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Sample records for factor sp1 leads

  1. 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

  2. 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.

  3. 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.

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

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    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.

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

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    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.

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

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    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.

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

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    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

  8. 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.

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

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    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

  10. 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.

  11. 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.

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

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    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.

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

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    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.

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

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    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

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

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    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.

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

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    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.

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

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    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

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

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    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.

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

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    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.

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

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    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.

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

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    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.

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

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    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

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

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    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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

    Science.gov (United States)

    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.

  18. 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...

  19. 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...

  20. 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.

  1. 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

  2. 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.

  3. 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.

    Science.gov (United States)

    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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. KEY PERFORMING FACTORS OF LEADING ROMANIAN COMPANIES

    Directory of Open Access Journals (Sweden)

    BURJA CAMELIA

    2014-08-01

    Full Text Available The analysis of financial economic ratios provides managers and external partners feedback on the results obtained from operational activities and the associated performance and risks. This paper studies the functional dependence of the companies’ success (on performance over internal financial management elements. The research was carried out for the most traded non-financial securities Bucharest listed companies and covers the period 2011- 2013. To carry out its purpose it analyzed the interdependence between the key financial ratios, studying the impact of liquidity ratios, solvency and efficiency on profitability. The study provides empirical evidences to identify factors that have ensured the performance of companies and their ranking in the segment of the most traded companies in Romania. Results suggest the view that the source of company success on the capital market lies in the positive signals sent to investors regarding profitability and the low risk of solvency. This study gives additional information for managerial decision-making in order to create more value and a better positioning of the companies in the market

  7. 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.

  8. Influence of social factors on lead exposure and child development

    Energy Technology Data Exchange (ETDEWEB)

    Bornschein, R.L.

    1985-10-01

    A brief overview of current views of child development is provided, with particular attention given to the role the child's physical and social environment plays in influencing the developmental process. Examples from the recent literature are used to illustrate how these factors can influence lead exposure and most importantly how they might interact with lead to ameliorate or exacerbate possible lead effects. An example is provided which demonstrates that failure to control adequately and to adjust the data statistically to correct for the influence of these factors can lead one erroneously to attribute cognitive and behavioral changes to lead. Finally, data from the Cincinnati Prospective Lead Study are presented to illustrate the application of structural equation modeling as a means for unraveling the complex web of sociodemographic, environmental and behavioral influences on childhood lead exposure.

  9. Factorization breaking in dijet photoproduction with a leading neutron

    Science.gov (United States)

    Klasen, M.; Kramer, G.

    2007-03-01

    The production of dijets with a leading neutron in ep interactions at HERA is calculated in leading order and next-to-leading order of perturbative QCD using a pion-exchange model. Differential cross sections for deep-inelastic scattering and photoproduction are presented as a function of several kinematic variables. By comparing the theoretical predictions for DIS dijets to recent H1 data, the pion flux factor together with the parton distribution functions of the pion is determined. The dijet cross sections in photoproduction show factorization breaking if compared to the H1 photoproduction data. The suppression factor is S=0.48 (0.64) for resolved (global) suppression.

  10. Factorization breaking in dijet photoproduction with a leading neutron

    Energy Technology Data Exchange (ETDEWEB)

    Klasen, M. [Universite Joseph Fourier/CNRS-IN2P3, Laboratoire de Physique Subatomique et de Cosmologie, Grenoble (France); Universitaet Hamburg, II. Institut fuer Theoretische Physik, Hamburg (Germany); Kramer, G. [Universitaet Hamburg, II. Institut fuer Theoretische Physik, Hamburg (Germany)

    2007-03-15

    The production of dijets with a leading neutron in ep interactions at HERA is calculated in leading order and next-to-leading order of perturbative QCD using a pion-exchange model. Differential cross sections for deep-inelastic scattering and photoproduction are presented as a function of several kinematic variables. By comparing the theoretical predictions for DIS dijets to recent H1 data, the pion flux factor together with the parton distribution functions of the pion is determined. The dijet cross sections in photoproduction show factorization breaking if compared to the H1 photoproduction data. The suppression factor is S=0.48 (0.64) for resolved (global) suppression. (orig.)

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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).

  13. Influence of social and environmental factors on dust, lead, hand lead, and blood lead levels in young children

    Energy Technology Data Exchange (ETDEWEB)

    Bornschein, R.L.; Succop, P.; Dietrich, K.N.; Clark, C.S.; Que Hee, S.; Hammond, P.B.

    1985-10-01

    The roles of environmental and behavioral factors in determining blood lead levels were studied in a cohort of young children living in an urban environment. The subjects were observed at 3-month intervals from birth to 24 months of age. Repeated measurements were made of the children's blood lead levels, environmental levels of lead in house dust, and in the dust found on the children's hands. A qualitative rating of the residence and of the socioeconomic status of the family was obtained. Interviews and direct observation of parent and child at home were used to evaluate various aspects of caretaker-child interactions. Data analysis consisted of a comparison of results obtained by (a) simple correlational analysis, (b) multiple regression analysis, and (c) structural equations analysis. The results demonstrated that structural equation modeling offers a useful approach to unraveling the complex interactions present in the data set. In this preliminary analysis, the suspected relationship between the levels of lead in house dust and on hands and the blood lead level was clearly demonstrated. Furthermore, the analyses indicated an important interplay between environmental sources and social factors in the determination of hand lead and blood lead levels in very young children.

  14. 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.

  15. A Study of the Factors Leading English Teachers to Burnout

    Science.gov (United States)

    Cephe, Pasa Tevfik

    2010-01-01

    This paper reports a research study carried out on teacher burnout with a group of English instructors (N=44) in order to identify the major factor(s) leading instructors to burnout at various levels. A survey research model was first applied to find out the instructors (N=37) with a burnout problem and categorize them at different levels of…

  16. A Study of the Factors Leading English Teachers to Burnout

    Science.gov (United States)

    Cephe, Pasa Tevfik

    2010-01-01

    This paper reports a research study carried out on teacher burnout with a group of English instructors (N=44) in order to identify the major factor(s) leading instructors to burnout at various levels. A survey research model was first applied to find out the instructors (N=37) with a burnout problem and categorize them at different levels of…

  17. Environmental lead exposure among preschool children in Shanghai, China: blood lead levels and risk factors.

    Directory of Open Access Journals (Sweden)

    Jia Cao

    Full Text Available OBJECTIVE: To determine blood lead levels and to identify related risk factors among children in Shanghai; to explore the lead change trend of children after industrial transformation and to provide data for policy development to control environmental lead pollution in Shanghai. METHODS: A stratified-clustered-random sampling method was used. A tungsten atomizer absorption spectrophotometer was employed to determine blood lead levels. RESULTS: The arithmetic mean, geometric mean and median of blood lead levels of 0- to 6-year-old children from Shanghai were 22.49 µg/L, 19.65 µg/L and 19.5 µg/L, including 0.26% (6/2291 with concentrations ≥100 µg/L and 2.7% (61/2291 with concentrations ≥50 µg/L. Boys' levels (23.57 µg/L were greater than those of girls (21.2 µg/L. The blood lead levels increased with age. This survey showed that the Chongming district was the highest and Yangpu district was the lowest, this result is completely opposite with the earlier survey in Shanghai. Risk factors for lead contamination included housing environment, parents' education levels, social status, hobbies, and children's nutritional status. CONCLUSIONS: The blood lead levels of children in Shanghai were lower than the earlier data of Shanghai and those of published studies in China, but higher than the blood lead levels of developed countries. The blood lead levels of urban districts are higher than the central districts with the industrial transformation. Society and the government should take an active interest in childhood lead poisoning of urban areas.

  18. 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.

  19. 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.

  20. Factorization breaking in dijet photoproduction with a leading neutron

    Energy Technology Data Exchange (ETDEWEB)

    Klasen, M. [Universite Joseph Fourier/CNRS-IN2P3, Grenoble (France). Lab. de Physique Subatomique et de Cosmologie]|[Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Kramer, G. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2006-08-15

    The production of dijets with a leading neutron in ep-interactions at HERA is calculated in leading order and next-to-leading order of perturbative QCD using a pion-exchange model. Differential cross sections for deep-inelastic scattering (DIS) and photoproduction are presented as a function of several kinematic variables. By comparing the theoretical predictions for DIS dijets to recent H1 data, the pion flux factor together with the parton distribution functions of the pion is determined. The dijet cross sections in photoproduction show factorization breaking if compared to the H1 photoproduction data. The suppression factor is S=0.48(0.64) for resolved (global) suppression. (orig.)

  1. Factorization Breaking in Dijet Photoproduction with a Leading Neutron

    CERN Document Server

    Klasen, M

    2007-01-01

    The production of dijets with a leading neutron in ep-interactions at HERA is calculated in leading order and next-to-leading order of perturbative QCD using a pion-exchange model. Differential cross sections for deep-inelastic scattering (DIS) and photoproduction are presented as a function of several kinematic variables. By comparing the theoretical predictions for DIS dijets to recent H1 data, the pion flux factor together with the parton distribution functions of the pion is determined. The dijet cross sections in photoproduction show factorization breaking if compared to the H1 photoproduction data. The suppression factor is S = 0.48 (0.64) for resolved (global) suppression.

  2. 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.

  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. Blood lead levels and risk factors for lead poisoning among children in Jakarta, Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Albalak, Rachel; Noonan, Gary; Buchanan, Sharunda; Flanders, W. Dana; Gotway-Crawford, Carol; Blumenthal, Wendy; Curtis, Gerald; McGeehin, Michael A. [Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention, 1600 Clifton Rd. Mailstop E-19, Atlanta, GA 30333 (United States); Kim, Dennis; Tan, Regina [Epidemic Intelligence Service, Epidemiology Program Office, Centers for Disease Control and Prevention, 1600 Clifton Rd. Mailstop D-18, Atlanta, GA 30333 (United States); Jones, Robert L. [Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 1600 Clifton Rd. Mailstop F-18, Atlanta, GA 30333 (United States); Sulaiman, Rini [Swisscontact, Jl. Wijaya XII No. 44, Jakarta (Indonesia) 12160

    2003-01-01

    The phase-out of leaded gasoline began in Jakarta, Indonesia on July 1, 2001. We evaluated mean blood lead levels (BLLs) and the prevalence of elevated BLLs of Jakarta school children and assessed risk factors for lead exposure in these children before the beginning of the phase-out activities. The study involved a population-based, cross-sectional blood lead survey that included capillary blood lead sampling and a brief questionnaire on risk factors for lead poisoning. A cluster survey design was used. Forty clusters, defined as primary schools in Jakarta, and 15 2nd- and 3rd-grade children in each cluster were randomly selected for participation in the study. The average age of children in this study was 8.6 years (range 6-12) and the geometric mean BLL of the children was 8.6 {mu}g/dl (median: 8.6 {mu}g/dl; range: 2.6-24.1 {mu}g/dl) (n=397). Thirty-five percent of children had BLLs {>=}10 {mu}g/dl and 2.4% had BLLs {>=}20 {mu}g/dl. Approximately one-fourth of children had BLLs 10-14.9 {mu}g/dl. In multivariate models, level of education of the child's primary caregiver, water collection method, home varnishing and occupational recycling of metals, other than lead, by a family member were predictors of log BLLs after adjustment for age and sex. BLLs of children who lived near a highway or major intersection were significantly higher than those of children who lived near a street with little or no traffic when level of education was not included in the model. Water collection method was a significant predictor of BLLs {>=}10 {mu}g/dl after adjustment for age and sex. BLLs in children in this study were moderately high and consistent with BLLs of children in other countries where leaded gasoline is used. With the phase-out of leaded gasoline, BLLs of children in Jakarta are expected to rapidly decline as they have in other countries that have phased lead out of gasoline.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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.

  8. Preliminary Study on Causative Factors Leading to Construction Cost Overrun

    Directory of Open Access Journals (Sweden)

    Aftab Hameed Memon

    2011-07-01

    Full Text Available Cost is the fundamental component for any construction project. However, cost overrun is observed as one of the most frequently occurring issues in construction projects worldwide and need to be studied more to alleviate this issue in the future. This trend is more severe in developing countries where these overruns sometimes exceeds 100% of the anticipated cost of the project.   Like other countries, construction industry in Malaysia is also facing a lot of challenges such as the delay to complete the project in time, the expenditure exceeding the budget, the building defects and over dependent of foreign workers. The ultimate effects of project delay also results in exceeding cost. This leads to serious need of addressing the critical issue of construction cost overrun. To avoid construction cost overrun, very first and most important step is to identify and understand the causes and factors responsible for that. Hence, this paper is aimed to identify various factors responsible for construction cost overrun. Through a comprehensive study of literature review, common factors causing cost overrun resulting in identification of 78 factors were mapped in frequency table. A questionnaire survey and interviews were carried out amongst selected experienced personnel for expert opinion to identify the significant factors causing cost overrun in Malaysia. Five respondents were selected from each of the respondents groups including client, consultant and contractor. The questionnaire responses were analyzed by average index method, which resulted in identification of 59 common factors causing construction cost overrun in Malaysia. Results show that poor design & delays in Design, unrealistic contract duration & requirements imposed, lack of experience, late delivery of materials & equipment, relationship between management & labour, delay preparation & approval of drawings, inadequate planning & scheduling, poor site management & supervision and

  9. Lead

    Science.gov (United States)

    ... found? Who is at risk? What are the health effects of lead? Get educational material about lead Get certified as a Lead Abatement Worker, or other abatement discipline Lead in drinking water Lead air pollution Test your child Check and maintain your home ...

  10. 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.

  11. Factors leading to refractory asthma in patients from Saudi Arabia

    Science.gov (United States)

    Al-Moamary, Amal M.; Al-Hajjaj, Mohamed S.; Al Moamary, Mohamed S.

    2017-01-01

    AIM: The aim of this study was to study the clinical characteristic of patient with refractory asthma (RA) from Saudi Arabia. METHODS: This paper prospectively studied in a university hospital factors leading to RA in a cohort of patients who have inadequately controlled asthma or with frequent exacerbations despite optimum controller therapy. It also studied patients with asthma that requires extended periods of oral steroids to control. RESULTS: The mean age was 45.1 years (±9.1) where 74 patients were enrolled in this study with the age group (37–48 years) is having the highest percentage (64.8%). Female patients represented 62.2%. The two major comorbid conditions were allergic rhinitis (54.1%) and gastroesophageal reflux (33.8%). The vast majority (72 patients) had at least one trigger factor for asthma (97.3%). The asthma control test showed that 86.4% had an uncontrolled status. Spirometry showed mild disease in 9.5%, moderate in 47.3%, and severe in 43.2%. Eosinophilia was seen in only 16.2%. Immunoglobulin E level between 70 and 700 μg/L was found in 58.1% of patients. CONCLUSION: RA has certain clinical characteristics and associated comorbid conditions as well as precipitating factors that facilitate the identifications of these cases. PMID:28197221

  12. 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.

  13. 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

  14. Investigation and Evaluation of Children's Blood Lead Levels around a Lead Battery Factory and Influencing Factors.

    Science.gov (United States)

    Zhang, Feng; Liu, Yang; Zhang, Hengdong; Ban, Yonghong; Wang, Jianfeng; Liu, Jian; Zhong, Lixing; Chen, Xianwen; Zhu, Baoli

    2016-05-28

    Lead pollution incidents have occurred frequently in mainland China, which has caused many lead poisoning incidents. This paper took a battery recycling factory as the subject, and focused on measuring the blood lead levels of environmental samples and all the children living around the factory, and analyzed the relationship between them. We collected blood samples from the surrounding residential area, as well as soil, water, vegetables. The atomic absorption method was applied to measure the lead content in these samples. The basic information of the generation procedure, operation type, habit and personal protect equipment was collected by an occupational hygiene investigation. Blood lead levels in 43.12% of the subjects exceeded 100 μg/L. The 50th and the 95th percentiles were 89 μg/L and 232 μg/L for blood lead levels in children, respectively, and the geometric mean was 94 μg/L. Children were stratified into groups by age, gender, parents' occupation, distance and direction from the recycling plant. The difference of blood lead levels between groups was significant (p factory, the higher the value of BLL and lead levels in vegetable and environment samples. The lead level in the environmental samples was higher downwind of the recycling plant.

  15. 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.

  16. Lead

    Science.gov (United States)

    ... Chapter 6 Chapter 7 Chapter 8 Chapter 9 Appendix I Appendix II Tables Figures State Programs Alabama Alaska Arizona ... Tool Kit Resources Healthy Homes and Lead Poisoning Prevention Training Center (HHLPPTC) Training Tracks File Formats Help: ...

  17. 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

  18. Risk factors for lead complications in cardiac pacing

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nøhr, Ellen Aagaard;

    2011-01-01

    Lead complications are the main reason for reoperation after implantation of pacemakers (PM) or cardiac resynchronization therapy (CRT-P) devices.......Lead complications are the main reason for reoperation after implantation of pacemakers (PM) or cardiac resynchronization therapy (CRT-P) devices....

  19. Factors affecting lead release in sodium silicate-treated partial lead service line replacements.

    Science.gov (United States)

    Zhou, Emily; Payne, Sarah Jane O; Hofmann, Ron; Andrews, Robert C

    2015-01-01

    Water quality parameters affecting sodium silicate performance in partial lead service line replacements were examined using a fractional factorial experimental design and static pipe systems. An external copper wire was used to create a galvanic connection between a former lead service line and a new copper pipe. The pipe systems were filled with lab prepared water made to mimic real water quality. Water was changed on a three times per week basis. A 2(4-1) fractional factorial design was used to evaluate the impact of alkalinity (15 mg L(-1) or 250 mg L(-1) as CaCO3), nitrate (1 mg L(-1) or 7 mg L(-1) as N), natural organic matter (1 mg L(-1) or 7 mg L(-1) as dissolved organic carbon), and disinfectant type (1 mg L(-1) chlorine or 3 mg L(-1) monochloramine), resulting in eight treatment conditions. Fractional factorial analysis revealed that alkalinity, natural organic matter and monochloramine had a significant positive effect on galvanic current. Natural organic matter and monochloramine also had a significant positive effect with respect to both total and dissolved lead release. For the treatment conditions examined, 67-98% of the lead released through galvanic currents was stored as corrosion scales and predominantly comprised of particulate lead (96.1-99.9%) for all eight treatments. The use of monochloramine and the presence of natural organic matter (7 mg L(-1)) were not favourable for corrosion control in sodium silicate-treated partial lead service line replacements, although further studies would be required to characterize optimal water quality parameters for specific water quality types. For utilities operating with sodium silicate as a corrosion inhibitor, this work offers further evidence regarding the consideration of chlorine as a secondary disinfectant instead of monochloramine, as well as the value of controlling natural organic matter in distributed water.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Factors Leading to Students' Satisfaction in the Higher Learning Institutions

    Science.gov (United States)

    Siming, Luo; Niamatullah; Gao, Jianying; Xu, Dan; Shaf, Khurrum

    2015-01-01

    There is an increasing need to understand factors that affect satisfaction of students with learning. This study will explore the relationship between student satisfaction and teacher-student relationship, teacher preparedness, campus support facilities and experiences provided by the institute to the students. Study is a necessary activity that…

  5. 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.

  6. 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.

  7. 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.

  8. Investigation and Evaluation of Children’s Blood Lead Levels around a Lead Battery Factory and Influencing Factors

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2016-05-01

    Full Text Available Lead pollution incidents have occurred frequently in mainland China, which has caused many lead poisoning incidents. This paper took a battery recycling factory as the subject, and focused on measuring the blood lead levels of environmental samples and all the children living around the factory, and analyzed the relationship between them. We collected blood samples from the surrounding residential area, as well as soil, water, vegetables. The atomic absorption method was applied to measure the lead content in these samples. The basic information of the generation procedure, operation type, habit and personal protect equipment was collected by an occupational hygiene investigation. Blood lead levels in 43.12% of the subjects exceeded 100 μg/L. The 50th and the 95th percentiles were 89 μg/L and 232 μg/L for blood lead levels in children, respectively, and the geometric mean was 94 μg/L. Children were stratified into groups by age, gender, parents’ occupation, distance and direction from the recycling plant. The difference of blood lead levels between groups was significant (p < 0.05. Four risk factors for elevated blood lead levels were found by logistic regression analysis, including younger age, male, shorter distance from the recycling plant, and parents with at least one working in the recycling plant. The rate of excess lead concentration in water was 6.25%, 6.06% in soil and 44.44% in leaf vegetables, which were all higher than the Chinese environment standards. The shorter the distance to the factory, the higher the value of BLL and lead levels in vegetable and environment samples. The lead level in the environmental samples was higher downwind of the recycling plant.

  9. 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.

  10. 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.

  11. Mortality factors and lead contamination of wild birds from Korea.

    Science.gov (United States)

    Nam, Dong-Ha; Lee, Doo-Pyo

    2011-07-01

    Wild birds have frequently been found dead in their natural habitats, but little is known about what ecological stressors may impact health of wild populations. Here, we report the potentially harmful lead (Pb) levels in tissues along with necropsies on 69 individuals of cranes, raptors, and waterfowl found dead between 2000 and 2003 in Korea. In all samples diagnosed, trauma (n = 22), severe emaciation (n = 15), and infectious diseases (n = 11) were identified. In the survey, injury with Pb shot or bullet fragments was associated with three of the deaths; one of three showed lesions suggestive of Pb poisoning in the tissues. Of 69 birds, 12 had >25 ppm dry wt. (equivalent to 8 ppm wet wt.) in liver or kidney, which is known to be a potentially lethal level of Pb in wild birds. Three individuals had hepatic Pb levels of 101.3 ppm (Whooper swan), 120.4 ppm (Great white-fronted goose), and 1,059 ppm (Mandarin duck), with evidence of Pb pellets in their gizzard. This study suggests that many birds examined may be suffering from excessive Pb exposure that may be of health concern with respect to a potential cause of their mortality. The need for additional research is heightened when considering that some migrants are classified as a globally protected species by the International Union for the Conservation of Nature.

  12. 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.

  13. Blood lead levels and risk factors for lead poisoning in children and caregivers in Chuuk State, Micronesia.

    Science.gov (United States)

    Brown, Lisa M; Kim, Dennis; Yomai, Anamaria; Meyer, Pamela A; Noonan, Gary P; Huff, Daniel; Flanders, W D

    2005-01-01

    Lead poisoning is a preventable environmental disease. Children and developing fetuses are especially vulnerable; even low blood lead levels (BLLs) are linked with learning and behavioral problems. We assessed children's and their caregivers' BLLs and risk factors for lead exposure in Chuuk State, Federated States of Micronesia. Children aged 2-6 years were randomly selected within 20 randomly selected villages. Children and caregivers provided venous blood, and caregivers offered information about possible risk factors for lead exposure. Mean BLLs were 39 microg/l for children and 16 microg/l for caregivers. Children with BLLs of > or = 100 microg/l (elevated) were 22.9 (95% CI: 4.5-116.0) times more likely to have a caregiver with an elevated BLL, 6.2 (95% CI: 1.4-27.3) times more likely to live on an outer island, and 3.4 (95% CI: 1.7-6.9) times more likely to have a family member who made lead fishing weights than did other children even after controlling for age and sex. For children, 61% of elevated BLLs could be attributed to making fishing weights. Caregivers with elevated BLLs were 5.9 (95% CI: 1.5-23.7) times more likely to live in a household that melted batteries than other caregivers even after controlling for age and education. For caregivers, 37% of the elevated BLLs could be attributed to melting batteries. The association of elevated BLLs in children and their caregiver suggests a common environmental exposure. Melting batteries to make fishing sinkers is a preventable source of lead exposure for children and their caregivers in Chuuk. Published by Elsevier GmbH.

  14. 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?

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Lead in New York City Community Garden Chicken Eggs: Influential Factors and Health Implications

    Science.gov (United States)

    Spliethoff, Henry M.; Mitchell, Rebecca G.; Ribaudo, Lisa N.; Taylor, Owen; Shayler, Hannah A.; Greene, Virginia; Oglesby, Debra

    2014-01-01

    Raising chickens for eggs in urban areas is becoming increasingly common. Urban chickens may be exposed to lead, a common urban soil contaminant. We measured lead concentrations in chicken eggs from New York City (NYC) community gardens and collected information on factors that might affect those concentrations. Lead was detected between 10 and 167 μg/kg in 48% of NYC eggs. Measures of lead in eggs from a henhouse were significantly associated (plead concentrations in soil. The association between soil and egg lead has been evaluated only once before, by a study of a rural region in Belgium. In our study, the apparent lead soil-to-egg transfer efficiency was considerably lower than that found in Belgium, suggesting that there may be important geographic differences in this transfer. We developed models that suggested that, for sites like ours, lead concentrations in >50% of eggs from a henhouse would exceed store-bought egg concentrations (lead concentrations >120 mg/kg, and that the concentration in one of six eggs from a henhouse would exceed a 100 μg/kg guidance value at soil lead concentrations >410 mg/kg. Our models also suggested that the availability of dietary calcium supplements was another influential factor that reduced egg lead concentrations. Estimates of health risk from consuming eggs with the lead concentrations we measured generally were not significant. However, soil lead concentrations in this study were lead transfer to chicken eggs and associated exposure are recommended for urban chicken keepers. PMID:24287691

  20. 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.

  1. Prenatal exposure to lead in Spain: cord blood levels and associated factors.

    Science.gov (United States)

    Llop, Sabrina; Aguinagalde, Xabier; Vioque, Jesus; Ibarluzea, Jesús; Guxens, Mònica; Casas, Maribel; Murcia, Mario; Ruiz, María; Amurrio, Ascensión; Rebagliato, Marisa; Marina, Loreto Santa; Fernandez-Somoano, Ana; Tardon, Adonina; Ballester, Ferran

    2011-05-01

    Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. ≥ vs < 2μg/dL). A low percentage of cord blood samples with lead levels ≥ 2μg/dL were found (5.9%). Geometric mean and maximum were 1.06μg/dL and 19μg/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels ≥ 2μg/dL. In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. A factorization approach to next-to-leading-power threshold logarithms

    NARCIS (Netherlands)

    Bonocore, D.; Laenen, E.; Magnea, L.; Melville, S.; Vernazza, L.; White, C. D.

    2015-01-01

    Threshold logarithms become dominant in partonic cross sections when the selected final state forces gluon radiation to be soft or collinear. Such radiation factorizes at the level of scattering amplitudes, and this leads to the resummation of threshold logarithms which appear at leading power in th

  4. PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

    Science.gov (United States)

    Swaddiwudhipong, Witaya; Kavinum, Suporn; Papwijitsil, Ratchadaporn; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Umpan, Jiraporn; BoonthuM, Ratchaneekorn; Kaewnate, Yingyot; Boonmee, Sasis; Thongchub, Winai; Rodsung, Thassanee

    2014-11-01

    A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population.

  5. 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

  6. Association of dental enamel lead levels with risk factors for environmental exposure.

    Science.gov (United States)

    Olympio, Kelly Polido Kaneshiro; Naozuka, Juliana; Oliveira, Pedro Vitoriano; Cardoso, Maria Regina Alves; Bechara, Etelvino José Henriques; Günther, Wanda Maria Risso

    2010-10-01

    To analyze household risk factors associated with high lead levels in surface dental enamel. A cross-sectional study was conducted with 160 Brazilian adolescents aged 1418 years living in poor neighborhoods in the city of Bauru, southeastern Brazil, from August to December 2008. Body lead concentrations were assessed in surface dental enamel acid-etch microbiopsies. Dental enamel lead levels were measured by graphite furnace atomic absorption spectrometry and phosphorus levels were measured by inductively coupled plasma optical emission spectrometry. The parents answered a questionnaire about their children's potential early (05 years old) exposure to well-known lead sources. Logistic regression was used to identify associations between dental enamel lead levels and each environmental risk factor studied. Social and familial covariables were included in the models. The results suggest that the adolescents studied were exposed to lead sources during their first years of life. Risk factors associated with high dental enamel lead levels were living in or close to a contaminated area (OR = 4.49; 95% CI: 1.69;11.97); and member of the household worked in the manufacturing of paints, paint pigments, ceramics or batteries (OR = 3.43; 95% CI: 1.31;9.00). Home-based use of lead-glazed ceramics, low-quality pirated toys, anticorrosive paint on gates and/or sale of used car batteries (OR = 1.31; 95% CI: 0.56;3.03) and smoking (OR = 1.66; 95% CI: 0.52;5.28) were not found to be associated with high dental enamel lead levels. Surface dental enamel can be used as a marker of past environmental exposure to lead and lead concentrations detected are associated to well-known sources of lead contamination.

  7. Association of dental enamel lead levels with risk factors for environmental exposure

    Directory of Open Access Journals (Sweden)

    Kelly Polido Kaneshiro Olympio

    2010-10-01

    Full Text Available OBJECTIVE: To analyze household risk factors associated with high lead levels in surface dental enamel. METHODS: A cross-sectional study was conducted with 160 Brazilian adolescents aged 14-18 years living in poor neighborhoods in the city of Bauru, southeastern Brazil, from August to December 2008. Body lead concentrations were assessed in surface dental enamel acid-etch microbiopsies. Dental enamel lead levels were measured by graphite furnace atomic absorption spectrometry and phosphorus levels were measured by inductively coupled plasma optical emission spectrometry. The parents answered a questionnaire about their children's potential early (05 years old exposure to well-known lead sources. Logistic regression was used to identify associations between dental enamel lead levels and each environmental risk factor studied. Social and familial covariables were included in the models. RESULTS: The results suggest that the adolescents studied were exposed to lead sources during their first years of life. Risk factors associated with high dental enamel lead levels were living in or close to a contaminated area (OR = 4.49; 95% CI: 1.69;11.97; and member of the household worked in the manufacturing of paints, paint pigments, ceramics or batteries (OR = 3.43; 95% CI: 1.31;9.00. Home-based use of lead-glazed ceramics, low-quality pirated toys, anticorrosive paint on gates and/or sale of used car batteries (OR = 1.31; 95% CI: 0.56;3.03 and smoking (OR = 1.66; 95% CI: 0.52;5.28 were not found to be associated with high dental enamel lead levels. CONCLUSIONS: Surface dental enamel can be used as a marker of past environmental exposure to lead and lead concentrations detected are associated to well-known sources of lead contamination.

  8. Exploring Contributing Factors Leading to the Decision to Drop out of School by Hispanic Males

    Science.gov (United States)

    Kent, Jennifer; Jones, Don; Mundy, Marie-Anne; Isaacson, Carrie

    2017-01-01

    The purpose of this study was to identify factors leading Hispanic male students in a mid-sized community in South Texas to dropping out of school, and to determine which, if any, of the factors caused the participant to first consider leaving school at an early age. This quantitative study tested academic systems within Tinto's theory of…

  9. Lead in New York City community garden chicken eggs: influential factors and health implications.

    Science.gov (United States)

    Spliethoff, Henry M; Mitchell, Rebecca G; Ribaudo, Lisa N; Taylor, Owen; Shayler, Hannah A; Greene, Virginia; Oglesby, Debra

    2014-08-01

    Raising chickens for eggs in urban areas is becoming increasingly common. Urban chickens may be exposed to lead, a common urban soil contaminant. We measured lead concentrations in chicken eggs from New York City (NYC) community gardens and collected information on factors that might affect those concentrations. Lead was detected between 10 and 167 μg/kg in 48 % of NYC eggs. Measures of lead in eggs from a henhouse were significantly associated (p 50 % of eggs from a henhouse would exceed store-bought egg concentrations (120 mg/kg and that the concentration in one of six eggs from a henhouse would exceed a 100 μg/kg guidance value at soil lead concentrations >410 mg/kg. Our models also suggested that the availability of dietary calcium supplements was another influential factor that reduced egg lead concentrations. Estimates of health risk from consuming eggs with the lead concentrations we measured generally were not significant. However, soil lead concentrations in this study were <600 mg/kg, and considerably higher concentrations are not uncommon. Efforts to reduce lead transfer to chicken eggs and associated exposure are recommended for urban chicken keepers.

  10. The Risk Factors of Child Lead Poisoning in China: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    You Li

    2016-03-01

    Full Text Available Background: To investigate the risk factors of child lead poisoning in China. Methods: A document retrieval was performed using MeSH (Medical subject heading terms and key words. The Newcastle-Ottawa Scale (NOS was used to assess the quality of the studies, and the pooled odd ratios with a 95% confidence interval were used to identify the risk factors. We employed Review Manager 5.2 and Stata 10.0 to analyze the data. Heterogeneity was assessed by both the Chi-square and I2 tests, and publication bias was evaluated using a funnel plot and Egger’s test. Results: Thirty-four articles reporting 13,587 lead-poisoned children met the inclusion criteria. Unhealthy lifestyle and behaviors, environmental pollution around the home and potential for parents’ occupational exposure to lead were risk factors of child lead poisoning in the pooled analyses. Our assessments yielded no severe publication biases. Conclusions: Seventeen risk factors are associated with child lead poisoning, which can be used to identify high-risk children. Health education and promotion campaigns should be designed in order to minimize or prevent child lead poisoning in China.

  11. Effect of lead factors on the embrittlement of RPV SA-508 cl 3 steel

    Energy Technology Data Exchange (ETDEWEB)

    Kempf, Rodolfo, E-mail: kempf@cnea.gov.ar [CNEA, Unidad Actividad Combustibles Nucleares, División Caracterización, Avda. Gral Paz 1499, C.P.B1650KNA, San Martín, Buenos Aires (Argentina); Troiani, Horacio, E-mail: troiani@cab.cnea.gov.ar [Centro Atómico Bariloche (CNEA) e Instituto Balseiro (UNCU), CONICET, Av. Bustillo 9500, CP 8400, Rio Negro (Argentina); Fortis, Ana Maria, E-mail: fortis@cnea.gov.ar [CNEA, Departamento Estructura y Comportamiento, UNSAM, Avda. Gral Paz 1499, C.P.B1650KNA, San Martín, Buenos Aires (Argentina)

    2013-03-15

    This paper presents a project to study the effect of lead factors on the mechanical behaviour of the SA-508 type 3 Reactor Pressure Vessel (RPV) steel used in the reactor under construction Atucha II in Argentina. Charpy-V notch specimens of this steel were irradiated at the RA1 experimental reactor at a temperature of 275 °C with two lead factors (186 and 93). The neutron flux was 3.71 × 10{sup 15} n m{sup −2} s{sup −1} and 1.85 × 10{sup 15} n m{sup −2} s{sup −1} (E > 1 MeV) respectively. In both cases, the fluence was 6.6 × 10{sup 21} n m{sup −2}, which is equivalent to that received by the PHWR Atucha II RPV in 10 years of full power irradiation. The results of Charpy tests revealed significant embrittlement both in the ΔT = 14 °C and ΔT = 21 °C shifts of the ductile–brittle transition temperatures (DBTT) and in the reduction of the maximum energy absorbed. This result shows that the shift of the DBTT with a lead factor of 93 is larger than that obtained with a lead factor of 186. Then, the results of irradiation in experimental reactors (MTR) with high lead factors may not be conservative with respect to the actual RPV embrittlement.

  12. Prenatal exposure to lead in Spain: Cord blood levels and associated factors

    Energy Technology Data Exchange (ETDEWEB)

    Llop, Sabrina, E-mail: llop_sab@gva.es [Centre of Public Health Research (CSISP), Av Catalunya 21, 46020, Valencia (Spain); Carlos III Health Institute (ISCIII), 20220 Majadahonda, Madrid (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Aguinagalde, Xabier [Public Health Laboratory of Alava, Direccion de Salud Publica, Gobierno Vasco, Santiago 11, 01002, Vitoria-Gasteiz, Basque Country (Spain); Vioque, Jesus [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Universidad Miguel Hernandez, Av de Alicante KM 87, 03550, Sant Joan d' Alacant (Spain); Ibarluzea, Jesus [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Departamento de Sanidad Gobierno Vasco, Subdireccion de Salud Publica de Gipuzkoa, Avenida de Navarra 4, 20013 San Sebastian (Spain); Biodonostia, Instituto de Investigacion Biomedica, San Sebastian (Spain); Guxens, Monica [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); Casas, Maribel [Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); Murcia, Mario [Centre of Public Health Research (CSISP), Av Catalunya 21, 46020, Valencia (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Ruiz, Maria [Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); and others

    2011-05-01

    Introduction and Objective: Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). Methods: A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. {>=} vs < 2 {mu}g/dL). Results: A low percentage of cord blood samples with lead levels {>=} 2 {mu}g/dL were found (5.9%). Geometric mean and maximum were 1.06 {mu}g/dL and 19 {mu}g/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels {>=} 2 {mu}g/dL. Conclusion: In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. - Research Highlights: {yields} Pb is a ubiquitous environmental pollutant with harmful effects on neurodevelopment. {yields} Cord blood Pb levels in

  13. 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.

  14. 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.

  15. 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.

  16. Lead ingestion as a potential contributing factor to the decline in vulture populations in southern Africa.

    Science.gov (United States)

    Naidoo, V; Wolter, K; Botha, C J

    2017-01-01

    Vulture populations in southern Africa have been on the decline for years, which unlike the Asian vulture crisis, has no one specific cause. Reasons attributable are deliberate and secondary poisonings, drowning, power line injuries, electrocutions, traditional medicine ("muti" trade) and calcium deficiencies. However, lead toxicity as a potential causal factor is hardly mentioned. The potential for lead toxicity needs to be considered as substantial game hunting occurs in the region with little regulatory control on bullet types. In this study, we determined the whole blood lead concentrations of captive and wild vulture populations in South Africa and Namibia (n=185). Results were compared to previous published ranges indicative of background exposure (lead concentrations were higher for wild African White-backed vultures (Gyps africanus)(AWBV) than Cape vultures (G. coprotheres)(CGV) at 15.54±12.63μg/dL vs 12.53±8.88μg/dL (non-significantly different), while in the Bearded vultures (Gypaetus barbatus) no indication of exposure was evident. Very similar exposures resulted irrespective of the birds being in captivity or under wild, free-roaming conditions. A proportion of wild birds did, however, appear to be exposed to another source of lead than purely environmental (±12% and 30.6% for AWBV and CGV respectively). One bird, which had a whole blood concentration of 100μg/dL, died soon after capture. To find the relationship between whole blood lead concentration and likely exposure factors, birds were compared by their rural/urban location, vicinity to mines and surrounding soil lead concentrations. With no relationship being present for the latter factors, we believe that this is evidence that the portion of southern African vultures being exposed to unknown source of lead, which we suggest arises from leaded ammunition remaining from hunting. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Effect of occupational exposure to lead on new risk factors for cardiovascular diseases.

