng, Yulin

    2016-04-05

    Radiation is of clinical importance during glioma therapy; however, vasculature damage is observed over the treatment course. This type of tissue damage might lead to starvation conditions, affecting tumor metastasis. To test this possibility, we compared starvation conditions in conjunction with radiation treatment to monitor metastatic ability in the U251 glioma cell line. Transcriptome, western blot, and immunofluorescence analyses were used to measure the RNA and protein expression changes of the U251 cells after various treatments. We found that starvation combined with radiation treatment yielded the most significant expression changes in metastasis-related factors compared to that in the control groups. In addition, a metastasis assay was used to directly measure the metastatic ability of the treated cells, which confirmed that the U251 cells treated with starvation combined with radiation possessed the highest metastatic ability. Furthermore, bioinformatics analysis demonstrated that SP1 represented a common transcription factor associated with changes in metastasis-related factors. Blocking SP1 activity by an inhibitor suppressed the starvation-plus-radiation treatment-mediated enhancement of U251 cell metastasis. Our study provides the first evidence that starvation caused by radiation might play a significant role in enhancing the ability of the glioma cell line U251 to metastasize via regulation of the transcription factor SP1.

  20. Starvation after Cobalt-60 γ-Ray Radiation Enhances Metastasis in U251 Glioma Cells by Regulating the Transcription Factor SP1

    Directory of Open Access Journals (Sweden)

    Tuo Zhao

    2016-04-01

    Full Text Available Radiation is of clinical importance during glioma therapy; however, vasculature damage is observed over the treatment course. This type of tissue damage might lead to starvation conditions, affecting tumor metastasis. To test this possibility, we compared starvation conditions in conjunction with radiation treatment to monitor metastatic ability in the U251 glioma cell line. Transcriptome, western blot, and immunofluorescence analyses were used to measure the RNA and protein expression changes of the U251 cells after various treatments. We found that starvation combined with radiation treatment yielded the most significant expression changes in metastasis-related factors compared to that in the control groups. In addition, a metastasis assay was used to directly measure the metastatic ability of the treated cells, which confirmed that the U251 cells treated with starvation combined with radiation possessed the highest metastatic ability. Furthermore, bioinformatics analysis demonstrated that SP1 represented a common transcription factor associated with changes in metastasis-related factors. Blocking SP1 activity by an inhibitor suppressed the starvation-plus-radiation treatment-mediated enhancement of U251 cell metastasis. Our study provides the first evidence that starvation caused by radiation might play a significant role in enhancing the ability of the glioma cell line U251 to metastasize via regulation of the transcription factor SP1.

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

    Science.gov (United States)

    Bikbova, Guzel; Oshitari, Toshiyuki; Baba, Takayuki; Yamamoto, Shuichi

    2015-01-01

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

  2. Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by sp1 binding factors

    DEFF Research Database (Denmark)

    Heegaard, Anne-Marie; Xie, Zhongjian; Young, Marian Frances;

    2004-01-01

    Biglycan is a small leucine-rich proteoglycan which is localized in the extracellular matrix of bone and other specialized connective tissues. Both biglycan mRNA and protein are up-regulated by transforming growth factor-beta(1) (TGF-beta(1)) and biglycan appears to influence TGF-beta(1) activity...

  3. Transcription factors Sp1 and p73 control the expression of the proapoptotic protein NOXA in the response of testicular embryonal carcinoma cells to cisplatin.

    Science.gov (United States)

    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

    2012-08-03

    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 ΔNp73, 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.

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

    Directory of Open Access Journals (Sweden)

    Guzel Bikbova

    2015-01-01

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

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

    Science.gov (United States)

    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

    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.

  6. Qualitatively monitoring binding and expression of the transcription factor Sp1 as a useful tool to evaluate the reliability of primary cultured epithelial stem cells in tissue reconstruction.

    Science.gov (United States)

    Gaudreault, Manon; Larouche, Danielle; Germain, Lucie; Guérin, Sylvain L

    2013-01-01

    Electrophoretic mobility shift assay and Western blot are simple, efficient, and rapid methods for the study of DNA-protein interactions and expression, respectively. Primary cultures and subcultures of epithelial cells are widely used for the production of tissue-engineered substitutes and are gaining popularity as a model for gene expression studies. The preservation of stem-cells through the culture process is essential to produce high quality substitutes. However as such cells are passaged in culture, they often lose their ability to proliferate, a process likely to be determined by the altered expression of nuclear-located transcription factors such as Sp1, whose expression has been documented to be required for cell adhesion, migration, and differentiation. Our recent studies demonstrated that reconstructed tissues exhibiting poor histological and structural characteristics are also those that were produced with epithelial cells in which expression and DNA binding of Sp1 was reduced in vitro. Therefore, monitoring both the expression and DNA binding of this transcription factor in human skin and corneal epithelial cells might prove a particularly useful tool for selecting which cells are to be used for tissue reconstruction.

  7. Transcription of human resistin gene involves an interaction of Sp1 with peroxisome proliferator-activating receptor gamma (PPARgamma.

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    Anil K Singh

    Full Text Available BACKGROUND: Resistin is a cysteine rich protein, mainly expressed and secreted by circulating human mononuclear cells. While several factors responsible for transcription of mouse resistin gene have been identified, not much is known about the factors responsible for the differential expression of human resistin. METHODOLOGY/PRINCIPAL FINDING: We show that the minimal promoter of human resistin lies within approximately 80 bp sequence upstream of the transcriptional start site (-240 whereas binding sites for cRel, CCAAT enhancer binding protein alpha (C/EBP-alpha, activating transcription factor 2 (ATF-2 and activator protein 1 (AP-1 transcription factors, important for induced expression, are present within sequences up to -619. Specificity Protein 1(Sp1 binding site (-276 to -295 is also present and an interaction of Sp1 with peroxisome proliferator activating receptor gamma (PPARgamma is necessary for constitutive expression in U937 cells. Indeed co-immunoprecipitation assay demonstrated a direct physical interaction of Sp1 with PPARgamma in whole cell extracts of U937 cells. Phorbol myristate acetate (PMA upregulated the expression of resistin mRNA in U937 cells by increasing the recruitment of Sp1, ATF-2 and PPARgamma on the resistin gene promoter. Furthermore, PMA stimulation of U937 cells resulted in the disruption of Sp1 and PPARgamma interaction. Chromatin immunoprecipitation (ChIP assay confirmed the recruitment of transcription factors phospho ATF-2, Sp1, Sp3, PPARgamma, chromatin modifier histone deacetylase 1 (HDAC1 and the acetylated form of histone H3 but not cRel, C/EBP-alpha and phospho c-Jun during resistin gene transcription. CONCLUSION: Our findings suggest a complex interplay of Sp1 and PPARgamma along with other transcription factors that drives the expression of resistin in human monocytic U937 cells.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kai-Wei [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); Wong, Zong-Ruei; Su, Peng-Han [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); Ju, Tsai-Kai [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)

    2013-05-17

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

  9. Sp1 is essential for p16 expression in human diploid fibroblasts during senescence.

    Directory of Open Access Journals (Sweden)

    Junfeng Wu

    Full Text Available BACKGROUND: p16(INK4a tumor suppressor protein has been widely proposed to mediate entrance of the cells into the senescent stage. Promoter of p16(INK4a gene contains at least five putative GC boxes, named GC-I to V, respectively. Our previous data showed that a potential Sp1 binding site, within the promoter region from -466 to -451, acts as a positive transcription regulatory element. These results led us to examine how Sp1 and/or Sp3 act on these GC boxes during aging in cultured human diploid fibroblasts. METHODOLOGY/PRINCIPAL FINDINGS: Mutagenesis studies revealed that GC-I, II and IV, especially GC-II, are essential for p16(INK4a gene expression in senescent cells. Electrophoretic mobility shift assays (EMSA and ChIP assays demonstrated that both Sp1 and Sp3 bind to these elements and the binding activity is enhanced in senescent cells. Ectopic overexpression of Sp1, but not Sp3, induced the transcription of p16(INK4a. Both Sp1 RNAi and Mithramycin, a DNA intercalating agent that interferes with Sp1 and Sp3 binding activities, reduced p16(INK4a gene expression. In addition, the enhanced binding of Sp1 to p16(INK4a promoter during cellular senescence appeared to be the result of increased Sp1 binding affinity, not an alteration in Sp1 protein level. CONCLUSIONS/SIGNIFICANCE: All these results suggest that GC- II is the key site for Sp1 binding and increase of Sp1 binding activity rather than protein levels contributes to the induction of p16(INK4a expression during cell aging.

  10. TGF-β1 induction of the adenine nucleotide translocator 1 in astrocytes occurs through Smads and Sp1 transcription factors

    Directory of Open Access Journals (Sweden)

    Wallace Douglas C

    2004-01-01

    Full Text Available Abstract Background The adenine nucleotide translocator 1 (Ant1 is an inner mitochondrial membrane protein involved with energy mobilization during oxidative phosphorylation. We recently showed that rodent Ant1 is upregulated by transforming growth factor-beta (TGF-β in reactive astrocytes following CNS injury. In the present study, we describe the molecular mechanisms by which TGF-β1 regulates Ant1 gene expression in cultured primary rodent astrocytes. Results Transcription reporter analysis verified that TGF-β1 regulates transcription of the mouse Ant1 gene, but not the gene encoding the closely related Ant2 isoform. A 69 basepair TGF-β1 responsive element of the Ant1 promoter was also identified. Electrophoretic mobility shift assays demonstrated that astrocyte nuclear proteins bind to this response element and TGF-β1 treatment recruits additional nuclear protein binding to this element. Antibody supershift and promoter deletion analyses demonstrated that Sp1 consensus binding sites in the RE are important for TGF-β1 regulation of Ant1 in astrocytes. Additionally, we demonstrate that Smad 2, 3 and 4 transcription factors are expressed in injured cerebral cortex and in primary astrocyte cultures. TGF-β1 activated Smad transcription factors also contribute to Ant1 regulation since transcription reporter assays in the presence of dominant negative (DN-Smads 3 and 4 significantly reduced induction of Ant1 by TGF-β1. Conclusion The specific regulation of Ant1 by TGF-β1 in astrocytes involves a cooperative interaction of both Smad and Sp1 binding elements located immediately upstream of the transcriptional start site. The first report of expression of Smads 2, 3 and 4 in astrocytes provided here is consistent with a regulation of Ant1 gene expression by these transcription factors in reactive astrocytes. Given the similarity in TGF-β1 regulation of Ant1 with other genes that are thought to promote neuronal survival, this interaction may

  11. Transcription Factors Ets2 and Sp1 Act Synergistically with Histone Acetyltransferase p300 in Activating Human Interleukin-12 p40 Promoter

    Institute of Scientific and Technical Information of China (English)

    Hai-Jing SUN; Xin XU; Xiu-Li WANG; Liang WEI; Fen LI; Jun LU; Bai-Qu HUANG

    2006-01-01

    There has been considerable interest in researching the regulatory mechanisms that control the synthesis of interleukin (IL)-12, which plays a central role in the differentiation of T-helper-1 cells. In this study, we performed a series of transient transfection experiments designed to elucidate the functional relationship between the IL-12 promoter-specific transcription factors (Ets2 and Spl) and histone acetylation modification in IL-12 regulation mediated by p300 and various histone deacetylases (HDACs). Results presented in this report demonstrated that the transcription factors Ets2 and Spl acted synergistically with p300to activate the human IL-12 promoter. The histone acetyltransferase (HAT) activity of p300 was required for this synergic effect, because the adenovirus E1A protein inhibited the synergy. Conversely, HDACs repressed the synergic effect of transcription factors and histone acetylation on the activation of IL-12, while p300 was able to rectify it. These data indicated that Ets2 and Sp1 worked concertedly and synergistically with p300 in the regulation of human IL-12 expression.

  12. A functional polymorphism in the Eta-1 promoter is associated with allele specific binding to the transcription factor Sp1 and elevated gene expression

    DEFF Research Database (Denmark)

    Hummelshoj, Tina; Ryder, Lars P; Madsen, Hans O

    2005-01-01

    Early T lymphocyte activator 1 (Eta-1), also known as Osteopontin, is a cytokine produced by macrophages and T lymphocytes. It is involved in the regulation of IL-12 and IL-10 expression in macrophages and stimulates the polarization of T cells to the Th1 subset. Three promoter polymorphisms...... of the human Eta-1 gene, -443T/C, -156delG/G, -66T/G, were investigated for possible influence on gene expression. Electrophoretic mobility shift assays (EMSA) with nuclear extract from the human myeloid leukaemia premonocyte cell line, THP-1, revealed sequence specific binding of the transcription factor Sp1...... to the -66T allele but not the -66G allele, and haplotype -443C/-156G/-66T showed a marked increase in promoter activity of a luciferase reporter gene. Thus, a substitution of the T-base with G at position -66 in the Eta-1 promoter modulates the promoter activity of the Eta-1 gene, which might influence...

  13. Constitutive Fas ligand gene transcription in Sertoli cells is regulated by Sp1.

    Science.gov (United States)

    McClure, R F; Heppelmann, C J; Paya, C V

    1999-03-19

    The transcriptional regulation of the Fas ligand (FasL) gene in Sertoli cells was investigated, as these cells are known to have constitutive expression of FasL and hence maintain an "immune privileged" environment within the testicle. Using the Sertoli cell line TM4, it was demonstrated that a gene segment of the 5'-untranslated region located between -318 and -237 relative to the translation start site is required for constitutive FasL transcription. Deletion and mutation analysis demonstrate that an Sp1 rather than an NFAT or NFKB-like DNA binding motif present within this region is necessary and sufficient for constitutive FasL gene transcription. Nuclear extracts of Sertoli cells contain Sp1 and Sp3 that specifically binds to the Sp1 motif present in the FasL gene, and overexpression of Sp1 but not Sp3 leads to a further increase of transcription from the FasL promoter-enhancer region. The data presented demonstrates that constitutive FasL gene transcription in Sertoli cells is regulated by Sp1. In addition, it is shown that basal FasL expression in Jurkat T cells is also controlled by Sp1 and this is in contrast to induced FasL expression, which is NFAT-dependent.

  14. Levels of [(3)H]pirenzepine binding in Brodmann's area 6 from subjects with schizophrenia is not associated with changes in the transcription factor SP1 or BACE1.

    Science.gov (United States)

    Dean, Brian; Soulby, Andrew; Evin, Geneviève M; Scarr, Elizabeth

    2008-12-01

    Decreased muscarinic M1 receptor (CHRM1) mRNA has been reported in Brodmann's area (BA) 6 from subjects with schizophrenia. We have extended this study by measuring levels of CHRM1 ([(3)H]pirenzepine binding), CHRM3 ([(3)H]4-DAMP binding), the transcription factor SP1 and the CHRM1 downstream target beta-site APP-cleaving enzyme 1 (BACE1) in BA 6 from 19 subjects with schizophrenia and 19 control subjects. Radioligand binding was quantified using either in situ radioligand binding with autoradiography or, in cohorts of 10 control subjects and 10 subjects with schizophrenia, membrane enriched fraction (MEF) CNS ([(3)H]pirenzepine binding only). Levels of SP1 and BACE1 were measured by Western blotting. [(3)H]pirenzepine binding to tissue sections was in two layers, binding to tissue sections (Binding layer 1: p<0.01; Binding layer 2: p<0.001) and MEF (p<0.05) were decreased in schizophrenia. Levels of [(3)H]4-DAMP binding, SP1 and BACE1 were not altered in subjects with the disorder. This study shows a decrease in levels of CHRM1 in BA 6 from subjects with schizophrenia; as CHRM1 and BA 6 are important in maintaining normal cognitive function, these data support the hypothesis that decreased levels of cortical CHRM1 may contribute to the cognitive deficits associated with schizophrenia. Our findings on BACE1 suggest that the schizophrenia phenotype reported in BACE(-/-) mice is not simply due to lack of that protein in the cortex.

  15. Metallaphotoredox-catalysed sp3-sp3 cross-coupling of carboxylic acids with alkyl halides

    Science.gov (United States)

    Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.

    2016-08-01

    In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp3-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3-sp3 bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp3-sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp3-sp3 coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3-sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for

  16. Differential effects of Sp cellular transcription factors on viral promoter activation by varicella-zoster virus (VZV) IE62 protein.

    Science.gov (United States)

    Khalil, Mohamed I; Ruyechan, William T; Hay, John; Arvin, Ann

    2015-11-01

    The immediate early (IE) 62 protein is the major varicella-zoster virus (VZV) regulatory factor. Analysis of the VZV genome revealed 40 predicted GC-rich boxes within 36 promoters. We examined effects of ectopic expression of Sp1-Sp4 on IE62- mediated transactivation of three viral promoters. Ectopic expression of Sp3 and Sp4 enhanced IE62 activation of ORF3 and gI promoters while Sp3 reduced IE62 activation of ORF28/29 promoter and VZV DNA replication. Sp2 reduced IE62 transactivation of gI while Sp1 had no significant influence on IE62 activation with any of these viral promoters. Electrophoretic mobility shift assays (EMSA) confirmed binding of Sp1 and Sp3 but not Sp2 and Sp4 to the gI promoter. Sp1-4 bound to IE62 and amino acids 238-258 of IE62 were important for the interaction with Sp3 and Sp4 as well as Sp1. This work shows that Sp family members have differential effects on IE62-mediated transactivation in a promoter-dependent manner.

  17. Physical and functional interactions between USF and Sp1 proteins regulate human deoxycytidine kinase promoter activity.

    Science.gov (United States)

    Ge, Yubin; Jensen, Tanya L; Matherly, Larry H; Taub, Jeffrey W

    2003-12-12

    Deoxycytidine kinase (EC 2.7.1.74, dCK) is central to drug activity of anticancer and antiviral agents such as cytosine arabinoside (araC) and gemcitabine. HepG2 hepatocellular carcinoma cells were used to study the transcriptional regulation of dCK. 5'-Deletion and site-directed mutagenesis of the dCK upstream region (positions -464 to -27) confirmed the importance of two GC-boxes (positions -317 to -309 and -213 to -206) and two E-boxes (positions -302 to -297 and -278 to -273). In vitro electromobility shift assays with HepG2 nuclear extracts and in vivo chromatin immunoprecipitation assays with HepG2 chromatin extracts confirmed the presence of bound Sp1/Sp3 and USF1/2. Co-transfections in HepG2 cells showed that USF1 and USF2a stimulated and Sp1 repressed promoter activity from a dCK-luciferase reporter gene construct. In Sp- and USF-null Drosophila Mel-2 cells, both Sp1 and USF1 stimulated dCK promoter activity in a dose-dependent manner, however, both Sp3 and USF2a were effectively inert. Combined Sp1 and USF1 showed additive transactivation at lower concentrations of Sp1. Sp1 was inhibitory at higher levels. Stimulation by combined USF1/USF2a with Sp1 was similar to that for USF1 alone with Sp1, whereas transactivation by Sp1 and USF2a without USF1 was synergistic. Physical interactions between USF and Sp proteins were confirmed by immunoprecipitations with Sp- and USF-specific antibodies. Domain mapping of USF1 and USF2a localized the functional interactions between USF and Sp proteins to the DNA binding domain of USF. Identifying the physical and functional interactions between Sp and USF proteins may lead to a better understanding of the basis for differential expression of the dCK gene in tumor cells and may foster strategies for up-regulating dCK gene expression and improving chemotherapy with araC and gemcitabine.

  18. Inhibition of Sp1 functions by its sequestration into PML nuclear bodies.

    Directory of Open Access Journals (Sweden)

    June Li

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

  19. Sp1 facilitates DNA double-strand break repair through a nontranscriptional mechanism.

    Science.gov (United States)

    Beishline, Kate; Kelly, Crystal M; Olofsson, Beatrix A; Koduri, Sravanthi; Emrich, Jacqueline; Greenberg, Roger A; Azizkhan-Clifford, Jane

    2012-09-01

    Sp1 is a ubiquitously expressed transcription factor that is phosphorylated by ataxia telangiectasia mutated kinase (ATM) in response to ionizing radiation and H(2)O(2). Here, we show by indirect immunofluorescence that Sp1 phosphorylated on serine 101 (pSp1) localizes to ionizing radiation-induced foci with phosphorylated histone variant γH2Ax and members of the MRN (Mre11, Rad50, and Nbs1) complex. More precise analysis of occupancy of DNA double-strand breaks (DSBs) by chromatin immunoprecipitation (ChIP) shows that Sp1, like Nbs1, resides within 200 bp of DSBs. Using laser microirradiation of cells, we demonstrate that pSp1 is present at DNA DSBs by 7.5 min after induction of damage and remains at the break site for at least 8 h. Depletion of Sp1 inhibits repair of site-specific DNA breaks, and the N-terminal 182-amino-acid peptide, which contains targets of ATM kinase but lacks the zinc finger DNA binding domain, is phosphorylated, localizes to DSBs, and rescues the repair defect resulting from Sp1 depletion. Together, these data demonstrate that Sp1 is rapidly recruited to the region immediately adjacent to sites of DNA DSBs and is required for DSB repair, through a mechanism independent of its sequence-directed transcriptional effects.

  20. Sulindac sulfide inhibits colon cancer cell growth and downregulates specificity protein transcription factors

    OpenAIRE

    Li, Xi; Pathi, Satya S.; Safe, Stephen

    2015-01-01

    Background Specificity protein (Sp) transcription factors play pivotal roles in maintaining the phenotypes of many cancers. We hypothesized that the antineoplastic effects of sulindac and its metabolites were due, in part, to targeting downregulation of Sp transcription factors. Methods The functional effects of sulindac, sulindac sulfone and sulindac sulfide on colon cancer cell proliferation were determined by cell counting. Effects of these compounds on expression of Sp1, Sp3, Sp4 and pro-...

  1. Medium Optimization of Tetraselmis sp.-1 Using Response Surface Methodology

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Response surface methodology (RSM) is used to optimize the medium of Tetraselmis sp.-1 which is cell fused microalgae capable of growing under mixotrophic condition. Empirical models are developed to describe the relationships between the operating variables (glucose, urea, sodium dehydrogenate phosphate, sodium chloride) and responses (cell density). Statistical analysis indicates that glucose and urea have significant effects on the microalgae cell density, but other two factors (sodium dehydrogenate phosphate, sodium chloride) have no obvious effect. The path of steepest ascent is used to approach the optimal region of medium composition. Optimal cell density (2.638 g dry weight/L) was reached when the operating conditions were glucose concentration (30.75 %), urea concentration (0.440 g/L), sodium dehydrogenate phosphate (15 mg/L) and sodium chloride (28 g/L).

  2. Sp1 and KLF15 regulate basal transcription of the human LRP5 gene

    Directory of Open Access Journals (Sweden)

    Zou Yongxin

    2010-02-01

    Full Text Available Abstract Background LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. However, how the expression of human LRP5 gene is regulated remains unclear. Results In order to characterize the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and -53 bp contribute to the transcriptional activation of human LRP5 promoter. Chromatin immunoprecipitation assay demonstrated that the ubiquitous transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2 cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner dependent on the presence of Sp1-binding and KLF15-binding motifs. Conclusions Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5 promoter. This study provides the first insight into the mechanisms by which transcription of human LRP5 gene is regulated.

  3. Mixotrophic Cultivation of Tetraselmis sp.-1 in Airlift Photobioreactor

    Institute of Scientific and Technical Information of China (English)

    Shen Jihong(沈继红); Yu Junhong; Lin Xuezheng; Li Guangyou; Liu Fayi

    2003-01-01

    Tetraselmis sp.-1 is a new microalgae strain constructed by cell fusion technique. In this paper, the mixotrophic cultivation of Tetraselmis sp.-1 in airlift photobioreactor is investigated. Firstly, the paper calculates the light attenuation in the mixotrophic medium, and sets the light attenuation model. Secondly, it uses the same dissolved oxygen coefficient (Kd) of flask culture to select the aeration of bioreactor. Finally, it sets the growth kinetic model, production (chlorophyll-a and total lipid) kinetic models and substrate (glucose) consumption kinetic model of Tetraselmis sp.-1 in airlift photobioreactor.

  4. Silver-Catalyzed C(sp(3))-H Chlorination.

    Science.gov (United States)

    Ozawa, Jun; Kanai, Motomu

    2017-03-17

    A silver-catalyzed chlorination of benzylic, tertiary, and secondary C(sp(3))-H bonds was developed. The reaction proceeded with as low as 0.2 mol % catalyst loading at room temperature under air atmosphere with synthetically useful functional group compatibility. The regioselectivity and reactivity tendencies suggest that the chlorination proceeded through a radical pathway, but an intermediate alkylsilver species cannot be ruled out.

  5. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

    Directory of Open Access Journals (Sweden)

    Pathi Satya

    2011-08-01

    Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

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

    LENUS (Irish Health Repository)

    Yu, Hoi-Tin

    2010-03-01

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

  7. Room temperature organic magnets derived from sp3 functionalized graphene

    Science.gov (United States)

    Tuček, Jiří; Holá, Kateřina; Bourlinos, Athanasios B.; Błoński, Piotr; Bakandritsos, Aristides; Ugolotti, Juri; Dubecký, Matúš; Karlický, František; Ranc, Václav; Čépe, Klára; Otyepka, Michal; Zbořil, Radek

    2017-02-01

    Materials based on metallic elements that have d orbitals and exhibit room temperature magnetism have been known for centuries and applied in a huge range of technologies. Development of room temperature carbon magnets containing exclusively sp orbitals is viewed as great challenge in chemistry, physics, spintronics and materials science. Here we describe a series of room temperature organic magnets prepared by a simple and controllable route based on the substitution of fluorine atoms in fluorographene with hydroxyl groups. Depending on the chemical composition (an F/OH ratio) and sp3 coverage, these new graphene derivatives show room temperature antiferromagnetic ordering, which has never been observed for any sp-based materials. Such 2D magnets undergo a transition to a ferromagnetic state at low temperatures, showing an extraordinarily high magnetic moment. The developed theoretical model addresses the origin of the room temperature magnetism in terms of sp2-conjugated diradical motifs embedded in an sp3 matrix and superexchange interactions via -OH functionalization.

  8. Room temperature organic magnets derived from sp3 functionalized graphene

    Science.gov (United States)

    Tuček, Jiří; Holá, Kateřina; Bourlinos, Athanasios B.; Błoński, Piotr; Bakandritsos, Aristides; Ugolotti, Juri; Dubecký, Matúš; Karlický, František; Ranc, Václav; Čépe, Klára; Otyepka, Michal; Zbořil, Radek

    2017-01-01

    Materials based on metallic elements that have d orbitals and exhibit room temperature magnetism have been known for centuries and applied in a huge range of technologies. Development of room temperature carbon magnets containing exclusively sp orbitals is viewed as great challenge in chemistry, physics, spintronics and materials science. Here we describe a series of room temperature organic magnets prepared by a simple and controllable route based on the substitution of fluorine atoms in fluorographene with hydroxyl groups. Depending on the chemical composition (an F/OH ratio) and sp3 coverage, these new graphene derivatives show room temperature antiferromagnetic ordering, which has never been observed for any sp-based materials. Such 2D magnets undergo a transition to a ferromagnetic state at low temperatures, showing an extraordinarily high magnetic moment. The developed theoretical model addresses the origin of the room temperature magnetism in terms of sp2-conjugated diradical motifs embedded in an sp3 matrix and superexchange interactions via –OH functionalization. PMID:28216636

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

    Science.gov (United States)

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

    2014-12-16

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

  10. Polymorphic phases of sp3-hybridized superhard CN

    Science.gov (United States)

    Wang, Xiaoli

    2012-11-01

    It is well established that carbon nitride (CN) is a potential superhard material as its bond in network structures is slightly shorter than the C-C bond in diamond. However, the structure of superhard CN materials is yet to be determined experimentally. We have performed an extensive structural search for the high pressure crystalline phases of CN using the particle swarm optimization technique; seven low-energy polymorphic structures of sp3-hybridized CN have been found in an unbiased search. Density-functional theory calculations indicate that, among the seven low-energy crystalline structures, Pnnm structure (8 atoms/cell) is energetically more favorable than the previously reported most stable crystalline structure with 1:1 stoichiometry. Furthermore, Pnnm possesses the highest hardness (62.3 GPa). Formation enthalpies demonstrate that this material can be synthesized at pressure 10.9 GPa, lower than needed by β-C3N4 (14.1 GPa).

  11. Imperatorin inhibits HIV-1 replication through an Sp1-dependent pathway.

    Science.gov (United States)

    Sancho, Rocío; Márquez, Nieves; Gómez-Gonzalo, Marta; Calzado, Marco A; Bettoni, Giorgio; Coiras, Maria Teresa; Alcamí, José; López-Cabrera, Manuel; Appendino, Giovanni; Muñoz, Eduardo

    2004-09-03

    Coumarins and structurally related compounds have been recently shown to present anti-human immunodeficiency virus, type 1 (HIV-1) activity. Among them, the dietary furanocoumarin imperatorin is present in citrus fruits, in culinary herbs, and in some medicinal plants. In this study we report that imperatorin inhibits either vesicular stomatitis virus-pseudotyped or gp160-enveloped recombinant HIV-1 infection in several T cell lines and in HeLa cells. These recombinant viruses express luciferase as a marker of viral replication. Imperatorin did not inhibit the reverse transcription nor the integration steps in the viral cell cycle. Using several 5' long terminal repeat-HIV-1 constructs where critical response elements were either deleted or mutated, we found that the transcription factor Sp1 is critical for the inhibitory activity of imperatorin induced by both phorbol 12-myristate 13-acetate and HIV-1 Tat. Moreover in transient transfections imperatorin specifically inhibited phorbol 12-myristate 13-acetate-induced transcriptional activity of the Gal4-Sp1 fusion protein. Since Sp1 is also implicated in cell cycle progression we further studied the effect of imperatorin on cyclin D1 gene transcription and protein expression and in HeLa cell cycle progression. We found that imperatorin strongly inhibited cyclin D1 expression and arrested the cells at the G(1) phase of the cell cycle. These results highlight the potential of Sp1 transcription factor as a target for natural anti-HIV-1 compounds such as furanocoumarins that might have a potential therapeutic role in the management of AIDS.

  12. The Cyclin-dependent Kinase Inhibitor p16INK4a Physically Interacts with Transcription Factor Sp1 and Cyclin-dependent Kinase 4 to Transactivate MicroRNA-141 and MicroRNA-146b-5p Spontaneously and in Response to Ultraviolet Light-induced DNA Damage*

    Science.gov (United States)

    Al-Khalaf, Huda H.; Mohideen, Peer; Nallar, Shreeram C.; Kalvakolanu, Dhananjaya V.; Aboussekhra, Abdelilah

    2013-01-01

    p16INK4a is a tumor suppressor protein involved in several stress-related cellular responses, including apoptosis. Recent lines of evidence indicate that p16INK4a is also a modulator of gene expression. However, the molecular mechanisms underlying this novel function are still obscure. Here, we present clear evidence that p16INK4a modulates the levels of various microRNAs, with marked positive effect on miR-141 and miR-146b-5p. This effect is mediated through the formation of the p16-CDK4-Sp1 heterocomplex, which binds to Sp1 consensus-binding motifs present in the promoters of miR-141 and miR-146b-5p, and it enables their transcription. In addition, we have shown that p16INK4a interacts with Sp1 through the fourth ankyrin repeat, which is crucial for Sp1 binding to the miR-141 and miR-146b-5p promoters and their transcriptional activation. The physiological importance of this association was revealed by the inability of cancer-related p16INK4a mutants to interact with Sp1. Moreover, we have shown p16-CDK4-Sp1-dependent up-regulation of miR-141 and miR-146b-5p following UV light-induced DNA damage and the role of these two microRNAs in mediating p16-related induction of apoptosis in response to this genotoxic stress. Together, these results indicate that p16INK4a associates with CDK4 not only to inhibit the cell cycle but also to enable the transcription of two important onco-microRNAs, which act as downstream effectors. PMID:24163379

  13. Contribution of Sp1 to Telomerase Expression and Activity in Skin Keratinocytes Cultured With a Feeder Layer.

    Science.gov (United States)

    Bisson, Francis; Paquet, Claudie; Bourget, Jean-Michel; Zaniolo, Karine; Rochette, Patrick J; Landreville, Solange; Damour, Odile; Boudreau, François; Auger, François A; Guérin, Sylvain L; Germain, Lucie

    2015-02-01

    The growth of primary keratinocytes is improved by culturing them with a feeder layer. The aim of this study was to assess whether the feeder layer increases the lifespan of cultured epithelial cells by maintaining or improving telomerase activity and expression. The addition of an irradiated fibroblast feeder layer of either human or mouse origin (i3T3) helped maintain telomerase activity as well as expression of the transcription factor Sp1 in cultured keratinocytes. In contrast, senescence occurred earlier, together with a reduction of Sp1 expression and telomerase activity, in keratinocytes cultured without a feeder layer. Telomerase activity was consistently higher in keratinocytes grown on the three different feeder layers tested relative to cells grown without them. Suppression of Sp1 expression by RNA inhibition (RNAi) reduced both telomerase expression and activity in keratinocytes and also abolished their long-term growth capacity suggesting that Sp1 is a key regulator of both telomerase gene expression and cell cycle progression of primary cultured human skin keratinocytes. The results of the present study therefore suggest that the beneficial influence of the feeder layer relies on its ability to preserve telomerase activity in cultured human keratinocytes through the maintenance of stable levels of Sp1 expression. © 2014 Wiley Periodicals, Inc.

  14. A New Empirical Model for Estimation of sp3 Fraction in Diamond-Like Carbon Films

    Institute of Scientific and Technical Information of China (English)

    DAI Hai-Yang; WANG Li-Wu; JIANG Hui; HUANG Ning-Kang

    2007-01-01

    A new empirical model to estimate the content of sp3 in diamond-like carbon (DLC) films is presented, based on the conventional Raman spectra excited by 488nm or 514nm visible light for different carbons. It is found that bandwidth of the G peak is related to the sp3 fraction. A wider bandwidth of the G peak shows a higher sp3 fraction in DLC films.

  15. NF1, Sp1 and HSF1 are synergistically involved in sulfide-induced sqr activation in echiuran worm Urechis unicinctus

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaolong; Qin, Zhenkui; Li, Xueyu; Ma, Xiaoyu; Gao, Beibei; Zhang, Zhifeng, E-mail: zzfp107@ouc.edu.cn

    2016-06-15

    Highlights: • Sulfide activates sqr transcription against respiratory toxicity in Urechis unicinctus. • Sulfide increases expressions and activities of NF1, Sp1 and HSF1 in a time-dependent manner. • NF1 and Sp1 participate in both basal and early sulfide-induced sqr transcription. • HSF1 functions more significantly than NF1 and Sp1 in sulfide-induced sqr transcription. • Transcription factors NF1, Sp1 and HSF1 enhance sqr promoter activity synergistically. - Abstract: Background: Sulfide is a well-known environmental toxic substance. Mitochondrial sulfide oxidation is a main mechanism of sulfide detoxification in organisms, and sulfide: quinone oxidoreductase (SQR) is a key enzyme which is involved in transferring electrons from sulfide to ubiquinone and converting sulfide into thiosulfate. Previous studies have revealed the SQR-mediated mitochondrial sulfide oxidation exists in the echiuran worm Urechis unicinctus, and its sqr mRNA level increased significantly when the worm is exposed to sulfide. In this study, we attempt to reveal the synergistic regulation of transcription factors on sulfide-induced sqr transcription in U. unicinctus. Methods: ChIP and EMSA were used to identify the interactions between sqr proximal promoter (from −391 to +194 bp) and transcription factors NF1 (nuclear factor 1) and Sp1 (specificity protein 1). Site-directed mutation and transfection assays further revealed their binding sites and synergistic roles of HSF1, NF1 and Sp1 in the sqr transcription. When U. unicinctus were exposed to 150 μM sulfide, the expression levels and nuclear contents of NF1 and Sp1 were examined by Western blotting, and the binding contents between NF1 or Sp1 and the sqr promoter were also detected by ChIP. Results: Transcription factors NF1 and Sp1 were confirmed to interact with the sqr proximal promoter, and their binding sites were identified in −75 to −69 bp for NF1 and −210 to −201 bp for Sp1. Transfection assays showed mutation

  16. Message passing performance of Intel Paragon, IBM SP1 and Cray T3D using PVM

    Energy Technology Data Exchange (ETDEWEB)

    Manke, J.W.; Patterson, J.C. [Boeing Computer Services, Seattle, WA (United States)

    1995-12-01

    For distributed applications on MPP machinse, message passing performance is a critical factor in the overall speed and scalability of the application. This is particularly true when all-to-all communication between nodes is required. In this study we measured the message passing performance of our PVM implementation of an all-to-all communication method called recursive doubling. The measurements were done on an Intel Paragon, IBM SP1 and CRAY T3D. Using a model of message passing times for recursive doubling, we developed several measures that can be used to compare the message passing performance of MPP machines.

  17. Thiazolidinediones mimic glucose starvation in facilitating Sp1 degradation through the up-regulation of beta-transducin repeat-containing protein.

    Science.gov (United States)

    Wei, Shuo; Chuang, Hsiao-Ching; Tsai, Wan-Chi; Yang, Hsiao-Ching; Ho, Shiuh-Rong; Paterson, Andrew J; Kulp, Samuel K; Chen, Ching-Shih

    2009-07-01

    This study investigated the mechanism by which the transcription factor Sp1 is degraded in prostate cancer cells. We recently developed a thiazolidinedione derivative, (Z)-5-(4-hydroxy-3-trifluoromethylbenzylidene)-3-(1-methylcyclohexyl)-thiazolidine-2,4-dione (OSU-CG12), that induces Sp1 degradation in a manner paralleling that of glucose starvation. Based on our finding that thiazolidinediones suppress beta-catenin and cyclin D1 by up-regulating the E3 ligase SCF(beta-TrCP), we hypothesized that beta-transducin repeat-containing protein (beta-TrCP) targets Sp1 for proteasomal degradation in response to glucose starvation or OSU-CG12. Here we show that either treatment of LNCaP cells increased specific binding of Sp1 with beta-TrCP. This direct binding was confirmed by in vitro pull-down analysis with bacterially expressed beta-TrCP. Although ectopic expression of beta-TrCP enhanced the ability of OSU-CG12 to facilitate Sp1 degradation, suppression of endogenous beta-TrCP function by a dominant-negative mutant or small interfering RNA-mediated knockdown blocked OSU-CG12-facilitated Sp1 ubiquitination and/or degradation. Sp1 contains a C-terminal conventional DSG destruction box ((727)DSGAGS(732)) that mediates beta-TrCP recognition and encompasses a glycogen synthase kinase 3beta (GSK3beta) phosphorylation motif (SXXXS). Pharmacological and molecular genetic approaches and mutational analyses indicate that extracellular signal-regulated kinase-mediated phosphorylation of Thr739 and GSK3beta-mediated phosphorylation of Ser728 and Ser732 were critical for Sp1 degradation. The ability of OSU-CG12 to mimic glucose starvation to activate beta-TrCP-mediated Sp1 degradation has translational potential to foster novel strategies for cancer therapy.

  18. aPKC-ι/P-Sp1/Snail signaling induces epithelial-mesenchymal transition and immunosuppression in cholangiocarcinoma.

    Science.gov (United States)

    Qian, Yawei; Yao, Wei; Yang, Tao; Yang, Yan; Liu, Yan; Shen, Qi; Zhang, Jian; Qi, Weipeng; Wang, Jianming

    2017-10-01

    Cholangiocarcinoma (CCA) is a highly malignant bile duct cancer that tends to invade and metastasize early. The epithelial-mesenchymal transition (EMT) has been implicated in cancer cell invasion and metastasis, as well as in cancer cell evasion of host immunity. In this study, we investigated the interaction between atypical protein kinase C-iota (aPKC-ι) and Snail in the regulation of EMT and its relationship to CCA immunosuppression. Our results demonstrated that aPKC-ι, Snail, and infiltrated immunosuppressive cells were significantly up-regulated in CCA tumor tissues and linked to poor prognosis. aPKC-ι induced EMT and immunosuppression by regulating Snail in vitro and in vivo, although aPKC-ι did not directly interact with Snail in coimmunoprecipitation experiments. To further clarify the molecular interaction between aPKC-ι and Snail in relation to EMT, quantitative iTRAQ-based phosphoproteomic analysis and liquid chromatography-tandem mass spectrometry were conducted to identify the substrates of aPKC-ι-dependent phosphorylation. Combined with coimmunoprecipitation, we showed that specificity protein 1 (Sp1) was directly phosphorylated by aPKC-ι on Ser59 (P-Sp1). Both Sp1 and P-Sp1 were up-regulated in CCA tumor tissues and associated with clinicopathological features and poor prognosis in CCA patients. Moreover, using chromatin immunoprecipitation assays, we found that P-Sp1 regulated Snail expression by increasing Sp1 binding to the Snail promoter. P-Sp1 also regulated aPKC-ι/Snail-induced EMT-like changes and immunosuppression in CCA cells. Our findings further indicated that CCA cells with EMT-like features appear to generate immunosuppressive natural T regulatory-like cluster of differentiation 4-positive (CD4(+) )CD25(-) cells rather than to increase CD4(+) CD25(+) natural T regulatory cells, in part by mediating T regulatory-inducible cytokines such as transforming growth factor β1 and interleukin 2. These results demonstrate that a

  19. Pregnancy-specific beta-1-glycoprotein (SP1) in cultured amniotic fluid cells.

    Science.gov (United States)

    Heikinheimo, M; Wahlström, T; Aula, P; Virtanen, I; Seppälä, M

    1980-12-01

    The synthesis of pregnancy-specific beta-1-glycoprotein (SP1) was studied in amniotic fluid cell cultures using RIA, immunoperoxidase, and immunofluorescence techniques. SP1 was found by RIA in all 11 sonicates and in 21 of 26 culture media. The SP1-immunoreactive material was immunologically similar to maternal serum SP1. Immunoperoxidase and indirect immunofluorescence staining were positive in large cells identified as epithelial amniotic cells by labeling with antikeratin antibodies. Fibroblast-like cells were occasionally found in cultures, but they did not contain demonstrable amounts of SP1. The physiological significance of the findings presented remains unclear.

  20. Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter

    Directory of Open Access Journals (Sweden)

    Rivero Samuel

    2011-12-01

    Full Text Available Abstract Background DLK2 is an EGF-like membrane protein, closely related to DLK1, which is involved in adipogenesis. Both proteins interact with the NOTCH1 receptor and are able to modulate its activation. The expression of the gene Dlk2 is coordinated with that of Dlk1 in several tissues and cell lines. Unlike Dlk1, the mouse Dlk2 gene and its locus at chromosome 17 are not fully characterized. Results The goal of this work was the characterization of Dlk2 mRNA, as well as the analysis of the mechanisms that control its basal transcription. First, we analyzed the Dlk2 transcripts expressed by several mouse cells lines and tissues, and mapped the transcription start site by 5' Rapid Amplification of cDNA Ends. In silico analysis revealed that Dlk2 possesses a TATA-less promoter containing minimal promoter elements associated with a CpG island, and sequences for Inr and DPE elements. Besides, it possesses six GC-boxes, considered as consensus sites for the transcription factor Sp1. Indeed, we report that Sp1 directly binds to the Dlk2 promoter, activates its transcription, and regulates its level of expression. Conclusions Our results provide the first characterization of Dlk2 transcripts, map the location of the Dlk2 core promoter, and show the role of Sp1 as a key regulator of Dlk2 transcription, providing new insights into the molecular mechanisms that contribute to the expression of the Dlk2 gene.

  1. Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa).

    Science.gov (United States)

    He, Jinru; Zheng, Lianming; Zhang, Wenjing; Lin, Yuanshao

    2015-01-01

    The genus Aurelia is one of the major contributors to jellyfish blooms in coastal waters, possibly due in part to hydroclimatic and anthropogenic causes, as well as their highly adaptive reproductive traits. Despite the wide plasticity of cnidarian life cycles, especially those recognized in certain Hydroza species, the known modifications of Aurelia life history were mostly restricted to its polyp stage. In this study, we document the formation of polyps directly from the ectoderm of degenerating juvenile medusae, cell masses from medusa tissue fragments, and subumbrella of living medusae. This is the first evidence for back-transformation of sexually mature medusae into polyps in Aurelia sp.1. The resulting reconstruction of the schematic life cycle of Aurelia reveals the underestimated potential of life cycle reversal in scyphozoan medusae, with possible implications for biological and ecological studies.

  2. Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa.

    Directory of Open Access Journals (Sweden)

    Jinru He

    Full Text Available The genus Aurelia is one of the major contributors to jellyfish blooms in coastal waters, possibly due in part to hydroclimatic and anthropogenic causes, as well as their highly adaptive reproductive traits. Despite the wide plasticity of cnidarian life cycles, especially those recognized in certain Hydroza species, the known modifications of Aurelia life history were mostly restricted to its polyp stage. In this study, we document the formation of polyps directly from the ectoderm of degenerating juvenile medusae, cell masses from medusa tissue fragments, and subumbrella of living medusae. This is the first evidence for back-transformation of sexually mature medusae into polyps in Aurelia sp.1. The resulting reconstruction of the schematic life cycle of Aurelia reveals the underestimated potential of life cycle reversal in scyphozoan medusae, with possible implications for biological and ecological studies.

  3. Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2.

    Directory of Open Access Journals (Sweden)

    Dorit Ben-Shachar

    Full Text Available BACKGROUND: The prevailing hypothesis regards schizophrenia as a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed in schizophrenia, and consequently can affect the expression of genes implicated in this disorder. METHODOLOGY/PRINCIPAL FINDINGS: mRNA of Sp1 and of mitochondrial complex I subunits (NDUFV1, NDUFV2 was analyzed in three postmortem brain regions obtained from the Stanley Foundation Brain Collection, and in lymphocytes of schizophrenic patients and controls. Sp1 role in the transcription of these genes was studied as well. Sp1 was abnormally expressed in schizophrenia in both brain and periphery. Its mRNA alteration pattern paralleled that of NDUFV1 and NDUFV2, decreasing in the prefrontal cortex and the striatum, while increasing in the parieto-occipital cortex and in lymphocytes of schizophrenic patients as compared with controls. Moreover, a high and significant correlation between these genes existed in normal subjects, but was distorted in patients. Sp1 role in the regulation of complex I subunits, was demonstrated by the ability of the Sp1/DNA binding inhibitor, mithramycin, to inhibit the transcription of NDUFV1 and NDUFV2, in neuroblastoma cells. In addition, Sp1 activated NDUFV2 promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin. CONCLUSIONS/SIGNIFICANCE: These findings suggest that abnormality in Sp1, which can be the main activator/repressor or act in combination with additional transcription factors and is subjected to environmental stimuli, can contribute to the polygenic and clinically heterogeneous nature of schizophrenia.

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

    Science.gov (United States)

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

    2014-01-01

    VaSP1, a serine proteinase from Vipera ammodytes ammodytes venom, is a glycosylated monomer of 31.5 kDa, as determined by MALDI mass spectrometry, showing multiple isoelectric points between pH 6.5 and pH 8.5. Partial amino acid sequencing of VaSP1 by Edman degradation and MS/MS analysis identified sequences which allowed its classification among the so-called snake venom serine proteinase homologues, members of the peptidase S1 family, however being devoid of the canonical catalytic triad. Only few representatives of this group have been identified so far with just two of them characterised in detail at the protein level. Despite substitution of His57 with Arg, VaSP1 possesses proteolytic activity which can be inhibited by Pefabloc, benzamidine, Zn²⁺ ions, DTT and trypsin inhibitor II, a Kunitz/BPTI group member. It hydrolyses N(α)-benzoyl-Phe-Val-Arg-p-NA, exhibiting Michaelis-Menten behaviour with K(m) = 48.2 μM and V(m) = 0.019 nM s⁻¹. The pH for optimal activity on tested substrate is around 9.0. VaSP1 also cleaves insulin B-chain, digesting it at positions His¹⁰-Leu¹¹, Ala¹⁴-Leu¹⁵ and Tyr¹⁶-Leu¹⁷. Furthermore, the novel serine proteinase is active towards wide array of proteins involved in haemostasis where its degradation of fibrinogen, fibrin, prothrombin, factor X and plasminogen in vivo probably results in depletion of coagulation factors in blood circulation. The possibility that VaSP1 possesses anticoagulant properties has been further indicated by its ability to prolong prothrombin time and activated partial thromboplastin time. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. The physiological and molecular response of Aurelia sp.1 under hypoxia.

    Science.gov (United States)

    Wang, Guoshan; Zhen, Yu; Yu, Zhigang; Shi, Yan; Zhao, Qing; Wang, Jianyan; Mi, Tiezhu

    2017-05-08

    Few studies have been published on the mechanisms of hypoxia response and tolerance in jellyfish, especially with respect to the regulatory mechanism at the molecular level. In this study, Aurelia sp.1, which is frequently found in Chinese coastal waters, was cultivated in a hypoxic system to determine the molecular mechanisms underlying its hypoxic response by studying the physiological activity, gene expression and metabolite contents in the prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) oxygen-sensing system. Physiological activity; the expression of PHD, HIF, ALDO (fructose-bisphosphate aldolase), PDK (pyruvate dehydrogenase kinase), and LDH (lactate dehydrogenase) genes; and the lactic acid content in medusae were significantly affected by hypoxia. The up-regulation of ALDO, PDK and LDH, which was directly or indirectly induced by HIF, mediated the transition from aerobic respiration to anaerobic glycolysis in the medusae. In polyps, there was a slight increase in the expression of HIF, PHD and ALDO, no obvious change in that of PDK and a slight decrease in that of LDH throughout the experiment; however, these changes were insufficient to induce the shift. This study provides a scientific basis for elucidating the regulatory mechanism underlying the PHD-HIF oxygen-sensing system in Aurelia sp.1.

  6. Direct Acylation of C(sp(3))-H Bonds Enabled by Nickel and Photoredox Catalysis.

    Science.gov (United States)

    Joe, Candice L; Doyle, Abigail G

    2016-03-14

    Using nickel and photoredox catalysis, the direct functionalization of C(sp(3))-H bonds of N-aryl amines by acyl electrophiles is described. The method affords a diverse range of α-amino ketones at room temperature and is amenable to late-stage coupling of complex and biologically relevant groups. C(sp(3))-H activation occurs by photoredox-mediated oxidation to generate α-amino radicals which are intercepted by nickel in catalytic C(sp(3))-C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross-coupling while avoiding limitations commonly associated with transition-metal-mediated C(sp(3))-H activation, including requirements for chelating directing groups and high reaction temperatures.

  7. 破解Vista SP1的TCP/IP连接数限制

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    我升级了Windows Vista到SP1,找了多个软件如Vista优化大师都无法破解Vista SP1的TCP/IP连接数限制,现在迅雷、BT等下载速度极其缓慢。请问有什么软件可以破解Vista SP1的TCP/IP连接数限制?

  8. Effect of tea saponin on ephyrae and polyps of the moon jellyfish Aurelia sp.1.

    Science.gov (United States)

    Dong, Zhijun; Sun, Tingting; Liang, Likun; Wang, Lei

    2017-01-01

    The moon jellyfish (Aurelia sp.1) is thought to be a nuisance for the sea cucumber aquaculture, which commonly occur in the sea cucumber (Apostichopus japonicus) culture ponds of the Yellow Sea, China. To develop an appropriate method to control Aurelia sp.1 blooms, the toxic effects of tea saponin on Aurelia sp.1 ephyrae and polyps were tested in laboratory experiments. Our results revealed that tea saponin caused significant morphological changes, behavioral abnormality and mortality in Aurelia sp.1 ephyrae and polyps in 24 h and 48 h exposure experiments. The 24 h and 48 h median lethal concentrations (LC50) values of tea saponin for Aurelia sp.1 ephyrae were 1.9 and 1.1 mg L-1 respectively, while the LC50 value for Aurelia sp.1 polyps was 0.4 mg L-1 after 24h and 48 h of exposure to tea saponin. Comparison with literature results of tea saponin on A. japonicus indicates that the resistance of A. japonicus to tea saponin is 12-18 times greater than that of Aurelia sp.1 ephyrae. Therefore, the appropriate tea saponin dosage for the control of Aurelia sp.1 should be paid enough attention in order to minimize possible damage for sea cucumber. We suggest that the recommended level of tea saponin to eradicate Aurelia sp.1 ephyrae and polyps in sea cucumber culture ponds be lower than 1.35 mg L-1.

  9. Functional Characterization of AtSP1, A Sucrose-Responsive Receptor-Like Kinase

    Institute of Scientific and Technical Information of China (English)

    Xuna Wu; Kerstin Zander; Eugenia Maximova; Gerhard Obermeyer; Waltraud Schulze

    2012-01-01

    Sucrose is the main product of photosynthesis and an important metabolite.It functions as signaling molecule,also potentially being involved in the regulation of growth and development in plants.AtSP1 is one of putative RLKs identified in sucrose resupply after starvation experiment and hypothesized to be involved in sucrose-related regulatory processes (Niittyl(a) et al.,2007).The aim of this work was to characterize the effect of AtSP1 and its phosphorylation site Ser744 on sucrose induced phosphorylation cascade.Therefore,proteins which changed their phosphorylation status upon sucrose supply were compared in WT,the sp1 mutant,complementation lines (35S::AtSP1-GFP/sp1),and two mutagenesis lines (35S::AtSP1S744A-GFP/sp1 and 35S::AtSP1S744D-GFP/sp1).Proteins with altered phosphorylation response in the mutant lines are candidates for direct or indirect substrates of AtSP1.To test this,Arabidopsis seedlings were cultured for 24 h without sucrose in JPL medium,and either sucrose or mannitol was resupplied for 3 min.The treatment time of 3 min was chosen as the maximum phosphorylation change of AtSP1 occurred after 3 min (Niittyl(a) et al.,2007).Seedlings were then harvested.The soluble proteins and microsome fraction were isolated and identified via LC-MS/MS.The phosphorylated amino acids were identified by MAXQUANT and quantified based on normalized ion intensities.The quantified phosphoproteins in five genotypes were compared to find candidate proteins which could be regulated by AtSP1 in response to sucrose resupply after starvation.The analysis of the short term effects regulated by AtSP1 provided new insights about sucrose-induced regulatory processes.In total,93 phosphoproteins were identified,42 of which showed a significant lower phosphorylation in the sp1 mutant.These results indicated that when expression levels of AtSP1 were severely reduced,multiple other proteins were impaired in their phosphorylation upon sucrose reply,linking them potentially with AtSP

  10. Down-regulation of EPHX2 gene transcription by Sp1 under high-glucose conditions.

    Science.gov (United States)

    Oguro, Ami; Oida, Shoko; Imaoka, Susumu

    2015-09-15

    sEH (soluble epoxide hydrolase), which is encoded by the EPHX2 gene, regulates the actions of bioactive lipids, EETs (epoxyeicosatrienoic acids). Previously, we found that high-glucose-induced oxidative stress suppressed sEH levels in a hepatocarcinoma cell line (Hep3B) and sEH was decreased in streptozotocin-induced diabetic mice in vivo. In the present study, we investigated the regulatory mechanisms underlying EPHX2 transcriptional suppression under high-glucose conditions. The decrease in sEH was prevented by an Sp1 (specificity protein 1) inhibitor, mithramycin A, and overexpression or knockdown of Sp1 revealed that Sp1 suppressively regulated sEH expression, in contrast with the general role of Sp1 on transcriptional activation. In addition, we found that AP2α (activating protein 2α) promoted EPHX2 transcription. The nuclear transport of Sp1, but not that of AP2α, was increased under high glucose concomitantly with the decrease in sEH. Within the EPHX2 promoter -56/+32, five Sp1-binding sites were identified, and the mutation of each of these sites showed that the first one (SP1_1) was important in both suppression by Sp1 and activation by AP2α. Furthermore, overexpression of Sp1 diminished the binding of AP2α by DNA-affinity precipitation assay and ChIP, suggesting competition between Sp1 and AP2α on the EPHX2 promoter. These findings provide novel insights into the role of Sp1 in transcriptional suppression, which may be applicable to the transcriptional regulation of other genes.