    Science.gov (United States)

    Prokopowicz, Adam; Sobczak, Andrzej; Szuła-Chraplewska, Magdalena; Zaciera, Marzena; Kurek, Jolanta; Szołtysek-Bołdys, Izabela

    2017-05-01

    The cardiovascular effects of lead are caused primarily through an effect on blood pressure but are not just limited to an increased risk of hypertension. The aim of our study was to determine to what extent chronic exposure to lead affects new risk factors for cardiovascular disease (CVD) development, such as biomarkers of inflammation (C reactive protein (CRP) and fibrinogen) and biomarkers of endothelial dysfunction (homocysteine, asymmetric dimethylarginine (ADMA) and L-homoarginine). A cross-sectional study was performed on a sample of 231 male volunteers, aged 20-60 years, working for at least 2 years in jobs with exposure to lead during the mining and processing of lead-zinc ores. The association between lead in blood and CVD biomarkers was evaluated using multiple linear regression, and the effects of exposure level were observed in workers divided into subgroups according to their blood lead concentration: 400 µg/L. Lead in the blood correlated with new risk factors for CVD except for ADMA. Multiple regression analysis revealed that predictive properties for lead in the blood increased for particular biomarkers in the following order: L-homoarginine, fibrinogen, CRP and homocysteine. Among the specified groups, significant differences were observed only between the groups with the most and least exposure to lead, which differed in concentrations by 54.3% for CRP, 19.3% for fibrinogen, 10.6% for homocysteine and -25.5% for L-homoarginine. These findings support the hypothesis that occupational exposure to lead can promote atherosclerosis, particularly in highly exposed individuals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Quantitative and qualitative factors that leads to slip and fall incidents

    CERN Document Server

    Syahrom, Ardiyansyah; Tap, Masine Md; Rohani, Jafri Mohd

    2017-01-01

    This book investigates the factors that lead to slip and fall incidents and establishes a relationship between the coefficient of friction (COF), floor slipperiness and floor roughness. It also examines human perception of slipperiness through measured coefficient of friction (COF). On the basis of questionnaire surveys among manufacturing workers, it identifies potential risk factors and assesses human perceptions of slipperiness. It also uses a tribology approach to relate the interaction between contaminants, floor and footwear materials.

  19. Understanding Factors Leading to Participation in Supplemental Instruction Programs in Introductory Accounting Courses

    Science.gov (United States)

    Goldstein, James; Sauer, Paul; O'Donnell, Joseph

    2014-01-01

    Although studies have shown that supplemental instruction (SI) programs can have positive effects in introductory accounting courses, these programs experience low participation rates. Thus, our study is the first to examine the factors leading to student participation in SI programs. We do this through a survey instrument based on the Theory of…

  20. A factorization approach to next-to-leading-power threshold logarithms

    CERN Document Server

    Bonocore, D; Magnea, L; Melville, S; Vernazza, L; White, C D

    2015-01-01

    Threshold logarithms become dominant in partonic cross sections when the selected final state forces gluon radiation to be soft or collinear. Such radiation factorizes at the level of scattering amplitudes, and this leads to the resummation of threshold logarithms which appear at leading power in the threshold variable. In this paper, we consider the extension of this factorization to include effects suppressed by a single power of the threshold variable. Building upon the Low-Burnett-Kroll-Del Duca (LBKD) theorem, we propose a decomposition of radiative amplitudes into universal building blocks, which contain all effects ultimately responsible for next-to-leading power (NLP) threshold logarithms in hadronic cross sections for electroweak annihilation processes. In particular, we provide a NLO evaluation of the "radiative jet function", responsible for the interference of next-to-soft and collinear effects in these cross sections. As a test, using our expression for the amplitude, we reproduce all abelian-lik...

  1. [Factors associated with the blood levels of lead in residents of Mexico City].

    Science.gov (United States)

    Lara-Flores, E; Alagón-Cano, J; Bobadilla, J L; Hernández-Prado, B; Ciscomani-Begoña, A

    1989-01-01

    A study aimed at detecting risk factors for high blood lead levels in Mexico City inhabitants, undertaken at the local National Institute of Public Health, is described. Measurements of blood lead levels for a sample of 300 civil servants were related to several potential risk factors. The statistical analysis was based on analysis of variance and logistic regression. The results of the analysis seem to suggest differences in blood levels by sex, zone of residence, hours of transportation and eating habits, such as the consumption of canned meals and the use of "earthenware dishes" in the preparation of meals. The nature of the study is exploratory, but it seems to suggest directions of research in the complex problem of lead levels in people of polluted cities.

  2. 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.

  3. Investigation and Evaluation of Children’s Blood Lead Levels around a Lead Battery Factory and Influencing Factors

    Science.gov (United States)

    Zhang, Feng; Liu, Yang; Zhang, Hengdong; Ban, Yonghong; Wang, Jianfeng; Liu, Jian; Zhong, Lixing; Chen, Xianwen; Zhu, Baoli

    2016-01-01

    Lead pollution incidents have occurred frequently in mainland China, which has caused many lead poisoning incidents. This paper took a battery recycling factory as the subject, and focused on measuring the blood lead levels of environmental samples and all the children living around the factory, and analyzed the relationship between them. We collected blood samples from the surrounding residential area, as well as soil, water, vegetables. The atomic absorption method was applied to measure the lead content in these samples. The basic information of the generation procedure, operation type, habit and personal protect equipment was collected by an occupational hygiene investigation. Blood lead levels in 43.12% of the subjects exceeded 100 μg/L. The 50th and the 95th percentiles were 89 μg/L and 232 μg/L for blood lead levels in children, respectively, and the geometric mean was 94 μg/L. Children were stratified into groups by age, gender, parents’ occupation, distance and direction from the recycling plant. The difference of blood lead levels between groups was significant (p recycling plant, and parents with at least one working in the recycling plant. The rate of excess lead concentration in water was 6.25%, 6.06% in soil and 44.44% in leaf vegetables, which were all higher than the Chinese environment standards. The shorter the distance to the factory, the higher the value of BLL and lead levels in vegetable and environment samples. The lead level in the environmental samples was higher downwind of the recycling plant. PMID:27240393

  4. 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

  5. An Analysis of the Factors Leading to Rising Credit Risk in the Zimbabwe Banking Sector

    Directory of Open Access Journals (Sweden)

    Maxwell Sandada

    2016-02-01

    Full Text Available The study sought to analyse the factors that lead to rising credit risk in the Zimbabwean banking sector. The objective was to ascertain the impact of macroeconomic, industry and bank specific factors on rising credit risk in in Zimbabwe. The study aimed at contributing to credit risk management literature by providing evidence Sub Saharan context. Being anchored on the positivist quantitative research approach, a survey was carried out gather the data that were analysed using descriptive, correlation and regression analyses. The results revealed that the most significant factors leading to credit risk in the Zimbabwean banking sector were macroeconomic and bank specific factors. The industry factors did not show a significant influence on the rising credit risk. The research findings of this study will a valuable addition to the existing knowledge and provide a platform for further research on how the credit risk problems can be dealt with. While credit risk is known as one of the risks inherent to any banking institutions, the alarming levels of credit risk in the Zimbabwe banking sector has motivated this current study to critically analyse the factors that have led to the high credit risk levels.

  6. The ρ-meson time-like form factors in sub-leading pQCD

    Science.gov (United States)

    de Melo, J. P. B. C.; Ji, Chueng-Ryong; Frederico, T.

    2016-12-01

    The annihilation/production process e+ +e- →ρ+ +ρ- is studied with respect to the universal perturbative QCD (pQCD) predictions. Sub-leading contributions are considered together with the universal leading pQCD amplitudes such that the matrix elements of the ρ-meson electromagnetic current satisfy the constraint from the light-front angular condition. The data from the BaBar collaboration for the time-like ρ-meson form factors at √{ s} = 10.58 GeV puts a stringent test to the onset of asymptotic pQCD behavior. The e+ +e- →ρ+ +ρ- cross-section for s between 60 GeV2 and 160 GeV2 is predicted where the sub-leading contributions are still considerable.

  7. The ρ-meson time-like form factors in sub-leading pQCD

    Directory of Open Access Journals (Sweden)

    J.P.B.C. de Melo

    2016-12-01

    Full Text Available The annihilation/production process e++e−→ρ++ρ− is studied with respect to the universal perturbative QCD (pQCD predictions. Sub-leading contributions are considered together with the universal leading pQCD amplitudes such that the matrix elements of the ρ-meson electromagnetic current satisfy the constraint from the light-front angular condition. The data from the BaBar collaboration for the time-like ρ-meson form factors at s=10.58 GeV puts a stringent test to the onset of asymptotic pQCD behavior. The e++e−→ρ++ρ− cross-section for s between 60 GeV2 and 160 GeV2 is predicted where the sub-leading contributions are still considerable.

  8. Calculation of point isotropic buildup factors of gamma rays for water and lead

    Directory of Open Access Journals (Sweden)

    A. S. H.

    2001-12-01

    Full Text Available   Exposure buildup factors for water and lead have been calculated by the Monte-Carlo method for an isotropic point source in an infinite homogeneous medium, using the latest cross secions available on the Internet. The types of interactions considered are ,photoelectric effect, incoherent (or bound-electron Compton. Scattering, coherent (or Rayleigh scattering and pair production. Fluorescence radiations have also been taken into acount for lead. For each material, calculations were made at 10 gamma ray energies in the 40 keV to 10 MeV range and up to penetration depths of 10 mean free paths at each energy point. The results presented in this paper can be considered as modified gamma ray exposure buildup factors and be used in radiation shielding designs.

  9. Factors affecting lead and cadmium levels in house dust in industrial areas of eastern Germany.

    Science.gov (United States)

    Meyer, I; Heinrich, J; Lippold, U

    1999-08-30

    The indoor exposure of 381 women (52-59 years old) to lead and cadmium was assessed by measuring the levels of the contaminants in sedimented house dust. The study was conducted in the areas surrounding the towns of Hettstedt, a region of mining and smelting of non-ferrous ores, of Bitterfeld, a centre of chemical production and coal mining, and of Zerbst, a primarily agricultural area. Factors that were significantly associated with lead and cadmium surface loading rates included the city area of residence, urban environment of dwelling, ventilation behaviour, type of heating, year of construction of building and crowding in the sampling room. In metal-contaminated areas, the transport of heavy metals into the home from external sources and their subsequent resuspension into the air due to normal household activities are significant factors in the exposure to heavy metals, whereas in unpolluted areas indoor sources play the major role.

  10. Psychosocial and Cultural Factors Related to Risky Sexual Behavior Leading to HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Levent Kiylioglu

    2016-12-01

    Full Text Available Starting from adolescence, importance of sexuality increases in the lives of young people. When done without necessary prevention measures, sexuality may lead to deadly infections in health. Of them, perhaps the most important is HIV/AIDS. Although resulting from sexual behavior the probability of HIV transmission is low, AIDS can be deadly. The aim of this study is to review psycho-social and cultural factors claimed to explain and related with risky sexual behavior that can lead to HIV/AIDS. These factors are gender roles, religiosity, sexual sensation seeking, self-efficacy for AIDS prevention, and HIV/AIDS knowledge. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(4.000: 367-379

  11. The inhibiting factors that principal investigators experience in leading publicly funded research projects

    OpenAIRE

    Cunningham, James; O'Reilly, Paul; O'Kane, Conor; Mangematin, Vincent

    2014-01-01

    International audience; Securing public funding to conduct research and leading it by being a principal investigator (PI) is seen as significant career development step. Such a role brings professional prestige but also new responsibilities beyond research leadership to research management. If public funding brings financial and infrastructure support, little is understood about the inhibiting factors that publicly funded PIs face given the research autonomy offered by publicly funded researc...

  12. The Gluon-Induced Mueller-Tang Jet Impact Factor at Next-to-Leading Order

    CERN Document Server

    Hentschinski, Martin; Murdaca, Beatrice; Vera, Agustín Sabio

    2014-01-01

    We complete the computation of the Mueller-Tang jet impact factor at next-to-leading order (NLO) initiated in arXiv:1406.5625 and presented in arXiv:1404.2937 by computing the real corrections associated to gluons in the initial state making use of Lipatov's effective action. NLO corrections for this effective vertex are an important ingredient for a reliable description of large rapidity gap phenomenology within the BFKL approach.

  13. 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.

  14. Leading-edge flow criticality as a governing factor in leading-edge vortex initiation in unsteady airfoil flows

    Science.gov (United States)

    Ramesh, Kiran; Granlund, Kenneth; Ol, Michael V.; Gopalarathnam, Ashok; Edwards, Jack R.

    2017-08-01

    A leading-edge suction parameter (LESP) that is derived from potential flow theory as a measure of suction at the airfoil leading edge is used to study initiation of leading-edge vortex (LEV) formation in this article. The LESP hypothesis is presented, which states that LEV formation in unsteady flows for specified airfoil shape and Reynolds number occurs at a critical constant value of LESP, regardless of motion kinematics. This hypothesis is tested and validated against a large set of data from CFD and experimental studies of flows with LEV formation. The hypothesis is seen to hold except in cases with slow-rate kinematics which evince significant trailing-edge separation (which refers here to separation leading to reversed flow on the aft portion of the upper surface), thereby establishing the envelope of validity. The implication is that the critical LESP value for an airfoil-Reynolds number combination may be calibrated using CFD or experiment for just one motion and then employed to predict LEV initiation for any other (fast-rate) motion. It is also shown that the LESP concept may be used in an inverse mode to generate motion kinematics that would either prevent LEV formation or trigger the same as per aerodynamic requirements.

  15. 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.

  16. 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.

  17. Blood Lead Levels During Pregnancy and Its Influencing Factors in Nanjing, China

    Institute of Scientific and Technical Information of China (English)

    Kang-sheng Liu; Jia-hu Hao; Juan Shi; Chun-fang Dai; Xi-rong Guo

    2013-01-01

    Objective Toinvestigate the blood lead levels (BLLs) in the duration of pregnancy and 6-12 weeks after delivery, and analyze the influencing factors of BLLs in healthy pregnant women.MethodsPregnant women were recruited from September 2009 to February 2010 at the prenatalclinic inNanjing Maternity and Child Health Care Hospital. Altogether 174 healthy pregnant women without pregnant or obstetric complications or abnormal pregnancy outcomes were enrolled as the gravidagroup, and 120 healthy non-pregnant women as the control group. BLLs during pregnancy were determinedby flame atomic absorption spectroscopy.ResultsBLLs in all the three pregnancy trimesters and postpartum were 59.8±24.3, 55.4±20.1,55.9±19.7, and 67.6±17.4 μg/L, respectively, and the mean BLL in control group was 67.5±21.3 μg/L. BLLs during all the three trimesters were lower in the gravida group than in the control group (P=0.043, 0.021, and 0.028). Furthermore, occupations, nutrients supplementation, and time ofhouse/apartmentpainted were associated with BLLs in pregnant women. Lead-related occupations, cosmetics use, and livingin a house painted less than 1 year beforeare risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors.Conclusion Supplementing calcium, iron, zinc, and milk, or avoiding contact with risk factors may help people, especially pregnant women, to reduce lead exposure.

  18. 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.

  19. Failed anterior cruciate ligament reconstruction: analysis of factors leading to instability after primary surgery

    Institute of Scientific and Technical Information of China (English)

    MA Yong; AO Ying-fang; YU Jia-kuo; DAI Ling-hui; SHAO Zhen-xing

    2013-01-01

    Background Revision anterior cruciate ligament (ACL) surgery can be expected to become more common as the number of primary reconstruction keeps increasing.This study aims to investigate the factors causing instability after primary ACL reconstruction,which may provide an essential scientific base to prevent surgical failure.Methods One hundred and ten revision ACL surgeries were performed at our institute between November 2001 and July 2012.There were 74 men and 36 women,and the mean age at the time of revision was 27.6 years (range 16-56 years).The factors leading to instability after primary ACL reconstruction were retrospectively reviewed.Results Fifty-one knees failed because of bone tunnel malposition,with too anterior femoral tunnels (20 knees),posterior wall blowout (1 knee),vertical femoral tunnels (7 knees),too posterior tibial tunnels (12 knees),and too anterior tibial tunnels (10 knees).There was another knee performed with open surgery,where the femoral tunnel was drilled through the medial condyle and the tibial tunnel was too anterior.Five knees were found with malposition of the fixation.One knee with allograft was suspected of rejection and a second surgery had been made to take out the graft.Three knees met recurrent instability after postoperative infection.The other factors included traumatic (48 knees) and unidentified (12 knees).Conclusion Technical errors were the main factors leading to instability after primary ACL reconstructions,while attention should also be paid to the risk factors of re-injury and failure of graft incorporation.

  20. Determination of an ageing factor for lead/acid batteries. 1. Kinetic aspects

    Science.gov (United States)

    Armenta-Deu, C.; Donaire, T.

    The capacity of lead/acid batteries decreases with the number of cycles. This process is known as ageing. The reduction of capacity affects not only the operation time but also the performance of the accumulator and of the system attached to the battery. One of the main procedures affected by the battery ageing is the determination of the state-of-charge. In this paper, a parameter called 'ageing factor', fa, which represents the reduction of the available energy in lead/acid batteries, is introduced. A method to calculate this factory and its incidence on battery performance has also been developed. The method is intended to predict 'ageing' effects on lead/acid batteries as a non-destructive method, as well as on-line battery operation. The method is based on the effective reduction in electrolyte specific gravity in a fully charged lead/acid battery computed from the change of the slope of the electrolyte density during charge with the number of cycles, and the subsequent reduction in discharge time. A correlation process between the reduction of the energy delivered by the electrochemical cell, the reduction of the discharge time, and the apparent change of the slope of electrolyte density has been developed, resulting in an analytical expression that may be used to compute the effective reduction in available energy in lead/acid batteries. The results of the experiments have proven the merit of the proposed system: the predicted values are in good agreement with experimental data, the associated error in the a estimation being lower than 9%, a result which has been considered acceptable to validate the proposed method.

  1. The confounding factors leading to plagiarism in academic writing and some suggested remedies: A systematic review.

    Science.gov (United States)

    Guraya, Salman Yousuf; Guraya, Shaista Salman

    2017-05-01

    There is a staggering upsurge in the incidence of plagiarism of scientific literature. Literature shows divergent views about the factors that make plagiarism reprehensible. This review explores the causes and remedies for the perennial academic problem of plagiarism. Data sources were searched for full text English language articles published from 2000 to 2015. Data selection was done using medical subject headline (MeSH) terms plagiarism, unethical writing, academic theft, retraction, medical field, and plagiarism detection software. Data extraction was undertaken by selecting titles from retrieved references and data synthesis identified key factors leading to plagiarism such as unawareness of research ethics, poor writing skills and pressure or publish mantra. Plagiarism can be managed by a balance among its prevention, detection by plagiarism detection software, and institutional sanctions against proven plagiarists. Educating researchers about ethical principles of academic writing and institutional support in training writers about academic integrity and ethical publications can curtail plagiarism.

  2. 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

  3. 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.

  4. Environmental factors predicting blood lead levels in pregnant women in the UK: the ALSPAC study.

    Directory of Open Access Journals (Sweden)

    Caroline M Taylor

    Full Text Available Lead is a widespread environmental toxin. The behaviour and academic performance of children can be adversely affected even at low blood lead levels (BLL of 5-10 µg/dl. An important contribution to the infant's lead load is provided by maternal transfer during pregnancy.Our aim was to determine BLL in a large cohort of pregnant women in the UK and to identify the factors that contribute to BLL in pregnant women.Pregnant women resident in the Avon area of the UK were enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC in 1991-1992. Whole blood samples were collected at median gestational age of 11 weeks and analysed by inductively coupled plasma dynamic reaction cell mass spectrometry (n = 4285. Self-completion postal questionnaires were used to collect data during pregnancy on lifestyle, diet and other environmental exposures. Statistical analysis was carried out with SPSS v19.The mean±SD BLL was 3.67±1.47 (median 3.41, range 0.41-19.14 µg/dl. Higher educational qualification was found to be one of the strongest independent predictor of BLL in an adjusted backwards stepwise logistic regression to predict maternal BLL <5 or ≥5 µg/dl (odds ratio 1.26, 95% confidence interval 1.12-1.42; p<0.001. Other predictive factors included cigarette smoking, alcohol and coffee drinking, and heating the home with a coal fire, with some evidence for iron and calcium intake having protective effects.The mean BLL in this group of pregnant women is higher than has been found in similar populations in developed countries. The finding that high education attainment was independently associated with higher BLL was unexpected and currently unexplained. Reduction in maternal lead levels can best be undertaken by reducing intake of the social drugs cigarettes, alcohol and caffeine, although further investigation of the effect of calcium on lead levels is needed.

  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. Factors Leading to Variability of Emission Factors, Single Scattering Albedo, and Elemental Carbon Fraction from Biofuel Emissions

    Science.gov (United States)

    Roden, C. A.; Bond, T. C.; Conway, S.; Osorto Pinel, B.; Maccarty, N.

    2006-12-01

    In a three-year study of field and laboratory emissions of traditional and improved biofuel cookstoves, we found that field measured particulate emissions of actual cooking events average 2.5 times those of reproduced lab emissions. Emission factors are highly dependent on the care and skill of the operator, and the resulting combustion; these do not appear to be accurately reproduced in the lab. The single scatter albedo (SSA) of the emissions is very low in both lab and field measurements, averaging about 0.3 for lab tests and around 0.5 for field tests, indicating that the primary particles are climate warming. In Honduras, improved stoves generally had lower emission factors than traditional stoves. Over the course of 3 summers we have measured field emissions from traditional cookstoves, relatively-new improved cookstoves, and "broken-in" improved cookstoves. For improved stoves, the presence of a chimney generally resulted in lower emission factors but left the SSA unaffected. Traditional cookstoves had an average PM emission factor of 8.5 g/kg significantly larger than previous studies. Particulate emission factors for improved cookstoves without and with chimneys averaged about 5.7 g/kg and 3.5 g/kg respectively. The elemental carbon (EC) fraction of PM varied significantly between individual tests, but averaged about 25% for each of the categories. Wood type affects on the PM emission factor, the SSA of the emissions and EC fraction. During our 2006 field measurements, we performed multiple emission measurements on the same stove while varying the fuel. Pine wood generally produced more PM than oak per kilogram of fuel. Additionally, Ocote, a resinous pitch pine often used in Central America for lighting fires, produces emissions which have a very low SSA and high EC fraction. We present the elemental carbon fraction and mass emission factors for different type of stoves and testing conditions. We summarize the characteristics of the particles emitted

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

    Science.gov (United States)

    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.

  8. 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.

  9. 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.

  10. Cardiovascular Risk Factors Promote Brain Hypoperfusion Leading to Cognitive Decline and Dementia

    Directory of Open Access Journals (Sweden)

    Jack C. de la Torre

    2012-01-01

    Full Text Available Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an important risk factor in the development of cognitive decline and Alzheimer’s disease (AD. This paper examines the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular deficits in the development of cognitive impairment preceding AD. The evidence indicates a strong association between AD and cardiovascular risk factors, including ApoE4, atrial fibrillation, thrombotic events, hypertension, hypotension, heart failure, high serum markers of inflammation, coronary artery disease, low cardiac index, and valvular pathology. In elderly people whose cerebral perfusion is already diminished by their advanced age, additional reduction of cerebral blood flow stemming from abnormalities in the heart-brain vascular loop ostensibly increases the probability of developing AD. Evidence also suggests that a neuronal energy crisis brought on by relentless brain hypoperfusion may be responsible for protein synthesis abnormalities that later result in the classic neurodegenerative lesions involving the formation of amyloid-beta plaques and neurofibrillary tangles. Insight into how cardiovascular risk factors can induce progressive cognitive impairment offers an enhanced understanding of the multifactorial pathophysiology characterizing AD and ways at preventing or managing the cardiovascular precursors of this dementia.

  11. 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.

  12. 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...

  13. Hamstring strain injuries: factors that lead to injury and re-injury.

    Science.gov (United States)

    Opar, David A; Williams, Morgan D; Shield, Anthony J

    2012-03-01

    Hamstring strain injuries (HSIs) are common in a number of sports and incidence rates have not declined in recent times. Additionally, the high rate of recurrent injuries suggests that our current understanding of HSI and re-injury risk is incomplete. Whilst the multifactoral nature of HSIs is agreed upon by many, often individual risk factors and/or causes of injury are examined in isolation. This review aims to bring together the causes, risk factors and interventions associated with HSIs to better understand why HSIs are so prevalent. Running is often identified as the primary activity type for HSIs and given the high eccentric forces and moderate muscle strain placed on the hamstrings during running these factors are considered to be part of the aetiology of HSIs. However, the exact causes of HSIs remain unknown and whilst eccentric contraction and muscle strain purportedly play a role, accumulated muscle damage and/or a single injurious event may also contribute. Potentially, all of these factors interact to varying degrees depending on the injurious activity type (i.e. running, kicking). Furthermore, anatomical factors, such as the biarticular organization, the dual innervations of biceps femoris (BF), fibre type distribution, muscle architecture and the degree of anterior pelvic tilt, have all been implicated. Each of these variables impact upon HSI risk via a number of different mechanisms that include increasing hamstring muscle strain and altering the susceptibility of the hamstrings to muscle damage. Reported risk factors for HSIs include age, previous injury, ethnicity, strength imbalances, flexibility and fatigue. Of these, little is known, definitively, about why previous injury increases the risk of future HSIs. Nevertheless, interventions put in place to reduce the incidence of HSIs by addressing modifiable risk factors have focused primarily on increasing eccentric strength, correcting strength imbalances and improving flexibility. The response to

  14. Factors leading to cesarean section delivery at Felegehiwot referral hospital, Northwest Ethiopia: a retrospective record review.

    Science.gov (United States)

    Abebe, Fantu Eyowas; Gebeyehu, Abebaw Worku; Kidane, Ashebir Negasi; Eyassu, Gizached Aynalem

    2016-01-20

    Cesarean section is the commonest obstetric operative procedure worldwide. When used appropriately cesarean sections can improve infant and/or maternal outcomes. However, when used inappropriately the potential harm may exceed the potential benefit of cesarean section. Appreciating the limited information in this area the current study assessed the rate and factors associated with cesarean section in Felegehiwot referral hospital, Bahir Dar, northwest Ethiopia. The study was a retrospective analysis of eligible patient records that included 2967 pregnant women who had underwent either cesarean or vaginal delivery from July 1, 2012 to June 31, 2013. The data were double entered to EPI-INFO 3.5.2 and analyzed with SPSS. Binary logistic regression model was fitted to identify independent factors associated with cesarean section. The proportion of women who underwent cesarean section in this study was 25.4%. Obstructed labor (30.7%), fetal distress (15.9%) and abnormal presentation (13.4%) were the major obstetric indications for cesarean section. The odd of undergoing cesarean section was higher among mothers in rural residence (AOR = 1.63, 95% CI: 1.21, 2.20), mothers reported to have pregnancy risk factors (AOR = 2.31, 95% CI: 1.74, 3.07) and lower among mothers in age category of 15-19 (AOR = 0.63, 95% CI: 0.43, 0.93). Obstetric factors occurring around birth, including obstructed labor and fetal distress were the main reasons leading to Cesarean Section rather than background characteristics assumed to be a risk. The results imply that there is a need for timely and accurate screening of women during obstetric care and, decision to perform cesarean section should be based on clear, compelling and well-supported justifications.

  15. Choosing to lead the motivational factors of underrepresented minority librarians in higher education

    CERN Document Server

    Olivas, Antonia

    2017-01-01

    Choosing to Lead: The Motivational Factors of Underrepresented Minority Librarians in Higher Education takes a positive inquiry approach by providing first-hand accounts of success stories, best practices, and practical advice from a collection of diverse authors. Instead of looking at academic library "failures" when it comes to diversifying the leadership workforce, this book highlights what's going right and how to implement it across the profession-with an emphasis on building strengths and fully leveraging one's interests, behaviors, and passions, while never ignoring or deemphasizing the prevailing challenges that exist for diverse LIS professionals who wish to advance their leadership skills. Through case studies, promising practices, and specific strategies for cultivating diversity in academic library leadership, this is a resource for both librarians of color who wish to seek leadership positions and current library leaders who want to nurture these future leaders.

  16. Lead, Manganese, and Methylmercury as Risk Factors for Neurobehavioral Impairment in Advanced Age

    Directory of Open Access Journals (Sweden)

    Bernard Weiss

    2011-01-01

    Full Text Available Contamination of the environment by metals is recognized as a threat to health. One of their targets is the brain, and the adverse functional effects they induce are reflected by neurobehavioral assessments. Lead, manganese, and methylmercury are the metal contaminants linked most comprehensively to such disorders. Because many of these adverse effects can appear later in life, clues to the role of metals as risk factors for neurodegenerative disorders should be sought in the exposure histories of aging populations. A review of the available literature offers evidence that all three metals can produce, in advanced age, manifestations of neurobehavioral dysfunction associated with neurodegenerative disease. Among the critical unresolved questions is timing; that is, during which periods of the lifespan, including early development, do environmental exposures lay the foundations for their ultimate effects?

  17. Investigating factors leading to fogging of glass vials in lyophilized drug products.

    Science.gov (United States)

    Abdul-Fattah, Ahmad M; Oeschger, Richard; Roehl, Holger; Bauer Dauphin, Isabelle; Worgull, Martin; Kallmeyer, Georg; Mahler, Hanns-Christian

    2013-10-01

    Vial "Fogging" is a phenomenon observed after lyophilization due to drug product creeping upwards along the inner vial surface. After the freeze-drying process, a haze of dried powder is visible inside the drug product vial, making it barely acceptable for commercial distribution from a cosmetic point of view. Development studies were performed to identify the root cause for fogging during manufacturing of a lyophilized monoclonal antibody drug product. The results of the studies indicate that drug product creeping occurs during the filling process, leading to vial fogging after lyophilization. Glass quality/inner surface, glass conversion/vial processing (vial "history") and formulation excipients, e.g., surfactants (three different surfactants were tested), all affect glass fogging to a certain degree. Results showed that the main factor to control fogging is primarily the inner vial surface hydrophilicity/hydrophobicity. While Duran vials were not capable of reliably improving the level of fogging, hydrophobic containers provided reliable means to improve the cosmetic appearance due to reduction in fogging. Varying vial depyrogenation treatment conditions did not lead to satisfying results in removal of the fogging effect. Processing conditions of the vial after filling with drug product had a strong impact on reducing but not eliminating fogging.

  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. Factors leading to the computer vision syndrome: an issue at the contemporary workplace.

    Science.gov (United States)

    Izquierdo, Juan C; García, Maribel; Buxó, Carmen; Izquierdo, Natalio J

    2007-01-01

    Vision and eye related problems are common among computer users, and have been collectively called the Computer Vision Syndrome (CVS). An observational study in order to identify the risk factors leading to the CVS was done. Twenty-eight participants answered a validated questionnaire, and had their workstations examined. The questionnaire evaluated personal, environmental, ergonomic factors, and physiologic response of computer users. The distance from the eye to the computers' monitor (A), the computers' monitor height (B), and visual axis height (C) were measured. The difference between B and C was calculated and labeled as D. Angles of gaze to the computer monitor were calculated using the formula: angle=tan-1(D/A). Angles were divided into two groups: participants with angles of gaze ranging from 0 degree to 13.9 degrees were included in Group 1; and participants gazing at angles larger than 14 degrees were included in Group 2. Statistical analysis of the evaluated variables was made. Computer users in both groups used more tear supplements (as part of the syndrome) than expected. This association was statistically significant (p syndrome is the angle of gaze at the computer monitor. Pain in computer users is diminished when gazing downwards at angles of 14 degrees or more. The CVS remains an under estimated and poorly understood issue at the workplace. The general public, health professionals, the government, and private industries need to be educated about the CVS.

  4. Lead exposure in Laysan albatross adults and chicks in Hawaii: prevalence, risk factors, and biochemical effects.

    Science.gov (United States)

    Work, T M; Smith, M R

    1996-07-01

    Prevalence of lead exposure and elevated tissue lead was determined in Laysan albatross (Diomedea immutabilis) in Hawaii. The relationship between lead exposure and proximity to buildings, between elevated blood lead and droopwing status, and elevated liver lead and presence of lead-containing paint chips in the proventriculus in albatross chicks was also examined. Finally, the effects of lead on the enzyme delta-aminolevulinic acid dehydratase (ALAD) was determined. There was a significant association between lead exposure or elevated tissue lead and proximity to buildings in albatross chicks and presence of lead paint chips in the proventriculus and elevated liver lead in carcasses. Although there was a significant association between elevated blood lead and droopwing chicks, there were notable exceptions. Prevalence of elevated tissue lead in albatross chicks was highest on Sand Island Midway and much less so on Kauai and virtually nonexistent in other areas. Prevalence of lead exposure decreased as numbers of buildings to which chicks were exposed on a given island decreased. Laysan albatross adults had minimal to no lead exposure. There was a significant negative correlation between blood lead concentration and ALAD activity in chicks. Based on ALAD activity, 0.03-0.05 microg/ml was the no effect range for blood lead in albatross chicks.

  5. Lead exposure in Laysan albatross adults and chicks in Hawaii: prevalence, risk factors, and biochemical effects.

    Science.gov (United States)

    Work, T.M.; Smith, M.R.

    1996-01-01

    Prevalence of lead exposure and elevated tissue lead was determined in Laysan albatross (Diomedea immutabilis) in Hawaii. The relationship between lead exposure and proximity to buildings, between elevated blood lead and droopwing status, and elevated liver lead and presence of lead-containing paint chips in the proventriculus in albatross chicks was also examined. Finally, the effects of lead on the enzyme δ-amino-levulinic acid dehydratase (ALAD) was determined. There was a significant association between lead exposure or elevated tissue lead and proximity to buildings in albatross chicks and presence of lead paint chips in the proventriculus and elevated liver lead in carcasses. Although there was a significant association between elevated blood lead and droopwing chicks, there were notable exceptions. Prevalence of elevated tissue lead in albatross chicks was highest on Sand Island Midway and much less so on Kauai and virtually nonexistent in other areas. Prevalence of lead exposure decreased as numbers of buildings to which chicks were exposed on a given island decreased. Laysan albatross adults had minimal to no lead exposure. There was a significant negative correlation between blood lead concentration and ALAD activity in chicks. Based on ALAD activity, 0.03-0.05 μg/ml was the no effect range for blood lead in albatross chicks.

  6. Factors Leading to Self-Removal from the Bariatric Surgery Program After Attending the Orientation Session.

    Science.gov (United States)

    Yang, Kai; Zhang, Binghao; Kastanias, Patti; Wang, Wei; Okraniec, Allan; Sockalingam, Sanjeev

    2017-01-01

    Bariatric surgery orientation sessions are often the first point of contact and a recommended component of pre-bariatric surgery assessment. Self-removal rates after bariatric program orientation are as high as 25 % despite the proven efficacy of this procedure. The objective of this study was to identify factors contributing to patient self-removal after orientation using a mixed method approach. Patients who attended the Toronto Western Hospital Bariatric Surgery Program orientation between 2012 and 2013 and then self-removed from the program (N = 216) were included in the study. Subjects were interviewed via telephone using a semi-structured interview guide, generating both quantitative and qualitative data. Factors leading to discontinuation were rated on a five-point Likert scale. Qualitative data was analyzed using constant comparative methodology. The response rate was 59 % with a 40.7 % completion rate (N = 88). Concerns about potential surgical risks and complications and the ability to adapt to changes in eating and drinking post-operatively were identified as the top two factors for patients' self-removal from the program. Thematic analysis uncovered 11 major themes related to patient self-removal. Unexpected themes include perceived personal suitability for the surgery, family impact of surgery, miscommunication with the family physician, and fears related to the orientation information. This is one of the first studies examining barriers to bariatric surgery in the pre-operative setting and offers new insights into the reasons patients self-remove from bariatric surgery programs. This study may inform bariatric orientation program changes resulting in improved access to this effective surgical intervention.

  7. Levels of Aggression among Turkish Adolescents and Factors Leading to Aggression.

    Science.gov (United States)

    Avci, Dilek; Kilic, Mahmut; Tari Selcuk, Kevser; Uzuncakmak, Tugba

    2016-07-01

    Aggression, an increasing problem among adolescents, is a potential threat to public health as it can lead to violence. Determining the factors causing aggression plays an important role in taking measures to reduce violence. This study aimed at determining the level of aggression among adolescents and at identifying the factors associated with high levels of aggression. This cross-sectional study was conducted with 2,409 Turkish adolescents. Data were collected with the Socio-demographic Questionnaire, Aggression Scale, Perceived Social Support Scale, and Communication Skills Attitude Scale. Data were analyzed using descriptive statistics, the chi-square test, t-test, and logistic regression. The participants' mean aggression score was 91.83 ± 24.05, and 24.0% of the adolescents' aggression levels rated high. According to the logistic regression model, aggression was 1.26 times higher among males, 1.92 times higher among those who perceived their mental health as poor, 1.58 times higher among those with suicidal ideation, 1.29 times higher among those who did not get prepared for university entrance exams, and 1.62 times higher among those who perceived their school performance as poor. Perceived family social support was a protective factor against high aggression. Approximately one out of every four adolescents in the two Turkish high schools where the study was conducted was determined to display high levels of aggression. Therefore, in order to reduce aggression among adolescents, programs such as coping management and coping with anger should be applied by nurses. Programs should include not only students but also families.

  8. 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 ...

  9. Creating novel activated factor XI inhibitors through fragment based lead generation and structure aided drug design.

    Directory of Open Access Journals (Sweden)

    Ola Fjellström

    Full Text Available Activated factor XI (FXIa inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1'-S2' FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1'-S2' binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1'-S2' binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds.

  10. Employing Lead Thiocyanate Additive to Reduce the Hysteresis and Boost the Fill Factor of Planar Perovskite Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Weijun [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education of China, School of Physics and Technology, Wuhan University, Wuhan 430072 China; National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Xiao, Chuanxiao [National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Wang, Changlei [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; Saparov, Bayrammurad [Department of Mechanical Engineering and Materials Science, Duke University, Durham NC 27708 USA; Department of Chemistry, Duke University, Durham NC 27708 USA; Duan, Hsin-Sheng [Department of Mechanical Engineering and Materials Science, Duke University, Durham NC 27708 USA; Zhao, Dewei [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Xiao, Zewen [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; Schulz, Philip [National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Harvey, Steven P. [National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Liao, Weiqiang [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; Meng, Weiwei [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; Yu, Yue [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; Cimaroli, Alexander J. [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA; Jiang, Chun-Sheng [National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Zhu, Kai [National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Al-Jassim, Mowafak [National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Fang, Guojia [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education of China, School of Physics and Technology, Wuhan University, Wuhan 430072 China; Mitzi, David B. [Department of Mechanical Engineering and Materials Science, Duke University, Durham NC 27708 USA; Department of Chemistry, Duke University, Durham NC 27708 USA; Yan, Yanfa [Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo OH 43606 USA

    2016-05-04

    Lead thiocyanate in the perovskite precursor can increase the grain size of a perovskite thin film and reduce the conductivity of the grain boundaries, leading to perovskite solar cells with reduced hysteresis and enhanced fill factor. A planar perovskite solar cell with grain boundary and interface passivation achieves a steady-state efficiency of 18.42%.

  11. Employing Lead Thiocyanate Additive to Reduce the Hysteresis and Boost the Fill Factor of Planar Perovskite Solar Cells.

    Science.gov (United States)

    Ke, Weijun; Xiao, Chuanxiao; Wang, Changlei; Saparov, Bayrammurad; Duan, Hsin-Sheng; Zhao, Dewei; Xiao, Zewen; Schulz, Philip; Harvey, Steven P; Liao, Weiqiang; Meng, Weiwei; Yu, Yue; Cimaroli, Alexander J; Jiang, Chun-Sheng; Zhu, Kai; Al-Jassim, Mowafak; Fang, Guojia; Mitzi, David B; Yan, Yanfa

    2016-07-01

    Lead thiocyanate in the perovskite precursor can increase the grain size of a perovskite thin film and reduce the conductivity of the grain boundaries, leading to perovskite solar cells with reduced hysteresis and enhanced fill factor. A planar perovskite solar cell with grain boundary and interface passivation achieves a steady-state efficiency of 18.42%.

  12. Million hearts: prevalence of leading cardiovascular disease risk factors--United States, 2005-2012.

    Science.gov (United States)

    Ritchey, Matthew D; Wall, Hilary K; Gillespie, Cathleen; George, Mary G; Jamal, Ahmed

    2014-05-30

    Each year, approximately 1.5 million U.S. adults have a heart attack or stroke, resulting in approximately 30 deaths every hour and, for nonfatal events, often leading to long-term disability. Overall, an estimated 14 million survivors of heart attacks and strokes are living in the United States. In 2011, the U.S. Department of Health and Human Services, in collaboration with nonprofit and private organizations, launched Million Hearts (http://www.millionhearts.hhs.gov), an initiative focused on implementing clinical and community-level evidence-based strategies to reduce cardiovascular disease (CVD) risk factors and prevent a total of 1 million heart attacks and strokes during the 5-year period 2012-2016. From 2005-2006 to the period with the most current data, analysis of the Million Hearts four "ABCS" clinical measures (for aspirin, blood pressure, cholesterol, and smoking) showed 1) no statistically significant change in the prevalence of aspirin use for secondary prevention (53.8% in 2009-2010), 2) an increase to 51.9% in the prevalence of blood pressure control (in 2011-2012), 3) an increase to 42.8% in the prevalence of cholesterol management (in 2011-2012), and 4) no statistically significant change in the prevalence of smoking assessment and treatment (22.2% in 2009-2010). In addition, analysis of two community-level indicators found 1) a decrease in current tobacco product smoking (including cigarette, cigar, or pipe use) prevalence to 25.1% in 2011-2012 and 2) minimal change in mean daily sodium intake (3,594 mg/day in 2009-2010). Although trends in some measures are encouraging, further reductions of CVD risk factors will be needed to meet Million Hearts goals by 2017.

  13. Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis

    Directory of Open Access Journals (Sweden)

    Nakamura Shinichiro

    2011-01-01

    Full Text Available Abstract Background Runt-related transcription factor 3 (RUNX3 is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC. Methods RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results RUNX3 protein expression was frequently inactivated in the HCC cell lines (91% and tissues (90%. RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

  14. Chest tube insertion is one important factor leading to intercostal nerve impairment in thoracic surgery.

    Science.gov (United States)

    Miyazaki, Takuro; Sakai, Tetsuya; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Tagawa, Tsutomu; Hatachi, Go; Tomoshige, Koichi; Mine, Mariko; Nagayasu, Takeshi

    2014-01-01

    Chest tube insertion seems to be one important factor leading to intercostal nerve impairment. The purpose of this prospective study was to objectively evaluate intercostal nerve damage using current perception threshold testing in association with chest tube insertion. Sixteen patients were enrolled in this study. Intercostal nerve function was assessed with a series of 2000-Hz (Aβ fiber), 250-Hz (Aδ fiber), and 5-Hz (C fiber) stimuli using current perception threshold testing (Neurometer CPT/C(®)). Current perception threshold values at chest tube insertion were measured before surgery, during chest tube insertion and after removal of the chest tube. Intensities of ongoing pain were also assessed using a numeric rating scale (0-10). Current perception thresholds at each frequency after surgery were significantly higher than before surgery. Numeric rating scale scores for pain were significantly reduced from 3.3 to 1.9 after removal of the chest tube (p = 0.004). The correlation between current perception threshold value at 2000 Hz and intensity of ongoing pain was marginally significant (p = 0.058). This is the first study to objectively evaluate intercostal nerve damage at chest tube insertion. The results confirmed that chest tube insertion has clearly deleterious effects on intercostal nerve function.

  15. 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.

  16. 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.

  17. [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.

  18. 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.

  19. Influencing factors of colostrum exposure to low-level lead and their relationship with early neural development of infants

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Exposure to low-level lead has a toxic effect on the development of neonates, which has attracted wide attention. Colostrum lead level can be used as the indication of lead exposure.OBJECTIVE: To observe the relationship of colostrum lead level and the neurobehavioral development of infants.DESIGN: A prospective control observation.SETTING: Center for Maternal and Child Health, Shanxi Provincial Children's Hospital.PARTICIPANTS: Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history or fetus intrauterine developmental lag. Pregnant women had no various acute and chronic diseases in pregnancy, family history of neurological disease or occupational lead exposure. 128 portions of colostrum sample of full-term normal delivery were collected. Informed consents of detected items were obtained from the puerperants and their relatives.METHODS: ①Experimental grouping: Lead level in the colostrum was determined by atomic absorption spectrometry. According to lead level in the colostrum, the neonates were classified into two exposure groups of greater than or equal to 0.24 μ mol/L in a high-level lead group and less than 0.24 μ mol/L in a low-level lead group. ② Experimental evaluation: Mental developmental index (MDI) and psychological developmental index (PDI) of 3-month-old infants were evaluated with Bayley Scales of Infant Development (BSID). The relationships of MDI, PDI and colostrum lead level were performed correlation regression analysis; The relationship of colostrum lead level and development was performed multi-factor analysis with family environment and health questionnaires.MAIN OUTCOME MEASURES: ① Evaluation results of MDI and PDI. ② Multi-factor analysis results.RESULTS: Totally 128 neonates were involved in the study. Ten

  20. Lead Burden as a Factor for Higher Complication Rate in Patients With Implantable Cardiac Devices

    Directory of Open Access Journals (Sweden)

    Christopher Kolibash

    2015-01-01

    Full Text Available Purpose: Lead revisions have increased over the last decade. Patients who do not undergo lead extraction face an increased lead burden. Consequences of increased lead burden have not been fully defined. We sought to characterize the complication rate and outcomes in patients with sterile redundant leads. Methods: We retrospectively reviewed 242 consecutive patients [mean age 74 ± 12 years; 66.9% male] who underwent lead revision that resulted in an abandoned lead from January 2005 to June 2010. Patients were placed in a cohort based on number of leads after last recorded procedure (Group A: ≤2 [n=58]; Group B: 3-4 [n=168]; Group C: ≥5 [n=16]. Prespecified inhospital and long-term follow-up events were compared. Mortality rates were obtained from Social Security Death Index. Median follow-up was 2 years. Results: Baseline age, gender and race demographics were similar among the three groups. Increasing lead burden was associated with more adverse periprocedural events (A: 3.4%, B: 10.1%, C: 25.0%; P=0.031 and long-term device-related events (A: 1.7%, B: 13.0%, C: 18.8%; P=0.031. Device-related readmissions increased in frequency as lead burden increased (A: 3.5%, B: 18.5%, C: 37.5%; P=0.002. Combined periprocedural and late events also increased with more redundant leads (A: 5.2%, B: 23.2%, C: 44.0%; P=0.001. Total major events were infrequent (3.3%. There was no procedure-related mortality. Long-term all-cause mortality was not significantly different (A: 17.2%, B: 23.8%, C: 25.0%; P=0.567. Conclusions: Greater lead burden was associated with increased number of periprocedural and long-term minor events. It did not significantly impact major events or mortality.

  1. Factors related to health outcomes and health risk behaviors of adolescents with lead exposure. A pilot study

    OpenAIRE

    2013-01-01

    This pilot study was an approach to determine the health outcomes (nutritional status, cognitive status, mental health and educational status), and the presence of health risk behaviors (aggressive behavior/ delinquency, hazardous/harmful drinking, substance use/abuse and tobacco use) of adolescents who have been exposed all their lives to lead. Besides, we could identify individual, familial and social factors, such as lead exposure, that were related to them. The sample included 40 adolesce...

  2. Blood lead levels and risk factors for lead exposure among pregnant women in western French Guiana: the role of manioc consumption.

    Science.gov (United States)

    Rimbaud, Diane; Restrepo, Marion; Louison, Anne; Boukhari, Rachida; Ardillon, Vanessa; Carles, Gabriel; Lambert, Véronique; Jolivet, Anne

    2017-01-01

    Concerns regarding lead (Pb) poisoning in French Guiana first arose in 2011 following the discovery of excessively high levels of the metal amongst children in a small neighborhood without any apparent source of Pb. Since 2012, blood lead level (BLL) measurement has been proposed for all pregnant women in western French Guiana. The aim of this study was to determine BLL in pregnant women in this region and identify factors associated with elevated BLL. An observational study of a consecutive sample of women who delivered in the maternity ward of the hospital was conducted. Risk factors were investigated using a questionnaire administered postdelivery by midwives (N = 531). Approximately 25 and 5% of women displayed BLL of ≥50 μg/L and ≥100 µg/L, respectively. The geometric mean was 32.6 μg/L. Factors that were significantly associated with an elevated BLL after modeling (multivariate linear regression) included place of residence along the Maroni river, low level of education, daily consumption of manioc derivatives, weekly and daily consumption or personal preparation of manioc flour during pregnancy, and weekly consumption of wild game. This study provides insight into the regional and social disparities in BLL in French Guiana and potential sources of exposure. Evidence indicates that foods that are primarily produced and consumed in the Guiana Shield significantly affect BLL levels. Taken together with existing data, our results demonstrate that specific actions in terms of prevention, screening, and care are required to be adapted and put into place in order to reduce exposure.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  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.

    Science.gov (United States)

    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. Strontium Insertion in Methylammonium Lead Iodide: Long Charge Carrier Lifetime and High Fill-Factor Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Pérez-del-Rey, Daniel [Instituto de Ciencia Molecular, Universidad de Valencia, C/J. Beltran 2 46980 Paterna Spain; Forgács, Dávid [Instituto de Ciencia Molecular, Universidad de Valencia, C/J. Beltran 2 46980 Paterna Spain; Hutter, Eline M. [Department of Chemical Engineering, Delft University of Technology, Van der Maasweg 9 2629 HZ Delft The Netherlands; Savenije, Tom J. [Department of Chemical Engineering, Delft University of Technology, Van der Maasweg 9 2629 HZ Delft The Netherlands; Nordlund, Dennis [Stanford Linear Accelerator Campus, Stanford Synchrotron Laboratory, Menlo Park CA 94025 USA; Schulz, Philip [National Center for Photovoltaics, National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Berry, Joseph J. [National Center for Photovoltaics, National Renewable Energy Laboratory, 15013 Denver West Parkway Golden CO 80401 USA; Sessolo, Michele [Instituto de Ciencia Molecular, Universidad de Valencia, C/J. Beltran 2 46980 Paterna Spain; Bolink, Henk J. [Instituto de Ciencia Molecular, Universidad de Valencia, C/J. Beltran 2 46980 Paterna Spain

    2016-09-22

    The addition of Sr2+ in CH3NH3PbI3 perovskite films enhances the charge carrier collection efficiency of solar cells leading to very high fill factors, up to 85%. The charge carrier lifetime of Sr2+-containing perovskites is in excess of 40 us, longer than those reported for perovskite single crystals.

  12. The Effects of Occupational Work Adjustment on Factors Leading to High School Drop Out in Rural Northwest Ohio.

    Science.gov (United States)

    Dietrich, Angela

    The effect of four Occupational Work Adjustment (OWA) programs on risk factors leading to students dropping out of high school was assessed. Data were gathered from four OWA teachers in high schools in Northwest Ohio; information was provided for 27 individual students and 2 groups of 28 students each for the 1992-93 school year. The following…

  13. The electric dipole form factor of the nucleon in chiral perturbation theory to sub-leading order

    NARCIS (Netherlands)

    Mereghetti, E.; de Vries, J.; Hockings, W. H.; Maekawa, C. M.; van Kolck, U.

    2011-01-01

    The electric dipole form factor (EDFF) of the nucleon stemming from the QCD (theta) over bar term and from the quark color-electric dipole moments is calculated in chiral perturbation theory to sub-leading order. This is the lowest order in which the isoscalar EDFF receives a calculable, non-analyti

  14. 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.

  15. 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.

  16. Factors associated with elevated blood lead levels in inner ·city ...

    African Journals Online (AJOL)

    cent of children had blood lead levels;;:' 25 ~g/dl, the present USA 'action' level. Dusty homes and homes in a poor state of repair, over-crowding, low parental education and income .... potential ill-effects associated with increased exposure.

  17. Risk Factors Leading to Free Flap Failure: Analysis From the National Surgical Quality Improvement Program Database.

    Science.gov (United States)

    Sanati-Mehrizy, Paymon; Massenburg, Benjamin B; Rozehnal, John M; Ingargiola, Michael J; Hernandez Rosa, Jonatan; Taub, Peter J

    2016-11-01

    The objective of this study was to identify risk factors for free flap failure among various anatomically based free flap subgroups. The 2005 to 2012 American College of Surgeons National Surgical Quality Improvement Program database was queried for patients undergoing microvascular free tissue transfer based on current procedural terminology codes. Univariate analysis was performed to identify any association between flap failure and the following factors: age, gender, race, body mass index (BMI), diabetes, smoking, alcohol use, hypertension, intraoperative transfusion, functional health status, American Society of Anesthesiologists class, operative time, and flap location. Factors yielding a significance of P free flap reconstruction met inclusion criteria. Multivariate logistic regression identified BMI (adjusted odds ratio [AOR] = 1.07, P = 0.004) and male gender (AOR = 2.16, P = 0.033) as independent risk factors for flap failure. Among the "breast flaps" subgroup, BMI (AOR = 1.075, P = 0.012) and smoking (AOR = 3.35, P = 0.02) were independent variables associated with flap failure. In "head and neck flaps," operative time (AOR = 1.003, P = 0.018) was an independent risk factor for flap failure. No independent risk factors were identified for the "extremity flaps" or "trunk flaps" subtypes. BMI, smoking, and operative time were identified as independent risk factors for free flap failure among all flaps or within flap subsets.

  18. 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

  19. [Air kerma transmission factors of Scattered X-rays in the maze of a Linac room for lead shield].

    Science.gov (United States)

    Kato, Hideki

    2005-01-20

    Spectra of scattered X-rays in the maze of a Linac (X-ray energies of 4, 6, and 10 MV) room were estimated by means of the Monte Carlo simulation, and air kerma transmission factors of the X-rays scattered through a lead shield were evaluated based on those spectra. Spectra of scattered X-rays showed a maximum in the energy area below 200 keV. The higher the accelerated electron energy, also, the smaller the scattering angle that tended to spread to the higher energy area of the distribution of spectra. The air kerma transmission factor of 120 degrees scattered X-rays of 4 MV X-rays obtained in this study was larger than the transmission factors of 124 degrees scattered photons of (60)Co gamma rays through a lead shield given in ICRP. The air kerma transmission factors of 120 degrees scattered X-rays of 6 MV X-rays were smaller than the transmission factors of 90 degrees scattered photons of (60)Co gamma rays. The air kerma transmission factors of 120 degrees scattered X-rays of 10 MV X-rays was slightly larger than transmission factors of 90 degrees scattered photons of (60)Co gamma rays. Therefore, in the case of a 4 MV X-ray Linac room, the calculation method given in the "Manual of Practical Shield Calculation of Radiation Facilities (2000)" causes underestimation of leakage doses.

  20. Investigations of the factors causing performance losses of lead/acid traction batteries

    Science.gov (United States)

    Kronberger, H.; Fabjan, Ch.; Gofas, N.

    A failure analysis is carried out with a lead/acid traction battery after a two-years' test run in an electric passenger car. A survey of the operational data, in combination with laboratory tests and chemical and physical analyses, reveals the main causes of battery damage and performance loss: insufficiencies of the charging procedure, inadequate maintainance (water-refilling system), antimony-contamination and loss of the active material due to grid corrosion and shedding of PbO 2.

  1. Intangible factors leading to success in research: strategy, innovation and leadership.

    Science.gov (United States)

    Hecker, Louise; Birla, Ravi K

    2008-03-01

    At the heart of research is the scientific process, which includes identifying a knowledge gap, execution of experiments, and finally, presentation of scientific data. Identifying a systematic way to undertake research is important; however, equally important are intangible factors, including strategy, innovation and leadership, in determining the outcome of any research project. These intangible factors, although often unspoken, are the essence of success in research. Strategy determines the direction of research and the ability to respond to acute changes in the field to ensure a competitive advantage. Innovation involves generating novel ideas, and at the heart of innovation is the ability to create a positive work environment. Leadership is the ability to exercise influence so as to create change; empowerment and the ability to create leaders at every level are central to effective leadership. Collectively, defining and implementing aspects of these intangible factors will strengthen any research endeavor.

  2. 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.

  3. 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.

  4. CGC factorization for forward particle production in proton-nucleus collisions at next-to-leading order

    CERN Document Server

    Iancu, E; Triantafyllopoulos, D N

    2016-01-01

    Within the Color Glass Condensate effective theory, we reconsider the next-to-leading order (NLO) calculation of the single inclusive particle production at forward rapidities in proton-nucleus collisions at high energy. Focusing on quark production for definiteness, we establish a new factorization scheme, valid thru NLO, in which all the radiative corrections are encoded into a single piece: a NLO impact factor, built with the produced quark and its (not necessarily soft) daughter gluon, which together scatter off the gluon distribution in the nucleus and thus measure its high-energy evolution to next-to-leading order. The NLO impact factor was previously computed in [1,2], but the reorganization of the perturbation theory that we propose is new. The non-linear evolution of the dense nucleus is not known beyond leading order, but we manage to reformulate it as the NLO evolution of the dilute projectile, amended by collinear improvement. As compared to the previous proposal in [1,2], in our factorization sch...

  5. 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.

  6. 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

  7. 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

  8. Who Will Lead? The Top 10 Factors That Influence Teachers Moving into Administration.

    Science.gov (United States)

    Shen, Jianping; Cooley, Van

    1999-01-01

    A survey of educational-administration students revealed 10 factors influencing teachers' reluctance to move into administration: nature of work responsibilities, working conditions, emotional aspects, district location, superintendent reputation, effects on home life, quality of community life, community support, salary/responsibility issues, and…

  9. Twelve Factors Leading to Fundamental Pedagogical Change in a Primary School: A Case-Study

    Science.gov (United States)

    Norris, Cathleen; Soloway, Elliot

    2016-01-01

    A school can change. In this case study, the authors describe the 12 factors they have identified as being key in the transformation of the core pedagogical practices at Nan Chiau Primary School, Singapore, from direct instruction to inquiry, from a 20th to a 21st century school. While the adoption of 1:1 mobile devices played a catalytic role in…

  10. Antidotes to anthrax lethal factor intoxication. Part 2: structural modifications leading to improved in vivo efficacy.

    Science.gov (United States)

    Kim, Seongjin; Jiao, Guan-Sheng; Moayeri, Mahtab; Crown, Devorah; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A; Leppla, Stephen H; Johnson, Alan T

    2011-04-01

    New anthrax lethal factor inhibitors (LFIs) were designed based upon previously identified potent inhibitors 1a and 2. Combining the new core structures with modifications to the C2-side chain yielded analogs with improved efficacy in the rat lethal toxin model.

  11. Students as Protégés: Factors That Lead to Success

    Science.gov (United States)

    Bear, Stephen; Jones, Gwen

    2017-01-01

    This study provides insight into the factors that influence satisfaction with an Internet-based practitioner-student mentoring relationship that is part of an undergraduate business school curriculum. Practitioner mentors are especially important because they can help student protégés learn the skills needed for their professional development,…

  12. Socioeconomic and behavioral factors leading to acquired bacterial resistance to antibiotics in developing countries.

    OpenAIRE

    Okeke, I. N.; Lamikanra, A; Edelman, R

    1999-01-01

    In developing countries, acquired bacterial resistance to antimicrobial agents is common in isolates from healthy persons and from persons with community-acquired infections. Complex socioeconomic and behavioral factors associated with antibiotic resistance, particularly regarding diarrheal and respiratory pathogens, in developing tropical countries, include misuse of antibiotics by health professionals, unskilled practitioners, and laypersons; poor drug quality; unhygienic conditions account...

  13. 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

  14. 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。

  15. Factorization for groomed jet substructure beyond the next-to-leading logarithm

    CERN Document Server

    Frye, Christopher; Schwartz, Matthew D; Yan, Kai

    2016-01-01

    Jet grooming algorithms are widely used in experimental analyses at hadron colliders to remove contaminating radiation from within jets. While the algorithms perform a great service to the experiments, their intricate algorithmic structure and multiple parameters has frustrated precision theoretic understanding. In this paper, we demonstrate that one particular groomer called soft drop actually makes precision jet substructure easier. In particular, we derive a factorization formula for a large class of soft drop jet substructure observables, including jet mass. The essential observation that allows for this factorization is that, without the soft wide-angle radiation groomed by soft drop, all singular contributions are collinear. The simplicity and universality of the collinear limit in QCD allows us to show that to all orders, the normalized differential cross section has no contributions from non-global logarithms. It is also independent of process, up to the relative fraction of quark and gluon jets. In f...

  16. Verification of g-factors for lead monofluoride ground state, PbF

    CERN Document Server

    Skripnikov, L V; Titov, A V; Mawhorter, R J; Baum, A L; Sears, T J; Grabow, J -U

    2015-01-01

    We report the results of our theoretical study and analysis of earlier experimental data for the g-factor tensor components of the ground $^2\\Pi_{1/2}$ state of free PbF radical. The values obtained both within the relativistic coupled-cluster method combined with the generalized relativistic effective core potential approach and with our fit of the experimental data from [R.J. Mawhorter, B.S. Murphy, A.L. Baum, T.J. Sears, T. Yang, P.M. Rupasinghe, C.P. McRaven, N.E. Shafer-Ray, L.D. Alphei, J.-U. Grabow, Phys. Rev. A 84, 022508 (2011); A. Baum, B.S. thesis, Pomona College, 2011]. The obtained results agree very well with each other but contradict the previous fit performed in the cited works. Our final prediction for g-factors is $G_{\\parallel}= 0.081(5)$, $G_{\\perp}=-0.27(1)$.

  17. FACTORS LEAD TO DEPRESION DURING ANTENATAL CARE EVERY TRIMESTER OF PREGNANT MOTHER

    OpenAIRE

    Eddy Surya Kurniawan; Nyoman Ratep; Wayan Westa

    2013-01-01

    The most important factor in reducing maternal and infant mortality rates began during pregnancy. In 2000, one in twenty children die before reaching the age of five years and a mother died of childbirth out of every 325 live births. The death rate in research mainly indicated comparable levels of depression due to stress in pregnant women. The occurrence of symptoms of depression during the perinatal period can be easily recognized. Depression during pregnancy is a common mood disorder such ...

  18. Language Contact in Algeria and the Leading Factors towards Language Death: Modern Standard Arabic

    OpenAIRE

    Belaskri, Mohammed Yassine

    2016-01-01

    The aim of this present research is to shed light on the language contact and it outcomes towards language death in Algeria. The Algerian linguistic situation is very complex due to several factors, some of which being historical, others political and others socio-cultural. This diversity of language manifestations can cause damage to the native language. What foreigners think about Algeria’s language is not applicable when they once come and see, there is an absolute fact that...

  19. Tissue factor triggers procoagulation in transplanted mesenchymal stem cells leading to thromboembolism.

    Science.gov (United States)

    Tatsumi, Kohei; Ohashi, Kazuo; Matsubara, Yoshinori; Kohori, Ayako; Ohno, Takahiro; Kakidachi, Hiroshi; Horii, Akihiro; Kanegae, Kazuko; Utoh, Rie; Iwata, Takanori; Okano, Teruo

    2013-02-01

    Mesenchymal stem cells (MSCs) have shown extreme clinical promise as a therapeutic regenerative system in the treatment of numerous types of diseases. A recent report, however, documented lethal pulmonary thromboembolism in a patient following the administration of adipose-derived MSCs (ADSCs). In our study, we designed experiments to examine the role of tissue factor (TF), which is highly expressed at the level of mRNA and localized to the cell surface of cultured MSCs, as a triggering factor in the procoagulative cascade activated by infused MSCs. A high mortality rate of ~85% in mice was documented following intravenous infusion of mouse ADSCs within 24 h due to the observation of pulmonary embolism. Rotation thromboelastometry and plasma clotting assay demonstrated significant procoagulation by the cultured mouse ADSCs, and preconditioning of ADSCs with an anti-TF antibody or usage of factor VII deficient plasma in the assay successfully suppressed the procoagulant properties. These properties were also observed in human ADSCs, and could be suppressed by recombinant human thrombomodulin. In uncultured mouse adipose-derived cells (ADCs), the TF-triggered procoagulant activity was not observed and all mice infused with these uncultured ADCs survived after 24 h. This clearly demonstrated that the process of culturing cells plays a critical role in sensitizing these cells as a procoagulator through the induction of TF expression. Our results would recommend that clinical applications of MSCs to inhibit TF activity using anti-coagulant agents or genetic approaches to maximize clinical benefit to the patients.

  20. Choosing Surgery: Identifying Factors Leading to Increased General Surgery Matriculation Rate.

    Science.gov (United States)

    Pointer, David T; Freeman, Matthew D; Korndorffer, James R; Meade, Peter C; Jaffe, Bernard M; Slakey, Douglas P

    2017-03-01

    Tulane graduates have, over the past six years, chosen general surgical residency at a rate above the national average (mean 9.6% vs 6.6%). With much of the recent career choice research focusing on disincentives and declining general surgery applicants, we sought to identify factors that positively influenced our students' decision to pursue general surgery. A 50-question survey was developed and distributed to graduates who matched into a general surgery between the years 2006 and 2014. The survey evaluated demographics, exposure to surgery, and factors affecting interest in a surgical career. We achieved a 54 per cent (61/112) response rate. Only 43 per cent considered a surgical career before medical school matriculation. Fifty-nine per cent had strongly considered a career other than surgery. Sixty-two per cent chose to pursue surgery during or immediately after their surgery clerkship. The most important factors cited for choosing general surgery were perceived career enjoyment of residents and faculty, resident/faculty relationship, and mentorship. Surgery residents and faculty were viewed as role models by 72 and 77 per cent of responders, respectively. This study demonstrated almost half of those choosing a surgical career did so as a direct result of the core rotation experience. We believe that structuring the medical student education experience to optimize the interaction of students, residents, and faculty produces a positive environment encouraging students to choose a general surgery career.

  1. Economic and Political Factors that Lead to the Budget Deficit in Hong Kong from 1998 to 2003

    Institute of Scientific and Technical Information of China (English)

    Fan Chun Wai

    2006-01-01

    Despite the adverse impact of the budget deficit in Hong Kong has been alleviated since the economic recovery from 2003,the fiscal deficit may return when there is another downturn in the economy if the problem is not handled fundamentally. Based on the economic and political situation from 1998 to 2003, the factors that lead to the budget deficit in Hong Kong are analyzed in four perspectives, including (a) increase in public expenditure; (b) decrease in public revenues; (c) poor management of public money and (d) weak administration. With a better understanding on these factors,possible solutions to the fiscal problem faced by the government may be developed.

  2. Risk factors associated with the blood lead levels of children in the Community of Madrid in 2010

    Directory of Open Access Journals (Sweden)

    José María Ordóñez-Iriarte

    2013-12-01

    Full Text Available Introduction: Lead is a toxic element for humans, with children being the most vulnerable population.Objective: To find out the risk factors associated to the existing blood lead levels (BLLs of children in the Community of Madrid, after 9 years of lead being banned in gasoline.Methods: A cross-sectional study was carried out in 2010 with a sample of 85 children, less than 15 years of age, recruited via the outpatients’ service of the Pediatrics Department of the Hospital Clínico San Carlos in Madrid. Routine blood tests provided the opportunity for determining other blood parameters. Lead levels were measured using electrothermal-atomization atomic absorption spectrometry with the Zeeman-effect background correction. In addition, a survey was undertaken directed to the parents for gathering information about a series of socioeconomic and environmental variables.Results: The arithmetic mean of the BLLs in the children was 1.1 μg/dL (SD=0.7 μg/dL with a range from 0.1 μg/dL to 3.4 μg/dL. The geometric mean was 0.9 μg/dL (SD= 1.1 μg/dL. The risk factors associated to these BLLs are the following: playing in the street; low educational level of the parents; leisure activities of one of the parents linked to lead; tobacco smoking of the father; and drinking tap water.Conclusions: The BLLs of the children in the Community of Madrid have decreased, but there are still sociodemographic and environmental risk factors associated to the present levels.

  3. Lead (Pb) and other metals in New York City community garden soils: factors influencing contaminant distributions.

    Science.gov (United States)

    Mitchell, Rebecca G; Spliethoff, Henry M; Ribaudo, Lisa N; Lopp, Donna M; Shayler, Hannah A; Marquez-Bravo, Lydia G; Lambert, Veronique T; Ferenz, Gretchen S; Russell-Anelli, Jonathan M; Stone, Edie B; McBride, Murray B

    2014-04-01

    Urban gardens provide affordable fresh produce to communities with limited access to healthy food but may also increase exposure to lead (Pb) and other soil contaminants. Metals analysis of 564 soil samples from 54 New York City (NYC) community gardens found at least one sample exceeding health-based guidance values in 70% of gardens. However, most samples (78%) did not exceed guidance values, and medians were generally below those reported in NYC soil and other urban gardening studies. Barium (Ba) and Pb most frequently exceeded guidance values and along with cadmium (Cd) were strongly correlated with zinc (Zn), a commonly measured nutrient. Principal component analysis suggested that contaminants varied independently from organic matter and geogenic metals. Contaminants were associated with visible debris and a lack of raised beds; management practices (e.g., importing uncontaminated soil) have likely reduced metals concentrations. Continued exposure reduction efforts would benefit communities already burdened by environmental exposures.

  4. Combined impact of lead, cadmium, polychlorinated biphenyls and non-chemical risk factors on blood pressure in NHANES

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Junenette L., E-mail: petersj@bu.edu; Patricia Fabian, M., E-mail: pfabian@bu.edu; Levy, Jonathan I., E-mail: jonlevy@bu.edu

    2014-07-15

    High blood pressure is associated with exposure to multiple chemical and non-chemical risk factors, but epidemiological analyses to date have not assessed the combined effects of both chemical and non-chemical stressors on human populations in the context of cumulative risk assessment. We developed a novel modeling approach to evaluate the combined impact of lead, cadmium, polychlorinated biphenyls (PCBs), and multiple non-chemical risk factors on four blood pressure measures using data for adults aged ≥20 years from the National Health and Nutrition Examination Survey (1999–2008). We developed predictive models for chemical and other stressors. Structural equation models were applied to account for complex associations among predictors of stressors as well as blood pressure. Models showed that blood lead, serum PCBs, and established non-chemical stressors were significantly associated with blood pressure. Lead was the chemical stressor most predictive of diastolic blood pressure and mean arterial pressure, while PCBs had a greater influence on systolic blood pressure and pulse pressure, and blood cadmium was not a significant predictor of blood pressure. The simultaneously fit exposure models explained 34%, 43% and 52% of the variance for lead, cadmium and PCBs, respectively. The structural equation models were developed using predictors available from public data streams (e.g., U.S. Census), which would allow the models to be applied to any U.S. population exposed to these multiple stressors in order to identify high risk subpopulations, direct intervention strategies, and inform public policy. - Highlights: • We evaluated joint impact of chemical and non-chemical stressors on blood pressure. • We built predictive models for lead, cadmium and polychlorinated biphenyls (PCBs). • Our approach allows joint evaluation of predictors from population-specific data. • Lead, PCBs and established non-chemical stressors were related to blood pressure.

  5. Grainyhead-like factor Get1/Grhl3 regulates formation of the epidermal leading edge during eyelid closure.

    Science.gov (United States)

    Yu, Zhengquan; Bhandari, Ambica; Mannik, Jaana; Pham, Thu; Xu, Xiaoman; Andersen, Bogi

    2008-07-01

    Grainyhead transcription factors play an evolutionarily conserved role in regulating epidermal terminal differentiation. One such factor, the mammalian Grainyhead-like epithelial transactivator (Get1/Grhl3), is important for epidermal barrier formation. In addition to a role in barrier formation, Grainyhead genes play roles in closure of several structures such as the mouse neural tube and Drosophila wounds. Consistent with these observations, we found that Get1 knockout mice have an eye-open at birth phenotype. The failure of eyelid closure appears to be due to critical functions of Get1 in promoting F-actin polymerization, filopodia formation, and the cell shape changes that are required for migration of the keratinocytes at the leading edge during eyelid closure. The expression of TGFalpha, a known regulator of leading edge formation, is decreased in the eyelid tip of Get1(-/-) mice. Levels of phospho-EGFR and phospho-ERK are also decreased at the leading edge tip. Furthermore, in an organ culture model, TGFalpha can increase levels of phospho-EGFR and promote cell shape changes as well as leading edge formation in Get1(-/-) eyelids, indicating that in eyelid closure Get1 acts upstream of TGFalpha in the EGFR/ERK pathway.

  6. 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.

  7. Factors leading to poor water sanitation hygiene among primary school going children in Chitungwiza

    Directory of Open Access Journals (Sweden)

    Blessing Dube

    2012-03-01

    Full Text Available Although the world has progressed in the area of water and sanitation, more than 2.3 billion people still live without access to sanitation facilities and some are unable to practice basic hygiene. Access to water and basic sanitation has deteriorated in Chitungwiza and children are at risk of developing illness and missing school due to the deterioration. We sought to investigate the predisposing, enabling and reinforcing factors that are causally related to water- and sanitation- related hygiene practices among school going children. A random sample of 400 primary school children (196 males, 204 females in four schools in Chitungwiza town, Zimbabwe was interviewed. Behavioural factors were assessed through cross examination of the PROCEED PRECEDE Model. The respondents had been stratified through the random sampling where strata were classes. A structured observation checklist was also administered to assess hygiene enabling facilities for each school. Children’s knowledge and perceptions were inconsistent with hygienic behaviour. The family institution seemed to play a more important role in life skills training and positive reinforcement compared to the school (50% vs 27.3%. There was no association between a child’s sex, age and parents’ occupation with any of the factors assessed (P=0.646. Schools did not provide a hygiene enabling environment as there were no learning materials, policy and resources on hygiene and health. The challenges lay in the provision of hygiene enabling facilities, particularly, the lack of access to sanitation for the maturing girl child and a school curriculum that provides positive reinforcement and practical life skills training approach.

  8. Migraine patients should be cautiously followed for risk factors leading to cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ivan Rocha Ferreira da Silva

    2013-02-01

    Full Text Available Migraine and ischemic strokes are two of the most prevalent diseases worldwide. Besides having a coincident symptomatology, for long researchers have been searching for a possible causal relation between these diseases. Current evidence based on data suggest that patients with aura migraine could have a doubled risk of developing an ischemic stroke, when compared to the rest of the population. At the same time, migraine sufferers apparently have higher incidences of risk factors for cardiovascular events. The aim of this review was not only to dissect some of the more compelling evidence based on data regarding this association, but also to discuss the possible clinical and therapeutic implications.

  9. Examination of factors that lead to complications for new home parenteral nutrition patients.

    Science.gov (United States)

    de Burgoa, Lori Jeris; Seidner, Douglas; Hamilton, Cindy; Stafford, Judy; Steiger, Ezra

    2006-01-01

    Home parenteral nutrition carries a risk of infectious, metabolic, and mechanical complications that cause significant morbidity and mortality. This study investigated the incidence and the causative factors of these complications that occur within the first 90 days after discharge from the hospital to home. Data were prospectively collected and analyzed for 97 adult patients. A complication developed in one third of the patients, and the majority required rehospitalization. Infectious complications were the most prevalent, followed by mechanical and then metabolic complications. The authors describe their methods of collecting data in a quantifiable manner with the ultimate goal of improving patient outcomes.

  10. 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.

  11. 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.

  12. Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas.

    Directory of Open Access Journals (Sweden)

    Jonaina Fiorim

    Full Text Available Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent dose 0.05 µg/100 g, i.m. to cover daily loss or vehicle; blood levels attained at the end of treatment were 9.98 µg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP; reduction of contractile response to phenylephrine (1 nM-100 µM of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 µM or sodium nitroprusside (0.01 nM-0.3 µM. Endothelium removal, N(G-nitro-L-arginine methyl ester (100 µM and tetraethylammonium (2 mM increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 µM increased but losartan (10 µM and enalapril (10 µM reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na(+/K(+-ATPase functional activity, plasma angiotensin-converting enzyme (ACE activity, protein expression of the Na(+/K(+-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS, and inducible nitric oxide synthase (iNOS. Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+/K(+-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP.