  11. Selective sp3 C-H alkylation via polarity-match-based cross-coupling

    Science.gov (United States)

    Le, Chip; Liang, Yufan; Evans, Ryan W.; Li, Ximing; MacMillan, David W. C.

    2017-07-01

    The functionalization of carbon-hydrogen (C-H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence. Although many C-H functionalization reactions involve C(sp3)-C(sp2) coupling, there is a growing demand for C-H alkylation reactions, wherein sp3 C-H bonds are replaced with sp3 C-alkyl groups. Here we describe a polarity-match-based selective sp3 C-H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C-H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl-alkyl fragment coupling. The sp3 C-H alkylation is highly selective for the α-C-H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

  12. Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer.

    Science.gov (United States)

    Zhao, Jing; Ye, Wei; Wu, Juan; Liu, Lijuan; Yang, Lina; Gao, Lu; Chen, Biliang; Zhang, Fanglin; Yang, Hong; Li, Yu

    2015-07-01

    CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells.

  13. A Reinvestigation of a Superhard Tetragonal sp3 Carbon Allotrope

    Directory of Open Access Journals (Sweden)

    Mengjiang Xing

    2016-06-01

    Full Text Available I 4 ¯ –carbon was first proposed by Zhang et al., this paper will report regarding this phase of carbon. The present paper reports the structural and elastic properties of the three-dimensional carbon allotrope I 4 ¯ –carbon using first-principles density functional theory. The related enthalpy, elastic constants, and phonon spectra confirm that the newly-predicted I 4 ¯ –carbon is thermodynamically, mechanically, and dynamically stable. The calculated mechanical properties indicate that I 4 ¯ –carbon has a larger bulk modulus (393 GPa, shear modulus (421 GPa, Young’s modulus (931 GPa, and hardness (55.5 GPa, all of which are all slightly larger than those of c-BN. The present results indicate that I 4 ¯ –carbon is a superhard material and an indirect-band-gap semiconductor. Moreover, I 4 ¯ –carbon shows a smaller elastic anisotropy in its linear bulk modulus, shear anisotropic factors, universal anisotropic index, and Young’s modulus.

  14. 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.

    Science.gov (United States)

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

    2014-02-01

    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.

  15. Improved Reconstruction Quality of Bioluminescent Images by Combining SP3 Equations and Bregman Iteration Method

    Directory of Open Access Journals (Sweden)

    Qiang Wu

    2013-01-01

    Full Text Available Bioluminescence tomography (BLT has a great potential to provide a powerful tool for tumor detection, monitoring tumor therapy progress, and drug development; developing new reconstruction algorithms will advance the technique to practical applications. In the paper, we propose a BLT reconstruction algorithm by combining SP3 equations and Bregman iteration method to improve the quality of reconstructed sources. The numerical results for homogeneous and heterogeneous phantoms are very encouraging and give significant improvement over the algorithms without the use of SP3 equations and Bregman iteration method.

  16. Raman activity of sp3 carbon allotropes under pressure: A density functional theory study

    Science.gov (United States)

    Flores-Livas, José A.; Lehtovaara, Lauri; Amsler, Maximilian; Goedecker, Stefan; Pailhès, Stéphane; Botti, Silvana; San Miguel, Alfonso; Marques, Miguel A. L.

    2012-04-01

    Raman spectroscopy is a powerful tool to study the intrinsic vibrational characteristics of crystals, and, therefore, it is an adequate technique to explore phase transitions of carbon under pressure. However, the diamond-anvil cell, which is used in experiments to apply pressure, appears as a broad intense feature in the spectra. This feature lies, unfortunately, in the same range as the principal modes of recently proposed sp3 carbon structures. As these modes are hard to distinguish from the diamond cell background, we analyze all Raman-active modes present in the sp3 carbon structures in order to find detectable fingerprint features for an experimental identification.

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

    Directory of Open Access Journals (Sweden)

    Botella Luisa M

    2010-06-01

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

  18. Enantioselective carbenoid insertion into C(sp3)–H bonds

    Science.gov (United States)

    Santiago, J V

    2016-01-01

    Summary The enantioselective carbenoid insertion into C(sp3)–H bonds is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area. PMID:27340479

  19. Application of the new MultiTrans SP3 radiation transport code in BNCT dose planning.

    Science.gov (United States)

    Kotiluoto, P; Hiisamäki, P; Savolainen, S

    2001-09-01

    Dose planning in boron neutron capture therapy (BNCT) is a complex problem and requires sophisticated numerical methods. In the framework of the Finnish BNCT project, new deterministic three-dimensional radiation transport code MultiTrans SP3 has been developed at VTT Chemical Technology, based on a novel application of the tree multigrid technique. To test the applicability of this new code in a realistic BNCT dose planning problem, cylindrical PMMA (polymethyl-methacrylate) phantom was chosen as a benchmark case. It is a convenient benchmark, as it has been modeled by several different codes, including well-known DORT and MCNP. Extensive measured data also exist. In this paper, a comparison of the new MultiTrans SP3 code with other methods is presented for the PMMA phantom case. Results show that the total neutron dose rate to ICRU adult brain calculated by the MultiTrans SP3 code differs less than 4% in 2 cm depth in phantom (in thermal maximum) from the DORT calculation. Results also show that the calculated 197Au(n,gamma) and 55Mn(n,gamma) reaction rates in 2 cm depth in phantom differ less than 4% and 1% from the measured values, respectively. However, the photon dose calculated by the MultiTrans SP3 code seems to be incorrect in this PMMA phantom case, which requires further studying. As expected, the deterministic MultiTrans SP3 code is over an order of magnitude faster than stochastic Monte Carlo codes (with similar resolution), thus providing a very efficient tool for BNCT dose planning.

  20. The identification of trans-acting factors that regulate the expression of GDF5 via the osteoarthritis susceptibility SNP rs143383.

    Directory of Open Access Journals (Sweden)

    Catherine M Syddall

    2013-06-01

    Full Text Available rs143383 is a C to T transition SNP located in the 5'untranslated region (5'UTR of the growth differentiation factor 5 gene GDF5. The T allele of the SNP is associated with increased risk of osteoarthritis (OA in Europeans and in Asians. This susceptibility is mediated by the T allele producing less GDF5 transcript relative to the C allele, a phenomenon known as differential allelic expression (DAE. The aim of this study was to identify trans-acting factors that bind to rs143383 and which regulate this GDF5 DAE. Protein binding to the gene was investigated by two experimental approaches: 1 competition and supershift electrophoretic mobility shift assays (EMSAs and 2 an oligonucleotide pull down assay followed by quantitative mass spectrometry. Binding was then confirmed in vivo by chromatin immunoprecipitation (ChIP, and the functional effects of candidate proteins investigated by RNA interference (RNAi and over expression. Using these approaches the trans-acting factors Sp1, Sp3, P15, and DEAF-1 were identified as interacting with the GDF5 5'UTR. Knockdown and over expression of the factors demonstrated that Sp1, Sp3, and DEAF-1 are repressors of GDF5 expression. Depletion of DEAF-1 modulated the DAE of GDF5 and this differential allelic effect was confirmed following over expression, with the rs143383 T allele being repressed to a significantly greater extent than the rs143383 C allele. In combination, Sp1 and DEAF-1 had the greatest repressive activity. In conclusion, we have identified four trans-acting factors that are binding to GDF5, three of which are modulating GDF5 expression via the OA susceptibility locus rs143383.

  1. Growth Characteristics of Tetraselmis sp.-1 in Phototrophic, Mixotrophic and Heterotrophic Conditions

    Institute of Scientific and Technical Information of China (English)

    Shen Jihong(沈继红); Yu Junhong; Lin Xuezheng; Li Guangyou; Liu Fayi

    2004-01-01

    Tetraselmis sp.-1 is a new microalgae strain constructed by cell fusion technique. In this paper, the growth characteristics of Tetraselmis sp.-1 under different culture conditions are investigated. The growth kinetic models are obtained, the assimilation of C and NH4+ is investigated and the assimilation efficiency of Tetraselmis sp.-1 under different culture conditions is calculated. The results show that different culture conditions do not have obvious influence on carbon absorbance, but have significant influence on nitrogen absorbance, C∶N is maximum under heterotrophic condition, while minimum under phototrophic condition. The assimilation efficiency (η) of Tetraselmis sp.-1 has the highest value in heterotrophic condition and largely higher than those in phototrophic and mixotrophic conditions.

  2. An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation.

    Science.gov (United States)

    Schur, Florian K M; Obr, Martin; Hagen, Wim J H; Wan, William; Jakobi, Arjen J; Kirkpatrick, Joanna M; Sachse, Carsten; Kräusslich, Hans-Georg; Briggs, John A G

    2016-07-29

    Immature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation inhibitors (MIs), thereby abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation and is the target of MIs. We applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 angstrom resolution and built an atomic model. The structure reveals a network of intra- and intermolecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease. We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1.

  3. The conjugate gradient NAS parallel benchmark on the IBM SP1

    Energy Technology Data Exchange (ETDEWEB)

    Trefethen, A.E.; Zhang, T. [Cornell Univ., Ithaca, NY (United States)

    1994-12-31

    The NAS Parallel Benchmarks are a suite of eight benchmark problems developed at the NASA Ames Research Center. They are specified in such a way that the benchmarkers are free to choose the language and method of implementation to suit the system in which they are interested. In this presentation the authors will discuss the Conjugate Gradient benchmark and its implementation on the IBM SP1. The SP1 is a parallel system which is comprised of RS/6000 nodes connected by a high performance switch. They will compare the results of the SP1 implementation with those reported for other machines. At this time, such a comparison shows the SP1 to be very competitive.

  4. The Deconfinement Phase Transition of Sp(2) and Sp(3) Yang-Mills Theories in 2+1 and 3+1 Dimensions

    CERN Document Server

    Holland, K; Wiese, U J

    2003-01-01

    Some time ago, Svetitsky and Yaffe have argued that -- if the deconfinement phase transition of a (d+1)-dimensional Yang-Mills theory with gauge group G is second order -- it should be in the universality class of a d-dimensional spin model symmetric under the center of G. For d=3 these arguments have been confirmed numerically only in the SU(2) case with center Z(2), simply because all SU(N) Yang-Mills theories with N>=3 seem to have non-universal first order phase transitions. The symplectic groups Sp(N) also have the center Z(2) and provide another extension of SU(2) = Sp(1) to general N. Using lattice simulations, we find that the deconfinement phase transition of Sp(2) Yang-Mills theory is first order in 3+1 dimensions, while in 2+1 dimensions stronger fluctuations induce a second order transition. In agreement with the Svetitsky-Yaffe conjecture, for (2+1)-d Sp(2) Yang-Mills theory we find the universal critical behavior of the 2-d Ising model. For Sp(3) Yang-Mills theory the transition is first order b...

  5. Maximal Expression of the Evolutionarily Conserved Slit2 Gene Promoter Requires Sp1.

    Science.gov (United States)

    Saunders, Jacquelyn; Wisidagama, D Roonalika; Morford, Travis; Malone, Cindy S

    2016-08-01

    Slit2 is a neural axon guidance and chemorepellent protein that stimulates motility in a variety of cell types. The role of Slit2 in neural development and neoplastic growth and migration has been well established, while the genetic mechanisms underlying regulation of the Slit2 gene have not. We identified the core and proximal promoter of Slit2 by mapping multiple transcriptional start sites, analyzing transcriptional activity, and confirming sequence homology for the Slit2 proximal promoter among a number of species. Deletion series and transient transfection identified the Slit2 proximal promoter as within 399 base pairs upstream of the start of transcription. A crucial region for full expression of the Slit2 proximal promoter lies between 399 base pairs and 296 base pairs upstream of the start of transcription. Computer modeling identified three transcription factor-binding consensus sites within this region, of which only site-directed mutagenesis of one of the two identified Sp1 consensus sites inhibited transcriptional activity of the Slit2 proximal promoter (-399 to +253). Bioinformatics analysis of the Slit2 proximal promoter -399 base pair to -296 base pair region shows high sequence conservation over twenty-two species, and that this region follows an expected pattern of sequence divergence through evolution.

  6. Nanocrystalline sp 2 and sp 3 carbons: CVD synthesis and applications

    Science.gov (United States)

    Terranova, M. L.; Rossi, M.; Tamburri, E.

    2016-11-01

    The design and production of innovative materials based on nanocrystalline sp 2- and sp 3-coordinated carbons is presently a focus of the scientific community. We present a review of the nanostructures obtained in our labs using a series of synthetic routes, which make use of chemical vapor deposition (CVD) techniques for the selective production of non-planar graphitic nanostructures, nanocrystalline diamonds, and hybrid two-phase nanostructures.

  7. Short term effects by acupuncture to SP3 on the autonomic blood flow control.

    Science.gov (United States)

    Lee, Seungmin; Chae, Younbyoung; Kim, Seung-Nam; Kim, Song-Yi; Park, Ji-Yeun; Kwark, Young-Rong; Kang, O-Seok; Lee, Hyejung; Yin, Chang Shik; Park, Hi-Joon

    2010-02-01

    In this study, we investigated the short term effects of acupuncture on autonomic control of blood flow in healthy subjects. We also studied whether deqi (obtaining qi) sensations are correlated with these autonomic hemodynamic changes. The experiment had a randomized, crossover design. Five healthy volunteers (age: 18-26 years) participated in this study. Acupuncture (2 Hz rotations for 10 seconds to 20 mm deep) was applied either to the acupuncture point SP3 or KI2 for 5 minutes. Non-invasively obtained continuous hemodynamic measurements of ultrasound Dopplerography were recorded at the radial artery before, during and after acupuncture stimulation. Cardiovascular autonomic tone was also recorded using power spectral analysis of heart rate variability. After acupuncture stimulation, the participants completed the acupuncture perception scales to measure the degree of deqi or pain they had experienced. Acupuncture stimulation to the acupuncture point SP3, when compared to the acupuncture point KI2, decreased the maximum systolic velocity. It also decreased low frequency component and increased high frequency component of heart rate variability, indicating that the decrease in systolic blood flow velocity was due to the increased parasympathetic response. Interestingly, warm, radiating and energetic feeling, which are related to deqi, had close correlations with the decrease in blood flow velocity. Acupuncture stimulation to the acupuncture point SP3 modulates the autonomic cardiovascular responses by enhancing parasympathetic function, and this may help to understand the therapeutic effects of acupuncture.

  8. A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp3)-H amination

    Science.gov (United States)

    Paradine, Shauna M.; Griffin, Jennifer R.; Zhao, Jinpeng; Petronico, Aaron L.; Miller, Shannon M.; Christina White, M.

    2015-12-01

    C-H bond oxidation reactions underscore the existing paradigm wherein high reactivity and high selectivity are inversely correlated. The development of catalysts capable of oxidizing strong aliphatic C(sp3)-H bonds while displaying chemoselectivity (that is, tolerance of more oxidizable functionality) remains an unsolved problem. Here, we describe a catalyst, manganese tert-butylphthalocyanine [Mn(tBuPc)], that is an outlier to the reactivity-selectivity paradigm. It is unique in its capacity to functionalize all types of C(sp3)-H bond intramolecularly, while displaying excellent chemoselectivity in the presence of π functionality. Mechanistic studies indicate that [Mn(tBuPc)] transfers bound nitrenes to C(sp3)-H bonds via a pathway that lies between concerted C-H insertion, observed with reactive noble metals such as rhodium, and stepwise radical C-H abstraction/rebound, as observed with chemoselective base metals such as iron. Rather than achieving a blending of effects, [Mn(tBuPc)] aminates even 1° aliphatic and propargylic C-H bonds, demonstrating reactivity and selectivity unusual for previously known catalysts.

  9. A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp(3))-H amination.

    Science.gov (United States)

    Paradine, Shauna M; Griffin, Jennifer R; Zhao, Jinpeng; Petronico, Aaron L; Miller, Shannon M; Christina White, M

    2015-12-01

    C-H bond oxidation reactions underscore the existing paradigm wherein high reactivity and high selectivity are inversely correlated. The development of catalysts capable of oxidizing strong aliphatic C(sp(3))-H bonds while displaying chemoselectivity (that is, tolerance of more oxidizable functionality) remains an unsolved problem. Here, we describe a catalyst, manganese tert-butylphthalocyanine [Mn((t)BuPc)], that is an outlier to the reactivity-selectivity paradigm. It is unique in its capacity to functionalize all types of C(sp(3))-H bond intramolecularly, while displaying excellent chemoselectivity in the presence of π functionality. Mechanistic studies indicate that [Mn((t)BuPc)] transfers bound nitrenes to C(sp(3))-H bonds via a pathway that lies between concerted C-H insertion, observed with reactive noble metals such as rhodium, and stepwise radical C-H abstraction/rebound, as observed with chemoselective base metals such as iron. Rather than achieving a blending of effects, [Mn((t)BuPc)] aminates even 1° aliphatic and propargylic C-H bonds, demonstrating reactivity and selectivity unusual for previously known catalysts.

  10. Inhibition of SP1 by the mithramycin analog EC-8042 efficiently targets tumor initiating cells in sarcoma

    Science.gov (United States)

    Tornin, Juan; Martinez-Cruzado, Lucia; Santos, Laura; Rodriguez, Aida; Núñez, Luz-Elena; Oro, Patricia; Hermosilla, Maria Ana; Allonca, Eva; Fernández-García, Maria Teresa; Astudillo, Aurora; Suarez, Carlos; Morís, Francisco; Rodriguez, Rene

    2016-01-01

    Tumor initiating cells (TICs), responsible for tumor initiation, and cancer stem cells (CSCs), responsible for tumor expansion and propagation, are often resistant to chemotherapeutic agents. To find therapeutic targets against sarcoma initiating and propagating cells we used models of myxoid liposarcoma (MLS) and undifferentiated pleomorphic sarcoma (UPS) developed from human mesenchymal stromal/stem cells (hMSCs), which constitute the most likely cell-of-origin for sarcoma. We found that SP1-mediated transcription was among the most significantly altered signaling. To inhibit SP1 activity, we used EC-8042, a mithramycin (MTM) analog (mithralog) with enhanced anti-tumor activity and highly improved safety. EC-8042 inhibited the growth of TIC cultures, induced cell cycle arrest and apoptosis and upregulated the adipogenic factor CEBPα. SP1 knockdown was able to mimic the anti-proliferative effects induced by EC-8042. Importantly, EC-8042 was not recognized as a substrate by several ABC efflux pumps involved in drug resistance, and, opposite to the chemotherapeutic drug doxorubicin, repressed the expression of many genes responsible for the TIC/CSC phenotype, including SOX2, C-MYC, NOTCH1 and NFκB1. Accordingly, EC-8042, but not doxorubicin, efficiently reduced the survival of CSC-enriched tumorsphere sarcoma cultures. In vivo, EC-8042 induced a profound inhibition of tumor growth associated to a strong reduction of the mitotic index and the induction of adipogenic differentiation and senescence. Finally, EC-8042 reduced the ability of tumor cells to reinitiate tumor growth. These data suggest that EC-8042 could constitute an effective treatment against both TIC and CSC subpopulations in sarcoma. PMID:27105533

  11. Involvement of Sp1 in Butyric Acid-Induced HIV-1 Gene Expression

    Directory of Open Access Journals (Sweden)

    Kenichi Imai

    2015-09-01

    Full Text Available Background/Aims: The ability of human immunodeficiency virus-1(HIV-1 to establish latent infection and its re-activation is considered critical for progression of HIV-1 infection. We previously reported that a bacterial metabolite butyric acid, acting as a potent inhibitor of histone deacetylases (HDACs, could lead to induction of HIV-1 transcription; however, the molecular mechanism remains unclear. The aim of this study was to investigate the effect of butyric acid on HIV-1 gene expression. Methods: Butyric acid-mediated HIV-1 gene expression was determined by luciferase assay and Chromatin immunoprecipitation assay. Western blot analysis and ELISA were used for the detection of HIV-1. Results: We found that Sp1 binding sites within the HIV-1 promoter are primarily involved in butyric acid-mediated HIV-1 activation. In fact, Sp1 knockdown by small interfering RNA and the Sp1 inhibitor mithramycin A abolished the effect of butyric acid. We also observed that cAMP response element-binding-binding protein (CBP was required for butyric acid-induced HIV-1 activation. Conclusions: These results suggest that butyric acid stimulates HIV-1 promoter through inhibition of the Sp1-associated HDAC activity and recruitment of CBP to the HIV-1 LTR. Our findings suggest that Sp1 should be considered as one of therapeutic targets in anti-viral therapy against HIV-1 infection aggravated by butyric acid-producing bacteria.

  12. Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp transcription factors by targeting microRNAs

    Directory of Open Access Journals (Sweden)

    Gandhy Shruti U

    2012-11-01

    Full Text Available Abstract Background Curcumin inhibits growth of several cancer cell lines, and studies in this laboratory in bladder and pancreatic cancer cells show that curcumin downregulates specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 and pro-oncogenic Sp-regulated genes. In this study, we investigated the anticancer activity of curcumin and several synthetic cyclohexanone and piperidine analogs in colon cancer cells. Methods The effects of curcumin and synthetic analogs on colon cancer cell proliferation and apoptosis were determined using standardized assays. The changes in Sp proteins and Sp-regulated gene products were analysed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a, miR-20a, miR-17-5p and ZBTB10 and ZBTB4 mRNA expression. Results The IC50 (half-maximal values for growth inhibition (24 hr of colon cancer cells by curcumin and synthetic cyclohexanone and piperidine analogs of curcumin varied from 10 μM for curcumin to 0.7 μM for the most active synthetic piperidine analog RL197, which was used along with curcumin as model agents in this study. Curcumin and RL197 inhibited RKO and SW480 colon cancer cell growth and induced apoptosis, and this was accompanied by downregulation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 and Sp-regulated genes including the epidermal growth factor receptor (EGFR, hepatocyte growth factor receptor (c-MET, survivin, bcl-2, cyclin D1 and NFκB (p65 and p50. Curcumin and RL197 also induced reactive oxygen species (ROS, and cotreatment with the antioxidant glutathione significantly attenuated curcumin- and RL197-induced growth inhibition and downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes. The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of microRNAs (miR-27a, miR-20a and miR-17-5p that regulate these repressors

  13. Structural Analysis of Planar sp3 and sp2 Films: Diamond-Like Carbon and Graphene Overlayers

    KAUST Repository

    Mansour, Ahmed

    2011-07-07

    smooth and sp3-rich DLC films on model Si substrates. Graphene has attracted worldwide attention since its recent discovery in 2004, due to its extraordinary properties. One of the most promising applications of graphene is its use as a transparent conducting electrode in photovoltaic and display applications. Unfortunately, large scale deposition of graphene is still a challenge and a limiting factor. Solution processing of graphene oxide, a type of chemically derived graphene that forms well dispersed single sheet solutions, is an easy method of depositing large scale graphene films. Subsequent reduction allows recovering part of the properties of graphene. However, residual defects and oxide groups remain in the sheet even after optimal reduction processes, making it difficult to achieve the extraordinary electrical and transport properties of graphene. We investigate the structural, chemical, and morphological implications of plasma oxidation of CVD graphene to better understand the nature of graphene oxide. One of the common threads of this study is the use of Raman spectroscopy (RS) X-ray photoelectron spectroscopy (XPS), and Atomic force microscopy (AFM) to understand the structural and compositional changes of both FCVA-deposited DLC films and plasma-oxidized graphene. In both cases, the analysis allows to obtain detailed insight into structural evolution of sp3 and sp2-rich films during plasma processing. Optimum FCVA deposited DLC films were obtained at a deposition angle of 70° for 30 sec deposition time on a biased substrate (-100 V), in terms of both surface roughness and sp3 content. RMS roughness of deposited films were around 0.15 nm with a ~50% sp3 content. Structural and chemical changes of oxygen plasma treated CVD graphene were shown to vary over three distinct stages depending on the time of plasma exposure. Initial exposure up to 3 seconds was mainly accompanied by structural changes without net uptake of oxygen, introducing more defects and

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

    Science.gov (United States)

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

    2014-07-15

    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.

  15. Functional analysis of the transcription factors Sp3 and Sp4

    NARCIS (Netherlands)

    R.J.P. Bouwman (Peter)

    2002-01-01

    textabstractBiological processes are largely controlled by the synthesis and the modulation of proteins. For the synthesis of proteins. two steps are of critical importance. Firstly, the genetic information for the protein has to be transcribed from the DNA of the gene encoding the protein to the mR

  16. An investigation of the factors that regulate muscarinic receptor expression in schizophrenia.

    Science.gov (United States)

    Seo, Myoung Suk; Scarr, Elizabeth; Dean, Brian

    2014-09-01

    We previously identified a group of subjects with schizophrenia who, on average, have a 75% decrease in cholinergic receptor, muscarinic 1 (CHRM1) in Brodmann's area (BA) 9. To extend this finding, we determined i) if the decrease in CHRM1 was present in another functionally related CNS region (BA6), ii) whether the marked decrease in CHRM1 was accompanied by changes in levels of other CHRMs and iii) potential factors responsible for the decreased CHRM1 expression. We measured CHRM1 and CHRM3 using in situ radioligand binding with [(3)H]pirenzepine and [(3)H]4-DAMP respectively in BA6 from 20 subjects with schizophrenia who had low levels of CHRM1 in BA9 (SzLow[(3)H]PZP), 18 subjects with schizophrenia whose levels of CHRM1 were similar to controls (SzNormal[(3)H]PZP) and 20 control subjects. Levels of CHRM1, 3 and 4 mRNA were measured using qPCR and levels of the transcription factors, SP1 and SP3, were determined using Western blots. In BA6, the density of [(3)H]pirenzepine binding was decreased in subjects with SzLow[(3)H]PZP (p<0.001) compared to controls. The density of [(3)H]4-DAMP binding, levels of CHRM1, 3 and 4 mRNA and levels of SP1 and SP3 was not significantly different between the three groups. This study shows that the previously identified decrease in CHRM1 expression is not confined to the dorsolateral prefrontal cortex but is present in other cortical areas. The effect shows some specificity to CHRM1, with no change in levels of binding to CHRM3. Furthermore, this decrease in CHRM1 does not appear to be associated with low levels of CHRM1 mRNA or to simply be regulated by the transcription factors, SP1 and SP3, suggesting that other mechanisms are responsible for the decreased CHRM1 in these subjects. Copyright © 2014. Published by Elsevier B.V.

  17. Amniotic fluid pregnancy-specific beta 1-glycoprotein (SP1) in fetal developmental disorders.

    Science.gov (United States)

    Heikinheimo, M; Jalanko, H; Leisti, J; Kolho, K L; Salonen, R; Von Koskull, H; Aula, P

    1984-01-01

    Concentration of pregnancy-specific beta 1-glycoprotein (SP1) was studied in second and third trimester amniotic fluid from pregnancies with various fetal developmental disorders. The material consisted of 26 cases with chromosomal disorders and 19 cases with non-chromosomal fetal malformations. The SP1 concentration was elevated in two cases of Meckel's syndrome (mean +2.7-4.0 S.D.) as well as in one case of fetal triploidy (mean +22 S.D.), while it was normal in all other 14 different fetal disorders.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gropp, W. [ed.

    1993-11-01

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

  19. Two-Dimensional Phosphorus Carbide: Competition between sp(2) and sp(3) Bonding.

    Science.gov (United States)

    Guan, Jie; Liu, Dan; Zhu, Zhen; Tománek, David

    2016-05-11

    We propose previously unknown allotropes of phosphorus carbide (PC) in the stable shape of an atomically thin layer. Different stable geometries, which result from the competition between sp(2) bonding found in graphitic C and sp(3) bonding found in black P, may be mapped onto 2D tiling patterns that simplify categorizing of the structures. Depending on the category, we identify 2D-PC structures that can be metallic, semimetallic with an anisotropic Dirac cone, or direct-gap semiconductors with their gap tunable by in-layer strain.

  20. Molecular dynamics simulation of the formation of sp3 hybridized bonds in hydrogenated diamondlike carbon deposition processes.

    Science.gov (United States)

    Murakami, Yasuo; Horiguchi, Seishi; Hamaguchi, Satoshi

    2010-04-01

    The formation process of sp3 hybridized carbon networks (i.e., diamondlike structures) in hydrogenated diamondlike carbon (DLC) films has been studied with the use of molecular-dynamics simulations. The processes simulated in this study are injections of hydrocarbon (CH3 and CH) beams into amorphous carbon (a-C) substrates. It has been shown that diamondlike sp3 structures are formed predominantly at a subsurface level when the beam energy is relatively high, as in the "subplantation" process for hydrogen-free DLC deposition. However, for hydrogenated DLC deposition, the presence of abundant hydrogen at subsurface levels, together with thermal spikes caused by energetic ion injections, substantially enhances the formation of carbon-to-carbon sp3 bonds. Therefore, the sp3 bond formation process for hydrogenated DLC films essentially differs from that for hydrogen-free DLC films.

  1. Sex determination and differentiation in Aurelia sp.1: the absence of temperature dependence

    Science.gov (United States)

    Liu, Chunsheng; Gu, Zhifeng; Xing, Mengxin; Sun, Yun; Chen, Siqing; Chen, Zhaoting

    2017-03-01

    Cnidarians, being regarded as `basal' metazoan animals, are considered to have relatively high plasticity in terms of sex reversal. In this study we used an experimental approach to demonstrate sexual differentiation and plasticity in benthic polyps and pelagic medusae of Aurelia sp.1 maintained at different temperatures. Results indicated that in Aurelia sp.1, sex differentiation has been determined at the polyp stage and that all medusae originating from a given polyp are, phenotypically, of the same sex. In addition, the sex of polyps budding from the same clone (either male or female) at different temperatures appears to be the same as that of the parent. The sex of medusae that had originated from a known-sex polyp was observed to remain the same as that of the parent, irrespective of differences in strobilation or rearing temperatures. These results indicate that the mechanism of sex determination of Aurelia sp.1. is not influenced by prevailing temperature regimes. A comparison of variability in terms of sexual plasticity of Aurelia sp.1 with that of Hydrozoa and Anthozoa suggests that species characterized by a free-swimming medusa life stage have a high dispersal potential, which probably results in a lower rate of sex reversal.

  2. 玲珑小巧的Melody SP3胆机

    Institute of Scientific and Technical Information of China (English)

    军娥

    2005-01-01

    说到Helody SP3胆机,各位自不陌生,这是Helody改型后推出的第一部作品。是Melody的一次突破,一次大改革,外形更加趋于年轻化.极具Art Taste,应当说是近年国产放大器中外型最为独具品味的胆机,声靓形俊,着实迷人。前面板厚实却并不笨重,带有些许的弧度和一定的上拱使它显得更为精简,外凸的音量电位器使它看来更为雅致大度,瑰丽大气,开关电源和输入选择掣设于机身两侧,是一个极人性化的设计,顺手而不碍眼。别看这部SP3相比起我们常见的胆机小了许多,只有275mm×185mm×350mm,但它的重量可是不轻,足有20kg。

  3. Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the β-globin locus control region in vivo

    Science.gov (United States)

    Gillemans, Nynke; Tewari, Rita; Lindeboom, Fokke; Rottier, Robbert; de Wit, Ton; Wijgerde, Mark; Grosveld, Frank; Philipsen, Sjaak

    1998-01-01

    The locus control region of the β-globin cluster contains five DNase I hypersensitive sites (5′HS1–5) required for locus activation. 5′HS3 contains six G-rich motifs that are essential for its activity. Members of a protein family, characterized by three zinc fingers highly homologous to those found in transcription factor Sp1, interact with these motifs. Because point mutagenesis cannot distinguish between family members, it is not known which protein activates 5′HS3. We show that the function of such closely related proteins can be distinguished in vivo by matching point mutations in 5′HS3 with amino acid changes in the zinc fingers of Sp1 and EKLF. Testing their activity in transgenic mice shows that EKLF is a direct activator of 5′HS3. PMID:9744863

  4. AHR promoter variant modulates its transcription and downstream effectors by allele-specific AHR-SP1 interaction functioning as a genetic marker for vitiligo.

    Science.gov (United States)

    Wang, Xiaowen; Li, Kai; Liu, Ling; Shi, Qiong; Song, Pu; Jian, Zhe; Guo, Sen; Wang, Gang; Li, Chunying; Gao, Tianwen

    2015-09-15

    Vitiligo is an acquired depigmentation disorder largely caused by defective melanocyte- or autoimmunity-induced melanocyte destruction. The aryl hydrocarbon receptor (AHR) is essential for melanocyte homeostasis and immune process, and abnormal AHR was observed in vitiligo. We previously identified the T allele of AHR -129C > T variant as a protective factor against vitiligo. However, biological characterization underlying such effects is not fully certain, further validation by mechanistic research is warranted and was conducted in the present study. We showed that -129T allele promoted AHR transcriptional activity through facilitating its interaction with SP1 transcription factor (SP1) compared with -129C allele. We subsequently found reduced peripheral AHR and SP1 transcript expressions in vitiligo and a negative correlation of AHR level with disease duration. We also investigated AHR-related cytokines and observed increased serum TNF-α concentration and diminished serum levels of IL-10 and TGF-β1 in vitiligo. Further genetic analysis showed that -129T carriers possessed higher levels of AHR and IL-10 than -129C carriers. Therefore, our study indicates that the modulation of AHR transcription by a promoter variant has a profound influence on vitiligo, not only advancing our understanding on AHR function but also providing novel insight into the pathogenesis of degenerative or autoimmune diseases including vitiligo.

  5. Hepatitis B virus X protein upregulates Lin28A/Lin28B through Sp-1/c-Myc to enhance the proliferation of hepatoma cells.

    Science.gov (United States)

    You, X; Liu, F; Zhang, T; Lv, N; Liu, Q; Shan, C; Du, Y; Kong, G; Wang, T; Ye, L; Zhang, X

    2014-01-23

    Hepatitis B virus X protein (HBx) plays critical roles in the pathogenesis of hepatocellular carcinoma (HCC). Here, we were interested in knowing whether the oncogene Lin28A and its homolog Lin28B are involved in the hepatocarcinogenesis mediated by HBx. We showed that the expression levels of Lin28A and Lin28B were increased in clinical HCC tissues, HepG2.2.15 cell line and liver tissues of p21-HBx transgenic mice. Interestingly, the expression levels of HBx were positively associated with those of Lin28A/Lin28B in clinical HCC tissues. Moreover, the overexpression of HBx resulted in the upregulation of Lin28A/Lin28B in hepatoma HepG2/H7402 cell lines by transient transfection, suggesting that HBx was able to upregulate Lin28A and Lin28B. Then, we examined the mechanism by which HBx upregulated Lin28A and Lin28B. We identified that the promoter region of Lin28A regulated by HBx was located at nt -235/-66 that contained Sp-1 binding element. Co-immunoprecipitation showed that HBx was able to interact with Sp-1 in HepG2-X cells. Moreover, chromatin immunoprecipitation (ChIP) demonstrated that HBx could bind to the promoter of Lin28A, which failed to work when Sp-1 was silenced. Electrophoretic mobility shift assay (EMSA) further identified that HBx was able to interact with Sp-1 element in Lin28A promoter via transcription factor Sp-1. In addition, we found that c-Myc was involved in the activation of Lin28B mediated by HBx. In function, Lin28A/Lin28B played important roles in HBx-enhanced proliferation of hepatoma cells in vitro and in vivo. In conclusion, HBx activates Lin28A/Lin28B through Sp-1/c-Myc in hepatoma cells. Lin28A/Lin28B serves as key driver genes in HBx-induced hepatocarcinogenesis.

  6. Sp1 upregulates the proximal promoter activity of the mouse collagen α1(XI) gene (Col11a1) in chondrocytes.

    Science.gov (United States)

    Watanabe, Keijirou; Hida, Mariko; Sasaki, Takako; Yano, Hiroyuki; Kawano, Kenji; Yoshioka, Hidekatsu; Matsuo, Noritaka

    2016-02-01

    Type XI collagen is a cartilage-specific extracellular matrix, and is important for collagen fibril formation and skeletal morphogenesis. We have previously reported that NF-Y regulated the proximal promoter activity of the mouse collagen α1(XI) gene (Col11a1) in chondrocytes (Hida et. al. In Vitro Cell. Dev. Biol. Anim. 2014). However, the mechanism of the Col11a1 gene regulation in chondrocytes has not been fully elucidated. In this study, we further characterized the proximal promoter activity of the mouse Col11a1 gene in chondrocytes. Cell transfection experiments with deletion and mutation constructs indicated that the downstream region of the NF-Y binding site (-116 to +1) is also necessary to regulate the proximal promoter activity of the mouse Col11a1 gene. This minimal promoter region has no TATA box and GC-rich sequence; we therefore examined whether the GC-rich sequence (-96 to -67) is necessary for the transcription regulation of the Col11a1 gene. Luciferase assays using a series of mutation constructs exhibited that the GC-rich sequence is a critical element of Col11a1 promoter activity in chondrocytes. Moreover, in silico analysis of this region suggested that one of the most effective candidates was transcription factor Sp1. Consistent with the prediction, overexpression of Sp1 significantly increased the promoter activity. Furthermore, knockdown of Sp1 expression by siRNA transfection suppressed the proximal promoter activity and the expression of endogenous transcript of the mouse Col11a1 gene. Taken together, these results indicate that the transcription factor Sp1 upregulates the proximal promoter activity of the mouse Col11a1 gene in chondrocytes.

  7. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study.

    Directory of Open Access Journals (Sweden)

    Stuart H Ralston

    2006-04-01

    Full Text Available Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes.Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI] BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2 lower in TT homozygotes than the other genotype groups (p < 0.001, and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2, (p = 0.039. These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08] in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77] that was independent of BMD, and unaltered in adjusted analyses.Allowing for the inevitable heterogeneity between participating teams, this study-which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene-demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases.

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

    Science.gov (United States)

    Kothinti, Rajendra K; Blodgett, Amy B; Petering, David H; Tabatabai, Niloofar M

    2010-05-01

    Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose transporters, SGLT1 and SGLT2 and that Sp1 from Cd-exposed cells displayed reduced binding to the GC boxes of the mouse SGLT1 promoter in vitro. Here, we identified a GC box upstream of mouse SGLT2 gene. ChIP assays on PMKC revealed that exposure to 5 microM Cd abolished Sp1 binding to SGLT1 GC box while it decreased Sp1 binding to SGLT2 GC sequence by 30% in vivo. The in vitro DNA binding assay, EMSA, demonstrated that binding of Sp1 from Cd (7.5 microM)-treated PMKC to the SGLT2 GC probe was 86% lower than in untreated cells. Sp1 is a zinc finger protein. Compared to PMKC exposed to 5 microM Cd alone, inclusion of 5 microM Zn restored SGLT1 and 2 mRNA levels by 15% and 30%, respectively. Cd (10 microM) decreased the binding of recombinant Sp1 (rhSp1) to SGLT1 and SGLT2 GC probes to 12% and 8% of untreated controls. Cd exerted no effect on GC-bound rhSp1. Co-treatment with Cd and Zn showed that added Zn significantly restored rhSp1 binding to the SGLT1 and SGLT2. Addition of Zn post Cd treatment was not stimulatory. We conclude that Cd can replace Zn in Sp1 DNA binding domain to reduce its binding to GC sites in mouse SGLT1 and SGLT2 promoters. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Palladium-Catalyzed Alkylation with Alkyl Halides by C(sp(3) )-H Activation.

    Science.gov (United States)

    Wu, Zhuo; Ma, Ding; Zhou, Bo; Ji, Xiaoming; Ma, Xiaotian; Wang, Xiaoling; Zhang, Yanghui

    2017-09-25

    Utilizing halogens as traceless directing goups represents an attractive strategy for C-H functionalization. A two C-H alkylation system, initiated by the oxidative addition of organohalides to Pd(0) , has been developed. The first reaction involves an intermolecular alkylation of palladacycles to form C(sp(3) )-C(sp(2) ) bonds followed by C(sp(2) )-H activation/cyclization to deliver alkylated benzocyclobutenes as the final products. In the second reaction, two C-C bonds are formed by the reaction of palladacycles with CH2 Br2 , and provides a facile and efficient method for the synthesis of indanes. The alkylated benzocyclobutene products can be transformed into tricyclic hyrocarbons, and the indane derivatives are essential structural motifs in bioactive and odorant molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Superhard sp3 carbon allotropes with odd and even ring topologies

    Science.gov (United States)

    Selli, Daniele; Baburin, Igor A.; Martoňák, Roman; Leoni, Stefano

    2011-10-01

    Four sp3 carbon allotropes with six, eight, and 16 atoms per primitive cell have been derived using a combination of metadynamics simulations and topological scan. A chiral orthorhombic phase oC16 (C2221) was found to be harder than monoclinic M-carbon and shows excellent stability in the high-pressure range. A second orthorhombic phase of Cmmm symmetry, by ˜0.028 eV/atom energetically lower than W-carbon, can be formed from graphite at ˜9 GPa. In general, the mechanical response under pressure was found to depend on the structure topology, which reflects the way rings are formed from an initial graphene layer stacking.

  11. K6 carbon: A metallic carbon allotrope in sp3 bonding networks

    Science.gov (United States)

    Niu, Chun-Yao; Wang, Xin-Quan; Wang, Jian-Tao

    2014-02-01

    We identify by first-principles calculations a new cubic carbon phase in I4132 (O8) symmetry, named K6 carbon, which has a six atom primitive cell comprising sp3 hybridized C3 triangle rings. The structural stability is verified by phonon mode analysis. The calculated elastic constants show that the K6 carbon is a high ductile material with a density even lower than graphite. Electronic band and density of states calculations reveal that it is a metallic carbon allotrope with a high electronic density of states of ˜0.10 states/eV per atom at the Fermi level. These results broaden our understanding of the structural and electronic properties of carbon allotropes.

  12. From zeolite nets to sp(3) carbon allotropes: a topology-based multiscale theoretical study.

    Science.gov (United States)

    Baburin, Igor A; Proserpio, Davide M; Saleev, Vladimir A; Shipilova, Alexandra V

    2015-01-14

    We present a comprehensive computational study of sp(3)-carbon allotropes based on the topologies proposed for zeolites. From ≈600,000 zeolite nets we identified six new allotropes, lying by at most 0.12 eV per atom above diamond. The analysis of cages in the allotropes has revealed close structural relations to diamond and lonsdaleite phases. Besides the energetic and mechanical stability of new allotropes, three of them show band gaps by ca. 1 eV larger than that of diamond, and therefore represent an interesting technological target as hard and transparent materials. A structural relation of new allotropes to continuous random networks is pointed out and possible engineering from diamond thin films and graphene is suggested.

  13. 恢复Windows XP SP3自定义桌面的IE选项

    Institute of Scientific and Technical Information of China (English)

    爱特

    2009-01-01

    微软在SP3的“自定义桌面”里去掉了Internet Explorer选项。如果桌面IE图标被误删除,但是又想恢复,而不是建立快捷方式(到C:\Program Files\Internet Explorer下发送一个快捷方式到桌面),该怎么办呢?网上有很多改注册表的办法,很麻烦,有的也不一定生效,这里有一个小诀窍:

  14. sp3-hybridized framework structure of group-14 elements discovered by genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Manh Cuong [Ames Laboratory; Zhao, Xin [Ames Laboratory; Wang, Cai-Zhuang [Ames Laboratory; Ho, Kai-Ming [Ames Laboratory

    2014-05-01

    Group-14 elements, including C, Si, Ge, and Sn, can form various stable and metastable structures. Finding new metastable structures of group-14 elements with desirable physical properties for new technological applications has attracted a lot of interest. Using a genetic algorithm, we discovered a new low-energy metastable distorted sp3-hybridized framework structure of the group-14 elements. It has P42/mnm symmetry with 12 atoms per unit cell. The void volume of this structure is as large as 139.7Å3 for Si P42/mnm, and it can be used for gas or metal-atom encapsulation. Band-structure calculations show that P42/mnm structures of Si and Ge are semiconducting with energy band gaps close to the optimal values for optoelectronic or photovoltaic applications. With metal-atom encapsulation, the P42/mnm structure would also be a candidate for rattling-mediated superconducting or used as thermoelectric materials.

  15. Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis

    DEFF Research Database (Denmark)

    List, Karin; Haudenschild, Christian C; Szabo, Roman

    2002-01-01

    development and neoplasia. Matriptase/MT-SP1-deficient mice developed to term but uniformly died within 48 h of birth. All epidermal surfaces of newborn mice were grossly abnormal with a dry, red, shiny, and wrinkled appearance. Matriptase/MT-SP1-deficiency caused striking malformations of the stratum corneum...

  16. Palladium(0)-Catalyzed Benzylic C(sp(3))-H Functionalization for the Concise Synthesis of Heterocycles and Its Applications.

    Science.gov (United States)

    Tsukano, Chihiro

    2017-01-01

    C-H functionalization reactions involve the activation of otherwise unreactive C-H bonds, and represent atom economical methods for the direct transformation of simple substrates to complex molecules. While transition metal-catalyzed C(sp(2))-H functionalization reactions are regularly used in synthesis, C(sp(3))-H functionalization is rarely applied to the synthesis of complex natural products because of the difficulties associated with controlling selectivity. With this in mind, we focused on the development of new palladium (Pd)(0)-catalyzed C(sp(3))-H functionalization reactions for the synthesis of complex molecules, resulting in several new methods capable of solving these problems. We initially developed a concise synthetic method for the facile construction of oxindoles and spirooxindoles via a Pd-catalyzed benzylic C(sp(3))-H functionalization reaction. This method was subsequently extended to the synthesis of various heterocycles, including 2-arylindoles, benzocarbazole, indolocarbazole, indoloquinazolinone, and indoloquinazolinedione, as well as the total synthesis of several pyrrolophenanthridine alkaloids without the need for any protecting groups. This method was also successfully applied to the synthesis of the right-hand fragment of benzohopane from tetrahydro-2H-fluorene, which was constructed by a Pd-catalyzed benzylic C(sp(3))-H functionalization. In this review, we provide a detailed discussion of our most recent investigations pertaining to Pd(0)-catalyzed benzylic C(sp(3))-H functionalization.

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

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Dong-Oh [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); Choi, Yung-Hyun [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); Kim, Gi-Young, E-mail: immunkim@jejunu.ac.kr [Department of Marine Life Sciences, Jeju National University, Jeju 690–756 (Korea, Republic of)

    2012-02-15

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

  18. Pro-inflammatory cytokine-driven PI3K/Akt/Sp1 signalling and H2S production facilitates the pathogenesis of severe acute pancreatitis.

    Science.gov (United States)

    Liu, Ying; Liao, Ribin; Qiang, Zhanrong; Zhang, Cheng

    2017-04-30

    Severe acute pancreatitis (SAP) is a disease usually associated with systemic organ dysfunction or pancreatic necrosis. Most patients with SAP suffer from defective intestinal motility in the early phase of the disease. Additionally, SAP-induced inflammation produces hydrogen sulphide (H2S) that impairs the gastrointestinal (GI) system. However, the exact mechanism of H2S in the regulation of SAP is yet to be elucidated. In the present paper, we used a rat model of SAP to evaluate the role of H2S on intestinal motility by counting the number of bowel movements and investigating the effect of H2S on inflammation. We treated colonic muscle cells (CMCs) with SAP plasma, tumour necrosis factor-α (TNF-α) or interleukin-6 (IL-6) and measured the expressions of H2S-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS) and Sp1 and PI3K/Akt by using quantitative PCR, Western blotting and immunohistochemical detection. We used the PI3K inhibitor LY294002 and the siRNA si-Sp1 to suppress the activity of the PI3K/Akt/Sp1 signalling pathway. We found that, in the SAP rat model, H2S facilitated an inhibitory effect on intestinal motility and enhanced the inflammatory response caused by SAP (PH2S plays a vital role in the pathogenesis of SAP and that SAP is modulated by inflammation driven by the PI3K/Akt/Sp1 signalling pathway. © 2017 The Author(s).

  19. Characterization of SP1, a Stress-Responsive, Boiling-Soluble, Homo-Oligomeric Protein from Aspen1

    Science.gov (United States)

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

    2002-01-01

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

  20. Molecular characterization of alkaline protease of Bacillus amyloliquefaciens SP1 involved in biocontrol of Fusarium oxysporum.

    Science.gov (United States)

    Guleria, Shiwani; Walia, Abhishek; Chauhan, Anjali; Shirkot, C K

    2016-09-02

    An alkaline protease gene was amplified from genomic DNA of Bacillus amyloliquefaciens SP1 which was involved in effective biocontrol of Fusarium oxysporum. We investigated the antagonistic capacity of protease of B. amyloliquifaciens SP1, under in vitro conditions. The 5.62 fold purified enzyme with specific activity of 607.69U/mg reported 24.14% growth inhibition of F. oxysporum. However, no antagonistic activity was found after addition of protease inhibitor i.e. PMSF (15mM) to purified enzyme. An 1149bp nucleotide sequence of protease gene encoded 382 amino acids of 43kDa and calculated isoelectric point of 9.29. Analysis of deduced amino acid sequence revealed high homology (86%) with subtilisin E of Bacillus subtilis. The B. amyloliquefaciens SP1 protease gene was expressed in Escherichiax coli BL21. The expressed protease was secreted into culture medium by E. coli and exhibited optimum activity at pH8.0 and 60°C. The most reliable three dimensional structure of alkaline protease was determined using Phyre 2 server which was validated on the basis of Ramachandran plot and ERRAT value. The expression and structure prediction of the enzyme offers potential value for commercial application in agriculture and industry. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Large scale artificial rearing of Anastrepha sp.1 aff. fraterculus (Diptera: Tephritidae in Brazil

    Directory of Open Access Journals (Sweden)

    Julio Marcos Melges Walder

    2014-08-01

    Full Text Available Some species of the genus Anastrepha (Diptera: Tephritidae are successfully managed by matching the sterile insect technique with parasitoid releases. Such strategies used in integrated pest management can be implemented only where insect mass-rearing programs are feasible. In this study, we show the process of domestication, rearing technology and quality control data obtained from 54 generations of Anastrepha sp.1 aff. fraterculus (Wiedemann, 1830 kept under fully artificial conditions. Eggs were collected by an artificial oviposition panel consisting of one side of the cage made of blue voile fabric externally covered with a thin layer of silicon rubber. They were then air-bubbled in water at 25 ºC for 48 h before seeding. Larvae were reared on the regular laboratory artificial diet with 66 % of agar reduction turning over a semi-liquid diet, which reduced costs and improved insect quality. The adult and larval diets were composed of local ingredients including hydrolyzed yeast. When large-scale production of this fly is contemplated, the critical stage is larval development. This system of artificial rearing for A. fraterculus sp.1 developed in Brazil, allows for the production of a large number of insects of excellent quality using local ingredients and less agar in diet composition than the original medium used for this species. By reducing the interval of egg collection, the system might be optimized in terms of insect yield and, therefore, meet the demands of A. fraterculus sp.1 with regard to integrated pest management purposes.

  2. Transcriptional regulation of oncogenic protein kinase Cϵ (PKCϵ) by STAT1 and Sp1 proteins.

    Science.gov (United States)

    Wang, HongBin; Gutierrez-Uzquiza, Alvaro; Garg, Rachana; Barrio-Real, Laura; Abera, Mahlet B; Lopez-Haber, Cynthia; Rosemblit, Cinthia; Lu, Huaisheng; Abba, Martin; Kazanietz, Marcelo G

    2014-07-11

    Overexpression of PKCϵ, a kinase associated with tumor aggressiveness and widely implicated in malignant transformation and metastasis, is a hallmark of multiple cancers, including mammary, prostate, and lung cancer. To characterize the mechanisms that control PKCϵ expression and its up-regulation in cancer, we cloned an ∼ 1.6-kb promoter segment of the human PKCϵ gene (PRKCE) that displays elevated transcriptional activity in cancer cells. A comprehensive deletional analysis established two regions rich in Sp1 and STAT1 sites located between -777 and -105 bp (region A) and -921 and -796 bp (region B), respectively, as responsible for the high transcriptional activity observed in cancer cells. A more detailed mutagenesis analysis followed by EMSA and ChIP identified Sp1 sites in positions -668/-659 and -269/-247 as well as STAT1 sites in positions -880/-869 and -793/-782 as the elements responsible for elevated promoter activity in breast cancer cells relative to normal mammary epithelial cells. RNAi silencing of Sp1 and STAT1 in breast cancer cells reduced PKCϵ mRNA and protein expression, as well as PRKCE promoter activity. Moreover, a strong correlation was found between PKCϵ and phospho-Ser-727 (active) STAT1 levels in breast cancer cells. Our results may have significant implications for the development of approaches to target PKCϵ and its effectors in cancer therapeutics.

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

    OpenAIRE

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

    2014-01-01

    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 ...

  4. High concordance of SP3 rabbit monoclonal antibody with FISH to evaluate HER2 in breast carcinoma.

    Science.gov (United States)

    Wludarski, Sheila C L; Bacchi, Carlos E

    2008-10-01

    HER2 gene amplification or HER2 protein overexpression predicts a more aggressive clinical course in breast cancer, with a worse response to hormonal therapy, and determines eligibility for the use of the anti-HER2 antibody trastuzumab. For these reasons, the diagnostic assays that determine HER2 status in breast carcinoma have become increasingly important. Our goal was to evaluate the concordance, sensitivity, and specificity of a rabbit monoclonal antibody directed to the extracellular domain of the HER2 receptor (SP3) and compare it with fluorescence in situ hybridization and HercepTest in 179 invasive breast carcinomas. We found that SP3 was in agreement with fluorescence in situ hybridization results in 94.6% of cases. HercepTest and fluorescence in situ hybridization results were in agreement in 95.1% of the cases. Only 4.3% (4/93) of the cases that scored 0/1+ by SP3 were amplified by fluorescence in situ hybridization, and 8.3% (3/36) of cases that scored 3+ were not amplified by fluorescence in situ hybridization. Comparing SP3 with HercepTest, we observed that HercepTest demonstrated higher sensitivity (100.0% vs. 89.0%) but SP3 demonstrated higher specificity (97.0% vs. 89.0%). An important advantage of SP3 (in comparison with HercepTest) is its higher discrimination power (72.1% vs. 34.1%). For these reasons, this antibody could be helpful in the determination of HER2 status in a routine basis.

  5. Correlation and comparison of immunohistochemistry for HER2/neu, using the antibody SP3 and chromogenic in situ hybridization in breast carcinomas samples

    Directory of Open Access Journals (Sweden)

    Franciele F. Wolf

    2015-12-01

    Full Text Available ABSTRACT Introduction: Advances in the field of molecular biology have provided the differentiation of molecular subtypes of breast tumors, providing better prognosis and important tools for the treatment of patients with breast cancer. Among these subtypes, the changes in the human epidermal growth factor receptor 2 gene (HER2/neu, increase its copy number and generating HER2 protein amplification. Studies show that patients with breast cancer HER2/neu amplified tend to relapse earlier and have shorter survival time, the monoclonal antibody Trastuzumab is the therapy indicated. The eligibility of patients for therapy is initially made by the immunohistochemistry (IHC technique, which evaluates the expression level of the HER2 protein. After this evaluation, the cases with equivocal diagnosis (score 2+, are referred to a more accurate technique, the chromogenic in situ hybridization (CISH. Objective: To analyze the sensitivity and specificity of the antibody SP3, and determine their level of agreement with the CISH technique. Material and methods: Retrospective study in the database of the anatomy-pathology laboratory, in CISH tests reports for HER2/neu. Conclusion: The results revealed that clone SP3 showed 100% specificity and 92% sensitivity. IHC reveals variability in its results; however, it is known that the technique is an important tool in the daily routine of laboratories, contributing to the initial screening of patients with breast cancer, which later showed satisfactory results when compared with the CISH technique.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, Jian-Ying [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); Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 701, Taiwan (China)

    2011-04-15

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

  7. THE CANNABINOID WIN 55,212-2 DECREASES SPECIFICITY PROTEIN (Sp) TRANSCRIPTION FACTORS AND THE ONCOGENIC CAP PROTEIN eIF4E IN COLON CANCER CELLS

    Science.gov (United States)

    Sreevalsan, Sandeep; Safe, Stephen

    2013-01-01

    2,3-Dihydro-5-methyl-3-([morpholinyl]methyl)pyrollo(1,2,3-de)-1,4-benzoxazinyl]-[1-naphthaleny]methanone [WIN 55,212-2 (WIN)] is a synthetic cannabinoid that inhibits RKO, HT-29 and SW480 cell growth, induced apoptosis, and downregulated expression of survivin, cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and its receptor (VEGFR1). WIN also decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4, and this is consistent with the observed downregulation of the aforementioned Sp-regulated genes. In addition, we also observed by RNA interference (RNAi) that the oncogenic cap protein eIF4E was an Sp-regulated gene also downregulated by WIN in colon cancer cells. WIN-mediated repression of Sp proteins was not affected by CB receptor antagonists or by knockdown of the receptor but was attenuated by the phosphatase inhibitor sodium orthovanadate or by knockdown of protein phosphatase 2A (PP2A). WIN-mediated repression of Sp1, Sp3 and Sp4 was due to PP2A-dependent downregulation of microRNA-27a (miR-27a) and induction of miR-27a-regulated ZBTB10 which has previously been characterized as an “Sp repressor”. The results demonstrate that the anticancer activity of WIN is due, in part, to PP2A-dependent disruption of miR-27a:ZBTB10 and ZBTB10-mediated repression of Sp transcription factors and Sp-regulated genes including eIF4E. PMID:24030632

  8. Stapled Peptides by Late-Stage C(sp(3) )-H Activation.

    Science.gov (United States)

    Noisier, Anaïs F M; García, Jesús; Ionuţ, Ioana A; Albericio, Fernando

    2017-01-02

    Despite the importance of stapled peptides for drug discovery, only few practical processes to prepare cross-linked peptides have been described; thus the structural diversity of available staple motifs is currently limited. At the same time, C-H activation has emerged as an efficient approach to functionalize complex molecules. Although there are many reports on the C-H functionalization of amino acids, examples of post-synthetic peptide C-H modification are rare and comprise almost only C(sp(2) )-H activation. Herein, we report the development of a palladium-catalyzed late-stage C(sp(3) )-H activation method for peptide stapling, affording an unprecedented hydrocarbon cross-link. This method was first employed to prepare a library of stapled peptides in solution. The compatibility with various amino acids as well as the influence of the size (i,i+3 and i,i+4) and length of the staple were investigated. Finally, a simple solid-phase procedure was also established.

  9. Synthesis, Structure, and Reactivity of Anionic sp(2) -sp(3) Diboron Compounds: Readily Accessible Boryl Nucleophiles.

    Science.gov (United States)

    Pietsch, Sabrina; Neeve, Emily C; Apperley, David C; Bertermann, Rüdiger; Mo, Fanyang; Qiu, Di; Cheung, Man Sing; Dang, Li; Wang, Jianbo; Radius, Udo; Lin, Zhenyang; Kleeberg, Christian; Marder, Todd B

    2015-05-04

    Lewis base adducts of tetra-alkoxy diboron compounds, in particular bis(pinacolato)diboron (B2 pin2 ), have been proposed as the active source of nucleophilic boryl species in metal-free borylation reactions. We report the isolation and detailed structural characterization (by solid-state and solution NMR spectroscopy and X-ray crystallography) of a series of anionic adducts of B2 pin2 with hard Lewis bases, such as alkoxides and fluoride. The study was extended to alternative Lewis bases, such as acetate, and other diboron reagents. The B(sp(2) )-B(sp(3) ) adducts exhibit two distinct boron environments in the solid-state and solution NMR spectra, except for [(4-tBuC6 H4 O)B2 pin2 ](-) , which shows rapid site exchange in solution. DFT calculations were performed to analyze the stability of the adducts with respect to dissociation. Stoichiometric reaction of the isolated adducts with two representative series of organic electrophiles-namely, aryl halides and diazonium salts-demonstrate the relative reactivities of the anionic diboron compounds as nucleophilic boryl anion sources.

  10. Systematic Enumeration of sp3 Nanothreads and Computational Study of their Properties

    Science.gov (United States)

    Xu, Enshi; Lammert, Paul E.; Crespi, Vincent H.

    2015-03-01

    A novel 1D allotrope of carbon arise from slow decompression of solid benzene in high-pressure (GPa) cells, wherein columns of benzene, guided by ``topochemical'' constraint as six-valent 1D super-atoms, rehybridize into a crystal of sp3 nanothreads. We exhaustively enumerate the allowed hexavalent bonding topologies and discovered several new low-energy allotropes not previously described. The intermediate conformational nature of these systems - stiffer than a polymer, more reconfigurable than a nanowire or nanotube - allows the translational repeat unit for interatomic connectivity (``topological unit cell'') to deviate from the crystallographic unit cell. A topological unit of 12 carbons accommodates thirty-seven distinct chemically stable nanothreads, fourteen of which are within 80 meV/carbon of the most stable member. Careful optimization of aperiodic helicity reveals the most stable structures to be chiral; several are stiffer (per carbon atom) than bulk diamond. They have the large gaps of saturated hydrocarbons, but reasonable routes exist towards producing semiconducting variants. We generalize Euler's rules for ring counting to cover these systems, and propose a naming convention that can be generalized to handle a broad range of pregenitor molecules.

  11. Visible light mediated efficient oxidative benzylic sp(3) C-H to ketone derivatives obtained under mild conditions using O2.

    Science.gov (United States)

    Yi, Hong; Bian, Changliang; Hu, Xia; Niu, Linbin; Lei, Aiwen

    2015-09-25

    A photooxygenation of benzylic sp(3) C-H reaction has been demonstrated using O2 mediated by visible light. This protocol provides a simple and mild route to obtain ketones from benzylic sp(3) C-H bonds. Various benzylic sp(3) C-H bonds can be transformed into the desired ketone derivatives in moderate to good yields. The (18)O2 labelling experiments demonstrated that the oxygen introduced into ketone originated from dioxygen. A plausible mechanism has been proposed accordingly.

  12. Direct sp(3)C-H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis.

    Science.gov (United States)

    Feng, Zhu-Jia; Xuan, Jun; Xia, Xu-Dong; Ding, Wei; Guo, Wei; Chen, Jia-Rong; Zou, You-Quan; Lu, Liang-Qiu; Xiao, Wen-Jing

    2014-04-07

    Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp(3) C-H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50-91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).

  13. SP1来了Vista普及主流进行时

    Institute of Scientific and Technical Information of China (English)

    高博

    2008-01-01

    @@ Windows Vista的兼容性一直被人诟病,因此,尽管微软在Vista的研发上投入了惊人的时间,人力和金钱,但Vista目前在全球的装机率却始终在20%左右徘徊……更多的用户等待Service Pack 1(补丁集,以下称SP1)的发布,希望解决兼容性问题后再安装Vista.

  14. Ricci Flow of Warped Product Metrics with Positive Isotropic Curvature on $S^{p+1}× S^1$

    Indian Academy of Sciences (India)

    H A Gururaja

    2012-11-01

    We study the asymptotic behaviour of the ODE associated to the evolution of curvature operator in the Ricci flow of a doubly warped product metric on $S^{p+1}× S^1$ with positive isotropic curvature.

  15. [Probiotic features of carotene producing strains Bacillus sp. 1.1 and B. amyloliquefaciens UCM B-5113].

    Science.gov (United States)

    Avdeeva, L V; Nechypurenko, O O; Kharhota, M A

    2015-01-01

    Researched probiotic properties of carotinproducing strains Bacillus sp. 1.1 and B. amyloliquefaciens UCM B-5113. It was established that Bacillus sp. 1.1 characterized by high and middle antagonistic activity against museums and actual test cultures and B. amyloliquefaciens UCM B-5113 shown middle and low activity. They grew up and formed a pigment at pH 6.0 in the presence of 0.4% bile. Bacillus sp. 1.1 and B. amyloliquefaciens UCM B-5113 were avirulent, had low antagonistic activity and characterized by susceptibility to antimicrobial agents, excluding colistin. The results suggested the possibility to create based on Bacillus sp. 1.1 and B. amyloliquefaciens UCM B-5113 probiotic preparation.

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

    Science.gov (United States)

    Chuang, Tyler Casey

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

  17. ANALISIS KESESUAIAN LAHAN TINGKAT SATUAN PEMUKIMAN MENGGUNAKAN AUTOMATED LAND EVALUATION SYSTEM (ALES: STUDI KASUS RANTAU PANDAN SP-1, PROVINSI JAMBI

    Directory of Open Access Journals (Sweden)

    Widiatmaka Widiatmaka

    2012-07-01

    Full Text Available Landuse planning according to biophysical and economical land suitability as well as basic allocation for transmigration should be done in order to improve the well-being of transmigrants. Suitability should be analyzed for the selection of commodities which are the most appropriate biophysically and profitable economically. The study was done in the settlements unit of Rantau Pandan SP-1, Jambi Province. The study was conducted to determine the suitability of each part of land for cultivation of food crops, vegetables and perennial crops and to see the biophysical suitability and economical feasibility. The goal is to recommend the most appropriate type of cultivation. This study integrate the Arc-View GIS and Automated Land Evaluation System (ALES in the analysis of land suitability. The results showed that four agricultural commodities were observed showing land suitability class domination of S3 (marginally suitable with the most dominant limiting factors were erosion and nutrient retention. The results of the analysis have been used for the determination of land use recommendations in the transmigration sites, presented spatially. Recommendations given based on the results of the analysis were not always in line with the land use recomended by government on dry land transmigration. Nonetheless, these results was suggested to be applied, either by considerations of conservation land and the consideration of economic benefit and farmers welfare. Key words: Land evaluation, transmigration, dry land farming, geographic information system

  18. Reusable ionic liquid-catalyzed oxidative coupling of azoles and benzylic compounds via sp(3) C-N bond formation under metal-free conditions.

    Science.gov (United States)

    Liu, Wenbo; Liu, Chenjiang; Zhang, Yonghong; Sun, Yadong; Abdukadera, Ablimit; Wang, Bin; Li, He; Ma, Xuecheng; Zhang, Zengpeng

    2015-07-14

    The heterocyclic ionic liquid-catalyzed direct oxidative amination of benzylic sp(3) C-H bonds via intermolecular sp(3) C-N bond formation for the synthesis of N-alkylated azoles under metal-free conditions is reported for the first time. The catalyst 1-butylpyridinium iodide can be recycled and reused with similar efficacies for at least eight cycles.

  19. Cloning and Sequence Analysis of Protease (SP1) Gene from Actinomucor elegans%雅致放射毛霉蛋白酶SP1基因的克隆及序列分析

    Institute of Scientific and Technical Information of China (English)

    柯野; 黄伟谦; 李家洲; 谢明权; 罗晓春

    2012-01-01

    雅致放射毛霉蛋白酶具有较好的脱苦味和水解豆类蛋白的能力.为了揭示其结构和功能的关系,促进其开发应用,文中通过RACE和PCR技术克隆获得丝氨酸蛋白酶SP1基因.根据生物信息学中的理论和方法,对SP1进行了较全面的预测和分析.结果表明:SP1基因由4个外显子和3个内含子组成,编码454个氨基酸残基.SP1属于蛋白酶K家族,与Rhizopus microsporus var.chinensis的丝氨酸蛋白酶同源性最高,亲缘关系最近.以蛋白酶K晶体结构(PDB code:1IC6)作为模板进行同源建模,通过对模拟结构的分析可知:SP1分子内无二硫键,具有1个Ca2+结合位点;SP1与蛋白酶K在底物结合区域、氢键、盐键和二硫键等方面均存在差异,这些差异可能就是SP1具有独特的水解作用和脱苦能力的原因.%Proteases produced from Actinomucor elegans (A. elegans) are of preferable debittering effect and high hydrolysis ability to soybean proteins. In order to reveal the relationship between the structure and the function and accelerate the development and application of the proteases, serine protease ( SP1) gene from A. elegans was obtained by means of PCR and RACE techniques, and was then predicted and analyzed in detail based on the bioin-formatics theory and technology. The results show that SP1 gene, which contains 4 exons and 3 introns, encodes 454 amino acid residues, and that SP1 belongs to Proteinase K family and exhibits the closest genetic relationship to Rhizopus microsporus var. chinensis with the highest homology. Moreover, according to the SP1 structure modeled via homology modeling with Proteinase K ( PDB code: 1IC6) as the crystal coordinate, it is found that SP1 has no disulfide bonds and possesses a Ca2+ binding site, and that the differences in substrate-binding region, hydrogen bond, salt bridge and disulfide bond between SP1 and Proteinase K are probably responsible for the special hydrolysis ability and debittering effect

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

    Science.gov (United States)

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

    1995-01-01

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

  1. EFFECTS OF SP1 SITE TO hTERT PROMOTER ACTIVITY AND ITS RESPONSE TO RETINOID ACID

    Institute of Scientific and Technical Information of China (English)

    应磊; 戴冰冰; 王楚; 卢健; 钱关祥

    2005-01-01

    Objective To investigate the function of Sp1 consensus sites to human telomerase reverse transcriptase (hTERT) promoter in different cell lines and in TRA-treated Held cell. Methods Different length of hTERT promoter was cloned and inserted into pGL3/basic reporter plasmid. The last four Sp1 sites were deleted by PCR and pGL3 B/TRTP413 A reporter plasmid was constructed. All reporter plasmids were transiently transfected into 293, A549, Hela and HepG2 cell lines. 48 h after transfection, luciferase activity was analyzed. hTERT promoter activity of Held cell which was treated with trans-retinoid acid (TRA) was tested too. Total RNA of these cells were extracted and reverse transcript. hTERT mRNA level was analyzed in all tested cells. c-Myc and Sp1 expression were examined in Hela cell before and after TRA treatment. U937 was used as a positive control in TRA treatment.Results hTERT was expressed at different level in all tested cell lines. 207bp promoter upstream of transcription start site maintained complete activity. Deletion of last 4 Sp1 sites greatly decreased activity of hTERT promoter, and almost eliminated its activity in HepG2. TRA increased the activity of different length hTERT promoters in Hela cell,but the activity of Sp1 site-deleted promoter decreased by 3 times. Unlike U937 cell, hTERT expression of Held cell increased after TRA treatment, and c-Myc and Sp1 mRNA level were relatively stable. Conclusion Sp1 site was required for transactivation of hTERT promoter and played an important role during TRA treatment.

  2. Genetic selection for context-dependent stochastic phenotypes: Sp1 and TATA mutations increase phenotypic noise in HIV-1 gene expression.

    Directory of Open Access Journals (Sweden)

    Kathryn Miller-Jensen

    Full Text Available The sequence of a promoter within a genome does not uniquely determine gene expression levels and their variability; rather, promoter sequence can additionally interact with its location in the genome, or genomic context, to shape eukaryotic gene expression. Retroviruses, such as human immunodeficiency virus-1 (HIV, integrate their genomes into those of their host and thereby provide a biomedically-relevant model system to quantitatively explore the relationship between promoter sequence, genomic context, and noise-driven variability on viral gene expression. Using an in vitro model of the HIV Tat-mediated positive-feedback loop, we previously demonstrated that fluctuations in viral Tat-transactivating protein levels generate integration-site-dependent, stochastically-driven phenotypes, in which infected cells randomly 'switch' between high and low expressing states in a manner that may be related to viral latency. Here we extended this model and designed a forward genetic screen to systematically identify genetic elements in the HIV LTR promoter that modulate the fraction of genomic integrations that specify 'Switching' phenotypes. Our screen identified mutations in core promoter regions, including Sp1 and TATA transcription factor binding sites, which increased the Switching fraction several fold. By integrating single-cell experiments with computational modeling, we further investigated the mechanism of Switching-fraction enhancement for a selected Sp1 mutation. Our experimental observations demonstrated that the Sp1 mutation both impaired Tat-transactivated expression and also altered basal expression in the absence of Tat. Computational analysis demonstrated that the observed change in basal expression could contribute significantly to the observed increase in viral integrations that specify a Switching phenotype, provided that the selected mutation affected Tat-mediated noise amplification differentially across genomic contexts. Our study

  3. Enhanced photocatalytic activity induced by sp 3 to sp 2 transition of carbon dopants in BiOCl crystals

    KAUST Repository

    Sun, Jianguo

    2017-09-19

    The insufficient light absorption and low quantum efficiency limit the photocatalytic performance of wide bandgap semiconductors. Here, we report a facile strategy to engineer the surface disordered defects of BiOCl nanosheets via carbon doping. The surface defects boost the light absorption and also the quantum yields, as the doped carbon atoms exhibit a transition from sp3 to sp2 hybridization at elevated temperature, corresponding to a change of assembly state from 3D cluster to 2D graphite-like structure. This transition results in an effective charge separation and thus one order of enhancement in photocatalytic activity toward phenol degradation under visible light. The current study opens an avenue to introduce sp3 to sp2 transition of carbon dopants for simultaneous increment of light absorption and quantum efficiency for application in photocatalysis and energy conversion.

  4. Hybrid radiosity-SP3 equation based bioluminescence tomography reconstruction for turbid medium with low- and non-scattering regions

    Science.gov (United States)

    Chen, Xueli; Zhang, Qitan; Yang, Defu; Liang, Jimin

    2014-01-01

    To provide an ideal solution for a specific problem of gastric cancer detection in which low-scattering regions simultaneously existed with both the non- and high-scattering regions, a novel hybrid radiosity-SP3 equation based reconstruction algorithm for bioluminescence tomography was proposed in this paper. In the algorithm, the third-order simplified spherical harmonics approximation (SP3) was combined with the radiosity equation to describe the bioluminescent light propagation in tissues, which provided acceptable accuracy for the turbid medium with both low- and non-scattering regions. The performance of the algorithm was evaluated with digital mouse based simulations and a gastric cancer-bearing mouse based in situ experiment. Primary results demonstrated the feasibility and superiority of the proposed algorithm for the turbid medium with low- and non-scattering regions.

  5. B-C-N Compounds with Mixed Hybridization of sp2-Like and sp3-Like Bonds

    Institute of Scientific and Technical Information of China (English)

    LUO Xiao-Guang; HE Ju-Long

    2012-01-01

    We perform first-principles calculations of the structural and electronic properties of hypothetical bc6-BC4N and N-substituted bc6-BC4N,which are derived from a body-center-cubic carbon structure.Our calculations show that the former is a semiconductor with an indirect band gap of 0.91 eV and the latter is metallic.The calculated bond length,bond population,and charge density of N-substituted bc6-BC4N indicate that one C-N bond has been broken after N-substitution,which means that the structure contains a mixed hybridization of sp2-like and sp3-1ike bonds.At the pressure above 100 GPa,the structure changes to a pure sp3-like hybridization.

  6. sp(2)-sp(3) diboranes: astounding structural variability and mild sources of nucleophilic boron for organic synthesis.

    Science.gov (United States)

    Dewhurst, Rian D; Neeve, Emily C; Braunschweig, Holger; Marder, Todd B

    2015-06-14

    Despite the widespread use of organoborane reagents in organic synthesis and catalysis, a major challenge still remains: very few boron-centered nucleophiles exist for the direct construction of B-C bonds. Perhaps the most promising emerging solution to this problem is the use of sp(2)-sp(3) diboranes, in which one boron atom of a conventional diborane(4) is quaternised by either a neutral or anionic nucleophile. These compounds, either isolated or generated in situ, serve as relatively mild and convenient sources of the boryl anion [BR2](-) for use in organic synthesis and have already proven their efficacy in metal-free as well as metal-catalysed borylation reactions. This Feature article documents the history of sp(2)-sp(3) diborane synthesis, their properties and surprising structural variability, and their burgeoning utility in organic synthesis.

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

    Science.gov (United States)

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

    2012-04-01

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

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

    Science.gov (United States)

    Nakanishi, Nagayasu; Hartenstein, Volker; Jacobs, David K

    2009-06-01

    We examined the development of the nervous system in the rhopalium, a medusa-specific sensory structure, in Aurelia sp.1 (Cnidaria, Scyphozoa) using confocal microscopy. The rhopalial nervous system appears primarily ectodermal and contains neurons immunoreactive to antibodies against tyrosinated tubulin, taurine, GLWamide, and FMRFamide. The rhopalial nervous system develops in an ordered manner: the presumptive gravity-sensing organ, consisting of the lithocyst and the touch plate, differentiates first; the "marginal center," which controls swimming activity, second; and finally, the ocelli, the presumptive photoreceptors. At least seven bilaterally arranged neuronal clusters consisting of sensory and ganglion cells and their neuronal processes became evident in the rhopalium during metamorphosis to the medusa stage. Our analysis provides an anatomical framework for future gene expression and experimental studies of development and functions of scyphozoan rhopalia.

  9. Coupling of C(sp(3))-H bonds with C(sp(2))-O electrophiles: mild, general and selective.

    Science.gov (United States)

    Gui, Yong-Yuan; Liao, Li-Li; Sun, Liang; Zhang, Zhen; Ye, Jian-Heng; Shen, Guo; Lu, Zhi-Peng; Zhou, Wen-Jun; Yu, Da-Gang

    2017-01-17

    Herein is reported the mild and general coupling of amine/ether C(sp(3))-H bonds with various kinds of C(sp(2))-O electrophiles with high selectivity and efficiency. Valuable allylic/benzylic amines are generated in moderate to excellent yields. The utility of this transformation is demonstrated by a broad substrate scope (>50 examples), good functional group tolerance and facile product modification.

  10. A Scalable Protocol for the Regioselective Alkylation of 2-Methylcyclohexane-1,3-dione with Unactivated sp3 Electrophiles

    Science.gov (United States)

    Sharpe, Robert J.; Portillo, Maribel; Vélez, Robert A.

    2015-01-01

    A method for the C-selective alkylation of 2-methylcyclohexane-1,3-dione with unactivated sp3 electrophiles is accomplished via alkylation and subsequent deprotection of the derived ketodimethyl hydrazones. The present method provides a high-yielding entry to dialkyl cycloalkanones that cannot be accessed via direct alkylation of 2-methylcyclohexane-1,3-dione. The title reaction may be useful in the scalable preparation of terpene and steroidal building blocks in the arena of natural product synthesis. PMID:26525231

  11. Effect of out-of-plane directional intra-layer coupling from graphene monolayer on sp3 type defect with gap-plasmonic structures

    Science.gov (United States)

    Park, Won-Hwa

    2016-09-01

    The author investigates an intra-layer coupling effect through transverse acoustic (TA) phonon modes along the z-direction at Au nanoparticle (NP)-graphene monolayer (GM)-Au thin film (TF) plasmonic junctions in regard with sp3 type defect effect. The oxidation and resulting disorder of GM with breaking of six-fold symmetry have been explored. Because a Raman-forbidden D peak can be activated due to unwanted single-phonon inter-valley and intra-valley scattering processes, the quantitative estimation of the sp3 type defect is being performed by the intensity ratio between G and D peaks. By exploring the difference of the maximum peak position (TA3-TA1) and the intensity ratio, (TA1/TA3) the author can reveal that a lower z-protruded GM accompanied with weak intra-coupling and a weaker RBLM intensity show relatively high D/G. It means that larger surface area of a GM to be functionalized by oxidization can secure more easily than the higher z-protruded. This investigation presents the importance of controlling the degree of z-protrusion of GM surface in terms of not only the presence of high D/G but also its related and detailed nano-structural surface shape, leading to the enhancement of electrical properties such as a carrier mobility and sheet resistance value. The out-of-plane phonon modes will be considered as a key factor in further exploring nano-physical deformation of 2D materials in sync with its electrical performance.

  12. The stimulatory effect of Pantoea sp. 3.5.1 on the seed germination, plant growth and development

    Directory of Open Access Journals (Sweden)

    L.R. Nigmatulina

    2016-04-01

    Full Text Available Recent years increasing pressure on the environment is extremely exacerbated by the increasing growth of the world population needs. According to world population prospects data [World Population Prospects: The 2015 Revision] human population will increase and by 2025 will estimate to reach approximately 8 billion people. That is why people needed to use herbicides, pesticides and fertilizers to increase agricultural productivity. But most of them are persistent environmental pollutants because of their resistance to degradation and remaining in the environment for years. It may accumulate to biohazard concentrations what leads to environment poisoning [Ritter et al., 2007]. At the same time application plant-growth promoting bacteria is environmentally friendly approach. Here we show that Pantoea sp. 3.5.1 capable to promote a strong plant growth. Also here we characterize main Pantoea sp. 3.5.1 plant growth promoting mechanisms. Thus Pantoea sp. 3.5.1 is discussed to show a great promise in development of environmentally save fertilizers.

  13. A Manganese Catalyst for Highly Reactive Yet Chemoselective Intramolecular C(sp3)—H Amination

    Science.gov (United States)

    Paradine, Shauna M.; Griffin, Jennifer R.; Zhao, Jinpeng; Petronico, Aaron L.; Miller, Shannon M.; White, M. Christina

    2016-01-01

    C—H bond oxidation reactions underscore the existing paradigm wherein high reactivity and high selectivity are inversely correlated. The development of catalysts capable of oxidizing strong aliphatic C(sp3)—H bonds while displaying chemoselectivity (i.e. tolerance of more oxidizable functionality) remains an unsolved problem. Herein, we describe a catalyst, manganese tert-butylphthalocyanine [Mn(tBuPc)], that is an outlier to the reactivity-selectivity paradigm. It is unique in its capacity to functionalize all types of C(sp3)—H bonds intramolecularly, while displaying excellent chemoselectivity in the presence of π-functionality. Mechanistic studies indicate that [Mn(tBuPc)] transfers bound nitrenes to C(sp3)—H bonds via a pathway that lies between concerted C—H insertion, observed with reactive noble metals (e.g. rhodium), and stepwise radical C—H abstraction/rebound, observed with chemoselective base metals (e.g. iron). Rather than achieving a blending of effects, [Mn(tBuPc)] aminates even 1° aliphatic and propargylic C—H bonds, reactivity and selectivity unusual for previously known catalysts. PMID:26587714

  14. Important roles of multiple Sp1 binding sites and epigenetic modifications in the regulation of the methionine sulfoxide reductase B1 (MsrB1 promoter

    Directory of Open Access Journals (Sweden)

    Favaloro Bartolo

    2007-05-01

    Full Text Available Abstract Background Methionine sulfoxide reductases (Msrs are enzymes that catalyze the reduction of oxidized methionine residues. Most organisms that were genetically modified to lack the MsrA gene have shown shortening of their life span. Methionine sulfoxide reductases B (MsrB proteins codified by three separate genes, named MsrB1, MsrB2, and MsrB3, are included in the Msrs system. To date, the mechanisms responsible for the transcriptional regulation of MsrB genes have not been reported. The aim of this study was to investigate the regulation of MsrB1 selenoprotein levels through transcriptional regulation of the MsrB1 gene in MDA-MB231 and MCF-7 breast carcinoma cell lines. Results A MsrB1 gene promoter is located 169 base pairs upstream from the transcription start site. It contains three Sp1 binding sites which are sufficient for maximal promoter activity in transient transfection experiments. High levels of MsrB1 transcript, protein and promoter activity were detected in low metastatic MCF7 human breast cancer cells. On the contrary, very low levels of both MsrB1 transcript and promoter activity were detected in the highly metastatic counterpart MDA-MB231 cells. A pivotal role for Sp1 in the constitutive expression of the MsrB1 gene was demonstrated through transient expression of mutant MsrB1 promoter-reporter gene constructs and chromatin immunoprecipitation experiments. Since Sp1 is ubiquitously expressed, these sites, while necessary, are not sufficient to explain the patterns of gene expression of MsrB1 in various human breast cancer cells. MDA-MB231 cells can be induced to express MsrB1 by treatment with 5-Aza-2'-deoxycytidine, a demethylating agent. Therefore, the MsrB1 promoter is controlled by epigenetic modifications. Conclusion The results of this study provide the first insights into the transcriptional regulation of the human MsrB1 gene, including the discovery that the Sp1 transcription factor may play a central role in its

  15. Regulation of Chloroplast Protein Import by the Ubiquitin E3 Ligase SP1 Is Important for Stress Tolerance in Plants.

    Science.gov (United States)

    Ling, Qihua; Jarvis, Paul

    2015-10-05

    Chloroplasts are the organelles responsible for photosynthesis in plants [1, 2]. The chloroplast proteome comprises ∼3,000 different proteins, including components of the photosynthetic apparatus, which are highly abundant. Most chloroplast proteins are nucleus-encoded and imported following synthesis in the cytosol. Such import is mediated by multiprotein complexes in the envelope membranes that surround each organelle [3, 4]. The translocon at the outer envelope membrane of chloroplasts (TOC) mediates client protein recognition and early stages of import. The TOC apparatus is regulated by the ubiquitin-proteasome system (UPS) in a process controlled by the envelope-localized ubiquitin E3 ligase SUPPRESSOR OF PPI1 LOCUS1 (SP1) [5, 6]. Previous work showed that SP1-mediated regulation of chloroplast protein import contributes to the organellar proteome changes that occur during plant development (e.g., during de-etiolation). Here, we reveal a critical role for SP1 in plant responses to abiotic stress, which is a major and increasing cause of agricultural yield losses globally [7]. Arabidopsis plants lacking SP1 are hypersensitive to salt, osmotic, and oxidative stresses, whereas plants overexpressing SP1 are considerably more stress tolerant than wild-type. We present evidence that SP1 acts to deplete the TOC apparatus under stress conditions to limit the import of photosynthetic apparatus components, which may attenuate photosynthetic activity and reduce the potential for reactive oxygen species production and photo-oxidative damage. Our results indicate that chloroplast protein import is responsive to environmental cues, enabling dynamic regulation of the organellar proteome, and suggest new approaches for improving stress tolerance in crops.

  16. MicroRNA-128 regulates the proliferation and differentiation of bovine skeletal muscle satellite cells by repressing Sp1.

    Science.gov (United States)

    Dai, Yang; Zhang, Wei Ran; Wang, Yi Min; Liu, Xin Feng; Li, Xin; Ding, Xiang Bin; Guo, Hong

    2016-03-01

    MicroRNAs (miRNAs) play essential roles in muscle cell proliferation and differentiation. The muscle-specific miRNAs miR-1 and miR-206 have been shown to regulate muscle development and promote myogenic differentiation; however, it is likely that a number of other miRNAs play important roles in regulating myogenesis as well. microRNA-128 (miR-128) has been reported to be highly expressed in brain and skeletal muscle, and we found that miR-128 is also up-regulated during bovine skeletal muscle satellite cell differentiation using microarray analysis and qRT-PCR. However, little is known about the functions of miR-128 in bovine skeletal muscle satellite cell development. In this study, we investigated the biological functions of miR-128 in bovine skeletal muscle cell development. Using a dual-luciferase reporter assay, we confirmed that miR-128 regulates the Sp1 gene. Over-expression of miR-128 reduced Sp1 protein levels and inhibited muscle satellite cell proliferation and differentiation. Inhibition of miR-128 increased Sp1 protein levels and promoted muscle satellite cell differentiation but also suppressed proliferation. Changes in miR-128 and Sp1 expression levels also affected the protein levels of MyoD and CDKN1A. Sp1, an activator of MyoD and a suppressor of CDKN1A, plays an important role in bovine muscle cell proliferation and differentiation. The results of our study reveal a mechanism by which miR-128 regulates bovine skeletal muscle satellite cell proliferation and myogenic differentiation via Sp1.

  17. Genome-wide occupancy of SREBP1 and its partners NFY and SP1 reveals novel functional roles and combinatorial regulation of distinct classes of genes.

    Directory of Open Access Journals (Sweden)

    Brian D Reed

    2008-07-01

    Full Text Available The sterol regulatory element-binding protein (SREBP family member SREBP1 is a critical transcriptional regulator of cholesterol and fatty acid metabolism and has been implicated in insulin resistance, diabetes, and other diet-related diseases. We globally identified the promoters occupied by SREBP1 and its binding partners NFY and SP1 in a human hepatocyte cell line using chromatin immunoprecipitation combined with genome tiling arrays (ChIP-chip. We find that SREBP1 occupies the promoters of 1,141 target genes involved in diverse biological pathways, including novel targets with roles in lipid metabolism and insulin signaling. We also identify a conserved SREBP1 DNA-binding motif in SREBP1 target promoters, and we demonstrate that many SREBP1 target genes are transcriptionally activated by treatment with insulin and glucose using gene expression microarrays. Finally, we show that SREBP1 cooperates extensively with NFY and SP1 throughout the genome and that unique combinations of these factors target distinct functional pathways. Our results provide insight into the regulatory circuitry in which SREBP1 and its network partners coordinate a complex transcriptional response in the liver with cues from the diet.

  18. The variances of Sp1 and NF-κB elements correlate with the greater capacity of Chinese HIV-1 B′-LTR for driving gene expression

    Science.gov (United States)

    Qu, Di; Li, Chuan; Sang, Feng; Li, Qiang; Jiang, Zhi-Qiang; Xu, Li-Ran; Guo, Hui-Jun; Zhang, Chiyu; Wang, Jian-Hua

    2016-01-01

    The 5′ end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles from major endemic Chinese subtypes are not well characterized. Here, by characterizing the sequences and functions of LTRs from endemic Chinese HIV-1 subtypes, we showed that nucleotide variances of Sp1 core promoter and NF-κB element are associated with varied LTR capacity for driving viral gene transcription. The greater responsiveness of Chinese HIV-1 B′-LTR for driving viral gene transcription upon stimulation is associated with an increased level of viral reactivation. Moreover, we demonstrated that the introduction of CRISPR/dead Cas9 targeting Sp1 or NF-κB element suppressed viral gene expression. Taken together, our study characterized LTRs from endemic HIV-1 subtypes in China and suggests a potential target for the suppression of viral gene expression and a novel strategy that facilitates the accomplishment of a functional cure. PMID:27698388

  19. Gene environment interaction in periphery and brain converge to modulate behavioral outcomes: Insights from the SP1 transient early in life interference rat model

    Science.gov (United States)

    Asor, Eyal; Ben-Shachar, Dorit

    2016-01-01

    It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages. The present article reviews the main theoretical and practical concepts in the research of gene environment interaction, emphasizing the need for models simulating real life complexity. We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes, by hindering the activity of the ubiquitous transcription factor specificity protein 1 (Sp1) is followed by later-in-life exposure of rats to stress. Finally, this review discusses the role of peripheral processes in behavioral responses, with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes. We suggest that models, which take into account the tripartite reciprocal interaction between the central nervous system, peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior. PMID:27679768

  20. Complete gene sequence of spider attachment silk protein (PySp1) reveals novel linker regions and extreme repeat homogenization.

    Science.gov (United States)

    Chaw, Ro Crystal; Saski, Christopher A; Hayashi, Cheryl Y

    2017-02-01

    Spiders use a myriad of silk types for daily survival, and each silk type has a unique suite of task-specific mechanical properties. Of all spider silk types, pyriform silk is distinct because it is a combination of a dry protein fiber and wet glue. Pyriform silk fibers are coated with wet cement and extruded into "attachment discs" that adhere silks to each other and to substrates. The mechanical properties of spider silk types are linked to the primary and higher-level structures of spider silk proteins (spidroins). Spidroins are often enormous molecules (>250 kDa) and have a lengthy repetitive region that is flanked by relatively short (∼100 amino acids), non-repetitive amino- and carboxyl-terminal regions. The amino acid sequence motifs in the repetitive region vary greatly between spidroin type, while motif length and number underlie the remarkable mechanical properties of spider silk fibers. Existing knowledge of pyriform spidroins is fragmented, making it difficult to define links between the structure and function of pyriform spidroins. Here, we present the full-length sequence of the gene encoding pyriform spidroin 1 (PySp1) from the silver garden spider Argiope argentata. The predicted protein is similar to previously reported PySp1 sequences but the A. argentata PySp1 has a uniquely long and repetitive "linker", which bridges the amino-terminal and repetitive regions. Predictions of the hydrophobicity and secondary structure of A. argentata PySp1 identify regions important to protein self-assembly. Analysis of the full complement of A. argentata PySp1 repeats reveals extreme intragenic homogenization, and comparison of A. argentata PySp1 repeats with other PySp1 sequences identifies variability in two sub-repetitive expansion regions. Overall, the full-length A. argentata PySp1 sequence provides new evidence for understanding how pyriform spidroins contribute to the properties of pyriform silk fibers. Copyright © 2017 The Authors. Published by

  1. Vista SP1简体中文版:知错能改 善莫大焉

    Institute of Scientific and Technical Information of China (English)

    曲高强

    2008-01-01

    对于使用Vista的用户来说,通过Windows自动更新程序可以将Vista系统升级到SP1补丁包,Vista SP1的推出对用户来说非常有意义,它将Vista提升到了一个更加安全、更加稳定、更有效率的高度,让用户的体验变得更加美好。

  2. 蜘蛛丝基因MaSp1在转基因家蚕中的表达分析%Expression analysis of spiderdragline silk gene MaSp1 in the transgenic silkworm

    Institute of Scientific and Technical Information of China (English)

    韩冷; 张磊; 中垣雅雄

    2013-01-01

    To study the biological properties and structure of fibroin genes and proteins from transgenic silkworms,the transgenic silkworms were analyzed with inverse PCR,real-time PCR and co-IP methods.The results showed the following:(1) At the DNA level,MaSp1(major ampullate spidroin 1) was integrated into the B.mori chromosome at scaffold 868; (2)At the RNA level,the transcription of MaSp1 did not affect the transcription of Fib-H,Fib-L or P25,and the transcription level of MaSp1 was higher than that of Fib-H; (3) At the protein level,MaSpl,the foreign silk protein,had low abundance among the total silk fibroin proteins (approximate 2%).Additionally,it had a protein-protein interaction with Fib-L through its LBS (L-chain-binding site) region through intermolecular disulfide bonds.%利用反向PCR、定量PCR以及免疫共沉淀等方法分析研究转基因家蚕的丝素蛋白及基因的结构和性质.结果表明:(1)在DNA水平上,MaSp1基因整合进了家蚕的基因组,插入位点位于scaffold 868; (2)在RNA水平上,MaSp1的表达并不干扰其他3个基因(Fib-H,Fib-L and P25)的表达水平,并且外源基因MaSp1的表达水平略高于Fib-H; (3)在蛋白质水平上,MaSp1蛋白的丰度大约占丝素总蛋白的2%,而且通过自身的LBS区段和轻链蛋白(Fib-L)形成分子间二硫键,从而融入蚕丝蛋白复合体.

  3. Significance of different microalgal species for growth of moon jellyfish ephyrae, Aurelia sp.1

    Science.gov (United States)

    Zheng, Shan; Sun, Xiaoxia; Wang, Yantao; Sun, Song

    2015-10-01

    The scyphozoan Aurelia aurita (Linnaeus) sp. l., is a cosmopolitan species-complex which blooms seasonally in a variety of coastal and shelf sea environments around the world. The effects of different microalgal species on the growth of newly-released Aurelia sp.1 ephyrae were studied under laboratory conditions. We fed ephyrae with four different microalgal species (diatom, autotrophic dinoflagellate, heterotrophic dinoflagellate, and chlorophyta) plus Artemia nauplii for 12-24 d at 18°C. Results showed that the growth rate diverged significantly for Artemia nauplii compared to other food types. In addition, there was no significant variation between the growth rates for Skeletonema costatum and Prorocentrum donghaiense, and no significant variation was found in the growth rates for N. scintillans and P. subcordiformis. Artemia nauplii could support the energy requirement for the newly-released ephyrae to develop to meduase, and the ephyrae with Artemia nauplii showed a significant average growth rate of 25.85% d-1. Newly-released ephyrae could grow slightly with some species of microalgae in the earliest development stage. Chain diatom Skeletonema costatum and autotrophic dinoflagellate Prorocentrum donghaiense, could not support the growth of the ephyrae, while heterotrophic dinoflagellate Noctiluca scintillans and chlorophyta Platymonas subcordiformis could support the growth of the ephyrae. However, none of the ephyrae fed with the tested phytoplankton could mature to medusae.

  4. Effect of decreasing temperature on the strobilation of Aurelia sp.1

    Science.gov (United States)

    Shi, Yan; Yu, Zhigang; Zhen, Yu; Wang, Guoshan; Wang, Xungong; Mi, Tiezhu

    2017-05-01

    The worldwide proliferation of marine jellyfish has become a crucial ecological and social issue, and as a cosmopolitan species, Aurelia spp. have received increasing scientific attentions. In the present study, the responses of strobilation in Aurelia sp.1 to decreasing temperature were illuminated through the expression levels of the retinoid x receptor (RxR) gene and the gene encoding a secreted protein, CL390. We observed that a higher final temperature decreased the strobilation prophase and strobilation interphase periods, and the growth rate of the strobilae ratio increased with increasing CL390 gene expression. The ratio of strobilae at 12°C was highest, and the strobilae showed the higher releasing ratios at both 12°C and 16°C compared with those at 4°C and 8°C. Furthermore, more ephyrae were released at the higher final temperature. Additionally, up-regulation and down-regulation of the CL390 gene were observed in response to the four decreasing temperatures. Although the four CL390 gene transcript levels increased more significantly than the transcript levels of the RxR gene, similar trends were observed in both genes.

  5. Desmodesmus sp. 3Dp86E-1-a novel symbiotic chlorophyte capable of growth on pure CO2.

    Science.gov (United States)

    Solovchenko, Alexei; Gorelova, Olga; Selyakh, Irina; Semenova, Larisa; Chivkunova, Olga; Baulina, Olga; Lobakova, Elena

    2014-10-01

    A novel chlorophyte Desmodesmus sp. 3Dp86E-1 isolated from a White Sea hydroid Dynamena pumila was cultivated at CO2 levels from atmospheric (the 'low-CO2' conditions) to pure carbon dioxide (the 5, 20, and 100 % CO2 conditions) under high (480 μE/(m(2) s) PAR) light. After 7 days of cultivation, the '100 % CO2' (but not 5 or 20 % CO2) cells possessed ca. four times higher chlorophyll content per dry weight (DW) unit than the low-CO2 culture. The rate of CO2 fixation under 100 % CO2 comprised ca. 1.5 L/day per L culture volume. After a lag period which depended on the CO2 level, biomass accumulation and volumetric fatty acid (FA) content of the Desmodesmus sp. 3Dp86E-1 bubbled with CO2-enriched gas mixtures increased and was comparable to that of the culture continuously bubbled with air. Under the low-to-moderate CO2 conditions, the FA percentage of the algal cells increased (to 40 % DW) whereas under high-CO2 conditions, FA percentage did not exceed 15 % DW. A strong increase in oleate (18:1) proportion of total FA at the expense of linolenate (18:3) was recorded in the '100 % CO2' cells. Electron microscopy and pulse-amplitude-modulated chlorophyll fluorescence investigation revealed no damage to or significant downregulation of the photosynthetic apparatus in '100 % CO2' cells grown at the high-PAR irradiance. Possible mechanisms of high-CO2 tolerance of Desmodesmus sp. 3Dp86E-1 are discussed in view of its symbiotic origin and possible application for CO2 biomitigation.

  6. Electrochemical conversion/combustion of a model organic pollutant on BDD anode: Role of sp3/sp2 ratio

    OpenAIRE

    Medeiros de Araújo, Danyelle; Cañizares Cañizares, Pablo; Martínez-Huitle, Carlos A.; Rodrigo Rodrigo, Manuel Andrés

    2014-01-01

    In this work, it is presented critical evidence about the influence of sp3/sp2 ratio on the performance of electrochemical oxidation (combustion or conversion) of Rhodamine B (RhB), used as a model organic pollutant. Results demonstrate that the higher the content in diamond-carbon, the greater are the TOC and COD decay rates and hence the oxidation of organic to CO2. The evidence of chromatographic analysis also indicates that the oxidation carried out by the diamonds with lower content of s...

  7. Recent advances in C(sp3)–H bond functionalization via metal–carbene insertions

    Science.gov (United States)

    Wang, Bo; Qiu, Di; Zhang, Yan

    2016-01-01

    Summary The recent development of intermolecular C–H insertion in the application of C(sp3)–H bond functionalizations, especially for light alkanes, is reviewed. The challenging problem of regioselectivity in C–H bond insertions has been tackled by the use of sterically bulky metal catalysts, such as metal porphyrins and silver(I) complexes. In some cases, high regioselectivity and enantioselectivity have been achieved in the C–H bond insertion of small alkanes. This review highlights the most recent accomplishments in this field. PMID:27340470

  8. Recent advances in C(sp3–H bond functionalization via metal–carbene insertions

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2016-04-01

    Full Text Available The recent development of intermolecular C–H insertion in the application of C(sp3–H bond functionalizations, especially for light alkanes, is reviewed. The challenging problem of regioselectivity in C–H bond insertions has been tackled by the use of sterically bulky metal catalysts, such as metal porphyrins and silver(I complexes. In some cases, high regioselectivity and enantioselectivity have been achieved in the C–H bond insertion of small alkanes. This review highlights the most recent accomplishments in this field.

  9. Quercetin Induces Antiproliferative Activity Against Human Hepatocellular Carcinoma (HepG2) Cells by Suppressing Specificity Protein 1 (Sp1).

    Science.gov (United States)

    Lee, Ra Ham; Cho, Jin Hyoung; Jeon, Young-Joo; Bang, Woong; Cho, Jung-Jae; Choi, Nag-Jin; Seo, Kang Seok; Shim, Jung-Hyun; Chae, Jung-Il

    2015-02-01

    Preclinical Research Quercetin, found in red onions and red apple skin can induce apoptosis insome malignant cells. However, the apoptotic effect of quercetin in hepatocellular carcinoma HepG2 cells via regulation of specificity protein 1 (Sp1) has not been studied. Here, we demonstrated that quercetin decreased cell growth and induce apoptosis in HepG2 cells via suppression of Sp1 using 3-(4,5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, Annexin V, and Western blot analysis, an effect that was dose- and time-dependent manner. Treatment of HepG2 cells with quercetin reduced cell growth and induced apoptosis, followed by regulation of Sp1 and Sp1 regulatory protein. Taken together, the results suggest that quercetin can induce apoptotic cell death by regulating cell cycle and suppressing antiapoptotic proteins. Therefore, quercetin may be useful for cancer prevention. Drug Dev Res 76 : 9-16, 2015. © 2015 Wiley Periodicals, Inc.

  10. Large-scale evidence for the effect of the COLIA1 Sp1 Polymorphism on Osteoporosis Outcomes: The GENOMOS study

    NARCIS (Netherlands)

    S.H. Ralston (Stuart); A.G. Uitterlinden (André); M.L. Brandi; S. Balcells (Susana); B.L. Langdahl (Bente); P. Lips (Paul); R. Lorenc (Roman); B. Obermayer-Pietsch (Barbara); S. Scollen (Serena); M. Bustamante (Mariona); L.B. Husted (Lise Bjerre); A. Carey (Alisoun); A. Diez-Perez (Adolfo); A.M. Dunning (Alison); A. Falchetti; E. Karczmarewicz (Elzbieta); M. Kruk (Marcin); J.P.T.M. van Leeuwen (Hans); J.B.J. van Meurs (Joyce); J. Mangion (Jon); F.E. McGuigan; L. Mellibovsky (Leonardo); F. Del Monte (Francesca); H.A.P. Pols (Huib); J. Reeve (Jonathan); D.M. Reid (David); W. Renner (Wilfried); F. Rivadeneira Ramirez (Fernando); N.M. van Schoor (Natasja); J.K. Sherlock (Jon); J.P.A. Ioannidis (John)

    2006-01-01

    textabstractBackground: Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2012-11-22

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

  13. A mutation in a functional Sp1 binding site of the telomerase RNA gene (hTERC promoter in a patient with Paroxysmal Nocturnal Haemoglobinuria

    Directory of Open Access Journals (Sweden)

    Mason Philip J

    2004-06-01

    Full Text Available Abstract Background Mutations in the gene coding for the RNA component of telomerase, hTERC, have been found in autosomal dominant dyskeratosis congenita (DC and aplastic anemia. Paroxysmal nocturnal hemoglobinuria (PNH is a clonal blood disorder associated with aplastic anemia and characterized by the presence of one or more clones of blood cells lacking glycosylphosphatidylinositol (GPI anchored proteins due to a somatic mutation in the PIGA gene. Methods We searched for mutations in DNA extracted from PNH patients by amplification of the hTERC gene and denaturing high performance liquid chromatography (dHPLC. After a mutation was found in a potential transcription factor binding site in one patient electrophoretic mobility shift assays were used to detect binding of transcription factors to that site. The effect of the mutation on the function of the promoter was tested by transient transfection constructs in which the promoter is used to drive a reporter gene. Results Here we report the finding of a novel promoter mutation (-99C->G in the hTERC gene in a patient with PNH. The mutation disrupts an Sp1 binding site and destroys its ability to bind Sp1. Transient transfection assays show that mutations in this hTERC site including C-99G cause either up- or down-regulation of promoter activity and suggest that the site regulates core promoter activity in a context dependent manner in cancer cells. Conclusions These data are the first report of an hTERC promoter mutation from a patient sample which can modulate core promoter activity in vitro, raising the possibility that the mutation may affect the transcription of the gene in hematopoietic stem cells in vivo, and that dysregulation of telomerase may play a role in the development of bone marrow failure and the evolution of PNH clones.

  14. The mineralocorticoid receptor-p38MAPK-NFκB or ERK-Sp1 signal pathways mediate aldosterone-stimulated inflammatory and profibrotic responses in rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Chuan-jiang ZHU; Qing-qing WANG; Jun-lan ZHOU; Han-zhi LIU; Fang HUA; Hong-zheng YANG; Zhuo-wei HU

    2012-01-01

    Aim:To explore the signalling pathways involved in aldosterone-induced inflammation and fibrosis in rat vascular smooth muscle cells (VSMCs).Methods:Using Western blotting and real-time RT-PCR,we investigated the effects of aldosterone on the expression of cyclooxygenase-2 (Cox-2) and IL-6,two important proinflammatory factors,and TGFβ1,a critical profibrotic factor,in VSMCs.Results:Aldosterone treatment significantly increased the expression of Cox-2 and IL-6 and activation of p38MAPK and NF-κB.The expression of both Cox-2 and IL-6 could be blocked by the mineralocorticoid receptor (MR) antagonist spironolactone and the p38MAPK inhibitor SB203580.Also,the rapid phosphorylation of p38MAPK could be suppressed by SB203580 but not by spironolactone,implicating in nongenomic effects of aldosterone.Similar to SB203580 and spironolactone,the NF-κB inhibitor α-p-tosyl-L-lysine chloromethyl ketone (TLCK) markedly attenuated expression of Cox-2,indicating that MR,p38MAPK and NF-KB are associated with aldosterone-induced inflammatory responses.Furthermore,aldosterone enhanced expression of TGFβ1 in rat VSMCs.This result may be related to activation of the MR/ERK-Sp1 signalling pathway because PD98059,an ERK1/2 inhibitor,significantly blocked the rapid phosphorylation of ERK1/2 and function of Sp1 and led to reduced expression of TGFβ1.Spironolactone was also shown to significantly inhibit TGFβ1 and Sp1 expression but not ERK1/2 phosphorylation.Conclusion:These results suggest that aldosterone-induced inflammatory responses and fibrotic responses may be mediated by the MR/p38MAPK-NF-κB pathways and the MR/ERK-Sp1 pathways in VSMCs,respectively.

  15. Sp1 regulates Raf/MEK/ERK-induced p21(CIP1) transcription in TP53-mutated cancer cells.

    Science.gov (United States)

    Karkhanis, Mansi; Park, Jong-In

    2015-03-01

    We previously reported that the upregulation of mortalin, an Hsp70 family chaperone, is important for B-Raf(V600E) tumor cells to bypass p21(CIP1) expression, which is activated as a tumor-suppressive mechanism in response to aberrant MEK/ERK activation (Wu et al., 2013). Interestingly, mortalin depletion induced p21(CIP1) transcription not only in wild-type TP53 but also in TP53-mutated B-Raf(V600E) cancer cells, suggesting the presence of an additional mechanism for p21(CIP1) regulation. In the present study, using luciferase reporter truncation analysis in a TP53-mutated B-Raf(V600E) cancer cell line, SK-MEL28, we identified a proximal p21(CIP1) promoter region responsive to mortalin depletion. Interestingly, when Sp1-like cis-elements in this promoter region were mutagenized, the p21(CIP1) promoter luciferase reporter was no longer responsive to mortalin depletion. Consistent with this, our ChIP analysis revealed that mortalin knockdown could induce Sp1 binding to p21(CIP1) promoter in a MEK/ERK-dependent manner. Moreover, RNA interference of Sp1 substantially attenuated p21(CIP1) expression induced by mortalin depletion in SK-MEL28 cells. Consistent with this observation in SK-MEL28 cells, Sp1 was necessary for the tamoxifen-regulated ∆Raf-1:ER to induce p21(CIP1) transcription in U251 cells, in which TP53 is mutated. However, in contrast, Sp1 was not necessary for ∆Raf-1:ER to induce p21(CIP1) transcription in LNCaP cells, in which TP53 is wild type. These data suggest that Sp1 may address TP53-independent p21(CIP1) transcription in Raf/MEK/ERK-activated cancer cells and that its requirement in Raf/MEK/ERK-induced p21(CIP1) transcription is subject to TP53 status.

  16. Radioimmunologic determination of SP-1 (gestational beta-1-glycoprotein) in the serum and amniotic fluid during normal and pathological courses of gestation. Radioimmunologische Bestimmung von SP-1 (schwangerschaftsspezifisches. beta. 1-Glycoprotein) im Serum und Fruchtwasser bei normalen und pathologischen Schwangerschaften

    Energy Technology Data Exchange (ETDEWEB)

    Courtial, A.