  13. Low-Level Lead Exposure Increases Systolic Arterial Pressure and Endothelium-Derived Vasodilator Factors in Rat Aortas

    Science.gov (United States)

    Fiorim, Jonaina; Ribeiro Júnior, Rogério F.; Silveira, Edna A.; Padilha, Alessandra S.; Vescovi, Marcos Vinícius A.; de Jesus, Honério C.; Stefanon, Ivanita; Salaices, Mercedes; Vassallo, Dalton V.

    2011-01-01

    Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent dose 0.05 µg/100 g, i.m. to cover daily loss) or vehicle; blood levels attained at the end of treatment were 9.98 µg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM–100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM–300 µM) or sodium nitroprusside (0.01 nM–0.3 µM). Endothelium removal, NG-nitro-L-arginine methyl ester (100 µM) and tetraethylammonium (2 mM) increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 µM) increased but losartan (10 µM) and enalapril (10 µM) reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na+/K+-ATPase functional activity, plasma angiotensin-converting enzyme (ACE) activity, protein expression of the Na+/K+-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS), and inducible nitric oxide synthase (iNOS). Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na+/K+-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP. PMID:21364929

  14. Delayed amputation in lower limb trauma: an analysis of factors leading to delayed amputation.

    Science.gov (United States)

    Thiagarajan, P

    1999-03-01

    An in-depth analysis of the course of events leading to 49 delayed amputation of the lower extremity in 47 patients with open lower limb fractures is presented. Seventeen amputations were performed within one month mainly for vascular reasons. Eleven were between one month and one year, due to persistent sepsis and 21 amputations were performed more than a year after the original injury for infected non-union. Below-knee amputation was done in 32 limbs, above-knee amputation in 13 limbs and Symes' amputation in 4 limbs. The delay in timing of the amputation was analysed with respect to the nature of the injury, the primary treatment and the Mangled Extremity Severity Score (MESS). The MESS score was computed for all injuries and a score of 7 or more predicted an early amputation. We suggest that in all severe lower limb injuries, particularly in Type III C fractures with associated neurological injury, the benefits of an early amputation be considered as an alternative to a limb salvage procedure.

  15. 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.

  16. 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

  17. 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) ...

  18. Half-lives and cluster preformation factors for various cluster emissions in trans-lead nuclei

    Science.gov (United States)

    Ni, Dongdong; Ren, Zhongzhou

    2010-08-01

    The generalized density-dependent cluster model (GDDCM) is extended to study cluster radioactivity in even-even and odd-A nuclei decaying to the doubly magic nucleus Pb208 or its neighboring nuclei. The microscopic cluster-daughter potential is numerically constructed in the double-folding model with M3Y nucleon-nucleon interactions plus proton-proton Coulomb interactions. Instead of the WKB barrier penetration probability, the exact solution of the Schrödinger equation with outgoing Coulomb wave boundary conditions is presented. The cluster preformation factor is well taken into account based on some available experimental cases. The calculated half-lives are found to be in good agreement with the experimental data. This indicates that a unified description of α decay and cluster radioactivity has been achieved by the GDDCM. Predictions of cluster emission half-lives are made for promising emitters, which may guide future experiments.

  19. A Review of Yoga Programs for Four Leading Risk Factors of Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Kyeongra Yang

    2007-01-01

    Full Text Available Yoga, a form of physical activity, is rapidly gaining in popularity and has many health benefits. Yet healthcare providers have been slow to recognize yoga for its ability to improve health conditions, and few interventions have been developed that take full advantage of its benefits. The purpose of this article is to review published studies using yoga programs and to determine the effect of yoga interventions on common risk factors of chronic diseases (overweight, hypertension, high glucose level and high cholesterol. A systematic search yielded 32 articles published between 1980 and April 2007. The studies found that yoga interventions are generally effective in reducing body weight, blood pressure, glucose level and high cholesterol, but only a few studies examined long-term adherence. Additionally, not enough studies included diverse populations at high risk for diabetes and its related common health problems.

  20. FACTORS LEAD TO DEPRESION DURING ANTENATAL CARE EVERY TRIMESTER OF PREGNANT MOTHER

    Directory of Open Access Journals (Sweden)

    Eddy Surya Kurniawan

    2013-03-01

    Full Text Available The most important factor in reducing maternal and infant mortality rates began during pregnancy. In 2000, one in twenty children die before reaching the age of five years and a mother died of childbirth out of every 325 live births. The death rate in research mainly indicated comparable levels of depression due to stress in pregnant women. The occurrence of symptoms of depression during the perinatal period can be easily recognized. Depression during pregnancy is a common mood disorder such as depression that occurs in the laity in general, where the incidence of depression will occur chemical changes in the brain. Each trimester of pregnancy are at risk of psychological disorders respectively. Antenatal care plays a very important for the safety of the mother and fetus, minimizing the risks of pregnancy, and reduce the number of neonatal deaths. Nursing antenatal care should have run in accordance with minimum standards for pregnant women to obtain a safe childbirth and satisfying.

  1. 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.

  2. Factors affecting lead, cadmium, and arsenic levels in house dust in a smelter town in eastern Germany.

    Science.gov (United States)

    Meyer, I; Heinrich, J; Lippold, U

    1999-07-01

    Hettstedt, a city in eastern Germany with a long history of mining and smelting of nonferrous ores, has several industrial sources of heavy metals. The indoor exposure to metals of children (5 to 14 years old) in the Hettstedt area was assessed by measuring the levels of lead, cadmium, and arsenic contamination in sedimented house dust. Factors which influence the dust loading rate and the surface loading rates of these contaminants in house dust were investigated. The geometric mean of the dust loading rate was 8.9 mg/m2 day. The geometric means of surface loading rates were 1.14, 0. 024, and 0.023 microg/m2 day for lead, cadmium, and arsenic, respectively. Factors that were significantly associated with surface loading rates included the city area of residence, automobile traffic near home, parent with occupational exposure to heavy metals, type of heating, housing characteristics, whether child's home is damp, number of persons living in the child's home, and parents' education. The most significant of these factors was the city area of residence, which reflects the distance from the metal sources; this factor accounted for about half of the variances explained by the regression models.

  3. Environmental exposures to lead, mercury, and cadmium among South Korean teenagers (KNHANES 2010-2013): Body burden and risk factors.

    Science.gov (United States)

    Kim, Nam-Soo; Ahn, Jaeouk; Lee, Byung-Kook; Park, Jungsun; Kim, Yangho

    2017-07-01

    Limited information is available on the association of age and sex with blood concentrations of heavy metals in teenagers. In addition, factors such as a shared family environment may have an association. We analyzed data from the Korean National Health and Nutrition Examination Survey (KNHANES, 2010-2013) to determine whether blood levels of heavy metals differ by risk factors such as age, sex, and shared family environment in a representative sample of teenagers. This study used data obtained in the KNHANES 2010-2013, which had a rolling sampling design that involved a complex, stratified, multistage, probability-cluster survey of a representative sample of the non-institutionalized civilian population in South Korea. Our cross-sectional analysis was restricted to teenagers and their parents who completed the health examination survey, and for whom blood measurements of cadmium, lead, and mercury were available. The final analytical sample consisted of 1585 teenagers, and 376 fathers and 399 mothers who provided measurements of blood heavy metal concentrations. Male teenagers had greater blood levels of lead and mercury, but sex had no association with blood cadmium level. There were age-related increases in blood cadmium, but blood lead decreased with age, and age had little association with blood mercury. The concentrations of cadmium and mercury declined from 2010 to 2013. The blood concentrations of lead, cadmium, and mercury in teenagers were positively associated with the levels in their parents after adjustment for covariates. Our results show that blood heavy metal concentrations differ by risk factors such as age, sex, and shared family environment in teenagers. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. [Factors related to the blood lead level in children 6 to 30 months old in the Prospective Lead Study in Mexico City].

    Science.gov (United States)

    Rothenberg, S J; Schnaas-Arrieta, L; Pérez-Guerrero, I A; Hernández-Cervantes, R; Martínez-Medina, S; Perroni-Hernández, E

    1993-01-01

    A majority of the sample of children (N = 160-121, ages 6-30 months) from the Mexico City Prospective Lead Study exceeds the lowest limit action level (10 micrograms/dl) of the Centers for Disease Control standards for childhood lead exposure. Over one-third of the sample at 18 months and 24 months exceeds the action level (15 micrograms/dl) for aggressive intervention. Diet plays an important role in regulating early childhood blood lead levels. Fresh milk and breast feeding are associated with lower lead levels, but extended breast feeding is related to elevated lead levels. Low income and poor maternal education are associated with higher lead concentration in children. Child consumption of canned milk and juice, up to this date, is associated with elevated child lead levels. Canned products sealed with lead are disappearing from Mexican markets. Efforts to improve childhood nutrition and poverty may be expected to have the additional benefit of lowering lead levels of Mexican children.

  5. A fresh look at factorization breaking in diffractive photoproduction of dijets at HERA at next-to-leading order QCD

    CERN Document Server

    Guzey, V

    2016-01-01

    We calculate the cross section of diffractive dijet photoproduction in $ep$ scattering at next-to-leading order (NLO) of perturbative QCD (pQCD), which we supplement by a model of factorization breaking for the resolved-photon contribution. In this model, the suppression depends on the flavor and momentum fraction of the partons in the photon. We show that within experimental and theoretical uncertainties, the resulting approach provides a good description of the available HERA data in most of the bins. Hence, taken together with the observation that NLO pQCD explains well the data on diffractive photoproduction of open charm in $ep$ scattering, our model of factorization breaking presents a viable alternative to the scheme based on the global suppression factor.

  6. A fresh look at factorization breaking in diffractive photoproduction of dijets at HERA at next-to-leading order QCD

    Energy Technology Data Exchange (ETDEWEB)

    Guzey, V. [Petersburg Nuclear Physics Institute (PNPI), National Research Center ' ' Kurchatov Institute' ' , Gatchina (Russian Federation); Klasen, M. [Westfaelische Wilhelms-Universitaet Muenster, Institut fuer Theoretische Physik, Muenster (Germany)

    2016-08-15

    We calculate the cross section of diffractive dijet photoproduction in ep scattering at next-to-leading order (NLO) of perturbative QCD (pQCD), which we supplement by a model of factorization breaking for the resolved-photon contribution. In this model, the suppression depends on the flavor and momentum fraction of the partons in the photon. We show that within experimental and theoretical uncertainties, the resulting approach provides a good description of the available HERA data in most of the bins. Hence, taken together with the observation that NLO pQCD explains well the data on diffractive photoproduction of open charm in ep scattering, our model of factorization breaking presents a viable alternative to the scheme based on the global suppression factor. (orig.)

  7. A fresh look at factorization breaking in diffractive photoproduction of dijets at HERA at next-to-leading order QCD

    Science.gov (United States)

    Guzey, V.; Klasen, M.

    2016-08-01

    We calculate the cross section of diffractive dijet photoproduction in ep scattering at next-to-leading order (NLO) of perturbative QCD (pQCD), which we supplement by a model of factorization breaking for the resolved-photon contribution. In this model, the suppression depends on the flavor and momentum fraction of the partons in the photon. We show that within experimental and theoretical uncertainties, the resulting approach provides a good description of the available HERA data in most of the bins. Hence, taken together with the observation that NLO pQCD explains well the data on diffractive photoproduction of open charm in ep scattering, our model of factorization breaking presents a viable alternative to the scheme based on the global suppression factor.

  8. Precipitating factors leading to decompensation of chronic heart failure in the elderly patient in South-American community hospital

    Institute of Scientific and Technical Information of China (English)

    Alejandro Diaz; Cleto Ciocchini; Mariano Esperatti; Alberto Becerra; Sabrina Mainardi; Alejandro Farah

    2011-01-01

    Background Exacerbations of heart failure appear frequently associated with precipitating factors not directly related to the evolution of cardiac disease. There still a paucity of data on the proportional distribution of precipitating factors specifically in elderly patients. The aim of this study was to examine prospectively the precipitating factors leading to hospitalization in elderly patients with heart failure in our community hospital. Methods We evaluate elderly patients who need admissions for decompensate heart failure. All patients were reviewed daily by the study investigators at the first 24 h and closely followed-up. Decompensafion was defined as the worsening in clinical NYHA class associated with the need for an increase in medical treatment (at minimum intravenously diuretics). Results We included 102 patients (mean age 79 ± 12 years). Precipitating factors were identified in 88.5%. The decompensation was sudden in 35% of the cases.Noncompliance with diet was identified in 52% of the patients, lack of adherence to the prescribed medications amounted to 30%. Others precipitating factors were infections (29%), arrhythmias (25%), acute coronary ischemia (22%), and uncontrolled hypertension (15%),miscellaneous causes were detected in 18% of the cases (progression of renal disease 60%, anemia 30% and iatrogenic factors 10%).Concomitant cause was not recognizable in 11.5%. Conclusions Large proportion heart failure hospitalizations are associated with preventable precipitating factors. Knowledge of potential precipitating factors may help to optimize treatment and provide guidance for patients with heart failure. The presence of potential precipitating factors should be routinely evaluated in patients presenting chronic heart failure.

  9. Targeting insulin-like growth factor 1 leads to amelioration of inflammatory demyelinating disease.

    Directory of Open Access Journals (Sweden)

    Matthew F Cusick

    Full Text Available In patients with multiple sclerosis (MS and in mice with experimental autoimmune encephalomyelitis (EAE, proliferating autoreactive T cells play an important role in the pathogenesis of the disease. Due to the importance of these myelin-specific T cells, these cells have been therapeutic targets in a variety of treatments. Previously we found that Lenaldekar (LDK, a novel small molecule, could inhibit exacerbations in a preclinical model of MS when given at the start of an EAE exacerbation. In those studies, we found that LDK could inhibit human T cell recall responses and murine myelin responses in vitro. In these new studies, we found that LDK could inhibit myelin specific T cell responses through the insulin-like growth factor-1 receptor (IGF-1R pathway. Alteration of this pathway led to marked reduction in T cell proliferation and expansion. Blocking this pathway could account for the observed decreases in clinical signs and inflammatory demyelinating disease, which was accompanied by axonal preservation. Our data indicate that IGF-1R could be a potential target for new therapies for the treatment of autoimmune diseases where autoreactive T cell expansion is a requisite for disease.

  10. Identifying the Factors Leading to Success: How an Innovative Science Curriculum Cultivates Student Motivation

    Science.gov (United States)

    Scogin, Stephen C.

    2016-06-01

    PlantingScience is an award-winning program recognized for its innovation and use of computer-supported scientist mentoring. Science learners work on inquiry-based experiments in their classrooms and communicate asynchronously with practicing plant scientist-mentors about the projects. The purpose of this study was to identify specific factors contributing to the program's effectiveness in engaging students. Using multiple data sources, grounded theory (Strauss and Corbin in Basics of qualitative research. Sage, Newbury Park, 1990) was used to develop a conceptual model identifying the central phenomenon, causal conditions, intervening conditions, strategies, contexts, and student outcomes of the project. Student motivation was determined to be the central phenomenon explaining the success of the program, with student empowerment, online mentor interaction, and authenticity of the scientific experiences serving as causal conditions. Teachers contributed to student motivation by giving students more freedom, challenging students to take projects deeper, encouraging, and scaffolding. Scientists contributed to student motivation by providing explanations, asking questions, encouraging, and offering themselves as partners in the inquiry process. Several positive student outcomes of the program were uncovered and included increased positivity, greater willingness to take projects deeper, better understanding of scientific concepts, and greater commitments to collaboration. The findings of this study provide relevant information on how to develop curriculum, use technology, and train practitioners and mentors to utilize strategies and actions that improve learners' motivation to engage in authentic science in the classroom.

  11. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function

    Directory of Open Access Journals (Sweden)

    Rickmann Michael

    2008-10-01

    Full Text Available Abstract Background The formation of functional synapses is a crucial event in neuronal network formation, and with regard to regulation of breathing it is essential for life. Members of the transforming growth factor-beta (TGF-β superfamily act as intercellular signaling molecules during synaptogenesis of the neuromuscular junction of Drosophila and are involved in synaptic function of sensory neurons of Aplysia. Results Here we show that while TGF-β2 is not crucial for the morphology and function of the neuromuscular junction of the diaphragm muscle of mice, it is essential for proper synaptic function in the pre-Bötzinger complex, a central rhythm organizer located in the brainstem. Genetic deletion of TGF-β2 in mice strongly impaired both GABA/glycinergic and glutamatergic synaptic transmission in the pre-Bötzinger complex area, while numbers and morphology of central synapses of knock-out animals were indistinguishable from their wild-type littermates at embryonic day 18.5. Conclusion The results demonstrate that TGF-β2 influences synaptic function, rather than synaptogenesis, specifically at central synapses. The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-β2 knock-out mice.

  12. Factors Leading to a Poor Functional Outcome in Spinal Meningioma Surgery: Remarks on 173 Cases.

    Science.gov (United States)

    Raco, Antonino; Pesce, Alessandro; Toccaceli, Giada; Domenicucci, Maurizio; Miscusi, Massimo; Delfini, Roberto

    2017-04-01

    Spinal meningiomas are common spinal tumors, in most cases benign and with a good surgical prognosis. However, specific location, infiltration of spinal cord, vascular encasement, or spinal root involvement can bring a less favorable prognosis. To correlate these data with clinical/functional outcome. Two hundred twenty-four consecutive patients with spinal meningiomas treated from 1976 to 2013 in our institution were analyzed; among these, 51 were excluded for incomplete clinical data or follow-up. The remaining 173 cases were classified in regards to sex, age, symptoms, axial location, Simpson grade resection, and functional pre-/postoperative status. Most recurring onset symptoms were pain (32.9%) and motor deficit (31.8%); thoracic spine was the most severely affected (69.8%). Functional improvement on the follow-up was observed in 86.7% of cases; 6.4% of patients resulted stable and 6.9% worsened. A low functional grade before surgery was connected to a lesser improvement after. Anterolateral meningiomas were the most represented (42.2%); a gross total resection (Simpson grades I and II) was conducted in 98.8%, and a macroscopically complete removal without dural resection or coagulation (Simpson grade III) was performed in 1.2%. Of the meningiomas, 98.3% were classified as WHO grade I. Recurrence rate was 2.3%, and 7 cases presented complications (4 of 7 required surgical procedure). We can affirm that negative prognostic factors in our study were anterior or anterolateral axial location, prolonged presentation before diagnosis, WHO grade >I, Simpson grade resections II and III, sphincter involvement, and worse functional grade at onset.

  13. Virtual touch tissue imaging and quantification (VTIQ) in the evaluation of thyroid nodules: the associated factors leading to misdiagnosis

    Science.gov (United States)

    Sun, Cheng-Yu; Lei, Kai-Rong; Liu, Bo-Ji; Bo, Xiao-Wan; Li, Xiao-Long; He, Ya-Ping; Wang, Dan; Ren, Wei-Wei; Zhao, Chong-Ke; Xu, Hui-Xiong

    2017-01-01

    To evaluate the associated factors leading to misdiagnosis with VTIQ for differentiation between benign from malignant thyroid nodules (TNs). The study included 238 benign TNs and 150 malignant TNs. Conventional ultrasound (US) features and VTIQ parameters were obtained and compared with the reference standard of histopathological and/or cytological results. Binary logistic regression analysis was performed to select independent variables leading to misdiagnosis. The maximum shear wave speed (SWS) (SWS-max), mean SWS (SWS-mean), SWS-ratio and standard deviation of SWS (SWS-SD) were significantly higher for malignant TNs compared with benign TNs (all P thyroid gland (OR: 0.033) were negatively associated with them. Nodule depth (OR: 0.881) and TI-RADS category (OR: 0.563) were negatively associated with false negative VTIQ findings. These US characteristic of TNs should be taken into consideration when interpreting the results of VTIQ examinations. PMID:28157195

  14. 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.

  15. 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.

  16. 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.

  17. 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).

  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 contro

  19. 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

  20. Risk factors leading to increased rehospitalization rates among adolescents admitted to an acute care child and adolescent psychiatric hospital.

    Science.gov (United States)

    McCarthy, Logan; Pullen, Lisa M; Savage, Jennifer; Cayce, Jonathan

    2017-09-18

    Suicide is the third leading cause of death in adolescents in the United States, with suicidal behavior peaking in adolescence. Suicidal and self-harming behavior is often chronic, with an estimated 15-30% of adolescents who attempt suicide having a second suicide attempt within a year. The focus of acute psychiatric hospitalization is on stabilization of these psychiatric symptoms resulting at times in premature discharge. Finding from studies based on high rehospitalization rates among adolescents admitted to an acute psychiatric hospital indicates that adolescents continue to experience crisis upon discharge from an acute psychiatric hospital, leading to the question of whether or not these adolescents are being discharged prematurely. A chart review was performed on 98 adolescent clients admitted to an acute psychiatric hospital to identify risk factors that may increase rehospitalization among adolescents admitted to an acute psychiatric hospital. Clients admitted to the hospital within a 12-month time frame were compared to clients who were not readmitted during that 12-month period. History of self-harming behavior and length of stay greater than 5 days were found to be risk factors for rehospitalization. Adolescent clients who are admitted to an acute psychiatric hospital with a history of self-harming behavior and extended length of stay need to be identified and individualized treatment plans implemented for preventing repeat hospitalizations. © 2017 Wiley Periodicals, Inc.

  1. Factors leading to poor outcome of noninvasive positive pressure ventilation in acute exacerbation of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    Ashok Kumar; Anoop Kumar; Kelash Rai; Shaista Ghazal; Nadeem Rizvi; Sunil Kumar; Sadhna Notani

    2015-01-01

    Objective:To determine frequency of factors leading to poor outcome of non-invasive positive pressure ventilation in acute exacerbation of chronic obstructive pulmonary disease. Methods:This cross sectional study was conducted at our center between May 2012 and November 2012. A total of 195 diagnosed patients of acute exacerbation of chronic obstructive pulmonary disease meeting the inclusion criteria were selected from the ER department. At the time of admission age was inquired BP, respiratory rate and oxygen saturation will be noted and pedal edema was assessed and investigations were sent for pH assessment. Noninvasive positive pressure ventilation (NIPPV) using BiPAP was applied in spontaneous mode by the help of oronasal mask. Presence of respiratory rate (less than 12/min), systolic blood pressure140 bpm was taken as poor outcome. Results:The average age of the cases was 61.9±9.3 years with male to female ratio being 1.5:1. NIPPV was successful in 151 (77.4%) cases and 44 (22.6%) cases were underwent endotracheal intubation. About 38 (44.7%) of patients with oxygen saturation (82%-86%) had poor prognosis. A total of 40 (55.6%) of patients with pH range 7.20-7.26, required endotracheal intubation, 43 (66.2%) with pedal edema underwent endotracheal intubation. While 29 (24.16%) patients of age>60 years needed endotracheal intubation. Conclusions:In this study, NIPPV was successful in 77.4%cases and 22.6%cases were underwent endotracheal intubation. Pedal edema was the most common factor leading to poor outcomes while age>60 years was the least common factor, 66.2%and 24.2%respectively.

  2. 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.

  3. 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.

  4. 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

  5. Revisiting the vector form factor at next-to-leading order in 1/N{sub C}

    Energy Technology Data Exchange (ETDEWEB)

    Rosell, Ignasi, E-mail: rosell@uch.ceu.e [Departamento de Ciencias Fisicas, Matematicas y de la Computacion, Universidad CEU Cardenal Herrera, c/ Sant Bartomeu 55, E-46115 Alfara del Patriarca, Valencia (Spain); IFIC, Universitat de Valencia - CSIC, Apt. Correus 22085, E-46071 Valencia (Spain)

    2010-10-15

    Using the Resonance Chiral Theory lagrangian, we perform a calculation of the vector form factor of the pion at the next-to-leading order (NLO) in the 1/N{sub C} expansion. Imposing the correct QCD short-distance constraints, one determines it in terms of F, G{sub V}, F{sub A} and resonance masses. Its low momentum expansion fixes then the low-energy chiral couplings L{sub 9} and C{sub 88} -C{sub 90} at NLO, keeping full control of their renormalization scale dependence. At {mu}{sub 0} = 0.77 GeV, we obtain L{sup r}{sub 9}({mu}{sub 0}) = (7.6 {+-} 0.6) . 10{sup -3} and C{sup r}{sub 88}({mu}{sub 0}) -C{sup r}{sub 90}({mu}{sub 0}) = (-4.5 {+-} 0.5) . 10{sup -5}.

  6. Epidermal growth factor treatment of the adult brain subventricular zone leads to focal microglia/macrophage accumulation and angiogenesis.

    Science.gov (United States)

    Lindberg, Olle R; Brederlau, Anke; Kuhn, H Georg

    2014-04-01

    One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

  7. Divalent lead cations induce cyclooxygenase-2 gene expression by epidermal growth factor receptor/nuclear factor-kappa B signaling in A431carcinoma cells.

    Science.gov (United States)

    Chou, Yii-Her; Woon, Peng-Yeong; Huang, Wan-Chen; Shiurba, Robert; Tsai, Yao-Ting; Wang, Yu-Shiuan; Hsieh, Tusty-Jiuan; Chang, Wen-Chang; Chuang, Hung-Yi; Chang, Wei-Chiao

    2011-06-10

    Divalent lead cations (Pb²+) are toxic metal pollutants that may contribute to inflammatory diseases in people and animals. Human vascular smooth muscle cells in culture respond to low concentrations of Pb²+ ions by activating mediators of inflammation via the plasma membrane epidermal growth factor receptor (EGFR). These include cyclooxygenase-2 (COX-2) and cytosolic phospholipase A₂ as well as the hormone-like lipid compound prostaglandin E₂. To further clarify the mechanism by which Pb²+ induces such mediators of inflammation, we tested human epidermoid carcinoma cell line A431 that expresses high levels of EGFR. Reverse transcription PCR and western blots confirmed A431 cells treated with a low concentration (1 μM) of Pb²+ in the form of lead (II) nitrate increased expression of COX-2 mRNA and its encoded protein in a time-dependent manner. Promoter deletion analysis revealed the transcription factor known as nuclear factor-kappa B (NF-κB) was a necessary component of the COX-2 gene response. NF-κB inhibitor BAY 11-7082 suppressed Pb²+-induced COX-2 mRNA expression, and EGFR inhibitors AG1478 and PD153035 as well as EGFR small interfering RNA reduced the coincident nuclear translocation of NF-κB. Our findings support the hypothesis that low concentrations of Pb²+ ions incite inflammation by inducing COX-2 gene expression via the EGFR/NF-κB signal transduction pathway. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. Reference values of lead in blood and related factors among Korean adolescents: the Korean National Health and Nutrition Examination Survey 2010-2013

    OpenAIRE

    Choi, Min-Gyu; Park, Mi-Jung; Kim, Shin-Hye

    2016-01-01

    Purpose This study aimed to assess the reference values and factors influencing blood lead levels among Korean adolescents. Methods The study population consisted of 1,585 adolescents (801 males, 784 females; aged 10-19 years) who participated in the Korea National Health and Nutrition Examination Survey 2010-2013. We analyzed blood lead concentrations in relation to demographic/lifestyle characteristics for all participants. "Reference values" of blood lead levels were calculated as the uppe...

  11. 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

  12. Epidermal Growth Factor Treatment of the Adult Brain Subventricular Zone Leads to Focal Microglia/Macrophage Accumulation and Angiogenesis

    Directory of Open Access Journals (Sweden)

    Olle R. Lindberg

    2014-04-01

    Full Text Available One of the major components of the subventricular zone (SVZ neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

  13. 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.

  14. 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.)

  15. 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.

  16. 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.

  17. Impacts of microRNA gene polymorphisms on the susceptibility of environmental factors leading to carcinogenesis in oral cancer.

    Directory of Open Access Journals (Sweden)

    Yin-Hung Chu

    Full Text Available BACKGROUND: MicroRNAs (miRNAs have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC. METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48 of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94 and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79 in younger patients (age<60. CONCLUSIONS: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese.

  18. Neuropilin-1 modulates vascular endothelial growth factor-induced poly(ADP-ribose)-polymerase leading to reduced cerebrovascular apoptosis.

    Science.gov (United States)

    Mey, Lilli; Hörmann, Mareike; Schleicher, Nadine; Reuter, Peter; Dönges, Simone; Kinscherf, Ralf; Gassmann, Max; Gerriets, Tibo; Al-Fakhri, Nadia

    2013-11-01

    Cerebral ischemia is encompassed by cerebrovascular apoptosis, yet the mechanisms behind apoptosis regulation are not fully understood. We previously demonstrated inhibition of endothelial apoptosis by vascular endothelial growth factor (VEGF) through upregulation of poly(ADP-ribose)-polymerase (PARP) expression. However, PARP overactivation through oxidative stress can lead to necrosis. This study tested the hypothesis that neuropilin-1 (NP-1), an alternative VEGF receptor, regulates the response to cerebral ischemia by modulating PARP expression and, in turn, apoptosis inhibition by VEGF. In endothelial cell culture, NP-1 colocalized with VEGF receptor-2 (VEGFR-2) and acted as its coreceptor. This significantly enhanced VEGF-induced PARP mRNA and protein expression demonstrated by receptor-specific inhibitors and VEGF-A isoforms. NP-1 augmented the inhibitory effect of VEGF/VEGFR-2 interaction on apoptosis induced by adhesion inhibition through the αV-integrin inhibitor cRGDfV. NP-1/VEGFR-2 signal transduction involved JNK and Akt. In rat models of permanent and temporary middle cerebral artery occlusion, the ischemic cerebral hemispheres displayed endothelial and neuronal apoptosis next to increased endothelial NP-1 and VEGFR-2 expression compared to non-ischemic cerebral hemispheres, sham-operated or untreated controls. Increased vascular superoxide dismutase-1 and catalase expression as well as decreased glycogen reserves indicated oxidative stress in the ischemic brain. Of note, protein levels of intact PARP remained stable despite pro-apoptotic conditions through increased PARP mRNA production during cerebral ischemia. In conclusion, NP-1 is upregulated in conditions of imminent cerebrovascular apoptosis to reinforce apoptosis inhibition and modulate VEGF-dependent PARP expression and activation. We propose that NP-1 is a key modulator of VEGF maintaining cerebrovascular integrity during ischemia. Modulating the function of NP-1 to target PARP could help to

  19. 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

  20. 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.

  1. 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.

  2. Lead exposure in the general population of the Metropolitan Area of Barcelona. Blood levels and related factors

    Energy Technology Data Exchange (ETDEWEB)

    Sole, E. [Pediatrics Service, Hospital Universitari Arnau de Vilanova, Lleida (Spain); Ballabriga, A.; Dominguez, C. [Centre d`Investigacions en Bioquimica y Biologia Molecular, Vall d`Hebron Hospitals, School of Medicine, Pediatrics Department, Universitat Autonoma de Barcelona, Barcelona (Spain)

    1998-12-11

    A cross-sectional was conducted on 254 individuals not occupationally exposed to lead to determine the degree of lead exposure in the general population of the Metropolitan Area of Barcelona. Blood lead levels (BPb) were analysed by atomic absorption spectrophotometry and zinc protoporphyrin (ZPP) by haemofluorimetry. Blood lead levels were analysed with respect to individuals` age, sex, area of residence, the season of the year the blood was drawn and ZPP. Mean blood lead in our series was 0.22{+-}0.011 {mu}mol/l (mean{+-}S.E.); no significant differences were found with respect to area of residence, sex or season. A linear relationship was observed between BPb and individuals` age (BPb=0.08+0.05xage; r=0.37). The prevalence of lead intoxication (BPb>0.48 {mu}mol/l) was 7.1%. No linear relationship was observed between BPb and ZPP. ZPP determination does not appear to be a good screening method for lead intoxication since it presents low specificity and sensitivity values with an area below the ROC curve similar to the null value line (area below the curve=0.5052, IC 95%=0.443-0.568). We conclude that lead exposure does not constitute a serious health problem in the area studied, since BPb levels found are far below the toxic limit and the prevalence of intoxication is similar to that reported in other studies conducted in other developed countries

  3. 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.

  4. Lead and cadmium in human teeth from Jordan by atomic absorption spectrometry: Some factors influencing their concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Alomary, A. [Department of Chemistry, Yarmouk University, Irbid (Jordan)]. E-mail: ahmedalomary1000@hotmail.com; Al-Momani, I.F. [Department of Chemistry, Yarmouk University, Irbid (Jordan); Massadeh, A.M. [Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid (Jordan)

    2006-10-01

    The aim of this study was to measure the concentrations of lead (Pb) and cadmium (Cd) in human teeth and to investigate the affecting factors. Teeth samples (n = 268) were collected from people living in different cities in Jordan including Amman, Zarqa, Al-Mafraq and Irbid and analyzed for Pb and Cd using atomic absorption spectrometry (AAS). A questionnaire was used to gather information on each person, such as age, sex, place where the patient lives, smoking, presence of amalgam fillings inside the mouth, and whether the patient uses toothpaste or not. The mean concentrations of Pb and Cd were 28.91 {mu}g/g and 0.44 {mu}g/g, respectively. The results indicate that there is a clear relation between Pb and Cd concentrations and the presence of amalgam fillings, smoking, and place of living. Pb was sex-dependent, whereas Cd was not. Our results show that Pb and Cd concentrations in samples obtained from Al-Mafraq and Irbid are higher than those obtained from Amman and Zarqa. Pb was highest in Mafraq, whereas Cd was highest in Irbid. The Pb and Cd concentrations in teeth from smokers (means: Pb = 31.89 {mu}g/g, Cd = 0.49 {mu}g/g) were significantly higher than those from nonsmokers (means: Pb = 24.07 {mu}g/g, Cd = 0.37 {mu}g/g). Pb and Cd concentrations in teeth of patients with amalgam fillings (means: Pb = 31.02 {mu}g/g and Cd = 0.52 {mu}g/g) were significantly higher than those from patients without amalgam fillings (means: Pb = 26.87 {mu}g/g and Cd = 0.41 {mu}g/g). Our results show that brushing the teeth daily with toothpaste does not significantly decrease the concentration of both Pb and Cd. The mean concentrations of Pb and Cd do not vary significantly between the ages 20-30, 31-40, and 41-50, but both increased rapidly at age 51-60.

  5. Chronic alterations in growth hormone/insulin-like growth factor-I signaling lead to changes in mouse tendon structure.

    Science.gov (United States)

    Nielsen, R H; Clausen, N M; Schjerling, P; Larsen, J O; Martinussen, T; List, E O; Kopchick, J J; Kjaer, M; Heinemeier, K M

    2014-02-01

    The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis is an important stimulator of collagen synthesis in connective tissue, but the effect of chronically altered GH/IGF-I levels on connective tissue of the muscle-tendon unit is not known. We studied three groups of mice; 1) giant transgenic mice that expressed bovine GH (bGH) and had high circulating levels of GH and IGF-I, 2) dwarf mice with a disrupted GH receptor gene (GHR-/-) leading to GH resistance and low circulating IGF-I, and 3) a wild-type control group (CTRL). We measured the ultra-structure, collagen content and mRNA expression (targets: GAPDH, RPLP0, IGF-IEa, IGF-IR, COL1A1, COL3A1, TGF-β1, TGF-β2, TGF-β3, versican, scleraxis, tenascin C, fibronectin, fibromodulin, decorin) in the Achilles tendon, and the mRNA expression was also measured in calf muscle (same targets as tendon plus IGF-IEb, IGF-IEc). We found that GHR-/- mice had significantly lower collagen fibril volume fraction in Achilles tendon, as well as decreased mRNA expression of IGF-I isoforms and collagen types I and III in muscle compared to CTRL. In contrast, the mRNA expression of IGF-I isoforms and collagens in bGH mice was generally high in both tendon and muscle compared to CTRL. Mean collagen fibril diameter was significantly decreased with both high and low GH/IGF-I signaling, but the GHR-/- mouse tendons were most severely affected with a total loss of the normal bimodal diameter distribution. In conclusion, chronic manipulation of the GH/IGF-I axis influenced both morphology and mRNA levels of selected genes in the muscle-tendon unit of mice. Whereas only moderate structural changes were observed with up-regulation of GH/IGF-I axis, disruption of the GH receptor had pronounced effects upon tendon ultra-structure.

  6. 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

  7. Hygienic aspects of lead osteotropicity as a risk factor of calcium-deficit pathology in man (literature survey

    Directory of Open Access Journals (Sweden)

    Biletska E.M.

    2014-06-01

    Full Text Available For today problem of chemical contamination of the environment and inner enviroment of the organism is extremely topical. Among all toxicants scientists pay special attention to lead, as it is characterized by a global prevalence in the enviroment and polytropic action on the human organism. Aim of the work – on the basis of analytical generalization of research data to establish peculiarities of lead impact on formation and functioning of bone tissue, calcium balance in the organism. It was determined that despite a low external exposure of metal, in man’s biosubstrates its levels are much higher than allowable. Herewith bone tissue due to its anatomy-physiology peculiarities accumulates lead selectively, forming inner additional source of its impact on the organism, potentiating toxic impact of xenobiotic. Therefore biomonitoring data on lead content in bone tissue is an important informative finding not only of danger but of duration, permanence and complex impact on the organism.

  8. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R

    1993-01-01

    homolog of DP-1. Human DP-1 and E2F-1 associate both in vivo and in vitro, and this interaction leads to enhanced binding to E2F DNA-binding sites. The association of E2F-1 and DP-1 leads to cooperative activation of an E2F-responsive promoter. Finally, we demonstrate that E2F-1 and DP-1 association...

  9. 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

  10. 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.

  11. 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.

  12. Evaluation of factors influencing child abuse leading to oro-facial lesions in Isfahan, Iran: A qualitative approach

    Directory of Open Access Journals (Sweden)

    Firoozeh Nilchian

    2012-01-01

    Conclusion: This study has identified a variety of factors influencing the incidence of child abuse. Therefore, dentists should meticulously pay attention to children who have these risk factors in order to discover child abuse events. Quantitative research would reveal the extent of these factors. Dentists′ knowledge of their roles in managing cases suffering from abuse might need to be assessed to see if dentists need further education in this important area.

  13. Roles of the non-medical prescribing leads within organisations across a Strategic Health Authority: perceived functions and factors supporting the role.