    1986-07-18

    While determinations of SP-1 in the amniotic fluid were found to be of rather limited diagnostic usefulness, both single and repeated measurements in the serum provided valuable information that permitted to predict the presumable patient outcome in cases of imminent abortion attributable to such conditions as diabetic fetopathy or severe gestosis associated with deficient fetal development (one limitation of the method's usefulness being a comparatively high percentage of false-positive results). (TRV).

  17. Schwangerschafts Protein 1 (SP1) adds little to the age-related detection of fetal Down syndrome in the first trimester of pregnancy

    NARCIS (Netherlands)

    Kornman, LH; Morssink, LP; Ten Hoor, KA; De Wolf, BTHM; Kloosterman, MD; Beekhuis, [No Value; Mantingh, A

    1998-01-01

    Schwangerschafts Protein 1 (SP1), being a placental protein appearing in the maternal circulation early in pregnancy, has been investigated as a potential marker for Down syndrome in the first trimester. Our study compared SP1 levels in 15 pregnancies with a Down syndrome fetus and 97 matched contro

  18. Schwangerschafts Protein 1 (SP1) adds little to the age-related detection of fetal Down syndrome in the first trimester of pregnancy

    NARCIS (Netherlands)

    Kornman, LH; Morssink, LP; Ten Hoor, KA; De Wolf, BTHM; Kloosterman, MD; Beekhuis, [No Value; Mantingh, A

    1998-01-01

    Schwangerschafts Protein 1 (SP1), being a placental protein appearing in the maternal circulation early in pregnancy, has been investigated as a potential marker for Down syndrome in the first trimester. Our study compared SP1 levels in 15 pregnancies with a Down syndrome fetus and 97 matched

  19. Application of “SP-3” and “SP-2” in the whole wheat beer brewing%“SP-3”与“SP-2”在全小麦啤酒酿造中应用研究

    Institute of Scientific and Technical Information of China (English)

    袁仲; 杨继远

    2011-01-01

    " SP-3 " was a new beer yeast strain, while " SP-02 " was the normal strain used in the production of malt beer. Comparison experiments of the application of" SP-3 " and " SP-2 " in production of wheat beer were conducted. The results showed that strains " SP-3 " is more adaptable in the whole wheat beer brewing than that of strain " SP-2 ". The parameters of beer by strain "SP-3 " were superior to that of" SP-2 ", which has pure taste, clean and soft, could meet for the current consumer's requirements.%“SP-3”是新选育的啤酒酵母菌株,而“SP-2”为通常生产大麦芽啤酒使用的啤酒酵母菌株,“SP-3”与“SP-2”啤酒酵母菌株在全小麦啤酒生产中应用对比试验结果表明,“SP-3”啤酒酵母菌株在全小麦芽啤酒的酿造中适用性较强,各项指标均优于“SP-2”啤酒酵母菌株,用其酿制的啤酒口感纯正、清爽、柔和,能够较好地适应当前消费者的口感需求.

  20. Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and p53.

    Science.gov (United States)

    Silva, Gabriel; Marins, Mozart; Fachin, Ana Lúcia; Lee, Seong-Ho; Baek, Seung Joon

    2016-10-01

    Osteosarcoma is the most common bone cancer. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Currently, much anticancer therapy uses drugs that affect oncogenes/tumor suppressor genes, such as p53 (up-regulation) and Sp1 (down-regulation). Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Building on this knowledge, we evaluated the ability of trans-chalcone to reduce viability, to induce apoptosis, and to alter gene expression of p53 and Sp1 in human osteosarcoma cell lines. We found that treatment of trans-chalcone inhibited growth of osteosarcoma cells in a dose- and time-dependent manner, with significant inhibition at 10 μM after 48 h; apoptosis was also induced in a dose-dependent manner, with 1.9- and 3.6-fold induction at 10 μM and 50 μM, respectively, compared to non-treated cells. Further experiments suggest that trans-chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. trans-chalcone and its derivatives could be important in the development of future clinical trials in osteosarcoma. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Nguyen Albert T

    2011-12-01

    Full Text Available Abstract 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 α-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.

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

    Science.gov (United States)

    2011-01-01

    Background Bevirimat, the prototype Human Immunodeficiency Virus type 1 (HIV-1) maturation inhibitor, is highly potent in cell culture and efficacious in HIV-1 infected patients. In contrast to inhibitors that target the active site of the viral protease, bevirimat specifically inhibits a single cleavage event, the final processing step for the Gag precursor where p25 (CA-SP1) is cleaved to p24 (CA) and SP1. Results In this study, photoaffinity analogs of bevirimat and mass spectrometry were employed to map the binding site of bevirimat to Gag within immature virus-like particles. Bevirimat analogs were found to crosslink to sequences overlapping, or proximal to, the CA-SP1 cleavage site, consistent with previous biochemical data on the effect of bevirimat on Gag processing and with genetic data from resistance mutations, in a region predicted by NMR and mutational studies to have α-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

  3. 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.

    Science.gov (United States)

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

    2014-03-01

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

  4. Toward ambient temperature operation with all-solid-state lithium metal batteries with a sp3 boron-based solid single ion conducting polymer electrolyte

    Science.gov (United States)

    Zhang, Yunfeng; Cai, Weiwei; Rohan, Rupesh; Pan, Meize; Liu, Yuan; Liu, Xupo; Li, Cuicui; Sun, Yubao; Cheng, Hansong

    2016-02-01

    The ionic conductivity decay problem of poly(ethylene oxide) (PEO)-based solid polymer electrolytes (SPEs) when increase the lithium salt of the SPEs up to high concentration is here functionally overcome by the incorporation of a charge delocalized sp3 boron based single ion conducting polymer electrolyte (SIPE) with poly(ethylene oxide) to fabricate solid-state sp3 boron based SIPE membranes (S-BSMs). By characterizations, particularly differential scanning calorimeter (DSC) and ionic conductivity studies, the fabricated S-BSMs showed decreased melting points and increased ionic conductivity as steadily increase the content of sp3 boron based SIPE, which significantly improved the low temperature performance of the all-solid-state lithium batteries. The fabricated Li | S-BSMs | LiFePO4 cells exhibit highly electrochemical stability and excellent cycling at temperature below melting point of PEO, which has never been reported so far for SIPEs based all-solid-state lithium batteries.

  5. Endomorphins interact with the substance P (SP) aminoterminal SP(1-7) binding in the ventral tegmental area of the rat brain.

    Science.gov (United States)

    Botros, Milad; Johansson, Tobias; Zhou, Qin; Lindeberg, Gunnar; Tömböly, Csaba; Tóth, Géza; Le Grevès, Pierre; Nyberg, Fred; Hallberg, Mathias

    2008-10-01

    We have recently identified a specific binding site for the tachykinin peptide substance P (SP) fragment SP(1-7) in the rat spinal cord. This site appeared very specific for SP(1-7) as the binding affinity of this compound highly exceeded those of other SP fragments. We also observed that endomorphin-2 (EM-2) exhibited high potency in displacing SP(1-7) from this site. In the present work using a [(3)H]-labeled derivative of the heptapeptide we have identified and characterized [(3)H]-SP(1-7) binding in the rat ventral tegmental area (VTA). Similarly to the [(3)H]-SP(1-7) binding in the spinal cord the affinity of unlabeled SP(1-7) to the specific site in VTA was significantly higher than those of other SP fragments. Further, the tachykinin receptor NK-1, NK-2 and NK-3 ligands showed no or negligible binding to the identified site. However, the mu-opioid peptide (MOP) receptor agonists DAMGO, EM-1 and EM-2 did, and significant difference was observed in the binding affinity between the two endomorphins. As recorded from displacement curves the affinity of EM-2 for the SP(1-7) site was 4-5 times weaker than that for SP(1-7) but about 5 times higher than that of EM-1. The opioid receptor antagonists naloxone and naloxonazine showed weak or negligible binding. It was concluded that the specific site identified for SP(1-7) binding in the rat VTA is distinct from the MOP receptor although it exhibits high affinity for EM-2.

  6. Silver-Catalyzed Oxidative C(sp(3) )-P Bond Formation through C-C and P-H Bond Cleavage.

    Science.gov (United States)

    Li, Lili; Huang, Wenbin; Chen, Lijin; Dong, Jiaxing; Ma, Xuebing; Peng, Yungui

    2017-08-21

    The silver-catalyzed oxidative C(sp(3) )-H/P-H cross-coupling of 1,3-dicarbonyl compounds with H-phosphonates, followed by a chemo- and regioselective C(sp(3) )-C(CO) bond-cleavage step, provided heavily functionalized β-ketophosphonates. This novel method based on a readily available reaction system exhibits wide scope, high functional-group tolerance, and exclusive selectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Promoting Maturation Effects of Lactobacillus plantarum SP-3 on Semi-hard Cheese and Influences on Its Flavor%植物乳杆菌SP-3对半硬质干酪的促熟作用及其对风味的影响

    Institute of Scientific and Technical Information of China (English)

    陈帅; 陈卫; 赵建; 刘振民

    2012-01-01

    [ Objective ] Semi-hard cheese was manufactured with Lactobacillus plantarum SP-3 as adjunct culture. The effects of SP-3 on cheese ripening and flavor during ripening were studied. [ Method ] The constituents and microorganism of raw milk and semi- hard cheese were analyzed, water soluble nitrogen( WSN) , WSN in 12% trichloroacetic acid (12% TCA-SN) and total free amino acid content of semi-hard cheese during ripening were determined, and its electrophoretic analysis and sensory evaluation were carried out. [ Result ] Adding SP-3 had no significant effects on normal production process and indices for the manufacture of semi-hard cheeses. SP-3 concentration reached maximum (3.4 × 108 cfu/g) at ripening 60 days in the experimental cheese. SP-3 had positive effects on cheese ripening, and total free amino acids content in the experimental cheese had almost two more times higher than their corresponding controls after ripening 60 days. Sensory assessment and principal component analysis show that SP-3 makes contribution to flavor formation of cheese especially to the milk flavor and nutty flavor. [ Conclusion ] Lactobacillus plantarum SP-3 can promote maturation of semi-hard cheese and is in favour of formation of the milk flavor and nutty flavor of cheese.%[目的]以植物乳杆菌SP-3作为附属发酵剂应用于半硬质干酪的生产,研究SP-3对干酪成熟和风味的影响.[方法]分析原料乳和干酪的组成及微生物,测定干酪成熟过程中可溶性氮(WSN)、12%三氯乙酸溶液中可溶性氮(12%TCA-SN)和总游离氨基酸含量,并对于酪进行电泳分析和感官评价.[结果]添加植物乳杆菌SP-3对半硬质干酪的正常生产工艺和产品指标无显著影响;试验组干酪在成熟60d时,SP-3浓度达到最大值3.4×108cfu/g;SP-3对干酪的成熟具有促进作用,成熟60d后,添加SP-3组干酪的总游离氨基酸含量几乎是对照组的2倍;干酪产品感官评定及主成分分析表明,添加植物乳杆菌SP

  8. Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

    Science.gov (United States)

    Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

    2017-03-01

    Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

  9. Amide-directed photoredox-catalysed C-C bond formation at unactivated sp3 C-H bonds

    Science.gov (United States)

    Chu, John C. K.; Rovis, Tomislav

    2016-11-01

    Carbon-carbon (C-C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C-C bond formation. Strategies that allow C-C bond formation at inert carbon-hydrogen (C-H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules. Here we report a method for the formation of C-C bonds by directed cleavage of traditionally non-reactive C-H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C-C bond formation at unactivated sp3 C-H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayed photoredox-catalysed oxidation of a nitrogen-hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C-H bonds through a strategy involving hydrogen-atom transfer.

  10. Tunable Room-Temperature Single-Photon Emission at Telecom Wavelengths from sp3 Defects in Carbon Nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Blackburn, Jeffrey L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ihly, Rachelle R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); He, Xiaowei [Los Alamos National Laboratory; Hartmann, Nicolai F. [Los Alamos National Laboratory; Ma, Xuedan [Los Alamos National Laboratory; Gao, Weilu [Rice University; Kono, Junichiro [Rice University; Yomogida, Yohei [Tokyo Metropolitan University; Hirano, Atsushi [Tokyo Metropolitan University; Tanaka, Takeshi [Tokyo Metropolitan University; Kataura, Hiromichi [Tokyo Metropolitan University; Htoon, Han [Los Alamos National Laboratory; Doorn, Stephen K. [Los Alamos National Laboratory; Kim, Younghee [Los Alamos National Laboratory

    2017-07-31

    Generating quantum light emitters that operate at room temperature and at telecom wavelengths remains a significant materials challenge. To achieve this goal requires light sources that emit in the near-infrared wavelength region and that, ideally, are tunable to allow desired output wavelengths to be accessed in a controllable manner. Here, we show that exciton localization at covalently introduced aryl sp3 defect sites in single-walled carbon nanotubes provides a route to room-temperature single-photon emission with ultrahigh single-photon purity (99%) and enhanced emission stability approaching the shot-noise limit. Moreover, we demonstrate that the inherent optical tunability of single-walled carbon nanotubes, present in their structural diversity, allows us to generate room-temperature single-photon emission spanning the entire telecom band. Single-photon emission deep into the centre of the telecom C band (1.55 um) is achieved at the largest nanotube diameters we explore (0.936 nm).

  11. Development of Ar-BINMOL-Derived Atropisomeric Ligands with Matched Axial and sp(3) Central Chirality for Catalytic Asymmetric Transformations.

    Science.gov (United States)

    Xu, Zheng; Xu, Li-Wen

    2015-10-01

    Recently, academic chemists have renewed their interest in the development of 1,1'-binaphthalene-2,2'-diol (BINOL)-derived chiral ligands. Six years ago, a working hypothesis, that the chirality matching of hybrid chirality on a ligand could probably lead to high levels of stereoselective induction, prompted us to use the axial chirality of BINOL derivatives to generate new stereogenic centers within the same molecule with high stereoselectivity, obtaining as a result sterically favorable ligands for applications in asymmetric catalysis. This Personal Account describes our laboratory's efforts toward the development of a novel class of BINOL-derived atropisomers bearing both axial and sp(3) central chirality, the so-called Ar-BINMOLs, for asymmetric synthesis. Furthermore, on the basis of the successful application of Ar-BINMOLs and their derivatives in asymmetric catalysis, the search for highly efficient and enantioselective processes also compelled us to give special attention to the BINOL-derived multifunctional ligands with multiple stereogenic centers for use in catalytic asymmetric reactions.

  12. Carboxylate-Assisted C(sp3)–H Activation in Olefin Metathesis-Relevant Ruthenium Complexes

    Science.gov (United States)

    2015-01-01

    The mechanism of C–H activation at metathesis-relevant ruthenium(II) benzylidene complexes was studied both experimentally and computationally. Synthesis of a ruthenium dicarboxylate at a low temperature allowed for direct observation of the C–H activation step, independent of the initial anionic ligand-exchange reactions. A first-order reaction supports an intramolecular concerted metalation–deprotonation mechanism with ΔG⧧298K = 22.2 ± 0.1 kcal·mol–1 for the parent N-adamantyl-N′-mesityl complex. An experimentally determined ΔS⧧ = −5.2 ± 2.6 eu supports a highly ordered transition state for carboxylate-assisted C(sp3)–H activation. Experimental results, including measurement of a large primary kinetic isotope effect (kH/kD = 8.1 ± 1.7), agree closely with a computed six-membered carboxylate-assisted C–H activation mechanism where the deprotonating carboxylate adopts a pseudo-apical geometry, displacing the aryl ether chelate. The rate of cyclometalation was found to be influenced by both the electronics of the assisting carboxylate and the ruthenium ligand environment. PMID:24731019

  13. Network type sp3 boron-based single-ion conducting polymer electrolytes for lithium ion batteries

    Science.gov (United States)

    Deng, Kuirong; Wang, Shuanjin; Ren, Shan; Han, Dongmei; Xiao, Min; Meng, Yuezhong

    2017-08-01

    Electrolytes play a vital role in modulating lithium ion battery performance. An outstanding electrolyte should possess both high ionic conductivity and unity lithium ion transference number. Here, we present a facile method to fabricate a network type sp3 boron-based single-ion conducting polymer electrolyte (SIPE) with high ionic conductivity and lithium ion transference number approaching unity. The SIPE was synthesized by coupling of lithium bis(allylmalonato)borate (LiBAMB) and pentaerythritol tetrakis(2-mercaptoacetate) (PETMP) via one-step photoinitiated in situ thiol-ene click reaction in plasticizers. Influence of kinds and content of plasticizers was investigated and the optimized electrolytes show both outstanding ionic conductivity (1.47 × 10-3 S cm-1 at 25 °C) and high lithium transference number of 0.89. This ionic conductivity is among the highest ionic conductivity exhibited by SIPEs reported to date. Its electrochemical stability window is up to 5.2 V. More importantly, Li/LiFePO4 cells with the prepared single-ion conducting electrolytes as the electrolyte as well as the separator display highly reversible capacity and excellent rate capacity under room temperature. It also demonstrates excellent long-term stability and reliability as it maintains capacity of 124 mA h g-1 at 1 C rate even after 500 cycles without obvious decay.

  14. Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells.

    Science.gov (United States)

    Pathi, Satya S; Lei, Ping; Sreevalsan, Sandeep; Chadalapaka, Gayathri; Jutooru, Indira; Safe, Stephen

    2011-01-01

    Ascorbic acid (vitamin C) inhibits cancer cell growth, and there is a controversy regarding the cancer chemoprotective effects of pharmacologic doses of this compound that exhibits prooxidant activity. We hypothesized that the anticancer activity of pharmacologic doses of ascorbic acid (colon cancer cell proliferation and induced apoptosis and necrosis, and this was accompanied by downregulation of Sp1, Sp3, and Sp4 proteins. In addition, ascorbic acid decreased expression of several Sp-regulated genes that are involved in cancer cell proliferation [hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor and cyclin D1], survival (survivin and bcl-2), and angiogenesis [vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2)]. Other prooxidants such as hydrogen peroxide exhibited similar activities in colon cancer cells, and cotreatment with glutathione inhibited these responses. This study demonstrates for the first time that the anticancer activities of ascorbic acid are due, in part, to ROS-dependent repression of Sp transcription factors.

  15. Free-Radical Triggered Ordered Domino Reaction: An Approach to C-C Bond Formation via Selective Functionalization of α-Hydroxyl-(sp(3))C-H in Fluorinated Alcohols.

    Science.gov (United States)

    Xu, Zhengbao; Hang, Zhaojia; Liu, Zhong-Quan

    2016-09-16

    A free-radical mediated highly ordered radical addition/cyclization/(sp(3))C-C(sp(3)) formation domino reaction is developed. Three new C-C bonds are formed one by one in a mixed system. Furthermore, it represents the first example of cascade C-C bond formation via selective functionalization of α-hydroxyl-C(sp(3))-H in fluorinated alcohols.

  16. Reveromycins A and B from Streptomyces sp. 3–10: Antifungal activity against plant pathogenic fungi in vitro and in a strawberry food model system

    Science.gov (United States)

    This study was conducted to determine the antifungal activity of the metabolites from Streptomyces sp. 3–10, and to purify and identify the metabolites. Meanwhile, the taxonomic status of strain 3–10 was re-evaluated. The cultural filtrates of strain 3–10 in potato dextrose broth were extract...

  17. On the "Tertiary Structure" of Poly-Carbenes; Self-Assembly of sp(3)-Carbon-Based Polymers into Liquid-Crystalline Aggregates

    NARCIS (Netherlands)

    Franssen, Nicole M. G.; Ensing, Bernd; Hegde, Maruti; Dingemans, Theo J.; Norder, Ben; Picken, Stephen J.; van Ekenstein, Gert O. R. Alberda; van Eck, Ernst R. H.; Elemans, Johannes A. A. W.; Vis, Mark; Reek, Joost N. H.; de Bruin, Bas

    2013-01-01

    The self-assembly of poly(ethylidene acetate) (st-PEA) into van der Waals-stabilized liquid-crystalline (LC) aggregates is reported. The LC behavior of these materials is unexpected, and unusual for flexible sp(3)-carbon backbone polymers. Although the dense packing of polar ester functionalities al

  18. On the “Tertiary Structure” of Poly-Carbenes; Self-Assembly of sp3-Carbon-Based Polymers into Liquid-Crystalline Aggregates

    NARCIS (Netherlands)

    Franssen, N.G.M.; Ensing, B.; Hegde, M.; Dingemans, T.J.; Norder, B.; Picken, S.J.; Alberda van Ekenstein, G.O.R.; van Eck, E.R.H.; Elemans, J.A.A.W; Vis, M.; Reek, J.N.H.; de Bruin, B.

    2013-01-01

    The self-assembly of poly(ethylidene acetate) (st-PEA) into van der Waals-stabilized liquid-crystalline (LC) aggregates is reported. The LC behavior of these materials is unexpected, and unusual for flexible sp(3)-carbon backbone polymers. Although the dense packing of polar ester functionalities al

  19. Copper-catalyzed C(sp(3))-H functionalization of ketones with vinyl azides: synthesis of substituted-1H-pyrroles.

    Science.gov (United States)

    Donthiri, Ramachandra Reddy; Samanta, Supravat; Adimurthy, Subbarayappa

    2015-10-28

    Copper-catalyzed C(sp(3))-H functionalization of ketones with vinyl azides for the synthesis of substituted pyrroles has been developed. The method is a straightforward and efficient way to access a series of 2,3,5-trisubstituted-1H-pyrroles in modest to excellent yields with broad functional group tolerance under mild conditions.

  20. Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo.

    Science.gov (United States)

    Zeng, Xingruo; Xu, Zhou; Gu, Jiayan; Huang, Haishan; Gao, Guangxun; Zhang, Xiaoru; Li, Jingxia; Jin, Honglei; Jiang, Guosong; Sun, Hong; Huang, Chuanshu

    2016-03-01

    Our recent studies found that isorhapontigenin (ISO) showed a significant inhibitory effect on human bladder cancer cell growth, accompanied with cell-cycle G0-G1 arrest as well as downregulation of Cyclin D1 expression at transcriptional level via inhibition of Sp1 transactivation in bladder cancer cells. In the current study, the potential ISO inhibition of bladder tumor formation has been explored in a xenograft nude mouse model, and the molecular mechanisms underlying ISO inhibition of Sp1 expression and anticancer activities have been elucidated both in vitro and in vivo. Moreover, the studies demonstrated that ISO treatment induced the expression of miR-137, which in turn suppressed Sp1 protein translation by directly targeting Sp1 mRNA 3'-untranslated region (UTR). Similar to ISO treatment, ectopic expression of miR-137 alone led to G0-G1 cell growth arrest and inhibition of anchorage-independent growth in human bladder cancer cells, which could be completely reversed by overexpression of GFP-Sp1. The inhibition of miR-137 expression attenuated ISO-induced inhibition of Sp1/Cyclin D1 expression, induction of G0-G1 cell growth arrest, and suppression of cell anchorage-independent growth. Taken together, our studies have demonstrated that miR-137 induction by ISO targets Sp1 mRNA 3'-UTR and inhibits Sp1 protein translation, which consequently results in reduction of Cyclin D1 expression, induction of G0-G1 growth arrest, and inhibition of anchorage-independent growth in vitro and in vivo. Our results have provided novel insights into understanding the anticancer activity of ISO in the therapy of human bladder cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weiwei; Chen, Lingxin; Liu, Dongyan [Chinese Academy of Sciences, Yantai, SD (China). Yantai Inst. of Coastal Zone Research (YICCAS); Chinese Academy of Sciences, Yantai, SD (China). Shandong Provincial Key Lab. of Coastal Zone Environmental Processes

    2012-02-15

    The Pseudomonas putida strain SP1 was isolated from marine environment and was found to be resistant to 280 {mu}M HgCl{sub 2}. SP1 was also highly resistant to other metals, including CdCl{sub 2}, CoCl{sub 2}, CrCl{sub 3}, CuCl{sub 2}, PbCl{sub 2}, and ZnSO{sub 4}, and the antibiotics ampicillin (Ap), kanamycin (Kn), chloramphenicol (Cm), and tetracycline (Tc). mer operon, possessed by most mercury-resistant bacteria, and other diverse types of resistant determinants were all located on the bacterial chromosome. Cold vapor atomic absorption spectrometry and a volatilization test indicated that the isolated P. putida SP1 was able to volatilize almost 100% of the total mercury it was exposed to and could potentially be used for bioremediation in marine environments. The optimal pH for the growth of P. putida SP1 in the presence of HgCl{sub 2} and the removal of HgCl{sub 2} by P. putida SP1 was between 8.0 and 9.0, whereas the optimal pH for the expression of merA, the mercuric reductase enzyme in mer operon that reduces reactive Hg{sup 2+} to volatile and relatively inert monoatomic Hg{sup 0} vapor, was around 5.0. LD50 of P. putida SP1 to flounder and turbot was 1.5 x 10{sup 9} CFU. Biofilm developed by P. putida SP1 was 1- to 3-fold lower than biofilm developed by an aquatic pathogen Pseudomonas fluorescens TSS. The results of this study indicate that P. putida SP1 is a low virulence strain that can potentially be applied in the bioremediation of HgCl{sub 2} contamination over a broad range of pH. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-01-01

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

  3. Novel Insights into Gastric Cancer: Methylation of R-spondins and Regulation of LGR5 by SP1.

    Science.gov (United States)

    Wilhelm, Franziska; Simon, Eva; Boger, Christine; Behrens, Hans-Michael; Kruger, Sandra; Rocken, Christoph

    2017-02-20

    Recently it was shown that leucine-rich repeat-containing receptor 5 (LGR5) expressing stem cells are the cellular origin of intestinal-type gastric cancer. The aim of our study was to uncover regulatory mechanisms of LGR5 expression in gastric mucosa and their implications for cancer development. Reporter assays identified a LGR5 promoter fragment, which is highly relevant for active LGR5 expression. Chromatin immunoprecipitation (ChIP) verified that SP1 is bound within this region and reporter activity increased in SP1 transfected cells. Subsequently, the expression of R-spondins (RSPO1 and RSPO2), ligands of LGR5, were explored in neoplastic and non-neoplastic gastric tissue and gastric cancer cell lines. Using immunohistochemistry (IHC), distinct spatial expression patterns of LGR5, RSPO1 and RSPO2 were found in non-neoplastic stomach mucosa and gastric cancer. RSPO expression was lower in gastric cancer compared with non-neoplastic mucosa on both the transcriptional (p=0.003 for RSPO1 and p=0.000 for RSPO2; n=50) and the translational level. Methylation-specific PCR showed higher methylation levels of RSPO1/2 and re-expression of RSPOs in the gastric cancer cell lines MKN45 and MKN74 was induced by demethylating 5-azaC treatment. Finally, expression patterns of LGR5 and RSPO were similar in gastric cancer.

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

    Science.gov (United States)

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

    2015-03-01

    Peroxisome proliferator-activated receptor γ coactivator-1α (PGC‑1α), a coactivator interacting with multiple transcription factors, regulates several metabolic processes. Although recent studies have focused on the role of PGC‑1α in cancer, the underlying molecular mechanism has not been clarified. Therefore, we evaluated the role of PGC‑1α in cell proliferation and tumorigenesis using human embryonic kidney (HEK)293 cells and colorectal cancer cells. We established stable HEK293 cell lines expressing PGC‑1α and examined cell proliferation, anchorage-independent growth, and oncogenic potential compared to parental HEK293 cells. To identify the molecular PGC‑1α 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‑1α in HEK293 cells promoted cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC‑1α 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‑1α (PGC‑1α-HEK293 cells) compared to those expressing an empty vector. In PGC‑1α, ACBP, and specificity protein 1 (Sp1) siRNA knockdown experiments in PGC‑1α-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‑1α may promote cell proliferation and tumorigenesis through upregulation of ACBP

  5. Functional interplay of SP family members and nuclear factor Y is essential for transcriptional activation of the human Calreticulin gene.

    Science.gov (United States)

    Schardt, Julian A; Keller, Manuela; Seipel, Katja; Pabst, Thomas

    2015-09-01

    Calreticulin (CALR) is a highly conserved, multifunctional protein involved in a variety of cellular processes including the maintenance of intracellular calcium homeostasis, proper protein folding, differentiation and immunogenic cell death. More recently, a crucial role for CALR in the pathogenesis of certain hematologic malignancies was discovered: in clinical subgroups of acute myeloid leukemia, CALR overexpression mediates a block in differentiation, while somatic mutations have been found in the majority of patients with myeloproliferative neoplasms with nonmutated Janus kinase 2 gene (JAK2) or thrombopoietin receptor gene (MPL). However, the mechanisms underlying CALR promoter activation have insufficiently been investigated so far. By dissecting the core promoter region, we could identify a functional TATA-box relevant for transcriptional activation. In addition, we characterized two evolutionary highly conserved cis-regulatory modules (CRMs) within the proximal promoter each composed of one binding site for the transcription factors SP1 and SP3 as well as for the nuclear transcription factor Y (NFY) and we verified binding of these factors to their cognate sites in vitro and in vivo.

  6. Purification and some properties of xylosidase from Aspergillus sp. 1-13%Aspergillus sp.1-13菌株β-木糖苷酶的提纯和部分性质

    Institute of Scientific and Technical Information of China (English)

    关宏

    2002-01-01

    通过80%饱和度硫酸钹沉淀、DEAE-Sephades A-50离子交换柱层析和Sephades G-100凝胶过滤柱层析等方法从Aspergillus sp1-13菌株的白酒丢糟固体培养物的抽提液中分离纯化到一种β-木糖苷酶.通过SDS-PAGE分析测定其分子量为110.9KD.该酶最适反应pH值为3.2~3.8之间,最适反应温度为70℃.该酶具有较宽的pH稳定性,并且在60℃以下较稳定.

  7. Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    Guida, Natascia; Laudati, Giusy [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Galgani, Mario; Santopaolo, Marianna [Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli (Italy); Montuori, Paolo; Triassi, Maria [Department of Preventive Medical Sciences, University Federico II, Via Pansini 5, 80131 Naples (Italy); Di Renzo, Gianfranco [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Canzoniero, Lorella M.T., E-mail: canzon@unisannio.it [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Division of Pharmacology, Department of Science and Technology, University of Sannio, Via Port' Arsa 11, 82100 Benevento (Italy); Formisano, Luigi, E-mail: cformisa@unisannio.it [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Division of Pharmacology, Department of Science and Technology, University of Sannio, Via Port' Arsa 11, 82100 Benevento (Italy)

    2014-10-01

    Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic effects in the rat brain. In the present study, chronic exposure to DEHP (0.1–100 μM) caused dose-dependent cell death via the activation of caspase-3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore, DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after 24 and 48 h exposures. However, Sp3 protein reduction was prevented by pre-treatment with MC-1568, suggesting the involvement of class II HDACs in causing this effect. Then, we investigated the possible relationship between DEHP-induced neuronal death and the post-translational mechanisms responsible for the down-regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4 inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced degradation of Sp3. Notably, Sp3 overexpression was able to counteract the detrimental effect induced by DEHP. Taken together, these results suggest that DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and afterwards, Sp3-polyubiquitination. - Highlights: • Di(2-ethylhexyl)phthalate (DEHP) is cytotoxic to SH-SY5Y cells and cortical neurons. • DEHP-induced cytotoxicity is mediated by apoptosis. • DEHP-induced apoptotic cell death is inhibited by class II HDAC MC-1568. • DEHP neurotoxicity is caused by HDAC4-mediated Sp3 degradation by ubiquitin.

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

    Directory of Open Access Journals (Sweden)

    Bo Hyung Lee

    2014-01-01

    Full Text Available 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.

  9. TGF-β-activated kinase 1 (TAK1 signaling regulates TGF-β-induced WNT-5A expression in airway smooth muscle cells via Sp1 and β-catenin.

    Directory of Open Access Journals (Sweden)

    Kuldeep Kumawat

    Full Text Available WNT-5A, a key player in embryonic development and post-natal homeostasis, has been associated with a myriad of pathological conditions including malignant, fibroproliferative and inflammatory disorders. Previously, we have identified WNT-5A as a transcriptional target of TGF-β in airway smooth muscle cells and demonstrated its function as a mediator of airway remodeling. Here, we investigated the molecular mechanisms underlying TGF-β-induced WNT-5A expression. We show that TGF-β-activated kinase 1 (TAK1 is a critical mediator of WNT-5A expression as its pharmacological inhibition or siRNA-mediated silencing reduced TGF-β induction of WNT-5A. Furthermore, we show that TAK1 engages p38 and c-Jun N-terminal kinase (JNK signaling which redundantly participates in WNT-5A induction as only simultaneous, but not individual, inhibition of p38 and JNK suppressed TGF-β-induced WNT-5A expression. Remarkably, we demonstrate a central role of β-catenin in TGF-β-induced WNT-5A expression. Regulated by TAK1, β-catenin is required for WNT-5A induction as its silencing repressed WNT-5A expression whereas a constitutively active mutant augmented basal WNT-5A abundance. Furthermore, we identify Sp1 as the transcription factor for WNT-5A and demonstrate its interaction with β-catenin. We discover that Sp1 is recruited to the WNT-5A promoter in a TGF-β-induced and TAK1-regulated manner. Collectively, our findings describe a TAK1-dependent, β-catenin- and Sp1-mediated signaling cascade activated downstream of TGF-β which regulates WNT-5A induction.

  10. Sp1-mediated transcriptional activation of miR-205 promotes radioresistance in esophageal squamous cell carcinoma

    Science.gov (United States)

    Tong, Xin; Li, Jingjing; Zhang, Sujie; Liu, Xing; Wang, Lingxiong; Wu, Liangliang; Chen, Rui; Wei, Huafeng; Li, Bohua; Li, Cheng; Yang, Yunsheng; Steer, Clifford J.; Zhao, Jian; Guo, Yajun

    2017-01-01

    Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). However, the roles and mechanisms of microRNAs in radioresistance are obscure. Here, we investigated that microRNA-205 (miR-205) was upregulated in radioresistant (RR) ESCC cells compared with the parental cells. Overexpression of miR-205 promoted colony survival post-IR, whereas depletion of miR-205 sensitized ESCC cells to IR in vitro and in vivo. Further, we demonstrated that miR-205 promoted radioresistance by enhancing DNA repair, inhibiting apoptosis and activating epithelial-mesenchymal transition (EMT). Mechanistically, miR-205, upregulated post-IR, was demonstrated to be activated by Sp1 in parallel with its host gene, miR-205HG, both of which showed a perfect correlation. We also identified and validated phosphatase and tensin homolog (PTEN), as a target of miR-205 that promoted radioresistance via PI3K/AKT pathway. Lastly, increased miR-205 expression was closely associated with decreased PTEN expression in ESCC tissues and miR-205 expression predicted poor prognosis in patients with ESCC. Taken together, these findings identify miR-205 as a critical determinant of radioresistance and a biomarker of prognosis. The Sp1-mediated transcriptional activation of miR-205 promotes radioresistance through PTEN via PI3K/AKT pathway in ESCC. Inhibition of miR-205 expression may be a new strategy for radiotherapy in ESCC. PMID:27974696

  11. Importance of fundamental sp, sp2, and sp3 hydrocarbon radicals in the growth of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Shukla, Bikau; Koshi, Mitsuo

    2012-06-05

    The most basic chemistry of products formation in hydrocarbons pyrolysis has been explored via a comparative experimental study on the roles of fundamental sp, sp(2), and sp(3) hydrocarbon radicals/intermediates such as ethyne/ethynyl (C(2)H(2)/C(2)H), ethene/ethenyl (C(2)H(4)/C(2)H(3)), and methane/methyl (CH(4)/CH(3)) in products formations. By using an in situ time-of-flight mass spectrometry technique, gas-phase products of pyrolysis of acetylene (ethyne, C(2)H(2)), ethylene (ethene, C(2)H(4)), and acetone (propanone, CH(3)COCH(3)) were detected and found to include small aliphatic products to large polycyclic aromatic hydrocarbons (PAHs) of mass 324 amu. Observed products mass spectra showed a remarkable sequence of mass peaks at regular mass number intervals of 24, 26, or 14 indicating the role of the particular corresponding radicals, ethynyl (C(2)H), ethenyl (C(2)H(3)), or methyl (CH(3)), in products formation. The analysis of results revealed the following: (a) product formation in hydrocarbon pyrolysis is dominated by hydrogen abstraction and a vinyl (ethenyl, C(2)H(3)) radical addition (HAVA) mechanism, (b) contrary to the existing concept of termination of products mass growth at cyclopenta fused species like acenaphthylene, novel pathways forming large PAHs were found succeeding beyond such cyclopenta fused species by the further addition of C(2)H(x) or CH(3) radicals, (c) production of cyclopenta ring-fused PAHs (CP-PAHs) such as fluoranthene/corannulene appeared as a preferred route over benzenoid species like pyrene/coronene, (d) because of the high reactivity of the CH(3) radical, it readily converts unbranched products into products with aliphatic chains (branched product), and (e) some interesting novel products such as dicarbon monoxide (C(2)O), tricarbon monoxide (C(3)O), and cyclic ketones were detected especially in acetone pyrolysis. These results finally suggest that existing kinetic models of product formation should be modified to include

  12. Inducible Expression of the De-Novo Designed Antimicrobial Peptide SP1-1 in Tomato Confers Resistance to Xanthomonas campestris pv. vesicatoria

    Science.gov (United States)

    Herrera Diaz, Areli; Kovacs, Izabella; Lindermayr, Christian

    2016-01-01

    Antimicrobial peptides (AMPs) are small peptides with less than 50 amino acids and are part of the innate immune response in almost all organisms, including bacteria, vertebrates, invertebrates and plants. AMPs are active against a broad-spectrum of pathogens. The inducible expression of AMPs in plants is a promising approach to combat plant pathogens with minimal negative side effects, such as phytotoxicity or infertility. In this study, inducible expression of the de-novo designed AMP SP1-1 in Micro Tom tomato protected tomato fruits against bacterial spot disease caused by Xanthomonas campestris pv. vesicatoria. The peptide SP1-1 was targeted to the apoplast which is the primary infection site for plant pathogens, by fusing SP1-1 peptide to the signal peptide RsAFP1 of radish (Raphanus sativus). The pathogen inducibility of the expression was enabled by using an optimized inducible 4XW2/4XS promoter. As a result, the tomato fruits of independently generated SP1-1 transgenic lines were significantly more resistant to X. campestris pv. vesicatoria than WT tomato fruits. In transgenic lines, bacterial infection was reduced up to 65% in comparison to the infection of WT plants. Our study demonstrates that the combination of the 4XW2/4XS cis-element from parsley with the synthetic antimicrobial peptide SP1-1 is a good alternative to protect tomato fruits against infections with X. campestris pv. vesicatoria. PMID:27706237

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

    Science.gov (United States)

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

    2004-03-01

    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.

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

    Science.gov (United States)

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

    2008-06-01

    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.

  15. ALOX5基因启动子SP-1结合位点多态性与儿童哮喘的相关性研究%Polymorphism of SP-1 binding motif in ALOX5 promoter may be associated with bronchial asthma susceptibility in Chinese Han chil-dren

    Institute of Scientific and Technical Information of China (English)

    刘占利; 陈岳明; 盛文彬; 黄先玫; 杨一华; 冯亚男; 黄晖; 郑绪阳

    2014-01-01

    factors for bronchial asthma in Han chil-dren (P0.05).The distributions of Al ele 4 and genotypes (4/4+4/5) in the case and control groups showed significant differences (P<0.05). Relative expression levels of ALOX5 mRNA in healthy children (0.20 ± 0.14) was significantly lower than that in asthmatic children (0.28 ± 0.15) (P<0.05). The expression level of ALOX5 mRNA in genotypes (4/4+4/5) individuals was higher than those in genotypes (5/5+5/6) (P<0.05). Conclusion The polymorphism of SP- 1 binding motif in ALOX5 promoter may be associated with the occurrence of bronchial asthma in Chinese Han children, which modulates ALOX5 mRNA expression.

  16. Surface-active derivative of inulin (Inutec® SP1) is a superior carrier for solid dispersions with a high drug load

    NARCIS (Netherlands)

    Srinarong, Parinda; Hämäläinen, Suvi; Visser, Marinella R.; Hinrichs, Wouter L.J; Ketolainen, Jarkko; Frijlink, Henderik W.

    2011-01-01

    The aim of this study was to compare the applicability of inulin, its surface-active derivative (Inutec® SP1), and polyvinylpyrrolidone (PVP) as carriers in high drug load solid dispersions (SDs) for improving the dissolution rate of a range of lipophilic drugs (diazepam, fenofibrate, ritonavir, and

  17. Isolation, Identification, and Optimization of Culture Conditions of a Bioflocculant-Producing Bacterium Bacillus megaterium SP1 and Its Application in Aquaculture Wastewater Treatment

    Directory of Open Access Journals (Sweden)

    Liang Luo

    2016-01-01

    Full Text Available A bioflocculant-producing bacterium, Bacillus megaterium SP1, was isolated from biofloc in pond water and identified by using both 16S rDNA sequencing analysis and a Biolog GEN III MicroStation System. The optimal carbon and nitrogen sources for Bacillus megaterium SP1 were 20 g L−1 of glucose and 0.5 g L−1 of beef extract at 30°C and pH 7. The bioflocculant produced by strain SP1 under optimal culture conditions was applied into aquaculture wastewater treatment. The removal rates of chemical oxygen demand (COD, total ammonia nitrogen (TAN, and suspended solids (SS in aquaculture wastewater reached 64, 63.61, and 83.8%, respectively. The volume of biofloc (FV increased from 4.93 to 25.97 mL L−1. The addition of Bacillus megaterium SP1 in aquaculture wastewater could effectively improve aquaculture water quality, promote the formation of biofloc, and then form an efficient and healthy aquaculture model based on biofloc technology.

  18. sp2/sp3 hybridization ratio in amorphous carbon from C 1s core-level shifts: X-ray photoelectron spectroscopy and first-principles calculation

    Science.gov (United States)

    Haerle, Rainer; Riedo, Elisa; Pasquarello, Alfredo; Baldereschi, Alfonso

    2002-01-01

    Using a combined experimental and theoretical approach, we address C 1s core-level shifts in amorphous carbon. Experimental results are obtained by x-ray photoelectron spectroscopy (XPS) and electron-energy-loss spectroscopy (EELS) on thin-film samples of different atomic density, obtained by a pulsed-laser deposition growth process. The XPS spectra are deconvoluted into two contributions, which are attributed to sp2- and sp3-hybridized atoms, respectively, separated by 0.9 eV, independent of atomic density. The sp3 hybridization content extracted from XPS is consistent with the atomic density derived from the plasmon energy in the EELS spectrum. In our theoretical study, we generate several periodic model structures of amorphous carbon of different densities applying two schemes of increasing accuracy in sequence. We first use a molecular-dynamics approach, based on an environmental-dependent tight-binding Hamiltonian to quench the systems from the liquid phase. The final model structures are then obtained by further atomic relaxation using a first-principles pseudopotential plane-wave approach within density-functional theory. Within the latter framework, we also calculate carbon 1s core-level shifts for our disordered model structures. We find that the shifts associated to threefold- and fourfold- coordinated carbon atoms give rise to two distinct peaks separated by about 1.0 eV, independent of density, in close agreement with experimental observations. This provides strong support for decomposing the XPS spectra into two peaks resulting from sp2- and sp3-hybridized atoms. Core-hole relaxations effects account for about 30% of the calculated shifts.

  19. LBD1 of Vitellogenin Receptor Specifically Binds to the Female-Specific Storage Protein SP1 via LBR1 and LBR3

    Science.gov (United States)

    Liu, Lina; Wang, Yejing; Li, Yu; Lin, Ying; Hou, Yong; Zhang, Yan; Wei, Shuguang; Zhao, Peng; Zhao, Ping; He, Huawei

    2016-01-01

    Storage proteins are the major protein synthesized in the fat body, released into hemolymph and re-sequestered into the fat body before pupation in most insect species. Storage proteins are important amino acid and nutrition resources during the non-feeding pupal period and play essential roles for the metamorphosis and oogenesis of insects. The sequestration of storage protein is a selective, specific receptor-mediated process. However, to date, the potential receptor mediating the sequestration of storage protein has not been determined in Bombyx mori. In this study, we expressed and purified the first ligand binding domain of Bombyx mori vitellogenin receptor (BmVgR), LBD1, and found LBD1 could bind with an unknown protein from the hemolymph of the ultimate silkworm larval instar via pull-down assay. This unknown protein was subsequently identified to be the female-specific storage protein SP1 by mass spectrometry. Furthermore, far western blotting assay, immunoprecipitation and isothermal titration calorimetry analysis demonstrated LBD1 specifically bound with the female-specific SP1, rather than another unisex storage protein SP2. The specific binding of LBD1 with SP1 was dependent on the presence of Ca2+ as it was essential for the proper conformation of LBD1. Deletion mutagenesis and ITC analysis revealed the first and third ligand binding repeats LBR1 and LBR3 were indispensable for the binding of LBD1 with SP1, and LBR2 and LBR4 also had a certain contribution to the specific binding. Our results implied BmVgR may mediate the sequestration of SP1 from hemolymph into the fat body during the larval-pupal transformation of Bombyx mori. PMID:27637099

  20. Biosorption of Pb(II) Ions by Klebsiella sp. 3S1 Isolated from a Wastewater Treatment Plant: Kinetics and Mechanisms Studies

    OpenAIRE

    Antonio Jesús Muñoz; Francisco Espínola; Manuel Moya; Encarnación Ruiz

    2015-01-01

    Lead biosorption by Klebsiella sp. 3S1 isolated from a wastewater treatment plant was investigated through a Rotatable Central Composite Experimental Design. The optimisation study indicated the following optimal values of operating variables: 0.4 g/L of biosorbent dosage, pH 5, and 34°C. According to the results of the kinetic studies, the biosorption process can be described by a two-step process, one rapid, almost instantaneous, and one slower, both contributing significantly to the overal...

  1. Unique regioselectivity in the C(sp3)-H α-alkylation of amines: the benzoxazole moiety as a removable directing group.

    Science.gov (United States)

    Lahm, Günther; Opatz, Till

    2014-08-15

    The benzoxazol-2-yl- substituent was found to act as a removable activating and directing group in the Ir-catalyzed alkylation of C(sp(3))-H bonds adjacent to nitrogen in secondary amines. It can be easily introduced by oxidative coupling or by an SNAr reaction, and it can be removed by hydroxide or by hydride reduction. For 1,2,3,4-tetrahydroisoquinolines, activation exclusively takes place in the 3-position. A variety of activated as well as unactivated terminal olefins are suitable reaction partners.

  2. INOCULANTES DE HONGOS MICORRÍZICOS ARBUSCULARES DE Glomus mosseae Y Glomus sp1 EN MEDIO LÍQUIDO

    Directory of Open Access Journals (Sweden)

    F. Fernández

    2005-01-01

    Full Text Available El trabajo tuvo como objetivo la evaluación de la viabilidad de los hongos micorrízicos (HMA Glomus mosseae (INCAM 2 y Glomus sp1 (INCAM 4 en soluciones líquidas. Se realizaron dos experimentos, uno donde se estudió la viabilidad fúngica de las esporas en un medio líquido de conservación y como control, agua destilada estéril durante ocho meses. En el segundo se estudió la capacidad de colonización de las esporas almacenadas durante ocho meses. En cada experimento se aplicó el ANOVA correspondiente y prueba de comparación de Tukey. En el medio líquido se logró un tiempo de viabilidad y estabilidad superior a los ocho meses, con importantes pérdidas de viabilidad de las esporas de ambas especies en el agua. Las cepas expresaron su capacidad germinativa hasta los 30 días de incubación, no detectándose diferencias significativas. En las esporas se encontraron elevados porcentajes de germinación, lo cual parece relacionarse con el fuerte estrés provocado a las paredes de estas, debido a la permanencia durante ocho meses en un medio líquido osmóticamente protector. Los ensayos de colonización permitieron aseverar que las esporas produjeron una fuerte colonización gradual a partir de los 14 días de iniciado el experimento, siendo muy similar en ambas especies. Finalmente, se puede aseverar que el inoculante líquido es efectivo desde el punto de vista biológico, logrando niveles de funcionamiento aceptados.

  3. Activation of TGF-β1 promoter by hepatitis C virus-induced AP-1 and Sp1: role of TGF-β1 in hepatic stellate cell activation and invasion.

    Science.gov (United States)

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

    2013-01-01

    Our previous studies have shown the induction and maturation of transforming growth factor-beta 1 (TGF-β1) in HCV-infected human hepatoma cells. In this study, we have investigated the molecular mechanism of TGF-β1 gene expression in response to HCV infection. We demonstrate that HCV-induced transcription factors AP-1, Sp1, NF-κB and STAT-3 are involved in TGF-β1 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-β1 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-β1 in human hepatic stellate cells (HSCs) activation and invasion. Using siRNA approach, we show that HCV-induced bioactive TGF-β1 is critical for the induction of alpha smooth muscle actin (α-SMA) and type 1 collagen, the markers of HSCs activation and proliferation. We further demonstrate the potential role of HCV-induced bioactive TGF-β1 in HSCs invasion/cell migration using a transwell Boyden chamber. Our results also suggest the role of HCV-induced TGF-β1 in HCV replication and release. Collectively, these observations provide insight into the mechanism of TGF-β1 promoter activation, as well as HSCs activation and invasion, which likely manifests in liver fibrosis associated with HCV infection.

  4. Activation of TGF-β1 promoter by hepatitis C virus-induced AP-1 and Sp1: role of TGF-β1 in hepatic stellate cell activation and invasion.

    Directory of Open Access Journals (Sweden)

    Lance D Presser

    Full Text Available Our previous studies have shown the induction and maturation of transforming growth factor-beta 1 (TGF-β1 in HCV-infected human hepatoma cells. In this study, we have investigated the molecular mechanism of TGF-β1 gene expression in response to HCV infection. We demonstrate that HCV-induced transcription factors AP-1, Sp1, NF-κB and STAT-3 are involved in TGF-β1 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-β1 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-β1 in human hepatic stellate cells (HSCs activation and invasion. Using siRNA approach, we show that HCV-induced bioactive TGF-β1 is critical for the induction of alpha smooth muscle actin (α-SMA and type 1 collagen, the markers of HSCs activation and proliferation. We further demonstrate the potential role of HCV-induced bioactive TGF-β1 in HSCs invasion/cell migration using a transwell Boyden chamber. Our results also suggest the role of HCV-induced TGF-β1 in HCV replication and release. Collectively, these observations provide insight into the mechanism of TGF-β1 promoter activation, as well as HSCs activation and invasion, which likely manifests in liver fibrosis associated with HCV infection.

  5. Biosorption of Pb(II) Ions by Klebsiella sp. 3S1 Isolated from a Wastewater Treatment Plant: Kinetics and Mechanisms Studies.

    Science.gov (United States)

    Muñoz, Antonio Jesús; Espínola, Francisco; Moya, Manuel; Ruiz, Encarnación

    2015-01-01

    Lead biosorption by Klebsiella sp. 3S1 isolated from a wastewater treatment plant was investigated through a Rotatable Central Composite Experimental Design. The optimisation study indicated the following optimal values of operating variables: 0.4 g/L of biosorbent dosage, pH 5, and 34°C. According to the results of the kinetic studies, the biosorption process can be described by a two-step process, one rapid, almost instantaneous, and one slower, both contributing significantly to the overall biosorption; the model that best fits the experimental results was pseudo-second order. The equilibrium studies showed a maximum lead uptake value of 140.19 mg/g according to the Langmuir model. The mechanism study revealed that lead ions were bioaccumulated into the cytoplasm and adsorbed on the cell surface. The bacterium  Klebsiella sp. 3S1 has a good potential in the bioremoval of lead in an inexpensive and effective process.

  6. Biosorption of Pb(II Ions by Klebsiella sp. 3S1 Isolated from a Wastewater Treatment Plant: Kinetics and Mechanisms Studies

    Directory of Open Access Journals (Sweden)

    Antonio Jesús Muñoz

    2015-01-01

    Full Text Available Lead biosorption by Klebsiella sp. 3S1 isolated from a wastewater treatment plant was investigated through a Rotatable Central Composite Experimental Design. The optimisation study indicated the following optimal values of operating variables: 0.4 g/L of biosorbent dosage, pH 5, and 34°C. According to the results of the kinetic studies, the biosorption process can be described by a two-step process, one rapid, almost instantaneous, and one slower, both contributing significantly to the overall biosorption; the model that best fits the experimental results was pseudo-second order. The equilibrium studies showed a maximum lead uptake value of 140.19 mg/g according to the Langmuir model. The mechanism study revealed that lead ions were bioaccumulated into the cytoplasm and adsorbed on the cell surface. The bacterium  Klebsiella sp. 3S1 has a good potential in the bioremoval of lead in an inexpensive and effective process.

  7. Cadmium treatment suppresses DNA polymerase δ catalytic subunit gene expression by acting on the p53 and Sp1 regulatory axis.

    Science.gov (United States)

    Antoniali, Giulia; Marcuzzi, Federica; Casarano, Elena; Tell, Gianluca

    2015-11-01

    Cadmium (Cd) is a carcinogenic and neurotoxic environmental pollutant. Among the proposed mechanisms for Cd toxic effects, its ability to promote oxidative stress and to inhibit, in vitro, the activities of some Base Excision DNA Repair (BER) enzymes, such as hOGG1, XRCC1 and APE1, have been already established. However, the molecular mechanisms at the basis of these processes are largely unknown especially at sub-lethal doses of Cd and no information is available on the effect of Cd on the expression levels of BER enzymes. Here, we show that non-toxic treatment of neuronal cell lines, with pro-mitogenic doses of Cd, promotes a significant time- and dose-dependent down-regulation of DNA polymerase δ (POLD1) expression through a transcriptional mechanism with a modest effect on Polβ, XRCC1 and APE1. We further elucidated that the observed transcriptional repression on Polδ is acted by through competition by activated p53 on Sp1 at POLD1 promoter and by a squelching effect. We further proved the positive effect of Sp1 not only on POLD1 expression but also on Polβ, XRCC1 and APE1 expression, suggesting that Sp1 has pleiotropic effects on the whole BER pathway. Our results indicated that Cd-mediated impairment of BER pathway, besides acting on the enzymatic functions of some key proteins, is also exerted at the gene expression level of Polδ by acting on the p53-Sp1 regulatory axis. These data may explain not only the Cd-induced neurotoxic effects but also the potential carcinogenicity of this heavy metal.

  8. A new PC(sp(3))P ligand and its coordination chemistry with low-valent iron, cobalt and nickel complexes.

    Science.gov (United States)

    Zhu, Gengyu; Li, Xiaoyan; Xu, Guoqiang; Wang, Lin; Sun, Hongjian

    2014-06-21

    A new PC(sp(3))P ligand N,N'-bis(diphenylphosphino)dipyrromethane [PCH2P] (1) was prepared and its iron, cobalt and nickel chemistry was explored. Two pincer-type complexes [PCHP]Fe(H)(PMe3)2 (2) and [PCHP]Co(PMe3)2 (4) were synthesized in the reaction of with Fe(PMe3)4 and Co(Me)(PMe3)4. 1 reacted with Co(PMe3)4 and Ni(PMe3)4 to afford Co(0) and Ni(0) complexes [PCH2P]Co(PMe3)2 (3) and [PCH2P]Ni(PMe3)2 (5). The structures of complexes 2-5 were determined by X-ray diffraction.

  9. Palladium-Catalyzed Directed C(sp(3))-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach.

    Science.gov (United States)

    Affron, Dominic P; Bull, James A

    2016-01-01

    Saturated heterocycles, such as THFs, pyrrolidines, piperidines and THPs, are essential components of many biologically active compounds. Examples of C-H functionalization on these important ring systems remain scarce, especially at unactivated positions. Here we report the development of conditions for the palladium-catalyzed stereoselective C(sp(3))-H arylation at unactivated 3-positions of 5- and 6-membered N- and O-heterocycles with aminoquinoline directing groups. Subtle differences in substrate structures altered their reactivity significantly; and different conditions were required to achieve high yields in each case. Successful conditions were developed using a short empirical optimization approach to cover reaction space with a limited set of variables. Excellent cis-selectivity was achieved in all cases, except for the THP substrate where minor trans-products were formed through a different palladacyclic intermediate. Here, differences in reactivity and selectivity with other directing groups were examined.

  10. Auto-correlation Effects on the sp3-d Exchange Interaction in Cd1-xMnxTe/CdTe Multilayers

    Institute of Scientific and Technical Information of China (English)

    K. Afif; A. Benyoussef; J. Diouri

    2002-01-01

    Band offsets and total energy of Wannier excitons in multilayers are affected by dimensional and auto-correlation effects, and sp3-d coupling is consequently modified. Thus, the calculation of the Zeeman splitting in the quantum wells has to take into account these effects, especially when the mismatch cannot be disregarded. In this work,the theoretical study of these combined effects has been performed for Cd1-xMnx Te/CdTe multilayers embedded by Cd1-yZny Te as the substrate (or the buffer) on one side and as a cladding layer on the other side. This sample allows us to highlight the role played by the substrate (buffer) and the growth direction on the Zeeman splitting in such multilayers.

  11. The role of the alcohol and carboxylic acid in directed ruthenium-catalyzed C(sp3)-H α-alkylation of cyclic amines.

    Science.gov (United States)

    Bergman, Sheba D; Storr, Thomas E; Prokopcová, Hana; Aelvoet, Karel; Diels, Gaston; Meerpoel, Lieven; Maes, Bert U W

    2012-08-13

    A general directed Ru-catalyzed C(sp(3))-H α-alkylation protocol for piperidines (less-reactive substrates than the corresponding five-membered cyclic amines) has been developed. The use of a hindered alcohol (2,4-dimethyl-3-pentanol) as the solvent and catalyst activator, and a catalytic amount of trans-1,2-cyclohexanedicarboxylic acid is necessary to achieve a high conversion to product. This protocol was used to effectively synthesize a number of 2-hexyl- and 2,6-dihexyl piperidines, as well as the alkaloid (±)-solenopsin A. Kinetic studies have revealed that the carboxylic acid additive has a significant effect on catalyst initiation, catalyst longevity, and reverses the reaction selectivity compared with the acid-free reaction (promotes alkylation versus competing alkene reduction).

  12. The influence of fusing conditions on the surface structure and morphology of SP1 SiO2 in dental resin composites%熔附条件对牙科复合树脂中SP1 SiO2表面结构及形态的影响

    Institute of Scientific and Technical Information of China (English)

    张颖丽; 李保泉; 孙宏晨; 杨柏

    2007-01-01

    目的:研究熔附温度和熔附时间对多微孔纳米二氧化硅粒子(SP1 SiO2)表面结构及形态的影响.方法:将SP1 SiO2以250 ℃/h的升温速度分别升至500、650、800、950、1 100 ℃,并分别保持10、30 min和3 h制作试样,进行表面结构及形态测试.结果:随烧结温度的增高和时间的延长,SP1 SiO2颗粒表面的Si-OH键特征峰值逐渐减弱,条件为950 ℃、10 min和30 min,650 ℃、3 h 时完全消失;随着熔附温度的升高和熔附时间的延长颗粒增大、粒度分布变窄.结论:熔附温度和熔附时间影响SP1 SiO2颗粒表面的Si-OH含量和颗粒大小、粒度分布.

  13. Transcriptional activation of p21(WAF¹/CIP¹) is mediated by increased DNA binding activity and increased interaction between p53 and Sp1 via phosphorylation during replicative senescence of human embryonic fibroblasts.

    Science.gov (United States)

    Kim, Hyun-Seok; Heo, Jee-In; Park, Seong-Hoon; Shin, Jong-Yeon; Kang, Hong-Jun; Kim, Min-Ju; Kim, Sung Chan; Kim, Jaebong; Park, Jae-Bong; Lee, Jae-Yong

    2014-01-01

    Although p21(WAF1/CIP1) is known to be elevated during replicative senescence of human embryonic fibroblasts (HEFs), the mechanism for p21 up-regulation has not been elucidated clearly. In order to explore the mechanism, we analyzed expression of p21 mRNA and protein and luciferase activity of full-length p21 promoter. The result demonstrated that p21 up-regulation was accomplished largely at transcription level. The promoter assay using serially-deleted p21 promoter constructs revealed that p53 binding site was the most important site and Sp1 binding sites were necessary but not sufficient for transcriptional activation of p21. In addition, p53 protein was shown to interact with Sp1 protein. The interaction was increased in aged fibroblasts and was regulated by phosphorylation of p53 and Sp1. DNA binding activity of p53 was significantly elevated in aged fibroblasts but that of Sp1 was not. DNA binding activities of p53 and Sp1 were also regulated by phosphorylation. Phosphorylation of p53 at serine-15 and of Sp1 at serines appears to be involved. Taken together, the result demonstrated that p21 transcription during replicative senescence of HEFs is up-regulated by increase in DNA binding activity and interaction between p53 and Sp1 via phosphorylation.

  14. Effect of miR-181b on cell proliferation and expression of Bcl-2 and SP1 in HepG2 cells%miR-181b对肝癌HepG2细胞增殖以及Bcl-2和SP1蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵文健; 杨亮; 李坚; 阳帆

    2010-01-01

    目的:研究miR-181b对人肝癌G2细胞(HepG2)中B细胞淋巴瘤/白血病-2(Bcl-2)和转录因子SP1蛋白及mRNA表达的调节作用,探讨miR-181b对HepG2细胞增殖的影响.方法:用人工合成的miR-181b相应的双链互补DNA片段,插入miRNASelectTM pEGP-miR载体中,经测序鉴定后克隆microRNA的高表达质粒;用脂质体将miR-181b高表达质粒转染进HepG2细胞,经嘌呤霉素筛选获得阳性克隆.用RT-PCR技术和Western blotting方法分别检测该细胞系中Bcl-2和SP1的mRNA和蛋白表达情况.用MTT法检测HepG2细胞增殖的变化情况.结果:Western blotting结果显示miR-181b能够减少Bcl-2和SP1蛋白质的表达,RT-PCR分析显示Bcl-2和SP1 mRNA表达减少.MTT显示转染后细胞的生长速率比未转染的细胞明显减慢. 结论:miR-181b抑制HepG2肝癌细胞增殖, 提示可能与其下调Bcl-2和SP1 的表达有关.

  15. A regioselective synthesis of benzopinacolones through aerobic dehydrogenative α-arylation of the tertiary sp3 C-H bond of 1,1-diphenylketones with aromatic and heteroaromatic compounds.

    Science.gov (United States)

    More, Nagnath Yadav; Jeganmohan, Masilamani

    2015-01-12

    A regioselective synthesis of symmetrical and unsymmetrical benzopinacolones through aerobic dehydrogenative α-arylation at the tertiary sp(3) C-H bond of substituted 1,1-diphenylketones with aromatic and heteroaromatic compounds, in the presence of K2S2O8 in CF3COOH at room temperature, is described. The reaction is proposed to go via a carbocation intermediate, which could be generated directly from cleavage of the sp(3) C-H bond of 1,1-diphenylketone. Subsequent α-arylation was achieved at the methene sp(3) carbon atom of the substituted ketone. A variety of substituted aromatic and heteroaromatic compounds were compatible with this reaction. In addition, benzopinacolones were converted into sterically hindered, tetrasubstituted alkenes and polycyclic aromatic compounds.

  16. 杀菌剂对甘薯致病菌Hypocrea sp.SP-4和Rhizopus stolonifer SP-1生长影响研究%Studies on Influence of Fungicide on Growth of Hypocrea sp.SP-4 and Rhizopus stolonifer SP-1 of Pathogenic Bacteria of Sweet Potato

    Institute of Scientific and Technical Information of China (English)

    段鹏; 张义正; 谭雪梅

    2011-01-01

    为了研究杀菌剂对甘薯致病菌 Hypocrea sp.SP-4和Rhizopus stolonifer SP-1生长的抑制效果,本文从腐烂的甘薯块根中分离到的匍枝根霉SP-1(Rhizopus stolonifer SP-1)和Hypocrea sp.SP-4的孢子接种在含有不同杀菌剂浓度的PDA培养基上,在13℃和28℃条件下培养.同时也将2种孢子接种在甘薯块根上,进行培养观察.结果表明:2株真菌低温条件下,在不含杀茵剂的培养皿上的生长速度明显比28℃条件下要缓慢些;甲基托布津和多茵灵对Hypocrea sp.SP-4和R.stolonifer SP-1生长抑制的稀释度分别为1000倍和500倍.在28℃条件下,2种杀菌剂对Hypocrea sp.SP-4都有良好的抑制效果,但对R.stolonifer SP-1抑制率,甲基托布津只有21%,多菌灵则有58%.在用杀菌剂抑制甘薯块根侵染的过程中还发现,甘薯块根在没有创伤的情况下,2株真菌在低温条件下不会引起腐烂,说明它们是通过伤口侵染甘薯块根的.综合几个指标可以得出:适度低温和避免甘薯块根出现伤口能够减少甘薯块根被真菌侵染.%In order to study on influence of fungicide on growth of Rhizopus stolonifer SP-1 and Hypocrea sp SP-4 of pathogenic bacteria of sweet potato, spores of Rhizopus stolonifer SP-1 and Hypocrea sp SP-4 isolated from spoilage root tuber of sweet potato were inoculated on PDA medium plate and root tuber of sweet potato including different concentrations of fungicide, and cultivated at 13℃ and 28℃. The results showed that they grew more slowly at 13℃ than 28℃. Dilution concentration of thiophanate-methyl and carbendazol to inhibit the growth of Hypocrea sp SP-4 and R. stolonifer SP-1 is 1000 and 500-fold, respectively. Both fungicides could efficiently inhibit the growth of Hypocrea sp SP-4. However, the inhibition rate of thiophanate-methyl and carbendazol to R. stolonifer SP-1 is 21% and 58%, respectively. The results also showed in the course of fungicide inhibiting the infection of root tuber of

  17. Nickel-Catalyzed Aminoxylation of Inert Aliphatic C(sp(3))-H Bonds with Stable Nitroxyl Radicals under Air: One-Pot Route to α-Formyl Acid Derivatives.

    Science.gov (United States)

    Wang, Chunxia; Zhang, Luoqiang; You, Jingsong

    2017-04-07

    Nickel-catalyzed aminoxylation of an unactivated C(sp(3))-H bond with a stable nitroxyl radical has been accomplished for the first time to offer various N-alkoxyamine derivatives, which further enables a one-pot approach to α-formyl acid derivatives. The aminoxylation process reported also provides direct evidence for the oxidative addition of a cyclometallic intermediate with a free radical, which is helpful for the reaction-mechanism study in transition-metal-catalyzed functionalization of inert C(sp(3))-H bonds.

  18. Identification of the para-nitrophenol catabolic pathway, and characterization of three enzymes involved in the hydroquinone pathway, in pseudomonas sp. 1-7

    Directory of Open Access Journals (Sweden)

    Zhang Shuangyu

    2012-03-01

    Full Text Available Abstract Background para-Nitrophenol (PNP, a priority environmental pollutant, is hazardous to humans and animals. However, the information relating to the PNP degradation pathways and their enzymes remain limited. Results Pseudomonas sp.1-7 was isolated from methyl parathion (MP-polluted activated sludge and was shown to degrade PNP. Two different intermediates, hydroquinone (HQ and 4-nitrocatechol (4-NC were detected in the catabolism of PNP. This indicated that Pseudomonas sp.1-7 degraded PNP by two different pathways, namely the HQ pathway, and the hydroxyquinol (BT pathway (also referred to as the 4-NC pathway. A gene cluster (pdcEDGFCBA was identified in a 10.6 kb DNA fragment of a fosmid library, which cluster encoded the following enzymes involved in PNP degradation: PNP 4-monooxygenase (PdcA, p-benzoquinone (BQ reductase (PdcB, hydroxyquinol (BT 1,2-dioxygenase (PdcC, maleylacetate (MA reductase (PdcF, 4-hydroxymuconic semialdehyde (4-HS dehydrogenase (PdcG, and hydroquinone (HQ 1,2-dioxygenase (PdcDE. Four genes (pdcDEFG were expressed in E. coli and the purified pdcDE, pdcG and pdcF gene products were shown to convert HQ to 4-HS, 4-HS to MA and MA to β-ketoadipate respectively by in vitro activity assays. Conclusions The cloning, sequencing, and characterization of these genes along with the functional PNP degradation studies identified 4-NC, HQ, 4-HS, and MA as intermediates in the degradation pathway of PNP by Pseudomonas sp.1-7. This is the first conclusive report for both 4-NC and HQ- mediated degradation of PNP by one microorganism.

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  1. 碳正离子Lewis酸催化氧化还原中性胺基α-C(sp3)H芳基化反应%Carbocation Lewis Acid Catalyzed Redox-Neutral α-C(sp3)H Arylation of Amines

    Institute of Scientific and Technical Information of China (English)

    张启超; 吕健; 罗三中

    2016-01-01

    研究了碳正离子作为Lewis酸催化三组分氧化还原中性胺基α-C(sp3)-H芳基化反应.在温和条件下,三苯甲基溴和NaBArF原位生成的[Ph3C][BArF]可以高效、高化学选择性的催化四氢异喹啉、芳香醛和吲哚的氧化还原中性胺基α-C(sp3)-H芳基化反应(产率最高达99%).并且其它的亲核试剂(如:β-萘酚、3-甲氧基苯酚、3-N,N-二甲基胺基苯酚和2,5-二甲基吡咯等)也能较好的完成该反应.

  2. 芳酮类化合物羰基邻位sp3-C—H键的乙酰氧基化反应研究%Study on the α-Acetoxylation of sp3-C—H Bonds Adjacent to Carbonyl of Arones

    Institute of Scientific and Technical Information of China (English)

    陈翠; 邱会华

    2016-01-01

    成功地发展了一种高效的芳酮类化合物羰基邻位sp3-C-H键的乙酰氧基化的方法,并构建出了一系列的α-乙酰氧基苯乙酮类型的化合物.考察了反应时间、多种铜盐和单质碘以及它们的用量等因素对反应的影响,确定了最优反应条件.提出了芳酮类化合物羰基邻位sp3-C-H键的乙酰氧基化反应机理.该方法具有操作简单、产率高等特点,为α-乙酰氧基苯乙酮衍生物的合成提供了一条新的途径..

  3. Recent Advances in Directed Intramolecular C(sp3)-H Amination Reactions for the Construction of Aza-heterocycles%配位导向的分子内C(sp3)-H键胺化反应构建含氮杂环的新进展

    Institute of Scientific and Technical Information of China (English)

    赵金钵; 张前

    2015-01-01

    含氮饱和杂环化合物,如β-内酰胺、氮杂环丙烷、四氢吡咯、哌啶及其苯并骨架吲哚啉、四氢喹啉、四氢异喹啉等结构单元是天然产物和药物分子中常见的“优势骨架”,在新药的发现中起到了极其重要的作用.配位导向的非活化C(sp3)-H键的直接胺化方法可高效构建C-N键,是C-H键活化反应方法学的重要研究内容之一.本文介绍了近期配位导向的非活化C(sp3)-H键的分子内直接胺化策略构建含氮杂环的新进展,其中包括双齿、单齿和分子内本身的二级胺作为定位基参与的活化模式,探讨了其反应机制、选择性、底物的适用性及其在合成中的应用.

  4. Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 up-regulation and proteasome-mediated c-FLIPS down-regulation.

    Science.gov (United States)

    Kim, Jin Yeop; Kim, Eun Hee; Park, Seok Soon; Lim, Jun Hee; Kwon, Taeg Kyu; Choi, Kyeong Sook

    2008-12-15

    This study demonstrates that combined treatment with subtoxic doses of quercetin (3',3',4',5,7-pentahydroxyflavone), a flavonoid found in many fruits and vegetables, plus tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant hepatocellular carcinoma (HCC) cells. Effective induction of apoptosis by the combined treatment with quercetin and TRAIL was not blocked by overexpression of Bcl-xL, which is known to confer resistance to various chemotherapeutic agents. These results suggest that this combined treatment may provide an attractive strategy for treating resistant HCCs. While the proteolytic processing of procaspase-3 by TRAIL was partially blocked in various HCC cells treated with TRAIL alone, co-treatment with quercetin efficiently recovered TRAIL-induced caspase activation. We found that quercetin treatment of HCC cells significantly up-regulated the mRNA and protein levels of DR5, a death receptor of TRAIL, in a transcription factor Sp1-dependent manner. Furthermore, treatment with quercetin significantly decreased the protein levels of c-FLIP, an inhibitor of caspase-8, through proteasome-mediated degradation. Finally, administration of small interfering RNA against DR5 or overexpression of c-FLIPS, but not c-FLIPL, significantly attenuated quercetin-stimulated TRAIL-induced apoptosis. Collectively, these findings show that quercetin recovers TRAIL sensitivity in various HCC cells via up-regulation of DR5 and down-regulation of c-FLIPS.

  5. sp_3sec.grd

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NGDC builds and distributes high-resolution, coastal digital elevation models (DEMs) that integrate ocean bathymetry and land topography to support NOAA's mission to...

  6. Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic fracture in Caucasian post-menopausal women: a meta-analysis.

    LENUS (Irish Health Repository)

    Ji, G-R

    2012-01-06

    This study was designed to summarize quantitatively the evidence for a relationship between collagen type I alpha1 (COLIA1) Sp1 polymorphism and osteoporotic fracture risk in Caucasian post-menopausal women. This meta-analysis included 16 studies, which analysed 2294 patients with fractures and 10 285 controls. The combined results showed that there was a significant difference in genotype distribution (SS odds ratio [OR] 0.72; Ss OR 1.18; ss OR 1.97) between patients with fractures and controls. When stratifying by the fracture site, it was found that: (i) patients with vertebral fractures had a significantly higher frequency of the Ss genotype and a lower frequency of the SS genotype than controls; and (ii) patients with non-vertebral fractures had a significantly higher frequency of the ss genotype and a lower frequency of the SS genotype than controls. This meta-analysis suggests that the COLIA1 Sp1 polymorphism may be associated with osteoporotic fracture in Caucasian post-menopausal women.

  7. Inhibition of breast cancer invasion by TIS21/BTG2/Pc3-Akt1-Sp1-Nox4 pathway targeting actin nucleators, mDia genes.

    Science.gov (United States)

    Choi, J-A; Jung, Y S; Kim, J Y; Kim, H M; Lim, I K

    2016-01-01

    The mammalian homolog of Drosophila diaphanous (mDia), actin nucleator, has been known to participate in the process of invasion and metastasis of cancer cells via regulating a number of actin-related biological processes. We have previously reported that tumor suppressor TIS21(/BTG2/Pc3) (TIS21) inhibits invadopodia formation by downregulating reactive oxygen species (ROS) in MDA-MB-231 cells. We herein report that TIS21(/BTG2/Pc3) downregulates diaphanous-related formin (DRF) expression via reducing NADPH oxidase 4 (Nox4)-derived ROS generation by Akt1 activation and subsequently impairs invasion activity of the highly invasive breast cancer cells. Knockdown of Akt1 by RNA interference recovered the TIS21(/BTG2/Pc3)-inhibited F-actin remodeling and ROS generation by recovering Nox4 expression. Furthermore, Sp1-mediated Nox4 transcription was downregulated by TIS21(/BTG2/Pc3)-Akt1 signals, leading to the inhibition of cancer cell invasion via F-actin remodeling by mDia genes. To our best knowledge, this is the first study to show that TIS21(/BTG2/Pc3)-Akt1 inhibited Sp1-Nox4-ROS cascade, subsequently reducing invasion activity via inhibition of mDia family genes.

  8. Sodium butyrate sensitizes TRAIL-mediated apoptosis by induction of transcription from the DR5 gene promoter through Sp1 sites in colon cancer cells.

    Science.gov (United States)

    Kim, Young-Ho; Park, Jong-Wook; Lee, Jai-Youl; Kwon, Taeg Kyu

    2004-10-01

    Sodium butyrate, a short-chain fatty acid naturally present in the human colon, is able to induce cell cycle arrest, differentiation and apoptosis in various cancer cells. Sodium butyrate is most probably related to the inhibition of deacetylases leading to hyperacetylation of chromatin components such as histones and non-histone proteins and to alterations in gene expression. In this study, we demonstrate for the first time that sodium butyrate selectively up-regulated DR5 but had no effect on the expression of the other TNF-alpha-related apoptosis-inducing ligand (TRAIL) receptor, DR4. Sodium butyrate-induced expression of DR5 involves the putative Sp1 site within the DR5 promoter region. Using a combination of the electrophoretic mobility shift assay and the luciferase reporter assay, we found that a specific Sp1 site (located at -195 bp relative to the transcription start site) is required for sodium butyrate-mediated activation of the DR5 promoter. When HCT116 cells were incubated with sodium butyrate and TRAIL, enhanced TRAIL-mediated apoptosis was observed. The enhanced apoptosis was measured by fluorescent activated cell sorting analysis, DNA fragmentation, poly (ADP-ribose) polymerase cleavage, down-regulation of XIAP and caspase activity. Taken together, the present studies suggest that sodium butyrate may be an effective sensitizer of TRAIL-induced apoptosis.

  9. Oxidative cross-coupling of pyridine N-oxides and ethers between C(sp(2))-H/C(sp(3))-H bonds under transition-metal-free conditions.

    Science.gov (United States)

    Sun, Wei; Xie, Zuguang; Liu, Jie; Wang, Lei

    2015-04-21

    A novel and efficient method based on the cross-coupling reactions of pyridine N-oxides with ethers between C(sp(2))-H/C(sp(3))-H bonds in the presence of TBHP was developed. The strategy provides an alternative approach to the pyridine moiety under transition-metal-free conditions.

  10. miRNA-199 a-5 p通过SP1调节ERK5抑制乳腺癌MDA-MB-231细胞侵袭的机制%miRNA-199 a-5 p inhibit the invasion of MDA-MB-231 cells via regulating ERK5 through SP1

    Institute of Scientific and Technical Information of China (English)

    翟丽敏; 杨硕; 李文通

    2015-01-01

    目的:探讨miR-199a-5p对乳腺癌MDA-MB-231细胞的侵袭影响及其作用机制。方法转染miR-199a-5p mimic至MDA-MB-231细胞,Transwell侵袭实验检测miR-199a-5p对MDA-MB-231细胞侵袭能力的影响。采用细胞免疫荧光、Western blot法检测上皮细胞-间充质转化( epithelial-mesenchymal transition, EMT)分子标志物 E-cadherin、vimentin 的表达。应用Western blot法检测miR-199a-5p mimic及其LNA-siRNA对ERK5、pERK5、EGF、SP1表达的影响。染色体免疫共沉淀( chroma-tin immunoprecipitation, CHIP)技术检测SP1是否与ERK5启动子区结合。结果 miR-199a-5p能抑制MDA-MB-231细胞的侵袭,降低vimentin的表达,增强E-cadherin的表达。同时,miR-199a-5p降低ERK5表达并抑制其磷酸化;EGF、SP1的表达也相应减少。相反,应用LNA-siRNA抑制miR-199a-5p后,ERK5、pERK5、EGF、SP1的表达上调。 CHIP结果显示SP1能与ERK5启动子区结合。结论 miR-199a-5p通过调节EGF、SP1下调ERK5的表达并抑制其磷酸化,进而发挥对乳腺癌MDA-MB-231细胞侵袭的抑制作用。%Purpose To study the effect and mechanism of miR-199a-5p on the invasion of breast cancer MDA-MB-231 cells. Meth-ods miR-199a-5p mimic was transfected into MDA-MB-231 cells. Influence of miR-199a-5p on the invasion of MDA-MB-231 cell was displayed by Transwell, the expression of epithelial-mesenchymal transition ( EMT) molecular markers ( E-cadherin, vimentin) regulated by miR-199a-5p was determined using immunofluorescence and Western blot. Western blot was employed to assess the levels of ERK5, pERK5, EGF and SP1 in MDA-MB-231 cells dealt with miR-199a-5p mimic and LNA-siRNA. Chromatin immunoprecipita-tion (CHIP) was applied for displaying the reaction of SP1 with ERK5 promoter. Results miR-199a-5p could inhibit the invasion of MDA-MB-231 cells, decrease the expression of vimentin and enhance E-cadherin. Meanwhile, miR-199a-5p decreased the expression of ERK5 and pERK5, the levels of EGF and SP1 were

  11. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp transcription factors.

    Directory of Open Access Journals (Sweden)

    Satya Pathi

    Full Text Available Acetylsalicylic acid (aspirin is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB. Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

  12. Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA

    Directory of Open Access Journals (Sweden)

    Ristic Natalia

    2010-09-01

    Full Text Available Abstract Background The viral genome of HIV-1 contains several secondary structures that are important for regulating viral replication. The stem-loop 1 (SL1 sequence in the 5' untranslated region directs HIV-1 genomic RNA dimerization and packaging into the virion. Without SL1, HIV-1 cannot replicate in human T cell lines. The replication restriction phenotype in the SL1 deletion mutant appears to be multifactorial, with defects in viral RNA dimerization and packaging in producer cells as well as in reverse transcription of the viral RNA in infected cells. In this study, we sought to characterize SL1 mutant replication restrictions and provide insights into the underlying mechanisms of compensation in revertants. Results HIV-1 lacking SL1 (NLΔSL1 did not replicate in PM-1 cells until two independent non-synonymous mutations emerged: G913A in the matrix domain (E42K on day 18 postinfection and C1907T in the SP1 domain (P10L on day 11 postinfection. NLΔSL1 revertants carrying either compensatory mutation showed enhanced infectivity in PM-1 cells. The SL1 revertants produced significantly more infectious particles per nanogram of p24 than did NLΔSL1. The SL1 deletion mutant packaged less HIV-1 genomic RNA and more cellular RNA, particularly signal recognition particle RNA, in the virion than the wild-type. NLΔSL1 also packaged 3- to 4-fold more spliced HIV mRNA into the virion, potentially interfering with infectious virus production. In contrast, both revertants encapsidated 2.5- to 5-fold less of these HIV-1 mRNA species. Quantitative RT-PCR analysis of RNA cross-linked with Gag in formaldehyde-fixed cells demonstrated that the compensatory mutations reduced the association between Gag and spliced HIV-1 RNA, thereby effectively preventing these RNAs from being packaged into the virion. The reduction of spliced viral RNA in the virion may have a major role in facilitating infectious virus production, thus restoring the infectivity of NLΔSL1

  13. Self-assembled semi-crystallinity at parallel β-sheet nanocrystal interfaces in clustered MaSp1 (spider silk) proteins.

    Science.gov (United States)

    Sintya, Erly; Alam, Parvez

    2016-01-01

    In this communication, we use molecular dynamics methods to model the self-assembly of semi-crystalline domains at β-sheet nanocrystal interfaces in clusters of spider silk (MaSp1) proteins. Our research elucidates that the energetics at interfaces between crystalline and amorphous domains control effectively, the extent to which semi-crystalline domains can form at interfaces. Stability at nanocrystal interfaces is not linearly related to the internal (bulk) stability of the β-sheet nanocrystal. Rather, interfacial stability is found to be highly sensitive to the number of alanine repeat units that make up each sheet. Intriguingly, the most stable interface for the development of semi-crystallinity is built up of polyalanine β-sheets of a length similar to that which is spun naturally in spider dragline silk. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Bartoli, P

    1983-01-01

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

  15. Control of intestinal promoter activity of the cellular migratory regulator gene ELMO3 by CDX2 and SP1

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Boyd, Mette; Olsen, Jørgen;

    2010-01-01

    An important aspect of the cellular differentiation in the intestine is the migration of epithelial cells from the crypt to the villus tip. As homeodomaine transcription factor CDX2 has been suggested to influence cell migration, we performed a genome-wide promoter analysis for CDX2 binding...... migration. However, no information is available about the transcriptional regulation of the ELMO3 gene. The aim of this study was to investigate the potential role of CDX2 in the regulation of the ELMO3 promoter activity. Electrophoretic mobility shift assays showed that CDX2 bound to conserved CDX2...... sequences and mutations of the CDX2-binding sites, significantly reduced the promoter activity. Reporter gene assays demonstrated that the region mediating ELMO3 basal transcriptional activity to be located between -270 and -31 bp. Sequence analysis revealed no typical TATA-box, but four GC-rich sequences...

  16. Mass production in liquid diet and radiosterilization of South American fruit fly Anastrepha sp.1 aff. fraterculus (Wied., 1830) (Diptera: Tephritidae); Criacao massal em dieta liquida e radioesterilizacao da mosca-sulamericana Anastrepha sp.1 aff. fraterculus (Wied., 1830) (Diptera: Tephritidae)

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Aline Cristiane

    2010-07-01

    Both the biological control techniques as the Sterile Insect Technique (SIT), are used in many countries to control, suppress and even eradicate fruit flies and other pests in agriculture and public health. The use of such techniques minimizes the continuous employment of insecticides, protects the environment and conforms to standards for food safety. However, it is necessary to implement such programs, technology to produce millions of parasitoids and the pest in its own laboratory with biological quality similar to the insects found in nature and cost competitive with chemical control. The objectives of this study was to establish protocols for artificial rearing of A. sp. 1 aff. fraterculus in liquid larval diet that will achieve levels of mass production for a possible reduction in the cost of establishing and determining the dose of radiation sterilization of adult A. sp. 1 aff. fraterculus meeting the quality parameters required by the Sterile Insect Technique with insects from the creation of Radioentomology Laboratory of CENA/USP. Seven experimental diets compared to the conventional diet used in Radioentomology Lab. of CENA/USP, which was used as control. All seven diets have in common the exclusion of agar in its formulation. Only two of the diets tested were suitable for larval development of the fly, they compared with the standard diet, showed inferior results with respect to the volume of recovered larvae, pupae and weight of emergency, however, no significant differences regarding the periods of development , pupal recovery, sex ratio and longevity under stress. It is possible to replace the diet with agar for liquid diets for artificial creation of A. sp. 1 aff. fraterculus, reduced cost and greater convenience of handling, but due to their quality standards lower than the standard diet, more tests are needed especially regarding the adaptability of the insect to the new environment. To determine the sterilizing dose this study examined the

  17. Deficient mRNA expression of specie protein 3 gene in peripheral blood mononuclear cells from patients with multiple sclerosis%多发性硬化患者外周血单个核细胞SP3基因mRNA表达缺失研究

    Institute of Scientific and Technical Information of China (English)

    林艾羽; 杨期东; 慕容慎行; 王柠; 吴秀丽; 林珉婷

    2008-01-01

    目的 研究我国多发性硬化(multiple sclerosis,Ms)患者外周血单个核细胞基因SP3(specificprotein 3)mRNA表达缺失的特点及其与临床表型的关系.方法 采集56例MS患者外周血单个核细胞,提取总RNA,设计SP3特异性引物,采用逆转录PCR方法观察SP3基因mRNA表达情况,并与其他疾病组、健康对照组进行比较.结果 56例MS患者中23例SP3为阴性结果,SP3表达缺失率为41.1%;健康对照组35例有5例为阴性结果,缺失率为8.6%;其它疾病对照组27例有4例为阴性结果,缺失率为14.3%.MS组与两对照组之间的差异有统计学意义(P<0.01).SP3表达缺失组与表达组急性期的改良残废程度量表评分差异无统计学意义,稳定期则差异有统计学意义(P<0.05).结论 通过对MS患者SP3基因mRNA表达的研究,观察到中国人MS存在该基因mRNA表达缺失.SP3与MS临床表现及其免疫学发病机制之间可能存在一定的相关性.%Objective To characterize the deficiency of the mRNA expression of specific protein 3(SP3)gene in peripheral blood mononuc|ear cells(PBMCs)from Chinese patients with multiple sclerosis(MS)and study its correlation with the disease phenotypes.Methods Fifty-six patients with definite MS were collected and total RNA was extracted from their PBMCs.Specific primers corresponding to SP3 gene were designed and the mRNA expression of SP3 gene was detected by reverse transcriptase-PCR(RT-PCR)method.The deficiency of SP3 expression was compared among MS patients,irrelavant disease group and normal controls.Results Of the 56 MS cases,23(41.1%)were SP3 -deficient.In contrast,the frequency of SP3-deficiency in normal subjects and irrelavant disease controls Was 8.6% (5/35)and 14.3%(4/27),respectively.The frequency of the SP3-expression deficiency in MS patients Was significantly higher than that in both control groups(P<0.01).Within the MS cases,the scores of expanded disability status scale(EDSS)in the SP3-expressing subjects

  18. Construction of spider draggling silk protein MaSp1 prokaryotic expression vector and its expression and purification in Escherichia coli%蜘蛛牵引丝蛋白MaSp1原核表达载体构建及其在大肠杆菌中的表达与纯化

    Institute of Scientific and Technical Information of China (English)

    乔鑫; 王妍; 李俊杰; 段翠密; 王海滨; 周瑾; 杜芝燕; 王常勇

    2014-01-01

    目的:通过基因工程手段实现牵引丝关键组成蛋白MaSp1在大肠杆菌中的异源表达,并对其进行分离纯化,从而建立基因工程蜘蛛丝基因序列串联拼接、载体构建以及原核表达与纯化的关键技术体系。方法利用同尾酶连接法对合成的基因工程蜘蛛丝基因单体序列进行串联拼接,获得多倍串联体克隆重组子,将鉴定正确的多倍串联体克隆重组子与原核表达载体pET28a(+)连接,转化至大肠杆菌BL21(DE3),IPTG诱导其表达,表达产物通过SDS-PAGE和Western印迹进行鉴定。在此基础上对工程菌进行高密度发酵,所获蛋白通过硫酸铵分级分离方法进行纯化。结果与结论成功构建了基因工程蜘蛛丝MaSp1多串联体的表达载体,原核表达蛋白的相对分子质量与预期一致,且纯化的目的蛋白纯度达80%以上。上述研究工作为开展基因工程蜘蛛丝蛋白的规模化制备建立了关键技术方法,并为后续基因工程蜘蛛丝的人工纺丝提供必要的前提和工作基础。%Objective To establish a key technological system for spider fibroin gene code tandem connection , vector construction , prokaryotic expression and purification using genetic engineering in order to achieve MaSp 1 heterologous ex-pression in Escherichia coli and its separation and purification .Methods Isocaudarner ligation method was used to connect synthetic spider fibroin gene monomer code in tandem , and a recombinant clone concatemer was obtained .The identified recombinant clones were connected with prokaryotic expression vector pET 28a(+), and then transformed into E.coli BL21 (DE3).After being induced by IPTG for 6 hours, the expression product was identified by SDS-PAGE and Western blot-ting.Engineering bacteria were fermented in high density , and the obtained protein was purified through ammonium sulfate fractionation.Results and Conclusion The expression plasmids of MaSp1

  19. Helical Conformation in the CA-SP1 Junction of the Immature HIV-1 Lattice Determined from Solid-State NMR of Virus-like Particles.

    Science.gov (United States)

    Bayro, Marvin J; Ganser-Pornillos, Barbie K; Zadrozny, Kaneil K; Yeager, Mark; Tycko, Robert

    2016-09-21

    Maturation of HIV-1 requires disassembly of the Gag polyprotein lattice, which lines the viral membrane in the immature state, and subsequent assembly of the mature capsid protein lattice, which encloses viral RNA in the mature state. Metastability of the immature lattice has been proposed to depend on the existence of a structurally ordered, α-helical segment spanning the junction between capsid (CA) and spacer peptide 1 (SP1) subunits of Gag, a segment that is dynamically disordered in the mature capsid lattice. We report solid state nuclear magnetic resonance (ssNMR) measurements on the immature lattice in noncrystalline, spherical virus-like particles (VLPs) derived from Gag. The ssNMR data provide definitive evidence for this critical α-helical segment in the VLPs. Differences in ssNMR chemical shifts and signal intensities between immature and mature lattice assemblies also support a major rearrangement of intermolecular interactions in the maturation process, consistent with recent models from electron cryomicroscopy and X-ray crystallography.

  20. Molecular cloning, characterization and expression profiling of a serine protease gene Pr-SP1 in Pieris rapae(Lepidoptera: Pieridae)%菜粉蝶丝氨酸蛋白酶基因Pr-SP1的克隆及其表达谱分析

    Institute of Scientific and Technical Information of China (English)

    朱洋铿; 方琦; 胡萃; 叶恭银

    2011-01-01

    隆获得了菜粉蝶丝氨酸蛋白酶家族基因Pr-SP1的cDNA片段,并利用RACE法扩增获得其全序列.该cDNA序列长1 489 bp,其中开放阅读框长1 059bp,共编码353个氨基酸残基.Pr-SP1含一长度为20个氨基酸残基的信号肽序列,其蛋白理论分子量为36.85 kDa,理论等电点为6.41.多序列比对结果表明,Pr-SP1与其他昆虫的同源蛋白基因序列上存在较高一致性,在N端有一个发夹结构域,而C端是一个具有催化活性的结构域.实时荧光定量RT-PCR及免疫印迹结果表明,蛹期Pr-SP1主要在颗粒血细胞内进行转录,其蛋白产物主要定位在血浆;Pr-SP1在不同虫态及虫龄都有转录,其蛋白产物在不同虫态及虫龄都有表达,其中5龄幼虫最高,卵期最低;Pr-SP1的转录水平及其蛋白产物的表达水平均会被大肠杆菌Escherichia coli、藤黄微球菌Micrococcus luteus和巴斯德毕赤酵母Pichia pastoris诱导.根据这些结果分析认为,Pr-SP1属于Sp(a)tzle蛋白酶前体激活酶,并参与菜粉蝶的先天免疫反应.

  1. The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid

    Directory of Open Access Journals (Sweden)

    Aiken Christopher

    2004-06-01

    Full Text Available Abstract Background Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells. Results Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the presence of the drug. Conclusions These results demonstrate that the CA-SP1 junction in Pr55Gag represents the primary viral target of DSB. They further suggest that the therapeutic application of DSB will be accompanied by emergence of mutant viruses that are highly resistant to the drug but which exhibit reduced fitness relative to wild type HIV-1.

  2. Production of extracellular polymeric substances (EPS) by Serratia sp.1 using wastewater sludge as raw material and flocculation activity of the EPS produced.

    Science.gov (United States)

    Bezawada, J; Hoang, N V; More, T T; Yan, S; Tyagi, N; Tyagi, R D; Surampalli, R Y

    2013-10-15

    Growth profile and extracellular polymeric substances (EPS) production of Serratia sp.1 was studied in shake flask fermentation for 72 h using wastewater sludge as raw material. Maximum cell concentration of 6.7 × 10(9) cfu/mL was obtained at 48 h fermentation time. EPS dry weight, flocculation activity and dewaterability of different EPS (tightly bound or TB-EPS, loosely bound or LB-EPS and broth-EPS or B-EPS) were also measured. The highest concentration of LB-EPS (2.45 g/L) and TB-EPS (0.99 g/L) were attained at 48 h of fermentation. Maximum flocculation activity and dewaterability (ΔCST) of TB-EPS (76.4%, 14.5s and 76.5%, 15.5s), LB-EPS (67.8%, 8.1s and 64.7%, 7.6s) and broth EPS (61%, 6.1s and 70.4%, 6.8s) were obtained at 36 and 48 h of growth. Higher flocculation activity and dewaterability were achieved with TB-EPS than with the two other EPS. Characterization of TB-EPS and LB-EPS was done in terms of their protein and carbohydrate content. Protein content was much higher in TB-EPS where as carbohydrate content was only slightly higher in TB-EPS than LB-EPS. Morphology of the Serratia strain after fermentation in sludge and TSB was observed under a scanning electron microscope and the cell size was found to be bigger in the sludge medium than the TSB medium.

  3. Structure of model peptides based on Nephila clavipes dragline silk spidroin (MaSp1) studied by 13C cross polarization/magic angle spinning NMR.

    Science.gov (United States)

    Yang, Mingying; Nakazawa, Yasumoto; Yamauchi, Kazuo; Knight, David; Asakura, Tetsuo

    2005-01-01

    To obtain detailed structural information for spider dragline spidroin (MaSp1), we prepared three versions of the consensus peptide GGLGGQGAGAAAAAAGGAGQGGYGGLGSQGAGR labeled with 13C at six different sites. The 13C CP/MAS NMR spectra were observed after treating the peptides with different reagents known to alter silk protein conformations. The conformation-dependent 13C NMR chemical shifts and peak deconvolution were used to determine the local structure and the fractional compositions of the conformations, respectively. After trifluoroacetic acid (solvent)/diethyl ether (coagulant) treatment, the N-terminal region of poly-Ala (PLA) sequence, Ala8 and Ala10, adopted predominantly the alpha-helix with a substantial amount of beta-sheet. The central region, Ala15, Ala18, and Leu26, and C-terminal region, Ala31, of the peptide were dominated by either 3(1)-helix or alpha-helix. There was no indication of beta-sheet, although peak broadening indicates that the torsion angle distribution is relatively large. After 9 M LiBr/dialysis treatment, three kinds of conformation, beta-sheet, random coil, and 3(1)-helix, appeared, in almost equal amounts of beta-sheet and random coil conformations for Ala8 and Ala10 residues and distorted 3(1)-helix at the central region of the peptide. In contrast, after formic acid/methanol and 8 M urea/acetonitrile treatments, all of the local structure tends to beta-sheet, although small amounts of random coil are also observed. The peak pattern of the Ala Cbeta carbon after 8 M urea/acetonitrile treatment is similar to the corresponding patterns of silk fiber from Bombyx mori and Samia cynthia ricini. We also synthesized a longer 13C-labeled peptide containing two PLA blocks and three Gly-rich blocks. After 8 M urea/acetonitrile treatment, the conformation pattern was closely similar to that of the shorter peptide.

  4. Effects of Matrine to Stenus (Stenus, s.str)sp.1 and Paedenus fuscipes Curtis%苦参碱对大眼隐翅虫和梭毒隐翅虫的影响

    Institute of Scientific and Technical Information of China (English)

    肖凡; 郑发科

    2005-01-01

    大眼隐翅虫Stenus ( Stenus, s.str ) sp.1 和梭毒隐翅虫Paedenus fuscipes Curtis是重要的天敌昆虫.用苦参碱在室内做了大眼隐翅虫和梭毒隐翅虫的药效实验.结果表明,苦参碱对大眼隐翅虫和梭毒隐翅虫有一定的毒杀作用.

  5. Cooperative catalysis of metal and O-H···O/sp3-C-H···O two-point hydrogen bonds in alcoholic solvents: Cu-catalyzed enantioselective direct alkynylation of aldehydes with terminal alkynes.

    Science.gov (United States)

    Ishii, Takaoki; Watanabe, Ryo; Moriya, Toshimitsu; Ohmiya, Hirohisa; Mori, Seiji; Sawamura, Masaya

    2013-09-27

    Catalyst-substrate hydrogen bonds in artificial catalysts usually occur in aprotic solvents, but not in protic solvents, in contrast to enzymatic catalysis. We report a case in which ligand-substrate hydrogen-bonding interactions cooperate with a transition-metal center in alcoholic solvents for enantioselective catalysis. Copper(I) complexes with prolinol-based hydroxy amino phosphane chiral ligands catalytically promoted the direct alkynylation of aldehydes with terminal alkynes in alcoholic solvents to afford nonracemic secondary propargylic alcohols with high enantioselectivities. Quantum-mechanical calculations of enantiodiscriminating transition states show the occurrence of a nonclassical sp(3)-C-H···O hydrogen bond as a secondary interaction between the ligand and substrate, which results in highly directional catalyst-substrate two-point hydrogen bonding.

  6. 1株鸽源鸡杆菌复合群3的分离和鉴定%Isolation and identification of one pigeon-origin Gallibacterium genomo sp3

    Institute of Scientific and Technical Information of China (English)

    杨晓林; 陈英; 余松城; 邹年莉; 吴瑞婷; 夏静; 牛婷; 王富妍; 黄勇

    2014-01-01

    报道我国鸽场中鸡杆菌的感染情况.四川某种鸽场的种鸽出现以消瘦、呼吸困难、气管和肺出血、腹膜炎、输卵管炎等为主要特征的疾病.选取代表性病例,进行细菌分离和病毒检测,并对分离菌进行形态学观察、生化鉴定、动物试验、药敏试验和16S rRNA 基因序列分析.结果显示,部分病鸽只检测到新城疫病毒;从肝、肺中分离到1株革兰阴性短杆菌,命名为 SC01,该菌株为致病菌,小鼠半数致死量(LD50)为1.26×109 CFU/mL,能发酵多数糖和醇类,对头孢类药物较敏感.将 SC01与 GenBank 中同源性较近的15株细菌的16S rRNA 基因序列进行同源性分析,发现 SC01株与4株鸡杆菌复合群3(Gallibacterium genomo sp.3)的同源性为98.5%~99.5%,其中与EU423996的同源性最高,为99.5%,证实该菌株为鸡杆菌复合群3.试验结果为鸡杆菌复合群3感染的流行病学调查、诊断与治疗提供了新的参考.%Summary Gallibacterium infection was a new infectious disease observed in some areas of China,which was mainly harmful for laying hen,resulting in salpingitis,oophoritis,peritonitis,septicemia,hepatitis,enteritis, respiratory tract diseases,and so on.So far,most of the G.anatis were isolated from poultry,including chickens, ducks,pigeons,geese,parrots,quail and guinea fowl,etc.Isolation of Gallibacterium from pigeons was not reported in China. A contagious disease occurred in one breeding farm of pigeon in Sichuan Province in January of 2013,with the characteristic signs of depressed wasting,dyspnea,diarrhea,and so on.The morbidity was about 43%,and the mortality was about 18%.The disease was mainly found in female pigeons,and female pigeons of different ages could be infected,especially pigeons of 1 to 1.5 years old.Mild bleeding and mucus could be observed in diseased pigeons,and other gross lesions could also be observed including hemorrhage of lung,peritonitis,salpingitis,mild bleeding of duodenum,and so on

  7. A comparison between the novel rabbit monoclonal antibodies (SP1 and B644 and mouse antibodies for evaluating estrogen receptor in breast tumors Uma comparação entre os novos anticorpos monoclonais de coelho (SP1 e B644 e anticorpos de camundongo para detecção de receptores de estrógeno em carcinomas mamários

    Directory of Open Access Journals (Sweden)

    Rafael Malagoli Rocha

    2007-12-01

    Full Text Available BACKGROUND: A novel generation of rabbit monoclonal antibodies has been released recently for estrogen (ER and progesterone (PR receptor evaluation in breast cancer by immunohistochemistry. Aims: We compared novel rabbit monoclonal antibodies anti-ER SP1 (LabVision® and B644 (Cell Marque® to mouse monoclonal antibodies 1D5 (Dako® and 6F11 (Novocastra® using a tissue microarray of breast carcinomas. METHODS: Two cylinders (2 mm diameter of formalin-fixed paraffin embedded tissue were obtained from 24 invasive breast carcinomas and immunostained by using the anti-ER rabbit and mouse antibodies and the streptavidin-biotin detection system (Biogenex®. Immunostaining was evaluated considering positive those tumors in which more than 10% of the tumor cell nuclei stained. The stain intensity was also evaluated as weak (1, moderate (2, and strong (3. Results: Both rabbit antibodies against ER have similar staining pattern to each other and also to 6F11, but significantly stronger scores compared to mouse 1D5. The rabbit antibodies allow better cost/benefit because of higher working dilutions compared to mouse antibodies using the same procedure. CONCLUSION: The new rabbit antibodies against ER are highly sensitive and reliable in clinical and research immunohistochemical testing of breast carcinomas.INTRODUÇÃO: Uma nova geração de anticorpos monoclonais de coelho tem sido produzida para detecção de receptores de estrógeno (RE e progesterona (RP pela imuno-histoquímica em câncer de mama. OBJETIVO: Comparamos os novos anticorpos monoclonais de coelho anti-RE SP1 (LabVision® e B644 (Cell Marque® com anticorpos monoclonais de camundongo 1D5 (DAKO® e 6F11 (Novocastra® utilizando um tissue microarray de carcinomas mamários. METODOLOGIA: Dois cilindros (2 mm de diâmetro de tecido fixado em formol e embebido em parafina foram retirados de 24 carcinomas mamários invasivos e corados pela imuno-histoquímica utilizando-se os anticorpos de

  8. Estimation of hormone receptor status in fine-needle aspirates and paraffin-embedded sections from breast cancer using the novel rabbit monoclonal antibodies SP1 and SP2.

    Science.gov (United States)

    Cano, Guillerma; Milanezi, Fernanda; Leitão, Dina; Ricardo, Sara; Brito, Maria José; Schmitt, Fernando Carlos

    2003-10-01

    We describe a method of immunocytochemical assessment of estrogen receptor (ER) status on alcohol-fixed smears obtained by fine-needle aspiration (FNA) from breast cancer patients, using a commercially available rabbit monoclonal antibody anti-ER (SP1) without any antigen retrieval. A series of 40 aspirates were analyzed and the results of ER status were compared with the respective formalin-fixed tissue using the same procedure and with assessment by the classical method using the mouse monoclonal antibody 6F11 (anti-ER) with antigen retrieval on paraffin sections. Twenty-four out of the 40 cases examined were positive at least by two methods and 16 were negative for all three determinations. The results obtained in the ER immunocytochemical assay on aspirates and paraffin sections using the antibody SP1 and those obtained on paraffin sections using the antibody 6F11 were quite similar. In one case the material was insufficient to interpret the reaction in the cytological specimen and only one case, with focal positivity reaction on paraffin sections, was negative in the cytological specimen. The intensity of nuclei staining in cytological smears of breast cancer cells was stronger than that observed by traditional methods. We also assessed progesterone receptor (PR) status on 40 paraffin-sections from breast cancer patients, using a commercially available rabbit monoclonal antibody anti-PR (SP2), with the same characteristics described for anti-ER (SP1). The results were compared with assessment by the classic method with mouse monoclonal antibody 1A6 (PR) on paraffin sections and total agreement was observed. Of the 40 cases examined, 18 were positive and 22 were negative for the two determinations. We conclude that the application of the ER method on alcohol-fixed smears/paraffin sections with the rabbit monoclonal antibody SP1, and the PR method on paraffin sections with the rabbit monoclonal antibody SP2, provide several advantages, such as high sensitivity

  9. Nearest-neighbor sp3s* tight-binding parameters based on the hybrid quasi-particle self-consistent GW method verified by modeling of type-II superlattices

    Science.gov (United States)

    Sawamura, Akitaka; Otsuka, Jun; Kato, Takashi; Kotani, Takao

    2017-06-01

    We report the determination of parameters for the nearest-neighbor sp3s* tight-binding (TB) model for GaP, GaAs, GaSb, InP, InAs, and InSb at 0, 77, and 300 K based on the hybrid quasi-particle self-consistent GW (QSGW) calculation and their application to a type II (InAs)/(GaSb) superlattice. The effects of finite temperature have been incorporated empirically by adjusting the parameter for blending the exchange-correlation terms of the pure QSGW method and local density approximation, in addition to the usage of experimental lattice parameters. As expected, the TB band gap shrinks with temperature and asymptotically with superlattice period when it is large. In addition, a bell curve in the band gap in the case of small superlattice period and slight and remarkable anisotropy in effective masses of electron and hole, both predicted by the hybrid QSGW method, respectively, are reproduced.

  10. 云南美登木共生放线菌菌株3C产生的苯丙素类化合物%Phenylpropanoids produced by Streptomyces sp.3C,a commensal microbe of Maytenus hookeri

    Institute of Scientific and Technical Information of China (English)

    鲁春华; 沈月毛

    2005-01-01

    从云南美登木共生放线菌菌株3C的发酵提取物中分离得到两个苯丙素类化合物1和2.通过谱学特征鉴定了化合物的结构,其中,化合物2为新化合物.通过乙酰化反应得到了相应的乙酰化产物,并通过纸片扩散法测定了所有化合物的抗细菌活性.%Two phenylpropanoids(1 and 2)were isolated from the fermentation extracts of commensal microbe of Maytenus hookeri(Streptomyces sp.3C).Their structures were elucidated on the basis of NMR and EIMS techniques and compound 2 was a new one.Their acetylated products,1a,1b and 2a,were obtained by acetylation with Ac2O-pyridine.The antibacterial activities of all the five compounds were performed by paper-disc assay method,and potential activities were observed.

  11. The variances of Sp1 and NF-κB elements correlate with the greater capacity of Chinese HIV-1 B′-LTR for driving gene expression

    OpenAIRE

    2016-01-01

    The 5′ end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles...

  12. Down-regulation of beta1,4-galactosyltransferase V is a critical part of etoposide-induced apoptotic process and could be mediated by decreasing Sp1 levels in human glioma cells.

    Science.gov (United States)

    Jiang, Jianhai; Shen, Jialin; Wu, Tao; Wei, Yuanyan; Chen, Xiaoning; Zong, Hongliang; Zhang, Si; Sun, Maoyun; Xie, Jianhui; Kong, Xiangfei; Yang, Yanzhong; Shen, Aiguo; Wang, Hanzhou; Gu, Jianxin

    2006-11-01

    beta1,4-Galactosyltransferase V (beta1,4GalT V; EC 2.4.1.38) is considered to be very important in glioma for expressing transformation-related highly branched N-glycans. Recently, we have characterized beta1,4GalT V as a positive growth regulator in several glioma cell lines. However, the role of beta1,4GalT V in glioma therapy has not been clearly reported. In this study, interfering with the expression of beta1,4GalT V by its antisense cDNA in SHG44 human glioma cells markedly promoted apoptosis induced by etoposide and the activation of caspases as well as processing of Bid and expression of Bax and Bak. Conversely, the ectopic expression of beta1,4GalT V attenuated the apoptotic effect of etoposide on SHG44 cells. In addition, both the beta1,4GalT V transcription and the binding of total or membrane glycoprotein with Ricinus communis agglutinin-I (RCA-I) were partially reduced in etoposide-treated SHG44 cells, correlated well with a decreased level of Sp1 that has been identified as an activator of beta1,4GalT V transcription. Collectively, our results suggest that the down-regulation of beta1,4GalT V expression plays an important role in etoposide-induced apoptosis and could be mediated by a decreasing level of Sp1 in SHG44 cells, indicating that inhibitors of beta1,4GalT V may enhance the therapeutic efficiency of etoposide for malignant glioma.