    Science.gov (United States)

    Lim, Rosemary Hwee Mei; Courtenay, Molly; Fleming, Gail

    2013-04-01

    Extending the roles of nurses, pharmacists and allied health professionals to include prescribing has been identified as one way of improving service provision. In the UK, over 50 000 non-medical healthcare professionals are now qualified to prescribe. Implementation of non-medical prescribing ( NMP) is crucial to realise the potential return on investment. The UK Department of Health recommends a NMP lead to be responsible for the implementation of NMP within organisations. The aim of this study was to explore the role of NMP leads in organisations across one Strategic Health Authority (SHA) and to inform future planning with regards to the criteria for those adopting this role, the scope of the role and factors enabling the successful execution of the role. Thirty-nine NMP leads across one SHA were approached. Semi-structured telephone interviews were conducted. Issues explored included the perceived role of the NMP lead, safety and clinical governance procedures and facilitators to the role. Transcribed audiotapes were coded and analysed using thematic analytical techniques. In total, 27/39 (69.2%) NMP leads were interviewed. The findings highlight the key role that the NMP lead plays with regards to the support and development of NMP within National Health Service trusts. Processes used to appoint NMP leads lacked clarity and varied between trusts. Only two NMP leads had designated or protected time for their role. Strategic influence, operational management and clinical governance were identified as key functions. Factors that supported the role included organisational support, level of influence and dedicated time. The NMP lead plays a significant role in the development and implementation of NMP. Clear national guidance is needed with regards to the functions of this role, the necessary attributes for individuals recruited into this post and the time that should be designated to it. This is important as prescribing is extended to include other groups of

  14. First rehabilitation consultation in patients of non-native origin: factors that lead to tension in the patient-physician interaction.

    NARCIS (Netherlands)

    Sloots, M.; Scheppers, E.F.; Bartels, E.A.; Geertzen, J.H.; Dekker, J.

    2009-01-01

    To explore which factors lead to tension in the patient-physician interaction in the first consultation by rehabilitation physicians of patients with chronic non-specific low back pain of Turkish and Moroccan origin. In-depth semi-structured, face to face interviews were conducted with 12 patients o

  15. First rehabilitation consultation in patients of non-native origin: factors that lead to tension in the patient-physician interaction.

    NARCIS (Netherlands)

    Sloots, M.; Scheppers, E.F.; Bartels, E.A.; Geertzen, J.H.; Dekker, J.

    2009-01-01

    To explore which factors lead to tension in the patient-physician interaction in the first consultation by rehabilitation physicians of patients with chronic non-specific low back pain of Turkish and Moroccan origin. In-depth semi-structured, face to face interviews were conducted with 12 patients o

  16. First rehabilitation consultation in patients of non-native origin : Factors that lead to tension in the patient-physician interaction

    NARCIS (Netherlands)

    Sloots, M.; Scheppers, E. F.; Bartels, E. A. C.; Dekker, J. H. M.; Geertzen, J. H. B.; Dekker, J.

    2009-01-01

    Purpose. To explore which factors lead to tension in the patient-physician interaction in the first consultation by rehabilitation physicians of patients with chronic non-specific low back pain of Turkish and Moroccan origin. Method. In-depth semi-structured, face to face interviews were conducted w

  17. First rehabilitation consultation in patients of non-native origin: Factors that lead to tension in the patient-physician interaction

    NARCIS (Netherlands)

    Sloots, M.; Scheppers, E.F.; Bartels, E.A.C.; Geertzen, J.; Dekker, J.

    2009-01-01

    Purpose. To explore which factors lead to tension in the patient-physician interaction in the first consultation by rehabilitation physicians of patients with chronic non-specific low back pain of Turkish and Moroccan origin. Method. In-depth semi-structured, face to face interviews were conducted w

  18. Determination of ring correction factors for leaded gloves used in grab sampling activities at Hanford tank farms

    Energy Technology Data Exchange (ETDEWEB)

    RATHBONE, B.A.

    1999-06-24

    This study evaluates the effectiveness of lead lined gloves in reducing extremity dose from two sources specific to tank waste sampling activities: (1) sludge inside glass sample jars and (2) sludge as thin layer contamination on the exterior surface of sample jars. The response of past and present Hanford Extremity Dosimeters (ring) designs under these conditions is also evaluated.

  19. Strontium insertion in methlyammonium lead iodide: long charge carrier lifetime and high fill factor solar cells (Conference Presentation)

    Science.gov (United States)

    Momblona, Cristina; Gil-Escrig, Lidón; Ávila, Jorge; Pérez-Del-Rey, Daniel; Forgács, David; Sessolo, Michele; Bolink, Hendrik J.

    2016-09-01

    Organic-inorganic (hybrid) lead halide perovskites are taking the lead among the emerging photovoltaics technologies, thanks to the demonstration of power conversion efficiencies exceeding 20 %. Hybrid perovskites have a wide spectrum of desirable properties; they are direct bandgap semiconductors with very high absorption coefficients, high and balanced hole and electron mobility, and large diffusion length. A unique feature of these materials is their versatility in terms of bandgap energy, which can be tuned by simple exchange of their components. In this paper we present vacuum and hybrid deposition routes for the preparation of different organic-inorganic lead perovskite thin films, and their incorporation into efficient solar cells. The influence of the type of organic semiconductors used as hole/electron transport layer in p-i-n solar cells will be presented. We also discuss their electroluminescence properties, either for applications in light-emitting diodes or as a diagnostic tool of the optical and electronic quality of perovskite thin films. Finally, the effect of additives and dopants in the perovskite absorber as well as in the charge selective layers will be described.

  20. Continuum limit of the leading order HQET form factor in B{sub s}→Klν decays

    Energy Technology Data Exchange (ETDEWEB)

    Bahr, Felix; Banerjee, Debasish; Koren, Mateusz; Simma, Hubert; Sommer, Rainer [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Bernardoni, Fabio [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Technische Univ. Dresden (Germany). Medizinische Fakultaet ' ' Carl Gustav Carus' ' ; Joseph, Anosh [Cambridge Univ. (United Kingdom). Dept. of Applied Mathematics and Theoretical Physics (DAMTP); Collaboration: ALPHA Collaboration

    2016-01-15

    We discuss the computation of form factors for semi-leptonic decays of B-, B{sub s}- mesons in lattice QCD. Considering in particular the example of the static B{sub s} form factors we demonstrate that after non-perturbative renormalization the continuum limit can be taken with confidence. The resulting precision is of interest for extractions of V{sub ub}. The size of the corrections of order 1/m{sub b} is just estimated at present but it is expected that their inclusion does not pose significant difficulties.

  1. 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.

  2. Factors Leading African Americans and Black Caribbeans to Use Social Work Services for Treating Mental and Substance Use Disorders

    Science.gov (United States)

    Cheng, Tyrone C.; Robinson, Michael A.

    2013-01-01

    This secondary analysis of 5,000 African Americans and black Caribbeans explored how their use of social work services to address mental and substance use disorders was associated with the disorder involved as well as their perceived need for services, belief system, family resources, proximity to services, social-structural factors, and…

  3. 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

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

    Science.gov (United States)

    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.

  5. 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.

  6. Choosing to comply with the U.S.-India civil nuclear agreement. Factors leading to state compliance

    Directory of Open Access Journals (Sweden)

    Octavio González Segovia

    2014-12-01

    Full Text Available State compliance with international commitments is uneven. However, the perception of which countries will and will not comply and to what extent can be biased. Some scholars assume that the U.S. will abide by the India-U.S. 123 civil nuclear agreement, which main objective is to supply India with nuclear fuel. At the same time, some other researchers doubt that India would honor its respective commitments, namely, to maintain safeguard measures in its nuclear facilities. The present study expands the knowledge of the factors affecting compliance within the realm of nuclear trade by analyzing a non-binding instrument negotiated between two asymmetrical actors. Drawing on Peter Haas’ compliance theories, the author analyzes the incidence as well as the relevance of international institutional and ideational factors which, in combination with domestic politics and structures, can influence the actor’s decision to comply. The paper’s findings suggest that India can be expected to more fully comply with the provisions of the treaty than the United States. Depending on whether certain institutional or ideational factor intervenes, Washington is either not capable or is not willing to comply. Its will to comply could be affected, inter alia, by important domestic actors concerned with the application of the Hyde Act, as evidenced during the ratification process. Therefore, contrary to the mainstream view, the 123 Agreement neither enables India to achieve energy security nor ends thirty-four years of nuclear isolation.

  7. THE INVESTIGATION OF THE FACTORS WHICH LEAD TO THE DESTRUCTION OF ORTHODOX CHURCH BUILDINGS AND THEIR PARTS

    Directory of Open Access Journals (Sweden)

    LYKHOHRAI V. V.

    2017-01-01

    Full Text Available Problem Statement. The main characteristic of the buildings, including Orthodox churches, is a reliability index. It depends on the service condition and includes reliability, durability, effective age of a structure and suitability of buildings and their separate elements to repairs [4; 10]. Despite the fact that the greatest losses Ukrainian architectural heritage have suffered from the policy of the communist regime and utilitarian, equally important factor was the low cultural standard of living. A number of lost churches as a result of neglect and "unconscious vandalism" is equal to the losses that were caused by the First and Second World Wars [2; 9]. As a result of the increase, the intensity of the adverse factors impact on Orthodox churches building their reliability is reduced. Since the dominant number of scientific publications dealing with technical condition and methods of restoration only for particular buildings, it is still no common data on the primary cause of the destruction of Orthodox churches. The main unexplored issues include the following: 1 what kinds of structural destructions have a mass character; 2 what kinds of what factors have a critical role in reducing building reliability index; 3 what are the main causes of the loss of interior decoration of churches. Research in this area will help to prioritize the development of constructive and technological solutions for the restoration of Ukrainian sacral architectural heritage. The purpose of the article. To identify factors which have the most impact on the durability of supporting structures of stone Orthodox churches (including which were built before 1917 and preserve their interior decoration on the basis of the expert survey. Conclusion. According to the results of expert evaluation and calculations, found that: cupolas, vaults (domes and vertical bearing structures suffered the most significant losses; the main destructive factors of Orthodox churches can be

  8. Chronic alterations in growth hormone/insulin-like growth factor-I signaling lead to changes in mouse tendon structure

    DEFF Research Database (Denmark)

    Nielsen, R H; Clausen, N M; Schjerling, P

    2014-01-01

    transgenic mice that expressed bovine GH (bGH) and had high circulating levels of GH and IGF-I, 2) dwarf mice with a disrupted GH receptor gene (GHR-/-) leading to GH resistance and low circulating IGF-I, and 3) a wild-type control group (CTRL). We measured the ultra-structure, collagen content and m......-/- mice had significantly lower collagen fibril volume fraction in Achilles tendon, as well as decreased mRNA expression of IGF-I isoforms and collagen types I and III in muscle compared to CTRL. In contrast, the mRNA expression of IGF-I isoforms and collagens in bGH mice was generally high in both tendon...

  9. Factors influencing uncertainties of in vivo bone lead measurement using a (109)Cd K X-ray fluorescence clover leaf geometry detector system.

    Science.gov (United States)

    Behinaein, Sepideh; Chettle, David R; Marro, Leonora; Malowany, Morie; Fisher, Mandy; Fleming, David E B; Healey, Norm; Inskip, Mike; Arbuckle, Tye E; McNeill, Fiona E

    2014-12-01

    A (109)Cd K X-ray fluorescence (KXRF) measurement system consisting of four detectors in clover-leaf geometry is a non-invasive, low-radiation-dose method of measuring bone lead concentration. Its high precision in estimating the bone lead content makes it a promising tool for the determination of the low levels of lead currently found in the general population. After developing the clover-leaf geometry system, the system was used for the first time in a major survey in 2008 to measure the lead levels of 497 smelter employees (an occupationally exposed group with high lead levels). Since the delivered effective dose of the bone lead system in clover-leaf geometry is small (on the order of nSv), the technique can be used to measure the bone lead of sensitive populations such as the elderly and children. This detector system was used from 2009 to 2011, in a pilot study that measured the bone lead concentration of 263 environmentally exposed individuals (termed the EG group) residing in Toronto, Ontario, Canada. In this paper, the factors that influence uncertainties in lead content in tibia (cortical bone) and calcaneus (trabecular bone) are discussed based on gender, age, and body mass index (BMI) by using analysis of variance (ANOVA) and multiple linear regression models. Results from the two study groups (the EG group versus the occupationally exposed smelter employees) are compared where appropriate (i.e. for males older than 20). Results from univariate analyses showed that females have higher tibia uncertainty compared to males. We observed significant differences for both calcaneus and tibia uncertainty measures (p < 0.0005) among different age groups, where the uncertainties were highest in the lowest age group (<11 years). Lastly, and perhaps most significantly, we found that the product of source activity and measurement time influenced the precision of measurements greatly, and that this factor alone could account for the higher uncertainties observed for

  10. 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

  11. Analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture following transurethral resection of prostate

    Science.gov (United States)

    Tao, Huang; Jiang, Yu Yong; Jun, Qi; Ding, Xu; Jian, Duan Liu; Jie, Ding; Ping, Zhu Yu

    2016-01-01

    ABSTRACT Purpose: To determine risk factors of postoperative urethral stricture (US) and vesical neck contracture (BNC) after transurethral resection of prostate (TURP) from perioperative parameters. Materials and Methods: 373 patients underwent TURP in a Chinese center for lower urinary tract symptoms suggestive of benign prostatic obstruction (LUTS/BPO), with their perioperative and follow-up clinical data being collected. Univariate analyses were used to determine variables which had correlation with the incidence of US and BNC before logistic regression being applied to find out independent risk factors. Results: The median follow-up was 29.3 months with the incidence of US and BNC being 7.8% and 5.4% respectively. Resection speed, reduction in hemoglobin (ΔHb) and hematocrit (ΔHCT) levels, incidence of urethral mucosa rupture, re-catheterization and continuous infection had significant correlation with US, while PSA level, storage score, total prostate volume (TPV), transitional zone volume (TZV), transitional zone index (TZI), resection time and resected gland weight had significant correlation with BNC. Lower resection speed (OR=0.48), urethral mucosa rupture (OR=2.44) and continuous infection (OR=1.49) as well as higher storage score (OR=2.51) and lower TPV (OR=0.15) were found to be the independent risk factors of US and BNC respectively. Conclusions: Lower resection speed, intraoperative urethral mucosa rupture and postoperative continuous infection were associated with a higher risk of US while severer storage phase symptom and smaller prostate size were associated with a higher risk of BNC after TURP. PMID:27256185

  12. Different Eukaryotic Initiation Factor Mutations Lead to Various Degrees of Intolerance to the Stress of Endoplasmic Reticulum in Oligodendrocytes

    Institute of Scientific and Technical Information of China (English)

    Na Chen; Yu-Wu Jiang; Hong-Jun Hao; Ting-Ting Ban; Kai Gao; Zhong-Bin Zhang; Jing-Min Wang

    2015-01-01

    Background:Vanishing white matter disease (VWM),a human autosomal recessive inherited leukoencephalopathy,is due to mutations in eukaryotic initiation factor 2B (eIF2B).eIF2B is responsible for the initiation of protein synthesis by its guanine nucleotide exchange factor (GEF) activity.Mutations ofeIF2B impair GEF activity at different degree.Previous studies implied improperly activated unfolded protein response (UPR) and endoplasmic reticulum stress (ERS) participated in the pathogenesis ofVWM.Autophagy relieves endoplasmic reticulum load by eliminating the unfolded protein.It is still unknown the effects of genotypes on the pathogenesis.In this work,UPR and autophagy flux were analyzed with different mutational types.Methods:ERS tolerance,reflected by apoptosis and cell viability,was detected in human oligodendrocyte cell line transfected with the wild type,or different mutations ofp.Arg 113His,p.Arg269* or p.Ser610-Asp613del in eIF2Bε.A representative UPR-PERK component of activating transcription factor 4 (ATF4) was measured under the basal condition and ERS induction.Autophagy was analyzed the flux in the presence of lysosomal inhibitors.Results:The degree of ERS tolerance varied in different genotypes.The truncated or deletion mutant showed prominent apoptosis cell viability declination afder ERS induction.The most seriously damaged GEF activity ofp.Arg269* group underwent spontaneous apoptosis.The truncated or deletion mutant showed elevated ATF4 under basal as well as ERS condition.Decreased expression of LC3-Ⅰ and LC3-Ⅱ in the mutants reflected an impaired autophagy flux,which was more obvious in the truncated or deletion mutants after ERS induction.Conclusions:GEF activities in different genotypes could influence the cell ERS tolerance as well as compensatory pathways of UPR and autophagy.Oligodendrocytes with truncated or deletion mutants showed less tolerable to ERS.

  13. High expression of nuclear factor 90 (NF90 leads to mitochondrial degradation in skeletal and cardiac muscles.

    Directory of Open Access Journals (Sweden)

    Takuma Higuchi

    Full Text Available While NF90 has been known to participate in transcription, translation and microRNA biogenesis, physiological functions of this protein still remain unclear. To uncover this, we generated transgenic (Tg mice using NF90 cDNA under the control of β-actin promoter. The NF90 Tg mice exhibited a reduction in body weight compared with wild-type mice, and a robust expression of NF90 was detected in skeletal muscle, heart and eye of the Tg mice. To evaluate the NF90 overexpression-induced physiological changes in the tissues, we performed a number of analyses including CT-analysis and hemodynamic test, revealing that the NF90 Tg mice developed skeletal muscular atrophy and heart failure. To explore causes of the abnormalities in the NF90 Tg mice, we performed histological and biochemical analyses for the skeletal and cardiac muscles of the Tg mice. Surprisingly, these analyses demonstrated that mitochondria in those muscular tissues of the Tg mice were degenerated by autophagy. To gain further insight into the cause for the mitochondrial degeneration, we identified NF90-associated factors by peptide mass fingerprinting. Of note, approximately half of the NF90-associated complexes were ribosome-related proteins. Interestingly, protein synthesis rate was significantly suppressed by high-expression of NF90. These observations suggest that NF90 would negatively regulate the function of ribosome via its interaction with the factors involved in the ribosome function. Furthermore, we found that the translations or protein stabilities of PGC-1 and NRF-1, which are critical transcription factors for expression of mitochondrial genes, were significantly depressed in the skeletal muscles of the NF90 Tg mice. Taken together, these findings suggest that the mitochondrial degeneration engaged in the skeletal muscle atrophy and the heart failure in the NF90 Tg mice may be caused by NF90-induced posttranscriptional repression of transcription factors such as PGC-1 and

  14. Frequency and changes in trends of leading risk factors of coronary heart disease in women in the city of Novi Sad during a 20-year period

    Directory of Open Access Journals (Sweden)

    Rakić Dušica

    2012-01-01

    Full Text Available Backround/Aim. From 1984 to 2004 the city of Novi Sad participated through its Health Center “Novi Sad” in the international Multinational MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA project, as one of the 38 research centers in 21 countries around the world. The aim of this study was to determine frequency and changes of trends in leading risk factors of coronary heart disease (CHD and to analyze the previous trend of movement of coronary event in women in Novi Sad during a 20- year period. Methods. In 2004, the fourth survey within MONICA project was conducted in the city of Novi Sad. The representative sample included 1,041 women between the age of 25 and 74. The prevalence of risk factors in CHD such as smoking, high blood pressure, elevated blood cholesterol, elevated blood glucose and obesity was determined. Also, indicators of risk factors and rates of coronary events in women were compared with the results from MONICA project obtained in previous three screens, as well as with the results from other research centres. χ2-test, linear trend and correlartion coefficient were used in statistical analysis of results obtained. Results. It was observed that during a 20-year period covered by the study, the prevalence of the leading risk factors for the development of CHD in the surveyed women was significantly increasing and in positive correlation with the values of linear trend. Also, the increase of morbidity rates and mortality rates of coronary event were in positive correlation. The decrease was only recorded in the period from 1985-1989 (the implementation of the intervention programme. Conclusion. Upon analysing the increase in prevalence of leading risk factors of CHD and significant increase in the rates of coronary event, we can conclude that health status of women in Novi Sad during a 20-year period was deteriorating.

  15. 37 years of scientific activity in a Biochemistry Department in Brazil: patterns of growth and factors leading to increased productivity.

    Science.gov (United States)

    Gomes, Urubatã E; Oliveira, Diogo L de; Berti, Luciana C; Amaral, Olavo; Souza, Diogo O; Wofchuk, Susana T

    2011-09-01

    Scientific activity in Brazil has experienced an accelerated growth in the past decades, with an increase in productivity that greatly surpasses the international average. This growth has occurred mostly at the expense of centers of excellence in public universities, which account for the vast majority of the country's scientific output. The aim of this study was to evaluate the production of the Department of Biochemistry of a large public university in southern Brazil (Universidade Federal do Rio Grande do Sul), as well as to identify internal and external policies that have influenced this growing production profile. We have performed a historical analysis of the scientific output of this Department of Biochemistry, which accounts for a considerable share of the indexed scientific production at this university. By focusing on the temporal course of its growth and drawing correlations between scientific output and important events in the history of the Department of Biochemistry and of the Brazilian science policies, we concluded that internal factors (as the creation of a postgraduation program, collaboration among researchers, experienced abroad researchers, qualification of faculty members) and external factors (as investments in the postgraduate education, the establishment of national scientific policies, such as financial stimuli for productive researchers and evaluation systems) influence scientific productivity in Brazil.

  16. The conjunction of factors that lead to formation of giant gold provinces and deposits in non-arc settings

    Science.gov (United States)

    Groves, David I.; Goldfarb, Richard J.; Santosh, M.

    2016-01-01

    It is quite evident that it is not anomalous metal transport, nor unique depositional conditions, nor any single factor at the deposit scale, that dictates whether a mineral deposit becomes a giant or not. A hierarchical approach thus is required to progressively examine controlling parameters at successively decreasing scales in the total mineral system to understand the location of giant gold deposits in non-arc environments. For giant orogenic, intrusion-related gold systems (IRGS) and Carlin-type gold deposits and iron oxide-copper-gold (IOCG) deposits, there are common factors among all of these at the lithospheric to crustal scale. All are sited in giant gold provinces controlled by complex fundamental fault or shear zones that follow craton margins or, in the case of most Phanerozoic orogenic giants, define the primary suture zones between tectonic terranes. Giant provinces of IRGS, IOCG, and Carlin-type deposits require melting of metasomatized lithosphere beneath craton margins with ascent of hybrid lamprophyric to granitic magmas and associated heat flux to generate the giant province. The IRGS and IOCG deposits require direct exsolution of volatile-rich magmatic-hydrothermal fluids, whereas the association of such melts with Carlin-type ores is more indirect and enigmatic. Giant orogenic gold provinces show no direct relationship to such magmatism, forming from metamorphic fluids, but show an indirect relationship to lamprophyres that reflect the mantle connectivity of controlling first-order structures.

  17. Groundwater Dynamics as an Essential Factor in the Precipitation of the Pine Point MVT Lead-Zinc Deposits

    Science.gov (United States)

    Weyer, K. U.

    2014-12-01

    Hypotheses on the genesis of MVT lead zinc deposits place that genesis generally well into the geological past with elevated temperatures in the 100 °C range. In the case of the Pine Point lead zinc deposits, the time of genesis has been assumed to have happened from the Middle Devonian age to the Tertiary age. It is generally said that, based on isotope data, the ore forming fluid there must have been hydrothermal in a temperature range of 100 °C or more. The average homogenized temperature in fluid inclusions in dolomite in the Pine Point area has been reported to be 116 °C and the burial temperature at about 70 °C. In the course of a former joint industry/governmental research project on regional and local groundwater flow, water chemistry, and water isotopes, all available regional and local geological and mineral data for exploration bore holes were collected. The massive body of these data indicated that in the Pine Point region, the present groundwater flow systems and their respective chemistry would support the continuous formation of ore bodies from glacial times to the present day. This body of data provides strong indications that the interplay of today's groundwater flow systems, their chemistry, and the associated microbiological activity may currently be forming MVT ore bodies and mineral showings even at low non-hydrothermal temperatures in the range of 3 °C. Upon abandonment of Pine Point Mines this suspicion was supported by the occurrence of a 'black smoker' discharging from a flowing hole near one of the formerly mined ore bodies (Figure 1). At Pine Point, MVT ore bodies are positioned within karstic rocks at the intersection of two active and very substantial groundwater flow systems. In one of these systems, groundwater carries sulphate, while the other, upwelling one, also carries NaCl and metals. At the ore bodies, microbiological populations of sulfur-reducing bacteria are present and participate in forming conditions for ore

  18. 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.

  19. Accumulation and Soil-to-Plant Transfer Factor of Lead and Manganese in some Plant Species in Semnan Province, Central Iran

    Directory of Open Access Journals (Sweden)

    Mohamad Sakizadeh

    2016-04-01

    Full Text Available Background: Heavy metals have detrimental effects on the health of human being. The values of manganese (Mn and lead (Pb in some plant species and soil samples in an arid area of Iran were evaluated in this study. Methods: The values of Pb and Mn in 94 plant samples from 8 plant species and the related soil samples in 2010 were considered in Shahroud and Damghan, central Iran. Moreover, the soil-to-plant transfer factors of these two elements were investigated. Results: Except for barley, the values of Pb in all of the considered plants were higher than the standard level of 0.3 mg/kg. The amounts of Mn in all of the plant species other than pistachio were higher than the standard level of 25 mg/kg. As a whole, the bio-concentration factor of Mn was higher than that of Pb in the study area. Conclusion: None of the soil-to-plant transfer factors exceeded one. Grape recorded the highest amounts of Pb and Mn compared with that of other investigated plant species. However, since its respective bio concentration factor (BCF was lower than one, it cannot be considered as a hyper accumulator of lead and manganese.

  20. Interaction of operational and physicochemical factors leading to Gordonia amarae-like foaming in an incompletely nitrifying activated sludge plant.

    Science.gov (United States)

    Asvapathanagul, Pitiporn; Huang, Zhonghua; Gedalanga, Phillip B; Baylor, Amber; Olson, Betty H

    2012-12-01

    The overgrowth of Gordonia amarae-like bacteria in the mixed liquor of an incompletely nitrifying water reclamation plant was inversely correlated with temperature (r = -0.78; P < 0.005) and positively correlated with the solids retention time (SRT) obtained a week prior to sampling (r = 0.67; P < 0.005). Drops followed by spikes in the food-to-mass ratio (0.18 to 0.52) and biochemical oxygen demand concentrations in primary effluent (94 to 298 mg liter(-1)) occurred at the initiation of G. amarae-like bacterial growth. The total bacterial concentration did not increase as concentrations of G. amarae-like cells increased, but total bacterial cell concentrations fluctuated in a manner similar to that of G. amarae-like bacteria in the pseudo-steady state. The ammonium ion removal rate (percent) was inversely related to G. amarae-like cell concentrations during accelerated growth and washout phases. The dissolved oxygen concentration decreased as the G. amarae-like cell concentration decreased. The concentrations of G. amarae-like cells peaked (2.47 × 10(9) cells liter(-1)) approximately 1.5 months prior to foaming. Foaming occurred during the late pseudo-steady-state phase, when temperature declines reversed. These findings suggested that temperature changes triggered operational and physicochemical changes favorable to the growth of G. amarae-like bacteria. Fine-scale quantitative PCR (qPCR) monitoring at weekly intervals allowed a better understanding of the factors affecting this organism and indicated that frequent sampling was required to obtain statistical significance with factors changing as the concentrations of this organism increased. Furthermore, the early identification of G. amarae-like cells when they are confined to mixed liquor (10(7) cells liter(-1)) allows management strategies to prevent foaming.

  1. The 2007 John Charnley Award. Factors leading to low prevalence of DVT and pulmonary embolism after THA: analysis of genetic and prothrombotic factors.

    Science.gov (United States)

    Kim, Young-Hoo; Kim, Jun-Shik

    2007-12-01

    We evaluated 136 hips (104 patients) to determine the prevalence of and contributing factors in deep vein thrombosis (DVT) and pulmonary embolism (PE) in those who were not given thromboprophylaxis when undergoing primary cementless total hip arthroplasty (THA). We performed coagulation assays, a full blood count, blood typing, and serum chemical profile tests for all patients on three separate occasions. Molecular genetic testing was performed preoperatively to detect the genetic traits involving DVT. DVT was diagnosed by roentgenographic venography, and PE was diagnosed by perfusion lung scanning. Our patients had a low prevalence of DVT and no patient had PE. Patients with bilateral THA had similar rates (p = 0.158; CI, -0.134-0.125) of venographic DVT as patients with unilateral THA (16 of 65 or 25% versus 12 of 72 or 17% respectively). We observed a relationship between DVT and factor V Leiden mutation, antithrombin-III level, and prothrombin promoter G20210A mutation. We saw no relationship between DVT and coagulation or thrombophilic data. We conclude combinations of absent thrombophilic polymorphisms with low clinical prothrombotic risk factors led to low prevalence of DVT and virtually absent PE after THA in the current series of patients, who had not received any form of prophylactic or therapeutic treatment for DVT.

  2. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  3. Accumulation of Peptidoglycan O-Acetylation Leads to Altered Cell Wall Biochemistry and Negatively Impacts Pathogenesis Factors of Campylobacter jejuni.

    Science.gov (United States)

    Ha, Reuben; Frirdich, Emilisa; Sychantha, David; Biboy, Jacob; Taveirne, Michael E; Johnson, Jeremiah G; DiRita, Victor J; Vollmer, Waldemar; Clarke, Anthony J; Gaynor, Erin C

    2016-10-21

    Campylobacter jejuni is a leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, its mechanisms of pathogenesis are poorly understood. Peptidoglycan (PG) is important for helical shape, colonization, and host-pathogen interactions in C. jejuni Therefore, changes in PG greatly impact the physiology of this organism. O-acetylation of peptidoglycan (OAP) is a bacterial phenomenon proposed to be important for proper cell growth, characterized by acetylation of the C6 hydroxyl group of N-acetylmuramic acid in the PG glycan backbone. The OAP gene cluster consists of a PG O-acetyltransferase A (patA) for translocation of acetate into the periplasm, a PG O-acetyltransferase B (patB) for O-acetylation, and an O-acetylpeptidoglycan esterase (ape1) for de-O-acetylation. In this study, reduced OAP in ΔpatA and ΔpatB had minimal impact on C. jejuni growth and fitness under the conditions tested. However, accumulation of OAP in Δape1 resulted in marked differences in PG biochemistry, including O-acetylation, anhydromuropeptide levels, and changes not expected to result directly from Ape1 activity. This suggests that OAP may be a form of substrate level regulation in PG biosynthesis. Ape1 acetylesterase activity was confirmed in vitro using p-nitrophenyl acetate and O-acetylated PG as substrates. In addition, Δape1 exhibited defects in pathogenesis-associated phenotypes, including cell shape, motility, biofilm formation, cell surface hydrophobicity, and sodium deoxycholate sensitivity. Δape1 was also impaired for chick colonization and adhesion, invasion, intracellular survival, and induction of IL-8 production in INT407 cells in vitro The importance of Ape1 in C. jejuni biology makes it a good candidate as an antimicrobial target. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Accumulation of Peptidoglycan O-Acetylation Leads to Altered Cell Wall Biochemistry and Negatively Impacts Pathogenesis Factors of Campylobacter jejuni*

    Science.gov (United States)

    Ha, Reuben; Frirdich, Emilisa; Sychantha, David; Biboy, Jacob; Taveirne, Michael E.; Johnson, Jeremiah G.; DiRita, Victor J.; Vollmer, Waldemar; Clarke, Anthony J.; Gaynor, Erin C.

    2016-01-01

    Campylobacter jejuni is a leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, its mechanisms of pathogenesis are poorly understood. Peptidoglycan (PG) is important for helical shape, colonization, and host-pathogen interactions in C. jejuni. Therefore, changes in PG greatly impact the physiology of this organism. O-acetylation of peptidoglycan (OAP) is a bacterial phenomenon proposed to be important for proper cell growth, characterized by acetylation of the C6 hydroxyl group of N-acetylmuramic acid in the PG glycan backbone. The OAP gene cluster consists of a PG O-acetyltransferase A (patA) for translocation of acetate into the periplasm, a PG O-acetyltransferase B (patB) for O-acetylation, and an O-acetylpeptidoglycan esterase (ape1) for de-O-acetylation. In this study, reduced OAP in ΔpatA and ΔpatB had minimal impact on C. jejuni growth and fitness under the conditions tested. However, accumulation of OAP in Δape1 resulted in marked differences in PG biochemistry, including O-acetylation, anhydromuropeptide levels, and changes not expected to result directly from Ape1 activity. This suggests that OAP may be a form of substrate level regulation in PG biosynthesis. Ape1 acetylesterase activity was confirmed in vitro using p-nitrophenyl acetate and O-acetylated PG as substrates. In addition, Δape1 exhibited defects in pathogenesis-associated phenotypes, including cell shape, motility, biofilm formation, cell surface hydrophobicity, and sodium deoxycholate sensitivity. Δape1 was also impaired for chick colonization and adhesion, invasion, intracellular survival, and induction of IL-8 production in INT407 cells in vitro. The importance of Ape1 in C. jejuni biology makes it a good candidate as an antimicrobial target. PMID:27474744

  5. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

    Directory of Open Access Journals (Sweden)

    Harini Lakshminarasimhan

    Full Text Available Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day causes growth of dendrites and spines in the basolateral amygdala (BLA, but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

  6. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

    Science.gov (United States)

    Lakshminarasimhan, Harini; Chattarji, Sumantra

    2012-01-01

    Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day) causes growth of dendrites and spines in the basolateral amygdala (BLA), but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h) leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

  7. The conjunction of factors that lead to formation of giant gold provinces and deposits in non-arc settings

    Institute of Scientific and Technical Information of China (English)

    David I. Groves; Richard J. Goldfarb; M. Santosh

    2016-01-01

    It is quite evident that it is not anomalous metal transport, nor unique depositional conditions, nor any single factor at the deposit scale, that dictates whether a mineral deposit becomes a giant or not. A hierarchical approach thus is required to progressively examine controlling parameters at successively decreasing scales in the total mineral system to understand the location of giant gold deposits in non-arc environments. For giant orogenic, intrusion-related gold systems (IRGS) and Carlin-type gold deposits and iron oxide-copper-gold (IOCG) deposits, there are common factors among all of these at the litho-spheric to crustal scale. All are sited in giant gold provinces controlled by complex fundamental fault or shear zones that follow craton margins or, in the case of most Phanerozoic orogenic giants, define the primary suture zones between tectonic terranes. Giant provinces of IRGS, IOCG, and Carlin-type deposits require melting of metasomatized lithosphere beneath craton margins with ascent of hybrid lamp-rophyric to granitic magmas and associated heat flux to generate the giant province. The IRGS and IOCG deposits require direct exsolution of volatile-rich magmatic-hydrothermal fluids, whereas the associa-tion of such melts with Carlin-type ores is more indirect and enigmatic. Giant orogenic gold provinces show no direct relationship to such magmatism, forming from metamorphic fluids, but show an indirect relationship to lamprophyres that reflect the mantle connectivity of controlling first-order structures. In contrast to their province scale similarities, the different giant gold deposit styles show contrasting critical controls at the district to deposit scale. For orogenic gold deposits, the giants appear to have formed by conjunction of a greater number of parameters to those that control smaller deposits, with resultant geometrical and lithostratigraphic complexity as a guide to their location. There are few giant IRGS due to their inferior fluid

  8. Interactive factors leading to dying-off Carex tato in Momoge wetland polluted by crude oil, Western Jilin, China.

    Science.gov (United States)

    Pan, Xiangliang; Zhang, Daoyong; Quan, Liu

    2006-12-01

    Momoge wetland is an internationally important wetland not only because it is a habitat for many rare bird species but also because it is an internationally important stopover for some rare global migratory bird species. However the petroleum exploitation in wetland has brought about many environmental problems. One of the most severe problems is crude oil pollution, which has caused the dying-off Carex tato and imposes great threat on survival of rare birds. This work studied the factors that caused the dying off of Carex tato. The results showed that death of Carex tato was the result narcosis toxicity of alcohols, intermediate biodegradation products of crude oil, on the root tissue, and the fragmentization of cuticle of leaves by light components of crude oil volatized from soil surface. However, the mechanism involved was much more complex and three interactive factors including crude oil pollution of soil, long-term drought and poor permeability of soil were responsible for the dying-off of Carex tato grassland. The distribution of crude oil in soil profile was characterized with high concentrations at top silty layer and the layer below root zone and low or no crude oil at root zone layer. This distribution was relative to root system characteristics and rhizospheric biodegradation. In root zone, substantive oxygen could be transported to root zone through dense root system and well developed aerenchyma. The crude oil in root zone was easily biodegraded by aerobic rhizosphere microbes. However, some toxic intermediate products, such as some alcohols, was sealed in root zone due to poor permeability of the top soil layer and the deeper soil layer and they had lethal effects on root tissue. Above ground, low molecular components of crude oil in top soil layer was easily volatized into atmosphere during long-term drought. Some of the volatized components were adsorbed onto leaves. SEM analysis showed that these components destroyed the leaves by fragmentization

  9. 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.

  10. 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.

  11. The Leading Factors in Cultural Land Quality of Huixian, Henan%河南省辉县市耕地质量主导因素分析

    Institute of Scientific and Technical Information of China (English)

    宋富强; 王令超; 毋黎明

    2015-01-01

    The analysis of the leading factors in cultural land quality helps to reveal the main problems in cultural land management and improves the efficiency of cultural land use. Based on the gradation on agriculture land quality of Huixian City,Henan Province,the leading factors of cultural land quality were analyzed by using linear regression and principal component analysis. The results showed that irrigation efficiency ,soil layer thickness and altitude were the leading factors in climate,topography,soil,cultural land conditions and socio-economic factors,which influenced the cultural land quality. This study provided the theoretical references of the cultural land quality monitoring and cultural land quality enhance measures.%耕地质量主导因素分析有助于揭示耕地管理存在的主要问题,提高耕地资源利用效率。在河南省辉县市耕地质量等别补充完善工作基础上,利用回归分析及主成分分析两种方法,探讨影响辉县市耕地质量的主导因素。结果表明:在影响耕地质量的气候、地形地貌、土壤、耕地基本条件和社会经济五方面因素中,灌溉保证率、有效土层厚度和海拔是影响耕地质量的主导因素。本研究为耕地质量监测工作的开展与耕地质量提升措施的选择提供了理论参考。

  12. Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss.