  13. Iridium complexes containing mesoionic C donors: selective C(sp3)-H versus C(sp2)-H bond activation, reactivity towards acids and bases, and catalytic oxidation of silanes and water.

    Science.gov (United States)

    Petronilho, Ana; Woods, James A; Mueller-Bunz, Helge; Bernhard, Stefan; Albrecht, Martin

    2014-11-24

    Metalation of a C2-methylated pyridylimidazolium salt with [IrCp*Cl2]2 affords either an ylidic complex, resulting from C(sp(3))-H bond activation of the C2-bound CH3 group if the metalation is performed in the presence of a base, such as AgO2 or Na2CO3, or a mesoionic complex via cyclometalation and thermally induced heterocyclic C(sp(2))-H bond activation, if the reaction is performed in the absence of a base. Similar cyclometalation and complex formation via C(sp(2))-H bond activation is observed when the heterocyclic ligand precursor consists of the analogous pyridyltriazolium salt, that is, when the metal bonding at the C2 position is blocked by a nitrogen rather than a methyl substituent. Despite the strongly mesoionic character of both the imidazolylidene and the triazolylidene, the former reacts rapidly with D(+) and undergoes isotope exchange at the heterocyclic C5 position, whereas the triazolylidene ligand is stable and only undergoes H/D exchange under basic conditions, where the imidazolylidene is essentially unreactive. The high stability of the Ir-C bond in aqueous solution over a broad pH range was exploited in catalytic water oxidation and silane oxidation. The catalytic hydrosilylation of ketones proceeds with turnover frequencies as high as 6,000 h(-1) with both the imidazolylidene and the triazolylidene system, whereas water oxidation is enhanced by the stronger donor properties of the imidazol-4-ylidene ligands and is more than three times faster than with the triazolylidene analogue. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Triptolide inhibits transcription of hTERT through down-regulation of transcription factor specificity protein 1 in primary effusion lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Long, Cong; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Wang, Huan; Wang, Chao; Liu, Yu [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan, 430072 (China)

    2016-01-01

    Primary effusion lymphoma (PEL) is a rare and aggressive non-Hodgkin's lymphoma. Human telomerase reverse transcriptase (hTERT), a key component responsible for the regulation of telomerase activity, plays important roles in cellular immortalization and cancer development. Triptolide purified from Tripterygium extracts displays a broad-spectrum bioactivity profile, including immunosuppressive, anti-inflammatory, and anti-tumor. In this study, it is investigated whether triptolide reduces hTERT expression and suppresses its activity in PEL cells. The mRNA and protein levels of hTERT were examined by real time-PCR and Western blotting, respectively. The activity of hTERT promoter was determined by Dual luciferase reporter assay. Our results demonstrated that triptolide decreased expression of hTERT at both mRNA and protein levels. Further gene sequence analysis indicated that the activity of hTERT promoter was suppressed by triptolide. Triptolide also reduced the half-time of hTERT. Additionally, triptolide inhibited the expression of transcription factor specificity protein 1(Sp1) in PEL cells. Furthermore, knock-down of Sp1 by using specific shRNAs resulted in down-regulation of hTERT transcription and protein expression levels. Inhibition of Sp1 by specific shRNAs enhanced triptolide-induced cell growth inhibition and apoptosis. Collectively, our results demonstrate that the inhibitory effect of triptolide on hTERT transcription is possibly mediated by inhibition of transcription factor Sp1 in PEL cells. - Highlights: • Triptolide reduces expression of hTERT by decreasing its transcription level. • Triptolide reduces promoter activity and stability of hTERT. • Triptolide down-regulates expression of Sp1. • Special Sp1 shRNAs inhibit transcription and protein expression of hTERT. • Triptolide and Sp1 shRNA2 induce cell proliferation inhibition and apoptosis.

  15. 海月水母(Aurelia sp.1)水螅体在空气中暴露存活研究%VIABILITY OF SCYPHISTOMAE OF A URELIA sp.1 EXPOSED IN THE AIR

    Institute of Scientific and Technical Information of China (English)

    冯颂; 孙松; 张芳; 李超伦

    2012-01-01

    In the laboratory, the viability of scyphistomae ofAurelia sp. 1 being exposed in air and in the seawater by turn are studied. The possibility of living in the intertidal zone was also analyzed. At the exposed 15min group, the viabil- ity rates of the scyphistomae are 100% in the experiment. At the exposed 30min group, its viability rate is 82.22% after twenty-fifth hour. At the exposed 45rain group, the scyphistomae's viability rate dramatically falls to 46.67% after twenty-fifth hour. At the exposed 1 hour group, the viability of the scyphistomae drop significantly to 46.67% after the third hour, then they fall to 26.67% after the twenty-fifth hour. At the exposed 2 hour group, the viability of the scyphistomae reduce significantly to 2.38% after 4h, then all the scyphistomae died is about 57 minute. According to the results, relia sp. 1 may survive in lower intertidal zone. scyphistomae are dead after 8h. The time when half of the it is preliminarily presumed that the scyphistomae of Aurelia sp. 1 may survive in lower intertidal zone.%在实验室内研究了海月水母水螅体交替淹没在海水、暴露在空气中的存活情况,分析了其在潮间带存活的可能性。结果表明,整个实验过程中,暴露15min组,海月水母水螅体存活率均为100%。暴露30min组,25h后,水螅体存活率为82.22%。暴露45min组,2.75h时,存活率显著降低为73133%:25h后,存活率下降为46,67%。暴露1h组,在3h时,水螅体存活率显著降低为46.67%;25h时存活率为26.67%。暴露2h组,4h时,水螅体存活率显著降低为2.38%;8h后水螅体全部死亡。整个实验过程中,海月水母水螅体暴露在空气中半数死亡的时间约57rain,根据实验结果,初步推测海月水母水螅体可能在低潮带生存,而在高、中潮带不可能存活。

  16. Cytogenetic Analysis of the South American Fruit Fly Anastrepha fraterculus (Diptera:Tephritidae) Species Complex: Construction of Detailed Photographic Polytene Chromosome Maps of the Argentinian Af. sp.1 Member.

    Science.gov (United States)

    Gariou-Papalexiou, Angeliki; Giardini, María Cecilia; Augustinos, Antonios A; Drosopoulou, Elena; Lanzavecchia, Silvia B; Cladera, Jorge L; Caceres, Carlos; Bourtzis, Kostas; Mavragani-Tsipidou, Penelope; Zacharopoulou, Antigone

    2016-01-01

    Genetic and cytogenetic studies constitute a significant basis for understanding the biology of insect pests and the design and the construction of genetic tools for biological control strategies. Anastrepha fraterculus is an important pest of the Tephritidae family. It is distributed from southern Texas through eastern Mexico, Central America and South America causing significant crop damage and economic losses. Currently it is considered as a species complex; until now seven members have been described based on multidisciplinary approaches. Here we report the cytogenetic analysis of an Argentinian population characterized as Af. sp.1 member of the Anastrepha fraterculus species complex. The mitotic karyotype and the first detailed photographic maps of the salivary gland polytene chromosomes are presented. The mitotic metaphase complement consists of six (6) pairs of chromosomes, including one pair of heteromorphic sex chromosomes, with the male being the heterogametic sex. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes that correspond to the five autosomes of the mitotic karyotype and a heterochromatic network corresponding to the sex chromosomes. Comparison of the polytene chromosome maps between this species and Anastrepha ludens shows significant similarity. The polytene maps presented here are suitable for cytogenetic studies that could shed light on the species limits within this species complex and support the development of genetic tools for sterile insect technique (SIT) applications.

  17. Cytogenetic Analysis of the South American Fruit Fly Anastrepha fraterculus (Diptera:Tephritidae Species Complex: Construction of Detailed Photographic Polytene Chromosome Maps of the Argentinian Af. sp.1 Member.

    Directory of Open Access Journals (Sweden)

    Angeliki Gariou-Papalexiou

    Full Text Available Genetic and cytogenetic studies constitute a significant basis for understanding the biology of insect pests and the design and the construction of genetic tools for biological control strategies. Anastrepha fraterculus is an important pest of the Tephritidae family. It is distributed from southern Texas through eastern Mexico, Central America and South America causing significant crop damage and economic losses. Currently it is considered as a species complex; until now seven members have been described based on multidisciplinary approaches. Here we report the cytogenetic analysis of an Argentinian population characterized as Af. sp.1 member of the Anastrepha fraterculus species complex. The mitotic karyotype and the first detailed photographic maps of the salivary gland polytene chromosomes are presented. The mitotic metaphase complement consists of six (6 pairs of chromosomes, including one pair of heteromorphic sex chromosomes, with the male being the heterogametic sex. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes that correspond to the five autosomes of the mitotic karyotype and a heterochromatic network corresponding to the sex chromosomes. Comparison of the polytene chromosome maps between this species and Anastrepha ludens shows significant similarity. The polytene maps presented here are suitable for cytogenetic studies that could shed light on the species limits within this species complex and support the development of genetic tools for sterile insect technique (SIT applications.

  18. SGK1 affects RAN/RANBP1/RANGAP1 via SP1 to play a critical role in pre-miRNA nuclear export: a new route of epigenomic regulation

    Science.gov (United States)

    Dattilo, Vincenzo; D’Antona, Lucia; Talarico, Cristina; Capula, Mjriam; Catalogna, Giada; Iuliano, Rodolfo; Schenone, Silvia; Roperto, Sante; Bianco, Cataldo; Perrotti, Nicola; Amato, Rosario

    2017-01-01

    The serum- and glucocorticoid-regulated kinase (SGK1) controls cell transformation and tumor progression. SGK1 affects mitotic stability by regulating the expression of RANBP1/RAN. Here, we demonstrate that SGK1 fluctuations indirectly modify the maturation of pre-miRNAs, by modulating the equilibrium of the RAN/RANBP1/RANGAP1 axis, the main regulator of nucleo-cytoplasmic transport. The levels of pre-miRNAs and mature miRNAs were assessed by qRT-PCR, in total extracts and after differential nuclear/cytoplasmic extraction. RANBP1 expression is the limiting step in the regulation of SGK1-SP1 dependent nuclear export. These results were validated in unrelated tumor models and primary human fibroblasts and corroborated in tumor-engrafted nude mice. The levels of pri-miRNAs, DROSHA, DICER and the compartmental distribution of XPO5 were documented. Experiments using RANGTP conformational antibodies confirmed that SGK1, through RANBP1, decreases the level of the GTP-bound state of RAN. This novel mechanism may play a role in the epigenomic regulation of cell physiology and fate. PMID:28358001

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

    Directory of Open Access Journals (Sweden)

    Jiarong Zhang

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

  20. Specificity Protein (Sp) Transcription Factors and Metformin Regulate Expression of the Long Non-coding RNA HULC

    Science.gov (United States)

    There is evidence that specificity protein 1 (Sp1) transcription factor (TF) regulates expression of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) cells. RNA interference (RNAi) studies showed that among several lncRNAs expressed in HepG2, SNU-449 and SK-Hep-1...

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

    Science.gov (United States)

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

    2013-01-01

    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.

  2. A conserved function of the zinc finger transcription factor Sp8/9 in allometric appendage growth in the milkweed bug Oncopeltus fasciatus

    OpenAIRE

    Schaeper, Nina; Prpic, Nikola-Michael; Wimmer, Ernst

    2009-01-01

    The genes encoding the closely related zinc finger transcription factors Buttonhead (Btd) and D-Sp1 are expressed in the developing limb primordia of Drosophila melanogaster and are required for normal growth of the legs. The D-Sp1 homolog of the red flour beetle Tribolium castaneum, Sp8 (appropriately termed Sp8/9), is also required for the proper growth of the leg segments. Here we report on the isolation and functional study of the Sp8/9 gene from the milkweed bug Oncopeltus fasciatus. We ...

  3. STUDY ON SUBSTRATE CHOICE AND SETTLEMENT PREFERENCES OF PLANULA LARVAE OF A URELIA SP.1%海月水母水螅体附着选择性研究

    Institute of Scientific and Technical Information of China (English)

    王彦涛; 孙松; 李超伦

    2012-01-01

    During ocean exploitation habitat for polyps might increase, thus increase jellyfish polyps populations, and then enhance jellyfish population. In this study, we examined planula of Aurelia sp.1 settlement on living-oyster, oyster shell, scallop shell, floor plates, netting and PV-pipe, proliferation of polyps on the surfaces of bamboo and cement block. The planula and polyps preferred man-made materials(floor plates,netting and PV-pipe). The underside of floor plates was strongly favorable for settlement. Polyps can form new polyps population through asexual reproduction on new habitat, the expanding process was limited by polyps population density. When the density was relatively low, polyps population in- creased rapidly, and this increase was slower when density was relatively high. Increasing litter (plastics,glassand wood) pollution and submarine constructions (maricultureand ocean engineering) providemore attachment surfaceand thus enlarge the areas of polyps distributionand form larger number of polyps populations.%通过室内实验研究了海月水母0ureliasp.1)浮浪幼虫在活体牡蛎、牡蛎壳、扇贝壳、波纹板、网衣(200gm)、PV管等材料上的附着选择性和水螅体在竹竿和水泥块上的增殖问题。实验表明,浮浪幼虫对人工材料(波纹板、网衣、PV管)具有偏好性,附着密度较大;水平放置的附着材料底部附着更多的水螅体。水螅体可以通过无性繁殖方式在新的栖息地形成水螅体种群,种群扩张过程中存在密度限制,较低密度时水螅体种群增长较快,高密度时水螅体种群增长较慢。作者认为,日益增加的海洋废弃物(塑料、玻璃、木材),以及海底构造物(海水养殖筏、海洋工程)为水螅体提供了更多的附着表面,这有利于水螅体栖息地的扩张,形成更大的水螅体种群。

  4. Predictive factors of breast cancer evaluated by immunohistochemistry Fatores preditivos do câncer de mama avaliados pela imuno-histoqu��mica

    Directory of Open Access Journals (Sweden)

    Helenice Gobbi

    2008-04-01

    Full Text Available Hormone receptor and Her2 protein overexpression evaluated by immunohistochemistry (IHC is widely validated as a predictive factor in breast cancer. The quality of the IHC reaction is influenced by tissue fixation and processing. Over- and underfixation deeply affect IHC results. Antigen retrieval may improve IHC but it does not recover tissue from autolysis or overfixation. The choice of primary antibody for IHC as to its sensitivity and specificity in relation to therapeutic response represents an important stage. Apart from mouse monoclonal antibodies, new rabbit monoclonal antibodies are commercially available, such as clones anti-ER SP1 and B644, anti-PR SP2 and B645 and anti-Her2 SP3 and 4B5. They represent an alternative to hormone receptor and Her2 evaluation by IHC. New polymeric non-biotinylated detection systems are also available and allow accurate and strong marking with no stromal and no non-specific cytoplasmic staining due to endogenous biotin. The most recommended cut off for estrogen and progesterone receptors (ER and PR is more than 1% of positive cells with moderate or strong staining intensity (Allred's scoring system. New guidelines for Her2 evaluation by IHC show a cut off of more than 30% of positive cells with strong intensity (3+ that correlates better with gene amplification. The 2+ cases are now considered indeterminate and should be confirmed by fluorescence in situ hybridisation (FISH or chromogenic in situ hybridisation CISH. A quality control of pre-analytical, analytical and post-analytical phases of IHC is recommended in order to optimize results.A superexpressão de receptores hormonais e Her2 avaliada pela imuno-histoquímica (IHQ é amplamente validada como fator preditivo em câncer de mama. A qualidade da reação imuno-histoquímica é influenciada pela fixação do tecido e seu processamento. A fixação insuficiente ou demasiada afeta profundamente os resultados da IHQ. A reativação antigênica pode

  5. THE MUTUAL PREDATORY RELATIONSHIP OF JELLYFISHES IN DIFFERENT LIFE STAGES BETWEEN A URELIA sp.1 AND RHOPILEMA ESCULENTA%生活史不同阶段的海月水母(Aurelia sp.1)与海蜇(Rhopilema esculenta)的相互捕食关系

    Institute of Scientific and Technical Information of China (English)

    李宗飞; 刘春胜; 庄志猛; 邹安革; 陈四清; 燕敬平; 刘长琳

    2012-01-01

    A laboratory experiment was conducted to investigate the predator-prey relationship at different life stages between Aurelia sp. 1 and Rhopilema esculenta. The results showed that Scyphistomae of Aurelia sp. 1, with l mm oral disk diameter, could prey on ephyrae and medusa ofR. esculenta whose oral disk was no more than 8mm in diameter; and in the ephyrae larval stage, Aurelia sp. 1 was able to prey on R. esculenta's; Aurelia sp. 1 medusa with 100mm bell diameter could still feed upon both ephyrae larval and early medusa (bell diameter ≤ 30mm) ofR. esculenta. However, the early medusa ofR. esculenta whose umbrella diameter was no less than 10mm could absolutely prey on Aurelia sp. 1 ephyrae larval. Au- relia sp.1 had stronger ability to prey on R. esculenta. These results revealed the relationship between the outbreak of Au- relia sp. 1 and the decrease ofR. esculenta resource. It was helpful to improve the effect of releasing R. esculenta.%采用交叉实验和水母体培养的方法,研究了不同生活史阶段的海月水母及海蜇之间的相互捕食关系。海月水母螅状体(口柄直径约为1mm)能够捕食海蜇碟状体及伞径≤8mm的海蜇幼体;海月水母的碟状体只能够捕食海蛰碟状体;伞径100mm的海月水母体能够捕食海蜇碟状体及伞径≤30mm的海蛰幼体。在海蜇对海月水母的捕食实验中发现,伞径≥10mm的海蜇幼体对海月水母的碟状体有捕食行为。通过对两种水母相互捕食关系的研究,笔者认为海月水母捕食海蜇的能力明显强于海蜇捕食海月水母的能力。这或许有助于解释近年来海月水母不断暴发而海蜇资源日渐减少的现象,有助于改进海蜇人工增殖放流措施,提高放流效果。

  6. Parathyroid hormone inhibition of Na{sup +}/H{sup +} exchanger 3 transcription: Intracellular signaling pathways and transcription factor expression

    Energy Technology Data Exchange (ETDEWEB)

    Neri, Elida Adalgisa; Bezerra, Camila Nogueira Alves, E-mail: camilab@icb.usp.br; Queiroz-Leite, Gabriella Duarte; Polidoro, Juliano Zequini; Rebouças, Nancy Amaral

    2015-06-12

    The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na{sup +}/H{sup +} exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the −61 to −42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. - Highlights: • PTH regulation of Nhe3 promoter depends on EGR1 binding. • EGR1, PKA and JAK/STAT are involved in PTH inhibition of the Nhe3 promoter. • PTH alters expression of EGR1 and Sp3. • PTH inhibits the Nhe3 promoter by regulating PKA and JAK/STAT signaling.

  7. 云南美登木共生放线菌菌株1B1产生的一个新的angucycline抗生素%New angucycline antibiotic produced by Streptomyces sp.1B1,a commensal microbe of Maytenus hookeri Loes

    Institute of Scientific and Technical Information of China (English)

    鲁春华; 沈月毛

    2003-01-01

    A compound from the fermentation extracts of the commensal microbe(Streptomyces sp.1B1)of Maytenus hookeri was elucidated as a new angucycline antibiotic on the basis of 1D-NMR,2D-NMR and HREIMS techniques.%从云南美登木共生放线菌菌株1B1的发酵提取物中分离得到了一个新的angucycline抗生素,并通过其谱学特征鉴定了化合物1的化学结构.

  8. Environmental factors affecting the distribution of Chironomid larvae of the Seybouse wadi, North-Eastern Algeria

    Directory of Open Access Journals (Sweden)

    Nadjla Chaib

    2013-03-01

    Full Text Available A survey of the Seybouse wadi (North-Eastern Algeria between 2008 and 2011 was conducted in 26 sampling sites located on the main river and its tributaries using chironomids. From 3264 collected larvae, forty-five chironomid species were identified, and were correlated to 13 environmental variables to predict determinant factors affecting their distribution. Indicator value (IndVal analysis was first performed to determine indicator chironomid species according to several factors (sites, seasons, source distance, granulometry, conductivity, water temperature, dissolved oxygen, water velocity, pollution and the abundance of filamentous algae. Co-inertia analysis (CoIA supported the IndVal results, emphasising an upstream/downstream gradient in the first axis, while a granulometry gradient was emphasised by the second axis. A pollution gradient was also highlighted in the plane of the first two axes, separating tolerant Chironomus sp. 1, Cricotopus bicinctus and Cricotopus (Isocladius sylvestris from intolerant species as Phaenopsectra flavipes, Rheotanytarsus sp.1 and Cladotanytarsus sp. 1.

  9. NELL-1, an osteoinductive factor, is a direct transcriptional target of Osterix.

    Directory of Open Access Journals (Sweden)

    Feng Chen

    Full Text Available NELL-1 is a novel secreted protein associated with premature fusion of cranial sutures in craniosynostosis that has been found to promote osteoblast cell differentiation and mineralization. Our previous study showed that Runx2, the key transcription factor in osteoblast differentiation, transactivates the NELL-1 promoter. In this study, we evaluated the regulatory involvement and mechanisms of Osterix, an essential transcription factor of osteoblasts, in NELL-1 gene expression and function. Promoter analysis showed a cluster of potential Sp1 sites (Sp1/Osterix binding sites within approximately 70 bp (from -71 to -142 of the 5' flanking region of the human NELL-1 transcriptional start site. Luciferase activity in our NELL-1 promoter reporter systems was significantly decreased in Saos-2 cells when Osterix was overexpressed. Mutagenesis study demonstrated that this suppression is mediated by the Sp1 sites. The binding specificity of Osterix to these Sp1 sites was confirmed in Saos-2 cells and primary human osteoblasts by EMSA in vitro and ChIP assay in vivo. ChIP assay also showed that Osterix downregulated NELL-1 by affecting binding of RNA polymerase II to the NELL-1 promoter, but not by competing with Runx2 binding to the OSE2 sites. Moreover, NELL-1 mRNA levels were significantly decreased when Osterix was overexpressed in Saos-2, U2OS, Hela and Glioma cells. Correspondingly, knockdown of Osterix increased NELL-1 transcription and osteoblastic differentiation in both Saos-2 cells and primary human osteoblasts. These results suggest that Osterix is a direct transcriptional regulator with repressive effect on NELL-1 gene expression, contributing to a delicate balance of regulatory effects on NELL-1 transcription with Runx2, and may play a crucial role in osteoblast differentiation and mineralization. These findings also extend our understanding of the molecular mechanism of Runx2, Osterix, and NELL-1 and demonstrate their crosstalk during

  10. Site-specific chromatin immunoprecipitation: a selective method to individually analyze neighboring transcription factor binding sites in vivo.

    Science.gov (United States)

    Schuch, Ronaldo; Agelopoulos, Konstantin; Neumann, Anna; Brandt, Burkhard; Bürger, Horst; Korsching, Eberhard

    2012-02-20

    Transcription factors (TFs) and their binding sites (TFBSs) play a central role in the regulation of gene expression. It is therefore vital to know how the allocation pattern of TFBSs affects the functioning of any particular gene in vivo. A widely used method to analyze TFBSs in vivo is the chromatin immunoprecipitation (ChIP). However, this method in its present state does not enable the individual investigation of densely arranged TFBSs due to the underlying unspecific DNA fragmentation technique. This study describes a site-specific ChIP which aggregates the benefits of both EMSA and in vivo footprinting in only one assay, thereby allowing the individual detection and analysis of single binding motifs. The standard ChIP protocol was modified by replacing the conventional DNA fragmentation, i. e. via sonication or undirected enzymatic digestion (by MNase), through a sequence specific enzymatic digestion step. This alteration enables the specific immunoprecipitation and individual examination of occupied sites, even in a complex system of adjacent binding motifs in vivo. Immunoprecipitated chromatin was analyzed by PCR using two primer sets - one for the specific detection of precipitated TFBSs and one for the validation of completeness of the enzyme digestion step. The method was established exemplary for Sp1 TFBSs within the egfr promoter region. Using this site-specific ChIP, we were able to confirm four previously described Sp1 binding sites within egfr promoter region to be occupied by Sp1 in vivo. Despite the dense arrangement of the Sp1 TFBSs the improved ChIP method was able to individually examine the allocation of all adjacent Sp1 TFBS at once. The broad applicability of this site-specific ChIP could be demonstrated by analyzing these SP1 motifs in both osteosarcoma cells and kidney carcinoma tissue. The ChIP technology is a powerful tool for investigating transcription factors in vivo, especially in cancer biology. The established site-specific enzyme

  11. Site-specific chromatin immunoprecipitation: a selective method to individually analyze neighboring transcription factor binding sites in vivo

    Directory of Open Access Journals (Sweden)

    Schuch Ronaldo

    2012-02-01

    Full Text Available Abstract Background Transcription factors (TFs and their binding sites (TFBSs play a central role in the regulation of gene expression. It is therefore vital to know how the allocation pattern of TFBSs affects the functioning of any particular gene in vivo. A widely used method to analyze TFBSs in vivo is the chromatin immunoprecipitation (ChIP. However, this method in its present state does not enable the individual investigation of densely arranged TFBSs due to the underlying unspecific DNA fragmentation technique. This study describes a site-specific ChIP which aggregates the benefits of both EMSA and in vivo footprinting in only one assay, thereby allowing the individual detection and analysis of single binding motifs. Findings The standard ChIP protocol was modified by replacing the conventional DNA fragmentation, i. e. via sonication or undirected enzymatic digestion (by MNase, through a sequence specific enzymatic digestion step. This alteration enables the specific immunoprecipitation and individual examination of occupied sites, even in a complex system of adjacent binding motifs in vivo. Immunoprecipitated chromatin was analyzed by PCR using two primer sets - one for the specific detection of precipitated TFBSs and one for the validation of completeness of the enzyme digestion step. The method was established exemplary for Sp1 TFBSs within the egfr promoter region. Using this site-specific ChIP, we were able to confirm four previously described Sp1 binding sites within egfr promoter region to be occupied by Sp1 in vivo. Despite the dense arrangement of the Sp1 TFBSs the improved ChIP method was able to individually examine the allocation of all adjacent Sp1 TFBS at once. The broad applicability of this site-specific ChIP could be demonstrated by analyzing these SP1 motifs in both osteosarcoma cells and kidney carcinoma tissue. Conclusions The ChIP technology is a powerful tool for investigating transcription factors in vivo, especially

  12. Adiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription factor specificity protein 1.

    Science.gov (United States)

    Liu, Jing; Lam, Janice B B; Chow, Kim H M; Xu, Aimin; Lam, Karen S L; Moon, Randall T; Wang, Yu

    2008-11-01

    Adiponectin (ADN) is an adipokine possessing growth inhibitory activities against various types of cancer cells. Our previous results demonstrated that ADN could impede Wnt/beta-catenin-signaling pathways in MDA-MB-231 human breast carcinoma cells [Wang,Y. et al. (2006) Adiponectin modulates the glycogen synthase kinase-3 beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res., 66, 11462-11470]. Here, we extended our studies to elucidate the effects of ADN on regulating the expressions of Wnt inhibitory factor-1 (WIF1), a Wnt antagonist frequently silenced in human breast tumors. Our results showed that ADN time dependently stimulated WIF1 gene and protein expressions in MDA-MB-231 cells. Overexpression of WIF1 exerted similar inhibitory effects to those of ADN on cell proliferations, nuclear beta-catenin activities, cyclin D1 expressions and serum-induced phosphorylations of Akt and glycogen synthase kinase-3 beta. Blockage of WIF1 activities significantly attenuated the suppressive effects of ADN on MDA-MB-231 cell growth. Furthermore, our in vivo studies showed that both supplementation of recombinant ADN and adenovirus-mediated overexpression of this adipokine substantially enhanced WIF1 expressions in MDA-MB-231 tumors implanted in nude mice. More interestingly, we found that ADN could alleviate methylation of CpG islands located within the proximal promoter region of WIF1, possibly involving the specificity protein 1 (Sp1) transcription factor and its downstream target DNA methyltransferase 1 (DNMT1). Upon ADN treatment, the protein levels of both Sp1 and DNMT1 were significantly decreased. Using silencing RNA approaches, we confirmed that downregulation of Sp1 resulted in an increased expression of WIF1 and decreased methylation of WIF1 promoter. Taken together, these data suggest that ADN might elicit its antitumor activities at least partially through promoting WIF1 expressions.

  13. A new family of sp3-hybridized carbon phases

    Science.gov (United States)

    Ning, Xu; Jian-Fu, Li; Bo-Long, Huang; Bao-Lin, Wang

    2016-01-01

    A new family of superhard carbon allotropes C48(2i + 1) is constructed by alternating even 4 and 8 membered rings. These new carbon allotropes are of a spatially antisymmetrical structure, compared with the symmetrical structures of bct-C4, Z-carbon, and P-carbon. Our calculations show that bulk moduli of C48(2i + 1) are larger than that of c-BN and smaller than that of cubic-diamond. C48(2i + 1) are transparent superhard materials possessing large Vicker hardness comparable to diamond. This work can help us understand the structural phase transformations of cold-compression graphite and carbon nanotubes. Project supported by the National Natural Science Foundation of China (Grant Nos. 11174242, 11204265, 11404278, 11147007, and 11274151), the Natural Science Foundation of Jiangsu Province, China (Grant No. BK2012248), and the Scientific Research Foundation of Yancheng Institute of Technology, China (Grant No. KJC2014024).

  14. Network based transcription factor analysis of regenerating axolotl limbs

    Directory of Open Access Journals (Sweden)

    Cameron Jo Ann

    2011-03-01

    Full Text Available Abstract Background Studies on amphibian limb regeneration began in the early 1700's but we still do not completely understand the cellular and molecular events of this unique process. Understanding a complex biological process such as limb regeneration is more complicated than the knowledge of the individual genes or proteins involved. Here we followed a systems biology approach in an effort to construct the networks and pathways of protein interactions involved in formation of the accumulation blastema in regenerating axolotl limbs. Results We used the human orthologs of proteins previously identified by our research team as bait to identify the transcription factor (TF pathways and networks that regulate blastema formation in amputated axolotl limbs. The five most connected factors, c-Myc, SP1, HNF4A, ESR1 and p53 regulate ~50% of the proteins in our data. Among these, c-Myc and SP1 regulate 36.2% of the proteins. c-Myc was the most highly connected TF (71 targets. Network analysis showed that TGF-β1 and fibronectin (FN lead to the activation of these TFs. We found that other TFs known to be involved in epigenetic reprogramming, such as Klf4, Oct4, and Lin28 are also connected to c-Myc and SP1. Conclusions Our study provides a systems biology approach to how different molecular entities inter-connect with each other during the formation of an accumulation blastema in regenerating axolotl limbs. This approach provides an in silico methodology to identify proteins that are not detected by experimental methods such as proteomics but are potentially important to blastema formation. We found that the TFs, c-Myc and SP1 and their target genes could potentially play a central role in limb regeneration. Systems biology has the potential to map out numerous other pathways that are crucial to blastema formation in regeneration-competent limbs, to compare these to the pathways that characterize regeneration-deficient limbs and finally, to identify stem

  15. Pseudopregnancy induces the expression of hepatocyte nuclear factor-1 beta and its target gene aminopeptidase N in rabbit endometrium via the epithelial promoter

    DEFF Research Database (Denmark)

    Classen-Linke, I; Sjöström, H; Norén, O

    1995-01-01

    The rabbit endometrium is an excellent model system allowing experimental manipulation of aminopeptidase N (APN) mRNA expression in vivo. By RNase mapping and sequencing of cloned PCR-amplified primer-extended RNA, it was demonstrated that endometrial APN expression is directed by the epithelial...... APN promoter and is increased in human-choriogonadotropin-induced pseudopregnancy. Cloning and sequencing of the rabbit APN epithelial promoter revealed conservation of the upstream footprint (UF), hepatocyte nuclear factor-1 (HNF1) and Sp1 elements known to be present in the pig and human promoters...... as well. The pseudopregnancy-induced APN expression was found to be accompanied by a parallel increase in the level of the transcription factor HNF1 beta, whereas a much smaller increase in Sp1 and UF-binding proteins was observed. This indicates that HNF1 beta acts as a switch triggering the pregnancy...

  16. 水母伞径和饵料密度对海月水母(Aureliasp.1)捕食率的影响%EFFECTS OF BELL DIAMETERS AND PREY CONCENTRATIONS ON INDIVIDUAL FEEDING RATES OF JELLYFISH AURELIA sp.1

    Institute of Scientific and Technical Information of China (English)

    王楠; 李超伦

    2012-01-01

    海月水母在全球范围内大量暴发,严重危害海洋生态系统的健康以及鱼类资源的可持续利用。本文以卤虫无节幼体为饵料,初步研究了水母伞径和饵料密度对海月水母个体捕食率的影响以及海月水母的昼夜捕食节律。研究结果表明,海月水母的伞径对其捕食率的影响极显著(P〈0.01),在1—8cm范围内,随着伞径的增加个体捕食率线性增加,两者之间的关系式为Y=O.044x+0.125(R2=0.9036)。饵料密度对海月水母捕食率的影响显著(P〈0.05),在0.25—26.11mgC/L范围内,随饵料密度的增加个体捕食率呈线性增加趋势,关系式为Y=0.508x(R2=0.958)。在饵料充足时,海月水母没有昼夜捕食节律。在高饵料密度下海月水母出现过剩捕食,但是捕食行为依然活跃。上述结果既为量化评估海月水母对浮游动物群体的捕食压力提供了基础参数,同时水母过剩捕食行为说明依据生物量和代谢率的推算结果可能低估自然海域水母队浮游动物的捕食压力。%The blooms ofAurelia aurita population greatly damage the health of marine ecosystem and the sustainabil- ity of fish resources utilization. To determine the effects of bell diameters and prey concentrations on the individual feeding rates of Aurelia sp.1, feeding rates of Aurelia sp. 1 on Artemia nauplius were studied in laboratory. Bell diameters signifi- cantly affected the individual feeding rates ofAurelia sp.1 (P〈0.01). When medusa bell diameters were in the range of 1 to 8cm, the relationship between bell diameters and individual feeding rates was y = 0.044x + 0.125 (R2 = 0.9036). A signifi- cantly linear relationship was also found between the prey concentrations and individual feeding rates of the medusae (P〈0.05). In the range of prey concentration, 0.25--26.1 l mgC/L, individual ingestion rates of Aurelia sp. 1 increased with the

  17. OVEREXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND THE DEVELOPMENT OF POST-TRANSPLANTATION CANCER

    Science.gov (United States)

    Basu, Aninda; Contreras, Alan G.; Datta, Dipak; Flynn, Evelyn; Zeng, Liling; Cohen, Herbert T.; Briscoe, David M.; Pal, Soumitro

    2009-01-01

    Cancer is an increasing and major problem following solid organ transplantation. In part, the increased cancer risk is associated with the use of immunosuppressive agents, especially calcineurin inhibitors. We propose that the effect of calcineurin inhibitors on the expression of vascular endothelial growth factor (VEGF) leads to an angiogenic milieu that favors tumor growth. Here, we used 786-0 human renal cancer cells to investigate the effect of Cyclosporine (CsA) on VEGF expression. Utilizing a full-length VEGF promoter-luciferase construct, we found that CsA markedly induced VEGF transcriptional activation through the PKC signaling pathway, specifically involving PKCζ and PKCδ isoforms. Moreover, CsA promoted the association of PKCζ and PKCδ with the transcription factor Sp1 as observed by immunoprecipitation assays. Using promoter deletion constructs, we found that CsA-mediated VEGF transcription was primarily Sp1-dependent. Furthermore, CsA-induced and PKC-Sp1-mediated VEGF transcriptional activation was partially inhibited by pVHL. CsA also promoted the progression of human renal tumors in vivo, where VEGF is overexpressed. Finally, to evaluate the in vivo significance of CsA-induced VEGF overexpression in terms of post-transplantation tumor development, we injected CT26 murine carcinoma cells (known to form angiogenic tumors) into mice with fully MHC mismatched cardiac transplants. We observed that therapeutic doses of CsA increased tumor size, VEGF mRNA expression, and also enhanced tumor angiogenesis. However, co-administration of a blocking anti-VEGF antibody inhibited this CsA-mediated tumor growth. Collectively, these findings define PKC-mediated VEGF transcriptional activation as a key component in the progression of CsA-induced post-transplantation cancer. PMID:18632621

  18. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    XU; Jinping(徐进平); YE; Linbai(叶林柏)

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  19. Inhibition of transforming growth factor-beta-induced liver fibrosis by a retinoic acid derivative via the suppression of Col 1A2 promoter activity.

    Science.gov (United States)

    Yang, Kun-Lin; Chang, Wen-Teng; Hung, Kuo-Chen; Li, Eric I C; Chuang, Chia-Chang

    2008-08-22

    Transforming growth factor-beta1 (TGF-beta1) mediates expression of collagen 1A2 (Col 1A2) gene via a synergistic cooperation between Smad2/Smad3 and Sp1, both act on the Col 1A2 gene promoter. In our previous study, we reported that a retinoic acid derivative obtained from Phellinus linteus (designated PL) antagonizes TGF-beta-induced liver fibrosis through regulation of ROS and calcium influx. In this continuing study we seek further the effect of PL on the Smad signaling pathway. We used a Col 1A2 promoter-luciferase construct to study the action of PL on Smad through TGF-beta. We found that PL decreases the promoter activity of Col 1A2, hinders the translocalization of phosphorylated Smad2/3-Smad 4 complex from cytosol into nucleus and inhibits Sp1 binding activity. These results suggest that PL inhibits TGF-beta1-induced Col 1A2 promoter activity through blocking ROS and calcium influx as well as impeding Sp1 binding and translocalization of pSmad 2/3-Smad4 complex into nucleus.

  20. O fator de condição de peixes de duas bacias no Estado de São Paulo, Sudeste do Brasil - DOI: 10.4025/actascibiolsci.v27i1.1368 The condition factor of fishes from two river basins in São Paulo state, Southeast of Brazil - DOI: 10.4025/actascibiolsci.v27i1.1368

    Directory of Open Access Journals (Sweden)

    Leandro Muller Gomiero

    2005-03-01

    Full Text Available Neste trabalho foi obtido o fator de condição relativo de Hypostomus strigaticeps, Astyanax altiparanae, Astyanax scabripinnis, Astyanax fasciatus, Astyanax sp1., Characidium aff. zebra, Piabina argentea, Hypostomus ancistroides, Hypostomus sp1., Parodon tortuosus, Serrapinus heterodon e Bryconamericus sp. da APA de São Pedro e Analândia (22°-23°S e 47°30’-48°30’W. O fator de condição fornece indicações do estado de bem estar do peixe no ambiente. Para a comparação de espécies distintas foi utilizado o fator de condição relativo, relacionando as variações deste fator ao longo do ano e conseqüentes alterações fisiológicas dos peixes. O fator de condição relativo mostrou-se eficaz como ferramenta para evidenciar as mudanças nas condições dos peixes durante as estações do anoThis work describes the relative condition factor of the Hypostomus strigaticeps, Astyanax altiparanae, Astyanax scabripinnis, Astyanax fasciatus, Astyanax sp1., Characidium aff. zebra, Piabina argentea, Hypostomus ancistroides, Hypostomus sp1., Parodon tortuosus, Serrapinus heterodon, and Bryconamericus sp., of the APA of São Pedro and Analândia (22° - 23°S and 47°30’ - 48°30’W. The condition factor provides information about the physical state of the animal in the environment. In order to compare different species, the relative condition factor was used. Variations in this factor were correlated with variations through the year and with subsequent alterations in the physiological state of the fishes. The relative condition factor was shown to be efficient in indicating changes in fish condition throughout the year

  1. EFFECTS OF TEMPERATURE AND FOOD ON ASEXUAL REPRODUCTION OF THE SCYPHOZOAN, A URELIA sp.1%温度、投饵频次对海月水母(Aurelia sp.1)水螅体生长和繁殖的影响

    Institute of Scientific and Technical Information of China (English)

    王彦涛; 孙松; 李超伦; 张芳

    2012-01-01

    Temperature and food play a vital role in determining asexual direction of jelly fish in its polyp stage. The combinations of four temperature grades (10, 15, 20 and 25℃) and three food levels (no food, feed once a week and feed everyday) were set up to exam Aurelia sp.1 life cycle strategy. Temperature could determine the strobilation and ephyrae release. Food determined the number of polyps. Temperature changing from 20℃ to 15℃and 10℃ induced ephyrae release. In suitable temperature range for strobilation, relatively higher temperature and sufficient food enabled polyps to produce more ephyrae. At temperatures beyond range for strobilation, sufficient food condition enabled polyp produce polyps. Higher temperature and lower food level induced higher polyp mortality.%水母暴发是一个全球广泛关注的生态问题,水螅体阶段的环境影响是研究水母暴发的重要切入点。本实验从温度(10,15,20,25℃)和投饵频次(无投喂,每周投喂,每天投喂)两个角度进行研究。结果表明,温度对横裂过程、碟状体产生过程影响显著,饵料对水螅体数量影响显著。水螅体从20℃降温至10℃和15℃可发生横裂产生碟状体,适宜横裂的温度范围内,相对高温和充足饵料有利于释放更多碟状体;适宜横裂的温度范围外,相对高温和充足饵料有利于水螅体数量的增加。适宜横裂的温度范围持续时间达到水螅体的响应时间阈值,才能够完成从底栖阶段的水螅体到浮游阶段水母体的转化。

  2. ARBUSCULAR MYCORRHIZAL FUNGI FROM THE RfflZOSPHERES OF SOYBEAN CROPS IN LAMPUNG AND WEST JAVA

    Directory of Open Access Journals (Sweden)

    K. KRAMADIBRATA

    1995-01-01

    Full Text Available The occurrence of arbuscular mycorrhizal (AM fungi in the rhizospheres of field-grown soybean crops in the provinces of Lampung and West Java was examined. Nineteen taxa of AM fungi were identified as follows: Acaulospora delicata, A. Foveata, A. rehmii, A. scrobiculata and A. tuberculata; Gigaspora cf. gigantea and Gigaspora sp. 1; Glomus clavisporum; Glomus cf. fasciculatum, Glomus micro-aggregatum, Glomus sp. 1, Glomus sp. 2, Glomus sp. 3 and Glomus sp. 4; Scutellospora cf. heterogama, Scutellospora cf. pellucida, Scutellospora sp. 1. Scutellospora sp.2. and Scutellospora sp. 3.

  3. Dinoflagellate cysts in recent marine sediment from Guangxi,China

    Institute of Scientific and Technical Information of China (English)

    Haifeng Gu; Qi Fang; Jun Sun; Dongzhao Lan; Feng Cai; Zhiyong Gao

    2003-01-01

    Total of 33 species of dinoflagellate cysts were discovered from surface sediment in the searegion of Guangxi, among them 12 cyst types (Diplopsalopsis sp. 1, D. sp.2, D. sp.3, Cochlodiniumsp., Protoperidinium sp. 1, P. sp. 2, P.compressum, Scrippsiella sp. 1, S. sp. 2, Alexandriumsp. 1, A. sp. 2, A. sp. 3) were first reported from the South China Sea. And one cyst type(Cochlodinium sp. ) was first reported in the world. Scrippsiella trochoidea is the dominant species inthis area, accounting for 45 % of all the cysts. There are 2 cysts of toxic dinoflagellate (Alexandriumtamarensis and Gymnodinium catenatum ). But there is no relationship between cyst number and grainsize distribution.

  4. miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network.

    Science.gov (United States)

    Santos, Márcia C T; Tegge, Allison N; Correa, Bruna R; Mahesula, Swetha; Kohnke, Luana Q; Qiao, Mei; Ferreira, Marco A R; Kokovay, Erzsebet; Penalva, Luiz O F

    2016-01-01

    The ventricular-subventricular zone harbors neural stem cells (NSCs) that can differentiate into neurons, astrocytes, and oligodendrocytes. This process requires loss of stem cell properties and gain of characteristics associated with differentiated cells. miRNAs function as important drivers of this transition; miR-124, -128, and -137 are among the most relevant ones and have been shown to share commonalities and act as proneurogenic regulators. We conducted biological and genomic analyses to dissect their target repertoire during neurogenesis and tested the hypothesis that they act cooperatively to promote differentiation. To map their target genes, we transfected NSCs with antagomiRs and analyzed differences in their mRNA profile throughout differentiation with respect to controls. This strategy led to the identification of 910 targets for miR-124, 216 for miR-128, and 652 for miR-137. The target sets show extensive overlap. Inspection by gene ontology and network analysis indicated that transcription factors are a major component of these miRNAs target sets. Moreover, several of these transcription factors form a highly interconnected network. Sp1 was determined to be the main node of this network and was further investigated. Our data suggest that miR-124, -128, and -137 act synergistically to regulate Sp1 expression. Sp1 levels are dramatically reduced as cells differentiate and silencing of its expression reduced neuronal production and affected NSC viability and proliferation. In summary, our results show that miRNAs can act cooperatively and synergistically to regulate complex biological processes like neurogenesis and that transcription factors are heavily targeted to branch out their regulatory effect. © 2015 AlphaMed Press.

  5. Corruption Factors

    OpenAIRE

    Polterovich, Victor

    1998-01-01

    Among the factors that give rise to corruption, it is suggested that three groups be distinguished: fundamental factors rooted in the imperfection of economic institutions and economic policy, organizational factors ("weakness of the government"), and societal factors that depend on the prehistory and are connected with the mass culture and norms of bureaucratic behavior. A model in which corruption equilibrium is supported by non-optimum tax policy or by slow technical progress is compared w...

  6. 海月水母(Aurelia sp.1)对中肋骨条藻(Skeletonema costatum)和东海原甲藻(Prorocentrum donghaiense)摄食的研究%THE GRAZING OF AURELIA sp.1 ON SKELETONEMA COSTATUM AND PROROCENTR UM DONGHAIENSE

    Institute of Scientific and Technical Information of China (English)

    郑珊; 孙晓霞; 孙松

    2012-01-01

    The effects of different microalgal species and cell densities on the feedings of polyps, ephyrae and medusae of.4urelia sp. 1 under controlled laboratory conditions were investigated. Two species of microalgae, Skeletonema costatum and Prorocentrum donghaiense, were used. Different microalgal species and cell densities had significant effects on the feedings of polyps, ephyrae and medusae. With the increasing of microalgal cell desities, the ingestion rates (IR) of polyps and ephyrae increased while the clearance rates (CR) decreased. The maximum IR of polyps on S. costatum and P. dong- haiense were 4623 and 4118 cells/(ind-h), respectively, while the maximum IR of ephyrae on S. costatum and P. dong- haiense were 174671 and 47218 cells/(ind-h), respectively. At similar microalgal cell densities, the IR of ephyrae on S. costatum were higher than those on P. donghaiense, and the IR of ephyrae were higher than those of polyps. The adaption of microalgae made IR of polyps increased about ten times. Medusae did not feed on S. costatum and P. donghaiense.%采用饵料浓度差减法,在实验条件下研究了不同细胞密度的中肋骨条藻和东海原甲藻对海月水母水螅体、碟状体和水母体摄食活动的影响。结果表明,不同种类和密度的微藻细胞密度对水螅体、碟状体和水母体的摄食有显著影响。在实验的藻细胞密度范围内,随藻细胞密度的增加,水螅体和碟状体对中肋骨条藻和东海原甲藻的摄食率一直升高。水螅体对中肋骨条藻和东海原甲藻的最大摄食率均发生在藻细胞密度最高处,分别为4623cells/(ind·h1和4118cells/(ind·h1。碟状体对中肋骨条藻和东海原甲藻的最大摄食率也是发生在藻细胞密度最高处,分别为174671cells/(ind_h)和47218cells/(ind.h)。清滤率随着藻细胞密度增加而降低。在相似细胞密度下,碟状体对中肋骨条藻的摄食率高于东海

  7. Structural features and inactivation of coagulation proteases of a sulfated polysaccharidic fraction from Caulerpa cupressoides var. lycopodium (Caulerpaceae, Chlorophyta - doi: 10.4025/actascitechnol.v35i4.16709

    Directory of Open Access Journals (Sweden)

    José Ariévilo Gurgel Rodrigues

    2013-10-01

    Full Text Available Studies on biopolymers from macroalgae suggested sulfated polysaccharides (SPs as research agents to investigate events related to haemostasis. Caulerpa cupressoides var. lycopodium is a marine green alga containing three SPs fractions (SP1, SP2 and SP3. SP2 had anticoagulant (in vitro and anti- and prothrombotic (in vivo actions; however, its effect on the coagulation system is not fully understood. This study aimed to determine the infrared (IR spectroscopy, chemical composition (CC, elemental microanalysis (EM, molecular weight (MW and the effect on coagulation proteases of SP2. The presence of sulfate ester, galactose-6-sulfate, uronic acid and glycoside linkages for IR spectrum; contents of sulfate (28%, total sugars (40% and uronic acids (7.18% for CC; and content of carbon (21.98%, sulfate (4.27%, nitrogen (1.3% and hydrogen (4.86% for EM were obtained. The average molecular weights of four different SPs (SP-1, SP-2, SP-3 and SP-4 subfractions from the SP2 ranged from ~ 8 to >100 kDa. SP2 was tested on coagulation proteases (thrombin and factor Xa in the presence of antithrombin (AT and heparin cofactor II (HCII using human plasma, being both thrombin and factor Xa target proteases inhibited, but requiring a concentration of about 2.5-fold higher of HCII than the thrombin inactivation by AT.   

  8. Variable structure motifs for transcription factor binding sites.

    Science.gov (United States)

    Reid, John E; Evans, Kenneth J; Dyer, Nigel; Wernisch, Lorenz; Ott, Sascha

    2010-01-14

    Classically, models of DNA-transcription factor binding sites (TFBSs) have been based on relatively few known instances and have treated them as sites of fixed length using position weight matrices (PWMs). Various extensions to this model have been proposed, most of which take account of dependencies between the bases in the binding sites. However, some transcription factors are known to exhibit some flexibility and bind to DNA in more than one possible physical configuration. In some cases this variation is known to affect the function of binding sites. With the increasing volume of ChIP-seq data available it is now possible to investigate models that incorporate this flexibility. Previous work on variable length models has been constrained by: a focus on specific zinc finger proteins in yeast using restrictive models; a reliance on hand-crafted models for just one transcription factor at a time; and a lack of evaluation on realistically sized data sets. We re-analysed binding sites from the TRANSFAC database and found motivating examples where our new variable length model provides a better fit. We analysed several ChIP-seq data sets with a novel motif search algorithm and compared the results to one of the best standard PWM finders and a recently developed alternative method for finding motifs of variable structure. All the methods performed comparably in held-out cross validation tests. Known motifs of variable structure were recovered for p53, Stat5a and Stat5b. In addition our method recovered a novel generalised version of an existing PWM for Sp1 that allows for variable length binding. This motif improved classification performance. We have presented a new gapped PWM model for variable length DNA binding sites that is not too restrictive nor over-parameterised. Our comparison with existing tools shows that on average it does not have better predictive accuracy than existing methods. However, it does provide more interpretable models of motifs of variable

  9. Variable structure motifs for transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Wernisch Lorenz

    2010-01-01

    Full Text Available Abstract Background Classically, models of DNA-transcription factor binding sites (TFBSs have been based on relatively few known instances and have treated them as sites of fixed length using position weight matrices (PWMs. Various extensions to this model have been proposed, most of which take account of dependencies between the bases in the binding sites. However, some transcription factors are known to exhibit some flexibility and bind to DNA in more than one possible physical configuration. In some cases this variation is known to affect the function of binding sites. With the increasing volume of ChIP-seq data available it is now possible to investigate models that incorporate this flexibility. Previous work on variable length models has been constrained by: a focus on specific zinc finger proteins in yeast using restrictive models; a reliance on hand-crafted models for just one transcription factor at a time; and a lack of evaluation on realistically sized data sets. Results We re-analysed binding sites from the TRANSFAC database and found motivating examples where our new variable length model provides a better fit. We analysed several ChIP-seq data sets with a novel motif search algorithm and compared the results to one of the best standard PWM finders and a recently developed alternative method for finding motifs of variable structure. All the methods performed comparably in held-out cross validation tests. Known motifs of variable structure were recovered for p53, Stat5a and Stat5b. In addition our method recovered a novel generalised version of an existing PWM for Sp1 that allows for variable length binding. This motif improved classification performance. Conclusions We have presented a new gapped PWM model for variable length DNA binding sites that is not too restrictive nor over-parameterised. Our comparison with existing tools shows that on average it does not have better predictive accuracy than existing methods. However, it does

  10. Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays

    Directory of Open Access Journals (Sweden)

    Regina Augustin

    2011-01-01

    Full Text Available The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases.

  11. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    1988-04-01

    Full Text Available RESUMEN El artículo  presenta, una conceptualización general de lo que es el factoring, el origen del mismo, su evolución y hace una clasificación de los distintos tipos de factoring.

  12. Robust factorization

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle;

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal...... effectively with errors in the tracked features. We propose a new and computationally efficient algorithm for applying an arbitrary error function in the factorization scheme. This algorithm enables the use of robust statistical techniques and arbitrary noise models for the individual features....... These techniques and models enable the factorization scheme to deal effectively with mismatched features, missing features, and noise on the individual features. The proposed approach further includes a new method for Euclidean reconstruction that significantly improves convergence of the factorization algorithms...

  13. MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Guangde Zhang

    Full Text Available Myocardial infarction (MI is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs and known human transcription factors (TFs, and we then identified 1,232 feed-forward loops (FFLs among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

  14. Polyfluoroalkylation of 2-Aminothiazoles: Unexpected sp3 C CI Substitution under Mild Conditions%Polyfluoroalkylation of 2-Aminothiazoles: Unexpected sp3 C CI Substitution under Mild Conditions

    Institute of Scientific and Technical Information of China (English)

    齐卿卿; 沈其龙; 吕龙

    2011-01-01

    An efficient, highly selective method for polyfluoroalkylation of 2-aminothiazole derivatives was described. Specifically, a di-polyfluoroalkylated derivative was produced when 2-amino-4-chloromethylthiazole was reacted with perfluoroalkyl iodides under very mild conditions.

  15. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    2015-04-01

    Full Text Available RESUMEN Se presenta la segunda parte del artículo aparecido en  el número 6 de la revista EAN. Su contenido es complementario a lo expuesto en dicho número, en está aparecen las ventajas del factoring, conveniencias, limitaciones así como la forma  de efectuar un factor en Colombia,  su necesidad, incidencia económica, etc.

  16. Apoptosis signal-regulating kinase 1 is involved in brain-derived neurotrophic factor (BDNF)-enhanced cell motility and matrix metalloproteinase 1 expression in human chondrosarcoma cells.

    Science.gov (United States)

    Lin, Chih-Yang; Chang, Sunny Li-Yun; Fong, Yi-Chin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2013-07-25

    Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis.

  17. Tumor Necrosis Factor-Alpha and the ERK Pathway Drive Chemerin Expression in Response to Hypoxia in Cultured Human Coronary Artery Endothelial Cells

    Science.gov (United States)

    Chua, Su-Kiat; Shyu, Kou-Gi; Lin, Yuh-Feng; Lo, Huey-Ming; Wang, Bao-Wei

    2016-01-01

    Background Chemerin, a novel adipokine, plays a role in the inflammation status of vascular endothelial cells. Hypoxia causes endothelial-cell proliferation, migration, and angiogenesis. This study was aimed at evaluating the protein and mRNA expression of chemerin after exposure of human coronary artery endothelial cells (HCAECs) to hypoxia. Methods and Results Cultured HCAECs underwent hypoxia for different time points. Chemerin protein levels increased after 4 h of hypoxia at 2.5% O2, with a peak of expression of tumor necrosis factor-alpha (TNF-alpha) at 1 h. Both hypoxia and exogenously added TNF-alpha during normoxia stimulated chemerin expression, whereas an ERK inhibitor (PD98059), ERK small interfering RNA (siRNA), or an anti-TNF-alpha antibody attenuated the chemerin upregulation induced by hypoxia. A gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between the chemerin promoter and transcription factor SP1. A luciferase assay confirmed an increase in transcriptional activity of SP1 on the chemerin promoter during hypoxia. Hypoxia significantly increased the tube formation and migration of HCAECs, whereas PD98059, the anti-TNF-alpha antibody, and chemerin siRNA each attenuated these effects. Conclusion Hypoxia activates chemerin expression in cultured HCAECs. Hypoxia-induced chemerin expression is mediated by TNF-alpha and at least in part by the ERK pathway. Chemerin increases early processes of angiogenesis by HCAECs after hypoxic treatment. PMID:27792771

  18. Structural Fingerprints of Transcription Factor Binding Site Regions

    Directory of Open Access Journals (Sweden)

    Peter Willett

    2009-03-01

    Full Text Available Fourier transforms are a powerful tool in the prediction of DNA sequence properties, such as the presence/absence of codons. We have previously compiled a database of the structural properties of all 32,896 unique DNA octamers. In this work we apply Fourier techniques to the analysis of the structural properties of human chromosomes 21 and 22 and also to three sets of transcription factor binding sites within these chromosomes. We find that, for a given structural property, the structural property power spectra of chromosomes 21 and 22 are strikingly similar. We find common peaks in their power spectra for both Sp1 and p53 transcription factor binding sites. We use the power spectra as a structural fingerprint and perform similarity searching in order to find transcription factor binding site regions. This approach provides a new strategy for searching the genome data for information. Although it is difficult to understand the relationship between specific functional properties and the set of structural parameters in our database, our structural fingerprints nevertheless provide a useful tool for searching for function information in sequence data. The power spectrum fingerprints provide a simple, fast method for comparing a set of functional sequences, in this case transcription factor binding site regions, with the sequences of whole chromosomes. On its own, the power spectrum fingerprint does not find all transcription factor binding sites in a chromosome, but the results presented here show that in combination with other approaches, this technique will improve the chances of identifying functional sequences hidden in genomic data.

  19. Behavioral factors.

    Science.gov (United States)

    Zero, D T; Lussi, A

    2006-01-01

    During and after an erosive challenge, behavioral factors play a role in modifying the extent of erosive tooth wear. The manner that dietary acids are introduced into the mouth (gulping, sipping, use of a straw) will affect how long the teeth are in contact with the erosive challenge. The frequency and duration of exposure to an erosive agent is of paramount importance. Night-time exposure (e.g. baby bottle-feeding) to erosive agents may be particularly destructive because of the absence of salivary flow. Health-conscious individuals tend to ingest acidic drinks and juices more frequently and tend to have higher than average oral hygiene. While good oral hygiene is of proven value in the prevention of periodontal disease and dental caries, frequent toothbrushing with abrasive oral hygiene products may enhance erosive tooth wear. Unhealthy lifestyles such as consumption of designer drugs, alcopops and alcohol abuse are other important behavioral factors.

  20. Vascular endothelial growth factor induces multidrug resistance-associated protein 1 overexpression through phosphatidylinositol-3-kinase/protein kinase B signaling pathway and transcription factor specificity protein 1 in BGC823 cell line

    Institute of Scientific and Technical Information of China (English)

    Juan Li; Xiaojun Wu; Jinling Gong; Jing Yang; Jiayan Leng; Qiaoyun Chen; Wenlin Xu

    2013-01-01

    Multidrug resistance (MDR) is one of the most important causes of chemotherapy failure and carcinoma recurrence.But the roles of the MDR-associated protein MRP1 in MDR remain poorly understood.Vascular endothelial growth factor (VEGF),one of the most active and specific vascular growth factors,plays a significant role in proliferation,differentiation,and metastasis of cancers.To explore the effect of VEGF on the expression of MRP1,we used recombinant human VEGF to stimulate K562 and BGC-823 cell lines.Quantitative real-time polymerase chain reaction and western blot analysis showed that the expression of MRP1 at both mRNA and protein levels was increased.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide results also showed that VEGF significantly enhanced the ICs0 of the cells treated with adriamycin.To explore the underlying regulatory mechanisms,we constructed MRP1 promoter and the luciferase reporter gene recombinant vector.The luciferase reporter gene assay showed that the activity of the MRP1 promoter was markedly increased by VEGF stimulation,while LY294002,an inhibitor of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway,reduced this effect.Transcription factor specificity protein 1 (SP1) binding site mutation partially blocked the up-regulation of MRP1 promoter activity by VEGF.In summary,our results demonstrated that VEGF enhanced the expression of MRP1,and the PI3K/Akt signaling pathway and SP1 may be involved in this modulation.

  1. Factor analysis

    CERN Document Server

    Gorsuch, Richard L

    2013-01-01

    Comprehensive and comprehensible, this classic covers the basic and advanced topics essential for using factor analysis as a scientific tool in psychology, education, sociology, and related areas. Emphasizing the usefulness of the techniques, it presents sufficient mathematical background for understanding and sufficient discussion of applications for effective use. This includes not only theory but also the empirical evaluations of the importance of mathematical distinctions for applied scientific analysis.

  2. A conserved function of the zinc finger transcription factor Sp8/9 in allometric appendage growth in the milkweed bug Oncopeltus fasciatus.

    Science.gov (United States)

    Schaeper, Nina D; Prpic, Nikola-Michael; Wimmer, Ernst A

    2009-08-01

    The genes encoding the closely related zinc finger transcription factors Buttonhead (Btd) and D-Sp1 are expressed in the developing limb primordia of Drosophila melanogaster and are required for normal growth of the legs. The D-Sp1 homolog of the red flour beetle Tribolium castaneum, Sp8 (appropriately termed Sp8/9), is also required for the proper growth of the leg segments. Here we report on the isolation and functional study of the Sp8/9 gene from the milkweed bug Oncopeltus fasciatus. We show that Sp8/9 is expressed in the developing appendages throughout development and that the downregulation of Sp8/9 via RNAi leads to antennae, rostrum, and legs with shortened and fused segments. This supports a conserved role of Sp8/9 in allometric leg segment growth. However, all leg segments including the claws are present and the expression of the leg genes Distal-less, dachshund, and homothorax are proportionally normal, thus providing no evidence for a role of Sp8/9 in appendage specification.

  3. Binding of transcription factors to Presenilin 1 and 2 promoter cis-acting elements varies during the development of mouse cerebral cortex.

    Science.gov (United States)

    Kumar, Ashish; Thakur, M K

    2016-08-15

    Previously, we reported differential expression of Presenilin (PS)1 and 2 and epigenetic modifications of their gene promoter in the cerebral cortex of mice during development. We identified the crucial role of DNA methylation and H3K9/14 acetylation in stage specific PS expression during brain development. Interestingly, we noted differential DNA methylation in putative binding sites of transcription factors considered pivotal for brain development. This prompted us to study the binding of transcription factors to cis-acting elements of PS1 and PS2 promoter in the cerebral cortex of mice during development. In-silico analysis revealed various cis-acting elements of PS1 and PS2 promoter and their putative transcription factors. We selected those cis-acting elements that were proven by wet lab experiments to interact with the transcription factors crucial for brain development. Electrophoretic mobility shift assay revealed that the binding of nuclear proteins to PS1 promoter cis-acting elements like HSF-1, Cdx1, Ets-1 and Sp1 significantly increased at embryonic day (E) 12.5, postnatal day (P) 45 and 20 weeks (w) as compared to P0. The binding pattern of these factors correlated well with the PS1 expression profile, indicating their cumulative influence on PS1 gene transcription. For PS2 promoter, the binding of Nkx2.2 and HFH-2 was high at prenatal stages (E12.5 and E18.5) while that of Cdx1 and NF-κB was maximum at postnatal stages (P45 and 20w). Taken together, our study shows that the binding of HSF-1, Cdx1, Ets-1 and Sp1 to PS1 promoter and that of Nkx2.2, HFH-2, Cdx1 and NF-κB to PS2 promoter regulate their differential expression during brain development.

  4. Differential regulation of the TLR4 signalling pathway in post-mortem prefrontal cortex and cerebellum in chronic schizophrenia: Relationship with SP transcription factors.

    Science.gov (United States)

    MacDowell, Karina S; Pinacho, Raquel; Leza, Juan C; Costa, Joan; Ramos, Belén; García-Bueno, Borja

    2017-08-10

    Alterations in innate immunity may underlie the pathophysiology of schizophrenia (SZ). Toll-like receptor-4 (TLR4) is a master element of innate immunity. The specificity proteins (SPs), transcription factors recently implicated in SZ, are putative regulatory agents of this. This work was aimed at describing alterations in the TLR4 signalling pathway in postmortem brain prefrontal cortex (PFC) and cerebellum (CB) of 16 chronic SZ patients and 14 controls. The possible association of TLR4 pathway with SP1 and SP4 and SZ negative symptomatology is explored. In PFC, TLR4/myeloid differentiation factor 88 (MyD88)/inhibitory subunit of nuclear factor kappa B alpha (IκBα) protein levels were lower in SZ patients, while nuclear transcription factor-κB (NFκB) activity, cyclooxygenase-2 (COX-2) expression and the lipid peroxidation index malondialdehyde (MDA) appeared increased. The pattern of changes in CB is opposite, except for COX-2 expression that remained augmented and MDA levels unaltered. Network interaction analysis showed that TLR4/MyD88/IκBα/NFκB/COX-2 pathway was coupled in PFC and uncoupled in CB. SP4 co-expressed with TLR4 and NFκB in PFC and both SP1 and SP4 co-expressed with NFκB in CB. In PFC, correlation analysis found an inverse relationship between NFκB and negative symptoms. In summary, we found brain region-specific alterations in the TLR4 signalling pathway in chronic SZ, in which SP transcription factors could participate at different levels. Further studies are required to elucidate the regulatory mechanisms of innate immunity in SZ and its relationship with symptoms. Copyright © 2017. Published by Elsevier Inc.

  5. Exchange 2003 SP1中的RPC over HTTP——利用SP1的受管理拓扑

    Institute of Scientific and Technical Information of China (English)

    KieranMcCorry; 蒋世滨

    2005-01-01

    Exchange Server 2003允许你使用Messaging API (MAPI) Remote Procedure Call over HTTP (即RPC over HTTP, 一般是指: Outlook over HTTP)将Microsoft Office Outlook 2003连接到一个Exchange服务器。当微软发行Exchange 2003时,用户为这个功能而欢呼,因为他们终于可以通过任何网络连接Outlook和Exchange了。

  6. Exposure to nerve growth factor worsens nephrotoxic effect induced by Cyclosporine A in HK-2 cells.

    Directory of Open Access Journals (Sweden)

    Donatella Vizza

    Full Text Available Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkA(NTR and p75(NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 (NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75(NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.

  7. Exposure to Nerve Growth Factor Worsens Nephrotoxic Effect Induced by Cyclosporine A in HK-2 Cells

    Science.gov (United States)

    Lofaro, Danilo; Toteda, Giuseppina; Lupinacci, Simona; Leone, Francesca; Gigliotti, Paolo; Papalia, Teresa; Bonofiglio, Renzo

    2013-01-01

    Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkANTR and p75NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A. PMID:24244623

  8. Brightening of carbon nanotube photoluminescence through the incorporation of sp3 defects.

    Science.gov (United States)

    Piao, Yanmei; Meany, Brendan; Powell, Lyndsey R; Valley, Nicholas; Kwon, Hyejin; Schatz, George C; Wang, YuHuang

    2013-10-01

    Semiconducting carbon nanotubes promise a broad range of potential applications in optoelectronics and imaging, but their photon-conversion efficiency is relatively low. Quantum theory suggests that nanotube photoluminescence is intrinsically inefficient because of low-lying 'dark' exciton states. Here we demonstrate the significant brightening of nanotube photoluminescence (up to 28-fold) through the creation of an optically allowed defect state that resides below the predicted energy level of the dark excitons. Emission from this new state generates a photoluminescence peak that is red-shifted by as much as 254 meV from the nanotube's original excitonic transition. We also found that the attachment of electron-withdrawing substituents to carbon nanotubes systematically drives this defect state further down the energy ladder. Our experiments show that the material's photoluminescence quantum yield increases exponentially as a function of the shifted emission energy. This work lays the foundation for chemical control of defect quantum states in low-dimensional carbon materials.

  9. Slicing Diamond-A Guide to Deriving sp(3) -Si Allotropes.

    Science.gov (United States)

    Jantke, Laura-Alice; Stegmaier, Saskia; Karttunen, Antti J; Fässler, Thomas F

    2017-02-24

    Silicon is the most important material for solar cells. However, its low conversion rate/quantum efficiency requires a rather high material consumption. Thus, researchers undertake enormous experimental and theoretical efforts to find alternative Si allotropes with a better efficiency and in the ideal case a direct electronic band gap. In recent years and months many new allotropic Si structures have been reported; however, they are often described incoherently and without context to existing structures. Our approach allows a classification of many of these allotropes and a relation of their structures to substructures of, for example, known Zintl phases. For this so-called "chemi-inspired" search for promising Si structures we present a "construction kit" as a guide to introducing a large number of tetrahedral Si allotropes, all derived by a modification of the pristine cubic diamond structure. In addition, this approach allows us to realize structural (topological) relationships between experimentally accessible Zintl phases of different composition, such as open tetrahedral frameworks, to a yet unknown extent, including even known phase transitions of specific Zintl phases. In topological, structural, and computational analyses (on a DFT-PBE0/SVP level of theory) we show the close relationship of ten low-energy Si structures derived from the cubic diamond modification; five of them are new, and some show quasi-direct band gaps. A simple deviation of this approach enables the construction of many more tetrahedral structures.

  10. Organic chemistry. Functionalization of C(sp3)-H bonds using a transient directing group.

    Science.gov (United States)

    Zhang, Fang-Lin; Hong, Kai; Li, Tuan-Jie; Park, Hojoon; Yu, Jin-Quan

    2016-01-15

    Proximity-driven metalation has been extensively exploited to achieve reactivity and selectivity in carbon-hydrogen (C-H) bond activation. Despite the substantial improvement in developing more efficient and practical directing groups, their stoichiometric installation and removal limit efficiency and, often, applicability as well. Here we report the development of an amino acid reagent that reversibly reacts with aldehydes and ketones in situ via imine formation to serve as a transient directing group for activation of inert C-H bonds. Arylation of a wide range of aldehydes and ketones at the β or γ positions proceeds in the presence of a palladium catalyst and a catalytic amount of amino acid. The feasibility of achieving enantioselective C-H activation reactions using a chiral amino acid as the transient directing group is also demonstrated.

  11. Characterization of sp(2)- and sp(3)-bonded carbon in wood charcoal

    NARCIS (Netherlands)

    Ishimaru, Kengo; Hata, Toshimitsu; Bronsveld, Paul; Nishizawa, Takashi; Imamura, Yuji

    2007-01-01

    Japanese cedar (Cryptomeria japonica) preheated at 700 degrees C was subsequently heated to 1800 degrees C and characterized by electron microscopy, X-ray diffraction, and micro-Raman spectroscopy. The degree of disorder of carbon crystallites and the amount of amorphous phase decreased considerably

  12. Enantiospecific sp(2)-sp(3) coupling of secondary and tertiary boronic esters.

    Science.gov (United States)

    Bonet, Amadeu; Odachowski, Marcin; Leonori, Daniele; Essafi, Stephanie; Aggarwal, Varinder K

    2014-07-01

    The cross-coupling of boronic acids and related derivatives with sp(2) electrophiles (the Suzuki-Miyaura reaction) is one of the most powerful C-C bond formation reactions in synthesis, with applications that span pharmaceuticals, agrochemicals and high-tech materials. Despite the breadth of its utility, the scope of this Nobel prize-winning reaction is rather limited when applied to aliphatic boronic esters. Primary organoboron reagents work well, but secondary and tertiary boronic esters do not (apart from a few specific and isolated examples). Through an alternative strategy, which does not involve using transition metals, we have discovered that enantioenriched secondary and tertiary boronic esters can be coupled to electron-rich aromatics with essentially complete enantiospecificity. As the enantioenriched boronic esters are easily accessible, this reaction should find considerable application, particularly in the pharmaceutical industry where there is growing awareness of the importance of, and greater clinical success in, creating biomolecules with three-dimensional architectures.

  13. Enantiospecific sp2-sp3 coupling of secondary and tertiary boronic esters

    Science.gov (United States)

    Bonet, Amadeu; Odachowski, Marcin; Leonori, Daniele; Essafi, Stephanie; Aggarwal, Varinder K.

    2014-07-01

    The cross-coupling of boronic acids and related derivatives with sp2 electrophiles (the Suzuki-Miyaura reaction) is one of the most powerful C-C bond formation reactions in synthesis, with applications that span pharmaceuticals, agrochemicals and high-tech materials. Despite the breadth of its utility, the scope of this Nobel prize-winning reaction is rather limited when applied to aliphatic boronic esters. Primary organoboron reagents work well, but secondary and tertiary boronic esters do not (apart from a few specific and isolated examples). Through an alternative strategy, which does not involve using transition metals, we have discovered that enantioenriched secondary and tertiary boronic esters can be coupled to electron-rich aromatics with essentially complete enantiospecificity. As the enantioenriched boronic esters are easily accessible, this reaction should find considerable application, particularly in the pharmaceutical industry where there is growing awareness of the importance of, and greater clinical success in, creating biomolecules with three-dimensional architectures.

  14. Synthesis of sp3-rich scaffolds for molecular libraries through complexity-generating cascade reactions

    DEFF Research Database (Denmark)

    Flagstad, Thomas; Min, Geanna; Bonnet, K.

    2016-01-01

    An efficient strategy for the synthesis of complex small molecules from simple building blocks is presented. Key steps of the strategy include tandem Petasis and Diels–Alder reactions, and divergent complexity-generating cyclization cascades from a key dialdehyde intermediate. The methodology is ...

  15. Sf-PHB2, A new transcription factor, Drives WSSV Ie1 Gene Expression via a 12-bp DNA Element

    Directory of Open Access Journals (Sweden)

    Ma Guoda

    2012-09-01

    Full Text Available Abstract Background The WSSV immediate early gene ie1 is highly expressed throughout viral infection cycle and may play a central role in initiating viral replication during infection. Results Here, a detailed characterization of the ie1 promoter was performed using deletion and mutation analyses to elucidate the role of the individual promoter motifs. Three results were obtained: 1 the ie1 promoter is a classical eukaryotic promoter that contains the initiator element (Inr and TATA box responsible for the basal promoter activity; 2 mutation or truncation of a predicted Sp1 site decreased the level of promoter activity by about 3-fold, indicating that the Sp1 site is an important cis-element of the promoter; and 3 truncation of a 12-bp sequence that resides at -78/-67 of the ie1 promoter decreased the level of promoter activity by about 14-fold, indicating that the 12-bp motif is a critical upstream element of the ie1 promoter for binding of a strong transcription factor to drive the ie1 gene expression in the cells. Further, the 12-bp DNA binding protein was purified from the nuclear proteins of Sf9 cells using DNA affinity chromatography, and was identified as a homologue of the prohibitin2 protein (named as Sf-PHB2 using mass spectrometry. Furthermore, the DNA binding activity of Sf-PHB2 was verified using a super shift analysis. Conclusion These results support that the Sf-PHB2 is a novel transcription factor that drives WSSV ie1 gene expression by binding to the 12-bp DNA element.

  16. Global Factor Trade with Differentiated Factor Prices and Factor Intensities

    OpenAIRE

    Yun-kwong Kwok

    2004-01-01

    Relaxing the assumption of internationally identical factor intensity techniques in the HOV model creates two challenges. First, computing actual factor intensity techniques of different countries requires detailed input-output tables and factor usage data, which are not always available. Second, determinants of the factor intensity technique differences across countries need to be identified. This paper explores the role of relative factor price differences in the determination of factor int...

  17. Two mutations in the locus control region hypersensitivity site-2 (5' HS-2) of haplotype 19 beta s chromosomes alter binding of trans-acting factors.

    Science.gov (United States)

    Morgan, J C; Scott, D F; Lanclos, K D

    1996-01-01

    There are five major haplotypes associated with sickle cell anemia (SS). Individuals homozygous for haplotypes 3 (Senegal) and 31 (Saudi Arabian) have high fetal hemoglobin (HbF) levels (15 to 30% of total hemoglobin) whereas individuals homozygous for haplotypes 17 (Cameroon), 19 (Benin), and 20 (Bantu) have low HbF levels (1 to 10%). We previously identified several point mutations in the LCR 5'HS-2 that were specific for haplotype 19 beta s chromosomes (compared to the GenBank HUMHBB reference sequence, T-->G at position 8580, A-->G at position 8598, and A-->T at position 9114). We postulated that one or more of these mutations may alter the binding of specific trans-acting factors and ultimately affect the expression of HbF in these sickle cell patients. We performed gel mobility shift assays using 32P-end-labeled double-stranded 19mers corresponding to each of the LCR 5'HS-2 normal (GenBank) and mutant sequences. Nuclear extracts prepared from HeLa and HEL cells were used in our experiments and neither the normal nor mutant sequence at position 8580 bound trans-acting factors in either nuclear extract. The 8598 mutant increased binding of Sp1; using purified protein and both nuclear extracts. HEL extracts were used to quantify the increase in Sp1 binding to the 8598 mutation and we found an increase in binding of 66 and 47%, respectively, in two shifted bands. The 9114 mutation sharply decreased binding of an unknown trans-acting factor by 74%. This factor was present in both HeLa and HEL nuclear extracts.

  18. Involvement of ubiquitous and tale transcription factors, as well as liganded RXRα, in the regulation of human SOX2 gene expression in the NT2/D1 embryonal carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Milivojević Milena

    2010-01-01

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

  19. An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

    Science.gov (United States)

    Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

    2016-06-24

    Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

  20. Hydrogen peroxide sensing, signaling and regulation of transcription factors

    Directory of Open Access Journals (Sweden)

    H. Susana Marinho

    2014-01-01

    Full Text Available The regulatory mechanisms by which hydrogen peroxide (H2O2 modulates the activity of transcription factors in bacteria (OxyR and PerR, lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4 and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1 are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1 synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M−1 s−1 and ≥1.3 × 103 M−1 s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for

  1. Calcium input potentiates the transforming growth factor (TGF)-beta1-dependent signaling to promote the export of inorganic pyrophosphate by articular chondrocyte.

    Science.gov (United States)

    Cailotto, Frederic; Reboul, Pascal; Sebillaud, Sylvie; Netter, Patrick; Jouzeau, Jean-Yves; Bianchi, Arnaud

    2011-06-03

    Transforming growth factor (TGF)-β1 stimulates extracellular PP(i) (ePP(i)) generation and promotes chondrocalcinosis, which also occurs secondary to hyperparathyroidism-induced hypercalcemia. We previously demonstrated that ANK was up-regulated by TGF-β1 activation of ERK1/2 and Ca(2+)-dependent protein kinase C (PKCα). Thus, we investigated mechanisms by which calcium could affect ePP(i) metabolism, especially its main regulating proteins ANK and PC-1 (plasma cell membrane glycoprotein-1). We stimulated articular chondrocytes with TGF-β1 under extracellular (eCa(2+)) or cytosolic Ca(2+) (cCa(2+)) modulations. We studied ANK, PC-1 expression (quantitative RT-PCR, Western blotting), ePP(i) levels (radiometric assay), and cCa(2+) input (fluorescent probe). Voltage-operated Ca(2+)-channels (VOC) and signaling pathways involved were investigated with selective inhibitors. Finally, Ank promoter activity was evaluated (gene reporter). TGF-β1 elevated cCa(2+) and ePP(i) levels (by up-regulating Ank and PC-1 mRNA/proteins) in an eCa(2+) dose-dependent manner. TGF-β1 effects were suppressed by cCa(2+) chelation or L- and T-VOC blockade while being mostly reproduced by ionomycin. In the same experimental conditions, the activation of Ras, the phosphorylation of ERK1/2 and PKCα, and the stimulation of Ank promoter activity were affected similarly. Activation of SP1 (specific protein 1) and ELK-1 (Ets-like protein-1) transcription factors supported the regulatory role of Ca(2+). SP1 or ELK-1 overexpression or blockade experiments demonstrated a major contribution of ELK-1, which acted synergistically with SP1 to activate Ank promoter in response to TGF-β1. TGF-β1 promotes input of eCa(2+) through opening of L- and T-VOCs, to potentiate ERK1/2 and PKCα signaling cascades, resulting in an enhanced activation of Ank promoter and ePP(i) production in chondrocyte.

  2. Calcium Input Potentiates the Transforming Growth Factor (TGF)-β1-dependent Signaling to Promote the Export of Inorganic Pyrophosphate by Articular Chondrocyte*

    Science.gov (United States)

    Cailotto, Frederic; Reboul, Pascal; Sebillaud, Sylvie; Netter, Patrick; Jouzeau, Jean-Yves; Bianchi, Arnaud

    2011-01-01

    Transforming growth factor (TGF)-β1 stimulates extracellular PPi (ePPi) generation and promotes chondrocalcinosis, which also occurs secondary to hyperparathyroidism-induced hypercalcemia. We previously demonstrated that ANK was up-regulated by TGF-β1 activation of ERK1/2 and Ca2+-dependent protein kinase C (PKCα). Thus, we investigated mechanisms by which calcium could affect ePPi metabolism, especially its main regulating proteins ANK and PC-1 (plasma cell membrane glycoprotein-1). We stimulated articular chondrocytes with TGF-β1 under extracellular (eCa2+) or cytosolic Ca2+ (cCa2+) modulations. We studied ANK, PC-1 expression (quantitative RT-PCR, Western blotting), ePPi levels (radiometric assay), and cCa2+ input (fluorescent probe). Voltage-operated Ca2+-channels (VOC) and signaling pathways involved were investigated with selective inhibitors. Finally, Ank promoter activity was evaluated (gene reporter). TGF-β1 elevated cCa2+ and ePPi levels (by up-regulating Ank and PC-1 mRNA/proteins) in an eCa2+ dose-dependent manner. TGF-β1 effects were suppressed by cCa2+ chelation or L- and T-VOC blockade while being mostly reproduced by ionomycin. In the same experimental conditions, the activation of Ras, the phosphorylation of ERK1/2 and PKCα, and the stimulation of Ank promoter activity were affected similarly. Activation of SP1 (specific protein 1) and ELK-1 (Ets-like protein-1) transcription factors supported the regulatory role of Ca2+. SP1 or ELK-1 overexpression or blockade experiments demonstrated a major contribution of ELK-1, which acted synergistically with SP1 to activate Ank promoter in response to TGF-β1. TGF-β1 promotes input of eCa2+ through opening of L- and T-VOCs, to potentiate ERK1/2 and PKCα signaling cascades, resulting in an enhanced activation of Ank promoter and ePPi production in chondrocyte. PMID:21471198

  3. Activation of Mechanosensitive Transcription Factors in Murine C2C12 Mesenchymal Precursors by Focused Low-Intensity Pulsed Ultrasound (FLIPUS).

    Science.gov (United States)

    Puts, Regina; Rikeit, Paul; Ruschke, Karen; Kadow-Romacker, Anke; Hwang, Soyoung; Jenderka, Klaus-Vitold; Knaus, Petra; Raum, Kay

    2016-10-01

    In this paper, we investigated the mechanoresponse of C2C12 mesenchymal precursor cells to focused low-intensity pulsed ultrasound (FLIPUS). The setup has been developed for in vitro stimulation of adherent cells in the defocused far field of the ultrasound propagating through the bottom of the well plate. Twenty-four-well tissue culture plates, carrying the cell monolayers, were incubated in a temperature-controlled water tank. The ultrasound was applied at 3.6-MHz frequency, pulsed at 100-Hz repetition frequency with a 27.8% duty cycle, and calibrated at an output intensity of ISATA = 44.5 ±7.1 mW/cm(2). Numerical sound propagation simulations showed no generation of standing waves in the well plate. The response of murine C2C12 cells to FLIPUS was evaluated by measuring activation of mechanosensitive transcription factors, i.e., activator protein-1 (AP-1), specificity protein 1 (Sp1), and transcriptional enhancer factor (TEAD), and expression of mechanosensitive genes, i.e., c-fos, c-jun, heparin binding growth associated molecule (HB-GAM), and Cyr-61. FLIPUS induced 50% ( p ≤ 0.05 ) and 70% ( p ≤ 0.05 ) increases in AP-1 and TEAD promoter activities, respectively, when stimulated for 5 min. The Sp1 activity was enhanced by about 20% ( p ≤ 0.05 ) after 5-min FLIPUS exposure and the trend persisted for 30-min ( p ≤ 0.05 ) and 1-h ( p ≤ 0.05 ) stimulation times. Expressions of mechanosensitive genes c-fos ( p ≤ 0.05 ), c-jun ( p ≤ 0.05 ), HB-GAM ( p ≤ 0.05 ), and cystein-rich protein 61 ( p ≤ 0.05 ) were enhanced in response to 5-min FLIPUS stimulation. The increase in proliferation of C2C12s occurred after the FLIPUS stimulation ( p ≤ 0.05 ), with AP-1, Sp1, and TEAD possibly regulating the observed cellular activities.

  4. Factor II deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor II is one such coagulation factor. Factor II deficiency runs in families (inherited) and is very rare. Both parents must ...

  5. Factor VII deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor VII is one such coagulation factor. Factor VII deficiency runs in families (inherited) and is very rare. Both parents must ...

  6. Heart disease - risk factors

    Science.gov (United States)

    Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

  7. Thyroid Cancer Risk Factors

    Science.gov (United States)

    ... Prevented? Thyroid Cancer Causes, Risk Factors, and Prevention Thyroid Cancer Risk Factors A risk factor is anything that ... Cancer? Can Thyroid Cancer Be Prevented? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  8. Akt and SHIP modulate Francisella escape from the phagosome and induction of the Fas-mediated death pathway.

    Directory of Open Access Journals (Sweden)

    Murugesan V S Rajaram

    Full Text Available Francisella tularensis infects macrophages and escapes phago-lysosomal fusion to replicate within the host cytosol, resulting in host cell apoptosis. Here we show that the Fas-mediated death pathway is activated in infected cells and correlates with escape of the bacterium from the phagosome and the bacterial burden. Our studies also demonstrate that constitutive activation of Akt, or deletion of SHIP, promotes phago-lysosomal fusion and limits bacterial burden in the host cytosol, and the subsequent induction of Fas expression and cell death. Finally, we show that phagosomal escape/intracellular bacterial burden regulate activation of the transcription factors sp1/sp3, leading to Fas expression and cell death. These data identify for the first time host cell signaling pathways that regulate the phagosomal escape of Francisella, leading to the induction of Fas and subsequent host cell death.

  9. Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition.

    Science.gov (United States)

    Tuo, Jingsheng; Ning, Baitang; Bojanowski, Christine M; Lin, Zhong-Ning; Ross, Robert J; Reed, George F; Shen, Defen; Jiao, Xiaodong; Zhou, Min; Chew, Emily Y; Kadlubar, Fred F; Chan, Chi-Chao

    2006-06-13

    This study investigates age-related macular degeneration (AMD) genetic risk factors through identification of a functional single-nucleotide polymorphism (SNP) and its disease association. We chose ERCC6 because of its roles in the aging process, DNA repair, and ocular degeneration from the gene disruption. Bioinformatics indicated a putative binding-element alteration on the sequence containing C-6530>G SNP in the 5' flanking region of ERCC6 from Sp1 on the C allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift assays displayed distinctive C and G allele-binding patterns to nuclear proteins. Luciferase expression was higher in the vector construct containing the G allele than that containing the C allele. A cohort of 460 advanced AMD cases and 269 age-matched controls was examined along with pathologically diagnosed 57 AMD and 18 age-matched non-AMD archived cases. ERCC6 C-6530>G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6 expression was observed in lymphocytes from healthy donors bearing ERCC6 C-6530>G alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6 C-6530>G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH SNPs may result from biological epistasis, because ERCC6 functions in universal transcription as a component of RNA pol I transcription complex.

  10. OWA在Exchange Server 2007 SP1中新装上阵

    Institute of Scientific and Technical Information of China (English)

    Brien Posey; 盛青(译)

    2009-01-01

    了解Outlook Web Access(OWA)的众多改进,例如更加强壮的OWA Light,个人分发列表(DL),以及对WebReady文档浏览新的或改进的支持,S/MIME,公共文件夹,每月日历,为用户提供了更好的Outlook webmail客户端。

  11. Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa): e0145314

    National Research Council Canada - National Science Library

    Jinru He; Lianming Zheng; Wenjing Zhang; Yuanshao Lin

    2015-01-01

      The genus Aurelia is one of the major contributors to jellyfish blooms in coastal waters, possibly due in part to hydroclimatic and anthropogenic causes, as well as their highly adaptive reproductive traits...

  12. Structural and Developmental Disparity in the Tentacles of the Moon Jellyfish Aurelia sp.1.

    Science.gov (United States)

    Gold, David A; Nakanishi, Nagayasu; Hensley, Nicholai M; Cozzolino, Kira; Tabatabaee, Mariam; Martin, Michelle; Hartenstein, Volker; Jacobs, David K

    2015-01-01

    Tentacles armed with stinging cells (cnidocytes) are a defining trait of the cnidarians, a phylum that includes sea anemones, corals, jellyfish, and hydras. While cnidarian tentacles are generally characterized as structures evolved for feeding and defense, significant variation exists between the tentacles of different species, and within the same species across different life stages and/or body regions. Such diversity suggests cryptic distinctions exist in tentacle function. In this paper, we use confocal and transmission electron microscopy to contrast the structure and development of tentacles in the moon jellyfish, Aurelia species 1. We show that polyp oral tentacles and medusa marginal tentacles display markedly different cellular and muscular architecture, as well as distinct patterns of cellular proliferation during growth. Many structural differences between these tentacle types may reflect biomechanical solutions to different feeding strategies, although further work would be required for a precise mechanistic understanding. However, differences in cell proliferation dynamics suggests that the two tentacle forms lack a conserved mechanism of development, challenging the textbook-notion that cnidarian tentacles can be homologized into a conserved bauplan.

  13. GenBank blastn search result: AK064582 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064582 002-112-F03 AY007820.1 Daucus carota ATPase8 (ATP8) gene, ATP8-Sp1b allele, complete cds; chimeric... ATPase9 (ATP9) gene, ATP9-Sp3 allele, complete cds; and chimeric ATPase6 (ATP6) gen

  14. Risk Factors and Prevention

    Science.gov (United States)

    ... Factors & Prevention Back to Patient Resources Risk Factors & Prevention Even people who look healthy and free of ... as possible. Share: The Normal Heart Risk Factors & Prevention Heart Diseases & Disorders Substances & Heart Rhythm Disorders Symptoms & ...

  15. Risk Factors for Scleroderma

    Science.gov (United States)

    ... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

  16. Transcriptional regulation by triiodothyronine requires synergistic action of the thyroid receptor with another trans-acting factor.

    Science.gov (United States)

    Voz, M L; Peers, B; Wiedig, M J; Jacquemin, P; Belayew, A; Martial, J A

    1992-09-01

    Human placental lactogen B (hCS-B) promoter activity is strongly stimulated by triiodothyronine (T3) in pituitary GC cells through interaction between the thyroid receptor and a thyroid receptor-binding element (TBE) spanning coordinates -67 to -41. This TBE is adjacent to the binding site for pituitary factor GHF1 (-95 to -68) which seems necessary for T3 stimulation of hCS-B promoter activity (M. L. Voz, B. Peers, A. Belayew, and J. A. Martial, J. Biol. Chem. 266:13397-13404, 1991). We here demonstrate actual synergy between the thyroid receptor and GHF1. Indeed, in placental JEG-3 cells devoid of factor GHF1, hCS promoter activity is barely stimulated by T3, while a strong response is observed in pituitary GC cells. In the latter, furthermore, neither the TBE nor the GHF1-binding site alone is sufficient to render the thymidine kinase promoter responsive to T3, while in combination they promote strong T3 stimulation. Close proximity between these sites is required for optimal synergy: T3 stimulation globally decreases with increased spacing. Furthermore, synergy occurs not only with a GHF1-binding site but also with all other factor recognition sequences tested (Sp1, NF1, CP1, Oct1, and CACCC boxes) and even with two other copies of the TBE. Nor is it specific to hCS TBE, since the palindromic sequence TCAGGTCA TGACCTGA (TREpal) also exhibits cooperativity.

  17. Latent transforming growth factor β-binding protein 4 is downregulated in esophageal cancer via promoter methylation.

    Directory of Open Access Journals (Sweden)

    Insa Bultmann

    Full Text Available Latent transforming growth factor β-binding protein 4 (LTBP4 is an extracellular matrix molecule that is a member of important connective tissue networks and is needed for the correct folding and the secretion of TGF-β1. LTBP4 is downregulated in carcinomas of various tissues. Here we show that LTBP4 is also downregulated in adenocarcinomas and squamous cell carcinomas of the esophagus in vitro and in vivo. Re-expression of LTBP4 in esophageal cancer cell lines reduced cell migration ability, whereas cell viability and cell proliferation remained unchanged. Hypermethylation of the promoter regions of the two main human LTBP4 transcriptional forms, LTBP4L and LTBP4S, was found to be involved in LTBP4 silencing. Detailed investigations of the methylation patterns of the promoter regions of LTBP4L and LTBP4S identified GATA1, SP1, E2F4 and SMAD3 as potential transcription factors involved in LTBP4 expression. In in vitro transcription factor activity studies we discovered E2F4 as novel powerful regulator for LTBP4S expression.

  18. Cocaine induces a differential dose-dependent alteration in the expression profile of immediate early genes, transcription factors, and caspases in PC12 cells: a possible mechanism of neurotoxic damage in cocaine addiction.

    Science.gov (United States)

    Imam, Syed Z; Duhart, Helen M; Skinner, John T; Ali, Syed F

    2005-08-01

    Cocaine is a widely used drug of abuse and psychostimulant that acts on the central nervous system by blocking the dopamine reuptake sites. PC12 cells, a rat pheochromocytoma clonal line, in the presence of nerve growth factor (NGF), multiply and differentiate into competent neurons that can synthesize, store, and secrete the neurotransmitter dopamine (DA). In the present study, we evaluated the effect of increasing doses of cocaine on the expression of immediate early genes (IEGs), c-fos and c-jun, and closely related transcription factors, SP-1 and NF-kbeta, at 24 h after the exposure to cocaine (50, 100, 200, 500, 1000, 2500 microM) in NGF-differentiated PC12 cells. Cocaine (50-500 microM) resulted in significant induction of the expression of c-fos, c-jun, SP-1, and NF-kbeta. However, higher concentrations of cocaine (1000 and 2500 microM) resulted in the downregulation of these expressions after 24 h. To further understand the role of dose-dependent changes in the mechanisms of cell death, we evaluated the protein expression of apoptotic markers. A concentration-dependent increase in the expression of caspase-9 and -3 was observed up to 500 microM cocaine. However, the higher dose did not show any expression. We also evaluated the effect of increasing doses of cocaine on DA concentration and the expression of dopamine transporter (DAT). A significant dose-dependent decrease in the concentration of DA as well as the expression of DAT was observed 24 h after the exposure of PC12 cells to cocaine. Therefore, in the present study, we reported that cocaine has both upstream and downstream regulatory actions on some IEGs and transcription factors that can regulate the mechanism of cell death, and these effects on gene expression are independent of its action on the dopaminergic system.

  19. Factor V deficiency

    Science.gov (United States)

    ... When certain blood clotting factors are low or missing, your blood does not clot properly. Factor V deficiency is rare. It may be caused by: A defective Factor V gene passed down through families (inherited) An antibody that interferes with normal Factor ...

  20. Foundations of factor analysis

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

    Introduction Factor Analysis and Structural Theories Brief History of Factor Analysis as a Linear Model Example of Factor AnalysisMathematical Foundations for Factor Analysis Introduction Scalar AlgebraVectorsMatrix AlgebraDeterminants Treatment of Variables as Vectors Maxima and Minima of FunctionsComposite Variables and Linear Transformations Introduction Composite Variables Unweighted Composite VariablesDifferentially Weighted Composites Matrix EquationsMulti

  1. KLF10, transforming growth factor-{beta}-inducible early gene 1, acts as a tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ki-Duk [Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921 (Korea, Republic of); Laboratory of Protein Engineering and Comparative Immunology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-921 (Korea, Republic of); Kim, Duk-Jung [The Institute of Hankook Life Science, 7-9 Myungryun-dong, Jongno-gu, Seoul 110-521 (Korea, Republic of); Lee, Jong Eun [Department of Anatomy, College of Medicine, Yonsei University, Seoul 120-752 (Korea, Republic of); Yun, Cheol-Heui [Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921 (Korea, Republic of); Laboratory of Protein Engineering and Comparative Immunology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-921 (Korea, Republic of); Lee, Woon Kyu, E-mail: wklee@inha.ac.kr [Laboratory of Developmental Genetics, School of Medicine, Inha University, Incheon 400-712 (Korea, Republic of); Brain Korea 21 Center for Advanced Medical Education, School of Medicine, Inha University, Incheon 400-712 (Korea, Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer KLF10{sup -/-} mice exhibited accelerated papilloma development after DMBA/TPA treatment. Black-Right-Pointing-Pointer KLF10{sup -/-} keratinocytes showed increased proliferation and apoptosis. Black-Right-Pointing-Pointer KLF10{sup -/-} MEFs yielded more colonies than wild-type one with H-Ras transfection. Black-Right-Pointing-Pointer KLF10 dose-dependently activated p21{sup WAF1/CIP1} transcription. Black-Right-Pointing-Pointer KLF10 is a tumor suppressor and that it targets p21{sup WAF1/CIP1} transcription. -- Abstract: Krueppel-like factor 10 (KLF10) has been suggested to be a putative tumor suppressor. In the present study, we generated KLF10 deficient mice to explore this hypothesis in vivo. KLF10 deficient mice exhibited increased predisposition to skin tumorigenesis and markedly accelerated papilloma development after DMBA/TPA treatment. On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis. In colony formation assays after oncogenic H-Ras transfection, KLF10 deficient mouse embryonic fibroblasts (MEFs) yielded more colonies than wild-type MEFs. Furthermore, KLF10 dose-dependently activated p21{sup WAF1/CIP1} transcription, which was independent of p53 and Sp1 binding sites in p21{sup WAF1/CIP1} promoter. This study demonstrates that KLF10 is a tumor suppressor and that it targets p21{sup WAF1/CIP1} transcription.

  2. Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control

    Science.gov (United States)

    Guaraldo, Michela; Santambrogio, Paolo; Rovelli, Elisabetta; di Savino, Augusta; Saglio, Giuseppe; Cittaro, Davide; Roetto, Antonella; Levi, Sonia

    2016-09-01

    Mitochondrial ferritin (FtMt) is an iron storage protein belonging to the ferritin family but, unlike the cytosolic ferritin, it has an iron-unrelated restricted tissue expression. FtMt appears to be preferentially expressed in cell types characterized by high metabolic activity and oxygen consumption, suggesting a role in protecting mitochondria from iron-dependent oxidative damage. The human gene (FTMT) is intronless and its promoter region has not been described yet. To analyze the regulatory mechanisms controlling FTMT expression, we characterized the 5‧ flanking region upstream the transcriptional starting site of FTMT by in silico enquiry of sequences conservation, DNA deletion analysis, and ChIP assay. The data revealed a minimal promoter region and identified the presence of SP1, CREB and YY1 as positive regulators, and GATA2, FoxA1 and C/EBPβ as inhibitors of the transcriptional regulation. Furthermore, the FTMT transcription is increased by acetylating and de-methylating agent treatments in K562 and HeLa cells. These treatments up-regulate FtMt expression even in fibroblasts derived from a Friedreich ataxia patient, where it might exert a beneficial effect against mitochondrial oxidative damage. The expression of FTMT appears regulated by a complex mechanism involving epigenetic events and interplay between transcription factors.

  3. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  4. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.;

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corr......This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  5. A Tandem Repeat in Decay Accelerating Factor 1 Is Associated with Severity of Murine Mercury-Induced Autoimmunity

    Directory of Open Access Journals (Sweden)

    David M. Cauvi

    2014-01-01

    Full Text Available Decay accelerating factor (DAF, a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA. Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

  6. Risk Factors for Thrombosis

    Institute of Scientific and Technical Information of China (English)

    包承鑫

    2002-01-01

    @@ Thrombotic disease is a multifactorial disease, multiple interactions between genetic and environmental factors contribute to the development of the disease.This review summarized some risk factors reported for arterial thrombosis and venous thrombosis in recent few years.

  7. Factoring Polynomials and Fibonacci.

    Science.gov (United States)

    Schwartzman, Steven

    1986-01-01

    Discusses the factoring of polynomials and Fibonacci numbers, offering several challenges teachers can give students. For example, they can give students a polynomial containing large numbers and challenge them to factor it. (JN)

  8. Coagulation Factors Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Coagulation Factors Share this page: Was this page helpful? ... else I should know? How is it used? Coagulation factor testing is performed to determine if a ...

  9. Annual Adjustment Factors

    Data.gov (United States)

    Department of Housing and Urban Development — The Department of Housing and Urban Development establishes the rent adjustment factors - called Annual Adjustment Factors (AAFs) - on the basis of Consumer Price...

  10. Environmental factors in autism

    OpenAIRE

    Andreas Martin Grabrucker

    2013-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an im...

  11. Environmental Factors in Autism

    OpenAIRE

    Andreas M. Grabrucker

    2013-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an im...

  12. Mesonic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Frederic D. R. Bonnet; Robert G. Edwards; George T. Fleming; Randal Lewis; David Richards

    2003-07-22

    We have started a program to compute the electromagnetic form factors of mesons. We discuss the techniques used to compute the pion form factor and present preliminary results computed with domain wall valence fermions on MILC asqtad lattices, as well as Wilson fermions on quenched lattices. These methods can easily be extended to rho-to-gamma-pi transition form factors.

  13. Multilevel Mixture Factor Models

    Science.gov (United States)

    Varriale, Roberta; Vermunt, Jeroen K.

    2012-01-01

    Factor analysis is a statistical method for describing the associations among sets of observed variables in terms of a small number of underlying continuous latent variables. Various authors have proposed multilevel extensions of the factor model for the analysis of data sets with a hierarchical structure. These Multilevel Factor Models (MFMs)…

  14. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  15. Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11β-hydroxysteroid dehydrogenase type 2 in a sex-specific manner

    Science.gov (United States)

    Kaur, Rajwinderjit; Hale, Merica A.; Bares, Allyson; Yu, Xing; Callaway, Christopher W.; McKnight, Robert A.; Lane, Robert H.

    2010-01-01

    Intrauterine growth restriction (IUGR) increases the risk of serious adult morbidities such as hypertension. In an IUGR rat model of hypertension, we reported a persistent decrease in kidney 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) mRNA and protein levels from birth through postnatal (P) day 21. This enzyme deficiency can lead to hypertension by limiting renal glucocorticoid deactivation. In the present study, we hypothesized that IUGR affects renal 11β-HSD2 epigenetic determinants of chromatin structure and alters key transcription factor binding to the 11β-HSD2 promoter in association with persistent downregulation of its mRNA expression. To test this hypothesis, we performed bilateral uterine artery ligation on embryonic day 19.5 pregnant rats and harvested kidneys at day 0 (P0) and P21. Key transcription factors that can affect 11β-HSD2 expression include transcriptional enhancers specificity protein 1 (SP1) and NF-κB p65 and transcriptional repressors early growth response factor (Egr-1) and NF-κB p50. Our most important findings were as follows: 1) IUGR significantly decreased SP1 and NF-κB (p65) binding to the 11β-HSD2 promoter in males, while it increased Egr-1 binding in females and NF-κB (p50) binding in males; 2) IUGR increased CpG methylation status, as well as modified the pattern of methylation in several CpG sites of 11β-HSD2 promoter at P0 also in a sex-specific manner; and 3) IUGR decreased trimethylation of H3K36 in exon 5 of 11β-HSD2 at P0 and P21 in both genders. We conclude that IUGR is associated with altered transcriptional repressor/activator binding in connection with increased methylation in the 11β-HSD2 promoter region in a sex-specific manner, possibly leading to decreased transcriptional activity. Furthermore, IUGR decreased trimethylation of H3K36 of the 11β-HSD2 gene in both genders, which is associated with decreased transcriptional elongation. We speculate that alterations in transcription factor binding and

  16. Analytic Couple Modeling Introducing Device Design Factor, Fin Factor, Thermal Diffusivity Factor, and Inductance Factor

    Science.gov (United States)

    Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

    2014-01-01

    A set of convenient thermoelectric device solutions have been derived in order to capture a number of factors which are previously only resolved with numerical techniques. The concise conversion efficiency equations derived from governing equations provide intuitive and straight-forward design guidelines. These guidelines allow for better device design without requiring detailed numerical modeling. The analytical modeling accounts for factors such as i) variable temperature boundary conditions, ii) lateral heat transfer, iii) temperature variable material properties, and iv) transient operation. New dimensionless parameters, similar to the figure of merit, are introduced including the device design factor, fin factor, thermal diffusivity factor, and inductance factor. These new device factors allow for the straight-forward description of phenomenon generally only captured with numerical work otherwise. As an example a device design factor of 0.38, which accounts for thermal resistance of the hot and cold shoes, can be used to calculate a conversion efficiency of 2.28 while the ideal conversion efficiency based on figure of merit alone would be 6.15. Likewise an ideal couple with efficiency of 6.15 will be reduced to 5.33 when lateral heat is accounted for with a fin factor of 1.0.

  17. Explicit correlation factors

    Science.gov (United States)

    Johnson, Cole M.; Hirata, So; Ten-no, Seiichiro

    2017-09-01

    We analyze the performance of 17 different correlation factors in explicitly correlated second-order many-body perturbation calculations for correlation energies. Highly performing correlation factors are found to have near-universal shape and size in the short range of electron-electron distance (0 1.5 a.u.) is insignificant insofar as the factor becomes near constant, leaving an orbital expansion to describe decoupled electrons. An analysis based on a low-rank Taylor expansion of the correlation factor seems limited, except that a negative second derivative with the value of around -1.3 a.u. correlates with high performance.

  18. Prey selection in the trap-nesting wasp Trypoxylon (Trypargilum) opacum Brèthes (Hymenprtera; Crabronidae).

    Science.gov (United States)

    Buschini, M L T; Borba, N A; Brescovit, A D

    2010-08-01

    The purpose of our research was to document and discuss the temporal patterns of prey use shown by the trap-nesting wasp Trypoxylon opacum in two different habitats in Southern Brazil. It was carried out from December 2001 to December 2004. Twenty nine species belonging to five families of spiders were captured by T. opacum. Araneidae was the most captured family and has been strongly represented by the genus Eustala. Through Bray-Curtis s coefficient and the unweighted pair group method average (UPGMA), the spiders can be divided into three groups: the smaller group includes the most abundant species (Alpaida sp2, Bertrana rufostriata, Eustala sp1, Eustala sp2, Eustala sp3 and Eustala sp4), the second group includes species with intermediate abundance (Alpaida, Alpaida gracia and Mangora sp2), and the third and largest group includes the less abundant species, (Acacesia villalobosi, Alpaida argenata, Alpaida sp1, Araneus blumenau, Araneus sicki, Crysometa boraceia, Crysometa sp3, Eustala sp8, Eustala sp11, Larinia t-notata, Mangora sp1, Ocrepeira aff gnomo, Sanogasta sp., Sanogasta sp2, Sanogasta sp3, Salticidae sp2, Theridion sp1, Theridion sp2, Wagneriana eupalaestris, Wagneriana iguape). Of 1,053 identified spiders, 362 were captured in the grassland areas and 691 in the swamp, since T. opacum built nests only in these two habitats. The diversity, richness and evenness of spiders in T. opacum nests were higher in grassland than in the swamp.

  19. Rh Factor Blood Test

    Science.gov (United States)

    Tests and Procedures Rh factor blood test By Mayo Clinic Staff Rhesus (Rh) factor is an inherited protein found on the surface of ... If your blood has the protein, you're Rh positive. If your blood lacks the protein, you' ...

  20. Baryon form factors

    CERN Document Server

    Kubis, B; Meißner, Ulf G; Mei{\\ss}ner, Ulf-G.

    1999-01-01

    We calculate the form factors of the baryon octet in the framework of heavy baryon chiral perturbation theory. The calculated charge radius of the show that kaon loop effects can play a significant role in the neutron electric form factor. Furthermore. we derive generalized Caldi-Pagels relations between various charge radii which are free of chiral loop effects.

  1. Overview of environmental factors

    Science.gov (United States)

    Purvis, C. K.

    1989-01-01

    The orbital environment is complex, dynamic, and comprised of both natural and system-induced components. Several environment factors are important for materials. Materials selection/suitability determination requires consideration of each and all factors, including synergisms among them. Understanding and evaluating these effects will require ground testing, modeling, and focused flight experimentation.

  2. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  3. Factors of schizoid personality.

    Science.gov (United States)

    Raine, A; Allbutt, J

    1989-02-01

    The increasing use of schizoid personality scales with normals has led to a number of validation studies, but to date there are no published analyses of the factorial structure of these scales. This study presents results of factor analyses of schizoid personality scales in an initial attempt to delineate their factorial structure. Questionnaires were administered to 114 male and female undergraduates and factor analysed using Varimax, Quartimax, and Oblique rotations. A two-factor varimax solution yielded a first factor accounting for 49 per cent of total unrotated variance with high (0.70 to 0.91) loadings from Hallucinatory predisposition, Perceptual aberration, Schizophrenism, STA and STB scales, and was interpreted as reflecting a general factor of schizoid personality disorder. Psychoticism and Social anhedonia loaded on a second factor accounting for 20 per cent of the variance which was uncorrelated (r = 0.09) with factor 1. This factor solution was closely replicated using quartimax and oblimin rotation criteria. It is concluded that Social anhedonia and Psychoticism represent a separate dimension from other scales which reflect the more positive features of schizoid personality.

  4. Cp*Rh(iii)-catalyzed C(sp(3))-H alkylation of 8-methylquinolines in aqueous media.

    Science.gov (United States)

    Kim, Saegun; Han, Sangil; Park, Jihye; Sharma, Satyasheel; Mishra, Neeraj Kumar; Oh, Hyunjung; Kwak, Jong Hwan; Kim, In Su

    2017-03-09

    The rhodium(iii)-catalyzed cross-coupling reaction of 8-methylquinolines with a range of allylic alcohols in water is described. This approach leads to the synthesis of various γ-quinolinyl carbonyl compounds, which are synthetically useful precursors for the construction of bioactive tetrahydroquinoline and azasteroid derivatives.