    Science.gov (United States)

    Winship, Amy; Correia, Jeanne; Krishnan, Tara; Menkhorst, Ellen; Cuman, Carly; Zhang, Jian-Guo; Nicola, Nicos A; Dimitriadis, Evdokia

    2015-08-14

    The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been shown to regulate trophoblast adhesion and invasion in vitro, however its precise role in vivo is unknown. We hypothesized that LIF would be required for normal placental development in mice. LIF and LIFRα were immunolocalized to placental trophoblasts and fetal vessels in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via intraperitoneal administration of our specific LIFRα antagonist, PEGLA, resulted in abnormal placental trophoblast and vascular morphology and reduced activated STAT3 but not ERK. Numerous genes regulating angiogenesis and oxidative stress were altered in the placenta in response to LIF inhibition. Pregnancy viability was also significantly compromised in PEGLA treated mice. Our data suggest that LIF plays an important role in placentation in vivo and the maintenance of healthy pregnancy.

  13. Small interfering RNA against transcription factor STAT6 leads to increased cholesterol synthesis in lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Richa Dubey

    Full Text Available STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460 using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc.

  14. The conjunction of factors that lead to formation of giant gold provinces and deposits in non-arc settings

    Directory of Open Access Journals (Sweden)

    David I. Groves

    2016-05-01

    In contrast to their province scale similarities, the different giant gold deposit styles show contrasting critical controls at the district to deposit scale. For orogenic gold deposits, the giants appear to have formed by conjunction of a greater number of parameters to those that control smaller deposits, with resultant geometrical and lithostratigraphic complexity as a guide to their location. There are few giant IRGS due to their inferior fluid-flux systems relative to orogenic gold deposits, and those few giants are essentially preservational exceptions. Many Carlin-type deposits are giants due to the exceptional conjunction of both structural and lithological parameters that caused reactive and permeable rocks, enriched in syngenetic gold, to be located below an impermeable cap along antiformal “trends”. Hydrocarbons probably played an important role in concentrating metal. The supergiant Post-Betze deposit has additional ore zones in strain heterogeneities surrounding the pre-gold Goldstrike stock. All unequivocal IOCG deposits are giant or near-giant deposits in terms of gold-equivalent resources, partly due to economic factors for this relatively poorly understood, low Cu-Au grade deposit type. The supergiant Olympic Dam deposit, the most shallowly formed deposit among the larger IOCGs, probably owes its origin to eruption of volatile-rich hybrid magma at surface, with formation of a large maar and intense and widespread brecciation, alteration and Cu-Au-U deposition in a huge rock volume.

  15. Consistency in trophic magnification factors of cyclic methyl siloxanes in pelagic freshwater food webs leading to brown trout.

    Science.gov (United States)

    Borgå, Katrine; Fjeld, Eirik; Kierkegaard, Amelie; McLachlan, Michael S

    2013-12-17

    Cyclic volatile methyl siloxanes (cVMS) concentrations were analyzed in the pelagic food web of two Norwegian lakes (Mjøsa, Randsfjorden), and in brown trout (Salmo trutta) and Arctic char (Salvelinus alpinus) collected in a reference lake (Femunden), in 2012. Lakes receiving discharge from wastewater treatment plants (Mjøsa and Randsfjorden) had cVMS concentrations in trout that were up to 2 orders of magnitude higher than those in Femunden, where most samples were close to the limit of quantification (LOQ). Food web biomagnification of cVMS in Mjøsa and Randsfjorden was quantified by estimation of trophic magnification factors (TMFs). TMF for legacy persistent organic pollutants (POPs) were analyzed for comparison. Both decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) biomagnified with TMFs of 2.9 (2.1-4.0) and 2.3 (1.8-3.0), respectively. Octamethylcyclotetrasiloxane (D4) was below the LOQ in the majority of samples and had substantially lower biomagnification than for D5 and D6. The cVMS TMFs did not differ between the lakes, whereas the legacy POP TMFs were higher in Mjøsa than inRandsfjorden. Whitefish had lower cVMS bioaccumulation compared to legacy POPs, and affected the TMF significance for cVMS, but not for POPs. TMFs of D5 and legacy contaminants in Lake Mjøsa were consistent with those previously measured in Mjøsa.

  16. Business On-Line? An Empirical Study of Factors Leading to the Adoption of Internet Technologies by Australian SMEs

    Directory of Open Access Journals (Sweden)

    Peter Slade

    2002-11-01

    Full Text Available E-commerce technologies such as a Web site, email and the use of Web browsers enable access to large amounts of information, facilitate communication and provide niche companies with an effective mechanism for competing with larger organisations world-wide. However, recent literature has shown Australian SMEs have been slow in the uptake of these technologies. The aim of this research was to determine which factors were important in impacting on small firms’ decision making in respect of information technology and e-commerce adoption. Findings indicate that generally, the more a firm was concerned about its competitive position, so such a firm was likely to develop a Web site. Moreover, the ‘Industry and Skill Demands’ dimension suggested that as the formal education of the owner/manager increased, coupled with the likelihood that the firm was in the transport and storage or communication services industries, and realising the cost of IT adoption was in effect an investment, then such a firm would be inclined to develop a Web site. Firms that were presented with relatively geographically dispersed markets, and realising it was necessary to go through the time consuming process of adopting various IT to reach these markets, were more likely to adopt Web sites. Lastly, owners/managers who reported their knowledge of business uses of computers was poor and who were likely to ask for support in installing and utilizing IT were also more likely to use Web sites than those who did not share these characteristics.

  17. High blood levels of lead in children aged 6-36 months in Kathmandu Valley, Nepal: A cross-sectional study of associated factors.

    Science.gov (United States)

    Dhimal, Meghnath; Karki, Khem Bahadur; Aryal, Krishna Kumar; Dhimal, Bimala; Joshi, Hari Datt; Puri, Sajan; Pandey, Achyut Raj; Dhakal, Purushotam; Sharma, Arun Kumar; Raya, Ganendra Bhakta; Ansari, Imran; Groneberg, David A; Müller, Ruth; Kuch, Ulrich

    2017-01-01

    Young children are at greatest risk of exposure to lead and its effects. Although lead is one of the most widely used elements with known health hazard, there is little data on the blood lead level (BLL) of children in the Kathmandu Valley. Thus, this study aimed to assess factors associated with high BLL in children who were 6-36 months of age and resided in the Kathmandu Valley. In this hospital-based cross-sectional study 6-36 month-old children visiting the Paediatrics Outpatient Department of Tribhuvan University Teaching Hospital, Patan Hospital, and Siddhi Memorial Hospital were enrolled. All three hospitals are located in different areas inside the Kathmandu Valley. Written informed consent was obtained from the parents, and exposure data were collected using a structured questionnaire. Portable Anodic Stripping Voltammetry (ASV) was used to determine BLLs in children. Data were analyzed using SPSS version 16. Of 312 children enrolled in the study, 64.4% had BLLs ≥5μg/dl. A significant association was found between BLL and exposure to enamel paints in the household in the form of painting materials used in different parts of the house like walls, windows and doors (p = 0.001). Furthermore, multivariate analyses showed that BLLs were 4.5 times higher in children playing with dirt and dust (p = 0.006) and that children belonging to the community of lower caste/ethnicity groups had significantly higher BLLs compared to those from the upper caste groups (p = 0.02). Our study demonstrated that children living in households that have used enamel paints, children belonging to lower caste/ethnic groups, and children frequently playing with dirt and dust had significantly higher BLLs. The results of this study highlight the importance of policy decisions to limit environmental lead contamination, and to roll out awareness building measures designed to limit lead exposure and break the poverty cycle associated with chronic lead poisoning.

  18. Identification of factors involved in medication compliance: incorrect inhaler technique of asthma treatment leads to poor compliance

    Directory of Open Access Journals (Sweden)

    Darbà J

    2016-02-01

    Full Text Available Josep Darbà,1 Gabriela Ramírez,2 Antoni Sicras,3 Laura García-Bujalance,4 Saku Torvinen,5 Rainel Sánchez-de la Rosa6 1Department of Economics, Universitat de Barcelona, 2BCN Health Economics & Outcomes Research S.L., 3Department of Planning, Badalona Serveis Assistencials S.A., Barcelona, 4Market Access Department, Teva Pharmaceutical, Madrid, Spain; 5Market Access Department, Teva Pharmaceuticals Europe BV, Amsterdam, the Netherlands; 6Medical Department, Teva Pharmaceutical, Madrid, Spain Objective: To identify the impact of delivery device of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA on asthma medication compliance, and investigate other factors associated with compliance. Materials and methods: We conducted a retrospective and multicenter study based on a review of medical registries of asthmatic patients treated with ICS/LABA combinations (n=2,213 whose medical devices were either dry powder inhalers (DPIs, such as Accuhaler®, Turbuhaler®, and NEXThaler® or pressurized metered-dose inhalers (pMDI. Medication compliance included persistence outcomes through 18 months and medication possession ratios. Data on potential confounders of treatment compliance such as asthma exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also explored. Results: The probability of asthma medication compliance in case of DPIs was lower compared to pMDIs, which suggests that inhaler devices influence inhalation therapies. There were additional confounding factors that were considered as explanatory variables of compliance. A worse measure of airflow obstruction (forced expiration volume in 1 second, comorbidities and general practitioner (GP consultations more than once per month decreased the probability of compliance. Within comorbidities, alcoholism was positively associated with compliance. Patients of 29–39, 40–50, and 51–61 age groups or suffering from more than two

  19. 37 years of scientific activity in a Biochemistry Department in Brazil: patterns of growth and factors leading to increased productivity

    Directory of Open Access Journals (Sweden)

    Urubatã E. Gomes

    2011-09-01

    Full Text Available Scientific activity in Brazil has experienced an accelerated growth in the past decades, with an increase in productivity that greatly surpasses the international average. This growth has occurred mostly at the expense of centers of excellence in public universities, which account for the vast majority of the country's scientific output. The aim of this study was to evaluate the production of the Department of Biochemistry of a large public university in southern Brazil (Universidade Federal do Rio Grande do Sul, as well as to identify internal and external policies that have influenced this growing production profile. We have performed a historical analysis of the scientific output of this Department of Biochemistry, which accounts for a considerable share of the indexed scientific production at this university. By focusing on the temporal course of its growth and drawing correlations between scientific output and important events in the history of the Department of Biochemistry and of the Brazilian science policies, we concluded that internal factors (as the creation of a postgraduation program, collaboration among researchers, experienced abroad researchers, qualification of faculty members and external factors (as investments in the postgraduate education, the establishment of national scientific policies, such as financial stimuli for productive researchers and evaluation systems influence scientific productivity in Brazil.A atividade científica no Brasil apresentou um crescimento acelerado nas últimas décadas, com um aumento na produtividade que ultrapassou os valores médios internacionais. Este crescimento tem ocorrido através dos centros de excelência em pesquisa nas Universidades Públicas, as quais são responsáveis pela maior parte da produção científica do país. O presente estudo tem como objetivo avaliar a produção do Departamento de Bioquímica de uma grande universidade pública do sul do Brasil (Universidade Federal

  20. Combining qualitative and quantitative evidence to determine factors leading to late presentation for antiretroviral therapy in Malawi.

    Directory of Open Access Journals (Sweden)

    Fiona R Parrott

    Full Text Available BACKGROUND: Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa. OBJECTIVE: To better understand antiretroviral treatment (ART seeking behaviour in HIV-infected adults in rural Malawi. METHODS: Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009. RESULTS: 43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3-3.9 and never being married (adjusted OR 4.1, 95% CI1.5-11.5 were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15-0.63, compared to those with no dependent children. CONCLUSION: Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.

  1. Lead Toxicity

    Science.gov (United States)

    ... including some imported jewelry. What are the health effects of lead? • More commonly, lower levels of lead in children over time may lead to reduced IQ, slow learning, Attention Deficit Hyperactivity Disorder (ADHD), or behavioral issues. • Lead also affects other ...

  2. Niveles de plomo en sangre y factores de exposición en niños del estado de Morelos, México Blood lead levels and exposure factors in children of Morelos State, Mexico

    Directory of Open Access Journals (Sweden)

    Fernando Meneses-González

    2003-01-01

    Full Text Available OBJETIVO: Evaluar los niveles de plomo en sangre de niños morelenses y sus factores de exposición. MATERIAL Y MÉTODOS: Estudio transversal para analizar, por voltametría anódica, los niveles de plomo en sangre de 232 niños de 1 a 12 años de edad, que acudieron de junio a octubre de 1996 al Hospital del Niño Morelense de Cuernavaca, Morelos, México. Los factores de exposición se indagaron por cuestionario. El valor de concentración de plomo se transformó al logaritmo natural; se estimó la razón de momios para algunos factores de exposición que se incorporaron a un modelo de ANOVA. RESULTADOS: Se reclutaron 232 niños (50% mujeres; 73% residentes en Cuernavaca. La media geométrica de plomo en sangre fue 6.7 µg/dl; 29.7% rebasaron los 10 µg/dl; 66% tenían antecedente de cocinar alimentos en barro vidriado; 36% de almacenar alimentos, y 19%, consumo de líquidos en ese material. CONCLUSIONES: Los niveles encontrados son similares a los reportados en otras poblaciones pediátricas mexicanas en los últimos años. Entre los principales factores de exposición destacan el uso de barro vidriado para consumo de alimentos o líquidos y la intensidad del tráfico donde viven. Este es el primer estudio que documenta los niveles de plomo en sangre en población infantil de Morelos, México, y sus resultados son punto de partida para acciones futuras de control y prevención.OBJECTIVE: To assess blood lead levels and lead exposure factors in children living in Morelos State, Mexico. MATERIAL AND METHODS: A cross-sectional study was conducted between June and October 1996, in 232 children aged 1-12 years, at Hospital del Niño Morelense de Cuernavaca, Morelos, Mexico. Blood lead levels were measured by anodic voltameter, and exposure factors were collected by questionnaire. The lead concentration value was log transformed for statistical analysis. Odds ratios were obtained for some risk factors. The statistical significative risk factors

  3. [Simultaneous determination of trace amounts of zinc, cadmium, lead and copper by the method of anodic voltammetry using factor experimental design].

    Science.gov (United States)

    Koen, E

    1975-01-01

    Using the method of factor planning of the experiment, the author studies and demonstrates the influence exerted by the potential and time of electrolysis, and by the concentration of the background and elements on the heights of anodal peaks upon simultaneous determination of zinc, cadmium, lead and copper microconcentrations. On the ground of statistical elaboration of the results, the optimal condition for polarographic determination through anodal voltamperometry are outlined. According to the cyclic voltametry method, the electrod processes reversibility for zinc, cadmium and lead, as well as the incomplete reversibility for copper are established; the number of electrons participating in the electrochemical reaction are found using the method of gas coulometry. The possibility of simultaneous determination of the four elements' ultramicroconcentrations after the method of voltamperometry with enrichment is proved. The standard deviation is in the range 3.02 to 4.9.

  4. THE PREVALENCE OF ARTERIAL HYPERTENSION AS ONE OF THE LEADING FACTORS OF THE STROKE RISK IN THE MOSCOW REGION ON THE EXAMPLE OF THE SMALL REGIONAL SETTLEMENT

    Directory of Open Access Journals (Sweden)

    V. V. Kоzyaikin

    2013-01-01

    Full Text Available Analysis of the clinical-and-epidemiological parameters of the stroke was carried out and the prevalence of arterial hypertension was studied as one of the leading factors of stroke development among the residents of the small regional settlement of the Moscow Region. The epidemiological data obtained are indicative of the high stroke morbidity. A significant prevalence of the arterial hypertension was found in the population studied as well as an insufficient control and low understanding by patients of the necessity of regular taking antihypertensive drugs.

  5. 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.

  6. Reworking Intensity—A Key Factor Leading to the Formation of Superlarge Gold Deposits in Greenstone Belts and Metamorphosed Microclastic Rocks in China

    Institute of Scientific and Technical Information of China (English)

    王秀璋; 陆德复; 等

    1999-01-01

    The greenstone belt and metamorphosed microclastic rock-type superlarge gold deposits in China are hosted in metamorphic rocks and later intrusive bodies.Sedimentation.regional metamorphism and mineralization contributed a lot to the formation of the deposits,so did remelting magmatic process to some deposits,but the deposits were finally formed by reworking processes.The key factor leading to the formation of superlarge gold deposits is the reworking intensity,which for superlarge gold deposits is reflected by the large-scale reworked source rocks and even ore materials of various sources,strongly oxidized ore-forming fluids with a long and repeated active history and stable geothermal heat current.The factor which decides the reworking intensity is the network consisting of structures of different classes.

  7. Associated factors for higher lead and cadmium blood levels, and reference values derived from general population of São Paulo, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Kira, Carmen Silvia, E-mail: carmkira@ial.sp.gov.br [Instituto Adolfo Lutz, Centro de Materiais de Referência, Av. Dr. Arnaldo, 355, São Paulo, SP CEP 01246-000 (Brazil); Sakuma, Alice Momoyo [Instituto Adolfo Lutz, Centro de Materiais de Referência, Av. Dr. Arnaldo, 355, São Paulo, SP CEP 01246-000 (Brazil); De Capitani, Eduardo Mello [Universidade Estadual de Campinas — UNICAMP, Faculdade de Ciências Médicas, Departamento de Clínica Médica, Centro de Controle de Intoxicações (Brazil); Umbelino de Freitas, Clarice [Secretaria de Estado da Saúde/SP, Coordenadoria de Controle de Doenças (Brazil); Cardoso, Maria Regina Alves [Universidade de São Paulo, Faculdade de Saúde Pública, Departamento de Epidemiologia (Brazil); Gouveia, Nelson [Universidade de São Paulo — USP, Faculdade de Medicina, Departamento de Medicina Preventiva (Brazil)

    2016-02-01

    Human activities are associated with emissions of various metals into the environment, among which the heavy metals lead and cadmium stand out, as they pose a risk to human life even at low concentrations. Thus, accurate knowledge of the levels of these metals exhibited by the overall population, including children, is important. The aim of this study was to estimate the concentrations of lead and cadmium in the blood of adults, adolescents and children residing in the city of São Paulo, assess factors associated with higher lead and cadmium blood levels, and to establish reference values for this population. The study sample consisted of 669 adults over 20 years old, 264 adolescents aged 12 to 19 years old and 391 children under 11 years old from both genders. The samples were collected at the end of 2007 and during 2008 in different city zones. Higher blood lead concentration was significantly associated with gender, smoking, offal intake, area of residence and age. The blood cadmium concentration was significantly associated with gender, smoking, consumption of distilled beverages and age. The reference values of lead and cadmium established for adults above 20 years old were 33 μg/L and 0.6 μg/L, respectively, for adolescents (12 to 19 years old) were 31 μg/L and 0.6 μg/L, respectively and for children under 11 years old were 29 μg/L and 0.2 μg/L, respectively. The results of this study indicate that the exposure levels of the investigated population to lead and cadmium are low. - Highlights: • The exposure of population of São Paulo city to lead and cadmium is low. • Pb level was associated with gender, smoking, offal intake, area of residence, age. • Cd level was associated with gender, smoking, distilled beverages, age. • RV for Pb in blood for children and adolescents were 29 and 31 μg/L, respectively. • RV for Cd in blood for children and adolescents were 0.2 and 0.6 μg/L, respectively.

  8. A polynomial–based function approach to point isotropic gamma-ray buildup factor data in double layered spherical shield of water and lead

    Directory of Open Access Journals (Sweden)

    M. H. Alamatsaz

    2014-03-01

    Full Text Available As the input of MCNP code (Monte Carlo N - Particle code system, a monoenergetic and isotropic point source with the energy rangeg from 0.3 to 10 MeV was placed at the center of a spherical material surrounded by another one. The first shielding material was water and the second one was lead. The total thickness of the shield varied between 2 to 10 mfp. Then, using the output of MCNCP, exposure build up factor was calculated. The MCNP computed data were analyzed by plotting the buildup factor as a function of each independent variable (energy, first material thickness and second material thickness and observing the trends. Based on the trends, we examined many different expressions with different number of constants. By MINUIT the FORTRAN program, the constants were calculated, which gave the best agreement between the MCNP-computed exposure buildup factors and those obtained by the formula. At last, we developed a polynomial formula with 11 constants that reproduced exposure buildup factor with a relative error below 2% (in comparison with the MCNP result.

  9. Lead Poisoning

    Science.gov (United States)

    ... lead is of microscopic size, invisible to the naked eye. More often than not, children with elevated ... majority of the childhood lead poisoning cases we see today. Children and adults too can get seriously ...

  10. Prevalence of self-reported diagnosis of diabetes mellitus and associated risk factors in a national survey in the US population: SHIELD (Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes)

    OpenAIRE

    Reed Michael L; Lewis Sandra J; Green Andrew J; Gavin James R; Clark Nathaniel G; Bazata Debbra D; Bays Harold E; Stewart Walter; Chapman Richard H; Fox Kathleen M; Grandy Susan

    2007-01-01

    Abstract Background Studies derived from continuous national surveys have shown that the prevalence of diagnosed diabetes mellitus in the US is increasing. This study estimated the prevalence in 2004 of self-reported diagnosis of diabetes and other conditions in a community-based population, using data from the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD). Methods The initial screening questionnaire was mailed in 2004 to a stratified rando...

  11. Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis.

    Science.gov (United States)

    Sethi, Gautam; Ahn, Kwang Seok; Sung, Bokyung; Aggarwal, Bharat B

    2008-06-01

    Pinitol (3-O-methyl-chiroinositol), a component of traditional Ayurvedic medicine (talisapatra), has been shown to exhibit anti-inflammatory and antidiabetic activities through undefined mechanisms. Because the transcription factor nuclear factor-kappaB (NF-kappaB) has been linked with inflammatory diseases, including insulin resistance, we hypothesized that pinitol must mediate its effects through modulation of NF-kappaB activation pathway. We found that pinitol suppressed NF-kappaB activation induced by inflammatory stimuli and carcinogens. This suppression was not specific to cell type. Besides inducible, pinitol also abrogated constitutive NF-kappaB activation noted in most tumor cells. The suppression of NF-kappaB activation by pinitol occurred through inhibition of the activation of IkappaBalpha kinase, leading to sequential suppression of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Pinitol also suppressed the NF-kappaB reporter activity induced by tumor necrosis factor receptor (TNFR)-1, TNFR-associated death domain, TNFR-associated factor-2, transforming growth factor-beta-activated kinase-1 (TAK-1)/TAK1-binding protein-1, and IkappaBalpha kinase but not that induced by p65. The inhibition of NF-kappaB activation thereby led to down-regulation of gene products involved in inflammation (cyclooxygenase-2), proliferation (cyclin D1 and c-myc), invasion (matrix metalloproteinase-9), angiogenesis (vascular endothelial growth factor), and cell survival (cIAP1, cIAP2, X-linked inhibitor apoptosis protein, Bcl-2, and Bcl-xL). Suppression of these gene products by pinitol enhanced the apoptosis induced by TNF and chemotherapeutic agents and suppressed TNF-induced cellular invasion. Our results show that pinitol inhibits the NF-kappaB activation pathway, which may explain its ability to suppress inflammatory cellular responses.

  12. Relational Leading

    DEFF Research Database (Denmark)

    2015-01-01

    This first chapter presents the exploratory and curious approach to leading as relational processes – an approach that pervades the entire book. We explore leading from a perspective that emphasises the unpredictable challenges and triviality of everyday life, which we consider an interesting......, relevant and realistic way to examine leading. The chapter brings up a number of concepts and contexts as formulated by researchers within the field, and in this way seeks to construct a first understanding of relational leading....

  13. 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.

  14. 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.

  15. 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.

  16. Lead Test

    Science.gov (United States)

    ... months, and at 3, 4, 5, and 6 years of age. A blood lead level test should be done only if the risk ... recommended if the person is symptomatic at any level below 70 mcg/dL. Because lead will pass through the blood to an unborn child, pregnant ...

  17. A Important Factor of Leading to Teenagers Hunchback-the Endorsement Package%致青少年驼背的重要因素-书包

    Institute of Scientific and Technical Information of China (English)

    郑桂波; 谢渝拉

    2015-01-01

    Objective A correct understanding of the restlting endorsement package hunchback factors,Abandon the unhealthy endorsement package ,concerned about growth of the youth.Methods Through to some students in the first grade to the nineth grade 450 people,long term weight and weight of the endorsement package ,The time of the survey ,biomedical analysts .Control over the age of 30 without the endorsement package behavior of the crowd.Knowledge is an important factor leading to the endorsement package adolescent humpback.Results Enforcement package weight will appear the chest and abdominal muscle strength enhancement .Fall back muscles strength ,before and after the imbalance. The late cause of head and neck outstretched , thoracic irreversible wedge shape change ,curvature increase .Conclusion Teenagers have long endorsed the package leads to head and neck outstretched ,long time later leading to adolescent humpback.%目的:正确认识背书包这一致驼背因素,摒弃不利健康的背书包习惯,关心青少年的健康成长。方法通过对某学校中小学生一年级至初三年级450人,长期负重情况及背书包重量、时间的调查,进行生物力学分析,对照30岁以上无背书包行为的人群,认识背书包是青少年致驼的重要因素。结果背书包负重会出现前胸及腹肌肌力增强,背肌肌力下降,前后不平衡,后期引起头颈前伸,胸椎不可逆的呈楔形改变,曲度加大。结论青少年长期背书包致头颈前伸,双肩高耸,胸颈椎中上段屈度加大,且年龄越小影响越大,很难纠正,应引起足够的重视,建议:①书包尽可能轻;②采取背、前挂、左右斜挎、手提几种方法交替使用,预防驼背。

  18. 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

  19. 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.

  20. 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.

  1. Charge and Matter Form Factors of Two-Neutron Halo Nuclei in Halo Effective Field Theory at Next-to-leading-order

    CERN Document Server

    Vanasse, Jared

    2016-01-01

    Using halo effective field theory (EFT), an expansion in $R_{core}/R_{halo}$, where $R_{core}$ is the radius of the core and $R_{halo}$ the radius of the halo nucleus, we calculate the charge and neutron form factors of the two-neutron halo nuclei $^{11}$Li, $^{14}$Be, and $^{22}$C to next-to-leading-order (NLO) by treating them as an effective three-body system. From the form factors we extract the point charge and point matter radii, inter-neutron distance, and neutron opening angle. Agreement is found with existing experimental extractions. Results are given for the point charge and point matter radii for arbitrary neutron core scattering effective range, $\\rho_{cn}$, that can be used for predictions once $\\rho_{cn}$ is measured. Estimates for $\\rho_{cn}$ are also used to make NLO predictions. Finally, our point charge radii are compared to other halo-EFT predictions, and setting the core mass equal to the neutron mass our point charge radius is found to agree with an analytical prediction in the unitary l...

  2. 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.

  3. Chilling stress--the key predisposing factor for causing Alternaria alternata infection and leading to cotton (Gossypium hirsutum L. leaf senescence.

    Directory of Open Access Journals (Sweden)

    Jingqing Zhao

    Full Text Available Leaf senescence plays a vital role in nutrient recycling and overall capacity to assimilate carbon dioxide. Cotton premature leaf senescence, often accompanied with unexpected short-term low temperature, has been occurring with an increasing frequency in many cotton-growing areas and causes serious reduction in yield and quality of cotton. The key factors for causing and promoting cotton premature leaf senescence are still unclear. In this case, the relationship between the pre-chilling stress and Alternaria alternata infection for causing cotton leaf senescence was investigated under precisely controlled laboratory conditions with four to five leaves stage cotton plants. The results showed short-term chilling stress could cause a certain degree of physiological impairment to cotton leaves, which could be recovered to normal levels in 2-4 days when the chilling stresses were removed. When these chilling stress injured leaves were further inoculated with A. alternata, the pronounced appearance and development of leaf spot disease, and eventually the pronounced symptoms of leaf senescence, occurred on these cotton leaves. The onset of cotton leaf senescence at this condition was also reflected in various physiological indexes such as irreversible increase in malondialdehyde (MDA content and electrolyte leakage, irreversible decrease in soluble protein content and chlorophyll content, and irreversible damage in leaves' photosynthesis ability. The presented results demonstrated that chilling stress acted as the key predisposing factor for causing A. alternata infection and leading to cotton leaf senescence. It could be expected that the understanding of the key factors causing and promoting cotton leaf senescence would be helpful for taking appropriate management steps to prevent cotton premature leaf senescence.

  4. Lead Poisoning

    Science.gov (United States)

    ... Topics Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The Natural World Games ... OTHERS: Lead has recently been found in some plastic mini-blinds and vertical blinds which were made ...

  5. 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.

  6. 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

  7. 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.

  8. Chronic Lead Exposure and Mixed Factors of Gender×Age×Brain Regions Interactions on Dendrite Growth, Spine Maturity and NDR Kinase.

    Directory of Open Access Journals (Sweden)

    Yang Du

    Full Text Available NDR1/2 kinase is essential in dendrite morphology and spine formation, which is regulated by cellular Ca2+. Lead (Pb is a potent blocker of L-type calcium channel and our recent work showed Pb exposure impairs dendritic spine outgrowth in hippocampal neurons in rats. But the sensitivity of Pb-induced spine maturity with mixed factors (gender×age×brain regions remains unknown. This study aimed to systematically investigate the effect of Pb exposure on spine maturity in rat brain with three factors (gender×age×brain regions, as well as the NDR1/2 kinase expression. Sprague-Dawley rats were exposed to Pb from parturition to postnatal day 30, 60, 90, respectively. Golgi-Cox staining was used to examine spine maturity. Western blot assay was applied to measure protein expression and real-time fluorescence quantitative PCR assay was used to examine mRNA levels. The results showed chronic Pb exposure significantly decreased dendritic length and impaired spine maturity in both rat hippocampus and medial prefrontal cortex. The impairment of dendritic length induced by Pb exposure tended to adolescence > adulthood, hippocampus > medial prefrontal cortex and female > male. Pb exposure induced significant damage in spine maturity during adolescence and early adult while little damage during adult in male rat brain and female medial prefrontal cortex. Besides, there was sustained impairment from adolescence to adulthood in female hippocampus. Interestingly, impairment of spine maturity followed by Pb exposure was correlated with NDR1/2 kinase. The reduction of NDR1/2 kinase protein expression after Pb exposure was similar to the result of spine maturity. In addition, NDR2 and their substrate Rabin3 mRNA levels were significantly decreased by Pb exposure in developmental rat brain. Taken together, Pb exposure impaired dendrite growth and maturity which was subject to gender×age×brain regions effects and related to NDR1/2 signal expression.

  9. Ecotoxicology: Lead

    Science.gov (United States)

    Scheuhammer, A.M.; Beyer, W.N.; Schmitt, C.J.; Jorgensen, Sven Erik; Fath, Brian D.

    2008-01-01

    Lead (Pb) is a naturally occurring metallic element; trace concentrations are found in all environmental media and in all living things. However, certain human activities, especially base metal mining and smelting; combustion of leaded gasoline; the use of Pb in hunting, target shooting, and recreational angling; the use of Pb-based paints; and the uncontrolled disposal of Pb-containing products such as old vehicle batteries and electronic devices have resulted in increased environmental levels of Pb, and have created risks for Pb exposure and toxicity in invertebrates, fish, and wildlife in some ecosystems.

  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. Administration of granulocyte colony stimulating factor after liver transplantation leads to an increased incidence and severity of ischemic biliary lesions in the rat model

    Institute of Scientific and Technical Information of China (English)

    Olaf Dirsch; Haidong Chi; Yuan Ji; Yan Li Gu; Christoph E Broelsch; Uta Dahmen

    2006-01-01

    AIM: Recently it has been reported that granulocyte colony stimulating factor (G-CSF) can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model.METHODS: A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk.RESULTS: Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals.CONCLUSION: G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications.

  12. Determination of transfer factors of uranium, thorium, radium and lead from soil to agricultural product in Japan for estimating internal radiation dose through ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Tomozo [Radioactive Waste Management Funding and Research Center, Tokyo (Japan); Tashiro, Yoshikazu; Fujinaga, Hideshi [Sumitomo Metal Mining Co. Ltd., Tokai, Ibaraki (Japan); Ishii, Tomoaki; Gunji, Yasuyoshi [Nuclear Fuel Industries Ltd., Tokai, Ibaraki (Japan). Tokai Works

    2002-09-01

    The transfer factors (TFs) of uranium (U), thorium (Th), radium (Ra) and lead (Pb) from soil to agricultural products were determined in order to estimate the internal radiation dose to the human body through ingestion. Samples of rice, potato, onion, cabbage, mandarin orange, spinach, apple and soil were collected from various districts in Japan. After appropriate pretreatment of the samples, concentrations in the sample solutions were measured by Inductively coupled plasma-mass spectrometry (ICP-MS) (for U, Th and Pb) and liquid scintillation counter (for Ra). It was recognized that TFs were 4.9 x 10{sup -6} (apple) and 3.6 x 10{sup -4} (spinach) for U, 2.8 x 10{sup -6} (apple) and 2.3 x 10{sup -4} (spinach) for Th, and 4.0 x 10{sup -3} (hulled rice), 7.0 x 10{sup -5} (onion) and 5.0 x 10{sup -3} (hulled rice) for Pb. The TF of Ra, however, was not determined due to detection limitations. TF values obtained in the present study range from the same order of magnitude to 1/100 compared to the data in Technical Report Series No.364 (TRS364) as reported by IAEA. It was revealed that the internal radiation dose caused by the intake of uranium series radioactive nuclides through agricultural food ingestion was 16 {mu}Sv/y, where Pb was the most contributory nuclide. (author)

  13. $B\\to \\rho$ transition form factors within the QCD light-cone sum rules and the $\\rho$-meson leading-twist distribution amplitude

    CERN Document Server

    Fu, Hai-Bing; Han, Hua-Yong; Ma, Yang

    2014-01-01

    The QCD light-cone sum rules (LCSR) provides an effective way for dealing with the heavy-to-light transition form factors (TFFs), whose non-perturbative dynamics are parameterized into the light-meson's light-cone distribution amplitudes (LCDAs) with various twist structures. By taking the chiral correlator as the starting point, we calculate the LCSRs for the $B\\to\\rho$ TFFs up to twist-4 accuracy. As for the TFFs at the large recoil region, we observe that the twist-2 transverse DA $\\phi_{2;\\rho}^\\bot$ provides the dominant contribution, while the contributions from the remaining twist-3 and twist-4 terms are $\\delta^2$-suppressed. Thus, our present improved LCSRs provides a good platform for testing the $\\phi_{2;\\rho}^\\bot$ behavior. For the purpose, we suggest a convenient WH-model for the $\\rho$-meson leading-twist wavefunction, in which the parameter $B_{2;\\rho}^\\bot\\sim a^\\bot_2$ dominantly controls its longitudinal distribution. Typically, its DA $\\phi_{2;\\rho}^\\bot$ is CZ-like as $B_{2;\\rho}^\\bot\\sim...

  14. Leading men

    DEFF Research Database (Denmark)

    Bekker-Nielsen, Tønnes

    2016-01-01

    Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also...

  15. Lead grids

    CERN Multimedia

    1974-01-01

    One of the 150 lead grids used in the multiwire proportional chamber g-ray detector. The 0.75 mm diameter holes are spaced 1 mm centre to centre. The grids were made by chemical cutting techniques in the Godet Workshop of the SB Physics.

  16. CDC National Health Report: leading causes of morbidity and mortality and associated behavioral risk and protective factors--United States, 2005-2013.

    Science.gov (United States)

    Johnson, Nicole Blair; Hayes, Locola D; Brown, Kathryn; Hoo, Elizabeth C; Ethier, Kathleen A

    2014-10-31

    Although substantial progress has been made in improving the health of persons in the United States, serious problems remain to be solved. Life expectancy is increasing, and the rates of the leading causes of death are improving in many cases; however, numerous indicators (i.e., measures of observed or calculated data on the status of a condition) of the health and safety of the U.S. population remain poor. This report reviews population health in the United States and provides an assessment of recent progress in meeting high-priority health objectives. The health status indicators described in this report were selected because of their direct relation to the leading causes of death and other substantial sources of morbidity and mortality and should be the focus of prevention efforts. Data are reported starting in 2005 (or the earliest available year since 2005) through the current data year. Because data sources and specific indicators vary regarding when data are available, the most recent year for which data are available might range from 2010 to 2013. Data were obtained from 17 CDC surveys or surveillance systems and three non-CDC sources to provide a view of this particular point of time in the nation's health and trends in recent years. Data from the following CDC surveillance systems and surveys were used: Behavioral Risk Factor Surveillance System (BRFSS); Emerging Infections Program/Active Bacterial Core surveillance (EIP/ABCs); Foodborne Diseases Active Surveillance Network (FoodNet); Internet Panel Surveys: Influenza Vaccination Coverage Among Health-Care Personnel and Influenza Vaccination Coverage Among Pregnant Women; National Ambulatory Medical Care Survey (NAMCS); National Health and Nutrition Examination Survey (NHANES); National Health Interview Survey (NHIS); National Healthcare Safety Network (NHSN); National HIV Surveillance System; National Hospital Discharge Survey (NHDS); National Immunization Survey (NIS); National Immunization Survey

  17. 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

  18. Who Leads China's Leading Universities?

    Science.gov (United States)

    Huang, Futao

    2017-01-01

    This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

  19. Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation- sensitivity in breast cancer cells

    LENUS (Irish Health Repository)

    Thewes, Verena

    2010-05-11

    Abstract Background Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the

  20. Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury.

    Science.gov (United States)

    Proper, Steven P; Saini, Yogesh; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

    2014-02-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2α(Δ/Δ)) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2α(Δ/Δ) mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2α(Δ/Δ) and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung.

  1. Zebrafish as a model for investigating developmental lead (Pb) neurotoxicity as a risk factor in adult neurodegenerative disease: a mini-review.

    Science.gov (United States)

    Lee, Jinyoung; Freeman, Jennifer L

    2014-07-01

    Lead (Pb) exposure has long been recognized to cause neurological alterations in both adults and children. While most of the studies in adults are related to higher dose exposure, epidemiological studies indicate cognitive decline and neurobehavioral alterations in children associated with lower dose environmental Pb exposure (a blood Pb level of 10μg/dL and below). Recent animal studies also now report that an early-life Pb exposure results in pathological hallmarks of Alzheimer's disease later in life. While previous studies evaluating higher Pb exposures in adult animal models and higher occupational Pb exposures in humans have suggested a link between higher dose Pb exposure during adulthood and neurodegenerative disease, these newer studies now indicate a link between an early-life Pb exposure and adult neurodegenerative disease. These studies are supporting the "fetal/developmental origin of adult disease" hypothesis and present a new challenge in our understanding of Pb neurotoxicity. There is a need to expand research in this area and additional model systems are needed. The zebrafish presents as a complementary vertebrate model system with numerous strengths including high genetic homology. Several zebrafish genes orthologous to human genes associated with neurodegenerative diseases including Alzheimer's and Parkinson's diseases are identified and this model is starting to be applied in neurodegenerative disease research. Moreover, the zebrafish is being used in developmental Pb neurotoxicity studies to define genetic mechanisms of toxicity and associated neurobehavioral alterations. While these studies are in their infancy, the genetic and functional conservation of genes associated with neurodegenerative diseases and application in developmental Pb neurotoxicity studies supports the potential for this in vivo model to further investigate the link between developmental Pb exposure and adult neurodegenerative disease pathogenesis. In this review, the

  2. Stem cell factor leads to reduced blood processing during apheresis or the use of whole blood aliquots to support dose-intensive chemotherapy.