  5. THE STRAIN-STRESS STATE INVESTIGATION OF STRUCTURAL UNITS OF THE BALLAST PRISM BY TYPE SP3-5/UA

    Directory of Open Access Journals (Sweden)

    S. A. Kostrytsia

    2010-01-01

    Full Text Available In the article the results of analytical and experimental studies of the stressed-and-strained state of load-bearing elements of structure of ballast prism planner of SPZ-5/UA are presented. The analytical research is performed using the finite element method (FEM. Its results are used during realization of performance dynamic tests on durability. On the basis of analysis of the calculation and experimental data obtained the estimation of durability of construction of ballast prism planner SPZ-5/UA under the action of loads corresponding to the different operating modes is executed.

  6. Nickel-Catalyzed C sp2 –C sp3 Cross-Coupling via C–O Bond Activation

    KAUST Repository

    Guo, Lin

    2016-06-13

    A new and efficient nickel-catalyzed alkylation of CAr-O electrophiles with B-alkyl-9-BBNs is described. The transformation is characterized by its functional group tolerance and provides a practical and versatile access to various Csp2-Csp3 bonds through Csp2-O substitution, without the restriction of β-hydride elimination. Moreover, the advantage of the newly developed method was demonstrated in a selective and sequential C-O bond activation process. © 2016 American Chemical Society.

  7. Factorized Graph Matching.

    Science.gov (United States)

    Zhou, Feng; de la Torre, Fernando

    2015-11-19

    Graph matching (GM) is a fundamental problem in computer science, and it plays a central role to solve correspondence problems in computer vision. GM problems that incorporate pairwise constraints can be formulated as a quadratic assignment problem (QAP). Although widely used, solving the correspondence problem through GM has two main limitations: (1) the QAP is NP-hard and difficult to approximate; (2) GM algorithms do not incorporate geometric constraints between nodes that are natural in computer vision problems. To address aforementioned problems, this paper proposes factorized graph matching (FGM). FGM factorizes the large pairwise affinity matrix into smaller matrices that encode the local structure of each graph and the pairwise affinity between edges. Four are the benefits that follow from this factorization: (1) There is no need to compute the costly (in space and time) pairwise affinity matrix; (2) The factorization allows the use of a path-following optimization algorithm, that leads to improved optimization strategies and matching performance; (3) Given the factorization, it becomes straight-forward to incorporate geometric transformations (rigid and non-rigid) to the GM problem. (4) Using a matrix formulation for the GM problem and the factorization, it is easy to reveal commonalities and differences between different GM methods. The factorization also provides a clean connection with other matching algorithms such as iterative closest point; Experimental results on synthetic and real databases illustrate how FGM outperforms state-of-the-art algorithms for GM. The code is available at http://humansensing.cs.cmu.edu/fgm.

  8. Risk Factors for Tuberculosis

    Directory of Open Access Journals (Sweden)

    Padmanesan Narasimhan

    2013-01-01

    Full Text Available The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV, malnutrition, and young age, emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli.

  9. Environmental factors in autism.

    Science.gov (United States)

    Grabrucker, Andreas M

    2012-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.

  10. Environmental factors in autism

    Directory of Open Access Journals (Sweden)

    Andreas Martin Grabrucker

    2013-01-01

    Full Text Available Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.

  11. Factor V Leiden thrombophilia.

    Science.gov (United States)

    Kujovich, Jody Lynn

    2011-01-01

    Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism. Deep venous thrombosis and pulmonary embolism are the most common manifestations, but thrombosis in unusual locations also occurs. The current evidence suggests that the mutation has at most a modest effect on recurrence risk after initial treatment of a first venous thromboembolism. Factor V Leiden is also associated with a 2- to 3-fold increased relative risk for pregnancy loss and possibly other obstetric complications, although the probability of a successful pregnancy outcome is high. The clinical expression of Factor V Leiden is influenced by the number of Factor V Leiden alleles, coexisting genetic and acquired thrombophilic disorders, and circumstantial risk factors. Diagnosis requires the activated Protein C resistance assay (a coagulation screening test) or DNA analysis of the F5 gene, which encodes the Factor V protein. The first acute thrombosis is treated according to standard guidelines. Decisions regarding the optimal duration of anticoagulation are based on an individualized assessment of the risks for venous thromboembolism recurrence and anticoagulant-related bleeding. In the absence of a history of thrombosis, long-term anticoagulation is not routinely recommended for asymptomatic Factor V Leiden heterozygotes, although prophylactic anticoagulation may be considered in high-risk clinical settings. In the absence of evidence that early diagnosis reduces morbidity or mortality, decisions regarding testing at-risk family members should be made on an individual basis.

  12. Two-factor authentication

    CERN Document Server

    Stanislav, Mark

    2015-01-01

    During the book, readers will learn about the various technical methods by which two-factor authentication is implemented, security concerns with each type of implementation, and contextual details to frame why and when these technologies should be used. Readers will also be provided with insight about the reasons that two-factor authentication is a critical security control, events in history that have been important to prove why organization and individual would want to use two factor, and core milestones in the progress of growing the market.

  13. Teratogenic factors affect transcription factor expression.

    Science.gov (United States)

    Kojima, Takuya; Asano, Shinya; Takahashi, Naoki

    2013-01-01

    Chemical compounds are produced every day, many with adverse effects on human health, and hence it is vital to predict the risks to humans simply, rapidly, and accurately. Teratogens have a serious impact on fetal development. This has been studied mainly by phenotypic analysis of experimental animals. However, since phenotypes can vary within different species, we established a new evaluation system based on our recent finding that teratogens influence Hox gene expression in mice. Similarly to the Hox gene expression changes, the expression patterns of several transcription factors involved in development, including the Dlx, Irx, Sall, and T-box families, were altered after 6 h of exposure to retinoic acid (RA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The expression changes in Dlx4, Dlx6, Irx5, Sall2, Sall3, Sall4, Tbx10, and Tbx22 were linked to teratogen-induced phenotypes, and our results indicate that expression changes in developmental transcription factors can help to predict teratogenic risk.

  14. TMDs, universality and factorization

    CERN Document Server

    D'Alesio, Umberto

    2011-01-01

    We present a short overview on transverse momentum dependent parton distribution and fragmentation functions, giving their partonic interpretation and ways to access them. We then discuss the issue of their universality and its connection to factorization in perturbative QCD.

  15. Factor V Leiden

    Science.gov (United States)

    ... increase your chance of developing abnormal blood clots (thrombophilia), usually in your veins. Most people with factor ... sharp tools. References Bauer KA. Management of inherited thrombophilia. http://www.uptodate.com/home. Accessed June 6, ...

  16. New microbial growth factor

    Science.gov (United States)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  17. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  18. Factor X assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  19. Factor XII assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  20. Rheumatoid Factors: Clinical Applications

    Directory of Open Access Journals (Sweden)

    Francesca Ingegnoli

    2013-01-01

    Full Text Available Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.

  1. Heart Disease Risk Factors

    Science.gov (United States)

    ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke Heart Disease Risk Factors Recommend ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke File Formats Help: How do ...

  2. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  3. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S.; DiPietro, L A

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  4. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  5. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  6. General Factors in Graphs.

    Science.gov (United States)

    1986-07-01

    conjectured that the general factor problem can be solved in polynomial time when, in each Bi, all the gaps (if any) have length one. We prove this conjecture...exactly bi edges incident with node i, for each i. This problem is well-solved. A polynomial algorithm is known (Edmonds and Johnson (1970)) as well as a...powerful theorem to characterize the existence of solutions ( Tutte (1952)). The following generalization of the factor problem was studied by Lovtsz

  7. Factors Impacting Knowledge Sharing

    DEFF Research Database (Denmark)

    Schulzmann, David; Slepniov, Dmitrij

    The purpose of this paper is to examine various factors affecting knowledge sharing at the R&D center of a Western MNE in China. The paper employs qualitative methodology and is based on the action research and case study research techniques. The findings of the paper advance our understanding...... about factors that affect knowledge sharing. The main emphasis is given to the discussion on how to improve knowledge sharing in global R&D organizations....

  8. Los factores de riesgo

    Directory of Open Access Journals (Sweden)

    Justo Senado Dumoy

    1999-01-01

    Full Text Available Sobre el fundamento filosófico de los conceptos de la Dialéctica Materialista, se presenta un análisis en relación con el concepto e interpretación de los Factores de Riesgo.A analysis on the concept and interpretation of risk factors is presented based on the philosophical foundation of the concepts of materialist dialectics.

  9. Factors affecting emotional divorce

    Directory of Open Access Journals (Sweden)

    Karim Said Shabanlou

    2016-03-01

    Full Text Available Emotional Divorce is the most important factor in the rupture of the most fundamental structures of society, the family.Due to the sensitivity and position of the familyAnd its functions specifically to investigate the factors underlying emotional divorce has of particular importance.Emotional Divorce phenomenon is not a single factor, but rather a set of related factors together led to Emotional Divorce.In this paper the role of psychological factors such as early maladaptive schemas, negative body image, perfectionism is discussed on an emotional divorce.Also quality of life and family relationships of couples with emotional divorce,Such as quality of health, sexual dissatisfaction, ignoring the needs, expectations and opinions of women by men or vice versa,And also social and economic factors such as subcultures families, couples, the quality of social relationships, social networks couple,Economic situation of the families of the couple, financial crisis, unemployment and economic revenues couples studied and some suggestions are presented based on the findings.

  10. Inducing goat pluripotent stem cells with four transcription factor mRNAs that activate endogenous promoters.

    Science.gov (United States)

    Chen, Hao; Zuo, Qisheng; Wang, Yingjie; Song, Jiuzhou; Yang, Huilin; Zhang, Yani; Li, Bichun

    2017-02-13

    Traditional approaches for generating goat pluripotent stem cells (iPSCs) suffer from complexity and low preparation efficiency. Therefore, we tried to derive goat iPSCs with a new method by transfecting exogenous Oct4, Sox2, Klf4 and c-Myc mRNAs into goat embryonic fibroblasts (GEFs), and explore the mechanisms regarding the transcription regulation of the reprogramming factors in goat iPSCs induction. mRNAs of the four reprogramming factors were transfected into GEFs, and were localized in nucleus with approximately 90% transfection efficiency. After five consecutive transfections, GEFs tended to aggregate by day 10. Clones appeared on day 15-18, and typical embryonic stem cell -like clones formed on day 20. One thousand AKP staining positive clones were achieved in 10(4) GEFs, with approximately 1.0% induction efficiency. Immunofluorescence staining and qRT-PCR detection of the ESCs markers confirmed the properties of the goat iPSCs. The achieved goat iPSCs could be cultured to 22nd passage, which showed normal karyotype. The goat iPSCs were able to differentiate into embryoid bodies with three germ layers. qRT-PCR and western blot showed activated endogenous pluripotent factors expression in the later phase of mRNA-induced goat iPSCs induction. Epigenetic analysis of the endogenous pluripotent gene Nanog revealed its demethylation status in derived goat iPSCs. Core promoter regions of the four reprogramming factors were determined. Transcription factor binding sites, including Elf-1, AP-2, SP1, C/EBP and MZF1, were identified to be functional in the core promoter regions of these reprogramming genes. Demethylation and deacetylation of the promoters enhanced their transcription activities. We successfully generated goat iPSCs by transfection of Oct4, Sox2, Klf4 and c-Myc mRNAs into GEFs, which initiated the endogenous reprogramming network and altered the methylation status of pluripotent genes. Core promoter regions and functional transcription binding sites of

  11. Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells.

    Science.gov (United States)

    Schwartz, Anton M; Putlyaeva, Lidia V; Covich, Milica; Klepikova, Anna V; Akulich, Kseniya A; Vorontsov, Ilya E; Korneev, Kirill V; Dmitriev, Sergey E; Polanovsky, Oleg L; Sidorenko, Svetlana P; Kulakovskiy, Ivan V; Kuprash, Dmitry V

    2016-10-01

    Signaling lymphocytic activation molecule family member 1 (SLAMF1)/CD150 is a co-stimulatory receptor expressed on a variety of hematopoietic cells, in particular on mature lymphocytes activated by specific antigen, costimulation and cytokines. Changes in CD150 expression level have been reported in association with autoimmunity and with B-cell chronic lymphocytic leukemia. We characterized the core promoter for SLAMF1 gene in human B-cell lines and explored binding sites for a number of transcription factors involved in B cell differentiation and activation. Mutations of SP1, STAT6, IRF4, NF-kB, ELF1, TCF3, and SPI1/PU.1 sites resulted in significantly decreased promoter activity of varying magnitude, depending on the cell line tested. The most profound effect on the promoter strength was observed upon mutation of the binding site for Early B-cell factor 1 (EBF1). This mutation produced a 10-20 fold drop in promoter activity and pinpointed EBF1 as the master regulator of human SLAMF1 gene in B cells. We also identified three potent transcriptional enhancers in human SLAMF1 locus, each containing functional EBF1 binding sites. Thus, EBF1 interacts with specific binding sites located both in the promoter and in the enhancer regions of the SLAMF1 gene and is critical for its expression in human B cells.

  12. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M

    2009-08-13

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198CG SNP (odds ratio8.6; P0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5?-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198CG SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression. © 2010 Macmillan Publishers Limited. All rights reserved.

  13. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis.

    Science.gov (United States)

    Heckmann, J M; Uwimpuhwe, H; Ballo, R; Kaur, M; Bajic, V B; Prince, S

    2010-01-01

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198C>G SNP (odds ratio=8.6; P=0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5'-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198C>G SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression.

  14. Hepatitis C Virus Activates a Neuregulin-Driven Circuit to Modify Surface Expression of Growth Factor Receptors of the ErbB Family.

    Directory of Open Access Journals (Sweden)

    Sabine Stindt

    Full Text Available Recently, the epidermal growth factor (EGF receptor (EGFR, a member of the ErbB receptor family, and its down-stream signalling have been identified as co-factors for HCV entry and replication. Since EGFR also functions as a heterodimer with other ErbB receptor family members, the subject of the present study was to investigate a possible viral interference with these cellular components. By using genotype 1b replicon cells as well as an infection-based system we found that while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, HCV induced a substantial reduction of ErbB3 and ErbB4 expression. Down-regulation of ErbB3 expression by HCV involves specificity protein (Sp1-mediated induction of Neuregulin (NRG1 expression as well as activation of Akt. Consistently, at transcript level disruption of ErbB3 expression by HCV can be prevented by knockdown of NRG1 or Sp1 expression, whereas reconstitution of ErbB3 protein levels requires inhibition of HCV-induced NRG1 expression and of Akt activity. Interestingly, the NRG1-mediated suppression of ErbB3 expression by HCV results in an enhanced expression of EGFR and ErbB2 on the cell surface, which can be mimicked by siRNA-mediated knockdown of ErbB3 expression. These data delineate a novel mechanism enabling HCV to sway the composition of the ErbB family members on the surface of its host cell by an NRG1-driven circuit and unravels a yet unknown cross-regulation between ErbB3 and the two other family members ErbB2 and EGFR. The shift of the receptor surface expression of the ErbB family towards enhanced expression of ErbB2 and EGFR triggered by HCV was found to promote viral RNA replication and infectivity. This suggests that HCV rearranges expression of ErbB family members to adapt the cellular environment to its requirements.

  15. CATTELL AND EYSENCK FACTOR SCORES RELATED TO COMREY PERSONALITY FACTORS.

    Science.gov (United States)

    Comrey, A L; Duffy, K E

    1968-10-01

    The Eysenck Personality Inventory, the Cattell 16 PF Inventory, and the Comrey Personality Inventory were administered to 272 volunteers. Eysenck and Cattell factor scores were correlated with scores over homogeneous item groups (FHIDs) which define the Comrey test factors. This matrix was factor analyzed to relate the Eysenck and Cattell factor scores to the factor structure underlying the Comrey test. The Eysenck Neuroticism, Comrey Neuroticism, and Cattell second-order Anxiety factors appeared to match. The Eysenck Introversion and the Comrey Shyness factors also matched. The 16 Cattell primary factors overlapped but did not match with the Comrey factors.

  16. Breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2015-09-01

    Full Text Available Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women’s ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual’s life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence.

  17. [Prognostic factors in resuscitation].

    Science.gov (United States)

    Bahloul, F; Le Gall, J R; Loirat, P; Alperovitch, A; Patois, E

    1988-10-08

    The outcome from intensive care is known to be influenced by such factors as age, previous health status, severity of the disease and diagnosis. In order to assess the influence of each individual factor, 3,687 patients from 38 French intensive care units were studied. For each patient were recorded: age, simplified acute physiological score (SAPS), previous health status, diagnosis, type of intensive care unit (medicine, scheduled or elective surgery) and immediate outcome. Each of these factors was found to influence the immediate survival rate. A multivariate analysis ranked the factors in the following order: SAPS, age, type of intensive care unit and previous health status. Diagnosis played a role in the prognosis since with a 10-15 points SAPS mortality was nil for drug overdose, 12 per cent for chronic obstructive pulmonary disease and 38 per cent for cardiogenic shock. However, a single diagnosis was made in only 37 per cent of the patients, as against 3 diagnoses in 17 per cent and 4 diagnoses or more in 7 per cent. When the type of intensive care unit was considered, the mean death rate was 20 per cent in medicine, 27 per cent in scheduled surgery and 5 per cent in elective surgery (P less than 0.001). Since this study showed a definite influence of each of the four factors on immediate survival, intensive care patients can be described and classified according to this system. However, it must be stressed that individual prognoses are extremely vague.

  18. Geothermal Plant Capacity Factors

    Energy Technology Data Exchange (ETDEWEB)

    Greg Mines; Jay Nathwani; Christopher Richard; Hillary Hanson; Rachel Wood

    2015-01-01

    The capacity factors recently provided by the Energy Information Administration (EIA) indicated this plant performance metric had declined for geothermal power plants since 2008. Though capacity factor is a term commonly used by geothermal stakeholders to express the ability of a plant to produce power, it is a term frequently misunderstood and in some instances incorrectly used. In this paper we discuss how this capacity factor is defined and utilized by the EIA, including discussion on the information that the EIA requests from operations in their 923 and 860 forms that are submitted both monthly and annually by geothermal operators. A discussion is also provided regarding the entities utilizing the information in the EIA reports, and how those entities can misinterpret the data being supplied by the operators. The intent of the paper is to inform the facility operators as the importance of the accuracy of the data that they provide, and the implications of not providing the correct information.

  19. Multi-factor authentication

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  20. The focus factor

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2015-01-01

    Introduction. We present a new bibliometric indicator to measure journal specialisation over time, named the focus factor. This new indicator is based on bibliographic coupling and counts the percentage of re-citations given in subsequent years. Method. The applicability of the new indicator....... To validate re-citations as caused by specialisation, other possible causes were measured and correlated (obsolescence, journal self-citations and number of references). Results. The results indicate that the focus factor is capable of distinguishing between general and specialised journals and thus...... effectively measures the intended phenomenon (i.e., journal specialisation). Only weak correlations were found between journal re-citations and obsolescence, journal self-citations, and number of references. Conclusions. The focus factor successfully measures journal specialisation over time. Measures based...

  1. La adolescencia: factores criticos

    Directory of Open Access Journals (Sweden)

    Noé Ardila Espinel

    1980-01-01

    Full Text Available Ten factors, tbat are considered by several psychologists as sensitive and characterístíc of the adolescent period, were tested by means of a Lykert type scale of 50 ítems, Seventy-eight subjects divided in three groups (U·13 years, early adolescence; 14·17 years, middle adolescence; 18-22 years, late adolescence answered the scale, Results índicate age differences. The factors that are in conflict duríng the middle adolescente are: emotional control, self control, social behavior, logical thinking, tendeney toward independency, economic índependency, family índependency, relígíous independency, rules conflict,and affective development, The factors change in direction before, during, and after adolescence

  2. Model Correction Factor Method

    DEFF Research Database (Denmark)

    Christensen, Claus; Randrup-Thomsen, Søren; Morsing Johannesen, Johannes

    1997-01-01

    The model correction factor method is proposed as an alternative to traditional polynomial based response surface techniques in structural reliability considering a computationally time consuming limit state procedure as a 'black box'. The class of polynomial functions is replaced by a limit...... statebased on an idealized mechanical model to be adapted to the original limit state by the model correction factor. Reliable approximations are obtained by iterative use of gradient information on the original limit state function analogously to previous response surface approaches. However, the strength...... of the model correction factor method, is that in simpler form not using gradient information on the original limit state function or only using this information once, a drastic reduction of the number of limit state evaluation is obtained together with good approximations on the reliability. Methods...

  3. Orthogonal factorizations of digraphs

    Institute of Scientific and Technical Information of China (English)

    Guizhen LIU

    2009-01-01

    Let G be a digraph with vertex set V(G) and arc set E(G) and let g = (g-,g+) and f = (f-, f+) be pairs of positive integer-valued functions defined on V(G) such that g-(x) ≤ f-(x) and g+(x) ≤ f+(x) for each x ∈ V(G). A (g, f)-factor of G is a spanning subdigraph H of G such that g-(x) ≤ idH(x) ≤ f-(x) and g+(x) ≤ odu(x) ≤ f+(x) for each x ∈ V(H); a (g, f)-factorization of G is a partition of E(G) into arc-disjoint (g, f)-factors. Let = {F1,F2,...,Fm} and H be a factorization and a subdigraph of G, respectively, is called k-orthogonal to H if each FI, 1 ≤ I ≤ m, has exactly k arcs in common with H. In this paper it is proved that every (mg+m-1, mf-m+1)-digraph has a (g, f)-factorization k-orthogonal to any given subdigraph with km arcs if k ≤ min{g-(x),g+(x)} for any x ∈ V(G) and that every (mg, mf)-digraph has a (g, f)-factorization orthogonal to any given directed m-star if 0 ≤ g(x) ≤ f(x) for any x ∈ V(G). The results in this paper are in some sense best possible.

  4. Factores de riesgo psicosocial

    OpenAIRE

    Fernández, Borja

    2012-01-01

    Tras un año de estudio de la Prevención de Riesgos Laborales he podido ir adquiriendo, todavía más, una clara concienciación sobre el estudio, supresión y mejora de los factores de riesgo que afectan a los trabajadores en la ejecución de su trabajo. Algo que es fácil de darse cuenta al entrar en profundidad en estas cuestiones, es de la escasa conciencia que tienen las organizaciones y los trabajadores sobre lo perjudiciales que pueden ser para su salud los factores de riesgo ergonómicos. ...

  5. Graph factors modulo k

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2014-01-01

    We prove a general result on graph factors modulo k . A special case says that, for each natural number k , every (12k−7)-edge-connected graph with an even number of vertices contains a spanning subgraph in which each vertex has degree congruent to k modulo 2k.......We prove a general result on graph factors modulo k . A special case says that, for each natural number k , every (12k−7)-edge-connected graph with an even number of vertices contains a spanning subgraph in which each vertex has degree congruent to k modulo 2k....

  6. Endodontic surgery prognostic factors.

    Science.gov (United States)

    Azarpazhooh, Amir; Shah, Prakesh S

    2011-01-01

    Medline, (PubMed) and the Cochrane databases together with hand searching of the following journals: Journal of Endodontics, International Endodontic Journal, Oral Surgery Oral Medicine Oral Pathology (name changed to Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontics in 1995), Endodontics and Dental Traumatology (name changed to Dental Traumatology in 2001), Journal of Oral and Maxillofacial Surgery, and International Journal of Oral and Maxillofacial Surgery. Clinical studies evaluating apical surgery with placement of a root-end filling were included. Studies on apical surgery with orthograde root canal filling or about apicectomy alone without root-end filling were excluded, as were experimental and animal studies. Only studies with ≥ ten patients with a minimum six month follow-up period and clearly defined radiographic and clinical healing criteria, with healing reported for at least two categories of a specific prognostic factor were accepted. Studies reporting in English, German, French, Spanish, Italian, Portuguese and Scandinavian languages were included. All studies were assessed separately by two of the three authors, with disagreements resolved by discussion. Prognostic factors were divided into patient related, tooth-related or treatment-related factors. The reported percentages of healed teeth were pooled per category. The statistical method of Mantel-Haenszel was applied to estimate the odds ratios and their 95% confidence intervals. Homogeneity was assessed using Woolf's test. With regard to tooth-related factors, the following were identified as predictors of healing: absence of preoperative pain or signs, good density of the root canal filling and a periapical lesion size of ≤ 5 mm. With regard to treatment-related factors, teeth treated with the use of an endoscope tended to have higher healed rates than teeth treated without the use of an endoscope. Although the clinician may be able to control treatment

  7. STEREOTYPICAL FACTORS IN TOURISM

    Directory of Open Access Journals (Sweden)

    Cristina-Elena ALBU

    2013-06-01

    Full Text Available International tourism has grown rapidly nowdays, contributing to the growth of the global economy. The purpose of this essay is to identify and analyze stereotypical factors in the development of strategies concerning the offer for the tourism industry: the image of a tourist destination, brand, country of origin and customer behaviour. Documentary study was the research method used: representative articles were analysed, as recent as possible, to determine the factors mentioned above. Professionals in the industry of tourism need to understand cultural differences between tourists, as well as those of the host country, to be able to create tourist reception offers that live up to the standards expected by clients.

  8. The transcription factor encyclopedia.

    Science.gov (United States)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  9. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  10. Factors stimulating content marketing

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2016-02-01

    Full Text Available This paper presents an empirical investigation to determine factors influencing on content marketing in banking industry. The study designs a questionnaire consists of 40 questions in Likert scale and distributes it among 550 randomly selected regular customers of Bank Mellat in city of Tehran, Iran and 400 properly filled questionnaires are collected. Cronbach alphas for all components of the survey are well above desirable level. Using principle component analysis with Varimax rotation, the study has determined six factors influencing the most on content marketing including organization, details, having new ideas, quality, sensitivity and power while the last component contains only two subcomponents and is removed from the study.

  11. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  12. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  13. Irrational factor races

    Indian Academy of Sciences (India)

    Sneha Chaubey; Milenda Lanius; Alexandru Zaharescu

    2014-11-01

    We investigate the behavior of the sum of the irrational factor function over arithmetic progressions. We first establish a general asymptotic formula for such a sum, and then obtain some further results in the case of arithmetic progressions 3 ± 1.

  14. Affective Factors: Anxiety

    Science.gov (United States)

    Tasnimi, Mahshad

    2009-01-01

    Affective factors seem to play a crucial role in success or failure in second language acquisition. Negative attitudes can reduce learners' motivation and harm language learning, while positive attitudes can do the reverse. Discovering students' attitudes about language will help both teacher and student in teaching learning process. Anxiety is…

  15. Hyperglycemia: a prothrombotic factor?

    NARCIS (Netherlands)

    B.A. Lemkes; J. Hermanides; J.H. Devries; F. Holleman; J.C.M. Meijers; J.B.L. Hoekstra

    2010-01-01

    Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and impaire

  16. FRUIT NUTRITIVE FACTOR NETWORK

    Institute of Scientific and Technical Information of China (English)

    Yanqing QU; Yumei JIANG; Daren HE

    2009-01-01

    As an research example of the widely existing cooperation-competition systems, the authors present an empirical investigation on a fruit nutritive factor network. It is described by a node-weighted bipartite graph. The fruit nutritive factors are defined as the nodes, and two nodes are connected by an edge if at least one fruit contains these two nutritive factors. The fruits are defined as the collaboration acts. The node-weight Writ, which signifies the "importance degree" of each actor node, is defined as the content of a nutritive factor in a fruit. The empirical investigation results show some unique features.The node-weight distributions take so-called "shifted power law" function forms, but the act-weight distribution takes a normal form. The degree and act-degree distributions show impulsive-spectrum like forms. These observations may be helpful for the study of fruits. The network description method proposed in this article may be universal for a kind of cooperation-competition systems.

  17. Environmental factors and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, L.

    1985-01-01

    Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. 35 references.

  18. Factor Analysis and AIC.

    Science.gov (United States)

    Akaike, Hirotugu

    1987-01-01

    The Akaike Information Criterion (AIC) was introduced to extend the method of maximum likelihood to the multimodel situation. Use of the AIC in factor analysis is interesting when it is viewed as the choice of a Bayesian model; thus, wider applications of AIC are possible. (Author/GDC)

  19. eta ' transition form factors

    NARCIS (Netherlands)

    Amo Sanchez, del P.; Raven, H.G.; Snoek, H.; BaBar, Collaboration

    2011-01-01

    eta((')) transition form factors in the momentum-transfer range from 4 to 40 GeV(2). The analysis is based on 469 fb(-1) of integrated luminosity collected at PEP-II with the BABAR detector at e(+)e(-) center-of-mass energies near 10.6 GeV.

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

    NARCIS (Netherlands)

    J.N.J. Philipsen (Sjaak); G. Suske

    1999-01-01

    textabstractOne 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

  1. Some Boletes of Thailand

    Directory of Open Access Journals (Sweden)

    Te-chato, S.

    2007-05-01

    Full Text Available The objective of this study was to collect and identify some Boletes of Thailand. Through periodical excursions in woodland area in the north, northeast and south of Thailand, and regular visits to markets inthe areas during 1995-2005, 20 species of Boletes were collected and identified. These were Boletellus ananas (M.A.Curtis Murrill, Boletellus emodensis (Berk. Singer, Boletellus sp. 1, Boletellus sp. 2, Boletellus sp. 3,Boletinus sp., Boletus griseipurpureus Corner, Boletus bicolor Peck, Boletus nanus (Massee. Singer, Boletus sp. 1, Boletus sp. 2, Boletus sp. 3, Heimiella retispora (Pat. & C.F. Baker Boedijn, Phlebopus colossus (R.Heim Singer, Phylloporus pelletieri (Lev. Quel., Pulveroboletus ravenelii (Berk. & M.A.Curtis Murrill, Pulveroboletus sp., Strobilomyces confusus Singer, Strobilomyces floccopus (Vahl P. Karst., and Tylopilusalbo - ater (Schwein Murrill.

  2. Identificar Factores de Riesgo

    Directory of Open Access Journals (Sweden)

    Luis Carlos Silva Ayçaguer

    2005-01-01

    Full Text Available Se exponen el contexto histórico y las condiciones en que se ha configurado lo que podría caracterizarse como una verdadera "cacería de factores de riesgo" en la epidemiología contemporánea. Entre otros problemas, se ha extendido la práctica de encarar el problema de la determinación o identificación de factores de riesgo a través de un ritual estadístico que roza la caricatura y, lo más importante, que la mayor parte de las veces no conduce a conseguir el objetivo de la investigación, ni a obtener nuevos conocimientos. El trabajo caracteriza dicho ritual y examina críticamente sus pasos. Se realiza una detallada discusión de la endeblez metodológica de tal procedimiento y se ilustra profusamente su empleo.

  3. Smad transcription factors.

    Science.gov (United States)

    Massagué, Joan; Seoane, Joan; Wotton, David

    2005-12-01

    Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-beta (TGFbeta) pathway. Recent progress has shed light into the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and assembly of transcriptional complexes. A rich repertoire of regulatory devices exerts control over each step of the Smad pathway. This knowledge is enabling work on more complex questions about the organization, integration, and modulation of Smad-dependent transcriptional programs. We are beginning to uncover self-enabled gene response cascades, graded Smad response mechanisms, and Smad-dependent synexpression groups. Our growing understanding of TGFbeta signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior.

  4. Precipitating factors of asthma.

    Science.gov (United States)

    Lee, T H

    1992-01-01

    Asthma is characterised by bronchial hyperresponsiveness. This feature of the asthmatic diathesis predisposes patients to wheezing in response to a number of different factors. These precipitating factors include specific allergen acting via sensitised mediator cells through an IgE-dependent mechanism. There are irritants which may work through a non-specific manner, or stimuli such as exercise and hyperventilation, which probably also act through mediator release via a non-IgE-dependent manner. The mechanism whereby physical stimuli such as exercise induce bronchoconstriction is of interest, because it increases the context in which the mast cell may participate in acute asthmatic bronchoconstriction. Respiratory infections also commonly provoke asthma, especially in infants and may, indeed, precipitate the asthmatic state itself. Finally, drugs can often trigger asthma attacks and the mechanisms of asthma precipitated by non-steroidal anti-inflammatory drugs such as aspirin have been the subject of recent research.

  5. Helicopter human factors

    Science.gov (United States)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  6. [Streptococcus pyogenes pathogenic factors].

    Science.gov (United States)

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection.

  7. Power factor compensation

    Energy Technology Data Exchange (ETDEWEB)

    Barra R, Felipe [Schneider Electric Chile (Chile)

    2010-07-01

    Every company is looking for ways to increase productivity as a way to gain a competitive advantage. Energy is a significant element in making any product and so it is important to assess production processes from an energy perspective. This paper discusses the impact of power factor compensation on energy efficiency. The life cycle solution for energy efficiency involves optimization of active energy using automation and regulation. A brief explanation is given of how each component of a company plays a part in this cycle. Examples include simulations and analysis, modeling, performance monitoring facilities, and environmental sustainability. Reactive energy suppliers and the installation of capacitors are also explained. Types of compensation include fixed and automation compensations. Economic advantages include a reduction in the electricity bill and active energy consumption. Technical advantages include reduction in voltage drop and an increase in available power. The power correction factor also improves reliability and contributes to conservation of the environment.

  8. On braid monodromy factorizations

    Energy Technology Data Exchange (ETDEWEB)

    Kharlamov, V M [Institut de Recherche Matematique Avanee Universite Louis Pasteur et CNRS 7 rue Rene Descartes (France); Kulikov, Vik S [Steklov Mathematical Institute, Russian Academy of Sciences (Russian Federation)

    2003-06-30

    We introduce and develop a language of semigroups over the braid groups to study the braid monodromy factorizations (bmf's) of plane algebraic curves and other related objects. As an application, we give a new proof of Orevkov's theorem on the realization of bmf's over a disc by algebraic curves and show that the complexity of such a realization cannot be bounded in terms of the types of factors of the bmf. We also prove that the type of a bmf distinguishes Hurwitz curves with singularities of inseparable type up to H-isotopy and J-holomorphic cuspidal curves in CP{sup 2} up to symplectic isotopy.

  9. The focus factor

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2015-01-01

    is demonstrated on a selection of general science journals and on a selection of medical journals. The reference lists of each journal are compared year by year, and the percentage of re-citations is calculated by dividing the number of re-citations with the total number of citations each year. Analysis......Introduction. We present a new bibliometric indicator to measure journal specialisation over time, named the focus factor. This new indicator is based on bibliographic coupling and counts the percentage of re-citations given in subsequent years. Method. The applicability of the new indicator....... To validate re-citations as caused by specialisation, other possible causes were measured and correlated (obsolescence, journal self-citations and number of references). Results. The results indicate that the focus factor is capable of distinguishing between general and specialised journals and thus...

  10. Cross-culturally recurrent personality factors : Analyses of three factors

    NARCIS (Netherlands)

    De Raad, B; Peabody, D

    2005-01-01

    This study proceeds from an earlier one that examined the 'Big Five' factors (Peabody & De Raad, 2002). That study considered the substantive nature of five factors from six European psycholexical studies. The results supported Big Five Factor III (Conscientiousness), but Factors I (Extraversion) an

  11. Information security factors systematization

    OpenAIRE

    Янченко, Вадим Николавевич; Ивченко, Александр Владимирович; Залога, Вильям Александрович; Дынник, Оксана Дмитриевна

    2015-01-01

    In this article the necessity of solving the theoretical and practical task, aimed on development the methodological basis for elaboration and implementation of information security management system, has been considered. Based on research results of scientific works and the requirements in the field of information security management the universal multilevel system of information security factors of organizations (enterprises) in the wood properties form was offered by using quality control ...

  12. The malingering factor.

    Science.gov (United States)

    Williams, J Michael

    2011-04-01

    The influence of malingering and suboptimal performance on neuropsychological tests has become a major interest of clinical neuropsychologists. Methods to detect malingering have focused on specialized tests or embedded patterns associated with malingering present in the conventional neuropsychology tests. There are two stages to the study of their validity. The first stage involves whether the method can discriminate malingering subjects from those who are not malingering. In the second stage, they must be examined for their relationship to the conventional tests used to establish impairment and disability. Constantinou, Bauer, Ashendorf, Fisher, and McCaffrey (2005. Is poor performance on recognition memory effort measures indicative of generalized poor performance on neuropsychological tests? Archives of Clinical Neuropsychology, 20, 191-198.) conducted the only study in which correlations are presented between a commonly used symptom validity test, the Test of Memory Malingering (TOMM) and the subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). A factor analysis was conducted using these correlations. It revealed a clear malingering factor that explained significant variance in the TOMM and the WAIS-R subtests. The relationship of malingering with cognitive tests is complex: some tests are sensitive to malingering and others are not. Factor analysis can summarize the magnitude of variance associated with each test and reveal the patterns of inter-relationships between malingering and clinical tests. The analysis also suggested that malingering assessment methods could be improved by the addition of timing the responses.

  13. Risk Factors for Cholelithiasis.

    Science.gov (United States)

    Pak, Mila; Lindseth, Glenda

    2016-01-01

    Gallstone disease is one of the most common public health problems in the United States. Approximately 10%-20% of the national adult populations currently carry gallstones, and gallstone prevalence is rising. In addition, nearly 750,000 cholecystectomies are performed annually in the United States; direct and indirect costs of gallbladder surgery are estimated to be $6.5 billion. Cholelithiasis is also strongly associated with gallbladder, pancreatic, and colorectal cancer occurrence. Moreover, the National Institutes of Health estimates that almost 3,000 deaths (0.12% of all deaths) per year are attributed to complications of cholelithiasis and gallbladder disease. Although extensive research has tried to identify risk factors for cholelithiasis, several studies indicate that definitive findings still remain elusive. In this review, predisposing factors for cholelithiasis are identified, the pathophysiology of gallstone disease is described, and nonsurgical preventive options are discussed. Understanding the risk factors for cholelithiasis may not only be useful in assisting nurses to provide resources and education for patients who are diagnosed with gallstones, but also in developing novel preventive measures for the disease.

  14. Nucleon Electromagnetic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Kees de Jager

    2004-08-01

    Although nucleons account for nearly all the visible mass in the universe, they have a complicated structure that is still incompletely understood. The first indication that nucleons have an internal structure, was the measurement of the proton magnetic moment by Frisch and Stern (1933) which revealed a large deviation from the value expected for a point-like Dirac particle. The investigation of the spatial structure of the nucleon, resulting in the first quantitative measurement of the proton charge radius, was initiated by the HEPL (Stanford) experiments in the 1950s, for which Hofstadter was awarded the 1961 Nobel prize. The first indication of a non-zero neutron charge distribution was obtained by scattering thermal neutrons off atomic electrons. The recent revival of its experimental study through the operational implementation of novel instrumentation has instigated a strong theoretical interest. Nucleon electro-magnetic form factors (EMFFs) are optimally studied through the exchange of a virtual photon, in elastic electron-nucleon scattering. The momentum transferred to the nucleon by the virtual photon can be selected to probe different scales of the nucleon, from integral properties such as the charge radius to scaling properties of its internal constituents. Polarization instrumentation, polarized beams and targets, and the measurement of the polarization of the recoiling nucleon have been essential in the accurate separation of the charge and magnetic form factors and in studies of the elusive neutron charge form factor.

  15. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  16. Accidents - personal factors

    Energy Technology Data Exchange (ETDEWEB)

    Zaitsev, S.L.; Tsygankov, A.V.

    1982-03-01

    This paper evaluates influence of selected personal factors on accident rate in underground coal mines in the USSR. Investigations show that so-called organizational factors cause from 80 to 85% of all accidents. About 70% of the organizational factors is associated with social, personal and economic features of personnel. Selected results of the investigations carried out in Donbass mines are discussed. Causes of miner dissatisfaction are reviewed: 14% is caused by unsatisfactory working conditions, 21% by repeated machine failures, 16% by forced labor during days off, 14% by unsatisfactory material supply, 16% by hard physical labor, 19% by other reasons. About 25% of miners injured during work accidents are characterized as highly professionally qualified with automatic reactions, and about 41% by medium qualifications. About 60% of accidents is caused by miners with less than a 3 year period of service. About 15% of accidents occurs during the first month after a miner has returned from a leave. More than 30% of accidents occurs on the first work day after a day or days off. Distribution of accidents is also presented: 19% of accidents occurs during the first 2 hours of a shift, 36% from the second to the fourth hour, and 45% occurs after the fourth hour and before the shift ends.

  17. Molecular factors in migraine

    Science.gov (United States)

    Kowalska, Marta; Prendecki, Michał; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

    2016-01-01

    Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease. PMID:27191890

  18. Relação entre fator de condição relativo (Kn e abundância de ectoparasitos de brânquias, em duas espécies de ciclídeos da bacia do rio Paraná, Brasil = Relation between the relative condition factor (Kn and the abundance of gill ectoparasites in two species of cichlids from the Paraná river basin, Brazil

    Directory of Open Access Journals (Sweden)

    Fábio Hideki Yamada

    2008-04-01

    Full Text Available Foram analisados 33 espécimes de Satanoperca pappaterra, capturados entre março de 2004 e junho de 2005, na planície de inundação do alto rio Paraná e 33 espécimes de Crenicichla niederleinii, capturados entre novembro de 2005 e novembro de 2006, no reservatório de Itaipu. Ambos estavam parasitados por monogenéticos, pertencentes ao gênero Sciadicleithrum e por metacercárias de Ascocotyle sp. O fator de condição relativo (Kn não diferiu significativamente entre indivíduos parasitados e não-parasitados das duas espécies de hospedeiros. Apenas Sciadicleithrum sp.1 parasito de S. pappaterra apresentou correlação positiva e significativa entre o fator de condição relativo (Kn e a abundância de parasitismo. Por outro lado, Ascocotyle sp. de ambos os hospedeiros e Sciadicleithrum sp.2parasito de C. niederleinii não apresentaram correlações entre o Kn e a abundância de parasitismo.The study analyzed 33 specimens of Satanoperca pappaterra, captured from the Upper Paraná River floodplain between March 2004 and June of 2005, and 33 specimens of Crenicichla niederleinii captured from the Itaipu Reservoir between November 2005 and November 2006. Both were parasitized by monogeneans pertaining to the genus Sciadicleithrum and by metacercariae of Ascocotyle sp. The relative condition factor (Kn did not differ significantly between parasitized and unparasitized individuals from the two host species. Only Sciadicleithrum sp.1, parasite of S. pappaterra, presented positive and significant correlation between the relative condition factor (Kn and the abundance of parasitism. On the other hand, Ascocotyle sp. in both hosts and Sciadicleithrum sp.2 parasite of C. niederleiniidid not present correlations between the Kn and the abundance of parasitism.

  19. Constant Phycobilisome Size in Chromatically Adapted Cells of the Cyanobacterium Tolypothrix tenuis, and Variation in Nostoc sp. 1

    Science.gov (United States)

    Ohki, Kaori; Gantt, Elisabeth; Lipschultz, Claudia A.; Ernst, Marjorie C.

    1985-01-01

    Phycobilisomes of Tolypothrix tenuis, a cyanobacterium capable of complete chromatic adaptation, were studied from cells grown in red and green light, and in darkness. The phycobilisome size remained constant irrespective of the light quality. The hemidiscoidal phycobilisomes had an average diameter of about 52 nanometers and height of about 33 nanometers, by negative staining. The thickness was equivalent to a phycocyanin molecule (about 10 nanometers). The molar ratio of allophycocyanin, relative to other phycobiliproteins always remained at about 1:3. Phycobilisomes from red light grown cells and cells grown heterotrophically in darkness were indistinguishable in their pigment composition, polypeptide pattern, and size. Eight polypeptides were resolved in the phycobilin region (17.5 to 23.5 kilodaltons) by isoelectric focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Half of these were invariable, while others were variable in green and red light. It is inferred that phycoerythrin synthesis in green light resulted in a one for one substitution of phycocyanin, thus retaining a constant phycobilisome size. Tolypothrix appears to be one of the best examples of phycobiliprotein regulation with wavelength. By contrast, in Nostoc sp., the decrease in phycoerythrin in red light cells was accompanied by a decrease in phycobilisome size but not a regulated substitution. Images Fig. 1 Fig. 2 Fig. 4 PMID:16664550

  20. Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer

    Science.gov (United States)

    Arora, Nivedita; Alsaied, Osama; Dauer, Patricia; Majumder, Kaustav; Modi, Shrey; Giri, Bhuwan; Dudeja, Vikas; Banerjee, Sulagna; Von Hoff, Daniel; Saluja, Ashok

    2017-01-01

    Background Gastric cancer is the third leading cause of cancer related mortality worldwide with poor survival rates. Even though a number of chemotherapeutic compounds have been used against this disease, stomach cancer has not been particularly sensitive to these drugs. In this study we have evaluated the effect of triptolide, a naturally derived diterpene triepoxide and its water soluble pro-drug Minnelide on several gastric adenocarcinoma cell lines both as monotherapy and in combination with CPT-11. Methods Gastric cancer cell lines MKN28 and MKN45 were treated with varying doses of triptolide in vitro. Cell viability was measured using MTT based assay kit. Apoptotic cell death was assayed by measuring caspase activity. Effect of the triptolide pro-drug, Minnelide, was evaluated by implanting the gastric cancer cells subcutaneously in athymic nude mice. Results Gastric cancer cell lines MKN28 and MKN45 cells exhibited decreased cell viability and increased apoptosis when treated with varying doses of triptolide in vitro. When implanted in athymic nude mice, treatment with Minnelide reduced tumor burden in both MKN28 derived tumors as well as MKN45 derived tumors. Additionally, we also evaluated Minnelide as a single agent and in combination with CPT-11 in the NCI-N87 human gastric tumor xenograft model. Conclusion Our results indicated that the combination of Minnelide with CPT-11 resulted in significantly smaller tumors compared to control. These studies are extremely encouraging as Minnelide is currently undergoing phase 1 clinical trials for gastrointestinal cancers. PMID:28192510

  1. Co-expression of a Saccharomyces diastaticus glucoamylase-encoding gene and a Bacillus amyloliquefaciens alpha-amylase-encoding gene in Saccharomyces cerevisiae.

    Science.gov (United States)

    Steyn, A J; Pretorius, I S

    1991-04-01

    A glucoamylase-encoding gene (STA2) from Saccharomyces diastaticus and an alpha-amylase-encoding gene (AMY) from Bacillus amyloliquefaciens were cloned separately into a yeast-integrating shuttle vector (YIp5), generating recombinant plasmids pSP1 and pSP2, respectively. The STA2 and AMY genes were jointly cloned into YIp5, generating plasmid pSP3. Subsequently, the dominant selectable marker APH1, encoding resistance to Geneticin G418 (GtR), was cloned into pSP3, resulting in pSP4. For enhanced expression of GtR, the APH1 gene was fused to the GAL10 promoter and terminated by the URA3 terminator, resulting in pSP5. Plasmid pSP5 was converted to a circular minichromosome (pSP6) by the addition of the ARS1 and CEN4 sequences. Laboratory strains of Saccharomyces cerevisiae transformed with plasmids pSP1 through pSP6, stably produced and secreted glucoamylase and/or alpha-amylase. Brewers' and distillers' yeast transformed with pSP6 were also capable of secreting amylolytic enzymes. Yeast transformants containing pSP1, pSP2 and pSP3 assimilated soluble starch with an efficiency of 69%, 84% and 93%, respectively. The major starch hydrolysis products produced by crude amylolytic enzymes found in the culture broths of the pSP1-, pSP2- and pSP3-containing transformants, were glucose, glucose and maltose (1:1), and glucose and maltose (3:1), respectively. These results confirmed that co-expression of the STA2 and AMY genes synergistically enhanced starch degradation.

  2. The Non-Classical Boltzmann Equation, and Diffusion-Based Approximations to the Boltzmann Equation

    CERN Document Server

    Frank, Martin; Larsen, Edward W; Vasques, Richard

    2014-01-01

    We show that several diffusion-based approximations (classical diffusion or SP1, SP2, SP3) to the linear Boltzmann equation can (for an infinite, homogeneous medium) be represented exactly by a non-classical transport equation. As a consequence, we indicate a method to solve diffusion-based approximations to the Boltzmann equation via Monte Carlo, with only statistical errors - no truncation errors.

  3. Perinatal risk factors for strabismus

    DEFF Research Database (Denmark)

    Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry;

    2010-01-01

    Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype.......Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype....

  4. Milestones and Impact Factors

    Directory of Open Access Journals (Sweden)

    Grandjean Philippe

    2010-07-01

    Full Text Available Abstract Environmental Health has just received its first Impact Factor by Thomson ISI. At a level of 2.48, this achievement is quite satisfactory and places Environmental Health in the top 25% of environmental science journals. When the journal was launched in 2002, it was still unclear whether the Open Access publishing model could be made into a viable commercial enterprise within the biomedical field. During the past eight years, Open Access journals have become widely available, although still covering only about 15% of journal titles. Major funding agencies and institutions, including prominent US universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent of digital media and its decentralized mode of distribution - the internet - have dramatically changed the control and financing of scientific information dissemination, while facilitating peer review, accelerating editorial handling, and supporting much needed transparency. Both the meaning and means of "having an impact" are therefore changing, as will the degree and way in which scientific journals remain "factors" in that impact.

  5. Milestones and impact factors.

    Science.gov (United States)

    Ozonoff, David M; Grandjean, Philippe

    2010-07-08

    Environmental Health has just received its first Impact Factor by Thomson ISI. At a level of 2.48, this achievement is quite satisfactory and places Environmental Health in the top 25% of environmental science journals. When the journal was launched in 2002, it was still unclear whether the Open Access publishing model could be made into a viable commercial enterprise within the biomedical field. During the past eight years, Open Access journals have become widely available, although still covering only about 15% of journal titles. Major funding agencies and institutions, including prominent US universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent of digital media and its decentralized mode of distribution - the internet - have dramatically changed the control and financing of scientific information dissemination, while facilitating peer review, accelerating editorial handling, and supporting much needed transparency. Both the meaning and means of "having an impact" are therefore changing, as will the degree and way in which scientific journals remain "factors" in that impact.

  6. A New Factorization Method to Factorize RSA Public Key Encryption

    Directory of Open Access Journals (Sweden)

    Bhagvant Ram Ambedkar

    2011-11-01

    Full Text Available The security of public key encryption such as RSA scheme relied on the integer factoring problem. The security of RSA algorithm is based on positive integer N, because each transmitting node generates pair of keys such as public and private. Encryption and decryption of any message depends on N. Where, N is the product of two prime numbers and pair of key generation is dependent on these prime numbers. The factorization of N is very intricate. In this paper a New Factorization method is proposed to obtain the factor of positive integer N. The proposed work focuses on factorization of all trivial and nontrivial integer numbers and requires fewer steps for factorization process of RSA modulus N. The New Factorization method is based on Pollard rho factorization method. Experimental results shown that factorization speed is fast as compare existing methods.

  7. Cultural Factors in Reading

    Institute of Scientific and Technical Information of China (English)

    孔敏

    2005-01-01

    Reading is a basic ability in learning English and reading comprehension exercise is a common way to assess this ability.Since reading is a communicative activity between author and reader in written form,there are some different rules and regulations of this communication in different countries.Therefore,cultural factors,existing in reading,decide,help,and influence the percentage of the right answers.This article attempts to analyze the effects of cultural differences in reading and the barriers in comprehension,and aims to improve students awareness of cultural differences in reading.

  8. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  9. Auxin response factors.

    Science.gov (United States)

    Chandler, John William

    2016-05-01

    Auxin signalling involves the activation or repression of gene expression by a class of auxin response factor (ARF) proteins that bind to auxin response elements in auxin-responsive gene promoters. The release of ARF repression in the presence of auxin by the degradation of their cognate auxin/indole-3-acetic acid repressors forms a paradigm of transcriptional response to auxin. However, this mechanism only applies to activating ARFs, and further layers of complexity of ARF function and regulation are being revealed, which partly reflect their highly modular domain structure. This review summarizes our knowledge concerning ARF binding site specificity, homodimer and heterodimer multimeric ARF association and cooperative function and how activator ARFs activate target genes via chromatin remodelling and evolutionary information derived from phylogenetic comparisons from ARFs from diverse species. ARFs are regulated in diverse ways, and their importance in non-auxin-regulated pathways is becoming evident. They are also embedded within higher-order transcription factor complexes that integrate signalling pathways from other hormones and in response to the environment. The ways in which new information concerning ARFs on many levels is causing a revision of existing paradigms of auxin response are discussed.

  10. Robust and Sparse Factor Modelling

    DEFF Research Database (Denmark)

    Croux, Christophe; Exterkate, Peter

    Factor construction methods are widely used to summarize a large panel of variables by means of a relatively small number of representative factors. We propose a novel factor construction procedure that enjoys the properties of robustness to outliers and of sparsity; that is, having relatively few...... nonzero factor loadings. Compared to the traditional factor construction method, we find that this procedure leads to a favorable forecasting performance in the presence of outliers and to better interpretable factors. We investigate the performance of the method in a Monte Carlo experiment...

  11. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... targeting specific cis-acting elements in genes, and by the significant lack of fixed tertiary structure in their extensive intrinsically disordered regions. Recent research in protein intrinsic disorder (ID) has changed our understanding of transcriptional activation domains from 'negative noodles' to ID...... them to participate in large interactomes, how they use only a few hydrophobic residues, short sequence motifs, prestructured motifs, and coupled folding and binding for their interactions with co-activators, and how their accessibility to post-translational modification affects their interactions...

  12. Pion form factor

    Energy Technology Data Exchange (ETDEWEB)

    Ryong Ji, C.; Pang, A.; Szczepaniak, A. [North Carolina State Univ., Raleigh, NC (United States)

    1994-04-01

    It is pointed out that the correct criterion to define the legal PQCD contribution to the exclusive processes in the lightcone perturbative expansion should be based on the large off-shellness of the lightcone energy in the intermediate states. In the lightcone perturbative QCD calculation of the pion form factor, the authors find that the legal PQCD contribution defined by the lightcone energy cut saturates in the smaller Q{sup 2} region compared to that defined by the gluon four-momentum square cut. This is due to the contribution by the highly off-energy-shell gluons in the end point regions of the phase space, indicating that the gluon four-momentum-square cut may have cut too much to define the legal PQCD.

  13. Unity power factor converter

    Science.gov (United States)

    Wester, Gene W. (Inventor)

    1980-01-01

    A unity power factor converter capable of effecting either inversion (dc-to-dc) or rectification (ac-to-dc), and capable of providing bilateral power control from a DC source (or load) through an AC transmission line to a DC load (or source) for power flow in either direction, is comprised of comparators for comparing the AC current i with an AC signal i.sub.ref (or its phase inversion) derived from the AC ports to generate control signals to operate a switch control circuit for high speed switching to shape the AC current waveform to a sine waveform, and synchronize it in phase and frequency with the AC voltage at the AC ports, by selectively switching the connections to a series inductor as required to increase or decrease the current i.