    Science.gov (United States)

    Weaver, A; Testa, N G

    1998-07-01

    The addition of stem cell factor (SCF) to G-CSF and chemotherapy results in a dose-dependent, significantly increased mobilisation of peripheral blood progenitor cells compared with the use of chemotherapy and G-CSF alone. The enhanced mobilisation may benefit patients in several ways. Firstly, in clinical settings where currently multiple aphereses are having to be performed to obtain a specified target number of cells, the addition of SCF may lead to a reduction in this number. Alternatively, when only a single apheresis is currently being performed to obtain sufficient cells then the addition of SCF to the mobilisation regimen would allow between 5- and 8-fold reduction in the volume of blood required to be processed during the apheresis procedure to obtain a specified target of GM-CFC, CD34+ cells and LTC-IC for those receiving the highest dose of SCF (20 microg/kg) plus G-CSF following chemotherapy compared with those patients receiving G-CSF alone following chemotherapy. The increased mobilisation resulting from the addition of SCF to the regimen makes feasible the use of whole blood aliquots to support dose-intensive therapy. We have calculated that in patients mobilised using cyclophosphamide 3 g/m2, SCF 20 microg/kg and G-CSF 5 microg/kg a median 512 ml aliquot of whole blood would contain 2 x 10(6)/kg CD34+ cells and over 3.7 x 10(5)/kg GM-CFC. This aliquot would be sufficient to rescue the patient following a myeloablative therapy. Significantly, because less individual variation was seen after the administration of SCF the patient who showed the worst mobilisation in that group would have the usually required content of 2 x 10(6) CD34+ cells/kg and 1 x 10(5) GM-CFC/kg in only 731 ml of blood.

  3. Loss of Hypoxia-Inducible Factor 2 Alpha in the Lung Alveolar Epithelium of Mice Leads to Enhanced Eosinophilic Inflammation in Cobalt-Induced Lung Injury

    Science.gov (United States)

    Proper, Steven P.; Saini, Yogesh; LaPres, John J.

    2014-01-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2αΔ/Δ) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2αΔ/Δ mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2αΔ/Δ and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung. PMID:24218148

  4. 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

  5. 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.

  6. [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.

  7. 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...

  8. Leading Cities

    DEFF Research Database (Denmark)

    Pogner, Karl-Heinz

    2017-01-01

    and technical engineering; Smart Cities) is very prominent in the traditional mass media discourse, in PR / PA of tech companies and traditional municipal administrations; whereas the second one (participation; Livable Cities) is mostly enacted in social media, (local) initiatives, movements, (virtual......) communities, new forms of urban governance in municipal administration and co-competitive city networks. Both forms seem to struggle for getting voice and power in the discourses, negotiations, struggles, and conflicts in Urban Governance about the question how to manage or lead (in) a city. Talking about...

  9. SELF-PURIFICATION OF THE DNIPROVS’KE RESERVOIR AS A LEADING FORMING FACTOR FOR THE ECOLOGICALLY SAFE HABITAT OF FISHES

    Directory of Open Access Journals (Sweden)

    А. Dvoretsky

    2014-12-01

    factor of improvement of the reservoir water quality and, consequently, the formation of environmentally safe habitat for fish. This is the main regularity, which affects the formation of self-cleaning processes and is reflected through the relations between hydrochemical, toxicological and hydrobiological indexes, the leading role in which is played by phytoplankton «blooming». Originality. For the fist time we showed that the correlation coefficient of the parameter with It gives an estimate of the contribution of the corresponding component of the reservoir ecosystem to the result of its toxification and self-purification. Practical value. The relationships, which relate It to ecosystem components, are important for the development of models for water quality and fish-productivity management.

  10. Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study.

    Science.gov (United States)

    Chevallier, Marie; Debillon, Thierry; Pierrat, Veronique; Delorme, Pierre; Kayem, Gilles; Durox, Mélanie; Goffinet, François; Marret, Stephane; Ancel, Pierre Yves

    2017-05-01

    Intraventricular hemorrhage is a major risk factor for neurodevelopmental disabilities in preterm infants. However, few studies have investigated how pregnancy complications responsible for preterm delivery are related to intraventricular hemorrhage. We sought to investigate the association between the main causes of preterm delivery and intraventricular hemorrhage in very preterm infants born in France during 2011 between 22-31 weeks of gestation. The study included 3495 preterm infants from the national EPIPAGE 2 cohort study who were admitted to neonatal intensive care units and had at least 1 cranial ultrasound assessment. The primary outcome was grade I-IV intraventricular hemorrhage according to the Papile classification. Multinomial logistic regression models were used to study the relationship between risk of intraventricular hemorrhage and the leading causes of preterm delivery: vascular placental diseases, isolated intrauterine growth retardation, placental abruption, preterm labor, and premature rupture of membranes, with or without associated maternal inflammatory syndrome. The overall frequency of grade IV, III, II, and I intraventricular hemorrhage was 3.8% (95% confidence interval, 3.2-4.5), 3.3% (95% confidence interval, 2.7-3.9), 12.1% (95% confidence interval, 11.0-13.3), and 17.0% (95% confidence interval, 15.7-18.4), respectively. After adjustment for gestational age, antenatal magnesium sulfate therapy, level of care in the maternity unit, antenatal corticosteroids, and chest compressions, infants born after placental abruption had a higher risk of grade IV and III intraventricular hemorrhage compared to those born under placental vascular disease conditions, with adjusted odds ratios of 4.3 (95% confidence interval, 1.1-17.0) and 4.4 (95% confidence interval, 1.1-17.6), respectively. Similarly, preterm labor with concurrent inflammatory syndrome was associated with an increased risk of grade IV intraventricular hemorrhage (adjusted odds ratio

  11. Prevalence of self-reported diagnosis of diabetes mellitus and associated risk factors in a national survey in the US population: SHIELD (Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes

    Directory of Open Access Journals (Sweden)

    Reed Michael L

    2007-10-01

    Full Text Available Abstract Background Studies derived from continuous national surveys have shown that the prevalence of diagnosed diabetes mellitus in the US is increasing. This study estimated the prevalence in 2004 of self-reported diagnosis of diabetes and other conditions in a community-based population, using data from the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD. Methods The initial screening questionnaire was mailed in 2004 to a stratified random sample of 200,000 households in the US, to identify individuals, age ≥ 18 years of age, with diabetes or risk factors associated with diabetes. Follow-up disease impact questionnaires were then mailed to a representative, stratified random sample of individuals (n = 22,001 in each subgroup of interest (those with diabetes or different numbers of risk factors for diabetes. Estimated national prevalence of diabetes and other conditions was calculated, and compared to prevalence estimates from the National Health and Nutrition Examination Survey (NHANES 1999–2002. Results Response rates were 63.7% for the screening, and 71.8% for the follow-up baseline survey. The SHIELD screening survey found overall prevalence of self-reported diagnosis of diabetes (either type 1 or type 2 was 8.2%, with increased prevalence with increasing age and decreasing income. In logistic regression modeling, individuals were more likely to be diagnosed with type 2 diabetes if they had abdominal obesity (odds ratio [OR] = 3.50; p 2 (OR = 4.04; p Conclusion The SHIELD design allowed for a very large, community-based sample with broad demographic representation of the population of interest. When comparing results from the SHIELD screening survey (self-report only to those from NHANES 1999–2002 (self-report, clinical and laboratory evaluations, the prevalence of diabetes was similar. SHIELD allows the identification of respondents with and without a current diagnosis of the

  12. Changes of brain derived neurotrophic factor in hippocampus of chronic lead exposed rats%慢性染铅大鼠海马脑源性神经营养因子的改变

    Institute of Scientific and Technical Information of China (English)

    李积胜; 刘亚华; 杨峰

    2004-01-01

    Objective: To investigate the changes of brain derived neurotrophic factor(BDNF) in hippocampus of chronic lead exposed rats. Methods: Wistar rats were exposed to lead by drinking 0.02%、0.2% lead acetate solution for three months, respectively. Investigate the changes of learning and memory ability by Y-labyrinth experiment, study the changes of BDNF positive neuron in CA1, CA3 and dentate gyrus in hippocampus of rats by immunohistochemistry. Results: BDNF positive neurons distribute everywhere in the hippocampus under normal condition. Compared with the contral group, the number of BDNF positive neurons in the hippocampus subregions were decreased significantly of two different dosage (0.02%, 0.2% ) chronic lead exposed groups( P < 0. 05). Conclusion: These results suggest that the reduction of BDNF positive neuron in hippocampus might be related to the impact of lead on learning and memory.

  13. 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

  14. Protease cleavage leads to formation of mature trimer interface in HIV-1 capsid.

    Directory of Open Access Journals (Sweden)

    Xin Meng

    Full Text Available During retrovirus particle maturation, the assembled Gag polyprotein is cleaved by the viral protease into matrix (MA, capsid (CA, and nucleocapsid (NC proteins. To form the mature viral capsid, CA rearranges, resulting in a lattice composed of hexameric and pentameric CA units. Recent structural studies of assembled HIV-1 CA revealed several inter-subunit interfaces in the capsid lattice, including a three-fold interhexamer interface that is critical for proper capsid stability. Although a general architecture of immature particles has been provided by cryo-electron tomographic studies, the structural details of the immature particle and the maturation pathway remain unknown. Here, we used cryo-electron microscopy (cryoEM to determine the structure of tubular assemblies of the HIV-1 CA-SP1-NC protein. Relative to the mature assembled CA structure, we observed a marked conformational difference in the position of the CA-CTD relative to the NTD in the CA-SP1-NC assembly, involving the flexible hinge connecting the two domains. This difference was verified via engineered disulfide crosslinking, revealing that inter-hexamer contacts, in particular those at the pseudo three-fold axis, are altered in the CA-SP1-NC assemblies compared to the CA assemblies. Results from crosslinking analyses of mature and immature HIV-1 particles containing the same Cys substitutions in the Gag protein are consistent with these findings. We further show that cleavage of preassembled CA-SP1-NC by HIV-1 protease in vitro leads to release of SP1 and NC without disassembly of the lattice. Collectively, our results indicate that the proteolytic cleavage of Gag leads to a structural reorganization of the polypeptide and creates the three-fold interhexamer interface, important for the formation of infectious HIV-1 particles.

  15. MONEY LAUNDERING AS AN ISOLATED PHENOMENON AND LEADING FACTOR IN WHITE-COLLAR CRIMINALITY, PUTS MOLDOVA CASE JUDICIARY ON THE SPOT

    Directory of Open Access Journals (Sweden)

    Jacob RUB

    2015-11-01

    Full Text Available Money laundering is a leading factor in white-collar criminality, with a big effect upon Gross National Product of the Israeli and Moldova economies. Israel and Moldova have made the first steps In order to cope with money laundering phenomenon. The model of handling the phenomenon in the USA has been studied that constitutes a role model of fighting money laundering. The vast majority (77% of all frauds were committed by individuals working in one of six departments: accounting, operations, sales, executive/upper management, customer service and purchasing. In Moldova, money laundering for the most part is connected to traditional forms and activities sources of illegal proceeds .Moldova is a transit country for money laundering. A money-laundering scandal is casting Moldova’s judiciary in an unfavorable light and is raising concerns about the government’s commitment to reforms needed to keep European Union integration on track. It is a need to address corruption as a national priority, and the priority of the relations between the EU and Moldova. The money laundering scandal indicates that Moldova is reluctant to wade deeply into judicial reform. In fact, the laundered of $20 billion, is an amount more than twice the size of Moldova’s GDP in 2013, and may be that it is just the tip of the iceberg, probably. White-collar criminality in Israel and Moldova means success of coping of the enforcement and judicial systems. In order to cope with this phenomenon, Israel makes its first steps. Anyway, the message must pave the way through a creation of a new model for dealing with reduction the isolated phenomenon of money laundering in both states.SPĂLAREA DE BANI, UN FENOMEN IZOLAT ŞI UN FACTOR IMPORTANT ÎN CRIMINALITATEA GULERELOR ALBE, PUNE PRACTICA JUDICIARĂ DIN REPUBLICA MOLDOVA INTR-O SITUAŢIE DIFICILĂSpălarea de bani este un factor important în criminalitatea gulerelor albe, având un efect semnificativ asupra produ-sului na

  16. Principales lesiones bucales y factores de riesgo presentes en población mayor de 60 años Leading oral lesions and risk factors present in a population aged over 60 years

    Directory of Open Access Journals (Sweden)

    Rosa María Gonzáles Ramos

    2010-03-01

    distribution according age and sex and also to identify the type of lesion and its anatomic location. A total of 352 elderlies were studied by means of a survey to identify the presence of risk factors and an oral cavity and neck physical examination to detect the lesions and their locations. Leading results showed that the 60.7 % of elderlies had risk factors where the more frequent were: seasoned and hot foods ingestion in the 83.4 %, smoking in the 82.1 % followed by the use of prostheses and alcoholism, both for a 72.4 %. Male sex was the more involved in a 58.2 %, the predominant risk factor was the alcohol ingestion in a 75.7 %. In female sex the use of prostheses was the predominant risk factor with a 73.3 % followed by smoking; the more involved age was over 80 years sin a 41.7 %. The 48.5 % has lesions; the fissure of epulis was more representative in a 39.1 %, the subprosthetic stomatitis with a 35.6 %. The more involved anatomical location founded was the hard palate, lower gum and cheek mucosa. With these results it was possible to confirm the quality lack of health education activities since there were lifestyles harmful for health.

  17. THE FACTORS THAT LEAD NAMIK KEMAL TO VICTOR HUGO ABSTRACT NAMIK KEMAL’İ VICTOR HUGO’YA GÖTÜREN ETKENLER

    Directory of Open Access Journals (Sweden)

    Abdulhalim AYDIN

    2011-09-01

    Full Text Available In terms of or literary history, Tanzimat literature has a special place. This, undoubtedly, is resulted form its being the beginning of modernization process. However, there is another important and distinctive feature of the artists of that period. That is their approach style to literature. Şinasi, Kemal, Hamid, Ekrem and others regarded literature not only to produce literature, to produce an art work and to create a new literature against classical approach but also to support Tanzimat Movement that was newly born through literature, to contribute to that social transformation project both as an intellectual and an artist. One of the ones who fulfilled this was Namık Kemal. Our poet performed that by following French poet Victor Hugo whom he saw mainly as a master and model. While Hugo was the opening of a new literature for art and literature for him, in terms of his ideas about society and social order that we mention he had been the source of social transformation. In this respect, the ideas of Hugo that he supported in his works, especially in his drama, was followed with great interest and attention by Kemal. In this study, in this context, the factors that lead Kemal to Hugo will be tried to be asserted. Edebiyat tarihimiz açısından Tanzimat edebiyatının özel bir yeri vardır. Bu, kuşkusuz modernleşme sürecinin başlangıcı olmasından kaynaklanmaktadır. Ancak bu dönem sanatçılarının bir önemli ve ayırıcı özellikleri daha vardır. O da, edebiyata yaklaşım tarzlarıdır. Şinasi, Kemal, Hamid, Ekrem ve diğerleri edebiyatı yalnızca edebi üretim yapmak, sanat eseri meydana getirmek ve klasik anlayışa karşı yeni bir edebiyat yaratmak değil, fakat aynı zamanda başlamış olan Tanzimat Hareketine edebiyat aracılığıyla destek vermek, bu toplumsal dönüşüm projesine hem aydın, hem de sanatçı kimliğiyle katkı sunmak olmuştur. Bunu yapanlardan biri de Namık Kemal olmuştur. Şairimiz bunu b

  18. Lead toxicity: Current concerns

    Energy Technology Data Exchange (ETDEWEB)

    Goyer, R.A. (Univ. of Western Ontario, London (Canada))

    1993-04-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium-mediated control of vascular smooth muscle contraction and on the renin-angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. 97 refs.

  19. 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

  20. Guanine nucleotide exchange factor αPIX leads to activation of the Rac 1 GTPase/glycogen phosphorylase pathway in interleukin (IL)-2-stimulated T cells

    DEFF Research Database (Denmark)

    Llavero, Francisco; Urzelai, Bakarne; Osinalde, Nerea

    2015-01-01

    Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation. In the lymphoid system, Rac 1 and in general other small GTPases of the Rho family participate in the sig...

  1. Occupational exposures to solvents and lead as risk factors for Alzheimer's disease: A collaborative re-analysis of case-control studies

    NARCIS (Netherlands)

    A.B. Graves; C.M. van Duijn (Cock); V. Chandra; L. Fratiglioni (Laura); A. Heyman; A.F. Jorm; E. Kokmen (Emre); K. Kondo; J.A. Mortimer; W.A. Rocca; S.L. Shalat; H. Soininen; A. Hofman (Albert)

    1991-01-01

    textabstractA meta-analysis, involving the secondary analysis of original data from 11 case-control studies of Alzheimer's disease, is presented for occupational exposures to solvents and lead. Three studies had data on occupational exposure to solvents. Among cases, 21.3% were reported to have been

  2. 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.

  3. 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.

  4. Fast food consumer´s awareness about the health risks and factors leading to preference for this type of meals

    OpenAIRE

    BENÝŠKOVÁ, Ivetta

    2014-01-01

    Consumption of fast-food style meals increases the risk of occurrence of health problems that might result in some diseases called lifestyle diseases or diseases of civilization. Frequent fast food consumption and related inadequate eating habits lead to increased morbidity and mortality linked particularly to obesity, diabetes, hypertension, cardiovascular diseases and other health problems even from early age. This thesis analyses the problems of eating at fast food restaurants and stands f...

  5. Fast food consumer´s awareness about the health risks and factors leading to preference for this type of meals

    OpenAIRE

    BENÝŠKOVÁ, Ivetta

    2014-01-01

    Consumption of fast-food style meals increases the risk of occurrence of health problems that might result in some diseases called lifestyle diseases or diseases of civilization. Frequent fast food consumption and related inadequate eating habits lead to increased morbidity and mortality linked particularly to obesity, diabetes, hypertension, cardiovascular diseases and other health problems even from early age. This thesis analyses the problems of eating at fast food restaurants and stands f...

  6. Interaction between x-irradiated plateau-phase bone marrow stromal cell lines and co-cultivated factor-dependent cell lines leading to leukemogenesis in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Naparstek, E.; Anklesaria, P.; FitzGerald, T.J.; Sakakeeny, M.A.; Greenberger, J.S.

    1987-03-01

    Plateau-phase mouse clonal bone marrow stromal cell lines D2XRII and C3H cl 11 produce decreasing levels of M-CSF (CSF-1), a specific macrophage progenitor cell humoral regulator, following X-irradiation in vitro. The decrease did not go below 40% of control levels, even after irradiation doses of 50,000 rad (500 Gy). In contrast, a distinct humoral regulator stimulating growth of GM-CSF/IL-3 factor-dependent (FD) hematopoietic progenitor cell lines was detected following radiation to doses above 2000 rad. This humoral factor was not detectable in conditioned medium from irradiated cells, weakly detected using factor-dependent target cell populations in agar overlay, and was prominently detected by liquid co-cultivation of factor-dependent cells with irradiated stromal cell cultures. Subclonal lines of FD cells, derived after co-cultivation revealed karyotypic abnormalities and induced myeloblastic tumors in syngeneic mice. Five-eight weeks co-cultivation was required for induction of factor independence and malignancy and was associated with dense cell to cell contact between FD cells and stromal cells demonstrated by light and electron microscopy. Increases in hematopoietic to stromal cell surface area, total number of adherent cells per flask, total non-adherent cell colonies per flask, and cumulative non-adherent cell production were observed after irradiation. The present data may prove very relevant to an understanding of the cell to cell interactions during X-irradiation-induced leukemia.

  7. 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.

  8. Do polypills lead to neglect of lifestyle risk factors? Findings from an individual participant data meta-analysis among 3140 patients at high risk of cardiovascular disease

    NARCIS (Netherlands)

    Selak, Vanessa; Bullen, Chris; Stepien, Sandrine; Arroll, Bruce; Bots, Michiel; Bramley, Dale; Cass, Alan; Grobbee, Diederick; Hillis, Graham S.; Molanus, Barbara; Neal, Bruce; Patel, Anushka; Rafter, Natasha; Rodgers, Anthony; Thom, Simon; Tonkin, Andrew; Usherwood, Tim; Wadham, Angela; Webster, Ruth

    2016-01-01

    Aim The aim of this study was to investigate whether polypill-based care for the prevention of cardiovascular disease (CVD) is associated with a change in lifestyle risk factors when compared with usual care, among patients with CVD or high calculated cardiovascular risk. Methods We conducted an ind

  9. Factors Leading to Membership in Professional Associations and Levels of Professional Commitment as Determined by Active and Inactive Members of Delta Pi Epsilon

    Science.gov (United States)

    McCroskey, Stacey; O'Neil, Sharon Lund

    2010-01-01

    Purpose: This study was undertaken with grant funds provided by the Delta Pi Epsilon (DPE) Research Foundation, Inc., to assess the factors of professional commitment related to membership. Additionally, the respondents' perceptions about DPE affiliating with the National Business Education Association (NBEA) were investigated. Method: Of the…

  10. Plant nuclear factor Y (NF-Y) B subunits confer drought tolerance and lead to improved corn yields on water-limited acres.

    Science.gov (United States)

    Nelson, Donald E; Repetti, Peter P; Adams, Tom R; Creelman, Robert A; Wu, Jingrui; Warner, David C; Anstrom, Don C; Bensen, Robert J; Castiglioni, Paolo P; Donnarummo, Meghan G; Hinchey, Brendan S; Kumimoto, Roderick W; Maszle, Don R; Canales, Roger D; Krolikowski, Katherine A; Dotson, Stanton B; Gutterson, Neal; Ratcliffe, Oliver J; Heard, Jacqueline E

    2007-10-16

    Commercially improved crop performance under drought conditions has been challenging because of the complexity of the trait and the multitude of factors that influence yield. Here we report the results of a functional genomics approach that identified a transcription factor from the nuclear factor Y (NF-Y) family, AtNF-YB1, which acts through a previously undescribed mechanism to confer improved performance in Arabidopsis under drought conditions. An orthologous maize transcription factor, ZmNF-YB2, is shown to have an equivalent activity. Under water-limited conditions, transgenic maize plants with increased ZmNF-YB2 expression show tolerance to drought based on the responses of a number of stress-related parameters, including chlorophyll content, stomatal conductance, leaf temperature, reduced wilting, and maintenance of photosynthesis. These stress adaptations contribute to a grain yield advantage to maize under water-limited environments. The application of this technology has the potential to significantly impact maize production systems that experience drought.

  11. A study of the prevalence and risk factors leading to HIV infection among a sample of street children and youth of Kathmandu

    Directory of Open Access Journals (Sweden)

    Karmacharya Dibesh

    2012-08-01

    Full Text Available Abstract Background The true prevalence of HIV and other sexually transmitted diseases among street children in Nepal is virtually unknown while information on related behavioural risk factors in this population is non-existent. The risk of HIV infection among street children and adolescents may be especially high due to their marginalized social and economic conditions. This study was conducted to determine the prevalence of HIV infection among a sample of street children and youth of Kathmandu and to identify risk factors associated with HIV infection in this group. A sample of street children and youth was recruited based on the purposive sampling of ten streets in Kathmandu, Nepal, known to have a high density of street children and youth. A total of 251 street children (aged 11–16 years and youth (aged 17–24 years were enrolled, with informed consent, from November, 2008 through June, 2009. Most of the participants (95% were male. Case status was determined by serological assessment of HIV status; data on risk factors were obtained using structured survey interviews. HIV prevalence and rates of a number of behavioural risk factors suspected to play a role in HIV transmission among street children and youth were determined, including unprotected sex, intravenous drug use, and other risky sex and substance use behaviours. Results Among the 251 children and youth, we found an overall HIV prevalence of 7.6%. As the sample size of females was small (n = 13 and the behavioural risk factors are likely to be quite different for boys and girls, we conducted separate analyses by gender. As our small sample of females is unlikely to be representative and lacks power for statistical testing, our report focuses on the results for the males surveyed.The strongest behavioural risk factor to emerge from this study was intravenous drug use; 30% of the male subjects were injecting drug users and 20% of those were HIV positive. Furthermore

  12. 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.

  13. 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.

  14. Math Achievement is Important, but Task Values are Critical, Too: Examining the Intellectual and Motivational Factors Leading to Gender Disparities in STEM Careers

    Directory of Open Access Journals (Sweden)

    Mingte eWang

    2015-02-01

    Full Text Available Although young women now obtain higher course grades in math than boys and are just as likely to be enrolled in advanced math courses in high school, females continue to be underrepresented in some STEM occupations. This study drew on expectancy-value theory to assess (1 which intellectual and motivational factors in high school predict gender differences in career choices and (2 whether students’ motivational beliefs mediated the pathway of gender on STEM career via math achievement by using a national longitudinal sample in the United States. We found that math achievement in twelfth grade mediated the association between gender and attainment of a STEM career by the early to mid-thirties. However, math achievement was not the only factor distinguishing gender differences in STEM occupations. Even though math achievement explained career differences between men and women, math task value partially explained the gender differences in STEM career attainment that were attributed to math achievement. The identification of potential factors of women’s underrepresentation in STEM will enhance our ability to design intervention programs that are optimally tailored to female needs to impact STEM achievement and occupational choices.

  15. Math achievement is important, but task values are critical, too: examining the intellectual and motivational factors leading to gender disparities in STEM careers

    Science.gov (United States)

    Wang, Ming-Te; Degol, Jessica; Ye, Feifei

    2015-01-01

    Although young women now obtain higher course grades in math than boys and are just as likely to be enrolled in advanced math courses in high school, females continue to be underrepresented in some Science, Technology, Engineering, and Mathematics (STEM) occupations. This study drew on expectancy-value theory to assess (1) which intellectual and motivational factors in high school predict gender differences in career choices and (2) whether students’ motivational beliefs mediated the pathway of gender on STEM career via math achievement by using a national longitudinal sample in the United States. We found that math achievement in 12th grade mediated the association between gender and attainment of a STEM career by the early to mid-thirties. However, math achievement was not the only factor distinguishing gender differences in STEM occupations. Even though math achievement explained career differences between men and women, math task value partially explained the gender differences in STEM career attainment that were attributed to math achievement. The identification of potential factors of women’s underrepresentation in STEM will enhance our ability to design intervention programs that are optimally tailored to female needs to impact STEM achievement and occupational choices. PMID:25741292

  16. Math achievement is important, but task values are critical, too: examining the intellectual and motivational factors leading to gender disparities in STEM careers.

    Science.gov (United States)

    Wang, Ming-Te; Degol, Jessica; Ye, Feifei

    2015-01-01

    Although young women now obtain higher course grades in math than boys and are just as likely to be enrolled in advanced math courses in high school, females continue to be underrepresented in some Science, Technology, Engineering, and Mathematics (STEM) occupations. This study drew on expectancy-value theory to assess (1) which intellectual and motivational factors in high school predict gender differences in career choices and (2) whether students' motivational beliefs mediated the pathway of gender on STEM career via math achievement by using a national longitudinal sample in the United States. We found that math achievement in 12th grade mediated the association between gender and attainment of a STEM career by the early to mid-thirties. However, math achievement was not the only factor distinguishing gender differences in STEM occupations. Even though math achievement explained career differences between men and women, math task value partially explained the gender differences in STEM career attainment that were attributed to math achievement. The identification of potential factors of women's underrepresentation in STEM will enhance our ability to design intervention programs that are optimally tailored to female needs to impact STEM achievement and occupational choices.

  17. LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp)

    DEFF Research Database (Denmark)

    Poulsen, Ebbe Toftgaard; Nielsen, Nadia Sukusu; Jensen, Morten Mørk;

    2016-01-01

    at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo...... laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC......-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after...

  18. Expression of HIV-1 Vpu leads to loss of the viral restriction factor CD317/Tetherin from lipid rafts and its enhanced lysosomal degradation.

    Directory of Open Access Journals (Sweden)

    Ruth Rollason

    Full Text Available CD317/tetherin (aka BST2 or HM1.24 antigen is an interferon inducible membrane protein present in regions of the lipid bilayer enriched in sphingolipids and cholesterol (often termed lipid rafts. It has been implicated in an eclectic mix of cellular processes including, most notably, the retention of fully formed viral particles at the surface of cells infected with HIV and other enveloped viruses. Expression of the HIV viral accessory protein Vpu has been shown to lead to intracellular sequestration and degradation of tetherin, thereby counteracting the inhibition of viral release. There is evidence that tetherin interacts directly with Vpu, but it remains unclear where in the cell this interaction occurs or if Vpu expression affects the lipid raft localisation of tetherin. We have addressed these points using biochemical and cell imaging approaches focused on endogenous rather than ectopically over-expressed tetherin. We find i no evidence for an interaction between Vpu and endogenous tetherin at the cell surface, ii the vast majority of endogenous tetherin that is at the cell surface in control cells is in lipid rafts, iii internalised tetherin is present in non-raft fractions, iv expression of Vpu in cells expressing endogenous tetherin leads to the loss of tetherin from lipid rafts, v internalised tetherin enters early endosomes, and late endosomes, in both control cells and cells expressing Vpu, but the proportion of tetherin molecules destined for degradation rather than recycling is increased in cells expressing Vpu vi lysosomes are the primary site for degradation of endogenous tetherin in cells expressing Vpu. Our studies underlie the importance of studying endogenous tetherin and let us propose a model in which Vpu intercepts newly internalised tetherin and diverts it for lysosomal destruction rather than recycling to the cell surface.

  19. Magnesium Diboride Current Leads

    Science.gov (United States)

    Panek, John

    2010-01-01

    A recently discovered superconductor, magnesium diboride (MgB2), can be used to fabricate conducting leads used in cryogenic applications. Dis covered to be superconducting in 2001, MgB2 has the advantage of remaining superconducting at higher temperatures than the previously used material, NbTi. The purpose of these leads is to provide 2 A of electricity to motors located in a 1.3 K environment. The providing environment is a relatively warm 17 K. Requirements for these leads are to survive temperature fluctuations in the 5 K and 11 K heat sinks, and not conduct excessive heat into the 1.3 K environment. Test data showed that each lead in the assembly could conduct 5 A at 4 K, which, when scaled to 17 K, still provided more than the required 2 A. The lead assembly consists of 12 steelclad MgB2 wires, a tensioned Kevlar support, a thermal heat sink interface at 4 K, and base plates. The wires are soldered to heavy copper leads at the 17 K end, and to thin copper-clad NbTi leads at the 1.3 K end. The leads were designed, fabricated, and tested at the Forschungszentrum Karlsruhe - Institut foer Technische Physik before inclusion in Goddard's XRS (X-Ray Spectrometer) instrument onboard the Astro-E2 spacecraft. A key factor is that MgB2 remains superconducting up to 30 K, which means that it does not introduce joule heating as a resistive wire would. Because the required temperature ranges are 1.3-17 K, this provides a large margin of safety. Previous designs lost superconductivity at around 8 K. The disadvantage to MgB2 is that it is a brittle ceramic, and making thin wires from it is challenging. The solution was to encase the leads in thin steel tubes for strength. Previous designs were so brittle as to risk instrument survival. MgB2 leads can be used in any cryogenic application where small currents need to be conducted at below 30 K. Because previous designs would superconduct only at up to 8 K, this new design would be ideal for the 8-30 K range.

  20. The contribution of leading diseases and risk factors to excess losses of healthy life in eastern Europe: burden of disease study

    Directory of Open Access Journals (Sweden)

    Vander Hoorn Stephen

    2005-11-01

    Full Text Available Abstract Background The East/West gradient in health across Europe has been described often, but not using metrics as comprehensive and comparable as those of the Global Burden of Disease 2000 and Comparative Risk Assessment studies. Methods Comparisons are made across 3 epidemiological subregions of the WHO region for Europe – A (very low child and adult mortality, B (low child and low adult mortality and C (low child and high adult mortality – with populations in 2000 of 412, 218 and 243 millions respectively, and using the following measures: 1. Probabilities of death by sex and causal group across 7 age intervals; 2. Loss of healthy life (DALYs to diseases and injuries per thousand population; 3. Loss of healthy life (DALYs attributable to selected risk factors across 3 age ranges. Results Absolute differences in mortality are most marked in males and in younger adults, and for deaths from vascular diseases and from injuries. Dominant contributions to east-west differences come from the nutritional/physiological group of risk factors (blood pressure, cholesterol concentration, body mass index, low fruit and vegetable consumption and inactivity contributing to vascular disease and from the legal drugs – tobacco and alcohol. Conclusion The main requirements for reducing excess health losses in the east of Europe are: 1 favorable shifts in all amenable vascular risk factors (irrespective of their current levels by population-wide and personal measures; 2 intensified tobacco control; 3 reduced alcohol consumption and injury control strategies (for example, for road traffic injuries. Cost effective strategies are broadly known but local institutional support for them needs strengthening.

  1. Biochemical and molecular analysis of pink tomatoes: deregulated expression of the gene encoding transcription factor SlMYB12 leads to pink tomato fruit color.

    Science.gov (United States)

    Ballester, Ana-Rosa; Molthoff, Jos; de Vos, Ric; Hekkert, Bas te Lintel; Orzaez, Diego; Fernández-Moreno, Josefina-Patricia; Tripodi, Pasquale; Grandillo, Silvana; Martin, Cathie; Heldens, Jos; Ykema, Marieke; Granell, Antonio; Bovy, Arnaud

    2010-01-01

    The color of tomato fruit is mainly determined by carotenoids and flavonoids. Phenotypic analysis of an introgression line (IL) population derived from a cross between Solanum lycopersicum 'Moneyberg' and the wild species Solanum chmielewskii revealed three ILs with a pink fruit color. These lines had a homozygous S. chmielewskii introgression on the short arm of chromosome 1, consistent with the position of the y (yellow) mutation known to result in colorless epidermis, and hence pink-colored fruit, when combined with a red flesh. Metabolic analysis showed that pink fruit lack the ripening-dependent accumulation of the yellow-colored flavonoid naringenin chalcone in the fruit peel, while carotenoid levels are not affected. The expression of all genes encoding biosynthetic enzymes involved in the production of the flavonol rutin from naringenin chalcone was down-regulated in pink fruit, suggesting that the candidate gene underlying the pink phenotype encodes a regulatory protein such as a transcription factor rather than a biosynthetic enzyme. Of 26 MYB and basic helix-loop-helix transcription factors putatively involved in regulating transcription of genes in the phenylpropanoid and/or flavonoid pathway, only the expression level of the MYB12 gene correlated well with the decrease in the expression of structural flavonoid genes in peel samples of pink- and red-fruited genotypes during ripening. Genetic mapping and segregation analysis showed that MYB12 is located on chromosome 1 and segregates perfectly with the characteristic pink fruit color. Virus-induced gene silencing of SlMYB12 resulted in a decrease in the accumulation of naringenin chalcone, a phenotype consistent with the pink-colored tomato fruit of IL1b. In conclusion, biochemical and molecular data, gene mapping, segregation analysis, and virus-induced gene silencing experiments demonstrate that the MYB12 transcription factor plays an important role in regulating the flavonoid pathway in tomato fruit

  2. de novo design and synthesis of Candida antarctica lipase B gene and α-factor leads to high-level expression in Pichia pastoris.

    Science.gov (United States)

    Yang, Jiang-Ke; Liu, Li-Ying; Dai, Jiang-Hong; Li, Qin

    2013-01-01

    Candida antarctica lipase B (CALB) is one of the most widely used and studied enzymes in the world. In order to achieve the high-level expression of CALB in Pichia, we optimized the codons of CALB gene and α-factor by using a de novo design and synthesis strategy. Through comparative analysis of a series of recombinants with different expression components, we found that the methanol-inducible expression recombinant carrying the codon-optimized α-factor and mature CALB gene (pPIC9KαM-CalBM) has the highest lipase production capacity. After fermentation parameters optimization, the lipase activity and protein content of the recombinant pPIC9KαM-CalBM reached 6,100 U/mL and 3.0 g/L, respectively, in a 5-L fermentor. We believe this strategy could be of special interest due to its capacity to improve the expression level of target gene, and the Pichia transformants carrying the codon-optimized gene had great potential for the industrial-scale production of CALB lipase.

  3. Overexpression of the maize GRF10, an endogenous truncated growth-regulating factor protein, leads to reduction in leaf size and plant height

    Institute of Scientific and Technical Information of China (English)

    Lei Wu; Dengfeng Zhang; Ming Xue; Jianjun Qian; Yan He; and Shoucai Wang

    2014-01-01

    It has long been thought that growth‐regulating factors (GRFs) gene family members act as transcriptional activators to play important roles in multiple plant develop-mental processes. However, the recent characterization of Arabidopsis GRF7 showed that it functions as a transcriptional repressor of osmotic stress‐responsive genes. This highlights the complex and diverse mechanisms by which different GRF members use to take action. In this study, the maize (Zea mays L.) GRF10 was functional y characterized to improve this concept. The deduced ZmGRF10 protein retains the N‐terminal QLQ and WRC domains, the characteristic regions as protein‐interacting and DNA‐binding domains, respectively. However, it lacks nearly the entire C‐terminal domain, the regions executing transactivation activity. Consistently, ZmGRF10 protein maintains the ability to interact with GRF‐interacting factors (GIFs) proteins, but lacks transactivation activity. Overexpression of ZmGRF10 in maize led to a reduction in leaf size and plant height through decreasing cel proliferation, whereas the yield‐related traits were not affected. Tran-scriptome analysis revealed that multiple biological pathways were affected by ZmGRF10 overexpression, including a few transcriptional regulatory genes, which have been demon-strated to have important roles in control ing plant growth and development. We propose that ZmGRF10 aids in fine‐tuning the homeostasis of the GRF‐GIF complex in the regulation of cel proliferation.

  4. de novo design and synthesis of Candida antarctica lipase B gene and α-factor leads to high-level expression in Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Jiang-Ke Yang

    Full Text Available Candida antarctica lipase B (CALB is one of the most widely used and studied enzymes in the world. In order to achieve the high-level expression of CALB in Pichia, we optimized the codons of CALB gene and α-factor by using a de novo design and synthesis strategy. Through comparative analysis of a series of recombinants with different expression components, we found that the methanol-inducible expression recombinant carrying the codon-optimized α-factor and mature CALB gene (pPIC9KαM-CalBM has the highest lipase production capacity. After fermentation parameters optimization, the lipase activity and protein content of the recombinant pPIC9KαM-CalBM reached 6,100 U/mL and 3.0 g/L, respectively, in a 5-L fermentor. We believe this strategy could be of special interest due to its capacity to improve the expression level of target gene, and the Pichia transformants carrying the codon-optimized gene had great potential for the industrial-scale production of CALB lipase.

  5. The over-expression of two transcription factors, ABS5/bHLH30 and ABS7/MYB101, leads to upwardly curly leaves.

    Directory of Open Access Journals (Sweden)

    Rui An

    Full Text Available Proper leaf development is essential for plant growth and development, and leaf morphogenesis is under the control of intricate networks of genetic and environmental cues. We are interested in dissecting these regulatory circuits genetically and report here the isolation of two Arabidopsis dominant mutants, abnormal shoot5-1D (abs5-1D and abs7-1D identified through activation tagging screens. Both abs5-1D and abs7-1D display an intriguing upwardly curly leaf phenotype. Molecular cloning showed that the elevated expression of a bHLH transcription factor ABS5/T5L1/bHLH30 or a MYB transcription factor ABS7/MYB101 is the cause for the abnormal leaf phenotypes found in abs5-1D or abs7-1D, respectively. Protoplast transient expression assays confirmed that both ABS5/T5L1 and ABS7/MYB101 are targeted to the nucleus. Interestingly, the expression domains of auxin response reporter DR5::GUS were abnormal in leaves of abs5-1D and ABS5/T5L1 over-expression lines. Moreover, cotyledon venation analysis showed that more areoles and free-ending veins are formed in abs5-1D. We found that the epidermis-specific expressions of ABS5/T5L1 or ABS7/MYB101 driven by the Arabidopsis Meristem Layer 1 promoter (PAtML1 were sufficient to recapitulate the curly leaf phenotype of abs5-1D or abs7-1D. In addition, PAtML1::ABS5 lines exhibited similar changes in DR5::GUS expression patterns as those found in 35S-driven ABS5/T5L1 over-expression lines. Our work demonstrated that enhanced expressions of two transcription factors, ABS5/T5L1 and ABS7/MYB101, are able to alter leaf lamina development and reinforce the notion that leaf epidermis plays critical roles in regulating plant organ morphogenesis.

  6. The experiences of female high school students and interest in STEM: Factors leading to the selection of an engineering or computer science major

    Science.gov (United States)

    Genoways, Sharon K.

    STEM (Science, Technology, Engineering and Math) education creates critical thinkers, increases science literacy, and enables the next generation of innovators, which leads to new products and processes that sustain our economy (Hossain & Robinson, 2012). We have been hearing the warnings for several years, that there simply are not enough young scientists entering into the STEM professional pathways to replace all of the retiring professionals (Brown, Brown, Reardon, & Merrill, 2011; Harsh, Maltese, & Tai, 2012; Heilbronner, 2011; Scott, 2012). The problem is not necessarily due to a lack of STEM skills and concept proficiency. There also appears to be a lack of interest in these fields. Recent evidence suggests that many of the most proficient students, especially minority students and women, have been gravitating away from science and engineering toward other professions. (President's Council of Advisors on Science and Technology, 2010). The purpose of this qualitative research study was an attempt to determine how high schools can best prepare and encourage young women for a career in engineering or computer science. This was accomplished by interviewing a pool of 21 women, 5 recent high school graduates planning to major in STEM, 5 college students who had completed at least one full year of coursework in an engineering or computer science major and 11 professional women who had been employed as an engineer or computer scientist for at least one full year. These women were asked to share the high school courses, activities, and experiences that best prepared them to pursue an engineering or computer science major. Five central themes emerged from this study; coursework in physics and calculus, promotion of STEM camps and clubs, teacher encouragement of STEM capabilities and careers, problem solving, critical thinking and confidence building activities in the classroom, and allowing students the opportunity to fail and ask questions in a safe environment. These

  7. Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice.

    Science.gov (United States)

    Takeda, Yosuke; Oue, Hiroshi; Okada, Shinsuke; Kawano, Akira; Koretake, Katsunori; Michikawa, Makoto; Akagawa, Yasumasa; Tsuga, Kazuhiro

    2016-12-05

    It is known that tooth loss is known to be a risk factor for Alzheimer's disease and soft diet feeding induces memory impairment. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is associated with tooth loss or soft diet in young animal model, and that BDNF expression is decreased in patients with Alzheimer's disease. However, single or combined effect of tooth loss and/or soft diet on brain function has not fully understood. Here we examined the effect of molar loss and powder diet on memory ability and the expression of BDNF mRNA in the hippocampus of adult C57BL/6J mice. Twenty eight-weeks-old C57BL/6J mice were divided into intact molar group and extracted molar group. They were randomly divided into the I/S group (Intact upper molar teeth/Solid diet feeding), the E/S group (Extracted upper molar teeth/Solid diet feeding), the I/P group (Intact upper molar teeth/Powder diet feeding), and the E/P group (Extracted upper molar teeth/Powder diet feeding). The observation periods were 4 and 16-week. To analyze the memory ability, the step-through passive avoidance test was conducted. BDNF-related mRNA in the hippocampus was analyzed by real-time polymerase chain reaction (RT-PCR). At 4 weeks later, we performed memory test and isolated brains to analyze. There were no differences in memory function and BDNF mRNA level between these four groups. However, at 16 weeks later, E/S and E/P group showed memory impairment, and decreased level of BDNF mRNA. Whereas, the powder diet had no effect on memory function and BDNF mRNA level even at 16 weeks later. These results suggest that the effect of molar loss and powder diet on memory function and BDNF mRNA levels were different, molar loss may have a greater long-term effect on memory ability than powder diet does.

  8. Can generalized distribution factors lead to ''objective'' transmission toll allocations? Some lessons from the recent Chilean experience

    Energy Technology Data Exchange (ETDEWEB)

    Galetovic, Alexander [Facultad de Ciencias Economicas y Empresariales, Universidad de los Andes, Av. San Carlos de Apoquindo 2200, Santiago (Chile); Palma-Behnke, Rodrigo [Department of Electrical Engineering, University of Chile, Av. Tupper 2007, Santiago (Chile)

    2008-03-15

    How to charge for transmission lines in a liberalized electricity market is still a conceptually unresolved issue and the literature offers many methods to determine who ''uses'' a given line and how to allocate tolls among users. But there seems to be some agreement that once a given method is chosen, calculating use and toll allocations is a mere technical matter. We suggest, by contrast that this belief is not warranted. We apply one power flow identification method - generalized load distribution factors - to allocate transmission tolls among the users of the Chilean transmission system and show that almost any allocation of tolls can be achieved by suitably choosing parameter values. Essentially, the method affords many degrees of freedom to the person responsible for setting the parameters needed to apply it. We argue that this suggests that setting parameter values is a central feature of transmission regulation. Moreover, our results suggest that an allocation method cannot answer the key unresolved question in the literature: what is the structure of tolls that gives economically adequate expansion incentives. (author)

  9. Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: Study design, methods and feasibility

    Directory of Open Access Journals (Sweden)

    Guo Xiu

    2006-06-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12, previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p = 0.001-0.03. These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrolment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC.

  10. Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Sunker, Asma; Morsy, Heba; Al-Sheddi, Tarfa; Shamseldin, Hanan E; Adly, Nouran; Hashem, Mais; Alkuraya, Fowzan S

    2011-08-12

    Adams-Oliver syndrome (AOS) is defined by the combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD). It is usually inherited as an autosomal-dominant trait, but autosomal-recessive inheritance has also been documented. In an individual with autosomal-recessive AOS, we combined autozygome analysis with exome sequencing to identify a homozygous truncating mutation in dedicator of cytokinesis 6 gene (DOCK6) which encodes an atypical guanidine exchange factor (GEF) known to activate two members of the Rho GTPase family: Cdc42 and Rac1. Another homozygous truncating mutation was identified upon targeted sequencing of DOCK6 in an unrelated individual with AOS. Consistent with the established role of Cdc42 and Rac1 in the organization of the actin cytoskeleton, we demonstrate a cellular phenotype typical of a defective actin cytoskeleton in patient cells. These findings, combined with a Dock6 expression profile that is consistent with an AOS phenotype as well as the very recent demonstration of dominant mutations of ARHGAP31 in AOS, establish Cdc42 and Rac1 as key molecules in the pathogenesis of AOS and suggest that other regulators of these Rho GTPase proteins might be good candidates in the quest to define the genetic spectrum of this genetically heterogeneous condition.

  11. Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer's Disease.

    Science.gov (United States)

    Brewer, George J

    2015-12-02

    It has become clear that copper toxicity is playing a major role in Alzheimer's disease; but why is the brain copper toxicity with cognition loss in Alzheimer's disease so much different clinically than brain copper toxicity in Wilson's disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer's is at least in part, a copper-2 toxicity disease, while Wilson's is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer's epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure.

  12. Kresoxim-methyl primes Medicago truncatula plants against abiotic stress factors via altered reactive oxygen and nitrogen species signalling leading to downstream transcriptional and metabolic readjustment.

    Science.gov (United States)

    Filippou, Panagiota; Antoniou, Chrystalla; Obata, Toshihiro; Van Der Kelen, Katrien; Harokopos, Vaggelis; Kanetis, Loukas; Aidinis, Vassilis; Van Breusegem, Frank; Fernie, Alisdair R; Fotopoulos, Vasileios

    2016-03-01

    Biotic and abiotic stresses, such as fungal infection and drought, cause major yield losses in modern agriculture. Kresoxim-methyl (KM) belongs to the strobilurins, one of the most important classes of agricultural fungicides displaying a direct effect on several plant physiological and developmental processes. However, the impact of KM treatment on salt and drought stress tolerance is unknown. In this study we demonstrate that KM pre-treatment of Medicago truncatula plants results in increased protection to drought and salt stress. Foliar application with KM prior to stress imposition resulted in improvement of physiological parameters compared with stressed-only plants. This protective effect was further supported by increased proline biosynthesis, modified reactive oxygen and nitrogen species signalling, and attenuation of cellular damage. In addition, comprehensive transcriptome analysis identified a number of transcripts that are differentially accumulating in drought- and salinity-stressed plants (646 and 57, respectively) after KM pre-treatment compared with stressed plants with no KM pre-treatment. Metabolomic analysis suggests that the priming role of KM in drought- and to a lesser extent in salinity-stressed plants can be attributed to the regulation of key metabolites (including sugars and amino acids) resulting in protection against abiotic stress factors. Overall, the present study highlights the potential use of this commonly used fungicide as a priming agent against key abiotic stress conditions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  13. Sociological Evaluation of Social Factors Leading Women to Aesthetic Surgery for the Eye in the Shemiran District (District 1 of Tehran, in 2014

    Directory of Open Access Journals (Sweden)

    Fatemeh Mahdipur Azar

    2016-03-01

    Full Text Available Gravitation to aesthetics is a commonality among humans and is a way to manage the body. Yet, in recent years, we have witnessed significant increase in gravitation to various beautification surgeries among which eye aesthetic surgery is the most modern method of change in appearance and face for individuals. Therefore, the purpose of this research was sociological evaluation of social factors effective on women’s gravitation to aesthetic eye surgery. In this line, after a review of past research, statement of the problem and importance and necessity for the research, from among women in the Shemiran District (District 1, a sample with participation of 250 individuals were selected and hypotheses under consideration were analyzed by preparation of questionnaire and performance of interviews. Results of this research using survey methodology show that meaningful correlation exists between socioeconomic status, interest in novelty, being influenced by spouse and peers, motto of finding the desired spouse, level of use of public media and body management with aesthetic surgery for the eye. Additionally, analyses performed have led to the conclusion that meaningful correlation does not exist between level of self-esteem and tendency to aesthetic eye surgery. In addition, for our purpose for completion of research already performed, field study, documental research and analysis of advertisement brochures have been taken advantage of. Ultimately, after evaluation of the results obtained, strategies for improvement of research by other researchers have been presented.

  14. Derivation of reliable empirical models describing lead transfer from metal-polluted soils to radish (Raphanus sativa L.): Determining factors and soil criteria.

    Science.gov (United States)

    Zhang, Sha; Song, Jing; Cheng, Yinwen; Christie, Peter; Long, Jian; Liu, Lingfei

    2017-09-10

    Reliable models describing Pb transfer from soils to food crops are useful in the improvement of soil protection guidelines. This study provides mechanistic insights from in-situ soil solution measurement on the Pb uptake in the root tissues (RF) of radish, grown in 25 representative Pb-contaminated agricultural soils. Lead speciation and regression analysis indicate that >88.6% of the variation in RF Pb is attributable to free Pb(2+) activity (aPb(2+)) in the soil solution, which is predominantly controlled by pH and DOC. Higher DOC would increase the total dissolved Pb (CSol-Pb) in the soil solution but reduce the bioavailability of Pb to radish. CSol-Pb performs poorly in predicting RF Pb unless pH and DOC are included. However, 0.01M CaCl2 extractable Pb (CCC-Pb) alone can satisfactorily predict RF Pb, attributable to the fact that CCC-Pb is consistent with aPb(2+). CCC-Pb can be predicted using CSol-Pb and pH. Total soil Pb (CT-Pb), or 0.43M HNO3 extractable Pb (CNA-Pb) has a strong, non-linear correlation with CSol-Pb or CCC-Pb and it is therefore not surprising that CT-Pb or CNA-Pb, together with pH and CEC, can also satisfactorily predict RF Pb. Derived models are effective in identification of soils where RF Pb exceeds the food quality standard (FQS). Soil Pb criteria based on CT-Pb, CNA-Pb and CCC-Pb are derived by inverse use of empirical models. The derived Pb criterion (target value) based on CCC-Pb is 0.02mgkg(-1) and the stricter criterion (safe value) is 0.01mgkg(-1), which allows a 5% probability for RF Pb to exceed FQS. Safe values based on CT-Pb and CNA-Pb ranged from 26 to 1036mgkg(-1) and 9 to 745mgkg(-1), respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 深圳市儿童血铅水平及相关因素分析%Study on blood lead level and related factors of children in Shenzhen

    Institute of Scientific and Technical Information of China (English)

    罗小娟; 曹科; 徐霞

    2012-01-01

    目的 调查深圳市儿童血铅水平,探讨儿童铅中毒的危险因素,为制定积极有效的干预措施提供科学依据.方法 以某院儿童保健科常规体检儿童作为研究对象,采集儿童静脉血,用原子吸收光谱仪测定血铅值,分析血铅水平与儿童年龄、性别的关系,并对儿童家长进行问卷调查,对儿童铅中毒相关因素进行条件Logistic回归变量筛选.结果 16 076名儿童血铅浓度平均值为(41.22±25.93)μg/L,铅中毒儿童共264例,总检出率为1.64%,男童血铅水平明显高于女童(P<0.01),0~6岁儿童血铅浓度及铅中毒率随着年龄增长呈明显增高趋势,6岁以后维持在一个相对稳定水平.导致儿童铅中毒的主要危险因素有吮吸手指、啃咬异物,常吃松花蛋、爆米花等膨化食品及居住在加油站附近,经常进食肉蛋奶类或补充锌钙铁剂类为保护因素.结论 深圳儿童血铅水平低于中国其他城市,但高于美国等发达国家.不良的生活和饮食习惯及外界环境的污染是儿童铅中毒的主要危险因素.现阶段对儿童进行健康教育,养成良好的卫生行为习惯,调整营养膳食是减少儿童铅中毒的最有效和经济实用的方法.%OBJECTIVE To investigate the blood lead level of children in Shenzhen, analyze the effect factors of increase of blood lead level, and promote reasonable and effective preventive measures to reduce the blood lead level of children. METHODS Children of health examination in department of child health were randomly selected, the lead level in blood was detected by atomic absorption spectrometer, and analyze the relation of the blood lead level and children's age or sex. Their parents were surveyed and asked to finish a questionnaire. Conditional Logistic regression was used for the main effect factors for increasing blood lead level. RESULTS The average of 16076 children blood lead (x ± s) was (41.22 ± 25.93) μg/L 264 children have lead

  16. 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.

  17. Trinucleotide Repeat Expansion in the Transcription Factor 4 (TCF4) Gene Leads to Widespread mRNA Splicing Changes in Fuchs' Endothelial Corneal Dystrophy

    Science.gov (United States)

    Wieben, Eric D.; Aleff, Ross A.; Tang, Xiaojia; Butz, Malinda L.; Kalari, Krishna R.; Highsmith, Edward W.; Jen, Jin; Vasmatzis, George; Patel, Sanjay V.; Maguire, Leo J.; Baratz, Keith H.; Fautsch, Michael P.

    2017-01-01

    Purpose To identify RNA missplicing events in human corneal endothelial tissue isolated from Fuchs' endothelial corneal dystrophy (FECD). Methods Total RNA was isolated and sequenced from corneal endothelial tissue obtained during keratoplasty from 12 patients with FECD and 4 patients undergoing keratoplasty or enucleation for other indications. The length of the trinucleotide repeat (TNR) CTG in the transcription factor 4 (TCF4) gene was determined using leukocyte-derived DNA analyzed by a combination of Southern blotting and Genescan analysis. Commercial statistical software was used to quantify expression of alternatively spliced genes. Validation of selected alternative splicing events was performed by using RT-PCR. Gene sets identified were analyzed for overrepresentation using Web-based analysis system. Results Corneal endothelial tissue from FECD patients containing a CTG TNR expansion sequence in the TCF4 gene revealed widespread changes in mRNA splicing, including a novel splicing event involving FGFR2. Differential splicing of NUMA1, PPFIBP1, MBNL1, and MBNL2 transcripts were identified in all FECD samples containing a TNR expansion. The differentially spliced genes were enriched for products that localize to the cell cortex and bind cytoskeletal and cell adhesion proteins. Conclusions Corneal endothelium from FECD patients harbors a unique signature of mis-splicing events due to CTG TNR expansion in the TCF4 gene, consistent with the hypothesis that RNA toxicity contributes to the pathogenesis of FECD. Changes to the endothelial barrier function, a known event in the development of FECD, was identified as a key biological process influenced by the missplicing events. PMID:28118661

  18. Combined inhibition of epidermal growth factor receptor and cyclooxygenase-2 leads to greater anti-tumor activity of docetaxel in advanced prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jianzhong Lin

    Full Text Available The epidermal growth factor receptor (EGFR and cyclooxygenase-2(COX-2 play a critical role in disease progression, relapse and therapeutic resistance of advanced prostate cancer (PCa. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking EGRF and/or COX-2 (using gefitinib and NS-398, respectively in terms of improving the efficacy of the conventional clinical chemotherapeutic drug docetaxel in vitro and vivo. We showed that EGFR and COX-2 expression was higher in metastatic than non-metastatic PCa tissues and cells. Docetaxel, alone or in combination with gefitinib or NS-398, resulted in a small decrease in cell viability. The three drug combination decreased cell viability to a greater extent than docetaxel alone or in combination with gefitinib or NS-398. Docetaxel resulted in a modest increase in apoptotic cell in metastatic and non-metastatic cell lines. NS-398 markedly enhanced docetaxel-induced cell apoptosis. The combination of the three drugs caused even more marked apoptosis and resulted in greater suppression of invasive potential than docetaxel alone or in association with gefitinib or NS-398. The combination of all three drugs also resulted in a more marked decrease in NF-ΚB, MMP-9 and VEGF levels in PC-3M cells. These in vitro findings were supported by in vivo studies showing that docetaxel in combination with gefitinib and NS-398 was significantly more effective than any individual agent. Based on previous preclinical research, we conclude that simultaneously blocking EGFR and COX-2 by gefitinib and NS-398 sensitizes advanced PCa cells to docetaxel-induced cytotoxicity.

  19. Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice

    Science.gov (United States)

    Allard, Joanne S.; Perez, Evelyn J; Fukui, Koji; Carpenter, Priscilla; Ingram, Donald K.; de Cabo, Rafael

    2016-01-01

    Long-term use of anti-diabetic agents has become commonplace as rates of obesity, metabolic syndrome and diabetes continue to escalate. Metformin, a commonly used anti-diabetic drug, has been shown to have many beneficial effects outside of its therapeutic regulation of glucose metabolism and insulin sensitivity. Studies on metformin’s effects on the central nervous system are limited and predominantly consist of in vitro studies and a few in vivo studies with short-term treatment in relatively young animals; some provide support for metformin as a neuroprotective agent while others show evidence that metformin may be deleterious to neuronal survival. In this study, we examined the effect of long-term metformin treatment on brain neurotrophins and cognition in aged male C57Bl/6 mice. Mice were fed control (C), high-fat (HF) or a high-fat diet supplemented with metformin (HFM) for 6 months. Metformin decreased body fat composition and attenuated declines in motor function induced by a HF diet. Performance in the Morris water maze test of hippocampal based memory function, showed that metformin prevented impairment of spatial reference memory associated with the HF diet. Quantitative RT-PCR on brain homogenates revealed decreased transcription of BDNF, NGF and NTF3; however protein levels were not altered. Metformin treatment also decreased expression of the antioxidant pathway regulator, Nrf2. The decrease in transcription of neurotrophic factors and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation. PMID:26698400

  20. Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats.

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    Nicholas W Gilpin

    Full Text Available Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (~postnatal days 28-42 in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF cell in the lateral portion of the central amygdala (CeA, a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity, an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects

  1. Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice.

    Science.gov (United States)

    Allard, Joanne S; Perez, Evelyn J; Fukui, Koji; Carpenter, Priscilla; Ingram, Donald K; de Cabo, Rafael

    2016-03-15

    Long-term use of anti-diabetic agents has become commonplace as rates of obesity, metabolic syndrome and diabetes continue to escalate. Metformin, a commonly used anti-diabetic drug, has been shown to have many beneficial effects outside of its therapeutic regulation of glucose metabolism and insulin sensitivity. Studies on metformin's effects on the central nervous system are limited and predominantly consist of in vitro studies and a few in vivo studies with short-term treatment in relatively young animals; some provide support for metformin as a neuroprotective agent while others show evidence that metformin may be deleterious to neuronal survival. In this study, we examined the effect of long-term metformin treatment on brain neurotrophins and cognition in aged male C57Bl/6 mice. Mice were fed control (C), high-fat (HF) or a high-fat diet supplemented with metformin (HFM) for 6 months. Metformin decreased body fat composition and attenuated declines in motor function induced by a HF diet. Performance in the Morris water maze test of hippocampal based memory function, showed that metformin prevented impairment of spatial reference memory associated with the HF diet. Quantitative RT-PCR on brain homogenates revealed decreased transcription of BDNF, NGF and NTF3; however protein levels were not altered. Metformin treatment also decreased expression of the antioxidant pathway regulator, Nrf2. The decrease in transcription of neurotrophic factors and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation.

  2. A point mutation in translation initiation factor 2B leads to a continuous hyper stress state in oligodendroglial-derived cells.

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    Liraz Kantor

    Full Text Available BACKGROUND: Mutations in eukaryotic translation initiation factor 2B (eIF2B cause Childhood Ataxia with CNS Hypomyelination (CACH, also known as Vanishing White Matter disease (VWM. The disease is manifested by loss of brain myelin upon physiological stress. In a previous study, we showed that fibroblasts isolated from CACH/VWM patients are hypersensitive to pharmacologically-induced endoplasmic reticulum (ER stress. Since brain cells from affected individuals are not available for research, we wished to assess the effect of eIF2B mutation on oligodendroglial-derived cells. METHODOLOGY/PRINCIPAL FINDINGS: A rat oligodendroglial-derived cell line was used for a stable knock-down of eIF2B5 followed by stable expression of mutated eIF2B5(R195H cDNA. In response to a pharmacological ER-stress agent, eIF2B5(R195H expressing cells exhibited heightened ER-stress response demonstrated by hyper induction of ATF4, GADD34, Bip, PDIA1, PDIA3, PDIA4 and PDIA6 proteins. Moreover, even in the absence of a pharmacological stress agent, eIF2B5(R195H-expressing cells exhibited high basal levels of ATF4, GADD34 and ER-associated Bip, PDIA1 and PDIA3. SIGNIFICANCE: The data provide evidence that oligodendroglial-derived cells expressing a mutated eIF2B constantly use their stress response mechanism as an adaptation mean in order to survive. The current study is the first to demonstrate the effects of eIF2B5 mutation on ER homeostasis in oligodendroglial-derived cells.

  3. Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer’s Disease

    Science.gov (United States)

    Brewer, George J.

    2015-01-01

    It has become clear that copper toxicity is playing a major role in Alzheimer’s disease; but why is the brain copper toxicity with cognition loss in Alzheimer’s disease so much different clinically than brain copper toxicity in Wilson’s disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer’s is at least in part, a copper-2 toxicity disease, while Wilson’s is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer’s epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure. PMID:26633489

  4. Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer’s Disease

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    George J. Brewer

    2015-12-01

    Full Text Available It has become clear that copper toxicity is playing a major role in Alzheimer’s disease; but why is the brain copper toxicity with cognition loss in Alzheimer’s disease so much different clinically than brain copper toxicity in Wilson’s disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer’s is at least in part, a copper-2 toxicity disease, while Wilson’s is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer’s epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure.

  5. MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction.

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    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.

  6. Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice.

    Science.gov (United States)

    Morioka, Norimitsu; Zhang, Fang Fang; Nakamura, Yoki; Kitamura, Tomoya; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2015-10-01

    Spinal cord astrocytes are critical in the maintenance of neuropathic pain. Connexin 43 (Cx43) expressed on spinal dorsal horn astrocytes modulates synaptic neurotransmission, but its role in nociceptive transduction has yet to be fully elaborated. In mice, Cx43 is mainly expressed in astrocytes, not neurons or microglia, in the spinal dorsal horn. Hind paw mechanical hypersensitivity was observed beginning 3days after partial sciatic nerve ligation (PSNL), but a persistent downregulation of astrocytic Cx43 in ipsilateral lumbar spinal dorsal horn was not observed until 7days post-PSNL, suggesting that Cx43 downregulation mediates the maintenance and not the initiation of nerve injury-induced hypersensitivity. Downregulation of Cx43 expression by intrathecal treatment with Cx43 siRNA also induced mechanical hypersensitivity. Conversely, restoring Cx43 by an adenovirus vector expressing Cx43 (Ad-Cx43) ameliorated PSNL-induced mechanical hypersensitivity. The sensitized state following PSNL is likely maintained by dysfunctional glutamatergic neurotransmission, as Cx43 siRNA-induced mechanical hypersensitivity was attenuated with intrathecal treatment of glutamate receptor antagonists MK801 and CNQX, but not neurokinin-1 receptor antagonist CP96345 or the Ca(2+) channel subunit α2δ1 blocker gabapentin. The source of this dysfunctional glutamatergic neurotransmission is likely decreased clearance of glutamate from the synapse rather than increased glutamate release into the synapse. Astrocytic expression of glutamate transporter GLT-1, but not GLAST, and activity of glutamate transport were markedly decreased in mice intrathecally injected with Cx43-targeting siRNA but not non-targeting siRNA. Glutamate release from spinal synaptosomes prepared from mice treated with either Cx43-targeting siRNA or non-targeting siRNA was unchanged. Intrathecal injection of Ad-Cx43 in PSNL mice restored astrocytic GLT-1 expression. The cytokine tumor necrosis factor (TNF) has been

  7. Analysis of Blood Concentrations of Zinc, Germanium, and Lead and Relevant Environmental Factors in a Population Sample from Shandong Province, China

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    Long Li

    2017-02-01

    Full Text Available Trace elements, including zinc (Zn and germanium (Ge, are essential for health; deficiency or excess levels of trace elements results is harmful. As a result of industrial and agricultural production, Pb widely exists in people’s living environment. It is absorbed mainly through the respiratory and digestive tracts, producing systemic harm. Reference values for a normal, healthy population are necessary for health assessment, prevention and treatment of related diseases, and evaluation of occupational exposures. Reference ranges for the Chinese population have not been established. From March 2009 to February 2010; we collected data and blood samples (n = 1302 from residents aged 6–60 years living in Shandong Province, China. We measured blood concentrations of Zn, Ge, and Pb using inductively coupled plasma mass spectrometry to determine reference ranges. Results were stratified by factors likely to affect the concentrations of these trace elements: sex, use of cosmetics or hair dye, age, alcohol intake, smoking habits, and consumption of fried food. The overall geometric mean (GM concentrations (95% confidence interval were 3.14 (3.08–3.20 mg/L for Zn, 19.9 (19.3–20.6 μg/L for Ge, and 24.1 (23.2–25.1 μg/L for Pb. Blood Zn concentrations were higher in women than in men (p < 0.001, while the opposite was found for Pb (p < 0.001 and sex did not influence Ge (p = 0.095. Alcohol use was associated with higher blood concentrations of Zn (p = 0.002, Ge (p = 0.002, and Pb (p = 0.001. The GM concentration of Zn was highest in 20–30-year-olds (p < 0.001, while Pb concentrations were highest in 12–16-year-olds (p < 0.001. Use of hair dye was associated with lower blood concentrations of Ge (p < 0.05. GM blood concentrations of Pb differed significantly between those who consumed fried foods 1–2 times/month (18.7 μg/L, 1–2 times/week (20.9 μg/L, and every day (28.5 μg/L; p < 0.001. Blood Pb concentrations were higher in subjects

  8. Key factors leading to reduced recruitment and retention of health professionals in remote areas of Ghana: a qualitative study and proposed policy solutions

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    Dzodzomenyo Mawuli

    2011-05-01

    Full Text Available Abstract Background The ability of many countries to achieve national health goals such as the Millennium Development Goals remains hindered by inadequate and poorly distributed health personnel, including doctors. The distribution of doctors in Ghana is highly skewed, with a majority serving in two major metropolitan areas (Accra and Kumasi, and inadequate numbers in remote and rural districts. Recent policies increasing health worker salaries have reduced migration of doctors out of Ghana, but made little difference to distribution within the country. This qualitative study was undertaken to understand how practicing doctors and medical leaders in Ghana describe the key factors reducing recruitment and retention of health professionals into remote areas, and to document their proposed policy solutions. Methods In-depth interviews were carried out with 84 doctors and medical leaders, including 17 regional medical directors and deputy directors from across Ghana, and 67 doctors currently practicing in 3 regions (Greater Accra, Brong Ahafo, and Upper West; these 3 regions were chosen to represent progressively more remote distances from the capital of Accra. Results and discussion All participants felt that rural postings must have special career or monetary incentives given the loss of locum (i.e. moonlighting income, the higher workload, and professional isolation of remote assignments. Career 'death' and prolonged rural appointments were a common fear, and proposed policy solutions focused considerably on career incentives, such as guaranteed promotion or a study opportunity after some fixed term of service in a remote or hardship area. There was considerable stress placed on the need for rural doctors to have periodic contact with mentors through rural rotation of specialists, or remote learning centers, and reliable terms of appointment with fixed end-points. Also raised, but given less emphasis, were concerns about the adequacy of clinical

  9. Key factors leading to reduced recruitment and retention of health professionals in remote areas of Ghana: a qualitative study and proposed policy solutions.

    Science.gov (United States)

    Snow, Rachel C; Asabir, Kwesi; Mutumba, Massy; Koomson, Elizabeth; Gyan, Kofi; Dzodzomenyo, Mawuli; Kruk, Margaret; Kwansah, Janet

    2011-05-21

    The ability of many countries to achieve national health goals such as the Millennium Development Goals remains hindered by inadequate and poorly distributed health personnel, including doctors. The distribution of doctors in Ghana is highly skewed, with a majority serving in two major metropolitan areas (Accra and Kumasi), and inadequate numbers in remote and rural districts. Recent policies increasing health worker salaries have reduced migration of doctors out of Ghana, but made little difference to distribution within the country. This qualitative study was undertaken to understand how practicing doctors and medical leaders in Ghana describe the key factors reducing recruitment and retention of health professionals into remote areas, and to document their proposed policy solutions. In-depth interviews were carried out with 84 doctors and medical leaders, including 17 regional medical directors and deputy directors from across Ghana, and 67 doctors currently practicing in 3 regions (Greater Accra, Brong Ahafo, and Upper West); these 3 regions were chosen to represent progressively more remote distances from the capital of Accra. All participants felt that rural postings must have special career or monetary incentives given the loss of locum (i.e. moonlighting income), the higher workload, and professional isolation of remote assignments. Career 'death' and prolonged rural appointments were a common fear, and proposed policy solutions focused considerably on career incentives, such as guaranteed promotion or a study opportunity after some fixed term of service in a remote or hardship area. There was considerable stress placed on the need for rural doctors to have periodic contact with mentors through rural rotation of specialists, or remote learning centers, and reliable terms of appointment with fixed end-points. Also raised, but given less emphasis, were concerns about the adequacy of clinical equipment in remote facilities, and remote accommodations. In

  10. Substitution of a highly conserved histidine in the Escherichia coli heat shock transcription factor, sigma32, affects promoter utilization in vitro and leads to overexpression of the biofilm-associated flu protein in vivo.

    Science.gov (United States)

    Kourennaia, Olga V; Dehaseth, Pieter L

    2007-12-01

    The heat shock sigma factor (sigma(32) in Escherichia coli) directs the bacterial RNA polymerase to promoters of a specific sequence to form a stable complex, competent to initiate transcription of genes whose products mitigate the effects of exposure of the cell to high temperatures. The histidine at position 107 of sigma(32) is at the homologous position of a tryptophan residue at position 433 of the main sigma factor of E. coli, sigma(70). This tryptophan is essential for the strand separation step leading to the formation of the initiation-competent RNA polymerase-promoter complex. The heat shock sigma factors of all gammaproteobacteria sequenced have a histidine at this position, while in the alpha- and deltaproteobacteria, it is a tryptophan. In vitro the alanine-for-histidine substitution at position 107 (H107A) destabilizes complexes between the GroE promoter and RNA polymerase containing sigma(32), implying that H107 plays a role in formation or maintenance of the strand-separated complex. In vivo, the H107A substitution in sigma(32) impedes recovery from heat shock (exposure to 42 degrees C), and it also leads to overexpression at lower temperatures (30 degrees C) of the Flu protein, which is associated with biofilm formation.

  11. Lead Poisoning Prevention Tips

    Science.gov (United States)

    ... or removed safely. How are children exposed to lead? Lead-based paint and lead contaminated dust are ... What can be done to prevent exposure to lead? It is important to determine the construction year ...

  12. Lead (Pb) Air Pollution

    Science.gov (United States)

    ... States Environmental Protection Agency Search Search Lead (Pb) Air Pollution Share Facebook Twitter Google+ Pinterest Contact Us As ... and protect aquatic and terrestrial ecosystems. Lead (Pb) Air Pollution Lead Air Pollution Basics How does lead get ...

  13. Niveles de plomo en sangre y factores de exposición en niños del estado de Morelos, México Blood lead levels and exposure factors in children of Morelos State, Mexico

    OpenAIRE

    Fernando Meneses-González; Vesta Richardson; Montserrat Lino-González; María Teresa Vidal

    2003-01-01

    OBJETIVO: Evaluar los niveles de plomo en sangre de niños morelenses y sus factores de exposición. MATERIAL Y MÉTODOS: Estudio transversal para analizar, por voltametría anódica, los niveles de plomo en sangre de 232 niños de 1 a 12 años de edad, que acudieron de junio a octubre de 1996 al Hospital del Niño Morelense de Cuernavaca, Morelos, México. Los factores de exposición se indagaron por cuestionario. El valor de concentración de plomo se transformó al logaritmo natural; se estimó la razó...

  14. Leading Factors Determining Lateral Transfer Success

    Science.gov (United States)

    2013-03-01

    Postgraduate School NROTC Naval Reserve Officer Training Corps OCEANO Oceanography Officer OCM Officer Community Manager OCS Officer Candidate School OMF...Oceanography ( OCEANO ), Public Affairs (PAO), Aerospace Engineering Duty Officer (AEDO), Aviation Maintenance Duty Officer (AMDO) and Foreign Area Officer...FAO). Designator Community Current Inventory 1200 HR 414 1440 EDO 670 1510 AEDO 319 1650 PAO 230 17X0 FAO 408 1800 OCEANO 289 1810 IW 923

  15. Lead Aprons Are a Lead Exposure Hazard.

    Science.gov (United States)

    Burns, Kevin M; Shoag, Jamie M; Kahlon, Sukhraj S; Parsons, Patrick J; Bijur, Polly E; Taragin, Benjamin H; Markowitz, Morri

    2017-05-01

    To determine whether lead-containing shields have lead dust on the external surface. Institutional review board approval was obtained for this descriptive study of a convenience sample of 172 shields. Each shield was tested for external lead dust via a qualitative rapid on-site test and a laboratory-based quantitative dust wipe analysis, flame atomic absorption spectrometry (FAAS). The χ(2) test was used to test the association with age, type of shield, lead sheet thickness, storage method, and visual and radiographic appearance. Sixty-three percent (95% confidence interval [CI]: 56%-70%) of the shields had detectable surface lead by FAAS and 50% (95% CI: 43%-57%) by the qualitative method. Lead dust by FAAS ranged from undetectable to 998 μg/ft(2). The quantitative detection of lead was significantly associated with the following: (1) visual appearance of the shield (1 = best, 3 = worst): 88% of shields that scored 3 had detectable dust lead; (2) type of shield: a greater proportion of the pediatric patient, full-body, and thyroid shields were positive than vests and skirts; (3) use of a hanger for storage: 27% of shields on a hanger were positive versus 67% not on hangers. Radiographic determination of shield intactness, thickness of interior lead sheets, and age of shield were unrelated to presence of surface dust lead. Sixty-three percent of shields had detectable surface lead that was associated with visual appearance, type of shield, and storage method. Lead-containing shields are a newly identified, potentially widespread source of lead exposure in the health industry. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  16. 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

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